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Biomedical subjects

D L Roberts

Publications and source records attributed to D L Roberts.

At least 55 records · Page 3Linked to original sources
PubMed1995

Nefazodone: aspects of efficacy.

BACKGROUND: Nefazodone hydrochloride, a 5-HT2 receptor antagonist and serotonin (5-HT) uptake inhibitor, was evaluated in four Phase 3 double-blind, imipramine- and placebo-controlled studies involving outpatients with major depression. METHOD: Patients who qualified for well-controlled efficacy trials in major depression were enrolled in a series of active- and placebo-controlled trials to establish the comparative efficacy of nefazodone and a standard tricyclic antidepressant drug. The primary efficacy measures employed were the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Improvement (CGI) scale. Safety profiles were also compared as well as survival analyses of double-blind acute and continuation treatment of patients in efficacy trials. RESULTS: Three of four Phase 3 active- and placebo-controlled studies showed nefazodone to be an effective antidepressant drug with overall efficacy generally similar to that of imipramine. The remaining study did not differentiate either active drug from placebo controls. Superiority of nefazodone and imipramine over placebo was evidenced by greater improvement on core depression symptoms in addition to the primary outcome measures (HAM-D-17 and CGI). The incidence of side effects and premature treatment discontinuations for imipramine-treated patients was higher than for nefazodone therapy. Both drugs showed evidence of continuing efficacy during long-term treatment with significantly fewer dropouts (p < .05) than for placebo controls. CONCLUSION: Nefazodone, an antidepressant that modulates serotonin receptors and enhances serotonin-mediated neurotransmission, has been shown to be an effective and well-tolerated new antidepressant drug with greater patient acceptability and safety than imipramine.

Ambulatory Care↗
PubMed1994

Identification of the site of phosphorylation on the osmosensor, EnvZ, of Escherichia coli.

EnvZ is a membrane-bound histidine kinase that functions as an osmotic sensor capable of phosphorylating the regulator protein OmpR in Escherichia coli. To characterize the site of phosphorylation biochemically, we overexpressed a 36-kDa truncated EnvZ protein (Glu-106 to Gly-450) that formed inclusion bodies in the cell. After solubilization, the inclusion body form of EnvZ was cleaved into two major fragments with molecular weights of 25,000 and 10,000. The 25-kDa fragment, EnvZc, was purified and found to exist as a dimer. N-terminal sequence analysis established that cleavage had occurred at Arg-214, indicating that EnvZc contained most of the cytoplasmic domain of EnvZ. After labeling EnvZc with [gamma-32P]ATP, the protein was proteolytically digested, and the resulting peptides were separated by reverse phase chromatography using high performance liquid chromatography. One major radioactive peptide containing greater than 90% of the recovered peptide-associated radioactivity was isolated. Amino acid analysis of this purified peptide indicated that the composition was consistent with a peptide that contained His-243. The amino acid sequence of this peptide was determined to be MAGVSHDLRTP (residues 238-248). These results indicate that His-243 is the major site of phosphorylation on EnvZ and represents the first biochemical characterization of the site of phosphorylation of a membrane histidine kinase of the two-component regulatory family of molecules in bacteria.

Amino Acid Sequence↗
PubMed1994

Characterization of random amplified polymorphic DNA (RAPD) products from Xanthomonas campestris and some comments on the use of RAPD products in phylogenetic analysis.

As part of our research to determine phylogenetic relationships of organisms within the phytobacterial species Xanthomonas campestris, we have examined the use of the random amplified polymorphic DNA (RAPD) technique. The objective of this aspect of our research was to determine if a valid cladistic character analysis could be carried out by direct comparison of RAPD products separated on ethidium bromide-stained agarose gels. RAPD products were amplified from 47 Xanthomonas campestris DNA templates using a single oligonucleotide primer. These RAPD products were compared and variation was characterized by Southern analysis of both RAPD products and genomic DNA of the 47 bacterial strains using two cloned RAPD products as probes. Analysis of the data set revealed that the RAPD products were not necessarily homologous or independent, crucial prerequisites for characters to be analyzed in a cladistic phylogenetic analysis. It has been commonly assumed that RAPD variation occurs due to insertion/deletion events or alterations in the primer binding site. Within our data set, we demonstrate absence phenotypes arising from the apparent absence of corresponding loci and also due to the preferred synthesis of alternative RAPD products from unrelated loci. These different types of variation are a reflection of different types of genotypic variation, and direct examination of RAPD products did not allow us to distinguish by which mechanism a particular absence phenotype arose. Although this may not be important for phenetic analyses, for analyses of homologous characters using a cladistic approach it is critical. We also detected unrelated, co-migrating RAPD products and multiple related RAPD products within reaction mixtures. These could both contribute to errors in estimates of similarity, important in any phylogenetic analysis. All of these characteristics of RAPD products should be taken into consideration when RAPD products are used for phylogenetic comparisons.

Blotting, Southern↗
PubMed1994

The reductive acetyl coenzyme A pathway: sequence and heterologous expression of active methyltetrahydrofolate:corrinoid/iron-sulfur protein methyltransferase from Clostridium thermoaceticum.

The methyltransferase (MeTr) from Clostridium thermoaceticum transfers the N5-methyl group of (6S)-methyltetrahydrofolate to the cobalt center of a corrinoid/iron-sulfur protein in the acetyl coenzyme A pathway. MeTr was purified to homogeneity and shown to lack metals. The acsE gene encoding MeTr was sequenced and actively expressed in Escherichia coli at a level of 9% of cell protein. Regions in the sequence of MeTr and the E. coli cobalamin-dependent methionine synthase were found to share significant homology, suggesting that they may represent tetrahydrofolate-binding domains.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1994

The treatment of lead poisoning from gunshot wounds with succimer (DMSA)

Lead poisoning is an unusual complication of gunshot wounds that occurs when retained lead bullet fragments are in contact with body fluids capable of solubilizing lead. The epidemic of violence by gunfire may result in increasing numbers of lead poisoning cases from this exposure. The use of oral chelation for toxicity resulting from this mode of exposure has not been previously discussed. Cases of lead poisoning arising from bullet lead in the synovial cavity of the hip, synovial cavity of the chest, and pleural space are reported. A combination of surgical debridement and chelation therapy with oral succimer produced a satisfactory outcome in all three cases. Oral succimer may be a safe and effective chelation agent for treating lead toxicity in adults with high lead levels secondary to gun shot wounds.

Adult↗
PubMed1994

Long-term treatment of depression with nefazodone.

The utility of double-blind continuation data in assessing long-term efficacy was evaluated in an analysis of data from the development program of a new antidepressant, nefazodone. The benefit of nefazodone therapy was examined during continuation treatment of patients who improved during the 6-8 week acute phase of efficacy studies. Discontinuation for lack of efficacy was used as an indicator of relapse. Pooled long-term data from the extension phases of placebo-controlled, acute efficacy trials were analyzed by the Kaplan-Meier method to estimate survival curves for time to discontinuation. Both nefazodone (p < .01) and imipramine (p < .05) were more effective than placebo during long-term continuation therapy. The findings demonstrate the value of double-blind continuation data in the evaluation of long-term drug benefit and provide an early assessment of nefazodone's effectiveness in continuation treatment of major depression.

Antidepressive Agents↗
PubMed1994

A double-blind comparison of nefazodone, imipramine, and placebo in major depression.

BACKGROUND: Nefazodone is a 5-HT2-receptor antagonist and serotonin (5-HT) selective reuptake inhibitor. This study evaluates the safety and efficacy of nefazodone in patients with major depressive disorder (MDD) in comparison to imipramine and placebo treatments. It also compares two dose ranges of nefazodone to investigate its optimal dose range. METHOD: Nefazodone was evaluated in a 6-week, double-blind trial of novel design involving 180 patients meeting Research Diagnostic Criteria for major depressive disorder and having a minimum pretreatment score of 22 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Patients were randomly assigned to placebo (2-10 capsules/day), imipramine (50-250 mg/day), or nefazodone in two dose ranges (50-250 mg/day or 100-500 mg/day). RESULTS: Improvement on depression measures with nefazodone in the 100-500-mg/day dose range (endpoint mean = 460 mg/day) and imipramine (endpoint mean = 214 mg/day) exceeded that with placebo. Some benefit was also observed in the nefazodone 50-250-mg/day treatment group (endpoint mean = 242 mg/day), but it was suboptimal. Evidence of nefazodone's efficacy as an antidepressant was consistently observed on physician- (HAM-D, Clinical Global Impressions [CGI]) and patient-rated (CGI-patient rated) scales. By patient self-report, improvement of anxiety symptoms associated with depression was evident with nefazodone as early as the first week of treatment, and benefit was seen with both nefazodone dosage groups. Analyses of the physician's global assessments of therapeutic effect and side effects at end of treatment showed therapeutic benefit for both nefazodone and imipramine treatments; however, patients in the nefazodone treatment groups were significantly less troubled by adverse experiences than were imipramine-treated patients, resulting in a lower dropout rate for adverse experience. CONCLUSION: Nefazodone is a well-tolerated and effective antidepressant for the treatment of major depressive disorder.

Adult↗
PubMed1991

Familial multiple blue naevi.

Blue naevi are benign melanocytic neoplasms. They are usually solitary blue or blue-black nodules or plaques. Multiple blue naevi have been reported rarely and there is one report of familial solitary blue naevus. However, familial multiple blue naevi have not been reported previously. We report the case of a family with multiple blue naevi occurring in three generations with an autosomal-dominant inheritance pattern.

Female↗
PubMed1990

Combined kainate and ischemia produces 'mesial temporal sclerosis'.

In the hippocampi of individuals with temporal lobe epilepsy, cells in CA1, CA3, and the dentate hilus are often gone, but dentate granule cells and CA2 are relatively spared. Several animal models have been developed which mimic portions of this damage. In the present work, combined intraventricular kainate and forebrain ischemia produced a lesion most like that observed clinically; the dentate granule cells and a resistant cluster of pyramidal cells, which received mossy fiber input, were the only principle neurons remaining. This preparation may be valuable both in determining the nature of cells that survive and in understanding the consequences of such damage.

Animals↗
PubMed1990

The use of glucocorticosteroids to lessen the inflammatory sequelae following third molar surgery.

Acceptance of the use of glucocorticosteroids in density to control postsurgical inflammation has been impaired by concerns over side effects, adrenal suppression, and efficacy. The pattern of administration generally used is characterized as short-term, high-dose or pulse therapy, which has not been associated with significant side effects or adrenal suppression beyond 10 days. The selection of an appropriate glucocorticosteroid with minimal mineralocorticoid activity and extended biological activity is desirable. Oral and parenteral dosing are possible, and the latter can be administered as acetates (repository) or esters. The efficacy of glucocorticosteroids in reducing pain, swelling, and trismus after third molar surgery is difficult to ascertain because of methodological inconsistencies between investigations. In general, studies that used low dosing schedules have failed to produce dramatic and prolonged results. High-dosing intravenous (IV) studies have demonstrated significant short-term improvements, but the effects were not sustained. Combining IV administration with multiple oral dosing or a single intramuscular (IM) dose may be required to extend short-term improvement. High-dosing IM studies have shown significant and sustained anti-inflammatory effects with a single dose administered either pre- or post-operatively.

Glucocorticoids↗
PubMed1990

Incidence of non-melanoma skin cancer in West Glamorgan, South Wales.

A population-based epidemiological study of non-melanoma skin cancer incidence was carried out over 6 months in an area of South Wales. A much higher incidence than expected of nonmelanoma skin cancer was found with crude annual rates per 100,000 population of 137.7 for basal cell carcinomas and 35.8 for squamous cell carcinomas, giving a combined rate of 173.5. When age was adjusted to the standardized world population the corresponding rates were 83.1, 19.0 and 102.1. Males were affected more than females and the ratio of basal cell carcinomas to squamous cell carcinomas was 4:1. These figures are at least 60% higher than previous estimates of the incidence of non-melanoma skin cancer in the U.K. There may be a higher incidence in this area because of the indigenous Celtic population, but there is almost certainly a substantial under-recording of non-melanoma skin cancers throughout the U.K.

Adult↗