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Biomedical subjects

D Roth

Publications and source records attributed to D Roth.

At least 145 records · Page 8Linked to original sources

Ameroid constriction of the proximal left circumflex coronary artery in swine. A model of limited coronary collateral circulation.

Gradual narrowing and occlusion of a coronary artery in patients with atherosclerotic heart disease frequently causes enlargement of the collateral circulation. Although these vessels may protect from development of myocardial infarction, they frequently do not supply sufficient blood flow to prevent ischemia during periods of augmented myocardial oxygen demand. The purpose of this study was to develop a model of the collateral circulation in pigs, a species that previously has been shown to develop sparse collateral vessels. Eighteen pigs were instrumented with an Ameroid constrictor around the proximal left circumflex artery and left atrial and aortic catheters. In four animals the constrictor was placed just distal to a large proximal obtuse marginal vessel. Seven of the pigs were treated daily with oral aspirin (325 mg) and disopyramide (200 mg) throughout the study; the other 11 served as controls. After an average of 24 days postoperatively, radioactive microspheres were injected at rest, during exercise (mean heart rate = 245 beats/min), and during intravenous infusion of dypridamole (700 micrograms/kg). At autopsy the extent of necrosis was assessed by a point counting technique in the bed at risk. We found that 75-83% of the bed at risk remained viable. Although aspirin and disopyramide did not significantly alter the extent of infarction (37 +/- 36% untreated vs 17 +/- 6% treated), there was less variability of infarction in the treated group, and subendocardial blood flow during exercise was higher in the treated group compared to controls. The majority of infarction occurred in the subendocardial region. Animals with a large obtuse marginal branch developed significantly smaller infarcts (8 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Receptor-assay for endogenous inhibitors of Na-K ATPase.

It is now accepted that there is an endogenous digitalis-like substance (EDLS), previously called natriuretic factor, present in different mammalian species which participates to the regulation of the sodium balance and at least in some situations, to the genesis of hypertension. The physiological and pathophysiological role of this substance is well recognized. However, its chemical nature remains elusive. Our purpose was to define a receptor assay for this EDLS in order to be able to measure its concentration in urine and blood. To do so, we first prepared a pool of lyophylised urine from salt loaded men. The active material was isolated by Sephadex G25 chromatography. Using the same active fraction, we investigated its biological effects. Series of experiments have demonstrated the various properties of the EDLS: inducing natriuresis when injected into a rat, diminishing short circuit current in toad's bladder and colonic mucosa of rat in in vitro preparations, inhibiting Na-K ATPase activity in isolated toad's bladder cells, binding to ouabain receptors and cross-reacting with different antibodies directed against digoxin. Among these properties, the binding to ouabain receptors offers the unique opportunity to progress in our knowledges of the substance, making possible the calculation of its constant of affinity and the estimation of the molality of the active material contained in a gram of crude extract. Knowing the constant of affinity of the EDLS for its receptor would provide the best identification of the substance as long as we do not know its exact chemical nature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Homelessness and mental health policy: developing an appropriate role for the 1980s.

Previous research has reported prevalence rates of mental health problems among homeless individuals that range from 20% to 90%. Attempting to validly verify prevalence rates is important because of the implications concerning both deinstitutionalization and developing an appropriate mental health policy over the next decade. In the present research, which used as its sample the largest homeless sample assessed to date, prevalence was found to fall at the lower range of previously cited data. Despite the fact that the prevalence of mental health problems among the homeless population was found to be relatively low, it was found that homeless people with mental health problems are, at best, only marginally served by the mental health system. Implications for community mental health policymakers and program designers are discussed.

Chronic Disease

New perspectives on homelessness: findings from a statewide epidemiological study.

The social problem of homelessness is of increasing concern to mental health professionals. In a large-scale study of homelessness in Ohio, data were collected in face-to-face interviews with 979 homeless people in 19 counties. The median length of homelessness was 60 days. Almost half the respondents cited economic factors, such as unemployment or problems paying rent, as the major reason for their homelessness. Thirty percent had been hospitalized at least once for mental health reasons, and 31 percent showed symptoms serious enough to require mental health services. Findings are also presented in relation to a typology of the homeless--street people, shelter people, and resource people--and urban and rural respondents are compared. These and other findings support the principal conclusions that homelessness is clearly a multidimensional problem and that service strategies must reflect the multiple needs and varying characteristics of homeless people.

Employment

The biologic significance of the mixed lymphocyte kidney culture in humans.

The mixed lymphocyte kidney culture (MLKC) in humans has been studied in normal and abnormal clinical conditions. Human renal cortical cells were extracted by collagenase treatment from the kidneys of "normal" heart-beating cadaver organ donors (n = 13), patients with end-stage renal disease (ESRD) at pretransplant bilateral nephrectomy and splenectomy (n = 13), and from irreversibly rejected renal allografts at the time of graft nephrectomy (n = 5). Proliferation of peripheral blood T lymphocytes of 2-DR-mismatched volunteers occurred in response to kidney cortical cells extracted from each of the 3 donor categories in a reaction termed the allogeneic mixed lymphocyte kidney culture. Additionally, splenic T cells from cadavers and patients with ESRD were seen to react to their autologous kidney cells. The renal cortical cells extracted from ESRD kidneys were more stimulatory in the allogeneic and autologous MLKC responses than those extracted from "normal" cadaver kidneys even when the ESRD kidneys were 99% depleted of passenger T and B lymphocytes by treatment with monoclonal antibodies T11 and B1. In order to help define the antigens operative in the MLKC, we pretreated stimulating lymphocytes and renal cortical cells with anti-class II monoclonal antibodies. The allogeneic mixed lymphocyte reaction and MLKC were inhibited ca. 80% and 30%, respectively. The autologous MLKC was unaffected by this treatment. To further support that tissue-specific immune mechanisms were operative in the reaction, experiments were performed with infiltrating lymphocytes isolated from the ESRD kidneys, which were seen to generate a proliferative response when stimulated with autologous cortical cells. However, the response of these same infiltrating lymphocytes when stimulated with allogeneic lymphocytes (MLR), was markedly weaker than the response of the patients' autologous spleen cells. In addition, two kidneys were obtained at rejection from recipients that had received grafts from HLA-MLR-identical sibling donors. A lymphoproliferative reaction of recipient peripheral blood T lymphocytes occurred in response to (donor) renal cortical cells, but not to donor peripheral blood lymphocytes. In contrast, infiltrating (recipient) kidney lymphocytes responded to the kidney cortical cells and to donor peripheral blood lymphocytes. Moreover, peripheral blood T lymphocytes of the HLA-identical donor responded to his own kidney cortical cells, which were isolated from the rejected recipient kidney, and did not respond to recipient peripheral blood lymphocytes. Finally, a "normal" cadaveric kidney was fortuitously available at the same time that a rejected transplant (cadaver)

Graft Rejection

T cell lines and clones preferentially recognizing kidney-associated antigens in end-stage renal disease.

The specificity in the mixed lymphocyte kidney culture (MLKC) of T cell lines and clones derived from human end-stage renal disease (ESRD) kidneys was studied using collagenase dispersed kidney cells compared with lymphocytes as stimulating cells. These experiments were performed because of previous studies in which infiltrating lymphocytes freshly isolated from ESRD kidney tissue at nephrectomy (as well as autologous splenic T cells) were seen to directly generate this lymphoproliferative MLKC response when stimulated with autologous renal cortical cells. In the current studies, histopathologic staining of tissues and suspensions of infiltrating kidney lymphocytes showed predominance of OKT4 labeled phenotypes, and the stimulation indices in MLKC in general showed a direct relationship with the percentage of helper cells seen in the infiltrates. When T cell lines and clones derived from lymphocytes infiltrating the ESRD kidneys were tested in MLKC, there was evidence of kidney-associated, as opposed to lymphocyte-associated (MLC) reactivity using (3H) thymidine uptake as a reflection of a lymphoproliferative response. Several cell lines and clones derived from these T lymphocytes exhibited a dual reactivity. They served as responding cells in the MLKC reaction and completely suppressed a non-specific allogeneic MLC when added as third-party cells. Quantitatively, some clones suppressed when third-party x-irradiated cells were only 5% of the responding cell number in coculture. In addition to the dual reactivity, phenotypic analysis of these same cell lines and clones employing monoclonal antibodies revealed that individual cells expressed both OKT4 and OKT8 determinants. However, approximately 90% of the cells in the MLC enhancing line were labeled with OKT4. These results indicate that there is a complexity in the autologous MLKC response in that cells with both helper/inducer and suppressor/cytotoxic function take part in the reaction. Although delayed-type hypersensitivity to kidney-associated antigens is inferred as a result of these in vitro assays, nonspecific suppression of other Ia-dependent reactions can simultaneously occur.

Antibodies, Monoclonal

Repair mechanisms involved in muscle regeneration following partial excision of the rat gastrocnemius muscle.

The sequential cytological events of the regeneration process, after partial excision of the gastrocnemius muscle in the rat, were followed by light and electron microscopy. During the first 2 days after injury leukocytes and macrophages infiltrate into the traumatized area. Myogenic regeneration is then characterized by mainly two repair mechanisms. Mononucleated cells, that populate the excised area, most probably fuse together to give rise to newly formed multinucleated myotubes that further develop to striated myofibers. Another mechanism involves the repair of injured muscle fibers by the possible fusion of mononucleated cells with their necrotic cut ends. Consequently, by addition of nuclei and new muscular material, sarcoplasmic outgrowths from the injured fibers are formed. It is concluded that mainly two repair mechanisms are involved in the regeneration process following partial excision of a muscle: addition of new muscle fibers in a process similar to that of embryonic myogenesis and also meristic growth from the injured fibers.

Animals

Cognitive group psychotherapy of depression: the close-ended group.

One of the most important recent contributions to the understanding and treatment of depression is that of the cognitive theory and cognitive-behavior therapy developed by A. T. Beck. This paper describes the rationale and the technique of a short-term group psychotherapy based on Beck's Cognitive Therapy. The therapy was conducted with small closed-membership groups of patients with major depressive illness who were participating in a treatment-outcome study. Details of the role induction, session structure, roles of therapist and cotherapist, phases of group treatment course, and possible effectiveness are discussed. The technique presented here includes two individual cognitive sessions for purposes of role induction and establishing a therapeutic relationship before the first group session. We make use of flipcharts and a blackboard to illustrate various cognitive techniques, highly structured sessions with specific individualized agendas, defined therapist and cotherapist roles. The usual phases in a 15-session group course are described and our present experience of the techniques effectiveness are discussed.

Cognition