Sulfonated dyes attenuate the toxic effects of beta-amyloid in a structure-specific fashion.

We recently reported that several sulfate-containing glycosaminoglycans, a class of compounds associated with the beta-amyloid plaques of Alzheimer's disease, attenuate the toxic effects of beta-amyloid fragments beta 25-35 and beta 1-40. The amyloid-binding sulfonated dye Congo Red was shown to have a similar effect. Using two clonal cell lines, we now demonstrate that several sulfonated dyes attenuate beta-amyloid toxicity and that the protective effect appears specific for compounds whose sulfonate groups can interact with the beta-pleated structure of aggregated amyloid.

Inositol monophosphatase--a putative target for Li+ in the treatment of bipolar disorder.

Attenuation of the phosphatidylinositol (PI) signal transduction pathway as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as the mechanism for the efficacy of Li+ in the treatment of bipolar disorder. Nevertheless, Li+ also affects other aspects of PI signal transduction, and it is therefore not clear whether modulation of PI responses by Li+ can be attributed solely to inhibition of IMPase. However, inhibitors of IMPase mimic the effects of Li+ on some aspects of PI cell signalling, thus highlighting the potential of IMPase as a target for the treatment of bipolar disorder.

No significant association between HLA antigens and classic Kaposi sarcoma: molecular analysis of 49 Jewish patients.

Because of the abundance of the classical form of Kaposi sarcoma (CKS) among Jews and people of Mediterranean origin, studies have been conducted to find an association between CKS and HLA antigens. No conclusive results have been drawn, although in a number of these investigations an increased incidence of HLA-DR5 was reported. In our study 49 CKS patients of Jewish origin were serologically analyzed for HLA class I and class II antigens.

Occupational Injuries: Epidemiology, Prevention, and Treatment.

The authors review the current data on patterns of adolescent employment and examine the epidemiology of work-related injuries among adolescents in the U.S. They summarize the laws that have been created to protect adolescents against exploitation and injury in the workplace and the erosion of those measures that has occurred since 1980.

Anxiety disorders among patients in a general emergency service in Israel.

Objective: Several studies have suggested that many patients with anxiety disorders present in nonpsychiatric medical settings such as primary care facilities, emergency services, and general practice. This study examined the prevalence of panic disorder and generalized anxiety disorder among patients admitted to the general emergency service at an urban medical center in Israel.

Methods: Four groups totaling 517 patients were assessed.

Real-time calcium response of cultured bone cells to fluid flow.

Using a parallel-plate flow chamber and fura-2 fluorescence microscopy, intracellular calcium was measured cell by cell in preconfluent primary culture rat calvarial bone cells to 18, 35, and 70 dynes/cm2 of fluid-induced shear stress. A heterogeneous response with respect to peak amplitude and latency was observed for the culture, with an overriding dose-dependent relationship between the mean peak amplitude of response and shear-stress magnitude. A dose dependence was observed between the number of responsive cells (responding > 50% over basal levels) and shear-stress magnitude.

Structure and mechanism of inositol monophosphatase.

Since lithium inhibits IMPase and modulates phosphatidylinositol (PtdIns) cell signalling at therapeutically relevant concentrations (0.5-1.0 mM), IMPase has attracted attention as a putative molecular target for lithium in the treatment of manic depression.

Postictal and chronic psychoses in patients with temporal lobe epilepsy.

Objective: This study sought to elucidate the relation of clinical, neuropsychological, and seizure variables to chronic and postictal psychoses in patients with temporal lobe epilepsy.

Method: Forty-four patients with treatment-refractory temporal lobe epilepsy were given formal psychiatric evaluations; 29 patients had no psychiatric disorder or a nonpsychotic disorder, eight patients had postictal psychoses, and seven patients had chronic psychoses. Comparisons of clinical, neuropsychological, magnetic resonance imaging, and seizure variables were made between the nonpsychotic and the psychotic patients and, secondarily, between the patients with transient postictal psychoses and those with chronic psychoses.

Plasma clozapine levels and clinical response for treatment-refractory schizophrenic patients.

Objective: The purpose of this study was to determine if plasma clozapine levels were associated with treatment response.

Method: To examine this question, neuroleptic nonresponsive patients with schizophrenia or schizoaffective disorder were given clozapine, which was titrated to 500 mg/day by day 14 of treatment, and the dose was held fixed at least through day 21. Subsequently, clozapine doses were adjusted as clinically indicated, up to a maximum of 900 mg/day.

Sulfated glycosaminoglycans and dyes attenuate the neurotoxic effects of beta-amyloid in rat PC12 cells.

Glycosaminoglycan (GAG)-containing proteoglycans are associated with the neuritic plaques and cerebrovascular beta-amyloid deposits of Alzheimer's disease as well as with the amyloid deposits of prion and other disorders. GAGs and other sulfate-containing compounds have previously been shown to bind beta-amyloid peptide in vitro, suggesting possible effects of beta-amyloid deposition and/or toxicity in vivo. Using reduction of the redox dye 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) to measure beta-amyloid neurotoxicity in rat pheochromocytoma PC12 cells, several polysulfated GAGs and synthetic sulfate-containing compounds were found to attenuate the neurotoxic effects of beta-amyloid fragments beta 25-35 and beta 1-40.

Comparative study of wound healing in porcine skin with CO2 laser and other surgical modalities: preliminary findings.

Background: The CO2 laser is a common surgical modality in dermatology. To clarify conflicting reports on the histological healing properties of CO2 laser on incisional or ablative wounds, we have applied it in a miniature hairless porcine skin model at power settings similar to those used in clinical practice.

Methods: Histological parameters of wound healing in skin incisions using the CO2 laser were compared with those using scalpel, hot scalpel, and electrosection, and in dermal ablation using CO2 laser, fraize, wire brush, and electrofulguration alone or with curettage.

Zeta potential of bone from particle electrophoresis: solution composition and kinetic effects.

The morphology of bone may be influenced by many factors, including electromechanical ones such as electric potentials, electric fields, or zeta potentials. Stress-generated potential studies in bone and particle electrophoresis studies using calcium-deficient hydroxyapatite have shown that the zeta potential depends on the composition of the steeping fluid and steeping time. To better quantify and understand these in situ potential changes in bovine cortical bone, the effects of alterations in calcium, phosphate, and fluoride concentrations in Neuman's Fluid (NF), which simulates in vivo bone extracellular fluid, were investigated using particle electrophoresis.

Maturation of murine natural killer precursor cells in the absence of exogenous cytokines requires contact with bone marrow stroma.

To test whether differentiation of natural killer (NK) precursor cells in unsupplemented long-term bone marrow culture requires contact with stromal cells, bone marrow cells (BMC) that were depleted of NK 1.1+ and Thy-1+ cells were cultured either directly on established, irradiated bone marrow stroma or in cell culture inserts separated from the stroma by a 0.45-micron microporous membrane.

A comparison of European and American dosing regimens of schizophrenic patients on clozapine: efficacy and side effects.

We present a comparison of the results from two studies of patients on clozapine. The American study (n = 84; Hillside Hospital, Glen Oaks, NY) and the European study (n = 63; Innsbruck University Clinics, Innsbruck, Austria) both examine efficacy and side effects in schizophrenic patients on this atypical neuroleptic. There is a very substantial difference in the dosing regimen used on both continents and this is reflected in the studies reported.

Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome.

Objective: This study addressed the unique clinical properties attributed to the atypical antipsychotic clozapine, including its efficacy in patients with treatment-refractory psychosis and against negative symptoms, its lack of acute extrapyramidal side effects, and the longer time course of its therapeutic effects.

Method: The clinical responses of 84 schizophrenic inpatients (66 with treatment-refractory illness and 18 who were intolerant of antipsychotic treatment) were examined. After all previous antipsychotic medications had been withdrawn, the patients were treated with clozapine according to a standardized titration and dosage schedule.

An empirical method to refine personality disorder classification using stepwise logistic regression modeling to develop diagnostic criteria and thresholds.

This study of DSM-III-R personality disorder (PD) classification provides an empirical approach to determine (1) the discriminative power of each criterion and (2) the optimal number of criteria needed to diagnose the presence of each PD. A semistructured assessment of 110 outpatients was performed for the 11 PDs and their 104 diagnostic criteria. Sensitivity, specificity, and predictive powers were calculated for each criterion item.

The use of clozapine in neurologic disorders.

The advent of clozapine has marked a major advance in the treatment of schizophrenia because of its low incidence of extrapyramidal side effects and superior efficacy. Because of a relatively high incidence of agranulocytosis, approved indications for use are limited to treatment-refractory or neuroleptic-intolerant patients with schizophrenia. However, an emerging body of literature suggests that clozapine may be preferable to typical neuroleptics for treating psychosis in certain neurologic disorders.

Clozapine dose in the United States and Europe: implications for therapeutic and adverse effects.

The report (1) provides an overview of clozapine doses used in trials conducted in Europe and the United States, (2) compares data on efficacy, and (3) compares side effects of clozapine from recent European and U.S. investigations.

Clozapine, negative symptoms, and extrapyramidal side effects.

The importance of persistent negative symptoms in schizophrenia as a limiting factor in psychosocial and vocational rehabilitation has been increasingly emphasized. As a result, treatment trials and new drug development programs are focusing more attention on negative symptoms. Unfortunately, there is enormous phenomenological overlap between negative symptoms and neuroleptic-induced parkinsonism.

Cerebral morphometry and clozapine treatment in schizophrenia.

Studies of brain morphology in schizophrenia may be informative about basic pathophysiologic processes, provide clinically useful indicators of treatment response, and lead to the identification of markers for selective treatment effects. This paper reviews findings from magnetic resonance imaging studies of patients with schizophrenia conducted at Hillside Hospital, with special attention to (1) findings that have helped distinguish patients who respond well to typical neuroleptics from those who have gone on to trials of clozapine, (2) the capacity of morphological measures to predict clozapine treatment response, and (3) the possibility that selective hypertrophy of striatal structure may be caused by chronic treatment with typical neuroleptics, but not by clozapine.