Efficacy of bicozamycin in preventing traveler's diarrhea

Bicozamycin was compared with a placebo in a prospective, randomized, double-blind study of the prevention of acute diarrhea among 30 American travelers newly arrived in Guadalajara, Mexico. None of the 11 subjects given bicozamycin orally for 3 wk at a dosage of 500 mg four times a day developed diarrhea as compared with an incidence of 53% diarrhea (10 of 19 subjects) in the placebo group (p = 0.003). Bicozamycin was well tolerated. Studies of changes in predominant aerobic fecal flora among the 11 subjects treated with bicozamycin showed the appearance of only one highly resistant Citrobacter freundii at the end of 1 wk of therapy and only a total of six resistant isolates at the end of 3 wk. All resistant isolates failed to transfer this resistance to a recipient Escherichia coli. Bicozamycin seems to be well suited and safe as a prophylactic agent against traveler's diarrhea.     

Efficacy and adverse effects of nateglinide in early type 2 diabetes. Comparison with voglibose in a cross-over study

An open-label prospective cross-over trial was performed to compare the efficacy and adverse effects of nateglinide with those of voglibose on Japanese early type 2 diabetes (who were oral hypoglycemic agent na?ve and whose HbA(1C) levels were between 7.0 and 7.9% before treatment). Fourteen patients received 270 mg/day of nateglinide and 15 patients received 0.6 mg/day of voglibose. After 12 weeks of either therapy, the drugs were switched and treatment was continued for another 12 weeks. After 3-month treatment with each drug, HbA(1C) value decreased significantly (baseline HbA(1C) 7.24 +/- 0.42%, 6.70 +/- 0.47% with nateglinide: p<0.01, 6.93 +/- 0.62% with voglibose: p<0.05) but the difference in the effect between nateglinide and voglibose was not significant (p = 0.121). Symptoms related to hypoglycemia (e.g., increased appetite, palpitation, sweating, tremor) were scarcely observed with either voglibose or nateglinide treatments. Abdominal fullness/borborygmi was frequently reported, with variable severity, by patients on voglibose but this was absent or mild in those on nateglinide. After completion of both arms of the study, more patients favored nateglinide than voglibose. Our results suggest that nateglinide is an effective and safe drug in the treatment of early type 2 diabetes, similar to voglibose.     

Penicillamine in rheumatoid arthritis: adverse effects.

The use of penicillamine in rheumatoid arthritis (RA) is limited by the incidence of adverse effects, some of which are potentially hazardous. However, adverse effects are dose-related and the advantages and disadvantages of different fixed and flexible dose regimes are discussed. The incidence of adverse effects is significantly greater in patients previously treated with gold who developed toxicity to that drug--no such increase being found in gold treated patients whose only reason for stopping gold was ineffectiveness. Rashes which develop after several months of treatment are variants of pemphigus and their various presentations are described. Fatal reactions, fortunately rare, are predominantly associated with aplasia of the bone marrow. Monthly haematological checks coupled with meticulous charting of the results may reveal trends as well as numerical changes and serve as an early warning of marrow damage.     

Efficacy of zinc supplementation in preventing acute hepatitis in Long-Evans Cinnamon rats.

OBJECTIVES: Long-Evans Cinnamon (LEC) rats are characterized by an abnormal hepatic deposition of copper (Cu) due to a lack of the Cu-transporter P-type adenosine triphosphatase: accordingly, the strain is a good animal model of Wilson's disease. The effect of oral zinc (Zn) acetate treatment on the development of acute hepatitis and the biochemical parameters of Cu-induced liver damage was studied in 5-week-old LEC rats (n=52). METHODS: Rats receiving 50 or 80 mg/ml/day Zn acetate by gavage and control rats receiving a daily dose of glucose solution 0.02 g/ml by gastric intubation were killed at 1, 2 or 8 weeks after the start of treatment. RESULTS: Treatment with Zn acetate resulted in the prevention of acute hepatitis: 10 of the 13 untreated rats developed signs and symptoms compatible with acute hepatitis between the 6th and 7th week of treatment. Tissue metallothionein (MT) significantly increased in the treated rats and positively correlated with Zn concentrations within the liver. Control rats had a significantly higher iron concentration in the liver and kidneys compared with supplemented rats, after both short- and long-term experiments. 8-hydroxy-2'-deoxyguanosine amounts were significantly lower in untreated rats. CONCLUSIONS: Zn acetate prevents acute hepatitis, by increasing tissue MT concentrations, reducing Cu absorption and interfering with Fe metabolism.     

Role of pharmacist counseling in preventing adverse drug events after hospitalization

BACKGROUND: Hospitalization and subsequent discharge home often involve discontinuity of care, multiple changes in medication regimens, and inadequate patient education, which can lead to adverse drug events (ADEs) and avoidable health care utilization. Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs. METHODS: We conducted a randomized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital. Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later. Interventions focused on clarifying medication regimens; reviewing indications, directions, and potential side effects of medications; screening for barriers to adherence and early side effects; and providing patient counseling and/or physician feedback when appropriate. The primary outcome was rate of preventable ADEs. RESULTS: Pharmacists observed the following drug-related problems in the intervention group: unexplained discrepancies between patients' preadmission medication regimens and discharge medication orders in 49% of patients, unexplained discrepancies between discharge medication lists and postdischarge regimens in 29% of patients, and medication nonadherence in 23%. Comparing trial outcomes 30 days after discharge, preventable ADEs were detected in 11% of patients in the control group and 1% of patients in the intervention group (P = .01). No differences were found between groups in total ADEs or total health care utilization. CONCLUSIONS: Pharmacist medication review, patient counseling, and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge. Medication discrepancies before and after discharge were common targets of intervention.     

Medication-attributed adverse effects in placebo groups: implications for assessment of adverse effects

Medication-attributed adverse effects are a frequent reason for poor compliance in practice and in clinical studies and are also common in patients receiving placebo. The occurrence of adverse effects in placebo groups can clarify the assessment of adverse event reporting. We analyzed data from randomized, placebo-controlled trials of statin drugs published since 1992 with sample sizes larger than 100 subjects. Reports of adverse effects and discontinuation rates in placebo groups were evaluated. We compared data on adverse effect profiles in placebo groups between trials and with expected rates from population-based studies. We also sought to determine the range of adverse effect ascertainment methods used in different studies. Methods of ascertainment of adverse events varied widely across studies. Overall, 4% to 26% of patients in the control groups of large trials of statin drugs discontinued placebo use because of perceived adverse effects. The symptom rate in placebo groups varied substantially across trials (up to a ratio of 13:1 for possibly drug-related symptoms, eg, headache, 0.2%-2.7%, or abdominal pain, 0.9%-3.9%) and were often markedly lower than those found in the general population (eg, fatigue, 1.9%-3.4%) in trials of statin drugs vs 17.7% in the general population. In conclusion, the widely varying rates of adverse effects reported by patients taking placebo and the high prevalence of such symptoms in the general population should be considered by both trialists and clinicians. In addition, variability of adverse effect ascertainment is considerable and suggests the need for better standardization in research.     

Efficacy,plasma concentrations and adverse effects of a new sustained release procainamide preparation

To assess the efficacy, plasma drug concentrations and adverse effects of a new sustained release preparation of procainamlde, 33 patients with heart disease were studied in an acute dose-ranging protocol and a chronic treatment protocol. Patients initially received a daily dose of 3 g of sustained release procainamide; this dose was increased by 1.5 g daily until ventricular premature depolarizations were suppressed by 75 percent or more, adverse drug effects occurred or a total daily dose of 7.5 g of sustained-release procainamide was reached. Twenty-five patients (76 percent) had at least a 75 percent reduction (range 75 to 100 percent [mean ± standard deviation 91 ± 8.2]) in ventricular premature depolarization frequency at a dosage of 4.8 ± 1.46 g/day (range 3.0 to 7.5). Despite the 8 hour dosing interval, the variation between maximal and minimal plasma procainamide and N-acetylprocainamide concentrations under steady state conditions was very small. Mean maximal procainamide and N-acetylprocainamide plasma concentrations were 10.4 +- 6.02 and 12.0 ± 7.40 μg/ml, respectively. The respective mean minimal concentrations were 6.8 ± 4.50 and 8.7 ± 5.99 μg/ml In nine patients (27 percent) treatment with sustained release procainamide resulted in conversion of the antinuclear antibody test from negative to positive. Adverse drug effects occurred in 17 (52 percent) of the subjects. In general, adverse effects were minor and abated within 24 hours after administration of the drug was stopped. One patient had the procainamide-induced systemic lupus erythematosus-like syndrome.     

Lack of any estrogenic effect of ipriflavone in postmenopausal women.

Estrogen replacement therapy (ERT) has been demonstrated to prevent osteoporosis in postmenopausal women (PMW). However, several contraindications exist for ERT and many PMW cannot be treated. It has also been shown that too low doses of ERT are able to exert therapeutical effects on some climacteric symptoms but not on bone and compounds exerting synergic actions with ERT on bone without effects on other organs could be useful. The isoflavone derivative, ipriflavone, seems to have this effect but data are lacking on its endocrine effect in humans; thus, this study was undertaken to clarify in PMW whether ipriflavone exerts estrogenic activity. Evaluation of LH and FSH secretion during a 24-h period was performed in a group of 15 PMW after a single oral dose of 600 or 1,000 mg of ipriflavone or placebo, and after 7, 14 and 21 days of oral treatment with ipriflavone 600 mg and 1,000 mg/daily, administered in three divided doses. LH secretion was also evaluated during naloxone infusion before and after 21 days of ipriflavone, placebo or conjugated estrogen treatment (0.625 mg/day; CE). LH response to NAL treatment was absent during ipriflavone and placebo such as it was observed before treatments. By contrast, a significant increase of LH plasma levels was measured during naloxone infusion in CE-treated women. This result demonstrates that ipriflavone is unable to exert the same effects that estrogens do in PMW. In addition, no changes like in placebo group were seen on vaginal cytology in this group of subjects after 21 days, whereas a significant increase of superficial vaginal cells was observed after 21 days of CE treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

静脉胺碘酮的主要不良反应分析

目的了解静脉胺碘酮在实际应用中出现的主要不良反应情况，探讨如何进一步规范使用胺碘酮，减少其副作用。方法对本院在2003年10月到2005年9月的静脉使用胺碘酮的全部住院病历进行回顾性研究，对出现不良反应的病例进行统计与分析。结果静脉胺碘酮后出现肝功能异常的发生率为12．6％，男性比女性更容易发生肝功能异常。重度肝功能异常的病例9例，需干预的严重心动过缓7例，需干预的低血压4例，过敏反应1例。结论尽管静脉胺碘酮有可能导致一些副作用，但只要密切监测，早期发现，早期处理，其使用是安全有效的。     

Efficacy of glucocorticoids in preventing mitochondrial metabolic failure in endotoxemia

Endotoxemia was induced in rats and guinea pigs by an intraperitoneal injection of E coli endotoxin. In the rat, the dose used (3 mg/100 g body weight) resulted in a 60% mortality in 24 h. The same dose in the guinea pig resulted in a similar mortality at 24 h, and a 100% mortality by 3 days. Methylprednisolone Na-succinate, a glucocorticoid, given simultaneously with the endotoxin, prevented mortality in the rats. No animals died during the observation period. In the guinea pigs the same treatment protected all animals for 24 h, and resulted in an 80% survival rate over a 6-day observation period. Administration of glucocorticoids 1 or 2 h after endotoxin showed diminished efficacy. About 60% of the guinea pigs died during the 6-day observation period. Rat kidney and guinea pig brain and kidney mitochondria were isolated and analyzed for their function in untreated and treated animals 24 h after the injection of endotoxin. Rat kidney mitochondrial O2 utilization and ATP synthesis function, as well as Ca++ transport activity, were significantly below normal in the untreated animals, but did not differ from normal in glucocorticoid-treated animals. In untreated and at zero time treated guinea pigs similar results were found in brain and kidney mitochondrial functions. If treatment was delayed for 1 or 2 h, however, brain mitochondrial O2 utilization and ATP synthesis rates were significantly below normal, and both brain and kidney mitochondrial Ca++ transport capacities remained significantly lowered. The data support the efficacy of early glucocorticoid treatment in endotoxemia. Early glucocorticoid treatment prevents the deterioration of brain and kidney mitochondrial function.     

Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge.

The protective efficacy of oral bovine immunoglobulin concentrates derived from colostrum against challenge with Shigella flexneri was studied in healthy adult volunteers in a randomized, double-blind fashion. Volunteers were given a product consisting of hyperimmune immunoglobulin concentrate with a high titer of anti-S. flexneri 2a lipopolysaccharide (LPS) with sodium bicarbonate or a control preparation with sodium bicarbonate three times a day for seven days. On the third day of treatment, volunteers received a challenge of 10(3) colony-forming units of S. flexneri 2a strain 2457T. None of the volunteers who received the high-titered hyperimmune product became ill, compared with 45% of volunteers who received the placebo (P less than 0.05). The duration of shedding of the challenge organism was decreased, and the active immune responses to S. flexneri LPS were less frequent and of lower magnitude in volunteers given the immunoglobulin concentrate than in those in the control group. High-titered, orally administered bovine immunoglobulin concentrate protects against shigellosis and may be useful in preventing shigellosis among travelers, military personnel, and individuals at risk during a Shigella outbreak.     

Bretylium Tosylate; adverse effects in acute myocardial infarction.

The effects of bretylium tosylate in managing acute myocardial infarction were studied in 16 patients within 24 hours from the onset of symptoms and were compared to those of lidocaine in a comparable group of 15 patients. Both drugs were equally effective in preventing cardiac arrhythmias during the 48 hours of trial. No deleterious hemodynamic effects were associated with lidocaine treatment. However, marked supine hypotension developed in seven patients treated with bretylium. No changes occurred simultaneously in heart rate, left ventricular ejection time, or central venous pressure. The occurrence of hypotension correlated with a poor initial hemodynamic state. The substantial and unpredictable circulatory effects of bretylium in acute myocardial infarction contraindicates its routine use in the prevention of infarction arrhythmias.     

Efficacy of immunized milk for preventing viral infection

This paper investigated the efficacy of passive protection provided by milk (immunized milk) against enterovirus infection in mice experimentally infected with enterovirus. Milk with a high antibody titer against six enterovirus serotypes was prepared from hyperimmunized goat. In vivo and in vitro experiments were performed and the results showed that immunized milk has an antiviral activity against enterovirus infection. Further observation was performed using Coxsackie B 3 virus (CVB 3). When immunized milk was orally applied to mice prior to oral inoculation with CVB 3, preventive effects against viral infection such as reduction of histopathological changes in the heart and reduced detection of the virus genome in the organs were seen. The antiviral effect was also indicated by the increase of CD4+T cells proportion in the i-IEL. The proportion of virus specific CD4+T cells was increased in mice treated with immunized milk, whereas no such increase was detected in control mice. These results suggest that oral application of immunized milk is not only capable of preventing viral infection but also induces specific immunological responses. These phenomena may play an important role in host defense mechanisms.     

Changes in antihypertensive therapy--the role of adverse effects and compliance.

In a German multicentre study (1603 patients, 320 private practices), adverse effects and patient compliance during antihypertensive therapy were investigated using standardized questionnaires for both patient and physician. Patients with a change in antihypertensive therapy during the last six months were included in this study. The single most important reason for the change in therapy was inadequate blood pressure control (48.4%), followed by adverse effects (30.1%), patient dissatisfaction (20.0%), non-compliance (16.8%) and cost (4.9%). The most frequent adverse effects noted by the doctors were cough (51.9%), oedema (36.9%), flush (36.6) and dizziness (27.8%). In comparing the answers of the physicians and patients, it becomes obvious that compliance may be overestimated by the doctors (good: 41.7%; medium: 57.3%; bad: 1.0%), since only 32.3% of the patients stated that they never missed a dose, 54.8% were occasionally non-compliant and 12.9% admitted missing a dose frequently. The predominant reasons for non-compliance (assessed by the patients) were forgetfulness (40.4%), followed by adverse effects (9.6%) and irregular lifestyle (6.5%). Thus, lack of effectiveness and adverse effects/patient dissatisfaction/non-compliance contributed roughly equally to the decision to change therapy. In addition, forgetfulness was shown to be an important contributor to suboptimal compliance. Lastly, physicians may still underestimate the extent of non-compliance.