Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Noninvasive Estimation of Blood Alcohol Concentrations: Ethanol Vapor Above the Eye

The present study describes, in animals, a novel approach to the in vivo, noninvasive determination of alcohol in the body. The concentration of ethanol in vapor above the lacrimal fluid in the eye was analyzed in situ by the use of a fast (1-min) gas sensor method developed previously for biological liquids. After an oral dose of 1 g/kg to 11 animals, eye vapor measurements and blood samples were obtained over 4 hr. The correlation of 61 blood ethanol concentrations obtained by the two methods yielded a correlation coefficient of 0.92 and a slope of 0.99. The metabolic rates of ethanol determined by gas chromatographic analysis of blood and by ethanol eye vapor analysis are virtually identical. The data suggest that ethanol eye vapor analysis may be an attractive, noninvasive method for the determination of ethanol in animals. The method is not subject to false high readings due to alcohol in the buccal cavity and thus might constitute an alternative to breath analysis in the human. In a separate series, ethanol was determined by head space gas chromatography in samples of blood and lacrimal fluid while the animals were under ketamine anesthesia. The correlation of ethanol concentrations in blood and lacrimal fluid (r = 0.99) shows that ethanol is distributed in lacrimal fluid which comprises part of total body water.     

The evolution of a biodegradable membrane for use in urological surgery. A summary of 109 in vivo experiments

The evolution of a collagen/vicryl composite membrane designed as a prosthetic material for use in urinary tract surgery is described. The early experiments in which collagen film alone was used to repair experimental ureterotomies are reviewed together with our first experiments with the collagen/vicryl prosthesis in the repair of partial nephrectomies and of full thickness defects created in the urinary bladder of experimental rabbits. These early results led to the preparation of a composite using a more highly purified collagen and employing a method of sterilisation (gamma irradiation) which would be acceptable for regular use in medical products. The results of a further series of partial nephrectomy and full thickness bladder repairs show that irradiation does not compromise the efficacy of the collagen/vicryl composite in vivo.     

Percutaneous double-balloon angioplasty of a stenotic modified Fontan aortic homograft conduit

A 28-year-old woman with pulmonary atresia underwent a modified Fontan procedure that utilized a valved aortic homograft; she developed stenosis of the distal anastomosis between the homograft and the pulmonary artery. Because of the increased risk of reoperation, balloon angioplasty of this stenotic lesion was performed successfully. In the subsequent 11 months she has remained asymptomatic. Balloon angioplasty was a successful alternative to reoperation in this patient.     

Event-related Potentials as Markers for Alcoholism Risk in High Density Families

One hundred sixty-eight adult siblings and parents from affected and control families were tested for ERP characteristics using two tasks involving an auditory oddball paradigm. Significant within family differences among affected families suggest that risk for developing alcoholism may be seen even in adult subjects who have had experience consuming alcohol. Further, analysis of quantity and recency of drinking in the past seven days were not correlated with either amplitude or latency of P300, suggesting that the within-family differences observed reflect relative risk for developing alcoholism rather than experience with alcohol.     

Antibiotic resistance: effect of different criteria for classifying isolates as duplicates on apparent resistance frequencies.

OBJECTIVE: To investigate the effect of screening specimens and different criteria for exclusion of duplicate isolates when surveillance of antimicrobial resistances is performed. MATERIALS AND METHODS: Trends in resistance were analysed for recent isolates of selected organisms from Guy's and St Thomas' Hospitals with the use of various criteria for the exclusion of duplicates, including time since the last isolate and antibiogram pattern, and the effect of excluding screening specimens. RESULTS: There was a significant difference of about 8% in the apparent frequency of methicillin resistance in Staphylococcus aureus in inpatients if the time limit for duplicates was set at 5 rather than 30 days; it was about 10% if a 5 day limit was compared with a 365 day limit. There was also a significant difference, of 6-10%, in apparent resistance frequencies if isolates from screening specimens were excluded. Apparent gentamicin resistance rates in Klebsiella spp. varied between 11% and 28%, and the number of apparent patient isolates of gentamicinresistant organisms varied by up to 35%, depending on the duplicate exclusion criteria chosen. Effects were smaller, though still significant, for vancomycin resistance in Enterococcus spp. There was little effect for amoxicillin or cefuroxime resistance in Escherichia coli isolates from general practitioners, where the proportion of duplicates was small. CONCLUSION: Improved surveillance of antibiotic resistance is needed. However, care needs to be taken in setting the criteria for classifying isolates as duplicates and in comparing results where these criteria may be different or unknown.     

'Not everything that can be counted counts and not everything that counts can be counted'– towards a critical exploration of modes of satisfaction measurement in sheltered housing

This paper reflects on a research project funded by a consortium of leading sheltered housing (SH) providers and their regulatory body, the Housing Corporation. The project aimed to ascertain which aspects of SH older people perceived to be central to their satisfaction and the methods they judged most appropriate to measuring this. We outline key policy developments of importance to SH (specifically the development of performance measurement regimes), and changes in the nature of SH, which are driving providers to re‐evaluate how they measure user satisfaction. We discuss the aims of the project, our methodology and findings, and conclude by raising critical questions about the process of measuring satisfaction within an increasingly managerialised housing system. We argue that this favours standardised methods of information gathering (such as questionnaires) rather than engage with clients in order to develop methods and systems capable of eliciting qualitative issues of concern to them. Our conclusions are, we believe, applicable to health and social care provision, where similar tensions exist around performance measurement and user satisfaction.     

Combined Excimer Laser and Topical Tacrolimus for the Treatment of Vitiligo: A Pilot Study

Background. Vitiligo is an acquired skin disorder that is characterized by well-defined, often symmetric white patches. Although current therapeutic modalities are directed toward increasing melanocyte melanin production, few treatment modalities address the immunologic nature of the disease.
Objective. To determine whether excimer laser, a known therapeutic modality, in combination with tacrolimus, a topical immunomodulator, accelerate response time and/or improve the degree of response in patients with this disorder.
Methods. Eight subjects diagnosed with vitiligo were recruited to participate in this institutional review board–approved double-blind, placebo-controlled study. Twenty-four symmetric vitiliginous patches (elbows, knees) from eight subjects received excimer laser treatment three times per week for 24 treatments or 10 weeks. Additionally, topical tacrolimus 0.1% ointment (Protopic) and placebo (Aquaphor) were applied to randomized patches (left or right) twice daily throughout the length of the trial. Vitiliginous patches were monitored with photographs at baseline, every 2 weeks, and 6 months after treatment. Biopsies were performed on subjects with significant results.
Results. Twenty vitiliginous patches from six subjects qualified for evaluation. Fifty percent of patches treated with combination excimer laser and tacrolimus achieved a successful response (75% repigmentation) compared with 20% for the placebo group. Subjects who responded successfully repigmented faster (19%) with combination therapy compared with excimer laser alone. Additionally, three subjects experienced transient hyperpigmentation in lesions treated with combination therapy.
Conclusion. Combining topical immunomodulators with known phototherapeutic modalities may represent a key advancement in the treatment of disease.     

Nontuberculous mycobacteria in bronchiectasis: Prevalence and patient characteristics.

The aim of the current study was to investigate the prevalence and clinical associations of nontuberculous mycobacteria (NTM) in a well-characterised cohort of patients with adult-onset bronchiectasis. The sputum of all patients attending a tertiary referral bronchiectasis clinic between April 2002 and August 2003 was examined for mycobacteria as part of an extensive diagnostic work-up. NTM-positive patients subsequently had further sputa examined. A modified bronchiectasis scoring system was applied to all high-resolution computed tomography (HRCT) scans from NTM-positive patients, and a matched cohort without NTM. Out of 98 patients attending the clinic, 10 had NTM in their sputum on first culture; of those, eight provided multiple positive cultures. Three patients were treated for NTM infection. A higher proportion of NTM-positive than -negative patients were subsequently diagnosed with cystic fibrosis (two out of nine versus two out of 75). On HRCT scoring, more patients in the NTM-positive group had peripheral mucus plugging than in the NTM-negative group. In the current prospective study of a large cohort of patients with bronchiectasis, 10% cultured positive for nontuberculous mycobacteria in a random clinic sputum sample. Few clinical parameters were helpful in discriminating between groups, except for a higher prevalence of previously undiagnosed cystic fibrosis and of peripheral mucus plugging on high-resolution computed tomography in the nontuberculous mycobacteria group.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.