Ethnic variation of IL-4 intron 3 VNTR gene polymorphism; its association with type 2 diabetes mellitus and its complication (neuropathy) in Egyptian subjects.

Type 2 diabetes mellitus (T2DM) has multigenetic and environmental interactive factors. Although diabetic neuropathies (DPN) are the most common, but at the same time, the least recognized and understood long-term complication of diabetes. This study aimed to investigate the association of IL-4 VNTR gene polymorphism with T2DM complicated with neuropathy in Egyptian subjects. This is a case control study including 102 T2DM Egyptian patients, plus 188 unrelated healthy individuals as controls. They were evaluated for variable number tandem repeat (VNTR); 70 base pair repeats located in the intron 3; of IL-4 gene using the PCR technique. Homozygote frequency of the three-repeat allele (A1/A1) genotype of IL-4 VNTR was nearly equal among diabetic cases and controls (60.8% vs. 62.2%, respectively). Heterozygous frequency of (A1/A2) genotype was higher among controls compared to cases (33.5% vs. 19.6%, respectively) but not statistically significant. The (A2) allele had a significantly higher frequency in diabetic cases compared to controls (29.3% vs. 21.0%, respectively) while the (A1) allele had lower frequency but not significant one (70.7% vs. 79.0%, respectively). Comparing cases complicated with diabetic neuropathy vs. noncomplicated cases regarding their polymorphic IL-4 (VNTR) genotypes revealed a nonsignificant lower frequency of (A1A1) genotype (57.1% vs. 65.1%, respectively, p = .57) with a higher combined (A2A2 + A1/A2) genotype frequency (42.9% vs. 34.9%, respectively). Only two haplotypes (A1) & (A2) of IL-4 (VNTR) gene were recognized among Egyptian population; (A2) allele may influence in diabetes but not its complication (neuropathy) among Egyptian diabetic patients.

Factors influencing parental consent for participation in clinical research involving their children in Egypt.

Factors affecting parents' decision to involve their children in clinical research have not been studied in all cultural backgrounds. We aimed to explore the attitudes and beliefs influencing parents' decision to involve their children in clinical research in Mansoura, Egypt. Of 523 families approached, 357 filled the questionnaire. Only 98 (27.5%) parents consented to involve their child in clinical research. The children of consenters were significantly older than refusers: 8.6 (SD 7.2) versus 2.6 (SD 1.2) years. Factors favouring consent were: research of benefit to child (84.7%), enough explanation about the benefits (40.8%) and to learn more about child's condition (29.6%). Factors favouring refusal were: use of new drugs or vaccines (89.6%) and invasive procedures (84.2%). Parents' rate of consent was positively correlated with the research being non-invasive and the belief that research was of benefit to their child and negatively correlated with belief that refusal may negatively affect the care provided to their child.

Factors influencing parental consent for participation in clinical research involving their children in Egypt

Factors affecting parents' decision to involve their children in clinical research have not been studied in all cultural backgrounds.We aimed to explore the attitudes and beliefs influencing parents' decision to involve their children in clinical research in Mansoura, Egypt.Of 523 families approached, 357 filled the questionnaire.Only 98 [27.5%]parents consented to involve their child in clinical research.The children of consenters were significantly older than refusers:8.6 [SD 7.2]versus 2.6 [SD 1.2]years.Factors favouring consent were:research of benefit to child [84.7%], enough explanation about the benefits [40.8%]and to learn more about child's condition [29.6%]. Factors favouring refusal were:use of new drugs or vaccines [89.6%]and invasive procedures [84.2%]. Parents' rate of consent was positively correlated with the research being non-invasive and the belief that research was of benefit to their child and negatively correlated with belief that refusal may negatively affect the care provided to their child

لم تخضع العوامل التي تؤثر على موافقة الوالدين على إشراك أطفالهم في البحوث السريرية، للدراسة في جميع الخلفيات الثقافية. وهدف الباحثون إلى التعرف على المواقف والمعتقدات التي تؤثر على القرارات التي يتخذها الوالدان حول مشاركة أطفالهم في البحوث السريرية في المنصورة في مصر. وقد تواصل الباحثون مع 523 أسرة، استكملت الاستبيانات منها 357 أسرة، واتضح أن 98 من الوالدين [27.5%]، فقط قد وافقوا على مشاركة أطفالهم في البحوث السريرية، وأن متوسط أعمار الأطفال الذين وافق الوالدان على مشاركتهم بالبحوث وهو 8.6 عاما [7.2 +/- ] أكبر بمقدار يعتد به إحصائيا من متوسط أعمار الأطفال الذين رفض الوالدان مشاركتهم بها وهو 2.6 عاما [1.2 +/- ]، وأن العوامل التي ترجح الموافقة هي:البحوث التي تعود بالنفع على الطفل [84.7 %]والشرح الوافي عن المنافع [40.8%]والتعلم أكثر عن حالة الطفل [29.6 %]أما العوامل التي ترجح رفض الموافقة فهي: استخدام أدوية أو لقاحات جديدة [89.6%]، والإجراءات الباضعة [84.2 %]. وكان هناك ترابطا إيجابي بين معدل موافقة الوالدين مع كون البحوث غير باضعة وكذلك مع الاعتقاد بأن البحوث نافعة لطفلها، وكان هناك ترابط سلبي مع الاعتقاد بأن رفض المشاركة قد يؤثر سلبيا على الرعاية التي تقدم لطفلها

Les facteurs influant sur la décision des parents de laisser leur enfant participer à une étude de recherche clinique n'ont pas été étudiés dans tous les contextes culturels.L'objectif de 'étude était d'examiner les attitudes et les croyances influant sur la décision des parents de laisser participer leur enfant à une étude de recherche à Mansoura [Egypte]. Sur 523 familles contactées, 357 ont rempli le questionnaire.Seuls 98 parents [27, 5 %]consentaient à laisser participer leur enfant a une recherche clinique.Les enfants des parents qui avaient donné leur consentement étaient nettement plus âgés que ceux dont les parents avaient refusé:8, 6 ans [ET 7, 2]contre 2, 6 ans [ET 1, 2]. Les facteurs favorisant le consentement étaient les suivants:une recherche bénéfique pour l'enfant [84, 7 %], des explications suffisantes sur les avantages [40, 8 %]et l'occasion de mieux connaitre l'affection de leur enfant [29, 6%]. Les facteurs favorisant le refus étaient les suivants:l'utilisation de nouveaux médicaments ou vaccins [89, 6 %]et des actes invasifs [84, 2 %]. Le taux de consentement des parents était positivement corrélé à une recherche non invasive et à la croyance que la recherche serait bénéfique pour leur enfant, et négativement corrélé à la croyance selon laquelle un refus pourrait négativement influer sur les soins fournis à leur enfant

Eosinophilic cationic protein: is it useful in assessing control of childhood asthma?

This study evaluated peripheral eosinophil and serum eosinophilic cationic protein (s-ECP) levels as markers of asthma control. A total of 38 children with asthma (16 controlled and 22 partially controlled) were compared with 16 age- and sex-matched healthy children. Total asthma cases had higher eosinophil counts and s-ECP levels than healthy children and partially controlled asthmatics had significantly higher levels of both markers than controlled asthmatics. Controlled asthma cases showed non-significant changes in both parameters versus healthy children. A negative correlation was noted between degree of asthma control and both eosinophil counts and s-ECP levels (r = -0.60 and -0.75 respectively). s-ECP as well as peripheral eosinophil count may be helpful in the assessment of asthma control.

Eosinophilic cationic protein: is it useful in assessing control of childhood asthma?

This study evaluated peripheral eosinophil and serum eosinophilic cationic protein [s-ECP] levels as markers of asthma control. A total of 38 children with asthma [16 controlled and 22 partially controlled] were compared with 16 age- and sex-matched healthy children. Total asthma cases had higher eosinophil counts and s-ECP levels than healthy children and partially controlled asthmatics had significantly higher levels of both markers than controlled asthmatics. Controlled asthma cases showed non-significant changes in both parameters versus healthy children. A negative correlation was noted between degree of asthma control and both eosinophil counts and s-ECP levels [r = -0.60 and -0.75 respectively]. s-ECP as well as peripheral eosinophil count may be helpful in the assessment of asthma control

Gene polymorphisms of TNF-alpha(-308), IL-10(-1082), IL-6(-174), and IL-1Ra(VNTR) related to susceptibility and severity of rheumatic heart disease.

Rheumatic heart disease (RHD) is an inflammatory disease of the heart tissues caused by interactive immune, genetic, and environmental factors. The objective of this study is to test for the association of polymorphisms related to cytokine genes with susceptibility and severity of RHD among affected children from the Nile Delta region of Egypt. The study included 50 children with chronic RHD (29 males and 21 females), with a mean age of 12.2 years, in addition to 98 healthy unrelated controls. Cases were further classified on the basis of echocardiographic findings into those with only mitral valve disease (MVD) or multivalvular lesions (MVLs) and also as mild, moderate, or severe valve lesions. For all cases and controls, DNA was extracted and amplified using polymerase chain reaction with sequence-specific primers for detection of single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes tumor necrosis factor (TNF)-alpha(-308 )G/A, interleukin (IL)-10(-1082 )G/A, and IL-6(-174 )G/C as well as a variable number of tandem repeats (VNTRs) in intron 2 of the IL-1Ra gene. All cases showed a significantly higher frequency of homozygous genotypes of TNF-alpha(-308 )A/A [odds ratio (OR) = 5.7, p < 0.001], IL-10(-1082) A/A (OR = 3.1, p < 0.05), IL-10(-1082) G/G (OR = 5.2, p < 0.05), and IL-1Ra A1/A1 (OR = 2.2, p < 0.05). Cases with MVD showed higher frequencies of genotypes TNF-alpha(-308 )A/A, G/G; IL-10(-1082) G/G; and IL-1Ra(VNTR) A1/A1 (p < 0.05). Cases with MVL showed a significantly higher frequency of homozygous A/A genotype of both TNF-alpha(-308 )(OR = 10.6, p < 0.05) and IL-10(-1082) (OR = 5.2, p < 0.05). The same was observed for cases with severe valve lesions. On the other hand, all studied groups showed significantly lower frequency of heterozygous genotypes of TNF-alpha(-308 )G/A, IL-10(-1082) G/A, and IL-1Ra(VNTR) A1/A2. No significant difference was found regarding the frequency of IL-6(-174 )G/C polymorphisms in total cases or subgroups compared to controls (p > 0.05). Predisposition to RHD is influenced by genetic factors including cytokine gene polymorphisms, with possible susceptibility to severe disease with multivalvular affection among cases with composite polymorphism (TNF-alpha(-308 )A/A and IL-10(-1082) A/A) and (TNF-alpha(-308 )A/A and IL-10(-1082) G/G).

Prognostic cytogenetic markers in childhood acute lymphoblastic leukemia.

OBJECTIVE: To evaluate children with acute lymphoblastic leukemia (ALL) showing resistance to immediate induction chemotherapy in relation to conventional and advanced cytogenetic analysis. METHODS: This work was conducted on 63 ALL children (40 males and 23 females) with age range 4.5 months-16 years (mean = 7.76 years). They included 37 cases attained true remission and 26 complicated by failure of remission, early relapse or death. They were subjected to history, clinical examination and investigations including CBC, BM examination, karyotyping, FISH for translocations and flowcytometry for immunophenotyping and minimal residual disease diagnosis. RESULTS: Cases aged 50.000/mm3 also showed better but non-significant remission rates. Most of the present cases were L2 with better remission compared to other immunophenotypes. Forty informative karyotypes were subdivided into 15 hypodiploid, 10 pseudodiploid, 8 normal diploid and 7 hyperdiploid cases; the best remission rates were noticed among the most frequent ploidy patterns. Chromosomes 9, 11 and 22 were the most frequently involved by structural aberrations followed by chromosomes 5, 12 and 17. Resistance was noted with aberrations not encountered among remission group; deletions involving chromosomes 2p, 3q, 10p and 12q; translocations involving chromosome 5; trisomies of chromosomes 16 and 21; monosomies of 5 and X and inversions of 5 and 11. CONCLUSION: Some cytogenetic and molecular characterizations of childhood ALL could add prognostic criteria for proper therapy allocation.

Prognostic cytogenetic markers in childhood acute lymphoblastic leukemia: cases from Mansoura Egypt.

The objective of the work was to evaluate children with acute lymphoblastic leukemia (ALL) showing resistance to immediate induction chemotherapy in relation to conventional and advanced cytogenetic analysis. The study was conducted on 63 ALL children (40 males and 23 females) with age range 4.5 months-16 years (mean = 7.76 years). They included 37 cases who attained a true remission and 26 complicated by failure of remission, early relapse or death. They were subjected to history, clinical examination and investigations including CBC, BM examination, karyotyping, FISH for translocations and flowcytometry for immunophenotyping and minimal residual disease diagnosis. Cases aged < 5 years; male sex with organomegaly had better remission although statistically insignificant. Initially low HB < 8 gm/dl, high WBCs and platelet counts >50.000/mm(3) also showed better but non-significant remission rates. Most of our cases were L(2) with better remission compared to other immunophenotypes. About 40 informative karyotypes were subdivided into 15 hypodiploid, 10 pseudodiploid, 8 normal diploid and 7 hyperdiploid cases; the best remission rates were noticed among the most frequent ploidy patterns. Chromosomes 9, 11 and 22 were the most frequently involved by structural aberrations followed by chromosomes 5, 12 and 17. Resistance was noted with aberrations not encountered among remission group; deletions involving chromosomes 2p, 3q, 10p and 12q; translocations involving chromosome 5; trisomies of chromosomes 16 and 21; monosomies of 5 and X and inversions of 5 and 11. Our conclusions were that cytogenetic and molecular characterizations of childhood ALL could add prognostic criteria for proper therapy allocation.

Association of cytokine gene polymorphism with susceptibility and clinical types of leprosy.

BACKGROUND: Both pro- and anti-inflammatory cytokines are implicated in development and prognosis of leprosy so the genetic regulation of such cytokines could play an important role. OBJECTIVE: . This study was planned for testing the association of cytokine gene polymorphisms with susceptibility and clinical types of leprosy among Egyptian cases. SUBJECTS: This study included 47 cases (29 men, 18 females, mean age = 46.3 years) with leprosy in addition to 98 healthy unrelated controls (52 males, 46 females, mean age = 44.9 years). Cases were recruited from Leprosy Clinics, Delta region of Egypt. Cases were classified into paucibacillary (PB) (n = 17; 10 males, 7 females; mean age 42.6 years) and multibacillary (MB) (n = 29; 19 males, 10 females; mean age 43.9 years). METHODS: For all cases and controls, DNA was extracted and amplified using polymerase chain reaction with sequence specific primers (PCR-SSP) for detection of single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes, TNF-α-308 (G/A), IL-10-1082(G/A), IL-6-174(G/C) as well as IL-1RaVNTR in intron 2 of the gene. RESULTS: COMPARED TO CONTROLS, ALL CASES HAVE SHOWN INCREASED FREQUENCY OF HOMOZYGOUS GENOTYPES : IL-10-1082 (GG) (Odds ratio 6.6, P <0.05), homozygous TNF-α-308 (GG) (Odds ratio =3.23), and homozygous IL-1Ra (11) (Odds ratio = 3.6, P<0.05) with increased frequency of IL10 G and ILRa 1 alleles (P<0.05). BP subgroup showed increased frequency of homozygous IL-10-1082 (GG) (Odds ratio = 18.6, P<0.05) with increased frequency of IL10 G allele (P<0.05). On the other hand, MB subgroup showed increased frequency of homozygous TNF-α-308 (GG) (Odds ratio = 5.84, P<0.05) and homozygous IL-1Ra (11) (Odds ratio = 4, P<0.05) with increased frequency of IL-1Ra 1 allele (P<0.05). There is predominance for heterozygous IL-6-174 (G/C) polymorphism in all studies patient subgroups as well as controls with no significant difference among them. CONCLUSION: Genetic polymorphisms related to TNF-α-308 and IL-10-1082 and IL-1Ra may be used as genetic markers for susceptibility and clinical outcome of leprosy among Egyptian cases from the Nile Delta.

Prognostic cytogenetic markers in childhood acute lymphoblastic leukemia: cases from Mansoura, Egypt.

OBJECTIVE: To evaluate children with acute lymphoblastic leukemia (ALL) showing resistance to immediate induction chemotherapy in relation to conventional and advanced cytogenetic analysis. SUBJECTS AND METHODS: This work was conducted on 63 ALL children (40 males and 23 females) with age range 4.5 months-16 years (mean = 7.76 years). They included 37 cases who attained true remission and 26 complicated by failure of remission, early relapse or death. They were subjected to history, clinical examination and investigations including CBC, BM examination, karyotyping, FISH for translocations and flow cytometry for immunophenotyping and minimal residual disease diagnosis. RESULTS: Cases aged < 5 years; male sex with organomegaly had better remission although statistically insignificant. Initially low Hb < 8 gm/dl, high WBCs and platelet counts > 50,000/mm(3) also showed better but non-significant remission rates. Most of our cases were L(2) with better remission compared to other immunophenotypes. Forty informative karyotypes were subdivided into 15 hypodiploid, 10 pseudodiploid, 8 normal diploid and 7 hyperdiploid cases; the best remission rates were noticed among the most frequent ploidy patterns. Chromosomes 9, 11 and 22 were the most frequently involved by structural aberrations followed by chromosomes 5, 12 and 17. Resistance was noted with aberrations not encountered among remission group; deletions involving chromosomes 2p, 3q, 10p and 12q; translocations involving chromosome 5; trisomies of chromosomes 16 and 21; monosomies of 5 and X and inversions of 5 and 11. CONCLUSIONS: Cytogenetic and molecular characterizations of childhood ALL may add prognostic criteria for optimal therapy allocation.

Susceptibility to and severity of rheumatoid arthritis in multicase families.

Fifteen sibships, each having two or more siblings affected by classical or definite RA were studied. They comprised 31 patients with RA (all in remission) and 21 normal siblings. The total severity index of RA was assessed by clinical and radiological indices. For all the patients the following investigations were carried out: (1) HLA antigens determination for nine antigens at A locus and 15 at B locus and 6 at DR locus; (2) rheumatoid factor. We found: (1) RA disease is genetically controlled and the responsible genes are linked to the HLA system; (2) association between seropositivity and DR4 and DR4/B27 genotypes; (3) significant effect of the genotype DR4/B27 on the age of onset; (4) association between the increase in disease severity both clinical and radiological and DR4/X and DR4/B27 phenotypes. Thus the genetic control is probably composed of two types of genes: disease susceptibility genes and disease severity genes linked to DR4/X and DR4/B27 phenotypes.

Haemodynamic and pharmacokinetic study of intravenous fenoldopam in patients with hepatic cirrhosis.

1. The effect of intravenous fenoldopam-an arterial vasodilator-was assessed in twelve patients with cirrhosis and portal hypertension. Six patients had compensated (Grade A or B Child-Pugh classification) and six decompensated (Grade C) liver disease. 2. A significant dose dependent reduction in systemic blood pressure with a concomitant fall in systemic vascular resistance and increase in cardiac index was observed. Estimated portal pressure (WHVP-FHVP) increased (15.4 +/- 3.2 to 19.3 +/- 3.7 mm Hg, P less than 0.05) due to a rise in wedged hepatic venous pressure (24.6 +/- 4.3 to 29.0 +/- 5.8 mm Hg, P less than 0.05). Hepatic blood flow did not change significantly. Similar haemodynamic effects were observed in both compensated and decompensated patients. 3. Fenoldopam plasma clearance and ICG clearance were found to decrease with increasing infusion concentration, indicating possible increase of the intrahepatic shunting. 4. With the observed rise in portal pressure there must be some concern with respect to the long-term use of this drug in patients with previous variceal bleeding.