Short-term chemoprophylaxis with ceftizoximevs. Five-day aminoglycoside with metronidazole in ‘contaminated’ lower gastrointestinal surgery

In a prospective, open, randomized controlled trial, 173 patients requiring surgery for potentially contaminated lower gastrointestinal surgery were allocated to receive either two doses of ceftizoxime (2 gm) with one dose of metronidazole (1.5 gm) or gentamicin 3 mg/kg/day for five days with one dose of metronidazole (1.5 gm). Eighty-nine patients received ceftizoxime and 84 patients received gentamicin. The groups were comparable with respect to diagnosis, procedure, type of anastomosis, and wound closure. The incidence of withdrawal due to failure to respond to the study drug (11.5 percent) was equivalent in the two groups. There was no difference in the overall incidence of postsurgical infection between the ceftizoxime and metronidazole group (22.2 percent) and the gentamicin and metronidazole group (25.7 percent). The incidence of wound infection (ceftizoxime and metronidazole, 6.9 percent; gentamicin and metronidazole, 10 percent) and deep sepsis (ceftizoxime and metronidazole, 15.3 percent; gentamicin and metronidazole, 15.7 percent) was similar.     

Intrinsic physiological and morphological properties of principal cells of the hippocampus and neocortex in hamsters infected with scrapie.

Scrapie is a transmissible spongiform encephalopathy, or "prion disease." We investigated the effects of intracerebral Sc237 scrapie inoculation in hamsters on the physiology and morphology of principal cells from neocortical and hippocampal slices. Scrapie inoculation resulted in increased branching of basal dendrites of hippocampal CA1 pyramidal cells (Sholl analysis), reduced amplitudes of medium and late afterhyperpolarizations (AHPs) in CA1 pyramidal cells and layer V neocortical cells, loss of frequency potentiation of depolarizing afterpotentials (DAPs), and double action potentials in synaptically evoked CA1 pyramidal cell responses. Postsynaptic double action potentials could also be evoked in normal hamster CA1 pyramidal cells by acute pharmacological block of AHPs, suggesting that the depressed AHPs in scrapie-infected hamsters caused the action potential doublets. Both the AHP and the DAP potentiations depend on increased intracellular calcium, which suggests that the underlying deficit, in hamsters infected with Sc237 scrapie, may lie in calcium entry and/or homeostasis. Fast IPSPs, passive membrane properties, and density of dendritic spines remained unchanged. These last two results differ markedly from recent studies on mice infected with ME7 scrapie, indicating diversity of pathophysiology in this group of diseases, perhaps associated with the progressive and substantial neuronal loss found in the ME7, and not the Sc237, model.     

The Massachusetts Behavioral Health Program Year 5: Transition to a New Managed Care Organization

Year 5 of the Massachusetts Behavioral Health Program was a transition to management by a new private managed care organization. Fifty-eight providers interviewed for an ongoing panel survey reported slightly lower levels of quality, access, utilization, and length of stay than a year earlier. Relationships with providers and advocates improved after an initial difficult period, while consumer and family involvement at all levels remained low. The greatest changes in managed care appeared to take place during the initial transition from fee-for-service care, but intractable problems continue, and full participation of stakeholders seems difficult to achieve.     

Vaccination for control of Salmonella in poultry.

Salmonella spp. are facultative intracellular pathogens causing localised or systemic infections, in addition to a chronic asymptomatic carrier state. They are of worldwide economic and public health significance. In poultry, which represent important sources of cheap protein throughout the world, fowl typhoid and pullorum disease continue to cause economic losses in those parts of the world where the poultry industries are continuing to intensify and where open sided housing is common. A number of serotypes that cause human gastro-enteritis are also increasing. The costs or impracticality of improvements in hygiene and management together with the increasing problems of antibiotic resistance suggest that vaccination in poultry will become more attractive as an adjunct to existing control measures. However, our understandings of the immunology of Salmonella infections in poultry is rudimentary and much poorer than that of equivalent infections in mice and live vaccine development for poultry has therefore been largely empirical. In addition to the killed Salmonella vaccines which have been used over the past few years with variable efficacy, a number of live vaccines have become available and some new vaccines will appear on the market over the next few years. These new vaccines should fulfil the criteria of efficacy, safety and compatibility with existing systems for monitoring infection before they are released on to a mass market. In this review we attempt to summarise the current understanding of Salmonella immunology in poultry together with the progress that has been made in poultry vaccine development.     

Studentschool bonding and adolescent problem behavior

Adolescent problem behavior, including substance use, schoolmisconduct and delinquency, is a national concern. Implicitin the concept of middle school is the recognition that studentswho develop positive social bonds with their school are morelikely to perform well academically, and refrain from misconductand other antisocial behavior. However, little scientific attentionhas been given to the complex interactions between middle schoolstudents and the school environment. Prior to implementing amiddle school problem behavior prevention program we conducteda survey in the seven middle schools in one US school district.Out of 4668 grade 6–8 students enrolled, 4263 (91.3%)completed the survey. Student–school bonding was positivelycorrelated with school adjustment (r = 0.49) and perceived schoolclimate (r = 0.77), but inversely correlated with problem behavior(r = –0.39 to –0.43). Problem behavior was significantlyhigher (P < 0.001) among males than females and among studentsin higher grades. Conversely, school bonding, climate and adjustmentwere significantly higher (P < 0.001) among females thanmales, but declined significantly from one grade to the next.The data support the conclusion that school bonding is associatedwith problem behavior. We describe the development of a multiple-componentintervention in middle schools designed to increase student–schoolbonding and prevent problem behavior.     

Phase II trial of circadian infusion floxuridine (FUDR) in hormone refractory metastatic prostate cancer

Circadian administration of chemotherapy has been reported to decrease toxicity and possibly enhance efficacy. Between March 1991 and December 1993, 18 evaluable patients with progressive, hormone-refractory metastatic prostate cancer were treated in this phase II trial of circadian infusion floxuridine (FUDR). The drug was delivered through a central venous catheter using a CADD-Plus computerized pump such that approximately 70% of the drug was administered between 3 and 9 p.m. and the rest (30%) was administered between 9 p.m. and 3 p.m. The dose of FUDR was 0.15 mg/kg/day × 14 days every 4 weeks. A total of 79 complete cycles was administered.Two of 18 evaluable patients (11.1%) had decreases in PSA lasting five and eight months. No objective responses or improvement in bone scans was noted. The major toxicity observed was diarrhea. Although circadian infusion FUDR is feasible and tolerable, it has limited activity in hormone refractory prostate cancer.     

Effects of a high-selenium yeast supplement on celecoxib plasma levels: a randomized phase II trial.

A combination of celecoxib and selenium was used in a randomized double-blind Phase II trial as a preliminary study to a multicenter Phase III colorectal cancer chemoprevention trial using these two agents together. The purpose of this trial was to determine whether high-selenium baker's yeast [(Saccharomyces cerevisiae) 200 microg once daily] in combination with celecoxib (400 mg once daily) altered the steady-state plasma concentration of celecoxib or produced clinically significant toxicities. Seventy-three healthy subjects (ages 40-75 years) were recruited to the 6-week study from the general local population and were randomized to either the celecoxib plus selenized baker's yeast group or the celecoxib plus placebo group after a 2-week run in period of celecoxib only. Blood samples were taken at baseline (to document that there was no evidence of celecoxib intake), after the 2-week run-in period on celecoxib to verify steady-state blood levels of this agent, and at end of study (4 weeks postrandomization). Toxicities were monitored at 2 weeks after initiation of celecoxib, at 4 weeks after initiation, and at the end of the study. Blood level concentrations of celecoxib did not differ between the two groups as determined by high-performance liquid chromatography analysis nor were there significant differences in blood chemistry values between the two groups. Subjects' self-report of general physical toxicities was uncommon and limited to National Cancer Institute toxicity grade 2 or less; however, 2 female participants (3%) were removed from the study medications because of grade 2 edema and significant weight gain after 2 and 2.5 weeks of celecoxib administration. In conclusion, high-selenium yeast and celecoxib can be taken at the described doses with minimum short-term negative effects. In future Phase III chemoprevention trials of celecoxib, weight gain should be carefully monitored, and participants should be made aware of this potential side effect before study entry.     

Estimating the cost of cancer: results on the basis of claims data analyses for cancer patients diagnosed with seven types of cancer during 1999 to 2000.

PURPOSE: Cancer accounts for 60.9 billion dollars in direct medical costs and 15.5 billion dollars for indirect morbidity costs. These estimates are derived primarily from national surveys or Federal databases. We derive estimates of the costs of cancer using administrative databases, which include claims and employment-related information on individuals insured by private or Medicare supplemental health plans. METHODS: A retrospective matched-cohort control analysis was performed using 1998 to 2000 databases with information on insurance claims, benefits, and health productivity for 3 million privately insured employees, their dependents, and early retirees. Study patients had new diagnoses of one of seven types of cancer (n = 12,709). Controls without cancer were matched at a 3:1 ratio by demographics. A variable follow-up length was used (maximum of 2 years). Direct costs included health care costs for patients and deductibles and copayments for caregivers. Indirect costs of work absence and short-term disability (STD) were calculated for a subgroup of cancer patients and caregivers. RESULTS: Mean monthly health care costs ranged from 2,187 dollars for prostate cancer to 7,616 dollars for pancreatic cancer, most often driven by hospitalization. Costs for controls were 329 dollars per month. Indirect morbidity costs to employees with cancer averaged 945 dollars, a result of a mean monthly loss of 2.0 workdays and 5.0 STD days. CONCLUSION: The economic burden of cancer is substantial. It is feasible to derive tumor-specific estimates of direct and indirect costs for large numbers of cancer patients using administrative databases. Policy makers charged with providing annual cost-of-cancer estimates should incorporate data obtained from a broad range of sources.     

Serologic evidence of human papillomavirus 16 and 18 infections and risk of prostate cancer.

Human papillomavirus (HPV) subtypes 16 and 18 are sexually transmitted and have been associated with an increased incidence of several anogenital tumors. Although previous epidemiological studies have suggested that sexual behaviors such as an early age at first intercourse and larger numbers of sexual partners are also related to an increased risk of prostate cancer, seroepidemiological studies of these infectious agents in relation to prostate cancer have produced differing results. To further evaluate this potential relationship, we completed a population-based control study in King County, Washington. Middle-aged (40-64 years) men diagnosed with prostate cancer (n = 642) were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry between January 1993 and December 1996. Controls (n = 570) of similar age were selected from the same population as the cases by random digit dialing. Overall, there was no association between serological evidence of prior HPV-16 (adjusted odds ratio, 1.06; 95% confidence interval, 0.71-1.57) or HPV-18 (adjusted odds ratio, 1.36; 95% confidence interval, 0.69-2.69) infection and the risk of prostate cancer. Analyses of clinical features demonstrated no relationship between HPV infection status and Gleason score, stage of disease, or a combined measure of disease aggressiveness. Our findings indicate that HPV-16 and HPV-18 are not associated with prostate cancer risk.     

Smoking exposure as a risk factor for prevalent and recurrent colorectal adenomas.

Colorectal adenomatous polyps are considered to be the precursor lesion of colorectal cancer (1-3). Greater understanding of the association between smoking and adenoma development enable better detection and prevention of colorectal cancer. This study was conducted in men and women, ages 40-80, participating in a randomized trial testing the effects of wheat bran fiber supplement on adenoma recurrence. First, we investigated smoking exposure (status, cigarettes/day, and years of smoking) and colorectal adenoma characteristics (location, histology, size, and multiplicity) at baseline colonoscopy (n = 1429). Second, we evaluated smoking exposure and adenoma recurrence (n = 1304). The prevalence of distal versus proximal adenomas was greater for < or =30 cigarettes/day [odds ratio (OR), 1.48; 95% CI, 1.02-2.16] and 15 to <25 years of smoking (OR, 1.95; 95% CI, 1.23-3.09) compared with never smokers. Tubular versus villous histology prevalence was increased for > or =30 cigarettes and > or =35 years of smoking (OR, 1.74; 95% CI, 1.21-2.49 and OR, 1.74; 95% CI, 1.24-2.45, respectively) compared with never-smokers. Years of smoking increased prevalence of multiple versus single adenomas, whereas cigarettes/day and years of smoking were associated with large adenomas (> or =1 cm) prevalence as compared with small lesions (< or =0.5 cm). Greater than 35 years of smoking was significantly associated with an increased risk of adenoma recurrence (OR, 1.42; 95% CI, 1.01-1.98). These results suggest that the association between smoking and adenoma prevalence varies by the characteristic of the lesion. Furthermore, the association between smoking and adenoma recurrence is modest and was only significant after a long duration of exposure. Additional investigations that characterize the genetic changes in specific subgroups of prevalent and recurrent adenomas associated with smoking exposure are needed.