Common bile duct stones: an unusual case of diarrhoea through a mucous fistula.

We present a very unusual case of diarrhoea in a 77-year-old man. He had a previously complicated surgical history, with a loop ileostomy and a colonic mucous fistula. He developed a sudden onset of diarrhoea from his mucous fistula. A contrast enema suggested a cholecystocolonic fistula and subsequent computed tomography demonstrated a common bile duct stone caused a degree of obstruction. The patient was treated successfully by endoscopic retrograde cholangiopancreatography and stone extraction. This case demonstrated the role that contrast enema may still play in unusual cases of diarrhoea.

Orexin-A, an hypothalamic peptide with analgesic properties.

The hypothalamic peptide orexin-A and the orexin-1 receptor are localized in areas of the brain and spinal cord associated with nociceptive processing. In the present study, localization was confirmed in the spinal cord and demonstrated in the dorsal root ganglion for both orexin-A and the orexin-1 receptor. The link with nociception was extended when orexin-A was shown to be analgesic when given i.v. but not s.c. in mouse and rat models of nociception and hyperalgesia. The efficacy of orexin-A was similar to that of morphine in the 50 degrees C hotplate test and the carrageenan-induced thermal hyperalgesia test. However, involvement of the opiate system in these effects was ruled out as they were blocked by the orexin-1 receptor antagonist SB-334867 but not naloxone. Orexin-1 receptor antagonists had no effect in acute nociceptive tests but under particular inflammatory conditions were pro-hyperalgesic, suggesting a tonic inhibitory orexin drive in these circumstances. These data demonstrate that the orexinergic system has a potential role in the modulation of nociceptive transmission.

Out-patient and home-parenteral antibiotic therapy (OHPAT): evaluation of the impact of one year's experience in Tayside.

OBJECTIVE: An out-patient and home parenteral antibiotic therapy programme for the treatment of suitable infections was developed over a four year period. This paper describes the impact of one year's experience of its implementation on various measures of outcome. DESIGN: Each patient treatment has a full integrated care pathway (ICP) and patient satisfaction questionnaire completed. The ICP documents the clinical progress of the patient and incorporates various measures of quality of care on the 101 number of patients treated from April 1998 to March 1999 are presented here. SETTING: Dundee Teaching Hospitals NHS Trust (now Tayside University Hospitals NHS Trust). SUBJECTS: Patients with a range of infections requiring intravenous antibiotics. MAIN MEASURES: Number of patients treated with various infections, clinical and microbiological outcome, drug and vascular access complication rates, impact on drug costs and in-patient bed days, and measurement of patient satisfaction/quality of life. RESULTS: Patients were treated over a 12 month period. 51.5 per cent had skin & soft tissue infections and 22.8 per cent bone & joint sepsis. 57 per cent of patients received out-patient and 34 per cent self or carer administered home therapy. Ninety-four per cent of patients were cured or improved following treatment. Only 7.5 per cent of patients required an unscheduled admission to hospital. Twelve per cent of patients had some type of vascular device related adverse event (partly due to a faulty batch of lines) and six per cent of patients had a drug related reaction. The additional daily cost of drugs was minimal (< 12 Pounds/day) and more than 1,461 bed days have been saved across the Directorates. The patient satisfaction level was high.

Cost-effectiveness of vitamin E therapy in the treatment of patients with angiographically proven coronary narrowing (CHAOS trial). Cambridge Heart Antioxidant Study.

Epidemiologic studies have suggested that vitamin E (alpha-tocopherol) may play a preventive role in reducing the incidence of atherosclerosis. The aim of this paper was to conduct a cost-effectiveness analysis of vitamin E supplementation in patients with coronary artery disease using data from the Cambridge Heart Antioxidant Study (CHAOS). The study compared cost-effectiveness in the context of Australian and United States (US) health care utilization. The main clinical outcome used in the economic evaluation was the incidence of acute myocardial infarction (AMI) which was nonfatal. Utilization of health care resources was estimated by conducting a survey of Australian clinicians and published Australian and US cost data. Cost savings of $127 (A$181) and $578/patient randomized to vitamin E therapy compared with patients receiving placebo were found for Australian and US settings, respectively. Savings in the vitamin E group were due primarily to reduction in hospital admissions for AMI. This occurred because the vitamin E group had a 4.4% lower absolute risk of AMI than did the placebo group. Less than 10% of health care costs in the Australian evaluation was due to vitamin E ($150 [A$214/patient]). Our economic evaluation indicates that vitamin E therapy in patients with angiographically proven atherosclerosis is cost-effective in the Australian and US settings.

The identification of novel gene sequences of the human adult testis.

To facilitate the characterization of genetic expression in human adult testis, expressed sequence tag analysis of cDNAs from this tissue has been undertaken. Over 180 kb of DNA sequence has been determined and used to search the GenBank database. The results from the first 359 cDNA clones analyzed indicate that the sequences could be sorted into several categories with a high proportion being novel. Twenty-five clones (7%) showed 100% identity with human genes, 11 (3%) with prokaryotic sequences, 21 (5%) with between 60 and 95% similarity to human genes, 27 (8%) with between 60 and 95% similarity to genes from other species, and 33 (9%) with matches to human repeat sequences. Two hundred forty-two (67%) showed no significant matches and thus are likely to represent novel transcripts. In comparison to similar studies on human brain tissue and a hepatoma cell line, the findings indicate that the matches in the testis transcript population appear to be identifying a different spectrum of gene sequences.

Efficacy of temafloxacin versus ciprofloxacin or amoxicillin for lower respiratory tract infections in smokers and the elderly.

The purpose of this study was to determine the effects of smoking history and age on the efficacy and safety of temafloxacin versus ciprofloxacin or amoxicillin in patients with lower respiratory tract infections (LRTIs). Data were pooled from six clinical trials designed to evaluate the efficacy and safety of temafloxacin in bacterial infections of the lower respiratory tract. Patients were selected for this analysis based on smoking history (n = 256) and age (greater than or equal to 65 years of age [n = 328]). Results in the smoker and elderly subgroups were compared between treatment groups and with those in nonsmoker and nonelderly subgroups. Temafloxacin 300 mg or 600 mg b.i.d., ciprofloxacin 500 mg or 750 mg b.i.d., or amoxicillin 500 mg t.i.d. was administered orally for 7-14 days. Patients were assessed at enrollment, on study days 3-7, 24-72 hours post-treatment, and at 5-9 days post-treatment. Temafloxacin and the reference drugs demonstrated comparable clinical efficacy for treatment of LRTI in smokers (93.7% and 92.5%, respectively) and the elderly (94.6% and 89.3%, respectively). However, eradication of baseline pathogens in individual patients was significantly more common after temafloxacin therapy than that following treatment with the reference drugs in both smokers (99.2% versus 91.2%, p = 0.006) and elderly patients (97.5% versus 91.5%, p = 0.028). Overall, eradication rates for pretreatment pathogens were also significantly higher in smokers (99.3% versus 91.8%, p = 0.006) and in the elderly (97.8% versus 92.3%, p = 0.027). Neither age nor smoking status had a consistent effect on the rate of premature discontinuation of study drugs. Adverse events occurred at a similar rate between treatment groups in the elderly and in the smokers. Temafloxacin appears to be a promising alternative to therapy with either ciprofloxacin or amoxicillin in the treatment of respiratory infections in high-risk patients, smokers, and the elderly.

Comparative study of clindamycin, imipenem, oxacillin and vancomycin in the infected granuloma pouch model.

In a rat granuloma pouch model, Staphylococcus aureus infection was treated with clindamycin, oxacillin or vancomycin and Bacteroides fragilis infection with clindamycin or imipenem. The model simulates a subcutaneous abscess and has the advantage of permitting frequent sampling of exudate for bacterial counts and antibiotic levels in the same animal. In staphylococcal infection all drugs reduced the bacterial counts in the infected pouch by 1-1.7 log, with a significant effect lasting for 3 h after the last injection. A 1.06-1.4 log reduction lasted for 24 h with clindamycin and oxacillin, but there was only an 0.3 log reduction at 24 h with vancomycin. The ratio of the drug concentration in the infected pouch to the MIC was highest with clindamycin (2.3) compared to oxacillin (1.6) and vancomycin (0.8). With Bact. fragilis infection the bacterial counts dropped 1.5 log at 3 h after the last injection with clindamycin and imipenem. At 24 h the counts were reduced 1.0 log with clindamycin and 0.5 log with imipenem. The ratios of pouch fluid concentration to MIC was 7.6 and 4.08 for imipenem and clindamycin, respectively, at 3 h, and 1.0 and 2.3 for imipenem and clindamycin at 24 h.

Cost-benefit analysis of cephradine and mezlocillin prophylaxis for abdominal and vaginal hysterectomy.

Four hundred patients (300 abdominal and 100 vaginal hysterectomies) were randomized to receive a single, pre-operative intravenous injection of saline (placebo), 2 g cephradine or 5 g mezlocillin. The frequency of wound and pelvic infections was significantly reduced (P less than 0.05, chi 2- or Fisher's exact test) in the abdominal hysterectomy patients who received cephradine (16% vs 23% mezlocillin, 29% placebo) and in the vaginal hysterectomy patients who received cephradine or mezlocillin (0% mezlocillin, 6% cephradine vs 27% placebo). These results are similar to those of previous studies and suggest that prophylaxis is more effective for vaginal than for abdominal hysterectomy. However, a cost-benefit analysis supported the opposite conclusion. Cephradine prophylaxis for abdominal hysterectomy resulted in cost savings to the hospital and the community health services with measurable benefits to the patient. In contrast, cephradine or mezlocillin prophylaxis for vaginal hysterectomy resulted in increased costs to the hospital, no savings to community services and no significant benefit to the patient. We conclude that cost-benefit analysis provided valuable additional information to the conventional, statistical analysis of wound or pelvic infection rates.

Comparative efficacy of clindamycin, erythromycin and spiramycin against Staphylococcus aureus in the rat croton oil pouch model.

Spiramycin, a macrolide antibiotic, has inferior in-vitro activity to erythromycin, but superior tissue penetration. Recent publications have suggested that the in-vivo activity of spiramycin should be re-assessed. The efficacy of clindamycin, erythromycin and spiramycin was compared against Staphylococcus aureus infections in the rat croton oil pouch model. The concentration of spiramycin in the pouch fluid was lower than the concentration of clindamycin or erythromycin after single or multiple intraperitoneal injections. In contrast, the concentration of spiramycin in the pouch wall (73.3 +/- 14.5 micrograms/g) was markedly higher than that of erythromycin (less than 7.5 micrograms/g). Multiple doses of spiramycin had no significant effect upon bacterial growth in the pouch, whereas clindamycin and erythromycin had a significant bactericidal effect. The results suggest that spiramycin is bound to tissues, diffuses poorly into tissue fluid and may therefore be ineffective against infections in large collections of tissue fluid.

Dose response of experimental Pseudomonas endophthalmitis to ciprofloxacin, gentamicin, and imipenem: evidence for resistance to "late" treatment of infections.

Single intravitreal doses of ciprofloxacin, gentamicin, or imipenem were administered to rabbits with pseudomonas endophthalmitis for determination of the maximally effective dose. Treatment was given 24 hr ("early") or 48 hr ("late") after infection. With early treatment the dose-response relationship between the drug concentration and the diminution in bacterial counts in the vitreous humor was linear with all three drugs. By contrast, with late treatment the same vitreal concentrations had no significant effect on bacterial counts. The failure of late treatment was not due to an increased rate of clearance of drugs from the eyes and could not be reproduced with a similar bacterial inoculum in vitro. Bacteria cultured from treated eyes were fully sensitive when plated directly onto drug-containing agar. The poor bactericidal effect of late treatment may in part be related to transient phenotypic alterations in the bacteria in response to changes in the environment of infection such as hypoxia, low pH, and exhaustion of critical bacterial nutrients.