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Biomedical subjects

C Thomas

Publications and source records attributed to C Thomas.

At least 361 records · Page 20Linked to original sources
PubMed1990

Vascular lesions in the central nervous system in sickle cell disease (neuropathology).

The incidence of serious neurologic complications in sickle cell disease ranges from 6% to 30% in various series. Our experience indicates that the incidence in adults is approximately 15%. The clinical and neuropathologic correlations at autopsy in 20 sickle cell disease patients are discussed in this paper. Some patients had massive infarcts and/or hemorrhages in the cerebral hemispheres as the terminal event. In some, both infarction and hemorrhage occurred simultaneously; others had thrombosis of major branches of the circle of Willis and in the internal carotid artery on one or both sides. Prominent large arterial occlusive disease in the terminal intracranial portions of the internal carotid arteries and proximal segments of their main branches was frequently observed. The pathology of the brain showed diffuse chronic gliotic scars of microinfarcts in the deep white matter and cerebral gray matter, even when no past neurologic history was recorded. We hypothesize that the vague, nonspecific complaints, including chronic alteration of intellectual and emotional function, of some sickle cell disease patients prior to their death, may constitute the clinical counterpart of disseminated microscopic lesions resulting from small-vessel disease. The pathogenesis of vaso-occlusive disease includes altered cerebral blood flow, platelet response to endothelial injury, and sickled erythrocyte adhesion to endothelium.

Adolescent↗
PubMed1990

Measuring and interpreting organizational culture.

Organizational culture is an abstract, yet potent managerial concept. With roots in several disciplines, several perspectives and definitions of organizational culture have emerged. One perspective focuses on norms and expectations within the organization. In this article, the authors present a quantitative approach to measuring and interpreting organizational culture based on established norms and expected behavior.

Humans↗
PubMed1990

Who asks permission for an autopsy?

A survey was undertaken of all hospitals with more than 400 beds in North East Thames Region to ascertain the way in which permission for an autopsy was obtained, in an attempt to explore reasons for declining autopsy rates. We found that there was a considerable variation in autopsy rates, and in the systems within hospitals whereby permission for autopsy is sought. The responsibility for requesting an autopsy is often delegated to younger doctors who have not received any training in how it should be done. A sensitive lay person can achieve high rates of permission for autopsy. Most consultants interviewed stated that they requested less autopsies now than 5 or 10 years ago. They seldom attended autopsies, and one-third of pathologists have given up contacting the clinician before an autopsy.

Autopsy↗
PubMed1989

Dispensing habits of Johannesburg pharmacists in treating acute infantile diarrhoea.

Sixty pharmacists in Johannesburg were randomly selected and questioned on their suggested treatment of acute infantile diarrhoea as well as their knowledge of oral rehydration therapy (ORT); 53 (88%) responded. Of 51 pharmacists who had treated diarrhoea in children, 8 (16%) had never heard of ORT, while 20 (39%) treated this condition with antidiarrhoeal drugs. These findings are perturbing, because acute diarrhoeal disease is the biggest cause of mortality of children aged 1-4 years in South Africa and ORT is recognised as an effective means of prevention of death.

Diarrhea, Infantile↗
PubMed1989

Epidermal growth factor stimulates phosphatidylinositol turnover in human foreskin fibroblasts without activation of protein kinase C.

Epidermal growth factor stimulates phosphatidylinositol turnover in human foreskin fibroblasts. This is a primary cell culture with normal numbers of epidermal growth factor receptors that is stimulated to divide by epidermal growth factor. Increases are seen in the inositol phospholipids and inositol phosphates. Despite this activation of phosphatidylinositol turnover, there is no detectable activation of protein kinase C.

Cell Division↗
PubMed1989

Analysis of the hypoplastic right ventricle utilizing electrocardiographic body surface potential mapping (BSPM).

The authors present electrocardiographic body surface potential maps (BSPMs) of 11 patients with hypoplastic right ventricle (HRV) of three types: type I, HRV with pulmonary atresia; type II, HRV with tricuspid atresia; and type III, HRV with tricuspid artesia and transposition of the great arteries. The BSPMs of all 11 patients demonstrated evidence for epicardial right ventricular breakthrough, indicating conduction through an intact right bundle branch and Purkinje system. Nonetheless, the BSPMs strongly suggested profound morphological, probably embryological, differences among the right ventricles of the three groups. The four patients with type I HRV had no evidence for conduction abnormality. The five patients with type II, HRV however, had very marked conduction abnormality. In four of these five, the standard ECG and VCG had initial forces suggesting left lateral wall myocardial infarction. The BSPMs showed no evidence for infarction but demonstrated very complicated slow initial activation, explaining why the initial QRS vector was to the right and posterior before extending leftward. In addition, in all five the initial positive potentials were unusually inferior and the initial negative potentials unusually superior. After the evidence for epicardial right ventricular breakthrough, the positive and negative potentials rapidly changed positions so that the positive potentials were unusually superior and the negative potentials unusually inferior, consistent with the BSPM of endocardial cushion defects. In four of these five there was marked delay of total ventricular activation time. Of the two patients with type III HRV, one had an initial QRS similar to that of type II. Neither had rapid change of inferior and superior positive and negative potentials after right ventricular breakthrough, and both had intraventricular slowing, one with partial left bundle branch block.

Adolescent↗
PubMed1989

Multiple distinct intracranial tumors: association of pinealoma and craniopharyngioma. Case report.

We report the case of a patient with multiple primary brain neoplasms. A pinealoma was treated with radiotherapy and surgical resection in 1983. In 1987, a craniopharyngioma was resected surgically. Various possible determinants of multiple brain tumors have been described in the literature and are discussed. The possibility of an unknown underlying pathologic mechanism predisposing to multiple malignancies must be considered, but we are unable to conclude that this particular occurrence is more than a random chance finding.

Adult↗
PubMed1989

Popliteal lymph node reactions in mice induced by the drug zimeldine.

The antidepressant drug zimeldine was screened for immune modulating properties using the popliteal lymph node (PLN) assay as a test system in mice. In immunocompetent as well as congenitally athymic nude mice, footpad injection of 1.0 mg zimeldine triggered a bimodal footswelling. A transient oedematous swelling, histologically characterized by mast cell degranulation, was followed by infiltration of polymorphnuclear cells. A dose-dependent PLN enlargement to the agent was observed, which appeared to be more pronounced in immunocompetent mice as compared with athymic nude mice, and in H-2b mice as compared with H-2d mice. After injection of 1.0 mg zimeldine into the footpad of C57BL/10 mice, significant enlargement was already observed by 3 days after injection, was optimal around day 9 and persisted for at least 30 days. Histologically, PLN reactions were characterized by blast transformation of lymphocytes and expansion of paracortical areas prior to germinal center reactions in enlarged follicles. Size of both areas gradually decreased as the medulla filled with plasma cells, 7-30 days after injection. The observed reactions could not be transferred with syngeneic lymph node cells after prior exposition to zimeldine in vivo or in vitro. We conclude that zimeldine induces strong and persistent PLN enlargement, blastogenesis and prominent germinal center reactions. Immunocompetent T-cells are apparently conducive, but not prerequisite to these reactions, which suggests involvement of multiple mechanisms including those mediated by inflammatory reactions in the foot. It is unlikely that the observed enlargement of PLN can be attributed to a direct chemical modification of leukocyte membranes by zimeldine. The protracted nature of the reaction may indicate that zimeldine somehow interferes with inhibitory feedback mechanisms.

Animals↗
PubMed1989

The popliteal lymph node assay in mice to screen for the immune disregulating potential of chemicals--a preliminary study.

Low mol. wt compounds were tested in the popliteal lymph node (PLN) assay to study whether PLN reactivity could be related to the ability of the compounds to induce autoimmune disorders in man. PLN reactions were measured 7 days after a single subcutaneous (s.c.) injection of dissolved compounds in amounts of 0.3-2.0 mg into one hind footpad of mice and assessed as the weight increase of the draining PLN relative to the PLN weight of the untreated contralateral paw. Hydralazine, chlorpromazine, diphenylhydantoin, carbamazepine, phenylbutazone and nitrofurantoin, all being drugs with a documented potential to induce systemic immunological disorders in man, caused marked PLN reactions. False negative PLN responses were observed following injection of procainamide and isoniazid. Among systemic drugs without known potential to induce autoimmune reactions in humans, quinacrine, denzimol and niridazole significantly increased PLN weights, while phenobarbital, levamisole and disulfiram had no effect. Chemicals with a well-known capacity to induce contact dermatitis in man like 2,4-dinitro-1-chlorobenzene, alpha-methylene-gamma-butyrolactone, p-phenylenediamine, 5-nitro-2-furaldehyde semicarbazone, 2-mercapto-benzothiazol and 1,3-dibutyl-2-thiourea caused marked PLN reactions, while the non-sensitizer 2,4-dichloro-1-nitrobenzene failed to do so. It is concluded that the PLN assay as applied in this study may give a rapid first indication of immunomodulating potential of low mol. wt compounds, but it does not discriminate as to the kind of immunomodulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Significance of toxin-coregulated pili as protective antigens of Vibrio cholerae in the infant mouse model.

The infant mouse cholera model has been used to evaluate the relative importance of toxin-coregulated pili (TCP) as protective antigens of Vibrio cholerae 01. Electron microscopic and immunoblotting analyses revealed that, under the cultural conditions examined, TCP were only expressed by strains of classical biotype. Antibodies to TCP were sufficient to confer protection against two such strains, and were more efficient if the challenge vibrios were cultured for TCP expression. In contrast, such antibodies did not protect mice against challenge with any of four strains of El Tor biotype. Since two of the latter have previously been shown to possess non-lipopolysaccharide protective antigens, these results suggest that TCP are not the only such antigen in this model.

Animals↗
PubMed1989

New high O2 carrying perfluorochemical emulsions: toxicity, radiosensitivity of GM-CFC and development of metastases in mice.

The effects of two new concentrated perfluorochemical emulsions based on F-66E and PFOB, which carry significantly more oxygen than Fluosol-DA 20%, were tested on normal tissues (toxicity and radiation response) and on the development of metastases from Lewis Lung Carcinoma (3LL) in female C57 BL/6 mice. Twenty one days after injection of F-66E or PFOB emulsions (15 ml/kg body weight), the spleen and liver weights were significantly increased but had returned to normal after 2-3 months. Splenomegaly already observed in 3LL bearing mice was significantly increased by F-66E emulsion injection. The radiosensitivity of GM-CFC was not altered when unanesthetized GM-CFC was not altered when unanesthetized mice were pretreated with F-66E emulsions and/or carbogen 1 hr prior to and during irradiation. The rate of tumor take and the period before detection of tumors were not modified when an emulsion of F-66E was injected simultaneously or 10 days after 3LL cells. Mean survival of mice, and the number of metastases on lung surfaces were similar in F-66E injected mice and control mice.

Animals↗
PubMed1989

New high O2 carrying perfluorochemical emulsions and/or carbogen: reactions of a human tumor xenograft to irradiation.

The effects of two new perfluorochemical emulsions based on F-66E and PFOB which carry, in combination with carbogen, more oxygen than Fluosol-DA 20% were investigated on a human tumor xenograft (HRT18). Tumor bearing mice were pretreated with 15 ml/kg of F-66E emulsion (50 w/v%) or PFOB (100 w/v%) emulsion in the presence of carbogen for 1 hr prior to and during irradiation. F-66E emulsion was non toxic in vitro. In vivo, the dose modifying factor was 1.8 for mice pretreated with carbogen and F-66E emulsion whereas it was 1.6 for carbogen-breathing mice. Results with PFOB emulsion were similar to those obtained with F-66E emulsion. The effect of F-66E emulsion was studied using a fractionated radiation treatment: 12 Gy were delivered in 6 fractions of 2 Gy with an interval of 8 hrs between fractions. A single dose of F-66E emulsion was injected before the first irradiation. Surviving fractions were 0.35 for air-breathing mice, 0.091 for carbogen-breathing mice and 0.099 for carbogen-breathing mice pretreated with F-66E emulsion. These results showed that carbogen alone or carbogen plus F-66E or PFOB emulsion were very efficient even with low doses of radiation.

Animals↗
PubMed1989

Ro 03-8799: preferential relative uptake in human tumor xenografts compared to a murine tumor: comparison with SR-2508.

The pharmacokinetics of Ro 03-8799 and SR-2508 were studied in 6 tumor cell lines (5 human, 1 murine) transplanted into athymic nude mice. The human tumors were rectocolic adenocarcinomas (HRT18, HT29) and melanomas (Be11, Na11+, Na11-), the rodent tumor was a mammary tumor (EMT6). The concentrations of drugs in tumor, blood, plasma, and red cells were measured by HPLC 15, 30, and 45 minutes after the simultaneous i.v. injection of 0.1 mg/g of each compound. Little or no difference was found between the concentrations in the plasma, blood, and red cells for either drug; SR-2508 concentration was higher than that of Ro 03-8799. Both compounds were concentrated in all the tumors, the concentration increases or decreases as a function of the time, depending on the cell line; there was more Ro 03-8799 in the pigmented melanomas than in the other tumors. The relative uptake of Ro 03-8799 and SR-2508 in the tumor was evaluated by the ratio of drug concentrations in the tumor and in the blood. The results suggest that Ro 03-8799 and SR-2508 accumulated in all the tumors, the relative uptake of Ro 03-8799 was higher than that of SR-2508. For human tumors, the ratios increased between 15 and 45 minutes. They ranged from 1.2 to 3.6 for SR-2508 and from 3.1 to 14.6 for Ro 03-8799. For Ro 03-8799, the highest ratios were found for the melanomas; the uptake was higher in the pigmented Na11+ tumors than in the non-pigmented Na11-. The ratios for EMT6 were about 2.3 for SR-2508 and 4.7 for Ro 03-8799; these ratios varied slightly between 15 and 45 minutes.

Animals↗
PubMed1989

Exogenous immunosuppression with methylprednisolone does not reactivate a type D retrovirus in rhesus monkeys.

To determine whether immunosuppression would result in retrovirus expression in previously infected rhesus monkeys, chronic high dose methyl prednisolone therapy was administered to two groups of animals for 4 weeks. One group was antibody positive for a type D retrovirus, designated Type D/3/wisc. The second group of animals had no known exposure to Type D/3/wisc and was antibody negative to this virus. The monkeys were evaluated for immunosuppression and retrovirus re-expression following the corticosteroid therapy. Although this treatment induced a marked cellular immunosuppression in all animals, as measured by in vitro assays, in none of the animals was retrovirus viremia or retrovirus-associated disease detected.

Animals↗
PubMed1989

Nucleolar organizer regions (NORs). Basic concepts and practical application in tumor pathology.

The purpose of this investigation is to give an introduction to a novel method in tumor pathology, namely the Ag-NOR technique. The basis of this method is the argyrophilic staining of intranucleolar, non-histone proteins which are specifically associated with transcriptionally active sites of ribosomal DNA. They can therefore be considered as a marker for the protein synthesis and thus the proliferation rate of a given cell. The morphologic basis of the argyrophilic reaction is presented by metaphasic and interphasic tissue culture cells. The applicability of Ag-NOR technique to tumor pathology is exemplified by main results of three studies dealing with tissue sections of 65 meningiomas, whole organ sections of 50 renal carcinomas, and cytospin preparations of 30 urinary washout specimens. These studies document the considerable value of the Ag-NOR content for both, malignancy diagnosis and tumor grading. With the help of image analysis it can be shown that besides the mean number of Ag-NORs the mean area per Ag-NOR dot is of diagnostic significance. In conclusion the Ag-NOR technique is a simple inexpensive and accurate method which can be applied both to formalin fixed, paraffin-embedded tissue and cytologic specimens. As a marker of malignancy it is an invaluable new tool for the diagnostic pathologist.

Cell Line↗
PubMed1989

Cognitive-behavioral therapy and relationship therapy in the treatment of children referred for antisocial behavior.

The present study evaluated alternative treatments for children (N = 112, ages 7-13) referred for severe antisocial behavior. Children were randomly assigned to one of three treatments: problem-solving skills training (PSST), problem-solving skills training with in vivo practice (PSST-P), which included therapeutically planned activities to extend training to settings outside of treatment, or client-centered relationship therapy (RT). PSST and PSST-P children showed significantly greater reductions in antisocial behavior and overall behavior problems, and greater increases in prosocial behavior than RT children. These effects were evident on measures obtained immediately after treatment and at a 1-year follow-up, and on measures of child performance at home and at school. PSST-P children showed greater changes than PSST children on measures of functioning at school at posttreatment, but these differences were no longer evident at follow-up. Children in both PSST conditions showed significant reductions in deviant behavior and improvements in prosocial behavior from pretreatment to follow-up, whereas RT children tended to remain at their pretreatment level of functioning. Notwithstanding the significant improvements, comparisons with nonclinic (normative) samples revealed that the majority of youth remained outside of the normal range of deviant behavior. Possible directions for improving treatment for antisocial youth are highlighted.

Adolescent↗