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Biomedical subjects

K Morris

Publications and source records attributed to K Morris.

At least 145 records · Page 8Linked to original sources
PubMed1996

Temporal lobe epilepsy caused by mesial temporal sclerosis and temporal neocortical lesions. A clinical and electroencephalographic study of 46 pathologically proven cases.

This study aims to determine whether there are important clinico-electrical differences between patients with temporal lobe epilepsy (TLE) secondary to mesial temporal sclerosis (MTS) and those with TLE secondary to a discrete temporal neocortical lesion (NL). The case histories, interictal EEG, seizure semiology, ictal EEG and postoperative outcome of 46 pathologically proven patients (31 MTS and 15 NL) were compared. A history of febrile convulsions (FC) was more common in MTS patients (58% versus 26%, P < 0.05), as was a history of a significant cerebral event at < 4 years of age (22% versus 0%, P < 0.05). There were no statistically significant differences in the incidence or nature of auras. No statistically significant differences between the groups were found in the interictal-EEG. With ictal semiology dystonic posturing occurred more frequently in MTS patients (mean 52% versus 26%, P < 0.05). Facial grimacing/ twitching occurred earlier in the seizures of NL patients (median 19 s versus 35 s, P < 0.05). There was an increased frequency of fast rhythmic sharp waves (> 4 Hz) in the ictal-EEG of MTS patients (mean 81% versus 60%, P = 0.05). The patients with NL developed bilateral ictal EEG changes more often (mean 55% versus 26%, P < 0.05) and more rapidly (mean 23 s versus 74 s, P < 0.005). The onset of ictal EEG seizure activity was bilateral more often in patients with NL (20% versus 4%, P < 0.005). There were no significant differences between the two groups for any of the video-EEG features, in terms of whether or not the feature occurred at least once in an individual patients. There was a tendency for MTS patients to have a higher seizure-free postsurgical outcome (87% versus 60%, P = 0.057). However, all the NL patients who were not free of seizures had had an incomplete lesion resection. We conclude that there are a number of clinico-electrical differences between patients with mesial TLE (MTLE) and patients with neocortical TLE (NCTLE), but that none of these are sufficient to allow a distinction to be made in an individual patient.

Adolescent↗
PubMed1996

Prospective clinical evaluation of Sunsoft Multifocal contact lens.

PURPOSE: We conducted a 3-month prospective clinical study to evaluate the clinical performance of the Sunsoft Multifocal contact lens as well as to determine the subjective factors that influence the decision to purchase a multifocal soft contact lens for the correction of presbyopia. METHODS: In this study, 215 patients at 16 sites were initially fit with the Sunsoft Multifocal contact lens. At 1 month, 179 patients were still wearing the lens successfully. Slit lamp evaluation of lens-cornea relationship, any change in ocular surface characteristics from initial fitting, and visual acuities were recorded at 1-month and 3-month follow-up visits. At the 1-month visit, patients completed evaluation forms to rate their perceptions of handling, comfort, visual performance, overall satisfaction, and whether they would purchase the lens if given the opportunity. RESULTS: Most patients who would choose to purchase lenses (80%) were in the group that achieved 20/25 or better binocular acuity both at distance and at near. Statistical analysis of all patients showed no difference in age, refractive error, comfort, handling, or near addition between those who would or would not purchase lenses; however, there was a significantly smaller monocular acuity imbalance in the purchase group. Analyzing just that subgroup of the population with 20/25 or better vision, the statistical analysis again showed the difference was in the binocularity of the patients. The closer together the right and left eye were in absolute acuity, the more likely the patients were to be satisfied with their lenses. There were no adverse reactions and the most common reason for failure to complete the study was inadequate near vision. CONCLUSIONS: This study yielded valuable insight into the performance of the Sunsoft Multifocal as well as those factors that influence the purchase of a soft hydrogel multifocal option.

Adult↗
PubMed1995

Normalization of nitric oxide production corrects arterial vasodilation and hyperdynamic circulation in cirrhotic rats.

BACKGROUND & AIMS: Recent studies suggest that production of nitric oxide is increased in cirrhosis. This study determines to what extent this increased production contributes to arterial vasodilation and hyperdynamic circulation in cirrhosis. METHODS: Mean arterial pressure (MAP), cardiac index, and systemic vascular resistance (SVR) were determined in cirrhotic rats with ascites undergoing long-term treatment with different doses of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (3 mg or 0.5 mg.kg-1.day-1). Untreated cirrhotic rats with ascites and controls were also studied. The vascular production of NO was estimated by the aortic concentration of guanosine 3',5'-cyclic monophosphate (cGMP). RESULTS: Untreated cirrhotic rats had significantly lower MAP and SVR and higher cardiac index and aortic cGMP concentration than controls. When administrated to cirrhotic rats, an L-NAME dose of 3 mg.kg-1.day-1 induced a reduction of cGMP concentration less than normal levels. In these rats, MAP and SVR increased to greater than and cardiac index decreased to less than values in controls. By contrast, cirrhotic rats treated with 0.5 mg.kg-1.day-1 L-NAME had similar aortic cGMP concentrations as controls, suggesting a normalization of NO production. This was associated with a normalization of MAP, cardiac index, and SVR and a reduction in the elevated plasma renin activity and vasopressin concentration. CONCLUSIONS: Normalization of vascular NO production corrects systemic hemodynamic abnormalities in cirrhotic rats with ascites.

Animals↗
PubMed1995

Phase II trial of 5-fluorouracil, folinic acid, and N,N1,N11-triethylenethiophosphoramide (thiotepa) in patients with advanced breast cancer.

A total of 35 women with advanced, metastatic breast cancer were treated with combination chemotherapy consisting of folinic acid 500 mg/m2 over 2 hours administered with 600 mg/m2 of 5FU at the midpoint of the folinic acid infusion weekly for 6 weeks, plus 60 mg/m2 of thiotepa on day 1 and day 28. The cycle was repeated every 8 weeks. Patients were evaluated for toxicity weekly. Response was evaluated at the end of each 8-week cycle. The median age was 55 years (range: 34-67). Prior to this study 30 patients had received chemotherapy; 13 had 1 regimen; 17 had 2 or more regimens; 8 had 5FU treatment. The overall response rate was 40% (1 complete and 13 partial); median duration of response was 4 months. Four of 8 patients with prior 5FU responded. Hematologic toxicity was significant; nadir WBC count: < 1,000/mm3 (10 patients); 1,000-1,999/mm (13 patients); nadir platelet count: < 20,000/mm3 (8 patients): 20,000-49,000/mm3 (8 patients); 50,000-99,000/mm3 (10 patients). We conclude that the combination of thiotepa, 5FU, and leucovorin had significant myelotoxicity and do not recommend its routine use in the treatment of metastatic breast cancer.

Adult↗
PubMed1995

Increased aortic cyclic guanosine monophosphate concentration in experimental cirrhosis in rats: evidence for a role of nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis.

Arterial vasodilation is considered to be the key factor in the development of sodium and water retention leading to ascites formation in cirrhosis. To determine if nitric oxide (NO) is involved in the pathogenesis of arterial vasodilation in cirrhosis, we measured the concentration of cyclic guanosine monophosphate (cGMP), the second messenger of NO, in arterial tissue from rats with carbon tetrachloride-induced cirrhosis. Aortic cGMP concentration was markedly increased in cirrhotic rats, particularly in those with ascites (ascites, 826 +/- 70; no ascites, 597 +/- 48; controls, 331 +/- 25 fmol/mg, ANOVA F = 23.1, P < .0001), and correlated inversely with arterial pressure (r = -.56, P < .0001) and systemic vascular resistance (r = -.69, P = .014) and directly with cardiac index (r = .74, P < .01). The chronic administration of the NO synthesis inhibitor NG-nitro-L-arginine-methyl-ester (L-NAME) (10 mg/kg/day for 7 days) induced a marked reduction in aortic cGMP concentration in cirrhotic rats with ascites to similar values obtained in L-NAME-treated control rats (86 +/- 14 vs. 89 +/- 8 fmol/mg, respectively, NS), indicating that the high-aortic cGMP content in cirrhotic rats was caused by an increased NO synthesis. Mean arterial pressure after L-NAME treatment increased to similar values in both groups of animals. These results suggest that in cirrhosis there is an increased vascular production of NO that may play a role in the pathogenesis of arterial vasodilation.

Analysis of Variance↗
PubMed1994

An evaluation of program management: the West Park Hospital experience.

Program management as a way to structure hospital management has been attracting growing interest. Numerous hospitals are introducing it. West Park Hospital was one of the first hospitals to adopt program management in 1991 and mount a rigorous evaluation of the new approach, one which relied on external evaluators. This article reviews the emergence of program management in the hospital sector and reports on the evaluation of West Park's experience.

Attitude of Health Personnel↗
PubMed1994

Blockade of the neonatal rise in testosterone by a gonadotrophin-releasing hormone antagonist: effects on timing of puberty and sexual behaviour in the male marmoset monkey.

In primates, plasma testosterone concentrations are elevated for some 3 months from birth. The function of this rise is uncertain, but studies in rats suggest that its prevention by castration or administration of gonadotrophin hormone-releasing hormone (GnRH) analogues has effects on development and expression of social and sexual behaviours, and adverse long-term effects on fertility. The consequences of suppression of this rise in testosterone by treatment with the GnRH antagonist antide have been investigated in the marmoset monkey. Eight sets of male:male twins were used, one of each set receiving s.c. injections of antide (10 mg/kg), on days 0, 3 and 7, then weekly from birth to 98 days of age, with the twin receiving vehicle only. Plasma samples were taken at weekly intervals for the determination of testosterone concentrations from birth until 2 years of age. Treatment with antide completely abolished the neonatal rise in testosterone seen in control animals. The timing of the onset of the pubertal testosterone rise was not significantly affected by treatment; however, the subsequent pattern of circulating testosterone showed a tendency to decreased plasma concentrations in the neonatally treated group from weeks 25 to 42, relative to controls, and this difference was significant between 43 and 70 weeks. This was associated with a similar depression in bioactive LH concentrations around this time. Thereafter, the testosterone concentrations were similar between treated and control groups. There was no effect of treatment on growth, based on sequential body weight data. At 20 months the animals underwent behaviour tests with ovariectomized females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

End-stage kidneys are capable of increased erythropoietin production.

A relative deficiency of erythropoietin (EPO) is the most important factor responsible for the anaemia of end-stage renal failure. Patients on continuous ambulatory peritoneal dialysis usually maintain a higher haemoglobin concentration than patients on other forms of dialysis. The precise mechanism is uncertain, and there is disagreement over the role of increased EPO production. An 11-year-old boy with end-stage renal failure maintained on overnight cycling peritoneal dialysis developed a reticulocytosis, followed by a marked increase in haemoglobin concentration, shortly after his dialysis schedule was altered to include a full peritoneal cavity during the daytime. This improvement in erythropoiesis was closely associated with an increase in serum EPO concentration. We suggest that the alteration in dialysis may have resulted in enhanced clearance of an inhibitor of EPO production and discuss the possible mechanisms involved.

Anemia↗
PubMed1993

Assessment and communication of conscious level: an audit of neurosurgical referrals.

Telephone referrals of 100 head-injured patients to a neurosurgical service were assessed to determine if altered consciousness was adequately described by the referring doctor. Of the patients, 60 per cent were resuscitated, assessed and referred by SHOs. Only 30 per cent of doctors were fully conversant with the Glasgow Coma Scale and 18 per cent were unable to describe altered consciousness. Assessment of motor response was often described inaccurately and this was frequently due to the use of an inappropriate stimulus. The use of a pictorial guide to motor responses and a 'Head Injury Proforma' are suggested as means of improving referral and enhancing audit. The majority of doctors had not received formal training in the assessment of conscious level during their undergraduate or postgraduate training. Training video tapes from neurosurgical units showing standard examination methods and typical responses would allow self-assessment and training.

Adolescent↗
PubMed1993

Mechanism and kinetics of metal ion-mediated degradation of fosinopril sodium.

Fosinopril sodium (I), a new angiotensin converting enzyme inhibitor, is a diester prodrug of the active moiety II. We report here a novel transformation of fosinopril into beta-ketoamide, III, and a phosphonic acid, IV, mediated through metal ion participation. The interaction of fosinopril with magnesium ions was studied in a solution model system in which methanol was used as the solvent and magnesium acetate as the source of metal ions. Kinetic analysis indicated the degradation to be a bimolecular process, with the rate being first order in both metal ion and fosinopril concentration. The degradation products II, III, and IV effectively retarded the magnesium ion mediated reaction of fosinopril. Based on the results of 31P-NMR, 1H-NMR, Mn(II)-EPR spectroscopy experiments and mass spectrometry, a mechanism is postulated for this transformation. A key reactive intermediate has been characterized that supports the proposed mechanism. The results can account for the observed degradation profile of the fosinopril sodium in a prototype tablet formulation.

Electron Spin Resonance Spectroscopy↗
PubMed1993

Increase in activated T cells and reduction in suppressor/cytotoxic T cells in acute rheumatic fever and active rheumatic heart disease: a longitudinal study.

In a prospective study, patients with acute rheumatic fever (ARF) and active rheumatic heart disease (ARHD) showed a significant increase in CD4+ T cells, CD22+ B cells, and CD4:CD8 cell ratio but a significant decrease in the percentages of CD8+ and CD3+ T lymphocytes compared with patients with quiescent RHD (CRHD) or streptococcal pharyngitis (SP) and normal controls. The proportion of interleukin-2 receptor (IL-2R)+ (CD25+) cells was higher in peripheral blood mononuclear cell cultures (both before and after phytohemagglutinin stimulation) of ARF and ARHD patients than in those of CRHD or SP patients or controls; this finding persisted up to 48 weeks. In ARF patients, the percentage of CD8+ cells returned to within normal range at 48 weeks. Furthermore, the percentage of IL-2R+ cells correlated positively with the percentage of CD4+ but not of CD8+ lymphocytes, suggesting that helper/inducer T cells are in an immunologically activated state and may account for aberrations in the distribution of lymphocyte populations in peripheral blood of ARF and ARHD patients.

Acute Disease↗
PubMed1993

Enhancement of IL-1, IL-2 production and IL-2 receptor generation in patients with acute rheumatic fever and active rheumatic heart disease; a prospective study.

In a prospective study, patients with quiescent rheumatic heart disease (CRHD), streptococcal pharyngitis (SP) and healthy normal subjects produced comparable amounts of IL-1 and IL-2, but acute rheumatic fever (ARF) patients produced significantly elevated amounts of IL-1 and IL-2 at all intervals up to 48 weeks. In active rheumatic heart disease (ARHD), IL-1 activity returned to within normal range at 48 weeks, but IL-2 activity remained persistently elevated compared with CRHD, SP and healthy age- and sex-matched volunteers. CD4+ T lymphocytes were significantly increased in the peripheral blood of ARF and ARHD patients. The amount of IL-2 produced by ARF and ARHD patients correlated with the percentage of helper T lymphocytes (CD4+ cells) but not with the percentage of suppressor/cytotoxic T lymphocytes (CD8+ cells). Moreover, pre- and post-phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cell (PBMC) cultures from ARF and ARHD patients contained higher proportions of IL-2R+ (CD25+) cells than those from patients with SP, CRHD and normal individuals, which persisted up to 48 weeks. The percentage of CD25+ cells in both types of PBMC cultures directly correlated with the percentage of CD4+ cells and not with CD8+ cells in active rheumatic patients only. These findings indicate that the immune response in ARF and ARHD patients is skewed to produce activated helper T cells that release IL-2 which drives the accumulation of more T helper cells. The result is an undamped helper T cell response in the peripheral blood of these patients.

Adolescent↗
PubMed1993

Pulmonary and systemic vascular responsiveness to TNF-alpha in conscious rats.

Endotoxin decreases pulmonary vascular reactivity. Because tumor necrosis factor-alpha (TNF-alpha) is a primary mediator of endotoxemia, we tested whether TNF-alpha altered pulmonary vascular reactivity in conscious adult female rats. Osmotic pumps were implanted intraperitoneally, and low-dose TNF-alpha (62 micrograms, TNF62; n = 7), high-dose TNF-alpha (> or = 250 micrograms, TNF250; n = 5), or saline (n = 5) was administered for 2 wk. Pulmonary pressor responses to 14% O2 and angiotensin II (ANG II, 0.0206 micrograms/min for 10 min) were measured without (day 13) or after (day 14) administration of nitro-L-arginine (4.4 mg/kg iv), an inhibitor of endothelium-derived relaxing factor (EDRF). TNF-alpha administration slightly decreased (P < or = 0.08) baseline pulmonary arterial pressure in TNF250 rats and decreased (P < or = 0.05) hypoxia- and ANG II-induced constrictions in TNF62 and TNF250 rats. Whereas nitro-L-arginine potentiated (P < or = 0.05) pressure responses in control rats, it had no effect on hypoxic responses in TNF-alpha-treated rats. Nitro-L-arginine increased (P < or = 0.05) ANG II-induced vasoconstriction in TNF-alpha-treated rats, but the pulmonary arterial pressure response was still lower (P < or = 0.05) in TNF250 than in control and TNF62 rats. These results suggest that chronic TNF-alpha decreases 1) pulmonary vascular reactivity in the intact rat, 2) hypoxic pulmonary vasoconstriction by a mechanism that is independent of EDRF, and 3) ANG II-induced constriction by a mechanism that is partly EDRF dependent.

Angiotensin II↗
PubMed1992

Suppression of the renin-angiotensin-aldosterone axis with erythropoietin therapy by a negative feedback loop.

To investigate the pathophysiology of hypertension in patients receiving recombinant human erythropoietin (rHuEpo) we studied its effects on the renin-aldosterone axis of chronic haemodialysis (HD) patients not receiving antihypertensive drugs. Nine severely anaemic normotensive HD patients received rHuEpo 50 U/kg bodyweight, thrice weekly after each HD. The dose was increased by 25 U/kg bodyweight every 4 weeks to a maximum of 100 U/kg or until an increase of Hb or Hct of 2 g/dl or 7% was achieved. Blood samples were taken after 30 min supine rest and while seated 10 min later after gentle ambulation. Results expressed as mean +/- SEM: therapy in normotensive HD patients by a negative feedback loop, before the development of hypertension.

Adult↗
PubMed1992

Immunoneutralization and immunocytochemical localization of inhibin alpha subunit during the mid-luteal phase in the stump-tailed macaque.

The putative endocrine role of inhibin in the control of FSH secretion during the luteal phase in the primate was investigated by immunoneutralization. Antisera against the 1-23 amino acid sequence of the N-terminus of the human inhibin alpha subunit were raised in a ewe and three macaques. Antisera (10-20 ml) were administered to macaques on day 8/9 of the luteal phase and serum samples collected during the treatment cycle and post-treatment cycle for determination of FSH, oestradiol and progesterone. In addition, localization of inhibin within the macaque ovary at this stage of the luteal phase was investigated using the ovine antiserum. Intense immunostaining was localized within the granulosa-lutein cells of the corpus luteum with absence of staining in the theca-lutein cells or other ovarian compartments. Administration of antisera was without significant effect on serum concentrations of FSH when compared with control animals, either during the first 24 h of detailed observation or for the following 10-day period of the late luteal phase and subsequent early follicular phase. These results provide further evidence that the corpus luteum is the major source of inhibin immunoreactivity during the primate menstrual cycle, but fail to support an endocrine role for inhibin in the suppression of FSH secretion.

Animals↗