Optimised anaerobic treatment of house-sorted biodegradable waste and slaughterhouse waste in a high loaded half technical scale digester.

Anaerobic co-digestion of organic wastes from households, slaughterhouses and meat processing industries was optimised in a half technical scale plant. The plant was operated for 130 days using two different substrates under organic loading rates of 10 and 12 kgCOD.m(-3).d(-1). Since the substrates were rich in fat and protein components (TKN: 12 g.kg(-1) the treatment was challenging. The process was monitored on-line and in the laboratory. It was demonstrated that an intensive and stable co-digestion of partly hydrolysed organic waste and protein rich slaughterhouse waste can be achieved in the balance of inconsistent pH and buffering NH4-N. In the first experimental period the reduction of the substrate COD was almost complete in an overall stable process (COD reduction >82%). In the second period methane productivity increased, but certain intermediate products accumulated constantly. Process design options for a second digestion phase for advanced degradation were investigated. Potential causes for slow and reduced propionic and valeric acid degradation were assessed. Recommendations for full-scale process implementation can be made from the experimental results reported. The highly loaded and stable codigestion of these substrates may be a good technical and economic treatment alternative.     

Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion

Leukocyte depletion improves early postischemic ventricular performance in neonatal models of global myocardial ischemia. However, the rate of leukocyte reaccumulation after cardiopulmonary bypass and its subsequent impact on myocardial function is not known. This laboratory study examined the effect of leukocyte depletion on myocardial performance during the initial 6-hour period after bypass in an in situ, in vivo porcine model of neonatal cardiac surgery. Fifteen 3- to 5-day-old piglets (eight control and seven leukocyte depleted animals) were instrumented by placement of left ventricular short-axis sonomicrometry crystals and an intraventricular micromanometer catheter. Mechanical leukocyte depletion was achieved with Pall RC100 filters (Pall Biomedical, Inc., Fajardo, Puerto Rico) in the cardiopulmonary bypass circuit. Neonatal hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Two control animals died after the operation and were excluded from data analysis. Leukocyte filtration reduced the granulocyte count during initial myocardial reperfusion to 0.8% of control values. However, circulating granulocyte counts increased in leukocyte depleted animals throughout the postoperative period, reaching 68% of control values by 6 hours. Despite this rapid return of circulating granulocytes, animals subjected to leukocyte depletion had significantly better preservation of left ventricular performance (measured by preload recruitable stroke work, p < or = 0.02), left ventricular systolic function (measured by end-systolic pressure-volume relationship, p < or = 0.05), and ventricular compliance (p < or = 0.04) during the experiment. These changes in ventricular function were associated with a significant increase in left ventricular water content (p < or = 0.02) and tissue myeloperoxidase activity (p < or = 0.005) in control animals compared with leukocyte depleted animals. This study demonstrates that leukocyte depletion during initial reperfusion results in sustained improvement in postischemic left ventricular function despite the rapid return of granulocytes to the circulation.     

A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer

PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.     

Synapse elimination in the central nervous system: functional significance and cellular mechanisms

Recent research into the developmental elimination of supernumerary synapses has increased understanding of this process. In this review we discuss synapse elimination both at the neuromuscular junction and in the central nervous system, considering some possible underlying mechanisms suggested by recent studies. In addition a well-described example of central nervous system synapse elimination, the climbing fiber-Purkinje cell synapse of the cerebellum, is used to explore the functional significance of synaptic regression during brain development.     

Cadaver lungs for transplantation. Effect of ventilation with alveolar gas

In an effort to increase the donor pool for lung transplantation (LTX), we have demonstrated the feasibility of LTX from circulation-arrested cadavers in a canine LTX model. We hypothesized that ventilation of the cadaver lung with alveolar gas (20% O2, 5% CO2, balance N2) (AG) would be superior to ventilation with 100% oxygen (O2) after circulatory arrest of the donor. Twelve mongrel dogs were intubated, heparinized and euthanized by pentothal injection and ventilated with AG (n=6) or O2 (n=6). Four hours later, donor animals underwent sternotomy, and the lungs were flushed with cold modified Euro-Collins solution, harvested, and stored inflated in ice slush. Left lung allotransplantation was performed, and recipients were made dependent o n the transplanted lung by occlusion of the contralateral bronchus and pulmonary artery. Recipient animals were ventilated with an FiO2 of 0.4 and followed for 8 hr. Total ischemic time was 7.9 hr for both groups. Pulmonary edema developed in all recipients of AG lungs; one recipient survived the 8-hr observation period with poor oxygenation. In contrast, three of six recipients of O2-ventilated lungs survived for 8-hr with excellent gas exchange. Specimens of donor lungs before and after transplant were evaluated histologically utilizing trypan blue exclusion as an indicator of cell viability. At the time of organ retrieval 4 hr after death, 6% of cells were nonviable in the O2-ventilated cadaver lungs. Circulation-arrested cadaver lungs ventilated with 100% O2 prior to organ retrieval have superior pulmonary function after transplant compared with lungs ventilated with AG. Ventilation of cadaver lungs with AG induces pulmonary injury in this model. retrieval of donor lungs from circulation-arrested cadavers has potential for increasing the pulmonary donor pool.     

The specific antibacterial proliferation of reactive arthritis synovial T cells is not due to their higher proportion of CD45RO+ cells compared to peripheral blood

OBJECTIVE: To determine the role of synovial fluid (SF) compared to peripheral blood (PB) CD45RO+ T cells in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: We examined SF and PB of 8 patients with a specific lymphocyte proliferation to Yersinia enterocolitica (n = 5) and Chlamydia trachomatis (n = 3). After depletion of the CD45RA+ T cell subset by dynabeads, the remaining T cells (> 95% CD45RO+) from PB and SF of these patients were again stimulated with these bacterial antigens. RESULTS: The mean stimulation index (SI) of these 8 patients with ReA (n = 5) and undifferentiated oligoarthritis (n = 3) was 30.3 +/- 21.86 in SF compared to 1.36 +/- 0.75 in PB. The enrichment of CD45RO+ cells influenced the antigen specific proliferative response of T cells neither in PB (SI = 1.75 +/- 1.35) nor in SF (26.1 +/- 24.05); the initial difference remained unchanged. CONCLUSION: Our findings suggest that the antigen specific lymphocyte proliferation obtained with SF cells is not due to abundance of nonspecific CD45RO+ T cells but can rather be taken as an indication of specific recognition of local bacterial antigens in ReA.     

Neurochemical characterization of the alterations in the noradrenergic afferents to the cerebellum of adult rats exposed to X-irradiation at birth

A single dose of x-irradiation was applied on the cephalic end of newborn rats, and the alterations in the noradrenergic afferents to the cerebellum were studied 180 days later. A net increase in the noradrenaline content of cerebellum was found (122% of nonirradiated controls). The response of noradrenaline content to reserpine injection (0.9 mg/kg, i.p.) was similar in exposed and control rats. Likewise, the 3H release induced by Ro 4-1284 from cerebellar cortex slices labeled with [3H]noradrenaline was unmodified by x-rays, although a mild increase in the spontaneous efflux of 3H was found. The retention of 3H by the slices was reduced in exposed animals (58% of controls). Both the in vitro activity of tyrosine hydroxylase and the accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) were not significantly different between x-treated rats and controls. In contrast, monoamine oxidase activity was markedly reduced in x-irradiated cerebellum (38% of controls). The x-ray-induced decrease in cerebellar weight (-60%) resulted in marked increases in noradrenaline concentration (223%), tyrosine hydroxylase activity per milligram of protein (206%), and 3H retention (50%). The accumulation of L-DOPA per gram of tissue was also increased at every time considered. These data indicate that x-irradiation at birth produces a cerebellar loss not completely shared by the noradrenergic afferents, and a permanent imbalance between the noradrenergic afferent input and its target cells might eventually result.(ABSTRACT TRUNCATED AT 250 WORDS)     

Guidelines for clinical practice

Clinical practice guidelines are systematically developed statements that are intended to support medical decision making in well-defined clinical situations. Essentially, their object is to reduce the variability in medical practice, to improve quality, and to make appropriated control of the financial resources possible. Internationally, ever more organisations, associations, and institutions are concerned with the development of guidelines in many different areas of care. Making implicit knowledge explicit is one of the associated advantages of guidelines: they have a potential utility in training, in process evaluation, and in the reevaluation of outcome studies. In liability issues, their existence has a double effect: they can be used to justify medical behaviour, and they constitute a generally accepted reference point. A derivative problem is the legal liability of the compilers of the guidelines. The principle of the guideline approach can be challenged academically: science cannot give a definition of optimal care with absolute certainty. What is called objectivity often rests on methodologically disputable analyses; also the opinion of opinion leaders is not always a guarantee for scientific soundness. Moreover, patients are not all identical: biological variability, situational factors, patient expectations, and other elements play a role in this differentiation. Clinicians are often hesitant with respect to clinical guidelines: they are afraid of cookbook medicine and curtailment of their professional autonomy. Patients fear reduction of individualization of care and the use of guidelines as a rationing instrument. The effects of the introduction of clinical practice guidelines on medical practice, on the results and on the cost of care vary but are generally considered to be favourable. The choice of appropriate strategies in development, dissemination, and implementation turns out to be of critical importance. The article ends with concrete suggestions for the various steps in the development of guidelines and their actual compilation.