Cost-benefit analysis of walking to prevent coronary heart disease

OBJECTIVE: To quantify the cost-benefit relationship of walking to prevent coronary heart disease. DESIGN: Cost-benefit analysis. PARTICIPANTS: Hypothetical cohorts of sedentary men and women aged 35 to 74 years. MAIN OUTCOME MEASURES: Decision-analysis simulation was used to evaluate the cost-benefit relationship of walking, varying level of benefit from exercise, frequency of exercise to achieve benefit, participation rates, and costs of exercise and injury. RESULTS: At a relative risk of 1.9 for heart disease associated with sedentary behavior, $5.6 billion would be saved annually if 10% of adults began a regular walking program. A $4.3 billion savings is predicted if the entire sedentary population began walking regularly and the cost of the time an individual spends exercising is accounted for in those who dislike exercising. According to our baseline assumptions, walking is economically beneficial for men aged 35 to 64 years and for women aged 55 to 64 years. The threshold of relative risk at which economic benefit is found for walking in this population overall is estimated at 1.7, and under a volunteer model, most adults would benefit even at a relative risk of 1.15. CONCLUSIONS: There are significant sex and age differences in the economic benefits of walking to prevent heart disease. The value assigned to the time an individual spends exercising has a significant impact on the results. Overall, a substantial savings is predicted from encouraging sedentary individuals to participate in a regular walking program.     

Autocrine regulation of endothelial exocytosis: von Willebrand factor release is induced by prostacyclin in cultured endothelial cells

OBJECTIVE: To find out whether recombinant human erythropoietin (r-HuEPO) given perioperatively has any effect on haemostatic activity in patients undergoing elective colorectal resection. DESIGN: A placebo-controlled double-blind study. SETTING: Odense university hospital, Denmark. SUBJECTS: 24 patients undergoing elective colorectal resection, 13 of whom were given r-HuEPO (Eprex) and 11 placebo. MAIN OUTCOME MEASURES: Concentrations of haemoglobin, tissue-type plasminogen activator and plasminogen activator inhibitor-1; activated partial thromboplastin time; prothrombin time; platelet and reticulocyte counts; blood loss; and transfusions. RESULTS: There was no significant change in fibrinolytic activity, prothrombin time, or activated prothrombin time in the treatment group. Platelet counts differed slightly but not significantly, being higher in the r-HuEPO group. There was a significant increase in reticulocyte counts in the r-HuEPO group. CONCLUSION: R-HuEPO given perioperatively significantly increased erythropoiesis in patients undergoing elective colorectal operations but had no influence on haemostatic activity.     

Stable expression of manganese superoxide dismutase (MnSOD) in insulinoma cells prevents IL-1beta- induced cytotoxicity and reduces nitric oxide production

The fact that insulin-producing islet beta-cells are susceptible to the cytotoxic effects of inflammatory cytokines represents a potential hinderance to the use of such cells for transplantation therapy of insulin-dependent diabetes mellitus (IDDM). In the current study, we show that IL-1beta induces destruction of INS-1 insulinoma cells, while having no effect on a second insulinoma cell line RIN1046-38 and its engineered derivatives, and that this difference is correlated with a higher level of expression of manganese superoxide dismutase (MnSOD) in the latter cells. Stable overexpression of MnSOD in INS-1 cells provides complete protection against IL-1beta-mediated cytotoxicity, and also results in markedly reduced killing when such cells are exposed to conditioned media from activated human or rat PBMC. Further, overexpression of MnSOD in either RIN- or INS-1-derived lines results in a sharp reduction in IL-1beta-induced nitric oxide (NO) production, a finding that correlates with reduced levels of the inducible form of nitric oxide synthase (iNOS). Treatment of INS-1 cells with L-NMMA, an inhibitor of iNOS, provides the same degree of protection against IL-1beta or supernatants from LPS-activated rat PBMC as MnSOD overexpression, supporting the idea that MnSOD protects INS-1 cells by interfering with the normal IL-1beta-mediated increase in iNOS. Because NO and its derivatives have been implicated as critical mediators of beta-cell destruction in IDDM, we conclude that well regulated insulinoma cell lines engineered for MnSOD overexpression may be an attractive alternative to isolated islets as vehicles for insulin replacement in autoimmune diabetes.     

DSM-IV alcohol disorders in a general population sample of adolescents and young adults

AIMS/DESIGNS: As part of the Early Developmental Stages of Psychopathology (EDSP) study, results from the baseline cross-sectional assessment of DSM-IV alcohol disorders are presented for a sample of 14-24-year-olds residents in Munich, Germany (N = 3021; 71% response rate). FINDINGS: Life-time prevalence of DSM-IV alcohol abuse (men: 15.1%; women; 4.5%) was found to be considerably more prevalent than dependence (men: 10.0%; women 2.5%) with few cases among respondents younger than 16 years of age; 12-month prevalence of abuse was 8.4% among men and 2.7% among women and of dependence was 7.3% among men and 2.2% among women. Results show that peak incidence of alcohol disorders occurs at 16-17 years of age and that early initiation into alcohol use is associated with an increasing odds of disorder onset, especially for dependence among women. Exploratory analysis of retrospectively assessed diagnostic stability show: a temporal progression to abuse and then dependence, that nearly half of past abuse diagnoses are in remission, abuse remission is more common than progression to dependence, and dependence is highly persistent, especially among women. CONCLUSIONS: Alcohol disorders are frequent in adolescent and young adults being characterized by transient abuse and less prevalent but persistent dependence syndromes. The relatively high prevalence of dependence diagnoses in this young population wit few years of alcohol use is discussed with regard to the clinical validity of DSM-IV criteria in adolescents and young adults.     

Group cognitive-behavioral treatment of binge eating disorder: a comparison of therapist-led versus self-help formats

A new enzymatic assay for selectively measuring conjugated bilirubin concentration in serum with use of bilirubin oxidase (BOD) has been developed. At pH 5.5 BOD can oxidize only conjugated bilirubin in the presence of reagents such as sodium fluoride and N-acetylcysteine which can decrease BOD reactivity to unconjugated bilirubin and bilirubin covalently bound to albumin (delta bilirubin). The resulting decrease in absorbance at 450 nm is linearly related to the concentration of conjugated bilirubin in serum. The BOD in this new assay was confirmed to oxidize conjugated bilirubin, and neither unconjugated nor delta bilirubin, based on both its reactivity to unconjugated bilirubin and HPLC results. This assay was found to give satisfactory results, such as in terms of the range of measurement, the reproducibility of the results, the lack of interference with coexisting substances in serum and the stability of the reagent solutions, in practical applications. The serum conjugated bilirubin concentrations determined using this assay correlate well with those determined by the HPLC analysis. This assay can be used for accurate monitoring of changes in the conjugated bilirubin concentration in patient sera. These findings suggest that the conjugated bilirubin assay is useful for fractional determination of bilirubin in icteric sera.     

Antibiotic susceptibility profile of group B streptococcus acquired vertically

OBJECTIVE: To determine the contemporary antibiotic susceptibility profile of vertically acquired group B streptococcal isolates. METHODS: Susceptibility to ampicillin, penicillin G, erythromycin, clindamycin, cefazolin, and gentamicin was assessed by two methods, minimal inhibitory concentration and disc diffusion. RESULTS: The susceptibility profiles of 119 colonizing and eight invasive strains of group B streptococcus isolated from January 1996 to September 1997 at two hospitals in Birmingham, Alabama-University of Alabama at Birmingham and Cooper Green-were studied. Minimal inhibitory concentration determinations indicated that all colonizing strains were susceptible or moderately susceptible to ampicillin and penicillin G. Resistance was noted by at least one strain to each of the other antibiotics; all were resistant to gentamicin, whereas 27 (21%) were resistant to erythromycin, five (4%) to clindamycin, and one (1%) to cefazolin. All of the eight invasive strains were susceptible or moderately susceptible to ampicillin, penicillin G, clindamycin, and cefazolin; one (13%) was resistant to erythromycin, and all were resistant to gentamicin. Disc diffusion results generally were concordant with minimal inhibitory concentration results, although by disc diffusion fewer isolates were classified as susceptible, and more as moderately susceptible, to ampicillin and penicillin G than by minimal inhibitory concentration. CONCLUSION: Universal susceptibility of group B streptococcus to members of the penicillin family supports the continued use of penicillin G or ampicillin for early onset neonatal group B streptococcal disease prevention. For patients allergic to beta-lactam agents, clindamycin (4% resistance) may be a better alternative than erythromycin (21% resistance).     

Apolipoprotein (apo) B and apoII gene expression are both estrogen-responsive in chick embryo liver but only apoII is estrogen-responsive in kidney

Estrogen regulates the hepatic synthesis of a variety of proteins required for egg yolk production in oviparous vertebrates. In chickens, two of these proteins, apolipoprotein (apo) B and apoII, comprise the major protein components of specialized very low density lipoprotein particles that transport triacylglycerols and cholesterol to the developing egg yolk. In the adult, apoB is synthesized constitutively in liver, small intestine, and kidney but is estrogen-responsive only in the liver. In this work we have examined the embryonic expression of the apoB and apoII genes in yolk sac, liver, kidney, and small intestine. The 14 kb apoB mRNA was first detected at day 3 of development in vascular yolk sac, a tissue involved in the transfer of yolk lipids into the embryonic circulation. Constitutive apoB mRNA expression was detectable in liver at day 6.5 and in kidney at day 7.5, but in intestine was barely detectable before hatching. The hepatic apoB gene acquired estrogen-responsiveness at day 6.5 and its hormone-dependent expression increased throughout development in concert with the estrogen-responsive expression of the apoII gene. In contrast, the constitutively expressed apoB gene in kidney remained unresponsive to estrogen. Surprisingly, the apoII gene was found to be responsive to estrogen in both the embryonic kidney and small intestine. ApoII mRNA induction by estrogen in kidney at day 11 was at 10% of the level in the liver but estrogen-responsiveness decreased later in development and was low in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)     

Action of pure ethanol and some alcoholic beverages on the gastric mucosa in healthy humans: a descriptive endoscopic study

A method for the simultaneous determination of residues of 17 beta-trenbolone and 17 beta, 19-nortestosterone and their epimers in animal tissues is described, involving immunoaffinity chromatography clean-up and high-performance liquid chromatography with dual-wavelength UV detection. The method has been validated at 2 micrograms/kg in pig and cattle liver and corned beef with recoveries of 41% upwards. The method has been applied to the determination of incurred residues of 19-nortestosterone and trenbolone. Various alternative extraction steps for incurred trenbolone have been investigated, including direct extraction, protease digestion, heating and ultrasonic probe treatment. Glucuronidase digestion has been shown to be the most effective method for this analyte.     

Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer

Despite the advances in pre-, peri- and post-operative medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In previous studies we found that colorectal carcinomas have a marked increase of the urokinase-type of plasminogen activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type plasminogen activator (t-PA) is found to be decreased in comparison with adjacent normal mucosa. In the present study we evaluated the prognostic value of several plasminogen activation parameters, determined in both normal and carcinomatous tissue from colorectal resection specimens, for overall survival of 136 Dukes' stage B and C colorectal cancer patients, in relation to major clinicopathological parameters. Uni- and multivariate analyses indicated that a high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and a high u-PA/t-PA antigen ratio in adjacent normal mucosa are significantly associated with a poor overall survival. A high ratio of u-PA antigen in the carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to be predictive of a poor overall survival as well. All these parameters were found to be prognostically independent of the clinicopathological parameters. Multivariate analysis of combinations of these prognostically significant plasminogen activation parameters revealed that they are important independent prognostic indicators and have in fact a better prognostic value than their separate components. Based on these combined parameters, subgroups of patients with Dukes' stage B and C colorectal cancer could be identified as having either a high or a low risk regarding overall survival. In conclusion, these findings emphasize the relevance of the intestinal plasminogen activation system for survival prognosis of patients with colorectal cancer and, in the future, might constitute a patient selection criterion for adjuvant therapy.