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Biomedical subjects

D Cook

Publications and source records attributed to D Cook.

At least 199 records · Page 11Linked to original sources

Studies on polydnavirus transmission.

Polydnaviruses are thought to replicate only in the ovaries of certain hymenopteran species. Nevertheless, in the present study, polydnaviral DNA was found to exist in males of the braconid parasitoid species Cotesia melanoscela and in both male and female non-ovarian tissue of an ichneumonid, Hyposoter fugitivus; preliminary results suggest that viral DNA may be present in an unintegrated form, but whether or not it is encapsidated is unknown. Using interstrain genetic crosses, we demonstrated that C. melanoscela males can apparently transmit at least some viral DNA to female progeny. We suggest that polydnavirus DNAs may be present in most if not all tissues of certain parasitoid species, and are probably maintained within parasitoid populations by vertical transmission through the germ line. In parallel experiments, manually injected eggs of the ichneumonid parasitoid (H. fugitivus) survived and hatched in Malacosoma americanum larvae in the apparent absence of exogenous polydnavirus; female parasitoids reared in this manner nevertheless carried virus in their ovaries. Experiments utilizing different strains of C. melanoscela also suggest that per os transmission of polydnaviruses (to parasitoid larvae) does not occur, despite the fact that inoculum viral DNA can be shown to persist for several days in the tissues of parasitized host larvae.

Animals↗

Positive end-expiratory pressure increases plasma catecholamine levels in non-volume loaded dogs.

UNLABELLED: Positive end-expiratory pressure (PEEP) is commonly used in the treatment of critically ill patients whose sympathetic nervous system is stressed; however, PEEP's actions on sympathetic nervous system activity are unknown. We therefore measured the plasma noradrenaline response (an index of sympathetic nervous system activity) to graded doses of PEEP in nine mongrel dogs. After 30 minutes at each level of PEEP, plasma noradrenaline concentrations increased from baseline mean values of 300 (SD 108) pg/ml to 388 (SD 225) pg/ml (P less than 0.05) at 5 cm, 433 (SD 255) pg/ml (P less than 0.01) at 10 cm and 1194 (SD 882) pg/ml (P less than 0.01) at 20 cm water pressure of PEEP. The increases in plasma noradrenaline concentrations correlated inversely (r = -0.43, P less than 0.01) with PEEP-induced changes in cardiac output. Plasma adrenaline levels did not change significantly in response to 5 or 10 cm of PEEP; however, plasma adrenaline increased, while heart rate and mean arterial blood pressure fell, at 20 cm water pressure of PEEP (P less than 0.05). Within 15 minutes after discontinuation of PEEP, the plasma catecholamine concentrations returned to baseline levels. CONCLUSIONS: 1. PEEP significantly increases sympathetic nervous system activity in a rapid, dose-dependent, reversible manner; 2. the PEEP-induced increases in sympathetic activity may explain the reductions in organ blood flow which others have observed following the initiation of PEEP; 3. PEEP-related changes in sympathetic nervous system activity are a consequence of PEEP-induced reductions in cardiac output.

Animals↗

Opiate receptor blockade and diurnal pituitary and adrenal hormone levels.

Peripheral pituitary hormone levels exhibit circadian variations though the mechanism of these changes is unknown. In order to investigate the possible role of endogenous opiates in such changes we have studied the influence of opiate receptor blockade with naloxone (6.8 mg) on pituitary hormones in the morning and again in the evening in six normal male volunteers. Basal ACTH, cortisol, aldosterone and prolactin were higher in the morning than in the evening. Following naloxone at 0700h both ACTH and cortisol rose indicating a tonic inhibition of ACTH by endogenous opiates at that time. At 2230h cortisol rose following naloxone but ACTH did not, suggesting that endogenous opiates do not play an important role in the diurnal rhythm of this hormone and consistent with the suggestion that endogenous opiates can effect cortisol levels independently of their action on ACTH. Neither aldosterone nor prolactin were influenced by naloxone. In contrast TSH was unaffected by naloxone in the morning but fell in the evening (mean + SE decrement over 120 min -0.6 +/- 0.3 mU/l as compared with the control +0.6 +/- 0.4 mU/l; p less than 0.01). Thus, endogenous opiates probably tonically stimulates TSH levels in the evening when TSH may increase and possibly play a role in the circadian rhythm of TSH.

Adrenal Cortex Hormones↗

Assessment of calcium homeostasis in the critically ill surgical patient. The diagnostic pitfalls of the McLean-Hastings nomogram.

Hypocalcemia is a common problem in critically ill surgical patients. We prospectively evaluated whether measurement of the total serum calcium (Ca) concentration or calculation of the serum ionized Ca level (by the McLean-Hastings nomogram) accurately reflects the measured serum ionized Ca level. Although 71% and 58% of 156 predominantly surgical intensive care unit (ICU) patients were hypocalcemic by the total serum Ca or calculated ionized Ca level, respectively, only 12% were hypocalcemic by directly measured serum ionized Ca measurement. The total serum Ca and calculated ionized Ca concentrations were sensitive (95% and 89%, respectively) but lacked specificity (32% and 46%, respectively) in predicting ionized hypocalcemia. Analyses of Ca binding to albumin in the serum of surgical ICU patients and normal subjects suggested that there is a circulating factor in critically ill patients that increases the binding of Ca to albumin. These observations may explain why the McLean-Hastings nomogram underestimates the protein-induced changes in serum Ca in critically ill surgical subjects. We conclude that: total serum Ca and calculated ionized Ca concentrations are poor indicators of the true serum ionized Ca status in critically ill surgical patients, and we recommend direct measurement of serum ionized Ca levels in these patients; and variability in the affinity of Ca for binding proteins in critical illness may explain the poor correlation between serum total and ionized Ca measurements.

Blood Proteins↗

The response of obese subjects to continuous infusion of human pancreatic growth hormone-releasing factor 1-44.

The growth hormone (GH) response of seven obese subjects to a 4 h continuous infusion of human pancreatic GH-releasing factor, 0.3 micrograms/kg/h, has been compared with that obtained in seven sex and age matched controls. The pattern of response was normal in the obese but peak GH levels (mean +/- SEM: 13.8 +/- 1.9 compared to 30.9 +/- 4.7 mU/l, P less than 0.01) and integrated GH levels (mean +/- SEM: 27.1 +/- 3.6 compared to 62.0 +/- 9.7 mU/l/h, P less than 0.01) were reduced in obese subjects. There was a negative correlation between the integrated GH response and the percentage ideal body weight (r = -0.80, P less than 0.05), but no significant correlation with somatomedin-C levels (r = +0.72; P = 0.07). Obese subjects have an impaired GH response to infusion of GH-releasing factor which is not related to negative feedback by somatomedins.

Adult↗

Prolactin secretion and biological activity in females with galactorrhoea and normal circulating prolactin concentrations at rest.

Prolactin secretion and biological activity have been investigated in 20 females with persistent idiopathic galactorrhoea who had normal resting serum prolactin levels at presentation. Results were compared with those in 34 normal controls. Hyperprolactinaemia, which was persistent in one and intermittent in the other, developed in two patients over an observation period of 1.5 to 8.5 years. Resting prolactin levels stayed normal in the remaining eighteen who were further investigated. Menstruation was disordered in only six of the 18, while ovulation occurred (serum progesterone greater than 20 nmol/l) in all seven patients who were studied over a 5 week period. Serum prolactin concentrations over 24 h were similar in patients and controls (24 h mean +/- SEM prolactin, 288 +/- 36 mU/l, patients, n = 7; 291 +/- 21 mU/l, controls, n = 9) as were prolactin levels estimated twice weekly for 5 weeks. Prolactin responses to thyrotrophin-releasing hormone, 200 micrograms (at 20 min, 2417 +/- 658 mU/l, patients, n = 7; 2113 +/- 424 mU/l, controls, n = 8), the dopamine antagonist, domperidone, 10 mg (at 30 min, 5949 +/- 536 mU/l, patients, n = 7; 5858 +/- 460 mU/l, controls, n = 8) and insulin-induced hypoglycaemia (at 60 min, 1441 +/- 551 mU/l, patients, n = 7; 1298 +/- 183 mU/l, controls, n = 7) were similar in patients and controls. Two different radioimmunoassays using two different antisera gave similar estimates of serum prolactin levels and prolactin bioactivity in serum was normal in an in-vitro bioassay based on the ability of prolactin to stimulate proliferation of Nb2 node rat lymphoma cells (basal bioassayable prolactin, patients 355 +/- 43 mU/l, n = 10; controls 348 +/- 64 mU/l, n = 7). Metabolic abnormalities similar to those previously noted in hyperprolactinaemia were observed in the patients' 24 h profiles. These included mild hyperglycaemia (24 h mean +/- SEM glucose, 5.47 +/- 0.08 mmol/l, patients; 5.05 +/- 0.14 mmol/l, controls; P less than 0.05) and elevations in circulating lactate, pyruvate and alanine. Blood glycerol was decreased (24 h mean +/- SEM, 0.044 +/- 0.004 versus 0.058 +/- 0.004 mmol/l, P less than 0.05). In the majority of patients with idiopathic galactorrhoea, prolactin concentrations, regulation of secretion and bioactivity in vitro are normal. The galactorrhoea and metabolic abnormalities suggest increased tissue sensitivity to the lactogenic and metabolic actions of prolactin, while ovarian cyclical function is relatively spared.

Adult↗

Nimodipine and chronic vasospasm in monkeys: Part 1. Clinical and radiological findings.

The efficacy of the calcium channel blocker nimodipine in the prevention of chronic cerebral vasospasm (VSP) and delayed ischemia after subarachnoid hemorrhage (SAH) in monkeys was examined in a blind, randomized, placebo-controlled trial. The primate model developed in this laboratory reliably induces chronic cerebral vasospasm and can induce pathologically proven delayed ischemic neurological deficits (DINDs). With standard microsurgical procedures, an average 6.4-ml autologous hematoma was placed directly against the major anterior cerebral vessels in the right basal subarachnoid spaces of 24 monkeys. The monkeys were randomized to one of four groups and were treated orally q8h for 7 days with nimodipine (3, 6, or 12mg/kg)or placebo. An additional 2 monkeys underwent the surgical procedure without clot placement. Drug administration began between 14 and 20 hours after clot placement. Indices monitored before and after SAH included neurological status, angiographic cerebral vessel caliber, and cerebral blood flow. Significant VSP (25 to 100% reduction in vessel caliber) was present on Day 7 on the clot side in 83% of the animals (P less than or equal to 0.001). There was no significant difference (P greater than 0.05) in the incidence of VSP among the four groups. Similarly, there was no significant difference (P greater than 0.05) in the mean vessel caliber reduction after SAH among the four treatment groups. There was no VSP present on Day 7 in the sham-operated animals. One animal receiving high dose nimodipine (12 mg/kg p.o. q8h) developed a DIND on Day 5 after SAH. A second animal in the 12-mg/kg group developed a transient neurological deficit between Days 4 and 7.

Animals↗

Nimodipine and chronic vasospasm in monkeys: Part 2. Pharmacological studies of vessels in spasm.

The effect of nimodipine on the in vitro reactivity of cerebral vessels after subarachnoid hemorrhage (SAH) was studied. With the use of a primate model of chronic cerebral vasospasm, 12 female cynomolgous monkeys underwent the induction of a SAH by the direct placement of an average 6.4-ml autologous hematoma against the major anterior cerebral vessels in the right basal subarachnoid spaces (Day 0). The animals were then randomized to one of four groups and within 14 to 20 hours after clot placement were started on oral q8h therapy with nimodipine (3, 6, or 12 mg/kg) or placebo. On Day 7, the animals were killed and the right and left middle cerebral arteries (MCAs) were immediately resected and placed in oxygenated Krebs' solution. Ring preparations from the arteries were suspended in organ baths, and dose-effect curves to varying concentrations of norepinephrine, 5-hydroxytryptamine, and potassium chloride were obtained. There was a highly significant reduction in the response of the MCA on the clot side (right) relative to the nonclot side (left) to all three agonists. The clot side contractility was not influenced by nimodipine treatment at any of the four doses tested. The nonclot side arteries of the 12-mg/kg treatment group demonstrated significantly enhanced reactivity for all three agonists. Oral treatment with high dose nimodipine enhances the reactivity of normal cerebral vessels to the agonists tested, but it does not seem to affect the reactivity of arteries in chronic spasm at any of the four doses tested.

Animals↗

Failure of superoxide dismutase to alter equine arachidonic acid-induced platelet aggregation, in vitro or ex vivo.

Superoxide dismutase (SOD), a free radical scavenger with anti-inflammatory activity, was administered IM to horses. Ex vivo platelet aggregation in response to arachidonic acid was monitored to determine whether exogenous SOD altered equine platelet prostaglandin metabolism. Preparations of platelet-rich plasma obtained before SOD administration were incubated with different concentrations of SOD and were aggregated with arachidonic acid. Superoxide dismutase did not exert a demonstrable effect, either ex vivo or in vitro. Aspirin abolished arachidonic acid-induced platelet aggregation in vitro. This indicates that SOD (in the resting state) does not exert an effect on platelet-derived free radicals that could alter the arachidonic acid pathway of equine platelets, that equine platelets do not release free radicals, or that equine platelets are insensitive to the products formed from free radicals by SOD.

Animals↗

Congenital heart disease: functional abilities in young adults.

Muscular endurance, motor abilities, childhood activities, school experiences, work plans, and social behaviors of 188 young adults aged 16 to 23 years with congenital heart disease were examined. The subjects had isolated aortic stenosis, pulmonary stenosis, or tetralogy of Fallot. Overall, physical function scores were slightly below average. Childhood activities had been affected in about 30% of the cases, but seriously disrupted in only 17%. School experiences had been positive, and 68% of the students in school planned to continue on to college or university or were already there. Normal social behavior was much more common than antisocial behavior. Subjects had few specific health worries, although many wanted more information about lifestyle implications of their heart disease.

Adolescent↗