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AIMS: To ascertain the effect of enhanced surveillance following an outbreak of waterborne cryptosporidiosis on the number of faecal specimens submitted to the local microbiology laboratory and the number positive for common enteric pathogens. The outbreak provided an opportunity to estimate the extent of routine under ascertainment of common enteric pathogens. METHOD: Retrospective search of the computerised microbiology system database for details of faecal examination requests for the period 26 April to 6 June in 1998 and 1999 (period of outbreak). RESULTS: Specimens were received from 378 community patients during the six week period 26 April to 6 June 1999. This was double that for the same period in 1998 (a non-outbreak year). Oocysts of Cryptosporidium parvum were detected in 59 patients, an eightfold increase compared with the same period in 1998. Despite the greater number of patients tested, the detection of other pathogens in patients with gastroenteritis was not altered when compared with the same period in the previous year. CONCLUSION: This study found no evidence of under ascertainment of gastrointestinal infection (common bacterial pathogens and rotavirus) by local general practitioners.

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In this series of experiments, the Unified System components of the HeartSaver Ventricular Assist Device (VAD) version 5.0 were isolated from the controller and power supply for independent assessment. Five systems with external controller/power supply via a percutaneous lead configuration were tested in 13 male calves (101.8+/-4.3 kg). Two studies were ended acutely because of improper filling and air embolism, respectively. Duration of support was from 2.2 hours to 30 days (mean, 99+/-62 hours). The 30 day survivor was euthanized electively. Study termination was related to postoperative complications in five calves: two with bleeding/tamponade, one with thromboembolism caused by inadequate anticoagulation, and two with respiratory insufficiency. Other causes of termination were: one caused by main building power failure, two from errors in communication between the device and controller, and two caused by hydraulic fluid loss related to housing defects. From these experiments, an intrathoracic position for the calf has been defined, the procedure for implantation without cardiopulmonary bypass has been developed, refinements to the controller have been made, and inflow and outflow cannulae have been reinforced. Hydraulic fluid losses will be solved by proceeding with use of a titanium housing instead of polyurethane. In conclusion, the development of the HeartSaver VAD is progressing, in part because of these experimental and informative animal studies. Further in vivo evaluation of the final version will be conducted before clinical trials.

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Clinical practice guidelines are increasingly being recognised as integral to the clinical effectiveness agenda. According to the recent Scottish White Paper, Scotland "leads the way in clinical effectiveness". The Scottish Intercollegiate Guidelines Network (SIGN), established in 1993, has produced over 20 clinical practice guidelines, and plans to produce at least as many more, while reviewing existing guidelines at a minimum of every two years. This represents a substantial investment of NHS resources. This paper investigates whether this investment is being recouped in Scottish NHS acute trusts via the implementation of SIGN guidelines, and whether their implementation is being audited properly. It is argued that without clinical audit, guideline implementation is unlikely to succeed. This has important ramifications for the implementation of clinical governance.

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If the exclusive promotion of values inimical to our basic humanity extends to the health care policy arena, we face a defensive, restricted, impersonal and ultimately impoverished health care system. Americans known it already as 'managed-care'. This is why it is crucial for health policy analysts to make explicit the role of values in policy-making, especially that involving the input of 'value-neutral' economics. The nature of any clinical effectiveness policy will be determined by the understanding of cost-effectiveness employed in its design and implementation. Given that cost-effectiveness is nowadays usually defined according to health economists' criteria, the battle over the meaning of clinical effectiveness is a significant development in health economics' move to assume control of the NHS.

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The increasing popularity of economic evaluation methods, especially cost effectiveness analysis, brings with it the danger of decisions being made on the basis of faulty criteria. This paper explores the underlying faults of orthodox economics, and offers tentatively an alternative means of decision appraisal via John Dewey's philosophy of instrumentalism and the methods of institutionalist economics.

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Drug resistance among yeasts is an increasing problem. Isolates of Candida krusei and Candida glabrata are recognized as having reduced susceptibility to fluconazole and resistance to this drug has also arisen in Candida albicans isolated from AIDS patients on long term azole therapy. Candida tropicalis (CT) is being increasingly isolated from human disease and is associated with invasive infection, however, data regarding this organism's drug susceptibility is limited. We report our findings on 60 isolates of CT isolated from patients with serious infection in the North West of England. Over 60% of isolates were from adult Intensive Care Unit (ICU) patients, and almost half were from the respiratory tract. Susceptibility to fluconazole, flucytosine, itraconazole and ketoconazole were tested by standardised methods - 48% of the isolates were resistant to fluconazole (MIC > 12.5 mg/l), and 10% had intermediate susceptibility (MIC 6.25-12.5 mg/l). For flucytosine 17% of isolates were resistant (MIC > 8 mg/l) and 22% had intermediate susceptibility (MIC 2-8 mg/l). Three isolates were resistant to both drugs. For itraconazole 17% of isolates were resistant (MIC > 1 mg/l), and 12% showed intermediate susceptibility (MIC 0.5-1 mg/l). Resistance to ketoconazole was seen in 33% of isolates (MIC > 1 mg/l) and 10% showed intermediate susceptibility (MIC 0.5-1 mg/l). Differences in the degree of cross resistance between the azole drugs was observed. Candida tropicalis should be added to the list of yeasts in which drug resistance is commonly found. Given the high invasiveness of Candida tropicalis, its affinity for patients on ICU and the high incidence of drug resistance in this species, identification and susceptibility tests should be performed on all yeast isolates from patients on ICU.

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A totally implantable intrathoracic electrohydraulic ventricular assist device has been developed at the University of Ottawa Heart Institute. In vivo testing has been instrumental in its progressive development. A total of 15 experiments (4 acute, 11 performance) have been performed using male calves (62-117 kg). Data from the acute experiments, human fit trials, fluid dynamic studies, and hydraulic/energy efficiency analyses formed the basis for the development of a compact, single piece ventricular assist device called the Unified System in which the volume displacement chamber, motor, and blood chamber are housed within a compact 600 cc, 740 g unit. The performance experiments indicated that the unified system could support calves for periods up to 96 hr. The mean postoperative cardiac output was 7.1 +/- 0.7 L/ min (range = 4.9-11), mean blood pressure was 99.7 +/- 5.8 mmHg, and mean pulmonary artery pressure was 32.1 +/- 1.2 mmHg. The operative technique for intrathoracic implantation has been developed. The major problems encountered were of respiratory failure, improved by device repositioning in the calf; decreased blood inflow to the device that was improved by cannula redesign; circuit board fracture corrected by design modification; and a power supply problem that was limited to a single unit. The preliminary experiments have helped in the design modifications of the Unified System. The improved version of the system will undergo formal performance, reliability, and chronic in vivo testing before human implantation.

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Photosensitizing drugs are selectively taken up by lipid-rich lesions such as atheromatous plaque which when exposed to light render the drugs cytotoxic. However, skin photosensitivity which persists for many weeks is a significant side effect. We investigated the cytotoxicity of a new photosensitizing drug, the benzoporphyrin derivative BPD verteporfin (Quadra Logic Technologies), which does not have this deleterious side effect. Vascular smooth muscle cells (VSMC) from normal human mammary and diseased human coronary arteries were grown in culture from explants and characterized with respect to their growth rates. The sensitivity to BPD with and without light was assessed by measuring viability after treatment. The lethal dose of drug for 50% viability loss (LD50) for BPD with light was approximately 12.5 ng/ml for mammary artery, with 52 +/- 8% cell survival (n = 6). The coronary artery VSMC from all patient sources, although differing significantly in growth rate, had a survival of 44 +/- 6% (n = 12) at the same concentration of BPD used for the mammary artery SMC (p = NS). Our results established the LD50 for BPD using human arterial sources of SMC and showed that the growth rates of the cells did not affect the cytotoxicity of the drug.

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The outcome of stent implantation for children with pulmonary venous obstruction has been characterized by late reocclusion associated with a marked vessel neointimal proliferation. The purpose of this study was to compare the responses of the systemic vein and pulmonary vein to the presence of an intravascular stent, using a Yorkshire swine (N = 10) model. Under cardiopulmonary bypass, a single Palmaz stent was placed in the inferior vena cava (IVC) and right lower pulmonary vein (PV) with sacrifice at 4.9-6.1 months. Angiography and hemodynamic data were determined at 1 and 3 months post-stent implant and prior to euthanasia. All stents were found to be patent, with no difference in degree of thrombosis or neointimal formation. No statistical difference was found in the initial and final stent diameter for both inferior vena cava and pulmonary vein stents (PV initial 6.8 +/- 0.9; final 7.1 +/- 0.6) (IVC initial 10.4 +/- 1.2; final 10.4 +/- 1.2). Electron microscopy demonstrated smooth endothelialization of both pulmonary and systemic venous stent devices. No thrombosis was found on gross morphology. The data indicate that there is no intrinsic difference in the response of the pulmonary vein to the presence of a stent device. The clinical experience of restenosis following stent implantation for pulmonary vein stenosis appears to be more related to variables of final stent diameter combined with the marked intrinsic abnormal vessel architecture, as seen with this condition.

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Complete two-dimensional echocardiography and Doppler flow studies were performed on 17 swine as part of an experimental protocol involving cardiopulmonary bypass with circulatory arrest. Indices of left ventricular function and pulmonary vein morphology and flow velocity were taken before (17/17) and after bypass (11/17). A total of 70 measurements were available for analysis. Doppler flow velocity within the right pulmonary vein was 0.5 +/- 0.06 m/sec and was 0.52 +/- 0.05 m/sec in the left pulmonary vein. The swine were found to have a marked reduction in left ventricle function compared with that in previous reports, though no statistical difference was seen between pre- and post-cardiopulmonary bypass studies (preoperative shortening fraction was 21 +/- 5% and ejection fraction was 41 +/- 8%; postoperative shortening fraction was 23 +/- 5% and ejection fraction was 42 +/- 7%). Swine with shortening and ejection fractions of < 20% were found to have more unstable hemodynamics during cardiopulmonary bypass.

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Three hundred and forty-eight isolates of Candida spp. from patients treated at a regional infectious diseases unit for AIDS, immunocompromised patients admitted to the Hope Hospital and isolates referred from around the North West of England were tested for their in-vitro susceptibility to amphotericin B, fluconazole and flucytosine using standardized methods. Candida albicans comprised 73% of isolates, Candida glabrata 10% and Candida parapsilosis 7%. Ninety-six percent of isolates were susceptible to amphotericin B and resistance to > or = 12.5 mg/L fluconazole was found in 61 (17.5%) of the 348 isolates tested. Among isolates from patients with AIDS the incidence of fluconazole resistance was 33% whereas in other patients the incidence was only 11%. Flucytosine resistance was seen in only 12 (3.4%) isolates, 11 of which were C. albicans and in 6.5% of isolates from patients with AIDS. Resistance to fluconazole and flucytosine is now sufficiently prevalent among Candida spp. isolated from patients with AIDS to warrant routine susceptibility testing of yeast isolates.

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A patient with persistent dural fistula, CSF rhinorrhoea and a history of recurrent bacterial meningitis developed meningitis with a penicillin-resistant strain of Streptococcus pneumoniae while on prophylactic ampicillin. The microbiological aspects of management are discussed.

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A transcutaneous energy transfer (TET) system has been developed to power implantable devices such as artificial hearts, defibrillators, and electrical stimulators. Transcutaneous coupling of power to these implanted devices remains a favorable alternative as percutaneous lines are avoided in order to eliminate the potential of infection and allow patient mobility. In vitro, in vivo, ex vivo, and human cadaver studies of the electrohydraulic ventricular assist device TET have demonstrated that power can be transmitted over a range of skin thicknesses of 3-15 mm and can tolerate radial misalignments of up to 20 mm. Sensitivity to coil separation and radial misalignment variations has been addressed by the development of an auto-tuning TET. The system has only a 10% attenuation in secondary coil voltage when metallic objects are in contact with the primary coil. The system has demonstrated a power transfer efficiency of 60-80% for power demands from 5 to 70 W. The TET secondary coil will provide an output voltage of 10-25 V for current demands from 0.5 to 4.0 A. TET chronic studies in porcine models have demonstrated no adverse effect to the tissue when up to 40 W of power can be delivered to an implanted load without the tissue-contacting surface of the coil exceeding 42 degrees C. In conclusion, the TET is a feasible alternative for tether-free power transmission.

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