Treatment refractory schizophrenia: how should we proceed?

A substantial portion of schizophrenic patients demonstrate suboptimal response to conventional antipsychotics. These agents are primarily effective in the treatment of psychotic symptoms; their efficacy in other domains of psychopathology such as negative symptoms, chronic aggressive behavior, and cognitive deficits, is limited or non-existent. In this group of refractory patients, the novel atypical antipsychotic clozapine has demonstrated robust efficacy, with response rates approaching 60% after twelve weeks of treatment. Efficacy of clozapine extends to symptom domains other than psychosis, including negative symptoms, mood stabilization, aggressive behavior and compulsive water drinking. Several novel agents, each of which shares some, but not all, of the preclinical and clinical characteristics that make clozapine so unique, have been introduced in the last 4 years. These agents demonstrate a broader spectrum of efficacy and an improved side effect profile in non-refractory patients. Initial data on their efficacy in refractory patients suggests that olanzapine does not achieve overall superior efficacy in this patient population compared to conventional agents although there is some evidence of relatively greater efficacy in negative symptoms and aggressivity. Several studies suggest that the efficacy of risperidone is superior to that of conventional agents in refractory patients. Preliminary conclusions are not possible for quetiapine because of a paucity of data in the literature. The literature supports a risperidone trial prior to a clozapine trial in a treatment algorithm for refractory patients because of its more favorable risk/benefit profile.     

Staurosporine inhibits interferon alpha-induced gene expression in Friend erythroleukemia cells through a PKC independent pathway

Diabetes mellitus is associated with typical patterns of long term vascular complications which vary with the organ involved. The microvascular kidney disease (Olgemoller and Schleicher, 1993) is characterized by thickening of the capillary basement membranes and increased deposition of extracellular matrix components (ECM), while loss of microvessels with subsequent neovascularisation is predominant in the eye and peripheral nerves. On the other hand macrovascular disease is characterized by accelerated atherosclerosis. These complications are dependent on long term hyperglycemia. Specific biochemical pathways linking hyperglycaemia to microvascular changes were proposed: the polyol pathway (Greene et al., 1987), non-enzymatic glycation of proteins (Brownlee et al., 1988), glucose autooxidation and oxidative stress (Hunt et al., 1990), hyperglycemic pseudohypoxia (Williamson et al., 1993) enhanced activation of protein kinase C by de novo-synthesis of diacyl glycerol (Lee et al., 1989; DeRubertis and Craven 1994) and others. These pathways are not mutually exclusive (Larkins and Dunlop, 1992; Pfeiffer and Schatz, 1992). They may be linked to alterations in the synthesis of growth factors particularly since atherosclerosis and angioneogenesis are associated with increased proliferation of endothelial and smooth muscle cells. Increased synthesis of ECM components is stimulated by growth factors like transforming growth factor beta (TGF beta) (Derynck et al., 1984) and insulin-like growth factor I (IGF-I) (Moran et al., 1991). This review will summarize some of the recent evidence for an involvement of growth factors in diabetic vascular complications and will attempt to assign their emergence in the sequence of events leading to vascular complications.     

The Saeed Six-Shooter: a prospective study of a new endoscopic multiple rubber-band ligator for the treatment of varices

BACKGROUND AND STUDY AIMS: Rubber-band ligation is superior to sclerotherapy, and is considered to be the endoscopic treatment of choice for bleeding varices. The single-shot mechanism of the ligation device generally used is inherently inefficient, and makes the procedure tedious. It also requires overtube placement, associated with discomfort and complications. This study describes the Saeed Six-Shooter, a multiple ligation device. PATIENTS AND METHODS: Twenty-seven consecutive patients with variceal bleeding were prospectively studied. After initial endoscopic ligation, subsequent sessions were every 7-10 days. The parameters studied were the ease of use, the ability to control active bleeding and eradicate varices, survival, and complications. RESULTS: Active bleeding was controlled in all seven (100%) patients. Esophageal varices were eradicated in 70% (3.2 +/- 1.2 sessions), and gastric varices in 88% of patients (2 +/- 1.2 sessions). Five patients re-bled, two from esophageal varices, two from gastric varices, and one from treatment-induced ulcer. There were four deaths, none due to exsanguination. A single complication, esophageal stricture, resolved with balloon dilation. Intubation was no more difficult with the endoscope loaded with the Six-Shooter than with the endoscope alone (P > 0.3). Six ligations were performed in 39% of cases within 60 seconds, and in 74% of cases within 90 seconds. For gastric varices, the device was effectively used with the endoscope retroflexed. CONCLUSIONS: The Saeed Six-Shooter is a safe and efficient instrument for the endoscopic ligation of varices, and has overcome the limitations of the single-shot ligator.     

A new method of nonradioactive labelling of oligonucleotides and their use as allele-specific probes for detecting mutations causing beta-thalassemia

We have developed simple and efficient methods for synthesis of biotin and horseradish peroxidase (HRP)-labeled oligonucleotides. Biotinylated oligonucleotides were obtained in quantitative yields, and oligonucleotide conjugates with HRP in 60-80% yields. Allele-specific oligonucleotide probes for the diagnostics of IVS 1-110 mutation in the beta-globin gene causing beta-thalassemia were thus obtained. Temperature conditions for the non-radioactive ASO hybridization with the amplified segment of the human beta-globin gene and wash conditions were selected. HRP-labelled probes were used in hybridization without preliminary separation after synthesis. To decrease nonspecific enzyme binding we have elaborated special conditions for membrane blocking. Detection of the biotinylated probe was carried out with the help of a streptavidin--HRP conjugate. O-Dianisidine was used as a chromogenic substrate. We have demonstrated the usefulness of this method in the analysis of amplified samples of DNA obtained from blood of patients homozygous in the mutant gene, and heterozygous carriers.     

一种基于时钟差的双端数据同步方法

文章对已有的双端数据采样同步方法进行了对比分析并指出了其优缺点.随着自愈环网和可变路由的光纤通道在高压电网中的普遍应用,采样数字同步网络复用通道作为传输信道时有可能出现通信路由不一致的情况,为了解决收、发通道延时不一致时的数据同步问题,文章引入装置“时钟差”的概念,以传统的“乒乓对时”为主,辅助以电气量对时,可以解决由...     

Genital herpes complicating pregnancy

The seroprevalence of herpes simplex virus type 2 (HSV-2) infections among reproductive-aged women in the United States in prevalent. This article discusses HSV and how it effects the pregnant women and neonates. Management of the disease is reviewed, and recommendations for management of HSV during pregnancy are given.     

Hepatic artery ligation for liver metastasis of a acinar cell carcinoma of the pancreas revealed by a nodular panniculitis

We report the case of a 67-year-old-man presenting with pancreatic acinar cell carcinoma revealed by dermatological manifestations of cytosteatonecrosis and treated by hepatic artery ligation. The pancreatic etiology of these lesions was suspected due to hyperlipasemia, and was confirmed by abdominal computerized tomography showing a pancreatic tumor and multiple liver nodules, and by histological examination of one of these lesions. Because of symptomatic treatment failure, rapid impairment of patient's general condition, and by analogy with the treatment of hepatic metastases of neuroendocrine tumors, hepatic artery ligation was performed. Lipasemia decreased markedly and symptoms disappeared for 45 days. Hepatic artery obstruction may be used for emergency treatment of secreting liver metastases.     

Capillaria hepatica: a cause of septal fibrosis of the liver

Fine, long, fibrous septa were observed as a late change developing in the acinar zone III of the liver of rats experimentally infected with the helminth Capillaria hepatica. Hepatic septal fibrosis begun 30 days after inoculation of embryonated eggs into the stomach of rats and became clearly evident from the 40th day onwards. Experimental observation was undertaken for 170 days. Septal fibrosis increased progressively with time and was most marked when the parasitic nodules formed around larvae, disintegrating worms and eggs were involving. Septal fibrosis of the liver has not been previously recognized as a manifestation of hepatic capillariasis. The presence of sequestered parasite antigens, probably being slowly released within the liver, appears to be a major factor in the pathogenesis of hepatic septal fibrosis observed in rats with C. hepatica infection.     

Major stress protein Hsp70 interacts with NF-kB regulatory complex in human T-lymphoma cells

Utilization of psychiatric in-patient care among 537 new patients was studied in the Department of Psychiatry in Oulu, Finland, during a 3-year follow-up period. Hospitalization during the second and third years of the follow-up was predicted by hospitalization and number of emergency out-patient contacts during the first year of the study, diagnosis of functional psychosis or personality disorder, and previous in-patient care. In total, 5% of the cohort fulfilled our criteria for 'revolving-door' patients. The 'revolving-door' phenomenon was associated with in-patient care at the first contact with the psychiatric services and diagnosis of psychosis or personality disorder. In total, 2% of the cohort became long-stay hospital patients, and this was predicted by psychosis diagnosis. The clinical implications of these findings are that increased attention should be paid to the first assessment of new patients and to the interaction between psychiatric services and patients during the first year of care.