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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
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↗
PubMed1996

Risk factors for nasopharyngeal carriage of resistant Streptococcus pneumoniae and detection of a multiply resistant clone among children living in the Yukon-Kuskokwim Delta region of Alaska.

BACKGROUND: Children < 2 years old living in the Yukon-Kuskokwim Delta (YKD) region of Alaska have one of the highest pneumococcal bacteremia rates of in the world. METHODS: To determine the prevalence of and risk factors for infection with intermediate or resistant Streptococcus pneumoniae in the YKD, we cultured nasopharyngeal secretions of healthy children < or = 5 years old, reviewed their hospital records and administered questionnaires to accompanying parents. RESULTS: Of 185 children evaluated we obtained 95 pneumococcal isolates; drug susceptibility patterns and serotyping results were available for 92. Of these, 33 (36%) were intermediate or resistant to at least one drug class tested; 27 isolates were intermediate (minimum inhibitory concentration 0.1 to 1.0 mg/l) and none were resistant to penicillin. Compared with other isolates, capsular serotype 6B isolates were more likely to be intermediate or resistant to at least one drug (relative risk, 5.3; P < 0.001) and to more than one drug (relative risk, 17.0; P < 0.001). The majority of 6B isolates had identical pneumococcal surface protein A patterns. Carriage of intermediate or resistant pneumococcus was associated with age < 2 years (relative risk, 3.0; P < 0.001) but not with antibiotic use or other evaluated risk factors. CONCLUSIONS: Young age but not antibiotic use was associated with carriage of intermediate or resistant S. pneumoniae in the YKD region of Alaska. Much of the intermediate or resistant pneumococcus in the YKD may have resulted from the proliferation of a single capsular serotype 6B clone.

Alaska↗
PubMed1996

Cognitive functioning in late-life schizophrenia: a comparison of elderly schizophrenic patients and patients with Alzheimer's disease.

OBJECTIVE: Previous studies have suggested that geriatric inpatients with chronic schizophrenia manifest profound cognitive impairments. This study investigated how these cognitive impairments resemble those seen in degenerative dementing conditions. METHOD: The neuropsychological battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), widely used to characterize the cognitive deficits of patients with Alzheimer's disease, was used to compare patterns of cognitive impairment in 66 triads of subjects consisting of one elderly patient with Alzheimer's disease, one elderly, institutionalized patient with chronic schizophrenia, and one elderly, cognitively normal comparison subject who were matched on age, gender, and education. For some analyses, the two groups of patients were divided into subgroups according to the degree of their cognitive impairment (mild, moderate, or severe) as determined by their scores on the Mini-Mental State examination. RESULTS: Relative to the comparison subjects, both groups of patients showed cognitive deficits on each of the neuropsychological measures. The schizophrenic patients performed worse than the patients with Alzheimer's disease on tests of naming and constructional praxis but were less impaired on the test of delayed word recall. These differences were consistent across all levels of severity of globally measured cognitive impairment. CONCLUSIONS: Consistent with earlier findings from postmortem studies, these findings suggest that major differences exist in the neurobiologic mechanisms responsible for cognitive impairment in schizophrenia and Alzheimer's disease. Effects directly attributable to social and environmental differences between these two groups of patients may also play a role.

Age Factors↗
PubMed1996

Clinical characteristics of Kraepelinian schizophrenia: replication and extension of previous findings.

OBJECTIVE: Subtypologies of schizophrenia based on cross-sectional criteria, such as the nomenclature of the DSMs, have not been successful in identifying valid diagnostic subgroups among patients with schizophrenia. A subtypology that uses criteria to classify individuals on the basis of longitudinal deficits in self-care may identify a more valid subgroup of schizophrenic patients. METHOD: This study describes the clinical characteristics of a group of schizophrenic patients identified on the basis of a longitudinal criterion: at least 5 years of continuous and complete dependence on others for obtaining and maintaining the basic necessities of life, including food, clothing, and shelter. RESULTS: Sixty-one "Kraepelinian" schizophrenic inpatients, when compared to 80 non-Kraepelinian schizophrenic inpatients who were similar in years of illness, age, and education, demonstrated more severe negative symptoms and more severe formal thought disorder; yet the severity of their delusions, hallucinations, and bizarre behavior did not differ significantly. None of the Kraepelinian patients and eight non-Kraepelinian patients met DSM-III-R criteria for schizoaffective disorder. CONCLUSIONS: Data from this replication study suggest that Kraepelinian schizophrenic patients, identified on the basis of a longitudinal course characterized by severe dysfunctions in self-care, may represent an alternative, and possibly more valid, method of subtyping schizophrenia.

Activities of Daily Living↗
PubMed1996

Event-related potentials in schizotypal personality disorder.

This study examined whether abnormalities in event-related potentials (ERPs), reported in schizophrenia, extend to patients with schizotypal personality disorder (SPD). Auditory ERPs in an oddball paradigm were obtained in 19 SPD patients, 17 schizophrenic patients, and 20 normal control subjects (NCs). Schizophrenic patients had lower P300 amplitude than NCs; the P300 amplitude of SPD patients was intermediate, showing a linear trend but not a significant group difference. P200 amplitudes showed a similar trend. SPD patients had N100 and N200 amplitudes intermediate to schizophrenic patients and NCs, without significant group differences. Results suggest diminished P300 amplitude may not be as prominent in SPD as in schizophrenia. Studies with larger sample sizes, multiple lead assessment strategies, and more demanding tasks may further characterize ERP deficits in schizophrenia-spectrum disorders such as SPD.

Adult↗
PubMed1996

Dihydrorhodamine 123 identifies impaired mitochondrial respiratory chain function in cultured cells harboring mitochondrial DNA mutations.

Several human diseases have been found to be caused by mitochondrial DNA (mtDNA) mutations. Pathogenic mutated (mut) mtDNAs are usually "heteroplasmic," coexisting intracellularly with wild-type (wt) mtDNAs. For some mtDNA mutations, cells have normal levels of respiratory chain function unless the percentage of mut-mtDNA is very high. Although progress in understanding the molecular basis of mitochondrial diseases has been remarkable, the heterogeneity of mut-mtDNA distribution, even among cells of the same tissue, makes it difficult to clearly delineate the relationships between mtDNA mutations, gene dosage, and clinical phenotypes. In a search for screening methods for identifying cultured cells with deficient mitochondrial function, we incubated living cells harboring mut-mtDNAs with dihydrorhodamine 123 (DHR123), an uncharged, nonfluorescent agent that can be converted by oxidation to the fluorescent laser dye rhodamine 123 (R123). Bright mitochondrial staining was observed in cells that respired normally. Fluorescence was significantly reduced in cells with mitochondrial respiratory chain dysfunction resulting from very high levels of mut-mtDNAs. The data show that DHR123 is useful for assessing mitochondrial function in single cells, and can be used for isolating viable, respiratory chain-deficient cells from heterogeneous cultures.

Cell Survival↗
PubMed1996

Cyclophosphamide and cisplatin versus paclitaxel and cisplatin: a phase III randomized trial in patients with suboptimal stage III/IV ovarian cancer (from the Gynecologic Oncology Group).

Administration of an alkylating agent plus a platinum coordination complex is standard therapy for advanced epithelial ovarian cancer in the United States. The most commonly used combination is cyclophosphamide/ cisplatin; however, the benefit of this combination in overall survival has not been compelling. We report a prospective comparison of this regimen versus a combination of cisplatin with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a new and well-tolerated agent with documented activity in cisplatin-refractory ovarian cancer. Three hundred eighty-six patients with advanced ovarian cancer and greater than 1 cm residual masses following initial surgery 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. Dose reductions in cyclophosphamide or paclitaxel were permitted for significant toxicity. In 216 patients with measurable disease, responses were reported in 73% of those randomized to the cisplatin/paclitaxel arm and in 60% randomized to the cisplatin/cyclophosphamide arm. Progression-free survival was significantly longer (P < .001) with cisplatin/paclitaxel (median, 12.9 v 17.9 months). Overall survival was also significantly longer (P < .001) with cisplatin/paclitaxel (median, 37.5 v 24.4 months). Incorporating paclitaxel into first-line therapy for patients with suboptimally debulked stage III and stage IV ovarian cancer can increase the duration of the progression-free interval and extend overall survival while maintaining an acceptable toxicity profile.

Adult↗
PubMed1996

The economic burden of Alzheimer's disease in Israel.

Owing to expected increases in the number of persons at risk for developing Alzheimer's disease and the expected decrease in the number of potential caregivers, the economic burden on society and families is expected to rise. Given changes in demographics and labor force participation, it is likely that the burden will be transferred from informal to formal paid services. Understanding the burden and cost of caring for this large population of patients is essential in order to make rational decisions with regard to allocating resources and providing quality care.

Alzheimer Disease↗
PubMed1995

Cognitive function and biological correlates of cognitive performance in schizotypal personality disorder.

There is evidence that some schizophrenic patients have deficits on tests of cognitive function, particularly tests of executive function, including the Wisconsin Card Sorting Test (WCST) and the Trail-making Test, Part B. This study was conducted to determine the generalizability of these findings across the schizophrenia spectrum to schizotypal personality disorder (SPD). Forty DSM-III SPD patients, 56 nonschizophrenia-related other personality disorder (OPD) patients, and 32 normal volunteers from two medical centers performed tests of executive function such as the WCST, Trail-making Part B, Stroop Word-Color Test, and Verbal Fluency, as well as tests of more general intellectual functioning such as the Wechsler Intelligence Scale-Revised Vocabulary and Block Design subtests, and Trail-making Part A. SPD patients performed more poorly on the WCST and on Trail-making Part B than did OPD patients or normal subjects; the groups did not differ on tests of general intellectual functioning. SPD patients may share some of the cognitive deficits observed in schizophrenia.

Adult↗
PubMed1995

Cloning, expression, and chromosomal localization of a novel cadherin-related protein, protocadherin-3.

To study the diversity of the protocadherin family, the cDNA clones for a novel protocadherin were isolated by screening rat brain cDNA libraries with a cDNA fragment obtained by PCR, and some of the properties were then characterized. The overall structure of the protein defined by the clone is similar to that of previously identified protocadherins; however, the cytoplasmic domain is distinct from those of previously cloned protocadherins or any other protein sequences in the data bank. We named this protocad herin-3 (Pcdh3) since this is the third protocadherin of which the entire coding sequence has been determined. Most of the deduced amino acid sequences of other cDNA clones obtained by the screening show high homology with but are distinct from that of Pcdh3, indicating that most of these sequences correspond to homologous but different protocadherins. These results demonstrate that Pcdh3 and the protocadherins defined by these clones constitute a protocadherin subfamily. Chromosome mapping indicates that mouse Pcdh3 is located in a specific region of mouse chromosome 18, close to the location of previously cloned protocadherins, suggesting that various protocadherins form a cluster in this region. In situ hybridization results showed that Pcdh3 and its related proteins were expressed at various areas in brain. The expressed Pcdh3 protein from the cDNA in mouse L cells was about 100 kDa in molecular weight and was localized at cell-cell contact sites. In contrast to the classical cadherins, however, the expressed Pcdh3 was sensitive to trypsin even in the presence of Ca2+, and the transfectants did not show strong Ca(2+)-dependent cell aggregation activity. These results indicate the structural and possibly functional diversity of the protocadherin family and suggest a distinctive biological role for Pcdh3.

Amino Acid Sequence↗
PubMed1995

In vivo pharmacological study of spermine-induced neurotoxicity.

Spermine-induced neurotoxicity and its pharmacological manipulation was studied in the rat striatum in vivo. Spermine (50, 100, 250 nmol) was injected into the striatum and the volume of damage quantified by computer-based image analysis. Spermine produced a dose-dependent increase in the volume of damage. Co-administration of MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate; dizocilpine, 60 nmol), 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (25, 40 nmol) and pretreatment with pentobarbital (40 mg/kg, i.p.) significantly reduced the volume of damage induced by 100 nmol spermine. MK-801 (30 nmol) was also effective in reducing the damage induced by 50 nmol spermine. Treatment with a specific inhibitor of nitric oxide synthase, N omega-nitro-L-arginine methyl ester (50 mg/kg, i.p., twice daily for 10 days) was ineffective. These results suggest an involvement of both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the cascade of spermine-induced neurotoxicity.

Animals↗
PubMed1995

Spread of lumpy skin disease in Israeli dairy herds.

Fourteen of the 17 dairy herds in Peduyim, an Israeli village, became infected with lumpy skin disease during a period of 37 days in August and September 1989. One cow in one neighbouring village and four cows in another neighbouring village also became infected, probably through being treated by a veterinarian who treated cows in Peduyim. Circumstantial evidence suggests that the original infection was brought to Peduyim and spread by stable flies (Stomoxys calcitrans) carried by the wind from foci of the disease at El Arish in northern Sinai, or at Ismailiya and the Nile delta in Egypt. All the cattle and the small flocks of sheep and goats in the village were slaughtered.

Animals↗