Biomedical subjects

M Robinson

Publications and source records attributed to M Robinson.

At least 217 records · Page 12Linked to original sources

PubMed1994

Adult worm homogenate of the nematode parasite Heligmosomoides polygyrus induces proliferation of naive T lymphocytes without MHC restriction.

The documented in vitro response of mouse T cells to parasite antigens is typically anamnestic and H-2 restricted. As yet, there have been no confirmed reports of the existence of a non-H-2-restricted, superantigen type of response to the antigens of metazoan parasites. Reported here are data which show that antigens produced by the adult stage of the nematode parasite Heligmosomoides polygyrus (= Nematospiroides dubius) can stimulate naive T cells in vitro to proliferate and produce IL-2. A series of T cell hybridomas has been used to show that adult worm homogenate of H. polygyrus can stimulate parasite antigen naive T cells. This response is independent of the H-2 haplotype of the antigen-presenting accessory cells and does not appear to be influenced by the presence or absence of an H-2 E molecule. However, successful presentation of the H. polygyrus superantigen does require the presence of metabolically active accessory cells and fixation of the accessory cells with paraformaldehyde abrogates the response of the target cells. This discovery has important implications for the study of the role of superantigens in host/parasite interactions and will also help to expand current knowledge about the relationship between chronic intestinal nematodes and the host immune system.

Animals↗

PubMed1994

Immature CD45RA(low)RO(low) T cells in the human cord blood. I. Antecedents of CD45RA+ unprimed T cells.

A subset of resting T cells expressing low levels CD45RA and CD45RO molecules (< 1 x 10(3)/cell; CD45RA(low)CD45RO(low)) but high levels of CD45RB and CD38 (5 to 25 x 10(3)/cell) were identified in human cord blood. When these CD45RA(low)RO(low) cells were isolated, they failed to survive in culture (< 10% viability at day 3) unless they were co-cultured on fibroblast monolayers. During the co-culture with fibroblasts, these lymphocytes acquired high levels of cytoplasmic and then membrane CD45RA by day 3 without signs of activation. When stimulated with PHA in the absence of fibroblasts the CD45RA(low)RO(low) cells required monocytes or IL-1 to respond; they rapidly perished if neither were present. On optimal mitogenic stimulation for 48 h in the presence of monocytes, > 90% of CD45RA(low)RO(low) T cells showed only transient CD45RA expression and rapidly acquired CD45RO reactivity. After activation for 48 h the stimulated CD45RA(low)RO(low) subset synthesized high levels of IL-2, comparable to mature peripheral T cells. No IL-4 was detected in these stimulated cultures of cord blood T cells. These data taken together suggest that CD45RA(low)RO(low) T cells in the cord blood are the relatively immature antecedents of CD45RA+RO T cells that require stromal factors for survival in a resting state. The same cells need monocytes or IL-1 for their activation to develop after a short CD45RA+ stage into activated CD45RO+RA(low) T cells with potent IL-2 biosynthetic capacity. An additional study of these cells is warranted to confirm that they are in fact the recent emigrants from the thymus, as suggested by similar observations in animal models.

Adult↗

PubMed1994

The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a highly evolutionarily conserved, putative transcription factor.

The 8;21 translocation, t(8;21)(q22;q22.3), is seen only in acute myelogenous leukemia and is characteristically associated with the M2 subtype. Subsequent to our identification of the t(8;21) breakpoint region on chromosome 21, we reported that the translocation results in the fusion of the AML1 gene on chromosome 21 with a novel gene on chromosome 8 which we called ETO (for eight twenty-one). Recently, the AML1 portion of the fusion protein has been shown to correspond to the DNA-binding and dimerization domains of the mouse gene, polyoma enhancer binding protein 2 alpha B (pebp 2 alpha B). We report here the complete sequence of the ETO portion of the fusion transcript as compiled from complementary DNAs from a t(8;21) AML patient and compare this with the ETO sequence from a mouse brain transcript. The deduced amino acid sequences are 99% identical. ETO has several features consistent with it being a transcription factor. The ETO sequence is different from the portion of PEBP 2 alpha B it replaces in the AML1/ETO fusion protein, except for their common high content of proline, serine, and threonine residues. Because neither the putative zinc fingers nor the TAF110 homology domain of ETO is present in PEBP2 alpha B, one might expect functional differences in the ability of AML1/ETO protein to affect the levels of transcription of genes normally regulated to some degree by AML1 (PEBP2 alpha B) during myeloid differentiation. The relatively high levels of ETO in developing brain suggest that it could be involved in the regulation of some aspect of neural proliferation or differentiation.

Amino Acid Sequence↗

PubMed1994

Juxtacardiac pleural pressure during positive end-expiratory pressure ventilation: an intraoperative study in patients with open pericardium.

OBJECTIVES: This study was conducted to measure the cardiac constraining effect of the lungs during positive end-expiratory pressure and relate extracardiac pleural pressure (radial stress) to airway pressure, right atrial pressure and left ventricular filling. BACKGROUND: During positive end-expiratory pressure ventilation, the extracardiac pressure is elevated, and therefore intracavitary filling pressure does not reflect ventricular preload. Estimates of this pressure might be useful clinically to assess left ventricular preload. METHODS: In eight patients who had undergone coronary or valvular surgery and whose pericardium was left widely open, a flat pleural balloon transducer was placed over the anterolateral left ventricular wall. We recorded pulmonary capillary wedge pressure, right atrial pressure and left ventricular short-axis end-diastolic area by transesophageal echocardiography. Incremental positive end-expiratory pressure was applied. RESULTS: Extracardiac pleural pressure increased (p < 0.01) from 0.6 +/- 1.8 (+/- SD) to 2.4 +/- 1.8, 5.3 +/- 1.5 and 8.2 +/- 1.5 mm Hg at a positive end-expiratory pressure of 5, 10 and 15 cm H2O, respectively. The slope relating extracardiac pleural pressure to positive end-expiratory pressure (in mm Hg) was 0.70 +/- 0.10, and the intercept was zero. Increasing extracardiac pleural pressure was associated with a progressive increase in pulmonary capillary wedge pressure and a decrease in left ventricular end-diastolic area. Consequently, although pulmonary capillary wedge pressure and left ventricular area changed in opposite directions, the value of pulmonary capillary wedge pressure minus extracardiac pleural pressure correlated positively with left ventricular area (r = 0.95, p < 0.001). Changes in right atrial pressure (Pra) correlated with changes in extracardiac pleural pressure (Ppleural): delta Pra = -0.3 + 0.56. delta Ppleural (r = 0.89, p < 0.001). CONCLUSIONS: In postoperative patients with open pericardium, pulmonary capillary wedge pressure minus extracardiac pleural pressure predicts left ventricular end-diastolic area during positive end-expiratory pressure. Further studies should be done to determine whether the observed relations between airway pressure and extracardiac pleural pressure and between right atrial pressure and extracardiac pleural pressure may give clinically useful estimates of left ventricular preload during positive end-expiratory pressure.

Aged↗

PubMed1994

Gastroesophageal reflux disease. Selecting optimal therapy.

An understanding of the pathophysiology of gastroesophageal reflux disease should aid selection of appropriate therapy. Symptoms of mild reflux disease may be controlled by traditional management (ie, elevating the head of the bed, dietary and other lifestyle changes, antacid use). These conservative measures also should be encouraged in patients with complicated disease. Prescription histamine2 (H2) receptor blockers remain the mainstay of antireflux medical therapy. Use of prokinetic drugs and H+,K(+)-ATPase inhibitors may be considered in refractory cases. A small percentage of patients may require antireflux surgery. If over-the-counter preparations of H2 blockers become available, they would likely become a popular component of conservative therapy.

Diagnosis, Differential↗

PubMed1994

Assessing applicants for Part III accommodation: is a formal clinical assessment worthwhile?

Arrangements for the assessment of applicants for Part III accommodation vary, particularly for those currently living in their own homes. In one outer London borough, the traditional approach, involving an interview with a social worker combined with medical history supplied by the general practitioner, was supplemented by a formal multidisciplinary clinical assessment at a rehabilitation centre. A review of 199 cases seen between 1985 and 1989 revealed that the clinical assessment detected apparently unknown medical problems in 158 (79%) clients, most of which were amenable to treatment. Forty-nine out of 173 (29%) of the clients recommended for residential care on the basis of the social worker's assessment alone were judged to be better placed elsewhere after the complementary clinical assessment. In 25 cases (14%), the client's capacity and preference to stay in their own home appeared not to have been realised or taken into account by the social work assessment. These results suggest that there may be a case for a programme of formal clinical assessment for residential care applicants. The implementation of community care provides the opportunity for more conclusive evaluative studies to be carried out.

Aged↗

PubMed1994

Mesalamine capsules enhance the quality of life for patients with ulcerative colitis.

Patients with ulcerative colitis tend to be young, potentially at peak lifetime productivity levels, and the disease can be devastating in its effects on the quality of life in these individuals. No treatment for ulcerative colitis can be comprehensively evaluated without careful attention to its impact on such psychosocial issues. The quality of life was evaluated in 374 ulcerative colitis patients using mesalamine capsules at 1 g, 2 g, and 4 g daily versus placebo in an 8-week, randomized, dose-response, placebo-controlled, double-blind, multicentre trial. Function-related quality of life parameters were assessed in this study, including five pertinent clinical symptoms and seven general life capabilities. These parameters have been previously shown to be valid, reliable, and responsive to the disease activity of ulcerative colitis. All of the parameters were recorded using a 10-cm visual analogue scale, except trips to the toilet which were recorded in patients' diaries. The mean change was calculated from baseline and endpoint data. Mesalamine at 2 g and 4 g daily was significantly superior to placebo in improving each of the 12 quality of life parameters (P < 0.05). These results indicate that controlled-release mesalamine significantly enhances the quality of life for patients with either left-sided ulcerative colitis or pancolitis.

Administration, Oral↗

PubMed1994

Role of CD18 in the accumulation of eosinophils and neutrophils and local oedema formation in inflammatory reactions in guinea-pig skin.

1. Intradermal injection of the complement fragment C5a des Arg induces local oedema formation that, in rabbits and man, is dependent on circulating neutrophils. Monoclonal antibodies to the leukocyte adhesion molecule CD11/CD18 block neutrophil accumulation and prevent neutrophil-dependent oedema formation. The role of CD11/CD18 in mediating eosinophil accumulation in vivo is less established. In this study we have used an anti-human CD18 monoclonal antibody, 6.5E, to investigate the neutrophil-dependency of oedema formation induced by C5a des Arg in guinea-pig skin. We also studied the role of CD18 in mediating eosinophil accumulation in the same model. 2. Stimulated adhesion of 111In-labelled guinea-pig neutrophils and eosinophils to serum-coated plastic was inhibited in a dose-dependent manner by 6.5E suggesting that the monoclonal antibody recognizes and blocks the guinea-pig CD18 adhesion molecule. 3. The accumulation of 111In-labelled neutrophils induced by zymosan-activated plasma (ZAP, as a source of C5a des Arg) in skin sites was reduced by up to 89% in animals treated intravenously with F(ab')2 fragments of 6.5E. ZAP-induced accumulation of 111In-labelled eosinophils was also greatly reduced (by up to 78%) by treatment with 6.5E. 4. Despite the inhibition of ZAP-induced neutrophil accumulation by 6.5E, local oedema formation in the same skin sites was unaffected, except at the top dose of ZAP, by treatment with the anti-CD18 monoclonal antibody, suggesting that the oedema response was largely neutrophil-independent. Indeed, ZAP-induced oedema formation was reduced by up to 81% by the H1 receptor antagonist, mepyramine. 5. Accumulation of 111 In-labelled eosinophils in a passive cutaneous anaphylactic (PCA) reaction was also blocked by treatment with 6.5E, while oedema formation in the same skin sites was unaffected.Intradermal injection of cationic protein-containing extracts of Schistosoma mansoni larvae also induced the accumulation of 111 In-labelled neutrophils and eosinophils which was abrogated by intravenous 6.5E.In contrast, extract-induced local oedema formation was similar in control and 6.5E-treated guinea-pigs.6. In summary, the local accumulation of radiolabelled neutrophils at sites of inflammation in guinea pigskin was dependent on the adhesion molecule CD18 while, in contrast, there was no evidence for neutrophil-dependent oedema formation in this species. Accumulation of radiolabelled eosinophils was also dependent on CD18.

Animals↗

PubMed1994

Mucociliary clearance in patients with cystic fibrosis and in normal subjects.

The aim of this study was to examine baseline mucociliary clearance (MCC) in patients with cystic fibrosis (n = 30; mean +/- SEM age, 23 +/- 1 yr; FEV1, 68 +/- 5% pred; range, 14 to 126%) and a group of normal subjects (n = 12; mean age, 27 +/- 1 yr) after an aerosol deposition of 99mTc-sulphur colloid (mass median diameter, 4.8 microns; geometric standard deviation, 1.6). Dynamic geometric mean images were formed from gamma camera data, and the percent clearance of activity after 60 min (%C60) was calculated for the whole right lung. Initial deposition of the aerosol was determined in terms of the penetration index, the ratio of peripheral to central activity. For normal subjects, an increase in mean inspiratory flow rate (MIFR) (49 +/- 5 versus 21 +/- 3 L/min, p < 0.05) resulted in an increase in whole right lung MCC (%C60, 31 +/- 4 versus 18 +/- 2%; p < 0.05). When aerosol delivery was controlled (MIFR, 34 +/- 5 versus 36 +/- 5 L/min), there was excellent reproducibility between studies (whole lung %C60, 34 +/- 8 versus 31 +/- 7; NS). The measurement of MCC was highly reproducible in six patients studied on four occasions with a mean coefficient of variation of 3.3 +/- 1%. A breathing pattern to accentuate central deposition was utilized in the patient studies (MIFR, 49 +/- 4 L/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Ten and ninety-day toxicity studies of chloropicrin in Sprague-Dawley rats.

The toxicity of chloropicrin (CP) was assessed following its administration to rats via oral gavage for either 10 or 90 consecutive days at dose levels of 10, 20, 40, and 80 mg/kg and 2, 8 and 32 mg/kg, respectively. Control rats received corn oil at a dose of 1.0 ml/kg. Toxicological observations included organ and body weight measurements, necropsy and histopathology observations, urinalysis, clinical chemistry and hematology determinations. The most remarkable toxicological finding in both studies was the corrosive property of CP on forestomach tissue. Inflammation, necrosis, acantholysis, hyperkeratosis and epithelial hyperplasia of the forestomach were seen in all dose groups of the 10-day study. Similar changes were detected in only the high dose group in the 90-day study. Decreased red blood cell parameters were noted in the highest dose groups in both studies, possibly due to blood loss via the damaged stomach lining. CP may have been aspirated into the lungs of animals in the high dose group in the ninety day study resulting in pulmonary complications leading to the deaths of 60% of the males and 80% of the females starting at week five. The 8 mg/kg dose group in the ninety day study was considered to be the no observed adverse effect level.

Administration, Oral↗

PubMed1994

Ten and ninety-day toxicity studies of 1,2-dichloroethane in Sprague-Dawley rats.

Male and female Sprague-Dawley rats received 1,2-dichloroethane in corn oil by gavage for 10 or 90 consecutive days. The doses for the 10-day study were 10, 30, 100, and 300 mg/kg; the 90-day study doses were 37.5, 75, and 150 mg/kg. There were ten animals per sex per dose group. In the 10-day study, all female animals died in the high dose group and only 2 of 10 males survived. Final body weights and weight gain along with hematology and clinical chemistry findings were not different from controls. The only relative organ weight which was significantly different was the liver in males exposed to 100 mg/kg. The main histopathological lesion exhibited was multifocal to diffuse inflammation of the mucosal and submucosal layers of the forestomach in the 100 mg/kg dose group. This change was minimal in both males and females. In the 90-day study there were no treatment-related effects pertaining to clinical observations. Body weight gain and total food consumption were significantly decreased in high dose males. There were slight but significant differences in hemoglobin, hematocrit, red blood cell count, platelets, albumin, and alkaline phosphatase values in the 75 and/or 150 mg/kg groups in one or both sexes. In males, relative brain, kidney, and liver weights were significantly increased at 75 and 150 mg/kg. There were also differences in spleen, adrenal, and testes weights (absolute and/or relative). In females, absolute and/or relative kidney and liver weights were significantly increased at 150 mg/kg (liver) and at 75 and 150 mg/kg (kidney). There were no apparent treatment-related effects pertaining to mortality, ophthalmology, gross pathology, or histopathology.

Analysis of Variance↗

PubMed1994

The effects of total intravenous anesthesia using propofol, ketamine, and vecuronium on cardiovascular response and wake up time.

Total intravenous anesthesia (TIVA) can be an effective alternative to inhalational anesthesia. Various techniques of TIVA have been associated with significant cardiovascular alterations and prolonged wake up times. The purpose of this study was to determine if TIVA utilizing propofol, ketamine, and vecuronium would provide stable hemodynamics in normotensive ASA physical status I and II patients and allow rapid awakening upon completion of surgery. Anesthesia was induced with propofol 1.0 mg/kg intravenously (IV), followed immediately by ketamine 1.0 mg/kg IV and vecuronium 0.1 mg/kg IV. Anesthesia was maintained by constant infusion of propofol 100-200 micrograms/kg/min and ketamine 17-34 micrograms/kg/min. This combination maintained hemodynamic stability and provided a rapid wake up time in 80% of the 40 subjects. The remaining 20% experienced significant tachycardia and hypertension or premature ventricular contractions. The mean wake up time was 9.7 minutes from time of neuromuscular blocking reversal to time of extubation. TIVA can be accomplished with propofol, ketamine, and vecuronium; however, 20% of patients experienced side effects, which make this method less attractive compared to alternative anesthetic techniques.

Adolescent↗

PubMed1994

Nizatidine versus placebo in gastro-oesophageal reflux disease: a 12-week, multicentre, randomised, double-blind study.

Two doses of nizatidine (150 mg twice daily and 300 mg at bedtime), an H2-receptor antagonist, were compared with placebo in a 12-week, multicentre, randomised, double-blind, parallel study in 466 patients with endoscopically documented gastro-oesophageal reflux disease. Antacid tablets were given concomitantly as needed for pain. Compared with placebo, nizatidine 150 mg twice daily was highly effective in rapidly reducing the severity of heartburn, regardless of oesophagitis severity at entry. Significantly greater complete mucosal healing of oesophagitis occurred after 6 weeks of therapy with nizatidine 150 mg bid (vs nizatidine 300 mg at bedtime or placebo) only in patients with erosive oesophagitis [16/68 (24%) vs 8/65 (12%)] and erosive and ulcerative oesophagitis combined [21/99 (21%) vs 10/94 (11%)]. At week 12, healing with nizatidine 150 mg bid was also significantly greater than placebo in erosive [19/68 (28%) vs 9/65 (14%)], ulcerative [10/31 (32%) vs 3/29 (10%)], and erosive and ulcerative oesophagitis combined [29/99 (29%) vs 12/94 (13%)]. These results show that twice-daily therapy with nizatidine 150 mg is very effective at relieving heartburn, and can also heal erosive and ulcerative oesophagitis. Nizatidine 300 mg at bedtime was not effective at healing oesophagitis, compared with placebo.

Adult↗

PubMed1994

How readable are health education leaflets?

Leaflets are a comparatively cheap and potentially effective way of conveying health information, but how successfully do they get their message across? John Ormrod and Michelle Robinson tested some widely-produced examples for readability.

Cost-Benefit Analysis↗

PubMed1994

[Problem-based learning--a cautious approach].

Most medical schools in Canada have, over the last few years, introduced Problem Based Learning (PBL) into their undergraduate curricula. In contrast to some other schools which have radically transformed their entire curricula, the University of Western Ontario approach has been more cautious, setting aside 20 per cent of the time during the first two years of the curriculum to PBL, more traditional, didactic methods being used otherwise. The main challenges have been to integrate the underlying values of the two different approaches to teaching and learning to develop valid and reliable examination and evaluation procedures, and to sustain the enthusiasm and interest of a large, mostly voluntary, group of faculty members, continually improving their skills as tutors. The most beneficial results of this curricular change have been an increased interest in medical education reform in general, and an increased recognition of the importance of teaching in relation to appointments and promotions. Students have appreciated the break from a never ending stream of lectures, and many have welcomed the challenged to explore in depth areas of special interest.

Curriculum↗

PubMed1994

The pattern of nocturnal and diurnal esophageal acid exposure in the pathogenesis of erosive mucosal damage.

OBJECTIVES: The primary objective of the present investigation was to determine from variables obtained from 24-h esophageal pH monitoring significant discriminators between patients with and without erosive esophageal mucosal damage. METHODS: Data obtained from this study were from 24-h esophageal pH monitoring and the results of upper gastrointestinal endoscopy. Statistical methods included the use of multivariate discriminant analysis. RESULTS: The results revealed that the single best measure which discriminated patients with erosive and nonerosive esophagitis was the number of recumbent reflux episodes lasting greater than 5 min. CONCLUSIONS: We conclude from these data that 1) specific evaluation of recumbent reflux and acid exposure can add substantially to the interpretation of 24-h esophageal pH studies, particularly with regard to identifying patients at risk for the development of erosive esophagitis or other potential complications; 2) esophageal mucosal erosions are associated with an increase in percent acid contact time in both the upright and supine positions, but the pattern of reflux, particularly during the nocturnal interval in terms of the number of episodes greater than 5 min, adds significant predictive value in discriminating patients with erosive mucosal damage.

Adult↗

PubMed1994

TrkA mediates an NGF survival response in NGF-independent sensory neurons but not in parasympathetic neurons.

We have investigated the role of trkA, the tyrosine kinase NGF receptor in mediating the survival response of embryonic chicken neurons to NGF. Embryonic trigeminal mesencephalic (TMN) neurons, which normally survive in the presence of BDNF but not NGF, become NGF-responsive when microinjected with an expression vector containing rat trkA cDNA. In contrast, microinjection of CNTF-dependent embryonic ciliary neurons with the same construct does not result in the acquisition of NGF-responsiveness. RT-PCR shows that injected TMN and ciliary neurons do not differ in their ability to express rat trkA mRNA or protein. The failure of injected ciliary neurons to show an NGF-promoted survival response is not due to absence of the low-affinity NGF receptor, p75, in these neurons. Quantitative PCR and immunocytochemistry shows that TMN and ciliary neurons both express p75 mRNA and protein. These findings not only provide the first direct experimental demonstration of trkA mediating a physiological response in an appropriate cell type, i.e. NGF-promoted survival of embryonic neurons, but indicate that not all neurons are able to respond to a trkA-mediated signal transduction event.

Animals↗

PubMed1993

Orchidectomy versus goserelin plus flutamide in patients with metastatic prostate cancer (EORTC 30853). European Organization for Research and Treatment of Cancer--Genitourinary Group.

A total of 327 patients with metastatic prostate cancer were randomized to receive bilateral orchiectomy or treatment with Zoladex and flutamide. The trial aimed to evaluate subjective and objective time to progression, survival, and incidence and duration of response. Strict quality control and evaluation by independent ad hoc committees were organized. Progression was assessed for each of 13 parameters. The time to subjective and objective progression was in favor of the combination treatment, with statistical significances of P = 0.009 and P = 0.008, respectively. This delay in objective progression resulted in increased survival in favor of the combination treatment for death by cancer (P = 0.02) or overall survival (P = 0.05). Survival differences were more marked in the patients with better prognostic factors. The clinical significance of these differences for the individual patient requires detailed assessment.

Adult↗