Studies on antifungal agents. In vitro activity of novel cis-5-alkoxy (or acyloxy)alkyl-3-phenyl-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidine derivatives

The synthesis and in vitro antifungal activity of a novel series of cis-5-alkoxy(or acyloxy)alkyl-3-phenyl-3-(1H-imidazol-1-ylmethyl)- 2-methylisoxazolidine derivatives (6a-n) are described. The 5-[(4-chlorobenzyloxy)methyl] analogue 6h and the two 5-acyloxymethyl derivatives 6k,l demonstrated the best overall potency. Against Candida stellatoidea, the minimum inhibitory concentrations (MIC's) for 6h,k,l ranged between 0.7 and 2.0 micrograms/ml. The corresponding value for the standard drug ketoconazole was 7-20 micrograms/ml.     

Natural history of morbid obesity without surgical intervention.

BACKGROUND: To study the mortality among morbidly obese patients qualifying for bariatric surgery. Mortality from bariatric surgery for morbid obesity has been widely reported; however, little is known about the mortality in morbidly obese patients who defer surgery. METHODS: Consecutive patients evaluated for bariatric surgery with an initial encounter between 1997 and 2004 were identified. The Social Security Death Index and office records were used to identify mortality through 2006. We conducted telephone interviews to determine whether the 305 patients who did not undergo bariatric surgery at our institution had undergone the surgery elsewhere. Using Cox proportional hazards models, we compared the mortality in patients undergoing surgery with that of those who did not. To evaluate bias resulting from missing data, we conducted analyses assuming that all patients with missing data had (1) undergone surgery and (2) not undergone surgery. RESULTS: A total of 908 patients underwent bariatric surgery (880 patients at our institution and 28 patients elsewhere). A total of 112 patients did not undergo surgery. Data regarding surgery on 165 patients could not be obtained. The mortality in those patients who did not undergo surgery was 14.3% compared with 2.9% for those who did undergo surgery. Adjusting for age, gender, and body mass index, patients who had undergone surgery had an 82% reduction in mortality (hazard ratio 0.18, 95% confidence interval 0.09-0.35, P <.0001). Sensitivity analysis, assuming that all patients with missing data received surgery resulted in an 85% mortality reduction (P <.001) and assuming that patients did not receive surgery resulted in a 50% mortality reduction (P = .04). CONCLUSIONS: Mortality among morbidly obese patients without surgery was 14.3% during the study period. Surgical intervention offered a 50%-85% mortality reduction benefit.     

DXA-Generated Z-Scores and T-Scores May Differ Substantially and Significantly in Young Adults

Central dual-energy X-ray absorptiometry (DXA) is the gold standard for non-invasive measurement of bone mineral density (BMD). Using this value and subject demographics, DXA software calculates T-scores and Z-scores. Professional society guidelines for the management of osteoporosis are based on T-scores and Z-scores, rather than on the actual BMD value. Although one expects T-scores and Z-scores to be very similar in young men and women for any given BMD measurement, little literature exists on this issue. Our clinical experience shows that some younger adult individuals (premenopausal women and men younger than 50 yr) have larger than expected difference between their DXA T-score and Z-score. This cross-sectional study evaluates the extent of this discordance between Z-scores and T-scores in a sample of 4275 men and women aged 20–49 yr. All subjects were scanned by central DXA using equipment manufactured by GE Lunar, GE, Madison, WI, or Hologic, Inc., Bedford, MA. Significant differences between Z-scores and T-scores were seen within individuals at the lumbar spine, total hip, femoral neck, and trochanter (p value < 0.001) for both DXA systems. Although these differences were less than half a standard deviation (SD) in most instances, the magnitude of difference was substantial at times, being 1 or more SD in up to 11% of cases (range: −1.95 to +1.54 SD). The smallest differences were seen at the total hip and the largest differences were seen at the femoral neck for both technologies. This is in part because there is no single standard Z-score definition, resulting in different methods of calculation across, and even within, DXA manufacturers. Standardization of Z-score definition and method of calculation is indicated. DXA Z-scores should be interpreted with caution in men and women aged 20–50 yr.     

Fetal pancreas transplantation in miniature swine. IV. Suppression of DTH and MLR responses by treatment with ultraviolet light-irradiated peripheral blood lymphocytes

Irradiation of peripheral blood lymphocytes of miniature swine with ultraviolet light prevented them from initiating proliferative responses in allogeneic mixed lymphocyte reactions and also reduced IL-2 production in these MLRs. When pigs were injected in a series of 4-5 weekly transfusions with UV-irradiated allogeneic PBL differing at the MHC, PBL of recipient pigs progressively responded less strongly to donor PBL in MLRs over the treatment period. These pigs also gave negligible delayed-type hypersensitivity responses to donor PBL at the end of the treatment period. Of the seven UV-irradiated PBL-treated pigs, four produced no antidonor PBL antibody and three produced antibody. Serum from the three antibody-producing pigs also suppressed MLRs of unrelated PBL. By contrast, pigs that received a series of injections of untreated allogeneic PBL gave strong DTH responses to donor PBL and heightened proliferation in MLRs with donor PBL, and all produced antidonor PBL antibody.     

Selected predictors of health promotion counseling by three groups of allied health professionals

Three groups of allied health professionals, including dental hygienists, dietitians, and certified nurse-midwives, were surveyed to determine current practice, beliefs, and attitudes regarding health promotion and disease prevention. The study aimed to explore the power of selected variables drawn from social learning theory in predicting self-reported level of counseling. We conducted separate analyses for 10 areas of health promotion and disease prevention: high blood pressure, smoking, lack of exercise, overweight, high-fat diet, alcohol abuse, illicit drug use, stress, isolation and loneliness, and nonuse of safety belts. The predictor variables were respondents' professional group membership, confidence that they possess appropriate skills and knowledge to counsel patients (self-efficacy), belief that patients will follow through on recommendations (adherence expectation), and belief that reduction of risk will improve patients' health status (expectation of health impact). The level of counseling activity varied markedly across the risk areas, with blood pressure and weight receiving the most emphasis on average and isolation and loneliness and nonuse of safety belts receiving markedly less attention. There also was variation across the professional groups. Certified nurse-midwives had higher mean counseling scores in all topics except those related to diet, where the dietitians' mean scores were approximately the same. Of all the areas about which counseling might be increased, use of safety belts stands out as having the lowest reported prevalence, the least complexity in terms of implementation, and the most relevance to at least two of the professional groups. These findings suggest the importance of skills training, including the provision of actual or simulated counseling experience and modeling by others in the same professional group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of propranolol on nitrogen and energy metabolism in sepsis

Pharmacologic therapy designed to block adrenergic activity or alter hormonal milieu may modulate energy and protein metabolism in stress. The metabolic effects of propranolol (beta adrenergic receptor blocker) in sepsis was investigated in 22 well-nourished rats that underwent superior vena caval cannulation, cecal ligation, and puncture. Animals were randomly assigned to receive either a continuous infusion of 0.7 mg/day of propranolol combined with parenteral nutrition (n = 11) or parenteral nutrition alone (n = 11). Both groups received isocaloric, isonitrogenous, isovolemic, parenteral nutrition post-operatively for 24 hr. Nitrogen balance was better for the propranolol group than for the control group (+743 +/- 84 mg/kg/day versus +300 +/- 63 mg/kg/day, respectively, P less than 0.05). A significant difference between the pharmacologic therapy and control groups was noted for urinary 3-methylhistidine excretion versus control (0.99 +/- 0.08 micrograms/kg/day versus 7.5 +/- 0.37 micrograms/kg/day, respectively, P less than 0.01). Measured energy expenditure was similar for both pharmacologic therapy and control groups (149 +/- 20 kcal/kg/day versus 134 +/- 11 kcal/kg/day, respectively, P = N.S.). No statistically significant difference was demonstrated for 24-hr survival between propranolol and control groups (73 and 64%, respectively). Continuous, low-dose propranolol promotes nitrogen retention and decreases 3-methylhistidine excretion without altering energy expenditure in parenterally fed septic rats.