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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 703 records · Page 39Linked to original sources

A study on the possible role of chymotrypsin in the aetiology of equine chronic obstructive pulmonary disease (COPD).

The chymotrypsin activity of seven batches of Micropolyspora faeni and of five batches of Aspergillus fumigatus culture extracts, prepared for inhalation challenge in horses, was assayed and was found to range between 0.29 and 1.45 units/mg protein and 0.02 and 0.20 units/mg protein respectively. Horses affected with chronic obstructive pulmonary disease (COPD) were challenged with two batches of each antigen which had different chymotrypsin activities and no significant correlations were found between the degree of response to challenge and the chymotrypsin activity of the antigens. Inhalation of two doses of nebulised, purified chymotrypsin over 4 days did not induce signs of respiratory disease in COPD-affected horses. However, repeated chymotrypsin inhalations after an interval of 3 weeks caused an exacerbation of signs of COPD in one horse. These studies suggest that, although repeated inhalation of purified chymotrypsin may induce respiratory hypersensitivity in horses, the chymotrypsin-like enzymes of M. faeni and A. fumigatus do not play a major role in the precipitation of clinical signs of equine COPD.

Animals↗

Age-related changes in the hypothalamic-pituitary-testicular function of the rat.

The activity of the hypothalamic-pituitary-testicular axis was investigated in 3-4 months (young) and 24 months (old) rats. The results clearly demonstrate that aging reduces (p less than 0.01) the hypothalamic content of gonadotrophin releasing hormone (GnRH), decreases the capacity of the pituitary (p less than 0.01) to synthesize and or release follicle stimulating hormone and luteinizing hormone (LH) following a single stimulation of GnRH (50 ng/100 g body weight), lowers the capacity of the testes to produce testosterone (p less than 0.01) following multiple subcutaneous injections of human chorionic gonadotrophin (hCG 3IU/100 g body weight for 3 consecutive days), decreases the number of Leydig cell LH receptors and decreases the in vitro responsiveness of the hCG-challenged Leydig cell to synthesize testosterone (p less than 0.01). These phenomena are independent of a major alteration in the capacity of the hCG challenged Leydig cell to produce adenosine 3',5'-monophosphate. It is concluded that the decline in testicular activity accompanying senescence is not inherent to the testes only but is also associated with alteration in the function of the hypothalamus and pituitary which eventually lead to the loss of fecundity.

Aging↗

Metastatic carcinoma masquerading as scleritis.

A 36-year-old white man abruptly developed painless visual loss in his left eye. Fundoscopic evaluation revealed a shallow left superotemporal retinal detachment with an underlying yellowish choroidal infiltrate. Fluorescein angiography disclosed indistinct choroidal leakage, and both B-scan ultrasonography and computed tomography demonstrated superotemporal thickening of the choroid and the sclera. The patient was diagnosed clinically as having a scleritis and an associated exudative retinal detachment. He was placed on a several months' course of systemic prednisone, and despite this regimen, his condition worsened with the appearance of severe pain, proptosis and displacement of the eye, glaucoma, and intense episcleral and scleral injection. The eye was enucleated and displayed externally a massively thickened sclera superotemporally. Light microscopic evaluation of the enucleated globe revealed an extensively necrotic tumor growing diffusely within the choroid; infiltrating viable tumor cells were discovered within the sclera and episclera. The tumor cells had the characteristics of a well-differentiated, mucin-producing adenocarcinoma. Electron microscopic studies demonstrated lumen-forming tumor cells with apical villi, cytoplasmic pseudolumens, pools of cytoplasmic glycogen, and multiple types of inclusions, including mucin, lipid, and electron-dense secretory granules similar to those in pulmonary Clara cells. These findings were consistent with a bronchiolo-alveolar carcinoma. The patient subsequently developed bilateral reticulo-nodular pulmonary infiltrates, also typical of this tumor. The unusual clinical features of this case of "malignant scleritis" are discussed in light of the final diagnosis.

Adenocarcinoma, Bronchiolo-Alveolar↗

Atopy--a favourable prognostic factor for survival in Hodgkin's disease.

One hundred and forty-eight patients with Hodgkin's disease (HD) were stratified into 4 groups according to atopic status. Group 1 had a personal history of atopy and Group 2 a family history of atopy. In Groups 3 and 4 there was no history of atopy but high serum IgE levels (Group 3) and normal IgE levels (Group 4). Comparison of the survival of these groups by the logrank method showed a significant trend (P = less than 0.0001) where survival was ranked Group 1 greater than 2 greater than 3 greater than 4. Known prognostic factors in HD--age, sex, stage, symptoms and histology--had to be taken into account, since their distribution differed between the atopic groups. In Group I there was more stage IA and IIA disease and less "B" symptoms, in Group 3 more nodular sclerosis histology and more "B" symptoms and in Group 4 more lymphocyte-depleted histology and a higher mean age than expected from their distribution in the combined groups. Adjustment to allow for the variation in each of the other prognostic factors and for a combination of age, symptoms and histology still showed a significant trend of survival on the basis of atopic status. The increased survival of atopic patients suggests that atopic mechanisms or the genetic basis to atopy has a protective effect in HD either directly or by interaction with treatment.

Adult↗

Maximal shortening of inspiratory muscles: effect of training.

Normal subjects can increase their vital capacity by appropriate training. We tested whether that change can be achieved by greater maximal shortening of the inspiratory muscles without concomitant increases in peak static inspiratory pressures. Sixteen healthy volunteers participated in the study: eight were randomly assigned to make 20 inhalations to total lung capacity, held for 10 s with the glottis open, each day for 6 wk; the remainder served as nontraining controls. Before and after the 6-wk study period, we made multiple determinations of lung volumes and of curves relating lung volume to maximal static inspiratory (and expiratory) pressure. Control subjects had no significant changes from base line in any variable. In the training group, the mean vital capacity increased 200 +/- 74 ml (P less than 0.05) or 3.9 +/- 1.3% (P less than 0.02), without a significant change in residual volume. After training, the mean maximal inspiratory pressure at the airway opening (PI) at a lung volume equal to the base-line total lung capacity was 27 +/- 8 cmH2O in this group (vs. zero before training; P less than 0.02). Values of PI in the mid-vital capacity range did not change. We conclude that in response to appropriate training stimuli inspiratory muscles can contract to shorter minimal lengths, a capacity potentially important in progressive pulmonary hyperinflation.

Adolescent↗

Failure of delayed hypersensitivity skin testing to predict postoperative sepsis and mortality.

Delayed hypersensitivity skin reactions to a battery of recall antigens, haemoglobin and albumin concentrations, arm-muscle circumference, and percentage of ideal weight were determined before operation in 244 patients undergoing elective major surgery. Depressed skin reactions were found in 70 patients (28%), but this group did not have significantly higher sepsis or mortality rates when compared with patients with normal reactions. Significant associations were found between depressed skin reactions and increasing age, anaemia, hypoalbuminaemia, low arm-muscle circumference, and low weight. Patients with benign and malignant disease had similar distributions of skin reactions. Hypoalbuminaemia was associated with a higher rate of serious postoperative sepsis, and hypoalbuminaemia, low arm-muscle circumference, and low weight were all associated with a higher mortality. These results suggest that the routine use of delayed hypersensitivity skin testing in the preoperative assessment of surgical patients is not justified.

Abdomen↗

Familial dysalbuminemic hyperthyroxinemia: a syndrome that can be confused with thyrotoxicosis.

We investigated 15 euthyroid patients from eight families with a recently recognized syndrome, familial dysalbuminemic hyperthyroxinemia (FDH), that could be mistaken for thyrotoxicosis. The syndrome is characterized by elevations in serum thyroxine and the free-thyroxine index (FT4l), which are due to an abnormal serum albumin that preferentially binds thyroxine. This albumin has an abnormal binding site with a much greater affinity for thyroxine (relative to its affinity for triiodothyronine) than that of the hormone-binding site on thyroxine-binding globulin. Results of thyrotropin-releasing hormone and thyroid-suppression tests, as well as direct measurements of the free-thyroxine concentration by equilibrium dialysis, are normal in these patients, although the serum triiodothyronine concentration may be slightly elevated. Although its prevalence is uncertain, FDH may be more common than suspected; we have seen 26 cases within the past year.

Adolescent↗

Clostridium difficile in association with sporadic diarrhoea.

A total of 154 patients admitted to an infectious diseases unit were included in a year's prospective survey of sporadic diarrhoeal disease. Stools from 19 of them yielded Clostridium difficile, generally on more than one occasion. Twelve of these patients were assessed as having a severe or moderately severe gastrointestinal illness: Cl difficile was the only pathogen isolated from 10 of them, and two had an associated salmonella infection. Seven had had a recent course of antibiotics, but five had not taken antibiotics. Faeces from seven patients with moderate or mild gastrointestinal illness yielded Cl difficile, and two of these patients also had an associated salmonella infection. Two patients in this group had no antibiotic history. From these findings, the occurrence of C difficile in faeces could not be described as antibiotic-associated. Faecal Cl difficile cytotoxin was detected in only six patients, and generally at low levels. In such patients a more relevant pathogenic index might take account of the numbers of Cl difficile present and of their toxigenic potential.

Adult↗

The QT greater than QS2 syndrome: a new mortality risk indicator in coronary artery disease.

In the normal population the duration of electrical systole (QT) is shorter (mean -26 +/- 13 ms, 1 standard deviation) than that of electromechanical systole (QS2), which it closely parallels throughout the range of resting heart rate. This close association prompted the hypothesis that the duration of QT may be more closely linked physiologically to QS2 than to the heart rate and hence may provide a more potent prognostic indicator than the relation of QT to heart rate. The present study was designed to test this hypothesis. On hundred stable patients 14 months after myocardial infarction were followed up an average of 43 months. Twenty patients had prolongation of QT relative to QS2 (QT greater than QS2) and 13 patients had long QT corrected for heart rate (QTc). There were 20 deaths (16 sudden). The cumulative 5 year survival rate was 35% in patients with QT greater than QS2 and 91% in patients with QT greater than or equal to QS2 (p less than 0.001). There was no significant difference in survival in patients with long QTc compared with patients with normal QTc (69 versus 82%). Univariate and multivariate analysis for the association of QT greater than QS2 with known risk factors, clinical descriptors, drug therapy, systolic time intervals (preejection period/left ventricular ejection time), and frequency of 1, 2 and 3 vessel coronary occlusive artery disease revealed that only the presence of abnormal preejection period/left ventricular ejection time added significantly to the presence of QT greater than QS2 in stratifying 5-year survival into high and low risk groups. Thus, in patients with coronary artery disease, the presence of QT greater than QS2 provides a new risk indicator that is more potent than QT corrected for heart rate.

Aged↗

A simple autoradiographic method for checking HGPRT-deficiency in colonies of mammalian cells.

HGPRT enzyme activity in mutant colonies selected in 6-thioguanine can be assessed directly in petri dishes using an autoradiographic method. The application of this method to large-scale quantitative mutation experiments verifies that: (a) the maximum induced frequency of mutation of HGPRT-deficiency can be measured at short expression times, such as 3 days after treatment, when cells are respread into relatively low thioguanine concentrations, and (b) ionizing radiation induces predominantly mutants with zero HGPRT activity. Other potential applications of this method are discussed.

Animals↗

Cardiogenic oscillations: a potential mechanism enhancing oxygenation during apneic respiration.

Adequate oxygen uptake by the lungs for prolonged apneic periods is possible even in the absence of respiratory movements provided that 100% O2 is applied at the airway opening. The mechanism by which adequate gas mixing takes place during this apneic respiration is not entirely clear. We propose that a major mechanism producing O2 uptake during apnea is the enhanced gas mixing secondary to airflow generated by the beating heart.

Apnea↗

Delayed hypersensitivity skin testing does not influence the management of surgical patients.

Delayed hypersensitivity skin testing was performed at weekly intervals on 95 patients with major surgical illness. Patients with abnormal reactions on initial skin testing had a higher mortality than those who were normal initially (p less than 0.01), but this was not due to a greater rate of major septic complications. Significantly higher rates of sepsis (p less than 0.001) and mortality (p less than 0.001) were found in patients with abnormal reactions at any stage of their illness compared with patients who remained normal throughout. However, careful study of the temporal relationship between skin reactions and clinical events in individual patients suggested that these differences were not of value in clinical practice. Abnormal reactions usually followed obvious complications, such as sepsis or secondary hemorrhage, rather than predicted them. Deterioration of skin reactions from normal to abnormal was observed on 32 occasions in 25 patients but preceded the development of sepsis in only four patients.

Abdomen↗

Detection of species-specific and cross-reactive cell-surface antigens of Bacteroides species by an indirect enzyme-linked immunosorbent assay.

EDTA-released outer-membrane antigen complexes were prepared from 172 laboratory and reference strains and 43 fresh clinical or faecal isolates representing 20 species or subspecies of Bacteroides, together with 13 species of other genera. These antigens were titrated against antisera to whole, live cells of 21 species or subspecies of Bacteroidaceae in an indirect enzyme-linked immunosorbent assay (ELISA). The presence of species-specific antigens was investigated and cross reactions between species were noted. Results showed that a high proportion of the species possess species-specific antigens with little significant cross reactivity. We believe that the ELISA system described here detects antigens that represent the whole cell surface of bacteroides organisms. We have exploited the sensitivity of the system and its quantitative potential to define approaches for those wishing to use serological approaches for either the identification of Bacteroides species or for the titration of serum antibodies in patients with a possible bacteroides infection.

Antigens, Bacterial↗