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Biomedical subjects

J Webster

Publications and source records attributed to J Webster.

At least 37 records · Page 2Linked to original sources
PubMed1994

An assessment of lacidipine and atenolol in mild to moderate hypertension.

1. The aim of this randomised, double-blind four way crossover study was to assess the interaction between the new calcium antagonist, lacidipine and atenolol, in patients with mild to moderate hypertension. 2. Sitting blood pressure at 4 h post-dosing with lacidipine (4 mg) and atenolol (100 mg) alone was significantly lower compared with placebo (137/89 +/- 3/3 mmHg; 142/89 +/- 5/3 mmHg; and 154/98 +/- 5/3 mmHg respectively; P < 0.001). Co-administration of both drugs produced a significant additive effect compared with atenolol and lacidipine alone (124/80 +/- 4/2 mmHg; P < 0.002). 3. Heart rate on treatment with lacidipine alone was significantly greater at 4 h compared with placebo (86 +/- 1 beats min-1 and 74 +/- 2 beats min-1 respectively; P < 0.001). When both drugs were used in combination, there was a significant decrease in pulse rate compared with lacidipine alone (58 +/- 1 beats min-1 and 86 +/- 1 beats min-1 respectively; P < 0.001). 4. Home blood pressure recordings confirmed the statistically significant reduction in blood pressure on co-dosing (120/82 +/- 10/2 mmHg) compared with lacidipine (140/92 +/- 5/3 mmHg) and atenolol (146/90 +/- 6/3 mmHg) given alone (P < 0.05). 5. Lacidipine alone produced a significant exercise tachycardia compared with atenolol alone and the atenolol/lacidipine combination (97 +/- 8 beats min-1; 65 +/- 4 beats min-1 and 75 +/- 7 beats min-1 respectively; P < 0.001). Exercise tolerance was not adversely affected by the co-administration of both lacidipine and atenolol.

Adult↗
PubMed1994

Colestipol at varying dosage intervals in the treatment of moderate hypercholesterolaemia.

1. Bile acid sequestrants such as colestipol are effective lipid lowering agents but have a poor reputation for tolerability particularly when administered at the originally recommended doses. We have investigated a low dosage regimen with varying dosage intervals in order to assess efficacy and tolerability. 2. This double-blind, placebo controlled, parallel group study was conducted to investigate the effect of varying administration schedules of colestipol (10 g daily), against placebo in reducing LDL cholesterol levels in patients with moderate hypercholesterolaemia on the American Heart Association step 1 diet. 3. Colestipol or matched placebo, was administered as 5 g twice daily (COL am/pm) or 10 g once daily in the morning (COL am) or evening (COL pm) at fixed times with meals. 4. All 98 patients who entered the initial 16 week dietary phase, subsequently entered the 12 week active treatment phase and were randomised to placebo or active treatment and to one of the three treatment schedules. Fasting lipid profiles were performed every 4 weeks during both phases. 5. All active treatments significantly reduced LDL and total cholesterol compared with placebo (COL am: 17% and 10%, COL pm: 18% and 10%, COL am/pm: 19% and 12% (P = 0.0001)). HDL cholesterol rose significantly with COL am (5% (P = 0.021)) and COL am/pm (7% (P = 0.002)) when compared with placebo while a marginal increase was seen with COL pm (4% (P = 0.063)). Colestipol tended to increase serum triglyceride concentrations but the changes were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Angiotensin converting enzyme inhibition does not affect the response to exogenous angiotensin II in the human forearm.

Suppression of endogenous levels of angiotensin II by angiotensin converting enzyme inhibition, may result in up-regulation of vascular AT1 receptors. We have evaluated the effects of orally administered enalapril on angiotensin II induced vasoconstriction in the human forearm. Subjects received in random order, enalapril (20 mg) or matched placebo daily for 2 weeks. Forearm blood flow response to increasing doses of angiotensin II was measured using venous occlusion plethysmography at the beginning of the study and at the end of each 2 week treatment period. Treatment with enalapril significantly reduced plasma angiotensin II levels and supine blood pressure compared with placebo. The percentage reductions in forearm blood flow in the infused arm, in response to the maximum dose of angiotensin II (50,000 fmol min-1) were 48.1 +/- 3.6% at baseline, 57.5 +/- 3.6% on placebo and 54.5 +/- 4.2% on enalapril. The differences were not significantly different. This demonstrates that suppression of plasma angiotensin II for a 14 day period does not enhance the response to exogenous intra-arterial angiotensin II in the human forearm of healthy salt replete subjects.

Administration, Oral↗
PubMed1994

Pituitary stone: two cases of densely calcified thyrotrophin-secreting pituitary adenomas.

Calcification is a well recognized but relatively uncommon feature of prolactin-secreting, growth hormone-secreting and non-functional pituitary tumours. It varies in extent, but rarely exceeds a tiny amount histologically or radiologically. Thyrotroph adenomas are the rarest of the secretory pituitary tumours, accounting for less than 1% of cases, and partial calcification of such lesions has been reported in only three cases. We describe two patients in whom the clinical and biochemical features indicated the presence of a TSH-secreting adenoma and radiology demonstrated a large 'pituitary stone'. One patient, a 59-year-old female, initially presented with hyperthyroidism, aged 18, and was rendered euthyroid by two subtotal thyroidectomies before a pituitary lesion was suspected, over 20 years later. Autonomous secretion of thyrotrophin was demonstrated by dynamic tests, and the failure of exogenous T3 to reduce the serum TSH. In the absence of tumour expansion and compressive symptoms, pituitary surgery was not undertaken. At the age of 56, she developed symptoms of intermittent ataxia and diplopia, culminating in a focal seizure, and was found on CT scan to have, in addition to the pituitary lesion, a parasagittal meningioma. This was successfully removed at craniotomy. In the second patient, a 42-year-old male, the finding of hyperthyroidism in association with an elevated TSH concentration led to the discovery of a pituitary stone which was removed transethmoidally, together with surrounding adenomatous tissue which stained positively for TSH on immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

Elimination of methicillin-resistant Staphylococcus aureus from a neonatal intensive care unit after hand washing with triclosan.

Evaluating hand wash products in terms of user acceptability and effectiveness against methicillin-resistant Staphylococcus aureus (MRSA) has been part of a long-term strategy to eliminate endemic MRSA from the neonatal intensive care unit at the Royal Women's Hospital (Brisbane). Following the introduction of a new hand wash disinfectant (triclosan 1% wt/vol), new cases of MRSA colonization were monitored for 12 months. In addition, the use of antibiotics, the incidence of multi-resistant Gram-negative cultures and neonatal infections were noted. No changes were made to any procedures or protocols during the trial. All babies colonized with MRSA had been discharged from the nursery within 7 months of the introduction of triclosan and in the subsequent 9 months no new MRSA isolates had been reported. Reduction in the use of vancomycin has resulted in a cost saving of approximately $A17,000. The total number of Gram-negative isolates has not increased, although Pseudomonas aeruginosa is now reported more often. Compared with the previous 12 months, fewer antibiotics were prescribed and fewer nosocomial infections recorded (P < 0.05).

Colony Count, Microbial↗
PubMed1994

Optimal blood pressure control in treated hypertensive patients. Report from the Department of Health Hypertension Care Computing Project (DHCCP).

BACKGROUND: We wished to determine the range of treated systolic (SBP) and diastolic blood pressure (DBP) associated with the best survival in hypertensive patients. METHODS AND RESULTS: We conducted a cohort study of patients enrolled in the DoH Hypertension Care Computer Project. Five specialist hypertension clinics (95% of patients) and general practitioners (5%) followed 6214 patients (3070 men and 3144 women) with an average age of 52 years for a mean of 107 months. Total, cardiovascular, ischemic heart disease, (IHD) and stroke mortality were the outcome measures. Age-adjusted relative hazard rates were calculated giving the effect on mortality of systolic or diastolic pressure being higher by 1 mm Hg. In men the optimal level of SBP for all four measures of mortality was the lowest pressure range observed, 92 to 133 mm Hg (median 127). For women the treated SBP range of 96 to 148 mm Hg (median 137) was associated with a low total mortality and also with low to moderate rates for IHD and stroke mortality. Relative hazard rates (P < .001) for IHD mortality were 1.010 for men and 1.013 for women and for stroke mortality were 1.018 and 1.021, respectively. The results were similar in men under and over the age of 60. SBP and DBP tended to be more important in younger than older women. For treated DBP in men, a pressure of 55 to 94 mm Hg (median 87) was associated with a low total mortality. The lowest stroke mortality in men was observed for a DBP range of 55 to 83 mm Hg (median 80) but with a tendency for an increase in IHD mortality. For women DBP < 95 mm Hg (range 55 to 94, median 87) also was associated with a low total mortality. IHD mortality in women was not closely related to treated DBP, relative hazard rate = 1.003, [95% confidence index (CI); 0.990,1.017] but the relative hazard rate for men was 1.011, (95% CI; 1.000, 1.022). The relative hazard rates for treated DBP and stroke were high at 1.035 and 1.028 for men and women, respectively (P < .001). IHD mortality increased in the one third of patients with the greatest fall in DBP on treatment, provided they were not initially in the one-third group with highest untreated DBP. CONCLUSIONS: The best overall survival was associated with a treated SBP of < 134 mm Hg in men and < 149 mm Hg in women and a treated DBP of < 95 mm Hg.

Adult↗
PubMed1994

Insulin-like growth factor-1 activation of extracellular signal-related kinase-1 and -2 in growth hormone-secreting cells.

Intracellular pathways mediating feedback regulation by insulin-like growth factor-1 (IGF-1) of pituitary GH gene expression remain incompletely understood. Extracellular signal-related kinases (ERKs), a family of serine/threonine kinases, are activated by tyrosine kinase-associated growth factor receptors. To further define the IGF-1 postreceptor events occurring in GH-secreting cells, we investigated the activity of ERKs in response to IGF-1 in GC cells following stable transfection with either wild type human IGF-1 receptor cDNA (WT cells) or a mutant cDNA encoding a truncated, kinase-defective IGF-1 receptor with a dominant negative effect on endogenous receptor function (952STOP cells). Zymography of immunoprecipitated ERKs in myelin basic protein (MBP)-containing polyacrylamide gels demonstrated dose-dependent induction of ERK-1 and -2 activity by IGF-1 in GC cells with maximal activity occurring at 6 min. IGF-1-induced ERK activity in WT-transfected cells was up to 80-fold basal and 4-fold that observed in GC cells. 952STOP cells expressing the tyrosine kinase-deficient receptor were refractory to IGF-1 action, demonstrating minimal ERK induction. In contrast, 12-O-tetradecanoylphorbol 13-acetate stimulated ERK activity to the same degree in all three cell types regardless of their IGF-I receptor status. Forskolin (50 microM), isobutylmethylxanthine (0.5 mM), and forskolin/isobutylmethylxanthine in combination attenuated IGF-1-induced ERK activity in WT cells by 54, 55, and 75% respectively. The rapid, dose-dependent, and IGF-1 receptor-dependent activation of ERKs and the attenuation of this effect by cAMP suggest an interrelated role for both molecules in IGF-1 signal transduction in GH-secreting cells.

Animals↗
PubMed1994

The effect of antihypertensive therapy on responsiveness to local intra-arterial NG-monomethyl-L-arginine in patients with essential hypertension.

OBJECTIVE: The nitric oxide (NO) system is abnormal in essential hypertension and the response of the forearm vascular bed to local intra-arterial infusions of NG-monomethyl-L-arginine (L-NMMA) is diminished in patients with untreated essential hypertension. Animal data suggest that treatment of hypertension may restore normal NO-mediated responses. We have prospectively examined the effect of standard antihypertensive therapy on the responsiveness to local intra-arterial infusions of L-NMMA in 18 newly diagnosed hypertensive patients. DESIGN: This was a double-blind, randomized, parallel-group study. Patients were randomized to treatment with 10 mg enalapril daily, 5 mg amlodipine daily or matched placebo for 6 weeks (with dose titration after 2 weeks if necessary). METHODS: Forearm blood flow during direct infusion into the brachial artery of L-NMMA (1, 2 and 4 mumol/min) was measured using venous occlusion plethysmography at the beginning and end of the 6-week treatment period. RESULTS: Both enalapril and amlodipine reduced blood pressure significantly compared with placebo. After 6 weeks of antihypertensive therapy, forearm blood flow (+/- SEM) in response to the maximum dose of L-NMMA (4 mumol/min) was reduced by 54.8 (6.9)% (P = 0.012), 58.9 (7.0)% (P = 0.016) and 33.1 (3.0)% (P = 0.17) in the enalapril, amlodipine and placebo groups, respectively. There was no significant difference between enalapril and amlodipine treatment groups. CONCLUSIONS: The forearm arterial responsiveness to L-NMMA in newly diagnosed patients with essential hypertension returns to normal with normalization of blood pressure by antihypertensive drugs with different modes of action. It remains to be determined whether this phenomenon is a consequence of the change in pressure per se or a result of the action of either drug by a common or separate mechanism.

Amlodipine↗
PubMed1994

Cardiac monitoring in the neonatal intensive care unit: an evaluation of electrodes.

Two types of electrodes were evaluated over a six-week period in a neonatal intensive care nursery. Babies requiring monitoring were alternately assigned to either of two groups: Klear-Trace (n = 37) or Sentry (n = 51). Nursing staff monitored a range of variables daily. Klear-Trace electrodes, although slightly more expensive, lasted significantly longer than Sentry electrodes (p > .0001). Factors such as incubator temperature and the weight of the neonate did not affect results, nor was there any difference in the frequency of repositioning electrodes between the two products. Because Klear-Trace electrodes last three times as long as Sentry electrodes (six days as opposed to two days), there may be cost advantages in using Klear-Trace electrodes.

Cost Control↗
PubMed1993

The majority of G0 transgenic mice are derived from mosaic embryos.

Most transgenic mice are generated by the direct microinjection of DNA fragments into the pronuclei of fertilized eggs. It has been generally assumed that the majority of integration events occur prior to the first round of chromosomal DNA replication (Palmiter and Brinster, 1986). In this study we have determined by comparison of PCR, Southern blot and transmission frequencies that at least 62% of integration events generate a mosaic (somatic and/or germline) G0 transgenic mouse. Furthermore, the statistical probability of transgene-containing cells segregating to the various early embryo lineages implies that this is probably an underestimate of the true mosaic frequency. Thus, the majority of DNA injected into fertilized mouse eggs intergates after the first round of chromosomal DNA replication, therefore most G0 transgenic mice are derived from a mosaic embryo.

Animals↗
PubMed1993

A quality-of-care analysis of cascade iatrogenesis in frail elderly hospital patients.

Cascade iatrogenesis is defined as a related sequence of adverse events that are triggered by an initial medical intervention. In an attempt to determine whether such a phenomenon is be associated with the quality of care provided, physician reviewers identified iatrogenic cascades and the rated quality of care given to a sample of long-stay teaching hospital patients. The care was rated with a structured implicit review instrument. Cascade iatrogenesis was found to occur most frequently among the oldest patients, the most functionally impaired, and those with a high severity of illness on admission. Closer examination of these findings suggests that there is significant potential for improving physicians' initial functional and diagnostic assessment skills when treating frail elderly patients.

Aged↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗