Myelin thickenings in val 102/fs null mutation of MPZ gene

Painful sensory neuropathies consist of a wide range of neuropathies that can involve large as well as small nerve fibres. Even if most cases remain of unknown cause, some of them may be associated with an underlying disorder such as diabetes, HIV, infections, amyloidosis, and Sjogren's syndrome. Since in some cases an autoimmune mechanism has been postulated, we investigated a panel of circulating autoantibodies including anti‐gliadin (AGA), anti‐endomysium (EmA), anti‐transglutaminase (tTGA) and anti‐nuclear (ANA) antibodies in the sera of patients with unexplained painful sensory neuropathies in order to identify other potentially treatable disorders. We tested the sera of 10 patients (4M; 6F) previously investigated for other causes of neuropathies, including anti‐nerve, onconeural, anti‐extractable nuclear, anti‐neutrophil cytoplasmic, anti‐thyroglobulin (TgA) and anti‐peroxidase (TPOA) antibodies. We found the presence of AGA positivity in 4 patients (40%), ANA in 7 (70%) and AGA + ANA in 4 (40%), two of whom were negative for celiac disease by gastrointestinal biopsy. None of the patients had EmA positivity. Three (30%) had TgA and TPOA and none had anti‐nerve or onconeural antibodies. Whether the presence of circulating autoantibodies in patients with unexplained painful neuropathy reflects an autoimmune involvement which may be amenable to immune therapy and not only to symptomatic treatment remains to be established.     

Raloxifene prevents the growth of uterine leiomyomas in premenopausal women

OBJECTIVE: To evaluate the effects of raloxifene administration on uterine leiomyoma size in premenopausal women. DESIGN: Prospective, randomized, open-label, controlled clinical trial. SETTING: Tertiary care unit, University of Vienna, Austria. PATIENT(S): Twenty-five premenopausal women with uterine leiomyomas. INTERVENTION(S): Three months of treatment with raloxifene (180 mg/d) or no treatment. MAIN OUTCOME MEASURE(S): Baseline to end point percent change difference in leiomyoma volume between the therapy and control groups. RESULT(S): Raloxifene treatment prevented the progression of uterine leiomyomas. Compared with no medical intervention, raloxifene resulted in a decrease of myoma volume. Raloxifene was clinically well tolerated. No significant differences were detected in symptoms related to leiomyomas and hormonal status. CONCLUSION(S): In premenopausal women, high-dose raloxifene is well tolerated and inhibits the growth of leiomyomas.     

Austrian infliximab experience in Crohn's disease: a nationwide cooperative study with long-term follow-up

OBJECTIVE: To determine the nationwide experience with infliximab for the treatment of Crohn's disease in Austria. DESIGN: National multicentre retrospective postal questionnaire survey. SETTING AND PARTICIPANTS: All institutions using infliximab for Crohn's disease in the years 1999 and 2000 were identified by the registry of the local provider of this drug. OUTCOME MEASURES: Response after first treatment course according to physician global assessment, number of subsequent infliximab infusions, disease activity at end of follow-up, avoidance of steroids, frequency of surgery for Crohn's disease, and adverse events. RESULTS: Questionnaires were returned by 32/35 (91%) centres approached. A total of 748 infusions were administered to 153 patients. After the first treatment course an excellent or good response occurred in 48/58 (83%) patients with luminal disease, and in 67/95 (71%) patients with fistulous disease (P < 0.05). After the first treatment course 108 (71%) patients received further infliximab therapy. At a mean follow-up of 29 months, 50% of patients had improved since baseline without requiring surgery for Crohn's disease. Steroid withdrawal was achieved in 25% of patients. Surgery had been performed in one-third of patients and was associated with lacking response to the first treatment course (P < 0.001) and with fistulous disease (P = 0.012). Co-medication with azathioprine favoured the initial response and steroid withdrawal (P < 0.05). One patient died from myocarditis; other adverse events were consistent with that seen in other studies of infliximab. CONCLUSIONS: The Austrian experience with infliximab for Crohn's disease is in general accordance with results from clinical trials and post-marketing studies from single centres. A substantial subgroup of patients appear to have a prolonged benefit from infliximab therapy.     

Endometriosis: a genetic disease

Endometriosis is a multifactorial disease affecting up to 15% of women of reproductive age. This condition is characterized by the presence and growth of endometrial cells outside the uterus. Susceptibility to endometriosis depends on complex interactions of immunologic, hormonal, environmental and genetic factors. Although familial inheritance plays a role, multiple candidate genes appear to be involved. New studies investigating the influence of genetic variants on endometriosis are published with increasing frequency. A number of technologies have emerged to facilitate progress in this field, including subtractive cDNA hybridization to identify secretory endometrial genes, DNA chip technology, differential display polymerase chain reaction, cytogenetics evaluation of endometriotic cells and tissues, and complementary methods in proteomics and informatics. One general approach to uncovering genes pivotal to endometriosis is to search systematically for perturbations in selective candidate genes or chromosomal regions using polymerase chain reaction. We describe here novel association studies on obvious candidates, including genes governing cancer susceptibility, hormone sensitivity or immunology. The assessment of mutations and polymorphisms may allow individualization of therapies as well as primary and secondary prevention strategies for endometriosis, aimed at high-risk populations.     

The differentiation inducers phenylacetate and phenylbutyrate modulate camptothecin sensitivity in colon carcinoma cells in vitro by intracellular acidification

Aromatic fatty acids such as phenylbutyrate (PB) and its metabolite phenylacetate (PA) induce growth arrest, differentiation and apoptosis in solid tumor cells. Despite their antiproliferative action they were reported to exhibit a synergistic effect in combination with cytotoxic drugs like topotecan, and others. Since the activity of the camptothecines (CPTs) depends on local pH conditions, we investigated, whether PB/PA modulate CPT effects indirectly by affecting intracellular pH in SW620 and SW480 colon cancer cells. The results for the colon carcinoma cells show an antagonistic interaction for the combination of CPT and 0.25-5 mM PA in viability assays, resulting in an approximately 3-fold increase in IC50 (control: 20+/-7 nM). A synergistic effect with significantly increased numbers of late apoptotic/necrotic cancer cells (difference +21+/-4%) and 1.4-fold sensitization were detected upon inclusion of 2.5 mM PA during a 4-h CPT (10 micro;M) loading phase. In response to 0.25-1 mM PA/PB the cells exhibit a reversible decrease of pHi (0.1-0.31 pH units) in HEPES- or bicarbonate-buffered media. Dose-dependent acidification and pHi-recovery occurred following addition of PA and PB after an acid load and inhibition of the Na+/H+-antiporter and bicarbonate exchangers, pointing to a possible intracellular mechanism of cytoplasmic acidification. It is concluded that the synergistic modulation of CPT toxicity by short-term PA/PB treatment in colon carcinoma cells is caused by changes in intracellular pH, possibly affecting quantity and localization of the active closed lactone form of this drug.     

Contralateral inguinal hernia in childhood and youth: which child will develop a contralateral inguinal hernia?

This work addresses the controversial topic of the exploration of the contralateral side in the presence of a one-sided inguinal hernia in infancy. In a prospective study of 368 children with one-sided inguinal hernia, we demonstrated the consecutive development of a contralateral hernia in 22 (6%) of the children. We found that the child’s age at first operation represents a risk factor for the development of a consecutive hernia. At an age of less than two months we found a highly significant (P < 0.0001) accumulation of consecutive hernias. These consecutive contralateral hernias appear significantly often (P < 0.0009) within the first two post-operative months in children at least two months old. In view of these findings, we see an indication for routine simultaneous repair on both sides for children aged less than two months at first presentation.