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.      

Fluorescent light interferes with pulse oximetry

Arterial oxygen saturation (SaO₂) values displayed on the pulse oximeter dropped dramatically in 3 children undergoing neurosurgical procedures when a hand-held fluorescent light was used to observe the patients. Pulse rates were unchanged on both the electrocardiograph and pulse oximeter. Electromagnetic interference was excluded as the cause of desaturation. A great deal of energy was emitted by the hand-held light in the 660-nm region, which is one of the wavelengths used by the oximeter. False readings of pulse rate and SaO₂ values caused by ambient light could be avoided if oximeter probes were manufactured of black opaque material that does not transmit light or enclosed in an opaque plastic housing.     

EFFECT OF SUBCLINICAL LEAD INTOXICATION ON LARYNGEAL CANCER

SUMMARY In this study we investigated the possible relationship of laryngeal cancer and subclinical lead intoxication, using the depression of aminolevulinic acid dehydratase (ALAD) activity in blood as indicator. Twenty-six patients with laryngeal cancer and 53 normal controls met the criteria to enter the study. Blood ALAD activity values in the patients with laryngeal cancer ranged from 27.1 to 75.3 U/l with a mean of 50.79 U/l. The respective values in the control group ranged from 36.2 to 98 U/l with a mean of 59.76 U/l. There was a statistically significant difference between the two means (0.001 <p<0.01), whereas blood lead concentrations in all patients were within normal limits. These findings support the hypothesis that low level lead intoxication (subclinical blood lead levels), from cars, industries and products, may contribute to the risk of laryngeal cancer. Further investigation is needed to clarify the exact relationship between lead and cancer of the larynx.     

Neurotoxicity, anticoagulant activity and evidence of rhabdomyolysis in patients bitten by death adders (Acanthophis sp.) in southern Papua New Guinea

Thirty-two patients with enzyme-immunoassay-proven death adder (Acanthophis sp.) bites were studied in Port Moresby, Papua New Guinea. Eighteen were envenomed; local signs were rare and none had incoagulable blood, but all except one had signs of neurotoxicity. Five (27.7%) envenomed patients required intubation and ventilation. One patient developed renal failure, previously undescribed following death adder bites. Laboratory investigations showed mild prolongation of prothrombin and partial thromboplastin times in some patients. In vitro studies showed that the venom contains anticoagulant activity, but does not cause fibrinogenolysis. In contrast to taipan envenoming, neurotoxicity did not progress after antivenom administration, and there was reversal of neurotoxicity, evident within 6 h, in three severely envenomed patients treated less than 12 h after the bite. One patient treated with antivenom and anticholinesterases had the most dramatic response to treatment; the optimum management of bites by this species may include prompt treatment with both antivenom and anticholinesterases in addition to effective first aid.      

3D computational modeling and simulation of leukocyte rolling adhesion and deformation

A 3D computational fluid dynamic (CFD) model is presented to simulate transient rolling adhesion and deformation of leukocytes over a P-selectin coated surface in shear flow. The computational model is based on immersed boundary method for cell deformation, and stochastic Monte Carlo simulation for receptor/ligand interaction. The model is shown to predict the characteristic 'stop-and-go' motion of rolling leukocytes. Here we examine the effect of cell deformation, shear rate, and microvilli distribution on the rolling characteristics. Comparison with experimental measurements is presented throughout the article. We observe that compliant cells roll more stably, and have longer pause times due to reduced bond force and increased bond lifetime. Microvilli presentation is shown to affect rolling characteristics by altering the step size, but not pause times. Our simulations predict a significant sideway motion of the cell arising purely due to receptor/ligand interaction, and discrete nature of microvilli distribution. Adhesion is seen to occur via multiple tethers, each of which forms multiple selectin bonds, but often one tether is sufficient to support rolling. The adhesion force is concentrated in only 1-3 tethered microvilli in the rear-most part of a cell. We also observe that the number of selectin bonds that hold the cell effectively against hydrodynamic shear is significantly less than the total adhesion bonds formed between a cell and the substrate. The force loading on individual microvillus and selectin bond is not continuous, rather occurs in steps. Further, we find that the peak force on a tethered microvillus is much higher than that measured to cause tether extrusion.