Value of systemic and local administration of antibiotics in soft tissue and bone infections

There is little data to support the efficacy of prophylactic antibiotics in traumatology. In closed fractures three randomized controlled studies using a 1-3 day prophylaxis with Cephalosporins of the first or second generation or a Penicillinase-resistent Penicillin demonstrated a reduction of the infection rate. For the Cephalosporins of the second generation it was shown, that a single dose was less efficient than five repeated applications over 24 hours. In hip-fractures a prophylaxis with Cephalothin or Cefotiam reduced the frequency of infections when compared with controls. In open fractures a treatment over 10 days using Cephalothin or Isoxazolyl-Penicillin showed a significant drop of the infection rate. If however the fractures were not treated using the principles of rigid internal fixation and were covered with Dicloxacillin over 2 days only there was no significant improvement. A multicenter study finally indicates that a one day course of cefonicid sodium is not inferior to a prolonged course of antibiotics for prevention of early postoperative fracture-site infections. We conclude, that open and closed fractures can profit from antibiotic prophylaxis which starts immediately before surgery and is continued over 24 hours. We favour Isoxazolyl-Penicillin because of its efficacy against staphylococcus aureus and epidermidis which predominate in early infection. In established bone and soft tissue infections antibiotics are used when there is local spreading, sepsis, involvement of joints or when reinterventions in the infectious focus are necessary. In these cases bacteriological testing in the laboratory is essential for the selection of antibiotics. Local application of antibiotics in irrigation-drainage solutions can not be recommended. PMMA-chains serve as temporary spacers, but should be removed early before their extraction becomes difficult and resistant bacteria develop. When defects are closed with cancellous bone or soft tissues the use of Gentamycin-fleece or Taurolin-gels is recommended.     

Targeted stent use in clinical practice based on evidence from the Basel Stent Cost Effectiveness Trial (BASKET): reply

We thank Agostini Pierfranco and colleagues for their interestin our analysis of the     

No evidence for involvement of the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus in early onset obesity

In light of evidence of linkage of obesity to chromosome 2q31-q37, we hypothesized that the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus (NIDDM) is involved in early onset obesity. We screened the NIDDM 'high-risk'-haplotype combination formed by the alleles 112 and 121 of the polymorphisms UCSNP-43, -19, and -63 in 166 families consisting of an extremely obese child or adolescent (mean BMI percentile: 99.3+/-1.38), one or more obese sibs (mean BMI percentile: 97.42+/-2.88), and both of their parents. Genotyping for three calpain-10 gene polymorphisms was performed by polymerase chain reaction (PCR) with (a) length polymorphism detection (UCSNP-19) or (b) allele-specific PCR (UCSNP-43 and -63). To allow for correct haplotype assignment all individuals were additionally genotyped for two microsatellite markers (D2S125 and D2S2338). We followed a hierarchical test procedure. As the first step, model-free linkage analysis was performed using maximum likelihood binomial statistics. The second stage consisted of a one-sided asymptotic pedigree disequilibrium test for the UCSNP-43 and on an exploratory level for the other SNP-markers and all haplotypes formed by the three SNPs. The final stage investigated the reported haplotype combination. We failed to detect an initial linkage of obesity to this region (LOD score <0.4). All subsequent exploratory analyses were negative. Our analysis of the relationship between the NIDDM 'high-risk' haplotype combination and extreme early onset obesity revealed no evidence for linkage and association.     

Copolymer effects on microglia and T cells in the central nervous system of humanized mice

The random amino acid copolymers FYAK and VWAK ameliorate EAE in a humanized mouse model expressing both a human transgenic myelin basic protein (MBP)85-99-specific T cell receptor and HLA-DR2. Here we show that microglia isolated from the central nervous system (CNS) of humanized mice with EAE induced by MBP85-99 and treated with these copolymers had reduced expression of HLA-DR, and thus reduced capacity to present MBP85-99 and activate transgenic T cells. In vitro microglia up-regulated empty HLA-DR2 upon activation with GM-CSF with or without LPS or IFN-gamma, but not with IL-4 or IL-10. Correspondingly, gene chip arrays showed that the CNS of untreated and YFAK-treated mice differentially expressed pro- and anti-inflammatory molecules during MBP85-99-induced EAE. Interestingly, microglia expressed the full-length gammabeta and alphabeta subunits of the tetrameric adaptor protein complexes AP-1 and AP-2 respectively, but after treatment with GM-CSF these complexes were cleaved, as had been found in immature dendritic cells derived from bone marrow. Strikingly, in vivo the perivascular lymphocyte infiltration seen in untreated mice immunized with MBP85-99 was composed of equal numbers of hVbeta2+ MPB85-99-specific transgenic and hVbeta2- endogenous T cells, while the much smaller infiltration seen after treatment with YFAK was composed predominantly of hVbeta2- endogenous T cells.     

CD8 is needed for positive selection but differentially required for negative selection of T cells during thymic ontogeny

During thymic development, immature thymocytes expressing major histocompatibility complex (MHC) class I-restricted T cell receptors (TcR) differentiate into CD8⁺ T cells with cytolytic functions. To evaluate the role of CD8 in positive and negative selection during thymic ontogeny, mice rendered CD8-null by gene targeting were bred with three lines of transgenic mice expressing unique MHC class I-restricted TcR. In all three instances CD8 was required for positive selection of MHC class I-restricted transgenic T cells. The efficiency of positive selection decreased in accordance with a reduced level of CD8 expression on thymocytes. Surprisingly, there was a differential requirement for CD8 expression in negative selection of MHC class I-restricted thymocytes, depending on the antigen specificity of TcR. These observations show that CD8 is essential for positive selection but is differentially required for negative selection of MHC class I-restricted T cells. Thus thymic selection, at least for negative selection, can occur in the absence of the CD8 accessory molecule.     

Coping with serious accidental injury: a one-year follow-up study

BACKGROUND: The aim of this study was to analyze changes of coping strategies in severely injured accident victims over time and to compare patients with high and low posttraumatic stress disorder (PTSD) symptom levels with regard to their coping patterns and accident-related cognitions. METHODS: 106 consecutive patients with severe accidental injuries admitted to a trauma surgery intensive care unit (ICU) were assessed within 1 month after the trauma and 6 and 12 months later. Assessments included a clinical interview, the Freiburg Questionnaire of Coping with Illness, the patients' accident-related cognitions, the Clinician-Administered PTSD Scale, the 90-item revised Symptom Checklist (SCL-90-R), and the Sense of Coherence Questionnaire (SOC). Patients who met the criteria for either full or subsyndromal PTSD at least once over the observation period (36 subjects; 34.0%) were assigned to a highly symptomatic group (HSG), the remainder (70 subjects; 66.0%) to a less symptomatic group. RESULTS: Overall, active problem-focused coping was predominant immediately after the accident and declined over time, with a stronger decrease in the HSG. Patients in the HSG scored higher on the SCL Global Severity Index and lower on the SOC. The patients' subjective appraisal of accident severity was higher in the HSG, whereas there was no group difference with regard to accident-related variables such as type of accident, injury severity and mild to moderate traumatic brain injury. CONCLUSIONS: Active problem-focused coping, although utilized most frequently and often regarded as protective, might be an inadequate strategy in face of acute stress following a severe accident. Clinicians should not expect their patients to cope very actively in the acute ICU phase. In the subsequent rehabilitation, active coping seems to be more adaptive.     

Prevalence of nosocomial infections in Swiss children's hospitals.

OBJECTIVE: To acquire data on pediatric nosocomial infections (NIs), which are associated with substantial morbidity and mortality and for which data are scarce. DESIGN: Prevalence survey and evaluation of a new comorbidity index. SETTING: Seven Swiss pediatric hospitals. PATIENTS: Those hospitalized for at least 24 hours in a medical, surgical, intensive care, or intermediate care ward. RESULTS: Thirty-five NIs were observed among 520 patients (6.7%; range per hospital, 1.4% to 11.8%). Bacteremia was most frequent (2.5 per 100 patients), followed by urinary tract infection (1.3 per 100 patients) and surgical-site infection (1.1 per 100 patients; 3.2 per 100 patients undergoing surgery). The median duration until the onset of infection was 19 days. Independent risk factors for NI were age between 1 and 12 months, a comorbidity score of 2 or greater, and a urinary catheter. Among surgical patients, an American Society of Anesthesiologists (ASA) score of 2 or greater was associated with any type of NI (P = .03). Enterobacteriaceae were the most frequent cause of NI, followed by coagulase-negative staphylococci; viruses were rarely the cause. CONCLUSIONS: This national prevalence survey yielded valuable information about the rate and risk factors of pediatric NI. A new comorbidity score showed promising performance. ASA score may be a predictor of NI. The season in which a prevalence survey is conducted must be considered, as this determines whether seasonal viral infections are observed. Periodic prevalence surveys are a simple and cost-effective method for assessing NI and comparing rates among pediatric hospitals.     

Carcinogenic activity of cigarette smoke gas phase and its modulation by beta-carotene and N-acetylcysteine.

Male strain A/J mice were exposed for six hours a day, five days a week for six months to either full tobacco smoke or to tobacco smoke drawn through a HEPA filter that removed more than 99% of particulate matter. After another four months in air, the animals were sacrificed and lung tumors were counted for calculation of multiplicities and incidences. Analysis of the chamber atmospheres showed that in the filtered smoke the concentrations of polycyclic aromatic hydrocarbons and tobacco smoke specific nitrosamines were reduced to from below 18% to even nondetectable levels of the original values measured in the unfiltered smoke. Aldehydes and other volatile organic compounds such as 1,3-butadiene, benzene, or acrolein were reduced to about 50 to 90% of the concentrations found in unfiltered smoke. Some potentially carcinogenic metals reached levels in filtered smoke ranging from 77% to less than 1% found in full smoke. The mice exposed to the filtered smoke atmosphere had practically identical lung tumor multiplicities and incidence as had the animals exposed to full smoke, significantly higher than in air exposed controls. Diets containing 0.5% beta-carotene or 0.4% N-acetylcysteine afforded some chemoprevention. It was tentatively concluded that 1,3-butadiene might be an important contributor to lung tumorigenesis in this mouse model of tobacco smoke carcinogenesis.