Stimulatory effect on DNA synthesis of thymus and spleen extract from leukemic AKR mice

Summary A 30,000–50,000 molecular weight (MW) extract of thymus and spleen from 11 age groups of untreated AKR mice, 1–210 days old, was tested for in vitro effect on thymide incorporation into normal AKR lymph node cells, normal spleen cells, and leukemic thymocytes. Extracts from mice up to 5 months of age mostly had slightly inhibitory effect but concomitant with emergence of thymus leukemia in the 6-month-old mice, the extract acquired a strongly mitogenic effect on normal lymph node cells. Seven-month-old, non-leukemic animals again yielded extracts with inhibitory effect.Supported by the US Health Education and Welfare grant no. IROI CA 26109-01, Commission of the European Communities contract no. 251-77-1 BIO DK, and The Carlsberg Foundation     

Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study.

The Medical Patients with Enoxaparin (MEDENOX) trial was a randomized, placebo-controlled study that defined the risk of venous thromboembolism (VTE) in acutely ill, immobilized, general medical patients and the efficacy of the low-molecular-weight heparin, enoxaparin, in preventing thrombosis. We performed a post-hoc analysis to evaluate the effect of 40 mg enoxaparin once daily on MEDENOX patient outcome in different types of acute medical illness (heart failure, respiratory failure, infection, rheumatic disorder and inflammatory bowel disease) and pre-defined risk factors (chronic heart and chronic respiratory failure, age, immobility, previous VTE and cancer). The primary outcome was the occurrence of documented VTE between days 1 and 14. The relative risk reduction [95% confidence intervals (CI)] for VTE comparing 40 mg enoxaparin with placebo in the subgroups were: acute heart failure, 0.29 (95% CI, 0.10-0.84); acute respiratory failure, 0.25 (95% CI, 0.10-0.65); acute infectious disease, 0.28 (95% CI, 0.09-0.81); and acute rheumatic disorder, 0.48 (95% CI, 0.11-2.16). The relative risk reduction for VTE in the pre-defined risk factor subgroups were: chronic heart failure, 0.26 (95% CI, 0.08-0.92); chronic respiratory failure, 0.26 (95% CI, 0.10-0.68); age, 0.22 (95% CI, 0.09-0.51); immobility, 0.53 (95% CI, 0.14-1.72); previous VTE, 0.49 (95% CI, 0.15-1.68); and cancer, 0.50 (95%o CI, 0.14-1.72). The beneficial effects of enoxaparin extend to a wide range of acutely ill medical patients.     

Forty-six patients with primary sclerosing cholangitis: radiological bile duct changes in relationship to clinical course and concomitant inflammatory bowel disease

The clinical features of primary sclerosing cholangitis were studied in 46 consecutive patients. Jaundice was the most common symptom (57%), followed by pruritus (28%), pain (24%), and fever (15%). Thirty-three per cent of the patients had no symptoms, merely laboratory changes. No significant relationship was observed between a numerical score of radiological bile duct changes at diagnosis and the clinical picture, or the clinical course during follow-up. If clinical deterioration occurred, this seemed to happen within the first eight years after the clinical presentation. Patients with only intra-hepatic bile duct changes (n = 10) did not differ clinically from those with extrahepatic changes as well. Forty-three out of 44 patients examined had inflammatory bowel disease, usually ulcerative colitis, with total colitis in 84%. Radiological bile duct changes had a significantly higher score in patients who had to be treated with a combination of sulfasalazine and steroids, suggesting a weak relationship between severity of bowel disease and bile duct disease.     

The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis

Sprouting angiogenesis is critical to blood vessel formation, but the cellular and molecular controls of this process are poorly understood. We used time-lapse imaging of green fluorescent protein (GFP)-expressing vessels derived from stem cells to analyze dynamic aspects of vascular sprout formation and to determine how the vascular endothelial growth factor (VEGF) receptor flt-1 affects sprouting. Surprisingly, loss of flt-1 led to decreased sprout formation and migration, which resulted in reduced vascular branching. This phenotype was also seen in vivo, as flt-1(-/-) embryos had defective sprouting from the dorsal aorta. We previously showed that loss of flt-1 increases the rate of endothelial cell division. However, the timing of division versus morphogenetic effects suggested that these phenotypes were not causally linked, and in fact mitoses were prevalent in the sprout field of both wild-type and flt-1(-/-) mutant vessels. Rather, rescue of the branching defect by a soluble flt-1 (sflt-1) transgene supports a model whereby flt-1 normally positively regulates sprout formation by production of sflt-1, a soluble form of the receptor that antagonizes VEGF signaling. Thus precise levels of bioactive VEGF-A and perhaps spatial localization of the VEGF signal are likely modulated by flt-1 to ensure proper sprout formation during blood vessel formation.     

Urinary free cortisol excretion shortly after ischaemic stroke

The cortisol axis and catecholamine excretion were studied in 20 patients within the first week after acute ischaemic stroke. Urine free cortisol and plasma cortisol levels after dexamethasone were significantly higher in stroke patients than in 80-year-old volunteers (n = 32; P = 0.03 and P = 0.003, respectively). Catecholamine excretion was found to be significantly correlated with urine cortisol concentration (r = 0.54, P less than 0.05) and limb paresis (r = 0.52, P less than 0.05). In a multiple regression analysis, urine cortisol values were shown to be positively associated with limb paresis (P = 0.003), disorientation (P = 0.03) and body temperature (P = 0.03). High cortisol excretion was associated with a poorer functional outcome in a discriminant analysis (P = 0.001). Thus acute ischaemic stroke is associated with an increased activity in the cortisol axis. This may have a number of negative effects on organ functioning, and is a predictor of a poorer functional outcome.     

Lipids, apolipoproteins and steroids in serum and in fluid from stimulated and non-stimulated human ovarian follicles

Steroid production depends on the cholesterol (CH) substrate supplied by circulating lipoproteins which are internalised in the cells by receptor-mediated mechanisms. Low density lipoproteins (LDL) stimulate progesterone production in vitro. However, studies on follicles indicate low levels of LDL in follicular fluid (FF1). In the present study FF1 was obtained by ultrasound-guided punctures just before ovulation from 17 women participating in an in vitro fertilization programme. Serum was obtained simultaneously. Follicular development was stimulated with hMG-HCG or clomiphene-hMG-hCG combinations. In another 8 women FF1 was collected in connection with surgery for sterilization. FF1 levels of CH, triglycerides (TG), phospholipids (PL), apolipoprotein A1 and B (apoA1; apoB), oestradiol and progesterone were assayed in both groups as were the corresponding serum levels in the stimulated patient group. The FF1 levels of apoA1, TG and PL were approximately half of the levels in HDL in normal serum in both groups. However, CH was slightly lower in the stimulated group. ApoB was not detectable in FF1. Oestradiol was similar in both groups while progesterone was much higher in the stimulated than in the non-stimulated cycles. FF1 levels of apoA1 correlated positively to CH and PL in both groups and to progesterone in the stimulated follicles, while the correlation was negative in the other group. The absence of apoB and the levels of CH, TG, PL and apoA11 indicate that high density lipoprotein (HDL), but not LDL is present in FF1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leptin is associated with increased risk of myocardial infarction

OBJECTIVES AND DESIGN: Leptin is involved in the regulation of bodyweight and metabolism in man and might also be involved in the pathophysiology of the insulin resistance syndrome, which is associated with the development of cardiovascular diseases. We tested whether leptin is a risk factor for acute myocardial infarction (AMI) in a nested case-referent study. SUBJECTS AND METHODS: Sixty-two men with first-ever AMI were identified who, prior to AMI, had participated in population-based health surveys in Northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographical region. Blood pressure, body mass index (BMI) and the presence of smoking, diabetes and hypertension were recorded. Total cholesterol, apolipoprotein A-1 (apo A-1), apolipoprotein B (apo B), plasminogen activator inhibitor (PAI-1), insulin, and leptin were analysed in stored samples. Their influences on first-ever AMI were analysed by conditional logistic regression analysis. RESULTS: Men with first-ever AMI had higher BMI, plasma insulin and leptin, and diastolic blood pressure than the referents. Furthermore, they had lower plasma apo A-1 and were more often smokers. Smoking, high leptin, PAI-1 and cholesterol, and low apo A-1 levels were significant risk factors for first-ever AMI in univariate analysis. High leptin (OR 8.97; 95% CI: 1.73-46.5) and cholesterol (OR 5.18; 95% CI: 1.34-20.0) levels remained significant risk factors for AMI in a multivariate model. High apo A-1 was protective (OR = 0.13; 95% CI: 0.03-0.55). The combination of high leptin and low apo A-1 was associated with a particularly pronounced increased risk for AMI. CONCLUSION: Plasma leptin strongly predicts first-ever AMI. Our data support the hypothesis that leptin is an important link in the development of cardiovascular disease in obesity.