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Biomedical subjects

J Barrett

Publications and source records attributed to J Barrett.

At least 199 records · Page 11Linked to original sources
PubMed1993

Women and clinical oncology.

In the United Kingdom 20% of consultants and 23% of senior registrars are female. A questionnaire sent to female clinical oncologists revealed that 90% have full-time contracts, although 36% had spent time in part-time training. Sixty-seven per cent of the total have children and the husbands of 51% of the 74% who are married are doctors. Twenty-four per cent believe they have experienced sexual discrimination in clinical oncology and 10% believe they have failed to be appointed to a post because of their gender. Problems highlighted were of inadequate funding for locums to cover maternity leave and poor child care facilities.

Female↗
PubMed1993

Very hot intravenous fluid in the treatment of hypothermia.

The efficacy and safety of very hot (65 degrees C/149 degrees F) intravenous fluid (IVF) were compared with those of conventional warm (38 degrees C/100.4 degrees F) IVF in the treatment of hypothermia. Eight anesthetized beagles (11-20 kg) were studied. Blood pressure (BP), pulse (P), and core temperature (cT degrees) were recorded at baseline, during hypothermia, and during rewarming. The plasma free hemoglobin (PFHg) was measured to assess hemolysis. Each subject was cooled to 32 degrees C/89.6 degrees F and assigned to receive either 65 degrees C or 38 degrees C IVF via a specially designed multiport balloon-tipped catheter in the superior vena cava (SVC). The IV fluid rate was 80% of the blood volume per hour. Conventional rewarming methods were used in all subjects. After 2 hours the subjects were killed and the SVC was examined for injury. The rate of rewarming was 2.9 degrees C/hour in the 65 degrees C IVF group and 1.25 degrees C/hour in the 38 degrees C IVF group. The cT degrees was significantly different in all subjects after 1 (35.2 degrees +/- 1.03 degrees C vs. 33.2 degrees +/- 0.5 degrees C; p < 0.006) and 2 (37.6 degrees +/- 1.17 degrees C vs. 34.3 degrees +/- 0.9 degrees C; p < 0.004) hours of rewarming. The BP, P, and PFHg were not different. Visual examination of the SVC revealed two lesions in the 65 degrees C IVF group and one in the 38 degrees C group. Mechanical or thermal injury could not be differentiated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Biochemical markers of bone turnover in women with surgically treated carcinoma of the breast.

Biochemical markers of bone turnover were measured in fasting urine and blood samples obtained from 38 postmenopausal women with previous surgical treatment of breast cancer combined with adjuvant chemotherapy, tamoxifen, or placebo. Significantly elevated urinary pyridinoline as nmol mmol-1 creatinine (47.5 and 42.5 in tamoxifen and placebo treated patients compared with 26.3 in normal controls, both P < 0.001) and deoxypyridinoline (11.9 and 10.5 compared with 6.3, P < 0.001 and P = 0.002 respectively) were found with unchanged urinary hydroxyproline, serum alkaline phosphatase and procollagen I carboxyterminal peptide (PICP). These findings suggest enhanced bone resorption resulting from the humoral osteoclast activating effect of the previous breast cancer or underlying carcinoma recurrence. Alternatively the raised pyridinium excretion might indicate an altered crosslinking composition of bone collagen. No specific effect on bone metabolism was found with tamoxifen treatment as all measured parameters were similar in both tamoxifen ex-users and non-users. This confirmed the safety of tamoxifen therapy with respect to bone.

Aged↗
PubMed1993

Enhancement by atropine of the pancreatic exocrine secretions evoked by vagal stimulation in the pithed rat.

1. Pancreatic secretions were collected in response to 15 min periods of bilateral stimulation of the cervical vagus nerves in the pithed rat. 2. The weight of juice, total HCO3- and total protein evoked by a second period of vagal stimulation were essentially similar to those of the first period of vagal stimulation. 3. When the second period of vagal stimulation was preceded by an intravenous bolus injection of atropine sufficient to block the vagally induced bradycardia, the weight of secretion and total protein were greatly potentiated over an extended time course far exceeding that of the period of vagal stimulation. Total HCO3- was unchanged. 4. By contrast, atropine was effective in antagonizing the stimulatory effects of the muscarinic agonist methacholine injected intravenously. 5. The putative VIP (vasoactive intestinal polypeptide) antagonist [D-p-chloro-Phe6, Leu17]-VIP injected intravenously also increased the vagally evoked weight of juice, with total HCO3- and total protein unchanged. This was explicable by a partial agonist effect which was additive to the stimulatory action of vagal stimulation. 6. To explain these results, it is proposed that endogenously released acetylcholine exerts a negative feedback effect on the postganglionic varicosities which release both acetylcholine and another cotransmitter which was not excluded as being VIP. In the presence of atropine, the cotransmitter is proposed to be released from the inhibitory feedback, thus enhancing the response to vagal stimulation.

Animals↗
PubMed1993

MK-383 (L-700,462), a selective nonpeptide platelet glycoprotein IIb/IIIa antagonist, is active in man.

BACKGROUND: Fibrinogen-dependent cross-linking of glycoprotein (GP) IIb/IIIa on activated platelets is the final mechanism leading to platelet aggregation. Inhibition of this mechanism may result in a novel antithrombotic agent. We studied the activity of MK-383 (L-700,462), a new, nonpeptide GPIIb/IIIa antagonist, in vitro and in vivo, in man. METHODS AND RESULTS: MK-383, a nonpeptide tyrosine derivative, dose-dependently inhibited fibrinogen-dependent platelet aggregation, in vitro. Binding of 125I-labeled fibrinogen to activated platelets was prevented in a competitive manner with an IC50 of 10 +/- 4.2 nmol/L. The activity and tolerability of MK-383 were evaluated in a two-part double-blind, placebo-controlled, dose-escalation study in healthy male subjects using 1- and 4-hour intravenous infusions. Effects on ADP- and collagen-induced ex vivo platelet aggregation (APA or CPA) and template bleeding time (TBT) were evaluated. Twenty-four subjects participated in the 1-hour part. Six received placebo and 18 MK-383 in doses ranging from 0.05 to 0.40 microgram.kg-1 x min-1. MK-383 inhibited platelet aggregation and prolonged bleeding time in a dose-dependent manner. APA and CPA were totally inhibited at the end of infusion of 0.4 microgram.kg-1 x min-1 and returned to 55% and 89% of baseline, respectively, at 3 hours after infusion. TBT was prolonged at this dose from 5.0 +/- 1.3 minutes predose to 22.7 +/- 6 minutes at the end of the infusion (P < .01) and was normalized by 3 hours after infusion. In the 4-hour infusion part, 15 subjects received MK-383 (0.1 to 0.2 microgram.kg-1 x min-1), and five received placebo. Complete inhibition of ex vivo platelet aggregation was seen at 0.15 and 0.2 microgram.kg-1 x min-1. At 0.2 microgram.kg-1 x min-1, TBT was prolonged from 4.4 +/- 1.2 to 23.9 +/- 4.3 minutes at the end of infusion (P < .01) and remained slightly prolonged 3 hours after infusion (7.2 +/- 1.8 minutes). No adverse effects were observed in any of the 33 subjects receiving MK-383. CONCLUSIONS: The results from this study indicate that MK-383 appears to be well tolerated and active in man. It is the first nonpeptide GPIIb/IIIa antagonist that can be used to investigate the antithrombotic potential of this new class of antiplatelet agents.

Bleeding Time↗
PubMed1993

Sensory cues and the suppression of reproduction in subordinate female marmoset monkeys, Callithrix jacchus.

Subordinate female marmoset monkeys remain anovulatory and have low plasma concentrations of luteinizing hormone (LH) when maintained with their dominant females. Olfactory cues from the dominant female have been implicated in maintaining this reproductive suppression. Subordinate females that received either ablation of the vomeronasal organ (an accessory olfactory organ; n = 3), ablation of the main olfactory epithelium (n = 4), or both lesions (n = 5) did not ovulate in the following 7 weeks while housed with their dominant female. Plasma LH concentrations following either or both lesions were similar to pre-lesion concentrations. Olfactory lesions (verified by histological and behavioural trials) did not impair reproductive activity, as olfactory-lesioned dominant females underwent ovarian cycles of similar duration to intact dominant females. Lesioned subordinate females (n = 6), maintained in visual-only contact with their dominant female and group ovulated 29.1 +/- 9.3 days (mean +/- SEM) after physical separation from their dominant females; this first onset of ovulation was significantly delayed (P < 0.05) compared with intact subordinate females completely isolated from their dominant females and group (10.8 +/- 1.3 days, n = 8). Behavioural and visual cues together with olfaction all appear to play important roles in maintaining the suppression of ovulation in subordinate female marmoset monkeys.

Animals↗
PubMed1993

A comparison of pentastarch and lactated Ringer's solution in the resuscitation of patients with hemorrhagic shock.

Pentastarch is a colloid that is chemically similar to Hetastarch. It has a shorter half-life (12 hr), and produces volume expansion at least 1.5 times the administered volume. We compared Pentastarch to Ringer's lactate in 41 patients (21 Pentastarch, 20 Ringer's lactate) presenting with hemorrhagic shock. The groups were similar in age, sex, race, and type of injury. Significantly less volume of Pentastarch was required initially to resuscitate to a normal blood pressure and urine output than Ringer's lactate (P < 0.005). Coagulation parameters (prothrombin time, partial thromboplastin time, fibrinogen, and factor VIII) were measured for 48 hr post-resuscitation, and no abnormalities were noted in the Pentastarch group. Serum albumin was the same in both groups throughout the study period; however, serum colloid oncotic pressure was elevated at 1 hr post-resuscitation in the Pentastarch group (P < 0.005). There was no difference in ventilatory parameters, blood gases, pulmonary function tests, ventilator days, or hospital days between the two groups. We conclude that Pentastarch is safe and effective for the initial resuscitation from hemorrhagic shock.

Blood Coagulation↗
PubMed1993

The sleep-evoked decrease of body temperature.

The circadian rhythm of deep body temperature consists of both an endogenous component and evoked components resulting from exogenous influences. Previous studies of the sleep-evoked effect have failed to control confounding influences, so that the effect of sleep per se has not been established. In the present study, eight good sleepers had their rectal temperatures recorded for 24 hours in each of two laboratory conditions employing a constant routine to control exogenous influences. Sleep was allowed at night in one condition. Following sleep onset, body temperature dropped more rapidly and remained lower than when wakefulness continued over the same time, resulting in a mean sleep-evoked decrease of 0.31 +/- 0.09 degree C. Fourier regression analysis showed a significant 24-hour (circadian) temperature rhythm, together with a 12-hour harmonic rhythm, in each condition. Circadian rhythm parameters were also altered by the sleep-evoked (or masking) effect, with the amplitude increased and the mean decreased when subjects slept at night in the constant routine. It was suggested that a constant routine methodology be used in studies of circadian rhythm differences and that Fourier regression be used in preference to simple cosine curve fitting to give a better approximation of the temperature rhythm.

Adult↗
PubMed1992

Social support and depressive symptoms in the elderly.

The purpose of this study was to examine the effect of characteristics of social networks and support on depressive symptoms in the elderly. The subjects were 1,962 noninstitutionalized persons 65 years and older from the New Haven Establishment of Populations for Epidemiologic Study of the Elderly in 1982, who were available to give a complete follow-up interview in 1985. Baseline depression, functional disability in 1982, and any change in disability by 1985 were considered as additional influences on 1985 depression, requiring adjustment along with sociodemographic variables. Multiple regression procedures were used to simultaneously examine the variables. Baseline depression, functional disability, and change in functional disability made the largest contribution to explaining the variance in depression. Among the social support and network characteristics, loss of a spouse, adequacy of emotional support, and its change during 1982-1985 made the largest contributions. Other significant characteristics in relative order of magnitude of effect, based on contrast tests, included tangible support adequacy and its change, loss of a confidant between 1982 and 1985, number of children making weekly visits and change in this number by 1985, and the absence of a confidant in both 1982 and 1985. For mental health outcomes, these findings emphasize the need to consider specific dimensions of social support and networks rather than global measures.

Aged↗
PubMed1992

Exosurf treatment investigational new drug phase: effect of an individualized third dose in infants with respiratory distress syndrome.

Of 95 infants treated with the synthetic surfactant, Exosurf, under a Treatment Investigational New Drug protocol, 17 received one dose, 40 received two, and 38 received three doses. Seventy-six (80%) of the infants were treated by rescue protocol. We retrospectively reviewed the clinical course of the 67 surviving rescue infants. We found that, compared to one- and two-dose infants, those treated with three doses of Exosurf were more premature, smaller, required a longer ventilator course, and had more frequent complications, including patent ductus arteriosus (PDA), intraventricular hemorrhage, nosocomial pneumonia, and apnea. They required higher oxygen concentrations starting 8 hr after their first dose and higher mean airway pressure (MAP) from the time of their second dose. These trends continued during all subsequent time points, as compared to infants treated with two doses. The third dose was administered an average of 17 hr after the second, resulting in little change of MAP, but some reduction in oxygen requirements. By 24 hr after the last dose, only 4% of three-dose infants were extubated compared with 30% of the two-dose and 71% of one-dose infants. In conclusion, repeated administration of Exosurf is not equally effective in every treated infant with respiratory distress syndrome (RDS) and complications of prematurity may affect or accompany poor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Administration Schedule↗
PubMed1992

Biochemical characterisation of the enzyme responsible for "activated L-serine sulphydrase" activity in nematodes.

The biochemical properties of the enzyme responsible for nematode "activated L-serine sulphydrase" activity (L-cysteine + R-SH----cysteine thioether + H2S) have been investigated using primarily the gastro-intestinal nematodes Nippostrongylus brasiliensis and Haemonchus contortus. The activated L-serine sulphydrase enzyme was found to be cytosolic in origin and exhibited maximal activity at pH 9.0. Enzyme activity was widely distributed amongst the major tissues of adult female Ascaris suum but was particularly abundant in longitudinal muscle. The enzyme appeared to have a rigid specificity for L-cysteine as the primary thiol substrate, but was capable of utilising a number of sulphur amino acids (and derivatives) and nonphysiological thiols as second substrates. The best second thiol substrates were nonphysiological, hydroxyl-containing thiols that showed some structural similarity to the standard second substrate, 2-mercaptoethanol. Kinetic analyses revealed that the enzyme operates by a sequential catalytic mechanism, and the absolute Michaelis constants were: KL-cysteine = 0.21 +/- 0.02 mM and K2-mercaptoethanol = 5.58 +/- 0.59 mM. The enzyme was relatively insensitive to inhibition by a variety of substrate analogues and known inhibitors of pyridoxal 5'-phosphate dependent enzymes, whilst plant phenols caused significant levels of inhibition. The most potent inhibitors discovered were the anthelmintics bithionol, dichlorophene and hexachlorophene. Further characterisation revealed that hexachlorophene was a parabolic competitive inhibitor of the activated L-serine sulphydrase enzyme.

Animals↗
PubMed1992

The identification of a variant form of cystathionine beta-synthase in nematodes.

Characterization of the physical and catalytic properties of the enzyme responsible for nematode "activated L-serine sulfhydrase" activity (L-cysteine + R-SH-->cysteine thioether + H2S) has led to its identification as a novel, variant form (allelozyme) of cystathionine beta-synthase that is distinct from a mammalian-type synthase also present in nematodes. Additional work has demonstrated the ability of live Panagrellus redivivus to produce H2[35S] from exogenous L-[35S]cysteine and 2-mercaptoethanol, thus providing preliminary evidence for the in vivo operation of the activated L-serine sulfhydrase reaction in nematodes.

Animals↗
PubMed1992

Long term effects of tamoxifen. Biological effects of Tamoxifen Working Party.

A total of 153 breast cancer patients who participated in two trials of adjuvant tamoxifen and who had not recurred were recruited into a study of the long term effects of tamoxifen. There were 60 controls (no tamoxifen), 73 ex-users (mostly for 2 years) and 20 current users (median treatment duration 72 months) and the median follow-up time was 7 years. A wide ranging study of lipids, hormones, bone density and haemostasis was undertaken. When compared with controls, current users had lower cholesterol levels (especially low density cholesterol), and increased triglyceride levels. Thyroid hormones were higher and sex hormone binding globulin was almost doubled. Bone density was non-significantly higher, clotting times were slightly shorter and fibrinogen and antithrombin III levels were reduced. However few of these changes persisted in ex-users, suggesting that most of the biological effects of treatment are reversible on cessation of treatment. This is reassuring for potentially negative side-effects, but also indicates that potentially positive 'side-effects' such as cholesterol lowering only occur while on active treatment.

Bone Density↗