Metabolic fate of valproic acid in the rhesus monkey. Formation of a toxic metabolite, 2-n-propyl-4-pentenoic acid

The metabolic fate of an iv bolus dose (13.5 mg kg-1) of valproic acid (VPA) was studied in adult male rhesus monkeys. Renal excretion proved to be the major route of elimination of the drug and a total of 17 metabolites, accounting collectively for some 82% of the administered dose, were identified in urine by GC-MS techniques. Many of these metabolites were present largely in the form of glucuronide conjugates, as was VPA itself. The principal pathways of VPA biotransformation were, in order of decreasing quantitative importance, ester glucuronide formation, omega-oxidation, beta-oxidation and (omega-1)-hydroxylation. In addition, three mono-unsaturated metabolites, identified as (E)-delta 2-, (E)-delta 3-, and delta 4-VPA, were detected in both plasma and urine. Quantitative analysis of these unsaturated VPA metabolites indicated that the delta 4 olefin, which is known to be a potent hepatotoxic agent, was the predominant isomer of the group.     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Epstein-Barr virus latent and replicative gene expression in oral hairy leukoplakia

Oral hairy leukoplakia is an epithelial lesion of the tongue associated with productive infection by Epstein-Barr virus (EBV). However, no data concerning the pattern of EBV latent gene expression have been reported, and it remains unresolved whether true latent infection occurs in basal cell layers of oral hairy leukoplakia. We have studied six cases of oral hairy leukoplakia using monoclonal antibody immunohistology for EBV latent--EB nuclear antigen (EBNA) 1, EBNA 2 and latent membrane protein 1 (LMP 1); immediate-early (BZLF1); and replicative (EA, VCA, MA) proteins, and for the EBV-receptor (CD21 antigen). EBV DNA was demonstrated by nucleic acid in situ hybridization. Mid- to upper-zone keratinocytes contained EBV DNA and co-expressed EBNA 1, EBNA 2 (5 of 6 cases), LMP 1, BZLF1 protein, EA, VCA and MA. No EBV genome or gene expression could be demonstrated in basal or parabasal cells. Spinous keratinocytes were labelled by anti-CD21 antibodies HB5 and B2, but did not express the EBV-receptor as defined by reactivity with OKB7. The co-expression of latent and replicative infection-associated antigens is striking, indicating possible functional roles for latent proteins during the productive cycle. Our results suggest that oral hairy leukoplakia is caused by repeated direct infection of upper epithelial cells with virus from saliva or adjacent replicatively infected cells, rather than by a latent EBV infection of basal epithelial cells with a differentiation-dependent switch to productive infection as previously proposed.     

Assessment of Women for Partner Abuse

Nearly 4 million women in the United States were physically hurt by their husbands or boyfriends in 1994. The health and well-being of these women and their children, as well as the women who are overlooked in these statistics, are jeopardized by past and current experiences with abuse within intimate relationships. Strategies for nurses in women's health care settings to screen women for current or past abuse within their intimate personal relationships, guidelines for effective responses to disclosure of abuse, and supportive interventions are described.     

多索茶碱及其片剂的高效液相色谱分析

多索茶碱及其片剂的高效液相色谱分析刘春胜，何秀峰，王云萍，谷士杰，周同惠（中国医学科学院、中国协和医科大学药物研究所，北京１０００５０）多索茶碱（ｄｏｘｏｆｙｌｌｉｎｅ）是用于治疗支气管哮喘合并支气管痉挛的慢性阻塞性肺部疾病的新一代黄嘌吟衍生物，其药...     

Isolation, regulation, and DNA-binding properties of three Drosophila nuclear hormone receptor superfamily members.

We have designed a rapid cloning and screening strategy to identify new members of the nuclear hormone receptor superfamily that are expressed during the onset of Drosophila metamorphosis. Using this approach, we isolated three Drosophila genes, designated DHR38, DHR78, and DHR96. All three genes are expressed throughout third-instar larval and prepupal development. DHR38 is the Drosophila homolog of NGFI-B and binds specifically to an NGFI-B response element. DHR78 and DHR96 are orphan receptor genes. DHR78 is induced by 20-hydroxyecdysone (20E) in cultured larval organs, and its encoded protein binds to two AGGTCA half-sites arranged as either direct or palindromic repeats. DHR96 is also 20E-inducible, and its encoded protein binds selectively to the hsp27 20E response element. The 20E receptor can bind to each of the sequences recognized by DHR78 and DHR96, indicating that these proteins may compete with the receptor for binding to a common set of target sequences.     

Asbestos-related focal lung masses: manifestations on conventional and high-resolution CT scans

In 260 asbestos-exposed individuals evaluated by means of computed tomography (CT), 43 unsuspected pulmonary masses were found in 27 individuals. The masses included fissural pleural plaques (n = 10), dense fibrotic bands (n = 3), round atelectasis (n = 11), carcinomas (n = 3), and other presumed benign masses (n = 16). The most helpful features in the diagnosis of rounded atelectasis with CT were (a) contiguity to areas of diffuse pleural thickening, (b) a lentiform or wedge-shaped outline, (c) evidence of volume loss in the adjacent lung, and (d) a characteristic "comet tail" of vessels and bronchi sweeping into the margins of the mass. Less advanced areas of focal atelectasis had fewer classic features. Intrafissural pleural plaques were readily identified with high-resolution CT. In asbestos-related masses, the demonstration of stability over time is necessary. Careful interpretation of CT and high-resolution CT features and close surveillance can obviate the need for biopsy in the majority of instances.