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Biomedical subjects

S Henderson

Publications and source records attributed to S Henderson.

At least 145 records · Page 8Linked to original sources

Evidence for a general neurotic syndrome.

Neurotic syndromes are defined by characteristic patterns of symptoms, but the validity of the distinction between one syndrome and another depends on associations between the syndromes and clinical history, or treatment response factors that are independent of the defining phenomena. In both a group of twin volunteers and a group of patients with panic disorder/agoraphobia, the lifetime experience of more than one diagnosis of a neurotic syndrome was common but there was no evidence of patterns of co-occurrence of diagnoses being associated with particular syndromes. Receiving a diagnosis was associated with abnormal scores on measures of neuroticism and locus of control, the extent of the abnormality increasing with the number of different diagnoses satisfied. It is argued that the concept of a general neurotic syndrome depends in part on the presence of such predisposing personality factors, and that reduction in this predisposition to neurosis should be the focus of treatment.

Adolescent↗

Diltiazem versus propranolol in essential hypertension: responses of rest and exercise blood pressure and effects on exercise capacity.

Both beta-blocking and calcium channel-blocking drugs are being used with increasing frequency as initial therapy for essential hypertension. The present study was designed to compare the antihypertensive effects of a beta-blocking drug, propranolol, with a calcium channel-blocking drug, diltiazem, at rest and during upright bicycle exercise and to determine whether exercise capacity is altered by these therapies. Twenty-one patients with uncomplicated systemic hypertension and a diastolic blood pressure (BP) of 95 to 110 mm Hg without medication were randomly assigned to propranolol or diltiazem therapy in a double-blind manner. The total daily dosages were titrated as needed, from 160 to 480 mg of propranolol (mean 371 mg) and 120 to 360 mg of diltiazem (mean 307 mg) over 12 weeks, and the titrated dose was maintained for 4 additional weeks. Both drugs significantly reduced supine BP (from 149 +/- 14/101 +/- 4 to 136 +/- 17/89 +/- 10 mm Hg with propranolol and from 157 +/- 14/103 +/- 4 to 144 +/- 13/93 +/- 8 with diltiazem. Only diltiazem reduced BP during submaximal exercise, but both agents produced significant responses during maximal exercise. Diltiazem had no effect on maximal heart rate, exercise duration or O2 uptake, whereas propranolol reduced maximal VO2 from 27 +/- 6 to 22 +/- 6 ml/min/kg (p less than 0.01) and also shortened duration of exercise. Propranolol, despite its effects on heart rate, maintained the workload VO2 relation at submaximal loads, suggesting an increased oxygen delivery. However, these adaptive mechanisms appear to be insufficient during maximal effort.

Blood Pressure↗

Diltiazem prevents hypertrophy progression, preserves systolic function, and normalises myocardial oxygen utilisation in the spontaneously hypertensive rat.

The effects of diltiazem, a calcium channel blocker, and methyldopa, an adrenergic blocker, on left ventricular hypertrophy and left ventricular function were assessed in spontaneously hypertensive rats and Wistar-Kyoto controls. Diltiazem (30 mg.kg-1/day), methyldopa (400 mg.kg-1/day), or placebo were given with water for six months. Left ventricular function was studied in 12 month old animals using an isovolumetrically contracting heart preparation by measuring maximum developed pressure and myocardial oxygen consumption. Systolic blood pressure was reduced by both drugs but more so by methyldopa. Despite its lesser antihypertensive effect, diltiazem reduced heart to body weight ratios in the spontaneously hypertensive rat to a similar degree as methyldopa (3.4(0.2) and 3.4(0.1) compared with placebo 3.7(0.2), p less than 0.05). Maximum developed pressure increased with methyldopa and diltiazem compared with placebo (188(11) and 200(11) vs 166(11) mmHg, p less than 0.05). Myocardial oxygen consumption was lower in the spontaneously hypertensive rat receiving placebo than in the controls (22.8(3.2) vs 28.3(3.8) ml.min-1.100 g-1, p less than 0.05) and was significantly increased by diltiazem but not by methyldopa (27.9(0.4) vs 24.5(0.6) ml.min-1.100 g-1, p less than 0.05 and NS respectively vs the spontaneously hypertensive rat receiving placebo). Diltiazem and methyldopa normalised the isomyosin composition in the spontaneously hypertensive rat. Myocardial concentrations of energy related metabolites obtained at maximum developed pressure were not different between spontaneously hypertensive rats receiving placebo and controls. However, both diltiazem and methyldopa treated spontaneously hypertensive rats showed a significant reduction in adenosine triphosphate and phosphocreatine and a rise in inorganic phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

LTB4 production and lysosomal enzyme release by rat alveolar macrophages: effects of phagocytosis, receptor binding, and ionophore stimulation.

We have previously shown that the predominant lipoxygenase product of arachidonic acid metabolism in rabbit alveolar macrophages is leukotriene (LT) B4. LTB4 was not detectable in normal unstimulated rabbit macrophages, but its production was increased following calcium ionophore A23187 stimulation, especially after in vivo activation of the immune system. In the present study, we describe that (a) rat alveolar macrophages produced LTB4 in response to natural, biological stimuli such as binding of Fc receptors and complement receptors, as well as zymosan phagocytosis and ionophore stimulation. In contrast, binding of lectin receptors such as concanavalin A and phytohemagglutinin failed to elicit significant increase of LTB4. (b) The predominant LT that was produced was LTB4 regardless of the type of stimulus. This pattern is similar to that of rabbit lung macrophages, but rat alveolar macrophages released higher quantities of LTB4, which can be easily quantitated by high-performance liquid chromatography (HPLC). (c) Phorbol myristate acetate by itself was a weak agonist for LTB4 release. Yet, in combination with a low dose of calcium ionophore A23187 it resulted in LTB4 production. (d) There was a general correlation between release of LTB4 and lysosomal enzymes. In other words, the stimulus that is effective for eliciting enzyme release was usually also effective in causing LTB4 production. (e) A considerable proportion of the LTB4 produced was retained intracellularly. This phenomenon was especially pronounced when zymosan was used as stimulus. (f) Despite the parallelism between LTB4 production and lysosomal enzyme release, the former probably does not regulate the latter. The time courses of their release are dissimilar, and nordihydroguaiaretic acid fails to inhibit lysosomal enzyme release by a dose markedly inhibiting LTB release. (g) Contrary to rabbit lung macrophages rat lung macrophages showed a predominance of lipoxygenase pathway over cyclooxygenase pathway following zymosan ingestion. However, macrophages from both species produced mainly cyclooxygenase products in response to exogenous arachidonic acid.

Animals↗

A transcriptional terminator is a novel element of the promoter of the mouse ribosomal RNA gene.

Sequences flanking residue-168 of the mouse rRNA gene are essential to direct efficient transcription in transfected cells and are stimulatory in vitro on closed circular templates. This promoter domain evidently functions by the unprecedented mechanism of terminating polymerase I-directed transcripts. It inhibits transcripts from reading into the initiation region, acting cotranscriptionally to end these RNAs at residue--182 and release them from the template. Most likely, polymerases on tandem genomic rRNA genes are not released upon completing each 40-47S transcript, but traverse the entire spacer to the next promoter-terminator, where they are made available and positioned to favor reinitiation. Through such polymerase recycling, plus the binding of free polymerase, the rDNA promoters could achieve their characteristically high level of transcription.

Animals↗

Heavy charged particle therapy of bone and soft tissue sarcoma. A phase I-II trial of the University of California Lawrence Berkeley Laboratory and the Northern California Oncology Group.

At the University of California Lawrence Berkeley Laboratory and the Northern California Oncology Group, a preliminary study of heavy charged particle radiotherapy in soft tissue and bone sarcoma has been carried out. Fifty-two patients with bone or soft tissue tumors were treated wholly or in part with heavy charged particles from 1978 to 1985. Eleven patients, considered inevaluable for purposes of this analysis, received less than 50 Gray-equivalents (GyE) because of the following: progressive disease (three patients); palliative treatment due to recurrent disease after previous radiation therapy (three patients); or since they were part of preliminary studies of relative biological effectiveness (RBE) (five patients). Forty-one patients received from 50 to 78.5 GyE, with a mean of 65 GyE. They had an average of 23 months follow-up, ranging from 4 to 78 months. In patients with paraspinal chondrosarcoma 9 of 11 had local control, with a mean follow-up time of 32 months. In the remaining patients with other histologies, 19 of 30 were controlled within the irradiated area, with a mean follow-up time of 20 months. Serious complications were encountered in the CNS (four patients), in the bowel (one patient), and in bone (one patient). Heavy charged particle radiotherapy appears to be of value in treating bone or soft tissue sarcoma; further trials are planned.

Actuarial Analysis↗

The biosynthesis of leukotriene B4, the predominant lipoxygenase product in rabbit alveolar macrophages, is enhanced during immune activation.

Rabbit alveolar macrophages synthesize prostaglandins in response to various stimuli. We have previously shown that prostaglandin production was decreased in immunologically activated (live Bacillus Calmette-Guérin (BCG)-injected) animals. (Hsueh, W., Lamb, R. and Gonzalez-Crussi, F. (1982) Biochim. Biophys. Acta 710, 406-414). In the present study, we examined the lipoxygenase products of alveolar macrophages from normal and immunologically activated rabbits injected intravenously with live BCG or complete Freund's adjuvant. We found: unstimulated lung macrophages produced no detectable leukotrienes; the predominant lipoxygenase product upon stimulation was leukotriene B4; alveolar macrophages did not significantly degrade leukotriene B4 into its 20-hydroxy derivative, and the total degradation of leukotriene B4 during 90 min of incubation was minimal; the production of leukotriene B4 reached the peak at 30 min after A23187 stimulation, while zymosan caused a much slower and smaller release; following stimulation, immunologically activated lung macrophages produced more leukotriene B4 than resident macrophages. It is possible that the increased leukotriene B4 production in immunologically activated lung macrophages was related to the immunoregulatory function of this substance, such as enhancing cytotoxicity, interferon production and proliferation of suppressor-cytotoxic T cells.

Animals↗

Work performance in the iron-deficient rat: improved endurance with exercise training.

The effect of an endurance training regimen on muscle oxidative enzymes and work performance was studied in iron-deficient and -sufficient rats. Three-week-old male Sprague-Dawley rats (n = 40) were randomly assigned to diets containing either 6 mg iron/kg (iron deficient) or 50 mg iron/kg (iron sufficient). After 2 wk, each group of rats was further divided into untrained or endurance-trained subgroups. Training consisted of daily treadmill running of gradually increasing duration for a 1-mo period. After the training period, sedentary and endurance-trained iron-deficient rats were anemic (Hgb approximately 8 g/dl compared with 16 g/dl in the 2 control groups) and had significantly lower skeletal muscle cytochrome c concentration, cytochrome oxidase activity, and succinic oxidase activity compared with the iron-sufficient groups. In response to training iron-deficient rats also generally had a substantial increase in skeletal muscle oxidative enzymes (P less than 0.05), in contrast to iron-sufficient animals, in which there was little or no training effect. Work performance in response to training in the iron-deficient rats improved more than sixfold in an endurance type of exercise (P less than 0.05), but maximal oxygen consumption during a brief, intense type of exercise was not significantly affected. The results suggest that endurance training of iron-deficient rats results in a milder anemia and less drastic reduction of skeletal muscle oxidative enzymes which in turn allows better performance in an endurance type of exercise.

Animals↗

Detection and quantification of previous myocardial infarction by exercise-redistribution tomographic thallium-201 scintigraphy.

Although myocardial perfusion scintigraphy at rest accurately diagnoses myocardial infarction (MI), the prevalence and size of previous MI is overestimated by exercise-redistribution thallium-201 studies. A new, quantitative approach to the analysis of tomographic thallium-201 scintigrams was developed in order to determine whether the presence and extent of MI could be determined. Sixty patients undergoing cardiac catheterization for chest pain syndromes, including 28 with previous MI, were studied by exercise and 3-hour delayed thallium-201 scintigraphy, with use of the 7-pinhole tomographic technique. Circumferential profiles of the postexercise and 3-hour radiotracer distribution were generated from apical, midventricular and basal left ventricular slices. The 3-hour profile fell below normal limits in 24 of 28 patients (86%) with remote MI, but was also abnormal in 9 of 22 patients (41%) with coronary disease but no MI. All missed MIs were either inferior or subendocardial and were associated with normal ejection fractions. To distinguish between MI and slowly resolving ischemic defects, a quantitative approach was used. MI area was calculated as the area in which the 3-hour profile fell below the 3-hour normal limits, and a redistribution area in the MI zone was determined as the area between the postexercise and 3-hour profiles in the region where the 3-hour profile was abnormal. The MI area was 1,000 +/- 980 units in patients with MI, vs 79 +/- 120 units in patients without MI (p less than 0.001), whereas the redistribution area was higher in patients without MI (1,240 +/- 810 vs 430 +/- 400 units, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of training and exhaustive exercise on the mitochondrial oxidative capacity of brown adipose tissue.

Oxidation of pyruvate, alpha-ketoglutarate, palmitoylcarnitine, succinate, and ferrocytochrome c by interscapular-brown-adipose-tissue (BAT) mitochondria of untrained and trained rats were measured at rest and after running to exhaustion. At rest, BAT mitochondria from trained rats showed significantly lower activities (less than 50%) for the oxidation of all the substrates. In untrained rats the activities of the enzymes for the oxidation of all the substrates except pyruvate and succinate were lower at exhaustion compared to the resting state when expressed on a per-gram-fresh-weight basis. In trained rats all of the enzyme activities increased as a result of exhaustive exercise. These differences between the two groups of rats in the post-exercise changes in oxidative capacities suggest that following an initial adaptation, resulting in a large decrease in mitochondrial oxidative activity, training protects the residual oxidative pathways against exercise-induced inactivation. These data show that unlike exposure to cold, or overfeeding, a physiological stimulus such as exercise reduces the oxidative capacity of BAT, and therefore may reduce the thermogenic activity of the tissue in endurance-trained rats as has been addressed in the scientific literature.

Adipose Tissue, Brown↗

Quantitative analysis of seven-pinhole tomographic thallium-201 scintigrams: improved sensitivity and estimation of the extent of coronary involvement by evaluation of radiotracer uptake and clearance.

Recent studies have shown that the sensitivity of conventional thallium-201 scintigraphy can be increased by the quantitative assessment of myocardial radiotracer clearance rates in conjunction with the evaluation of radionuclide uptake. In this study, a similar analysis of tomographic scintigrams was performed to determine the feasibility and value of this approach, particularly in estimating the extent of disease and detecting three vessel coronary involvement. Seventy patients undergoing cardiac catheterization for chest pain were studied by exercise and 3 hour delayed thallium-201 scintigrams using the seven-pinhole tomographic technique. Each study was evaluated by visual inspection of the tomographic sections and quantitative analysis. The latter approach consisted of comparing circumferential profiles of the initial post-exercise radionuclide uptake and the 3 hour clearance rates generated from each of three left ventricular slices with similar profiles representing the lower 95% confidence limits derived from 15 middle-aged volunteers. An abnormality was considered present when a patient's profile fell below these limits for a 30 degrees arc, and was ascribed to disease in a particular artery when it involved that vessel's usual distribution. Among the 61 patients without apparent primary myocardial or valvular disease, the diagnostic sensitivity of thallium scintigraphy was increased from 86% (43 of 50) to 96% (48 of 50) without a change in specificity (both 9 of 11 or 82%). More importantly, the quantitative approach permitted detection of 85% (107 of 126) of significantly obstructed coronary vessels compared with 47% (59 of 126) by visual analysis (p less than 0.001), again without sacrificing specificity (85 versus 87%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A simple method for generation of antibodies with specificity for 1,25-dihydroxyergocalciferol and 1,25-dihydroxycholecalciferol.

A simple method for production of antisera with high affinity and selectivity for 1 alpha, 25-dihydroxyergocalciferol and 1 alpha, 25-dihydroxychole-calciferol is described. 1 alpha-Hydroxy-25,26,27-trisnorcholecalciferol-24-oic acid was coupled directly to bovine serum albumin. Rabbits immunized with this conjugate rapidly produced antibodies that bound 3H-1 alpha,-25-dihydroxycholecalciferol with high affinity and demonstrated nearly equal reactivity with 1 alpha, 25-dihydroxyergocalciferol and poor reactivity with 25-hydroxycholecalciferol; 24,25-dihydroxycholecalciferol; 25,26-dihydroxycholecalciferol; and 1 beta,25-dihydroxycholecalciferol. The use of one of these antisera has led to the development of a specific assay for 1 alpha,25-dihydroxyergocalciferol and 1 alpha,25-dihydroxycholecalciferol in human serum.

Animals↗

Computed tomography and ultrasound of retained placenta from abdominal pregnancy.

The computed tomographic (CT) and ultrasound findings in a case of retained placenta from an abdominal pregnancy are presented. To our knowledge, this is the first published report of CT findings in retained placenta of abdominal pregnancy. The complementary role of CT and ultrasound in managing this disorder are discussed.

Adult↗