[Hospital hygiene and antibiotherapy counselling: an operational dual solution against the spreading of multiresistant bacteria]. / L'hygiène hospitalière et le conseil en antibiothérapie: un duo opérationnel face au problème de la diffusion des bactéries multirésistantes aux antibiotiques.

OBJECTIVES: The authors had for aim to show that preventing the diffusion of multidrug-resistant organism (MRO) is possible thanks to the coordination of recommended preventive actions and the implementation of a sensible anti-infective prescription policy. They also wanted to highlight the role played by the nursing care staff in enforcing recommendations. METHOD: We compared the results of two health care facilities having both implemented the same strategy aimed at preventing cross-transmission and prescribing anti-infective drugs. RESULTS: Audits reported a very variable enforcement of recommendations. The results obtained from microbiological monitoring confirmed the essential impact of protocol enactment by every team, on the control of MRO diffusion. The antibiotherapy specialist has a key role in the suggested strategy, allowing a significant decrease in the number of anti-infective prescriptions and a more rational use. CONCLUSION: The collaboration of a hygiene specialist with an antibiotherapy specialist has proved operational in the fight against MRO diffusion, as long as the competences of both specialists are acknowledged and their cross-disciplinary activities accepted. For the entire staff, enacting a corporate culture is a crucial asset.

Medical learning curves and the Kantian ideal.

A hitherto unexamined problem for the "Kantian ideal" that one should always treat patients as ends in themselves, and never only as a means to other ends, is explored in this paper. The problem consists of a prima facie conflict between this Kantian ideal and the reality of medical practice. This conflict arises because, at least presently, medical practitioners can only acquire certain skills and abilities by practising on live, human patients, and given the inevitability and ubiquity of learning curves, this learning requires some patients to be treated only as a means to this end. A number of ways of attempting to establish the compatibility of the Kantian Ideal with the reality of medical practice are considered. Each attempt is found to be unsuccessful. Accordingly, until a way is found to reconcile them, we conclude that the Kantian ideal is inconsistent with the reality of medical practice.

Behavioral sequelae of perinatal insults and early family adversity at 8 years of age.

OBJECTIVE: This prospective longitudinal study investigated the simultaneous impact of early biological and psychosocial risk factors on behavioral outcome at school age. METHOD: A cohort of 362 children born between 1986 and 1988 with different biological (perinatal insults) and psychosocial risk factors (family adversity) was followed from birth to school age. When their children were aged 8 years, parents of 89.0% of the initial sample completed the Child Behavior Checklist (CBCL). RESULTS: More externalizing as well as internalizing problems were found in children born into adverse family backgrounds, whereas no differences at broad-band syndrome level were apparent between groups with varying obstetric complications. Children with family risk factors had higher scores on 5 of the 8 CBCL scales (including attention, delinquent, and aggressive problems), whereas children with perinatal risk factors had more social and attention problems than children in the nonrisk groups. With one exception, no interactions between risk factors emerged, indicating that perinatal and family risk factors contributed independently to outcome. The differences between risk groups applied irrespective of gender. CONCLUSIONS: The adverse impact of family adversity clearly outweighed the influence of obstetric complications in determining behavioral adjustment at school age.

Immunocytological determination of lymphocytes and monocytes/macrophages in urinary sediments of renal allograft recipients.

BACKGROUND: Urinary studies using Papanicolaou staining following kidney transplantation led to the conjecture that acute allograft rejection might be accompanied by an increased lymphocyturia. However, it is difficult to distinguish lymphoid cells from other urinary cells using conventional stains. METHODS: Staining of urinary lymphocytes using FITC-labelled antibodies is complicated by a high unspecific fluorescence that limits the evaluation. Therefore, we developed a method to stain urinary lymphocytes using enzyme-linked antibodies. The cells were cytocentrifuged onto microscope slides and were fixed. RESULTS: By means of a combined evaluation of Papanicolaou and immunocytochemical staining, CD3-positive pan T cells, CD4-positive T-helper cells, CD8-positive cytotoxic/suppressor cells, and CD14-positive monocytes/macrophages of urinary sediments were determined in 41 kidney graft recipients following renal transplantation. During periods of normal graft function, neither positive lymphocytes nor positive monocytes/macrophages were found in the urinary sediments. However, in the course of acute allograft rejection a significant increase in positive lymphocytes and positive monocytes/macrophages could be observed. Interestingly, in cases of acute allograft rejection the distribution of urinary lymphocytes and monocytes was comparable to the distribution of infiltrating immunocompetent cells in renal allograft biopsies. CONCLUSION: The present study demonstrates that immunocytochemical staining via enzyme-conjugated antibodies is a reliable method to visualize T lymphocytes and monocytes/macrophages in the urinary sediment, and that this technique may be of special diagnostic value in the diagnosis of acute allograft rejection.

Telemedicine: application of telepathology-remote microscopy for intraoperative diagnoses on frozen sections.

Due to the time delay, intraoperative consultations result in an extension of operation times, leading to prolonged anesthesia and idle time during surgery. Using a remote controlled microscope for telepathology, transfer times between hospital and pathologist can be eliminated and pathological expertise obtained independently of the geographic location of the hospital. In cooperation with a community hospital located 100 km apart from the Institute of Pathology of the Justus Liebig University Giessen, telepathological intraoperative consultations have been performed since 1999. After preparation and staining of the cryosection in the hospital, the slide was examined in our institute using a remote-controlled microscope (Leica DMRXA) and a special telepathological software (Leica TPS1). Data were transferred via two ISDN connections in parallel. The telepathology system contains an additional macroscopic examination equipment. Up to now more than 40 telepathological consultations have been done. Time required for the microscopic diagnosis ranged between 4 and 25 minutes. The amount of time saved, compared to the transfer to the next available pathologist, was approximately 45 minutes. In our experience, telepathological diagnoses were fully in accordance with conventional diagnoses routinely performed afterwards. The application of telepathology can lead to a significant shortening of surgery time if a pathologist is locally not available. In the study presented, no diagnostic errors occurred. The additional application of a macroscopic equipment allows inspection and interactive guidance for sampling, thus preventing sampling errors.

Soluble CD-4 and CD-8 as markers of immunological activation in renal transplant recipients.

BACKGROUND: T lymphocytes are activated following kidney transplantation in cases of acute graft rejection and viral infections. In plasma, elevated levels of T-cell markers can be measured in soluble form. The reason for this shedding is still not entirely understood. METHODS: Plasma concentrations of soluble CD-4 and CD-8 (sCD-4, sCD-8) were determined in 78 patients following kidney transplantation by commercially available enzyme-linked immunosorbent assay (ELISA) test kits. RESULTS: The concentrations of both soluble T-cell markers increased significantly in the course of acute allograft rejections and cytomegalovirus (CMV) infections. Frequently, the parameters increased shortly before clinical diagnosis and decreased under successful therapy. Additionally, sCD-8 showed significant higher plasma concentrations in cases of CMV infection as compared with acute allograft rejections. Accordingly, the sCD-4/sCD-8 ratio increased in cases of acute allograft rejection and decreased during CMV infections. Cyclosporin A nephrotoxicity caused no significant changes in the sCD-4 and sCD-8 levels in plasma. CONCLUSION: The present study demonstrates that sCD-4 and sCD-8 are markers of immunological activation and may enable a further differentiation of T-cell activation if serial measurements are performed. However, further prospective investigations are necessary to elucidate the diagnostic potential of sCD-4 and sCD-8 for monitoring acute rejection and viral infection in kidney graft recipients.

A patient dose survey for femoral arteriogram diagnostic radiographic examinations using a dose-area product meter.

We present a method for dealing with a complex radiographic procedure (which involves multiple radiographs and fluoroscopy) in an attempt to provide a simple way of calculating effective dose from which a general risk factor can be determined. A useful index of harm can be obtained by recording the number of radiographs in each region, and the fluoroscopy time, from which the effective dose may be easily calculated. A patient dose survey was carried out using a PTW diamentor for femoral arteriogram procedures in a large teaching hospital. The procedure involves fluoroscopy to the pelvic region to locate a guide wire and catheter, followed by a series of radiographs extending from the pelvic area to the feet to form a collage image of the entire arterial system. Radiographs are taken whilst a bolus of contrast media is injected into the arterial system. These measurements extend a continuing survey of doses for common diagnostic radiographic examinations which have previously included the simple examinations of lumbar spine, abdomen and pelvis.

A patient dose survey for three common diagnostic radiographic examinations using a dose-area product meter.

A patient dose survey was carried out for three common diagnostic radiographic examinations: lumbar spine, abdomen and pelvis. A dose-area product meter was used to determine the dose-area product delivered to the patient. The patient dose results reported in this study are lower than the results of the dose survey for United Kingdom hospitals which was recently published by the National Radiological Protection Board. Our data were also used to calculate the mean energy imparted and the mean effective dose from the examinations.

Fluoroimmunoassay studies with solubilized antigens from Borrelia burgdorferi.

Sodium deoxycholate-solubilized Borrelia burgdorferi antigen was prepared for use in a solid-phase fluoroimmunoassay (FIA-L) to detect antibodies in Lyme disease. Serum specimens were tested by FIA-L and by a microimmunofluorescence test. The FIA-L results are comparable to those of the standard microimmunofluorescence test. The overall agreement was 0.98. Moreover, the FIA-L procedure is simple and rapid; fluorescence is objectively determined and is proportional to antibody titer.

The pharmacokinetics of salicylate in the pregnant Wistar rat.

Sodium salicylate, in a single dose of 50 mg/kg, was administered by iv injection to nonpregnant female and 20-day pregnant Wistar rats. Blood samples (for serum) and urine were collected and analyzed for salicylate, gentisic acid, salicyluric acid, and salicyl glucuronides by HPLC. Pregnant rats showed a significant decrease in body weight-normalized total clearance but no change in absolute total clearance of salicylate. On a body weight-adjusted basis there was a slight increase in the apparent volume of salicylate distribution in pregnancy but this increase becomes highly significant if expressed in absolute terms. The biological half-life of salicylate was significantly increased in late pregnancy. Serum protein binding of salicylate is decreased in pregnancy relative to nonpregnant females but in both groups binding shows a concentration dependence. The partial clearances of both salicyluric and gentisic acids were reduced by pregnancy in the rat whereas that of the salicyl glucuronides appeared unchanged. This latter result in intact pregnant animals contrasts with previously reported decreases in glucuronyltransferase activity in isolated liver preparations from pregnant rats.

Evidence for a free radical mechanism of styrene-glutathione conjugate formation catalyzed by prostaglandin H synthase and horseradish peroxidase.

We have proposed, using styrene as a model, a new mechanism for the formation of glutathione conjugates that is independent of epoxide formation but dependent on the oxidation of glutathione to a thiyl radical by peroxidases such as prostaglandin H synthase or horseradish peroxidase. The thiyl radical reacts with styrene to yield a carbon-centered radical which subsequently reacts with molecular oxygen to give the styrene-glutathione conjugate. We have used electron spin resonance spin trapping techniques to detect the proposed free radical intermediates. A styrene carbon-centered radical was trapped using the spin traps 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and t-nitrosobutane. The position of the carbon-centered radical was confirmed to be at carbon 7 by the use of specific 2H-labeled styrenes. The addition of the spin trap DMPO inhibited both the utilization of molecular oxygen and the formation of styrene-glutathione conjugates. Under anaerobic conditions additional styrene-glutathione conjugates were formed, one of which was identified by fast atom bombardment mass spectrometry as S-(2-phenyl)ethylglutathione. The glutathione thiyl radical intermediate was observed by spin trapping with DMPO. These results support the proposed free radical-mediated formation of styrene-glutathione conjugates by peroxidase enzymes.

The formation of styrene glutathione adducts catalyzed by prostaglandin H synthase. A possible new mechanism for the formation of glutathione conjugates.

The metabolism of styrene by prostaglandin hydroperoxidase and horseradish peroxidase was examined. Ram seminal vesicle microsomes in the presence of arachidonic acid or hydrogen peroxide and glutathione converted styrene to glutathione adducts. Neither styrene 7,8-oxide nor styrene glycol was detected as a product in the incubation. Also, the addition of styrene 7,8-oxide and glutathione to ram seminal vesicle microsomes did not yield styrene glutathione adducts. The peroxidase-generated styrene glutathione adducts were isolated by high pressure liquid chromatography and characterized by NMR and tandem mass spectrometry as a mixture of (2R)- and (2S)-S-(2-phenyl-2-hydroxyethyl)glutathione. (1R)- and (1S)-S-(1-phenyl-2-hydroxyethyl)glutathione were not formed by the peroxidase system. The addition of phenol or aminopyrine to incubations, which greatly enhances the oxidation of glutathione to a thiyl radical by peroxidases, increased the formation of styrene glutathione adducts. We propose a new mechanism for the formation of glutathione adducts that is independent of epoxide formation but dependent on the initial oxidation of glutathione to a thiyl radical by the peroxidase, and the subsequent reaction of the thiyl radical with a suitable substrate, such as styrene.

Review and case report: primary melanoblastosis of the leptomeninges.

A case of primary diffuse leptomeningeal melanoblastosis in a 46-year-old male is reported. His symptoms included headaches, transient hemiparesis, epileptic seizures and a progressive psychosyndrome. CT brain scans showed a slight enhancement of density in the subarachnoidal space. The disease was diagnosed by CSF cytology, using light microscopy, electron microscopy, autoradiography and cell culture. Systemic combined chemotherapy using Cisplatinum, DTIC, and Vindesine was without any significant response and he died 18 weeks after onset of the first complaints. Autopsy showed a diffuse infiltration of the entire leptomeninges by melanotic melanoblastoma cells invading the sagittal superior sinus. A thorough dissection including the orbital contents and skin nevi failed to reveal a primary tumor outside the CNS.

Hepatic drug metabolism in pregnancy.

The results of both isolated tissue and whole animal experimentation, whilst showing some unexplored inconsistencies, suggest that late pregnancy is associated with a reduced ability of the liver to metabolise foreign compounds. The mechanism of this reduced capacity and the physiological reason for it are unclear but such change does have implication for therapeutic response in pregnancy. Available results from the limited and often poorly structured studies of drug levels in pregnant women neither prove nor disprove the existence of similar changes in hepatic monooxygenase activity during human pregnancy.

Pyridine nucleotide involvement in rat hepatic drug metabolism: pyridine nucleotide kinetics of aniline parahydroxylation.

Apparent kinetic constant (NADPH) have been calculated for NADPH-cytochrome P450 reductase and parahydroxylase in the presence of aniline with hepatic microsomes from both phenobarbital pre-treated and untreated rats. The addition of NADH gave similar stimulation of both aniline parahydroxylation and NADPH-cytochrome P450 reductase activity in the presence of aniline. It is proposed that the increase in aniline metabolism with NADH is due to an increase in the NADPH-cytochrome P450 reductase activity which is rate limiting in microsomes from both phenobarbital and untreated rats.

Serum protein binding of drugs during and after pregnancy in humans.

The serum protein binding of three weakly acidic drugs (salicylic acid, sulfisoxazole, and phenytoin), one week base (diazepam), and one steroid (dexamethasone) was determined in pregnant women at seven time periods during pregnancy and at two periods post partum, as well as in a group of nonpregnant women of childbearing age. The serum free fraction values (ratio of concentrations, free to total drug) of all drugs rose during pregnancy, primarily after 15 wk of gestation, and remained elevated for at least 1 to 5 days post partum. Pregnancy had the greatest effect on protein binding of sulfisoxazole, diazepam, and salicylic acid. The magnitude of this effect is such that quantitatively significant changes in the pharmacokinetic and pharmacodynamic characteristics of certain drugs may be expected to occur during pregnancy (in addition to possible changes caused by other pregnancy-related effects such as altered activity of drug-metabolizing enzyme systems). All drugs but dexamethasone exhibited significant negative correlations between free fraction values and serum albumin concentrations during pregnancy. The serum protein binding of salicylic acid, but not the other drugs tested, was more extensive in nonpregnant women who were not taking oral contraceptives than in those who were.

Antipyrine pharmacokinetics in the pregnant rat.

Pronounced differences in pharmacokinetic parameters of antipyrine have been found in the 20-day pregnant hooded Wistar rat when compared with nonpregnant controls. Total body clearance falls significantly from 5.93 to 3.5 ml/min/kg in the pregnant rat whereas no significant increase in antipyrine volume of distribution occurs. These changes result in an increase in antipyrine half-life from 109 to 223 min in the pregnant rat. This study demonstrates that reduced hepatic mono-oxygenase capacity exists in the pregnant rat and that this can markedly affect drug clearance in there animals.