Biomedical subjects
Publications and source records attributed to D A Morgan.
Haemangiopericytoma is an uncommon vascular tumour which has rarely been recorded in the larynx. The diagnostic and histopathological difficulties are discussed. A total laryngectomy was performed because of the size and site of the tumour, the associated risk of local recurrence and the high metastatic rate.
Development of salt-induced hypertension in Dahl salt-sensitive (S) rats is dependent on sympathetic overactivity which may be partially related to arterial baroreflex dysfunction and, therefore, is regionally selective. Our first experiment was designed to determine which regions have elevated sympathetic activity in Dahl S compared with Dahl salt-resistant (R) rats. Weanling (4-week-old) female Dahl R and S rats were fed low or high salt diets (0.13% and 8% NaCl) until 10 weeks of age. Norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the fractional decline of NE concentration was measured in various tissues. Dahl S rats with increases in both arterial pressure and left ventricular weight demonstrated increased NE turnover in the sinoatrial node, the atrial appendages, the cardiac ventricles, and the renal cortex. In all of these tissues except the cardiac ventricle, increases were associated with high salt intake. Our second experiment was designed to test if arterial baroreflex dysfunction could account for regional increases in sympathetic activity. Separate groups of Dahl R and S rats fed high salt were subjected to either sham surgery or sinoaortic baroreceptor denervation 1 week prior to turnover determinations. Sinoaortic baroreceptor denervation abolished differences in NE turnover between salt-fed Dahl R and S rats in the cardiac sinoatrial node and the atrial appendages, but not in the cardiac ventricles and the renal cortex. Sinoaortic baroreceptor denervation also abolished differences between salt-fed Dahl S and R rats in the spleen but not the duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)
Lesions in forebrain areas richly innervated by noradrenergic terminals and involved in cardiovascular function reduce or prevent hypertension in the Dahl salt-sensitive (S) rats fed a high (H) salt diet. This led us to examine two questions. (1) Is the noradrenergic activity altered in discrete forebrain and brainstem areas of SH rats? (2) Are these changes in noradrenergic activity eliminated by sinoaortic denervation (SAD)? Studies were done in 10-week-old female SH and Dahl salt-resistant (RH) rats. Half of the rats in each group had SAD surgery 1 week prior to study. An index of norepinephrine (NE) turnover was determined by measuring the decline in tissue NE concentration 8 h after administering alpha-methyl-p-tyrosine, a NE synthesis blocker, to animals from each of four groups: sham-RH, SAD-RH, sham-SH, and SAD-SH (n = 18-20 per group). Various discrete brain areas were obtained using the "punch technique." In SH rats the index of NE turnover was increased in the median preoptic nucleus and decreased in the paraventricular nucleus compared with RH rats regardless of SAD. In contrast, in SH rats the index of NE turnover was increased in the supraoptic nucleus and locus ceruleus compared with RH rats; however, SAD-RH had greater turnover of NE at these sites than SAD-SH. In summary, changes in noradrenergic activity in the median preoptic nucleus and the paraventricular nucleus may be related to genetic predisposition to hypertension in SH rats. In contrast, changes in the locus ceruleus and the supraoptic nucleus of SH rats may be related to impaired baroreflexes and thereby contribute to hypertension.
The goal of this study was to determine if the baroreflex abnormality previously shown in Dahl-sensitive (DS) rats would increase blood pressure and heart rate (HR) variability. Mean arterial pressure (MAP) and HR were sampled every 2 s for 24 h from Dahl-resistant (DR) and DS rats on low- and high-salt diets (n = 12-13 in each group). MAP +/- SD was significantly elevated in the DS rats on high-salt diets (DSH); the SD of MAP in the DSH rats was also significantly higher compared with similar measurements in rats on high-salt diets (DRH) and DS rats on low-salt diets (DSL) when SD was divided by MAP. MAP was higher at night than during the day in the DSH rats. In contrast, HR and HR variability were not significantly different between the groups. The baroreflex control of HR, determined by means of graded injections of phenylephrine, was least in the DSH rats and increased, respectively, with DSL rats, DRH rats, and DR rats on low-salt diets. There was no significant correlation between the baroreflex control of HR and MAP or the SD of MAP in the DSH rats, suggesting that there is not a simple relationship between baroreflex gain and the overall behavior of MAP in DSH rats.
The reflex mechanisms that produce the neurocirculatory adjustments to hemorrhagic hypotension are incompletely understood. The goal of this study was to determine if hemorrhagic hypotension in rats produces differential effects on sympathetic outflow to the adrenal gland and kidney and if the two sympathetic nerve responses are governed by different reflex mechanisms. We performed simultaneous multifiber recordings of adrenal and renal sympathetic nerve activity (SNA) during 8 minutes of sustained hemorrhagic hypotension to a mean arterial pressure of 50 mm Hg in chloralose-anesthetized Sprague-Dawley rats with a) baroreceptors intact, b) cervical vagotomy, c) sinoaortic baroreceptor denervation, and d) combined vagotomy plus sinoaortic denervation. During hemorrhagic hypotension in rats with intact baroreceptors, renal SNA decreased by 31 +/- 10% (mean +/- SEM, p less than 0.05 vs. control) and heart rate decreased from 384 +/- 13 to 365 +/- 16 beats per minute (p less than 0.05), but adrenal SNA increased by 69 +/- 10% over control (p less than 0.05). The decreases in renal SNA and heart rate were reversed by cervical vagotomy but not by atropine, which indicates vagal afferent mediation. In contrast, the increases in adrenal SNA during hemorrhage were not affected by vagotomy alone or by sinoaortic denervation alone but were markedly attenuated by combined sinoaortic denervation and vagotomy, which indicates redundancy in the baroreflex control of adrenal SNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Low frequencies of renal sympathetic nerve stimulation increase renal tubular sodium reabsorption without causing renal hemodynamic changes. We tested the hypothesis that the natriuretic responses to synthetic atrial peptides (atriopeptin III [APIII], 24 amino acids) are modulated by the renal tubular actions of the renal nerves. Responses to intravenous infusions of APIII (0.5 and 2.0 micrograms/kg/min) were examined in three groups of chloralose-anesthetized rats. Bilateral renal function studies were done in all three groups in which the right kidney was denervated and the left kidney was either left innervated (group I, n = 10) or the distal portion of the transected left renal nerves was stimulated at 15 V, 1 msec, and 0.5 Hz (group II, n = 8) or 1.0 Hz (group III, n = 8). In groups I, II, and III, diuretic and natriuretic responses to APIII were significantly (p less than 0.05) less in the kidneys with intact innervation or low-frequency (0.5 and 1.0 Hz) renal nerve stimulation than in the denervated kidneys. In conclusion, renal excretory responses to APIII are substantially modulated by the renal tubular actions resulting from low-frequency renal nerve stimulation. We speculate that the decrease in renal excretory responses to atrial peptides in pathophysiologic states such as congestive heart failure, nephrotic syndrome, and cirrhosis may result in part from an increase in the prevailing level of renal sympathetic nerve activity.
The voices of 12 patients who had been treated by radiotherapy for Stage I squamous carcinoma of the glottis at least 10 years previously, and who had shown no signs of recurrent disease, were assessed. A speech therapist detected significant abnormalities in all patients, but these did not detract from the overall high satisfaction of the patients with their voice quality.
A common feature of reporting head and neck squamous cancer statistics in recent years has been to consider patients dying with no evident disease (NED) as successfully treated. We present two patients who died with no clinically evident squamous cancer and who could therefore have been reported as cured but for autopsy findings which showed significant distant spread. These findings are supported by several reports of distant metastases in squamous head and neck cancer and it is suggested that rates of post-mortem examinations be included in survival figures in the future.
Hemorrhage in rats produces reflex decreases in heart rate (HR) and renal sympathetic nerve activity (RSNA). Because serotonergic antagonists attenuate hemorrhage-induced vagal-mediated bradycardia, we determined whether blockade of serotonin synthesis by p-chlorophenylalanine (PCPA) or of serotonin receptors with methysergide would also abolish the renal sympathoinhibition. Mean arterial pressure (MAP), HR, and RSNA were recorded in chloralose-anesthetized rats pretreated with PCPA (300 mg.kg-1.day-1 X 3 days ip, n = 12) or vehicle (0.3 ml saline, n = 9). During hemorrhage, where MAP was maintained at 50 mmHg for 8 min, vehicle-treated rats decreased HR by 27 +/- 13 beats/min and RSNA by -55 +/- 7%. In PCPA-treated rats, HR and RSNA did not change. Cervical vagotomy abolished the bradycardia and sympathoinhibition during hemorrhage. After acute administration of methysergide (400 micrograms/kg iv, n = 8) hemorrhage produced increases of RSNA, whereas vehicle (0.5 ml saline, n = 7) preserved the renal sympathoinhibition to hemorrhage in conscious rats. Finally, volume expansion (0.88 ml blood/100 g body wt) produced comparable decreases in RSNA in sinoaortic-denervated rats pretreated with PCPA (n = 11) or vehicle (n = 10) (-58 +/- 9 vs. 47 +/- 7%, respectively). We conclude that serotonergic mechanisms are critically involved in vagal afferent inhibition of RSNA during severe hemorrhage in rats.
Previous studies have identified two distinct types of cardiac vagal afferents, mechanosensitive and chemosensitive. We tested the hypothesis that these two types of vagal afferents mediate different reflex sympathetic nerve responses. We compared effects of stimulation of chemosensitive and mechanosensitive vagal afferents on renal and adrenal sympathetic nerve activity in rats. In anesthetized, sinoaortic baroreceptor-denervated rats, we measured arterial pressure, heart rate, and renal and adrenal sympathetic nerve activity during intrapericardial administration of phenyl diguanide as a stimulus for chemosensitive afferents and during volume expansion and acute occlusion of the ascending aorta as stimuli for mechanosensitive afferents. Stimulation of chemosensitive afferents with phenyl diguanide (3, 10, and 30 micrograms/kg intrapericardially) caused decreases in renal sympathetic nerve activity (-36 +/- 5, -52 +/- 11, and -71 +/- 5%; p less than 0.01) and in arterial pressure and heart rate but increased adrenal sympathetic nerve activity (+14 +/- 27, +63 +/- 21, and +83 +/- 28%; p less than 0.05). These responses were abolished by vagotomy. Intrapericardial injection of saline vehicle did not change renal and adrenal sympathetic nerve activity. In contrast to the effects of phenyl diguanide, activation of mechanosensitive afferents by volume expansion with intravenous infusion of 6% dextran in 0.9% saline (Dextran 75) decreased both renal and adrenal sympathetic nerve activity. Stimulation of mechanosensitive afferents by acute occlusion of the ascending aorta also decreased both renal and adrenal sympathetic nerve activity. These results indicate that chemosensitive and mechanosensitive cardiac vagal afferents produce different reflex responses: Chemosensitive afferents increase and mechanosensitive afferents decrease adrenal sympathetic outflow.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Eighty-seven postmenopausal patients have been randomised to receive either radiotherapy or Nolvadex (tamoxifen) as first line treatment for locally advanced (stage III) breast cancer. After a median follow-up of two years no significant differences have been found in the rate of progression of local disease, the time to development of overt metastases or survival.
Chemotherapy prolongs survival of patients with small-cell lung cancer, but very few are cured, and the treatment is unpleasant. Thirty patients, 28 with advanced disease, were treated with etoposide 250 mg/m2 orally, daily for 5 days, plus vincristine 2 mg intravenously on the first day, the cycle being repeated 3-weekly, to a maximum of 6. There was a response rate of 70%, a median survival of 249 days, and an 11% 2-year survival. Symptomatic side-effects were less pronounced than with most other regimens of comparable efficacy.
Herpes simplex virus (HSV) types 1 and 2 were shown to replicate in a newly described human cell line (Meg) derived from the peripheral blood of a healthy volunteer. The cell line has both megakaryocyte-like and B cell-like properties. Upon infection with HSV-1 or -2, at a m.o.i. between 0.5 and 5, unlike B and T cells, the Meg cells were growth-arrested and this was accompanied by cytopathic effects and virus replication. The HSV proteins and glycoproteins B and D (gB and gD) made in the blood-derived Meg cells were compared to the corresponding proteins made in the non-blood-derived cell lines, Vero (African green monkey kidney cell) and HEp-2 (human epidermoid carcinoma cell). The maximum level of HSV protein synthesis occurred earlier in the Meg cells than in the Vero and HEp-2 cells. The electrophoretic pattern of HSV-1 and -2 proteins made in the Meg cell line was similar to the corresponding proteins made in the Vero and HEp-2 cell lines; however, some qualitative and quantitative differences were evident. There were no apparent differences detected in the migration pattern of gB made in all three cell lines while significant differences were observed with the gD species. However, upon hydrolysis with Staphylococcus aureus V-8 protease of the monoclonal antibody-purified gB and gD, distinct differences were observed in the electrophoretic pattern of the generated peptide fragments of both gB and gD made in the three cell lines. The results demonstrate that a human blood cell can support HSV replication and that species-specific post-translational modification of gB and gD occurs in HSV-infected Vero cells as compared to HSV-infected human cells.
Vagal afferent pathways contribute to vasomotor inhibition and renal sodium handling by modulating sympathetic nerve activity in rats. Low pressure or cardiopulmonary baroreflex inhibition of sympathetic nerve activity is attenuated in normotensive Dahl salt-sensitive (S) rats fed a low-salt diet. The aim of the study was to record activity in single-fiber vagal filaments from left atrial endings in Dahl S and resistant (R) rats to evaluate the mechanism for the attenuated low pressure baroreflex. Rats were fed a low-salt diet (0.1% NaCl) for 5-7 wk. Seven Dahl R and six S rats were anesthetized with urethan, and catheters were placed in the aorta and left atrium. Single-fiber recordings were obtained from the right cervical vagus. The relationship between left atrial pressure and receptor discharge was obtained during graded aortic snaring. Mean threshold for increased activation of the vagal afferents during volume expansion was 10.4 +/- 0.6 mmHg (means +/- SE) in S and 6.0 +/- 0.4 mmHg in R rats (P less than 0.002). Pressure-discharge curves were significantly shifted to the right in S rats. Maximal sensitivity of the endings expressed as delta discharge/delta LAP was not significantly different in R vs. S, but the right shift in threshold reduced the discharge of endings over a physiological range of filling pressures. We also measured left ventricular end-diastolic pressure (LVEDP) in conscious S and R rats to determine if the resetting of left atrial sensory endings could be explained by elevated left heart filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
We tested the hypothesis that high dietary calcium attenuates hypertension in Dahl salt-sensitive rats by neural as opposed to vascular mechanisms. Four-week-old Dahl salt-sensitive rats were fed a high salt diet (3.3% sodium) with either high (4.0%; n = 21) or normal (0.4%; n = 21) calcium content until they were 10 to 11 weeks old. Total plasma calcium concentration was increased and plasma phosphorus concentration was decreased by the high calcium diet. At 10 weeks, food intake and intestinal absorption of sodium were not altered by the high calcium diet. There were three major observations. First, mean arterial pressure was lower in awake rats fed a high versus normal calcium diet (137 +/- 7, n = 11, vs 165 +/- 6 mm Hg, n = 10, respectively; p less than 0.05). This pressure difference was dependent on intact autonomic transmission, since ganglionic blockade eliminated the significant difference between pressures in rats fed high (78 +/- 5 mm Hg) and normal (85 +/- 6 mm Hg) calcium diets. Second, high calcium intake augmented baroreceptor reflex inhibition of renal sympathetic nerve activity and heart rate during ramp increase in arterial pressure produced by infusion of phenylephrine. Reflex suppression of renal sympathetic nerve activity was twofold greater in rats fed the high (vs normal) calcium diet (-2.79 +/- 0.25 vs -1.34 +/- 0.14% delta/delta mm Hg, respectively; n = 9 rats per group; p less than 0.05). Third, high calcium intake did not attenuate vascular responsiveness, since pressor responses to norepinephrine and angiotensin II did not differ between rats fed high and normal calcium diets after ganglionic blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Fifteen patients with stage III or IV squamous cell carcinoma of the larynx were treated by primary radiotherapy using a schedule of 3 small (1.1-1.5 Gy) fractions per day, an interval between fractions of 3-4 h, and a total dose of approximately 60 Gy. Primary tumour control was achieved in 13 cases, but in one of these neck node metastases were not controlled. Acute mucosal reactions were brisk, but tolerable; late complications were severe in 3 patients. Early, encouraging results in terms of tumour response must be tempered by caution over the late damage: a number of factors probably contribute to this, especially interval between fractions and total dose. From a practical viewpoint, the latter may be easier to influence, if 3 small fractions per day are to continue to be used.