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Biomedical subjects

K L Davis

Publications and source records attributed to K L Davis.

At least 163 records · Page 9Linked to original sources
PubMed1993

Functional decline in Alzheimer's disease: a longitudinal study.

OBJECTIVE: To assess the reliability of activities of daily living (ADL) measures and determine the rate and pattern of longitudinal ADL change in patients with Alzheimer's disease (AD). DESIGN: Longitudinal study with evaluations every 6 months. SETTING: Alzheimer's Disease Research Center Clinics at Mount Sinai Medical Center, New York, and the Veterans Affairs Medical Center, Bronx, New York. PATIENTS: 104 patients meeting NINCDS-ADRDA criteria for probable AD were followed an average of 31 months. MEASUREMENTS: Physical Self-Maintenance Scale (PSMS) and Instrumental Activities of Daily Living Scale (IADLS) of Lawton and Brody and the Blessed Test of Information, Memory, and Concentration. RESULTS: For men there was inconsistency over time in the decision about whether or not some IADLS items such as "Laundry" were appropriate for a given patient. Test-retest and inter-rater reliabilities were high for all PSMS items and for IADLS items that were judged to be appropriate. IADLS scores changed an average of 2.06 (+/- 3.27) points annually, and change scores were smaller for patients with severe dementia. PSMS scores changed an average of 2.44 (+/- 3.87) points annually with virtually all change occurring in severely demented patients. There was a marked ceiling effect for the IADLS and a curvilinear relationship of PSMS annual change with PSMS baseline. CONCLUSIONS: Both PSMS and IADLS measures can be reliable in AD patients, but better IADLS items for males need to be developed. IADLS scores are sensitive to change in mild and moderately demented AD patients, while PSMS scores are sensitive to change in more severely demented patients.

Activities of Daily Living↗
PubMed1993

Distribution, propagation, and coordination of contractile activity in lymphatics.

The propagation and coordination of lymphatic contractions were studied in the mesentery of the rat small intestine using in situ microscopic observation. Indexes of lymphatic diameter were simultaneously measured at two adjacent lymphangions in spontaneously contracting lymphatics (n = 51). Diameter index, contraction frequency, and the percentage of the intersegmental contractions that were propagated and coordinated (PP) were determined at both sites. The conduction velocity of the contractile activity and the percentage of the coordinated contractions that were propagated both antegrade to the direction of lymph flow and retrograde to the flow stream were determined. The results indicate that 1) 80-90% of the lymphatic contractions in the vessels we evaluated were propagated, 2) the wave of contractile activity propagated both centrally and peripherally, and 3) the conduction velocity of the contractile activity was approximately 4-8 mm/s. We tested the hypothesis that gap junctional communication is responsible for the coordination of the contractile event. To accomplish this, we used the gap junction blockers n-heptanol and oleic acid. PP was 90 +/- 4% under normal conditions and fell to a minimum value of 55 +/- 7% during the gap junction blockade. These results indicate that gap junctional communication played an important role in the propagation and coordination of contractions that occurred in spontaneously active lymphatics.

Alcohols↗
PubMed1993

Schizophrenia-related and affective personality disorder traits in relatives of probands with schizophrenia and personality disorders.

OBJECTIVE: The possible heterogeneity of the schizophrenia-related personality disorder traits associated with DSM-III criteria for schizotypal personality disorder was investigated using the family history method. A familial relationship to schizophrenia was hypothesized for schizophrenia-related personality disorder traits without coexisting affective personality disorder traits, pure schizophrenia-related personality disorder traits. Alternatively, a familial relationship with borderline personality disorder was hypothesized for schizophrenia-related personality disorder traits with comorbid affective personality disorder traits. METHOD: Criteria for schizophrenia-related and affective personality disorder traits were used to assess the 588 nonpsychotic first-degree relatives of 55 chronic schizophrenic probands and 67 probands with personality disorders. The probands with one or more DSM-III personality disorders were categorized as having schizotypal personality disorder without borderline personality disorder (pure schizotypal personality disorder), borderline personality disorder without schizotypal personality disorder (pure borderline personality disorder), both disorders, or neither. RESULTS: The morbid risk of all cases of schizophrenia-related personality disorder traits was higher in relatives of probands with schizophrenia and pure schizotypal personality disorder than in relatives of probands with neither schizotypal nor borderline personality disorder; however, it differed only slightly from that observed in the relatives of probands with both schizotypal and borderline personality disorders and pure borderline personality disorder. In contrast, the risk of pure schizophrenia-related personality disorder traits was higher in relatives of probands with schizophrenia and pure schizotypal personality disorder, while the risk of coexisting schizophrenia-related and affective personality disorder traits was lower in both of these groups than among the relatives of probands with both schizotypal and borderline personality disorders and pure borderline personality disorder. CONCLUSIONS: These results offer preliminary indications that schizotypal personality disorder features present without comorbid affective personality disorder traits may more specifically characterize the personality characteristics familially related to schizophrenia. Furthermore, they indicate that schizotypal personality disorder features as currently defined are found in relatives of patients other than those with schizophrenia or schizotypal personality disorder.

Adult↗
PubMed1993

Serotonin function and treatment response to clozapine in schizophrenic patients.

OBJECTIVE: Clozapine is the only compound proven to be effective in the 20% of schizophrenic patients refractory to treatment with conventional neuroleptics. Although its mechanism of action has not been elucidated, clozapine appears, in contrast to most conventional neuroleptics, to be a potent serotonin (5-HT) antagonist. This study hypothesized that 5-HT function is increased in patients who benefit from clozapine treatment relative to patients who fail to improve on it. METHOD: The 5-HT receptor agonist m-chlorophenylpiperazine (MCPP) was used as a probe to examine 5-HT function. MCPP (0.35 mg/kg p.o.) was administered in a placebo-controlled design after a 3-week drug-free period to 19 schizophrenic patients. ACTH, prolactin, body temperature, behavior, and MCPP blood level were measured. Patients were then treated with a conventional neuroleptic, and, having failed to respond to it, were treated with clozapine for 5 weeks (up to 600 mg/day). RESULTS: Patients who responded to clozapine had significantly higher ACTH responses to MCPP during the drug-free state than the patients who failed to benefit from clozapine. Moreover, the degree of improvement with clozapine, particularly the improvement in psychotic symptoms, was strongly correlated with the magnitude of MCPP-induced ACTH release. Other MCPP-induced responses and MCPP blood level were similar for the two groups and did not correlate with the degree of symptomatic improvement with clozapine. CONCLUSIONS: Results of this study suggest that MCPP-induced ACTH release, and by inference 5-HT receptor function, may be increased in patients who benefit from treatment with clozapine relative to patients who fail to improve on this drug.

Adrenocorticotropic Hormone↗
PubMed1993

Antipeptide antibodies as probes of the recombinant and endogenous murine erythropoietin receptors.

The binding of erythropoietin (Epo) to its plasma membrane receptor activates signal pathways that result in erythroid cell proliferation and differentiation. To elucidate the structural features of the receptor that are important for hormone binding and signaling, we have developed a series of site-specific antibody probes. These antibodies were raised against synthetic peptides homologous to six exoplasmic domains and one cytoplasmic domain of the murine receptor and were affinity-purified by binding to their respective peptide antigen, immobilized on agarose. Western blot analyses demonstrated that the recombinant receptor expressed transiently in COS-7 cells is synthesized as three protein species of 62, 64, and 66 kd, consistent with previous observations. Importantly, probing the endogenous receptor in both virally transformed erythroleukemia cells and normal erythroid cells demonstrated similar 62- to 66-kd receptor species. The affinity-purified antibodies also recognized several antigenically related proteins. An examination of the capacity of the antireceptor antibodies to block receptor activation by Epo revealed that antibodies to five of the six exoplasmic domains blocked the receptor. This was reversed with excess Epo. Inhibition of receptor activation by antibody probes to five discrete hydrophilic domains suggests that receptor function may be critically dependent on the structural integrity (conformation) of the entire exoplasmic portion.

Amino Acid Sequence↗
PubMed1993

A sensitive new bioassay for erythroid colony-stimulating factor.

Erythroid colony-stimulating factor (E-CSF) is a B cell-derived membrane protein that specifically affects the growth and development of human and murine committed erythroid progenitors. We report the development of a sensitive new bioassay for E-CSF, based on the ability of the growth factor to stimulate 3H-thymidine incorporation into cloned Rauscher murine erythroleukemia cells. The assay has among its advantages the ability to measure growth factor activity on a purified target cell population in the absence of endogenous growth factor-producing accessory cells. In addition, this assay measures E-CSF's proliferative effect on erythroid progenitors in the absence of erythropoietin (Epo) after 72 to 96 hours. In contrast, the standard bone marrow fibrin clot assay traditionally used to measure E-CSF requires the addition of Epo to promote the development of hemoglobinized erythroid colonies that are quantified after 7 days (for murine cells) to 12 days (for human cells). With the use of this new Rauscher cell bioassay, we have identified an E-CSF-producing human cell line and, further, have measured E-CSF activity derived from nonhuman splenic B lymphocytes.

Animals↗
PubMed1993

Inhibition of the active lymph pump in rat mesenteric lymphatics by hydrogen peroxide.

The lymphatic system plays an important role in the regulation of fluid and macromolecular exchange. It is a key "safety factor" against the formation of gross edema. Spontaneous contractions in collecting lymphatics of the rat intestine are necessary for the normal transportation of lymph. Hydrogen peroxide is one of the compounds released in inflammation. Therefore, the effects of H2O2 on the pumping activity of spontaneously contracting lymphatics were evaluated in the anesthetized rat (n = 16). Diameter oscillations of the mesenteric collecting lymphatics were monitored before and after the application of H2O2 (4 and 37 microM). The activity of the lymph pump was evaluated using: contraction frequency (F), stroke volume (SV), ejection fraction (EF), and lymph pump flow (LPF). These parameters were determined from the lymphatic diameter tracings. The following changes in lymphatic activity were seen after a 20 minute exposure to 37 microM H2O2: 1) F declined 85%, from 11.6 +/- 1.5 to 1.9 +/- 1.9 cpm. 2) SV fell over 93%. 3) EF decreased 93%, from 0.57 +/- .07 to 0.05 +/- .04. 4) LPF fell dramatically (> 95%) from 41.5 +/- 10.5 to 2.6 +/- 2.5 nl/min. In conclusion, H2O2 produced an intense inhibition of the active lymph pump and it is possible that the inhibition of the active pump contributes to the edema which occurs during inflammation.

Animals↗
PubMed1992

A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. The Tacrine Collaborative Study Group.

BACKGROUND: In Alzheimer's disease, there is a marked decline in the function of cholinergic neurons in the brain. However, studies of treatment with cholinesterase inhibitors have produced conflicting results. We conducted a multicenter trial to evaluate whether the cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate) could improve cognition in patients with Alzheimer's disease. METHODS: Of 632 eligible patients with probable Alzheimer's disease, 215 improved while receiving tacrine during a preliminary crossover phase to determine responsiveness and the best dose. The 215 patients were randomly assigned to receive either placebo or their best dose of tacrine (10 or 20 mg four times a day) in a six-week, double-blind trial. The primary measures of efficacy were the cognitive subscale of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale; the secondary measures included the Mini-Mental State Examination and the assessment of the activities of daily living. RESULTS: At the end of the six-week trial, the patients receiving tacrine had a mean adjusted cognitive-subscale score of 30.3 (Alzheimer's Disease Assessment Scale) as compared with 32.7 in patients receiving placebo. This represents a smaller decline (by 2.4 points) in cognitive performance in the tacrine group (P < 0.001). There were no differences between the groups in their global-rating scores. The tacrine group had a significantly smaller decline in the activities of daily living. The results of the Mini-Mental State Examination favored tacrine, but the differences were small and not statistically significant (a score of 16.0 with tacrine vs. 15.3 with placebo; P = 0.08). Gastrointestinal symptoms, elevation of aminotransferase levels, and headache were the most frequent side effects; all could be reversed by reducing the dose or discontinuing treatment. CONCLUSIONS: In this short-term study in patients with Alzheimer's disease who were selected for apparent responsiveness to tacrine, treatment with tacrine resulted in a statistically significant reduction in the decline of cognitive function, although this reduction was not large enough to be detected by the study physicians' global assessments of the patients.

Activities of Daily Living↗
PubMed1992

Acrylamide polymerization kinetics in gel electrophoresis capillaries. A Raman microprobe study.

The formation of 3.5% T, 3.3% C cross-linked polyacrylamide is monitored in 75-microns-i.d. electrophoresis capillaries by Raman microprobe spectroscopy. The disappearance of the acrylamide 1292-cm-1 band is followed with 60-s time resolution for 30 min, and 2-4 min resolution for up to 10 h. Polymerization is 98% complete in 1.5 h and greater than 99% complete after 2 h. In the 900-1700-cm-1 region no bands attributable to cross-linking are observable. Reaction in the capillary follows second-order kinetics. The reaction is faster in the bulk system because heat dissipation is not sufficient to maintain a constant temperature.

Acrylamide↗
PubMed1992

Does modulation of glutamatergic function represent a viable therapeutic strategy in Alzheimer's disease?

Although glutamate dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD), it is unclear which direction a glutamatergic strategy should take in this illness. Increasing glutamate function may enhance excitotoxicity and neuronal death, whereas decreasing activity in this excitatory amino acid pathway may impair memory processes. Pharmacological modulation of the different NMDA and nonNMDA receptor sites, together with the concept of an agonist versus antagonist approach, are discussed in this review. It would appear that a glutamatergic approach may represent a new and exciting option to pursue in the experimental pharmacotherapeutics of AD.

Aged↗
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

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

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↗