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Biomedical subjects

D S Robinson

Publications and source records attributed to D S Robinson.

At least 109 records · Page 6Linked to original sources

Cost-effective management of breast cancer.

The 5-year survival of cancer of the breast in socioeconomically disadvantaged women is much too low because treatment is given for late stage disease. A screening mammography program at primary-care facilities for medically underserved women has markedly increased in situ and local stage of disease and decreased distant disease. This has produced an estimated 50% decrease in mortality and a significant decrease in treatment costs. Unacceptable delay from positive mammogram to biopsy and pathologic diagnosis remained, so a one-stop breast center was established to perform breast physical examination, screening mammography, biopsy, and pathologic interpretation at one site on one visit for optimal cost-effectiveness.

Breast Neoplasms↗

Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma.

BACKGROUND: In atopic asthma, activated T helper lymphocytes are present in bronchial-biopsy specimens and bronchoalveolar-lavage (BAL) fluid, and their production of cytokines may be important in the pathogenesis of this disorder. Different patterns of cytokine release are characteristic of certain subgroups of T helper cells, termed TH1 and TH2, the former mediating delayed-type hypersensitivity and the latter mediating IgE synthesis and eosinophilia. The pattern of cytokine production in atopic asthma is unknown. METHODS: We assessed cells obtained by BAL in subjects with mild atopic asthma and in normal control subjects for the expression of messenger RNA (mRNA) for interleukin-2, 3, 4, and 5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon gamma by in situ hybridization with 32P-labeled complementary RNA. Localization of mRNA to BAL T cells was assessed by simultaneous in situ hybridization and immunofluorescence and by in situ hybridization after immunomagnetic enrichment or depletion of T cells. RESULTS: As compared with the control subjects, the subjects with asthma had more BAL cells per 1000 cell that were positive for mRNA for interleukin-2 (P less than 0.05), 3 (P less than 0.01), 4 (P less than 0.001), and 5 (P less than 0.001) and GM-CSF (P less than 0.001). There was no significant difference between the two groups in the number of cells expressing mRNA for interferon gamma. In the subjects with asthma, mRNA for interleukin-4 and 5 was expressed predominantly by T lymphocytes. CONCLUSIONS: Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.

Adult↗

Axillary node dissection for early breast cancer: some is good, but all is better.

Optimal management of the axillary lymphatics in breast cancer patients remains a contentious subject. Axillary recurrence, while infrequent, may have very significant clinical consequences in the affected patient. Axillary sampling, partial and total axillary lymphadenectomy, radiotherapy, and surgery plus radiotherapy are discussed with attention to efficacy in prevention of axillary recurrence, accuracy of nodal staging, and morbidity. The incidence of axillary recurrence decreases and accuracy of staging increases with the number of lymph nodes resected. There is little difference in incidence of morbidity between partial and total axillary lymphadenectomy. Radiotherapy is not as effective as lymphadenectomy for regional disease control and, when administered following a surgical staging procedure, increases the risk of lymphedema of the ipsilateral upper extremity and, in patients undergoing breast-conserving surgery, the ipsilateral breast. We believe that total axillary lymphadenectomy provides optimal regional disease control and axillary staging with morbidity comparable to that of partial lymphadenectomy.

Axilla↗

Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma.

We have studied the phenotype and activation status of leukocytes in the bronchial mucosa in patients with isocyanate-induced asthma. Fiberoptic bronchial biopsy specimens were obtained from nine subjects with occupational (five toluene- and four methylene diisocyanate-sensitive) asthma, 10 subjects with extrinsic asthma, and 12 nonatopic healthy control subjects. Bronchial biopsy specimens were examined by immunohistology with a panel of monoclonal antibodies and the alkaline phosphatase-antialkaline phosphatase method. There was a significant increase in the number of CD25+ cells (interleukin-2 receptor-bearing cells, presumed "activated" T-lymphocytes; p less than 0.01) in isocyanate-induced asthma compared with that of control subjects. There were also significant increases in major basic protein (BMK-13)-positive (p less than 0.02) and EG2-positive (p less than 0.01) cells that represent total and "activated" eosinophil cationic protein-secreting eosinophils, respectively. In agreement with our previous findings, CD25+ (p less than 0.01), BMK-13 (p less than 0.03), and EG2+ (p less than 0.01) cells were also elevated in extrinsic asthma. No significant differences were observed in the numbers of T-lymphocyte phenotypic markers (CD3, CD4, and CD8) between subjects with asthma (isocyanate-induced and extrinsic) and control subjects. Similarly, no significant differences in immunostaining for neutrophil elastase (neutrophils) or CD68 (macrophages) were observed. The results suggest that isocyanate-induced occupational asthma and atopic (extrinsic) asthma have a similar pattern of inflammatory cell infiltrate. The results support the view that T-lymphocyte activation and eosinophil recruitment may be important in asthma of diverse etiology.

Adult↗

Immunohistology of the nasal mucosa following allergen-induced rhinitis. Identification of activated T lymphocytes, eosinophils, and neutrophils.

We have studied the immunohistology of the nasal mucosa in allergen-induced rhinitis. Sixteen grass pollen-sensitive patients were challenged twice by randomly allocated allergen or control solutions applied on filter paper disks to the inferior turbinate. All had immediate nasal responses, but late-phase responses were equivocal and only evident as nostril blockage. When cell counts in the nasal submucosa were compared with control values 24 h after allergen, there were no changes in CD45+ (total leukocytes), CD3+, or CD8+ cells. Significant increases were found in the numbers of CD4+ T-helper cells (p less than 0.05) and CD25+ [interleukin-2 receptor (IL-2R+)] cells (p less than 0.02). Increases in eosinophils (anti-major basic protein, p less than 0.01) and neutrophils (antineutrophil elastase, p less than 0.01) were also observed. There were increases in tissue macrophages and HLA-DR-positive immunostaining and a reduction in mast cells (tryptase positive), but none of these changes was statistically significant. No significant changes in epithelial thickness, cross-sectional area, or integrity were observed. There was a significant correlation between CD4+ and CD25+ cells (r = 0.61, p less than 0.01) but not between macrophages and CD25+ cells (r = 0.18). The changes in the nasal submucosa were not merely a reflection of alterations in circulating cell populations since it was shown that a significant increase in the lymphocyte CD4/CD8 ratio (p less than 0.05) was observed in nasal biopsies but not in peripheral blood after allergen challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness.

Using immunohistochemistry and a panel of monoclonal antibodies, we have compared T-lymphocyte, eosinophil, macrophage, and neutrophil infiltration in bronchial biopsies from 10 intrinsic (nonallergic) asthmatics (IA) and seven extrinsic (allergic) asthmatic (EA), with similar degrees of disease severity. The results were compared with 12 normal healthy nonatopic controls (NC). All subjects were nonsmokers and were not taking oral or inhaled corticosteroids. An intense mononuclear cell infiltrate was identified in IA with an increase in the number of CD45+ cells (total leukocytes), CD3+ and CD4+ lymphocytes, and CD68+ macrophages (p < 0.03, p < 0.01, p < 0.03, and p < 0.03, respectively), compared with NC. Increases were also found in CD4+ (p < 0.05) and CD68+ (p < 0.05) cell numbers between IA and EA. IL-2 receptor-bearing cells (CD25+) and the number of total (MBP+) and actively secreting (EG2+) eosinophils, were also increased in IA compared with NC (p < 0.01, p < 0.01, and p < 0.01, respectively). Similar increases in EG2+ eosinophils and CD25+ (IL-2 receptor-positive) cells were observed in EA (p < 0.01 and p < 0.02, respectively). No differences were detected in the three groups for the number of elastase-positive cells (neutrophils). EG2+ numbers in IA correlated with the Aas asthma symptoms score (r = 0.65, p < 0.05), whereas EG2+ cell numbers in all asthmatics (IA + EA) correlated with airway methacholine responsiveness (r = -0.55, p < 0.03) and with the Aas asthma symptom score (r = 0.54, p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of mastectomy versus lumpectomy on emotional adjustment to breast cancer: a prospective study of the first year postsurgery.

PURPOSE: Procedure (mastectomy v lumpectomy) and choice of procedure were examined as predictors of adjustment to breast cancer in a prospective study of the experiences of the first year after surgery. PATIENTS AND METHODS: Breast cancer patients were interviewed the day before surgery, 10 days after surgery, and at the 3-month, 6-month, and 12-month follow-ups. Patients included 24 women who received mastectomy on strong recommendation, 24 who chose mastectomy for other reasons, and 15 who chose lumpectomy. Subjective well-being was assessed in terms of mood disturbance, perceived quality of life, life satisfaction, marital satisfaction, perceptions of social support, and self-rated adjustment. RESULTS: Surgical groups differed in well-being in only one respect: lumpectomy patients reported a higher-quality sex life at 6 and 12 months postsurgery than mastectomy patients. Choice of surgical procedure predicted higher levels of life satisfaction at 3 months. CONCLUSION: The lack of difference between surgical groups in areas other than sexual adjustment replicates previous findings, but extends them by (1) using a fully prospective design, (2) providing data on the period surrounding the surgery (as well as later periods), and (3) examining a broader range of indices of well-being than usual.

Adaptation, Psychological↗

Co-expression of CD25 and CD3 in atopic allergy and asthma.

In an attempt to identify the phenotype of the CD25+ cells previously demonstrated in late-phase allergic reactions in skin and nasal mucosa, and in the bronchial mucosa in atopic asthma we have investigated the co-expression of CD3 and CD25 using double immunofluorescent staining. Fluorescein isothiocyanate (FITC) conjugated anti-CD3 monoclonal antibody and a biotinylated anti-CD25 monoclonal antibody (which was later developed with Texas Red streptavidin) were applied simultaneously to cryostat sections or cytospins of freshly prepared samples. Skin and nasal biopsies were from antigen-induced late-phase reactions, and bronchial biopsies and cytospins of bronchoalveolar lavage cells were from subjects with moderate atopic asthma. Four to 14% of CD3+ cells in these tissues were CD25+ and 61-100% of CD25+ cells also expressed CD3. However, CD25 was also expressed on non-CD3+ cells, assumed to be non-T cells. These results were comparable to that observed with a positive control of a tuberculin-challenged skin biopsy. Thus the majority of cells expressing CD25 in various types of atopic allergic inflammation in man were T lymphocytes.

Antigens, CD↗

Total axillary lymphadenectomy in the management of breast cancer.

The optimal extent of axillary dissection in patients with breast cancer remains unclear. We report 278 total axillary lymphadenectomies (levels I, II, and III and Rotter's [interpectoral] nodes) that were performed in 264 closely followed up private patients. There have been no axillary recurrences to date (mean follow-up, 50 months). If only level I and II nodes had been removed, the false-negative staging error would have been only 2.6%. However, 29 (31.5%) of 92 pathological node-positive axillae contained apical and/or Rotter's metastases. The incidence of complications was comparable with that reported for partial lymphadenectomy. Arm lymphedema developed in 6% of nonirradiated patients; postoperative radiotherapy and gross nodal disease were significant risk factors for lymphedema. Total axillary lymphadenectomy largely prevents axillary, recurrence, eliminates the small staging error inherent in partial lymphadenectomy, and has acceptable morbidity, provided radiotherapy to the regional nodal areas is avoided.

Adult↗

TNF alpha mRNA expression in allergic inflammation.

Using the technique of in situ hybridization, we have attempted to identify messenger RNA for tumour necrosis factor-alpha (TNF alpha) in cells infiltrating allergen-induced late phase reaction (LPR) of the skin and the nose of atopic subjects. We have also compared the number of TNF alpha mRNA positive cells in bronchoalveolar lavage (BAL) from atopic asthmatics and normal controls. Twenty-four hours after local allergen challenge, 12/14 skin biopsies and 9/10 nasal biopsies had positive hybridization signals for TNF alpha mRNA whereas only 4/14 and 2/10 biopsies were positive in the relevant diluent controls. Compared with diluent sites significantly increased numbers of cells expressing mRNA for TNF alpha were observed in the LPR of skin (P less than 0.004) and nose (P less than 0.006). All BAL from asthmatics (n = 10) and from normal volunteers (n = 10) had cells showing positive hybridization signals for TNF alpha mRNA but these were at increased frequency in asthmatics (P less than 0.001). These results suggest that TNF alpha may be an important cytokine in atopic allergic inflammation.

Adolescent↗

Diagnostic value of lung clearance of 99mTc DTPA compared with other non-invasive investigations in Pneumocystis carinii pneumonia in AIDS.

Various non-invasive investigations were carried out in patients infected with HIV who had respiratory symptoms with and without pneumocystis pneumonia (with pneumonia, n = 13 (five smokers); without pneumonia, n = 22 (13 smokers]. These included chest radiography; lung function tests (forced expiratory volume in one second, forced vital capacity; transfer factor and coefficient for carbon monoxide); arterial blood gas tensions; arterial oxygen saturation at rest and on exercise; and lung clearance of diethylenetriaminepenta-acetic acid labelled with technetium-99m (99mTc DTPA). The effect of scan time (seven v 45 minutes from peak counts) and subtraction of background counts were examined. There were no significant differences between the two groups in lung function tests or arterial blood gas tensions at rest. The median clearance half time of inhaled 99mTc DTPA for the first seven minutes from peak counts was 7.2 minutes for patients with pneumocystis pneumonia and 22 minutes for those without. The median arterial oxygen desaturation on exercise was 5% in patients with pneumocystis pneumonia and 2% in those without. 99mTc DTPA lung clearance was better than the other non-invasive tests in discriminating pneumocystis pneumonia from other pulmonary disorders in patients positive for HIV. A short scan time of seven minutes was as sensitive and specific as the longer scan time of 45 minutes, and this allows the clearance of 99mTc DTPA to become a rapid screening test.

Adult↗

Comparison of coronary angiographic features and oral dipyridamole thallium 201 tomography.

Coronary angiography and left ventriculography is commonly used to identify those patients with incomplete infarctions and therefore, a need for revascularization. The authors compared coronary angiography and left ventriculography with thallium 201 tomography using oral dipyridamole to identify patients with potential ischemia in the infarct zone indicating viable tissue. Forty-five patients (37 men, 8 women) with acute myocardial infarctions (29 anterior, 16 inferior) who received intravenous thrombolytic therapy were studied. On the basis of the left ventriculograms, only 16 patients were judged to have residual function in the infarct zone. Six of these patients had no thallium redistribution in the infarct zone, indicating lack of residual ischemia. Of the 29 patients with no residual function in the infarct zone, 18 had redistribution in the infarct zone, suggesting residual ischemic myocardium and thus viable tissue. Among the 32 patients with open infarct vessels, 15 had no redistribution in the infarct zone, but of the remaining 13 patients with occluded infarct vessels, 9 had redistribution in the infarct zone indicating residual ischemia and thus viable tissue. The authors' data suggest that neither wall motion analysis by left ventriculography nor the angiographic status of the infarct vessel identifies those patients with residual ischemia as evidenced by thallium tomography using oral dipyridamole.

Adult↗

Continuation and maintenance treatment of major depression with the monoamine oxidase inhibitor phenelzine: a double-blind placebo-controlled discontinuation study.

Long-term treatment with antidepressant drugs has received little attention until recently. A study is reported comparing the effectiveness of maintenance treatment with phenelzine in responding major depression patients. If they responded initially to nonblind phenelzine treatment and sustained remission for 16 weeks, patients were randomized to 2-year double-blind treatment with phenelzine 60 mg/day, phenelzine 45 mg/day, or placebo. Both doses of phenelzine were significantly better than placebo in preventing relapse of depression. Phenelzine 45 mg/day may be an optimal maintenance dose for many patients.

Adult↗

The preferential uptake of very-low-density lipoprotein cholesteryl ester by rat liver in vivo.

The removal from the blood and the uptake by the liver of injected very-low-density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time.

Animals↗

Segmental mastectomy without radiotherapy for T1 and small T2 breast carcinomas.

We describe 111 patients with invasive breast cancer treated by segmental mastectomy at the University of Miami (Fla) since 1975. Postoperative adjuvant radiotherapy was recommended as optional rather than mandatory to 64 of these patients based on small (2.5 cm or less) primary tumor size, adequate resection margins, no lymphatic or vascular invasion within the segmental mastectomy specimen, and minimal associated in situ cancer. Fifty-one of these patients elected to forego postoperative adjuvant radiotherapy. At 72 months median follow-up, relapse occurred in the ipsilateral breast in three patients who elected to forego postoperative adjuvant radiotherapy (6% by Kaplan-Meier analysis). Retrospective pathologic review revealed that tumor grade may also be important in determining whether postoperative adjuvant radiotherapy is necessary following segmental mastectomy. These data suggest that postoperative adjuvant radiotherapy may not be required in every patient treated by segmental mastectomy. Further studies to define which patients can be spared the inconvenience, expense, and potential morbidity of postoperative adjuvant radiotherapy are warranted.

Adenocarcinoma↗

A double-blind comparison of buspirone, clobazam, and placebo in patients with anxiety treated in a general practice setting.

Sixty patients being treated for anxiety in a primary care facility received (double-blind) buspirone, the benzodiazepine drug clobazam, or placebo for 3 weeks. The mean daily dose at the end of treatment was 23 mg for buspirone and 21 mg for clobazam. Patients were assessed weekly using the Hamilton Rating Scale for Anxiety and Clinical Global Impression scale. Both active treatments produced significant improvement in anxiety symptoms compared with placebo as early as the first week of treatment, and there was progressive improvement over the subsequent 2 weeks. Response to buspirone was equally favorable in anxious patients who experienced depressive symptomatology.

Adult↗

Buspirone therapy in anxious elderly patients: a controlled clinical trial.

Forty patients over 65 years of age with anxiety symptoms due to an anxiety state (N = 20) or secondary to neurotic depression (N = 20) took part in a double-blind, placebo-controlled trial conducted in a primary care practice. All patients were receiving concomitant drug therapy for chronic medical conditions; 70% were receiving two or more nonpsychotropic drugs in addition to the study medication. Patients were randomly assigned to treatment with buspirone 5-30 mg/day or placebo for 4 weeks, with clinical evaluations made weekly. One buspirone-treated and two placebo-treated patients discontinued treatment after 2 weeks because of lack of efficacy. Buspirone treatment resulted in significantly greater (p less than or equal to 0.05) improvement on the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinical Global Impression assessment than did placebo. Mild adverse experiences were reported by five buspirone-treated and nine placebo-treated patients. Buspirone (mean dose, 18 mg/day) proved equally effective for elderly patients suffering anxiety states or neurotic depression at doses similar to those used in younger patients, and was well tolerated by elderly patients receiving treatment for other chronic medical conditions.

Aged↗