Mesalazine (5-aminosalicylic acid) alters faecal bacterial profiles, but not mucosal proteolytic activity in diarrhoea-predominant irritable bowel syndrome.

BACKGROUND: Imbalances in gut luminal bacteria may contribute to the pathogenesis of irritable bowel syndrome (IBS). AIM: To explore select bacteriological and anti-inflammatory effects of mesalazine (mesalamine; 5-aminosalicylic acid or 5ASA) and their relation to potential therapeutic effects in IBS. METHODS: Prospective pilot study of 12 women with diarrhoea-predominant IBS. Patients received oral mesalazine (1.5 g b.d.) for 4 weeks followed by a 4-week washout phase. Molecular profiling of stool bacterial communities and IBS symptoms were assessed before, during and after mesalazine treatment. Colonic mucosal biopsies were assessed for proteolytic activity. Qualitative and quantitative effects of mesalazine on stool microbiota, mucosal proteolytic activity and IBS symptoms were assessed. RESULTS: Faecal bacteria decreased by 46% on mesalazine treatment (P = 0.014), but returned to baseline during washout. Firmicutes and Bacteroidetes represented 95% of identified phylotypes, with a trend towards an increase in the proportion of Firmicutes at week 4 in symptomatic responders [median (IQR) 14% (49) increase] compared with nonresponders [median 5% (11) decrease, P = 0.088]. Rectosigmoid mucosal proteolytic activity did not change between baseline and treatment [median 23.2 (17.9) vs. 19.5 (46.7) mU activity/mg tissue, P = 0.433]. Eight of 12 (67%) patients responded favourably to mesalazine based on a global relief questionnaire, with significant decreases in days with discomfort and increases in bowel movement satisfaction. CONCLUSIONS: Mesalazine treatment is associated with a decrease in faecal bacteria abundance and rebalancing of the major constituents of the microbiota. Further study of the bacteriological and anti-inflammatory properties of mesalazine in IBS is warranted.

Embryonic development in vitro is compromised by the ICSI procedure.

The implantation rates achieved with intracytoplasmic sperm injection (ICSI) are equivalent to those with conventional in-vitro fertilization (IVF) but information on embryonic development in vitro after ICSI is scant. In this paper we compare blastocyst formation after IVF and ICSI; we have also investigated the effect of the ICSI procedure with internal control of extrinsic (including paternal) factors. The first series comprised cases of IVF treatment (n = 101) for tubal infertility and ICSI (n = 96) for male infertility. The proportions of embryos developing to the blastocyst stage was significantly lower after ICSI (8.9%, P < 0.001) than after conventional IVF (23.5%). In order to investigate the effect of the ICSI procedure in isolation, blastocyst formation was analysed in a second series of eight cases, in which sibling oocytes were non-selectively subjected to ICSI (n = 78) or IVF (n = 67) with spermatozoa from the same semen sample. It was found that 20% of ICSI embryos and 50% of IVF embryos formed blastocysts (P < 0.01), demonstrating that the ICSI procedure contributes to a reduced capacity for blastocyst formation in vitro.

Bilateral forefoot ischemia as a premonitory symptom of mixed cryoglobulinemia.

Cryoglobulins are composed of cold-sensitive immunoglobulins that precipitate upon cooling. As the cutaneous vasculature of the extremities is commonly exposed to colder temperatures than the body core, this precipitation often occurs in cutaneous, or even digital vessels. Hyperviscosity from the precipitated proteins can incite local thrombosis in otherwise normal vessels, which is manifested clinically as ischemic ulceration. In previously injured vessels, as seen with atherosclerotic occlusive disease, cryoglobulin precipitation can lead to thrombosis of larger vessels, with the consequence being more severe ischemic necrosis. A case of bilateral forefoot ischemia is presented where the precipitating cause of the gangrenous changes appears to be the development of a mixed cryoglobulinemia and a B-cell lymphoma. Tibial angioplasty, plasmaphoresis, and chemotherapy directed at the B-cell lymphoma allowed limb salvage with bilateral transmetatarsal amputations.

Metatarsus adductus and selected radiographic measurements of the first ray in normal feet.

Radiographic evaluation of hallux abducto valgus frequently involves the measurement of the metatarsus adductus angle, first-second intermetatarsal angle, hallux abductus angle, and proximal articular set angle. While the concept that there is a relationship between untreated metatarsus adductus and hallux abducto valgus deformity is not new, a quantifiable relationship between the metatarsus adductus angle and intermetatarsal angle, hallux abductus angle, and the proximal articular set angle in normal feet is relatively undocumented. The purpose of this study is to document relationships between the metatarsus adductus angle and the other three measurements, and to establish normal values for the intermetatarsal angle, hallux abductus angle, and proximal articular set angle within metatarsus adductus angle subgroups.

Oral, anti-inflammatory activity of a potent, selective, protein kinase C inhibitor.

The protein kinase C family of enzymes is thought to be important in mediating signal transduction. Ro 31-8830 is a novel, potent inhibitor of protein kinase C, derived from the non-selective protein kinase inhibitor staurosporine. In this paper we demonstrate the selectivity of Ro 31-8830 for protein kinase C over other protein kinases and its ability to inhibit protein kinase-C-mediated events in platelets and lymphocytes. In addition, we describe a novel system for the in vivo evaluation of inhibitors of protein kinase C, and we demonstrate the oral anti-inflammatory activity of Ro 31-8830. This finding has implications for the treatment of inflammatory disorders in the clinic.

Psychological consequences of burn injury.

The major psychological sequelae experienced by patients 1 year after burn injury were investigated. Data were collected on a consecutive series of adult burn patients, (n = 55), including major demographic and epidemiological characteristics. Participants (n = 23) completed the Hospital Anxiety Depression Scale (HADS), the Impact of Event Scale (IES) and a questionnaire covering functional impairment, visibility of the burn, experience of pain, etc. Over one-third of the patients (36.4 per cent) were found to have premorbid characteristics which could predispose them to injury. Over one-third (34.7 per cent) were still experiencing significant psychological problems. Anxiety was most common, followed by posttraumatic stress symptoms and depression. The visibility of the burn was found to be a useful factor in the prediction of psychological outcome (P = 0.001-0.018). No additional variables were found to increase the significance of prediction. Patients indicated that practical advice in the form of staff-led discussions, before or immediately after discharge, would be the most valuable help.