Costs and effects of microsurgery versus radiosurgery in treating acoustic neuroma

This study analyses costs and effects of treating acoustic neuroma patients by using microsurgery compared to radiosurgery. Radiosurgery is the stereotactic application of radiotherapy and an innovative medical technology. Cost and effect estimates of conventional treatment were based on a retrospective study in the Netherlands. Similar data for a comparable group of patients in Sweden were collected for radiosurgery, as this treatment option is currently not available in the Netherlands. Fifty-three acoustic neuroma patients who had been operated on the University Hospital Rotterdam between November 1990 and February 1995 were included. This group was compared with 92 acoustic neuroma patients treated with radiosurgery (Gamma Knife. Stockholm, Sweden) in the same period. Data on health care use were collected from patient files. To obtain data on production losses and quality of life, a questionnaire was sent by mail in February 1995. This booklet consisted of the Health and Labour-questionnaire (HLQ), the Short Form-36 (SF36) and the EuroQol. The response rate was 92%. Direct costs for microsurgery amounted to Dfl. 20.072,- and for radiosurgery to Dfl. 14.272,-. Indirect costs were respectively Dfl. 16.400,- and Dfl. 1.020,-. General health rating was better for radiosurgery than for microsurgery. On the whole, differences in clinical outcomes between the two patient groups were small. Assuming a reasonable occupancy rate of the expensive radiosurgery equipment, we demonstrated that for the short term treating patients with acoustic neuroma with an extra-meatal tumour diameter of less than 3 centimeters, radiosurgery is more cost-effective than microsurgery.     

Detoxication in opiate addiction and prevention of recurrence: administration of naltrexone and cognitive behavior therapy

Rapid opiate withdrawal and relapse prevention in opiate addicts are made possible by naltrexone, clonidine and diazepam in combination with cognitive behavioural therapy according to the Community Reinforcement Approach. In an open pilot experiment 12 addicted patients achieved initial detoxification. At follow-up after a minimum of 6 months, 10 of these had not relapsed. Good results with this detoxification method could be booked by selecting highly motivated opiate addicts.     

Tau protects beta in the leading-strand polymerase complex at the replication fork

Replication forks formed in the absence of the tau subunit of the DNA polymerase III holoenzyme produce shorter leading and lagging strands than when tau is present. We show that one reason for this is that in the absence of tau, but in the presence of the gamma-complex, leading-strand synthesis is no longer highly processive. In the absence of tau, the size of the leading strand becomes proportional to the concentration of beta and inversely proportional to the concentration of the gamma-complex. In addition, the beta in the leading-strand complex is no longer resistant to challenge by either anti-beta antibodies or poly(dA):oligo(dT). Thus, tau is required to cement a processive leading-strand complex, presumably by preventing removal of beta catalyzed by the gamma-complex.     

Fluvoxamine in the treatment of binge-eating disorder: a multicenter placebo-controlled, double-blind trial

OBJECTIVE: The purpose of this study was to assess the efficacy of fluvoxamine in the treatment of binge-eating disorder. Binge-eating disorder is a newly described eating disorder characterized by recurrent episodes of binge eating but without purging behaviors. Uncontrolled reports have suggested that serotonin selective reuptake inhibitors (SSRIs) may be effective in treating this disorder. METHOD: Eighty-five outpatients with a DSM-IV diagnosis of binge-eating disorder were randomly assigned to receive either fluvoxamine (N=42) or placebo (N=43) in a 9-week, parallel-group, double-blind, flexible dose (50-300 mg) study at three centers. The primary outcome measures were frequency of binge eating, expressed as log ([binges/week]+1), and Clinical Global Impression (CGI) scale ratings. Secondary measures included the level of response (based on the percentage change in frequency of binges), body mass index, and Hamilton Rating Scale for Depression score. Except for the level of response, the outcome measures were analyzed by random regression methods; the treatment-by-time interaction was the measure of treatment effect. RESULTS: Compared with placebo, fluvoxamine was associated with a significantly greater rate of reduction in the frequency of binges, rate of reduction in CGI severity scores, rate of increase in CGI improvement scores, level of response for patients who completed the 9-week study, and rate of reduction in body mass index. There was no significant difference between placebo and fluvoxamine groups in the rate of decrease in Hamilton depression scale scores. A significantly greater proportion of patients receiving fluvoxamine than those receiving placebo discontinued treatment because of an adverse medical event. CONCLUSIONS: In this placebo-controlled trial, fluvoxamine was found to be effective according to most outcome measures in the acute treatment of binge-eating disorder.     

A pilot study of a short cognitive-behavioral group treatment for female recurrent suicide attempters

The SLT2(MPK1) mitogen-activated protein kinase signal transduction pa thway has been implicated in several biological processes in Saccharomyces cerevisiae, including the regulation of cytoskeletal and cell wall structure, polarized cell growth, and response to nutrient availability, hypo-osmotic shock and heat shock. We examined the conditions under which the SLT2 pathway is activated. We found that the SLT2 kinase is tyrosine phosphorylated and activated during periods in which yeast cells are undergoing polarized cell growth, namely during bud formation of vegetative cell division and during projection formation upon treatment with mating pheromone. BCK1(SLK1), a MEK kinase, is required for SLT2 activation in both of these situations. Upstream of BCK1(SLK1), we found that the STE20 kinase was required for SLT2 activation by mating pheromone, but was unnecessary for its activation during the vegetative cell cycle. Finally, SLT2 activation during vegetative growth was partially dependent on CDC28 in that the stimulation of SLT2 tyrosine phosphorylation was significantly reduced directly after a temperature shift in cdc28 ts mutants. Our data are consistent with a role for SLT2 in promoting polarized cell growth.     

The granaticin biosynthetic gene cluster of Streptomyces violaceoruber Tü22: sequence analysis and expression in a heterologous host

BACKGROUND: The granaticins are members of the benzoisochromanequinone class of aromatic polyketides, the best known member of which is actinorhodin made by Streptomyces coelicolor A3(2). Genetic analysis of this class of compounds has played a major role in the development of hypotheses about the way in which aromatic polyketide synthases (PKSs) control product structure. Although the granaticin nascent polyketide is identical to that of actinorhodin, post-PKS steps involve different pyran-ring stereochemistry and glycosylation. Comparison of the complete gene clusters for the two metabolites is therefore of great interest. RESULTS: The entire granaticin gene cluster (the gra cluster) from Streptomyces violaceoruber T-22 was cloned on either of two overlapping cosmids and expressed in the heterologous host, Streptomyces coelicolor A3(2), strain CH999. Chemical analysis of the recombinant strains demonstrated production of granaticin, granaticin B, dihydrogranaticin and dihydrogranaticin B, which are the four known metabolites of S. violaceoruber. Analysis of the complete 39,250 base pair sequence of the insert of one of the cosmids, pOJ466-22-24, revealed 37 complete open reading frames (ORFs), 15 of which resemble ORFs from the act (actinorhodin) gene cluster of S. coelicolor A3(2). Among the rest, nine resemble ORFs potentially involved in deoxysugar metabolism from Streptomyces spp. and other bacteria, and six resemble regulatory ORFs. CONCLUSIONS: On the basis of these resemblances, putative functional assignments of the products of most of the newly discovered ORFs were made, including those of genes involved in the PKS and tailoring steps in the biosynthesis of the granaticin aglycone, steps in the deoxy sugar pathway, and putative regulatory and export functions.     

Month of birth and schizophrenia in Taiwan: effect of gender, family history and age at onset

Schizophrenic patients have been shown to have a moderate excess of winter births in the areas where seasonal variations in weather are large. In this report, we examined the seasonality of schizophrenic births in Taiwan, which has a subtropical climate. Using nationwide hospitalization data (2429 male and 1320 female schizophrenic patients), we applied the life table method to compare the risk of schizophrenia among 12 cohorts of month-of-birth for males and females, respectively. Differences among the risks of the 12 cohorts were tested using the logrank test. The samples were further stratified by family history and age at onset. There was a significant association between the risk of being admitted as a schizophrenic and month of birth for both males and females. The cohorts born in November and January had the highest risks. After stratification, the association was significant only for non-familial, male, and early onset schizophrenic patients. The results indicate that seasonally varying factors might increase the risk of schizophrenia, especially in those without a family history of the disease. Men are more vulnerable to such factors than women, and the schizophrenics resulting from such insults tend to be early onset.     

Allo- and self-restricted cytotoxic T lymphocytes against a peptide library: evidence for a functionally diverse allorestricted T cell repertoire

BALB/c-derived spleen cells were depleted of cytotoxic T lymphocytes (CTL) recognizing allogeneic (H2b) and TAP-negative cells followed by stimulation with the same cells loaded with a synthetic library binding to H2-Kb. The resulting CTL lines were found to differ widely in peptide specificity and to exhibit an avidity towards the library as that demonstrated for syngeneic CTL. These results demonstrate that positive selection in the context of a certain MHC molecule does not seem to be required for generating high-avidity TCR that are restricted by the same molecule. However, positive selection increases the frequency of such CTL. By raising T cell lines from a repertoire which did not undergo negative selection by the restriction element in question, it becomes possible to produce effective self-peptide/ MHC as well as nonself-peptide/MHC-specific CTL as tools for adoptive tumor immunotherapy.