Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated - an open-label pilot study.

Background: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules. Methods: Seven patients with active UC, aged 27-50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months. Results: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p = .001) and 6 (p = .001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800 mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported. Conclusion: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.

Glucose evaluation trial for remission (GETREM) in type 1 diabetes: a European multicentre study.

OBJECTIVE: Strict metabolic control during the 1st year of type 1 diabetes is thought to be a key factor for achieving clinical remission. The aims of this study were two-fold: (i) to evaluate the frequency and duration of spontaneous remission (defined according to the parameters issued by the International Diabetic Immunotherapy Group (IDIG)) in a European population of consecutive recent onset type 1 diabetes patients (aged 5-35 years), followed-up for a period of 36 months with a common protocol of intensive insulin therapy and without adjunct immune-intervention; and (ii) to identify the predictive factors for clinical remission. RESEARCH DESIGN AND METHOD: A total of 189 consecutive patients with newly diagnosed type 1 diabetes according to ADA criteria were recruited in participating centres (Belgium, Czech Republic, Estonia, France, Germany, Hungary, Italy, Poland, Romania, Sweden and Turkey) and followed-up for a period of up to 36 months. In all patients, intensive insulin therapy was implemented consisting of three or four injections of regular insulin daily with NPH insulin at bedtime. Adjustment of insulin dose was made according to a common protocol. Various clinical characteristics (age, gender, severity of presentation, etc.), history (presence of diabetic siblings in the family, etc.) and integrated parameters of metabolic control (HbA(1c), blood glucose, the total insulin dose at hospital discharge adjusted for body weight) were collected. RESULTS: Twenty-two patients (11.6%) experienced remission. The median duration of remission was 9.6 months and the range was 31 months. There was a wide variation among centres. Logistic regression analysis focused on the centre as the main variable in achieving remission. CONCLUSION: Remission was shown to be very heterogeneous between centres depending on 'other factors' such as patient care and family awareness of the disease rather than on 'measurable factors' such as sex, age, HbA(1c) and severity of presentation at diagnosis. Using intensive insulin therapy and optimisation of metabolic control, remission occurred in nearly one out of eight patients.

Meta-analysis of nicotinamide treatment in patients with recent-onset IDDM. The Nicotinamide Trialists.

OBJECTIVE: Nicotinamide, a vitamin of the B group, has in vitro actions capable of interfering with the pathogenetic process leading to IDDM. Since 1987, several studies have evaluated nicotinamide as a means of protecting beta-cells from end-stage destruction in insulin-treated patients with newly diagnosed IDDM. The aim of the study was to determine whether nicotinamide protects residual beta-cell function when given at IDDM diagnosis. RESEARCH DESIGN AND METHODS: We performed a meta-analysis of the integrated parameters of metabolic control (C-peptide, glycosylated hemoglobin, insulin dose) in 10 randomized (5 of which were placebo) controlled trials conducted in recent-onset IDDM patients for a total of 211 nicotinamide-treated patients. Data on the adverse effects of nicotinamide were also collected from an additional four trials to yield a grand total of 291 nicotinamide-receiving patients. RESULTS: One year after diagnosis, baseline C-peptide was significantly higher in nicotinamide-treated patients, compared with control patients (0.73 +/- 0.65 vs. 0.32 +/- 0.56 ng/ml, P < 0.005). This statistical difference remained also when the five placebo-controlled trials only were considered (P < 0.05). No differences were observed in the insulin dose required or glycosylated hemoglobin values between nicotinamide and control patients. Adverse effects were reported in few patients (transient elevation of transaminase, n = 2; skin rash, n = 2; recurrent hypoglycemia, n = 2). CONCLUSIONS: This combined analysis demonstrates a therapeutic effect of nicotinamide in preserving residual beta-cell function when given at IDDM diagnosis in addition to insulin. Since adverse effects were negligible, we suggest that prolonged use of nicotinamide after IDDM diagnosis should be tested to see whether residual beta-cell function can be preserved for longer periods.

Integrin expression in primary breast cancer and its relation to axillary nodal status.

BACKGROUND: Integrins are transmembrane receptors that modulate cell adhesion. Each is a heterodimer of varying alpha and beta subunits. In malignancy, loss of integrin expression may result in less adhesive cells more likely to metastasize. Our aim was to characterize the integrins in human breast tissue and to examine the relationship between integrin expression and nodal metastasis in breast cancer. METHODS: Cryostat sections from 12 benign and 61 malignant (50 ductal and 11 lobular) samples were stained by the avidin-biotin complex method with monoclonal antibodies to the beta 1, beta 3, beta 4, and beta 5 subfamilies. All slides were read by two independent assessors with consensus agreement. Integrin expression was compared to variables by using the chi-squared test with Yates' correction and multivariate analysis based on logistic regression. RESULTS: All integrin subunits studied were significantly reduced on breast cancer compared with benign cells (chi-squared test) but were not related to tumor differentiation. Loss of alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, alpha v beta 1, and alpha v beta 5 were related to the presence of axillary metastasis. Independently the integrins were of limited clinical value as predictors of axillary spread. However, on multivariate analysis the combination of beta 1, alpha v, alpha 1, tumor size, and vascular invasion gave a cumulative overall accuracy in predicting nodal disease of 97%. CONCLUSIONS: Integrin expression is reduced in breast cancer and may explain tumor progression. Measuring the integrins might thus provide a means of selection for aggressive axillary treatment.

Social networks, health, and emotional well-being among the oldest old in London.

A survey of the health and social circumstances of 662 people aged 85 and over, living at home in inner London, was conducted in 1987. A primary aim was to analyze the structure of social support networks of the sample in relation to respondents' emotional well-being and met and unmet needs for practical help. The conceptual and methodological framework that was applied to the study was derived from the theory of social networks. In confirmation of the common assumption that people aged 85+ are different from younger elderly people, as they are the "survivors," high levels of social support and informal help were given to most respondents. Although associations were found between social network variables and the provision of informal help, multifactorial analysis showed that health status explained more of the variation in emotional well-being.

The effect of ranitidine, alone and in combination with clemastine, on allergen-induced cutaneous wheal-and-flare reactions in human skin.

The effect of intradermal ranitidine (administered alone and in combination with clemastine) on allergen-mediated wheal-and-flare reactions has been evaluated in a double-blind study on 10 healthy atopic volunteers. Ranitidine alone, administered in doses over a 10(4)-fold concentration range, had no effect on the size either of allergen-induced wheal or flare reactions. Clemastine alone evoked a dose-related inhibition of both wheal and flare. Compared to the inhibition achieved by clemastine alone, the combination of ranitidine with clemastine produced a small but significant increase in inhibition of allergen-induced flare at ranitidine concentrations of 10(-5) mol/L (p less than 0.001) and 10(-6) mol/L (p less than 0.01), and of allergen-induced wheal at ranitidine concentration 10(-5) mol/L (p less than 0.01). Our results provide further evidence for the presence of cutaneous histamine H2 receptors and their participation in the formation of allergen-mediated skin reactions but indicate that the contribution of cutaneous histamine H2-receptor stimulation to the production of immediate wheal-and-flare reactions evoked by allergen is only modest.

The influence of ranitidine, alone and in combination with clemastine, on histamine-mediated cutaneous weal and flare reactions in human skin.

Significant, (P less than 0.05) inhibition of histamine induced cutaneous weal and flare reactions by ranitidine at 10(-5) M concentration has been demonstrated in a double blind, in vivo study; the results support the evidence for cutaneous H2-histamine receptors provided by previous studies using cimetidine and metiamide. The degree of inhibition of histamine mediated cutaneous reactions achieved by clemastine was increased by the administration of clemastine and ranitidine together, for ranitidine concentrations 10(-5) M (P less than 0.001) and 10(-6) M (P less than 0.05). The magnitude of the inhibitory effect of ranitidine, both administered alone and in combination with clemastine, suggests that in the production of histamine induced cutaneous weal and flare reactions, the contribution afforded by stimulation of cutaneous H2-histamine receptors is only small.

Anaesthesia for suction termination of pregnancy.

The effect of three anaesthetic techniques on blood loss and intra-uterine pressure changes in response to Syntocinon were studied in patients undergoing routine first trimester suction termination of pregnancy. All patients received a standard premedication, a bolus dose of fentanyl, intravenous induction of anaesthesia and maintenance with nitrous oxide and oxygen plus either intravenous supplementation or 0.5% halothane. Intra-uterine pressure was related to the anaesthetic technique used although blood loss was unrelated either to anaesthetic technique or to intra-uterine pressure changes.

The MCQ in the primary FRCS(Eng).

Analysis of the primary fellowship results showed that on average candidates were scoring a significantly higher mark in the MCQ than in the essay or viva. The level of MCQ marking has therefore been reset to the standards of the other parts of the examination. The need for continually monitoring the results of all examinations is emphasised.

Long-term phenothiazine treatment does not cause pituitary tumours.

In order to explore the possibility that prolactinomas may be caused by prolonged under-inhibition of prolactin-secreting cells we examined the pituitary fossa in 69 patients on long-term phenothiazine treatment. The average duration of treatment was 12.5 years and 55 (80 per cent) of the patients had persistently raised serum prolactin levels. The incidence of radiologically detectable pituitary fossa abnormalities was not significantly different to that in control populations. In 62 per cent of patients the skull x-rays from an earlier admission were available. Comparison of these with earlier films did not show a higher incidence of pituitary fossa abnormalities after prolonged exposure to phenothiazines.