Carbohydrate sulfotransferases: mediators of extracellular communication

Sulfated carbohydrates mediate diverse extracellular recognition events in both normal and pathological processes. The sulfotransferases that generate specific carbohydrate 'sulfoforms' have recently been recognized as key modulators of these processes and therefore represent potential therapeutic targets.     

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.     

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.     

Hepatic hemangioma. Analysis of 103 cases. Clinical considerations and imaging methods

Hemangiomas are the most common benign vascular tumor found in the liver. In this study, 103 cases of hepatic hemangiomas were analysed in a retrospective manner. Image aspects such as those seen in ultrassonography, computed tomography, nuclear magnetic resonance and arteriography are discussed. The incidence was higher amongst the female sex, between individuals from 40 to 60 years old, which presented predominantly without symptoms (66%) and localized mainly in the right hepatic lobe (74%). The meaning of those aspects, when adopted, permits the clinicians to differentiate benign from malignant nodular lesions in the liver.     

Fetal assessment based on fetal biophysical profile scoring. VIII. The incidence of cerebral palsy in tested and untested perinates

OBJECTIVE: The intent of this comparative clinical study was fourfold: (1) to determine the incidence of cerebral palsy in a large obstetric population, (2) to compare the incidence of cerebral palsy in patients at high risk referred for and managed according to the fetal biophysical profile score result with the incidence among unreferred and untested patients, (3) to determine the relationship, if any, between the last fetal biophysical profile score and the incidence of cerebral palsy, and (4) to categorize cases of cerebral palsy according to the clinical parameters and the probable time and nature of the damaging insult. STUDY DESIGN: In this retrospective 5-year comparative study (1987 to 1991) the incidence of cerebral palsy was determined by analysis of International Classification of Diseases, Ninth Revision, -coded related medical services. The clinical records were then sought and reviewed in index cases and obstetric, neonatal, and postnatal clinical data were abstracted. Cross-correlation with partial registries was done to confirm completeness of capture of index cases. The population of referred high-risk patients who received serial fetal biophysical profile scoring and were managed according to test results was determined by review of a prospective computer-stored database and by review of patient log books. The population of untested patients was calculated as the residual of total cases minus tested cases. The rate of cerebral palsy for all patients and for the tested and untested population was calculated and compared. The tested and untested perinates were compared for birth age, weight, and assigned timing or etiology of cerebral palsy. In the tested population the distribution of test results by last recorded biophysical profile score was determined and the relationship between the last test result and cerebral palsy and predictive accuracy parameters of the fetal biophysical profile score were calculated. RESULTS: The incidence of cerebral palsy among the 84,947 live births was 3.68 per 1000 live births (313 cases). The rate of cerebral palsy in the 26,290 referred high-risk tested patients was 1.33 per 1000 (35 cases) compared with a rate of 4.74 per 1000 live births in the 58,657 untested mixed low-risk/high-risk patients (278 cases). These differences were highly significant. A significant declining trend in the annual incidence of cerebral palsy was observed in the total population and the untested population, whereas the rate in the tested population remained relatively constant over the 5-year study interval. The differences in the cerebral palsy rate between the tested and untested population were not related to differences in gestational age, birth weight, or assigned timing or etiology category. In the tested population the relationship between the incidence of cerebral palsy and the last test fetal biophysical profile score was inverse, exponential, and highly significant. CONCLUSIONS: Antepartum assessment by fetal biophysical profile scoring is associated with a significant reduction in the incidence of cerebral palsy compared with untested patients. The relationship between the last test score and the incidence of cerebral palsy is inverse and exponential, suggesting that antenatal asphyxia is an important and potentially avoidable cause of cerebral palsy.