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.     

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.      

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.     

Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies

One hundred and sixty eight adult patients with B-cell non-Hodgkin's lymphoma (NHL) and other hematologic malignancies who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic-uremic syndrome (HUS). All patients were conditioned with cyclophosphamide and total body irradiation. When examined at 3-month intervals for the first year post-BMT, all patients had uniform measurements of hematocrit (Hct) and serum creatinine. Sixteen patients who initially exhibited Hct and creatinine values that were normal range for the BMT populations developed a sudden decrease in Hct and increase in creatinine between 3 and 11 months post-BMT and fulfilled the clinical and laboratory criteria for HUS. None of these patients had known active cytomegalovirus infection, graft-versus-host disease, or cyclosporine administration. The degree of decrease in Hct and creatinine elevation ranged from solely laboratory abnormalities to a clinically significant syndrome. Twelve of the 16 patients developed acute clinical complications of congestive heart failure, hypertension (HTN), or peripheral edema. Twelve patients required red blood cell support, whereas only four patients required platelet transfusions. Both hemolytic anemia and thrombocytopenia have resolved in virtually all cases. At a mean follow up of 18 months postdiagnosis, creatinine elevations have persisted along with HTN. All patients have survived without life-threatening long-term sequelae. With the increasing use of BMT as a curative modality for patients with hematologic malignancies, it becomes important to prospectively monitor patients for the development of HUS and its potential long-term impact on renal function.     

Polymorphic glycoprotein-1 on mouse platelets: possible role of Pgp-1 and LFA-1 in antibody-dependent platelet cytotoxicity involving complement

The presence of the Pgp-1 glycoprotein on mouse platelets is demonstrated by antibody-binding techniques, by immunoprecipitation, and by transblotting using the monoclonal antibody (MoAb) C71/26 against Pgp-1. C71/26 immunoprecipitates as a broad band of mol wt 87,000 to 100,000 as determined by radioiodination of the platelet cell surface and by the 3H-sodium borohydride labeling technique. Immunoblotting showed Pgp-1 expression on platelets to be quantitatively similar to its presence on macrophages and resolved platelet Pgp-1 into two bands of mol wt 87,000 and 97,000 whereas Pgp-1 on parasite-elicited peritoneal macrophages showed 82,000 and 87,000 mol wt species. Platelets and monocyte/macrophage cells from either peripheral blood or from the peritoneal cavity showed homogeneous binding of Pgp-1 antibody to greater than 97% of cells by flow cytometry. In contrast, lymphocytes from peripheral blood or from the spleen showed a heterogeneous binding pattern with 20% to 30% of cells being negative, and the majority weakly positive. In functional studies, MoAbs against CR1 and CR3 substantially inhibited platelet immune adherence, whereas C71/26 showed only marginal inhibitor. In contrast, C71/26 and other MoAbs against Pgp-1 inhibited platelet- dependent cytotoxicity of antibody-coated sheep erythrocytes in the presence of C5-deficient mouse plasma whereas M1/70 against CR3 showed no effect. In this assay, MoAbs against the alpha- and beta-subunits of leukocyte functional molecule LFA-1 also inhibited platelet cytotoxicity. These results show that the platelet cell surface moieties Pgp-1 and LFA-1 are involved in or closely associated with antibody-dependent cellular cytotoxicity by platelets.     

克罗恩病的第一个易感基因,NOD2(CARD15)

炎症性肠病 (ＩＢＤ)具有遗传易感性 ,主要表现在家族聚集现象和双胎同胞的共患率[1] 。近年来 ,随着人类基因组和多基因疾病研究以及统计学方法的进展 ,相继发现ＩＢＤ的基因易感位点 ,证实ＩＢＤ的遗传易感性涉及多个基因位点[2 ] 。 1996年Ｈｕｇｏｔ等[3 ] 采用非参数连锁分析 (ｎｏｎｐａｒａｍｅｔｒｉｃｌｉｎｋａｇｅａｎａｌｙｓｉｓ,ＮＰＬ)法 ,对ＩＢＤ患病同胞 (ａｆｆｅｃｔｅｄｓｉｂｌｉｎｇｐａｉｒｓ,ＡＳＰ)进行基因组位点微卫星标记研究 ,发现克罗恩病 (ＣＤ)的易感位点位于第 16条染色体的着丝点附近 ,称为ＩＢＤ1位点 …     

Studies of in vitro activated CD5+ B cells

Human B lymphocytes undergo distinct phenotypic changes following activation with antigen and polyclonal mitogens. Increasing interest has focused on the unique subpopulation of B cells that expresses the CD5 antigen. In this study, we examined the signals that induce the expression of CD5 on normal splenic B cells. Only 12-O- tetradecanoylphorbol-13-acetate (TPA) induced CD5 expression on highly purified splenic B cells, whereas anti-immunoglobulin (anti-Ig), Epstein-Barr virus, anti-CD20, recombinant interleukin-1 (rIL-1), rIL- 2, rIL-4, recombinant interferon-gamma (rINF-gamma), and B-cell growth factor all failed to induce CD5 expression. The expression of CD5 was detected on the cell surface by 48 hours and decreased by 96 hours. Dual-fluorochrome analysis demonstrated that the CD5+ B cells coexpressed the B-cell activation antigens B5, IL-2 receptor, and CD23, thereby providing phenotypic evidence that this B-cell subpopulation is activated. In vitro studies of dual-fluorochrome-sorted, TPA-stimulated splenic B cells demonstrated significantly greater tritiated thymidine incorporation and Ig secretion by the CD20+ CD5- cells than by the CD20+ CD5+ subset. These phenotypic and functional studies are consistent with the notion that TPA-induced CD5+ B cells are a subset of in vitro activated B lymphocytes.