Renal failure after flunixin meglumine administration.
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Acute Kidney Injury↗
Biomedical subjects
K Simpson
Publications and source records attributed to K Simpson.
Recovery from experimental parkinsonism in primates with GM1 ganglioside treatment.
A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with GM1 ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with GM1 ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry. These results suggest that GM1 ganglioside may hold promise as a therapeutic agent for the treatment of Parkinson's disease.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Search for retrovirus in the chronic fatigue syndrome.
AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus. METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques. RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus. CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.
Blotting, Southern↗
Randomised controlled trial of weightlifting exercise in patients with chronic airflow limitation.
UNLABELLED: BACKGROUND PATIENTS: with chronic airflow obstruction are often limited by muscle fatigue and weakness. As exercise rehabilitation programmes have produced modest improvements at best a study was designed to determine whether specific muscle training techniques are helpful. METHODS: Thirty four patients with chronic airflow limitation (forced expiratory volume in one second (FEV1) 38% of predicted values) were stratified for FEV1 to vital capacity (VC) ratio less than 40% and arterial oxygen desaturation during exercise and randomised to a control or weightlifting training group. In the experimental group training was prescribed for upper and lower limb muscles as a percentage of the maximum weight that could be lifted once only. It was carried out three times a week for eight weeks. RESULTS: Three subjects dropped out of each group; results in the remaining 14 patients in each group were analysed. Adherence in the training group was 90%. In the trained subjects muscle strength and endurance time during cycling at 80% of maximum power output increased by 73% from 518 (SE69) to 898 (95) s, with control subjects showing no change (506 (86) s before training and 479 (89) s after training). No significant changes in maximum cycle ergometer exercise capacity or distance walked in six minutes were found in either group. Responses to a chronic respiratory questionnaire showed significant improvements in dyspnoea and mastery of daily living activities in the trained group. CONCLUSIONS: Weightlifting training may be successfully used in patients with chronic airflow limitation, with benefits in muscle strength, exercise endurance, and subjective responses to some of the demands of daily living.
Aged↗
An in vitro technique to assess oxygenator potential for respiratory failure therapies.
To assess microporous membrane oxygenators (MMO) for long-term respiratory support, an in vitro test of 4 days duration has been developed. The objective is to screen oxygenators before they undergo expensive animal trials. As a sensitive indicator of performance change, CO2 transfer rates (VCO2) are determined with fresh bovine blood at the start, after 48 hours and after 96 hours of perfusion. Blood is used only for gas exchange evaluation and is replaced with plasma in the intervening periods. Data are obtained at blood flow rates (QB) of 1.0, 1.5 and 2.0 l/min for gas: blood flow ratios (QG:QB) of 2:1 and 5:1. The test has been conducted on Bentley BOS-CM50 oxygenators (n = 10). With heated dry air ventilation there was no significant change in VCO2 with time for all QB and QG:QB combinations. Plasma leakage did not occur into the gas compartment of the MMO. Similar results were obtained with heated humidified air ventilation. The findings are in agreement with existing animal studies of 4-7 days duration.
Animals↗
Malignant mastocytosis with circulating mast cells.
A case of malignant mastocytosis with peripheral blood involvement is presented. The course of the patient's illness was complicated by recurrent hypotensive episodes, presumed to have been caused by mast cell degranulation. Treatment with hydroxyurea was associated with persistent hypotension which resulted in death. It has been proposed that the diagnosis of mast cell leukemia be given to patients presenting with greater than 10% atypical mast cells in the blood. However, review of 16 published cases of malignant mastocytosis with circulating mast cells reveals that the clinical manifestations, complications, and survival do not vary significantly with the percentage of peripheral blood mast cells. Patients with malignant mastocytosis with significant involvement by atypical mast cells in the bone marrow and peripheral blood should be considered as having an aggressive disease, regardless of the percentage of circulating mast cells.
Biopsy↗
Progressive interstitial collagen deposition in Coxsackievirus B3-induced murine myocarditis.
Myocardial fibrosis can be produced in certain inbred strains of mice after coxsackievirus B subtype 3 (CVB3) infection. The mechanism responsible for this interstitial matrix alteration is unknown. The presumption is that fibrosis occurs in areas of myocyte damage and inflammation associated with viral infection, analogous to scar formation after cell injury in other organ systems. To test this hypothesis, we examined the hearts of A/J strain mice infected with three CVB3 variants (Crowell [CVB3-CR], Woodruff [CVB3-WD], and Lerner [CVB3-LR]), each known to cause different degrees of acute myocardial injury. With these three variants, virus was present in the heart until day 28 after inoculation but was absent thereafter. Fourteen days after inoculation, inflammation with myocyte necrosis was seen in discrete foci throughout the myocardium with all three variants. Collapse and disorganization of the usually delicate connective tissue matrix identifiable by silver impregnation was seen in these areas of myocyte injury. Persistent, diffuse lymphocytic infiltration of the myocardium was seen 55 days after inoculation with CVB3-WD and CVB3-LR, but hearts initially infected with CVB3-CR showed only rare interstitial lymphocytes comparable to uninfected control hearts. The focal scars produced by myocyte necrosis 14 days after inoculation were accentuated and heavily collagenized 55 days after inoculation with CVB3-WD and CVB3-LR; however, these foci were indistinct 55 days after inoculation with CVB3-CR. Furthermore, the usually delicate network of interstitial collagen fibers surrounding individual myocytes became thickened throughout the heart 55 days after inoculation with CVB3-WD and CVB3-LR, away from visibly scarred areas produced early after infection with these variants. This diffuse reticulin thickening was not seen after infection with the Crowell variant. Only the virus variants associated with persistent interstitial inflammation at day 55 developed major collagen matrix alterations and interstitial fibrosis. We conclude that this persistent interstitial lymphocytic infiltration reflects altered immune function related to specific virus variants in this animal strain. We postulate that these lymphocytes are part of a delayed immunopathogenic response uncoupled from the original viral injury and inflammatory damage. Potential mechanisms by which this interstitial lymphocytic infiltration results in fibrosis are discussed.
Animals↗
Coxsackievirus-B3-induced myocarditis: virus receptor antibodies modulate myocarditis.
Two variants of coxsackievirus group B, type 3 (CVB3) differ in ability to induce myocarditis in Balb/cCUM mice. Infection with the highly pathogenic variant (CVB3M) stimulates autoimmunity to normal cardiocyte antigens, and tissue injury results primarily from an autoreactive cytolytic T lymphocyte (ACTL). Animals infected with the less pathogenic CVB3o variant do not develop ACTL, although CVB3o replicates to high titers in the heart and polyclonal neutralizing antisera fail to distinguish between the two variant virions. The present study uses two IgM mAb derived by fusing spleen cells from CVB3M-infected mice with NS-1 cells. These mAb investigate important differences between the virus variants that may explain why only selected infections trigger autoimmunity. mAb 8A6 is a virus-neutralizing antibody that prevents infection of HeLa cells and cultured cardiocytes by attaching to the virus. mAb 10A1 also interferes with infection but presumably reacts to the virus receptor on the susceptible cells and shows little or no binding to the virions. While 8A6 is equally effective in neutralizing both CVB3o and CVB3M, suggesting that antigenic epitopes on both variants are either identical or highly cross-reactive, 10A1 distinguishes between the variants, suggesting that the pathogenic and less pathogenic viruses use distinct cell surface receptors. Competitive binding studies using radiolabeled CVB3M and either of the unlabeled variants confirm this hypothesis. Both mAb effectively prevent CVB3M-induced cardiac damage in vivo. mAb 10A1 also inhibits autoreactive ACTL lysis of cardiocytes, indicating that the autoimmune effectors may recognize the virus receptor, and that the receptor utilized by a virus may prove important in triggering auto-sensitization.
Animals↗
Tissue specific defect of complex I of the mitochondrial respiratory chain.
Deficiency of complex I is one of the most commonly reported defects of the mitochondrial respiratory chain in man. Clinical evidence of tissue specific expression of complex I deficiency has not previously been confirmed biochemically. We report here slow oxidation of NAD+-linked substrates, low activity of complex I and low amounts of immunoreactive complex I peptides in skeletal muscle mitochondria from a patient with muscle weakness and lactic acidosis. In liver mitochondria complex I activity was normal and all the immunoreactive subunits of complex I were present in normal amounts.
Child↗
Community psychiatric nursing--a research-based profession?
This paper examines the relationship between research and professionalism, and considers the question of why research is necessary for the development of nursing. Suggestions which have been made for areas suitable for community psychiatric nursing research are looked at, and comments from various authors regarding the lack of evaluative (as opposed to descriptive or prescriptive) studies are noted. The paper goes on to look at recent CPN research, and finds mainly small-scale and locally-oriented studies. Three studies which look at the work of community psychiatric nurses (CPNs) in detail are examined; two of these found CPN practice to be lacking in any research or theory base, and in effect suggested therapeutic incompetence in dealing with neurotic clients. The third concluded the opposite, but suggested a need for more specialized training. The paper, which includes an appendix an overview of 36 recent (1983-1988) research studies of interest to CPNs, concludes that, if research is necessary precursor to autonomous professional development, such research into CPN practice has yet to be done.
Community Mental Health Services↗
Coxsackievirus-induced disease. CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice.
DBA/2 male mice inoculated intraperitoneally with 1.8 X 10(5) plaque-forming units (PFU) coxsackievirus B-3 (CVB3) showed extensive inflammatory cell infiltration of the myocardium and acinar tissue of the pancreas in 7 days. Selective depletion of T lymphocyte subpopulations indicated that CD4 cells were either completely or partially responsible for cell damage in both organs. Other organs such as the liver were infected and contained virus titers equivalent to those seen in the heart and pancreas but showed no apparent tissue injury. The role of the CD4 cell was confirmed by positive selection of either T cell subpopulation from CVB3-immune lymphocytes in vitro and adoptive transfer of these cells into T cell-deficient (thymectomized, irradiated, bone marrow reconstituted, TXBM) DBA/2 recipients. Lymphocytes from CVB3-infected donor mice were adsorbed to myocyte, skin fibroblast, or liver vascular endothelial cell (VEC) monolayers. The adherent population was retrieved and adoptively transferred into uninfected syngeneic recipients. When killed 7 days later, the animals receiving unfractionated immune lymphocytes or cells eluted from heart monolayers developed both myocarditis and pancreatitis. Anti-Thy 1.2 and C' treatment of the unfractionated cells completely abrogated transfer of disease. Cells eluted from either fibroblast or liver VEC monolayers showed no pathogenicity. Adsorption of immune cells to heart monolayers in the presence of anti-IAd (class II major histocompatibility complex antigen, MHC) inhibited attachment of the pathogenic T cell, whereas anti KdDd (a class I MHC antigen) had no effect.
Animals↗
Surgical therapy for left ventricular aneurysms. A ten-year experience.
We reviewed retrospectively the surgical results of left ventricular aneurysm reduction in 197 consecutive patients operated on in 1977-1987. There were 19 hospital deaths (9.6%) and 38 late deaths. The cumulative 5- and 10-year survival probabilities were 79% and 67%. Of the 140 late survivors, 130 underwent follow-up study in 1988 (mean, 5 years postsurgery). We analyzed preoperative, perioperative, and postoperative variables to evaluate the efficacy of surgical therapy. The risk of early mortality was increased by worsening preoperative New York Heart Association class, operation within 30 days of myocardial infarction, combinations of ventricular arrhythmia and congestive heart failure, renal failure, and preoperative cardiogenic shock. There was a trend toward increased early mortality with multivessel coronary artery disease. Late mortality and length of survival were not predicted by any variable examined.
Actuarial Analysis↗
Influence of haemodialysis membranes on the release of granulocyte elastase.
The advantages of multiparameter assessment in the evaluation of the blood compatibility of biomaterials underline the importance of investigating possible relevant parameters. In this respect, a study has been made of granulocyte elastase to establish the influence of haemodialysis membranes on the release of this serine proteinase. Plasma levels of granulocyte elastase were determined as a complex with its natural inhibiter, alpha 1-proteinase. This elastase - alpha 1 proteinase (E- alpha 1 Pi) inhibitor complex was measured by a highly sensitive enzyme-linked immunoassay. The membranes evaluated were Cuprophan (15-11, Travenol) and polysulphone (F40, Fresenius). Samples were taken from patients undergoing maintenance haemodialysis, before the start of dialysis, after 15 and 90 minutes and again at the end of dialysis (4 h). This investigation clearly demonstrates the different response of the dialysers, and on correcting for surface area, the end-dialysis level of E-alpha 1 Pi remained significantly greater for the Cuprophan membrane. The results support the view that the release of granulocyte elastase is a relevant parameter for inclusion in membrane compatibility assessment.
Biocompatible Materials↗
Immunopathogenic mechanisms in experimental picornavirus-induced autoimmunity.
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Animals↗
Haemodynamic response to magnesium administration in mineralocorticoid-salt and two-kidney, one clip renovascular hypertension.
Recent interest has centred on the role of divalent cations in hypertension, particularly in relation to the renin-angiotensin system. This study was undertaken to determine the hypotensive effect of magnesium administration in relation to the state of activation of the renin-angiotensin system. The mean blood pressure (MBP) and heart rate (HR) response to either the acute intravenous administration of a pharmacological dose of MgSO4 or vehicle was determined in conscious mineralocorticoid-salt (DOCA-salt, low-renin) and two-kidney, one clip renovascular, high-renin hypertensive rats. Baseline MBP was higher in the renovascular than in the DOCA-salt rats, while there was no difference in HR or serum Mg concentration between the two. Following administration of MgSO4, serum Mg increased equally in both the DOCA-salt (1.4 +/- 0.8 to 4.9 +/- 0.16 mEq/l; P less than 0.001) and in the renovascular rats (1.8 +/- 0.14 to 4.4 +/- 0.27 mEq/l; P less than 0.001). Magnesium administration significantly lowered MBP over the 1-h infusion in the DOCA-salt (167 +/- 8 to 145 +/- 5 mmHg, P less than 0.001) but not the renovascular hypertensive rats (191 +/- 5 to 183 +/- 4, NS). We conclude that the blood pressure lowering effect of Mg is related, in part, to the state of activation of the renin-angiotensin system. The mechanism of this differential effect remains to be determined.
Animals↗
Unknown syndrome: abnormal facies, congenital heart defects, hypothyroidism, and severe retardation.
We present a female infant with (1) abnormal facies: microcephaly, blepharophimosis, small, low set, posteriorly rotated ears, bulbous nose, carp shaped mouth, micrognathia; (2) congenital heart abnormalities: large atrial and ventricular septal defects; (3) congenital hypothyroidism; (4) severe global retardation.
Abnormalities, Multiple↗
Microcephaly, microphthalmos, and retinal folds: report of a family.
A retarded boy with microcephaly, microphthalmos, and retinal folds is described. His mother and sister showed microphthalmos and the sister was also microcephalic. Another family showing similar findings has been described, indicating that this combination of abnormalities constitutes a discrete entity showing single gene inheritance.
Abnormalities, Multiple↗
Serum oxalate in chronic renal failure.
Serum oxalate is easily controlled in patients with chronic renal failure not yet on dialysis by dietary protein restriction but poorly controlled by both haemodialysis and continuous ambulatory peritoneal dialysis (CAPD). In the control of serum oxalate in chronic renal failure dietary protein restriction is effective in the pre-dialysis patient whereas both CAPD and haemodialysis are relatively inefficient in end-stage renal failure.
Adult↗