Direct determination of the driving forces for taurocholate uptake into rat liver plasma membrane vesicles.

To determine directly the driving forces for bile acid entry into the hepatocyte, the uptake of [3H]taurocholic acid into rat liver plasma membrane vesicles was studied. The membrane preparation contained predominantly right-side-out vesicles, and was highly enriched in plasma membrane marker enzymes. The uptake of taurocholate at equilibrium was inversely related to medium osmolarity, indicating transport into an osmotically sensitive space. In the presence of an inwardly directed sodium gradient (NaCl or sodium gluconate), the initial rate of uptake was rapid and taurocholate was transiently accumulated at a concentration twice that at equilibrium (overshoot). Other inwardly directed cation gradients (K+, Li+, choline+) or the presence of sodium in the absence of a gradient (Na+ equilibrated) resulted in a slower initial uptake rate and did not sustain an overshoot. Bile acids inhibited sodium-dependent taurocholate uptake, whereas bromsulphthalein inhibited both sodium-dependent and sodium-independent uptake and D-glucose had no effect on uptake. Uptake was temperature dependent, with maximal overshoots occurring at 25 degrees C. Imposition of a proton gradient across the vesicle (pHo less than pHi) in the absence of a sodium gradient failed to enhance taurocholate uptake, indicating that double ion exchange (Na+-H+, OH- -anion) is unlikely. Creation of a negative intravesicular potential by altering accompanying anions or by valinomycin-induced K+-diffusion potentials did not enhance taurocholate uptake, suggesting an electroneutral transport mechanism. The kinetics of taurocholate uptake demonstrated saturability with a Michaelis constant at 52 microM and maximum velocity of 4.5 nmol X mg-1 X protein X min-1. These studies provide definitive evidence for a sodium gradient-dependent, carrier-mediated, electrically neutral transport mechanism for hepatic taurocholate uptake. These findings are consistent with a model for bile secretion in which the basolateral enzyme Na+,K+-ATPase provides the driving force for "uphill" bile acid transport by establishing a trans-membrane sodium gradient.

Outcome of penicillin-susceptible streptococcal prosthetic joint infection treated with debridement and retention of the prosthesis.

Debridement with retention of the prosthesis was the initial treatment modality for 19 cases of penicillin-susceptible streptococcal prosthetic joint infection that occurred in 18 patients who presented to the Mayo Clinic (Rochester, Minnesota) during 1969-1998. All of the cases of prosthetic joint infection occurred >30 days after implantation of the prosthesis, which was well fixed at the time of debridement. The median duration of symptoms before debridement was 4 days (range, 1-10 days). Treatment failure (defined as relapse of infection with the original microorganism) occurred in 2 cases (10.5%) during a median follow-up period of 3.9 years (range, 0.3-21.7 years). The 1-year cumulative risk of relapse was 11% (95% confidence interval, 0%-26%). Relapse of prosthetic joint infection due to penicillin-susceptible streptococci after debridement and retention of the prosthesis is uncommon. For patients who present with a well-fixed prosthesis and a short duration of symptoms, debridement with retention appears to be an effective treatment modality.

Comparative gastrointestinal enzyme activity and activation of the promutagen 2,6-dinitrotoluene in male CD-1 mice and male Fischer 344 rats.

Comparative intestinal nitroreductase, azo reductase, beta-glucuronidase, dechlorinase and dehydrochlorinase activities in young male Fischer 344 rats and young male CD-1 mice were measured in vitro while the comparative biotransformation of 2,6-dinitrotoluene to mutagenic metabolites was determined in vivo. The mice, which exhibit a high spontaneous incidence of hepatomas, had markedly greater nitroreductase activity and metabolized significantly more 2,6-dinitrotoluene to mutagenic metabolites than did Fischer 344 rats, which show a low incidence of liver tumors. Results of this study indicate that species differences in the incidence of hepatomas may be influenced by microbial flora and/or the biotransformation of xenobiotics in the G.I. tract.

Staphylococcus aureus prosthetic joint infection treated with prosthesis removal and delayed reimplantation arthroplasty.

OBJECTIVE: To estimate in patients with Staphylococcus aureus prosthetic joint infection after total hip arthroplasty (THA) or total knee arthroplasty (TKA) the microorganism-specific cumulative probability of treatment failure after prosthesis removal and delayed reimplantation arthroplasty. PATIENTS AND METHODS: All patients with S aureus THA or TKA infection, according to a strict case definition, who were treated with prosthesis removal and delayed reimplantation arthroplasty at Mayo Clinic Rochester between 1980 and 1991 were identified. The study group comprised patients who were free of infection at the time of reimplantation arthroplasty. This cohort was followed up until treatment failure, infection with another organism, prosthesis removal, death, or loss to follow-up occurred. The Kaplan-Meier survival method was used to estimate the cumulative probability of treatment failure. RESULTS: Among 120 S aureus prosthetic joint infections treated with prosthesis removal during the study period, 38 episodes (22 THA, 16 TKA) in 36 patients met the study inclusion criteria. After a median of 7.4 years (range, 0.9 year-16.4 years) of follow-up, treatment failure occurred in 1 (2.6%) of 38 episodes 1.4 years after reimplantation arthroplasty. The 5-year cumulative probability of treatment failure was 2.8% (95% confidence interval, 0%-8.2%). CONCLUSIONS: These data suggest that prosthesis removal and delayed reimplantation arthroplasty is an effective treatment to limit the recurrence of S aureus prosthetic joint infection, provided there is no evidence of infection at the time of reimplantation arthroplasty.

Mucosal invasion in campylobacter enteritis.

Campylobacter fetus subspecies jejuni has recently been recognized as a significant cause of enteritis in humans. The organism has been previously postulated to cause illness by direct invasion of the mucosa of the gastrointestinal tract, but this has not been documented. Reported is a case of Campylobacter enteritis in which mucosal ulceration and crypt sbscesses were seen on rectal biopsy, suggesting that the pathogenesis of Campylobacter fetus enteritis involves direct mucosal invasion.

Effect of lindane on nitroreductase and dechlorinase enzyme activity in the gastrointestinal tract.

A previously reported acceleration of parathion metabolism in the gastrointestinal (GI) tract of lindane-pretreated rats could have been due to either a prolonged residence time of parathion or increased GI nitroreductase activity or both. Thus to determine the effect on GI nitroreductase and dechlorinase activity, 20 mg/kg lindane or 535 mg/kg neomycin were administered daily, by gavage, to weanling F-344 rats. Enzyme activity in the small intestine and cecum were assayed after 2 weeks and 5 weeks of treatment. Neomycin treatment inhibited the activity of both enzymes in the cecum but had no significant effect on enzyme activity in the small intestine, suggesting the presence of mucosal nitroreductase and dechlorinase in the small intestine. In contrast, lindane, which had no effect on enzyme activity in the cecum, significantly increased nitroreductase activity in the small intestine after treatment for 5 weeks. This increased nitroreductase may account for the previously reported lindane-parathion interaction and could influence the metabolism, toxicity, and risk assessment of many other environmental nitro-compounds that become toxic, mutagenic or carcinogenic upon reduction of their nitro-groups.

Determining priorities for change in primary care: the value of practice-based needs assessment.

BACKGROUND: Primary care is being expected to expand the range of services it provides, and to take on many of the tasks traditionally provided in secondary care. At the same time, general practitioners (GPs) will become increasingly responsible for assessing their patients' health care needs and commissioning care from other providers. This article describes an approach taken in one general practice to meet these difficult challenges. AIM: To examine whether information on health and health care needs, when used as the basis for a priority setting exercise, can provide a useful first step in planning primary care provision within a practice. METHOD: A three-stage process of information-gathering from a number of sources, including continuous data recording of patient contacts and a postal survey of all adults registered with the practice, identification of key findings and discussion of associated issues, and priority setting of proposals for practice development using the nominal group technique. RESULTS: Continuous data recording of patient contacts with GPs and the practice nurse provided data on 4489 GP contacts with 2027 patients, 1000 district nurse contacts with 101 patients, and 361 health visitor contacts with 172 clients. More than 70% of patient records had been computerized, with 600 diagnostic READ codes identified and 11,500 separate entries made. The socioeconomic and health survey questionnaire achieved an 84% response rate. Following the priority-setting exercise, 28 proposed practice developments were identified. These were reduced to a final list of eight. CONCLUSION: A comprehensive method of practice-based needs assessment, when used as the basis for some form of priority setting, has great potential in helping to plan primary care services within a practice. The success of such initiatives will require a substantial investment of resources in primary care and fundamental changes to the way in which primary care is funded.

Prosthetic joint infection due to Mycobacterium tuberculosis: a case series and review of the literature.

Prosthetic joint replacement is being performed more frequently for patients with prior septic arthritis due to Mycobacterium tuberculosis. Prosthetic joint infection due to Mycobacterium tuberculosis does occur, but is rare. We report the clinical characteristics and outcome of seven cases of Mycobacterium tuberculosis prosthetic joint infection seen at our institution over a 22-year period and summarize the English-language literature regarding current prophylaxis and treatment strategies. Tuberculous prosthetic joint infection most often represents reactivation of prior tuberculous septic arthritis. The diagnosis of tuberculous prosthetic joint disease is often delayed, because a history of prior Mycobacterium tuberculosis septic arthritis is not known. Treatment of tuberculous prosthetic joint infection requires a combined medical and surgical approach. Removal of the prosthesis has been the traditional surgical modality, followed by appropriate antituberculous therapy, but other surgical methods have been used successfully in selected cases. To decrease the risk of reactivation of infection after prosthesis implantation in patients with quiescent tuberculous septic arthritis who have not received prior antituberculous therapy, consideration should be given to preoperative or perioperative antituberculous prophylaxis.

Spontaneous reactivation of chronic hepatitis B infection leading to fulminant hepatic failure. Report of two cases and review of the literature.

Reactivation of chronic hepatitis B viral (HBV) infection, defined as conversion from the low level replicative phase (HBV-DNA negative) to the high level replicative phase (HBV-DNA positive) with continued hepatitis B surface antigen positivity, occurs after immunosuppressive therapy, chemotherapy, and rarely spontaneously. Development of hepatic failure after spontaneous reactivation of chronic HBV is rare. We report two patients with chronic HBV infection and stable cirrhosis in whom spontaneous reactivation lead to hepatic failure. In one, spontaneous reactivation lead to severe jaundice, ascites, and encephalopathy. Treatment with alpha-interferon resulted in transient improvement, but the patient ultimately died with hepatorenal syndrome. In the second, severe liver failure required orthotopic liver transplantation. Spontaneous reactivation is an unusual cause of hepatic decompensation in patients with chronic HBV infection and may lead to fulminant hepatic failure. The role of interferon or liver transplantation in the management of spontaneous reactivation remains to be clarified.

The practice characterization model: the importance of organizational life cycles and targeted interventions in general medical practice.

In response to a climate of constant change and increasing demand for services, general practice in the UK has undergone significant modification over the last 10 years. It has become a multi-disciplinary organisation encouraged by funding bodies to plan for service delivery using a more structured team based approach. In Tayside in 1996, practices were charged with producing formal Practice Development Plans (PDPs) which would focus on priority areas aligned with the Health Boards own strategic plan--those were teamwork, information management and technology, and clinical service delivery. The University of Dundee's Department of General Practice successfully applied for funding to develop ways of facilitating practices so that they could a) identify their own development priorities, and b) plan and implement action and learning to see these priorities through. Using action research methodology, the project attempted to create a climate for change, provide support and training to see the changes implemented, and ensure commitment to the changes from all members of the practice team. The Facilitator adopted a flexible style varying her role between expert, guide and support. Analysis of progress made by different practices, coupled with the Facilitator's in depth knowledge of them, suggested the importance of certain key aspects of practice organisation and culture. A practice characterisation model identified practices which were stable, currently coping, proactive and ready to face the challenge of change as best placed to engage in a full scale development programme. Other profiles suggested a range of alternative interventions as more likely to be acceptable and productive.

Staphylococcus aureus prosthetic joint infection treated with debridement and prosthesis retention.

Debridement and retention of the prosthesis was the initial treatment modality in 30 patients with 33 Staphylococcus aureus prosthetic joint infections (PJIs) who presented to the Mayo Clinic between 1980 and 1991. Treatment failure, defined as relapse of S. aureus PJI or occurrence of culture-negative PJI during continuous antistaphylococcal therapy, occurred in 21 of 33 prosthetic joints. The 1-year and 2-year cumulative probabilities of treatment failure were 54% (95% confidence interval [CI], 36%-71%) and 69% (95% CI, 52%-86%), respectively. A median of 4 additional surgical procedures (range, 1-9) were required to control the infection in the 21 prosthetic joints for which treatment failed. Prostheses that were debrided >2 days after onset of symptoms were associated with a higher probability of treatment failure than were those debrided within 2 days of onset (relative risk, 4.2; 95% CI, 1.6-10.3). These data suggest that debridement and retention of the prosthesis as the initial therapy for PJI due to S. aureus is associated with a high cumulative probability of treatment failure and that the probability of treatment failure may be related to the duration of symptoms.

Risk factors for prosthetic joint infection: case-control study.

We conducted a matched case-control study to determine risk factors for the development of prosthetic joint infection. Cases were patients with prosthetic hip or knee joint infection. Controls were patients who underwent total hip or knee arthroplasty and did not develop prosthetic joint infection. A multiple logistic regression model indicated that risk factors for prosthetic joint infection were the development of a surgical site infection not involving the prosthesis (odds ratio [OR], 35.9; 95% confidence interval [CI], 8.3-154.6), a National Nosocomial Infections Surveillance (NNIS) System surgical patient risk index score of 1 (OR, 1.7; 95% CI, 1.2-2.3) or 2 (OR, 3.9; 95% CI, 2.0-7.5), the presence of a malignancy (OR, 3.1; 95% CI, 1.3-7.2), and a history of joint arthroplasty (OR, 2.0; 95% CI, 1.4-3.0). Our findings suggest that a surgical site infection not involving the joint prosthesis, an NNIS System surgical patient risk index score of 1 or 2, the presence of a malignancy, and a history of a joint arthroplasty are associated with an increased risk of prosthetic joint infection.