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T S Harrison

Publications and source records attributed to T S Harrison.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effect of infection with human immunodeficiency virus on the anticryptococcal activity of lymphocytes and monocytes.

The effect of infection with human immunodeficiency virus (HIV) on the capacity of human lymphocytes and monocytes to inhibit and kill Cryptococcus neoformans in an 18-h assay was examined. In vitro infection of the Jurkat human T cell line with each of 3 HIV strains caused significant loss of anticryptococcal activity, which peaked 3-4 weeks after HIV infection. Lymphocytes from HIV-seropositive and -seronegative persons had similar activity, even if highly enriched for CD4 cells. The activity of lymphocytes from both seropositive and seronegative donors was increased by culture with interleukin-2 and phytohemagglutinin, but only activated lymphocytes from seronegative donors caused a reduction in C. neoformans colony-forming units. Both peripheral blood mononuclear cells and monocytes from HIV-positive persons had significantly reduced antifungal activity compared with cells from seronegative donors. Thus, under defined conditions, infection with HIV can impair the anticryptococcal activity of both lymphocytes and monocytes. Such qualitative defects may contribute, together with CD4 lymphocytopenia, to the particular susceptibility of HIV patients to cryptococcosis.

CD4 Antigens↗
PubMed1995

Mechanisms of inhibition of Cryptococcus neoformans by human lymphocytes.

Recently, our laboratory and others have demonstrated that human peripheral blood T and NK lymphocytes directly inhibit the growth of Cryptococcus neoformans. In this study, we further define the conditions under which lymphocyte-mediated fungistasis against C. neoformans occurs and examine whether mechanisms implicated in lymphocyte-mediated activities against other target cells are also involved in anticryptococcal activity. The addition of whole or broken heat-killed C. neoformans modestly inhibited lymphocyte-mediated fungistasis, whereas other particulates had no effect. The hydroxyl radical scavenger catechin, but not diethyl urea or propyl gallate, profoundly inhibited fungistasis. Salicylic acid inhibited fungistasis in a dose-dependent fashion. However, two other cyclooxygenase inhibitors, piroxicam and indomethacin, had no effect, suggesting that the mechanism of inhibition by salicylic acid was cyclooxygenase independent. Reagent prostaglandin E2, at concentrations shown by others to inhibit NK cell-mediated bactericidal and tumorlytic activities, had no effect on lymphocyte-mediated fungistasis. The addition of selected monoclonal antibodies or ligands reactive with receptors on human lymphocytes had no significant effect on lymphocyte-mediated fungistasis. Acapsular, small-capsuled, and large-capsuled C. neoformans organisms were inhibited by lymphocytes to an approximately equal extent. These data demonstrate that lymphocyte-mediated activity against C. neoformans proceeds regardless of the presence of capsule and by mechanisms at least in part dissimilar from those seen with other target cells.

Antibodies, Monoclonal↗
PubMed1994

A criterion based audit of community-acquired pneumonia.

UNLABELLED: We undertook a prospective audit of patients admitted to a specialist respiratory unit in order to assess: (a) the completeness of the objective assessment of severity of community-acquired pneumonia in patients on admission to hospital, and whether such indices were useful in predicting outcome; (b) the completeness of microbiological testing and whether maximizing the number of specimens sent to the laboratory would increase the frequency of positive microbiological diagnoses and; (c) the influence of the above on clinical management. Forty-eight patients with consolidation on chest X-ray were studied in two audit periods: 1 February 1991 to 1 May 1991 and 2 May 1991 to 16 March 1992. After the first audit period, a rubber stamp with a check list of microbiological investigations was used in the patients' notes. Seven 'markers of severity' of pneumonia, were recorded consistently throughout the study and these were useful in predicting outcome (P < 0.01). In the first audit period sputum culture, blood culture and acute serology were recorded in approximately 50% of patients. Following the introduction of the rubber stamp, the requesting of sputum, blood and urine antigen rose from none in the first audit period to 40-60%. The increase in the number of specimens obtained was not associated with an increase in the proportion of positive microbiological diagnoses. Clinical management was altered in 10 patients because of the microbiological reports and in four patients with negative microbiology (chi2 = 8.19; P < 0.01). CONCLUSION: The standard of initial assessment was high in this specialist unit, and the presence of two or more 'markers of severity' did help predict outcome. A simple change in work practice resulted in a significant improvement in the thoroughness of microbiological investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Hypothalamic and gastric myoelectrical responses during vection-induced nausea in healthy Chinese subjects.

The physiology of nausea, a uniquely human symptom, is poorly understood. The purpose of this study was to measure the temporal sequences of neurohormonal responses and gastric myoelectrical activity in healthy subjects during the rotation of an optokinetic drum that produced nausea and other symptoms of motion sickness. Plasma catecholamines, vasopressin, and cortisol were measured at baseline, during minutes 1-5, 6-10, and 11-15 of drum rotation, and after rotation stopped. Electrogastrograms were recorded throughout the study. Twelve subjects (80%) developed nausea and 4-9 cycles/min of gastric tachyarrhythmias; three subjects had no nausea and no gastric dysrhythmias. Tachyarrhythmias began 3.4 +/- 0.8 min after the onset of drum rotation, and nausea was reported, on average, 3 min later. During minutes 6-10 of drum rotation, vasopressin levels significantly increased in the subjects with nausea compared with subjects without nausea (P < 0.04). In the subjects with nausea, epinephrine and vasopressin increased significantly (P < 0.05) compared with baseline during minutes 6-10 and 11-15 of drum rotation. As nausea resolved during recovery, vasopressin decreased by 74%, whereas epinephrine increased 13%. We conclude that 1) in nauseated subjects, endogenous vasopressinergic and sympathetic circuits are activated before hypothalamic-pituitary-adrenal pathways, 2) plasma vasopressin levels correlate most closely with the temporal onset and resolution of nausea, and 3) peripheral gastric dysrhythmias may have a role in activating central vasopressinergic neurons.

Adult↗
PubMed1990

Neuroendocrine and gastric myoelectrical responses to illusory self-motion in humans.

We compared gastric myoelectrical activity and endogenous neuroendocrine responses in subjects with and without motion sickness elicited by illusory self-motion or vection. Rotating a drum with black and white vertical stripes around seated stationary subjects (n = 22) produced vection. Gastric myoelectrical activity was recorded with cutaneous electrodes. Thirteen subjects developed gastric dysrhythmias [4- to 9-cycles/min (cpm) signals] and motion sickness during vection, whereas nine subjects maintained normal 3-cpm gastric rhythms and remained symptom free. Base-line plasma cortisol and beta-endorphin levels were significantly greater (P less than 0.01) in the subjects who would develop gastric dysrhythmias and nausea compared with the subjects who would not develop motion sickness. Norepinephrine levels increased in the nauseated group immediately after vection ceased (354.6 +/- 41.1 pg/ml) compared with the symptom-free subjects (223.1 +/- 22.8 pg/ml, P less than 0.05). Epinephrine increased significantly (P less than 0.05) after vection only in the nauseated subjects, whereas dopamine levels were not altered by vection in either group. We conclude that 1) anticipatory increases in plasma cortisol and beta-endorphin occurred in subjects who would develop nausea and gastric tachyarrhythmias during vection; 2) endogenous epinephrine and norepinephrine were increased in subjects who had vection-induced nausea and gastric dysrhythmias; and 3) vection stimulates brain-gut interactions, resulting in gastric tachyarrhythmias and complex neuroendocrine responses in subjects with motion sickness.

Adult↗
PubMed1987

Site-dependent central effects of aldosterone in rats.

A relationship between the subcommissural organ (SCO) and the adrenal glands has long been suspected. This report provides further information about the effects of a continuous D-aldosterone infusion into the SCO area of conscious, adult male Sprague-Dawley rats. A 6-day aldosterone infusion (5 ng/h) increased urinary sodium excretion, decreased adrenal medullary cross-sectional area, elevated adrenal corticosterone content and terminal plasma epinephrine concentration. Mineralocorticoid infusions directly into a lateral cerebral ventricle did not affect these parameters but, unlike SCO area infusions, decreased consummatory behavior. Infusions of tritiated aldosterone into the SCO area revealed that radioactivity was mainly confined to dorsomedial portions of the brain near the SCO, whereas the pineal body contained only background radioactivity. The data support the concept that the SCO area interacts with physiological systems related to both the adrenal cortex and medulla.

Adrenal Glands↗
PubMed1986

Thallium-technetium parathyroid scan. A useful noninvasive technique for localization of abnormal parathyroid tissue.

We studied the usefulness of the thallium-technetium scan in 60 patients with suspected parathyroid disorders. The scan correctly localized abnormal parathyroid tissue in 82% of patients with surgically proved primary hyperparathyroidism due to a single adenoma and in 60% of patients operated on for primary hyperplasia. The scan was particularly useful in patients who had undergone previous neck explorations, since it successfully identified residual adenomatous or hyperplastic tissue in six of seven patients. False-positive images were consistently produced in all patients with coexisting thyroid disease. We conclude that the thallium-technetium scan is useful for localizing abnormal parathyroid tissue. We recommend its routine use in patients with persistent or recurrent hypercalcemia following neck exploration for primary hyperparathyroidism who have no evidence of thyroid disorders.

Adenoma↗
PubMed1986

Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity.

In an evaluation of 213 patients from 15 kindreds with familial medullary thyroid carcinoma (MTC), we detected 41 subjects from two kindreds (L and O) who had MTC but no extra-thyroidal manifestations (hyperparathyroidism, phaeochromocytomas or mucosal neuromas) of multiple endocrine neoplasia (MEN) type IIa or IIb. In screening 178 members of the L and O kindreds, we found no evidence that any of them had died from MTC. To assess whether the malignancy was relatively indolent in these families, 20 selected subjects from the two kindreds were compared with 33 MEN IIa subjects. Both groups had clinically occult disease which was diagnosed biochemically by documenting elevated plasma calcitonin (CT) levels following stimulation with intravenous calcium and pentagastrin. There were no differences in the peak stimulated plasma CT levels at the time of diagnosis (1055 +/- 236 pg/ml versus 1096 +/- 191 pg/ml) or the incidence of regional lymph node metastases (0/20 versus 1/33) in the two groups. The mean age at diagnosis, however, was significantly higher in patients of the L and O kindreds than in patients with MEN IIa (43.1 +/- 3.4 years versus 21.1 +/- 2.2 years; P less than 0.001) indicating that in the two kindreds the MTC either developed at a later age or grew more slowly. This study demonstrates that MTC may occur in a familial pattern distinct from its presentation as MEN IIa or MEN IIb. In this setting it appears to be the least aggressive form of MTC yet described.

Adolescent↗
PubMed1986

Autoregulation and regional blood flow of the dog during hemorrhagic shock.

In 42 anesthetized dogs, we studied autoregulation and regional blood flow in the adrenal gland during hemorrhagic hypotension at 70, 50, and 30 mmHg of mean arterial pressure and in trimethaphan camsylate (TMP)-induced hypotension at 50 mmHg. Blood flow was measured by nonradioactive microspheres. Renal blood flow was significantly reduced at 50 mmHg, but total adrenal blood flow did not significantly decrease until the blood pressure fell below 30 mmHg. The autoregulatory response was clearly different between the kidney and adrenal gland. Cortical blood flow decreased significantly at 50 mmHg, but medullary blood flow increased in contrast to the reduction of blood pressure below 70 mmHg and returned at 30 mmHg to the flow rate seen in normotensive control. TMP induced a similar response in the medulla to that at 50 mmHg of hemorrhagic hypotension, and atropine reversed this TMP-induced change. Opposite microvascular responses were observed during hypotension: medullary blood flow increased and cortical flow decreased. This medullary vascular response is considered to contribute to the maintenance of total adrenal blood flow during hemorrhagic hypotension.

Adrenal Cortex↗
PubMed1986

Early postoperative function of suppressed parathyroid glands with microscopic hyperplasia.

Calcium-parathyroid hormone (Ca-PTH) relationships were studied perioperatively in 35 patients with primary hyperparathyroidism. Twenty-nine patients had solitary adenomas that caused preoperative hypercalcemia; those patients whose remaining glands were subjected to biopsy were classified as having either microscopic evidence of suppression in those glands (15 patients) or no evidence of suppression (less than or equal to 30% stromal fat on biopsy cross sections, 11 patients). Before surgery, all patients showed the expected positive slopes for Ca-PTH linear regression curves. After surgery, all patients with adenomas showed an immediate and sustained shift of the Ca-PTH regression to the right; this shift achieved statistical significance only in those patients whose remaining glands showed microscopic evidence of suppression (greater than 30% fat, p less than 0.05). Moreover, the slope of the Ca-PTH regression curve for these patients assumed a negative value 1 month after surgery. All patients with adenomas were eucalcemic after surgery, regardless of the cellularity of the remaining in situ glands. We conclude that the absence of microscopic suppression in grossly suppressed parathyroid glands at the time of adenoma resection for hyperparathyroidism does not affect postoperative results. However, the presence of microscopic hyperplasia in macroscopically normal or suppressed glands may represent a persistent alteration in biologic function, evidenced by failure of these glands to achieve negative calcium regulation.

Adenoma↗
PubMed1985

Dual isotope subtraction parathyroid scintigraphy in the preoperative evaluation of suspected hyperparathyroidism.

Ninety-five percent of primary hyperparathyroidism is caused by either a solitary hyperfunctioning adenoma or chief cell hyperplasia. While there is a great deal of variation in the location of the parathyroid glands, 90-95% of all abnormal parathyroid tissue will be identified at initial exploration regardless of the preoperative localization procedure. Adenomas not identified at initial exploration are likely to be ectopic. Reexploration is a difficult and time-consuming procedure. The challenge, therefore, is to develop a reliable, noninvasive test that will locate aberrant parathyroid tissue preoperatively with the goal of simplifying the surgical procedure and reducing the incidence of reexploration. A radiopharmaceutical which localizes selectively in parathyroid tissue would be ideal. Currently, no single radiopharmaceutical is adequate. Recently, dual isotope subtraction scintigraphy using T1-201 chloride and Tc-99m pertechnetate has yielded promising results. The authors have investigated this procedure in 42 patients, 25 of whom to date have had surgical exploration. Of the 25 adenomas or focal hyperplasia sites found at surgery, 23 (92%) were correctly located preoperatively. There were two false-negative sites and five false-positive sites. The purpose of this paper is not only to describe the methods used and results obtained but also to discuss the merits and limitations of the technique in comparison with other imaging modalities so that its role, in today's climate of cost containment, may better be defined.

Adenoma↗
PubMed1985

Central role for angiotensin in control of adrenal catecholamine secretion.

Angiotensin II (ANG II) is required for unimpaired adrenal reflex secretion of catecholamines after hemorrhage in the dog. To test if ANG II acts centrally, experiments were performed under general anesthesia on bilaterally or sham-nephrectomized dogs hemorrhaged at 25 ml/kg. Ventriculocisternal perfusion of ANG II or its antagonist saralasin was accomplished via needles inserted in the left lateral cerebral ventricle and cisterna magna. Mean arterial pressure and adrenal secretion of catecholamines were measured before and after hemorrhage. Nephrectomized dogs receiving only artificial cerebrospinal fluid (CSF) by ventriculocisternal perfusion had a very small adrenal response to hemorrhage compared with animals receiving ANG II intraventricularly (IVT) (at 10 and 100 pg . kg-1 . min-1). This effect of ANG II IVT also depended on the rate of IVT infusion. Peripheral infusion of ANG II (10 pg . kg-1 . min-1) had no effect on adrenal catecholamine secretion. Animals with intact kidneys given saralasin IVT (0.06 ng/min) responded similarly to nephrectomized dogs receiving only CSF IVT. Intravenous saralasin did not blunt the response to hemorrhage. Thus ANG II appears to support catecholamine secretion via a central mechanism. This mechanism is physiologically significant because either nephrectomy or functional elimination of ANG II by saralasin greatly attenuates the adrenal medullary response to hemorrhage in vivo.

Adrenal Glands↗
PubMed1985

Angiotensin II restoration of reflex adrenal medullary secretion to anephric dogs is physiologically dose dependent.

Acute nephrectomy seriously impairs hypovolemic adrenal epinephrine (E) release in the anesthetized dog. That systemically delivered angiotensin II totally restores E release to acutely anephric dogs is equally clear, but the dose-response relationship of this angiotensin II effect is not known. Adrenal secretion rates and arterial plasma E, norepinephrine (NE), and dopamine levels were studied in nine groups of mongrel dogs (n = 5 in each group) under pentobarbital anesthesia: 1) resting animals; 2) hemorrhage (25 ml/kg); 3) hemorrhage after acute nephrectomy; 4-7) hemorrhage, acute nephrectomy, plus iv angiotensin II at a) 0.01 ng/kg X min, b) 0.10 ng/kg X min, c) 1.00 ng/kg X min, or d) 10.00 ng/kg X min; 8) no hemorrhage, acute nephrectomy, angiotensin II (10.00 ng/kg X min); and 9) hemorrhage, kidneys intact, iv angiotensin II (10.00 ng/kg X min). Arterial and adrenal blood were sampled during a baseline prehemorrhage period and 15, 30, 60, and 90 min after hemorrhage. We confirm blunting of reflex E release by acute nephrectomy in the anesthetized dog and show that angiotensin II restores E (P less than 0.01), NE (P less than 0.01), and dopamine (P less than 0.01) release in acutely anephric dogs. Aortic plasma E and NE were also restored to normal by angiotensin II (P less than 0.01 for each). Dogs with intact kidneys show a blunted hemorrhage response of arterial plasma E (P less than 0.01), NE (P less than 0.01), and DM (P less than 0.05) to our largest angiotensin II infusion rate (10 ng/kg X min). The study demonstrates that in acutely anephric conditions, angiotensin II support of reflex catecholamine release is sensitively dose dependent to physiological infusion rates of systemic angiotensin II and suggests further that this angiotensin II effect is restrained by the kidneys.

Adrenal Glands↗
PubMed1984

Renal modulation of electrically stimulated adrenal medullary secretion.

In acutely anephric dogs, depressed reflex adrenal medullary secretion (AMS) may be related to low plasma angiotensin. Either local (adrenal medulla) or central nervous system mechanisms are responsible. Local influences of acute bilateral nephrectomy on AMS were evaluated after left splanchnic nerve section. Two groups of five healthy, fasted mongrel dogs (16-20 kg) were prepared (Na pentobarbital iv anesthesia, 98% O2/2% CO2, Harvard volume ventilator) at celiotomy with blood pressure and sampling catheters per femoral arteriotomies and left adrenal-femoral venous T-shaped Silastic shunt. Group 2 dogs had acute bilateral nephrectomy. The acutely divided distal left splanchnic nerve was arranged for electrical stimulation (Grass, bipolar nerve stimulator, 1 0 V, 1-msec delay, 10 Hz, 10-msec square wave). Heparin anticoagulation was maintained and arterial pH monitored. Simultaneous adrenal vein, aortic blood sampling, and adrenal blood flow (F) determinations followed 10-min periods of alternating electrical stimulation and nerve rest. AMS for epinephrine (E) and norepinephrine (NE) was calculated [E and NE plasma concentration (single isotope radioenzymatic technique) differences of adrenal vein minus aorta multiplied by F]. Results were grouped, analyzed for variance, and compared (Wilcoxon unpaired rank sum, Student's test, Fischer's tables, ANOVA). Low aortic E, NE concentrations confirmed absent systemic adrenergic stimulation. The AMS ratio of NE:E was low in the anephric group. At the first stimulation interval NE:E was 0.28 +/- 0.14 (1 SD) in renal intact dogs vs 0.11 +/- 0.04 in anephric dogs, P less than 0.05. At rest NE:E was 0.33 +/- 0.12 in group 1 vs 0.17 +/- 0.02 in group 2 dogs, P less than 0.02. Plasma NE was also low in the anephric group (289 mg/liter +/- 126 (1 SD) vs 612 +/- 189, P = 0.033, resting).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1984

Solitary parathyroid microadenoma.

In our experience with operations for primary hyperparathyroidism, a recurring problem centers on patients whose solitary adenomas are too small to be appreciated at the initial exploration. We have seen four patients with parathyroid microadenomas, which we define as lesions less than 6 mm in diameter in externally undeformed parathyroid glands. Two such patients were fortuitously cured at the initial exploration even though the operative findings were inconclusive. One, a 25-year-old man, underwent excision of an externally normal gland that contained a 3 by 2 by 2 mm microadenoma. He is eucalcemic since the operation. The other patient, a 70-year-old woman with hypercalcemia, responded to prednisone. She then underwent a neck exploration at which the diagnosis of sarcoidosis was confirmed by lymph node biopsy examination. A 4 by 2 by 2 mm parathyroid microadenoma was incidentally removed. The patient is normocalcemic receiving low-dose steroid treatment since the operation. In a third patient, a 34-year-old practical nurse, three explorations were needed to find a parathyroid gland, which was negative for adenoma on frozen-section microscopy. The solitary adenoma, 6 by 3 by 3 mm, was appreciated only on permanent sections. The majority of oxyphil microadenomas should be suspected to be nonfunctioning, as in a 59-year-old woman in whom the lesion coexisted with primary chief cell parathyroid hyperplasia. The hyperparathyroidism responded well to three and a half-gland resection. The 2 by 2 by 2 mm oxyphil adenoma was also removed. Solitary parathyroid adenomas can be subtle and small. Appraisal of parathyroid disease at the operating table is not always straightforward. As more patients with early hyperparathyroidism appear on routine calcium screening, we may expect to see increasing numbers of challenging solitary parathyroid microadenomas.

Adenoma↗