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.      

DIAGNOSIS AND MANAGEMENT OF HYPERLIPIDAEMIA

Hyperlipidaemia is acknowledged as the major risk factor for coronary heart disease and atheroma progression. This review considers the strategies that should be followed to reduce overall cardiovascular risk in patients with hyperlipidaemia and deals with the identification and management of treating both polygenic and monogenic lipid disorders in the presence or absence of overt cardiovascular disease.     

Microwave dissociation of antigen-antibody complexes: a new elution technique to permit phenotyping of antibody-coated red cells

To evaluate the effectiveness of microwave irradiation in dissociating IgG from red cells (RBCs), the use of chloroquine diphosphate (CDP) was compared to that of microwaves. Fifteen paired samples of RBCs from 15 patients with positive direct antiglobulin tests (DATs) were treated with both CDP and microwave radiation. Total microwave exposure times ranged from 20 to 100 seconds. Posttreatment DATs were performed, and the reaction grades of the posttreatment DATs were compared. RBC phenotyping was also performed on repeatedly microwaved RBCs to demonstrate possible effects on RBC antigen expression. Microwaves successfully reduced the reaction grade of the DAT in 14 of 15 samples; CDP reduced the reaction grade in 12 of 15 samples. In samples with a DAT of 2+ or greater (n = 13), the microwave method yielded a greater reduction in DAT strength in six cases (results in the other 7 cases were identical with both methods) (p = 0.01). Five of eight cases with a DAT of 3+ showed a greater reduction in the DAT with microwave treatment than with CDP treatment; results in the remaining three cases were identical (p = 0.03). RBC antigenicity remained unchanged after exposure to microwave radiation (A, B, C, c, D, E, e, Fya, Fyb, Jka, Jkb, K, k, S, and s). Microwave treatment required less than 10 minutes per sample, while CDP treatment required 30 to 120 minutes per sample (mean, 88 min). The microwave technique of antigen-antibody dissociation from RBCs provides a rapid and accurate method of facilitating the phenotyping of RBCs coated with warm autoantibodies and is superior to other methods, which destroy RBC antigens.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.      

Antibodies to lactalbumin interfere with its radioimmunoassay in human plasma

Two radioimmunoassays for human lactalbumin have been established using a rabbit antiserum. One assay uses a second antibody to separate bound from free label; the other uses polyethylene glycol to precipitate gamma globulin non-specifically. We have confirmed that about half the normal human population have a substance in their blood which inhibits the binding of lactalbumin to the rabbit antibody. Comparison of the two assays has demonstrated that this material is not lactalbumin but a naturally occurring antibody. We have shown that it is in the IgG fraction of human plasma and is probably a cross-reacting antibody to bovine lactalbumin. None out of fifteen males and fourteen out of fifty eight non-pregnant, non-lactating females had low levels of lactalbumin in the their blood (0.6--2.0 ng/ml). Our assay could not detect a statistically significant difference between normal women and those with either benign breast disease or metastatic mammary carcinoma.     

Headache and psychiatric comorbidity: clinical aspects and outcome in an 8-year follow-up study

Migraine with juvenile onset changes over time. The existence of prognostic factors is a point of focus. A strict relationship between migraine or tension-type headache (TTH) and psychiatric factors has been suggested, but the exact role and the influence on evolution of headache is unknown. Objective . To analyze the evolution of migraine and TTH and psychiatric comorbidity (P-Co) from 1988 to 1996. Material and method . 100 subjects (40M, 60F; mean age 17.9 years; SD 2.7 years; range 12–26 years) were examined at our Center. The International Headache Society (IHS) criteria were employed. Psychometric tests and clinical interviews aided psychiatric diagnosis (DSM-III-R). SCID (Structured Clinical Interview for DSM-III-R) was employed in 1996. Chi square and logistic regression are used for statistical analysis. Findings . Migraine and TTH change their clinical characteristics, with a high tendency to remission (mostly in males). The presence of P-Co in 1988 is related to a worsening or unchanging situation in 1996. Headache-free subjects did not present any psychiatric disorders in 1996. Anxiety disorders in 1988 are related to enduring of headache. Migraine shows comorbidity with anxiety disorders and depression. Conclusion . P-Co is a notable problem in clinical practice. Diagnostic, prognostic, and treatment implications require a systematic assessment of P-Co.     

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.