Prevalence and Risk Factors of Postprandial Hypotension among Elderly People Admitted in a Geriatric Evaluation and Management Unit : An Observational Study.

OBJECTIVES: To explore the prevalence and potential risk factors of postprandial hypotension (PPH) among elderly patients in an acute geriatric ward. DESIGN: A prospective observational study. SETTING: Geriatric Unit in a Belgian tertiary-care University Hospital. PARTICIPANTS: Seventy-six hospitalized elderly patients after stabilization of their acute conditions. MEASUREMENTS: PPH and orthostatic hypotension (OH) measured by a non-invasive automated blood pressure device, demographic data, Katz's Basic Activities of Daily Living (ADL) and Lawton's instrumental ADL, Short Physical Performance Battery, Charlson Comorbidity Index, Mini Nutritional Assessment-Short Form, Timed Up and Go test, Get-up Early test, grip strength and 7 classes of drugs. RESULTS: Overall, the prevalence of PPH was 46% (n=35/76), and it was symptomatic in 31% of the patients (n=11/35). PPH is associated with OH in one-third of the cases (n=12/35). Two-thirds of the patients with HPP had a significant drop in systolic blood pressure within the first 75 minutes after a meal. In univariate analyses, risk factors of PPH were nursing home residence, alpha-blocker consumption, help needed for eating and a good level of global functional status. However, patients with a good functional status were at increased risk of alpha-blocker exposure. In multivariate analyses, only alpha-blocker consumption and help needed for eating remained statistically significant. CONCLUSION: PPH is frequent among hospitalized elderly people in a Geriatric Evaluation and Management Unit, affecting nearly one out of two people. The use of alpha-blockers is an important risk factor and may alert clinicians to the risk of PPH.

Cerebrospinal Aß11-x and 17-x levels as indicators of mild cognitive impairment and patients' stratification in Alzheimer's disease.

In the present work, the concentrations of Aß11-x and Aß17-x peptides (x=40 or 42), which result from the combined cleavages of ß-amyloid precursor protein (AßPP) by ß'/α or α/γ-secretases, respectively, were assessed in cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Specific multiplexed assays were set up using new anti-40 and anti-42 monoclonal antibodies (mAbs) for the capture of these N-truncated Aß peptides and anti-11 or anti-17 mAbs for their detection. The specificity, sensitivity and reproducibility of such assays were assessed using synthetic peptides and human cell models. Aß11-x and Aß17-x were then measured in CSF samples from patients with AD (n=23), MCI (n=23) and controls with normal cognition (n=21). Aß11-x levels were significantly lower in patients with MCI than in controls. Compared with the combined quantification of Aß1-42, total Tau (T-Tau) and phosphorylated Tau (P-Tau; AlzBio3, Innogenetics), the association of Aß11-40, Aß17-40 and T-Tau improved the discrimination between MCI and controls. Furthermore, when patients with MCI were classified into two subgroups (MCI ≤1.5 or ≥2 based on their CDR-SB (Cognitive Dementia Rating-Sum of Boxes) score), the CSF Aß17-40/Aß11-40 ratio was significantly higher in patients with CDR-SB ≤1.5 than in controls, whereas neither Aß1-42, T-Tau nor P-Tau allowed the detection of this subpopulation. These results need to be confirmed in a larger clinical prospective cohort.

[Frequency of plantar dermatophytosis. A retrospective study 2002-2003]. / Estimation de la fréquence des atteintes plantaires à dermatophytes.

BACKGROUND: Plantar dermatophytosis frequently goes unnoticed and can cause relapse or re-infestation at other sites. The purpose of this study was to evaluate the incidence of plantar dermatophytosis in association with onyxis and intertrigo involving dermatophytes. PATIENTS AND METHODS: This was a retrospective study in patients seen at mycology consultations between January 2002 and December 2003 and for whom culture revealed dermatophytes on the soles, interdigital spaces and/or toe nails. Gender, age and culture data were record from the laboratory workbooks. RESULTS: 716 patients were included, giving 1291 samples. The sex ratio M/F was 1.5 with a mean age of 48 years. Samples of toe nail were obtained from 591 patients, with plantar samples from 433 patients and intertrigo samples from 267 patients. Plantar dermatophytosis was seen in 66.6% of patients with interdigital-plantar signs, in 75.1% of those with ungual involvement and in 73.9% of cases involving both. T. rubrum was the most frequently isolated dermatophyte. DISCUSSION: Combine involvement of the sole, nail and/or interdigital space was seen in more than 2/3 of cases. Despite the retrospective nature of our study and the evident bias, our results suggest that plantar dermatophytosis is common and should be sought. The sensitivity and specificity of clinical screening methods merit investigation in a prospective study.

[Recommended techniques for obtaining nail specimens and mycologic diagnosis of onychomycosis]. / Prélèvements et diagnostics mycologiques des onychomycoses.

The diagnosis of onychomycosis requires an assessment of both clinical and laboratory features. The laboratory diagnosis is essential to confirm the fungal origin of the onyxis. Various types of onychomycosis need different methods to obtain a nail specimen. It requires a direct examination to confirm the presence of fungi, and a fungal culture to identify the specific genus and species of the pathogen. A good interpretation of these results is necessary to adapt the therapeutics.

[Profuse scabies: kinetic curves of parasitologic cure with an association of benzyl benzoate and sulfiram]. / Gale profuse: cinétique de guérison parasitologique avec l'association benzoate de benzyl et sulfiram.

BACKGROUND: In vitro exposure to benzyl benzoate (25 p. 100) kills Sarcoptes scabiei within three hours. The aim of our study was to determine in vivo elimination of Sarcopte scabiei with a benzyl benzoate-sulfiram association. METHODS: Medical charts of patients hospitalized for disseminated scabies from 1993 to 1999 were reviewed retrospectively. The diagnosis of scabies was confirmed by microscopic determination. Parasitological examinations were conducted every day or every two days until negative results. Patients were treated by successive applications of benzyl benzoate until parasitological cure. RESULTS: Twenty patients were included in the study. The median delay of parasitological cure was seven days. After 15 days, 95 p. 100 of patients were cured. Two cutaneous side-effects were reported. DISCUSSION: Despite immediate in vitro efficacy, benzyl benzoate action is delayed in vivo. The time of parasitological negativation after one application of benzyl benzoate is unknown. Therefore, it is not currently possible to determine whether our therapeutic regimen was excessive or not.

Pharmacological profile of SL 59.1227, a novel inhibitor of the sodium/hydrogen exchanger.

1. The NHE1 isoform of the Na(+)/H(+) exchanger plays an important role in the regulation of intracellular pH and in cardiac cell injury caused by ischaemia and reperfusion. SL 59.1227 is a novel imidazolypiperidine Na(+)/H(+) antiport inhibitor which is structurally unrelated to previously described acylguanidine inhibitors such as cariporide. 2. Recovery of pH(i) following an intracellular acid load was measured in CCL39-derived PS120 variant cells, selectively expressing either NHE1 or NHE2 isoforms of the Na(+)/H(+) exchanger. pH(i) recovery was potently and selectively slowed by SL 59.1227 in NHE1-expressing cells (IC(50) 3.3+/-1.3 nM) versus NHE2-expressing cells (2.3+/-1.0 microM). The respective IC(50) values for cariporide were 103+/-28 nM (NHE1) and 73+/-46 microM (NHE2). 3. In anaesthetized rats following left coronary artery occlusion (7 min) and reperfusion (10 min) SL 59.1227 (10 - 100 microg kg(-1) min(-1) i.v.) inhibited ischaemia-mediated ventricular tachycardia (71 - 100%) and reperfusion-induced ventricular fibrillation (75 - 87%) and prevented mortality. Bolus i.v. administration of SL 59.1227 (1 mg kg(-1)) produced anti-arrhythmic effects when administered either before or during ischaemia. 4. Cardiac infarct size was determined in anaesthetized rabbits following left coronary artery occlusion (30 min) and reperfusion (120 min). Infarct size measured as a percentage of the area at risk was 36.2+/-3.4% (control group) versus 15.3+/-3.9% (SL 59.1227 0.6 mg kg(-1) i.v.). 5. SL 59.1227 is the first example of a potent and NHE1-selective non-acylguanidine Na(+)/H(+) exchanger inhibitor. It possesses marked cardioprotective properties.

[Reflections apropos of the 3d cycle of general medicine in French universities]. / Réflexions à propos du 3e cycle de médecine générale dans les universités françaises.

Since more than thirty years following scientific advances and according to recommendations from (Brussels) European Community Commission, medical studies reform has continuously progressed. These reforms have been applied as well to the third cycle. The National Evaluation Community using comparative evaluation and notation for each medical university has tried to acknowledge the quality of these reforms. One cannot ignore the efforts made by medical schools, although results obtained in theoretical and practical learning for this third cycle of general practice are not altogether satisfying. Several reflections can be underlined: lack of definition of general practice is in part responsible for its marginalization along medical studies course; an obvious disinterest from university leaders in teaching medical practice, and an internship examination now essentially meant for specialization in is also to be blamed for social disqualification of general practice.

[Tinea capitis in Creteil. Trends over ten years]. / Teignes du cuir chevelu à Créteil. Evolution sur 10 ans.

INTRODUCTION: We analyzed tinea capitis data in a Paris suburban area over a 11-year period from (1985-1995) to evaluate epidemiology trends. PATIENTS AND METHODS: The following data were collected for patients seen at the Créteil myco-dermatology clinic with cultures positive for tinea capitis: sex, age, ethnic origin, fungal culture. RESULTS: Tinea capitis was observed in 336 cases (56 p. 100 females). Eight percent of the patients were under the age of 10 years and 11 p. 100 over 20 years. Trichophyton soudanense was isolated in 45 p. 100 of the patients. Anthropophilic agents rose over the 10 year period while the number of zoophilic agents remained stable. Specific dermatophytes appeared to predominate in populations of different ethnic origin. There was a two-fold increase in the number of tinea capitis cases in the 1990-1995 period compared with the five previous years. DISCUSSION: The percentage of adults with tinea capitis (11 p. 100) is higher than the 5 p. 100 reported in the literature. The rise in the number of anthropophilic tinea capitis cases resulted from an increase in T. soudanense (originating in Africa), probably related to the increasing immigrant population. This agent was identified in 95 p. 100 of the patients of African origin. Differing lifestyles and transmission between school children makes it quite difficult to interpret the correlation between ethnic origin and specific dermatophytes.

Tinea capitis in adults: misdiagnosis or reappearance?

BACKGROUND: According to the literature, tinea capitis in adults is supposed to be rare; we have recently observed a significant increase in cases. METHODS: Epidemiological, clinical and mycological features were studied in all adult tinea capitis diagnosed over 1 year in our department. RESULTS: Eight cases were observed: 75% of them were women, 50% never traveled and 62.5% had an underlying immunosuppressive disease. Scalp scaling and alopecia were the most frequent clinical features. A zoophilic dermatophyte was recovered in 50% of cases. CONCLUSION: These cases represent 11% of all tinea capitis observed in the same period of time (higher than the 3-5% observed in the literature). Secretion of sebum and colonization by Pityrosporon orbiculare are supported to protect the scalp against dermatophytic invasion after puberty, but an immune defect may also facilitate hair invasion. The erroneous notion of the disease being uncommon and the frequent atypical clinical presentation require a high degree of clinical suspicion.

Mortality of white South African gold miners.

OBJECTIVES: This two part study aimed to determine whether there was an excess mortality generally or for some diseases among middle aged white South African gold miners on the Witwatersrand and whether the underground dust exposure of these miners contributed to the development of lung cancer, chronic obstructive pulmonary disease (COPD), or ischaemic heart disease (IHD). METHODS: A cohort of 4925 white miners in South Africa, born between 1 January 1916 and 31 December 1930 who were alive and working in the vicinity of Johannesburg on 1 January 1970, then aged between 39 and 54, was followed up for 20 years by which time 2032 had died. Most were gold miners (about 87% had worked 85% or more of their shifts in gold mines). Standardised mortality ratios (SMRs) were calculated as percentages of the number of deaths observed in the cohort for a condition as stated on the death certificate divided by the number expected on the basis of concurrent mortality in the reference population (the total age specific white male population of South Africa). A case-control analysis was performed for three diseases (lung cancer, COPD, and IHD), the results of which are presented for those miners in the cohort who had spent at least 85% of their service on gold mines and had worked at least 15% of their shifts underground. RESULTS: The SMR for all causes of death was 129.6%, raised because of excess mortality due to the following causes: lung cancer (SMR = 139.8%), IHD (124.1%), COPD (189%) and cirrhosis of the liver (155.3%). Smoking was confirmed to be the main risk factor for lung cancer and COPD although cumulative dust exposure was found to increase the risk of COPD in conjunction with smoking. No significant risk of lung cancer resulted from exposure to dust. High blood pressure and smoking were found to increase the risk of IHD, but no association between IHD and the quetelet index (weight/height2) was found. CONCLUSIONS: The most significant and unexpected finding was the 30% increase in the SMR for all causes. Very little of this increase could be attributed to mining and the main factor for this was probably the adoption of an unhealthy lifestyle by these men (compared with other South African white men) particularly smoking (86% were smokers) and alcohol consumption.

[Withdrawal in opiate addicts in an internal medicine hospital unit]. / Sevrage des toxicomanes dépendant des opiacés, dans une unité hospitalière de médecine interne.

Withdrawal of opiates drug addicts in Internal Medicine is unusual in France. Four main preliminary conditions are requested: 1--Drug addict preparation and self motivation, 2--Inter and intra institution team collaboration, 3--Opening the hospital towards community agencies, 4--Hospital staff recruited on volunteer basis. Within two years (1992-1993), 210 opiates drug addicts were hospitalized for withdrawal. Two third were males, median age was 27, median years of addiction was 7. Thirty percent were seropositive for HIV, 70% for HCV. Hospitalisation lasted 7 days for heroin addicts and 10 days for morphin, codein or buprenorphin addicts. Successful withdrawn was observed for 70% patients but six months after withdrawal, only 15% remained abstinent.

Plasmodium falciparum: detection of P-glycoprotein in chloroquine-susceptible and chloroquine-resistant clones and isolates.

Recent studies have suggested the potential involvement of multidrug resistance (mdr) genes in resistance to quinoline-containing compounds in Plasmodium falciparum parasites. Three different antibodies were used to detect the malarial mdr 1 protein product by indirect immunofluorescence and/or immunoblot in fresh clinical isolates and clones of P. falciparum from different geographic origins. A 160-kDa protein was detected in all five parasite clones by immunoblot and around the food vacuole by IFA, regardless of the level of sensitivity to chloroquine and the modulation by desipramine of chloroquine accumulation. Our results suggest that chloroquine resistance is not correlated with the presence of the Pfmdr1 product.

Histone-poly(A) hybrid molecules as tools to block nuclear pores.

Histone-poly(A) hybrid molecules were used for transport experiments with resealed nuclear envelopes and after attachment of a cleavable cross-linker (SASD) to identify nuclear proteins. In contrast to histones, the hybrid molecules cannot be accumulated in resealed nuclear envelopes, and in contrast to poly(A), the export of hybrids from preloaded nuclear envelopes is completely impaired. The experiments strongly confirm the existence of poly(A) as an export signal in mRNA which counteracts the nuclear location signals (NLS) in histones. The contradicting transport signals in the hybrid molecules impair translocation through the nuclear pore complex. The failure to accumulate hybrid molecules into resealed nuclear envelopes results from the covalent attachment of polyadenylic acid to histones in a strict 1:1 molar ratio. This was demonstrated in control transport experiments where radiolabeled histones were simply mixed with nonlabeled poly(A) or radiolabeled poly(A) mixed with nonlabeled histones. In comparison, control uptake experiments with histones covalently linked to a single UMP-mononucleotide are strongly enhanced. Such controls exclude the conceivable possibility of a simple masking of the nuclear location signal in the histones by the covalent attached poly(A) moiety. Photoreactive histone-poly(A) hybrid analogs serve to identify nuclear envelope proteins--presumably in the nuclear pore--with molecular weights of 110, 80, and 71.4 kDa.

Investigation of the relative contributions of cigarette smoking and mineral dust exposure to activation of circulating phagocytes, alterations in plasma concentrations of vitamin C, vitamin E, and beta carotene, and pulmonary dysfunction in South African gold miners.

OBJECTIVES: To determine the relative effects of cigarette smoking and mineral dust exposure on numbers and activity of circulating phagocytes, plasma nutritional antioxidant state, and pulmonary function in South African gold miners. METHODS: Pulmonary function was assessed spirometrically, whereas reactive oxidant generation by circulating phagocytes, and plasma concentrations of the nutritional antioxidative nutrients vitamin C and vitamin E and beta carotene were measured with chemiluminescence, spectrophotometry, or high performance liquid chromatography respectively. RESULTS: Cigarette smoking, but not mineral dust exposure, was associated with increased numbers and pro-oxidative activity of circulating neutrophils and monocytes, decreased plasma concentrations of vitamin C, and pulmonary dysfunction. DISCUSSION: In this study group occupational exposure to mineral dust has not been found to promote increases in the numbers or reactivity of circulating phagocytes or to be a significant cause of pulmonary dysfunction, the changes found being due primarily to cigarette smoking.

Emphysema and airway obstruction in non-smoking South African gold miners with long exposure to silica dust.

OBJECTIVE: Occupational exposure to silica dust is associated with significant impairment of lung function. The present study investigates which pathological changes in the lung are associated with impairment of lung function in silica dust exposed workers who were life-long non-smokers. METHODS: 242 South African white gold miners who were lifelong non-smokers and who had a necropsy at death were studied. The pathological features identified at necropsy were the degree and type of emphysema, the presence of airway disease, and the degree of silicosis in the lung parenchyma and pleura. These features were related to lung function tests done a few years before death, to type of impairment (obstructive or restrictive), and to cumulative silica dust exposure. RESULTS: The degree of emphysema found at necropsy was not associated with a statistically significant impairment of lung function or with dust exposure. The degree of silicosis in the lung parenchyma and the large airways disease (based on mucus gland hyperplasia) were associated with a statistically significant impairment of lung function. The large airway disease was, however, not positively associated with dust exposure or silicosis. In miners with a moderate or a higher degree of limitation of airflow the main findings were silicosis, heart disease, and obesity. The presence of small airways disease could not be established from the necropsy material. CONCLUSION: The results indicate that the level of exposure to silica dust to which these miners were exposed, without a confounding effect of tobacco smoking, is not associated with a degree of emphysema that would cause a statistically significant impairment of lung function. Silicosis of the lung parenchyma was associated with loss of lung function. Other factors that may play a part in impairment of lung function in these miners are obesity and heart disease.

Occupational noise exposure and blood pressure: longitudinal and cross-sectional observations in a group of underground miners.

The question of an association between occupational noise exposure and blood pressure has important public health implications. The harmful effects of hypertension are well known, and noise is considered the most pervasive of all occupational exposures. Most previous studies have looked cross-sectionally at blood pressure and noise exposures in workers. The present study examined historic medical and personnel records of 2,197 white male South African miners. At approximately 3-y intervals, the job title, diastolic and systolic blood pressures, height, weight, and use of medication for hypertension were recorded. Noise levels were estimated, based on noise measurements of individual jobs and work areas. In the cross-sectional analyses, multiple linear regression was used with blood pressure as the dependent variable; age, body mass index (BMI), and noise exposure were the independent variables. Longitudinal analyses were performed for those miners who had observations at four or more time periods, by calculating regression coefficients for individuals for blood pressure and noise, controlling for age and BMI. Additional longitudinal analyses compared blood pressure changes between two points in time for individual miners with changes in noise exposure, controlling for changes in age and BMI. The results of the cross-sectional and longitudinal analyses indicated no association between blood pressure and noise exposure. On the basis of these results, it does not appear that occupational noise exposure has an effect on blood pressure. Inconsistencies in the literature and shortcomings in the present study indicate that additional study is needed.

Haloallylamine inhibitors of MAO and SSAO and their therapeutic potential.

Based on mechanistic understandings, molecular modeling and extensive quantitative structure-activity relationships, appropriately substituted haloallylamine derivatives were designed as potential mechanism-based inhibitors of MAO and/or SSAO. Potent inhibition of MAO-B and SSAO occurred with fluoroallylamines whereas chloroallylamines, such as MDL 72274A ((E)-2-phenyl-3-chloroallylamine hydrochloride), were selective and potent inhibitors of SSAO. MDL 72974A (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride is a potent (IC50 = 10(-9) M) inhibitor of both MAO-B and SSAO, with 190-fold lower affinity for MAO-A. In clinical studies, oral doses as low as 100 micrograms produced substantial inhibition of platelet MAO-B. Essentially complete inhibition occurred at 1 mg with the effect lasting 6-10 days. One or 4 mg MDL 72974A given daily for 28 days to 40 Parkinson's patients treated with L-dopa produced statistically significant reductions in the Unified Parkinson's Disease Rating Scale. MAO-B inhibitors, such as MDL 72974A and L-deprenyl, offer the potential of being neuroprotective in Parkinson's Disease and other neurogenerative disorders. Concommitant inhibition of SSAO may provide additional, but as yet unproven, advantages over pure inhibitors of MAO-B.