Linkage of proximal myotonic myopathy to chromosome 3q

We performed genetic linkage analysis in nine German proximal myotonic myopathy (PROMM) families using DNA-markers D3S1541 and D3S1589 from the region of the recently discovered gene locus of myotonic dystrophy type 2 (DM2) on chromosome 3q. Two-point analysis supplied an lod score of 5.9. We conclude that a gene causing PROMM is located on chromosome 3q. PROMM and DM2 may be allelic disorders or may be caused by closely linked genes.     

Laparoscopic vesicopsoas hitch for infiltrative ureteral endometriosis

Type-specific serologic assays for herpes simplex virus (HSV) types 1 and 2 based on glycoprotein G-1 (gG-1) (HSV-1) and gG-2 (HSV-2) discriminate between antibodies against HSV-1 and HSV-2. We previously developed a Western blot assay using gG-1 and gG-2 expressed in baculovirus, performed extensive validation studies, and determined that it was both sensitive and specific for type-specific detection of HSV antibody. Here we report that, among a cohort of Thai military recruits, the serostatus of some individuals changed from positive to negative over time (6.6% among those ever positive for HSV-1, and 14.9% among those ever positive for HSV-2). We tested a subset of these specimens in three other gG-based assays: an enzyme-linked immunosorbent assay, an immunoblot strip assay, and a Western blot assay. Positive-to-negative shifts occurred in every assay; the frequency of the shifts ranged from 6. 1% to 21.2% of the specimen sets tested. There was only limited agreement among the assays concerning which individuals lost reactivity. This inaccuracy, exhibited by all of the assay protocols, was not predicted by validation studies employing specimens from cross-sectional studies and was most pronounced in HSV-2 testing. This argues for the inclusion of serial blood specimens in serologic assay validation procedures.     

Stimulation of large-conductance Ca2+-activated K+ channels by Evans blue in cultured endothelial cells of human umbilical veins

The effect of Evans blue (EB) on large-conductance Ca2+-activated K+ (BKCa) channels was investigated in cultured endothelial cells of human umbilical veins. In whole-cell configuration, EB (50 microM) reversibly increased the amplitude of K+ outward currents (IK). When the patch pipettes were filled with 10 mM EGTA, its stimulatory effect on IK was unaltered. Further application of EB in the presence of suramin, a blocker of P2-purinergic receptor, or AOPCP, an inhibitor of 5'-nucleotidase, still increased IK. However, charybdotoxin (100 nM) suppressed EB-induced increase in IK. In inside-out configuration, bath application of EB (50 microM) did not change single channel conductance but significantly increased the activity of BKCa channels. The EB-induced increase in the activity of BKCa channels was independent on internal Ca2+. EB (50 microM) shifted the activation curve of BKCa channels to less positive membrane potentials by approximately 20 mV. The change in the kinetic behavior of BKCa channels caused by EB in these cells is due to an increase in mean open time and a decrease in mean closed time. These results indicate that EB can stimulate the activity of BKCa channel in endothelial cells. This effect is unrelated to its blockade of P2-purinergic receptors or inhibition of 5'-nucleotidase. The direct stimulation of these ionic channels by EB may contribute to its effect on capillary permeability.     

Hepatic transcatheter arterial chemoembolization alternating with systemic protracted continuous infusion 5-fluorouracil for gastrointestinal malignancies metastatic to liver: a phase II trial of the Puget Sound Oncology Consortium (PSOC 1104)

We assessed a regimen of alternating regional and systemic therapy in patients with gastrointestinal malignancies with liver-dominant metastases for feasibility, toxicity, response rate, response duration, patterns of progression, and progression-free and overall survival. Regional therapy comprised selective hepatic transcatheter arterial chemoembolization (TACE) using a suspension of cisplatin and particulate polyvinyl alcohol. This procedure was delivered between cycles of protracted continuous infusion 5-fluorouracil (PCI-5FU) as systemic chemotherapy. Patient eligibility criteria included: (a) having histologically documented adenocarcinoma arising from a gastrointestinal primary site with unresectable liver metastases bidimensionally measurable on computerized tomography scan; (b) age greater than 18 years; and (c) performance status 0-2 (Zubrod). PCI-5FU (250 mg/m2/day) was administered i.v. for 28 days, followed by the first TACE (TACE 1) delivered to the hepatic artery supplying the lobe with the greatest tumor burden. Restaging was performed before TACE 2 and TACE 3, which followed at monthly intervals. PCI-5FU for 21 days was sandwiched between each of the TACE treatments. After the final TACE, maintenance PCI-5FU was given for 28 days of each 35-day cycle until toxicity or progression. Between December 23, 1991, and January 19, 1995, 32 patients were registered in this trial, of whom 27 were eligible; 20 completed one or more treatment cycles and were evaluable for radiographic response. Patients with colorectal liver metastases predominated (74%). Twelve (44%) of 27 patients had failed one or more prior treatment regimens. There were no treatment-related deaths, and hematological and hepatic toxicities were generally manageable and reversible. Two patients, however, developed hepatic abscesses requiring drainage, and one patient developed an infarcted gallbladder, which necessitated cholecystectomy. There were no patients with complete responses; there were 8 (40%) with partial responses, 4 (20%) with minor responses, 2 (10%) with stable disease, and 6 (30%) who progressed on the treatment. The median duration of response for partial responders was 4.2 months (127 days; range, 56-245 days). The median reduction in carcinoembryonic antigen for responders was 87.5%. Two patients underwent subsequent resection of residual metastases; one of them is still alive at 58.4 months follow-up. The predominant site of disease progression was the liver; 25% of the patients progressed in extrahepatic sites. The median overall survival for the whole group is 14.3 months (95% confidence interval, 7.2-16.2). Actuarial overall survival for the whole group at 1 year and 2 years is 57 and 19%, respectively. Alternating systemic PCI-5FU and regional TACE (cisplatin/polyvinyl alcohol) is an active and feasible regimen with manageable toxicities in patients with metastatic gastrointestinal malignancies with liver-dominant disease and merits further investigation. The complications seen were in line with those reported at other specialized centers.     

Determining the cost of a clinical intervention through the use of shadow pricing

This article reviews the scientific literature in several areas important to the delivery of palliative care: multicultural issues, education, comprehensive outcome measures and ethics. Most of the research can be classified as fundamental rather than intervention research according to the Cancer Control Framework of the National Cancer Institute of Canada. Desired outcomes of interventions are most often defined from the health care professional's perspective but need to be defined from the patient's perspective. In areas such as multicultural issues and the effect of the volunteer on the patient, there is almost no research. The complexity of studying the best way to deliver palliative care would benefit from the input of colleagues who have experience addressing these issues in other patient populations.     

Preimplantation hormonal differences between the conception and non-conception menstrual cycles of 32 normal women

We compared daily urinary concentrations of oestrogen and progesterone metabolites in paired menstrual cycles (conception and non-conception) from 32 women. Volunteers with no known fertility problems were enrolled in the study at the time they began trying to become pregnant. They collected first-morning urine specimens and kept daily records of menstrual bleeding and sexual intercourse for 6 months or until they became clinically pregnant. Intercourse in non-conception cycles was close to the time of ovulation so that failure to conceive was caused by factors other than poorly timed intercourse. Compared with non-conception cycles, conception cycles had a steeper early luteal rise in progesterone and higher mid-luteal oestrogen and progesterone concentrations. These hormonal characteristics may be markers of better quality cycles, but because all these differences were in the luteal phase, we cannot rule out the possibility that the preimplantation embryo had stimulated early increases in steroid production. We propose an analysis strategy that could help support or refute the importance of preimplantation embryonic signalling, but our small sample size limits our own conclusions about this mechanism.     

Hprt- mutation spectrum in a closely related pair of human bladder tumour cell lines after gamma-irradiation at different dose-rates

Inactivation of p53 gene and overexpression of MDR1 gene are both associated with drug resistance. Previous studies have suggested that p53 gene can modulate the expression activity of MDR1 gene promoter in a promoter-CAT system. In the present study, wild-type p53 gene cDNA was introduced into a multidrug-resistant cell line, KBv200, in which endogenous p53 gene is aberrant. In wt-p53 transfected cells, the expression of MDRI gene was significantly increased, accumulation of adriamycin (ADM) was decreased, and the sensitivity to vincristine (VCR), ADM and 5-fluorouracil (5-FU) was increased compared with the parent KBv200 cells. After treatment with ADM and VCR, the p53-transfectants were more susceptible to apoptosis. The results suggest that the increase in drug sensitivity of the cells may be, at least in part, due to p53-dependent apoptosis induced by anticancer agents.     

Pregnancy-related impairments and the Americans with Disabilities Act

Congress passed the Americans with Disabilities Act (ADA) in 1990. The ADA's overriding purpose is to provide a national mandate for the elimination of discrimination against individuals with disabilities. This article addresses the emerging relationship between pregnancy-related disabilities and the employment provisions of the ADA, set forth in title I of the Act. In view of the high percentage of women who will become pregnant and their potential need for workplace accommodations during and after pregnancy, it is crucial that health professionals understand the impact of the ADA's employment provisions.