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Biomedical subjects

W Harrison

Publications and source records attributed to W Harrison.

At least 37 records · Page 2Linked to original sources
PubMed1998

Correlation of high-frequency ultrasound backscatter with tumor microstructure in iris melanoma.

OBJECTIVE: This study aimed to correlate histologic characteristics with high-frequency ultrasound backscatter spectra in malignant melanomas of the iris. DESIGN: The study design was a cohort (case series) study of patients diagnosed with iris melanoma in the authors' clinic. PARTICIPANTS: Sixteen patients with iris melanoma participated. INTERVENTION: The patients were scanned with a 50-MHz ultrasound unit equipped for digitization of raw echo data. Spectral parameter images representing the spatial distribution of size and concentration of tissue inhomogeneities were produced. MAIN OUTCOME MEASURES: The variation of spectral properties within and between tumors was determined. In the two tumors in this series for which histologic material was available, the authors compared scatterer concentration and size with histology and mathematically modeled the effect of melanocyte distribution on spectra. RESULTS: Ultrasound scattering characteristics differed considerably among tumors. Where histology was available, acoustic parameters correlated with the size and number of melanocytes present. CONCLUSIONS: Iris melanomas exhibited a wide range in acoustic backscatter properties. Whereas characteristics such as vascularity and necrosis might contribute to this, in the two cases examined here, backscatter characteristics could be largely accounted for by melanocyte distribution. A better understanding of the relationship of histology to noninvasive ultrasound data will enhance the diagnostic utility of this technique.

Adult↗
PubMed1998

Inversin, a novel gene in the vertebrate left-right axis pathway, is partially deleted in the inv mouse.

Visceral left-right asymmetry occurs in all vertebrates, but the inversion of embryo turning (inv) mouse, which resulted following a random transgene insertion, is the only model in which these asymmetries are consistently reversed. We report positional cloning of the gene underlying this recessive phenotype. Although transgene insertion was accompanied by neighbouring deletion and duplication events, our YAC phenotype rescue studies indicate that the mutant phenotype results from the deletion. After extensively characterizing the 47-kb deleted region and flanking sequences from the wild-type mouse genome, we found evidence for only one gene sequence in the deleted region. We determined the full-length 5.5-kb cDNA sequence and identified 16 exons, of which exons 3-11 were eliminated by the deletion, causing a frameshift. The novel gene specifies a 1062-aa product with tandem ankyrin-like repeat sequences. Characterization of complementing and non-complementing YAC transgenic families revealed that correction of the inv mutant phenotype was concordant with integration and intact expression of this novel gene, which we have named inversin (Invs).

Amino Acid Sequence↗
PubMed1997

Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group.

CONTEXT: Premenstrual dysphoric disorder is an important cause of symptoms and functional impairment in menstruating women. OBJECTIVE: To evaluate the efficacy of sertraline hydrochloride for treatment of premenstrual dysphoria by measuring changes in symptom expression and functional impairment. DESIGN: Two screening cycles followed by 1 single-blind placebo cycle and 3 cycles of randomized, double-blind, placebo treatment. SETTING: Twelve university-affiliated outpatient psychiatry and gynecology clinics. PATIENTS: Of the 447 women who requested participation, 243 met criteria for premenstrual dysphoric disorder and were randomized; 200 women completed the study. INTERVENTION: A flexible (50-150 mg) daily dose of sertraline hydrochloride. MAIN OUTCOME MEASURES: The Daily Record of Severity of Problems, Hamilton Rating Scale for Depression, Clinical Global Impression Scale, and Social Adjustment Scale. RESULTS: Mean (+/-SD) total daily symptom scores decreased significantly (P<.001) in the sertraline-treated (64+/-22 to 44+/-19) compared with the placebo-treated (62+/-22 to 54+/-24) groups. Significant improvement (P<.05) was found for all clinically derived symptom clusters (depressive, physical, and anger/irritability symptoms). Hamilton Rating Scale for Depression scores decreased by 44% and 29% in the sertraline and placebo groups, respectively (P<.002). End-point global ratings showed much or very much improvement in 62% of the active treatment group and 34% of the placebo treatment group (P<.001). Reported functional impairment was substantial at baseline. Improvement in psychosocial functioning with treatment was similar to what is found in studies of major depression. CONCLUSIONS: Sertraline was significantly better than placebo for treatment of premenstrual dysphoria as reflected by symptomatic improvement and change in reported functional impairment. Serotonin reuptake inhibitors such as sertraline are useful therapeutic options for women with premenstrual dysphoria.

1-Naphthylamine↗
PubMed1997

Treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis with intravitreal vancomycin and intravitreal dexamethasone.

The use of intravitreal steroids to treat bacterial endophthalmitis remains controversial. The efficacy of intravitreal vancomycin alone (group 1), intravitreal dexamethasone alone (group 2), and a combination of intravitreal vancomycin and dexamethasone (group 3) in the treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis was evaluated in a rabbit model: 24 h after bacterial inoculation of all eyes, right eyes were treated and left eyes served as infected controls. Vitreal aspirations and grading of vitreal inflammatory reaction were done regularly until sacrifice. Group 2 eyes demonstrated more inflammation histologically than control eyes. Vitreal aspirations demonstrated no growth by 5 days from groups 1 and 3 eyes. Although the clinical appearance was not significantly different between groups 1 and 3, the histologic appearance of group 3 eyes showed less intense intraocular inflammation. Treatment with dexamethasone in the absence of appropriate antibiotics was more harmful than no treatment at all (P < .05). Therapy with both intravitreal vancomycin and dexamethasone results in less inflammation than intravitreal vancomycin alone in this model.

Animals↗
PubMed1997

Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers.

In vitro studies have shown that fluoxetine and paroxetine are more potent inhibitors of cytochrome CYP2D6 than sertraline. The pharmacokinetics of desipramine when coadministered with the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline were studied in 24 healthy male volunteers (CYP2D6 extensive metabolizers). Desipramine (50 mg/day) was administered for 23 days in each phase of the crossover study with a 7-day drug-free period between phases. In addition, subjects were randomly assigned to receive concomitant paroxetine (20 mg/day on days 8 through 17 followed by 30 mg/day on days 18 through 20) or sertraline (50 mg/day on days 8 through 17 and 100 mg/day on days 18 through 20). SSRI treatments were switched between phases. After 10 days of coadministration at the lower dose, mean desipramine maximum concentration in plasma (Cmax) relative to baseline increased from 37.8 to 173 ng/mL (+358%) with paroxetine versus from 36.1 to 51.9 ng/mL (+44%) with sertraline; the mean desipramine 24-hour area under the concentration-time curve (AUC[24]) increased from 634 to 3,305 ng x h/mL (+421%) with paroxetine versus from 611 to 838 ng x h/mL (+37%) with sertraline; and the mean desipramine trough value (C0) increased from 18.5 to 113 ng/mL (+511%) with paroxetine versus from 18.3 to 21.8 ng/mL (+19%) with sertraline (all increases, p < 0.001). An approximately 10-fold increase in the Cmax and AUC(24) of paroxetine and an approximately 2-fold increase in these parameters for sertraline occurred simultaneously with the desipramine concentration changes. Thus, when coadministered with 50 mg/day desipramine, sertraline had significantly less pharmacokinetic interaction than paroxetine with desipramine at the recommended starting dosages of 50 mg/day and 20 mg/day, respectively.

1-Naphthylamine↗
PubMed1997

Intravascular papillary endothelial hyperplasia: collection of four cases and a review of the literature.

Intravascular papillary endothelial hyperplasia is a benign tumor that rarely presents in the orbit and ocular adnexa. Generally, it occurs as an isolated eyelid mass, not associated with systemic or local disease. Histopathologically, it can be easily confused with angiosarcoma or Kimura's disease. We present our experience with four cases of this tumor in the ocular adnexa, along with a literature review.

Adult↗
PubMed1996

A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia.

BACKGROUND: Despite the high prevalence of dysthymia and its associated morbidity, few controlled trials have evaluated the efficacy of antidepressant medication for this disorder. A 12-week, double-blind, placebo-controlled, randomized, multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia. METHODS: A total of 416 outpatients (271 women and 145 men) aged 25 to 65 years with DSM-III-R-defined, early-onset, primary dysthymia without concurrent major depression were randomized to 12 weeks of treatment with sertraline, imipramine, or placebo. RESULTS: Both active treatments resulted in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression (P = .04 and P = .01 for sertraline and imipramine vs placebo, respectively), the Montgomery-Asberg Depression Rating Scale (P = .01 and P = .003 vs placebo, respectively), Hopkins Symptom Checklist (P < .05), and the self-rated version of the Inventory of Depressive Symptoms (P < .05). With the use of a Clinical Global impressions improvement score of 1 or 2 (very much or much improved) to define response, response rates were 59% for sertraline, 64% for imipramine, and 44% for placebo (P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo). A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events (P = .001 and P < .001, respectively). CONCLUSIONS: Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder, with both sertraline and imipramine being more effective than placebo. The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication.

1-Naphthylamine↗
PubMed1996

Itraconazole in the treatment of orbital aspergillosis.

BACKGROUND: Sino-orbital aspergillosis is typically treated with surgical debridement and intravenous amphotericin B. Some authors have advocated intraorbital irrigation or injection of amphotericin B in specific cases. METHODS: An immunocompetent patient with recurrent sino-orbital aspergillosis is presented. After failing two attempts at traditional therapeutic modalities, treatment with oral itraconazole was initiated. RESULTS: The patient has had resolution of her sino-orbital disease without recurrence at 10 months of follow-up. CONCLUSION: In immunocompetent patients with orbital aspergillosis, itraconazole should be considered as a treatment option in patients who have recurrent or recalcitrant disease, or in those who cannot tolerate amphotericin B.

Administration, Oral↗
PubMed1996

Clinical and computed tomographic characteristics of amyloid tumor of the lacrimal gland.

BACKGROUND: Lacrimal gland masses, whose soft-tissue contour analysis, on computed tomographic (CT) scanning, shows molding to surrounding orbital structures, include inflammatory and lymphoproliferative lesions. The authors present a patient with orbital amyloidosis isolated to the lacrimal gland who also demonstrates this specific CT presentation. In addition, the literature on this rare condition is reviewed, and characterization of the typical presentation is provided. METHODS: A retrospective review of the four previously reported patients and the authors' additional patient with amyloid tumor of the lacrimal gland was performed. A summary of the clinical characteristics of the disorder was formulated. Special attention was given to to the unique CT findings of the authors' patient. RESULTS: Five patients with amyloid tumor of the lacrimal gland have been described. All patients have been women, with average age of 53 years, and who had the primary, localized variant of the disease. Neither visual impairment nor evidence of optic nerve dysfunction has developed in any of the patients. In the authors' patient, the CT soft-tissue contour analysis of the lacrimal gland mass demonstrated molding to adjacent orbital tissues. CONCLUSIONS: Amyloidosis of the lacrimal gland presents as a primary, localized disease process. It typically affects middle-aged women without visual morbidity. The early CT findings may mimic those seen in inflammatory or lymphoproliferative disorders of the lacrimal gland.

Aged↗
PubMed1996

Mucinous eccrine carcinoma of the eyelid.

A 78-year-old woman with recurrent chalazia of the upper eyelid was found to have mucinous eccrine carcinoma. This rare pathologic entity, with low metastatic potential, nevertheless has a significant recurrence rate. This case underscores the importance of considering this tumor in recalcitrant eyelid lesions and highlights the pathology of this tumor. A summary of previous cases is also presented.

Adenocarcinoma, Mucinous↗
PubMed1995

Treatment of chronic depression with sertraline or imipramine: preliminary blinded response rates and high rates of undertreatment in the community.

Despite the prevalence of chronic depression and its associated morbidity, there has been little systematic study of pharmacotherapy for this disorder. In this article, we report a preliminary analysis of the first 12-week phase of a multicenter clinical trial that will eventually include approximately 635 patients in acute, continuation, crossover, and maintenance studies of sertraline, a selective serotonin reuptake inhibitor (SSRI), and imipramine, a tricyclic antidepressant, for the treatment of chronic depression. Of the first 212 patients to enter the study, 168 completed all 12 weeks; of these, 61.3 percent were responders, including 58.9 percent of the 73 patients with chronic major depression and 63.2 percent of the 95 patients with double depression. Only 26.8 percent of the 198 patients for whom such data were available had ever had an adequate trial of an antidepressant medication, defined as 150 mg/day of imipramine or its equivalent taken for at least 4 consecutive weeks. In general, demographic and diagnostic characteristics were more similar than different for patients with chronic major and double depression. However, comorbid generalized anxiety disorder was significantly more common in patients with chronic major depression (11.2% threshold for chronic versus 4.9% threshold for double depression, p = .02). The results of this study provide preliminary evidence of the responsiveness of patients with chronic major or double depression to an SSRI or a tricyclic antidepressant.

1-Naphthylamine↗
PubMed1995

Are patients who are intolerant to one serotonin selective reuptake inhibitor intolerant to another?

BACKGROUND: The question was asked whether patients who discontinue one serotonin selective reuptake inhibitor (SSRI) because of side effects can be treated successfully with another SSRI. METHOD: 113 patients with major depression who had discontinued fluoxetine because of side effects were enrolled in an open, multicenter, 8-week study designed to evaluate the tolerability and efficacy 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 of sertraline once daily. Doses were titrated upward as necessary to a maximum daily dose of 200 mg. Depressive symptoms and adverse events were evaluated weekly. RESULTS: Based on the Clinical Global Impressions Scale, 79 (71.8%) of 110 patients evaluated for efficacy were "much" or "very much" improved relative to baseline. Only 11 (9.8%) of 112 patients discontinued sertraline because of adverse reactions. CONCLUSION: These results suggest that patients who discontinue one SSRI because of side effects can be treated successfully with another.

1-Naphthylamine↗
PubMed1994

Molecular cytogenetic determination of a deletion/duplication of 1q that results in a trisomy 18 syndrome-like phenotype.

We report on an infant who presented at birth with some characteristics of trisomy 18 syndrome, including low birth weight, facial abnormalities, overlapping fingers, and congenital heart defects. On chromosome analysis, no additional chromosome 18 was observed and both chromosome 18 homologues appeared normal. However, a small piece of chromosomal material of unknown origin was detected at the tip of the long arm of chromosome 1. Fluorescence in situ hybridization (FISH) using whole chromosome 18 painting probes disclosed no additional hybridization at the telomere of 1q, suggesting that the material was derived from another chromosome. Further chromosome painting experiments suggested that the telomeric addition was of chromosome 1 origin. To identify subchromosomal regions involved in the rearrangement, additional FISH analyses were performed using single copy and repetitive DNA probes mapping to different portions of chromosome 1. The analyses showed that probes mapping to 1q34-43 were duplicated in the derivative chromosome 1. In addition, a DNA probe mapping to 1q44 was found to be deleted from the derivative chromosome 1. Our composite analysis suggests that a deletion and a duplication of chromosome 1q can result in some of the clinical findings usually associated with trisomy 18 syndrome. These results demonstrate the usefulness of FISH analysis when karyotype analysis is not consistent with the clinical description.

Abnormalities, Multiple↗
PubMed1994

Conjunctival orbital cyst.

A 61-year-old woman had gradual onset of ptosis and painless proptosis of her left eye of 1-year duration. Orbital computed tomography (CT) showed a well-circumscribed superior nasal orbital tumor with uniform density. The mass was removed by anterior orbitotomy and histopathologically diagnosed as a conjunctival cyst. Recent reports have increased awareness of this entity. This case typifies findings of conjunctival orbital cysts. These cysts should be considered when a differential diagnosis is formulated for orbital tumors with a similar presentation.

Blepharoptosis↗
PubMed1994

Effect of imipramine on mood and enumerative measures of immune status in depressed patients with HIV illness.

OBJECTIVE: The authors' first objective was to ascertain whether imipramine is superior to placebo in treating axis I depressive disorders in the context of HIV illness. Supplementary questions were whether severity of immunodeficiency is associated with antidepressant response and whether patients with greater immunodeficiency can tolerate standard doses of imipramine. Second, the authors sought to determine whether imipramine treatment is associated with changes in immune status. METHOD: A double-blind, randomized placebo-controlled trial of imipramine was conducted in a university-affiliated research outpatient clinic. After 6 weeks of treatment, responders were maintained double-blind for another 6 weeks and nonresponders were removed from the study and treated openly. All patients were offered 26 weeks of treatment. Of the 97 patients who were randomly assigned to placebo or imipramine, 80 completed the 6-week phase. Main outcome measures included the Clinical Global Impression, the Hamilton Depression Rating Scale, the Brief Symptom Inventory, and CD4 cell count. RESULTS: Among study completers, 31 (39%) had AIDS. The response rate to imipramine was 74% and the response rate to placebo was 26%. There was no difference in depression response between patients with more or less severe immunodeficiency, nor was there a difference in medication dose or side effects. Neither type nor duration of treatment influenced CD4 cell count during the course of treatment. CONCLUSIONS: Depressed patients with HIV illness respond to imipramine at the same rate as medically healthy depressed patients. Severity of immunosuppression is not associated with imipramine treatment outcome. There is no evidence that imipramine has negative effects on enumerative measures of immune status.

Adolescent↗
PubMed1994

Molecular mapping of the Edwards syndrome phenotype to two noncontiguous regions on chromosome 18.

In an effort to identify regions on chromosome 18 that may be critical in the appearance of the Edwards syndrome phenotype, we have analyzed six patients with partial duplication of chromosome 18. Four of the patients have duplications involving the distal half of 18q (18q21.1-qter) and are very mildly affected. The remaining two patients have most of 18q (18q12.1-qter) duplicated, are severely affected, and have been diagnosed with Edwards syndrome. We have employed FISH, using DNA probes from a chromosome 18-specific library, for the precise determination of the duplicated material in each of these patients. The clinical features and the extent of the chromosomal duplication in these patients were compared with four previously reported partial trisomy 18 patients, to identify regions of chromosome 18 that may be responsible for certain clinical features of trisomy 18. The comparative analysis confirmed that there is no single region on 18q that is sufficient to produce the trisomy 18 phenotype and identified two regions on 18q that may work in conjunction to produce the Edwards syndrome phenotype. In addition, correlative analysis indicates that duplication of 18q12.3-q22.1 may be associated with more severe mental retardation in trisomy 18 individuals.

Abnormalities, Multiple↗