Cyclosporin nephrotoxicity in heart and lung transplant patients

Twenty-two patients with heart, lung or heart and lung transplants maintained on cyclosporin for periods ranging from 3 months to 10 years developed renal insufficiency which was investigated by renal biopsy. The histopathological changes were: (i) severe vascular and glomerular damage due to thrombotic microangiopathy (TM); (ii) a form of focal segmental glomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than being separate entities, these changes appeared to represent a spectrum of pathology, some biopsies showing all three forms of glomerular injury. In all cases the glomerular changes were accompanied by arteriolar and arterial pathology, and we identified novel ultrastructural changes in the arteriolar endothelial basal lamina. Tubular atrophy was a consistent feature, the severity of which reflected the severity of the glomerular sclerosis, and which appeared to be a consequence of glomerular loss. Our findings are consistent with the nephrotoxic effects of cyclosporin being mediated chiefly via damage to preglomerular vessels and glomerular capillary endothelium. From an analysis of the clinical aspects of these cases, the effects of cyclosporin appear to be to some extent idiosyncratic, and therefore not entirely preventable, but strict monitoring of blood cyclosporin levels is essential to minimize the risk of permanent renal damage. Monitoring urinary protein in addition to plasma creatinine may detect the onset of FSGS, as proteinuria precedes creatinine elevation.      

Influence of architectural design on nosocomial infections in intensive care units—a prospective 2-year analysis

Nosocomial infection rates in an old intensive care ward constructed in 1924 were compared with those in a new one constructed in 1986. The nosocomial infection rate in the old unit was 34.2% and that in the new unit 31.9%, with an average of 33%. The most frequent infections were: pneumonia, urinary tract infection, septicaemia and wound infection. After transfer of the intensive care unit (ICU) the incidence and profile of nosocomial infections remained the same. These findings suggest that the influence of architectural design has little impact on the incidence of nosocomial infections.     

Nosocomial and community-acquired infections in Germany. Summary of the results of the first national prevalence study (NIDEP)

Summary The first German national study on the prevalence of nosocomial and community-acquired infections was performed in 1994 in medical, surgical, gynaecological/obstetrical and intensive care departments. 14,966 patients in 72 German hospitals representatively selected according to size were investigated by outside physicians. These were trained in the use of CDC definitions for nosocomial infections, and their diagnoses validated. Community-acquired infections were recorded according to the assessment of the hospital physicians. For the diagnosis of nosocomial infections, only the opinion of the outside investigators was decisive. A prevalence of 3.5% was found for nosocomial infections and 10.0% for community-acquired infections. The use of antibiotics was documented in 17.7% of all patients on the prevalence day. Of the patients undergoing antibiotic therapy, 16.9% had a nosocomial infection, 47.9% a community-acquired one. In the remaining 35.1% neither a nosocomial nor a community-acquired infection was confirmed.     

Opportunities for the replacement of animals in the study of nausea and vomiting

Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics and identifying emetic liability in novel chemical entities rely on models that can recreate the complexity of these multi-system reflexes. Animal models (especially the ferret and dog) are the current gold standard; however, the selection of appropriate models is still a matter of debate, especially when studying the subjective human sensation of nausea. Furthermore, these studies are associated with animal suffering. Here, following a recent workshop held to review the utility of animal models in nausea and vomiting research, we discuss the limitations of some of the current models in the context of basic research, anti-emetic development and emetic liability detection. We provide suggestions for how these limitations may be overcome using non-animal alternatives, including greater use of human volunteers, in silico and in vitro techniques and lower organisms.     

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.     

Gastroallergic anisakiasis: findings in 22 patients

BACKGROUND AND AIMS: Ingestion of Anisakidae larvae in raw seafood may cause anisakiasis. However, despite the high level of consumption of seafood in Spain, only a few cases of anisakiasis have been reported until now. Anisakis simplex can cause allergic reactions in sensitized patients as a result of its parasitism in the gastrointestinal tract. The purpose of this study was to analyse the clinical findings in 22 patients with gastroallergic anisakiasis. METHODS: Patients with allergic and/or gastric symptoms after seafood ingestion were evaluated in the emergency room of the La Paz General University Hospital. Skin testing for Anisakis simplex and tests on the implicated seafood were performed and amounts of serum-specific immunoglobulin E were assessed. A gastroscopy was performed in those patients with severe allergic or/and persistent gastric symptoms after ingestion of raw or undercooked seafood. RESULTS: Twenty-two patients were diagnosed with gastroallergic anisakiasis in 1 year. Most patients presented to the emergency room of our hospital with allergic symptoms. Gastric symptoms were usually moderate. Gastroscopy revealed local mucosal oedema and gastric erosion at the point of fixation. Two or more worms were detected in three patients. The mean time of latency of allergic symptoms was 5 h, while the mean time for gastric symptoms was 3 h. CONCLUSION: Anisakis simplex parasitism was the causative agent of allergic and gastric symptoms. Gastroallergic anisakiasis appears to be a relatively common disease, that may have been underdiagnosed.     

Antibiotic use in Germany and European comparison

In view of increasing rates of antibiotic resistance worldwide and decreased research and development of new antibacterial compounds, programmes helping to better understand the complex relationship between antibiotic consumption and emergence of resistance have gained importance. Consequently, in addition to increased support for research projects that establish prospective surveillance and evaluation of antibiotic resistance and antimicrobial drug use, the EU has passed directives addressing political leadership in this respect. Information on antibiotic use in Germany is now available from databases independent from cost-oriented market research studies. This information allows estimation of antibiotic use in ambulatory and hospital care as compared with to other EU countries. According to results of current projects, the frequency of national antibiotic use in ambulatory care in Germany (4948 defined daily doses per 1000 population per year) falls within the lower third of EU countries. Upper boundaries in regional variation in antibiotic use are still much lower than values for high-use countries like France, Spain and Portugal. Hospital antibiotic use, in contrast, appears to be in the range of that reported for other countries. However, only rough estimates of hospital antibiotic use are available for Germany as well as most other EU countries due to data usually derived from non-representative hospital sampling.     

Cost-effectiveness of ceftazidime or imipenem/cilastatin versus ceftriaxone+aminoglycoside in the treatment of febrile episodes in neutropenic cancer patients in Germany

Summary A three-pronged cost-effectivess analysis of the treatment of febrile episodes in neutropenic cancer patients was conducted. It included a review of 37 randomized, controlled studies in the MEDLINE and EMBASE databases (1980–1996). Clinical outcomes as well as costs of treatment with imipenem/cilastatin, ceftazidime and ceftriaxone+aminoglycoside were compared. Primary therapy and modification, respectively, were successful in 62 and 27% of patients treated with imipenem/cilastatin, in 56 and 31% with ceftazidime and in 41 and 13% with ceftriaxone+aminoglycoside. From the perspective of a 1,800-bed teaching hospital, the average overall cost per successfully treated patient was DM 7,475 with imipenem/cilastatin, DM 7,810 with ceftazidime and DM 8,963 with ceftriaxone+netilmicin (DM 1=USD 0.56; 7/97). The costs for the German national economy were imipenem/cilastatin DM 23,828, ceftazidime DM 24,985 and ceftriaxone+netilmicin DM 29,838.     

MIC and serum bactericidal activity of clindamycin against methicillin-resistant and -sensitive Staphylococci

Summary Six volunteers were given 600 mg clindamycin intravenously to investigate the serum bactericidal activity (SBA) against 50 methicillin susceptible (MSSA) and 50 methicillin resistantStaphylococcus aureus (MRSA) strains. Minimal inhibitory concentrations (MIC) against MSSA, MRSA and 50 methicillin resistant strains ofStaphylococcus epidermidis (MRSE), of which 50% were slime-producing, were determined. SBA of clindamycin against MSSA and MRSA was equally high (mean reciprocal SBA titer against MSSAvs MRSA 1h after application was 13.0vs 13.45), although MICs against MRSA were markedly higher than against MSSA (MIC 90 of MRSAvs MSSA: 0.06vs>32 mg/l). There was no difference in MICs between slime- and non-slime-producing MRSE.

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MHK und Serumbakterizidie von Clindamycin gegen methicillinresistente und -empfindliche Staphylokokken

Zusammenfassung In dieser Studie wurde dieIn-vivo-Aktivität von Clindamycin gegen 50 Oxacillin-sensible (MSSA) und 50 Oxacillin-resistenteStaphylococcus aureus(MRSA-)Stämme mit dem Serumbakterizidie-Test/(SBA) untersucht. Sechs Probanden wurde einmalig 600 mg Clindamycin intravenös infundiert. Weiterhin wurde die minimale Hemmkonzentration (MHK) von Clindamycin gegen 50 Oxacillin-sensible und -resistenteS. aureus und 50 Oxacillin-resistenteStaphylococcus epidermidis-Stämme, von welchen die Hälfte Schleim produzierten, bestimmt. Clindamycin hatte eine gleich hohe Serumbakterizidie gegen Oxacillin-sensible und-resistenteS. aureus-Stämme (durchschnittlicher reziproker SBA Titer von MSSAvs MRSA 1h nach Applikation: 13,0vs 13,45), obwohl die MHK-Werte gegen die Oxacillin-sensiblenS. aureus deutlich geringer waren (MHK 90 von MSSAvs MRSA: 0,06vs 32 mg/l). Die MHK-Werte gegen die Oxacillin-resistentenS. epidermidis-Stämme waren ebenfalls niedrig, ein Unterschied zwischen Schleim-, beziehungsweise nicht schleimproduzierenden Stämmen bestand nicht.