Screening for cognitive impairment in older African-Caribbeans

BACKGROUND: There are increasing numbers of older African-Caribbeans in the United Kingdom. Screening instruments are commonly used in the detection of cognitive impairment, but have not been assessed within this population. This study aimed to develop culturally modified versions of screening instruments for cognitive impairment (Mini-Mental State Examination (MMSE) and Abbreviated Mental Test (AMT)) and to determine their sensitivity and specificity in the diagnosis of dementia. METHODS: The instruments were modified using a process involving a community group of African-Caribbeans and an academic group of health professionals. They were used in a two-stage study involving community resident African-Caribbeans aged 60 years or over in inner-city Manchester, comparing the screening instruments against a computerized diagnostic interview. RESULTS: One hundred and thirty people completed the study. The results for the largest subgroup, the Jamaicans (N = 96) were analysed. Effects of gender, age and education on the MMSE and AMT scores were evaluated. The correlations between the screening instruments and diagnostic interview were highly significant (P < 0.001). At appropriate cut-offs both screening instruments demonstrated high sensitivity and acceptable specificity levels. CONCLUSIONS: A defined process with lay input has assisted in producing culturally modified versions of the MMSE and AMT that perform well compared with a diagnostic interview, if an appropriate cut-off is used. They are easy to administer and acceptable to older African-Caribbean people. The results need to be viewed within the limitations of the current study.     

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.     

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.     

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.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

A model of whole-body protein turnover based on leucine kinetics in rodents

The measurement of fractional synthesis rate is based on the following assumptions: amino acids for protein synthesis are supplied by an intracellular pool; amino acids from protein degradation are not recycled preferentially to protein synthesis; and proteins turn over at a homogeneous rate. To test these assumptions, a mechanistic, theoretical model of protein turnover for a nongrowing 26-g mouse was developed on the basis of data from the literature. The model consisted of three protein pools turning over at fast (102 micromol Leu, t1/2= 11.5 h), medium (212 micromol Leu, t1/2 = 16.6 h) or slow (536 micromol Leu, t1/2 = 71.5 h) rates and extracellular (1.69 micromol Leu), leucyl-tRNA (0.0226 micromol Leu) and intracellular (5.72 micromol Leu) amino acid pools that exchanged amino acids. The flow of amino acids from the protein pools to the leucyl-tRNA pool determined the amount of recycling. The flow of amino acids from the extracellular pool to aminoacyl tRNA determined the amount of channeling. Two flooding dose data sets were used to evaluate specific radioactivity changes predicted by the model. Predictions of specific radioactivities using flooding dose, pulse dose or continuous infusion methods indicated that the model can be a useful tool in estimating the rates of channeling and recycling. However, it was found that use of data from flooding dose experiments might cause inaccurate predictions of certain fluxes.