Reduced expression of CD69 and adhesion molecules of T lymphocytes in asthmatic children receiving immunotherapy

T lymphocytes play a fundamental role in the initiation and regulation of chronic inflammatory responses in patients with asthma. CD69 is an early marker of T‐cell activation. The levels of intercellular adhesion molecule‐1 (ICAM‐1, CD54) and L ‐selectin have been reported to increase in patients with allergic diseases and asthma. The present study was therefore undertaken to investigate the expression of CD69, CD54, and L ‐selectin by T lymphocytes of children with asthma, before and after immunotherapy. Eighteen children newly diagnosed with asthma, 11 good and nine poor responders to immunotherapy, and 16 normal subjects, were enrolled in this study. The percentages of CD69⁺, CD54⁺, and CD62L⁺ cells in T lymphocytes were measured by using flow cytometry. The levels of CD69, CD54, and CD62L in serum and culture supernatants were determined by using enzyme‐linked immunosorbent assay (ELISA). The expression of CD69 and CD54 on CD3⁺ T lymphocytes was significantly higher in children with asthma than in control patients. All the patient groups expressed (spontaneously and following stimulation with phorbol myristate acetate and ionomycin together with mite‐extract proteins) greater amounts of CD69 and CD54 than did control subjects. With long‐term immunotherapy, the percentages of CD69⁺ and CD54⁺ T lymphocytes were significantly lower in patients with a good response to immunotherapy. Our results also showed significantly lower serum L ‐selectin levels following immunotherapy. In conclusion, successful immunotherapy resulted in decreased expression and production of CD69 and CD54. These results may explain, in part, the clinical efficacy of immunotherapy.     

Congenital anomalies among infants of diabetic mothers: a study of 466 cases at King Fahd Hospital of the University, Al-Khobar.

The purpose of the study was to determine the incidence of congenital anomalies among infants of diabetic mothers and compare this with the normal obstetric population in our hospital. Among 17 463 patients delivered at the King Fahd Hospital of the University, Al-Khobar, Saudi Arabia between January 1987 and December 1992 there were 466 diabetic mothers who delivered 466 singleton births. The incidence of diabetes was 2.6%. Among those 466 diabetic patients there were 132 with clinical diabetes which was present before pregnancy and which required insulin treatment during pregnancy and 334 with gestational diabetes. There were 14 lethal congenital anomalies among the infants of diabetic mothers (3%) compared with 69 anomalies in general obstetric population (0.4%). The difference = was very highly significant P = 0.001. Ten anomalies were responsible for 10 stillbirths and the other four anomalies resulted in four neonatal deaths. The most common anomalies were those of the central nervous system and multiple fetal anomalies, followed by cardiovascular system, renal and chromosomal anomalies. All those anomalies occurred in the infants whose mothers had clinical diabetes.     

Efficacy of short‐term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food‐cobalamin malabsorption: A study of 30 patients

Background: It has been suggested that oral cobalamin (vitamin B₁₂) therapy may be an effective therapy for treating cobalamin deficiencies related to food‐cobalamin malabsorption. However, the duration of this treatment was not determined. Patients and method: In an open‐label, nonplacebo study, we studied 30 patients with established cobalamin deficiency related to food‐cobalamin malabsorption, who received between 250 and 1000 μg of oral crystalline cyanocobalamin per day for at least 1 month. Endpoints: Blood counts, serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment. Results: During the first month of treatment, 87% of the patients normalized their serum cobalamin levels; 100% increased their serum cobalamin levels (mean increase, +167 pg/dl; P < 0.001 compared with baseline); 100% had evidence of medullary regeneration; 100% corrected their initial macrocytosis; and 54% corrected their anemia. All patients had increased hemoglobin levels (mean increase, +0.6 g/dl) and reticulocyte counts (mean increase, +35 × 10⁶/l) and decreased erythrocyte cell volume (mean decrease, 3 fl; all P < 0.05). Conclusion: Our findings suggest that crystalline cyanocobalamin, 250–1000 μg /day, given orally for 1 month, may be an effective treatment for cobalamin deficiencies not related to pernicious anemia.     

Intravenous magnesium sulphate effect on maternal serum and amniotic fluid cytokines levels in preterm labour patients.

Our objective was to evaluate the effect of intravenous magnesium sulphate administration to patients with preterm labour on maternal serum and amniotic fluid IL-1beta, IL-6, IL-10 and TNFalpha concentrations. Thirty-six patients at 24-34 weeks of singleton gestation, who presented with contractions (> or = 8 in 60 min) had amniocentesis to rule out intrauterine infection. The patients received intravenous MgSO4 for tocolysis. Twenty-six patients had amniocentesis performed before initiation of MgSO4 (controls) while 10 others had the procedure during tocolytic therapy (study patients). Magnesium, IL-1beta, IL-6, TNFalpha and IL-10 concentrations were measured. Study and control groups were statistically compared using Student t test. Mean magnesium levels were significantly higher in the study group (P < 0.01). There were no significant differences between the cytokines levels in maternal serum and in amniotic fluid between the groups. Our results suggest that the mechanism of magnesium as a tocolytic agent may not be mediated via the examined cytokines.     

A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.