Cytokine profile in patients with multiple sclerosis following vitamin D supplementation.

Multiple sclerosis (MS) patients were randomized, in a double blind design, and placed into either a vitamin D supplemented group or a placebo control group. As expected, serum 25-hydroxyvitamin D levels increased significantly following 6 month vitamin D supplementation (17+/-6 ng/ml at baseline to 28+/-8 ng/ml at 6 months). Vitamin D supplementation also significantly increased serum transforming growth factor (TGF)-beta 1 levels from 230+/-21 pg/ml at baseline to 295+/-40 pg/ml 6 months later. Placebo treatment had no effect on serum TGF-beta 1 levels. Tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-13 were not different following vitamin D supplementation. IL-2 mRNA levels decreased following vitamin D supplementation but the differences did not reach significance. Vitamin D supplementation of MS patients for 6 months was associated with increased vitamin D status and serum TGF-beta 1.

Low serum S100beta protein levels following coronary artery surgery with or without cardiopulmonary bypass.

BACKGROUND: S100beta protein has been used as a serum marker of brain injury during cardiac surgery. Previous studies may have been confounded by the re-transfusion of shed mediastinal blood, which has a high concentration of S100beta. AIM: To examine serum S100beta levels in coronary artery surgery patients in whom re-transfusion of shed mediastinal blood was avoided, and to compare levels with and without cardiopulmonary bypass (CPB). METHODS: Serum S100beta levels were measured preoperatively, pre-heparin, post-protamine and 24 h postoperatively in 31 patients undergoing elective coronary artery surgery with (n = 14) or without (n = 17) CPB. The postoperative values were compared to their preoperative controls using two-tailed paired t-tests. RESULTS: There was a minor increase in serum S100beta post-protamine in the CPB group only (0.41 ng/mL; P < 0.01). All other levels in both groups were within normal limits. CONCLUSIONS: Coronary artery surgery without CPB is not associated with an increase in serum S100beta. The observed increase in the CPB group was four- to ninefold lower than levels previously reported. A possible explanation for the lower level was the avoidance of retransfusing shed mediastinal blood. If elevated S100beta levels are thought to represent a cerebral insult caused by CPB, the magnitude of the insult might be less than previously assumed.

1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease.

Anecdotal data suggest that the amount of vitamin D available in the environment either from sunshine exposure or diet may be an important factor affecting the development of inflammatory bowel disease (IBD) in humans. We tested the vitamin D hypothesis in an experimental animal model of IBD. Interleukin (IL)-10 knockout (KO) mice, which spontaneously develop symptoms resembling human IBD, were made vitamin D deficient, vitamin D sufficient or supplemented with active vitamin D (1,25-dihydroxycholecalciferol). Vitamin D-deficient IL-10 KO mice rapidly developed diarrhea and a wasting disease, which induced mortality. In contrast, vitamin D-sufficient IL-10 KO mice did not develop diarrhea, waste or die. Supplementation with 50 IU of cholecalciferol (5.0 microgram/d) or 1, 25-dihydroxycholecalciferol (0.005 microgram/d) significantly (P < 0. 05) ameliorated symptoms of IBD in IL-10 KO mice. 1, 25-Dihydroxycholecalciferol treatment (0.2 microgram/d) for as little as 2 wk blocked the progression and ameliorated (P < 0.05) symptoms in IL-10 KO mice with already established IBD.

Drug therapy before coronary artery surgery: nitrates are independent predictors of mortality and beta-adrenergic blockers predict survival.

UNLABELLED: We conducted this study to evaluate whether there is an association between preoperative drug therapy and in-hospital mortality in patients undergoing coronary artery graft surgery. We collected data on 1593 consecutive patients undergoing coronary artery surgery. The relative risk of in-hospital mortality was determined by logistic regression with in-hospital mortality as the dependent variable, and independent variables that included known risk factors and preoperative cardioactive or antithrombotic drug treatment, i.e., age; left ventricular function; left main coronary artery disease; urgent priority; gender; previous cardiac surgery; concurrent cardiovascular surgery; chronic lung disease; creatinine concentration; hemoglobin concentration; diabetes; hypertension; cerebrovascular disease; recent myocardial infarction; prior vascular surgery; number of arteries bypassed; and regular daily treatment with beta-blockers, aspirin within 5 days, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, digoxin, or warfarin. In-hospital mortality was 3.3%. The relative risk of in-hospital mortality (with 95% confidence intervals of the relative risk) associated with the following drug treatments was: nitrates 3.8 (1.5-9.6), beta-blockers 0.4 (0.2-0.8), aspirin within 5 days 1.0 (0.5-1.9), calcium antagonists 1.1 (0.6-2.1), ACE inhibitors 0.8 (0.4-1.5), digoxin 0.7 (0.2-1.8), and warfarin 0.3 (0.1-1.6). We conclude that in-hospital mortality is positively associated with preoperative nitrate therapy and negatively associated with beta-adrenergic blocker therapy. A significant association between in-hospital mortality and the preoperative use of calcium antagonists, ACE inhibitors, aspirin, digoxin, and warfarin was not confirmed. IMPLICATIONS: We examined the association between common drug treatments for ischemic heart disease and short-term survival after cardiac surgery using a statistical method to adjust for patients' preoperative medical condition. Death after surgery was more likely after nitrate therapy and less likely after beta-blocker therapy.

Aortic valve replacement in elderly women with small aortic roots: comparing sorin pericardial and St. Jude Medical mechanical valves.

After implanting 19mm and 21mm Sorin pericardial aortic valves (AVR) in 35 women over the age of 60 years, it was our clinical impression that these patients had an unduly high incidence of residual valve stenosis. A retrospective comparison of our experience with this valve and the 19mm St. Jude mechanical AVR in a similar group of 26 patients, operated during the same period (October 1987 to July 1994), was carried out. In comparison to the 19mm St. Jude valve, the 19 mm Sorin Pericardial valve was associated with significant residual stenosis in elderly women despite similar body surface areas. This prosthesis/patient mismatch was not eliminated by the use of a 21 mm Sorin pericardial valve. Although the Sorin pericardial valves was associated with a reduced incidence of thromboembolism and anticoagulation related hemorrhage, it had a significantly increased risk of permanent valve related morbidity and mortality. As a result if this experience we have discontinued our use of the Sorin pericardial valve.

Stress-induced activation of the hippocampal cholinergic system and the pituitary-adrenocortical axis.

The septo-hippocampal cholinergic system in rats undergoes rapid activation after acute stress. This is expressed by rapid increases both in high affinity choline uptake and newly synthesized acetylcholine release. Administration of ACTH or corticosterone at a high dose led 10 min later to changes comparable to those observed after acute stress. Choline uptake and acetylcholine release were also elevated 2 days after adrenalectomy. The effects of adrenalectomy could be attenuated by corticosterone, but not by ACTH treatment. The results demonstrate that (a) after short term stress the septo-hippocampal cholinergic system is activated secondary to activation of the pituitary-adrenocortical axis and (b) major changes in circulating corticosterone can modulate the activity of the hippocampal cholinergic synapse.