Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease

There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. It was therefore of interest to study interleukin-8 (IL-8), a chemokine, in the peritoneal fluid and peripheral blood of women undergoing laparoscopic procedures. The presence and concentrations of IL-8 in relation to endometriosis, infertility and abdominal pain were evaluated. Samples of peritoneal fluid (n = 49) and peripheral blood (n = 50) were obtained from 50 consecutive patients undergoing laparoscopic surgery for various gynaecological indications (abdominal pain, infertility, sterilization). IL-8 was present in the peritoneal fluid of most women (87%). The concentration of IL-8 in the peritoneal fluid was higher in women with endometriosis compared to women without (P = 0.02). This difference was more pronounced in early (stage 1) endometriosis (P = 0.001). IL-8 concentrations in the peritoneal fluid were also higher in women with early endometriosis compared to women with later stages of the disease (P = 0.003). Peripheral blood concentrations did not correlate with peritoneal fluid concentrations of IL-8 and/or the presence of endometriosis. We conclude that IL-8 is an important factor that may contribute to the pathogenesis of endometriosis possibly by promoting neovascularization. This information can be a guide in the development of new therapeutic approaches for the treatment of endometriosis.      

A feasibility study to investigate the use of thin-plate splines to account for prostate deformation

Image registration is an important step in the radiotherapy treatment planning process. It provides a method of fusing different types of diagnostic imaging information. One such application is to combine magnetic resonance spectroscopic images (MRSI) of the prostate with anatomical MRI and/or computed tomography images that are routinely used in the radiation treatment planning of prostate cancer. MRSI provides in vivo information related to the underlying metabolic activity of tissues, and can be related to the presence of cancer. However, the inflated endorectal coil required during MRS imaging poses a potential problem by deforming the prostate when it is filled with approximately 100 cm3 of air during image acquisition. This pushes the prostate superiorly/anteriorly, deforming the prostate and consequently the spectroscopic imaging data in a nonlinear manner. In this application, the coil-deformed MRS images are warped back to a non-deformed state, using a single data set. A nonlinear warping algorithm is presented to achieve this. Results indicate that the algorithm attains an accuracy of 97% (4 cm3 difference) when reproducing the total prostate volume compared to a Radiation Oncologist defined prostate volume. This difference is slightly smaller than the measured intra-operator variance of +/-1.5 cm3 (deflated coil) and the measured algorithm variance of +/-1.0 cm3. Additionally, intraprostatic nodules were used to assess the accuracy of the warping algorithm in regions inside the prostate. While choosing anatomical tie points along the external prostate surface, analysis of the nodules revealed the algorithm accuracy reduced to 63-93%.     

Clerkship directors' perceptions of the effects of managed care on medical students' education.

PURPOSE: Little is known about the effect of managed care on medical students' education. Because clerkship directors (CDs) are especially well positioned to observe any changes, this study surveyed CDs from six medical specialties about their perceptions of the effects of managed care on medical students' education. METHOD: Anonymous questionnaires were mailed to 808 CDs from departments of six medical specialties at 125 U.S. allopathic medical schools between October 1997 and March 1998. Among other questions, respondents were asked whether they had observed changes in 19 different aspects of medical students' education, whether these changes were beneficial or detrimental, and whether they believed the changes were due to managed care and/or to other factors. Results were analyzed to determine perceptions of the overall magnitude and source(s) of changes, the perceived positive versus negative effect of managed care, and whether these outcomes were statistically associated with the perceived degree of managed care's market penetration. RESULTS: Five hundred questionnaires (61.9%) were returned. For full-time and voluntary faculty teaching, faculty availability for educational administration, directors' clinical responsibilities, and quality of professional life, the most common response was that managed care had an adverse effect. For faculty's enthusiasm for teaching, directors' administrative and educational duties, and clerkship training sites, the second most common response after "not changed" was that managed care had a negative effect. The majority of respondents held negative opinions of managed care and thought that medical students did not understand it. CONCLUSIONS: CDs in six medical specialties perceived that managed care has negatively affected medical students' education. These perceptions may influence medical students' education. Measures must be taken to ensure excellent education through adequate resources and training in the context of high-quality medical care.     

Upper tibial corticocancellous flap anatomy study (19.2.93)

Summary A cortico-cancellous flap from the anterolateral aspect of the upper third of the tibia was presented. Sixty lower limbs of fresh cadavers were dissected. The vascular bundle includes the anterior tibial artery and its recurrent collateral branches and recurrent and muscllo periostal arteries. The flap is harvested with the interosseous membrane and can be used either free or pedicled. We used this flap for two patients suffering from pseudarthrosis. Long range clinical and radiological results are good.

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Le transfert osseux vascularisé tibial superieur

Résumé Les auteurs décrivent un transfert ostéo-periosté vascularisé, prélevé sur la face antéro-latérale de l'extremité supérieure du tibia. L'étude anatomique porte sur soixante membres inférieurs, conservés au froid. La vascularisation métaphysaire du transfert provient de la branche récurrente tibiale antérieure et de ses rameaux, la vascularisation diaphysaire étant issue des branches musculo-périostiées proximales. Le transfert vascularisé est prélevé avec la membrane interosseuse et peut être pediculé ou libre. L'expérience clinique porte sur deux cas de pseudarthroses multiopérées. Les résultats cliniques et radiologiques sont bons à long terme.

     

The use of laparoscopic ovarian electrocautery in preventing cancellation of in-vitro fertilization treatment cycles due to risk of ovarian hyperstimulation syndrome in women with polycystic ovaries

Fifty women with polycystic ovaries took part in a prospective randomized study. All women required treatment by in-vitro fertilization (IVF) for reasons other than anovulation. They had all previously undergone ovarian stimulation with gonadotrophin therapy which had failed to result in pregnancy or had been abandoned due to high risk of developing ovarian hyperstimulation syndrome (OHSS). Twenty-five women were treated by long-term pituitary desensitization followed by gonadotrophin therapy, oocyte retrieval and embryo transfer (group 1). Twenty-five women underwent laparoscopic ovarian electrocautery after pituitary desensitization followed by gonadotrophin therapy, oocyte retrieval and embryo transfer (group 2). A significantly higher number of women in group 1 had to have the treatment cycle abandoned due to impending or actual OHSS, determined by endocrine and clinical findings. In addition, the development of moderate or severe OHSS in completed cycles was higher in group 1. The pregnancy rate and miscarriage rates in the two treatment groups were similar. The authors propose that laparoscopic ovarian electrocautery is a potentially useful treatment for women who have previously had an IVF treatment cycle cancelled due to risk of OHSS or who have suffered OHSS in a previous treatment cycle.      

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Helicobacter pylori products upregulate neutrophil superoxide anion production

Helicobacter pylori-neutrophil interactions may play a pathogenic role in H. pylori-induced gastritis and peptic ulcer disease. To understand these interactions, we explored the effects of H. pylori-derived products on neutrophil chemotaxis and superoxide anion production. H. pylori bacteria were cultured and supernatants fractionated. Neutrophil chemotactic activity was confirmed in the crude supernatants and in one fractionated peak corresponding to a previously described neutrophil chemotactic factor. H. pylori-derived crude supernatant, sonicate and all chromatography-derived peaks failed to directly stimulate neutrophil superoxide anion production. However, after pretreatment with sonicate, neutrophils demonstrated increased superoxide anion production (priming) following subsequent exposure to the secretagogue fmet-leu-phe. These results suggest that H. pylori products may attract neutrophils to the gastric mucosa without initially stimulating superoxide anion production or tissue injury. Oxygen radical-mediated gastric mucosal injury may subsequently result when these primed neutrophils undergo additional stimulation by as yet unidentified factors.