Acute administration of 25-hydroxycholecalciferol in man.

Serum 25-hydroxyvitamin D responses to oral doses of 25-hydroxycholecalciferol were measured in healthy volunteers. Peak serum 25-hydroxyvitamin D levels occurred 4 to 8 hours after doses of 1.5, 5, and 10 mug per kg of body weight. The mean increments above baseline serum 25-hydroxyvitamin D concentrations at 4 hours were linear over this dose range. Following a single oral dose, serum 25-hydroxyvitamin D levels fell to 33% of their peak values after one week. The serum 25-hydroxyvitamin D responses measured by competitive protein-binding radioassay were similar to the serum 3H responses exhibited by three volunteers who received simultaneous oral doses of 3H 25-hydroxycholecalciferol and 14C-cholecalciferol. The appearance of 14C in plasma was slower and less marked compared with 3H, probably reflecting a more rapid plasma clearance of the 14C-cholecalciferol. The disappearance of 25-hydroxycholecalciferol from the circulation of two volunteers following acute intravenous delivery of 1.0 mg of 25-hydroxycholecalciferol was multiphasic over 10 days. 60% of the dose administered remained in the circulation 24 hours after the dose. When analyzed several days after single 10 mug/kg oral doses of 25-hydroxycholecalciferol to 4 volunteers, the mean rate of decline to total serum 25-hydroxycholecalciferol was slow (t 1/2 = 22 days). When baseline serum 25-hydroxyvitamin D levels were subtracted, however, the apparent serum half-life of administered 25-hydroxycholecalciferol was 12 days, similar to that reported after tracer doses of 3H-25-hydroxycholecalciferol. The rapid and predictable serum 25-hydroxyvitamin D increases following the oral administration of 25-hydroxycholecalciferol suggest its possible therapeutic advantages compared with vitamin D administration.     

Ten-year heart transplantation experience at the MARITIME HEART CENTER: does volume affect results?

OBJECTIVE: To evaluate the experience of a small volume Canadian heart transplantation centre. DESIGN: Ninety-four consecutive primary heart transplants were performed from 1988 to 1998 at the Maritime Heart Center, Halifax, Nova Scotia, with 100% follow-up. Kaplan-Meier survival analysis was used. RESULTS: The mean recipient age was 48.5+/-12.3 years and donor age 33+/-13.2 years. Eighty per cent of recipients were men. The prevalence of elevated pulmonary vascular resistance (4 or more Wood units) was 20.2%. Etiology of heart failure was ischemic cardiomyopathy (50%), dilated cardiomyopathy (40.9%) and congenital heart disease (9.1%). Survival was 85.9% at one year (n=71), 75.3% at five years (n=33) and 60.5% at eight years (n=8). There was a trend toward survival benefit with human leukocyte antigen (HLA) -DR matching, body mass index ratio of donor to recipient greater than 0.8, ischemic time less than 90 mins and male donors. There was no effect on survival with donor or recipient age, recipient sex, diabetes, hypertension, hypercholesterolemia, elevated pulmonary vascular resistance and HLA-A/B mismatch. CONCLUSIONS: Excellent survival at one and five years following heart transplantation is reported that compares favourably with results published by the International Society for Heart and Lung Transplantation.     

Detection of coronary disease before valve surgery. Contribution of myocardial scintigraphy with dipyridamole

The detection of coronary disease before valve surgery remains difficult in the absence of coronary arteriography. The contribution of myocardial scintigraphy with dipyridamole (MS-DP) was studied in 34 consecutive patients with valve disease (11 mitral and 23 aortic) with a mean age of 63 +/- 11 years having undergone coronary arteriography before valve surgery. Coronary arteriography was performed because of angina (21 cases) or age (women greater than 50, men greater than 40). Positive criteria of coronary disease were the presence of at least one frank and clearly visible fault of myocardial perfusion (MS-DP positive) and at least one stenosis of greater than 70 per cent by coronary arteriography. Coronary disease existed in 13 patients (38 per cent). Ten patients (29 per cent) had a positive MS-DP. The sensitivity and specificity of MS-DP in detecting coronary disease were 69 per cent and 95 per cent respectively. Its positive predictive value was 90 per cent. MS-DP was negative in all asymptomatic patients (19 per cent of them having coronary disease) and in 11 symptomatic patients (18 per cent of them having coronary disease). The low positive predictive value of angina (52 per cent) increased to 90 per cent when combined with a positive MS-DP. Because of relatively low sensitivity, basing indications for coronary arteriography before valve surgery on the results of MS-DP cannot be advised.     

Studying host genetic background effects on multimorbidity of intestinal cancer development,type 2 diabetes and obesity in response to oral bacterial infection and high‐fat diet using the collaborative cross (CC) lines

BackgroundMultimorbidity of intestinal cancer (IC), type 2 diabetes (T2D) and obesity is a complex set of diseases, affected by environmental and genetic risk factors. High‐fat diet (HFD) and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.MethodsTo study the complexity of this multimorbidity, we used the collaborative cross (CC) mouse genetics reference population. We aimed to study the multimorbidity of IC, T2D, and obesity using CC lines, measuring their responses to HFD and oral bacterial infection. The study used 63 mice of both sexes generated from two CC lines (IL557 and IL711). For 12 weeks, experimental mice were maintained on specific dietary regimes combined with co‐infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum, while control groups were not infected. Body weight (BW) and results of a intraperitoneal glucose tolerance test (IPGTT) were recorded at the end of 12 weeks, after which length and size of the intestines were assessed for polyp counts.ResultsPolyp counts ranged between 2 and 10 per CC line. The combination of HFD and infection significantly reduced (P < .01) the colon polyp size of IL557 females to 2.5 cm², compared to the other groups. Comparing BW gain, IL557 males on HFD gained 18 g, while the females gained 10 g under the same conditions and showed the highest area under curve (AUC) values of 40 000‐45 000 (min mg/dL) in the IPGTT.ConclusionThe results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance, and this effect is gender related.     

Informed consent for medical procedures: local and national practices

BACKGROUND: No studies have assessed whether clinicians obtain informed consent for invasive medical procedures, and there are no explicit national standards to guide the process. HYPOTHESIS: Informed consent practices are inconsistent for commonly performed invasive medical procedures. METHODS: A simple questionnaire was electronically mailed and/or faxed to training program directors of critical care medicine and internal medicine departments, and to ICU directors in the state of Connecticut. The questionnaire listed common invasive medical procedures and asked the respondents to check those for which practitioners routinely obtain informed consent in their hospital. RESULTS: The three samples, national intensivists (88 respondents), Connecticut intensivists (29 respondents), and national internists (56 respondents) demonstrated heterogeneity of consenting practices. The rate of obtaining consent for common vascular access procedures ranged from 20 to 90%. The rates of obtaining consent for Foley catheterization and nasogastric intubation were uniformly < 10%, and those for endoscopic procedures were > 90%. Separate consent (beyond the general consent to treat) was not uniformly obtained for the transfusion of blood products (range, 74 to 93%) and common diagnostic medical procedures (eg, thoracentesis, paracentesis, or lumbar puncture; range, 77 to 96%). Surgical intensivists reported that the obtaining of consent for invasive procedures was less routine compared to medical intensivists. Lower rates of consent were noted by those respondents who used a "blanket" consent form, which was signed at the time of hospital admission, to cover subsequent procedures. CONCLUSIONS: In this relatively small sample, there was no uniform practice of informed consent for commonly performed invasive medical procedures. Consent was routinely obtained for GI endoscopy, bronchoscopy, and medical research, and was not obtained for Foley catheterization and nasogastric intubation. The obtaining of consent for vascular cannulation and diagnostic procedures was not routine in the ICUs of a substantial number of respondents. Explicit standards that delineate specifically which procedures require consent may be required to assure more uniform practices.