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Biomedical subjects

J Webster

Publications and source records attributed to J Webster.

At least 163 records · Page 9Linked to original sources
PubMed1992

Thermogenesis after surgery: effect of perioperative heat conservation and epidural anesthesia.

Body temperature, respiratory gas exchange, and plasma catecholamines were determined before and after surgery in three groups [control (C), warmed (W), and epidural (E) who received local anesthetic at T4-S5 dermatomes during and for 24 h after surgery] of patients undergoing colonic surgery under general anesthesia. At the end of surgery, group W were nursed in an ambient temperature of 28-30 degrees C, whereas the others were at 20-23 degrees C for a period of 24 h. Core (Tc) and dorsal hand temperature decreased during surgery in both C and E (P less than 0.05) but not in W. After surgery, Tc increased similarly in C and E and by a smaller amount in W. Plasma catecholamine concentrations increased significantly in C and W but not in E (P less than 0.001), with the greatest response occurring in C. Postoperative oxygen consumption and carbon dioxide production exceeded preoperative values (P less than 0.01) in C but not in W or E. After surgery, plasma albumin fell and C-reactive protein increased similarly in all three groups. Thus body heat conservation or epidural blockade attenuates or abolishes the rise in plasma catecholamines and oxygen consumption postoperatively but does not prevent the increase in Tc or the acute phase protein response.

Anesthesia, Epidural↗
PubMed1992

Relation between blood pressure and stroke mortality.

The relation between stroke mortality and blood pressure was investigated in 10,186 hypertensive patients followed up in the Department of Health Hypertension Care Computing Project for an average of 9 years. An untreated blood pressure measurement was available in 3,472 men and 3,405 women. The age-adjusted risk of stroke death increased by 1% for every 1 mm Hg increase in untreated systolic blood pressure. The relative hazard rate was 1.014 (95% confidence interval [CI], 1.007, 1.021) in men and 1.009 (1.003, 1.016) in women. The corresponding increases for 1 mm Hg for untreated diastolic blood pressure were almost 3% in men and again 1% in women (relative hazard rate 1.026 [95% CI, 1.014, 1.038] in men and 1.010 [1.000, 1.021] in women). Treated blood pressure measurements were available in 3,073 men and 3,148 women. Stroke mortality increased by 2% for a 1 mm Hg increase in treated systolic pressure and 3% for the corresponding increase in diastolic blood pressure. The relation between stroke mortality and blood pressure was similar over and under the age of 65, although the increase in mortality with pressure was greater for treated diastolic blood pressure in women under the age of 65 than over this age. There was no evidence for a J-shaped relation between stroke mortality and either systolic or diastolic pressure in men. In women there was a suggestion of such a relation, but since this relation was also observed for untreated pressures, any increase in risk at lower pressures is unlikely to be a result of treatment.

Blood Pressure↗
PubMed1992

Dopamine agonists and pituitary tumor shrinkage.

The primary aim of this review has been to clarify the tumor shrinking effects of dopamine agonists on pituitary macroadenomas of different cell types. Shrinkage is most dramatic for macroprolactinomas and is due to cell size reduction. Seventy-nine percent of 271 definite macroprolactinomas were reduced in size by at least 25%, and 89% shrank to some degree. Most shrinkage occurs during the first 3 months of treatment, although in a minority shrinkage is delayed. Dopamine agonist resistance during long-term therapy is exceptional. Drug withdrawal nearly always leads to a return of hyperprolactinemia, even after several years treatment, although early tumor reexpansion is unusual. About 10% of true macroprolactinomas do not shrink with dopamine agonists; the molecular mechanisms of such resistance have yet to be determined. Alternative formulations of BC and new dopamine agonists (CV 205-502 and cabergoline) are useful for the minority of patients unable to tolerate oral BC, but do not seem to further improve overall shrinkage rates. The risks of pregnancy have probably been overstated, and BC is suitable primary treatment for women with prolactinomas of all sizes; the drug can be used safely during pregnancy in the event of clinically relevant tumor expansion. The interpretation of different degrees of hyperprolactinemia is discussed and management strategies suggested. Most patients with macroprolactinomas now avoid surgery, but drug-induced, time-dependent tumor fibrosis should be remembered if surgery is contemplated. Nonfunctioning pituitary tumors are mostly of gonadotroph cell origin and may be associated with significant disconnection hyperprolactinaemia. Seventy-six of 84 well-characterized tumors showed no tumor shrinkage during dopamine agonist therapy. Possible explanations include abnormalities of dopamine receptor number and function. Preliminary evidence suggests that dopamine agonists may restrain the growth of some functionless tumors; most of these tumors, however, can be satisfactorily debulked using transsphenoidal surgery. In contrast to macroprolactinomas, other functioning pituitary tumors (GH-, TSH-, and ACTH-secreting) rarely shrink during dopamine agonist therapy, although the number of tumors studied is small.

Adenoma↗
PubMed1992

Child-care needs of patients at the Royal Women's Hospital, Brisbane.

Eight hundred and ninety-eight patients of the Royal Women's Hospital, Brisbane were surveyed by phone and questionnaire to identify their hospital related child-care needs. In addition, staff in acute admitting areas of the hospital were asked to provide details of child-care problems. Twenty-five (5.2%) of the sample reported hospital related child-care problems, 166 (39.7%) respondents stated that they would use a hospital child-care service on a casual basis and 45 (10.8%) that they would use one for the duration of their stay.

Child↗
PubMed1991

Caffeine restriction: effect on mild hypertension.

OBJECTIVE: To determine the effects on blood pressure of modifying dietary caffeine intake in patients with mild and borderline hypertension by monitoring ambulatory and clinic blood pressure. DESIGN: Four way, randomised, crossover trial of four consecutive two week dietary regimens: normal diet, caffeine free diet alone, caffeine free diet with decaffeinated instant coffee, caffeine free diet with caffeinated instant coffee (instant coffee phases conducted double blind). SETTING: Hospital hypertension clinic, Scotland. PATIENTS: 52 patients (23 men; aged 26-67 years) with untreated borderline or mild hypertension (diastolic blood pressure 90-105 mm Hg) who normally drank a minimum of three cups of coffee daily. MAIN OUTCOME MEASURES: Mean ambulatory blood pressure over 24 hours; mean morning, daytime, and night time ambulatory blood pressure; sitting clinic blood pressure at 1700; plasma caffeine concentration at 1700 on the last day of each regimen. RESULTS: Mean 24 hour ambulatory blood pressure was not different between regimens. There was no difference in blood pressure variability between regimens. During the caffeine free diet alone morning ambulatory diastolic blood pressure was higher (2.8 mm Hg) than during the caffeine free diet with caffeinated coffee. Mean sitting clinic systolic blood pressure was higher at 1700 (4.7 mm Hg) with a caffeine free diet than with the caffeine free diet with caffeinated coffee (p less than 0.05). Dietary compliance as assessed by plasma caffeine concentration was excellent. There was no significant correlation between plasma caffeine concentration and blood pressure. CONCLUSIONS: Drinking caffeinated instant coffee over a two week period does not adversely influence blood pressure in patients with borderline or mild hypertension; abstinence is of no benefit.

Adult↗
PubMed1991

Growth factors and the anterior pituitary.

Normal growth and secretion in the pituitary gland are dependent upon the co-ordinated action of a large number of extracellular growth factors, neuropeptides and peripheral hormones acting on their respective cellular receptors and via complex intracellular signalling pathways. The pituitary and hypothalamus are exposed to a large number of growth factors, several of which have well-documented effects on secretory function and may act as physiological modulators of pituitary hormone synthesis and release. IGF-I, for example, almost certainly acts as a feedback regulator of GH secretion. Despite well-documented mitogenic effects in other tissues, little is known about the role of these growth factors in normal pituitary cell turnover, compensatory hyperplasia or adenoma formation. There is now good evidence, however, that at least some of the hypothalamic releasing peptides are mitogenic for their respective pituitary cell subpopulations. The aetiology of pituitary tumours remains poorly understood but some appear to develop as a result of somatic mutation. Such mutations could enhance growth by causing altered expression of growth factors or their receptors, or constitutive activation of proteins involved in the intracellular mitogenic signal. Abnormalities have been documented at each of these levels in human pituitary tumours. The identification of an activating point mutation in the alpha subunit of Gs, the stimulatory regulatory peptide of adenylyl cyclase, in a proportion of somatotroph adenomas represents a major advance in our understanding of pituitary tumour pathogenesis. This and other findings may ultimately lead to new therapeutic approaches to the management of pituitary disease.

Animals↗
PubMed1991

Changes in speech breathing following cochlear implant in postlingually deafened adults.

Three postlingually deafened adults who received cochlear implants read passages before and after their prostheses were activated while their lung volumes were measured with an inductive plethysmograph that transduced the cross-sectional areas of the speaker's chest and abdomen. Lung volumes at the initiation and termination of the speakers' expiratory limbs, their average air flow, and the volume of air they expended per syllable were derived from tracings of calibrated lung volume displayed by computer. The activation of the speakers' cochlear prostheses was followed in every case by a significant change in average airflow, which rose for two subjects with initially low flow rates and fell for one subject who had a much higher average preimplant flow rate. These changes in average flow rate were accompanied by corresponding changes in volume of air expended per syllable, statistically reliable in two of the three cases. There were no significant changes in the levels at which speakers initiated their expiratory limbs, but one speaker, after his prosthesis was activated, reliably increased the level of air in his lungs at the end of expiratory limbs to an average value that no longer required him to draw on expiratory reserve volume.

Adult↗
PubMed1991

Postoperative protein metabolism: effect of nursing elderly patients for 24 h after abdominal surgery in a thermoneutral environment.

We have studied the effect of intraoperative body heat conservation and 24-h thermoneutrality on postoperative whole body protein turnover using stable isotope methodology in a group of elderly patients undergoing colorectal surgery for rectosigmoid adenocarcinoma. Two groups of eight patients were studied. One group (control, or cold) received routine intraoperative and postoperative care. All patients in the second group (warmed) were maintained at normothermia during anaesthesia and surgery; these patients were nursed after surgery in a warm room (ambient temperature 28-30 degrees C) for a period of 24 h. General anaesthesia, surgical care and nutritional support were similar in both groups. A constant nutritional intake, based on nitrogen 0.1 g kg-1 day-1 and energy 20 kcal kg-1 day-1, was provided orally for 7 days before surgery and i.v. after operation for 4 consecutive days. Whole body protein breakdown and synthesis, as assessed by stable isotope methodology, increased significantly 2 and 4 days after surgery in both groups (P less than 0.01), but the increase in protein breakdown in the warmed group on day 2 was significantly less than that in the cold group (P less than 0.05). The increase in leucine oxidation in the warmed group on the 2nd day after surgery was not significant, and was less than the increase observed in the cold group (P less than 0.05). However, by the 4th day, leucine oxidation was enhanced significantly in both groups (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1991

Metabolic response to colonic surgery: extradural vs continuous spinal.

We have examined the effect of intraoperative and postoperative (4 h) continuous spinal anaesthesia for colonic surgery on the postoperative glucose, lactate and cortisol responses. Twenty-one patients were studied; the first group (control) received general anaesthesia, the second group (extradural) an extradural block (T4-S5) and the third group (spinal) a continuous spinal block (T4-S5). Plasma concentration of glucose increased significantly in the control and extradural groups (P less than 0.05) after surgery, with a small change in the spinal group. Plasma concentration of lactate increased significantly (P less than 0.05) in the control group only. The postoperative increase in plasma concentration of cortisol was similar in both control and extradural groups, and significantly greater than that of the spinal group (P less than 0.05). Thus continuous spinal analgesia attenuated, but did not abolish, the increase in plasma concentration of cortisol associated with colonic surgery.

Aged↗
PubMed1991

Protein metabolism after abdominal surgery: effect of 24-h extradural block with local anaesthetic.

We have studied the effect of intraoperative and postoperative (24 h) extradural block with local anaesthetic on whole body protein turnover (stable isotope methodology) and urinary excretion of urea nitrogen, adrenaline, noradrenaline and cortisol in a group of well nourished elderly patients undergoing colorectal surgery who received a constant nutritional intake before (7 days) and after (4 days) surgery. One group (control, n = 8) received routine anaesthetic and surgical care. Patients in the test group (extradural, n = 9) received extradural bupivacaine, and sensory block (T4-S5) was maintained during and after surgery for a period of 24 h. Whole body protein breakdown and amino acid oxidation increased significantly after surgery in both groups (P less than 0.05), but the increase in protein breakdown in the extradural group was significantly less than that in the control group. Urinary excretion of urea nitrogen, adrenaline and noradrenaline increased in the control group after surgery, whilst the increase in the extradural group was very small. In contrast, urinary excretion of cortisol increased significantly in both groups after surgery. We conclude that extradural block maintained for 24 h after surgery significantly minimized postoperative protein breakdown without compromising whole body protein synthesis.

Abdomen↗
PubMed1991

Establishing pregnancies after follicular stimulation for IVF with clomiphene citrate and human menopausal gonadotrophin only.

Data are presented on establishing pregnancies by IVF during 1987 using only clomiphene citrate and human menopausal gonadotrophin for follicular stimulation. Of the 562 patients undergoing follicular stimulation, 80% reached oocyte recovery and 70% had at least one conceptus replaced. Patients having one or more (up to a maximum of four) conceptuses replaced demonstrated a significant increase in the establishment of pregnancies from one to two (14-29%: P = 0.035) and from two to three conceptuses (29-42%: P = 0.037). There was a significant decline in pregnancies when four conceptuses were replaced compared with three (P = 0.004). The data were also analysed according to the cause of infertility, specifically tubal, endometriosis, unexplained infertility and male factors only. After the replacement of conceptuses, the incidence of implantation and abortion was not significantly different. The incidence of pregnancy declined significantly after 35 years (26%) compared with women under 31 years (43%; P = 0.043). Of 129 women having three conceptuses replaced, in those greater than 35 years (63 patients) 23 (37%) became pregnant whereas in those less than 31 years (65 patients), 34 (52%; P = 0.05) became pregnant. Twenty-two per cent of stimulated cycles resulted in an endogenous LH surge and the incidence of patients having three conceptuses replaced in this group was lower than those in the HCG group (P = 0.007). Fertilization per oocyte was also significantly reduced (P less than 0.001) in patients with an LH surge. In total, 2824 oocytes were recovered and 57% fertilized with 54% of patients having three conceptuses replaced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Nicardipine sustained release in hypertension.

1. A novel formulation of nicardipine (25% standard, 75% sustained release--SR) was evaluated in mild hypertension in a double-blind, randomized, placebo-controlled comparison with standard nicardipine (STD), using clinic measurements (Hawksley) augmented by home recorded blood pressures (Copal UA 251). 2. At 2 h after dosing (peak effect) both STD nicardipine (30 mg three times daily) and SR nicardipine (60 mg twice daily) for 28 days produced a highly significant reduction in sitting and standing blood pressure. The mean sitting blood pressure was reduced by 20/16 mm Hg (STD) and by 25/18 mm Hg (SR) compared with placebo. 3. Predose (8-11 h after last dose of STD, 12-15 h after last dose of SR) the reductions in sitting blood pressure relative to placebo were 11/6 mm Hg (STD) and 14/7 mm Hg (SR). 4. Home recordings confirmed the hypotensive effect of both formulations. Both exhibited a distinct 'peak dose' effect between 1-3 h after dosing. The effect of the SR formulation was sustained throughout the 12 h dosing interval. 5. Of the 60 patients entering the study, one died of unexplained staphylococcal septicaema, two were withdrawn for non drug-related reasons and 14 (32%) were withdrawn because of adverse effects on active therapy (headaches, facial flushing, leg oedema, chest pain, dizziness). 6. In the 43 patients who completed the study adverse symptoms were reported more frequently while they were on the two active formulations of nicardipine compared with placebo. Most of these reactions were again of vasodilator origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A comparison of the chronic effects of oral xamoterol and enalapril on blood pressure and renal function in mild to moderate heart failure.

1. We compared the effects, after 3 weeks oral therapy, of xamoterol 200 mg twice daily and enalapril 2.5, 5 or 10 mg twice daily on home and clinic blood pressure, glomerular filtration rate (GFR) and renal plasma flow, stroke and minute distances, linear resistance and on plasma renin activity in 19 patients with mild to moderate heart failure in a single-blind randomised crossover study. 2. Enalapril reduced mean home blood pressure by 17/7 mm Hg compared with xamoterol (P less than 0.0001) and by 19/7 mm Hg compared with placebo. Compared with placebo xamoterol had no effect. Enalapril reduced predose blood pressure, compared with xamoterol, on average by 15/5 mm Hg (P = 0.02 systolic, 0.09 diastolic) and by 20/7 mm Hg compared with placebo. At 4 h post-dose the mean differences were: xamoterol-enalapril 13/10 mm Hg (P = 0.01 systolic, 0.0007 diastolic) and placebo-enalapril 23/9 mm Hg. 3. Stroke and minute distances were marginally less 4 h following xamoterol than following enalapril: mean (s.e. mean) values were 9.4 (0.7) vs 10.4 (0.8) cm (P = 0.23) and 699 (51.7) vs 767 (62.1) cm (P = 0.04) respectively. Linear resistance was reduced by enalapril, from the placebo value of 13.2 (1.2) to 11.0 (0.9) mm Hg m-1 and marginally increased by xamoterol, to 14.2 (1.2) mm Hg m-1, the difference between active treatments being statistically significant (P = 0.03). 4. Renal plasma flow, GFR and filtration fraction were not influenced by enalapril or xamoterol therapy. There were no significant correlations between glomerular filtration rate and either blood pressure or stroke distance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1991

The use of the GnRH analogue buserelin for IVF--does it improve fertility?

OBJECTIVE: To determine the effect of a short course of the GnRH analogue buserelin and human menopausal gonadotrophin (hMG), for ovarian stimulation in our IVF programme, on reproductive endocrinology and pregnancy rates compared with conventional clomiphene citrate and hMG treatment. DESIGN: Prospective randomized allocation to one of two ovulation stimulation regimens. SETTING: Fertility clinic. SUBJECTS: 373 infertile couples with various factors associated with their subfertility. All the women were less than 46 years of age and had normal menstrual cycles. INTERVENTION: The first group (n = 151) was given clomiphene citrate (CC) from days 2-6 of the menstrual cycle and hMG from day 5 onwards (CC/hMG). The second group (n = 222) was given buserelin from days 1-3 and hMG from day 2 (buserelin/hMG). MAIN OUTCOME MEASURES: Concentration of plasma luteinizing hormone (LH), oestradiol (E2) and progesterone, number of ovulatory follicles induced and the occurrence of pregnancy. RESULTS: Plasma LH, E2 and progesterone concentrations were reduced in the late follicular phase after buserelin/hMG compared with CC/hMG. Buserelin/hMG promoted the development of more follicles than CC/hMG. The overall pregnancy rate after buserelin/hMG was not significantly different from that following CC/hMG treatment. CONCLUSION: The chance of pregnancy is not improved by the short-term use of buserelin with hMG, provided adequate follicular phase management is maintained.

Adult↗
PubMed1991

Preliminary characterization of growth factors secreted by human pituitary tumors.

To investigate the secretion of mitogenic factors by human pituitary tumors we have cultured cells from 54 adenomas in serum-free medium. Conditioned media from 28 (52%) elicited dose-dependent stimulation of [3H]thymidine incorporation into rat GH3 cells (22-338% above control), while 14 (26%) inhibited GH3 proliferation. Stimulating activity was observed more frequently in nonfunctional tumor-conditioned medium (73%; n = 22) than in secretory tumor-conditioned medium (37%; n = 32). Of 10 tumour-conditioned media with mitogenic activity for GH3 cells, only 4 produced modest stimulation of HEp2 (human laryngeal carcinoma) cells. In contrast, [3H]thymidine incorporation into A431 (human squamous carcinoma) and PC12 (rat adrenal pheochromocytoma) cells was enhanced by each of 15 tumor-conditioned media (up to 342% and 275%, respectively), 8 of which had shown stimulatory and 2 inhibitory effects on GH3 cells. Gel filtration of pooled conditioned media from 10 nonfunctional tumors showed significant growth-promoting activity for GH3 cells in fractions corresponding to mol wt of 2-3 and 11-18 kDa. Proliferative activity on A431 cells also eluted in two positions; one corresponded to the higher mol wt peak seen with GH3 cells, while the other, not observed with GH3 cells, was in the 3- to 6-kDa range. These findings suggest that cells derived from human pituitary adenoma tissue synthesize and secrete several growth factors, each of which may have its own target cell specificities. These factors have yet to be characterized, but we suggest that they may have a role in stimulating the development or maintenance of human pituitary adenomas.

Adenoma↗
PubMed1990

Detection by immunofluorescence of surface molecules present in low copy numbers. High sensitivity staining and calibration of flow cytometer.

Receptors for lymphokines and growth factors are present on cell surfaces often at concentrations of 100-500 copies per cell. Although conventional immunofluorescence cannot detect such low levels, cell membrane antigens present at these concentrations can be detected using an optimally set up flow cytometer together with a three-layer immunofluorescence technique, consisting of monoclonal antibody reacted with selected batches of biotinylated horse anti-mouse immunoglobulin and phycoerythrin-streptavidin. In this study we purified and radiolabelled a number of monoclonal antibodies, determined the specific radioactivity by self-displacement analysis, and used the radiolabelled antibody in experiments where the number of molecules of antibody bound per cell and the fluorescence intensity were measured on the same sample. This permitted us to determine the sensitivity of the fluorescence procedure in molecules per cell, using several different antibody/target cell combinations. The method was consistently capable of detecting fewer than 100 molecules of antibody bound per cell.

Antibodies, Monoclonal↗