Cellular senescence in vivo: its relevance in ageing and cardiovascular disease

In most somatic mammalian cell types extensive replication and various types of cellular insults induce a permanent form of growth arrest called senescence. Senescence has been comprehensively characterised in cell culture, but its occurrence in vivo has only recently started to become appreciated. In this mini-review, we examine the evidence for the occurrence of senescence in vivo, with particular emphasis on the cardiovascular system. We also describe the senescent phenotype and discuss its pathophysiological implications. We examine findings in animal models of ageing and human genetic disorders that argue for and against a role of senescence in age-related pathologies in general and vascular disease in particular.     

Trends in the pharmacological treatment of patients with schizophrenia over a 12 year observation period

In this study we evaluated whether our efforts to promote evidence-based guidelines for the psychopharmacological treatment of patients with schizophrenia have led to measurable changes of treatment practice in our hospital by investigating three primary hypotheses: 1) Polypharmacy has become less common in recent years, 2) Conventional neuroleptics have been replaced by second generation antipsychotics; and 3) Dosing regimes have changed towards lower doses. We have therefore collected data from the clinical records of all in-patients with ICD-9/ICD-10 diagnoses of schizophrenia hospitalized at the Department of Psychiatry of the Medical University Innsbruck in the years 1989, 1995, 1998 and 2001. Data from 1989 to 1998 showed a significant decrease in the use of two or more antipsychotics given simultaneously. Contrary to our hypothesis, there was a significant increase in polypharmacy between 1998 and 2001. The predominant use of second generation antipsychotics became standard in schizophrenia treatment. In this context the decrease of concomitant anticholinergic medication is notable. Doses of conventional antipsychotics like haloperidol as well as doses of risperidone decreased whereas doses of other second generation antipsychotics increased. All in all, the pharmacological management of schizophrenia patients is increasingly in tune with current treatment guidelines.     

Sudden infant death syndrome risk questionnaire: a mirror of parental awareness rather than a prospective diagnostic tool

AIM: In 1989, a scoring system that aimed to identify infants at risk of sudden infant death syndrome (SIDS) by a structured questionnaire [SIDS risk questionnaire (SRQ)] consisting of 25 items was introduced in Styria (Austria). It was the aim of the study to compare SIDS rates in the population that had access to the SRQ with the population that had no access. Furthermore, for the population receiving the SRQ, the responding (compliant) and non-responding (non-compliant) groups were compared concerning the incidence of SIDS. METHODS: Within the study period, 53 865 births and 57 SIDS cases were recorded (incidence 1.06/1000) and analysed retrospectively. RESULTS: The incidence of SIDS was significantly higher in the non-responding population (2.36/ 1000) than in the responding group (0.81/1000, p < 0.001). However, the incidence of SIDS was not significantly different in the population that had access to the risk questionnaire (1.29/1000) and the group without access (0.86/1000, p = 0.145). CONCLUSION: The value of any questionnaire used for SIDS prevention may be limited by the existence of a non-compliant population which represents a risk group and should be targeted by other preventive measures.     

Isoflurane reduces glutamatergic transmission in neurons in the spinal cord superficial dorsal horn: evidence for a presynaptic site of an analgesic action

The minimum alveolar concentration (MAC) of a volatile anesthetic defines anesthetic potency in terms of a suppressed motor response to a noxious stimulus. Therefore, the MAC of an anesthetic might in part reflect depression of motor neuron excitability. In the present study we evaluated the effect of isoflurane (ISO) on neurons in the substantia gelatinosa driven synaptically by putative nociceptive inputs in an in vitro spinal cord preparation of the rat. Whole-cell patch-clamp recordings were performed in neurons with their soma in the substantia gelatinosa of transverse rat spinal cord slices. We investigated the effect of ISO on excitatory postsynaptic currents (EPSC) evoked by dorsal root stimulation (eEPSC), spontaneous (sEPSC), and miniature (mEPSC) EPSC. ISO reversibly reduced the amplitude of eEPSC to 39% +/- 22% versus control. ISO decreased the frequency of sEPSC and mEPSC to 39% +/- 26% and 63% +/- 7%. Neither the amplitudes nor the kinetics of mEPSC and sEPSC were altered by ISO. We conclude that ISO depresses glutamatergic synaptic transmission of putative nociceptive primary-afferent inputs, presumably by reducing the release of the excitatory transmitter. This effect may contribute to an antinociceptive action of volatile anesthetics at the spinal cord level. IMPLICATIONS: The present electrophysiological in vitro experiments provide evidence that the volatile anesthetic isoflurane reduces excitatory transmitter release at the first site of synaptic integration of nociceptive inputs, the spinal cord superficial dorsal horn. This effect may contribute to the anesthetic action of volatile anesthetics at the spinal cord level.     

The impact of nursing care and other healthcare attributes on hospitalized patient satisfaction and behavioral intentions

Healthcare organizations in the United States are struggling to find ways to survive in their uncertain and competitive environments. One of the survival strategies used by those organizations is to increase patient satisfaction. This article presents research on factors that influence hospitalized patients' satisfaction and their intention to return to and recommend the hospital. The first objective of this study was to find out, using a comprehensive set of healthcare attributes, which attributes play a more important role in increasing patient satisfaction and behavioral intentions. The second objective was to analyze the relative importance of those attributes and the nature of the relationships across the values of the attributes. More specifically, this study attempted to identify any existing curvilinear relationships among these variables. If any curvilinear relationships exist, do they show an increasing or a decreasing marginal-utility function? Included in this article is an example, featuring a hospital-discharged patient, that explains the importance and uniqueness of this curvilinear relationship. This study found that among six attributes, nursing care showed the largest parameter estimate for the patient satisfaction and behavioral intentions models. Thus, simply improving the nursing care attribute seems to be the most effective manner to enhancing patient satisfaction and behavioral intentions. However, nursing care also showed a diminishing marginal-utility function for both models. To assess the effect of this diminishing marginal-utility function, the impact of nursing care was computed for each unit of improvement together with other attributes. The finding from this study provides information needed to increase patient satisfaction and behavioral intentions and should result in more effective and efficient healthcare management.     

Does footwear affect ankle coordination strategies?

The hypothesis of this study was that shoe hardness and footwear affect ankle coordinative strategies during the running stance period. Subjects ran at a self-selected pace under three conditions-barefoot, wearing a hard shoe, and wearing a soft shoe-while sagittal and frontal view kinematic data were collected. Dynamic systems theory tools were used to explore ankle coordinative strategies under the three conditions. No significant differences in coordination were found between the two shoe conditions. However, significant differences in ankle coordinative strategies existed between the shoe conditions and the barefoot condition. Changes in coordinative strategies may be related to different mechanisms to attenuate impact forces while running barefoot.     

Spring constants of capsular tension rings

PURPOSE: To determine the spring constants of several types of capsular tension rings (CTRs). SETTING: Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany. METHODS: Fourteen models of CTRs provided by 9 companies were tested; all were 11.0 mm in diameter. The CTRs were positioned in a special retainer of a material-testing machine and compressed at a constant speed of 10.0 mm per minute. The distance and force values were recorded, and each CTR model was tested 3 times using a new specimen each time. The resulting measurements were used to calculate a mean spring constant for each CTR model. RESULTS: All tested CTRs showed linear proportionality between force and compression distance. Test results were repeatable and precise. Capsular tension rings of the same model had comparable mechanical properties, and different models had different mean spring constants ranging from 0.8162 to 4.5501 mN/mm. CONCLUSIONS: The spring constant of a CTR is a suitable mechanical characteristic to facilitate the choice of CTR model. A CTR with a low spring constant may be advantageous for the management of zonular dialysis, whereas a CTR with a higher spring constant may reduce capsular bag shrinkage more effectively.     

Donepezil for Alzheimer's disease in clinical practice--The DONALD Study. A multicenter 24-week clinical trial in Germany

This multicenter open-label clinical trial was designed to investigate the safety and efficacy of donepezil, a selective acetylcholinesterase inhibitor, in the treatment of Alzheimer's disease (AD) in routine clinical practice in Germany. A total of 237 patients with mild-to-moderate AD were treated with donepezil for 24 weeks, 186 completed the study according to the protocol. In the completer group, mean MMSE score for efficacy showed an improvement from baseline of +1.6 points at week 12 (95% CI +1.1 to +2.1) and of +1.1 points at week 24 (95% CI +0.5 to +1.7). In more than 80% of the patients, global tolerability was rated to be very good or good. There were only insignificant effects on ECG parameters. This study confirms the results obtained in previous double-blind trials, which showed that donepezil is effective and well tolerated in patients with mild-to-moderately severe AD.