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Biomedical subjects

W Harrison

Publications and source records attributed to W Harrison.

At least 55 records · Page 3Linked to original sources
PubMed1994

Duration of antidepressant trials: clinical and research implications.

The objective of our study was to demonstrate that additional antidepressant benefit occurs between weeks 4 and 6 in adult outpatients, even when dose is not increased. Response between weeks 4 and 6 was studied among depressed outpatients randomly assigned to imipramine, phenelzine, or placebo under double-blind conditions. Patients were selected for analysis only if they did not have a dose increase after the start of the fourth week of treatment (day 22). Eighty-eight patients met this condition. Conditional probability analysis was performed. Nonresponders to 4 weeks (28 days) of treatment had a significantly greater likelihood of responding by week 6 if they were on phenelzine rather than placebo. The same is probably true for patients on imipramine. In research and clinical care, 4 weeks is too short a trial of phenelzine to conclude a lack of efficacy. Four weeks is probably also too short a trial of imipramine.

Adult↗
PubMed1994

Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine.

The pharmacokinetic interactions of sertraline and fluoxetine with the tricyclic antidepressant desipramine were studied in 18 healthy male volunteers phenotyped as extensive metabolizers of dextromethorphan. Concentrations in plasma were determined after 7 days of desipramine (50 mg/day) dosing alone, during the 21 days of desipramine and selective serotonin reuptake inhibitor (SSRI) coadministration (fluoxetine, 20 mg/day; sertraline, 50 mg/day), and for 21 days of continued desipramine administration after SSRI discontinuation. Desipramine Cmax was increased 4.0-fold versus 31% and AUC0-24 was increased 4.8-fold versus 23% for fluoxetine versus sertraline, respectively, relative to baseline after 3 weeks of coadministration. Desipramine trough concentrations approached baseline within 1 week of sertraline discontinuation but remained elevated for the 3-week follow-up period after fluoxetine discontinuation. Concentrations of SSRIs and their metabolites correlated significantly with desipramine concentration changes (for fluoxetine/norfluoxetine, r = 0.94 to 0.96; p < 0.001; for sertraline/desmethylsertraline, r = 0.63; p < 0.01). Thus, sertraline had less pharmacokinetic interaction with desipramine than did fluoxetine at their respective, minimum, usually effective doses.

1-Naphthylamine↗
PubMed1994

Interstitial deletions are not the main mechanism leading to 18q deletions.

Most patients who present with the 18q- syndrome have an apparent terminal deletion of the long arm of chromosome 18. For precise phenotypic mapping of this syndrome, it is important to determine whether the deletions are terminal deletions or interstitial deletions. A human telomeric YAC clone has been identified that hybridizes specifically to the telomeric end of 18q. This clone was characterized and used to analyze seven patients with 18q deletions. By FISH and Southern blotting analysis, all patients were found to lack this chromosomal region on their deleted chromosome, demonstrating that the patients do not have cryptic interstitial deletions.

Base Sequence↗
PubMed1993

Sodium lactate infusion in late luteal phase dysphoric disorder.

The effects of sodium lactate infusion were compared in 13 women who sought treatment for marked premenstrual dysphoric changes that met criteria for late luteal phase dysphoric disorder and 7 control women. No subject had a lifetime history of panic disorder. The rate of blindly rated panic to sodium lactate was 7 (58%) in patients and 0% in controls. Nonpanicking patients also had higher Modified Acute Panic Inventory scores than control subjects. The differences cannot be fully explained on the basis of a history of panic attacks. Further study is warranted.

Adult↗
PubMed1993

Myositis ossificans masquerading as a recurrent spindle cell lipoma of the orbit.

A spindle cell lipoma developed in the right orbit of a 43-year-old woman whose medical history was only significant for chronic asthma. Sixteen months after nearly complete excision of the tumor, the patient presented with eyelid swelling, orbital pain, and a calcified apical mass as demonstrated by computerized tomography (CT). Recurrent tumor or a second neoplasm was suspected. Histologic examination revealed myositis ossificans. To our knowledge, this is the first reported case of myositis ossificans in the orbit.

Adult↗
PubMed1993

Confirmation of isochromosome 18p using whole chromosome arm-specific fluorescence in situ hybridization.

Fluorescent in situ hybridization (FISH) using a pool of DNA clones that have been mapped to the short arm of chromosome 18 is described. This arm-specific painting technique was used to analyze the chromosomes of two patients who displayed different clinical pictures. One patient had clinical features consistent with tetrasomy 18p, and the other patient had some of the clinical features associated with trisomy 18. The initial karyotype of both patients showed the presence of a small metacentric marker chromosome, thought to resemble an iso(18p). This interpretation of the karyotype was confirmed for both cases using a specific chromosome arm-painting strategy. While whole-chromosome paints may identify the origin of markers or detect translocations, arm-specific libraries will permit detailed analysis of chromosomal rearrangements when more precise information may be needed.

Adolescent↗
PubMed1993

Imipramine treatment of alcoholism with comorbid depression.

Of 60 depressed alcoholics who completed an open trial of imipramine, 27 (45%) responded with improvement in both mood and drinking behavior, and eight (13%) responded after further dosage increases or treatment with disulfiram. In a subsequent 6-month, randomized discontinuation trial, four of 13 subjects (31%) relapsed during imipramine treatment and seven of 10 (70%) relapsed while taking placebo. This suggests a potential treatment approach for a high-risk subgroup of alcoholics.

Adult↗
PubMed1993

Chronic depression: response to placebo, imipramine, and phenelzine.

We reanalyzed data from a larger, previously published study in order to directly address whether very chronically depressed patients could benefit from antidepressant medications. This study entered 598 depressed patients into a study randomizing patients to 6 weeks of double-blind treatment with imipramine, phenelzine, or placebo. Patients were assessed for chronicity on a four-point scale from "mostly well" to "virtually always depressed." The current analyses include only the 153 study completers who were rated as "virtually always depressed." In these patients, imipramine was effective for significantly more patients than was placebo (22 [46%] of 48 responding to imipramine vs. 9 [17%] of 52 responding to placebo; chi 2 = 9.50; p = 0.002), whereas phenelzine was significantly more effective than imipramine (37 [70%] of 53 responding to phenelzine; chi 2 = 5.96; p = .015). Patients with mild depression, early onset, or histories of panic attacks did not have substantially different outcomes than patients without these characteristics. These findings suggest that some chronically depressed patients may be good candidates for treatment with antidepressant medication. Because the majority (80%) of the sample met Columbia criteria for definite or probable atypical depression, too few chronic depressives were available to evaluate separately antidepressant efficacy in chronically depressed outpatients who did not have atypical depression. Hence, these results may be applicable only to patients with atypical depression.

Adult↗
PubMed1993

Columbia atypical depression. A subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo.

We summarise a series of studies using a MAOI to help establish the validity of a subgroup of depressives referred to as atypical depressives. Patients with reactive mood meeting DSM-III criteria for depressive illness who had associated atypical features (which include hyperphagia, hypersomnolence, leaden paralysis, and rejection sensitivity) were randomised to imipramine, phenelzine and placebo. Non-responders were crossed over, and in all there were over 400 patient trials. Phenelzine consistently was found to be superior to imipramine. Only in trials which included patients lacking atypical, vegetative symptoms was imipramine found to equal phenelzine. We conclude that the researcher and the clinician should consider the relevance of the atypical depressive syndrome.

Antidepressive Agents, Tricyclic↗
PubMed1993

Clinical and molecular evaluation of four patients with partial duplications of the long arm of chromosome 18.

Four individuals with partial duplications of the long arm of chromosome 18 were analyzed at the clinical, cytogenetic, and molecular levels. Two of the individuals had duplications of the long arm from 18q21.1-qter because of inheritance of an unbalanced translocation. Both of these individuals displayed the clinical phenotype characteristic of Edwards syndrome. Two other patients had de novo interstitial duplications of 18q but did not have a clinical diagnosis of Edwards syndrome. The extent of the duplicated material in each patient was determined initially by using cytogenetic analysis and subsequently with more detailed comparisons of the duplicated regions by using molecular probes derived from a chromosome 18-specific lambda phage library. The results demonstrated that one of the de novo interstitial duplications that did not result in the Edwards syndrome phenotype had a more proximal breakpoint than that of the partial duplications of the two patients with features of Edwards syndrome. These results suggest that a single critical region for Edwards syndrome in the proximal portion of 18q is unlikely.

Adolescent↗
PubMed1993

Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure.

The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is a self-report measure designed to enable investigators to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by subjects in various areas of daily functioning. The summary scores were found to be reliable and valid measures of these dimensions in a group of depressed outpatients. The Q-LES-Q measures were related to, but not redundant with, measures of overall severity of illness or severity of depression within this sample. These findings suggest that the Q-LES-Q measures may be sensitive to important differences among depressed patients that are not detected by the measures usually employed.

Adolescent↗
PubMed1992

Are patients who are intolerant to one SSRI intolerant to another?

One hundred patients with major depression who had discontinued fluoxetine because of side effects were enrolled in a multicenter, open, 8-week study of sertraline. After a washout period of at least 3 weeks following fluoxetine discontinuation and an additional 1-week, single-blind, placebo washout period, patients began treatment with 50 mg sertraline once daily. Based on the clinician's judgment of patient response, doses were titrated upward if necessary. The maximum daily dose of sertraline was 200 mg. Depressive symptoms and adverse events were assessed weekly. An interim analysis was conducted of the first 93 patients who completed the study. Of 91 evaluable patients, 69 sertraline-treated patients (75.8%) experienced significant improvement in depression. Only 8 of 93 patients (8.6%) discontinued sertraline because of side effects.

1-Naphthylamine↗
PubMed1991

The ultrastructural defect in conjunctiva from a case of recessive dystrophic epidermolysis bullosa.

The predominant feature in the several forms of epidermolysis bullosa is the formation of cutaneous bullous lesions arising after minimal mechanical trauma. Ocular involvement has been noted as a complication. To our knowledge to date, only four investigators have correlated clinical eye disease with light microscopic findings. Ultrastructure of the ocular lesions has not been described previously. We present four cases of recessive dystrophic epidermolysis bullosa emphasizing their associated ocular complications. Diagnosis was confirmed by skin biopsy specimen and in one patient by demonstrating light and electron microscopic findings in eyelid skin. This tissue exhibited ultrastructural recessive cutaneous lesions; namely, bullous separation occurring below the basal lamina and absence of anchoring fibrils in both bullous and nonbullous areas. By electron microscopy, the conjunctiva in this patient exhibited an absence of clear anchoring fibrils that were numerous in control tissue. This defect may increase the susceptibility of the conjunctiva to minor mechanical trauma, resulting in the bullous and cicatricial changes seen clinically.

Aged↗
PubMed1991

Response to phenelzine and imipramine in placebo nonresponders with atypical depression. A new application of the crossover design.

We employed a study design that permitted a double-blind 12-week contrast of imipramine hydrochloride and phenelzine sulfate therapies in patients who met Columbia University criteria for atypical depression and were unresponsive to 7 weeks of treatment with placebo. These patients were found to benefit selectively from therapy with monoamine oxidase inhibitors compared with tricyclic drug therapy. This supports our observation about treatment response in depressed patients with reversed vegetative features. The design we utilized in this study has not previously been reported, to our knowledge. It was hypothesized that it would offer the advantage of the removal of a portion of placebo responders and serve to replicate our original findings. Treatment response to therapy with both imipramine and pheneizine in placebo nonresponders was uniformly lower (roughly 20% less than corresponding rates for patients who did not participate in the initial 6-week placebo trial). This is consistent with the view that the lower response rates were a result of the removal of some "placebo" responders in the drug groups. We think this is a useful design that should be considered in all studies of placebo and two active treatment regimens.

Adult↗
PubMed1991

Metastatic Merkel cell carcinoma to the eye.

Merkel cell carcinoma is an infrequent but highly aggressive cutaneous neoplasm. Previous reports of ocular involvement have included primary eyelid carcinomas, eyelid and orbital metastases, and a clinically diagnosed choroidal metastasis. The authors report the histopathologic documentation of a metastatic lesion to the ciliary body, confirming the intraocular metastatic potential of this tumor.

Aged↗
PubMed1991

A randomised double-blind trial of cyclosporin and azathioprine in refractory rheumatoid arthritis.

Fifty-two patients with severe rheumatoid arthritis (RA) from four Australian centres were randomised to receive cyclosporin A (CSA) (n = 25) or azathioprine (AZA) (n = 27) for six months. Initial mean doses of CSA and AZA were 4.2 mg/kg and 1.7 mg/kg respectively. The mean doses of CSA and AZA at six months were 3.4 mg/kg and 1.9 mg/kg. Assessments of side-effects and outcomes of benefit were made monthly by independent, blinded observers. Both treatment groups exhibited statistically significant improvement in standard outcome parameters when compared with baseline values. However, there were no statistically significant differences in these parameters between the two groups. There was a mean increase in serum creatinine concentration associated with CSA; no persons were withdrawn from the study for this reason. Seven CSA recipients (three gastrointestinal symptoms, two neurological symptoms, two other) and 12 AZA recipients (six gastrointestinal symptoms, four inefficacy, two other) withdrew from treatment prematurely. Seven CSA recipients became hypertensive and four required anti-hypertensive therapy. Adverse events not requiring cessation of therapy were more commonly seen among CSA patients. In this group of severely affected patients with RA both cyclosporin and azathioprine were effective therapies. CSA toxicities were predictable and manageable but required close monitoring.

Adult↗
PubMed1991

Heterogeneity of clinical response during placebo treatment.

OBJECTIVE: The authors attempted to identify different patterns of improvement among patients receiving placebo during clinical trials. It was hypothesized that patients who improved abruptly would differ from patients whose improvement was gradual in that they would tend to improve earlier and would tend to have less persistent improvement. METHOD: The subjects were 144 patients who met the DSM-III criteria for depressive illness and were randomly assigned to placebo medication in four double-blind antidepressant drug trials. All studies lasted 6 weeks. Mood change was rated each week on a 7-point scale; a rating of 1 or 2 was considered an indication of improvement. Improvement was judged to be abrupt if the first score of 1 or 2 was immediately preceded by a score of 4 or worse, and it was classified as gradual if the first score of 1 or 2 was preceded by a score of 3 in at least 1 week. Improvement was considered persistent if a score of 1 or 2 was not followed by a score of 3 or worse in any subsequent week. RESULTS: Of the 144 patients, 72 showed clinical improvement during at least one weekly visit; 33 improved abruptly and 39 improved gradually. The abrupt improvements occurred significantly earlier in the trial and were less likely to persist than the gradual improvements regardless of when they occurred. CONCLUSIONS: These data suggest that among patients receiving placebo abrupt improvements are a form of placebo response and gradual responses may be the result of spontaneous remission. These preliminary observations require validation.

Adolescent↗