The role of aminosalicylates in the treatment of ulcerative colitis

Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their efficacy has been established. Since ulcerative colitis is limited to the distal colon in two thirds of the patients, topical therapy also plays an important role. In mild/moderate active disease 5-ASA 4 g/d is as effective as oral corticosteroids. Ulcerative proctitis is treated with 2 x 500 mg or 1 x 1 g suppositories and proctosigmoiditis with 1 to 4 g enemas. Oral 5-ASA is also safe in maintenance treatment and is generally well tolerated. The risk of colorectal tumours is increased in patients with longstanding ulcerative colitis and epidemiological evidence indicates that chronic 5-ASA treatment reduces this risk. However, at present there is insufficient evidence to maintain patients on life-long 5-ASA maintenance treatment for this indication.     

Recombinant human luteinizing hormone, lutropin alfa, for the induction of follicular development and pregnancy in profoundly gonadotrophin-deficient women

OBJECTIVE: To provide evidence of efficacy and safety for use of lutropin alfa in inducing follicular development and pregnancy in hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency. DESIGN: An open-label, noncomparative extension of a randomized, double-blind, placebo-controlled study PATIENTS: A total of 31 hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency in 23 medical centres in four countries were studied. INTERVENTIONS: Lutropin alfa 75 IU and follitropin alfa (75-225 IU), individually based on each patient's response as is consistent with usual medical practice. MEASUREMENTS: Follicular development as defined by (i) at least one follicle >or= 17 mm; (ii) preovulatory serum oestradiol level >or= 109 pg/ml on the day of hCG administration; and (iii) midluteal phase P(4) level >or= 7.9 ng/ml. Pregnancy and over-response leading to cycle cancellation were considered treatment successes. Pregnancy rates were assessed. RESULTS: In a total of 54 cycles, 27 of 31 (87.1%) profoundly gonadotrophin-deficient patients achieved follicular development within three cycles. Twenty of 27 patients (74.1%) who achieved follicular development and received hCG became pregnant; 16 (59.3%) continued to clinical pregnancy. One patient was hospitalized for severe ovarian hyperstimulation syndrome. Lutropin alfa was well tolerated. CONCLUSIONS: Coadministration of lutropin alfa 75 IU and follitropin alfa is safe and effective in inducing follicular development and pregnancy in hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency in a setting consistent with established medical practice.     

The tetraspanin CD9 mediates lateral association of MHC class II molecules on the dendritic cell surface

We have found that MHC class II (MHC II) molecules exhibit a distinctive organization on the dendritic cell (DC) plasma membrane. Both in DC lysates and on the surface of living cells, I-A and I-E molecules engaged in lateral interactions not observed on other antigen-presenting cells such as B blasts. Because DCs and B blasts express MHC II at comparable surface densities, the interaction was not due to simple mass action. Instead, it reflected the selective expression of the tetraspanin CD9 at the DC surface. I-A and I-E molecules coprecipitated with each other and with CD9. The association of heterologous MHC II molecules was abrogated in DCs from CD9(-/-) mice. Conversely, expression of exogenous CD9 in B cells induced MHC II interactions. CD9 is thus necessary for the association of heterologous MHC II, a specialization that would facilitate the formation of MHC II multimers expected to enhance T cell receptor stimulation by DCs.     

The plate half-full: status of research on the mechanisms of dietary restriction in Drosophila melanogaster

It has been almost two decades since dietary restriction was first shown to increase Drosophila lifespan. Since then, understanding this phenomenon advanced as groups worked to identify what quality of restricted diet matters: calories or a specific nutrient. The problem is complex because is it difficult to measure what a fly actually consumes. A powerful solution uses the geometric framework of nutrition where diets in many combinations can be tested for their effects on lifespan and reproduction while measuring intake. Applied to Drosophila, it is now clear that specific nutrients, not calories, mediate longevity. The geometric framework also reveals a nutritional basis for the trade-off between reproduction and lifespan. This complements a stable-isotope analysis that tracked the allocation of nitrogen, carbon and essential amino acids into eggs versus reproduction. Together, these studies show that it is not possible to explain how DR extends lifespan through a mechanism were resources are simply reallocated to somatic maintenance away from reproduction. Although promising in principle, genetic analysis of DR mechanisms has had limited success. To be productive, studies must include enough diets at appropriate concentrations. In reviewing the best data, there is little evidence to date for any gene to be required for DR to increase Drosophila lifespan, including insulin signaling or 4eBP. Strong analyses of genes required for DR should be a priority in future research with Drosophila and this may be made most robust by considering the effect of mutants in the context of the geometric framework.     

Medically assisted procreation and transmission of hepatitis C virus: absence of HCV RNA in purified sperm fraction in HIV co-infected patients

OBJECTIVE: The risk of hepatitis C virus (HCV) transmission in medically assisted procreation (MAP) is debated and some researchers have proposed to exclude MAP for HCV-positive infertile patients. The objectives of this study were to assess the presence of viral RNA in the final preparation of density gradient semen fractions collected from men with chronic HCV and HIV co-infection participating in a MAP program, and to assess whether HIV co-infection influences the rate of the presence of HCV RNA in the semen. DESIGN AND METHODS: The study was based on a cohort of 170 HCV-infected male patients (93 HIV co-infected) participating in a MAP program in a French center. Semen samples were subjected to standard MAP sperm preparation, using density-gradient centrifugation with 40 and 90% layers. All aliquots were tested with a commercially available HCV RNA assay (Roche Monitor), adapted for use with semen after a nucleic HCV RNA extraction modification (Organon Technika). RESULTS: Seminal plasma samples from 19 (11%) patients were HCV RNA positive. The positive HCV viral load in semen was less than 600 IU/ml. None of the 90% fractions from HCV-infected patients were HCV RNA positive. Among the 93 co-infected patients, 10 were positive for HCV RNA in semen and three were HIV/HCV RNA positive in semen. CONCLUSIONS: Although HCV RNA was found in the semen of 11% of patients, no purified sperm fraction, or spermatozoa used in MAP were HCV RNA positive. The 90% purified sperm fraction discards the virus and must be used with care in MAP.     

Long-term results of endoscopic management of pancreas divisum with recurrent acute pancreatitis

BACKGROUND: The long-term efficacy of endoscopic treatment in pancreas divisum is controversial. This study evaluated the long-term results of dorsal duct stent insertion and endoscopic sphincterotomy of the minor papilla in patients presenting with recurrent acute pancreatitis or chronic pain. METHODS: Pancreas divisum was diagnosed in 175 patients between 1980 and 1998. Twenty-four patients seen with recurrent acute pancreatitis without underlying chronic calcifying pancreatitis or significant alcohol consumption were included in this study with a follow-up of at least 24 months. Eight were treated by sphincterotomy of the minor papilla alone, and 16 underwent dorsal duct stent insertion for a median duration of 8 months. RESULTS: The median duration of follow-up after endoscopic management was 39 months (range 24-105; interquartile range 40.5). All patients had recurrent acute pancreatitis before endoscopic treatment during a median period of 5 years. At the end of the follow-up there were only 2 recurrences of acute pancreatitis (p < 0.01). The number of patients with chronic pain before endoscopic treatment and at the end of follow-up decreased from 20 of 24 (83%) to 7 of 24 (29%) without reaching statistical significance. The 25% recurrence rate was estimated at 50 months by Kaplan-Meier analysis. Nine patients presented with a dilated dorsal duct before endoscopic treatment. After stent insertion, dorsal duct dilatation appeared in all 16 patients who underwent stent placement, and pancreatic duct stenosis developed in 3. Four patients (19%) required further treatment for pain recurrence or acute pancreatitis, with surgical procedures being performed in 2 cases. Complications occurred in 9 of 24 patients (38%), mainly acute pancreatitis or stenosis of the minor papilla. All complications except one were managed conservatively. Complications seemed to be less frequent after minor papilla sphincterotomy than after pancreatic stent insertion (25% vs. 44%). CONCLUSION: In patients with pancreas divisum, both dorsal duct stent insertion and minor papilla sphincterotomy decrease the rate of recurrent acute pancreatitis, whereas relief of chronic pain was less obvious.     

Direct detection of myocardial fibrosis by MRI

Excessive collagen deposition is a major hallmark of cardiac disease. Fibrosis reduces cardiac function and plays a major role in cardiac arrhythmogeneity. Despite the clinical importance, there is no non-invasive technique for direct detection of myocardial fibrosis yet. Ultra short echo time (UTE) MRI has been shown to detect tissues with a fast T₂* signal decay. Collagen has a fast T₂* signal decay compared to myocardium and should therefore be detectable with UTE MRI. This study aims to investigate the use of UTE MRI to detect fibrosis after myocardial infarction without using exogenous contrast. In 7 male Lewis rats either myocardial infarction was created (n = 5) or sham surgery was performed (n = 2). Six weeks after surgery, hearts were isolated and visualized by MRI. Images were acquired with UTE (TE 0.15 ms), to detect tissue with a fast T₂* decay. Acquired conventional images (TE = 6.0 ms) were subtracted from UTE images to maintain only ‘short living signal’ (SLS): tissue with a fast decay. In infarcted hearts, SLS was observed in subtracted images, whereas in control hearts hardly any SLS was detected. Subtracted images were cross-referenced with histology and showed that the SLS area observed with UTE MRI corresponded to the collagen-rich areas observed in histology. Normalized SLS areas correlated well with the normalized collagen-rich areas; r = 0.7, p = 0.002. We show for the first time that UTE MRI technology can be used for direct detection of post-infarcted fibrosis without the use of contrast agents.     

Endomyocardial biopsy: Advantages of adding a posterior bend to the bioptome

A modification of the distal end of a flexible bioptome used for endomyocardial biopsy is described which facilitates the approach to the interventricular septum. Contact with the right ventricular free wall is avoided.