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Biomedical subjects

M Davidson

Publications and source records attributed to M Davidson.

At least 19 recordsLinked to original sources
PubMed1992

Effect of m-chlorophenylpiperazine on plasma homovanillic acid concentrations in healthy subjects.

In view of the abundant anatomical and functional interactions between serotonin and dopamine systems, this study examined the effect of the serotonin agonist, m-chlorophenylpiperazine (mCPP) on plasma concentrations of the dopamine metabolite, homovanillic acid. Plasma prolactin levels, body temperature, and mCPP blood level were also measured. mCPP (0.35 mg/kg) and placebo were administered orally to 10 healthy men in a randomized double-blind design. Variables were measured for 210 min after administration of capsules. mCPP raised prolactin and temperature as compared to placebo, but did not affect plasma homovanillic acid concentrations. Results suggest that mCPP does not alter dopamine function.

Administration, Oral↗
PubMed1992

The mitochondrial tRNA(Leu)(UUR)) mutation in MELAS: a model for pathogenesis.

The A----G transition at nucleotide 3243 of the mitochondrial tRNA(Leu)(UUR)) gene has been associated with MELAS, a maternally-inherited mitochondrial disorder. We recently transferred mitochondria harboring this mtDNA mutation into a human cell line devoid of endogenous mtDNA (rho degrees cells), and showed: (1) decreased rate of synthesis and of steady-state levels of mitochondrial translational products, (2) reduced respiratory chain function and (3) increased amounts of a novel unprocessed RNA species (termed by us RNA 19) derived from transcription of the 16S rRNA + tRNA(Leu)(UUR) + ND 1 genes. Because RNA 19 contains rRNA sequences, we propose that this molecule is incorporated into mitochondrial ribosomes, and interferes disproportionately with mitochondrial translation, thereby causing the phenotypic changes associated with MELAS.

Brain Diseases, Metabolic↗
PubMed1992

Prenatal diagnosis for the cystic fibrosis mutation 1717-1, G-->A using arms.

A family carrying two cystic fibrosis mutations, delta F508 and 1717-1, G-->A, requested prenatal diagnosis. In order to eliminate the need for labelling of allele-specific oligonucleotides and to simplify the analysis, 1717-1, G-->A was detected using an ARMS (amplification refractory mutation system) method (Newton et al., 1989). Fetal DNA was obtained by chorionic villus sampling (CVS) and the ARMS technique was used to exclude the 1717-1, G-->A mutation. The fetus was found to be heterozygous for the delta F508 mutation. ARMS is a simple, quick, non-radioactive method suitable for detecting DNA mutations in various clinical situations.

Adenine↗
PubMed1992

Cardiomyopathy in cattle induced by residues of the coccidiostat maduramicin in poultry litter given as a feedstuff.

An experimental feeding trial was conducted in order to substantiate an hypothesis on the aetiology of a previously unrecorded cardiomyopathic syndrome in beef cattle in Israel. It was believed that residues of the ionophore maduramicin (Cygro; American Cyanamid) in poultry litter fed to cattle, after the maduramicin had been incorporated into broiler feed as a coccidiostat, were the cause of the cardiomyopathy. Three groups of 5 heifers were fed for several weeks (1) poultry litter from a field case, containing 4.8 ppm maduramicin; (2) poultry litter to which maduramicin was added to give a concentration of 12 ppm; (3) poultry litter with no maduramicin (control). Clinical, biochemical, necropsy and histopathological findings showed that maduramicin residues are cardiotoxic, even at the lower level of maduramicin fed, which is commonly encountered in poultry litter in Israel.

Animal Feed↗
PubMed1992

Empirical assessment of the factorial structure of clinical symptoms in schizophrenia: negative symptoms.

The factor structure of the Scale for the Assessment of Negative Symptoms (SANS) was examined in a confirmatory factor analysis that used the LISREL procedure. Four models of negative symptom factors were tested in 130 hospitalized schizophrenic patients. A three-factor model of diminished expression, social dysfunction, and disorganization generated by the authors yielded a superior fit to the data relative to the two-factor model of Liddle (1987b) and a unifactorial severity model. A four-factor model based on the original subscale formulation of the SANS failed to fit the data.

Adult↗
PubMed1992

Deterioration on the Blessed test in Alzheimer's disease: longitudinal data and their implications for clinical trials and identification of subtypes.

One hundred eleven patients with probable Alzheimer's disease (AD) were given the Blessed test (BT) of information, memory, and concentration (scored 0-33) at 6-month intervals over periods of 6-96 months. For each patient, the change in the total BT score between pairs of visits at 6- and 12-month intervals was measured. Mean deterioration scores over 6 and 12 months were 2.2 (SD = 3.2) and 4.1 (SD = 4.1) points, respectively. There was no significant correlation between degree of dementia on the BT and the rate of deterioration. Gender, age of onset, and family history had no significant effect on the rate of deterioration. The implications of the results for treatment trials and investigations of clinical heterogeneity are discussed.

Adult↗
PubMed1992

Nocturnal growth hormone secretion in schizophrenic patients and healthy subjects.

Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.m. the next morning in 15 drug-free chronic schizophrenic male inpatients and 14 healthy males. Growth hormone secretion was significantly lower in the patients as compared with the controls. Growth hormone release peaked around 1 a.m. in the controls, but a growth hormone peak was absent in the patient group. Increased dopamine activity, increased serotonin activity, or both could explain the absence of a nocturnal growth hormone surge in the schizophrenic patients.

Adult↗
PubMed1992

Serotonin function in schizophrenia: effects of meta-chlorophenylpiperazine in schizophrenic patients and healthy subjects.

This study examined serotonin (5-hydroxytryptamine; 5HT) receptor responsivity in 22 chronic schizophrenic patients and 17 healthy control subjects. The 5HT agonist meta-chlorophenylpiperazine (MCPP) was used as a probe of serotonergic function. MCPP (0.35 mg/kg) or placebo was administered orally after a 3-week drug-free period in a randomized double-blind design. Hormonal (adrenocorticotropic hormone and prolactin), temperature, and behavioral responses and MCPP blood levels were assessed for 210 minutes after administration of the capsules. The schizophrenic patients had blunted temperature responses compared with those of the healthy control subjects: MCPP raised body temperature in the control subjects, but not in the patients. Behavioral responses also differed in the two groups: MCPP increased the total Brief Psychiatric Rating Scale (BPRS) score in the control subjects and tended to decrease it in the patients. In patients, MCPP decreased the BPRS psychosis subscore. Hormonal responses did not differ significantly in the two groups. These findings suggest that further exploration of 5HT function in schizophrenia is warranted.

Adrenocorticotropic Hormone↗
PubMed1992

Inactivated hepatitis A vaccine: a safety and immunogenicity study in health professionals.

The safety and immunogenicity of an inactivated hepatitis A vaccine (HM175 strain) were evaluated in 150 seronegative health professionals. The age range was 21-65 years and the mean age was 30 years. The vaccine was administered at a dose of 720 ELISA units (EU) to 73 vaccinees at 0, 1 and 6 months, and to 77 vaccinees at 0, 1 and 12 months. The seroconversion rates were 88 and 90% in the two groups, respectively, one month after the first inoculation and 99 and 100% one month after the second inoculation. The geometric mean antibody titres were similar in both groups, exceeding 3000 mIU/ml one month after the third inoculation. The vaccine was well tolerated. The most frequent side effect was transient soreness at the site of the inoculation. No serious adverse reactions were observed. The study demonstrated that the HM175 inactivated hepatitis A vaccine was safe and highly immunogenic.

Adult↗
PubMed1992

Assessment of dementia in elderly schizophrenics with structured rating scales.

Although a number of elderly institutionalized schizophrenic patients appear to suffer from dementia, little is known about the characteristics of the cognitive impairment or its prevalence in this population. In order to answer these questions it is necessary to first reliably and validly assess dementia in elderly schizophrenic patients. This paper reports the results of a study examining the reliability of assessments of the severity of dementia in schizophrenia using scales designed for other dementing conditions and examining the convergence of ratings of the severity of dementia generated from all available sources of information (patient, caregiver, and chart) versus the chart alone. It was found that the interrater reliability of these ratings was very high. On the other hand ratings generated from the hospital chart alone, without contact with either the patient or caregiver, manifested a systematic bias toward overestimation of the severity of dementia. These results suggest that dementia assessment in schizophrenia does not require different instrumentation from that used in other conditions but that relying on the medical chart alone would induce a systematic bias in the results.

Activities of Daily Living↗
PubMed1992

Homovanillic acid measurement in clinical research: a review of methodology.

Despite its serious limitations, measuring the concentrations of homovanillic acid (HVA) in body fluids is perhaps the most direct method currently available to assess the changing activity of central dopamine (DA) neurons in living humans. The concentrations of HVA in body fluids are determined not only by the activity of central DA neurons but also by a number of unrelated factors such as the other sources of HVA and the elimination of HVA from the body. This article reviews many factors that help to determine the concentrations of HVA in body fluids and therefore must be considered in studies employing HVA as a possible index of central DA neuronal activity. The need for further methodological work is indicated to improve the use of body fluid HVA measurements in clinical research.

Body Fluids↗
PubMed1992

Quantitation of pneumococcal C polysaccharide in sputum samples from patients with presumptive pneumococcal pneumonia by enzyme immunoassay.

Although the Gram stain and culture of expectorated sputum are considered standard methods for the diagnosis of presumptive pneumococcal pneumonia, these methods remain relatively insensitive and nonspecific. We developed an enzyme immunoassay (EIA) for the quantitation of pneumococcal C polysaccharide (PnC) in the sputum of patients with presumptive pneumococcal pneumonia. Of 34 patient sputum samples collected within 24 h of the first radiographic report of pneumonia, 12 grew Streptococcus pneumoniae on culture. By using a cutoff point of 0.5 micrograms of PnC per ml of sputum, all 12 specimens were positive (sensitivity, 100%) by EIA. PnC levels ranged from 1.43 to 57.53 micrograms/ml. Blood samples from 18 of the 34 patients were cultured. S. pneumoniae grew in the culture of a blood sample from one patient, whose sputum also had the highest PnC level. Of 22 sputum samples from patients with pneumonia that did not grow S. pneumonia, two were positive by EIA (specificity, 90.1%). Sputa from both patients had low levels of PnC (2.7 and 4.5 micrograms/ml), and both patients had received antibiotics before sputum collection. The positive predictive value of the quantitative EIA was 85.7%. Quantitation of PnC has the potential for improving the accuracy of sputum examination for S. pneumoniae, monitoring disease severity and the effectiveness of antibiotic therapy, and differentiating between those patients with invasive pneumococcal disease and those who are carriers of S. pneumoniae.

Bacteriological Techniques↗
PubMed1992

Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.

Cytoplasts from two unrelated patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) harboring an A----G transition at nucleotide position 3243 in the tRNA(Leu(UUR)) gene of the mitochondrial genome were fused with human cells lacking endogenous mitochondrial DNA (mtDNA) (rho 0 cells). Selected cybrid lines, containing less than 15 or greater than or equal to 95% mutated genomes, were examined for differences in genetic, biochemical, and morphological characteristics. Cybrids containing greater than or equal to 95% mutant mtDNA, but not those containing normal mtDNA, exhibited decreases in the rates of synthesis and in the steady-state levels of the mitochondrial translation products. In addition, NADH dehydrogenase subunit 1 (ND 1) exhibited a slightly altered mobility on polyacrylamide gel electrophoresis. The mutation also correlated with a severe respiratory chain deficiency. A small but consistent increase in the steady-state levels of an RNA transcript corresponding to 16S rRNA + tRNA(Leu(UUR)) + ND 1 genes was detected. However, there was no evidence of major errors in processing of the heavy-strand-encoded transcripts or of altered steady-state levels or ratios of mitochondrial rRNAs or mRNAs. These results provide evidence for a direct relationship between the tRNALeu(UUR) mutation and the pathogenesis of this mitochondrial disease.

Acidosis, Lactic↗
PubMed1992

Effect of marine lipids on cholesteryl ester transfer and lipoprotein composition in patients with hypercholesterolemia.

While the effects of omega-3 (n-3) fatty acids present in marine lipids on plasma lipoprotein levels have been intensively studied, less is known about their impact on reverse cholesterol transport. For this reason, for a 3-month period we studied the effects of the administration of n-3 fatty acids (6 g/day) as a dietary supplement on cholesteryl ester transfer (CET), a key step in this process, and lipoprotein composition in 12 outpatients with genetically heterogeneous forms of hypercholesterolemia. Before treatment, CET in hypercholesterolemic patients, estimated as the mass of cholesteryl ester (CE) transferred from high density lipoprotein (HDL) to very low density lipoprotein (VLDL) plus low density lipoprotein (LDL), was markedly accelerated, peaking after only 1-2 hours of incubation of whole plasma; this response differed significantly (p < 0.001) from the initial delayed curvilinear response of control subjects. Consistent with the accelerated CET occurring in vivo, their triglyceride to esterified cholesterol core lipid ratio before treatment was reduced in the intact VLDL fraction and VLDL1 but not in VLDL2 or VLDL3 and was reciprocally increased in HDL. In addition, the free (unesterified) cholesterol to lecithin ratio of VLDL1 was abnormally increased. Recombination experiments performed with individual lipoprotein fractions revealed that accelerated CET was specifically associated with the VLDL1 subfraction and not LDL, HDL, and cholesteryl ester transfer protein (CETP), although pretreatment levels of CETP were significantly increased (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Agitation and postdexamethasone cortisol levels in Alzheimer's disease.

The clinical correlates of hypothalamic-pituitary-adrenal (HPA) functioning were examined in 29 patients with probable Alzheimer's disease. The 8:00 a.m. postdexamethasone cortisol levels of these patients were highly correlated with higher agitation scores but not with the degree of depressed mood or memory impairment. The possible neural basis for the association between hypercortisolism and behavioral disturbance in Alzheimer's disease warrants further exploration and replication.

Alzheimer Disease↗
PubMed1992

Multidrug resistant Mycobacterium tuberculosis in patients with human immunodeficiency virus infection.

Multidrug resistant Mycobacterium tuberculosis (MDR-MTB) infection has not been recognized as a serious problem in patients with human immunodeficiency virus (HIV) infection. Multidrug resistance (MDR) has appeared in our medical center in 24 out of 72 patients between January 1990 and May 1991 compared to 8 out of 132 patients within the period from 1982 to 1987 (relative risk 5.50 with 95 percent confidence interval 2.61 to 11.61). We describe 19 patients with MDR in MTB (isoniazid and at least one additional first line drug), who had serologic evidence of HIV infection, 13 of whom were diagnosed with acquired immunodeficiency syndrome (AIDS). The MTB cultures from 10 out of 19 patients with MDR were resistant to three or more drugs. Fifteen patients died although 9 out of these 15 had received at least a four-drug regimen for a mean time of seven weeks (range 2 to 12). This increase in MDR was seen in ten homosexuals and nine intravenous drug users. This rapid appearance of MDR-MTB strains is worrisome. New strategies for empiric therapy of such patients while awaiting sensitivity data are needed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Pneumococcal endocarditis in Alaska natives. A population-based experience, 1978 through 1990.

BACKGROUND: Streptococcus pneumoniae is an uncommon cause of infective endocarditis (IE). We studied the presentation, microbiologic characteristics, and outcome of nine cases of S pneumoniae IE during a 12 1/2-year period in a population of 75,000 indigenous Alaska Natives (ANs), who have documented high rates of invasive pneumococcal disease. METHODS: Fifty-six cases of IE occurred in ANs statewide during 1978 through 1990. Medical records of all nine confirmed cases of S pneumoniae IE were reviewed. Incidence rates for S pneumoniae IE and all IE were calculated. RESULTS: Alaska Natives experience S pneumoniae IE as a fulminant illness, with acute aortic valve insufficiency (100%) frequently requiring emergent valve replacement, S pneumoniae meningitis (56%), and death (33%). No patient with S pneumoniae IE had known preexisting heart disease, and the most common underlying disease was alcoholism (56%). Pneumonia was diagnosed and embolic complications were suspected in 33%. All five S pneumoniae isolates examined were penicillin sensitive and were of serotypes included in the pneumococcal vaccine. Pneumococcal IE accounted for 15.8% of all IE diagnosed in ANs. Age- and sex-adjusted incidence rates for IE of all causes and S pneumoniae IE were 8.5 and 1.5 per 10(5) persons per year, respectively. During 1986 through 1988, 4.3% of AN adults diagnosed with S pneumoniae bacteremia developed S pneumoniae IE. CONCLUSIONS: Pneumococcal endocarditis in all but one AN case required emergent valve replacement and had a 33% mortality. The annual incidence rate of S pneumoniae IE in this population was five to 37 times higher than contemporary rates elsewhere. Increased efforts to prevent pneumococcal disease in ANs appear warranted. Clinicians everywhere should anticipate the possible development of S pneumoniae IE in adult patients with pneumococcal sepsis, especially with meningitis, even with previous vaccination and prompt adequate antimicrobial therapy.

Age Factors↗