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Biomedical subjects

S Reynolds

Publications and source records attributed to S Reynolds.

At least 19 recordsLinked to original sources

Wind-induced accidents of road vehicles.

This paper describes the results of a project that collected and collated data for wind-induced vehicle accidents that occurred in the United Kingdom during the major storm of 25 January 1990. The results of this data analysis are used to determine which vehicles are most at risk during windy periods, the nature of the accidents that were caused, and the likely values of accident wind speeds. Also the adequacy of a computer program that can predict such wind speeds (the program BLOWOVER) is assessed as far as the available data allows.

Accidents, Traffic

A randomised trial of dexamethasone, lorazepam and prochlorperazine for emesis in patients receiving chemotherapy.

To define further the place of dexamethasone in antiemetic combinations, lorazepam, prochlorperazine and placebo (LP) were compared with lorazepam, prochlorperazine and dexamethasone (DLP) in a randomised, double-blind, crossover study. Both patient and observer assessments were documented in 84 patients receiving both cisplatin and non-cisplatin chemotherapy. The addition of dexamethasone significantly reduced the severity of nausea (P = 0.002) and vomiting (P less than 0.0001), duration of nausea (P = 0.01) and vomiting (P = 0.002) and the number of vomiting episodes (P = 0.003). DLP was the superior regimen in subsets of patients receiving cisplatin and the non-cisplatin chemotherapy. The improvements produced by the dexamethasone regimen were large and of major benefit to our patients. Patients documented significantly improved tolerance to chemotherapy with DLP courses (P = 0.0006). Overall, significantly more patients preferred DLP (P less than 0.0001). Patient assessments produced results similar to observer assessments but gave a broader understanding of their experience. The addition of dexamethasone to prochlorperazine and lorazepam significantly improved our patients' experience while receiving chemotherapy.

Adult

Effect of abdominal compression on diaphragmatic tendon organ activity.

Previous studies suggest that afferents in the diaphragm participate in the reflex reduction in phrenic nerve efferent activation when the length of the diaphragm is increased by abdominal compression. The present study determined the response of tendon organ afferents in the diaphragm to increases in abdominal pressure. Five cats were anesthetized with thiopental sodium (60 mg/kg ip to induce, supplemented intravenously). Extracellular recordings from nine individual tendon organ afferents were made from right cervical dorsal root ganglia 5 and 6. Right crural electromyographic activity was recorded. The right extrathoracic phrenic nerve was isolated and stimulated to identify tendon organs on the basis of conduction velocity and response to twitch. The response to ramp-and-hold stretch of the diaphragm was used as an additional test to differentiate tendon organs from muscle spindles. The mean level of activity of the tendon organs during the 1st s of the inspiratory phase was 47 +/- 10 (SD) Hz. Abdominal compression was associated with a significant increase in the activity of these afferents to 61 +/- 11 Hz. Results indicate that increases in the activity of diaphragmatic tendon organs are associated with moderate increases in abdominal pressure and are likely the result of elevations in the active tension developed by the diaphragm. Combined with results from previous studies, it is possible that diaphragmatic tendon organs may play a role in the attenuation of respiratory muscle activation when abdominal pressure is increased.

Abdomen

Activation of K-ras by codon 13 mutations in C57BL/6 X C3H F1 mouse tumors induced by exposure to 1,3-butadiene.

1,3-Butadiene has been detected in urban air, gasoline vapors, and cigarette smoke. It has been estimated that 65,000 workers are exposed to this chemical in occupational settings in the United States. Lymphomas, lung, and liver tumors were induced in female and male C57BL/6 X C3H F1 (hereafter called B6C3F1) mice by inhalation of 6.25 to 625 ppm 1,3-butadiene for 1 to 2 years. The objective of this study was to examine these tumors for the presence of activated protooncogenes by the NIH 3T3 transfection and nude mouse tumorigenicity assays. Transfection of DNA isolated from 7 of 9 lung tumors and 7 of 12 liver tumors induced morphological transformation of NIH 3T3 cells. Southern blot analysis indicated that the transformation induced by 6 lung and 3 liver tumor DNA samples was due to transfer of a K-ras oncogene. Four of the 7 liver tumors that were positive upon transfection contained an activated H-ras gene. The identity of the transforming gene in one of the lung tumors has not been determined but was not a member of the ras family or a met or raf gene. Eleven 1,3-butadiene-induced lymphomas were examined for transforming genes using the nude mouse tumorigenicity assay. Activated K-ras genes were detected in 2 of the 11 lymphomas assayed. DNA sequencing of polymerase chain reaction-amplified ras gene exons revealed that 9 of 11 of the activating K-ras mutations were G to C transversions in codon 13. One liver tumor contained an activated K-ras gene with mutations in both codons 60 and 61. The activating mutation in one of the K-ras genes from a lymphoma was not identified but DNA sequence analysis of amplified regions in proximity to codons 12, 13, and 61 demonstrated that the mutation was not located in or near these codons. Activation of K-ras genes by codon 13 mutations has not been found in any lung or liver tumors or lymphomas from untreated B6C3F1 mice. Thus, the K-ras activation found in 1,3-butadiene-induced B6C3F1 mouse tumors probably occurred as a result of genotoxic effects of this chemical. The oncogenes most frequently detected in human pulmonary adenocarcinomas are K-ras genes. Activated K-ras genes have also been found in some human lymphomas. This suggest that activation of K-ras may be important in the induction of human pulmonary adenocarcinomas and lymphomas.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Purpura and dermal thinning associated with high dose inhaled corticosteroids.

OBJECTIVE: To assess the effect of high dose inhaled corticosteroids on skin. DESIGN: Cross sectional study of patients receiving treatment for chest diseases. SETTING: Outpatient chest clinic in a teaching hospital. PATIENTS: 68 Patients divided into four groups of similar age--namely, 15 receiving long term oral prednisolone, 21 receiving high dose inhaled corticosteroids, 15 receiving low dose inhaled corticosteroids, and 17 controls. MAIN OUTCOME MEASURES: Skin thickness at three sites measured by A scan ultrasound and clinical assessment of purpura. RESULTS: Compared with controls patients in both the oral prednisolone treated group and the high dose inhaled corticosteroid treated group had significantly thinner skin at all three sites (group median thicknesses: prednisolone treated group 28-33% less than controls; high dose inhaled corticosteroid treated group 15-19% less than controls). Differences in skin thicknesses between the low dose inhaled corticosteroid treated group and the controls were trivial. The prevalence of purpura was significantly greater in patients receiving oral prednisolone (12/15 patients) and high dose inhaled corticosteroids (10/21) than in controls (2/17). CONCLUSION: Skin thinning and purpura represent further evidence of systemic effects of high dose inhaled corticosteroids.

Administration, Inhalation

Effect of exercise on complement activity.

Complement measurements of C1, C1q, C2, C3, C4, C5; the anaphylatoxins, C3a, C4a, and C5a; and total hemolytic activity of the classical and alternative pathways were made in 26 experienced adult runners before and after shortterm aerobic exercise. The baseline results were compared with those of nonexercising age-matched controls. In most subjects tested, running resulted in nanogram increases in C3a and C4a with corresponding decreases in the hemolytic activity of C4 (C4H). Baseline values of C3 and C4H were decreased significantly in runners when compared with nonexercising controls. Preliminary studies measuring the effect of exercise on C3a levels were also done in three asthmatic runners. Mean resting and postexercise levels, and exercise-induced increases in C3a anaphylatoxin in the asthmatic subjects were significantly higher than in the nonasthmatic subjects. The findings indicate that short-term exercise results in the activation of C3 and C4 and subsequent generation of C3a and C4a anaphylatoxins, and suggest that both activation of the classical pathway of complement and a selective downregulation of C3 production may occur in persons regularly engaged in aerobic exercise. The exaggerated generation of C3a by asthmatic subjects during exercise raises the possibility that anaphylatoxins play an etiologic role in exercise-induced asthma.

Adult

Identification of the source of haematuria by automated measurement of red cell volume.

The mean corpuscular volume (MCV) of urinary erythrocytes was measured by a Coulter Counter in 42 patients with asymptomatic haematuria. All patients had the source of haematuria established by a renal biopsy, cystoscopy or radiology. The mean urine MCV was significantly less in those with glomerular disease (n = 21) than in those with non-glomerular haematuria (n = 21). In every patient with glomerulonephritis, urinary erythrocytes were smaller than those in their own venous blood. Conversely, urinary red cells larger than venous blood were confined to patients with a non-glomerular source. Coulter analysis of urine provides a simple and objective aid to the diagnosis of haematuria.

Erythrocyte Indices

Alpha-smooth muscle actin in parenchymal cells of bleomycin-injured rat lung.

Bleomycin causes focally diffuse interstitial fibrosis characterized by increases in the number and volume of contractile filament-laden parenchymal cells, as well as increased parenchymal contractility. However, the origin of these cells and their relationship to altered contractility, remain unknown. We now have used immunohistochemical methods to ask if cells containing smooth muscle actin and myosin are present in involved regions of parenchyma. Staining of the parenchyma of control lungs with a monoclonal antibody against alpha-smooth muscle actin is sparse, consisting of reactivity with the alveolar entrance ring (septal tip) cells as well as occasional reactivity of alveolar wall cells that may represent pericytes or contractile interstitial cells. Increased alpha-smooth muscle actin staining was observed in areas of parenchymal damage in lungs from animals sacrificed between 1 and 4 weeks postbleomycin instillation. This reactivity included altered staining of the airway and vessel smooth muscle coat as well as thickened septal tips. In addition, newly reactive cells were observed in interstitial and intraalveolar regions and in bands of thickened submesothelial tissue. Staining was most intense in the focal fibrotic lesions which are characteristic of this injury. By contrast, parenchymal reactivity with a polyclonal antibody against smooth muscle myosin at the later time points shows only a mild increase in punctate staining in the damaged foci. We hypothesize that the substantial increase in alpha-smooth muscle actin containing cells in fibrotic regions of involved parenchyma after bleomycin injury is responsible for the altered morphologic, biochemical, and mechanical properties that we have observed.

Actins

Sports injuries in a high school.

A 1-year study was undertaken investigating all sports injuries at a large high school. A total of 1283 student athletes participated in sports and suffered 280 injuries for an overall injury rate of 22%. The largest injury rate was in football (61%) followed by girls and boys gymnastics, wrestling, and boys basketball. Five sports had no injuries--boys' tennis, golf, boys' and girls' swimming, and girls' water polo. Severity of injury was measured by number of days lost per injury. Girls' track had the greatest number of days lost per injury (320) followed by girls' basketball, girls' cross country, boys' track, and boys' wrestling. Sprains and strains accounted for 57% of all injuries. Of the injured athletes, 87 were seen by a physician and only 5 athletes required surgery. The small number of serious injuries requiring surgery suggests that a motivated and competent pediatrician can play an integral role as a team physician.

Adolescent

Stability of the mandible following advancement: a comparison of three postsurgical fixation techniques.

This study examines short-term stability of the mandible following mandibular advancement surgery by means of three standard techniques of postsurgical fixation. Twenty-two adult female rhesus monkeys (Macaca mulatta) underwent sagittal ramus advancement osteotomy of approximately 4 to 6 mm. Six animals had dental maxillomandibular fixation alone. Six animals had dental plus skeletal maxillomandibular fixation with circummandibular wires connected to pyriform aperture wires. Ten animals had rigid internal fixation with bicortical bone screws between the proximal and distal segments without maxillomandibular fixation. Radiographic cephalograms with the aid of tantalum bone markers and dental amalgams were analyzed during the first 6 postoperative weeks to evaluate skeletal and dental stability. Rigid internal fixation and the use of dental plus skeletal maxillomandibular fixation were both equally effective in the prevention of postsurgical relapse. However, in the animals in which only dental maxillomandibular fixation was used, statistically significant changes (relapse) occurred when compared with either of the other groups.

Animals

Allergic bronchopulmonary aspergillosis progressing to allergic granulomatosis and angiitis (Churg-Strauss syndrome).

A 50-yr-old woman had a right upper lobectomy that revealed the pathologic changes of eosinophilic pneumonia and mucoid impaction. In the mucus plug within the segmental bronchus, aspergillus was demonstrated by direct staining. A diagnosis of allergic bronchopulmonary aspergillosis was made. After a latent period of 17 yr, she presented with the clinicopathologic features of the Churg-Strauss Syndrome. The putative role of aspergillus in the etiology of this syndrome is discussed.

Aged

Heterogeneous myocardial catecholamine concentrations in patients with congestive heart failure.

Left ventricular catecholamine and plasma norepinephrine levels were assayed in 39 patients undergoing cardiac transplantation to test the hypothesis that in congestive heart failure (CHF) the normally high concentration of myocardial norepinephrine is depleted while dopamine is increased because dopamine conversion to norepinephrine is the rate-limiting step in norepinephrine synthesis. Plasma norepinephrine was elevated in all patients (average 741 +/- 472 micrograms/ml), but myocardial norepinephrine was variable, ranging from 79 to 2,127 ng/g (average 512 +/- 392). Myocardial dopamine also varied considerably (range 0 to 713 ng/g, average 143 +/- 150). Nineteen patients had the expected pattern of low cardiac norepinephrine and elevated dopamine levels. However, myocardial catecholamine levels were normal (high norepinephrine, low dopamine) in 7 patients; both norepinephrine and dopamine were low in 6 patients; and norepinephrine levels were preserved but dopamine high in 7 patients. Cardiac norepinephrine level correlated only weakly with peripheral vascular resistance (r = 0.39, p less than 0.05), and examination of multiple other variables failed to reveal likely causes of the differences in cardiac norepinephrine and dopamine between patients. Thus, myocardial norepinephrine is not uniformly reduced in patients with severe CHF, and further attempts to delineate the factors regulating myocardial catecholamine concentration and adrenergic function in such patients are needed.

Adult

Comparison of nitroglycerin, morphine and furosemide in treatment of presumed pre-hospital pulmonary edema.

We compared four treatment protocols in 57 patients with presumed pre-hospital pulmonary edema. Group A patients were treated with nitroglycerin and furosemide, group B patients with morphine sulfate and furosemide, group C with all three agents, and group D with nitroglycerin and morphine, but without furosemide. Twenty-three percent of our patients were ultimately found not to have pulmonary edema, with pneumonia and/or exacerbations of chronic lung disease the most frequent alternate diagnoses. Group A patients had significantly greater improvement, both subjectively and objectively, than group B patients, a substantial number of whom failed to improve, or even worsened. There was no evident synergistic effect of any of the drugs, and some indication that furosemide might have caused clinically important problems with fluid and electrolyte management in some of the patients. Our data suggest that nitroglycerin is beneficial in the management of presumed pre-hospital pulmonary edema, while morphine and furosemide may not add anything to its efficacy, and may be potentially deleterious in some of these patients.

Aged

Regulation of cellular morphology by the Rous sarcoma virus src gene: analysis of fusiform mutants.

We have been interested in how Rous sarcoma virus (RSV) influences transformed cell morphology and compared the molecular properties of chicken embryo cells (CEC) infected with mutants of RSV that induce the fusiform transformed cell morphology with those of CEC infected by wild-type RSV, which induces the more normal round transformed cell morphology. We looked for properties shared by all fusiform mutant-infected cells, because these may be responsible for maintaining the fusiform morphology. Five different fusiform mutants, two wild-type RSVs, and one wild-type back revertant of a fusiform mutant were studied. In the fusiform mutant-infected cells, the localization and myristylation of pp60src were determined and the extent of expression of the extracellular matrix protein fibronectin was examined at both the mRNA and protein levels. The phosphorylation of vinculin on tyrosine also was examined in the same CEC. Within all fusiform mutant-transformed CEC, pp60src was dramatically absent from the adhesion plaque sites normally seen in cells transformed with wild-type RSV, and these transformed CEC all expressed more fibronectin mRNA and protein in the extracellular matrix than did the wild-type RSV-transformed CEC. The absence of pp60src from the adhesion plaques was not due to lack of myristylation of the src protein, and tyrosine phosphorylation of vinculin was not related to fibronectin expression. These results suggest that the inverse relationship between pp60src in the adhesion plaques and fibronectin expression in the extracellular matrix may be interconnected phenomena and could be related to the maintenance of the fusiform transformed morphology.

Animals

Ventricular myocardial catecholamines in primates.

We report myocardial catecholamine levels in primate ventricles assayed by high-pressure liquid chromatography with electrochemical detection. The norepinephrine content of the left ventricles of 11 monkeys (four rhesus and seven cynomolgus) was 1391 +/- 362 ng/gm (+/-SD) with a definite gradient from base (highest) to apex (lowest concentration). Dopamine and epinephrine were present in much lower concentrations (51.8 +/- 24.5 ng/gm and 59.2 +/- 20.0 ng/gm, respectively), but were similarly distributed throughout the left ventricle. There was considerable variation in norepinephrine concentration between animals, but the dopamine/norepinephrine ratio was very consistent within a given animal, averaging 3.7% +/- 1.4%. These values are probably indicative of what normal concentrations of catecholamines are likely to be in humans, and provide a basis for interpretation of results obtained in disease studies.

Animals