Short and long term modulation of oxidant induced ATP depletion--implications for effective treatment.
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Adenosine Triphosphate↗
Biomedical subjects
J Webster
Publications and source records attributed to J Webster.
Identification of a membrane receptor for the auxin binding protein.
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Electrophoresis, Polyacrylamide Gel↗
Accelerated hypertension--patterns of mortality and clinical factors affecting outcome in treated patients.
We evaluated the outcome of patients presenting with accelerated hypertension, as part of an audit of the Aberdeen Hypertension Clinic database. Of 3928 patients (2005 male, 1923 female) referred for assessment of hypertension, 128 (77 male, 51 female) presented with accelerated hypertension. The main outcome measures were systolic and diastolic pressure, length of time from referral to death or censor date, and cause of death. Accelerated hypertensives had a higher death rate than other hypertensives. Using life-table analysis, age and serum creatinine at referral were sufficient to predict survival. Almost 50% (15/31) of the deceased accelerated hypertensives died of acute myocardial infarction. Mean survival after referral was estimated as 18 years for accelerated hypertensives (mean referral age 52 years) and 21 years for other hypertensives (mean referral age 48 years). Blood pressure fell most during the first year of treatment, and declined steadily thereafter. Systolic blood pressure fell by a mean of 50 mmHg and diastolic pressure by 30 mmHg in the first year, and at about 2 (diastolic) and 1 (systolic) mmHg/year for the next 10 years. Thus although the prognosis for accelerated hypertensives is not quite as good as for other hypertensives, with suitable care they can survive for a considerable period.
Adult↗
Use of the Rand Structured Implicit Review Instrument for Quality of Care Assessment.
The Rand Structured Implicit Review Instrument is a 27-item instrument that rates process quality of care for patients with five common illnesses. This study reports on the use of this instrument for hospitalized patients with long lengths of stay. A total of 120 medical records were reviewed by multiple physician reviewers for patients discharged with congestive heart failure, acute myocardial infarction, and pneumonia. Mean inter-rater reliability was assessed for a subsample of six records by kappa score. A multiple regression analysis was used to estimate the relationship between process ratings for the quality of documentation, assessment, monitoring, and therapy and overall quality of care scores, controlled for physician judgments about patients' prognosis and selected patient characteristics. Each reviewer also evaluated the instrument. Mean kappa for trichotomized ratings of quality of care was 0.50. The majority of all quality of care ratings were in the good or very good range (77.5%). The full regression model, including process subscale quality ratings, prognostic items, and patient characteristics, accounted for 38% of the total variance in the quality of care ratings. Items measuring the quality of assessment (p < 0.0001), therapy (p < 0.02) and monitoring (p < 0.01) were significant. Physicians accepted the use of such a form moderately well. The Rand quality of care form shows consistency in rating overall quality of care and individual dimensions of quality. Achieving a high level of inter-rater reliability is difficult with implicit review. By focusing on specific areas of potentially deficient care, structured review instruments can improve clinical quality improvement efforts.
Humans↗
A comparison of amlodipine with enalapril in the treatment of moderate/severe hypertension.
1. The safety and efficacy of amlodipine vs enalapril as monotherapy was evaluated in patients with moderate/severe hypertension (supine DBP 105-125 mm Hg, SBP 140-220 mm Hg). 2. After 2 weeks placebo treatment 31 patients were randomised by the technique of minimisation in an observer-blind study to receive once daily treatment with either amlodipine (15 patients) 5-10 mg, or enalapril (16 patients) 5-20 mg for 8 weeks. The study design concluded with 2 weeks placebo treatment. In addition to clinic measurements, home blood pressure monitoring (Copal UA-251) was performed during the study. 3. Clinic supine systolic blood pressure was reduced from 177 to 152 mm Hg (amlodipine) and 183 to 169 mm Hg (enalapril) (95% CI for the intergroup difference -22.1, 0.3, P = 0.06) after 8 weeks treatment. 4. Clinic supine diastolic blood pressure was reduced from 110 to 93 mm Hg (amlodipine) and 109-102 mm Hg (enalapril) (95% CI for the intergroup difference -17.7, -2.7, P < 0.01) after 8 weeks treatment. 5. Home blood pressure recordings confirmed these reductions in blood pressure. Although the reduction in blood pressure was greater for the amlodipine treated group, the differences between treatments were not statistically significant. 6. Both drugs were reasonably well tolerated. The adverse events occurring most frequently in the amlodipine group were headache (5), peripheral oedema (3), upper respiratory infection (3) and anxiety (2). The adverse events occurring most frequently in the enalapril treated patients were headache (6), dizziness (3) and upper respiratory infection (2).
Adult↗
A comparison of amlodipine with enalapril in the treatment of isolated systolic hypertension.
1. The safety and efficacy of amlodipine and enalapril were compared in patients with isolated systolic hypertension (supine DBP < 95 mm Hg and supine SBP 160-200 mm Hg). 2. After 2 weeks treatment with placebo 31 patients were randomised by the technique of minimisation in an observer-blind study to receive once daily treatment with either amlodipine (16 patients) or enalapril (15 patients) for 8 weeks. The study design concluded with 2 weeks placebo treatment. In addition to clinic measurements, home blood pressure monitoring (Copal UA-251) was performed during the study. 3. Mean supine systolic blood pressure was reduced from 185 to 164 mm Hg (amlodipine) and 183 to 159 mm Hg (enalapril) (95% CI for the difference between the drugs -10.5, 15.3) after 8 weeks treatment. 4. Mean supine diastolic blood pressure was reduced from 86 to 80 mm Hg (amlodipine) and 88 to 80 mm Hg (enalapril) (95% CI for the difference between the drugs -4.9, 7.6) after 8 weeks treatment. 5. Home blood pressure recordings confirmed these reductions in blood pressure, although there was no significant difference between treatments for the reductions in blood pressure. 6. Both drugs were reasonably well tolerated. The adverse events occurring most frequently in the amlodipine group were headache (2), peripheral oedema (5) and palpitations (2). The adverse events occurring most frequently in the enalapril group were headache (2), peripheral oedema (2), palpitations (2) and dizziness (3).
Aged↗
The haemodynamic effects of GR 32191, a thromboxane A2 receptor antagonist, in patients with renal artery stenosis and hypertension.
This study was designed to determine if GR 32191 a thromboxane A2 receptor antagonist, would lower blood pressure in patients with hypertension and renal artery stenosis. Eight patients with unilateral atheromatous renal artery stenosis and hypertension were studied in a double-blind, single dose, placebo controlled, crossover study. The results show that, GR 32191, given orally, in doses of 20 mg and 40 mg, does not reduce the blood pressure to any clinically important degree.
Aged↗
The efficacy and tolerability of long-term cabergoline therapy in hyperprolactinaemic disorders: an open, uncontrolled, multicentre study. European Multicentre Cabergoline Study Group.
OBJECTIVE: We assessed the efficacy and safety of the new, long-acting dopamine agonist drug cabergoline during long-term therapy of hyperprolactinaemia. DESIGN: Open, prospective, multicentre study. PATIENTS: One hundred and sixty-two females with either a microprolactinoma (n = 100), idiopathic hyperprolactinaemia (n = 54), empty sella syndrome (n = 7) or residual hyperprolactinaemia after surgery for a macroprolactinoma (n = 1). All had previously been treated with cabergoline or placebo for 4 weeks as part of a dose-finding study. MEASUREMENTS: Menstrual pattern, adverse symptoms, blood pressure and pulse, serum PRL, blood count, liver and renal function were assessed after one month and subsequently at two-monthly intervals. RESULTS: Treatment was started at doses of 0.25 mg (n = 3), 0.5 mg (n = 8), 1 mg (n = 150) or 2 mg (n = 1) per week, given either as a single weekly dose (n = 8) or divided into twice-weekly doses (n = 154), and was continued for at least 49 weeks in 123 patients. Final treatment doses ranged from 0.25 mg fortnightly to 2 mg twice weekly: most patients finished the study taking 0.5 mg once (n = 31) or twice (n = 77) weekly. Stable normalization of PRL levels was achieved in 138 subjects (85%), in 129 of whom the effective dose was < 1 mg per week. In the subset of 114 patients completing 49 weeks of therapy and having dose adjustments according to the protocol, the biochemical success rate was 92%. Fifty-nine of the 65 previously amenorrhoeic women (91%) and 44 of the 49 (90%) who were previously oligomenorrhoeic resumed regular menses and/or became pregnant during the study. Adverse events were reported in 64 patients (39.5%). In 84% of cases with adverse events, the symptoms were of mild or moderate severity and most occurred during the first few weeks of therapy; five patients (3%) discontinued treatment because of poor tolerance. The most frequent symptoms were dizziness (13% of patients), headache (13%), nausea (10%) and weakness and/or fatigue (10%). Of 27 patients who had previously been poorly tolerant of other dopamine agonists, 17 (63%) did not experience any side-effects and only one was intolerant of cabergoline. No adverse haematological or biochemical effects were detected except for a slight downward trend in haemoglobin which may have been related to the resumption of regular menses in previously amenorrhoeic or oligomenorrhoeic women. A mild hypotensive effect was observed, mean systolic and diastolic blood pressures falling by 5 and 4 mmHg respectively during treatment. CONCLUSIONS: The results provide evidence for the long-term effectiveness and safety of cabergoline in the treatment of hyperprolactinaemia. Its ability to normalize PRL and restore gonadal function compares favourably with reported data on reference compounds while its tolerability profile and simple administration schedule offer potential advantages in terms of patient acceptability.
Adult↗
The independent metabolic effects of halothane and isoflurane anaesthesia.
Twelve healthy, unpremedicated women scheduled for total abdominal hysterectomy were given either isoflurane (n = 6) or halothane (n = 6) anaesthesia. They all received general anaesthesia for a period of 3 h, with surgery being carried out only in the last hour. The anaesthesia consisted of thiopentone, pancuronium and a mixture of oxygen-enriched air (FiO2 = 34%) supplemented with 1 MAC of either isoflurane or halothane. The patients were maintained normothermic, and with an arterial SaO2 above 95% throughout the period of the study. The following measurements were made before, during and after anaesthesia (with and without surgery): oxygen consumption (VO2), carbon dioxide production (VCO2); circulating concentrations of various hormones (insulin, growth hormone and cortisol); various metabolites; selected amino acids and albumin; forearm arterio-venous concentration difference of glucose, lactate, free fatty-acids and selected amino acids (four patients in each group). Whole body VO2 decreased significantly by over 20% during anaesthesia (with or without surgery), P < 0.05). Although the circulating concentration of most amino acids showed little or no change during anaesthesia alone, there was a tendency for the flux of most metabolites to decrease, and this persisted during surgery (P < 0.05). During anaesthesia alone there was a twofold reduction in the plasma cortisol concentration (P < 0.05), and a decrease in albumin concentration (P < 0.01). With the onset of surgery, plasma cortisol concentration increased rapidly (in association with several other hormones and metabolites) but hypoalbuminemia persisted.
Adult↗
An evaluation of patients' responses to LLETZ in an outpatient setting.
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Cervix Uteri↗
Quality assurance: measures of maternal knowledge and satisfaction.
This paper reviews the introduction and results of an Outcome Assessment system developed to determine if all women delivering at the Royal Women's Hospital, Brisbane were receiving an acceptable level of care. The system involves measurement of four outcome variables: nosocomial infection rate; medication error rate; accident rate; and a comprehensive patient questionnaire. Scores are combined and a monthly Quality of Care Score, and other information including the Caesarean delivery rate, bed occupancy rate, number of primiparas in the ward and percentage of women who failed to achieve a minimum acceptable score, is prepared for each ward. On another level, the system allows midwives to objectively evaluate the care provided in their ward by involving each patient's primary midwife, clinical nurse consultant and unit manager in the collection and review of data. The monthly feedback to wards, the Director of Nursing, Chief Executive Officer, Dietitian and Senior Domestic Supervisor has resulted in changes which had previously been difficult to achieve.
Female↗
Infants of less than 1250 grams birth weight at Groote Schuur Hospital: outcome at 1 and 2 years of age.
A prospective 2-year follow-up study of infants with birth weights of less than 1250 g was undertaken at Groote Schuur Hospital Neonatal Intensive Care Unit. For a 12-month period beginning July 1988, all live infants born at Groote Schuur Hospital or referred to the Neonatal Intensive Care Unit were included in the study cohort. The aim of the study was to document the morbidity, mortality, and neurodevelopmental outcome of these infants to 2 years of age. Of 235 liveborn infants, 143 (61%) survived to discharge. One hundred twenty-six infants were born weighing less than 1000 g; 42% survived to discharge. One hundred nine infants weighed 1000 g or more at birth, and 83% survived to discharge. Better survival was documented for infants whose mothers attended antenatal care, who weighed more than 900 g, and who were of greater than 30 weeks' gestation. Eleven infants died in the first 6 months after discharge. One hundred six infants (83% of survivors) underwent Griffiths developmental testing and clinical assessment at 1 year of age. Ninety-six (91%) of these survivors were seen and tested at 2 years of age. Of the 106 infants assessed at 1 year of age, 6 infants had cerebral palsy, 6 were globally developmentally delayed without signs of cerebral palsy, and 1 infant showed significant motor delay with a normal developmental quotient. At 2 years of age 1 additional infant had cerebral palsy and 9 more infants are likely to be mentally retarded. At 2 years of age the major handicap rate was, therefore, 22%. Sixty-nine percent of surviving infants, and all but 1 of the infants with cerebral palsy, were underweight for gestational age at birth. There was a tendency for these underweight-for-gestational-age infants to score less well at 2 years of age. Infants who received ventilation and infants with a birth weight of less than 1000 g were not found to score less well than other infants in the cohort.
Birth Weight↗
Handwashing in a neonatal intensive care nursery: product acceptability and effectiveness of chlorhexidine gluconate 4% and triclosan 1%.
The effectiveness of triclosan 1% w/v against methicillin-resistant Staphylococcus aureus (MRSA) and its effect on skin were compared with chlorhexidine gluconate 4% w/v ('Hibiclens') in a 7-week trial. Clinical information of MRSA rates obtained during the previous 10 months and results from earlier user acceptability trials were included. The average number of new cases of MRSA per week was reduced from 3.4 to 0.14 (P less than 0.0001) in the experimental ward whilst no significant changes occurred in the control ward. Staff reported less skin damage and a higher rate of acceptance with the experimental product. Based on results of the trial, a proposal to introduce triclosan for a 12-month study period has been accepted.
Aerosols↗
Relation between treated blood pressure and death from ischaemic heart disease at different ages: a report from the Department of Health Hypertension Care Computing Project.
OBJECTIVE: To determine the relation between mortality from ischaemic heart disease (IHD) and treated blood pressure at different ages. DESIGN: Prospectively, 6216 patients were studied for a mean of 107 months. SETTING: Of the total patients, 95% were followed in five hospital-based hypertension clinics and the remainder in four group general practices. PATIENTS: Respectively, 2250 and 2126 hypertensive men and women aged < 60 years and 822 and 1018 aged > or = 60 years. MAIN OUTCOME MEASURES: Mortality (any mention on the death certificate) from IHD. RESULTS: Four hundred and sixty-seven patients died with IHD mentioned on the death certificate. The relation between both diastolic blood pressure (DBP) and systolic blood pressure (SBP) during the first 3-12 months of treatment and subsequent IHD mortality was examined. Under the age of 60 years the relative hazard rate (RHR) for death from IHD tended to increase with DBP in both men and women. Above the age of 60 years there was no important or significant relation between IHD mortality and treated DBP. For SBP there was no reduction in the positive relation between IHD mortality and blood pressure in the older age groups. The RHR for SBP ranged between 1.008 and 1.021 in men and women over and under the age of 60 years. CONCLUSIONS: The positive relation between DBP and IHD mortality decreased with increasing age and, in women aged > or = 60 years, even inverted, partly explaining the negative relation reported between DBP and total mortality in the very old.
Adolescent↗
Dose-dependent suppression of serum prolactin by cabergoline in hyperprolactinaemia: a placebo controlled, double blind, multicentre study. European Multicentre Cabergoline Dose-finding Study Group.
OBJECTIVE: Dopamine agonists have a well established place in the treatment of hyperprolactinaemic disorders but their use is associated with a high incidence of adverse effects. We have investigated the biochemical efficacy and side-effect profile of a range of doses of the novel, long-acting dopamine agonist, cabergoline, in suppressing prolactin (PRL) in hyperprolactinaemic women. DESIGN: Multicentre, prospective, randomized, placebo controlled and double blind. PATIENTS: One hundred and eighty-eight women with hyperprolactinaemia secondary to microprolactinoma (n = 113), idiopathic disease (n = 67), empty sella syndrome (n = 7) or following failed surgery for a macroprolactinoma (n = 1). MEASUREMENTS: Weekly assessment of adverse symptoms, blood pressure and pulse, serum PRL, blood count, liver and renal function. RESULTS: Patients received either placebo (n = 20) or cabergoline 0.125 (n = 43), 0.5 (n = 42), 0.75 (n = 42) or 1.0 mg (n = 41) twice weekly for 4 weeks. The five treatment groups were comparable in age (mean 31.8, range 16-46 years), diagnosis, previous therapy, and pretreatment serum PRL. PRL was suppressed to below half the pretreatment level in 5, 60, 90, 95 and 98% and normalized in 0, 30, 74, 74 and 95% of patients taking placebo or cabergoline 0.125, 0.5, 0.75 or 1.0 mg twice weekly respectively (Armitage's test, chi 2 = 39.3, P < 0.01). Cabergoline therapy (all doses) restored menses in 82% of the amenorrhoeic women not previously treated with dopamine agonists. Adverse events were recorded in 45% of patients in the placebo group and in 44, 50, 50 and 58% of those taking 0.125, 0.5, 0.75 and 1.0 mg cabergoline twice weekly (Armitage's test, P > 0.05). Over 95% of reported symptoms were relatively trivial, most frequently transient nausea, headache, dizziness, fatigue and constipation. More severe adverse events, interfering significantly with the patients' lifestyle, occurred in 13 (7.7%) patients taking cabergoline; treatment withdrawal was necessary in only one case. No adverse effects were detected on blood pressure or haematological or biochemical parameters. CONCLUSIONS: We have shown a linear dose-response relationship for cabergoline in the treatment of hyperprolactinaemia in the range 0.125-1.0 mg twice weekly, with normalization of PRL in up to 95% of cases and acceptable tolerability throughout the dose range.
Adolescent↗
Low recurrence rate after partial hypophysectomy for prolactinoma: the predictive value of dynamic prolactin function tests.
OBJECTIVE: To determine the factors influencing the outcome of transethmoidal partial hypophysectomy for suspected prolactinoma and the predictive value of pre and post-operative dynamic PRL function tests. DESIGN: A retrospective study of patients undergoing surgery for a suspected prolactinoma in Cardiff between 1979 and 1989. PATIENTS: Eighty-two hyperprolactinaemic patients (75 women, seven men) diagnosed as having a prolactinoma on the basis of dynamic PRL function tests, radiological investigation and exclusion of other causes. MEASUREMENTS: TSH and PRL responses to domperidone (10 mg i.v.) and TRH (200 micrograms i.v.) measured preoperatively, 2 months post-operatively, and annually thereafter. CT scan performed preoperatively in 58 patients. Operative findings, including adenoma size, documented in each case. RESULTS: Forty-two patients (51%) had microadenomas (less than 10 mm), 37 (46%) had macroadenomas and in three no tumour was found at operation. Preoperatively, normal responses of both TSH (incremental rise less than 2.0 mU/l) and PRL (greater than 100% rise) to domperidone were observed in two patients only: both had an abnormal vascular supply to the pituitary rather than an adenoma. Serum PRL was normalized in the early post-operative period (less than 72 h; 'early cure') in 65 patients (79%). The highest early cure rate (96%, n = 26) was in patients with adenomas of 5-9 mm, lower rates being achieved for lesions of 10-19 mm (80%, n = 30), less than 5 mm (63%, n = 19) or greater than or equal to 20 mm (57%, n = 7). The early cure rate was strongly correlated with preoperative PRL, ranging from 100% in patients with PRL less than 1000 mU/l (n = 13) to zero in those with PRL greater than 10,000 mU/l. Dopamine agonist therapy of between 5 weeks and 4 years duration prior to surgery was associated with a significantly reduced early cure rate (60 vs 94%, P less than 0.02) in macroadenoma but not microadenoma patients. Recurrent hyperprolactinaemia during mean follow-up of 51.7 months occurred in eight patients (12%), in five cases within 2 months of surgery and in the others at 26, 48 and 50 months. Recurrence could not be predicted from any preoperative parameter, but a serum PRL greater than 150 mU/l 1-3 days following microadenomectomy was associated with early recurrence and probably indicates failed surgery. An abnormal response of TSH to domperidone was documented 2 months post-operatively in 11/60 patients with normal basal PRL, and preceded all three late recurrences. Of four patients with abnormal responses of both PRL and TSH at this time, two have relapsed to date. CONCLUSIONS: In carefully selected patients, partial hypophysectomy is an acceptable alternative to medical treatment for prolactinoma. Preoperatively, dynamic tests accurately identified those patients whose hyperprolactinaemia was non-adenomatous in origin and, post-operatively, identified a subgroup of patients at increased risk of late recurrence.
Adult↗
Insulin sensitivity and secretion in healthy elderly human subjects with 'abnormal' glucose tolerance.
Glucose tolerance deteriorates dramatically with advancing age. It is not known whether the underlying pathophysiology is different in older subjects. We employed a two step hyperinsulinaemic euglycaemic glucose clamp with [6(14)C] glucose infusion to compare peripheral and hepatic insulin sensitivity in eight elderly (EAGT) with eight young (YAGT) subjects with abnormal (matched) glucose tolerance and nine elderly subjects with normal glucose tolerance (ENGT). There was no difference in basal HGO (EAGT 14.5 +/- 0.9, YAGT 15.3 +/- 1.1 mumol kg-1 min-1). Glucose turnover was similar in both groups at step 1 (EAGT 13.2 +/- 0.8, YAGT 13.4 +/- 0.8 mumol kg-1 min-1) and step 2 (EAGT 25.1 +/- 3.1, YAGT 27.2 +/- 2.7 mumol kg-1 min-1). HGO was lower in the EAGT subjects at step 1 (2.3 +/- 0.4 vs. 4.3 +/- 0.6 mumol kg-1 min-1 P = 0.01). Incremental serum insulin response to oral glucose was comparable (EAGT 66.8 +/- 11.6 YAGT 57.8 +/- 12.2 mU l-1.h). Compared to the ENGT group the EAGT group was insulin resistant with a lower MCR of glucose at step 1 (2.03 +/- 0.28 vs. 3.23 +/- 0.44 ml kg-1 min-1 P = 0.04) and at step 2 (6.18 +/- 0.83 vs. 9.64 +/- 0.38 ml kg-1 min-1 P = 0.004) and had a lower early insulin response (AUC 0-30 min 5.9 +/- 1.1 vs. 9.8 +/- 1.4 mU l-1.h P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Speech of cochlear implant patients: a longitudinal study of vowel production.
Acoustic parameters were measured for vowels spoken in /hVd/ context by four postlingually deafened recipients of multichannel (Ineraid) cochlear implants. Three of the subjects became totally deaf in adulthood after varying periods of partial hearing loss; the fourth became totally deaf at age four. The subjects received different degrees of perceptual benefit from the prosthesis. Recordings were made before, and at intervals following speech processor activation. The measured parameters included F1, F2, F0, SPL, duration, and amplitude difference between the first two harmonic peaks in the log magnitude spectrum (H 1-H2). Numerous changes in parameter values were observed from pre- to post-implant, with differences among subjects. Many changes, but not all, were in the direction of normative data, and most changes were consistent with hypotheses about relations among the parameters. Some of the changes tended to enhance phonemic contrasts; others had the opposite effect. For three subjects, H 1-H2 changed in a direction consistent with measurements of their average air flow when reading; that relation was more complex for the fourth subject. The results are interpreted with respect to: characteristics of the individual subjects, including vowel identification scores; mechanical interactions among glottal and supraglottal articulations; and hypotheses about the role of auditory feedback in the control of speech production. Almost all the observed differences could be attributed to changes in the average settings of speaking rate, F0 and SPL, which presumably can be perceived without the need for spectral place information. Some observed F2 realignment may be attributable to the reception of spectral cues.
Adult↗