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Biomedical subjects

J Roberts

Publications and source records attributed to J Roberts.

At least 415 records · Page 23Linked to original sources

Gastrointestinal carcinoid tumors.

Fifty-five patients were evaluated and treated for gastrointestinal (GI) carcinoid tumors at our institution from 1968 through 1988. Thirty patients had primary tumors smaller than 1 cm and were treated surgically or endoscopically by local excision, whereas 25 underwent resection with regional lymphadenectomy for larger primaries. At the time of initial treatment 17 patients demonstrated metastasis. Although 13 of these patients had primary tumors larger than 2 cm, in four patients with ileal carcinoids, the primary measured 0.8 to 1.5 cm. Serosal involvement was present in nine of 17 patients with metastasis. With a follow-up range of 3 months to 20 years, six patients have died with metastatic carcinoid tumor, two patients died without evidence of disease, 12 patients are alive with metastasis, and 35 patients are alive, free of disease. In this series three determinants for risk of metastasis in GI carcinoid tumors were evident: primary size, serosal penetration, and primary site in the small intestine. In patients with any of these risk factors, resection with regional lymphadenectomy is recommended.

Adult↗

Response to toremifene (Fc-1157a) therapy in tamoxifen failed patients with breast cancer. Preliminary communication.

Nine patients with measurable lesions of locally advanced or recurrent breast cancer have been treated with toremifene 200 mg daily. A response rate of 33% [complete remission (CR) + partial remission (PR)] or 78% [CR + PR + no change (NC)] has been achieved so far. As all our patients had previously relapsed on anti-oestrogen therapy (tamoxifen), we postulate that our response rate was achieved by a direct oncolytic effect.

Aged↗

Selective inhibition of integrin function by antibodies specific for ligand-occupied receptor conformers.

We have hypothesized that ligand-induced binding sites (LIBS), i.e. sites expressed on cell surface receptors only after ligand binding causes the receptor to change shape, mediate subsequent biological events. To test this hypothesis, we have raised monoclonal antibodies that preferentially react with an integrin (platelet glycoprotein (GP) IIb-IIIa) after it bind Arg-Gly-Asp-containing ligands. The 13 anti-LIBS antibodies obtained define at least three distinct GPIIb-IIIa epitopes; one of these epitopes is also expressed following occupancy of another integrin, the vitronectin receptor. Certain of these LIBSs appear to mediate functions, since the antibodies that define them inhibit GPIIb-IIIa-mediated fibrin clot contraction or platelet adhesion to collagen. Nevertheless, none of the anti-LIBS antibodies inhibit binding of the primary ligand, fibrinogen. These data indicate that LIBS may mediate distinct consequences of receptor occupancy.

Amino Acid Sequence↗

Metastasizing thymoma and myasthenia gravis. Favorable response to glucocorticoids after failed chemotherapy and radiation therapy.

Myasthenia gravis (MG) occurs in up to 44% of patients with thymoma. Thirty-three percent of these neoplasms are invasive but extrathoracic disease is rare. Recently, we saw a patient with MG and recurrent, metastasizing mixed lymphoepithelial thymoma, whose disease was resistant to combination chemotherapy and radiotherapy but who responded dramatically to treatment with daily glucocorticoids. Thus, therapy with daily glucocorticoids should be considered in the treatment of invasive or metastatic thymoma associated with MG, including when conventional surgery, radiotherapy, and chemotherapy have failed.

Drug Administration Schedule↗

Action of potassium on neurochemical transmission at the cardiac adrenergic neuroeffector junction with aging.

The effect of age on potassium (K+)-induced norepinephrine release in the heart was studied in 6- and 24-month-old male Fischer-344 rats. Isolated hearts were perfused with Krebs-Ringer solution according to Langendorff method. K+ was employed as 2 ml bolus at the concentrations, of 70, 90, 100 and 120 microM. Norepinephrine content was measured by high pressure liquid-chromatography/electrochemical detection methodology. At each of the K- concentrations, the amount of norepinephrine released from preparations of 6-month-old animals was significantly greater than observed from preparations of 24-month-old animals. Since K(+)-induced release of norepinephrine is associated with calcium influx, the decrease in the capacity of K+ to cause norepinephrine release with age supports the hyothesis that diminution in transmitter release is due to altered calcium function.

Age Factors↗

Elective--a trip to Toronto.

Electives are an excellent opportunity to observe dentistry in another country. I chose Toronto in Canada, as it has always struck me as a very modern city and I was particularly interested in observing their recent advances in surgical orthodontics, which I find enthralling. I was aware that Toronto had a large, efficient orthodontic department which was invaluable for my project. I am also interested in the treatment of immunocompromised patients and hoped to visit the new AIDS clinic there.

Acquired Immunodeficiency Syndrome↗

Bovine retinal explants cultured in collagen gels. A model system for the study of proliferative retinopathy.

We have developed a model system for studying proliferative retinopathy in vitro using bovine retinal explants cultured in collagen gels. Cellular outgrowth from retinal explants occurred after 7 days as single cells from peripapillary explants or as cell sheets and tubular outgrowths from peripheral retinal explants. Single cell outgrowths were shown immunohistochemically to be endothelial cells or macrophages; sheetlike and tubular outgrowths also constituted cords of endothelial cells with stromal macrophages, but in addition glial cells were closely associated with the endothelial cells. Cellular outgrowths were preceded by extensive macrophage activation within the ischemic retinal explant, suggesting that macrophage-derived angiogenic factors may be important in inducing retinal endothelial cell proliferation. In addition, glial cell-derived factors may have a role in the development of vessellike tubular structures from endothelial cell outgrowths.

Animals↗

Analysis of hepatic T lymphocyte and immunoglobulin deposits in patients with primary biliary cirrhosis.

The histological findings in patients with primary biliary cirrhosis have been well-defined and are often used in the clinical staging of disease. However, it has only been with the development of reagents that phenotypically characterize the lymphoid infiltrate that attempts have been made to correlate pathophysiology with immune effector populations. Indeed, the inflammatory hepatic lesions in primary biliary cirrhosis have been described as containing CD4-positive and CD8-positive T cells. Less clear, however, have been the T cell receptors in these lesions. Further, the data on immunoglobulin deposits in hepatic lesions have been less well-defined; this deficit may be a result of the quality of polyspecific sera and difficulties in background. To address these issues, we have used a battery of well-defined monospecific and polyspecific reagents to phenotypically define the occurrence of lymphoid cells in the livers of patients undergoing transplantation. Furthermore, we have defined these same markers on T cell lines derived from liver, regional lymph node and peripheral blood. The predominant cell type in the mononuclear infiltrate is the CD3+, CD4+ T lymphocyte bearing the T cell receptor alpha beta. T cell lines from the same patients demonstrate similar findings. Of special importance, however, was the detection of CD20+ B cells and Ig+ cells in the lymphoid infiltrate. Indeed, we also readily demonstrated the presence of immunoglobulin on the surface of biliary epithelium. These data suggest that mechanisms involved in the pathophysiology of primary biliary cirrhosis may include both T cell and antibody mechanisms. The results also underscore the need to develop a functional, and not just a phenotypical, assay of the inflammatory infiltrate.

Antibodies, Monoclonal↗

Infection on a gynecologic oncology service.

Little information is available pertaining to infectious morbidity in women with genital malignancy. To define the magnitude of this problem, all patients admitted to the gynecologic oncology services at the University of Michigan Medical Center between January 1, 1986, and December 31, 1986, were followed prospectively for the development of infectious morbidity. One hundred nine bacteriologically confirmed infections occurred in 297 patients during 510 admissions. An additional 31 postoperative patients received empiric therapy for presumed infection. Urinary tract (54) and wound (22) infections were the most commonly confirmed infections. The pathogens isolated from oncology patients were significantly different in frequency of isolation and antibiotic sensitivity when compared with pathogens isolated from women developing infections on the benign gynecology service. Women with genital malignancies are at high risk for the development of a variety of infections by resistant pathogens, emphasizing the importance of obtaining cultures prior to initiation of therapy and carefully selecting the antibiotics to be prescribed.

Anti-Bacterial Agents↗

Neuropsychological deficits and sleep in myotonic dystrophy.

Eight patients with myotonic dystrophy underwent comprehensive neuropsychological testing and overnight polysomnography to assess whether the waking cognitive impairment might be attributable to sleep structure abnormalities or to sleep-related respiratory problems. Patients showed substantial neuropsychological deficits, fragmented nocturnal sleep and, in half the patients, sleep apnea and/or hypopnea both mainly of central type. There was no statistically significant correlation between the degree of daytime cognitive deficit and the degree of sleep fragmentation or of respiratory problems at night. It was concluded that the neuropsychological deficit in mytonic dystrophy cannot be attributed to a secondary effect of nocturnal sleep apnea or sleep disruption but probably represents a direct effect of CNS lesions.

Adolescent↗

Effect of age on upregulation of the cardiac adrenergic beta receptors.

Radioligand binding studies were performed to determine whether upregulation of postjunctional beta receptors occurs in sympathectomized hearts of aged animals. Fischer 344 rats 6, 12, and 24 months of age (n = 10) were used in these experiments. To produce sympathectomy, rats were injected with 6-hydroxydopamine hydrobromide (6-OHDA; 2 x 50 mg/kg iv) on days 1 and 8; the animals were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. 125I-Iodopindolol (IPIN), a beta adrenergic receptor antagonist, was employed to determine the affinity and total number of beta adrenergic receptors in the ventricles of the rat heart. The maximal number of binding sites (Bmax) was significantly elevated by 37%, 48%, and 50% in hearts from sympathectomized 6-, 12-, and 24-month-old rats, respectively. These results indicate that beta receptor mechanisms in older hearts can respond to procedures that cause upregulation of the beta adrenergic receptors.

Adrenergic beta-Antagonists↗

Definition of two distinct types of AIDS-associated non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) in a human immunodeficiency virus (HIV)-infected person is an AIDS-defining condition. There is both an increased incidence of NHL and a poorer prognosis for the disease in these HIV-infected persons, compared with patients who spontaneously develop NHL. A series of 41 consecutive patients with HIV-associated NHL treated at St Vincent's Hospital, Sydney, between 1984 and September 1989 was assessed. Of these, 36 had NHL proven on biopsy and NHL was diagnosed clinically in the other five. On histologic examination 11 had high-grade malignant lymphoma, small non-cleaved cell (SNCC) type, similar to Burkitt lymphoma, 18 had high-grade lymphoma large cell immunoblastic (LCI) type, and seven could not be classified due to inadequate material for assessment. The clinical features of these two groups were compared. Those patients with LCI had advanced CD4+ immunodeficiency and poor survival (median = 6 weeks). The other group with SNCC had better preserved immune function, and longer survival (median = 18 weeks). Three patients had survived longer than 3 years all of whom had SNCC lymphoma as their first AIDS-defining illness. The clinical features and prognostic factors demonstrated in this study document heterogeneity of NHL in HIV-infected patients and should be used as a guide to treatment of these patients, by reserving more intensive treatment for those persons with better prognostic features.

Acquired Immunodeficiency Syndrome↗

Reliability and learning from the objective structured clinical examination.

The difficulties in measurement of the clinical performance of students in the health professions are well known by educators. One innovative measure incorporated in several of the educational programmes, including the BSc in Nursing programme, in the Faculty of Health Sciences, at McMaster University, Hamilton, Ontario, Canada is the objective structured clinical examination (OSCE). The purpose of this study was to determine the reliability of this evaluation method, both within and between stations. One problem that has been noted by users of the OSCE method is that performance on individual OSCE stations is poorly correlated across stations, apparently regardless of the particular content of the station. A number of hypotheses have been advanced to attempt to explain this phenomenon: performance of any skill is sufficiently variable that the correlation is poor; different skills have little common basis, so that there is no generalizability from one to another, or reliability of assessment in any one station is low. To test these hypotheses, a study was designed for test-retest and interrater reliability. Students undergoing a 10-station OSCE also repeated their starting OSCE station at the end of the examination circuit. In addition, several stations were rated by more than one observer (interrater). This study of 71 first-year BScN students showed that the interrater reliability was high (ICC = 0.80 to 0.99), and test-retest reliability on the same station was good (ICC = 0.66 to 0.86); however, correlation across stations was low (alpha = 0.198). Thus it is apparent that there is high consistency of repeated performance of a skill but little consistency of performance on different skills.

Clinical Competence↗

Cardiac beta-adrenoceptor binding characteristics with age following adrenal demedullation.

1. The role of adrenal medullary catecholamines in the regulation of cardiac function becomes more important when adrenergic neural influences in the heart are decreased. Since adrenergic nervous input to the heart decreases with age, it would be expected that catecholamine influence on cardiac neuroeffector junction would increase. 2. Fischer-344 rats of 6-, 12- and 24-months were adrenal demedullated or sham-operated and the animals were killed at the end of two weeks. beta-Adrenoceptors were studied in the membrane preparations from the ventricles of rat hearts. [125I]-iodopindolol was used as the radioligand. The density of beta-receptors (Bmax), dissociation constant (KD) and the ratio of cardiac beta-adrenoceptor subtypes were studied. The relative percentages of beta-receptor subtypes were determined by use of ICI 89,406 (beta 1-selective antagonist) and ICI 118,551 (beta 2-selective antagonist). 3. In 24-month-old animals which were adrenal demedullated, hydrocortisone replacement was employed for one week; the animals were killed one week later. 4. The data indicate that there was a diminution of the Bmax following adrenal demedullation at all ages but that the ratios of beta 1: beta 2-adrenoceptors remain the same as in the controls (67:33). The effect of adrenal medullary catecholamines on cardiac beta-receptor binding characteristics did not seem to be influenced by age.

Adrenal Medulla↗

Women's views of second-stage labor as assessed by interviews and videotapes.

Twenty women were selected from public and private maternity services and interviewed by nurses and nurse-midwives on a research team. The women were shown videotapes of their second-stage labors that for 15 of them had been recorded by 2 other members of the research team. Four videos were provided by mothers who had had home births and one from a mother whose birth was filmed at a birth center. The interviews were analyzed for major themes; the theme reported here is women's experiences of pushing. Women reported wide variations in sensations during the second stage. Whereas 9 of 16 women expressed feelings of relief or pressure and stretching, 7 described pushing as painful, miserable, or horrible. Thirteen of 19 women had well defined urges to push, 1 had an intermittent urge, and 5 had no urge. Women often felt unprepared for the sensations and work of second-stage labor, and caregivers' instructions commonly did not seem to be in synchrony with physiological responses. We conclude that childbirth educators and caregivers must prepare women more realistically for the second stage. They would be more effective if they responded to maternal behavior, rather than giving arbitrary instructions about pushing.

Adolescent↗