[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.

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.

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.

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.

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.

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.

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.

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.

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.

[Metabolism of antiparkinson drugs. An example of competitive hydroxylation]. / Der Metabolismus von Antiparkinson-Mitteln. Ein Beispiel für konkurrierende Hydroxylierungen.

The investigation of the metabolism of the antiparkinson drugs trihexyphenidyl (1), pridinol (2) and biperiden (3) revealed a graduate tendency for hydroxylation in the different structural elements: If alicyclic, saturated heterocyclic and aromatic ring systems are present in one compound like in 1, the alicyclic ring system is attacked predominately. The amount of metabolites with hydroxy-groups in the saturated heterocyclic ring is much lower, and no hydroxylation takes place in the aromatic ring. In drugs without alicyclic ring systems like 2 the saturated heterocyclus is attacked preferentially, but also some phenolic metabolites are formed. Consequently the following arrangement of falling hydroxylation-tendency can be established: Formula: see text. Probably this arrangement is of common validity and therefore a prediction on the hydroxylation-tendency of other compounds seems to be possible.

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.

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

The serum protein binding of salicylic acid (SA), sulfisoxazole (SUL), phenytoin (P), dexamethasone (D), diazepam (DI) and bilirubin (B) was determined in Long-Evans rats during pregnancy and after parturition. Serum free fraction (f) values were obtained by equilibrium dialysis (drugs) and by a reaction rate method (B). Concurrent control experiments were carried out on nonpregnant animals. Values of f were not significantly different from controls during the first 10 to 15 days of pregnancy. Pronounced increases in f of SA, SUL, P and D were observed on the 20th and 21st day of pregnancy; the f of DI was increased only on the 21st day and the f of B was not significantly changed at any time. The f values for SA, SUL and P returned almost to control levels 2 days after parturition (D, DI and B were not studied at that time). Additional studies with SUL, P and D on the 20th day of pregnancy showed that the increase in f occurred over a wide concentration range. Total serum protein and albumin concentrations were significantly decreased only on the 21st day of pregnancy. Pretreatment with activated charcoal decreased f of SA, SUL, P and D (the other compounds were not studied) in serum of 20-day pregnant (but not control) animals. The decreased protein binding of drugs in serum of pregnant rats appears to be due, at least in part, to accumulation of endogenous displacing agents.

Hepatic microsomal metabolism of drugs during pregnancy in the rat.

A progressive depression in the in vitro hepatic microsomal enzyme metabolism of drug substrates, during pregnancy in the Wistar rat, was measured against various parameters. This depression was greatest with aniline para-hydroxylation and least with p-nitrobenzoic acid reduction. The depressed metabolism, which correlated with prolonged in vivo hexobarbital sleeping times, was paralleled by falls in hepatic microsomal cytochrome P-450 levels. There was a rapid reversal of this depression just before delivery, but these changes did not appear to be controlled by progesterone levels. The suggestion is advanced that the lower levels of hepatic microsomal enzyme activity might reflect a biological control mechanism to ensure the elevated levels of progesterone required to maintain the pregnant state. The relationship between changes in liver weight and enzyme activity was also examined as a possible explanation of the observed depression in drug metabolism during pregnancy.

[Exchange of aromatically bound halogen for OH- and SCH3-groups in metabolising clozapine in the human organism (author's transl)]. / Austausch aromatisch gebundenen Halogens gegen OH- und SCH3- bei der Metabolisierung des Clozapins im menchlichen Körper

8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo-(b,e)(1,4)-diazepine (clozapine, 1) is metabolized in humans by exchange of the aromatic halogen for a hydroxy- or a methylthio-group (compounds 2 and 3). Further metabolites are the N-demethyl derivatives of 2 and 3, the compounds 4 and 5. In addition a clozapine metabolite with the structure 6 with an oxidized piperazine ring was found. The presence of a metabolite with an oxidized sulfur atom is suggested. Possible ways for the formation of these metabolites are discussed.

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.