Biomedical subjects
Publications and source records attributed to C Pearson.
We describe a male infant with Yunis-Varón syndrome who has tetralogy of Fallot. This appears to be the first case of Yunis-Varón syndrome associated with congenital heart malformation.
The use of smaller sized catheters for coronary angiography (CA) is increasing, but little is known about the safety of CA with 6F catheters. The authors reviewed all cases of CA in which 6F and 8F catheters were used in adult patients between 1988 and June, 1990. There were 597 patients in the 6F group and 2,409 patients in the 8F group. Cases of CA with 6F catheters were more likely to be elective (95% vs 87%), to have no coronary disease (35% vs 24%), and to be performed by nonfirst-year fellows (70% vs 54%) when compared with CA with 8F catheters. There were 5 cases of coronary artery dissection. The incidence of dissections was significantly higher (p = .007) in the 6F group (0.67%) than in the 8F group (0.04%). The incidence of dissections was highest for first-year fellows using 6F catheters (1.7%), which was significantly higher (p = .008) than for first-year fellows using 8F catheters. The incidence of major vascular complications tended to be lower (p = .068) in the 6F group (0.17%) than in the 8F group (0.95%). In summary, CA with 6F catheters is associated with an increased risk of coronary artery dissection, particularly with less experienced operators, but tends to be associated with a lower risk of major vascular complications.
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We examined the phenomenon of dyspnea during the last weeks of life as it is experienced by patients with cancer and understood by the nurses providing their care. The literature on late-stage cancer suggests a discrepancy between the prevalence of this symptom and the degree to which it is considered clinically significant. Using a range of descriptive and interpretive approaches, we sought to interpret that discrepancy through an understanding of how patients and nurses interpret the nature and meaning of this serious and distressing symptom. Data sources included a pencil-and-paper survey of late-stage cancer patients, chart audit of a population of late-stage cancer patients in a metropolitan home-care hospice program, and intensive interviews with selected patients and nurses. The findings showed that although dyspnea seems to be a significant clinical problem for patients in late-stage cancer, and although effective intervention and management strategies are available, dyspnea often goes unreported by patients and unnoticed by healthcare professionals.
The cellular and molecular requirements for the autoimmune disease EAE are being defined in increasing detail through intense scrutiny of critical autoantigenic peptides, class II MHC molecules, and alpha beta TCRs involved in the disease process. This study has led to novel immunotherapeutic approaches, many of which are based on the administration of synthetic peptides. Since short peptides are understood to be the minimal antigenic units bound by MHC molecules for recognition by T cells, they are attractive experimental tools for finely modulating specific immune responses. It is clear that a large number of defined peptides can dramatically influence the course of EAE. Table IV lists a number of potential mechanisms which may mediate disease prevention. Increasing evidence supports the idea that prevention of autoimmune disease can result from MHC-blockade by peptides which competitively bind to class II molecules. However, for some peptides such as the perplexing partial agonist Ac1-11[4A], the mechanism by which these precisely defined units act is not yet fully understood. Numerous hurdles hinder immediate clinical application of peptide-based immunotherapy. Nevertheless, the knowledge gained by probing experimental autoimmunity with defined peptides promises to inspire original and practical approaches to treating human autoimmune disease.
This study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be important in the development of autoimmune thyroid disease. These factors were examined in (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone. Eight of 40 patients who were receiving lithium therapy were found to be positive for thyroid microsomal and/or thyroglobulin antibodies, compared to only 3/40 patients who were receiving some other form of treatment for their depression. Peripheral blood mononuclear cells from patients receiving lithium were found to have significantly reduced numbers of suppressor/cytotoxic T cells (P less than 0.05). In addition, suppressor T cells from these patients showed a significantly reduced response to stimulation with concanavalin A (P less than 0.01). These effects were greatest in patients found to be antibody positive. Increased B cell activity, as measured by increased IgG and IgM release following mitogen stimulation, was seen in patients receiving lithium and in those patients receiving other forms of treatment for their depression. This would suggest that the increase is a feature of primary affective disorders and is not due specifically to lithium treatment. It would appear from this study that lithium therapy induces antibody formation in susceptible individuals and this may ultimately lead to the development of thyroid disease.
This review is concerned with the individual and group treatment of clients who present with a history of sexual abuse in childhood. Almost all of the literature regarding the individual treatment of these clients is based on clinical reports; very little is experimentally based. Most of the reports of group treatment are of a similar nature, although some outcome research data are included. The clinical consensus, in terms of the issues, stages, goals and techniques of therapy, is described. In addition, an overview is provided of the identification of clients who may have a history of CSA, which includes guidelines for assisting disclosure. Finally, the issues raised for therapists in treating these clients are addressed. Much of the material reviewed in this article refers to the treatment of female, and in particular incestuously abused, victims; at the time of writing, very little information was available regarding the treatment of male victims.
The psychological problems and difficulties experienced by adults who report having been sexually abused in childhood are reviewed. These long-term effects include damage to the victims' emotional reactions and self-perceptions, relationship problems, problems with sexuality and difficulties in social functioning. Common presenting problems of victims of childhood sexual abuse (CSA) are described. Also discussed are the characteristics of incestuous abuse in terms of the victim, the abusive relationship and its termination; the contributions of the various aspects of CSA to the psychological impact of such abuse; and psychodynamic explanations of the development of long-term effects. The bulk of the published material regarding the long-term effects of CSA refers to female victims only, and this 'bias' is reflected in the review.
The expression of surface markers of T cell subsets in the peripheral blood of 30 Graves' disease patients was investigated pre and post therapy using two colour flow cytometry. Reduced numbers of total, helper/inducer and suppressor/cytotoxic T cells were found in untreated Graves' patients. Numbers of suppressor-inducer T cells which are associated with maintaining the normal immune response, did not differ significantly between untreated Graves' patients and controls. Although 8 weeks' Carbimazole therapy reversed the changes in total, helper/inducer and suppressor/cytotoxic T cells, PTU or 131I therapy did not. While suppressor-inducer T cell numbers were not affected by Carbimazole or PTU therapy, 131I treatment caused a decrease in suppressor-inducer T cell numbers.
The expression of c-myc protein was studied in primary cultures of rat hepatocytes and rat liver-derived epithelial cell lines. The levels of the protein were determined by flow cytometry using a monoclonal antibody to the c-myc protein. Freshly isolated hepatocytes from normal adult male Fischer F344 rats had low but detectable levels of the protein which were similar in the different ploidies. Higher levels were detected in immortalised but untransformed rat liver cell lines, and increased expression was observed during passage through the cell cycle. Following in vitro transformation of one of the immortalised epithelial cell lines by ras genes, similar levels of c-myc expression to those present in the untransformed cells was maintained. Transformation by activated aflatoxin B1 (AFB1) resulted in lower levels of expression. The cell cycle related level of expression was also seen in the transformed cells. Similar results to those observed in the in vitro ras transfected liver-derived cell lines were obtained from in vivo AFB1-induced rat hepatoma cell lines. These results demonstrate that continuously dividing rat liver-derived cell lines have higher levels of expression of c-myc protein than non-dividing, freshly isolated hepatocytes, and that there is no further elevation in the levels observed when these cell lines are transformed. In some cases decreased levels can result from malignant transformation.
Renin messenger (m) RNA distribution was studied in congenital mesoblastic nephroma, a usually benign renal tumour of early infancy which may be associated with excess renin production and hypertension. Using in situ hybridization with synthetic radiolabelled oligonucleotide probes combined with immunohistochemical studies, renin expression was found in areas of tumours containing recognizable cortical structures including glomeruli and tubules. Renin mRNA was also detected in vessels and larger vascular spaces within the tumour not associated with cortical structures. Cells in the tumour vessel walls and sinusoids which expressed renin also stained positively for vascular smooth muscle-specific alpha actin.
Three known local anesthetic agents were examined for their ability to inhibit platelet aggregation induced by adenosine diphosphate or epinephrine. Drug-treated platelet-rich plasma samples were filtered through agarose gel to remove free drug, and the ability of the platelets to aggregate was again determined. One of the local anesthetics contained a "one-armed" nitrogen mustard structure and appeared to produce an irreversible inhibition of aggregation. The other two agents gave a block of aggregation that was reversed upon gel filtration.
We have investigated levels of transcript homologous with glutathione S-transferase P (GST-P; GST 7-7) in tumours and hyperplastic lesions induced in the livers of rats by long-term gavage dosing with diethylnitrosamine (DEN) and 6-p-dimethylaminophenylazobenzothiazole (6BT). Detailed histopathological examination of the livers of the 90 animals used in this study at 6-8 months after initiation of daily dosing revealed that, of the 30 animals treated with carcinogen, 15 had developed tumours or hyperplastic lesions. Of these, 11 were areas of fibrosarcoma/fibrous hyperplasia. The remaining four were hepatocellular carcinomas. Northern blotting of total RNA purified from these tissues revealed the presence of transcripts of 3 and 0.75 kb. Evidence is presented to indicate that the former is a hitherto-undetected precursor of the 3-kbp rat GST-P gene, the latter representing the previously characterized mature GST-P transcript. Large elevations of the 0.75-kb transcript (30-35-fold) were encountered in all of the hepatocellular carcinomas, but in none of the other lesions, indicating a highly significant correlation (P = less than 0.001) between high elevations in levels of GST-P mRNA and liver tumours of hepatocellular origin. Minor elevations in transcript level (less than or equal to 5-fold) were encountered in several of the non-hepatocellular lesions. In regenerating livers, small increases in the level of the 3-kb transcript (approximately 3-fold) were routinely detected in total RNA from all partial hepatectomies, a concomitant decrease of approximately similar magnitude occurring in the 0.75-kb transcript, suggesting that minor elevations in levels of GST-P transcript, where encountered in non-hepatocellular lesions, are related to pre-neoplasia rather than to the proliferative rate of hyperplastic cells per se. The data extend previous observations, carried out largely using short-term regimes, to an analysis of transcripts homologous with GST-P in hyperplastic, pre-neoplastic and neoplastic lesions induced by long-term dosing with genotoxic carcinogens, and strongly lend support to the concept that high (30-fold) elevations in GST-P transcript correlate most strikingly with tumours of hepatocellular origin.
Twenty four patients were studied prior to and after 6 and 12 weeks therapy with isotretinoin (17 patients) for acne and related disorders, or with etretinate (7 patients) for psoriasis and related disorders. Patients treated with isotretinoin had a significant reduction in natural killer cell activity at an effector: target cell ratio of 100: 1 at 12 weeks and also a reduction in natural killer cell numbers at this time. Patients treated with etretinate had elevated natural killer cell activity and a significant elevation of natural killer cell numbers at 12 weeks. Other tests which were performed and showed no significant change at 6 or 12 weeks compared with starting levels included lymphocyte transformation in response to phytohaemagglutinin, pokeweed mitogen and concanavalin A, total numbers of circulating T lymphocytes, B lymphocytes and T helper and T suppressor subsets, numbers of epidermal Langerhans cells and serum levels of IgA, IgM and IgE. In view of the involvement of natural killer cells in the initial phase of organ rejection, these results suggest that isotretinoin is the safer of the two retinoids if administration to renal transplant recipients is considered, particularly in the immediate post-transplant period.
The aim of the study was to examine tri-iodothyronine, thyroxine, thyroid antibody and thyrotropin receptor antibody levels in thyroid and peripheral venous blood at the time of surgery in patients with Graves' disease. T cell subset patterns in peripheral and thyroidal venous blood were compared to the distribution of T cell subset patterns within the thyroid gland itself. The results showed that at the time of surgery there were no significant differences in any of the parameters measured between thyroidal and peripheral venous samples. T cell subset patterns within the thyroid gland were subjectively similar to those in the venous samples.
Carbimazole and Propylthiouracil (PTU) are widely used in the treatment of Graves' disease, although controversy still exists as to whether or not they have any direct effect on the immune system. While many previous studies have investigated the possible effects of one or other of these drugs on the immune system only a few have directly compared the effects of equivalent doses of each drug. This study aimed to examine the effects of both drugs, during the initial 8 weeks of treatment, on various biochemical and immunological parameters. The results obtained showed that while thyroid hormone levels fell at similar rates in both treatment groups, TRAb levels and T cell subset abnormalities returned towards normal more rapidly in patients receiving Carbimazole compared to PTU. These results indicate that the effects of Carbimazole on TRAb levels and T cell subset abnormalities are not due solely to its action in controlling the biochemical features of Graves' disease and provide indirect evidence of an action on the immune system in vivo.
A comparison of the sequence of two human 7SK RNA pseudogenes, covering approx. 190 and 240 base-pairs of the structural gene, is presented. Both repeated elements are flanked by direct repeats and begin at the 5' end of the gene. Each terminates approx. 90 base-pairs short of the 3' end, the latter representing a continuous sequence and the former carrying an internal deletion of about 40 base-pairs, this region being flanked in the progenitor gene by short repeated sequences. Southern blotting using a human 7SK pseudogene probe illuminated a series of multiple restriction fragments in mammalian genomes, with generally fewer fragments in the genomes of birds and reptiles and a single reactive fragment in DNA from terrapin (Pseudemys scripta elegans) and Xenopus laevis (South African clawed toad). In the latter case this fragment was only detectable on long exposure under the hybridization stringencies employed. 7SK transcripts were readily detectable in all mammalian, avian, reptilian and amphibian species analysed, although the gene appeared to be expressed at rather low levels in the ovaries of Xenopus laevis, possibly accounting for its failure to have become dispersed via 'retroposition' in this species.