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Biomedical subjects

F Moran

Publications and source records attributed to F Moran.

At least 19 recordsLinked to original sources

The cellular immune response to immunization with zona pellucida antigens.

The cellular immune response of mice to porcine and rat zona pellucida and cynomolgus macaques to porcine zona pellucida antigens was evaluated. Mice mounted a vigorous cellular response to both antigens, as determined by the T cell proliferation response in vitro. There was poor cross-reactivity to murine zonae by T cells or serum antibodies from mice immunized with rat zona pellucida. Nevertheless, ovaries from the mice immunized with rat zona had significantly fewer antral follicles than adjuvant-treated controls, suggesting that the immune response to the zona antigen disrupted follicular development. T cells from two macaques that had been immunized with porcine zona pelludica proteins proliferated in vitro in response to this antigen. Both macaques also had strong antibody responses. The patterns of urinary steroid metabolites in these animals provided clear evidence of ovarian malfunction following immunization. The data indicate that a significant cellular immune response is generated upon immunization of animals with zona pellucida antigens regardless of whether the antigens are cross reactive with the host zona antigens. Whether impaired ovarian function and follicular development are related to the cellular response must be determined in future studies.

Animals

Dopamine clearance in critically ill infants and children: effect of age and organ system dysfunction.

To learn if there are age-related differences in the pharmacokinetic behavior of dopamine, plasma dopamine clearance was determined in 27 acutely ill infants and children who were receiving a continuous intravenous infusion of the drug. Steady-state clearance was calculated from dopamine concentration in arterial blood. Dopamine clearance was 60.7 +/- 28.1 ml/kg/min. The age of the patient exerted an effect on clearance of dopamine (r = -0.63; p less than 0.05), and dopamine clearance was nearly twice as rapid in children younger than 2 years as it was in older children (82.3 +/- 27.7 ml/kg/min versus 45.9 +/- 17.0 mg/kg/min). Conjugated bilirubin exerted an age-independent effect on clearance of dopamine; clearance was 44.8 +/- 28.6 ml/kg/min in children with abnormal conjugated bilirubin (greater than or equal to 0.9 mg/dl) and 70.1 +/- 2.56 ml/kg/min in children with normal conjugated bilirubin (less than 0.9 mg/dl). Clearance was lowest (29.8 +/- 5.7 ml/kg/min) in the four children who had both hepatic and renal dysfunction. Age is an important determinant of dopamine clearance, explaining in part the clinical observation that infants and young children require higher infusion rates.

Adolescent

Lung scanning for pulmonary embolism: clinical and pulmonary angiographic correlations.

A group of 78 patients with suspected pulmonary embolism was studied by both ventilation perfusion lung scanning and pulmonary angiography. Symptoms and clinical signs were analysed using Bayesian techniques to produce pre-test odds for pulmonary embolism in individual patients. While, as a group, those with embolism could be discriminated from those without on this basis, major overlap existed between the groups, invalidating the use of this approach for individual patients. Strict diagnostic criteria for interpretation of lung scans were accurate using pulmonary angiography as the 'gold standard', but at the expense of a significant number of patients (38 per cent) in the indeterminate (non-diagnostic) group. In the 48 patients in whom the test yielded a diagnostic result, there was a sensitivity of 100 per cent (15/15) and a specificity of 97 per cent (32/33). In the series as a whole, the likelihood of lung scanning correctly diagnosing pulmonary embolism was 55 per cent (15/27) and of correctly excluding embolism, 63 per cent (32/51). By the use of strict criteria for interpretation of lung scanning, reliable information can be obtained on the presence or absence of pulmonary embolism in a large proportion of patients suspected of having the condition. Such information is more discriminating than clinical signs and symptoms.

Adult

Variation of breath sound and airway caliber induced by histamine challenge.

Inspiratory breath sounds were recorded from the chest wall during histamine challenge in five subjects with mild asthma (baseline FEV1 greater than 60% of predicted normal). The median frequency of the power spectrum of the breath sounds was found to correlate with the percentage change in FEV1 induced by histamine and with FEF50. The analysis suggests that for a decrease in FEV1 of 20%, the median frequency of breath sound would increase by 80 Hz. Variation in airway caliber produced a consistent alteration in the distribution of energy in inspiratory breath sound in the absence of wheeze. Spectral analysis of breath sound may be a useful addition to conventional spirometry in identifying changes in airway diameter.

Adult

Pulmonary abnormalities in Crohn's disease.

Abnormalities of pulmonary function in Crohn's disease have been described, although the results are conflicting and anecdotal accounts of lung involvement are few. In this study we assessed the prevalence of lung function abnormalities in Crohn's disease, and the relative contributions of age, sex, smoking and past medical history, and Crohn's disease activity to the pulmonary abnormalities found. Twenty-nine patients with Crohn's disease and 29 age-, sex- and smoking-matched volunteer controls underwent detailed respiratory assessment. Airways obstruction due to chronic bronchitis and asthma was present in 13 patients with Crohn's disease, but was not more prevalent than in the control group. FEV1 was similar in both Crohn's disease and control subjects (84.2 +/- 21.2% predicted, mean +/- SD; 93.7 +/- 16.3%, respectively: n.s.). The vital capacity was significantly lower in the Crohn's disease patients than in controls (86.7 +/- 16.6%; 95.9 +/- 12.7%; P less than 0.01), but this may have been influenced by the higher prevalence of past or intercurrent medical illnesses affecting the chest in Crohn's disease patients. No patient had evidence of fibrosing alveolitis or bronchiectasis. The haemoglobin corrected transfer factor was significantly lower in the Crohn's disease patients than in controls (100.4 +/- 17.4%; 113.2 +/- 25.1: P less than 0.05) but the diffusing coefficient was not significantly different. There was a significant correlation (r = 0.44, P less than 0.05) between the residual volume and the Crohn's disease activity index but otherwise no close relationship was observed between Crohn's disease activity, extent or duration and the indices of lung function. These findings suggest that the lungs are relatively unaffected by Crohn's disease.

Adult

Management of asthma in hospital: a prospective audit.

In a prospective study of management of asthma in hospital patients with acute asthma admitted to a single hospital over a calendar year were surveyed. Altogether 157 out of 194 admissions (81%) were studied. The patients (16 of whom had been admitted twice and one three times) were interviewed at home about two weeks after discharge, and their hospital records were reviewed. When interviewed an appreciable proportion of patients said that their asthma had been poorly controlled after their discharge from the hospital: 54 reported regular sleep disturbance due to wheeze, 78 tightness of the chest in the morning, and 77 wheeze after climbing one flight of stairs. Patients had been described on admission as having had symptoms of deteriorating asthma for a median of three days. Closer questioning of 71 patients, however, elicited that 50 had had regular symptoms indicating poor control for weeks or months. Most patients did not know how their drugs worked, and many did not have an appropriate plan of action in the event of a further attack. In all the cases studied 114 patients were treated with oral corticosteroids, only 70 had had their previous maintenance treatment increased at the time of discharge, and 107 had a follow up appointment booked for an average of three and a half weeks after discharge. These findings show that undersupervision and undertreatment of patients with asthma are common and not confined to those dying of the condition.

Asthma

Differences in hospital asthma management.

Asthma management was audited prospectively for one year in a large teaching hospital. Full details were available on 77% of all patients admitted, or readmitted, with asthma during that year (150 of 195 admissions). 64 patients were admitted to general wards with a special interest in respiratory medicine, and 86 to general wards without this specialist interest. Cases in the two groups were similar in terms of age, previous severity of asthma, previous treatment, and initial pulse rate. Fewer cases in the non-specialist group were treated with oral corticosteroids (67%, vs 83%), had regular peak flow recordings (42%, vs 73%), or were given return appointments (56%, vs 92%); and fewer had their regular inhaled therapy increased after discharge (28%, vs 55%). At interview 13 days later, more patients from the non-specialist group reported sleep disturbance (41%, vs 23%), morning chest tightness (55%, vs 37%), ow wheeze on 1 flight of stairs (58%, vs 34%). 20% of first admissions in the non-specialist group were readmitted within the year, compared to 2% of the group treated on wards with a specialist interest in respiratory medicine. These data suggest that the intensive management of asthmatic patients, practised in respiratory units, prevents much unnecessary morbidity.

Acute Disease

Dynamics of a biochemical system with multiple oscillatory domains as a clue for multiple modes of neuronal oscillations.

We analyze the behavior of a two-variable biochemical model in conditions where it admits multiple oscillatory domains in parameter space. The model represents an autocatalytic enzyme reaction with input of substrate both from a constant source and from non-linear recycling of product into substrate. This system was previously studied for birhythmicity, i.e. the coexistence between two stable periodic regimes (Moran and Goldbeter 1984), and for multi-threshold excitability (Moran and Goldbeter 1985). When two distinct oscillatory domains obtain as a function of the substrate injection rate, the system is capable of exhibiting two markedly different modes of oscillations for slightly different values of this control parameter. Phase plane analysis shows how the multiplicity of oscillatory domains depends on the parameters that govern the underlying biochemical mechanism of product recycling. We analyze the response of the model to various kinds of transient perturbations and to periodic changes in the substrate input that bring the system through the two ranges of oscillatory behavior. The results provide a qualitative explanation for experimental observations (Jahnsen and Llinas 1984b) related to the occurrence of two different modes of oscillations in thalamic neurones.

Models, Biological

Finding complex oscillatory phenomena in biochemical systems. An empirical approach.

Starting with a model for a product-activated enzymatic reaction proposed for glycolytic oscillations, we show how more complex oscillatory phenomena may develop when the basic model is modified by addition of product recycling into substrate or by coupling in parallel or in series two autocatalytic enzyme reactions. Among the new modes of behavior are the coexistence between two stable types of oscillations (birhythmicity), bursting, and aperiodic oscillations (chaos). On the basis of these results, we outline an empirical method for finding complex oscillatory phenomena in autonomous biochemical systems, not subjected to forcing by a periodic input. This procedure relies on finding in parameter space two domains of instability of the steady state and bringing them close to each other until they merge. Complex phenomena occur in or near the region where the two domains overlap. The method applies to the search for birhythmicity, bursting and chaos in a model for the cAMP signalling system of Dictyostelium discoideum amoebae.

Cyclic AMP

A retrospective survey of asthma management in hospital.

A retrospective survey of asthma admissions to general medical units during 1983 is described. 127 cases occurred, of whom 52 were males (44%). The average age was 45.2 years. Forty-eight per cent were receiving inhaled steroids or cromoglycate before admission and 16% regular oral steroids. Initial assessment seldom included peak flow measurement although these were made subsequently in 57%. No steroids were used in 32% of cases. No oxygen was given in 48% of cases and when used was usually at low flow rates. Apart from a reducing course of steroids, 46% of cases were discharged with no increase in pre-admission maintenance treatment and although follow-up was planned for 76% it was for an average 4.9 weeks later. This survey suggests a tendency to under-treatment and undersupervision of asthma patients admitted to acute general medical wards which may well be a cause of unnecessary morbidity.

Adolescent

A critical appraisal of a rapid radiographic method of determining total lung capacity.

We have demonstrated that the total lung capacities of normal caucasian adults, can be satisfactorily estimated by means of a regression equation derived from a single set of three measurements taken from a specially exposed plain X-ray film of the chest. However, these equations differ from those found by workers who have studied patients with lung disease. It is concluded from this that different regression equations are to be expected for normal and diseased lungs, and that, the appropriate equation will depend not only on the presence of disease, but also on its type and severity. It is also concluded that the rapid radiographic method of estimating total lung capacity can make little contribution to the diagnostic assessment of lung disease. However, the regression equations appropriate to particular ethnic groups could be used to measure TLC in normal subjects rapidly and inexpensively in places where specialised respiratory equipment and trained personnel are lacking.

Adult

Excitability with multiple thresholds. A new mode of dynamic behavior analyzed in a regulated biochemical system.

We analyze in a biochemical model the phenomenon of excitability in which suprathreshold perturbations of a stable steady state are amplified in a pulsatory manner. The two-variable model is that of an autocatalytic enzyme reaction with recycling of product into the substrate. This model was previously studied for the coexistence between two stable periodic regimes (birhythmicity). We show that the multiplicity of dynamic behavioral modes extends to the phenomenon of excitability. Whereas excitable behavior is generally characterized by a single threshold for excitation, two distinct thresholds may coexist in this model. Moreover, in these conditions, two different plateaux are obtained for the response amplitude when the stimulus is gradually increased. By means of phase plane analysis we explain the origin of multiple thresholds for excitability and predict the conditions for their occurrence. Implications of the phenomenon for excitable cells, in particular for neurons, are discussed.

Animals

Pulmonary involvement in systemic lupus erythematosus.

Several series have suggested that pulmonary function abnormalities are common in systemic lupus erythematosus. However, only isolated studies have attempted to relate these abnormalities to immunological aspects of the diseases. In the present study respiratory symptoms, pulmonary function tests, and immunological data were reviewed in 22 patients with systemic lupus erythematosus. Seventeen subjects had either clinical evidence or abnormalities of lung function suggestive of pulmonary involvement. A restrictive ventilatory defect or reduction in pulmonary diffusing capacity for carbon monoxide was demonstrated in 14 of the patients only 4 of whom were dyspnoeic. There was no correlation between pulmonary involvement, co-existent renal lupus, and immunological abnormality.

Adolescent