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تحميل الدليل التدريبي

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Abstracts of Published papers

 

1: El-Hazmi MA, Al-Swailem AR, Warsy AS, Al-Meshari AA, Sulaimani R, Al-Swailem AM, Magbool GM. Ann Saudi Med. 1999 Jul-Aug; 19(4):304-7.

Lipids and related parameters in Saudi type II diabetes mellitus patients.

College of Medicine, King Saud University, Ministry of Health, and College of Science, King Saud University, Riyadh, Saudi Arabia.

Background: Non-insulin dependent diabetes mellitus (type II DM) is frequently associated with abnormal levels of lipids, particularly in patients with poor diabetic control. This study was designed to investigate the influence of type II DM on levels of plasma lipids and other related parameters in Saudi patients. Saudi Arabia has a high prevalence of diabetes mellitus in the adult population. Since the Saudi population presents a unique group with different dietary habits, lifestyle and genetic make-up, we investigated the lipids, lipoprotein and apolipoprotein pattern in Saudi type II DM patients. Materials and Methods: This study was conducted on 2835 diabetic patients (1361 males, 1474 females) and 200 age-matched healthy adults from the same areas with no history of diabetes mellitus. Data collected included height, weight, body mass index (BMI), blood pressure and other relevant parameters. Lipids, lipoproteins and apolipoproteins were estimated, and correlation studies were carried out between these parameters. Lipids, lipoproteins and apolipoproteins were also correlated with the fasting blood glucose. Results: Our results showed significant elevation in cholesterol and triglyceride, apo A and apo B levels in the diabetic males and females compared to the controls. Approximately 37% of the total DM patients fell in the borderline risk group, while 28.4% fell in the high-risk group for development of cardiovascular disease. Lipoproteins did not differ significantly. Cholesterol, triglyceride, VLDL, LDL and Hb A1c correlated positively with glucose (P<0.05), while triglyceride, VLDL, HDL, LDL, apo A and apo B showed significant correlation with cholesterol, where all parameters increased with cholesterol except HDL, which decreased as cholesterol increased. Conclusion: The findings point toward high prevalence of dyslipidemia in type II DM Saudi patients.

2: El-Hazmi MAWarsy AS Ann Saudi Med.  2001 Jan-Mar; 21(1-2): 21-5.


Prevalence of plasma lipid abnormalities in Saudi children.

 Medical Biochemistry Department and WHO Collaborating Centre for Hemoglobinopathies, Thalassaemias and Enzymopathies, College of Medicine and KKUH , Riyadh, Saudi Arabia.

BACKGROUND: Lipid levels in children vary in different populations. Due to a close association between high lipid levels and development of atherosclerosis, considerable interest has been directed to investigating lipid levels in children. MATERIALS AND METHODS: We conducted this study on 2914 children with ages ranging from 1 year to <15 years, randomly selected during a national household screening program. Fasting blood samples were used for estimation of triglyceride and cholesterol levels. RESULTS: The overall range for cholesterol was 2.0-5.7 mmol/L and for triglyceride the overall range was 0.1-1.7 mmol/L. The children were separated into 14 groups depending on age, and the cholesterol and triglyceride levels were calculated in each age group. Using published guidelines for estimating "borderline" and "high risk" for coronary artery disease from cholesterol and triglyceride levels, the prevalence of borderline and high-risk groups was calculated. 7.72% of the children fell in the borderline risk group and 1.55% in the high-risk group using cholesterol values, while using triglyceride values, 1.4% and 0.55% fell in the borderline and high-risk groups, respectively. The prevalence of abnormality varied in the different age groups. CONCLUSION: The paper discusses the need for a lipid awareness program in Saudi children in an attempt to decrease the complications associated with dyslipidemias during adulthood.

3: El-Hazmi MA, Warsy AS. Ann Saudi Med.  2001 Jan-Mar; 21(1-2): 5-8.


Association of hypertension and non-insulin-dependent diabetes mellitus in the Saudi population.

Department of Medical Biochemistry, College of Medicine and King Khalid University Hospital, Riyadh, Saudi Arabia.

BACKGROUND: Saudi Arabia has a high prevalence of diabetes mellitus (DM). Several studies have shown that hypertension (HT) occurs frequently in obese individuals. This study was conducted to determine the prevalence of HT in Saudi diabetic patients. SUBJECTS AND METHODS: A total of 13,519 nondiabetic and 1286 diabetic adult subjects diagnosed during the National Program for the Study of DM, in which household screening was carried out, were included in the study. The diagnosis of DM and HT was based on the criteria of the World Health Organization. RESULTS: From the total group, the prevalence of HT in nondiabetic males and females was 4.48% and 2.8%, respectively, while it was 11.44% and 15.98% in the diabetic males and females, respectively. The subjects were classified according to the province to which they belonged, and the prevalence of HT was calculated in the diabetic and nondiabetic group. In the Central, Eastern and Western Provinces, female diabetics had a significantly higher HT prevalence compared to male diabetics, however, in the Southern and Northern Provinces, the prevalence rate was almost the same. In all provinces the increase in prevalence of HT in diabetics was significantly higher in the females compared to the males. CONCLUSION: Since HT prevalence increases significantly in diabetics, and this association leads to several cardiovascular complications, it is necessary to adopt measures for the control of DM and HT in the Saudi population.

4Warsy AS El-Hazmi MAAnn Saudi Med. 2001 May-Jul; 21(3-4): 174-7.

 

G6PD deficiency, distribution and variants in Saudi Arabia: an overview.

Departments of Medical Biochemistry, College of Medicine and King Khalid University Hospital, and Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.

BACKGROUND: The first report of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Saudi population of the Eastern Province paved the way for extensive investigations to determine the distribution and molecular pathogenesis of G6PD deficiency in Saudis in different parts of the country. MATERIALS AND METHODS: During a national study lasting from 1982 to 1993, 24,407 Saudis in 31 different areas of Saudi Arabia were screened for G6PD deficiency using spectrophoretic estimation of the enzyme activity and electrophoretic separation of the phenotypes. RESULTS: The results in the males and females were separately analyzed, and showed a statistically significant difference in the frequency in the male (0.0905) and female (0.041) population (P<0.05). The frequency in the male varied from 0 to 0.398, and in the female from 0 to 0.214. The phenotypes identified included G6PD-A(+), G6PDA-Mediterranean and G6PD-A(-), and G6PD-Med-like with G6PD-B(+) as the normal phenotype in all areas. CONCLUSION: This study shows that G6PD deficiency is a frequently identified single-gene disorder in Saudi Arabia and G6PDA-Mediterranean is the major variant producing the severe deficiency state in this population.

5: El-Hazmi MA, Warsy AS. Ann Saudi Med. 2001 May-Jul; 21(3-4): 165-9.


Normal reference values for hematological parameters, red cell indices, HB A2 and HB F from early childhood through adolescence in Saudis.

Department of Medical Biochemistry, College of Medicine, and King Khalid University Hospital, Riyadh, Saudi Arabia.

BACKGROUND: Values of hematological parameters are affected by factors such as age, sex, ethnic background and social, nutritional and environmental factors. The objective of this study was to determine the values of hematological parameters, red cell indices and Hb A2 and Hb F levels in normal Saudi children, living in the Central Province of Saudi Arabia. MATERIALS AND METHODS: The study was carried out on 1526 apparently healthy children, with ages ranging from 1-15 years, and selected during a household screening program. Hematological parameters, red cell indices, and hemoglobin types (Hb A2 and Hb F) were estimated, and the children were divided into 15 groups depending on the age. Male and female children were separated, and the mean and standard deviation of each parameter was calculated for each age group. RESULTS: No significant differences were observed in the red cell count in the male and female children. White blood cells gradually decreased from 2 years onwards, while hemoglobin and hematocrit levels increased significantly from 2 to 15 years. Mean cell volume and mean cell hemoglobin also showed slight increases, while mean cell hemoglobin concentration remained more or less constant. Hemoglobin A2 and Hb F showed slight but nonsignificant fluctuations. Comparison of the results with those reported in the literature shows that Saudi children have some values similar to Caucasians, while others have values which are intermediate between Caucasians and African children. CONCLUSION: The values reported in this study can be used as normal reference values for Saudi children and adolescents.


6: El-Hazmi MAWarsy AS Ann Saudi Med. 2002 Sep-Nov;22(5-6):303-7.


The prevalence of obesity and overweight in 1-18-year-old Saudi children.

 Department of Medical Biochemistry, College of Medicine, King Khalid University Hospital and King Saud University, Riyadh, Saudi Arabia. mohsen@ksu.edu.sa

OBJECTIVES: The aim of this study was to review the prevalence of overweight and obesity in Saudi children with ages ranging up to 18 years. SUBJECTS AND METHODS: The study was a cross-sectional national epidemiological household survey, and the study group included 12071 children (boys 6281; girls 6420), with ages ranging from 1-18 years. Their height and weight were measured and body mass index (BMI) was calculated. The study group was classified as obese or overweight, using age- and sex-specific cut-off points for BMI for determining overweight and obesity in children. RESULTS: The overall prevalence of overweight was 10.7% and 12.7% in the boys and girls, respectively, and obesity was 6.0% and 6.74% in the two groups, respectively. The children were grouped according to the province to which they belonged, and prevalence of obesity and overweight were calculated for each province. The highest frequency was in the Eastern Province, while the lowest was in the Southern Province. The children were further grouped into 1-6, 6-12 and 12-18-year-olds and prevalence of obesity and overweight was calculated. In addition, at yearly intervals, the prevalence of obesity and overweight was calculated. Among the boys and girls, the maximum prevalence of obesity was in the 2-3 year-olds. A decrease in prevalence was found in both males and females up to the age group of 8-13 years, and then the prevalence increased again up to the 18 years age. CONCLUSION: This epidemiological household survey shows the overweight and obesity trends in Saudi children based on the international sex-specific cut-off points for BMI. It also shows a variable prevalence in different age groups until after 13 years, when the prevalence rate increases.

 

7: El-Hazmi MAWarsy AS Ann Saudi Med. 2003 Jan-Mar;23(1-2):24-7.

 
Increased frequency of angiotensin-converting enzyme DD genotype in Saudi overweight and obese patients.

Department of Medical Biochemistry and the WHO Collaborating Centre, College of Medicine, King Khalid University Hospital and Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia, mohsen@ksu.edu.sa.

Background: Several studies have been carried out to investigate the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) in obese and normal weight individuals, often with contradictory results in different populatios. In some studies, the DD genotype occurs at a high frequency in obesity, while in others no association has been demonstrated. Since obesity and overweight are of frequent occurrence in the Saudi population, we initiated this study to investigate the I/D polymorphism of ACE in obese, overweight and normal weight Saudis. Patients and Methods: The study group included 457 Saudi males and females. The height and weight were measured and body mass index (BMI) was calculated. Based on the BMI value, the total study population was classified as normal, overweight and obese. A total of 117 obese (BMI >30 (kg/m(2))), 185 overweight (BMI=25-29.9 (kg/m(2))) and 155 normal weight individuals (BMI< (kg/m (2)) were enrolled. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used to study the ACE polymorphism. For the deletion (D) form, a 190 bp and for the insertion (I) form, 490 bp DNA fragment were obtained on 2% agarose gel electrophoresis. Results: The frequency of DD genotype was 76.9% in the obese, and 73.5% in the overweight individuals, compared to 19.66% and 24.86% of the ID genotype in the obese and overweight, respectively. Among the normal weight individuals, the frequency was significantly lower for DD and higher for the ID genotype, i.e., 58.7% for DD and 40% for ID. The allele frequencies in the obese were 0.867 and 0.133 for the D and I alleles, respectively. While in the overweight, the frequencies were 0.859 and 0.141 for these alleles, respectively, compared to 0.787 and 0.213 in the normal weight individuals. Conclusions: The DD genotype and D allele occur at a high frequency in Saudi overweight and obese individuals, and may have some role in fat accumulation by affecting metabolic pathways of fat, thus leading to the development of overweight and obesity.


8: Al-Atawi FS, Addar MH, Warsy AS Babay ZA. Saudi Med J. 2004   Nov; 25(11): 1617-22.


Leptin concentration during different trimesters of pregnancy and its relation to other pregnancy hormones.

College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

OBJECTIVE: To determine the levels of leptin and other pregnancy hormones (progesterone, estradiol, folliculi stimulating hormone, luteinizing hormone and beta human chorionic gonadotropin) in pregnant females during different stages of pregnancy and to correlate these levels to maternal weight, body mass index (BMI), babies weight and babies BMI. METHODS: Leptin level and other pregnancy hormones were measured in 36 pregnant females and 30 non-pregnant females followed at King Khaled University Hospital, Riyadh, Kingdom of Saudi Arabia in the year 2001 in a prospective study. Blood samples were collected at the first, 2nd and 3rd trimester and after delivery. Correlation analysis between leptin level and pregnancy hormones, in addition to maternal weight, BMI, babies weight and BMI. RESULTS: The mean leptin levels during pregnancy and postnatally were significantly higher in pregnant females compared to the non-pregnant controls. Serum concentration of leptin increased significantly (p=0.01) in the pregnant females from 21.24 +/- 9 ng/ml during the first trimester to 26.3 +/- 8.69 ng/ml during the 2nd trimester, but insignificantly decreased to 23.29 +/- 8.62 ng/ml during the 3rd trimester (p=0.073). After delivery leptin concentration significantly decreased to 17.36 +/- 7.95 ng/ml (p=0.0025). The changes in levels of leptin during pregnancy were independent to other pregnancy hormones which showed a different pattern of variation. CONCLUSION: The changes in levels of leptin during pregnancy were independent to other pregnancy hormones which showed a different pattern of variation.


9: Atawi FAWarsy AS Babay Z, Addar M. Clin Exp Obstet Gynecol. 2004; 31(3): 211-6.


Leptin concentration during different stages of pregnancy.
College of Science, King Saud University, Riyadh (Saudi Arabia).

OBJECTIVES: To determine the levels of leptin in pregnant females during different stages of pregnancy and to correlate these levels to maternal weight, body mass index (BMI), neonate weight and neonate BMI. MATERIAL & METHODS: A case control study was carried out in which 60 pregnant females were enrolled, but only 36 completed the study and 30 non-pregnant females were used as controls. Blood samples were collected at the 1st trimester, 2nd trimester and 3rd trimester, and after delivery. Serum was used for the estimation of leptin (by radioimmunoassay). RESULTS: The results showed that the levels of leptin were significantly higher in pregnant females compared to non-pregnant females, but significantly decreased after delivery. In pregnant females with gestational diabetes the leptin level was insignificantly higher. Conclusion: The increase of leptin levels may be due to the stimulatory effect of insulin on leptin secretion from adipose tissue.

10:  Babay ZA, Warsy AS El-Hazmi MA, Addar MH. Saudi Med J. 2004 Feb; 25(2): 212-4.


Leptin level in pregnant mothers at term and cord blood and the effect of newborns gender.
Department of Obstetrics and Gynecology, College of Medicine, King Khalid University Hospital, PO Box 7805, Riyadh 11472, Kingdom of Saudi Arabia. zbabay@hotmail.com

OBJECTIVE: To evaluate the leptin level in healthy pregnant mothers at term and in their newborns and its relationship to their body mass index (BMI) and gender of the newborn. METHODS: The leptin level was measured in serum of 187 pregnant women at term delivering at the King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia in July 2001 and their newborns. Correlation studies were made between leptin level and their growth parameters, and gender of the newborns. RESULTS: Leptin level of the mothers was significantly higher compared to their newborns. There was a significant correlation between leptin level in the pregnant women and their weight, BMI, and the newborns leptin level and weight, but not their height or BMI. A statistically significant difference was found between male and female newborns plasma leptin level. A significant correlation was found between male newborns leptin level and all their growth parameters, while in the female newborns there was no correlation between their leptin level and BMI. CONCLUSION: Leptin plays an important role in providing a growth promoting signal during pregnancy, but the fat mass does not seem to be the most important predictor of cord leptin level.


11: Al-Malki JS, Al-Jaser MHWarsy AS Int J Obes Relat Metab Disord. 2003 Jan; 27(1): 134-9.


Overweight and obesity in Saudi females of childbearing age.

Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.

OBJECTIVE: Overweight and obesity are among the most frequently encountered multifactorial disorders in most populations of the world. The aim of this study was to determine the prevalence of overweight and obesity in Saudi females of childbearing age. MATERIALS AND METHODS: The study was approved by the University Scientific Committee. It included a group of 600 randomly recruited healthy females with age ranging from 16-45 y. Four hundred and twenty one were students and 179 were housewives attending outpatient clinics for minor illnesses. Informed consent was obtained. Height and weight were recorded on one occasion. Body mass index (BMI) was calculated. RESULTS: Height, weight and BMI showed normal Gaussian distribution in these females and there was a significant positive correlation between BMI and age of each subject (r=0.505; P</=0.001). Prevalence of leanness, normal weight, overweight, obesity and morbid obesity were calculated in the total group and in different age groups. Significant increase in the prevalence of both overweight and obesity occurred with age. Unmarried and married females were compared and the latter had a higher prevalence of both overweight and obesity compared to the former. This difference persisted after taking into account differences in the age of the two groups. Students and housewives were compared but no differences in the prevalence were observed in the two groups. DISCUSSION: The results of this study show that overweight and obesity are frequently encountered in Saudi females of childbearing age. The prevalence of overweight and obesity was higher amongst a group of married women than among a group of single women. There is an urgent need to spread awareness about obesity, its consequences and ways and means of prevention among the females.

12: Babay ZA, Addar MH, Warsy AS, El-Hazmi MA.  Saudi Med J. 2002 Aug; 23(8): 943-6.


The inter-relationship hematological parameters between Saudi newborns and parents.

Department of Obstetrics & Gynecology, College of Medicine, King Khalid University Hospital, Riyadh 11472, Kingdom of Saudi Arabia. maddar2001@hotmail.com

OBJECTIVE: To determine the relationship of the hematological parameters between Saudi newborns and their parents. METHODS: This study was carried out at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, over a one-year period. Venous blood samples were taken from 82 healthy Saudi pregnant women in labor at full term, their husbands, and umbilical cord blood after delivery. Estimation of the hematological indices, in addition to transferrin level were performed. RESULTS: A statistically significant correlation was found between parents and cord blood with regards to red blood count, mean corpuscular volume, mean corpuscular hemoglobulin, mean corpuscular hemoglobulin concentration and packed cell volume, while no correlation was found with hemoglobulin and transferrin. CONCLUSION: Some of the hematological indices could be mainly genetically determined including red blood count, mean corpuscular volume, mean corpuscular hemoglobulin concentration, and packed cell volume as significant correlation was found between parents and their newborns while hemoglobulin and transferrin levels were not as these variables are mainly affected by environmental factors.

13: El-Hazmi MA, Warsy ASJ Trop Pediatr. 2002 Jun; 48(3): 172-7.


A comparative study of prevalence of overweight and obesity in children in different provinces of Saudi Arabia.

Department of Medical Biochemistry, College of Medicine & King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia. mohsen@ksu.edu.sa

The aim of this study was to determine the prevalence of overweight and obesity in Saudi children from different provinces of the country and in different age groups. A total of 12,701 children (6,281 boys and 6,420 girls) with ages ranging from 1 to 18 years were enrolled during a household screening programme in different provinces of Saudi Arabia and height and weight were recorded. Body Mass Index (BMI) was calculated and applying age and sex specific cut-off points for BMI the children were grouped into overweight and obese. The overall prevalence of overweight was 10.68 and 12.7 per cent and that of obesity was 5.98 and 6.74 per cent in the boys and girls, respectively. In the different provinces the prevalence of overweight ranged from 8.8 to 27.4 per cent and from 9.3 to 27.6 per cent and obesity ranged from 4.7 to 10.4 per cent and from 4.3 to 13.8 per cent in the boys and girls, respectively. Prevalence of overweight and obesity was also calculated after grouping the children into 17 groups according to age. It is concluded that overweight and obesity occur in all provinces of Saudi Arabia although at a variable prevalence. In general, girls have a higher prevalence of both overweight and obesity compared with boys. Eastern province children have the highest prevalence and the Southern province children have the lowest prevalence of overweight and obesity. When grouped according to age, overweight and obesity tend to increase with age. Suggestions are made to prevent overweight and obesity development in Saudi children.


14: Warsy AS, el-Hazmi MA. East Mediterr Health J. 1999 Nov; 5(6): 1236-42.

 
Diabetes mellitus, hypertension and obesity--common multifactorial disorders in Saudis.

Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.

Diabetes mellitus, hypertension and obesity are among the multifactorial disorders that occur at a higher prevalence in older age groups. Their prevalence is affected by both genetic and environmental factors. We investigated the distribution of diabetes mellitus, hypertension and obesity in Saudi males and females by conducting a household screening survey during the period 1992-1996 of the adult population (> 14 years) in five different areas of Saudi Arabia. Height, weight, age and other essential details were recorded and diastolic and systolic blood pressures measured. Glucose levels were measured in blood taken after fasting and 2 hours after a glucose load. The data were used to classify the individuals as diabetic, glucose intolerant and normal, using WHO criteria. The individuals were further classified as type 1 diabetes mellitus and type 2 diabetes mellitus. The overall prevalence of diabetes mellitus was 9.7% and 7.0%, obesity 13.05% and 20.26%, overweight 27.23% and 25.20%, and hypertension 5.39% and 3.65% in the adult male and female populations respectively. A significant increase was observed in the prevalence of diabetes, obesity and hypertension with age in both males and females. In addition, the prevalence of obesity and overweight was significantly higher in the individuals with diabetes mellitus.


15:  Warsy AS el-Hazmi MA. East Mediterr Health J. 1999 Nov; 5(6): 1208-12.


Glutathione reductase deficiency in Saudi Arabia.
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.

Glutathione reductase (GR) is a ubiquitous enzyme required for the conversion of oxidized glutathione (GSSG) to reduced glutathione (GSH) concomitantly oxidizing reduced nicotinamide adenine dinucleotide phosphate (NADPH) in a reaction essential for the stability and integrity of red cells. Mutations in the GR gene and nutritional deficiency of riboflavin, a co-factor required for the normal functioning of GR, can cause GR deficiency. We conducted a study on 1691 Saudi individuals to determine the overall frequency of GR deficiency and to identify whether the deficiency results from genetic or acquired causes or both. The activity of GR was measured in freshly prepared red cell haemolysate in the presence and absence of flavin adenine dinucleotide (FAD) and the activity coefficient (AC) was determined. Samples with low GR activity (> 2.0 IU/g haemoglobin) both in the presence and absence of FAD and an AC between 0.9 and 1.2 were considered GR-deficient. Samples with AC > or = 1.3 were considered riboflavin-deficient. The overall frequency of partial GR deficiency was 24.5% and 20.3% in males and females respectively. In addition, 17.8% of males and 22.4% of females suffered from GR deficiency due to riboflavin deficiency. This could be easily corrected by dietary supplementation with riboflavin. No cases of severe GR deficiency were identified.


16: El-Hazmi MAWarsy AS  East Mediterr Health J. 1999 Nov; 5(6): 1183-7.


Molecular studies on Yemeni sickle-cell-disease patients: Xmn I polymorphism.

Medical Biochemistry Department, WHO Collaborating Centre for Haemoglobinopathies, Thalassaemias and Enzymopathies, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

Our studies of the Saudi population have shown that in patients with mild presentation of sickle-cell disease (SCD) from Saudi Arabia's eastern region, the prevalence of polymorphic sites is high. However, the prevalence is very low in patients with severe SCD from the south-west of the country. We expanded these studies to a group of Yemeni patients with severe SCD, resident in Riyadh. We investigated a total of 60 chromosomes carrying the sickle-cell (Hb S) gene and 14 chromosomes carrying the Hb A gene. Amongst the Hb AA group, the prevalence was 42.9% and 57.1% for the presence (+) and absence (-) of Xmn I polymorphic sites. In the Hb SS individuals, the prevalence of Xmn I polymorphic sites was similar to the prevalence reported in the south-western region of Saudi Arabia.


17: El-Hazmi MA, Warsy AS.East Mediterr Health J. 1999 Nov; 5(6): 1159-64.


Pattern for alpha-thalassaemia in Yemeni sickle-cell-disease patients.
Medical Biochemistry Department, WHO Collaborating Centre for Haemoglobinopathies, Thalassaemias and Enzymopathies, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

A group of Yemeni patients with sickle-cell disease (SCD) and normal Hb AA individuals living in Riyadh were studied to determine the incidence of the alpha-gene molecular defect. Blood samples were obtained from 26 SCD patients and 19 controls (the Hb AA group). In the SCD patients the frequency of single alpha-gene deletion (-alpha/alpha alpha) was 0.346, compared to 0.263 in the Hb AA group. The frequency of two gene deletion (-alpha/-alpha) was 0.231 (0.0 for the Hb AA group). In one Hb AA case, a triple alpha-gene arrangement (alpha alpha alpha/alpha alpha) was found (frequency 0.053). The results suggest that alpha-thalassaemia occurs frequently in Yemeni SCD patients. Further studies to determine the overall frequency of alpha-thalassaemia in the Republic of Yemen would be of value for patient management.


18: El-Hazmi MA, Warsy AS, Bashir N, Beshlawi A, Hussain IR, Temtamy S, Qubaili F .East Mediterr Health J. 1999 Nov;5(6):1154-8.


Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease.

Medical Biochemistry Department, World Health Organization Collaborating Centre for Haemoglobinopathies, Thalassaemias and Enzymopathies, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

We collaborated with researchers from Egypt, Syrian Arab Republic and Jordan in a study of patients with sickle-cell disease from those countries, and from various parts of Saudi Arabia, in order to investigate the influence of genetics on the clinical presentation of the disease, and to attempt to determine the origin of the sickle-cell gene in Arabs. Our results suggest that beta-globin gene haplotypes influence the clinical presentation of sickle-cell disease, and that there are at least two major foci for the origin of the sickle-cell gene, one in the eastern part of Saudi Arabia, and the other in the populations of North Africa and the north-western part of the Arabian peninsula.


 

 

19: El-Hazmi MAWarsy AS East Mediterr Health J. 1999 Nov; 5(6): 1147-53.


Appraisal of sickle-cell and thalassaemia genes in Saudi Arabia.

Department of Medical Biochemistry, WHO Collaborating Centre for Haemoglobinopathies, Thalassaemias and Enzymopathies, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

A comprehensive national survey of the distribution of the sickle-cell (Hb S) gene and thalassaemia genes was initiated in 1982, with more than 30,055 blood samples collected. The Hb S, alpha- and beta-thalassaemia gene frequency range was 0.005-0.145, 0.01-0.40 and 0.01-0.15 respectively in various areas of Saudi Arabia. We present here an appraisal of sickle-cell and thalassaemia gene occurrence in the Saudi population, based on our studies conducted over 10 years in different regions of Saudi Arabia.

20: El-Hazmi MA, Warsy AS. East Mediterr Health J. 2000 Mar-May; 6(2-3): 276-82.


Prevalence of overweight and obesity in diabetic and non-diabetic Saudis.

Department of Medical Biochemistry, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

A total of 14,660 individuals were included in the study. A fasting blood sample and 2-hour post-glucose load blood sample from each participant were analysed for blood sugar. Participants were classified as diabetic or non-diabetic and as either obese (BMI > 30 kg/m2), overweight (BMI 25-29.9 kg/m2) or normal (BMI < 25 kg/m2). The prevalence of obesity was calculated in the total sample and separately for diabetic and non-diabetic males and females. The results showed obesity and overweight in 13.05% and 27.23% of males and 20.26% and 25.20% of females respectively. The prevalence of both obesity and overweight were significantly higher among diabetics than non-diabetics. In each province, diabetics had a significantly higher prevalence of obesity than non-diabetics. Several interprovincial variations were seen. Public education on obesity and overweight and ways to decrease them are recommended in Saudi Arabia.


21: El-Hazmi MA,Warsy AS.J Trop Pediatr. 2001 Jun; 47(3): 181-5.

 

Evaluation of serum cholesterol and triglyceride levels in 1-6-year-old Saudi children.

Department of Medical Biochemistry & WHO Collaborating Centre for Haemoglobinopathies, Thalassaemias and Enzymopathies, King Saud University, Riyadh, Saudi Arabia. mohsen@ksu.edu.sa

Estimations of cholesterol and triglyceride in serum are frequently requested tests due to the close association between elevated levels of these parameters and the risk of arteriosclerosis later leading to cardiovascular disease. Since lipid levels in children show considerable variations in different populations, this study was conducted with the aim of investigating levels of cholesterol and triglycerides in Saudi children less than 6 years old. The study group comprised 582 children with ages ranging from 1 to 6 years, randomly selected during a household screening programme. Fasting blood was used for the estimation of cholesterol and triglyceride using an autoanalyser. The overall range for cholesterol was 2.1-5.7 mmol/l and for triglyceride it was 0.1-1.84 mmol/l. The children were separated into five further groups depending on age, and the levels of cholesterol and triglycerides were obtained in each age group. Using published guidelines for cholesterol and triglyceride levels, to estimate 'borderline' and 'high risk' for arteriosclerosis and coronary artery disease, the prevalence of both risk groups were calculated in Saudi children. A total of 6.87 per cent of children fell in the borderline risk and 1.55 per cent in the high-risk group using cholesterol levels, while 1.89 per cent fell in the borderline-risk group and 1.2 per cent in the high-risk group using triglyceride levels. This paper presents the lipid values and discusses the need for lipid awareness programmes in the country.


22: El-Hazmi MA, Warsy AS. J Trop Pediatr. 2001 Jun; 47(3): 136-41.

 

A comparative study of haematological parameters in children suffering from sickle cell anaemia (SCA) from different regions of Saudi Arabia.

Department of Medical Biochemistry and WHO Collaborating Centre for Haemoglobinopathies, Thalassaemias and Enzymopathies, College of Medicine & King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia. Mohsen@ksu.edu.sa

Sickle cell anaemia (SCA) occurs frequently in several regions of Saudi Arabia but the haematological and clinical presentations are significantly variable. We investigated 264 Saudi children suffering from SCA originating from different regions of Saudi Arabia. Normal children from the same region were used as controls. Freshly obtained blood samples from patients and controls were used to estimate haematological parameters, red cell indices, Hb A2 and Hb F levels. The results of children from the different regions were separately analysed using the Statistical Analysis System (SAS). Significant variations were seen in the haematological parameters in SCA patients compared to controls in each region. In addition, comparison of patients from different areas also showed wide variations. The highest levels of haemoglobin, red blood cells and haematocrit were in the SCA children from the eastern province, and the lowest levels were from those in the western province. Red cell indices and Hb A2 levels did not differ significantly but HbF levels were significantly higher compared to the control group. Inter-regional differences were seen in the Hb F level. A slight but statistically significant increase was seen in the total haemoglobin with Hb F. This paper compares the haematological parameters of SCA in different regions of Saudi Arabia and shows a significant haematological heterogeneity in SCA in Saudis.


23: El-Hazmi MA, Warsy AS. Saudi Med J.  2001 Jan; 22(1): 44-8.


Prevalence of hypertension in obese and non-obese Saudis.

 Medical Biochemistry Department & WHO Collaborating Centre for Haemoglobinopathies, thalassaemias and enzymopathies, College of Medicine & King Khalid University Hospital, PO Box 2925, Riyadh 11461, Kingdom of Saudi Arabia. mohsen@ksu.edu.sa

OBJECTIVE: Obesity occurs at a high prevalence in the Saudi population. Studies in literature show that hypertension occurs more frequently in obese individuals. This study was designed to determine the prevalence of hypertension in obese Saudis in comparison with results obtained in non-obese individuals. METHODS: The screening involved a statistically designed household screening program. Only adults 14-70 years of age were included in the study. Blood pressure (systolic and diastolic) was measured when the individuals were in sitting position and height and weight were used to calculate Body Mass Index. All individuals with Body Mass Index > 30 were classified as obese and hypertension was measured as systolic blood pressure > 140 and diastolic blood pressure > 90 or both. The prevalence of hypertension was calculated in the obese and non-obese group. Chi square analysis was carried out to determine the significance of the difference in prevalence in different groups. RESULTS: In the non-obese males and females the prevalence of hypertension was 4.8% and 2.8%. While in the obese group the prevalence was almost 1.6 times higher in the males (8%) and 3.52 times higher (8%) in the female obese. The results were separated on the basis of the province to which the population belonged and hypertension prevalence was calculated in the obese and non-obese. In each region the prevalence of hypertension was higher in the obese group compared to the non-obese group. Non-obese females had significantly lower hypertension prevalence than the male in the same province but the hypertension prevalence was higher in the females compared to the male in the obese group. Male in the Eastern, Southern and Western provinces did not show an increased hypertension prevalence in the obese. CONCLUSION: Since the prevalence of obesity is high in Saudis and since obesity and hypertension occur together and cause serious complications, it is strongly suggested that measures are adopted to decrease prevalence of obesity and its underlying complications. Awareness programs are required at the level of the general public for successful implication of preventive programs.


24: El-Hazmi MA, Warsy AS. J Trop Pediatr.  2000 Feb; 46(1): 25-9.


Xmn I polymorphic site in Yemeni sickle cell disease patients.

Department of Medical Biochemistry, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

To investigate the molecular basis of severe clinical presentation in sickle cell disease (SCD) patients in Yemen, this study was conducted on 30 Yemeni SCD patients living in Riyadh and attending King Khalid University Hospital. Seven individuals without SCD were used as controls. Haematological parameters, red cell indices, Hb A2 and Hb F levels were estimated and haemoglobin variant were identified on electrophoresis profiling. DNA was extracted from the buffy coat separated from fresh blood samples and was treated with the restriction endonuclease: Xmn I. The fragments generated were separated on electrophoresis, transferred to nitrocellulose and hybridized to a 32P-labelled probe of gamma-globin gene. After extensive washing, two bands, 8.1 kb and 7.0 kb in size, were obtained. The frequency of occurrence of the presence of Xmn I polymorphic site (7.0 kb fragment) and its absence (8.1 kb fragment) were documented. The results in Yemeni SCD patients were compared with the results obtained previously in Saudi Arabs. Of the 30 SCD patients from Yemen 29 had only the 8.1 kb fragment and one had only the 7.0 kb fragment. This gave the frequency of 0.966 for the absence (-) and 0.033 (+) for the presence of Xmn I polymorphic site. This is the same result as that reported earlier for SCD patient from southwestern Saudi Arabia [(-) = 0.966; (+) = 0.033] but is significantly different from that reported in the eastern province [(-) = 0.068; (+) 0.932)] of Saudi Arabia. This paper presents the nature of molecular linkage in SCD patients from Yemen.

25: El-Hazmi MAWarsy AS J Trop Pediatr. 1999 Dec; 45(6): 370-4.


Alpha thalassaemia in Yemeni children with sickle cell disease.

Department of Medical Biochemistry, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Alpha thalassaemia frequently occurs in several of the Middle Eastern populations. This study was conducted on 26 sickle cell disease (SCD) patients from Yemen and 19 normal children (Hb AA) living in Riyadh, Saudi Arabia. Blood samples were extracted by venepuncture, and haematological and biochemical parameters were estimated. DNA was extracted from the buffy coat and analysed for alpha-gene arrangement using Bam HI and Bgl II. The frequency of alpha-gene deletion in the total Yemeni group (26 SCD + 19 Hb AA) was 0.311 for one alpha-gene deletion (-alpha/alpha alpha) and 0.13 for two alpha-gene deletions (-alpha/-alpha). When separated on the basis of the Hb phenotype the alpha-gene deletion frequency was significantly higher (-alpha/alpha alpha = 0.346 and -alpha/-alpha = 0.231) in the SCD patients compared to the normal Hb AA group (-alpha/alpha alpha = 0.263 and -alpha/-alpha = 0). In the Hb AA group one child had triple alpha-gene arrangement (alpha alpha alpha/alpha alpha) giving an overall frequency of triple alpha-gene as 0.022. Haematological parameters showed variations in the SCD patients with and without alpha-gene deletion. This paper shows for the first time that alpha-gene deletion occurs in the Yemenis and the frequency is higher in patients with SCD. Further population-based studies are required to determine the exact frequency of the different types of alpha-thalassaemias in the overall Yemeni population.


26: El-Hazmi MA, Warsy AS.J Trop Pediatr. 1999 Aug; 45(4): 221-5.


The pattern for common anaemia among Saudi children.

Medical Biochemistry Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Anaemia is of frequent occurrence in children in different parts of the world and poses a significant health problem. A few isolated reports indicate that anaemia occurs at a high prevalence rate in Saudi Arabia though the actual prevalence in several regions is not known. The aim of the present study was to determine the prevalence of different types of anaemias in Saudi children in different areas of the country. Blood samples were collected from 5381 children less than 14 years of age, and haematological analysis and red cell indices were determined. The results of haematological parameters were used to group the children as anaemic (Hb < 11.2 g/dl) and non-anaemic (Hb > 11.2 g/dl) and the red cell indices were used to classify the anaemia as hypochromic-microcytic, normochromic-normocytic, and normochromic-macrocytic. The overall prevalence of anaemia in Saudi children was 24.8 per cent. The prevalence was highest in the children from the Eastern province (41.3 per cent) and lowest in the central province (16.5 per cent). Within each province differences were obvious in the prevalence of anaemias in the different areas. The majority of the anaemia in the eastern and south-western provinces was hypochromic-microcytic, while in the north-western and central provinces normochromic-normocytic anaemia occurred most frequently. Macrocytic anaemia was not encountered in any of the screened areas of the central province and many areas of the eastern province. However, in north-western and south-western provinces it occurred at a frequency of 0.15-3.4 per cent. The data show that anaemia is a frequent problem in Saudi children living in different parts of Saudi Arabia and emphasizes the need for nutritional and genetic assessment to determine the nutritional contributions to anaemias and hence the correction of nutritional anaemias by proper dietary intervention.

 

27: Alzeer AH, Al-Arifi A, Warsy AS, Ansari Z, Zhang H, Vincent JL. Intensive Care Med. 1999 Jan; 25(1): 58-62.


Nitric oxide production is enhanced in patients with heat stroke.
Medical Department, King Khalid University Hospital, Riyadh, Saudi Arabia.

OBJECTIVE: To determine whether nitric oxide (NO) production is increased in heat stroke (HS) patients. DESIGN: A prospective analysis of nitrite and nitrate (NO2*/NO3) levels in ten HS patients was performed at the HS center in Makkah, Saudi Arabia. METHODS: Plasma (NO2*/NO3) levels were determined spectrophotometrically before cooling (0 time), and at 6, 12, and 24 h post-cooling. RESULTS: The mean level of NO in the ten HS victims before cooling was significantly higher than in eight control patients (35.6+/-37.0 vs. 3.0+/-4.2 micromol/l; p<0.01). The levels were higher in non-survivors than in survivors. NO also correlated positively with the Acute Physiology and Chronic Health Evaluation II score (r = 0.72, p<0.018). There was no correlation between the NO level before cooling and blood pressure, rectal temperature, or cooling time. CONCLUSION: HS is associated with excessive NO production, the magnitude of which is proportional to the severity of illness. NO may be an important mediator and integral part of the pathophysiological processes resulting in HS and may be a central factor linking the neurological and cardiovascular abnormalities observed in HS.

 

 28:  Alzeer AH, el-Hazmi MA, Warsy AS, Ansari ZA, Yrkendi MS. Clin Chem. 1997 Jul; 43(7): 1182-7.


Serum enzymes in heat stroke: prognostic implication.

Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

We measured serum creatine kinase (CK), lactate dehydrogenase (LD), aspartate aminotransferase (AST), and serum alanine aminotransferase (ALT) in 26 heat stroke (HS) victims and 10 control (non-heat-exhausted) subjects during annual Hajj in Makkah, Saudi Arabia. On admission to the HS treatment unit, serum CK, AST, ALT, and LD were higher in HS victims than controls (P < 0.05), and at 6, 12, and 24 h were higher than baseline concentration. The patient group was divided into three groups, (a) those who had a quick recovery, (b) those who were critically ill until the end of the Hajj period (7 days), and (c) those who died. Serum enzymes at the time of admission were significantly higher (P < 0.05) in the nonsurviving group (n = 6) and the severely ill (n = 9) than in those who had a quick recovery (n = 11). ROC curves were plotted for each enzyme. The most useful indicator was LD, as it could distinguish significantly between the groups who died and those who had a quick recovery (area under the curve = 0.991 +/- 0.0286). It was followed by CK and AST as useful prognostic factors. When compared with ROC curves for body temperature, anion gap, and serum potassium, the enzyme results were superior prognostic indicators.

29: El-Hazmi MA, Warsy ASAnn Saudi Med. 1997 May; 17(3): 302-6.


Prevalence of obesity in the Saudi population.

Department of Medical Biochemistry and W.H.O Collaborating Centre for Haemoglobinopathies, Thalassaemias and Enzymopathies and Department of Biochemistry, King Saud University, Riyadh, Saudi Arabia.

Obesity, i.e., excessive deposition of fat in the body, is the most common nutritional disorder in the developed countries. The aim of this study was to determine the prevalence of overweight and obesity in the population of Saudi Arabia living in different regions of the country. A total of 14,660 adult Saudi males and females (>14 years of age) in 35 areas were screened and information on height (m) and weight (kg) was recorded during a National Project to study various aspects of diabetes mellitus in Saudi Arabia. The Body Mass Index (BMI) was calculated and the data was used to group the males and females as overweight (BMI=25-29.9) and obese (BMI>30). In the total Saudi population the prevalence of overweight was 27.23% and 25.20% in the males and females respectively, while the prevalence of obesity was 13.05% and 20.26% in the males and females respectively. When separated on the basis of each region, the prevalence of obesity was highest in the females in Central Province and in the males in the Western Province, while overweight was more prevalent in both the male and female population of the Central Province. The data was further analyzed depending on each area within each province and significant differences were encountered. In general, overweight was more common in the males and obesity in the females. This high prevalence of obesity is a cause for concern, since obesity is associated with several complications which increase both morbidity and mortality. Awareness programs must be initiated and nationwide control and prevention programs need to be adopted to decrease the prevalence of obesity in the Saudi population.

 

30: Al-Nuaim L, Talib ZA, el-Hazmi MA, Warsy AS. J Trop Pediatr. 1997 Apr; 43(2): 71-4.


Sickle cell and G-6-PD deficiency gene in cord blood samples: experience at King Khalid University Hospital, Riyadh.

Department of Obstetrics & Gynaecology, College of Medicine, Riyadh, Saudi Arabia.

Cord blood samples (1039) collected at King Khalid University Hospital were analysed for abnormal haemoglobins using electrophoresis at alkaline and acid pH, for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency using spectrophotometric method and for G-6-PD phenotypes using electrophoresis and specific staining. Only two samples showed the presence of Hb AS and no case of sickle cell anaemia was identified. The Hb S gene frequency was 0.00096. This was the lowest frequency identified so far in different regions of Saudi Arabia. The frequency of G-6-PD deficiency was calculated separately in the males and females, and was found to be 3.605 per cent in the males and 0.195 per cent in the females. Phenotyping showed the presence of G-6-PD-B+ as the normal enzyme at a frequency of 0.943 in both males and females and G-6-PD-A+ at a frequency of 0.0208 in males and 0.0059 in females. The deficient variant was mainly G-6-PD Mediterranean which occurred at a frequency of 0.0341 and 0.0019 in males and females, respectively. Only one case of G-6-PD-A- was identified in the males giving a frequency of 0.0019. This is the first report of Hb S and G-6-PD deficiency genes in cord blood samples in Riyadh. Comparison of the results in Riyadh with values reported elsewhere showed that Riyadh had the lowest frequency of both Hb S and G-6-PD deficiency gene.

31: El-Hazmi MAWarsy AS Gene Geogr. 1996 Aug; 10(2): 87-91.


Frequency of sickle cell gene in Arabia.

 Medical Biochemistry Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

This study was conducted on the Saudi population from different regions of Saudi Arabia to determine the frequency of sickle cell gene (Hb S). The results revealed that Hb S was present in most of the regions though at significantly variable frequencies. The highest frequency (0.149) was found in Al-Qateef, an eastern province of Saudi Arabia, and the lowest (0.001) were found in the central region. In some areas a close correlation was evident between malaria endemicity and Hb S gene frequency although a low frequency was encountered in some malaria endemic regions.


 

32: El-Hazmi MA, Warsy AS, al-Swailem AR, al-Swailem AM, Bahakim HM.
 Hemoglobin. 1996 Aug;20(3):187-98.


Sickle cell gene in the population of Saudi Arabia.

Medical Biochemistry Department, College of Medicine King Saud University, Riyadh, Saudi Arabia.

A comprehensive screening program was initiated in Saudi Arabia in 1982 to determine the frequency of the sickle cell (Hb S) gene in the different regions of Saudi Arabia. Over a period of 10 years 30,055 samples were collected from 36 areas in the five provinces of Saudi Arabia; these were screened using electrophoretic techniques in alkaline and acid pH for the presence of Hb S in heterozygous and homozygous states. The overall prevalence of Hb AS was 7.36% and Hb SS was 1.06%, giving an Hb S gene frequency of 0.047. The results from the different regions were separated and the prevalence of Hb AS and Hb SS and Hb S gene frequencies were calculated in each province and each region. The prevalence of Hb AS and Hb SS cases ranged from O to 25.88% and O to 5.27%, respectively. No case of Hb AS or Hb SS were identified in certain areas of the central province (Al-Russ, Al-Unaiza, Al-Mesnab and Bkaria) and northern province (Qurayat and Al-Jouf). In the southern province both Hb S homozygotes and heterozygotes were encountered in all regions except Farasan Island. In all other regions the Hb S gene was encountered, but at a variable frequency. Applying Hardy-Weinberg equilibrium it was observed that in the majority of the regions the observed Hb S homozygotes were significantly higher compared to the number expected (p < 0.0001). This was believed to be due to bias as the samples were collected in the hospital. The Hb S gene frequency in the different regions ranged from 0 to 0.17 when the frequency was calculated on the basis of both Hb AS and Hb. SS cases, and 0 to 0.13 if the gene frequency was calculated after eliminating the Hb SS cases. A close correlation was observed between the Hb S gene frequency and malaria endemicity. This study shows that the Hb S gene occurs frequently in several regions of Saudi Arabia and there is an urgent need to implement control and prevention programs to reduce the number of Hb S homozygous cases.

 

33: El-Hazmi MA, Warsy AS, Al-Swailem AR, Al-Swailem AM, Sulaimani R, Al-Meshari AA. Ann Saudi Med. 1996 Jul;16(4):381-5.


Diabetes mellitus and impaired glucose tolerance in Saudi Arabia.

 College of Medicine and King Khalid University Hospital, King Saud University and College of Science, King Saud University, and Ministry of Health, Riyadh, Saudi Arabia.

This study was undertaken to determine the prevalence of diabetes mellitus (DM), insulin-dependent diabetes mellitus (IDDM), noninsulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in different areas of Saudi Arabia. A household survey was conducted in 34 different areas of Saudi Arabia. Demographic data and medical history were taken and filled. Fasting and two-hour "post-glucose load" blood samples were collected from 23,493 Saudi males and females and blood glucose was estimated immediately. The diagnoses of DM and IGT were made based on the criteria of the World Health Organization (WHO). Diabetic patients were subgrouped as IDDM and NIDDM on the basis of age of onset and mode of treatment. In the overall group (two to 70 years), the prevalence of IDDM, NIDDM and IGT was 0.193%, 5.503% and 0.498% in the Saudi males and 0.237%, 4.556% and 0.900% in the Saudi females. When grouped on the basis of age, there were 8762 children (<14 years). Of these children, 15 (0.171%) had IDDM and 13 (0.148%) had maturity onset diabetes of the young (MODY). The prevalence of IGT in this group was 0.250%. In the 14-70-year age group, the prevalence of IDDM, NIDDM and IGT was 0.239%, 9.50% and 0.717% in the males and 0.248%, 6.820% and 1.347% in the females, respectively. A significant increase (P<0.001) was obvious in the age group >30 years, where the prevalence of NIDDM and IGT rose to 17.32% and 1.30% in the males and 12.18% and 2.2% in the females, respectively. IDDM showed a slight decrease in those over the age of 60 years. These results place Saudi Arabia among the countries that have a high prevalence for DM and a moderate risk for IGT. In light of these findings, it is clear that carefully planned programs are needed to achieve control and prevention of diabetes mellitus in Saudi Arabia.


34: Alzeer A, al Arifi A, el-Hazmi MWarsy AS Nylen ES.  Eur J Endocrinol. 1996 Jun; 134(6): 727-30.


Thermal regulatory dysfunction of growth hormone in classical heat stroke.

 Department of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

Growth hormone (GH) secretion associated with classical (non-exertional) heat stroke (HS) was evaluated in 26 HS victims and 10 control (non heat-exhausted) subjects during the annual Hajj in Makkah, Saudi Arabia. On admission to the HS treatment unit, the GH level was 1.54 +/- 0.14 ng/ml (approximately 3.5-fold higher in the HS victims compared to controls; p = 0.005). The GH levels subsequently declined by 78% by 24 h. The categorized GH response was significantly associated with survival for those subjects with a GH level of < 5.53 ng/ml by 6 h (chi-squared test; p = 0.06). In those patients who died (N = 6), there was a continued increase in GH levels from the time of admission, which peaked at 6 h. In those patients who survived, the GH levels peaked at the time of admission and declined rapidly thereafter. There was a direct correlation of age and GH level upon admission (p = 0.02), as well as to peak GH (p = 0.041). However, there was no relationship of GH level to either body core temperature or the cooling time. In summary, HS induced significant GH secretion. The degree of GH response was not related to the body core temperature and was more pronounced in older individuals and in those that died. Although patients with GH deficiency and HS are characterized by anhidrosis/hypohidrosis, there does not appear to be dysfunction of GH response to heat stress-associated HS. In contrast, a vigorous GH response at 6 h suggested a worse outcome.

35:
El-Hazmi MA, Warsy AS al-Fawaz I, Opawoye AO, Taleb HA, Howsawi Z, Mohamed AA, Aly AW, Refai S, Sugathan PS, Rab AS, Ahmed HB, Abulaban M, Abdulkader AM, Farid M.  Acta Haematol.  1996; 96(4): 221-6.

Piracetam is useful in the treatment of children with sickle cell disease.

College of Medicine, King Saud University, Riyadh, Saudi Arabia.

The management of children suffering from sickle cell disease [sickle cell anaemia (SCA) and sickle cell beta degree-thalassaemia (S beta degree-thal.)] has been the concern of all clinicians caring for these patients. Several agents have been tried for treatment, often limited by toxic side effects. Piracetam (2-oxo-l-pyrrolidine acetamide, Nootropyl), a cyclic derivative of gamma-amino butyrate, used for the treatment of psychosenescent syndromes with no known side effects, was considered as a possible therapeutic agent for sickle cell disease. Interest was focused on the use of piracetam when it was shown that it had an antisickling effect, both in vivo and in vitro. We initiated multicentre double-blind investigations in two groups of children suffering from sickle cell disease ranging in age from 3-6 to 6-12 years. The total number of patients included in the study were 87 (SCA = 79 and Hb S beta degree-thal. = 8) in 13 centres in 10 different regions of Saudi Arabia. Coded boxes of the drugs were received from the company (UCB) and were administered as intravenous infusion during crises and orally during the follow-up, for a period of up to 1 year. After decoding the code at the end of the study, the patients were grouped into those receiving placebo (n = 39), i.e. controls, or piracetam (n = 48), i.e. study cases. In terms of age, weight, height and severity index, number of blood transfusions received and number of hospitalization, both groups were statistically homogenous. Data analysis showed that the clinical severity of the disease, the number of crises, the extent of hospitalization and the blood transfusion requirements significantly decreased during piracetam treatment (p < 0.001), though no statistically significant changes occurred in the placebo group. However, in the levels of the haematological and biochemical parameters no significant changes were documented in both groups. In addition, the improvement in the clinical presentation of the disease continued even several months after discontinuation of the drug in the majority of the children, as judged from the low severity index value. Though our results point to the recommendation that piracetam can be used for the treatment of children suffering from sickle cell disease, both SCA and S beta degree-thal, it is advisable to conduct long-term and close follow-up treatment programmes using piracetam to establish its therapeutic value particularly in adults and to ascertain that there are no long-term toxic side effects.

 

36: El-Hazmi MA, Al-Swailem A, Warsy AS, Al-Sudairy F, Sulaimani R, Al-Swailem A, Al-Meshari A. Ann Saudi Med. 1995 Nov; 15(6): 598-601.


The prevalence of diabetes mellitus and impaired glucose tolerance in the population of Riyadh.

King Khalid Hospital, Ministry of Health, King Saud University, and General Directorate of Health Affairs, Riyadh, Saudi Arabia.

This study was conducted in Riyadh to determine the prevalence of diabetes mellitus and impaired glucose tolerance. Blood samples (3981) were collected from Saudi male and female adults (2402) and children (1579) during a household screening program conducted over a period of two years from September 1991 to September 1993. Fasting blood samples were collected and each individual was given an oral glucose load. Two-hour postprandial blood glucose was estimated and the World Health Organization (WHO) criteria were used to diagnose diabetes and impaired glucose tolerance. The diabetic patients were further grouped into noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) depending on the age of onset and mode of treatment. The overall prevalence of diabetes mellitus (IDDM and NIDDM) was 4.76% in males and 4.10% in the females in the two-to 70-year age group. Ten individuals of the 3981 were suffering from IDDM, giving an incidence of two to three per 1000. When the children <14 years were removed, the prevalence increased to 8.235% and 6.476% in the males and females respectively, while in the >30 year old group, the prevalence increased to 16.0% and 12.34% in the males and females. Further significant increase in NIDDM and impaired glucose tolerance (IGT) was observed with age (P<0.05). NIDDM was more frequent in males while IGT was more frequent in females. This paper presents the results of screening in Riyadh and stresses the need for diabetes mellitus awareness programs in the Saudi population.


37: El-Hazmi MA, al-Swailem AR, Warsy AS Hum Hered. 1995 Sep Oct;45(5):278-85.


Molecular defects in beta-thalassaemias in the population of Saudi Arabia.


Medical Biochemistry Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

The beta-thalassaemias are a heterogeneous group of inherited disorders caused by mutations in and around the structural gene of the beta-chain of the adult haemoglobin (HbA). Studies at the gene level have identified a large number of beta-thalassaemia gene variations in different populations. These findings have implications for the use of molecular diagnosis for genetic counselling and prenatal detection of the beta-thalassaemias. In our unit, we initiated studies to investigate the molecular defects in beta-thalassaemias in Saudi Arabia using amplification-refractory mutation systems, dot blot analysis and restriction endonuclease analysis, and identified mutations producing beta(+)- and beta zero-thalassaemias. Twenty of the mutations encountered in the Asian, Mediterranean, Chinese and other Arab populations were investigated. The most commonly encountered mutations in Saudi beta-thalassaemia patients were IVS-I-110, IVS-II-1, CD 39, IVS-I-5 and IVS-I 3' end (-25), while frameshifts at CD 8/9, Cap+1 (A-->C) and CD 6 mutations were identified at a low frequency. These mutations account for 84.94% of the total beta-thalassaemia mutations. The remaining 15% remain unknown. This is the first report on the type and nature of mutations in Saudi beta-thalassaemia patients. It presents frequencies of twenty mutations and emphasises the need for further detailed investigations to clarify the whole spectrum of beta-thalassaemia mutations in the Saudi population.

38: El-Hazmi MA, al-Swailem AWarsy AS J Trop Pediatr. 1995 Aug;41(4):225-9.


Glucose-6-phosphate dehydrogenase deficiency and sickle cell genes in Bisha.

Medical Biochemistry Department, College of Medicine & University Hospitals, King Saud University, Riyadh, Saudi Arabia.

This study was conducted on 820 Saudi males and females from Bisha in the western province of Saudi Arabia. Blood samples were analysed to determine the frequency of glucose-6-phosphate dehydrogenase deficiency and haemoglobin S (Hb S) genes, and to investigate interactions between the two genes. Severe G-6-PD deficiency in this population was due to G-6-PD-Mediterranean; the African variant G-6-PD-A- was not detected. The normal and common form of the enzyme was G-6-PD-B+, occurring at a frequency of 0.8444 and 0.8177 in males and females, respectively. Variants included G-6-PD-A+, G-6-PD-Mediterranean, and G-6-PD-Mediterranean-like at frequencies of 0.0043, 0.0767, and 0.0746, respectively, in males and 0.0057, 0.05413, and 0.0855, respectively, in females. Sickle cell haemoglobin (Hb S) was encountered in the homozygous (4 per cent) and heterozygous (10 per cent) states at a gene frequency of 0.0860. No interaction between G-6-PD deficiency and Hb S gene was observed. A severe haematological and clinical presentation of the Hb SS disease was encountered in the children from Bisha.

39:  El-Hazmi MA, Warsy AS, al-Swailem A, al-Swailem A, Bahakim H. J Trop Pediatr. 1995 Aug; 41(4): 202-5.


Red cell genetic disorders and plasma lipids.

College of Medicine, King Saud University, Riyadh, Saudi Arabia.

To study the plasma lipid levels in patients with red cell genetic disorders, we investigated 400 normal individuals, 100 sickle cell disease (SCD) patients, 220 sickle cell heterozygotes (Hb AS), and 100 individuals suffering from glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Whole blood samples were used for the determination of haematological parameters and red cell indices, and plasma was used for the estimation of plasma lipids using Autoanalyser American Monitor 'Parallel'. Haemoglobin types in the haemolysates were separated by electrophoresis and G-6-PD activity was determined using kits from Boehringer Mannheim GmbH. The results from males and females were analysed separately. In each group cholesterol levels were slightly higher in the male population, while the reverse was true for triglyceride. Sickle cell disease patients had significantly (P < 0.05) lower cholesterol level compared to the normal individuals. In the Hb AS and G-6-PD deficient groups no significant differences were encountered. Multiple regression analysis between cholesterol and haematological parameters showed a statistically significant positive correlation (P < 0.01) between plasma cholesterol and total haemoglobin in each group, particularly in the sickle cell disease patients. The results suggest that increased utilization or decreased production may account for the lower cholesterol level in severely anaemic patients, particularly those with sickle cell anaemia.

40: El-Hazmi MA, al-Swailem AR, Warsy AS, al-Swailem AM, Sulaimani R, al-Meshari AA .J Med Genet. 1995 Aug; 32(8): 623-6.

Consanguinity among the Saudi Arabian population.

Department of Medical Biochemistry, King Khalid University Hospital, Riyadh, Saudi Arabia.

This study was conducted on 3212 Saudi families to investigate the prevalence of consanguineous marriages. The families were interviewed and the information on the relationship between the husband and wife was obtained. The overall rate of consanguinity shows that 57.7% of the families screened were consanguineous. The most frequent were first cousin marriages (28.4%) followed by distant relative marriages (15.2%) and second cousin marriages (14.6%). The families were grouped according to the province of their origin and the consanguinity rates were calculated accordingly. There were slight differences in the consanguinity rates in the five provinces, which ranged from 52.1% to 67.7%. In each province first cousin marriages were the most frequently encountered pattern, ranging from 17.9% to 40.9%. The inbreeding coefficient (F) was calculated for each province and ranged from 0.020 to 0.030. Within each province, there were several significant differences among the populations in the different areas. The highest rate of consanguinity was 80.6% in Samtah and the lowest rate was around 34% in Abha in the South Western province. These results place Saudi Arabia among the countries of the world with a high rate of consanguinity. The possible consequences of increased consanguinity are presented and discussed.

41: El-Hazmi MA, Warsy AS, al-Swailem AR. Hemoglobin.  1995; 19(6): 353-60.


The frequency of 14 beta-thalassemia mutations in the Arab populations.

Department of Medical Biochemistry, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

The beta-thalassemias are a heterogeneous group with respect to molecular pathogenesis, and different populations and ethnic groups differ with respect to the predominating mutations. This variable spectrum of beta-thalassemia mutations has resulted in extensive studies in each population and ethnic group to identify the major mutations. In this study we investigated the prevalence of 14 mutations in 253 beta-thalassemia patients drawn from eight Arab countries (i.e. Jordan, Egypt, Syria, Lebanon, Yemen, and Saudi Arabia), living in Saudi Arabia and attending Ministry of Health hospitals. The mutations investigated included IVS-I-110 (G-->A), IVS-II-1 (G-->A), IVS-I-5 (G-->C), codon 39 (C-->T), IVS-I-1 (G-->A), frameshift at codons 8/9 (+G), frameshift at codons 41/42 (-TTCT), codon 15 (TGG-->TAG), IVS-I-6 (T-->C), frameshift at codon 16 (-C), IVS-II-745 (C-->G), codon 6(-A), IVS-I, 3' end (-25 bp), and Cap +1 (A-->C). The most frequently encountered mutations were IVS-I-110 and IVS-II-1 which were identified in the population of each Arab country. The IVS-I-1 and IVS-II-745 mutations were encountered in Jordanians, Egyptians, and Syrians. The IVS-I-5, codon 39, codon 6, IVS-I, 3' end (-25 bp), and Cap +1 mutations were encountered only in Saudis and not in other Arabs, except codon 39 which was present in the Syrians and Lebanese. Other mutations were generally rare and not specific to any Arab ethnic group. This paper presents preliminary data on the prevalence of 14 mutations in the Arab populations and shows wide variation in the molecular basis of beta-thalassemia in different Arab ethnic groups. Further detailed studies to identify the entire spectrum of beta-thalassemia mutations are stressed.


42: El-Hazmi MA, al-Momen A, Warsy AS, Kandaswamy S, Huraib S, Harakati M, al-Mohareb F. Acta Haematol. 1995; 93(2-4): 57-61.


The pharmacological manipulation of fetal haemoglobin: trials using hydroxyurea and recombinant human erythropoietin.

 College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Hydroxyurea (HU) and recombinant human erythropoietin (rHuEpo) have been used in several studies to elevate Hb F level in sickle cell disease (SCD) patients and hence to ameliorate the clinical presentations of the disease. The treatment protocol and doses have varied in the different studies. We studied the effects of HU+rHuEpo combination therapy in sickle cell anaemia (SCA patients) to investigate the Hb F manipulation and hence treatment of SCA. Six patients with severe SCA were selected for treatment with HU (20-25 mg/kg body weight) and rHuEpo (400-800 U/kg body weight) combination therapy for 4 weeks followed by HU (20-25 mg/kg body weight) maintenance therapy for 6 months to 1 year. Iron and folic acid were administered during HU+rHuEpo treatment. Signs, symptoms and complications were recorded to obtain the severity index. Only patients with a severity index > or = 6 were included in the study. Haematological and biochemical parameter values, Hb A2, Hb F, Hb F distribution, Hb F cells, bilirubin level and reticulocyte count were assessed at least on 2-3 occasions prior to initiation of the therapy protocol to establish baseline values. During the treatment period, the clinical presentations were monitored and the estimation of the laboratory parameters was carried out every 4-8 weeks. The results of these parameters during HU and rHuEpo combination therapy and HU maintenance therapy were compared with baseline values using paired t test. The elevation in the level of Hb F, Hb F cells, total haemoglobin, red cell count and MCV were significant (p < 0.005), while reticulocyte count and total bilirubin were significantly decreased (p < 0.05). Each patient showed an individual pattern of Hb F elevation. The increase in Hb F level was correlated with the haematological and biochemical parameters using the General Linear Model Programme of Statistical Analysis System. In general, the clinical presentation improved as Hb F level increased in each patient. In addition, the positive correlation with the haematological parameters and negative correlation with reticulocytes and total bilirubin confirmed the beneficial effect of elevated Hb F level on reducing red cell haemolysis. No correlation could be demonstrated between the pretreatment Hb F level and the increase in Hb F during the treatment period. Daily doses of HU with a single intravenous rHuEpo and iron supplementation elevate Hb F and Hb F cells in SCA patients. The Hb F level can be maintained high on HU therapy alone.(ABSTRACT TRUNCATED AT 400 WORDS)


43: El-Hazmi MA, al-Momen A, Kandaswamy S, Huraib S, Harakati M, al-Mohareb FWarsy AS . Acta Haematol.  1995; 94(3): 128-34.


On the use of hydroxyurea/erythropoietin combination therapy for sickle cell disease.

Seven sickle cell disease (SCD) patients [sickle cell anaemia = 4 (males 2, females 2, age range 18-40 years), and sickle cell beta (0)-thalassaemia = 3 (all females, age range 20-47 years)], suffering from a severe form of the disease were enrolled in a treatment protocol using hydroxyurea (HU) for up to 12 months followed by a combination therapy with HU and human recombinant erythropoietin (rHuEpo; using 400 U/kg/week i.v.) for 3-4 weeks. Following the withdrawal of rHuEpo the patients were maintained on HU alone. The patients were characterised on the basis of the 'severity index' prior to the initiation of the therapy. Haematological and relevant biochemical parameters, Hb A2 fetal haemoglobin (HbF), HbF cells, reticulocytes and platelet counts were estimated at least at three occasions to determine the mean and range of the parameters. During the treatment period the patients were followed every 2-4 weeks where the haematological and biochemical parameters were assessed. The results were separately analysed and mean +/- SD were obtained for each parameter at the end of each protocol. The statistical significance of the difference in the results obtained on treatment and the baseline results was examined using the paired t test. No toxic side effects of HU and rHuEpo (as judged from reduction in platelet and white blood cell count) were documented during and after the whole period of treatment. The patients showed a significant clinical improvement. Total haemoglobin, haematocrit, red cell count, HbF and HbF cells increased, while white blood cells, reticulocyte counts and bilirubin level decreased. Platelet count decreased but remained within the normal range. The results revealed that 5 of the patients on HU treatment showed a significant increase in the HbF level and HbF cells, while 2 patients (1 sickle cell anaemia and 1 Hb S/beta(0)-thalassaemia patient) did not and were considered as 'non-responders'. The rHuEpo and HU combination therapy elevated the HbF level, with a varying degree, in all patients except 2, who had already reached a high HbF level and showed a decrease in HbF during the rHuEpo protocol. Variable individual response to both HU and rHuEpo therapy was a common feature. We recommend the use of HU for the treatment of SCD and a combination therapy using HU and rHuEpo for the non-responders.

44: El-Hazmi MAWarsy AS Ann Saudi Med. 1994 Nov; 14(6): 491-4.


The frequency of glucose-6-phosphate dehydrogenase phenotypes and sickle cell genes in Al-Qatif oasis.

 
This study was conducted on a selected population of Al-Qatif in Eastern Saudi Arabia to determine the gene frequencies of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell (HbS) genes and to study the extent of interaction between the two genes. A total of 960 blood samples collected from Saudi males (515) and females (445) attending the outpatient clinics and hospitals for minor illnesses were subjected to electrophoresis for separation of hemoglobin types and G-6-PD phenotyping and for spectrophotometric determination of G-6-PD activity. The prevalence of HbS heterozygotes was 25.9%, Hb S/b_-thalassemia was 1.563% and HbS homozygotes was 2.917%. The overall gene frequency of HbS was 0.1666. Severe glucose-6-phosphate dehydrogenase deficiency was encountered in a large percentage of the population with a frequency of 0.392 for G-6-PD Mediterranean and 0.0058 for G-6-PD-A- in the male population and 0.2020 and 0.0112 for G-6-PD Mediterranean and G-6-PD-A- in the female population respectively. Partial deficiency was encountered at a frequency of 0.0272 and 0.0697 in the male and female populations respectively. G-6-PD deficiency caused by G-6-PD Mediterranean occurred at a higher frequency in individuals with normal hemoglobin (Hb AA) (0.414 and 0.217 in males and females respectively) compared to the HbS heterozygotes (0.338 and 0.168 in males and females respectively) and HbS homozygotes and HbS bo-thalassemia cases (0.3125 and 0.1852 in males and females respectively). Compared to all areas of Saudi Arabia, Al-Qatif had the highest gene frequencies for HbS and G-6-PD deficiency genes.

45: El-Hazmi MAWarsy AS al-Fawaz I. J Trop Pediatr. 1994 Aug;40(4):219-24.


Iron-endocrine pattern in patients with beta-thalassaemia.

 Department of Medical Biochemistry, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.

Patients with beta-thalassaemia (major, minor, and in association with sickle cell gene) frequently suffer from growth retardation and delayed sexual development. This is believed to be due, at least in part, to a direct effect of iron overload on the endocrine mechanisms of puberty. The role of iron overload remains speculative in relation to the disease severity and ethnic variations. This study determined the level of testosterone, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), free thyroxine (T4), tri-iodothyronine (T3), growth hormone (GH), iron, ferritin, and haematological parameters in 44 beta-thalassaemia patients (21 = beta-thal. major, 23 beta-thal minor), 25 Hb S/beta zero-thalassaemia patients, and 50 normal controls with age range 2-15 years. The iron endocrine status and haematological findings were evaluated, and the results were correlated and compared with age- and sex-matched controls. In comparison with controls the beta-thalassaemia-major and the Hb S/beta zero-thalassaemia patients had a significantly higher level of plasma ferritin (P < 0.01) while the mean level of total haemoglobin was significantly lower. The level of LH, FSH, testosterone, and plasma cortisol were lower in both beta-thalassaemia-major and Hb S/beta zero-thalassaemia patients with a negative correlation with plasma ferritin level. Free T3 and T4 were raised, but the difference was not statistically significant. The data demonstrate the occurrence of impaired endocrine function in the beta-thalassaemia and Hb S/beta zero-thalassaemia patients.

46:
El-Hazmi MAWarsy AS Addar MH, Babae Z. Mol Cell Biochem. 1994 Jun 29; 135(2): 181-6.


Fetal haemoglobin level--effect of gender, age and haemoglobin disorders.

 Medical Biochemistry Department, College of Medicine, Riyadh, Saudi Arabia.

Fetal haemoglobin (Hb F) levels shows significant variations in health and disease states. In this study we investigated Hb F level in 75 cord bloods, 1266 healthy individuals, 1582 Hb S heterozygotes, 464 sickle cell anaemia, 93 Hb S/beta(0) -thalassaemia and 65 beta-thalassemia major patients. The age range of the study groups varied from newborn to over 60 years of age. Hb F level was measured by an alkali denaturation procedure and by radial immunodiffusion. The ratio of the level of G gamma-globin chains to the level of A gamma-globin chains (G gamma/A gamma) was determined in the patients group by high performance liquid chromatography. The Hb F level was significantly higher in the sickle cell anaemia and beta-thalassemia major patients compared to the Hb S heterozygotes and the normal individuals. Within each group Hb F level was higher in the female population compared to the age-matched male groups. This difference was statistically significant (P < 0.05) in the sickle cell disease patients and beta-thalassemia major patients but not in the normal individuals. After the age of 30 years, the difference in the value of Hb F in the male and female population become more apparent (P < 0.05) in the sickle cell disease and beta-thalassaemia major patients. No statistically significant sex differences were found in the G gamma/A gamma ratio in the patient groups, and the range of G gamma/A gamma ratio in the patients groups were similar to those in the control group. The results showed that age, sex and genetic disorders of haemoglobin are factors that affect Hb F level and indicate the possible involvement of an X-linked factor in control of Hb F production.

47: El-Hazmi MA, Warsy AS, al-Swailem AR, al-Faleh FZ, al-Jabbar FA. J Trop Pediatr. 1994 Jun;40(3):149-56.


Genetic compounds--Hb S, thalassaemias and enzymopathies: spectrum of interactions.

 Medical Biochemistry Department, College of Medicine & King Khalid University Hospital, Riyadh, Saudi Arabia.

In areas with high occurrence of the red cell genetic abnormalities, i.e. sickle cell gene, alpha- and beta-thalassaemias, and glucose-6-phosphate dehydrogenase deficiency, various genes frequently co-exist in the same population. Co-inheritance of two or more abnormal genes in the same individual is frequently encountered, particularly in certain 'closed' tribes in Arabia in which consanguinity is the norm. Such genetic interactions modify the clinical presentations of the disease state. During our studies, we encountered a large number of individuals who were carriers of two or more abnormal genes. The most frequent genetic compounds were double heterozygous HbS-beta zero-thalassaemia and HbS-beta(+)-thalassaemia with associated alpha-thalassaemia or G-6-PD deficiency. Clinical history, and assessment, as well as blood analysis for haematological, biochemical, and molecular pathology determinants were carried out. The patients were classified into subgroups, based on the genetic findings. The clinical, haematological and biochemical data were assessed separately for each group. Sickle cell anaemia (Hb SS) cases, without any other abnormal gene, were used as a reference group. The results showed severe anaemia in patients with HbS/beta zero-thalassaemia and associated alpha-thalassaemia and/or G-6-PD deficiency. Patients with HbS/beta zero-thalassaemia exhibited features similar to that of the sickle cell anaemia. While sickle cell anaemia patients with alpha-thalassaemia and G-6-PD deficiency exhibited a milder presentation. This paper presents various forms of genetic associations, their influence on the clinical presentation and the laboratory parameter data, and discusses the implications of the findings.

48: El-Hazmi MAWarsy AS Bahakim HH, al-Swailem A. J Trop Pediatr. 1994 Feb;40(1):12-6.

 

Glucose-6-phosphate dehydrogenase deficiency and the sickle cell gene in Makkah, Saudi Arabia.
 
Medical Biochemistry Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
This study was conducted on 689 Saudi males and females living in the Makkah area in the western province of Saudi Arabia. The frequency of severe glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in the male and female populations was 0.055 and 0.042 respectively. The normal G-6-PD was G-6-PD-B+ and the G-6-PD phenotypes identified included G-6-PD-A+, G-6-PD-A-, G-6-PD-Mediterranean, and G-6-PD-Mediterranean-like at gene frequencies of 0.0288, 0.0026, 0.05497, and 0.1969 in the male population and 0.026, 0.0146, 0.0407, and 0.02606 in the female population. The main variants producing severe and mild G-6-PD deficiency were G-6-PD-Mediterranean and G-6-PD-Mediterranean-like, respectively. The sickle cell gene was identified at a frequency of 0.029 and no interaction between sickle cell and G-6-PD deficiency genes was encountered.

49: El-Hazmi MAWarsy AS J Trop Pediatr. 1993 Aug;39(4):209-13.

 

On the molecular interactions between alpha-thalassaemia and sickle cell gene.

Medical Biochemistry Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Using the restriction endonucleases, Bam HI, Bgl II, Hind III and EcoRI, the alpha-gene arrangements were investigated in heterozygotes and homozygotes for the sickle cell haemoglobin (Hb S). In the heterozygotes (Hb AS) group the Hb S level showed a trimodal distribution due to presence of the normal alpha-globin genes (alpha alpha/alpha alpha) or of one (-alpha/alpha alpha) or two (-alpha/-alpha) alpha-genes deletions. The haematological analytes inversely correlated with the associated alpha-thalassaemia (alpha-thal.) genes. In the Hb S homozygotes (Hb SS), associated alpha-thalassaemia was found to ameliorate the clinical manifestations and improved the haematological values. Co-existing triple alpha-gene arrangement, alpha alpha alpha anti 3.7/, with Hb AS did not influence the haematological analytes. In Hb SS, presence of alpha alpha alpha anti 3.7/ resulted in a severe sickle cell anaemia (SCA) with a high severity index (> 11) and with frequent crises, transfusion requirements and hospitalizations. It is suggested that reduced level of alpha-chain ameliorates SCA while excess of alpha-globin chain production gives rise to a severe form of SCA.

 

50: el-Hazmi MA, Bahakim HMWarsy AS al-Momen A, al-Wazzan A, al-Fawwaz I, Huraib S, Harakati M. Mol Cell Biochem. 1993 Jul 7;124(1):17-22.


Does G gamma/A gamma ratio and Hb F level influence the severity of sickle cell anaemia.

College of Medicine & King Khalid Hospital, King Saud University, Riyadh, Saudi Arabia.

Sickle cell anaemia (SCA) exhibits significant variations in clinical presentation in different populations for which several genetic factors including SCA-associated alpha- and beta-thalassaemias, G-6-PD deficiency and elevated Hb F level have been implicated as possible ameliorating factors. Saudi Arabia is unique in that mild and severe forms of the disease occur at a high frequency. We investigated the G gamma/A gamma ratio and Hb F level and correlated these values with the severity of SCA. The results showed that Hb F level varies significantly in both groups of patients with no evident correlation with the mild clinical manifestations. However, G gamma/A gamma ratio correlated significantly with the disease severity where a high ratio was observed in patients with the mild and a low ratio in patients with the severe disease. The results are evaluated and discussed in the light of correlation studies and regression analysis.


51: El-Hazmi MA, Warsy AS, Bahakim HM, Al-Swailem A. Ann Saudi Med. 1993 May;13(3):250-4.

 

Glucose-6-phosphate dehydrogenase deficiency and sickle cell genes in two regions of western Saudi Arabia.
 
Department of Biochemistry, Department of Pediatrics, King Saud University and King Khalid University Hospital, Ministry of Health, Riyadh, Saudi Arabia.

This study was conducted on 1409 Saudi males and females living in Makkah and Bisha areas in the Western Province of Saudi Arabia to determine the frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and hemoglobin S (Hb S) genes and to investigate interactions between the two genes. The frequency of sever G-6-PD deficiency was 0.055 and 0.042 in males and females, respectively, from Makkah and 0.0767 and 0.0541 in males and females, respectively from Bisha. The normal enzyme was G-6-PD+ in both regions and the G-6-PD phenotypes identified included G-6-PD-A+, G-6-PD-Mediterranean and G-6-PD-Mediterranean-like with the frequencies 0.0288, 0.0026, 0.05497 and 0.1963, respectively in males and 0.0033, 0.0130, 0.0293 and 0.2696 respectively in the females in Makkah. In Bisha, the corresponding gene frequencies were 0.00436, 0, 0.0767 and 0.0746 in males and 0.00570, 0, 0.05413 and 0.0855 in females. Heterozygous females were not detected. The main variant producing severe and mild G-6-PD deficiency were G-6-PD-Mediterranean and G-6-PD-Mediterranean-like, respectively. Sickle cell gene was identified at a frequency of 0.029 and 0.0866 in Makkah and Bisha, respectively, and no interaction between sickle cell and G-6-PD deficiency genes were encountered.

52:
el-Hazmi MA, Warsy AS, Bahakim H. Acta Haematol. 1993;90(3):114-9.


Blood proteins C and S in sickle cell disease.

Medical Biochemistry Department, King Saud University, Riyadh, Saudi Arabia.

Proteins C and S are vitamin K-dependent proteins with an essential anti-coagulant function. Protein C exists in an inactive form and is activated by a thrombin-thrombomodulin complex. Protein S combines with protein C and forms a stoichiometric complex which regulates coagulation in the presence of calcium. As patients with sickle cell disease (SCD) bear a high risk of developing thrombo-embolic disorders, we studied the coagulation derangement in 100 patients and 40 normal age- and sex-matched controls. The patients were clinically assessed and classified into sickle cell homozygotes (Hb SS), Hb S heterozygotes (Hb AS) and double heterozygotes for Hb S/beta 0-thalassaemia based on haematological parameters, red cell indices, Hb A2 and F levels and genetic studies. The proteins C and S were estimated and related to the type of the gene defect. The results showed significantly reduced levels of proteins C and S in SCD patients with the highest prevalence of deficiency in patients with a severe disease and frequent episodes of crisis. However, no significant differences were encountered in the level of proteins C and S in the same patients during the steady state and during episodes of crisis. It was concluded that the lower protein C and S levels in SCD is either due to decreased production or increased consumption though this reduction does not seem to play a role in producing thrombo-embolic disorders.

53: El-Hazmi MAWarsy AS Ann Saudi Med. 1992 Sep;12(5):463-7.


The frequency of glucose-6-phosphate dehydrogenase phenotypes and sickle cell gene in Al-Qassim.

Departments of Medical Biochemistry, King Khalid University Hospital, Riyadh, and College of Science, Sciences and Medical Studies for Women Students, King Saud University, Riyadh, Saudi Arabia.

This study was conducted in the Al-Qassim area located in the central province of Saudi Arabia in order to estimate the frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell genes (Hb S). Blood samples from 1,015 Saudi males and females were analyzed for hemoglobin types, G-6-PD phonotypes and G-6-PD levels. Only two cases heterozygous to Hb S (ie Hb AS) were identified and the frequency of Hb S gene was 0.000985. The normal G-6-PD was G-6-PD-B+ occuring at a frequency of 0.944 and 0.966 in the male and female population, respectively. Variants identified included G-6-PD-A+, G-6-PD-Mediterranean, G-6-PD-A-, and G-6-PD-Mediterranean-like at frequencies of 0.0164, 0.0282, 0.0023, 0.0094 in the males and 0.0068, 0.0085, 0, 0.0102 in the female population, respectively. The severe G-6-PD deficiency was due mainly to G-6-PD Mediterranean and only one male with G-6-PD-A- (0.0023) was identified. These results showed that Al-Qassim had the lowest frequency of Hb S and G-6-PD deficiency genes compared to all other regions of Saudi Arabia that have been screened thus far.

54: el-Hazmi MA, Warsy AS. Hum Hered. 1992;42(6):360-6.


Triple alpha-genes (alpha alpha alpha anti3.7) in a patient with sickle cell anaemia.

Medical Biochemistry Department, College of Medicine and King Khalid Hospital, Riyadh, Saudi Arabia.

This paper reports the case of a 17-year-old male student from the Jaizan area in south-western Saudi Arabia who had sickle cell anaemia and possessed three alpha-genes on one chromosome (alpha alpha alpha anti3.7) and two on the other. The clinical manifestations were severe, with frequent blood transfusion requirements and frequent episodes of painful crises, severe anaemia and tissue involvement. In comparison with age and sex-matched sickle cell anaemia patients with one alpha-gene deletion (-alpha/alpha alpha), or a normal alpha-gene arrangement (alpha alpha/alpha alpha), a more severe disease presentation was obvious in the propositus. It is suggested that with the surplus alpha-globin chains, more severe haematological and clinical abnormalities occur, these influence the phenotypic expression of sickle cell anaemia. However, more patients with this type of gene arrangement must be studied before a definite conclusion can be reached regarding the influence of excess alpha-globin chains on the presentation of sickle cell anaemia.

55: el-Hazmi MAWarsy AS al-Momen A, Harakati M. Acta Haematol. 1992;88(4):170-4.
Hydroxyurea for the treatment of sickle cell disease.

Department of Medical Biochemistry, College of Medicine & King Khalid University Hospital, Riyadh, Saudi Arabia.

In this study 21 adults with severe form of sickle cell disease (SCD; sickle cell anaemia, n = 15; Hb S/beta degree-thal, n = 6) were treated with hydroxyurea (HU) to assess the effectiveness of the drug in managing SCD. The individual dose was selected for each patient. The dose selection was based on the HU clearance study. Thereafter, the patients received daily doses of 15-20 mg/kg body weight. An evaluation data form was filled out at the monthly visit. The severity index (SI) of the disease was determined and haematological parameters including red cell indices, platelet counts, reticulocyte counts, irreversibly sickled cells, red cell deformability, Hb F, Hb F cells, total and direct bilirubin levels were measured prior to treatment, at follow-up intervals during treatment and after cessation of treatment. The trial period lasted 3 months. Statistically significant improvement was observed in the clinical presentation, haematological and biochemical parameters. Hb F level and F cells showed a significant increase in most patients, but to a variable degree. A major resultant effect was an increase in mean cell volume. Our experience shows that HU can be used for the treatment of severe forms of SCD with no major side effects, provided that the doses are monitored and that laboratory investigations are regularly undertaken.

56: el-Hazmi MA, Bahakim HM, Warsy AS. Acta Haematol. 1992;88(2-3):61-6.

 

DNA polymorphism in the beta-globin gene cluster in Saudi Arabs: relation to severity of sickle cell anaemia.
 
College of Medicine & King Kahlid University Hospital, Riyadh, Saudi Arabia.

Significant DNA polymorphisms have been reported in the beta-globin gene cluster of epsilon-G gamma-A gamma-psi beta-delta-beta-gene region, in normal (Hb AA) individuals and in patients with sickle cell anaemia (SCA). Investigations of the extent of the DNA polymorphisms in the beta A- and beta S-globin gene cluster using Hind III, Hinc II, Ava II, Xmn I, and Hpa I, revealed several associations with mild SCA. The correlation of the presence (+) or absence (-) of the restriction endonuclease site to clinical severity in patients homozygous for beta S-gene showed that the mild form of SCA was associated mainly (> 90%) with the Xmn I polymorphic site 5' to G gamma, and to a lesser extent with Hinc II polymorphic site 5' to epsilon and in the psi beta-gene, with Hind III polymorphic site in G gamma and Hpa I polymorphic site 3' to the beta-globin gene, while in the severe form of SCA these polymorphic sites were absent in most patients. The polymorphism in the beta-globin gene cluster was significantly related to the expression of the beta S-gene and clinical severity of SCA.

57:
Warsy AS, El-Hazmi MA, Sedrani SH, Kinhal M. Ann Saudi Med. 1991 Mar;11(2):159-62.


Alpha-1-antitrypsin phenotypes in Saudi Arabia: A study in the central province.

 Departments of Biochemistry, College of Science, College of Medicine, and Department of Nutrition, College of Allied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

This study was conducted on 204 plasma samples obtained from Saudis living in the central province of Saudi Arabia, to determine the prevalence of alpha-1-antitrypsin (alpha1AT) phenotypes. The alpha1AT phenotypes were separated by isoelectric focusing on ampholine gels (pH 4-5). The prevalences of PiMM, MS, MZ, SZ, and ZZ were 0.8676, 0.0931, 0.0245, 0.0098, and 0.0049, respectively. The gene frequencies of the alpha1AT variants, i.e.., PiM, PiS, and PiZ, were 0.9265, 0.0515, 0.022, respectively. We describe and compare our results in a Saudi population with those reported for other populations.

58: el-Hazmi MA, al-Ballaa SR, Warsy AS, al-Arfaj H, al-Sughari S, al-Dalaan AN. Br J Rheumatol. 1991 Feb;30(1):21-3.

 

Transferrin C subtypes in patients with rheumatoid arthritis.

 Medical Biochemistry Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Transferrin (Tf) subtypes were investigated in 128 patients with rheumatoid arthritis (RA) and the frequencies of TfC subtypes were compared with the results in normal individuals. The frequencies of the Tf genes: C1, C2, C3, D1, and D2 were 0.4765, 0.3867, 0.0742, 0.0390 and 0.0234, respectively. The frequency of TfC2 gene was significantly higher in these patients (0.3867) compared to the value in the control group (C2 = 0.247). The relative risk of RA in association with TfC1C2 type was 2.0, while it was 0.18 in association with TfC1C1 type and the results were statistically significant. This paper confirms the significant association between TfC2 and RA. Furthermore, it appears from our results that TfC1 homozygous phenotype is protective for the development of RA. The results are discussed in the light of earlier suggestions that the TfC2 subtype confers an increased risk of cellular damage by enhancing hydroxyl radical formation, although it is possible that there exists a genetic linkage of Tf variant to some other locus which is influencing susceptibility to RA.

59: El-Hazmi MA, Jabbar FA, Al-Faleh FZ, Al-Swailem AR
Warsy AS
 Hum Hered. 1991;
41(1):26-34.

Patterns of sickle cell, thalassaemia and glucose-6-phosphate dehydrogenase deficiency genes in north-western Saudi Arabia.
 
Medical Biochemistry Department, College of Medicine, King Khalid Hospital, King Saud University, Riyadh, Saudi Arabia.

This study was conducted on 429 blood samples collected from Saudi males and females from Al-Ula in the north-western province of Saudi Arabia in order to determine the frequency of the sickle cell gene, glucose-6-phosphate dehydrogenase (G6PD) deficiency gene, and alpha- and beta-thalassaemia genes, and to investigate the pattern of their interactions. The frequency of the sickle cell gene was 0.0785, while that of the beta-thalassaemia gene was 0.1195. Heterozygous alpha-thalassaemia 2 (- alpha/alpha alpha) was encountered at a frequency of 0.121, while homozygous alpha-thalassaemia 2 (- alpha/- alpha) occurred at a frequency of 0.0046. HbH disease and hydrops fetalis were not encountered. One case with triple alpha-gene arrangement, alpha alpha alpha anti-3.7, was identified. The G6PD deficiency gene frequency was 0.08 and 0.032 in males and females, respectively. Several cases with 2 abnormal genes were encountered. The haematological and biochemical data from the patients with sickle cell disease suggest that the disease in this population is more severe in comparison with cases reported from the eastern population.

60: el-Hazmi MA, Warsy AS. Trop Geogr Med. 1991 Jan-Apr;43(1-2):174-9.

Glucose-6-phosphate dehydrogenase variants and sickle cell genes in Al-Qunfuda, Saudi Arabia.
Department of Medical Biochemistry College of Medicine, King Saud University, Riyadh, Saudi Arabia.

This study was conducted on 823 male and female subjects to determine the frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell gene in Al-Qunfuda, a densely populated and malaria endemic region in western Saudi Arabia. The results show the presence of both sickle cell and G-6-PD deficiency genes in this population. The prevalence of Hb S heterozygotes in the total population was 18.93% and that of homozygotes was 2.02%. The gene frequency of sickle cell gene was 0.121. G-6-PD-B+ was the normal enzyme and occurred at a frequency of 83.60% and 78.46% in the male and female population, respectively. G-6-PD variants identified included G-6-PD Mediterranean, G-6-PD-A+, G-6-PD-A- and G-6-PD-Mediterranean-like. The frequency of each variant in the male and female population was 10.65% and 9.74% for G-6-PD-Mediterranean, 2.30% and 1.53% for G-6-PD-A+, 0.46% and 0.51% for G-6-PD-A- and 3.0% and 9.74% for the G-6-PD-Mediterranean-like variants, respectively. No significant interaction between sickle cell and G-6-PD genes could be demonstrated.

61: el-Hazmi MA, al-Swailem AR, Warsy ASJ Trop Pediatr. 1990;36(5):223-9.

Case studies on haemoglobin S heterozygotes with severe clinical manifestations.

 Medical Biochemistry Department, College of Medicine, Riyadh, Saudi Arabia.

Generally, individuals who are heterozygous to haemoglobin S (Hb AS) are asymptomatic and do not present any haematological or clinical manifestations. However, other associated genetic abnormalities may influence the presentation in Hb AS cases. This study was conducted on twenty children heterozygous for HB S who presented clinical manifestations similar to those of sickle cell anaemia. All these children had anaemia associated with several red cell morphological abnormalities. The white blood cell counts were elevated in all patients and differential count studies showed a substantial increase in lymphocytes and polymorphonuclear leucocytes in the majority of the cases. Forty-five per cent of the patients had associated alpha-thalassaemia, 60 per cent had beta-thalassaemia, 30 per cent had G-6-PD deficiency and 10 per cent had partial glutathione reductase deficiency. Pyruvate kinase activity was normal in all cases. Riboflavin deficiency was encountered in 30 per cent of the patients and iron deficiency in 15 per cent of these Hb S heterozygotes. The major clinical findings were splenomegaly, hepatomegaly, and vaso-occlusive crisis. The majority of the patients had received blood transfusions. The hand and foot syndrome was identified in three (15 per cent) of the patients. The haematological and clinical findings in these twenty Hb S heterozygotes are presented in this paper and the possible causes for these abnormalities are discussed.

 

62: el-Hazmi MA, Bahakim HM, al-Swailem AM, Warsy AS.J Trop Pediatr. 1990 Aug;36(4):148-55.

 The features of sickle cell disease in Saudi children.

College of Medicine & King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.

Using a prospective and retrospective approach, the features of sickle cell disease (SCD) were investigated in 137 SCD children from the south-western region of Saudi Arabia. The patients were followed for a period of 2-5 years, during which period the severity of the disease was assessed and a 'severity index', was calculated for individual patients. The patients with SCD were classified into five groups based on the absence of thalassaemia (sickle cell anaemia, SCA), presence of beta zero-thalassaemia (HbS/beta zero-thalassaemia), SCA with alpha-thalassaemia.2 [heterozygotes (-alpha/alpha alpha) or homozygotes (-alpha/alpha)] and S/beta zero-thalassaemia with alpha-thalassaemia. The results showed a high prevalence of associated alpha-thalassaemia and variable levels of HbF in these patients. SCA patients with associated alpha-thalassaemia (-alpha/-alpha) and S/beta zero-thalassaemia patients with one alpha-gene deletion had the highest values for haematological parameters and lowest values of red cell indices. No specific difference could be identified in the clinical manifestations in the different groups with the exception that long bone crisis and hand-foot syndrome were not encountered in patients with associated alpha-thalassaemia. The frequency of hepatomegaly and splenomegaly was also lower in this group.

63: el-Hazmi MA, al-Swailem AR, Bahakim HM, al-Faleh FZ, Warsy AS.

 Trop Geogr Med.
1990 Jul;42(3):241-7.


Effect of alpha thalassaemia, G-6-PD deficiency and Hb F on the nature of sickle cell anaemia in south-western Saudi Arabia.

 
Medical Biochemistry Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

This study was conducted on sickle cell anaemia (SCA) patients from the south-western province (SWP) of Saudi Arabia to determine the effect of thalassaemias, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and Hb F level on the clinical presentation of sickle cell anaemia. The results showed that associated alpha-thalassaemia improved the haematological parameter values while associated G-6-PD deficiency and high Hb F level did not play a significant role in amelioration of the disease in these patients. Hb S/beta(0) -thalassaemia cases showed a severe anaemia similar to the SCA patients without alpha-thalassaemia. However, considerable improvement of the haematological parameters were found in patients with S/beta(0)-thalassaemia and associated alpha-thalassaemia. This paper reveals that alpha-thalassaemia may partially ameliorate the clinical manifestations of SCA in Saudi patients from the SWP, while high Hb F level and G-6-PD deficiency do not modify SCA to any statistically significant extent.

64:
el-Hazmi MAWarsy AS Med Lab Sci. 1990 Apr;47(2):80-4.


Correlation between red cell pyruvate kinase activity and haematological parameters.

Medical Biochemistry Dept, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Red cell pyruvate kinase (PK) activity was correlated with haematological parameters. A statistically significant negative correlation was obtained between the activity of PK and total haemoglobin, total red blood cell count, and packed cell volume, and a positive correlation with white blood cell count, reticulocyte count, and red cell indices in anaemic patients. In non-anaemic patients the correlation between PK and haematological parameters was similar except with reticulocytes, where a slightly negative, statistically non-significant correlation was obtained. It is suggested that in patients with anaemias, infections, and leucocytosis, the elevation in PK level will significantly mask PK deficiency due to associated PK deficient variants. It is therefore essential to eliminate white cells before conducting PK assays, and to make corrections for reticulocytes.

65:
el-Hazmi MA, Bahakim HM, Babikar MA, al-Swailem AM, Warsy AS. J Trop Pediatr. 1990 Apr;36(2):56-62.


Symptom-free intervals in sicklers: does pneumococcal vaccination and penicillin prophylaxis have a role?

College of Medicine & King Khalid Hospital, King Saud University, Riyadh, Saudi Arabia.

To investigate the combined effect of pneumococcal vaccination and penicillin prophylaxis on the progress of sickle cell disease, two groups of sickle cell disease patients, presenting with severe clinical manifestations of the disease were selected as cohorts. One group was vaccinated with the polyvalent pneumococcal vaccine and given penicillin prophylaxis, while the other group was not given the vaccine and penicillin. Clinical manifestations, frequency of hospitalization, crises and blood transfusion requirements, haematological parameters, and differential counts were recorded for each patient in the two groups. The 'severity index' of the sickle cell disease was calculated for each patient. No significant differences were encountered in the values of the haematological parameters except for the white cell count which was significantly higher in the non-vaccinated group. However, the frequency of hospitalization, crisis, and blood transfusion were significantly higher in the non-vaccinated group compared to the vaccinated group. Clinical symptoms frequently associated with severe sickle cell disease, were also encountered at a higher frequency in the non-vaccinated group. These results show that pneumococcal vaccination and penicillin prophylaxis increase the crisis-free interval in sickle cell disease patients, and play a significant role in decreasing the morbidity associated with sickle cell disease.

66: el-Hazmi MA, Warsy AS. Gene Geogr. 1990 Apr;4(1):15-9.

 Frequency of glucose-6-phosphate dehydrogenase variants and deficiency in Arabia.

Department of Medical Biochemistry, College of Medicine & King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.

Several variants of G6PD were found in different regions of Saudi Arabia. The variants were separated on the basis of their electrophoretic mobility and activity towards glucose-6-phosphate. G6PD*B was the most common enzyme found in all regions investigated. Variants included G6PD*A, G6PD*A-, G6PD*B weak and G6PD*def. The frequency of the variants shows significant differences among the regions of Saudi Arabia examined.

67: el-Kassimi FAWarsy AS Uz-Zaman A, Pillai DK. Respir Med. 1989 Mar;83(2):119-21.


Alpha 1-antitrypsin serum levels in widespread bronchiectasis.

Medical Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

This study found significantly higher serum levels of alpha 1-antitrypsin (alpha 1-AT) in 35 patients with widespread bronchiectasis compared with healthy controls. The results are in contradiction with a previous study and four case reports which found an association between alpha 1-AT deficiency and bronchiectasis. However, the validity of the association has been questioned in the literature on the grounds that most of the patients in those reports had other possible aetiologies for their bronchiectasis. We believe the raised level of alpha 1-AT in our patients represents a non-specific acute phase response to bronchial infection. Further studies are needed to clarify whether bronchiectasis, like emphysema, can be a manifestation of alpha 1-AT deficiency.

68: el-Hazmi MA, Warsy AS. Trop Geogr Med. 1989 Jan;41(1):52-6.


The effects of glucose-6-phosphate dehydrogenase deficiency on the haematological parameters and clinical manifestations in patients with sickle cell anaemia.

Medical Biochemistry Department, College of Medicine, Riyadh, Saudi Arabia.

This study was conducted on 81 children with sickle cell anaemia (SCA) from the south-western province of Saudi Arabia. Ten of these children had associated glucose-6-phosphate dehydrogenase (G-6-PD) deficiency due to the presence of the phenotype 'G-6-PD Mediterranean'. Slightly lower, statistically non significant, values of red blood cell count, total haemoglobin, packed cell volume and red cell indices were found in SCA patients with G-6-PD deficiency. However, certain clinical features were improved in these patients. Comparison was also made with results published from the eastern province of the country, where SCA is reported to be mild. It is suggested that G-6-PD deficiency due to G-6-PD 'Mediterranean' worsens certain manifestations and improves others in SCA patients with a severe form of SCA, while improvement in haematological parameters is observed in SCA patients with mild SCA.

69: el-Hazmi MAWarsy AS Trop Geogr Med. 1989 Jan;41(1):22-5.

 

Riboflavin status in Saudi Arabia--a comparative study in different regions.

Medical Biochemistry Department, College of Medicine, King Khalid Hospital, Riyadh, Saudi Arabia.

Riboflavin (vitamin B2) status was investigated in male and female Saudis of different age groups in different regions of Saudi Arabia using the assay of glutathione reductase (GR) in presence and absence of flavin adenine dinucleotide (FAD) and determination of the activity coefficient (AC) for GR. The overall prevalence of riboflavin deficiency as determined by an AC value of 1.3 or above, in the male population of Al-Hafouf, Jaizan and Riyadh was found to be 32.6%, 17.8% and 17.1%, respectively, while in the female population the prevalence was 41.5%, 22.3% and 37.9%, respectively. Within each region a marked variation was found in the different age groups. In this paper the riboflavin status and the prevalence of riboflavin deficiency in three regions of Saudi Arabia is presented and the possible causes for a high prevalence of riboflavin deficiency in the Saudi population are discussed.

70: el-Hazmi MAWarsy AS Haematologia (Budap). 1989;22(1):37-42.

 

Glutathione reductase in the south-western province of Saudi Arabia--genetic variation vs. acquired deficiency.

Medical Biochemistry Department, College of Medicine, King Saud University, Riyad, Saudi Arabia.

The activity of glutathione reductase (GR) is closely associated with the riboflavin level in diet. Dietary deficiency of this water-soluble vitamin causes glutathione reductase deficiency. Furthermore, a variable frequency of GR variants with reduced activity has been reported in several populations. In an attempt to determine GR deficiency due to genetic (GR variant) and acquired causes (riboflavin deficiency), red cell GR activity was estimated in 461 male and female Saudis from the South-Western province of Saudi Arabia. The frequency of genetic GR deficiency (GR variant) was 24.5% in Saudi males and 20.3% in females. The frequency of acquired GR deficiency (riboflavin deficiency) was 17.8% and 22.4%, respectively. Interaction between genetic GR deficiency and other genetic abnormalities, i.e. sickle cell gene and glucose-6-phosphate dehydrogenase deficiency were also estimated. No specific link could be demonstrated.

71: el-Hazmi MA, Warsy ASHum Hered. 1989;39(6):313-7.

 

Frequency of glucose-6-phosphate dehydrogenase phenotypes and deficiency in Al-Baha.

Medical Biochemistry Department, College of Medicine, Riyadh, Saudi Arabia.

This investigation was conducted on 847 males and females in Al-Baha, the mountainous western province of Saudi Arabia, to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) phenotypes and G6PD deficiency. Among the G6PD phenotypes, G6PD B+, G6PD A+, G6PD A-, G6PD Mediterranean and G6PD Mediterranean-like were identified with a gene frequency in the male population of 0.7769, 0.0119, 0.0020, 0.1255 and 0.0817, respectively, and in the females with a frequency of 0.722, 0.003, 0.003, 0.1128 and 0.1311, respectively. Heterozygous females with the phenotypes of G6PD B+/A+ and B+/A- were identified with a frequency of 0.0183 and 0.0090, respectively. The frequency of severe G6PD deficiency in this population was 0.1275 and 0.1158 in males and females, respectively.

72:
Sedrani SH, el-Hinnawi SI, Warsy AS. Am J Med Sci. 1988 Jul;296(1):22-6.

 

Establishment of a normal reference range for alpha 1-antitrypsin in Saudis using rate nephelometry.

Department of Biochemistry, King Saud University, Riyadh, Saudi Arabia.

Alpha 1-antitrypsin level was estimated in 543 healthy males and 603 healthy females using rate nephelometry, in order to establish a "normal reference range" in Saudis. A significantly higher mean and range were encountered in the females than in the males, and a positive correlation was obtained between the alpha 1-antitrypsin level and age. Since alpha 1-antitrypsin showed a positively skewed distribution, the normal reference ranges were established using the 2.5th to 97.5th percentile values. This article presents the normal reference range for alpha 1-antitrypsin as 100 to 250 mg/dl in children under 10 years of age, 95 to 275 mg/dl in adult males and 100 to 350 mg/dl in adult females. The results are discussed in light of the significant differences encountered in comparison with the results reported elsewhere and by the manufacturers of the kits.

73: el-Hazmi MA, Warsy AS. Med Lab Sci. 1988 Jul;45(3):255-60.


Correlation between red cell glucose-6-phosphate dehydrogenase level and haematological parameters.

74:
el-Hazmi MA, Warsy AS. Hum Hered. 1988;38(5):317-22.

 

Glucose-6-phosphate dehydrogenase deficiency in Saudi Arabia. A study in Al-Ula.

Medical Biochemistry Department, College of Medicine, Riyadh, Saudi Arabia.

This paper reports the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the male and female population of A1-Ula in the northwestern province of Saudi Arabia. The frequency of G6PD deficiency in the male population was 0.098 and in the females it was 0.028. This frequency is significantly lower than those reported for other malaria endemic regions in Arabia. The population was further subgrouped on the basis of their haemoglobin phenotypes and the highest frequency of G6PD deficiency was obtained in male Hb S heterozygotes followed by the male Hb S homozygotes. Phenotyping of G6PD revealed the presence of G6PD-Mediterranean, G6PDA+, G6PDA- and G6PD Mediterranean-like, and the frequency of these variants in Al-Ula was different from those reported in other regions of Saudi Arabia

75: el-Hazmi MA, Jabbar FA, Warsy AS. Scand J Clin Lab Invest. 1987 Jun;47(4):351-4.

Cholesterol and triglyceride level in patients with sickle cell anaemia.


This study was conducted on a group of 45 sickle cell anaemia (HbSS) patients and 45 age- and sex-matched controls with normal haemoglobin (HbAA) to determine the effect of anaemia due to genetic red cell defects on the value of cholesterol and triglyceride in plasma. The cholesterol level was found to be lower in the sickle cell anaemia patients compared with normals, and the difference in the level of cholesterol in the two groups was found to be statistically significant. A positive correlation was found between the haemoglobin level and the level of cholesterol. Since increase in cholesterol level increases the incidence of arteriosclerosis, coronary heart diseases, cholestasis and xanthomatosis, the patients with sickle cell anaemia may be at an advantage in having a protection against these disorders.

76: el-Hazmi MA, Warsy AS. Med Lab Sci. 1987 Apr;44(2):125-9.

 A normal reference range for erythrocyte glucose-6-phosphate dehydrogenase in a Saudi population.

77: El-Hazmi MA, Jabbar FA, Al-Faleh FZ, Al-Swailem AR, Warsy AS.Trop Geogr Med. 1987 Apr;39(2):157-62.

The haematological, biochemical and clinical--presentation of haemoglobin S in Saudi Arabia (i). Haematological & clinical expression.

The haematological and clinical expression of haemoglobin S (Hb S) was investigated in a group of male and female Saudis of haemoglobin genotype AS and SS, and the results compared with those from normal individuals (AA). The influence of alpha thalassaemia in each genotype was also investigated. The total haemoglobin concentration (Hb), red blood cell count (RBC) and packed cell volume (PCV) were significantly lower in the SS group without thalassaemia. In the thalassaemic group Hb, RBC and PCV levels were higher, while MCV and MCH were considerably lower. The clinical investigations reveal that almost 30% of the SS cases had not required blood transfusion, and none of the patients had suffered from leg ulceration or hand and foot syndrome. Comparison of the results obtained for Saudi sickle cell patients with those reported for Jamaicans show several differences, indicating a milder disease in the Saudis.

 78:
el-Hazmi MAWarsy AS Ann Nutr Metab. 1987;31(4):253-8.

Riboflavin status in a Saudi population--a study in Riyadh.

Riboflavin is essential for several metabolic processes taking place in the human body. A deficiency of riboflavin has been reported to occur at a high prevalence in several populations, particularly in children and adolescents from low-socioeconomic groups. We investigated the riboflavin status in 502 Saudi males and 213 Saudi females using a determination of red-cell glutathione reductase activity in the presence and absence of flavin adenine dinucleotide. The population was grouped according to age and the glutathione reductase activity coefficient (AC) was calculated in each of the groups. An AC value of 1.3 or above was recorded in 38% of the females and 17% of the males. In the female group the lowest percentage was in girls less than 12 years of age, and the highest in the age group 21-30 years, while among males boys of less than 12 years and men over 30 years of age had the highest percentage. In this paper we report and discuss the riboflavin status, as indicated by the glutathione reductase AC, in the Saudi male and female population in the Riyadh area.

79: el-Hazmi MA, Warsy AS. Trop Geogr Med. 1987 Jan;39(1):32-5.

Interaction between glucose-6-phosphate dehydrogenase deficiency and sickle cell gene in Saudi Arabia.

Sickle cell haemoglobin (Hb S) and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency occur at a variable prevalence in different regions of Saudi Arabia. The interaction between the two genes was investigated in 1859 Saudi males in different regions where the two genes were known to exist at both a high and a low frequency. The frequency of G-6-PD deficiency was the highest in the sickle cell anaemia (SS) cases. Furthermore, in all areas except Tehamat-Aseer (on the Red Sea), the frequency of G-6-PD deficiency was greater in the sickle cell heterozygotes (AS) than in the normal (AA) individuals. The interaction between G-6-PD deficiency and sickle cell gene in the homozygotes and heterozygotes may provide additional benefit against environmental and genetical factors, and may play a role in the amelioration of sickle cell disease in Saudis.

80: el-Hazmi MA, Jabbar FA, Al-Faleh FZ, Warsy AS, el-Hazmi MA, Jabbar FA, Al-Faleh FZ, Warsy AS. Acta Haematol. 1987;77(3):161-5.

 

Triple alpha genes in association with sickle cell and beta-thalassaemia gene in the Saudi population.

This paper describes the case of a 6-year-old Saudi male who had sickle cell heterozygosity, beta +-thalassaemia and possessed three alpha-genes of the haplotype alpha alpha alpha anti-3.7/as diagnosed by restriction endonuclease studies using Hpa I, Bam HI, Bgl II, Hind III and Xba I. Since the iron level was found to be normal, it is proposed that the coexistence of beta-thalassaemia with triple alpha-genes in Hb S heterozygotes may be the cause of the anemia. A possible mechanism for severe anaemia is presented.

81: el-Hazmi MA, Warsy AS. Hum Hered. 1987;37(4):237-40.

Beta-globin gene polymorphism in Saudis: 5.6 Hpa I fragment.

College of Medicine, King Saud University, Riyadh, Saudi Arabia.

To investigate beta-globin gene polymorphism in the Saudi population, samples from 436 individuals from the eastern and north-western provinces of Saudi Arabia were studied using restriction endonucleases Mst II and Hpa I. Three individuals with haemoglobin genotypes AA, AS and SS were identified to each have a 5.6-kilobase (kb) Hpa I fragment in addition to a 13.0-kb fragment. This paper reports for the first time in Saudis a linkage of both the beta A and beta B genes to a 5.6-kb Hpa I fragment.

82: el-Hazmi MA, Jabbar FA, Al-Swailem AR, Warsy AS. Hum Genet. 1986 Nov;74(3):313-5.


Beta-globin gene polymorphism in Saudis--triple Hpa I fragments.

In an attempt to investigate beta-globin gene polymorphism in the Saudi population, DNA samples were analysed using restriction endonucleases, Mst II and Hpa I. Both beta A and beta S genes showed extensive polymorphism and were found to be linked to 13.0 kb, 7.6 kb, 7.0 kb, and 5.6 kb Hpa I fragments. Three DNA samples out of a total of 436 analysed, had beta-globin gene linked to three Hpa I fragments of the sizes 13.0 kb, 7.6 kb, and 5.6 kb. In this paper we present our findings and discuss the possibility of multiple beta-globin loci.

83: 
el-Hazmi MA, Al-Swailem AR, Al-Faleh FZ, Warsy AS.Hum Hered. 1986;36(1):45-9.


Frequency of glucose-6-phosphate dehydrogenase, pyruvate kinase and hexokinase deficiency in the Saudi population.

The frequencies of glucose-6-phosphate dehydrogenase (G-6-PD), pyruvate kinase (PK) and hexokinase (HK) deficiency were determined in different regions of Saudi Arabia. G-6-PD deficiency was found to range from 0.045 to 0.220 for the male and 0.020 to 0.125 for the female population. The highest frequencies were found to exist in the regions which are endemic to malarial parasite and have high frequencies of sickle cell and thalassaemia genes. Partial deficiencies of PK and HK were encountered in each region, however, no case of complete deficiency of these enzymes was identified. Further investigations are in progress to determine the clinical manifestations of enzyme deficiencies in the Saudi population.

84:
el-Hazmi MA, Warsy AS. Hum Hered. 1986;36(1):24-30.


Glucose-6-phosphate dehydrogenase polymorphism in the Saudi population.

Glucose-6-phosphate dehydrogenase (G-6-PD) exhibits extensive heterogeneity in the Saudi population. The polymorphism of G-6-PD was investigated in different regions of Saudi Arabia, and G-6-PD variants were separated and identified on the basis of their electrophoretic mobility and activity towards glucose-6-phosphate. G-6-PD-B+ was found to be the most common phenotype, G-6-PD-A+ was found in each region but at a variable frequency ranging between 0.007 and 0.046. A second variant with normal activity but lower mobility than G-6-PD-B+ was identified among the Saudis at a frequency ranging from 0.000 to 0.028 in the different regions. In addition, a high frequency of variants with reduced activity was encountered in all regions. In males, a frequency of G-6-PD Mediterranean ranging from 0.046 to 0.261 was obtained, while G-6-PD-A- existed at a frequency ranging from 0.011 to 0.028. Furthermore, other variants with reduced activity but the same electrophoretic mobility as G-6-PD-B+ were detected at a high frequency among the Saudis.

85:
el-Hazmi MA, Warsy AS. Hum Hered. 1986;36(4):222-6.


Double heterozygote leftward/rightward deletion type alpha-thalassaemia in Saudi Arabs.

Restriction endonucleases have been used for the investigation of deletion type alpha-thalassaemias in the Saudi population. Using Bgl II digestion, we diagnosed 2 cases with 15.8- and 7.0-kb alpha-globin gene fragments. The 15.8-kb Bgl II fragment is obtained in cases with rightward deletion, while the 7.0-kb fragment occurs in cases with leftward deletion. The 2 cases reported in this paper are heterozygous leftward/rightward deletion cases. The Bam HI digestion results and haematological parameter values are reported. This is the first report of heterozygous leftward/rightward deletion in the Saudi population.

86:
el-Hazmi MAWarsy AS Acta Haematol. 1986;76(4):212-6.


On the nature of sickle cell disease in the south-western province of Saudi Arabia.

Sickle cell disease (SCD) occurs at a high prevalence in different parts of Saudi Arabia. Several reports indicate that the disease follows a mild clinical course in the Saudi population of the eastern province of Saudi Arabia, while little is known about the disease in other parts of the country. This study was conducted on 53 children from the Saudi Arabian south-western province with sickle cell disease and 53 age- and sex-matched normal controls (haemoglobin AA phenotype). A statistically significant difference was encountered in the haematological parameters investigated in the two groups. The SCD patients were divided into subgroups with high and low Hb F levels, alpha- and beta-thalassaemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. The haematological parameters were then compared in the different sub-groups. No significant difference could be demonstrated in the haematological parameters in patients with a high or low Hb F level. In patients without thalassaemia, the red cell count, total haemoglobin and haematocrit were significantly lower, while MCV, MCH and MCHC were higher. G-6 PD deficiency existed in association with thalassaemias, and apart from a reduction in MCV and MCH, no other statistically significant difference could be demonstrated. Clinical examination revealed a severe disease with several cases suffering from the hand and foot syndrome.

87: el-Hazmi MAWarsy AS Hum Hered. 1985;35(5):326-32.

 Glutathione reductase deficiency in association with sickle cell and thalassaemia genes in Saudi populations.


Glutathione reductase (GR) deficiency is reported to occur with a variable frequency in some populations of the world. In this study, the populations of two regions of Saudi Arabia which have a high frequency of sickle cell, thalassaemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, were screened for GR deficiency. Studies were also carried out to investigate the frequency of GR deficiency with other genetic blood disorders. The frequencies of complete GR deficiency were 0.0065 and 0.006, while those of partial deficiency were 0.146 and 0.074 in Al-Hafouf and Khaiber, respectively. GR deficiency was encountered in combination with the sickle gene, the G-6-PD deficiency gene and the thalassaemia gene in both regions. Individuals with GR deficiency showed slightly reduced haematological parameters. In thalassaemic/GR-deficient subjects, mean cell volume and mean cell haemoglobin were low, while in sickle cell anaemia patients with GR deficiency the haematological parameters were higher than in sickle cell anaemia patients without GR deficiency.

88: Warsy AS.Hum Hered. 1985;35(3):143-7.

 Frequency of glucose-6-phosphate dehydrogenase deficiency in sickle-cell disease. A study in Saudi Arabia.

The frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 50 Hb S homozygotes (SS) and 98 Hb S heterozygotes (AS) was determined and compared with the frequency obtained in individuals with normal haemoglobin (AA). The observed number of SS patients with G-6-PD deficiency was significantly greater than the expected value (p less than 0.05). The frequency of G-6-PD deficiency in AA, AS and SS was found to be 0.172, 0.214 and 0.420, respectively. A statistically significant increase of G-6-PD deficiency was apparent in the Saudi sicklers. The possibility that G-6-PD deficiency and Hb S gene interact, influencing the survival of the carriers of these genetic abnormalities, is discussed.

89: el-Hazmi MA, Warsy AS. Hum Genet. 1984;68(4):320-3.

 

Aspects of sickle cell gene in Saudi Arabia--interaction with glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell haemoglobin (Hb S) are red cell genetic abnormalities that occur at a high frequency in several areas of the world including several areas of Saudi Arabia. Genetic and clinical interactions between these two disorders are reported to occur in some populations. In the present investigations, samples from affected individuals were studied for the prevalence of G-6-PD deficiency and Hb S genes. The results of haematological parameters and common clinical findings in the Hb S homozygotes with and without G-6-PD deficiency are presented and the possibility that the two conditions interact beneficially is discussed.

90: El-Hazmi MA, Al-Faleh FZ, Al-Mofleh IA, Warsy AS, Al-Askah AK.

Trop Geogr Med. 1982;34(4):323-32.

 

Establishment of normal "reference" ranges for biochemical parameters for healthy Saudi Arabs.

 
Biochemical constituents in the blood of healthy individuals are subject to variations under the influence of several factors. Differences can be seen in the normal ranges established for populations living under different environmental and dietary conditions. Age and sex also affect the normal range values considerably. Normal "reference" ranges for 29 biochemical parameters, established by using blood samples from 578 male and 226 female students studying at various colleges at King Saud University, and of ages ranging between 20 and 29 years, are presented. Marked differences are found in the values for Saudi males and females. Comparison of the results obtained for Saudis with those reported for western populations also show differences in the majority of the parameters. The comparison of Saudi mean values with western mean values is presented.

91: Wright CL, Warsy AS, Holroyde MJ, Trayer IP. Biochem J. 1978 Oct 1;175(1):125-35.

 

Purification of the hexokinases by affinity chromatography on sepharose-N-aminoacylglucosamine derivates. Design of affinity matrices from free solution kinetics.

The purification is described of rat hepatic hexokinase type III and kidney hexokinase type I on a large scale by using a combination of conventional and affinity techniques similar to those previously used for the purification of rat hepatic glucokinase [Holroyde, Allen, Storer, Warsy, Chesher, Trayer, Cornish-Bowden & Walker (1976) Biochem. J. 153, 363-373] and muscle hexokinase type II [Holroyde & Trayer (1976) FEBS Lett. 62, 215-219]. The key to each purification was the use of a Sepharose-N-aminoacylglucosamine affinity matrix in which a high degree of specificity for a particular hexokinase isoenzyme could be introduced by either varying the length of the aminoacyl spacer and/or varying the ligand concentration coupled to the gel. This was predicted from a study of the free solution kinetic properties of the various N-aminoacylglucosamine derivatives used (N-aminopropionyl, N-aminobutyryl, N-aminohexanoyl and N-aminooctanoyl), synthesized as described by Holroyde, Chesher, Trayer & Walker [(1976) Biochem. J. 153, 351-361]. All derivatives were competitive inhibitors, with respect to glucose, of the hexokinase reaction, and there was a direct correlation between the Ki for a particular derivative and its ability to act as an affinity matrix when immobilized to CNBr-activated Sepharose 4B. Muscle hexokinase type II could be chromatographed on the Sepharose conjugates of all four N-aminoacylglucosamine derivatives, although the N-aminohexanoylglucosamine derivative proved best. This same derivative was readily able to bind hepatic glucokinase and hexokinase type III, but Sepharose-N-amino-octanoyl-glucosamine was better for these enzymes and was the only derivative capable of binding kidney hexokinase type I efficiently. Separate studies with yeast hexokinase showed that again only the Sepharose-N-amino-octanoylglucosamine was capable of acting as an efficient affinity matrix for this enzyme. Implications of these studies in our understanding of affinity-chromatography operation are discussed.

92: Holroyde MJ, Allen MB, Storer AC, Warsy AS, Chesher JM, Trayer IP, Cornish-Bowden A, Walker DG. Biochem J. 1976 Feb 1;153(2):363-73.

 

The purification in high yield and characterization of rat hepatic glucokinase.

A new improved procedure for the purification of rat hepatic glucokinase (ATP-d-glucose 6-phosphotransferase, EC 2.7.1.2) is given. A key step is affinity chromatography on Sepharose-N-(6-aminohexanoyl)-2-amino-2-deoxy-d-glucopyranose. A homogeneous enzyme, specific activity 150 units/mg of protein, is obtained in about 40% yield. The molecular weight of the pure enzyme was determined by several procedures. In particular, sedimentation-equilibrium studies under a variety of conditions indicate a molecular weight of 48000 and no evidence for dimerization; reports in the literature of other values are discussed in the light of this evidence on the pure enzyme. The amino acid composition suggests that hepatic glucokinase is closely related to rat brain hexokinase and also the wheat "light" hexokinases.

93: Wright CL, Holroyde MJ, Warsy AS, Trayer IP. Biochem Soc Trans. 1976;4(6):1052-3.

 

Purification of the mammalian hexokinases by affinity chromatography on sepharose-N-aminoacyl-glucosamine derivatives.

 

The Complexity of Genetics of Obesity 

Prof. Arjumand S. Warsy; *Prof. Mohsen A.F El-Hazmi,

 Obesity is one of the most frequently identified multifactorial abnormalities in many of the developed and developing countries. Several adoption, twin and family studies have confirmed the genetic nature of control of body weight in man.  Although several single-gene mutations have been shown to cause obesity in animal models, in humans the situation is complex, as most forms of human obesity arise from interaction of multiple genes, environmental factors and behavior, and this complex etiology makes the search for obesity genes very challenging. Exceptional mutations of the leptin gene and its receptor, pro-opiomelanocortine (POMC), prohormone convertase 1 (PC1) and more frequently, mutations in the melanocortin receptor 4 have been described. All these obesity genes encode proteins that are strongly connected as part of the same loop of the regulation of food intake.  It is suggested that obesity may be a disorder of the weight regulatory system. Current models of obesity propose that genes involved in body weight homeostasis act by sensing food intake, available energy stores and levels of activity. These sensory inputs are relayed to regulatory sites, particularly in the hypothalamus, where the information is integrated and a neural-humoral response is initiated. The exact contribution of genetic factors to a predisposition to obesity has been assessed and in monozygotic and dizygotic twins the estimates range from around ~ 40–70%. Thus several studies consistently show that ~ 40-70% of the variation in obesity-related phenotypes, such as body mass index (BMI), sum of skin fold thickness, fat mass and leptin levels, is heritable. An interesting observation is that some of these genes exert their effect across various ethnic populations, while others are more common in some ethnic groups and not in others. Genome-wide scans in different ethnic populations have localized major obesity loci on chromosomes 2, 5, 10, 11 and 20. We conducted an extensive survey of the Saudi population and identified that obesity and overweight occur in almost all regions of Saudi Arabia though at a variable prevalence. A significant increase was observed in the prevalence of both overweight and obesity with age, and males have a higher prevalence of overweight, while females have higher prevalence of obesity compared to the males. In an attempt to determine possible genetic markers of obesity in Saudi Population, we conducted a study on normal weight, overweight and obese Saudis. The levels of Lp(a), and leptin were estimated and ACE gene, SA gene, and leptin receptor gene polymorphism were investigated. This paper will present a comprehensive overview of the genetics of obesity and will outline the findings in Saudi population.

 

 

 


 

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