Effects of intracerebroventricular injections of 2-deoxy-D-glucose,d-glucose and xylose on operant feeding in pigs

The effects, on operant feeding, of injection into the lateral cerebral ventricle of 50 μmoles CaCl₂, 4 mmoles D-glucose, 2-deoxy-D-glucose (2DG) or xylose, or NaCl, have been studied in five pigs. All the sugars and CaCl₂ were given in 1 ml of normal saline. Each of the sugar solutions produced transient drinking. Only CaCl₂ and 2DG significantly increased food intake during the hour following injection. The results show that the mechanism by which the pig responds to intracerebroventricular 2DG is similar to that of the rat and different from that of the sheep.     

Detection of either rapidly cytolytic macrophages or NK cells in "activated" peritoneal exudates depends on the method of analysis and the target cell type

The nature of the cytotoxic cells present in the peritoneal cavity of rats treated with Bacille Calmette-Guérin (BCG) or Corynebacterium parvum was investigated using a 6 hr chromium release assay and a quantitative method of analysis based on consideration of target-cell killing as an enzyme-substrate reaction. When the results of cell-fractionation experiments were evaluated in terms of recovery of total lytic units and when appropriate target cells (such as sarcoma Mc7) were used, the simultaneous presence of both cytotoxic macrophages and NK cells in peritoneal exudates could be readily demonstrated. With certain other target cells different results were obtained. Thus, with normal thymocytes, normal hepatocytes, or myeloma P3NSI as targets, NK cells were preferentially detected, whereas with leukaemias L5178Y, P815, and EL4 as targets, cytotoxic macrophages were preferentially detected. These findings resolve the previously conflicting reports concerning the nature of cytotoxic cells in activated peritoneal exudates.     

Department of Veterans Affairs Cooperative Studies Program genetic linkage study of schizophrenia: ascertainment methods and sample description

To help clarify the genetics of schizophrenia, the Department of Veterans Affairs Cooperative Studies Program has completed data collection for a genetic linkage study of schizophrenia. This article describes the methodological details of the data collection. Subsequent articles will describe the results of our genome scan, which is now in progress. The data collection protocol included the Diagnostic Interview for Genetic Studies, the Family Interview for Genetic Studies, a review of medical records, and the collection of blood for transformation into lymphoblast cell lines. Among relatives of schizophrenic probands, we assessed auditory attention and verbal memory with neuropsychological tests. Among the 166 families ascertained for the study, 143 had a single affected sib-pair, 17 had three affected siblings, one had five affected siblings and five had two sets of affected siblings. There was a total of 216 affected sib-pairs in these families. Using the n-1 rule, these families contain 188 independent affected sib-pairs.     

Low-dose citrate continuous veno-venous hemofiltration (CVVH) and acid-base balance

OBJECTIVE: To evaluate the acid-base effect of low-dose regional citrate anticoagulation (RCA) during continuous veno-venous hemofiltration (CVVH). DESIGN: Prospective observational study. SETTING: ICUs of tertiary public and private hospitals. SUBJECTS: Thirty critically ill patients with acute renal failure at risk of bleeding or with a major contraindication to heparin-CVVH and/or short filter life. METHODS: We used a commercial citrate-based fluid (11 mmol/L, sodium: 140 mmol/L, chloride: 108 mmol/L and 1 mol/L of potassium) as pre-dilution replacement fluid during CVVH. Further potassium was added according to serum potassium levels. We measured all relevant variables for acid-base analysis according to the Stewart-Figge methodology. RESULTS: Before treatment, study patients had a slight metabolic acidosis, which worsened over 6 hours of RCA-CVVH (pH from 7.39 to 7.38, p < 0.005; bicarbonate from 23.2 to 21.6 mmol/L, p < 0.0001 and base excess from -2.0 to -3.0 mEq/L, p < 0.0001) due to a significant increase in SIG (from 5.8 to 6.6 mEq/L, p < 0.05) and a decrease in SIDa (from 37.5 to 36.6 mEq/L, p < 0.05). These acidifying effects were attenuated by hypoalbuminemia and a decrease in lactate (from 1.48 to 1.34 mmol/L, p < 0.005) and did not lead to progressive acidosis. On cessation of treatment, this acidifying effect rapidly self-corrected within six hours. CONCLUSIONS: Low dose RCA-CVVH induces a mild acidosis secondary to an increased strong ion gap and decreased SIDa which fully self-corrects at cessation of therapy. Clinicians need to be aware of these effects to correctly interpret changes in acid-base status in such patients.     

Role of the virology laboratory in diagnosis and management of patients with central nervous system disease.

A number of viruses cause acute central nervous system disease. The two major clinical presentations are aseptic meningitis and the less common meningoencephalitis. Clinical virology laboratories are now more widely available than a decade ago; they can be operated on a modest scale and can be tailored to the needs of the patients they serve. Most laboratories can provide diagnostic information on diseases caused by enteroviruses, herpesviruses, and human immunodeficiency virus. Antiviral therapy for herpes simplex virus is now available. By providing a rapid diagnostic test or isolation of the virus or both, the virology laboratory plays a direct role in guiding antiviral therapy for patients with herpes simplex encephalitis. Although there is no specific drug available for enteroviruses, attention needs to be paid to these viruses since they are the most common cause of nonbacterial meningitis and the most common pathogens causing hospitalization for suspected sepsis in young infants in the United States during the warm months of the year. When the virology laboratory maximizes the speed of viral detection or isolation, it can make a significant impact on management of these patients. Early viral diagnosis benefits patients with enteroviral meningitis, most of whom are hospitalized and treated for bacterial sepsis or meningitis or both; these patients have the advantage of early withdrawal of antibiotics and intravenous therapy, early hospital discharge, and avoidance of the risks and costs of unnecessary tests and treatment. Enteroviral infection in young infants also is a risk factor for possible long-term sequelae. For compromised patients, the diagnostic information helps in selecting specific immunoglobulin therapy. Good communication between the physician and the laboratory will result in the most benefit to patients with central nervous system viral infection.     

Evidence for association and epistasis at the DAOA/G30 and D-amino acid oxidase loci in an Irish schizophrenia sample.

The D-amino acid oxidase (DAO) signaling pathway has been implicated in schizophrenia pathogenesis. This may be mediated through modulation of NMDA function by DAO, which is in turn activated by DAO activator (DAOA, formerly G72). Chumakov et al. (2002); PNAS 99: 13675-13680, identifying the novel schizophrenia susceptibility gene DAOA/G30 and a number of independent studies have since reported evidence of association between the DAOA and DAO genes and schizophrenia. However, at least two studies have failed to replicate the epistatic interaction between these loci described in the original report and there have been differences in the associated alleles/haplotypes reported at each locus. In this study, we performed association and epistasis analyses of the DAOA/G30 and DAO loci in a sample of 373 cases with DSM-IV schizophrenia/schizoaffective disorder and 812 controls from the Republic of Ireland. Corrected for the number of tests performed, we found evidence for association between markers at both genes and schizophrenia: DAOA/G30 (P = 0.005, OR = 1.34 (1.09, 1.65)) and DAO (P = 0.003, OR = 1.43 (1.12, 1.84). The data suggest that evidence for association at DAO (marker rs2111902) is more consistent than previously realized, particularly in Caucasian schizophrenia populations. We identified evidence for epistatic interaction between the associated SNPs at DAOA and DAO genes in contributing to schizophrenia risk (OR = 9.3 (1.4, 60.5). Based on these data, more systematic investigation of genes involved in DAO signaling is required.     

Further Evidence for Embedded Performance Validity Tests in Children within the Conners’ Continuous Performance Test – Second Edition

Objective: To replicate previous research on Conners’ Continuous Performance Test – Second Edition subscales as performance validity tests (PVTs) in children.

Method: Classification accuracy for the Omissions (OMI), Hit Reaction Time (HRT), and Perseverations (PER) subscales was computed for 414 children and adolescents.

Results: Overall, OMI, HRT, and PER demonstrated good specificity but low and variable sensitivity across cutoffs.

Conclusions: Results suggest that OMI, HRT, and PER can function as embedded PVTs in mixed clinical samples of children, although their clinical utility is limited by their low sensitivity. Implications for the use of these PVTs in the context of attention-deficit/hyperactivity disorder evaluations, medication-seeking patients, and sports concussion clinics are discussed.     

Primary cardiac neoplasms. Early and late results of surgical treatment in 42 patients

Forty-two patients underwent resection of primary cardiac neoplasms at Stanford University Medical Center and the Palo Alto Veterans Administration Medical Center between 1961 and 1986. A total of 27 atrial myxomas, seven benign nonmyxomatous tumors, and eight malignant tumors were resected. The mean age was 47 years (range 8 to 79) in 27 female and 15 male patients. The clinical presentations included congestive heart failure in 24 patients, palpitations in nine, neurologic symptoms in six, recurrent cardiac tamponade in three, vasculitis in two, and chest pain in two. Thirty-one of 34 benign lesions were completely resected, although one patient required cardiac transplantation to resect completely an "inoperable" benign tumor. All gross tumor was resected in four of eight patients with malignant lesions. All patients survived operation, but three with malignant disease died within 30 days. Late outcome was known for 41 of 42 (98%) patients. Total follow-up for the series was 200.1 patient-years, for an average of 4.7 years (range 1 month to 18 years). Excellent early and late results were obtained in patients with benign lesions, as there was no known tumor recurrence even if resection was incomplete. Effective palliation and local control of disease is possible with extensive resection of malignant primary tumors, but more effective adjuvant therapy will be necessary to improve long-term prognosis.     

Systems in transition--the first 100 clients: implications of developing specialist units for elderly people

The progress of the initial group of one hundred clients was monitored following referral to a joint-funded assessment unit for "confused" elderly people. Data were collected on allocation and subsequent usage of a range of services available, and implications for clients are discussed. The establishment of specialist service systems for people who are elderly is reviewed in the context of the probable impact upon both clients and local neighbourhoods. The social policies of integration, segregation and congregation are briefly discussed with regard to data obtained. Implications for planning of future services are identified, together with a discussion of likely consequences of replicating such a service.     

L-654,284 a new potent and selective α2-adrenoceptor antagonist

Summary L-654,284 ((2R, 12bS)-N-(1,3,4,6,7,12b-hexahydro-2H-benzo[b]-furo[2,3-a] quinolizine-2-yl)-N-methyl-2-hydroxyethanesulfonamide) was tested in several in vitro and in vivo models for ₂-adrenoceptor antagonist activity and compared to several reference agents. In vitro L-654,284 competed for the binding of ³H-clonidine or ³H-rauwolscine (K _i's 0.8 nM, 1.1 nM) and blocked the presynaptic effects of clonidine in the rat isolated vas deferens (pA₂, 9.1). L-654,284 exhibited marked ₂- vs. ₁-adrenoceptor selectivity in vitro, inhibiting ³H-prazosin binding with a K _i of 110 nM and blocking the effects of methoxamine on the vas deferens with a pA₂ of 7.5. In vivo L-654,284 at 22 nmoles/kg i.v. doubled the ED₅₀ of clonidine to produce mydriasis in rats. Given orally, the potency of L-654,284 in this test was reduced by a factor of 5.5. L-654,284 also potently increased cerebrocortical NE turnover in the rat, another in vivo index of ₂-adrenoceptor blockade in the central nervous system. In the periphery, L-654,284 demonstrated ₂-adrenoceptor selectivity by preferentially blocking the pressor effects of UK 14304 versus those of methoxamine in the pithed rat. Overall, L-654,284 was generally a more potent ₂-adrenoceptor antagonist than RX 781094 with comparable ₂/₁ selectivity and was several times more potent and ₂-selective than WY 26703 or yohimbine. In addition, L-654,284 had better (5–6 times) oral bioavailability than RX 781094 or WY 26703.