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Biomedical subjects

J F Collins

Publications and source records attributed to J F Collins.

At least 19 recordsLinked to original sources
PubMed1992

A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group.

BACKGROUND: Valproate is approved for use primarily in patients with absence seizures, but the drug has a broad spectrum of activity against seizures of all types. Partial or secondarily generalized tonic-clonic seizures are often difficult to control adequately with standard treatment, usually carbamazepine or phenytoin. METHODS: We conducted a multicenter, double-blind trial that compared valproate with carbamazepine in the treatment of 480 adults with complex partial seizures (206 patients) or secondarily generalized tonic-clonic seizures (274 patients). The patients were randomly assigned to treatment with carbamazepine or divalproex sodium (valproate) at doses adjusted to achieve blood levels in the middle of the therapeutic range. Patients were followed for one to five years or until seizures became uncontrollable, treatment had unacceptable adverse effects, or both these events occurred. RESULTS: For the control of secondarily generalized tonic-clonic seizures, carbamazepine and valproate were comparably effective (in 136 patients and 138 patients, respectively). For complex partial seizures, four of five outcome measures favored carbamazepine (100 patients) over valproate (106 patients): the total number of seizures (2.7 vs. 7.6, P = 0.05), the number of seizures per month (0.9 vs. 2.2, P = 0.01), the time to the first seizure (P less than 0.02), and the seizure-rating score (P = 0.04). Carbamazepine was also superior according to a composite score that combined scores for the control of seizures and for adverse effects (P less than 0.001). Valproate was associated more frequently than carbamazepine with a weight gain of more than 5.5 kg (12 lb) (20 percent vs. 8 percent, P less than 0.001), with hair loss or change in texture (12 percent vs. 6 percent, P = 0.02), and with tremor (45 percent vs. 22 percent, P less than 0.001). Rash was more often associated with carbamazepine (11 percent vs. 1 percent, P less than 0.001). CONCLUSIONS: Valproate is as effective as carbamazepine for the treatment of generalized tonic-clonic seizures, but carbamazepine provides better control of complex partial seizures and has fewer long-term adverse effects.

Adolescent↗
PubMed1992

Course of depressive symptoms over follow-up. Findings from the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

We studied the course of depressive symptoms during an 18-month naturalistic follow-up period for outpatients with Major Depressive Disorder treated in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. The treatment phase consisted of 16 weeks of randomly assigned treatment with the following: cognitive behavior therapy, interpersonal therapy, imipramine hydrochloride plus clinical management (CM), or placebo plus CM. Follow-up assessments were conducted at 6, 12, and 18 months after treatment. Of all patients entering treatment and having follow-up data, the percent who recovered (8 weeks of minimal or no symptoms following the end of treatment) and remained well during follow-up (no Major Depressive Disorder relapse) did not differ significantly among the four treatments: 30% (14/46) for those in the cognitive behavior therapy group, 26% (14/53) for those in the interpersonal therapy group, 19% (9/48) for those in the imipramine plus CM group, and 20% (10/51) for those in the placebo plus CM group. Among patients who had recovered, rates of Major Depressive Disorder relapse were 36% (8/22) for those in the cognitive behavior therapy group, 33% (7/21) for those in the interpersonal therapy group, 50% (9/18) for those in the imipramine plus CM group, and 33% (5/15) for those in the placebo plus CM group. The major finding of this study is that 16 weeks of these specific forms of treatment is insufficient for most patients to achieve full recovery and lasting remission. Future research should be directed at improving success rates of initial and maintenance treatments for depression.

Adult↗
PubMed1992

Limits on alpha-helix prediction with neural network models.

Using a backpropagation neural network model we have found a limit for secondary structure prediction from local sequence. By including only sequences from whole alpha-helix and non-alpha-helix structures in our training and test sets--sequences spanning boundaries between these two structures were excluded--it was possible to investigate directly the relationship between sequence and structure for alpha-helix. A group of non-alpha-helix sequences, that was disrupting overall prediction success, was indistinguishable to the network from alpha-helix sequences. These sequences were found to occur at regions adjacent to the termini of alpha-helices with statistical significance, suggesting that potentially longer alpha-helices are disrupted by global constraints. Some of these regions spanned more than 20 residues. On these whole structure sequences, 10 residues in length, a comparatively high prediction success of 78% with a correlation coefficient of 0.52 was achieved. In addition, the structure of the input space, the distribution of beta-sheet in this space, and the effect of segment length were also investigated.

Amino Acid Sequence↗
PubMed1992

On the carcinogenicity of cadmium by the oral route.

Cadmium and cadmium compounds are carcinogenic both by inhalation and by injection. For purposes of risk assessment, a prudent public health approach has been that, if a chemical has been demonstrated to be carcinogenic by one route, it should be considered carcinogenic by all routes. This policy has been questioned for several toxic metals including cadmium. After reviewing the literature on cadmium carcinogenicity and genotoxicity, we think that cadmium should be considered noncarcinogenic by the oral route. The bases for this decision included: (1) a database for genotoxicity of cadmium with more negative test results than positive results and with most positive results in in vitro tests, indicating that cadmium has limited genotoxicity; (2) some epidemiologic evidence of respiratory tract cancer and prostatic cancer in people occupationally exposed to airborne cadmium but no reliable evidence of gastrointestinal tract cancers in workers; and (3) a large dietary oncogenicity study in rats of cadmium chloride at several dose levels, including a maximally tolerated dose (50 ppm) in males, which showed no increase of tumors due to cadmium ingestion in all of the 19 tissues examined. The conclusion that an agent, which has been shown to be carcinogenic by one route of exposure, is not carcinogenic by a second route should be made only in the presence of robust data which indicate the lack of effect via the second route of exposure.

Administration, Oral↗
PubMed1992

Fungal peritonitis in continuous ambulatory peritoneal dialysis--the Auckland experience.

Fungal infection is an uncommon cause of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). We report our center's experience with 38 episodes of fungal peritonitis occurring in 33 patients, out of a total of 503 patients managed on CAPD over 11 1/2 years, and review the relevant literature. Our usual management philosophy has been one of early peritoneal catheter removal without antifungal therapy. In those with worsening clinical features, and in those with persistence of signs and symptoms beyond 48 hours after catheter removal, antifungal drugs were administered. Only five patients received antifungal therapy initially, followed by later catheter removal. Seventy-six percent of patients treated by catheter removal alone (N = 21) and 64% of patients treated by catheter removal followed by antifungal therapy (N = 11) were successfully reestablished on CAPD. A policy of early catheter removal, usually alone, but followed by antifungal therapy in select cases, can be associated with a mortality rate of less than 15% and a high rate of return to effective peritoneal dialysis.

Adult↗
PubMed1992

c-myc antisense oligonucleotides inhibit the colony-forming capacity of Colo 320 colonic carcinoma cells.

Colo 320 cells are colonic carcinoma cells known to express abundant c-myc mRNA. Based on the response of several hematopoietic cell lines to chemical inducers of differentiation, we reasoned that such agents might have similar inductive activity in Colo 320 cells. Accordingly, we exposed Colo 320 cells to 5 mM sodium butyrate (NaBT) for 7 d. C-myc expression decreased threefold and self-replicative potential decreased (defined as a greater than 60% decrease in colony-forming capacity in soft agar that did not contain inducer). In an effort to demonstrate a direct cause and effect between myc expression and the colony-forming capacity of Colo 320 cells, we exposed these cells to a 15-base antisense c-myc oligonucleotide (complementary to the translation initiation region of exon II). Cells were also exposed to equimolar (20 microM) amounts of sense and missense oligonucleotides. Subsequently, cells were incubated at 10, 20, 30, and 40 microM antisense DNA for 16 h, then washed and plated in oligonucleotide-free agar medium. We demonstrated that: (a) the oligomers were stable in the extracellular medium and in the cell cytoplasm; (b) the uptake of the oligonucleotides was 0.7%; (c) sense and missense oligonucleotides had no effect on colony-forming capacity; and (d) the antisense c-myc oligonucleotide resulted in a 40-75% concentration-dependent decrease in colony-forming capacity. The specific inhibition of colony-forming capacity by antisense DNA suggests that the role of myc expression in Colo 320 cells is similar to its role in hematopoiesis, and that the failure to inhibit myc expression maintains colony-forming capacity. This system provides a new strategy for inducing differentiation and may provide further insight into the genetic factors that govern the process of colonic carcinogenesis.

Butyrates↗
PubMed1991

Elastase activity in bronchoalveolar lavage fluid from oxygen-exposed, Pseudomonas-infected baboons.

The adult respiratory distress syndrome is a major cause of morbidity and mortality in critical care patients. Lung injury in this syndrome is frequently associated with lung infection. The combined insults result in an influx of neutrophils and damage to the pulmonary epithelium. We investigated whether active neutrophil elastolytic activity was present in the bronchoalveolar fluid in baboons with mild or moderate hyperoxic lung injury and infection. Group A (N = 7) was exposed for 6 days to FIO2 = 0.8 and then inoculated by intratracheal bolus with Pseudomonas aeruginosa strain DGI-R130 (PA); the FIO2 was reduced to 0.5. Group B (N = 6) was exposed to similar concentrations of inspired oxygen but inoculated with buffered saline. Antibiotics included parenteral penicillin and topical gentamicin and polymyxin B. All 3 were given continuously in group B but stopped 24 h prior to PA inoculation in group A. Bronchoalveolar lavage fluid was collected 1 week before oxygen administration, when the FIO2 was reduced (day 6 or 7) and prior to necropsy (day 11). Hemodynamic, pulmonary function, microbiological, and biochemical variables were studied. Injured, infected animals (group A) had significant elevations of mean pulmonary artery pressure and decreases in total lung capacity and PaO2 compared both to baseline and to group B at day 11. At autopsy, group A had significant increases of bronchoalveolar lavage fluid (BALF) neutrophils and bacterial pathogens. Elastase levels in BALF (equal to 0 at baseline) rose to 136 +/- 98 ng/ml in group A vs. 6 +/- 14 ng/ml in group B. The elastase was inhibited by inhibitors of serine proteases including ones specific for neutrophil elastase. On Sephacryl S-300 chromatography the elastase activity eluted near human alpha 2-macroglobulin and separated from other proteolytic activity. These studies demonstrate a significant level of elastase in BALF from injured, infected baboons compared to injured, uninfected animals.

Acute Disease↗
PubMed1991

Risk assessment for benzo[a]pyrene.

Benzo[a]pyrene is the most studied carcinogenic polycyclic aromatic hydrocarbon and one of the most potent, and it is often used as a toxicological prototype or surrogate for all carcinogenic polycyclic aromatic hydrocarbons. Quantitative risk assessment of benzo[a]pyrene has been hampered by the quality of the data sets available for quantitation. The EPA has calculated both potency slopes and unit risks using the linearized multistage model. We have confirmed and refined that analysis. Risks based on feeding, inhalation, and intratracheal administration of benzo[a]pyrene show fairly good concordance. Others have applied the Moolgavkar two-stage model to the data and estimated a lower potency for benzo[a]pyrene. We think that such conclusion is premature. Longer term exposures of animals to benzo[a]pyrene are necessary to provide the data needed for more refined carcinogenic risk estimations.

Animals↗
PubMed1991

Test performance characteristics of the serum phenytoin concentration (SPC): the relationship between SPC and patient response. The Veterans Administration Epilepsy Cooperative Study Group.

A retrospective analysis of Veterans Administration (VA) Cooperative Study No. 118 was conducted to examine the relationship between serum phenytoin concentration (SPC) and various measures of patient response in 111 patients on monotherapy, mostly after 12 months of treatment. Using patient response rating scales specifically developed and validated for the VA study, we plotted SPC vs overall composite score as well as vs each of the three component ratings of neurotoxicity, systemic toxicity, and seizure type and frequency. No statistically significant association was noted between SPC and any of the response measures. We also calculated test performance characteristics for using SPC and a therapeutic range of 10-22 micrograms/ml to categorize patient status with regard to overall response, toxicity, and seizure frequency. Test sensitivities (0.13-0.53), specificities (0.62-0.81), and positive predictive values (0.08-0.44) were much lower than desirable. This results in a large proportion of false-positive and false-negative errors associated with the use of SPC as a test. Our retrospective evaluation suggests that the range of SPC values in successfully treated patients is quite broad; the value of the commonly accepted SPC therapeutic range in predicting various measures of patient response is quite limited; and patient response, therefore, should be the ultimate end point in monitoring patients on phenytoin. Prospective studies of the relationship between SPC and response should be conducted.

Double-Blind Method↗
PubMed1991

Effect of folic acid on recurrence of phenytoin-induced gingival overgrowth following gingivectomy.

This study examined the effect of folic acid supplementation on the recurrence of phenytoin-induced gingival overgrowth following gingivectomy. 8 residents of an institution for the developmentally disabled were randomly assigned to a treatment (N = 4) or control (N = 4) group. Subjects in the treatment group received an oral supplementation of 5 mg of folic acid daily during the study; those in the control group did not. A gingivectomy with an external beveled incision made to the crest of the alveolus was completed by quadrants. The following data were obtained prior to gingivectomy, 2 weeks following the last quadrant of surgery, and at 3 and 6 months post-surgery: plaque and gingival index scores, red blood cell folic acid levels, free phenytoin blood levels, photographs, and impressions. % change in overgrowth was determined from cross-sectional area measurements made on dies obtained from bucco-lingual cuts on stone models. Differences across time between and within groups were tested by a two-factor repeated measure analysis of variance. The groups did not differ in plaque and gingival index scores or free phenytoin blood levels. The treatment group had significantly higher red blood cell folic acid levels (p less than or equal to 0.0001). Reduction in gingival overgrowth as a result of surgery was similar in both groups. Although the treatment group had significantly less recurrence of gingival overgrowth (p less than or equal to 0.05), the mean differences amounted to only 6-7% at 3 and 6 months.

Adult↗
PubMed1991

Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program.

OBJECTIVE: The authors investigated patient characteristics predictive of treatment response in the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program. METHOD: Two hundred thirty-nine outpatients with major depressive disorder according to the Research Diagnostic Criteria entered a 16-week multicenter clinical trial and were randomly assigned to interpersonal psychotherapy, cognitive-behavior therapy, imipramine with clinical management, or placebo with clinical management. Pretreatment sociodemographic features, diagnosis, course of illness, function, personality, and symptoms were studied to identify patient predictors of depression severity (measured with the Hamilton Rating Scale for Depression) and complete response (measured with the Hamilton scale and the Beck Depression Inventory). RESULTS: One hundred sixty-two patients completed the entire 16-week trial. Six patient characteristics, in addition to depression severity previously reported, predicted outcome across all treatments: social dysfunction, cognitive dysfunction, expectation of improvement, endogenous depression, double depression, and duration of current episode. Significant patient predictors of differential treatment outcome were identified. 1) Low social dysfunction predicted superior response to interpersonal psychotherapy. 2) Low cognitive dysfunction predicted superior response to cognitive-behavior therapy and to imipramine. 3) High work dysfunction predicted superior response to imipramine. 4) High depression severity and impairment of function predicted superior response to imipramine and to interpersonal psychotherapy. CONCLUSIONS: The results demonstrate the relevance of patient characteristics, including social, cognitive, and work function, for prediction of the outcome of major depressive disorder. They provide indirect evidence of treatment specificity by identifying characteristics responsive to different modalities, which may be of value in the selection of patients for alternative treatments.

Adult↗
PubMed1991

Readability of the Depression Adjective Check Lists (DACL) and the Multiple Affect Adjective Check List-Revised (MAACL-R).

To determine the readability of the Depression Adjective Check Lists (DACL; Lubin, 1981) and the Multiple Affect Adjective Check List-Revised (MAACL-R; Zuckerman & Lubin, 1985), each adjective on the two instruments was assigned its grade level readability designation from the Dale and O'Rourke (1981) compendium. Median readability level of each of the seven DACL lists was sixth grade with an average of 80% of each list at or below the eighth-grade level. For the MAACL-R, median readability level for each of the seven scales was fourth grade except for Hostility, which was at the sixth-grade level. Approximately 87% of the MAACL-R is at or below the eighth-grade reading level. The discussion suggests that both the DACL and MAACL-R can be considered to be at the eighth-grade reading level.

Adult↗
PubMed1990

A possible role for the pcnB gene product of Escherichia coli in modulating RNA: RNA interactions.

The sequence of the PcnB protein of Escherichia coli, a protein required for copy number maintenance of ColE1-related plasmids, was compared with the PIR sequence database. Strong local similarities to the sequence of the E. coli protein tRNA nucleotidyltransferase were found. Since a substrate of the latter protein, tRNA, structurally resembles the RNAs that control ColE1 copy number we believe that we may have identified a region in PcnB that interacts with these RNAs. Consistent with this idea is our observation that PcnB is required for the replication of R1, a plasmid whose replication is also regulated by a small RNA.

Amino Acid Sequence↗
PubMed1990

Methemoglobinemia as a complication of 20% benzocaine spray for endoscopy.

Topical 20% benzocaine (Hurricaine, Beutlich, Inc., Niles, Ill.) spray is frequently used for oral anesthesia before upper endoscopy. Side effects attributed to this agent are exceedingly rare. The author reports one of these rare complications, drug-induced methemoglobinemia, in a patient with methemoglobin reductase deficiency. The mechanisms for the development of methemoglobinemia and its treatment are reviewed.

Adult↗
PubMed1990

Mode-specific effects among three treatments for depression.

In the NIMH Treatment of Depression Collaborative Research Program (TDCRP), 250 depressed outpatients were randomly assigned to interpersonal psychotherapy, cognitive-behavioral therapy, imipramine plus clinical management, or pill placebo plus clinical management treatments. Although all treatments demonstrated significant symptom reduction with few differences in general outcomes, an important question concerned possible effects specific to each treatment. The therapies differ in rationale and procedures, suggesting that mode-specific effects may differ among treatments, each of which was precisely specified, applied appropriately, and shown to be discriminable. Outcome measures were selected for presumed sensitivity to the different treatments. Findings provided only scattered and relatively insubstantial support for mode-specific differences. None of the therapies produced consistent effects on measures related to its theoretical origins.

Adult↗