Randomised double-blind placebo-controlled study of the effect of Lactobacillus paracasei NCC 2461 on skin reactivity.

In recent decades, the prevalence of subjects with reactive skin has considerably increased in industrialised countries. 50% of women and 30% of men report cutaneous discomfort classified under reactive/sensitive skin. Several topical approaches have been proposed, in particular through improvement of galenic forms or protection of epidermal surface. We propose to act differently, deeply from inside the body via an innovative nutritional approach. To this purpose, Lactobacillus paracasei NCC 2461 (ST11) was selected because of its specific beneficial skin properties discovered in in vitro studies, i.e. diminution of neurogenic inflammation and promotion of the recovery of skin barrier function. We designed a randomised double-blind placebo-controlled clinical study with a two-month supplementation in two female treatment groups (n=32 per group). A capsaicin test was performed to monitor the time course of skin sensitivity. Moreover, transepidermal water loss was assessed to analyse the rate of skin barrier function recovery; dryness of the leg and roughness of the cheeks was investigated by a dermatologist as well as by self-assessment. The results of the present clinical trial show that oral supplementation with the probiotic decreases skin sensitivity and increases the rate of barrier function recovery. Thus, the data provide evidence that daily intake of ST11 could improve reactive skin condition.

Effects of nonpathogenic gram-negative bacterium Vitreoscilla filiformis lysate on atopic dermatitis: a prospective, randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: Atopic dermatitis (AD) is associated with elevated IgE levels and Th2 responses. The oral administration of nonpathogenic bacteria such as probiotics may improve the course of atopic diseases. It is believed that nonpathogenic bacteria prevent the development of allergic diseases by modulating intestinal immune responses. However, the effects of oral probiotics on AD could not be reproduced in all studies and the direct immunomodulation of the skin-associated immune response by nonpathogenic bacteria has not yet been investigated. OBJECTIVES: We performed a prospective, double-blind, placebo-controlled clinical study with a cream containing a 5% lysate of the nonpathogenic bacteria Vitreoscilla filiformis. PATIENTS AND METHODS: Seventy-five volunteers with AD (6-70 years of age) were randomized to receive either V. filiformis cream 5% or vehicle cream daily for 30 days. Efficacy was evaluated by the SCORe of Atopic Dermatitis (SCORAD), transepidermal water loss (TEWL), assessment of microflora, and the patient's assessment of itch and loss of sleep. RESULTS: Compared with placebo, V. filiformis lysate significantly decreased SCORAD levels (P=0.0044) and pruritus (P=0.0171). Active cream significantly decreased loss of sleep from day 0 to day 29 (P=0.0074). Qualitative and quantitative assessment of cutaneous microbial colonization revealed that V. filiformis lysate reduced Staphylococcus aureus colonization of the skin. The skin barrier as determined by TEWL also improved significantly with the cream alone. CONCLUSIONS: V. filiformis lysate significantly improved AD. This may be in part due to reduction of S. aureus, but seems to relate in most parts to a direct immunomodulatory effect on skin-associated immune responses.

Bench testing of pressure support ventilation with three different generations of ventilators.

OBJECTIVE: The new generations of intensive care ventilators tend to be more innovative and sophisticated than previous ones, but little is known about their respective performance for delivering pressure support ventilation (PSV) and how they compare to previous generations. DESIGN: Active lung model bench test. APPARATUS: Twenty-two commercially available ventilators classified into three categories: new generation ventilators (after 1993, n=7), previous generation (before 1993, n=6), and recent piston or turbine-based ventilators ( n=9). MEASUREMENTS AND RESULTS: During PSV, the unloading efficacy of the assistance depends on the ventilator's ability to meet inspiratory flow demand. Three levels of flow (0.1 l/s, 0.6 l/s, and 1.2 l/s) were used to simulate inspiratory demand and the net area of the inspiratory airway pressure-time trace was calculated over the first 0.3 s, 0.5 s, and 1 s (Area (0.3), Area (0.5), and Area (tot)) with three levels of PSV (5 cmH(2)O, 10 cmH(2)O, and 15 cmH(2)O). To assess the respective role of pressure support delivery and triggering function, triggering sensitivity was assessed independently by measuring the time delay ( TD (tg)) and the pressure fall (Delta Paw (tg)) with two levels of inspiratory drive. All the new generation ventilators exhibited significantly better results than most of the previous generation ventilators regarding Area (0.3) and TD (tg), indicating large improvements in terms of triggering and pressurisation. CONCLUSION: Regarding PSV and trigger performance, the new generation ventilators - but also some piston and turbine-based ventilators - outperform most of previous generation ventilators.

Identification of clustered cells in human hair follicle responsible for MMP-9 gelatinolytic activity: consequences for the regulation of hair growth.

BACKGROUND: The control of human hair follicle growth and differentiation is dependent upon several well-identified factors, including androgens, cytokines, and growth factors. In humans, alopecia androgenetica is a common aging process thought to be regulated through complex genetic imbalances, which also involve several of these crucial identified factors (and probably others not yet characterized), alone or in combination. Among these factors, epidermal growth factor (EGF), as well as pro-inflammatory cytokines, play a pivotal role, as evidenced by their direct inhibitory effects on hair growth both in vitro and in vivo. Following such treatments, the in vitro growth of hair follicles was rapidly arrested and deleterious modifications of hair morphology were also observed. AIM: Because these cytokines act, at least partly, through the induction of matrix metalloproteinases (MMP), and because tissue remodeling occurs during the hair cycle, we attempted to identify and localize MMP in the human pilosebaceous unit. METHOD: We used zymography to observe human hair follicles in culture in vitro. RESULTS: We observed that human hair follicles in culture in vitro mainly and almost exclusively produce MMP-2 and MMP-9 gelatinolytic activities. Furthermore, after stimulation with EGF, tumor necrosis factor-alpha (TNF-alpha), or interleukin-1alpha (IL-1alpha), MMP-9 production was strongly increased. Using immunohistochemistry, we then precisely localized MMP-9 in the lower part of the inner root sheath (Henle's layer) of control human anagen hair follicles. CONCLUSIONS: Cytokine- and EGF-induced upregulation of MMP-9 in the lower epithelial compartment of the human hair bulb is a major mechanism through which hair follicle involution, observed in alopecia, may occur.

Neurogenic modifications induced by substance P in an organ culture of human skin.

Neurogenic inflammation of the skin observed after topical application of an irritant substance or environmental stimulation induces vascular changes and the production of inflammatory mediators. Substance P (SP) is one of the main neuropeptides which trigger an inflammatory response in the skin. So, with the aim to develop an alternative method to study neurogenic inflammation of the skin, we used an organ culture of human skin. SP was added onto epidermis or directly to culture medium in an attempt to reproduce ex vivo the effects described in vivo. Even disconnected from systemic blood circulation, in skin fragments in culture, we observed dose-dependent edema, vasodilation and extravasation of lymphocytes and mast cells through the microvascular wall. Moreover, the release of proinflammatory mediators interleukin 1alpha and tumor necrosis factor alpha was evidenced.

Relative efficiency of succinylcholine, xylazine, and carfentanil/xylazine mixtures to immobilize free-ranging moose.

We compared the efficiency of succinylcholine chloride, xylazine hydrochloride and carfentanil/xylazine mixtures in immobilizing 364 free-ranging moose (Alces alces) between 1987 and 1997 in Québec (Canada). With succinylcholine chloride (0.070, 0.062, 0.051 mg/kg of estimated body weight for calves, juveniles and adults), 63% of the 252 immobilization attempts led to complete immobilization and marking, whereas 7% of the darted animals died of respiratory paralysis during handling. The moose took an average of 13 min to lay down after darting (down time). Injection of xylazine (3.67-4.22 mg/kg) permitted sedation (the animal laid down but got up again when approached) or complete immobilization in 78% of the 40 darted adult moose, the mean down time being 8.7 min. No mortality was noted with this drug but 58% of the marked animals were only sedated. The use of RX821002A (0.058 mg/kg) as an antagonist, permitted a mean recovery time of 2.8 min after intravenous injection. With the carfentanil/xylazine mixtures (0.0071 and 0.181 mg/kg), 96% of the immobilization trials (n = 72) led to complete (88%) or partial (8%) immobilization, but 6% of the moose died several days after capture. The mean down time was 6.6 min, and injection of naltrexone (0.709 mg/kg) antagonized the effect of the immobilizing agent within 3.7 min. The respiratory rate was higher (P < 0.05) among moose immobilized with xylazine (35/min) than among those immobilized with carfentanil/xylazine mixtures (19/min) but this variation could be related to a longer pursuit time (z = 3.60; P < 0.01) and higher stress levels during handling. Rectal temperature also was higher with xylazine but the difference was small (39.7 vs. 39.3, P = 0.03) and did not differ significantly between the sexes (P > 0.05). Considering loss of materials and helicopter flight time due to non-successful marking trials, carfentanil/xylazine mixtures were the least expensive ($333 Cdn/animal).

Bilateral epiphysiolysis of the femoral heads in two dogs.

Two Shetland Sheepdogs that did not have a history of trauma were referred because of a gradual onset of lameness in the hind limbs. Bilateral slipped capital femoral epiphysis was diagnosed. Separation of the proximal femoral epiphysis that is not associated with trauma is recognized as a distinct clinical syndrome in adolescent human beings and swine, causing a condition called epiphysiolysis. The precise cause of this type of injury is unknown. Histologic lesions observed in the growth plates could have been the result of an abnormally high mechanical load imposed by obesity. It is not known whether cartilaginous lesions observed in the physis of 1 dog represented a preexisting cartilaginous defect (dyschondroplasia) or a late stage of repair after separation of the capital femoral epiphysis.

Socioeconomic status and severity of illness on admission in acute myocardial infarction patients.

The objective of this research is to test the hypothesis of the existence of an association between socioeconomic status and severity of illness of the patients admitted to the hospital with acute myocardial infarction. The design was a retrospective cohort study of consecutive patients admitted to the coronary care unit with the diagnosis of acute myocardial infarction in six public hospitals from the Spanish region of Valenciá. A total of 369 patients admitted to the intensive care units of the participating hospitals were studied. The socioeconomic status was measured using an ad hoc index based upon the occupational level, income and educational level of the patient. The patients below the 20% percentile were considered as disadvantaged, and the patients whose Killip class on admission was 3 or 4 were considered as complicated. The effect of potential confounders was controlled using unconditional logistic regression analysis. The results were validated in an independent but comparable population of 331 patients. The disadvantaged patients showed a higher prevalence of open cardiac failure on admission (Killip classes 3 or 4) than the remainder (crude odds ratio = 3.1, 95% confidence interval between 1.57 and 6.1). The association between socioeconomic status and severity of illness persisted after controlling for important covariates (age, diabetes mellitus, gender and marital status): adjusted odds ratio = 2.4, 95% confidence interval between 1.1 and 5.2. These results were highly consistent with those in the validation group. Our results suggest that socioeconomic status is an independent predictor of the severity of illness on admission to coronary care units in acute myocardial infarction patients. These results are consistent with the existence of a low accessibility of patients in the lower socioeconomic levels.

[Guépar's total radio-carpal prosthesis in the surgery of the rheumatoid wrist. Apropos of 72 cases reviewed]. / La prothèse totale radio-carpienne Guépar dans la chirurgie du poignet rhumatoïde. A propos de 72 cas revus.

PURPOSE OF THE STUDY: Total wrist arthroplasty is an alternative to arthrodesis in the treatment of the rheumatoid wrist. MATERIAL AND METHODS: Seventy-two GUEPAR total wrist arthroplasties in sixty-four patients with rheumatoid arthritis were reviewed 1 to 10 years after the operation (average follow-up of 4 years). GUEPAR total wrist arthroplasty is a bicondylar prosthesis. The radial component made of polyethylene is cemented in the radius. The carpal component made of metal is fixed by two screws in the second and the third metacarpal. This component is constitued by two pieces: a perforated lower part permitting the passage of the screws and its metacarpal fixation and a biconvex cover fixed on the lower part by a micro-screw. RESULTS: In preoperative evaluation, all patients had severe pain and loss of function. Post-operatively, 89 per cent had no pain or mild pain and 96 per cent had better function. The average arc of flexion-extension was 47 degrees preoperatively and 39 degrees postoperatively. There were no deep infections or dislocations. Seventy percent of the patients were satisfied but eleven wrists (15 per cent) required revision: 5 cases for prosthesis revision and 6 cases for implant removal and arthrodesis. Prosthesis revisions were justified by the unscrewing of the carpal component micro-screw: they gived good results. Arthrodesis was required for 4 radial component loosening and for 2 important bone resorptions under the carpal component. Radial component loosening was associated in 3 cases with unscrewing of the micro-screw. Radiographical analysis showed in nearly all cases of this serie a bone resorption under the carpal component. This resorption was 2 mm wide at an average of to 2 years and 4 mm wide at 4 years. DISCUSSION: Clinical results of this study are good but eleven wrists required revision. Nine of these revisions were due to anomalies of first prosthesis: the unscrewing of the carpal component micro-screw was accountable to abnormal use of polyethylene with reaction of the wear products and loosening of the radial component. This problem is now resolved. More disquieting is the bone resorption under the carpal component. In fact, this resorption was constant and evolutive. It was very likely due to micro-movements between the metacarpal screws and the carpal lower part. Also, the conception of the metacarpal-fixation of this prosthesis must be revised. CONCLUSION: In rheumatoid arthritis, wrist arthrodesis gives good results if nothings affects the fingers, elbow or shoulder. If they are affected, total wrist arthroplasty is an alternative. Long term loosening of total wrist arthroplasty is a significant problem so its indication must be reserved for old patients.

[Differences in therapeutic effort because of the socioeconomic level of patients with acute myocardial infarction]. / Diferencias de esfuerzo terapéutico en razón del nivel socioeconómico en pacientes con infarto agudo de miocardio.

OBJECTIVES: To assess the hypothesis of the existence of differential therapeutic effort according to the socioeconomic status of the patients admitted to the hospital by acute myocardial infarction. PATIENTS AND METHODS: We study retrospectively 592 patients admitted to the intensive care units from six public hospitals from the Spanish region of Valencia, using data from two cohort studies focused on the study of in-hospital inequalities in health. The socioeconomic status was measured using the British occupational classification. The therapeutic effort predicted for the severity of illness was determined using a regression model that included the logarithm of Therapeutic Intervention Scoring System (TISS) score as the dependent variable and Simplified Acute Physiology Score (SAPS) score and Killip group as predictors. The patients whose observed TISS was 3 or more pointless than predicted were considered as infra-treated. The effect of potential confounders was controlled using unconditional logistic regression analysis. RESULTS: The proportion of infra-treated patients was inversely related to socioeconomic status chi 2 for tendency = 4.31, P = 0.0378). The logistic regression analysis showed a negative association between age and therapeutic effort (p < 0.0001) but not between therapeutic effort and socioeconomic status, after controlling the effect of age (p = 0.2150). DISCUSSION: Our results suggest that older patients receive less relative therapeutic effort, measured by TISS score, than younger patients. The differential therapeutic effort observed in the crude analysis seem attributable to the higher age of the patients in the lower socioeconomic strata.

[Effect of social factors on quality of life of survivors of myocardial infarction]. / Efecto de los factores sociales sobre la calidad de vida de los supervivientes de un infarto de miocardio.

BACKGROUND: The aim of this study was to analyze the effect of the social environment on the quality of life of the survivors of an acute myocardial infarction. METHODS: A prospective cohort study was carried out with telephone follow up of patients admitted in the Intensive Care Units of six public hospitals in the region of Valencia (Spain). Three hundred eighty consecutive patients admitted for acute myocardial infarction were studied being followed a median of 3.4 years. Follow up was complete in 91.6% of the cases. RESULTS: The global quality of life was good. The component most affected was that of physical activity. Following control of the effect of the biologic and health care covariables, the quality of life was inversely and independently associated with age, female sex, low educative level and foreigness. CONCLUSIONS: Unequality was found in regard to the quality of life based on the socioeconomic level of survivors of acute myocardial infarction.

Evidence that cytochrome P450 2E1 is involved in the (omega-1)-hydroxylation of lauric acid in rat liver microsomes.

The present study examined changes in hepatic CYP2E1 content and (omega-1)-hydroxylation of lauric acid in rats treated with pyridine, pyrazole, acetone, ethanol and 3-methylcholanthrene. The (omega-1)-hydroxylase activity was strongly correlated with chlorzoxazone 6-hydroxylation (r = 0.76) and 4-nitrophenol-hydroxylase (r = 0.91). Both these activities are carried out by CYP2E1. (omega-1) hydroxylase activity was inhibited by ethanol (Ki = 3.5 mM), dimethylsulfoxide and diethyldithiocarbamate. Furthermore, polyclonal antibody directed against rat CYP2E1 inhibited (omega-1)-hydroxylation by more than 90% while it had no effect on the omega-hydroxylation. These results suggest that the (omega-1)-hydroxylation of lauric acid is mediated principally by the CYP2E1 enzyme in rat liver microsomes.

A multivariate analysis of clinicopathologic factors for predicting outcome in uterine sarcomas.

This study involved a comprehensive review of the histologic slides of 62 patients who were diagnosed with uterine sarcoma from 1978 through 1988 at a single institution. In addition, DNA content (ploidy level) could be determined from the H & E slides of these tumors using image analysis. Also, 42 of these cases had retrievable cell blocks on which DNA analysis was performed by means of flow cytometry. A linear regression analysis found a high degree of correlation (r = 0.8) between the measurement of the DNA index of these tumors by these two techniques. All cases were retrospectively restaged using the newly adopted FIGO surgical staging criteria which found the following distribution: 22 (35.5%) Stage I, 10 (16.1%) Stage II, 12 (19.4%) Stage III, and 18 (29%) Stage IV. A multivariate analysis of 60 evaluable patients using the Cox proportional hazard model found that surgical staging was the most significant prognostic factor with respect to the endpoint of overall survival (P = 0.00004). Both patient age at diagnosis and mitotic index were independent from surgical staging in predicting outcome. Furthermore, there was a trend suggesting that DNA index also had prognostic value. Of particular interest was that patients with diploid tumors (DNA index, 0.9-1.1) had a 5-year overall survival of 72% and did not approach median survival; however, hyperdiploid tumors (DNA index > 1.1) and hypodiploid tumors (DNA index < 0.9) were associated with median survivals of 18 and 12 months, respectively. In conclusion, this study supports the use of surgical staging of patients with uterine sarcomas in order to optimally determine their chance for survival. Further biologic investigations which may result in identifying those patients who could benefit from adjunctive treatment are recommended.

Clinical relevance of radiographic findings in proximal sesamoid bones of two-year-old standardbreds in their first year of race training.

Radiographs of all 4 fetlocks of 71 Standardbred racehorses were obtained at 3-month intervals for 1 year. Radiographic findings in the abaxial surface of the proximal sesamoid bones were classified into 3 types according to the severity of lesions, and correlation was made with clinical findings at time of examination. Type-1 lesions (1 or 2 linear defects less than or equal to 1 mm wide) were detected in 55% of horses at the start of training; clinical signs of disease were not manifested, and lesions did not become clinically relevant. Type-2 lesions (3 or more linear defects less than or equal to 1 mm wide) were detected in horses not manifesting clinical signs of disease, and were more frequently observed after 3 months of training. However, 66% of horses affected with diseases of the suspensory apparatus, including superficial flexor tendinitis and suspensory desmitis, also manifested this type of lesion. When lameness was observed, it was associated with the soft tissue problem, and the sesamoid bone changes were considered secondary. Type-3 lesions (wide, abnormally shaped linear defects) were detected in 7 horses at the start of the study; lesions remained in horses throughout the study and were consistently associated with lameness during training. Type-3 lesions were considered clinically relevant and indicative of primary sesamoiditis.

A retrospective study of nineteen ataxic horses.

A retrospective study of 19 ataxic horses admitted to the College of Veterinary Medicine of the University of Montreal during the period of January 1985 to December 1988 is presented. There were 11 cases of cervical vertebral malformation, four of equine degenerative myeloencephalopathy, two of equine protozoal myeloencephalitis, one each of vertebral osteomyelitis and intervertebral disc protrusion. The clinical diagnosis of ataxia in horses requires neurological, radiographic, myelographic, and laboratory examinations.