Evaluation of anaerobic performance capacity by the isokinetic Ariel computerized exercise system-reliability and validity.

The present study examines the reproducibility and validity of computerized muscle strength and endurance evaluation protocols using the Ariel Computerized Exercise System (ACE). Since the ACE has only recently become commercially available, there are no published normative data for various exercises, nor are the measurements' accuracy and validity for the various exercise protocols documented. Twenty males (17 to 30 years old) performed a set of isokinetic maximal leg and arm exercises on the ACE Multi Function Unit twice on 2 separate days. Test-retest correlation coefficient ranged from 0.44 (bench press) to 0.91 (bench pull and leg extension flexion). Thirty additional male subjects (16 to 31 years old) performed, on 2 separate days, the Wingate Anaerobic Test (WAnT) (leg), and various force and endurance leg exercises (squat) on the ACE. Correlation coefficients of the various performance indices between the 2 test systems ranged from -0.02 to 0.23. The results obtained on the ACE indicate moderate to high reproducibility and low concurrent validity with WAnT.     

Modulation of the macrophage respiratory burst by an acidic environment: the critical role of cytoplasmic pH regulation by proton extrusion pumps

Within the acidic milieu of an abscess or tumor, macrophages must be able to maintain their cytoplasmic pH (pHi) close to the physiologic range to ensure optimal cell function. Our recent studies have demonstrated that a proton-extrusion mechanism with the characteristics of an H+ adenosine triphosphatase mediates pHi recovery in acid-loaded macrophages. These studies were designed to examine the role of these H+ pumps in maintaining cell function in an acidic extracellular environment. Peritoneal macrophages were tested for superoxide production in response to phorbol myristate acetate at either physiologic or acidic extracellular pH (pHo; 7.35 or 6.70, respectively). pHi was measured with the fluorescent dye 2',7'-biscarboxy-ethyl-5(6)-carboxy-fluorescein. Bafilomycin A1, a specific H+ adenosine triphosphatase inhibitor, was used to examine the contribution of the H+ pump to pHi regulation and cell function. At pHo 7.35, bafilomycin A1 had no effect on pHi or phorbol myristate acetate-stimulated superoxide production. However, at pHo 6.70, bafilomycin A1 reduced pHi to 6.61 +/- 0.01 versus 6.79 +/- 0.01 in control cells (p less than 0.001) and caused a concomitant reduction in superoxide production to 4.8 +/- 1.2 versus 13.0 +/- 1.2 nmol/10(6) cells/40 min in control cells (p less than 0.001). To determine whether the observed reduction in superoxide formation was the result of the pHi reduction, superoxide production was measured in cells whose pHi was pharmacologically clamped at various levels according to the K+/nigericin method. Lowering pHi from 6.80 to 6.60 caused a significant reduction in superoxide production from 13.1 +/- 1.8 to 7.5 +/- 0.9 nmol/10(6) cells/40 min (p less than 0.01). Thus H+ extrusion pumps are important to maintenance of macrophage pHi at low pHo, permitting continued superoxide production under these conditions. By keeping pHi close to the physiologic range, these pumps serve to optimize cell function in an acidic extracellular environment.     

Cancer survival in Estonian migrants to Sweden.

OBJECTIVE: To quantify the eventual extra loss of life incurred to cancer patients in Estonia compared with those in Sweden that was possibly attributable to differences in society. DESIGN: Population based survival of cancer patients in Estonia was compared with that of Estonian immigrants to Sweden and that of all cancer patients in Sweden. The cancer sites studied were female breast and ovary, male lung and prostate, and male and female stomach and colon. SETTING: Data on incident cases of cancer were obtained from the population based Swedish and Estonian cancer registries. PARTICIPANTS: Data from Estonian patients in Sweden, Estonian patients in Estonia, and patients from the total Swedish population were included in the study. MAIN RESULTS: Differences in survival among the three populations, controlling for follow-up time and age at diagnosis, were observed in breast, colon, lung, ovarian, and prostate cancers. The survival rates of Estonians living in Sweden and the total population of Sweden were better than that of the Estonians living in Estonia. For cancers of the breast and prostate, the excess mortality in the older age group (75 and above) was much greater in Estonia than in the other populations. CONCLUSIONS: Most differences in cancer survival between Estonian and Swedish populations studied could be attributed to a longer delay in diagnosis, and also to inferior treatment (including access to treatment) in Estonia compared with Sweden. Estonia's lag in socioeconomic development, particularly in its public health organisation and funding, is probably the main source of the differences observed.     

Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients

A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due toCandida glabrata orCandida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p=0.39; one-sided 95% Cl, –8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p=0.66: one-sided 95% Cl, –12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p=0.52; chi-square test) and remained similar throughout the course of follow-up. Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.     

Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity

Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which permits continued menstrual cyclicity but alters gonadal- reproductive tract activity, was established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and amenorrhoea. A chronic low-dose regimen of the antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.      

Microbiologic features and treatment of persistent peritonitis in patients in the intensive care unit

The charts of 25 patients who died in the intensive care unit of persistent peritonitis after abdominal operations were reviewed to determine the microbial flora and the efficacy of antibiotic treatment. All patients had undergone two or more surgical procedures for abdominal sepsis and 23 had at least three-system organ failure. The most common organisms cultured were: Staphylococcus epidermidis, 24 cultures from 16 patients, Candida albicans, 19 cultures from 10 patients, Pseudomonas aeruginosa, 16 cultures from 12 patients, Enterobacter, 16 cultures from 8 patients and enterococcus, 14 cultures from 8 patients. The classic isolates, Escherichia coli (11 cultures from six patients) and Bacteroides fragilis (4 cultures from three patients) were found infrequently. To determine the adequacy of antimicrobial therapy for this "new" flora, we examined the ability of appropriate agents to eradicate the micro-organism upon subsequent culture. Candida sp. were eradicated in 54% (6 of 11) of the assessable cases, while enterococcus and S. epidermidis were cleared in only 25% and 28% respectively. The spectrum of intra-abdominal organisms cultured from critically ill surgical patients in the intensive care unit differs from that seen in those with acute peritonitis. Despite administration of appropriate antimicrobial agents, these organisms tend to persist, probably reflecting impaired host defences with multiple-system organ failure rather than antimicrobial failure.     

Reciprocal synergy between Escherichia coli and Bacteroides fragilis in an intra-abdominal infection model

The synergic relationship between Escherichia coli and Bacteroides fragilis was examined in a model of intra-abdominal abscess formation. The addition of B. fragilis to E. coli in the fibrin clot inoculum increased abscess weight and residual numbers of E. coli in the abscess at 7 days. In a reciprocal fashion, E. coli was capable of enhancing B. fragilis persistence in abscesses. Neither heat-killed E. coli nor heat-killed B. fragilis was able to mimic the synergic effect of its live counterpart. Furthermore, B. fragilis culture filtrate was unable to reproduce the ability of live B. fragilis to act synergically with E. coli. For B. fragilis to act synergically with E. coli, it had to be inoculated locally with E. coli in the peritoneal cavity, indicating that an effect on systemic resistance by B. fragilis was an unlikely mechanism for the production of bacterial synergy. These studies suggest that the synergic relationship between bacteria in polymicrobial infections is a complex one, resulting from intimate interactions between bacteria and the host in the local milieu of the infection.