Inhibition of bone repair in a rat model for chronic and excessive alcohol consumption.

Alcohol abuse is associated with increases in both the incidence of fractures and complications in fracture healing. The purpose of this study was to determine the dose-dependent effects of ethanol on bone repair in a rat model. Three-month-old male Wistar rats were continuously fed liquid diets containing ethanol as either 36% or 26% of total calories or control diets for 6 weeks. Then, a bone repair model was created in all rats. Bone healing and liver metabolism were evaluated 7 weeks after bone injury. For each dose, there were three ethanol-feeding groups receiving (1) ethanol for 13 weeks, (2) control diet for 13 weeks (pair-fed), and (3) ethanol before bone injury and control diet (pair-fed) after injury. Another group was fed ethanol (36%) before injury and given control diet ad libitum after injury. There were also two nutritional controls consuming control diet and standard rat chow ad libitum for 13 weeks. Abnormal liver metabolism was evident at the higher ethanol dose - increases in cytochrome P4502E1 specific activity (5-fold; P < .01), triglyceride content (4-fold; P < .02), and liver weight (25%; P = .05) - compared with pair-fed controls. The higher dose of ethanol resulted in deficient bone repair when compared with rats receiving ethanol-free control diet by pair-feeding: 26% less (P = .02) rigidity of the repaired bone, 41% less (P = .02) intrinsic stiffness, 24% less intrinsic strength (P = .05), and 14% less (P = .001) ash density of the repair tissue. The reduced food consumption of ethanol-fed rats compared with that in the nutritional controls did not contribute to this deficiency. Furthermore, removal of ethanol (as 36% of calories) from the diet after bone injury completely restored normal bone healing and nearly normalized the liver metabolism. The lower ethanol dose (26% of calories) had a minimal effect on liver metabolism and bone repair. We conclude that ethanol (as 36% of calories) in the rat diet, especially during the postinjury period, was solely responsible for the observed inhibition of bone repair.     

Preliminary assessment of an automated surveillance system for infection control.

BACKGROUND AND OBJECTIVE: Rapid identification and investigation of potential outbreaks is key to limiting transmission in the healthcare setting. Manual review of laboratory results remains a cumbersome, time-consuming task for infection control practitioners (ICPs). Computer-automated techniques have shown promise for improving the efficiency and accuracy of surveillance. We examined the use of automated control charts, provided by an automated surveillance system, for detection of potential outbreaks. SETTING: A 656-bed academic medical center. METHODS: We retrospectively reviewed 13 months (November 2001 through November 2002) of laboratory-patient data, comparing an automated surveillance application with standard infection control practices. We evaluated positive predictive value, sensitivity, and time required to investigate the alerts. An ICP created 75 control charts. A standardized case investigation form was developed to evaluate each alert for the likelihood of nosocomial transmission based on temporal and spatial overlap and culture results. RESULTS: The 75 control charts were created in 75 minutes and 18 alerts fired above the 3-sigma level. These were independently reviewed by an ICP and associate hospital epidemiologist. The review process required an average of 20 minutes per alert and the kappa score between the reviewers was 0.82. Eleven of the 18 alerts were determined to be potential outbreaks, yielding a positive predictive value of 0.61. Routine surveillance identified 5 of these 11 alerts during this time period. CONCLUSION: Automated surveillance with user-definable control charts for cluster identification was more sensitive than routine methods and is capable of operating with high specificity and positive predictive value in a time-efficient manner.     

Effects of Alendronate and Calcitonin on Bone Mineral Density in Postmenopausal Osteoporotic Women. An Observational Study

Objective: Alendronate and calcitonin are antiresorptive drugs that were used for the treatment of postmenopausal osteoporosis and were shown to increase bone mineral density (BMD). However, the effect of both drugs in daily clinical practice may differ from that observed in clinical trials.Method: About 50 postmenopausal osteoporotic women were observed during their first year of treatment. Among them, 32 patients used alendronate and 18 used calcitonin. Lumbar spine and femoral neck BMD were measured by dual energy X-ray absorptiometry (DXA) at baseline and after 1 year of therapy. Biochemical markers (B-ALP – bone-specific alkaline phosphatase, OTC – osteocalcin and DPD/UCr – deoxypyridinoline/creatinine ratio) of bone metabolism were measured at baseline and 6 months later. Patient compliance was assumed by tablet counting and verified at interview. Each patient was further questioned about her attitude towards the treatment, as well as her dairy product intake, physical activity, use of other medications, smoking and social status.Main outcome measure: (1) Annual percent change in BMD in lumbar spine and femoral neck after the one-year treatment with either alendronate or calcitonin. (2) The change in biochemical markers of bone turnover.Results: The lumbar spine BMD significantly increased by 7.0% (P < 0.001), the femoral neck BMD by 4.3% (P < 0.01). OTC, B-ALP and DPD/UCr decreased significantly during the therapy with alendronate. Compliance with therapy was 79% (95% CI 68–90%). In the calcitonin-treated group, the lumbar spine BMD significantly increased by 3.1 % (P < 0.05), while the femoral neck BMD remained unchanged. OTC, B-ALP and DPD/UCr did not change significantly during the treatment with calcitonin. Compliance with calcitonin therapy was 87% (95% CI 63–110%). The annual change of BMD in both treatment groups was independent on all questioned factors.Conclusion: In daily practice, alendronate enhanced significantly BMD both in lumbar spine and femoral neck. Calcitonin showed increase only in the lumbar spine BMD.     

A new metabolic pathway for N,N-dimethyltryptamine

N,N-Dimethyltryptamine (DMT) undergoes a major structural alteration when added to whole human blood or its red blood cells in vitro. A new high-pressure liquid chromatography (HPLC) peak is present in extracts of these treated tissues. The compound responsible for this peak has been identified by ultraviolet spectrophotometry and by mass spectrometry as dimethylkynuramine (DMK). The enzyme responsible for this appears to be different from tryptophan 2,3-dioxygenase and also from indoleamine 2,3-dioxygenase.     

Optimization of the High-Shear Wet Granulation Wetting Process Using Fuzzy Logic Modeling

A fuzzy model has been developed for the optimization of high-shear wet granulation wetting on a plant scale depending on the characteristics of pharmaceutical active substance particles. The model optimized on the basis of experimental data involves a set of rules obtained from expert knowledge and full-scale process data. The skewness coefficient of particle size distribution and the tapped density of the granulated mixture were chosen as the model input variables. The output of the fuzzy ruled system is the optimal quantity of wetting liquid. In comparison to manufacturing practice, a very strong sensitivity of the optimal quantity of the added wetting liquid to the size and shape of the active substance particles has been identified by fuzzy modeling.     

Hybridization of the 18 alpha-satellite probe to chromosome 1 revealed in PGD

Although the chromosome 18 alpha-satellite probe is considered to have a very low polymorphism rate, the routine use of this probe in prenatal diagnosis revealed rare variants in size and copy number of these sequences. A polymorphic signal was detected in preimplantation genetic diagnosis (PGD) for aneuploidy, in a patient with repeated early miscarriages. A third small signal of chromosome 18 alpha-satellite probe was observed in two of four evaluated embryos. Hybridization to the woman's metaphasic lymphocytes revealed that the small signal was localized in the pericentromeric region of chromosome 1. Reanalysis of blastomeres with telomeric probes for chromosome 18q confirmed the presence of only two copies of chromosome 18. Options for verifying PGD analysis results, to prevent misdiagnosis in cases of suspected polymorphism, are discussed. Although some authors speculate about a possible role of heterochromatin polymorphism in infertility, this rare polymorphism of 18 alpha-satellite sequences is in itself probably a normal variant. This is the third report of a cross-hybridization of the chromosome 18 alpha-satellite probe and the first report of the localization of the polymorphic 18 alpha-satellite signal to chromosome 1.     

Patterns of injuries: accident or abuse

This study uses two types of independent variables, age and the location of the physical wound, to develop a model of injury patterning that identifies violent behavior without direct observation of the assault. In this research, domestic violence injuries are compared to accidental injuries. The results indicate that there are specific and predictable injury patterns that separate abuse from other kinds of wounds. A logistic regression model was developed to identify the regions of the body most susceptible to injury from domestic assault. Using the age of the victim and the injury regions, probabilities were calculated to determine which wounds were caused by abuse.     

Beitrag zur Kenntnis septischer Exantheme

Ohne Zusammenfassung     

Advances in urinary proteome analysis and biomarker discovery

Noninvasive diagnosis of kidney diseases and assessment of the prognosis are still challenges in clinical nephrology. Definition of biomarkers on the basis of proteome analysis, especially of the urine, has advanced recently and may provide new tools to solve those challenges. This article highlights the most promising technological approaches toward deciphering the human proteome and applications of the knowledge in clinical nephrology, with emphasis on the urinary proteome. The data in the current literature indicate that although a thorough investigation of the entire urinary proteome is still a distant goal, clinical applications are already available. Progress in the analysis of human proteome in health and disease will depend more on the standardization of data and availability of suitable bioinformatics and software solutions than on new technological advances. It is predicted that proteomics will play an important role in clinical nephrology in the very near future and that this progress will require interactive dialogue and collaboration between clinicians and analytical specialists.