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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 361 records · Page 20Linked to original sources

Revisiting the role of the nurse practitioner in the 1990s: a Canadian perspective.

The role of the nurse practitioner was first introduced in the North American health care scene in the early 1960s. In the 1970s, the concept of an expanded practice role for nurses was gaining interest in Canada. The impetus for development of the role in the United States was stimulated by a shortage of physicians. In Canada, the original nurse practitioner (NP) movement was influenced by the changing role of the nurse, the debate over a new category of health care worker in the United States (the physician assistant), and a perceived physician shortage. Canadian nurses saw the NP role as an opportunity to expand their scope of practice. This role expansion into traditional medical areas of practice was operationalized in various settings largely outside of the tertiary care sector. The role was controversial at times in terms of title and role function. However, it did present the nursing profession with an opportunity to demonstrate the impact nurses have on the health status of Canadians.

Canada↗

Hypersensitivity reactions to procarbazine with mechlorethamine, vincristine, and procarbazine chemotherapy in the treatment of glioma.

The authors report the clinical features of hypersensitivity reactions believed to result from procarbazine in eight patients treated with mechlorethamine, vincristine, and procarbazine (MOP) for high-grade glioma. There was one instance of hypersensitivity in 7 patients treated for recurrent disease and seven instances in 16 patients treated with an adjuvant protocol using MOP directly after surgery. Maculopapular rash was seen in seven of eight, fever was seen in four of eight, and reversible abnormal liver function test results were seen in three of four patients. Pulmonary toxic effects were seen in five of eight patients and consisted of isolated interstitial pneumonitis in one, fever and infiltrate after rechallenge with procarbazine after previous rash in two, and cough accompanying rash in two. The toxic effects were mild to moderate in six patients but severe to life threatening in the two who were rechallenged after development of rash. The observed incidence of rash during adjuvant therapy was higher than that previously found by the authors for recurrent disease, and it appears to be higher than has been reported in Hodgkin's disease, lymphoma, and other solid tumors. The findings by the authors suggest that a high index of suspicion be kept for hypersensitivity reactions to procarbazine when treating primary brain tumors and that, contrary to the experience in other settings, procarbazine be stopped if rash develops.

Aged↗

FK-506 inhibits proliferation and IL-4 messenger RNA production by a T-helper 2 cell line.

FK-506 is a potent immunosuppressant which is known to decrease the generation of allospecific cytotoxic T cells, possibly through its effect on cytokine production. FK-506 has been reported to have a suppressive effect on cytokine synthesis and secretion by pooled lymphocytes; its action on more selective subsets of lymphocytes is unknown. We currently report the effect of FK-506 on proliferation and IL-4 messenger RNA production by the differentiated mouse T-helper 2 cell line Ly1+2-/9. Ly1+2-/9 cells were grown in culture and treated with (1) media alone, (2) Con A, (3) FK-506, and (4) Con A + FK-506. Proliferation to Con A was determined by treating cells with 10 micrograms/ml Con A +/- FK-506 and measuring [3H]TdR uptake. Reverse transcriptase-polymerase chain reaction amplification was used to quantitate the level of IL-4 mRNA expression. FK-506 markedly inhibits Con A-induced proliferation and IL-4 mRNA production by the T-helper 2 cell line Ly1+2-/9. The ability of FK-506 to block the proliferation and IL-4 production by this helper cell subset suggests that this effect may contribute to its observed marked immunosuppressive properties in vitro and in vivo.

Cell Division↗

Patterns of survival in patients with advanced Hodgkin's disease (HD) treated in a single centre over 20 years.

A total of 164 consecutive adults with newly confirmed stage IIIB, IVA or IVB Hodgkin's disease (HD) commenced cyclical combination chemotherapy comprising mustine, vinblastine, prednisolone and procarbazine (MVPP) every 6 weeks (145 patients) or minor variants (19) at St Bartholomew's Hospital between 1968 and 1984. The median follow-up period is 14 years. Complete remission (CR) was achieved in 97/164 (59%) and partial remission (PR) in 23/164 (14%) with lesser responses or death being documented in 44. Achievement of CR correlated with stage, serum albumin and serum beta2 microglobulin level at presentation on univariate and multivariate analysis; 55/97 (58%) remain in continuous CR, the median duration of remission not having been reached. Twelve patients died in first remission; there have been 30 recurrences, one occurring after 13 years. Second remission was achieved in 17/30; 6/17 remain in continuous second remission and two have died in second remission. There have been nine second recurrences, third remission being achieved in 6/9. Two continue in third remission, two patients have died in third remission: 82/164 patients are alive with a minimum follow-up of 6 years. Eighty-two patients have died; 66 with evidence of HD, six with second malignancy, one each of haemorrhage and infection, eight of unrelated causes, the cause of death was unknown in one. The overall median survival from presentation is 14 years, being the same for patients in CR and PR with minimal residual abnormality (good partial remission, GPR), and being better for those for whom remission was achieved than those for whom it was not. The median survival following first recurrence is 4 years, being significantly longer for younger patients (less than 50 years). These results emphasise the importance of long-term follow-up to determine the clinical course of HD and are vital for planning experimental chemotherapy at the time of early treatment failure or recurrence.

Adolescent↗

Effects of n-3 fatty acids on postprandial triacylglycerol and hormone concentrations in normal subjects.

The present study reports results from two investigations to determine effects of a 6-week period of moderate n-3 fatty acid supplementation (2.7 g/d) on fasting and on postprandial triacylglycerol and metabolic hormone concentrations in response to standard test meals. In the first study postprandial responses were followed for 210 min after an early morning test meal challenge; in the second study responses to an evening test meal were followed during the evening and overnight for a total period of 12 h. In both studies postprandial triacylglycerol responses to the test meals were significantly reduced after compared with before fish-oil supplementation. In the second study the triacylglycerol peak response seen between 200 and 400 min in subjects studied before supplementation with fish oils was almost completely absent in the same subjects after 6 weeks of n-3 fatty acid supplementation. Analysis of fasting concentrations of metabolites and hormones was carried out on the combined data from the two studies. There were no significant differences in total, low-density-lipoprotein- or high-density-lipoprotein-cholesterol concentrations during fish-oil supplementation, although there was considerable individual variation in cholesterol responses to the supplement. Concentrations of Apo-B and Apo-A1 were unchanged during supplementation with fish oils. Fasting and early morning postprandial GIP concentrations were lower in subjects taking fish oils, possibly due to acute effects of fish-oil capsules taken on the evening before the studies. In both studies fasting insulin and glucose and postprandial insulin concentrations remained unchanged following fish-oil supplementation. The results do not support the view that triacylglycerol-lowering effects of n-3 fatty acids are due to modulation of insulin secretion mediated via the enteroinsular axis. Further studies are required to determine the precise mechanism by which fish oils reduce both fasting and postprandial triacylglycerol concentrations.

Adult↗

Stress, sexual satisfaction, and marital adjustment in infertile couples.

A longitudinal study was designed to assess the effects of infertility as well as the influence of the subsequent medical investigation on marital functioning. During their initial visit at a fertility clinic, 165 couples underwent psychological assessment. Questionnaires were completed to assess stress, sexual satisfaction, and marital adjustment. Participants were categorized into those who became pregnant during the 12 months of the study (n = 48 couples) and those for whom treatment was not successful (n = 117 couples). Significant increases in stress and decreases in marital functioning were experienced by subjects as the treatment investigation progressed. Furthermore, greater levels of marital distress were observed in couples that did not conceive. Significant gender differences were observed.

Adult↗

Morphologic and histochemical characteristics of skeletal muscle after long-term intramuscular electrical stimulation.

The purpose of this investigation was to examine the morphologic and histochemical characteristics of paraspinal muscles in patients with scoliosis after long-term electrical stimulation. Thirty-six children with idiopathic scoliosis, who had been treated with implantable muscle stimulators, had paraspinal muscle biopsies at the time of implantable muscle stimulator removal. Group A patients whose curve did not progress, had 2.9 years of stimulation stopped at skeletal maturity, with a further 1.5 years of nonstimulation before implant removal and biopsy. In group B patients, who had an average of 2.3 years of stimulation, the curve progressed and stimulation was continued until fusion and biopsy. Neither group showed any increase in the frequency of pathologic changes of paraspinal muscles contrasted with values reported in the literature for scoliotic muscle. In group A patients there was an increased proportion of type 1 fibers on the convex side of the curve compared to the concavity. Despite this finding the curves did not require fusion, suggesting that the increased percentage of type 1 fibers was not the cause of the scoliosis. In group B patients there was an even higher type 1 concentration on the convex side contrasted to the convex side of group A patients.

Adolescent↗

Noncollagenous (NC1) domain of collagen VII resembles multidomain adhesion proteins involved in tissue-specific organization of extracellular matrix.

Type VII collagen (C7) is a stratified squamous epithelial basement membrane protein composed of three identical alpha chains, each consisting of a 145-kDa amino-terminal noncollagenous (NC1) domain and a 145-kDa carboxyl-terminal collagenous domain. Morphologic and biochemical studies have shown that tissue-specific aggregates of C7 dimers called anchoring fibrils may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV collagen. In this study, we cloned a cDNA encoding most of the NC1 domain of C7. The deduced amino acid sequence revealed motifs characteristic of multidomain ECM proteins that contribute to the tissue-specific organization of ECM including a region of 7 1/2 sequential fibronectin type III (Fn III) homology repeats, a potential collagen-binding region homologous to the A domain of von Willebrand factor (vWf) and an RGD sequence. A purified C7 fusion protein containing these motifs specifically bound to type IV collagen in a functional assay. These results suggest that regions within the NC1 domain of C7 mediate interactions with lamina densa and dermal ECM proteins including type IV collagen. Structural mutations and autoepitopes in these regions may represent mechanisms for the development of defective basement membrane organization and adherence in genetic and autoimmune forms of epidermolysis bullosa.

Amino Acid Sequence↗

Preoperative laser therapy in a patient with resectable bronchogenic carcinoma and severe coronary artery disease.

A 67 year old man with severe coronary artery disease was found to have a resectable bronchogenic carcinoma. Myocardial revascularisation and lung resection were considered to be unduly hazardous as either separate or combined operations. Preoperative laser therapy, however, enabled the two procedures to be performed in greater safety in the most appropriate sequence.

Aged↗

Can MR imaging effectively replace diagnostic arthroscopy?

A study was performed to determine whether magnetic resonance (MR) imaging is cost-effective and reduces the need for diagnostic arthroscopy of the knee. During a 9-month period, 103 consecutive patients with knee injury that justified diagnostic arthroscopy underwent MR imaging. The MR images were interpreted by means of consensus of three radiologists and reviewed with the referring sports medicine orthopedists. After the examination, 44 patients (42.7%) underwent immediate arthroscopy. The 59 other patients (57.3%) did not undergo arthroscopy; follow-up was performed in 55 of these 59 patients (93%) at a mean of 22 months. The outcome was successful in 49 of 55 patients (89%); 40 patients had normal function and no limitation in activity, six patients with chronic injury of the anterior cruciate ligament underwent reconstruction, and three patients underwent arthroscopy with negative findings. Without the use of MR imaging, all patients in this study would have undergone diagnostic arthroscopy. Because of the diagnoses based on MR images, 53 patients (51.4%) avoided a potentially unnecessary diagnostic arthroscopy, and, as a result, the net savings was $103,700 in the 103 patients.

Adolescent↗

Continuous arteriovenous hemofiltration: an alternative dialysis therapy in neonates.

Modifications have made it possible to perform CAVH in the neonate. One of these is decreasing the extravascular volume in the tubing and filter to a minimal amount to allow for adequate intravascular blood volume in the infant. Another is utilizing predilutional fluid to decrease the need for heparinization. A third modification is utilizing the suction-assist pumps to help control the amount of fluid removed from the infant. With modifications of this system to fit the special needs of neonates and intensive nursing and medical management, CAVH can be a successful alternative to traditional dialysis therapies in neonates.

Acute Kidney Injury↗

A high proportion of early response genes are constitutively activated in T cells by HTLV-I.

Immortalization of T cells by HTLV-I is mediated by the X region of the virus and probably involves transactivation of cellular genes. We show that T cells transformed by HTLV-I constitutively express a high proportion of early response genes that are normally transiently induced following antigenic or mitogenic activation of T cells. Thus, HTLV-I-infected T cells display an 'early activation' phenotype that is distinct from the gene expression pattern of continuously dividing T cells. Ten early response genes representing a diverse array of functional categories were assayed. Four DNA-binding proteins/transcription factors including the p50 subunit of NF-kappa B were evaluated. A protein(s) encoded by the X region of HTLV-I appeared to contribute to up-regulated expression of most, if not all, of the early response genes. For those genes that could be assayed, increased transcriptional rates, but not substantial changes in mRNA half-life, were demonstrated in the presence of pX-encoded proteins, suggesting that the transcriptional transactivator, Tax, affects the induction or maintenance of transcription for these mitogen-inducible genes. Therefore, Tax may mimic or interact with a component(s) of the signal transduction pathway activated by antigen or mitogen treatment. These data demonstrate that early response genes, some of which probably play roles in initiating or maintaining cellular proliferation, are frequent targets of HTLV-I activation.

Blotting, Northern↗

Regulation of skeletal muscle stiffness and elasticity by titin isoforms: a test of the segmental extension model of resting tension.

To explore the role of titin filaments in muscle elasticity, we measured the resting tension-sarcomere length curves of six rabbit skeletal muscles that express three size classes of titin isoform. The stress-strain curves of the split fibers of these muscles displayed a similar multiphasic shape, with an exponential increase in tension at low sarcomere strain followed by a leveling of tension and a decrease in stiffness at and beyond an elastic limit (yield point) at higher sarcomere strain. Significantly, positive correlations exist between the size of the expressed titin isoform, the sarcomere length at the onset of exponential resting tension, and the yield point of each muscle. Immunoelectron microscopic studies of an epitope in the extensible segment of titin revealed a transition in the elastic behavior of the titin filaments near the yield point sarcomere length of these muscles, providing direct evidence of titin's involvement in the genesis of resting tension. Our data led to the formulation of a segmental extension model of resting tension that recognizes the interplay of three major factors in shaping the stress-strain curves: the net contour length of an extensible segment of titin filaments (between the Z line and the ends of the thick filaments), the intrinsic molecular elasticity of titin, and the strength of titin thick filament anchorage. Our data further suggest that skeletal muscle cells may control and modulate stiffness and elastic limit coordinately by selective expression of specific titin isoforms.

Animals↗

Pulmonary hypertension induced by amosite asbestos: a physiological and morphologic study in the guinea pig.

Although there is increasing evidence that mineral dust exposure will produce obstructive lung disease, there is little information on the effects of mineral dust on the pulmonary vascular system. To examine whether exposure to amosite asbestos would affect the pulmonary vasculature and produce pulmonary hypertension, we instilled 5 mg amosite asbestor intratracheally into guinea pigs. After periods of 3 and 6 months, we examined their pulmonary and pulmonary vascular function, and compared these data to those obtained from groups of control animals. We found that, at both time periods, there was pulmonary arterial hypertension, with alteration of the vascular pressure-flow relationships. This was accompanied by abnormalities in the structure of the small pulmonary arterioles. The animals also showed airflow obstruction, with air trapping and an upward shift of the pressure-volume curve. There was evidence of emphysema, and the animals were moderately hypoxic. We found no consistent increase in inflammatory cells either in lavage or peripheral blood, and the histamine dose-response curves were similar in control and asbestos-exposed animals at 6 months. We conclude that intratracheal instillation of asbestos in the guinea pig produces pulmonary hypertension associated with modest hypoxia, emphysema, and airflow obstruction. Whether pulmonary hypertension reflects emphysema-induced hypoxia and loss of vascular bed, or is related to the brief but intense inflammatory infiltrate induced by asbestos, is unclear.

Animals↗