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Biomedical subjects

B Kennedy

Publications and source records attributed to B Kennedy.

At least 73 records · Page 4Linked to original sources
PubMed1995

Nonadrenal epinephrine-forming enzymes in humans. Characteristics, distribution, regulation, and relationship to epinephrine levels.

Animal studies indicate that nonadrenal tissues may synthesize epinephrine (E). Here we demonstrate phenylethanolamine N-methyltransferase (PNMT) and/or nonspecific N-methyltransferase (NMT) enzymatic activity in human lung, kidney, heart, liver, spleen, and pancreas. There was a significant overall correlation (r = 0.34) between tissue PNMT and E. PNMT and NMT in human tissues differed in substrate and inhibitor specificity, thermal stability, and antigenicity. By these criteria, PNMT in human lung and in human bronchial epithelial cells were indistinguishable from adrenal PNMT. PNMT and/or NMT activity were present in red blood cells (RBCs), and cancer cell lines. Human kidney, lung, and pancreas showed immunohistochemical staining with an antibody to adrenal PNMT. RBC PNMT activity was lower in males than females and was increased in hyperthyroidism and decreased in hypothyroidism. PNMT activity in a human bronchial epithelial cell line was dramatically increased by incubation with dexamethasone. E and 3H-E levels in plasma and urine during an intravenous infusion of 3H-E into humans indicated that kidney may synthesize half of urinary E. We conclude that PNMT and NMT are widely distributed in human tissues, that they may synthesize E in vivo and are influenced by glucocorticoid and thyroid hormones.

Adrenal Glands↗
PubMed1994

Comparison of stimulable phosphor technology and conventional screen-film technology in pediatric scoliosis.

One hundred consecutive patients being investigated for scoliosis were studied using a double cassette containing a conventional film screen and a stimulable phosphor plate. The images were separated, randomised and scored thrice by three radiologists for anatomic structure visualisation. The exposure to the plate and film and repeat rate were measured. Scoliosis angles were comparable on both sets of images, however, visualisation of vertebrae, vertebral end plates, pedicles, spinous processes and other structures were significantly improved (p < 0.0001). Intra- and inter-observer reliability was high with good intraclass correlation. There was a 40% potential exposure reduction, and retakes were decreased from 3 to 0%. We conclude that stimulable phosphor images give better anatomic structure visualisation with potential radiation exposure reduction and lower repeat rate.

Child↗
PubMed1994

Does chromostatin influence catecholamine release or blood pressure in vivo?

Although the structure of chromogranin A (CgA) is now known, its ultimate physiological role remains elusive. Recently, an interior fragment of CgA [CgA(124-143)], also called chromostatin, was reported to suppress catecholamine release from chromaffin cells in vitro. We therefore explored chromostatin's biological actions when administered in vivo to anesthetized rodents with normal (Wistar-Kyoto rats) or elevated blood pressure (spontaneously hypertensive rats). Neither mean arterial pressure nor plasma epinephrine concentrations were significantly altered following either chromostatin or vehicle administration. Plasma norepinephrine, on the other hand, tended to rise throughout all studies, with the rise reaching statistical significance only in the SHR subgroup receiving chromostatin. We conclude that, unlike its actions in vitro, chromostatin does not appear to suppress catecholamine release or modulate blood pressure in vivo.

Animals↗
PubMed1994

Patient knowledge of anaesthesia and peri-operative care.

One hundred and sixty six patients were questioned by means of a multiple choice questionnaire, to determine their knowledge of peri-operative care, anaesthesia and the rôle of anaesthetists. In general, knowledge was good, but there were some important misconceptions; in particular, 28.3% of respondents thought that fasting referred to food only, and not to fluid intake. In addition, 47.6% of respondents considered pain to be a necessary part of the healing process and 38.6% believed that it was something that just had to be endured. When forthcoming anaesthesia is discussed, anaesthetists need to ascertain that patients really do understand the language used.

Adult↗
PubMed1994

Sympatho-adrenal secretion in humans: factors governing catecholamine and storage vesicle peptide co-release.

1. In postganglionic sympathetic neurones and adrenal chromaffin cells, catecholamines are co-stored in vesicles with soluble peptides, including chromogranin A (CgA) and neuropeptide Y (NPY), which are subject to exocytotic co-release with catecholamines. 2. Plasma catecholamine, CgA and NPY responses to stimulators and inhibitors of sympatho-adrenal catecholamine storage and release were measured in humans. Short-term, high-intensity dynamic exercise, prolonged low-intensity dynamic exercise, and assumption of the upright posture, in decreasing order of potency, predominantly stimulated noradrenaline (NA) release from sympathetic nerve endings. Only high-intensity exercise elevated CgA and NPY, which did not peak until 2 min after exercise cessation. Stimulated NA correlated with plasma CgA 2 min after exercise, and with NPY 5 min after exercise. 3. Insulin-evoked hypoglycaemia and caffeine ingestion, in decreasing order of potency, predominantly stimulated adrenaline (AD) release from the adrenal medulla. During insulin hypoglycaemia AD and CgA rose, but NPY was unchanged. Neither NPY nor CgA were altered by caffeine. The rise in CgA after intense adrenal medullary stimulation was greater than its rise after intense sympathetic neuronal stimulation (1.4-versus 1.2-fold, respectively). 4. Infusion of tyramine, which disrupts sympathetic neuronal vesicular NA storage, elevated systolic blood pressure and NA, while NPY and CgA were unchanged. After reserpine, another disruptor of neuronal NA storage, NA transiently rose and then fell; NPY and CgA were unaltered. After the non-exocytotic adrenal medullary secretory stimulus glucagon. AD rose while NA, CgA and NPY did not change. After amantadine, an inhibitor of protein endocytosis, both CgA and fibrinogen rose, while NA and NPY remained unaltered. Neither CgA, NPY, nor catecholamines were altered by the catecholamine uptake and catabolism inhibitors desipramine, cortisol, and pargyline. 5. Human sympathetic nerve contained a far higher ratio of NPY to catecholamines than human adrenal medulla, while adrenal medulla contained far more CgA than sympathetic nerve. 6. It is concluded that peptides are differentially co-stored with catecholamines, with greater abundance of CgA in the adrenal medulla and NPY in sympathetic nerve. Activation of catecholamine release from either the adrenal medulla or sympathetic nerves, therefore, results in quite different changes in plasma concentrations of the catecholamine storage vesicle peptides CgA and NPY. Only profound, intense stimulation of chromaffin cells or sympathetic axons measurably perturbs plasma CgA or NPY concentration; lesser degrees of stimulation perturb plasma catecholamines only. Neither CgA nor NPY are released during non-exocytotic catecholamine secretion.

Adrenal Medulla↗
PubMed1994

Plasma norepinephrine variations correlate with peripheral vascular resistance in resting humans.

Plasma levels of norepinephrine (NE) vary rhythmically in humans and animals with an ultradian (shorter than 1 day) periodicity. We repeatedly measured plasma NE levels, blood pressure, cardiac output, and total peripheral resistance in nine normal resting subjects over 5 h. Plasma NE correlated with total peripheral resistance (Z = 0.322, P < 0.0002) and inversely with cardiac output (Z = -0.276, P < 0.0002) for the nine subjects overall. The correlations were strongest in subjects with the most spontaneous variability in total peripheral resistance. These findings suggest that spontaneous oscillations in plasma NE levels reflect alterations in sympathetic nervous activity to resistance blood vessels. The negative correlation between cardiac output and plasma NE levels may result from the very minor cardiac NE spillover into plasma and the inverse relationship between cardiac output and total peripheral resistance.

Activity Cycles↗
PubMed1993

A prospective study of the clinical outcome of femoral pseudoaneurysms and arteriovenous fistulas induced by arterial puncture.

PURPOSE: Although spontaneous thrombosis of femoral false aneurysms (FAs) and arteriovenous fistulas (AVFs) has been reported, the frequency of this occurrence is unknown. This prospective study was designed to establish the natural history of FA and AVF and to evaluate factors that might predict eventual thrombosis of these lesions. METHODS: Twenty-two patients with either femoral FAs (n = 16) or AVFs (n = 6) induced by percutaneous arterial punctures were evaluated prospectively. After an initial duplex scan, all patients were monitored with serial scans, either in hospital or weekly as outpatients, depending on the stability of the process. Operative repair was performed for the following indications: (1) a greater than 100% increase in size of a FA by duplex scan, (2) the development of symptoms, or (3) continued patency of the lesion after 2 months of observation. RESULTS: Nine of 16 FAs and four of six AVFs closed spontaneously; FAs greater than 6 cm3 (1.8 cm in diameter) required repair more often (p = 0.065). However, size was not an absolute predictor of the need for repair because two small aneurysms (1.6 and 0.7 cm3) remained patent, although both patients were discharged safely from the hospital, and two large aneurysms (13.2 and 10.7 cm3) thrombosed spontaneously. Three of seven patients whose aneurysms required repair received anticoagulation continuously from the time of catheterization until repair became necessary. None of the patients whose FAs closed spontaneously were receiving anticoagulants at the time of thrombosis (p = 0.02). Neither length of the FA neck, velocity in the FA cavity, size of original arterial puncture, nor velocity in the AVF correlated with thrombosis. CONCLUSIONS: We conclude that (1) all FAs do not thrombose spontaneously and at least one third require surgical repair, (2) patients receiving continuous anticoagulation should undergo aneurysm repair, (3) discharge of patients with FAs less than 6 cm3 is safe (the majority of these FAs will eventually thrombose spontaneously), and (4) many AVFs close spontaneously and repair is not required unless symptoms or signs of progressive enlargement develop.

Aneurysm, False↗
PubMed1993

Immune function in offspring of nonhuman primates (Macaca nemestrina) exposed weekly to 1.8 g/kg ethanol during pregnancy: preliminary observations.

A preliminary investigation of immune host response was conducted in a group of fetal alcohol-exposed nonhuman primates (Macaca nemestrina) who were part of a broader ongoing study of ethanol teratogenicity. The mothers of the offspring received weekly oral doses of ethanol (1.8 g/kg) for the first 3 or 6 or the entire 24 weeks of gestation. A control group received sucrose solution weekly throughout pregnancy. Four of the 18 ethanol-exposed animals (22%) died or were euthanized after infectious disease or failure to thrive during the first year of life; none of the seven control animals died. This imbalance in survival prompted the present review of immune function in the remaining offspring. Parameters assessed included: (1) white blood cell count (WBC), (2) peripheral blood leucocyte subsets (CD4+, CD8+, CD20+, and CD11c+), (3) T-cell proliferation after activation with phytohemagglutinin (PHA), staphylococcus enterotoxin B (SEB), and tetanus toxoid (TT), (4) phagocytic activity of monocytes, and (5) serum immunoglobulin levels and serum antibody titers after TT vaccination. Mean T-cell proliferation to TT was significantly decreased (p = 0.01) in all ethanol-exposed animals relative to controls, with near-significant decreases (p = 0.06) in response to SEB in the ethanol-exposed animals. Lymphocyte proliferation in response to PHA was not altered. Ethanol-exposed animals had significantly lower TT titers than controls after initial vaccination and booster. WBC, leukocyte subsets, serum immunoglobulins, and monocyte phagocytic activity were not significantly different from control values. These preliminary observations suggest that T-cell proliferation and antigen-specific memory responses may be altered in offspring exposed to weekly doses of ethanol in utero and warrant further evaluation for confirmation.

Animals↗
PubMed1993

Glucocorticoid elevation of mRNA encoding epinephrine-forming enzyme in lung.

The epinephrine-forming enzyme phenylethanolamine N-methyltransferase (PNMT) is present in lung and its activity is increased by the glucocorticoid dexamethasone. Chronic administration of dexamethasone (0.5 mg/kg twice daily) doubled levels of mRNA coding for PNMT in rat lung. Administration of the glucocorticoid antagonist RU 486 after 7 days of dexamethasone treated reduced PNMT mRNA by about two-thirds within 24 h. Lung epinephrine (E) levels correlated with lung PNMT activity in these dexamethasone-treated and control rats. In a separate experiment, lung PNMT mRNA levels were nearly tripled 6 h after dexamethasone (1 mg/kg sc). In a third experiment chronic administration of the PNMT inhibitor SKF 64139 (50 mg/kg twice daily) reduced in vitro lung PNMT activity in chronically dexamethasone-treated adrenalectomized rats by approximately 96% and reduced lung E levels by approximately 75%. We conclude that glucocorticoids increase lung PNMT activity by increasing levels of mRNA coding for this enzyme. The data also suggest that a substantial fraction of lung E is locally synthesized. We speculate that enhanced lung E synthesis may participate in glucocorticoid-induced dilation of the bronchioles.

Adrenal Glands↗
PubMed1993

Glucocorticoid hypertension and nonadrenal phenylethanolamine N-methyltransferase.

Several drugs that block epinephrine synthesis by inhibiting phenylethanolamine N-methyltransferase (PNMT) lower blood pressure in hypertensive rats. We investigated the mechanism by which these drugs lower blood pressure in rats made hypertensive with the glucocorticoid dexamethasone. We performed adrenalectomy or sham operation on several rats and then gave them either dexamethasone chronically or vehicle. The dexamethasone-treated adrenalectomized rats also received either the centrally acting PNMT inhibitor SKF 64139 chronically or an equal dose of the primarily peripherally acting PNMT inhibitor SKF 29661. Both SKF 64139 and SKF 29661 reduced blood pressure by more than 25 mm Hg. SKF 64139 also reduced PNMT activity in hypothalamus, medulla oblongata, skeletal muscle, and cardiac atria and ventricles; SKF 29661 inhibited PNMT in muscle and heart tissue by 40-75%, did not inhibit PNMT in hypothalamus, and inhibited PNMT by only 29% in medulla oblongata. PNMT activity in peripheral tissues was also more highly correlated with blood pressure than was PNMT activity in the brain areas studied. Neither drug reduced tissue epinephrine levels, but SKF 64139 elevated dopamine or norepinephrine levels or both in several tissues. We conclude that the blood pressure-lowering action of PNMT-inhibiting drugs in glucocorticoid hypertensive rats may be due to inhibition of peripheral nonadrenal PNMT. We speculate that elevations in nonadrenal PNMT may mediate glucocorticoid hypertension.

Adrenalectomy↗
PubMed1993

Catecholamine secretory vesicles. Augmented chromogranins and amines in secondary hypertension.

Chromogranins A and B are major soluble proteins in chromaffin granules. Their adrenomedullary content is increased in the spontaneously (genetic) hypertensive rat. Is augmented catecholamine vesicular storage of the chromogranins a specific feature of genetic hypertension? To explore this question, we measured chromogranin A immunoreactivity, using a novel, synthetic peptide radioimmunoassay, in rat adrenal medullas 4-6 weeks after induction of the two-kidney, one clip Goldblatt model of renovascular hypertension and in unmanipulated control animals. We also measured messenger RNAs of chromogranins A and B and dopamine beta-hydroxylase by Northern blot. Immunoreactive adrenal chromogranin A was 3.3-fold higher (p < 0.01) in clipped rat adrenals. Adrenal catecholamine concentrations and phenylethanolamine-N-methyltransferase activity were also higher in clipped rats. Adrenal dopamine beta-hydroxylase activity (both membrane-bound and soluble forms) and corticosterone (glucocorticoid) concentration did not significantly differ between the groups. Adrenal medullary chromogranin A messenger RNA levels in clipped rats were 3.2-fold higher (p = 0.029) than those in the control group, and chromogranin B messenger RNA levels were 4.6-fold higher (p = 0.05). Dopamine beta-hydroxylase messenger RNA levels were 2.9-fold higher (p = 0.038). Thus, augmented synthesis and storage of adrenomedullary chromogranins A and B, catecholamines, and their biosynthetic enzymes appear to be characteristic of both acquired and genetic hypertension.

Adrenal Medulla↗
PubMed1993

Glucocorticoid induction of epinephrine synthesizing enzyme in rat skeletal muscle and insulin resistance.

Rat skeletal muscle contains two enzymes which can make epinephrine: phenylethanolamine N-methyltransferase (PNMT) and nonspecific N-methyltransferase. We studied the time-course and mechanism by which the glucocorticoid dexamethasone increases muscle PNMT activity. We also examined the hypothesis that increased muscle E synthesis may contribute to glucocorticoid-induced insulin resistance. Dexamethasone (1 mg/kg s.c. for 12 d) increased muscle PNMT activity seven-fold but did not change NMT activity. Immunotitration with an anti-PNMT antibody indicated that the PNMT elevation was due to increased numbers of PNMT molecules. Dexamethasone rapidly increased PNMT activity and this elevation was largely maintained 6 d after glucocorticoid treatment stopped. Muscle epinephrine levels were transiently elevated by dexamethasone. Dexamethasone-treated rats had elevated insulin levels after a glucose load, and chronic administration of the PNMT inhibitor SKF 64139 reversed this increase. Chronic SKF 64139 improved glucose tolerance in normal rats. Dexamethasone induced muscle synthesis of the epinephrine-forming enzyme PNMT. A PNMT inhibitor lowered insulin levels in glucocorticoid-treated rats and glucose levels in untreated rats. These findings are compatible with antagonism of insulin-mediated glucose uptake by epinephrine synthesized in skeletal muscle.

Adrenal Medulla↗
PubMed1993

The effects of unilateral forced nostril breathing on the heart.

Three experiments are described that employ impedance cardiography to monitor the effects of unilateral forced nostril breathing (UFNB) on the heart. Experiment 1 includes 7 subjects (4 males, 3 females) with a respiratory rate of 6 breaths/min (BPM). Experiment 2 includes 16 trials using one subject to examine the intraindividual variability, at 6 BPM. Experiment 3 includes 10 trials with the same subject in experiment 2, but with a respiratory rate of 2-3 breaths/s. This rapid rate of respiration is a yogic breathing technique called "breath of fire" or "kapalabhatti" and employs a very shallow but rapid breath in which the abdominal region acts like a bellows. All 3 experiments demonstrated that right UFNB increases heart rate (HR) compared to left. Experiment 1 gave 7 negative slopes, or lowering in HR with left nostril breathing and 7 positive slopes, or increases in HR with right nostril breathing, p = .001. The second and third experiments showed differences in HR means in which right UFNB increases HR more than left, p = .013, p = .001, respectively. In experiment 2 stroke volume was higher with left UFNB, p = .045, compensating for lower HR. Left UFNB increased end diastolic volume as measured in both experiments 1 and 2, p = .006, p = .001, respectively. These results demonstrate a unique unilateral effect on sympathetic stimulation of the heart that may have therapeutic value.

Activity Cycles↗
PubMed1993

Accuracy of clinical examination in the evaluation of femoral false aneurysm and arteriovenous fistula.

A prospective study was undertaken to define the comparative value of physical examination versus duplex scanning in the detection of femoral false aneurysm and arteriovenous fistula after percutaneous femoral artery puncture. Fifty-three patients were referred to the vascular surgery service after femoral artery catheterization for evaluation of a groin hematoma or a new femoral bruit. All patients were evaluated initially by a vascular surgeon and then by duplex scan. The results of these evaluations were compared with the findings at operation. Physical examination was 100% sensitive and 100% specific in the diagnosis of arteriovenous fistula, whereas duplex scan achieved a sensitivity of only 58% and a specificity of 100%. Physical examination was 92% sensitive and 93% specific in the detection of femoral false aneurysm compared with a sensitivity of 83% and a specificity of 100% for duplex scanning. Physical examination is the best method for detecting and following patients with arteriovenous fistula. False aneurysms can be detected reliably by physical examination, although evaluation with a duplex scan is necessary to identify the precise size and anatomy of these lesions.

Aged↗
PubMed1992

Propranolol reduces rat dopamine-beta-hydroxylase activity and catecholamine levels.

Propranolol treatment (1 mg/kg i.p. twice daily for 8 days) reduced atrial dopamine-beta-hydroxylase (D beta H) activity by 60.5% and lung D beta H activity by 53.5% but did not alter ventricle D beta H activity. Propranolol also significantly reduced atrial noradrenaline (NA) by 66.3%, adrenaline (A) by 40%, dopamine (DA) by 72.4% and lung NA by 46.6% but did not change plasma or cardiac ventricle catecholamines. The addition of propranolol (10(-6) M) to cardiac and lung tissue homogenates in vitro did not inhibit tissue D beta H activities. The results suggest that chronic propranolol treatment inhibits NA synthesis and support the hypothesis of a centrally induced inhibition of sympathetic activity caused by beta-adrenoceptor blockade.

Animals↗
PubMed1992

Specificity of psychoanalytic hypotheses regarding the onset of adolescent psychoses: an empirical test of a psychodynamic model.

The specificity of psychodynamic hypotheses regarding the onset of adolescent psychosis was assessed in a group of rigorously diagnosed psychotic (N = 75) and depressed (N = 53) adolescents. None of the four operationally defined psychodynamic hypotheses purported to be etiologically specific in the onset of adolescent psychotic illness: success and its opportunities; intimacy and its attempts; intent to act autonomously; or involved in insight-oriented psychotherapy was more commonly observed in the psychotic than the depressed group, thereby not supporting the hypotheses. The consequences of this finding are discussed.

Adolescent↗
PubMed1992

Competitive strategies in the NHS.

The NHS has, of necessity since implementation of the NHS and Community Care Act 1990, strengthened its skills in business, marketing and other functions borrowed from industry and commerce. One area where, however, the NHS is currently weak is in competitive intelligence. Hazel Coad and Barbara Kennedy explain what this strategically important function is and how it can help financial viability.

Data Collection↗