Elevated mid-trimester maternal corticotrophin-releasing hormone levels in pregnancies that delivered before 34 weeks

Objective To test whether maternal corticotrophin-releasing hormone levels are elevated in the mid–trimester for those women who subsequently had spontaneous preterm delivery and to assess the clinical utility of the measurement in the prediction of preterm delivery.
Design A prospective observational study.
Setting Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong.
Population 1047 low risk pregnant women recruited at 15–20 weeks of gestation.
Methods Venous samples were assayed for levels of corticotrophin-releasing hormone. The investigators responsible for the laboratory assay were blinded to the obstetric outcome.
Main outcome measures Incidence of preterm, term and post-term pregnancies.
Results Those who were delivered spontaneously at a preterm gestational age (before 34 weeks) had significantly higher corticotrophin–releasing hormone levels in the mid–trimester, compared with those who were delivered at term or post–term. There was a trend towards lower corticotrophm–releasing hormone levels with more advanced gestational age at delivery. When the measurement of corticotrophin–releasing hormone was used to predict delivery before 34 weeks, the best cut off was 1.9 MoM, which produced a sensitivity of 72.7% and specificity of 78.4%. This translated to a positive predictive value of 3.6%, negative predlctive value of 99.6% and relative risk of 9.4 when the background prevalence of spontaneous preterm delivery before 34 weeks was 1.1%. The likelihood ratio was 3.4.
Conclusions Mid-trimester maternal corticotrophin-releasing hormone levels are elevated in pregnancies destined to deliver preterm before 34 weeks. When used alone in a low risk population, the measurement has a low predictive power for preterm delivery. However, the likelihood ratio of 3.4 implies that in high risk populations the test may be considerably more valuable.     

Effects of graded experimental compression on slow and fast axonal transport in rabbit vagus nerve

Effects of compression at low pressures on slow and fast axonal transport was investigated in rabbit vagus nerve. Proteins in the sensory fibres were radiolabelled by injection of [3H]leucine or [35S]methionine into the nodose ganglion. A small compression chamber and/or ligatures were applied around the cervical part of the vagus nerve for 8 h, at an appropriate time for the subsequent analysis of the effects of compression on both slow and fast transport of radiolabelled proteins. In normal nerves there were two waves of slowly transported proteins with rates of about 12-15 and 25-30 mm/day, respectively. SDS-polyacrylamide gel electrophoresis was used and confirmed that the main proteins which accumulated proximal to the ligatures had a molecular weight of 54 000-56 000. Neither compression of the nerve at 20 mm Hg nor sham-compression induced any statistically significant accumulation of slowly transported proteins at the site of compression. A higher pressure, i.e. 30 mm Hg, induced a marked but incomplete accumulation of slowly transported proteins. Fast transport was partially inhibited in some, but not all, nerves, when 20 mm Hg was applied for 8 h, in contrast to the lack of effect found previously with the same pressure applied for only 2 h. Despite these slight differences, the results indicate that both slow and fast transport are impaired by low pressure levels of around 20-30 mm Hg, which are comparable with those found in human compression neuropathies. The impaired provision of cytoskeletal elements to the distal axon may be of significance in the pathophysiology of nerve entrapment syndromes.     

Plasma B vitamins, homocysteine, and their relation with bone loss and hip fracture in elderly men and women

CONTEXT: Elevated homocysteine is a strong risk factor for osteoporotic fractures among elders, yet it may be a marker for low B-vitamin status. OBJECTIVE: Our objective was to examine the associations of plasma concentrations of folate, vitamin B12, vitamin B6, and homocysteine with bone loss and hip fracture risk in elderly men and women. DESIGN: This was a longitudinal follow-up study of the Framingham Osteoporosis Study. SETTING: Community dwelling residents of Framingham, MA, were included in the study. PARTICIPANTS: A total of 1002 men and women (mean age 75 yr) was included in the study. MAIN OUTCOME MEASURES: Baseline (1987-1989) blood samples were used to categorize participants into plasma B-vitamin (normal, low, deficient) and homocysteine (normal, high) groups. Femoral neck bone mineral density (BMD) measured at baseline and 4-yr follow-up was used to calculate annual percent BMD change. Incident hip fracture was assessed from baseline through 2003. RESULTS: Multivariable-adjusted mean bone loss was inversely associated with vitamin B6 (P for trend 0.01). Vitamins B12 and B6 were inversely associated with hip fracture risk (all P for trend < 0.05), yet associations were somewhat attenuated and not significant after controlling for baseline BMD, serum vitamin D, and homocysteine. Participants with high homocysteine (>14 micromol/liter) had approximately 70% higher hip fracture risk after adjusting for folate and vitamin B6, but this association was attenuated after controlling for vitamin B12 (hazard ratio = 1.49; 95% confidence interval 0.91, 2.46). CONCLUSIONS: Low B-vitamin concentration may be a risk factor for decreased bone health, yet does not fully explain the relation between elevated homocysteine and hip fracture. Thus, homocysteine is not merely a marker for low B-vitamin status.     

The role of passenger leukocyte genotype in rejection and acceptance of rat liver allografts

BACKGROUND: Although graft-resident passenger leukocytes are known to mediate acute rejection by triggering direct allorecognition, they may also act in an immunomodulatory fashion and play an important role in tolerance induction. Our purpose in the current study was to utilize rat bone marrow chimeras to evaluate the role of the genotype of passenger leukocytes in both acute rejection and tolerance of liver allografts. METHODS: The fate of livers bearing donor-type, recipient-type, and third-party passenger leukocytes was evaluated in the MHC class I and II mismatched rejector combination ACI-->LEW and the acceptor combination PVG-->DA. RESULTS: We report that although treatment of ACI liver donors with lethal irradiation does not lead to prolongation of graft survival in the ACI-->LEW strain combination, ACI livers bearing recipient-type (LEW) or third-party passenger leukocytes (BN) are rejected at a significantly slower rate. We confirm that lethal irradiation of PVG donor animals leads to abrogation of tolerance induction with acute rejection of their livers by DA recipients. However, the majority of PVG livers carrying donor-type (PVG), recipient-type (DA), or third-party (LEW) passenger leukocytes are accepted for >100 days. These DA recipients develop immune tolerance to the donor parenchyma (PVG). CONCLUSIONS: Our findings demonstrate that long-term acceptance of liver allografts and tolerance induction is not dependent on the presence of donor-type passenger leukocytes and can be achieved with organs carrying donor-type, recipient-type, or third-party passenger leukocytes. The importance of the MHC framework on the surface of passenger leukocytes as a critical regulator of the immune response after transplantation of chimeric organs is substantiated by the delayed tempo of rejection of ACI livers bearing recipient-type or third-party passenger leukocytes in the ACI-->LEW strain combination.     

Benefits and risks of clopidogrel pretreatment before coronary artery bypass grafting in patients with ST-elevation myocardial infarction treated with fibrinolytics in CLARITY-TIMI 28

The Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial was a randomized, double-blind, placebo-controlled study of clopidogrel in 3,491 patients receiving fibrinolytic therapy for ST-segment elevation myocardial infarction. Patients were randomized to clopidogrel or placebo begun at the time of fibrinolysis. This analysis reports the outcomes among the 136 patients in the trial population who underwent coronary artery bypass grafting (CABG) during the index hospitalization. There was no difference in the rates of TIMI major or minor bleeding between the clopidogrel and placebo groups from randomization to the end of follow-up (13.6% vs. 14.3%, P = 1.0) or from the time of CABG to the end of follow-up (9.1% vs. 11.4%, P = 0.78). When any day for study medication discontinuation ≤5 days prior to CABG was chosen as a cut point to evaluate bleeding risk for clopidogrel vs. placebo, there was no excess bleeding in the clopidogrel group. Among patients undergoing CABG, there was a trend toward reduction in the risk of cardiovascular death, recurrent MI, or recurrent ischemia requiring urgent revascularization at 30 days for those taking clopidogrel (OR 0.66, 95% CI 0.27–1.5; P = 0.37), consistent with the benefit seen in the overall trial population (OR 0.80, CI 0.65–0.97; P = 0.03). In conclusion, early clopidogrel treatment among CLARITY-TIMI 28 patients undergoing CABG was not associated with an increase in the rate of peri-operative bleeding and showed a trend toward reduction in 30-day ischemic events.