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Biomedical subjects

R Morris

Publications and source records attributed to R Morris.

At least 199 records · Page 11Linked to original sources
PubMed1995

Level of receptor-associated protein moderates cellular susceptibility to pseudomonas exotoxin A.

Pseudomonas exotoxin A (PE) enters mammalian cells via a receptor-mediated endocytic pathway. The initial step in this pathway is binding to the multiligand receptor termed the alpha 2-macroglobulin receptor/low-density lipoprotein receptor-related protein (LRP). Binding of toxin, and of the many other ligands that bind to LRP, is blocked by the addition of a 39-kDa receptor-associated protein (RAP). Here we show that approximately 40% of the cell-associated LRP is on the surface of toxin-sensitive mouse LM fibroblasts and thus accessible for toxin internalization. The remainder is located intracellularly, primarily in the Golgi region. Mammalian cells exhibit a wide range of sensitivity to PE. To investigate possible reasons for this, we examined the expression levels of both LRP and RAP. Results from a variety of cell lines indicated that there was a positive correlation between LRP expression and toxin sensitivity. In the absence of LRP, cells were as much as 200-fold more resistant to PE compared with sensitive cells. A second group of resistant cells expressed LRP but had a high level of RAP. Thus, a toxin-resistant phenotype would be expected when cells expressed either low levels of LRP or high levels of LRP in the presence of high levels of RAP. We hypothesize that RAP has a pivotal role in moderating cellular susceptibility to PE.

ADP Ribose Transferases↗
PubMed1995

Reduced in-hospital mortality from acute myocardial infarction with general adoption of thrombolytic treatment in the North West Thames health region 1979-1991.

OBJECTIVE: To determine the impact of studies of thrombolytic treatment in acute myocardial infarction on inhospital mortality. DESIGN: Retrospective study. SETTING: All 21 major hospitals in the North West Thames health region. PATIENTS: 63,903 patients with acute myocardial infarction. STUDY PERIOD: 1979-1991. MAIN OUTCOME MEASURES: in-hospital mortality. RESULTS: Overall mortality decreased by 5.2% from 25.4% to 20.2% (P < 0.0001) (95% confidence interval (CI) 3.4 to 6.6). Male mortality decreased by 6.5% from 22.3% to 15.8% (P < 0.0001) (95% CI 4.8 to 8.4); female mortality decreased by 4.3% from 32.6% to 28.3% (P < 0.01) (95% CI 1.3 to 7.4). Reductions in mortality occurred in all age and sex groups but were greater in younger patients. Logistic regression analysis of death rates showed that the odds ratio of death in 1991 compared with that in 1979 was 0.75 (95% CI 0.69 to 0.82). After allowing for the effects of age and sex, this odds ratio became 0.54 (95% CI 0.49 to 0.59), as more elderly patients were treated in 1991. Purchase of streptokinase increased 31-fold from 116 doses in 1983 to 3554 doses in 1991. There was a pronounced negative association between annual purchases of streptokinase and mortality (Kendall's rank correlation = -0.86, P = 0.003). Changes in clinical practice resulted in the saving of the lives of an estimated 600 patients with acute myocardial infarction in 1991. This extrapolates to an annual saving of 10,500 lives in the United Kingdom. CONCLUSIONS: In the past few years thrombolytic treatment has been widely adopted for the management of acute myocardial infarction. This has been paralleled by a substantial reduction in in-hospital mortality.

Adult↗
PubMed1995

Correlates of recurrent wheezing in school-age children. The Physicians of Raleigh Pediatric Associates.

Correlates of recurrent wheezing were examined in a case-control study involving 343 children ranging from 7 to 12 yr of age and recruited from a general pediatric practice. Positive skin tests for allergy were observed in 35% of a random sample of children without recurrent wheezing, and in 77% and 90% of children who had experienced from two to four episodes and five or more episodes, respectively, of recent wheezing. By logistic regression analysis, sensitization to dust mite (odds ratio [OR]: 5.2; 95% CI: 3.0 to 9.0), cat (OR: 15.5; 95% CI: 3.4 to 70.8), and Alternaria (OR: 6.8; 95% CI: 2.1 to 21.5) antigens was consistently associated with recurrent wheezing. Sensitization to pollen antigen(s), observed in 60% of allergic children, was not associated with wheezing. A family history of asthma was a significant predictor of recurrent wheezing (OR: 3.2; 95% CI: 1.7 to 5.9) after adjusting for its association with positive skin tests. Environmental tobacco smoke (ETS) exposure was associated with an increased risk of recurrent wheezing in nonallergic children and in allergic females, but not in allergic males. ETS exposure was not associated with positive skin tests for allergy. A history of wheezing with respiratory illness before 2 yr of age was associated with a modest risk of recurrent wheezing between 7 and 12 yr of age (OR: 2.3; 95% CI: 1.2 to 4.6), a risk that did not differ by allergic status or gender. Theoretically, the prevalence of recurrent wheezing in this population could be reduced approximately 65% by controlling exposure to indoor allergens and ETS.

Allergens↗
PubMed1995

Improvement in depression-related cognitive dysfunction following ECT.

Long-term cognitive changes were observed in 8 depressed patients whose pretreatment cognitive impairment (depressive dementia or pseudodementia) resolved after treatment with ECT. Improved performance on the Mattis Dementia Rating Scale was maintained throughout a 4-year follow-up period. Improvements on Memory and Initiation and Perseveration subscales were most consistent over time. These aspects of cognitive functioning may be the most susceptible to the effects of depression, and this may be a factor to consider in clinically evaluating older patients with both depression and cognitive impairment. The findings indicate that elderly patients with cognitive dysfunction secondary to depression may experience improvement in cognitive functioning that is stable over time with remission of the affective disorder.

Aged↗
PubMed1995

Percentage scattergram to depict changes in large amounts of data over time.

Graphical representation of changes in epidemiologic or clinical parameters over time is difficult when a large amount of data is involved. The traditional methods either cannot incorporate all necessary information (bar graphs, pie charts, tables) or are unable to depict information on more than a limited number of individuals (scattergrams). We have designed an effective way of visual presentation of the changes a variable demonstrates over time. The percentage scattergram provides accurate and complete depiction of any number of data points, allowing comprehensive and rapid analysis.

Data Display↗
PubMed1995

Development of speech perception and speech production in a primary school-age child using Tactaid VII.

An 11-year-old, profoundly deaf boy was fitted with a Tactaid VII in 1993, and he has received fortnightly training sessions since. There have been significant and functional gains in speech perception, speech production, and speech-reading, particularly in the perception and production of spectral features. These changes and the assessment results obtained will be discussed in the paper.

Child↗
PubMed1995

Understanding variations in lengths of stay between hospitals for fractured neck of femur patients and the potential consequences of reduced stay targets.

BACKGROUND: Economic incentives exist to scrutinize length of stay variations between hospitals. However, the reasons for variations can be complex, and without knowing these the feasibility of shorter stay targets, and their implications for patient outcome, are unclear. METHODS: This research compared care received by patients admitted for fractured neck of femur at an inner-city university teaching hospital, an inner-city associated teaching hospital and an associated teaching hospital in an urban setting. Multiple regression and descriptive analysis were used to examine how in-patient acute stay was affected by the severity of cases on admission and the supply of beds beyond the acute setting. Data on patient outcome were mortality up to three months post fracture and functional ability at in-patient discharge and three months post fracture. RESULTS: A total of 492 patients were recruited. Patient outcomes at three months were similar at the hospitals. Multiple regression revealed significant differences between the patient stay of the inner-city teaching hospital and the urban associated teaching hospital. A difference in stay of around 14 days was demonstrated, with the urban hospital having the shorter stay. These differences were linked it to having a greater supply of non-acute beds. CONCLUSION: Significant differences in patient stay between hospitals can be due to factors beyond the direct control of the acute unit. Economic incentives may mean that purchasers and providers ignore a full analysis of these factors and set length of stay targets which are not feasible in the short term. This could reduce the quality and impair the outcome of patient care.

Activities of Daily Living↗
PubMed1995

Grading of cellular rejection after orthotopic liver transplantation.

All 684 post-orthotopic liver transplantation (OLT) liver biopsies performed at the Royal Free Hospital (RFH) between 1988 and 1993, from 120 patients, were reviewed in order to try to define the relative importance of the histological features of immunosuppression-responsive cellular rejection. Twenty histological features considered to be possible contributors to the diagnosis of cellular rejection were documented in a binary (present/absent) fashion. These features in 106 biopsy specimens obtained 1 to 8 days after OLT were analyzed using stepwise logistic discriminant analysis. All clinical and treatment records were reviewed, and each biopsy specimen was assigned to a diagnostic category depending on these records and follow-up information. Important determinants of the histological diagnosis of cellular rejection (which occurred in 84 of the 106 cases) were moderate/severe mixed portal inflammation, eosinophils, endotheliitis, and bile duct damage. When these all occurred together, the odds of rejection increased 3.6-fold. The original histological diagnosis was recorded, and each biopsy specimen showing cellular rejection was regarded according to the specific criteria of Snover et al., Demetris et al., and a novel RFH scoring system. The latter consists of evaluating portal inflammation, endotheliitis, eosinophils, and bile duct damage, each on a 0 to 3 scale (none, mild, moderate, or severe, respectively) and summation. The resulting cellular rejection score thus can range from 0 to 12. The agreement between the different scoring systems was analyzed using K statistics, and there was good concordance (K, 0.64 to 0.78), despite different histological criteria being used to derive each score. Each system showed a similar degree of sensitivity (87% to 96%). The specificity ranged from 59% to 77%. We conclude that the histological diagnosis of cellular rejection relies mainly on the previously described features of mixed portal inflammation, endotheliitis, eosinophils, and duct damage. There is scope for unification and simplification of the existing grading systems, which depend on differing criteria, and we suggest one such scheme.

Biopsy↗
PubMed1995

Outcome following fractured neck of femur--variation in acute hospital care or case mix?

BACKGROUND: This study examined the quality of care given to patients admitted to hospital with a fractured neck of femur by assessing the link between outcome, case severity and resource use. Fractured neck of femur was chosen for this study as it is a common condition amongst elderly people which causes considerable morbidity and mortality, uses a high proportion of acute hospital resources and is a condition where virtually all new cases will come under the care of the hospital service. METHODS: Three hospitals which had different case fatality rates and costs were included in the study. These were an inner-city teaching hospital (Hospital 1), an inner-city associated teaching hospital (Hospital 2) and an associated teaching hospital in an urban location (Hospital 3). Patients were recruited for this study over a 12-month period. Details on case severity and basic demographic date were collected on admission, and information on the process of care was collected during the hospital stay. Four outcome measures were addressed: activities of daily living (ADL) before discharge and at three months post-fracture; mortality up to 12 months post-fracture; complications occurring after admission to hospital; and destination on discharge. RESULTS: A total of 492 patients were recruited into the study, with a male to female ratio of 1:4 and an age range of 60-101 years. Patients admitted to the three hospitals showed no difference with respect to the presence of co-morbidities, medication, pre-fracture ADL, mental state, age and sex. There were some differences observed in pre-fractured place of residence. Hospital 1 had the highest proportion of patients admitted from sheltered housing and other hospital. Hospital 2 the highest proportion from residential homes, and Hospital 3 the highest proportion admitted from their own homes. Hospital 3 discharged patients at an earlier stage of recovery in that a higher proportion were discharged with a poor ADL index. This hospital also had more orthopaedic complications but fewer medical complications; however, the outcome in terms of ADL at three months post-fracture and mortality at 12 months was similar in all three hospitals. The severity variables which predicted poor outcome were co-morbidities, impaired mental state, impaired ADL pre-fracture, increasing age and an extracapsular fracture. After controlling for severity variables, the resource variables had not further impact on mortality, either in hospital or within one year. An epidural anaesthetic was related to a poor ADL at three months and more orthopaedic complications but fewer medical complications. There was also a hospital effect in that Hospital 3, which performed the most epidurals, had the highest proportion of orthopaedic complications but the lowest proportion of medical complications. When the operating surgeon was a consultant, there were more orthopaedic complications, but this was not related to these patients having a worse case severity on admission. However, among the cases operated on by consultants, there were no hospital deaths. No other resource variables were related to ADL at three months, or orthopaedic or medical complications. CONCLUSIONS: The results show that a poor outcome following a fractured neck of femur was related to increased case severity at the time of fracture. The resource variables had very little impact on the outcome.

Activities of Daily Living↗
PubMed1994

Postnatal development of nitric oxide synthase type 1 expression in the lumbar spinal cord of the rat: a comparison with the induction of c-fos in response to peripheral application of mustard oil.

The distribution of the neuronal isoform of the enzyme nitric oxide synthase (type 1) has been investigated in the lumbar spinal cords of neonatal rats (2-20 days old). Large multipolar neurones were present from day 2 around the central canal, in a band across the neck of the dorsal horn and at the thoracic level in the intermediolateral cell column, whereas staining was absent from laminae II. By 20 days the laminae II staining was similar to that found in the adult. NOS expression in lamina II paralleled the development of c-fos expression in this lamina in response to peripheral application of mustard oil.

Administration, Topical↗
PubMed1994

The NO-cGMP pathway in neonatal rat dorsal horn.

Incubation of slices of neonatal rat spinal cord with nitric oxide donor compounds produced marked elevations in cyclic guanosine 3',5' monophosphate (cGMP) levels. The excitatory amino acid receptor agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) produced smaller increases, which were blocked by the nitric oxide synthase (NOS) inhibitor L-NG-nitroarginine (NOArg), indicating that these cGMP responses were mediated by nitric oxide. Immunocytochemistry revealed that, in response to NMDA, cGMP accumulated in a population of small cells and neuropil in laminae II and III of the dorsal horn. This area was also shown, by reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry, to contain NOS. These observations suggest that, in the rat spinal cord, NMDA receptor activation is linked to the formation of NO and, hence, of cGMP. This pathway is located selectively in the superficial dorsal horn, consistent with a role in the processing of nociceptive signals.

Amino Acid Oxidoreductases↗
PubMed1994

The use of N-(7-nitrobenz-2-oxa-1,3-diazole-4-yl)-labeled lipids in determining transmembrane lipid distribution.

Transbilayer lipid distribution of small unilamellar vesicles (SUVs) and large unilamellar vesicles (LUVs) was measured using 31P-nuclear magnetic resonance (NMR) spectroscopy, chemical modification with 2,4,6-trinitrobenzene sulfonic acid (TNBS) and dithionite reduction of N-(7-nitrobenz-2-oxa-1,3-diazole-4-yl)-labeled lipid (NBD-lipid). The dithionite assay was the most reproducible of the three assays, with 1.2% error for SUVs and 3.9% error for LUVs. The dithionite assay also agreed best with theoretical inner:outer leaflet ratios, based on vesicle diameters determined by electron microscopy (Thomas et al. (1989) Biochem. Biophys. Acta 978, 85-90). Dithionite assay measurements were within 2.7% of theoretical ratios for SUVs and 2.3% for LUVs, while the NMR assay for SUVs was 14% lower than theoretical ratios and 23% lower for LUVs. The accuracy of NBD-lipids as markers for total transbilayer lipid was investigated. NBD-labeled phosphatidylserine, phosphatidylcholine and phosphatidylglycerol were accurate markers for total transbilayer lipid distribution, as their distributions were in close agreement with theoretical ratios. However, NBD-labeled phosphatidylethanolamine displayed a slight preference for the inner leaflet at low mole fractions of phosphatidylethanolamine, while native phosphatidylethanolamine showed a preference for the outer leaflet at the same concentration. NBD-labeled phosphatidic acid also showed a slight preference for the inner leaflet. We conclude that although dithionite-based assessment of NBD-labeled lipids across membrane bilayers can be a powerful analytical tool, caution must be used in the interpretation of results.

4-Chloro-7-nitrobenzofurazan↗
PubMed1994

Transvalvular left ventricular assistance in cardiogenic shock secondary to acute myocardial infarction. Evidence for recovery from near fatal myocardial stunning.

OBJECTIVES: The purpose of this study was to test the hypothesis that transvalvular left ventricular assistance would support the circulation in patients with cardiogenic shock secondary to acute myocardial infarction and allow recovery of function in patients with a reversibly damaged (stunned) left ventricle. BACKGROUND: Cardiogenic shock occurs in 7.5% of patients presenting with acute myocardial infarction, resulting in survival of only 20%. Despite the use of aggressive interventional therapy in patients with shock secondary to anterior myocardial infarction, survival remains as low as 33%. METHODS: We studied 11 patients with acute myocardial infarction and cardiogenic shock, as defined by a cardiac index < 2 liters/min per m2, pulmonary capillary wedge pressure > 18 mm Hg and systolic blood pressure < 90 mm Hg during positive inotropic therapy. Patients were 57 +/- 13 years old (mean +/- SD) and had a mean left ventricular ejection fraction of 25 +/- 11%, mean arterial pressure of 69 +/- 13 mm Hg and mean cardiac index of 1.6 +/- 0.4 liters/min per m2 on admission to the study. RESULTS: During the 1st 24 h of left ventricular assistance, pulmonary capillary wedge pressure decreased from 26 +/- 4 to 16 +/- 4 mm Hg (p = 0.01), cardiac index increased from 1.6 +/- 0.4 to 2.4 +/- 0.4 liters/min per m2, and the dopamine hydrochloride dose decreased from 51 +/- 92 to 18 +/- 12 micrograms/kg body weight per min. In survivors, cardiac index improved to 3.2 +/- 0.5 liters/min per m2 (p = 0.01), and left ventricular ejection fraction improved to 34 +/- 5% (p < 0.05). The overall survival in the study group was 4 (36%) of 11 patients (95% confidence interval [CI] 8% to 65%), and 4 (66%) of 6 patients (95% CI 29% to 100%) with a Q wave anterior myocardial infarction survived. CONCLUSIONS: Transvalvular left ventricular support during cardiogenic shock complicating acute myocardial infarction is feasible and results in significant hemodynamic and functional improvement.

Female↗
PubMed1994

Cardiac rhythm disturbances due to caval occlusion during hepatic cryosurgery.

Cryoablation is used to treat inoperable hepatic malignancy. We investigated the safety of cryoablation close to the inferior vena cava. Our sheep model showed that it was impossible to create an iceball around the inferior vena cava (IVC) unless this vessel was clamped. When subsequently the IVC was clamped and frozen for 30 min, the anesthetized spontaneously breathing sheep (n = 3) exhibited cardiac arrhythmias typical of hyperkalemia on release of the clamp. The plasma potassium in these sheep rose from a baseline mean (SD) of 5.0 (0.7) mmol/liter to 9.5 (0.9) mmol/liter after release of the clamp at the end of the freeze. These sheep also developed acute hypercapnoea and acidosis. These changes were avoided in subsequent sheep by assisting ventilation mechanically and hyperkalemia and arrhythmias were not seen in this group. Iceball cracking did not occur and the IVC remained intact in all cases. This work suggests that during hepatic cryotherapy of lesions close to the IVC, intraoperative monitoring of potassium is indicated, particularly if caval occlusion is required to achieve adequate iceball thermal distribution.

Acidosis, Respiratory↗
PubMed1994

Epidemiology of motor vehicle crash-related serious eye injuries.

The Eye Injury Registry of Alabama has been collecting epidemiologic, treatment, final outcome, and rehabilitation information on serious ocular trauma since 1982. By December 31, 1989, 150 motor vehicle crash-related eye injuries had been registered. This is the largest series of motor vehicle crash-related serious eye injuries reported. The mean age of those injured was 29 years; 61% were between 16 and 35 years of age, and 73% were males. Ten individuals (7%) suffered bilateral eye injuries. The retina was injured in 47% of eyes. The initial visual acuity was 19/200 or worse (legal blindness) in 47% of eyes. Of eyes with at least 3 months of follow-up, 63% had worse than 20/200 initial visual acuity and 41% remained legally blind. Twelve percent of eyes required removal. Possibly due to the large number of blunt ruptures, motor vehicle crash-related eye trauma carries a particularly unfavorable treatment prognosis. Prevention of these injuries is therefore of extraordinary importance.

Accidents, Traffic↗