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Biomedical subjects

M Davidson

Publications and source records attributed to M Davidson.

At least 127 records · Page 7Linked to original sources
PubMed1997

Cost effectiveness of treatment to National Cholesterol Education Panel (NCEP) targets with HMG-CoA reductase inhibitors. Trial design.

HMG-CoA reductase inhibitors effectively reduce cholesterol levels, and this is associated with a lower rate of cardiovascular events. Some HMG-CoA reductase inhibitors are more effective than others in reducing low density lipoprotein (LDL) cholesterol, and such drugs should help patients achieve LDL cholesterol targets prescribed by the National Cholesterol Education Panel (NCEP). This paper describes the design of a trial comparing the clinical efficacy and cost effectiveness of four HMG-CoA reductase inhibitors in reducing LDL cholesterol to specified targets. This trial is being conducted in 30 physicians' practices in the USA. Its primary aim is to assess the resource use required to achieve and maintain NCEP targets by all patients randomised and followed up for one year.

Anticholesteremic Agents↗
PubMed1997

Comparison of combination therapy with paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with suboptimal stage III and stage IV ovarian cancer: a Gynecologic Oncology Group study.

This prospective study compared the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and cisplatin with the standard therapy of cyclophosphamide/cisplatin in women with suboptimal stage III and stage IV ovarian cancer. Of the initial 410 women who presented with advanced disease and greater than 1 cm residual masses after initial surgery, 386 met all eligibility criteria and were randomly assigned to receive a regimen of cisplatin 75 mg/m2 and cyclophosphamide 750 mg/m2 or cisplatin 75 mg/m2 and paclitaxel 135 mg/m2 delivered over 24 hours. Dosage reductions were permitted in the event of significant toxicity. Among 216 patients with measurable disease, responses were reported in 73% of those receiving cisplatin/paclitaxel and in 60% of those receiving cisplatin/cyclophosphamide. Median progression-free survival was significantly longer (P < .001) in the group treated with cisplatin/paclitaxel, compared with those receiving cisplatin/cyclophosphamide (17.9 v 12.9 months, respectively).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Cognitive impairment and negative symptoms in geriatric chronic schizophrenic patients: a follow-up study.

Cognitive impairment is increasingly recognized as an important aspect of schizophrenia. Since cognitive impairment has many features in common with the negative symptoms of the illness, it is possible that some of the characteristics attributed to negative symptoms are due to an association with cognitive impairments. In order to test this hypothesis, 174 chronically hospitalized geriatric schizophrenic patients were examined twice at a 1-year follow-up with ratings of the severity of their symptoms (using the Positive and Negative Syndrome Scale: PANSS) and assessments of cognitive functions with the Mini-Mental State Examination and a brief neuropsychological battery aimed at the typical impairments seen in dementia. Positive symptoms were unassociated with any of the cognitive variables, while negative symptom severity was correlated with each of the cognitive measures. In the cross-temporal analyses, cognitive impairments were more stable over time than negative symptom scores, but cognitive impairment did not predict the severity of any negative symptom over time. At each assessment, however, cognitive impairment was strongly correlated with each of the seven negative symptoms studied. These data indicate that cognitive impairments and negative symptoms are related, but discriminable, features in schizophrenia and that the considerable overlap between some negative symptoms and estimates of cognitive function may suggest a rethinking of the definition of some of these symptoms.

Aged↗
PubMed1996

Empirical evaluation of the factorial structure of clinical symptoms in schizophrenia: effects of typical neuroleptics on the brief psychiatric rating scale.

There has been little investigation of the effect of neuroleptic medication on the structure of symptoms in schizophrenia. In this study, 135 male schizophrenic patients were rated with the Brief Psychiatric Rating Scale (BPRS) after 4 weeks of treatment with typical neuroleptic medication and after 2 weeks free of neuroleptics, with the order of assessment varying across patients. Confirmatory factor analyses (CFA) found that there were no differences in symptom structure across medication status and no differences in the structure of symptoms in treatment responders and nonresponders. The typical 5-factor BPRS model fit the data poorly and the fit improved considerably through deletion of items measuring symptoms not associated with schizophrenia, suggesting that some of the symptoms that contribute to a total BPRS score may be adding primarily error variance. Although the sample size in this study is limited, the results suggest that using total BPRS scores to measure severity of schizophrenic symptoms should be reconsidered.

Adult↗
PubMed1996

Lack of effect of laboratory-provoked anxiety on plasma homovanillic acid concentration in normal subjects.

The present study was undertaken to investigate if acute anxiety can affect plasma concentrations of homovanillic acid (pHVA). Since elevated pHVA levels have been associated with severity of schizophrenic symptoms, the results of this study will help determine if the pHVA elevations are directly related to psychosis or if anxiety is also a contributory factor. Anxiety was provoked in 10 young normal subjects by a combined paradigm of mental arithmetic task and threat of electrical shock. A significant increase in self-ratings of anxiety, blood pressure, and plasma levels of norepinephrine, 3-methoxy-4-hydroxyphenylethyleneglycol and growth hormone indicated that the paradigm used was effective in provoking anxiety; however, anxiety did not affect pHVA concentrations. The results may support the notion that increased pHVA levels in severely ill schizophrenic patients are related to the schizophrenic pathophysiology rather than to anxiety.

Adult↗
PubMed1996

Cost-effectiveness of pravastatin in secondary prevention of coronary artery disease.

This study analyzed the cost-effectiveness of pravastatin in secondary prevention of coronary artery disease (CAD). The projected risk model in 445 male patients with established CAD and moderately elevated serum low-density lipoprotein cholesterol used results data from 2 placebo-controlled plaque regression trials: Pravastatin Limitation of Atherosclerosis in the Coronary Arteries and Pravastatin, Lipids, and Atherosclerosis in the Carotids. Framingham Heart Study data were used to project the risk of mortality 10 years after myocardial infarction (MI) for incremental male patients in the placebo group who had MI. A Markov process was used to estimate life-years saved, and decision analysis was used to estimate cost. Depending on the patient-risk profile, the midrange estimated cost per life-year saved with pravastatin in secondary prevention of CAD varied from $7,124 to $12,665, which is favorable compared with other widely accepted medical interventions.

Anticholesteremic Agents↗
PubMed1996

Isolation of a mouse theta glutathione S-transferase active with methylene chloride.

A glutathione S-transferase metabolizing methylene chloride has been isolated from mouse liver using a variety of chromatographic methods. N-terminal and internal amino acid sequences show that the enzyme, designated GST T1-1*, is closely related to the rat Theta-class GST 5-5. The mouse enzyme, molecular mass 25000 Da, has been isolated to homogeneity in active form with an approximate yield of 2% of the cytosolic activity towards methylene chloride. GST T1-1* has a specific activity of about 5.5 micromol/min per mg of protein whereas the rat GST 5-5 is reported to have a specific activity of about 11 micromol/min per mg of protein [Meyer, Coles, Pemble, Gilmore, Fraser and Ketterer (1991) Biochem. J. 274, 409-414], demonstrating that both the rat and mouse enzymes have similar activity with this substrate. Limited evidence was obtained for a second enzyme, with a similar molecular mass (25400 Da), which had an N-terminal sequence identical to that of rat GST 12-12. This protein, which was sequenced from a band on a gel, was extremely labile and could not be isolated to homogeneity. The partially purified enzyme was not active with methylene chloride.

Amino Acid Sequence↗
PubMed1996

Age disorientation in chronically hospitalized patients with mood disorders.

Age disorientation was studied in 45 geriatric patients with chronic mood disorders. In a yearly assessment of cognitive functions, subjects were questioned about their age, year of birth, and the current year. Patients who misstated their age by > or = 5 years were considered age disoriented. Among the 45 patients, age-disorientation data were available for 32 patients, with the remainder either stating that they did not know their age or providing age-delusional responses. Six of the 32 patients were characterized as age disoriented at baseline and again at 12- to 18-month follow-up assessment. Age-disoriented patients performed worse overall on the Mini-Mental State Examination compared with patients who did not show age disorientation. Future studies of brain function and structure should include poor-outcome patients with mood disorders as well as patients with schizophrenia in attempts to identify the possible neurological dysfunctions that may underlie the phenomenon of age disorientation.

Adult↗
PubMed1996

Neuropeptide deficits in schizophrenia vs. Alzheimer's disease cerebral cortex.

Neuropeptide concentrations were determined in the postmortem cerebral cortex from 19 cognitive-impaired schizophrenics, 4 normal elderly subjects, 4 multi-infarct dementia (MID) cases, and 13 Alzheimer's disease (AD) patients. Only AD patients met criteria for AD. The normal elderly and MID cases were combined into one control group. Somatostatin concentrations were reduced in both schizophrenia and AD. Neuropeptide Y concentrations were reduced only in schizophrenia, and corticotropin-releasing hormone concentrations were primarily reduced in AD. Concentrations of vasoactive intestinal polypeptide and cholecystokinin also were reduced in schizophrenia, although not as profoundly as somatostatin or neuropeptide Y. In AD, cholecystokinin and vasoactive intestinal peptide were unchanged. Neuropeptide deficits in schizophrenics were more pronounced in the temporal and frontal lobes than in the occipital lobe. The mechanisms underlying these deficits in schizophrenia and AD are likely distinct. In schizophrenia, a common neural element, perhaps the cerebral cortical gaba-aminobutyric acid (GABA)-containing neuron, may underlie these deficits.

Aged↗
PubMed1996

Symptom stability in geriatric chronic schizophrenic inpatients: a one-year follow-up study.

The results of previous studies of symptom stability in schizophrenia suggest that negative symptoms manifest traitlike characteristics while positive symptoms fluctuate over time. Various prospective studies of chronic schizophrenic patients have found consistent results, regardless of the follow-up period, yet there is little research addressing symptomatology in geriatric schizophrenic patients. Since these patients have a very poor outcome and more severe negative symptoms, their symptoms might differ from younger patients. This study examined the course of symptomatology in 178 geriatric schizophrenic inpatients who were assessed twice at a 1-year interval with the Positive and Negative Syndrome Scale (PANSS). Intraclass correlations revealed that the distribution of negative symptoms was considerably more stable than that of positive symptoms over the interval, and subtypes based on negative symptoms were the only ones that manifested consistent stability over time. There was also a significant increase in negative symptom severity for the sample, with a slight decrease in positive symptom severity. Thus, even in chronic inpatients, with a very extended illness, positive symptom severity is not particularly stable within patients. These data indicate that the characteristics of negative and positive schizophrenic symptoms are similar in younger and geriatric schizophrenic patients, suggesting a continuity of the illness process. Tentative evidence for increasing severity of negative symptoms over a brief follow-up period suggests the possibility of a steady worsening of clinical state in very elderly patients who remained hospitalized.

Age Factors↗
PubMed1996

Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer.

BACKGROUND: Chemotherapy combinations that include an alkylating agent and a platinum coordination complex have high response rates in women with advanced ovarian cancer. Such combinations provide long-term control of disease in few patients, however. We compared two combinations, cisplatin and cyclophosphamide and cisplatin and paclitaxel, in women with ovarian cancer. METHODS: We randomly assigned 410 women with advanced ovarian cancer and residual masses larger than 1 cm after initial surgery to receive cisplatin (75 mg per square meter of body-surface area) with either cyclophosphamide (750 mg per square meter) or paclitaxel (135 mg per square meter over 24 hours). RESULTS: Three hundred eighty-six women met all the eligibility criteria. Known prognostic factors were similar in the two treatment groups. Alopecia, neutropenia, fever, and allergic reactions were reported more frequently in the cisplatin-paclitaxel group. Among 216 women with measurable disease, 73 percent in the cisplatin-paclitaxel group responded to therapy, as compared with 60 percent in the cisplatin-cyclophosphamide group (P = 0.01). The frequency of surgically verified complete response was similar in the two groups. Progression-free survival was significantly longer (P < 0.001) in the cisplatin-paclitaxel group than in the cisplatin-cyclophosphamide group (median, 18 vs. 13 months). Survival was also significantly longer (P < 0.001) in the cisplatin-paclitaxel group (median, 38 vs. 24 months). CONCLUSIONS: Incorporating paclitaxel into first-line therapy improves the duration of progression-free survival and of overall survival in women with incompletely resected stage III and stage IV ovarian cancer.

Adult↗
PubMed1996

A novel mutation of presenilin 1 in familial Alzheimer's disease in Israel detected by denaturing gradient gel electrophoresis.

Germline mutations in the presenilin 1 (PS1) gene apparently account for the majority of early-onset, familial Alzheimer's disease (AD). Using a mutation-screening strategy (denaturing gradient gel electrophoresis; DGGE), we analyzed a large family with early onset AD and seizures. The patients in this family showed a novel missense mutation in exon 5 of the PS1 gene (A to T change in codon 120, altering glutamine to aspartic acid). This novel mutation is located within the second hydrophilic domain of the molecule, a region not particularly involved in previously described germline mutations, and is of unknown biological significance. These results also demonstrate that DGGE can be used effectively to screen for mutations within this gene.

Alzheimer Disease↗
PubMed1996

FOS and JUN as markers for ethanol-sensitive pathways in the rat brain.

The expression of proteins coded by the immediate early genes of the fos family and c-jun was used to study the effect of acute ethanol administration on convulsant-induced neuronal activity in rat brain. Immunoreactivity for both types of protein was induced by either SC injection of pentylenetetrazole or by IP injection of N-methyl-D-aspartic acid. Both agents elicited distinct patterns of behaviour and a high level of FOS-immunoreactivity in the cerebral cortex and hippocampus. Acute IP doses of ethanol (1.0-3.0 g/kg) significantly reduced the behaviours and FOS-immunoreactivity induced in the cerebral cortex by both pentylenetetrazole and N-methyl-D-aspartic acid. Pentylenetetrazole-induced FOS-immunoreactivity in the hippocampus was also inhibited by ethanol. In contrast, N-methyl-D-aspartic acid-induced FOS-immunoreactivity in the hippocampus was not inhibited by any dose of ethanol. c-JUN immunoreactivity showed a distinct pattern of induction in the hippocampus after injection of N-methyl-D-aspartic acid. Ethanol (3.0 g/kg) inhibited N-methyl-D-aspartic acid-induced c-JUN-immunoreactivity in the hippocampus and cerebral cortex. The differences in inhibition of immunoreactivity suggest that the sensitivity of the NMDA- and GABAA-related neuronal pathways to ethanol varies among different anatomical structures.

Animals↗
PubMed1996

Decreased severity of ethanol withdrawal behaviors in kainic acid-treated rats.

The involvement of kainate (KA)-sensitive regions in ethanol withdrawal behaviors was investigated in male Wistar rats given three intraperitoneal (IP) injections of KA (12 mg/kg) or saline each followed by recovery at 4 degrees C for 5 h and room temperature for 3 days and a final KA or saline injection at room temperature. Some animals received MK-801 (1 mg/kg, IP) 30 min after each injection and one group received saline only. The saline/saline, saline/MK-801, and KA/MK-801 groups displayed typical ethanol withdrawal behaviors 8-12 h after ethanol withdrawal. These behaviors were attenuated in the KA/saline group. Audiogenic seizures could be induced in all treatment groups 12 h after withdrawal. There was severe neuronal degeneration in the hippocampal CA region and the piriform cortex of the KA/saline-treated animals that was reduced by MK-801 treatment. The inferior colliculus remained intact. These results suggest that the N-methyl-D-aspartate receptor mediates KA-induced damage in limbic structures and that these regions may play an important role in typical, but not audiogenically induced ethanol-withdrawal behaviors.

Animals↗
PubMed1996

Internal fixation of displaced fractures of the sacrum.

The results of internal fixation in 30 patients with displaced fractures of the sacrum were retrospectively reviewed. All fractures were displaced at least 1 cm. Neurologic injuries occurred in 40% (12 of 30) patients. In 17 patients who underwent open reduction, the preoperative displacement averaged 24 mm and the postoperative displacement averaged 4 mm. In the 13 patients in whom percutaneous fixation was done, the preoperative displacement averaged 15 mm and the postoperative displacement averaged 5 mm. All 30 fractures united. This review of 30 patients with displaced sacral fractures suggests that open reduction and iliosacral screw fixation leads to better reduction of the fracture site than does closed reduction and percutaneous fixation. Functional assessment indicated that the presence of a neurologic injury is the most important predictor of compromised outcome in patients with displaced sacral fractures.

Activities of Daily Living↗