Comparison of ceftibuten once daily and amoxicillin-clavulanate three times daily in the treatment of acute exacerbations of chronic bronchitis

In medical practice, antibiotics are generally given empirically for the treatment of acute exacerbations of chronic bronchitis (AECB). To be effective, antibiotic therapy should be broad in spectrum, and it should also cover the common beta-lactamase-producing pathogens. In this multicenter, randomized, investigator-masked study, 469 patients with AECB were randomized (in a ratio of 2:1) to receive 400-mg oral ceftibuten capsules once daily or 500-mg amoxicillin-clavulanate tablets three times daily for 5 to 15 days. Patients receiving ceftibuten were further divided into those who took the capsule with a meal (fed) and those who took the capsule 1 hour before a meal (fasted). Clinical and microbiologic responses were evaluated after treatment at 0 to 6 days (end of treatment) and 7 to 21 days (follow-up). Overall clinical success was determined by cure/improvement of signs and symptoms of AECB at the end of treatment and at follow-up. Overall microbiologic assessment was graded as eradication, persistence, relapse, reinfection, colonization, superinfection, or unassessable. Tolerability was evaluated by grading observed adverse events. The mean duration of treatment was 10.4 days for patients who received ceftibuten and 10.1 days for patients who received amoxicillin-clavulanate. A total of 252 patients receiving ceftibuten and 117 patients receiving amoxicillin-clavulanate were evaluable for clinical efficacy, and 55 patients were evaluable for microbiologic response. Both treatments improved the signs and symptoms of bronchitis, and overall clinical success rates were equivalent for patients treated with ceftibuten (211 of 252 [84%]) and amoxicillin-clavulanate (93 of 117 [79%]) (95% confidence interval [CI], -4.5% to 13.6%). Overall microbiologic eradication rates were also similar for patients treated with ceftibuten (36 of 37 [97%]) and amoxicillin-clavulanate (12 of 14 [86%]) (95% CI, -5.2% to 21.2%). The most frequently reported treatment-related adverse events were gastrointestinal disturbances, which occurred in 15% (47 of 316) and 24% (36 of 152) of patients treated with ceftibuten and amoxicillin-clavulanate, respectively. No significant difference was observed in the ceftibutenfed and ceftibuten-fasted groups in overall clinical assessments of the clinical efficacy population and safety population. In conclusion, 400 mg oral ceftibuten once daily has a similar clinical success rate to 500 mg amoxicillin-clavulanate three times daily, with a trend toward fewer gastrointestinal side effects, in the treatment of patients with AECB.     

Five-day cefdinir treatment for streptococcal pharyngitis. Cefdinir Pharyngitis Study Group

A multicenter, randomized, controlled, investigator-blind study was performed to evaluate the safety and efficacy of oral cefdinir versus oral penicillin V for the treatment of pharyngitis due to group A beta-hemolytic streptococci (GABHS). Patients 13 years of age and older were randomized to receive either oral cefdinir (300 mg twice a day) for 5 days followed by placebo for 5 days or oral penicillin V (250 mg four times a day) for 10 days. Throat cultures were obtained, and signs and symptoms of pharyngitis were recorded at study admission and follow-up visits on study days 11 to 15, 16 to 20, and 25 to 31. Patients kept a diary to record medication intake and their assessment of throat pain at admission and at each day of study treatment. Five hundred fifty-eight patients were enrolled, of whom 432 (77.4%) were clinically and microbiologically evaluable. The GABHS eradication rates 5 to 10 days after completion of therapy were 193 of 218 (88.5%) in the cefdinir group and 176 of 214 (82.2%) in the penicillin group (P = 0.053). Clinical cure rates were 89.0 and 84.6%, respectively (P = 0.80). By the time of the long-term follow-up visit, 2 to 3 weeks after completion of treatment, 156 of 191 (81.7%) of the assessable cefdinir patients and 152 of 195 (77.9%) of the penicillin patients remained free of GABHS. Both treatments were well tolerated, with adverse reaction rates of 18.3% in the cefdinir study arm and 15.0% in the penicillin study arm (P = 0.278). Five-day treatment with cefdinir is safe and effective therapy for GABHS pharyngitis. Based on its twice-a-day dosage and shorter course of therapy, leading to potentially greater patient compliance, cefdinir may be considered for use in the treatment of pharyngitis caused by GABHS.     

Comparative effectiveness and safety of cefdinir and amoxicillin-clavulanate in treatment of acute community-acquired bacterial sinusitis. Cefdinir Sinusitis Study Group

Cefdinir is an extended-spectrum oral cephalosporin that is active against pathogens commonly seen in acute community-acquired bacterial sinusitis (ACABS), including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Two randomized, investigator-blind, multicenter trials (one in the United States and one in Europe) compared two dosage regimens of cefdinir (600 mg once a day for 10 days and 300 mg twice a day for 10 days) to amoxicillin-clavulanate (A-C) (500 mg three times a day for 10 days) for adult and adolescent patients with ACABS. Twelve hundred twenty-nine patients entered the U.S. study, 698 with antral puncture; 569 patients entered the European study, all with antral puncture. Clinical response (cure or improvement) was determined 7 to 14 days and 3 to 5 weeks posttherapy. Microbiologic eradication rates were determined 10 to 30 days posttherapy in a subset of patients who underwent pre- and posttherapy sinus aspirate culture. Rates of adverse events and treatment discontinuations due to adverse events were examined. Cefdinir, given once or twice daily, was as effective clinically (approximately 90% cure rate) as amoxicillin-clavulanate given three times daily in the treatment of ACABS. Microbiologic eradication rates were also similar in the three groups. The major side effect was mild diarrhea, occurring in approximately 20% of each group. Cefdinir caused fewer adverse events requiring treatment discontinuation.     

Management of acute otitis media caused by resistant pneumococci in infants

OBJECTIVES: To assess the clinical outcome and risk of failure after oral vs. intravenous treatment in otitis media caused by penicillin-resistant pneumococci. To determine the possible correlations between pneumococcal minimal inhibitory concentration (MIC) to penicillin and clinical outcome. DESIGN: Retrospective study of 156 cases collected between 1993 and 1995. Mean follow-up: 5 months. Setting. Two tertiary academic medical centers in Paris, France. PATIENTS AND METHODS: Pneumococcus was isolated from 191 of 570 ear samples obtained from children with otitis media and shown to be penicillin-resistant in 156. Medical history, antibiotic therapy during the previous 3 months and day-care center attendance were reviewed. For the current episode microbiologic characteristics of the isolated strains, type of treatment, therapy efficacy and clinical outcome were analyzed. Patients were predominantly young (76.3% were <1 year old) and bacteriologic samples were taken mainly because of previous treatment failure. RESULTS: Among 156 children with pneumococcal penicillin-resistant otitis media, 72.2% attended day-care centers, 71.8% had been previously treated with aminopenicillin and 52.5% with cephalosporins. Failure of previous empirical oral therapy was noted in 84% (one-third of these had been receiving amoxicillin-clavulanate). Patients treated intravenously had had a more protracted otitis but no greater number of previous episodes of acute otitis media than those receiving oral therapy. Acute mastoiditis occurred in 4 infants resulting in mastoidectomy. Oral treatment (mainly with high dose amoxicillin,120 to 150 mg/kg/day) and intravenous therapy (cephalosporin or glycopeptide) had been used in 59 and 41%, respectively. Mean duration of therapy was 10.7 days. Three failures (1.9%) and 10 recurrences (6.4%, average 28 days) occurred. No statistical difference was found between intravenous and oral therapy with respect to risk of recurrence. A high penicillin MIC value was correlated with previous antibiotic treatment but not with clinical outcome. CONCLUSIONS: Oral therapy appears to be as effective as intravenous therapy for the treatment of penicillin-resistant pneumococcal otitis media. Intravenous treatment should not necessarily be dictated by the penicillin susceptibility value but should be considered in cases of failure to thrive, persistent otitis or other complications.     

Unsatisfactory results of a first-generation modular femoral stem implanted without cement. A 4- to 9-year follow-up study

In a attempt to clarify the effects of methylprednisolone pulse therapy on the insidious (subacute) type of crescentic glomerulonephritis with slow, but steady deterioration of renal function and poor response to treatment, we analyzed the clinical course of 24 patients (male:female = 15:9) with a mean age of 48.5 years. They fulfilled the following criteria: 1) crescents were observed in more than 50% of the glomeruli, 2) the increment of serum creatinine (Cr) could be determined sequentially on three or more occasions before treatment, and reciprocals of serum Cr declined with slopes of less than 1.0 x 10(-2) dl/mg/day, 3) corticosteroids and/or immunosuppressants were administered. The patients were divided into two groups: pulse therapy group (P) (15 patients), to which methylprednisolone 500 or 1,000 mg a day was administered intravenously for three consecutive days, and a conventional therapy group (C) (9 patients). There were no differences between groups P and C in clinical parameters, including sex, age, underlying diseases, urinary protein, blood pressure, serum Cr and slope of 1/Cr before treatment, and pathological findings, including percentages of glomeruli with crescents and degree of interstitial lesions. However, improvement of serum Cr, which was defined as a decline to the normal range or less than half of the pretreatment level, was observed in 9 (60%) in group P vs. only 1 (11%) in group C (p < 0.05). Re-biopsies were performed after treatment in 6 patients of group P with an improvement of serum Cr, and showed a decrease in the rate of crescent formation and almost complete loss of cellular crescents. At 1, 2 and 3 years follow-up, the renal survival rates were 86, 70 and 53%, respectively, in group P vs. 67, 14 and 14% respectively, in group C (p < 0.05). No serious side effects were observed in group P. These results suggest that methylprednisolone pulse therapy may be very effective for the insidious type of crescentic glomerulonephritis.     

Temporal changes in the care and outcomes of elderly patients with acute myocardial infarction, 1987 through 1990

OBJECTIVE: To investigate changes between 1987 and 1990 in the care and outcomes associated with acute myocardial infarction (AMI) in elderly patients. DESIGN: Retrospective cohort study using a longitudinal database created from Medicare administrative files. PATIENTS: Cohorts comprising a total of 856,847 AMI patients insured by Medicare between 1987 and 1990. MAIN OUTCOME MEASURES: Annual rates of mortality at 30 days and 1 year following AMI, and the use of coronary angiography, coronary artery bypass graft surgery, and percutaneous transluminal coronary angioplasty during the first 90 days after a new AMI. RESULTS: Between 1987 and 1990, mortality rates decreased 10% overall from 26% to 23% at 30 days (P < .001) and from 40% to 36% at 1 year following AMI (P < .001). Declines in mortality and adjusted risks of 1-year mortality were similar in men and women and in blacks and whites, but mortality declines were more evident in those younger than 85 years. Meanwhile, the proportion of elderly AMI patients having angiography within the first 90 days after their index admission increased from 24% to 33% (P < .001); proportions increased for both genders and all races. The proportion of patients undergoing revascularization procedures increased from 13% to 21%; while rates of bypass surgery increased from 8% to 11%, rates of angioplasty doubled from 5% to 10% (all P < .001). CONCLUSIONS: Between 1987 and 1990, survival of elderly patients following AMI improved significantly. While changes in patient treatment may be responsible, the increased use of thrombolytic therapy appears to be only a partial explanation. Also, while the use of coronary angiography and revascularization procedures increased dramatically, the degree to which it caused the improvement in survival could not be determined.     

Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin

Following intravaginal inoculation of progesterone-treated outbred mice with Chlamydia trachomatis MoPn, 4 to 6 log10 inclusion-forming units were recovered in vaginal swabs for 21 days but all animals were culture negative after 28 days. Serum antibody titers were elevated and remained high for at least 70 days. Between 28 and 70 days, upper tract infection (inflammation and distension of the uterine horns, occlusion of oviducts with inflammatory exudate, pyosalpinx, and hydrosalpinx) was seen in > 80% of the animals. Mice were dosed orally, commencing at 7 days after infection, with minocycline, doxycycline, or amoxicillin-clavulanate. Further groups received azithromycin either as a single high dose or as lower once-daily doses. In addition, minocycline and amoxicillin-clavulanate were administered at 24 h after infection, and this early treatment prevented elevation of antibody titers whereas delayed therapy did not. Vaginal swabs from mice in all treatment regimens were culture negative except for 25% of mice receiving either early amoxicillin-clavulanate or low-dose azithromycin, which yielded low numbers (20 to 70 inclusion-forming units) of chlamydiae. Numbers of fertile mice in the early treatment regimens and their litter sizes were similar to those of noninfected controls, although 25% of amoxicillin-clavulanate-treated mice had unilateral hydrosalpinges. In comparison, 88% of untreated mice developed hydrosalpinges and only 25% conceived. Delayed dosing did not affect the outcome of amoxicillin-clavulanate therapy but did diminish the protective efficacy of minocycline such that 50% of treated mice had either unilateral hydrosalpinges or ovarian abscesses. Doxycycline and azithromycin were highly effective in restoring fertility. This model makes possible the study of both short- and long-term outcomes of chlamydial infection.     

Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions

A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy with liquid suspension fluconazole (100 mg once daily) or liquid nystatin (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients were clinically cured, as opposed to 52% in the nystatin-treated group (P < .001). Fluconazole eradicated Candida organisms from the oral flora in 60%, vs. a 6% eradication rate with nystatin (P < .001). The fluconazole group had fewer relapses noted on day 28 (18%, vs. 44% in the nystatin group; P < .001). This relapse difference no longer existed by day 42. Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral candidiasis in HIV-infected patients and provided a longer disease-free interval before relapse.     

Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease

PURPOSE: To evaluate in a randomized trial the impact of three versus six cycles of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) chemotherapy in favorable-prognosis and CVPP versus doxorubicin, vincristine, prednisone, and etoposide (AOPE) plus involved-field radiotherapy (RT) in intermediate-prognosis previously untreated Hodgkin's disease. PATIENTS AND METHODS: Of 256 patients evaluated, 80 with a favorable prognosis according to a prognostic index designed by the Grupo Argentina de Tratamiento de Leucemia Aguda (GATLA) were randomized to three versus six cycles of CVPP without RT and 176 with intermediate risk to CVPP versus AOPE, both for six cycles with RT between the third and fourth cycles of 30 Gy to the involved areas at diagnosis. CVPP consisted of intravenous (I.V.) cyclophosphamide and vinblastine on days 1 and 8, and oral procarbazine and prednisone on days 1 to 14, every 28 days. AOPE consisted of I.V. doxorubicin and vincristine on day 1, oral prednisone on days 1 to 5, and I.V. etoposide on days 1 and 3, every 28 days. RESULTS: Complete remission was obtained in 39 of 41 (95%) patients treated with three cycles of CVPP and 36 of 39 (92%) treated with six cycles in the favorable-risk group (difference not significant [NS]). In the intermediate-risk group, 89 of 92 (97%) treated with CVPP plus RT versus 75 of 84 (89%) treated with AOPE plus RT achieved a complete remission (P = .05). At 60 months, the event-free survival (EFS) and overall survival rates in the favorable-risk group were 80% and 91% for CVPP x 3 and 84% and 97% for CVPP x 6, respectively (P = NS). In the intermediate-risk group, 60-month EFS rate for CVPP plus RT was 85%, compared with 66% for AOPE plus RT (P = .009). The overall survival rate was 95% versus 87% respectively (P = .157). CONCLUSION: Three cycles of CVPP without RT are equally effective as six cycles in the favorable-risk group. However, in the intermediate-group, CVPP plus RT is superior to AOPE plus RT, with significantly fewer events before and after induction (P = .009), without a difference in overall survival.     

Lidocaine as a diluent for administration of benzathine penicillin G

OBJECTIVE: Benzathine penicillin G is recommended for secondary prophylaxis of rheumatic fever. Its main disadvantage is local pain and discomfort associated with the injection. Lidocaine as a diluent may reduce this discomfort. We compared the administration of benzathine penicillin G with two diluents; sterile water and lidocaine hydrochloride 1% for penicillin concentrations and pain of injection. DESIGN: In a randomized double blind, crossover trial, 18 children ages 11 to 19 years who required prophylactic treatment for rheumatic fever were randomly divided into two groups. One received an injection of benzathine penicillin G diluted with 3.2 ml of sterile water, followed 1 month later by an injection of benzathine penicillin G diluted in lidocaine hydrochloride 1%; the second group received the same regimen in the reverse order. Serum penicillin concentrations and subjective pain sensation were determined after each injection. RESULTS: Peak serum penicillin concentrations at 24 h after injection were similar for both preparations (0.100 microg/ml for water, 0.102 microg/ml for lidocaine), as were the other serum values measured throughout the month. After 28 days detectable concentrations (> or =0.020 microg/ml) were found in 44 and 291% of the subjects, respectively (P = 0.4). Urine penicillin concentrations on Day 28 were 1.81 +/- 0.25 and 2.31 +/- 0.25 microg/ml, respectively. The pain score immediately after the injection was significantly lower with the lidocaine than with the sterile water dilution. CONCLUSION: Use of lidocaine hydrochloride as a diluent for benzathine penicillin G does not change the penicillin concentration in body fluids and significantly reduces the pain of injection. We suggest the use of lidocaine hydrochloride 1% as a diluent for benzathine penicillin G.     

Pathogens isolated during treatment failures in otitis

OBJECTIVES: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure. METHODS: The study included 186 children with a mean age of 17.5 +/- 13.1 months. Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media. The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%). The average duration of antibiotic therapy was 6.9 +/- 2.65 days. Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid. RESULTS: One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates. In 60 children (32.3%) the culture of the ear pus was sterile. Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers. Thirty-six patients were infected by S. pneumoniae with penicillin MIC > or =1 mg/l. In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S. pneumoniae. Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively). Penicillin resistance was mainly associated with serogroups 23 and 14. CONCLUSIONS: Penicillin-resistant S. pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region.     

Risk profile of female sex workers who participate in a routine penicillin prophylaxis programme in Surabaya, Indonesia

We conducted a sexually transmitted disease (STD) prevalence survey of 1867 female sex workers in Surabaya, Indonesia, some of whom reported participation in a routine penicillin prophylaxis programme. In Surabaya, 34% of female sex workers had received a prophylactic penicillin injection programme from the government within 28 days. Sex workers who had received routine prophylaxis injection were more likely to be less educated, to work in brothel complexes, and to have more customers per week than other sex workers. The prevalence rates of syphilis, gonorrhoea, chlamydia, and trichomoniasis were higher among sex workers who received the routine penicillin treatment than among those who had not received antibiotic treatment in the last 28 days. However, after adjustment for age, education, fee per sex act, number of customers, and condom use in the previous 7 days, only trichomoniasis was still significantly different (adjusted odds ratio of 3.2). High-risk women were more likely to participate in the routine penicillin prophylaxis programme. The lack of a demonstrable individual-level protection from this prophylaxis treatment programme in this cross-sectional study appears due to differential uptake of penicillin prophylaxis by women at higher presumptive risk for STD. Randomized clinical trials and mathematical modelling, together with observational data such as presented here, all can contribute to optimal understanding of a complex intervention like mass chemoprophylaxis for STD among female sex workers.     

Staging endometrioid adenocarcinoma. Clinical and financial comparison of laparoscopic and traditional approaches

OBJECTIVE: To compare laparoscopically assisted surgical staging (LASS) of endometrioid adenocarcinoma with traditional surgical staging by laparotomy. STUDY DESIGN: A retrospective review of all cases of uterine cancer (n = 108) insured by one health maintenance organization during 1990-1995. During this period, 29 patients underwent successful LASS and were compared to 64 who underwent laparotomy for treatment of surgical stage I endometrioid adenocarcinoma. RESULTS: LASS was performed successfully in 29 of 32 attempted cases. All patients on whom LASS was attempted were found to have surgical stage I. Laparoscopic pelvic lymphadenectomy was highly successful, with no failures and a mean number of 14 nodes obtained. The overall complication rate was significantly higher for laparotomy than for LASS (28% vs. 7%, P < .001). The average length of stay for laparotomy was significantly higher than for LASS (5.1 vs. 2.3 days, P < .001). CONCLUSION: LASS for stage I endometrioid adenocarcinoma is an attractive alternative to traditional surgical staging. It causes fewer complications and shortens the hospital stay.     

Mortality differences between men and women following first myocardial infarction. RESCATE Investigators. Recursos Empleados en el Síndrome Coronario Agudo y Tiempo de Espera

CONTEXT: Mortality after acute myocardial infarction is worse in women than in men, even after adjustment for comorbidity and age dissimilarities between sexes. OBJECTIVE: To assess the influence of sex on survival after acute myocardial infarction. DESIGN: Inception cohort obtained in a prospective registry of patients with acute myocardial infarction from 1992 through 1994. SETTING: Four teaching hospitals in northeastern Spain. PATIENTS: All consecutive patients aged 80 years or younger with first acute myocardial infarction. A total of 331 women and 1129 men were included. MAIN OUTCOME MEASURE: Survival at 28 days and mortality or readmission at 6 months. RESULTS: Women were older (mean, 68.6 vs 60.1 years), presented more often with diabetes (52.9% vs 23.3%), hypertension (63.9% vs 42.3%), or previous angina (44.6% vs 37.4%), and developed more severe myocardial infarctions than men (acute pulmonary edema or cardiogenic shock occurred in 24.8% of women and 10.5% of men) (all P<.02). Men were more likely than women to receive thrombolytic therapy (41.3% vs 23.9%; P<.001), but rates of percutaneous transluminal angioplasty and coronary artery bypass graft surgery at 28 days were similar among men and women. The 28-day mortality rate was significantly higher among women (18.5% for women, 8.3% for men; P<.001). Revascularization procedures at 6 months were performed in a similar proportion of women and men. However, women had higher 6-month mortality rates (25.8% in women, 10.8% in men; P<.001) and readmission rates (23.3% for women, 12.2% for men; P<.001). After adjustment, women had greater risk of death than men at 28 days (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.12-2.65) and at 6 months (OR, 1.73; 95% CI, 1.18-2.52). CONCLUSIONS: In this study population, women experienced more lethal and severe first acute myocardial infarction than men, regardless of comorbidity, age, or previous angina.     

In vivo activities of amoxicillin and amoxicillin-clavulanate against Streptococcus pneumoniae: application to breakpoint determinations

The in vivo activities of amoxicillin and amoxicillin-clavulanate against 17 strains of Streptococcus pneumoniae with penicillin MICs of 0.12-8.0 mg/liter were assessed in a cyclophosphamide-induced neutropenic murine thigh infection model. Renal impairment was produced by administration of uranyl nitrate to prolong the amoxicillin half-life in the mice from 21 to 65 min, simulating human pharmacokinetics. Two hours after thigh infection with 10(5) to 10(6) CFU, groups of mice were treated with 7 mg of amoxicillin per kg of body weight alone or combined with clavulanate (ratio, 4:1) every 8 h for 1 and 4 days. There was an excellent correlation between the MIC of amoxicillin (0.03 to 5.6 mg/liter) and (i) the change in log10 CFU/thigh at 24 h and (ii) survival after 4 days of therapy. Organisms for which MICs were 2 mg/liter or less were killed at 1.4 to 4.2 and 1.6 to 4.1 log10 CFU/thigh at 24 h by amoxicillin and amoxicillin-clavulanate, respectively. The four strains for which MICs were >4 mg/liter grew 0.2 to 2.6 and 0.6 to 2. 3 logs at 24 h despite therapy with amoxicillin and amoxicillin-clavulanate, respectively. Infection was uniformly fatal by 72 h in untreated mice. Amoxicillin therapy resulted in no mortality with organisms for which MICs were 1 mg/liter or less, 20 to 40% mortality with organisms for which MICs were 2 mg/liter, and 80 to 100% mortality with organisms for which MICs were 4.0-5.6 mg/liter. Lower and higher doses (0.5, 2, and 20 mg/kg) of amoxicillin were studied against organisms for which MICs were near the breakpoint. These studies demonstrate that a reduction of 1 log10 or greater in CFU/thigh at 24 h is consistently observed when amoxicillin levels exceed the MIC for 25 to 30% of the dosing interval. These studies would support amoxicillin (and amoxicillin-clavulanate) MIC breakpoints of 1 mg/liter for susceptible, 2 mg/liter for intermediate, and 4 mg/liter for resistant strains of S. pneumoniae.     

Identification and treatment of leukocytospermia in couples with unexplained infertility

OBJECTIVE: To evaluate whether identifying men with leukocytospermia in couples with unexplained infertility and treating them with antibiotics improves pregnancy rates. STUDY DESIGN: A prospective, cohort study of men with and without leukocytospermia was identified on a smear of semen using Bryan-Leishman stain. Cumulative six-month pregnancy rates were determined for members of the leukocytospermic group who responded to treatment with resolution of their leukocytospermia on a semen smear, those who failed to respond to treatment, those not treated and those without leukocytospermia. RESULTS: Thirty-six of 53 men with leukocytospermia responded to antibiotic treatment, and 19 women in these 36 couples (53%) became pregnant within the six-month follow-up period. Only 7 of 17 (6%) of those who failed to respond to treatment had their partner become pregnant (P < .001). Partners of men with leukocytospermia and no treatment had a 6% pregnancy rate, and the women in 13% (5/42) of couples without leukocytospermia became pregnant (P < .001). CONCLUSION: Leukocytospermia exists in a significant number of males with unexplained infertility and normal semen analyses. Identifying and successfully treating such men results in a significant improvement in pregnancy rates. These men may be a subgroup with male infertility that can be identified and treated.     

Cryopreserved arterial allografts in the treatment of major vascular infection: a comparison with conventional surgical techniques

OBJECTIVE: Recent findings with cryopreserved heart valve allografts in the treatment of infectious endocarditis suggest that the use of cryopreserved arterial allografts may improve the outcome in patients with vascular infections. METHODS: Seventy-two patients with mycotic aneurysms (n = 29) or infected vascular prostheses (n = 43) of the thoracic (n = 26) or abdominal aorta (n = 46) were treated with in situ repair and extra-anatomic reconstruction using prosthetic material (n = 38) or implantation of a cryopreserved arterial allograft (n = 34). Disease-related survival and survival free of reoperation were assessed. Morbidity, cumulative lengths of intensive care, hospitalization, antibiotic treatment, and costs were calculated per year of follow-up. RESULTS: The use of cryopreserved arterial allografts was superior to conventional surgery in terms of disease-related survival (P =.008), disease-related survival free of reoperation (P =.0001), duration of intensive care per year of follow-up (median 1 vs 11 days; range 1 to 42 vs 2 to 120 days; P =.001), hospitalization (14 vs 30 days; range 7 to 150 vs 15 to 240 days; P =.002), duration of postoperative antibiotic therapy (21 vs 40 days; range 21 to 90 vs 60 to 365 days; P =.002), incidence of complications (24% vs 63%; P =.005), and elimination of infection (91% vs 53%; P =.001). In addition, costs were 40% lower in the group treated by allografts (P =.005). CONCLUSIONS: The use of cryopreserved arterial allografts is a more effective treatment for mycotic aneurysms and infected vascular prostheses than conventional surgical techniques.     

Homozygous and frequent deletion of proximal 8p sequences in human prostate cancers: identification of a potential tumor suppressor gene site

The mechanisms for hair cell recovery were investigated after intraortic application of 50 microg gentamicin into the perilymphatic space of the superior semicircular canal of the chinchilla. Histologic evaluation of one normal group and four posttreatment groups (7, 14, 28, and 56 days) was made with light and transmission electron microscopic techniques. The numeric changes of hair cells and supporting cells was quantified with the dissector technique. At 7 and 14 days after treatment, no type I hair cells were present, and 85% and 88% of type II hair cells were lost. Supporting cells decreased to 76% at 7 days, but they recovered to 91% at 14 days. Recovery of the epithelia was evident 28 days after treatment; 83% were type II hair cells, and 3% were type I hair cells. The supporting cell number remained close to normal (86%). Between 14 and 28 days after treatment, there was an increase of 1758 of type II hair cells, representing approximately 125 new hair cells per day. At the same time interval the number of supporting cells remained near normal. These results suggest that new hair cells might be the result of supporting cell mitotic division and differentiation.     

Human and clinical perspectives on leptin

The neurochemical coding of neurones located in ganglia of the nerve trunk accompanying the chicken ureter was analysed and quantified using NADPH-diaphorase reactivity and immunohistochemistry against tyrosine hydroxylase (TH), nitric oxide synthase (NOS), calbindin (CAL), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and calcitonin gene-related peptide (CGRP) in untreated or colchicine-treated preparation. Almost all neurones were either positive for TH (38%) or for SOM (60%). Only 4% of the neurones were both TH- and SOM-positive and 3% of the neurones exhibited neither TH nor SOM immunoreactivity. The relative numbers of NPY-, NOS-, CAL- and VIP-positive neurones were 57%, 28%, 14% and 7%, respectively. No SP- or CGRP-positive neurones were observed. All NADPH-diaphorase-positive neurones expressed NOS immunoreactivity. Only in some TH-positive neurones was NPY and/or NOS found. Four major subpopulations were found in the ureteric ganglia. The SOM-positive neurones were subdivided into SOM/NPY/NOS- (28% of all neurones), SOM/NPY- (18%) and SOM/CAL/NPY-positive neurones (14%). A subpopulation of these peptid- ergic neurones also contained VIP. About 35% of the neurones contained TH only. Neurones of all subpopulations (72% of the neurones), except most of the CAL-positive neurones, were encircled by dense plexus of varicose SP/CGRP-positive, presumably sensory nerve fibres. Dense plexus of VIP-positive fibres were observed around 89% of the neurones. The chemical coding of the neuronal subpopulations identified in the ganglia accompanying the chicken ureter resembled that observed in the ganglia of Remak's nerve but was remarkably different from that of the autonomic neurones described in mammalian species.     

New one-week, low-dose triple therapy for the treatment of duodenal ulcer with Helicobacter pylori infection

BACKGROUND: Antimicrobial therapy is the recommended treatment for duodenal ulcer associated with Helicobacter pylori infection. The eradication of bismuth-based triple therapy with bismuth subcitrate, metronidazole and amoxicillin is limited by low compliance, drug resistance and side-effects. Two-week proton pump inhibitor (PPI)-based triple therapy has a higher eradication rate but is costly. This study was designed to compare the efficacy, patient compliance and cost of short-term PPI-based triple therapy with those of bismuth-based triple therapy. METHODS: Ninety patients with active duodenal ulcer disease and H pylori infection, proven with the 13C-urea breath test and CLO test (Campylobacter-like organism test) were treated randomly in three therapeutic groups: Group A, DeNol 120 mg, amoxicillin 500 mg and metronidazole 250 mg four times a day orally for 14 days; Group B, omeprazole 20 mg plus clarithromycin 500 mg twice a day and amoxicillin 500 mg four times a day for 14 days; Group C, omeprazole 20 mg, clarithromycin 250 mg and metronidazole 500 mg twice a day for seven days. Nizatidine 150 mg twice a day was given continuously following the end of anti-H pylori therapy for each group. Two months later, endoscopy, the CLO test and 13C-urea breath test were repeated to assess the eradication rate of H pylori and the ulcer-healing rate. Drug tolerance was evaluated by patients themselves by daily recording of any side-effects. RESULTS: Eighty-four patients completed the entire course of therapy and evaluation for H pylori infection. The H pylori eradication rates in Groups A, B and C were 75% (21/28), 93% (26/28) and 89% (25/28), respectively (p = 0.466). The ulcer healing rate was 86% (24/28) in Group A and 89% (25/28) in Groups B and C (p = 0.764). A total of 74 patients (88%) were free from symptoms at the end of the triple therapy. Symptom relief was faster in patients with PPI-based triple therapy (Groups B and C) (days 3 and 4) than for patients with bismuth-based triple therapy (day 5). The cost of Group C therapy was lower than that for Groups A and B. There were no major side-effects in any of the patients. CONCLUSIONS: One-week triple therapy with omeprazole, clarithromycin and metronidazole is highly effected for the eradication of H pylori. A therapeutic regime of one week's duration with lower cost, good compliance and mild side-effects may offer a good choice for treatment of duodenal ulcer associated with H pylori infection in clinical practice.