Treatment of urinary incontinence with anticholinergics in patients taking cholinesterase inhibitors for dementia

Clinicians often encounter patients with dementia and urge incontinence who might benefit from both an anticholinergic medication and a cholinesterase inhibitor. At first glance, this combination would seem to violate basic principles of geriatric pharmacology, as the drugs appear to be working at cross-purposes and anticholinergic medications are notorious for worsening cognitive function in susceptible patients. A case is presented and discussed in which this combination was clinically effective and pharmacologically sound.     

Molecular and clinical epidemiology of vancomycin-resistant Enterococcus faecalis

OBJECTIVES: With the recent emergence of vancomycin-resistant (VR) Staphylococcus aureus, subsequent to the suggested transfer of the vanA resistance gene from Enterococcus faecalis, we sought to determine risk factors for acquisition of VR E. faecalis and to evaluate the molecular epidemiology of this less-prevalent and less-studied species of VR enterococcus. METHODS: We compared clinical isolates of VR E. faecalis from 71 patients, collected over 12 years in a large community teaching hospital, with isolates from 126 patients with vancomycin-susceptible E. faecalis. RESULTS: Risk factors for VR E. faecalis acquisition by multivariate analysis were nursing home residence (P = 0.0005), haemodialysis (P = 0.009), decubitus ulcers (P = 0.03) and receipt of parenteral vancomycin (P = 0.0002). Twenty-one percent of VR E. faecalis demonstrated vanA and 79% vanB resistance. The number of VanA isolates increased over time. Molecular analysis showed vanA or vanB in multiple PFGE groups. CONCLUSIONS: The results of this study suggest gene dissemination among some isolates and intra-hospital spread of other isolates. The risk factors identified clearly suggest that VR E. faecalis is a nosocomial pathogen and should be considered in infection control practices. Further surveillance of VR E. faecalis is warranted, due to the potential spread of vancomycin resistance among enterococci and staphylococci.     

Human PET/CT scanners: feasibility for oncological in vivo imaging in mice

PET/CT imaging is a highly valuable oncological imaging modality. The combination of positron emission tomography (PET) and computed tomography (CT) provides the ability to accurately register molecular and metabolic aspects of cancers with anatomical and morphological findings in human clinical routine examinations and for animals in vivo research. Small animal models of mice are widely used in biomedical research for mimicking and studying the human nature, because of their genetic resemblance and the feasibility of gene transfer and gene modification. The recent generation of high performance human PET/CT scanners combines a state of the art full-ring 3D PET scanner and a high-end 16-slice CT scanner (biograph Sensation 16, Siemens AG, Erlangen, Germany). Small animals can be examined with special scanning and reconstruction protocols. The examination of tumor-bearing small animals using a modern human PET/CT revealed excellent image quality. CT can be performed with a maximum spatial resolution of 0.6 x 0.6 x 0.6 mm and PET with a maximum spatial resolution of 6.3 x 6.3 x 6.0 mm. The examination of tumor-bearing small animals using human PET/CT allowed accurate correlation and evaluation of metabolic and anatomical information and is promising for in vivo research purposes. Although image quality is limited by spatial resolution, human PET/CT is widely available and expected to contribute significantly to research with small animal imaging. The investigation of cancer in small animals with PET/CT is probably one of the most challenging tasks in nuclear medicine for the evaluation of tumor growth and growth inhibition factors; development of new anti-tumor drugs and measuring of anti-tumor effects; and cancer treatment response of immunotherapy, chemotherapy and radiation therapy.     

A functional-structural model to understand cardiac autonomic nervous system (ANS) dysregulation in affective illness and to elucidate the ANS effects of antidepressive treatment

Numerous studies provide evidence that major depression (MD) is associated with certain disorders of cardiac autonomic nervous system (ANS) function, in particular, with an autonomic neurocardiac imbalance characterized by a low cardiovagal modulation, a raised sympathetic nerve activity and a high resting heart rate. We assume that such MD-associated cardiac ANS disorders are mainly caused by functional-structural abnormalities within the central autonomic network (CAN), in particular, by well-defined abnormalities of hypothalamic structures in MD. In view of the well-known association between an autonomic neurocardiac imbalance and the risk for cardiac arrhythmias, we assume that MD-associated cardiac ANS disorders are at least partly responsible for the high cardiovascular mortality risk in MD. It is, however, still unclear whether antidepressive treatment will lower the risk for cardiovascular complications in MD. There is convincing evidence that a successful antidepressive treatment with electroconvulsive therapy, cognitive behavioral therapy, or pharmacotherapy with primarily non-antimuscarinergic antidepressants can improve an initially disturbed cardiac ANS function in MD. These studies correspond well to our findings that treatment with both, nefazodone or reboxetine, can induce a reduction of central sympathetic nerve activity and an increase of the initially lowered cardiovagal modulation depending on the improvement of depressive symptoms after treatment. Since both effects occured obviously independent from the primarily serotonergic or noradrenergic action of the antidepressants, our findings suggest the existence of a generally supraordinate and uniform mechanism underlying the ANS effects of antidepressive treatment with drugs inhibiting serotonin- or noradrenaline reuptake.     

German-Austrian recommendations for HIV-therapy in pregnancy: update May 2003

In Germany during the past years about 200-250 HIV infected pregnant women delivered a baby per year, a number that is currently increasing. To determine the HIV-status early in pregnancy voluntary HIV-testing of all pregnant women is recommended in Germany and Austria as part of prenatal care. In those cases, where HIV infection was known during pregnancy, since 1995 the rate of vertical transmission of HIV was reduced to 1-2%. - This low transmission rate has been achieved by the combination of anti-retroviral treatment of pregnant women, elective caesarean section before onset of labor, anti-retroviral post exposition prophylaxis in the newborn and refraining from breast-feeding by the HIV infected mother. To keep pace with new results in research, approval of new anti-retroviral drugs and changes in the general treatment recommendations for HIV infected adults, in 1998 and 2001 an interdisciplinary consensus meeting was held. Gynaecologists, infectious disease specialists, pediatricians, pharmacologists, virologists and members of the German AIDS Hilfe (NGO) were participating in this conference to update the prevention strategies. A third update became necessary in 2003. The updating process was started in January 2003 and was terminated in July 2003. The guidelines provide new recommendations on the indication and the starting point for HIV-therapy in pregnancies without complications, drugs and drug combinations to be used preferably in these pregnancies and updated information on adverse effects of anti-retroviral drugs. Also the procedures for different scenarios and risk constellations in pregnancy have been specified again. - With these current guidelines in Germany and Austria the low rate of vertical HIV-transmission should be further maintained or even further lowered.     

Test-retest reliability of temporal and spatial gait characteristics measured with an instrumented walkway system (GAITRite<Superscript>®</Superscript>)

Background

The purpose of this study was to determine the test-retest reliability of temporal and spatial gait measurements over a one-week period as measured using an instrumented walkway system (GAITRite^®).

Methods

Subjects were tested on two occasions one week apart. Measurements were made at preferred and fast walking speeds using the GAITRite^® system. Measurements tested included walking speed, step length, stride length, base of support, step time, stride time, swing time, stance time, single and double support times, and toe in-toe out angle.

Results

Twenty-one healthy subjects participated in this study. The group consisted of 12 men and 9 women, with an average age of 34 years (range: 19 – 59 years). At preferred walking speed, all gait measurements had ICC's of 0.92 and higher, except base of support which had an ICC of 0.80. At fast walking speed all gait measurements had ICC's above 0.89 except base of support (ICC = 0.79),

Conclusions

Spatial-temporal gait measurements demonstrate good to excellent test-retest reliability over a one-week time span.

     

A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry

Context  Accurate estimation of risk for untoward outcomes after patients have been hospitalized for an acute coronary syndrome (ACS) may help clinicians guide the type and intensity of therapy. Objective  To develop a simple decision tool for bedside risk estimation of 6-month mortality in patients surviving admission for an ACS. Design, Setting, and Patients  A multinational registry, involving 94 hospitals in 14 countries, that used data from the Global Registry of Acute Coronary Events (GRACE) to develop and validate a multivariable stepwise regression model for death during 6 months postdischarge. From 17 142 patients presenting with an ACS from April 1, 1999, to March 31, 2002, and discharged alive, 15 007 (87.5%) had complete 6-month follow-up and represented the development cohort for a model that was subsequently tested on a validation cohort of 7638 patients admitted from April 1, 2002, to December 31, 2003. Main Outcome Measure  All-cause mortality during 6 months postdischarge after admission for an ACS. Results  The 6-month mortality rates were similar in the development (n = 717; 4.8%) and validation cohorts (n = 331; 4.7%). The risk-prediction tool for all forms of ACS identified 9 variables predictive of 6-month mortality: older age, history of myocardial infarction, history of heart failure, increased pulse rate at presentation, lower systolic blood pressure at presentation, elevated initial serum creatinine level, elevated initial serum cardiac biomarker levels, ST-segment depression on presenting electrocardiogram, and not having a percutaneous coronary intervention performed in hospital. The c statistics for the development and validation cohorts were 0.81 and 0.75, respectively. Conclusions  The GRACE 6-month postdischarge prediction model is a simple, robust tool for predicting mortality in patients with ACS. Clinicians may find it simple to use and applicable to clinical practice.      

No alternative? The regulation and professionalization of complementary and alternative medicine in the United Kingdom

In conjunction with its growing popularity, complementary and alternative medicine (CAM) in the United Kingdom has witnessed increasing professionalization, partly prompted by the landmark Parliamentary Inquiry that reported in November 2000. Professionalization has become a significant strategy for practitioner associations and a key focus for the government, media, and patient groups. It is being driven by concern over the interests of patients and consumers, and in relation to the possible integration of certain forms of CAM into publicly funded healthcare. It is, moreover, being reconfigured in explicitly national terms. This paper draws on research into practitioner associations representing nine CAM modalities in the UK-aromatherapy, Chinese herbal medicine, chiropractic, crystal healing, feng shui, 'lay' homeopathy, medical homeopathy, osteopathy, and Radionics-, examining the recent wave of professionalization in relation to Foucault's concern with 'techniques of the self.' It highlights the contrasting experience of an association of Chinese herbalists seeking statutory self-regulation (SSR) and an association of chiropractors that was instrumental in securing SSR for chiropractic.     

Synthesis and biological evaluation of a new class of geldanamycin derivatives as potent inhibitors of Hsp90

The heat shock protein Hsp90 has increasingly become an important therapeutic target especially for treatment of cancers. Inhibition of the ATPase activity of Hsp90 by natural products (e.g., 17-allylaminogeldanamycin or radicicol) leads to the ubiquitination of oncogenic client proteins such as Her-2, Raf-1, and p-Akt followed by their proteasomal degradation. Hsp90 inhibitors simultaneously target multiple oncogenic proteins and provide an advantage for cancer therapy due to the potential for increased efficacy and overcoming drug resistance. In an effort to convert geldanamycin into a druglike compound with better pharmacokinetic properties and efficacy in human tumor xenograft models, geldanamycin was derivatized on the 17-position to prepare new analogues such as 17-geldanamycin amides, carbamates, and ureas and 17-arylgeldanamycins. All the compounds were first evaluated ex vivo using a cell-based Her-2 degradation assay and in vitro using biochemical assays that measure recombinant Hsp90 (rHsp90) competitive binding and changes in rHsp90 conformation. In addition, we confirmed the selectivity of geldanamycin analogues for Hsp90 derived from tumor cells using a novel cell lysate binding assay.