The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia

Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-&bgr;-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common 'thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% for the top 5, 10 and 20% of individuals repectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole establishing that the mutation is a major determinant of homocystein levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individuals.      

Microsomal CA2+ uptake in human platelets is stimulated by calmodulin

Calcium accumulating vesicles were prepared from washed human platelets. Ca2+ uptake could be stimulated with calmodulin. The stimulation of Ca2+ uptake was not abolished by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine, thus excluding enhanced cAMP formation as a possible cause for the calmodulin effect. Our findings suggest that, in addition to cAMP, calmodulin is also involved in the regulation of platelet free Ca2+ concentrations, i.e. Ca2+ homeostasis in platelets is under dual control.     

HIV/AIDS related mortality among adult medical patients in a tertiary health institution in South–South,Nigeria

ObjectiveTo determine the causes of death among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients as a step to planning strategies to improve mortality from this condition.MethodsThis study retrospectively analyzed the mortality pattern of adult HIV/AIDS patients in the University of Calabar Teaching Hospital from January 2005 to December 2007. The data were obtained from sexually transmitted infection/acquired immunodeficiency syndrome (STI/AIDS) clinic register, admissions and discharge/death registers as well as the patients' case records and the hospitals monthly mortality reviews. Information obtained included age, sex, diagnosis and cause(s) of death. The causes of death considered were the direct causes of death, since the originating antecedent cause of death is the same in all the patients, in this case, HIV/AIDS. Data was analysed using Epi Info 2002.ResultsThe total number of mortalities during the study period was 350,100 were HIV positive representing 28.6% of all deaths. While advanced HIV/AIDS disease was the leading cause of death in our study representing 27.0%, tuberculosis was the single leading cause of deaths in HIV/AIDS patients constituting about 24.0% of deaths. This was followed by sepsis and septicaemia (13.0%), meningitis and encephalitis, and anaemia accounting for 11.0%, while respiratory diseases constituted 5.0% of the mortality burden. The highest number of deaths occurred in those aged between 21–50 years (82.0%).ConclusionsThe study has shown that HIV/AIDS is a major cause of morbidity and mortality in our hospital. The causes of death reflect the varied spectrum of infection and other forms of organ involvement that affect HIV/AIDS patients. The present dismal situation of adult patients living with HIV/AIDS calls for enhanced strategies to decrease the mortality trend observed in Nigeria and sub-Saharan Africa.     

Patient-Related and Angiographic Predictors of Restenosis After Excimer Laser Coronary Angioplasty

Excimer laser coronary angioplasty (ELCA) is a useful technique for the treatment of selected complex coronary lesions. However, this technology has been limited by significant restenosis and, to date, predictors of restenosis after use of this device are not clearly defined. In order to determine predictors of restenosis after ELCA, 43 lesions presenting with restenosis (> 50% diameter stenosis) at angiographic follow-up were compared to 46 lesions without restenosis, based on patient-related, qualitative and quantitative angiographic parameters. Univariate analysis revealed 9 variables with at least a borderline (p < 0.15) significant relation to restenosis: (1) age (p = 0.0759), (2) proximal left anterior descending site (p = 0.074), (3) presence of a restenotic lesion (p = 0.104), (4) lesion length (p = 0.0034), (5) reference diameter of the treated vessel (p = 0.0076), (6) post laser minimal luminal diameter (MLD) (p = 0.1160), (7) post-procedural MLD (p = 0.0001), (8) post-procedural stenosis (p = 0.0250) and (9) total procedural gain (p = 0.0051). After entering stepwise logistic regression analysis, only 3 variables emerged as independent predictors of restenosis: treatment of a restenotic lesion (p = 0.0255), lesion length (p = 0.0291) and post-procedural MLD (p = 0.0007). Based on these data, we conclude that post-procedural MLD is the most important predictor of restenosis after ELCA. Lesion length and the treatment of restenotic lesions are also independently associated with an increased risk of restenosis after ELCA. Therefore, achieving the best possible luminal result at the time of the first intervention should be the goal of the procedure, especially when treating high restenosis risk lesions.