Does use or withdrawal of long-acting beta 2-adrenoceptor induce desensitisation?
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to N Moore.
Explore the source record for details and available documents.
AIMS: To assess the frequency and cost of drug reactions causing or prolonging hospitalization. METHODS: All patients admitted to an internal medicine ward over 6 months were evaluated to identify serious adverse reactions. The number of drug classes on admission or at the time of the adverse drug reaction (ADR) was counted. Excess ADR-related hospital stay was computed using a) raw excess duration of hospital stay, b) correction of duration of hospital stay by age, sex, and number of drug classes, and c) estimation by investigator of excess hospital stay. RESULTS: Three hundred and twenty-nine patients were evaluated: 212 male, 117 female, mean age 57.2 (males: 52.2, females: 66.2 (P < 0.05)), range 17-95 years. They stayed a total of 3720 hospital days (mean stay 11.3 days). 298 had no ADR (mean age 55.8, taking a mean of 2.7 drug classes, 10.7 days hospital stay); 31 had ADRs: in 10, the ADR caused admission in patients with a mean age of 84 (P < 0.01 vs the two other groups), taking 6.3 drug classes, who stayed a mean of 15.1 days; 21 occurred in hospital in patients with a mean age of 63.6, taking 4.2 drug classes (P < 0.01), who stayed a mean of 19.2 days (P < 0.01 vs patients without ADRs). In four the ADR was fatal (13% of ADRs, 40% of deaths). Raw ADR-related excess hospital stay was 318 days (8.6% of all hospital days), after multivariate correction 282 days (7.6% of all hospital days), and with investigator estimation 197 days (5.3% of all hospital days). Point prevalence of ADRs at admission was 3%, incidence rate in hospital was 5.6/1000 patient-days. CONCLUSIONS: 3% of the admissions were related to ADRs. In addition, 6.6% of hospitalized patients had significant ADRs. Between 5 and 9% of hospital costs were related to ADRs. In 24 of the 31 patients with ADRs (77%), these were related to the pharmacological properties of the involved drugs, and may possibly have been avoidable.
Manipulating the odor of a ewe's own and alien lambs has been used to facilitate fostering a second lamb on ewes with a single offspring (add-on fostering). Previous research has demonstrated that familiar odor cues must be present on the own and alien young to achieve successful and rapid adoptions. Familiar odors may consist of natural own-lamb odors or artificial odors previously applied to the lambs involved. In the present study (Exp. 1), an artificial odorant (neatsfoot oil) was applied to the own and alien lambs shortly after birth to establish a common familiar odor. Acceptance tests were conducted daily over a 72 h period. In Exp. 2, neatsfoot oil was again used as a common artificial odorant to facilitate add-on fostering, but, in addition, the natural odors of own and alien lambs were transposed by exchanging cloth stockinette jackets worn by the lambs. In Exp. 1, 9 of 18 ewes (50%) met the criteria for accepting their own and alien lambs within 72 h. Seven of these nine ewes (78%) accepted the alien lamb immediately. In Exp. 2, 24 of 30 ewes (80%) accepted their own and alien young, and 20 of the 24 acceptances (83%) were immediate. We conclude that add-on fostering may be limited only by our inability to properly match familiar-odor cues on own and alien lambs.
OBJECTIVE: To evaluate, in healthy volunteers, the effects of acute administration of two calcium antagonists with different pharmacological profiles, verapamil and amlodipine, on haemodynamics at rest and during exercise. SUBJECTS AND METHODS: Six healthy volunteers (aged 20-29 years) were randomly assigned to receive single oral doses of amlodipine (5 mg), slow-release verapamil (240 mg) or a placebo during a double-blind cross-over study. Systolic (SAP), diastolic and mean arterial pressures (measured using a cuff sphygmomanometer), heart rate (HR), cardiac index (CI, bioimpedance), rate-pressure product (SAP x HR), and noradrenaline and adrenaline plasma levels were measured at rest before drug administration, and at rest and during graded bicycle exercise (steps of 50, 100 and 150 W during 3, 3 and 4 min, respectively) started 3 h after drug administration. RESULTS: At rest arterial pressure, HR, rate-pressure product and catecholamine plasma levels did not change after verapamil or amlodipine administration, whereas CI significantly decreased after verapamil (from 3.9 +/- 0.4 to 3.3 +/- 0.4 l/min per m2) but not after amlodipine (3.9 +/- 0.3 and 4.1 +/- 0.5 l/m per m2) administration. During exercise the increases in SAP and HR were slightly but not significantly higher after amlodipine than after verapamil administration, rate-pressure product and CI were higher after amlodipine (22 +/- 1 x 10(3) mmHg x beats/min and 13 +/- 2 l/min per m2, respectively) than after verapamil (20 +/- 1 x 10(3) mmHg x beats/min and 10 +/- 2 l/min per m2, respectively) administration. Plasma levels of noradrenaline and adrenaline were similar at rest after each treatment and were slightly more increased after amlodipine administration during exercise. CONCLUSIONS: In contrast to amlodipine, verapamil induced a slight myocardial depressive effect at rest and did not potentiate the myocardial effects of the sympathetic stimulation induced by exercise. The myocardial action of verapamil is such as to induce some decrease in myocardial oxygen demand, both at rest and during exercise.
Explore the source record for details and available documents.
We describe a model of dynamic contrast enhancement in breast MRI designed to aid the radiologist in cases for which X-ray mammography is ineffective. The breasts are segmented from the image slices by a dynamic programming algorithm after morphological opening. A pharmacokinetic model has been derived to fit the rise in intensities after injection of a contrast agent, in a way that facilitates investigation of the effects of different models of bolus injection. The pharmacokinetic model is used in a modified Horn-Schunck algorithm to correct for motion effects during the seven minute acquisition period. The results show significant localization of tumours and enable discrimination of cancerous tissue. In particular, we illustrate the approach with an image that shows a carcinoma, whose appearance and localization are greatly improved by the registration algorithm.
AIMS: To test the existence of an association between reports of hypoglycaemia and angiotensin converting enzyme inhibitors, in a spontaneous reports database. METHODS: The French Pharmacovigilance database was examined for an association between adverse drug reaction reports mentioning hypoglycaemia, and angiotensin converting enzyme inhibitors (ACEI) using the case/non-case methodology, with reports of hypoglycaemia as cases and all other reports as comparators. The association between ACEI or other chosen drugs and hypoglycaemia was also tested in the subgroups of patients taking or not antidiabetic agents (ADA). RESULTS: 428 of 93,338 reports mentioned hypoglycaemia (202/2227 with ADA (OR 40, 95% CI 33-48)). 46/5717 reports mentioned ACEI (OR 1.8 (1.25-2.54)). Other study drugs associated with hypoglycaemia were cibenzoline (OR 80 (57-112)), disopyramide (OR 32 (22-46)), nifedipine (OR 2.16 (1.32-3.51)), diltiazem (OR 1.76 (1.01-3.06)) nitrates (nitroglycerin, molsidomine) (OR 1.91 (1.16-3.16)) and frusemide (OR 1.89 (1.31-1.76)), but not nicardipine, amlodipine, felodipine or nitrendipine, diazepam, atenolol or combination thiazide diuretics. However, ACEI and other drugs were associated with ADA, so that in the subgroups of patients taking or not ADA, the association of ACEI with hypoglycaemia disappeared (OR 0.9 (0.5-1.4) and 1.2 (0.7-2.2), respectively). The same was found for other drugs except cibenzoline. CONCLUSION: The association between reporting of hypoglycaemia and ACE inhibitors was related to concomitant use of antidiabetic agents. This was true also for other drugs used in arterial disease or renal failure, such as calcium channel blockers, nitrates, and frusemide.
BACKGROUND: An altered arterial nitric oxide (NO) pathway could partly explain the damage to arteries observed in haemodialyzed (HD) patients. The present study was designed to non-invasively evaluate the NO pathway of peripheral conduit arteries in HD patients. METHODS: Twelve normotensive, non-diabetic HD patients treated with erythropoietin and 12 matched healthy controls (C) were included in the study. The effect of endogenous release of NO was assessed by measuring the flow-dependent vasodilatation of the radial artery (post-ischaemic hyperaemia), and the response to exogenous NO assessed using sublingual glyceryl trinitrate administration (GTN). RESULTS: Radial artery diameter (echo-tracking), radial blood flow (RBF: Doppler) and mean arterial pressure (Finapres) were identical at baseline in HD patients and in healthy subjects. The flow-dependent vasodilatation of the radial artery was decreased in HD patients (C: 9 +/- 1% vs HD: 3 +/- 05%, P < 0.05). The decrease in radial vascular resistance (C: -44 +/- 4% vs HD: -24 +/- 2%, P < 0.05) and the increase in radial diameter (C: 31 +/- 2% vs HD: 25 +/- 2%, P < 0.05) after GTN administration were less in HD patients than in controls. The ratio between the increase in diameter after hyperaemia to the increase in diameter after GTN, was also diminished in HD patients (C: 30 +/- 3% vs HD: 13 +/- 2%, P < 0.001). CONCLUSIONS: The flow-dependent vasodilatation of peripheral conduit arteries is altered in HD patients and is associated with a slight but significant decrease in the vasodilating response to exogenous NO. These results suggest, in the absence of changes in basal radial vascular resistance and arterial diameter, more a decrease in endothelial NO bioavailability, than an increase in basal vascular tone.
OBJECTIVES: To review the first 50 patients to receive extracorporeal membrane oxygenation (ECMO) for respiratory failure at Glenfield Hospital, and to compare them with published series of patients receiving positive pressure ventilation. DESIGN: Retrospective chart review. SETTING: Extracorporeal Life Support Organization/European Extracorporeal Life Support Organization recognized ECMO center. PATIENTS: Fifty consecutive patients referred for ECMO with respiratory failure refractory to conventional management between 1989 and 1995. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Primary end point was survival to hospital discharge, 66%. Other data (mean and SD): Murray Lung Injury Score, 3.4 (0.5); ratio of PaO2 to fraction of inspired oxygen, 65 (36.9) mm Hg; duration of ventilation pre-ECMO, 76.5 (83.7 h); peak airway pressure, 39.6 (7.4) cm H2O; end-expiratory pressure, 10 (3.3) cm H2O; minute ventilation, 12.6 (3.32) L/min; age, 30.1 (10.8) years; duration of ECMO, 207.4 (177.8) h; and units of blood transfused, 19 (17.3). Survival was significantly better than two previously reported series of patients receiving positive pressure ventilation (55.6% and 42% survival), p=0.036 and p=0.0006. Odds ratio for improved survival was 0.46 (95% confidence interval, 0.22 to 0.97, p=0.036). CONCLUSIONS: Survival with ECMO is 66% for adults with severe respiratory failure. ECMO should be considered in patients who remain hypoxic despite maximal positive pressure ventilation.
A simple, rapid, specific and sensitive high-performance liquid chromatography method has been developed for quantitation of 5-fluorouracil (5-FU) in human plasma. The method involves deproteinization of a small sample volume of plasma (150 microliters) followed by HPLC on a cation-exchange resin column, Aminex HPX-87H (300 x 7.8 mm I.D.), preceded by a similar guard cartridge with UV detection at 265 nm. This method allows a good separation of 5-FU with a retention time of 24 min and a detection limit at 25 ng/ml. The calibration curve was linear from 25 to 2000 ng/ml. The coefficient of variation was < or = 4.4% for within-day reproducibility and < or = 9.5% for day-to-day reproducibility.
OBJECTIVE: To assess the safety, tolerability and efficacy of low-dose ketoprofen (75-150 mg daily for 5 to 15 days) in a general practice setting. DESIGN: Open label, non-controlled study of ketoprofen 25 mg tablets in the treatment of pain in ENT diseases, dysmenorrhoea, and musculoskeletal disorders. SETTING: General practice, 600 investigators SUBJECTS: Four thousand and sixty-eight patients, aged 13-93 years, mean 42.3 years, 1009 with ENT diseases (mean age 38.8 (13-83) years, 53% female), 978 with dysmenorrhoea (mean age 30.3 (13-60) years, 100% female), 2081 with musculoskeletal disorders (mean age 49.6 (16-93) years, 54% female). MAIN OUTCOME MEASURES: Occurrence of adverse events, on patient and physician evaluation; dose and duration of treatment prescribed/taken (diary); global evaluation of efficacy by patient and physician. RESULT: Twenty-two patients were lost to follow-up (<1%); dose effectively taken was lower than prescribed (3.3 versus 3.6 tablets/day); treatment was stopped prematurely in 3.3% of patients because of adverse events, in 17.1% because of early success of therapy. Gastrointestinal adverse events (AE) were the most frequent (76%) of AE), occurring in 10% of patients. They were more frequent in patients with musculoskeletal pain, who were older and had more associated diseases. Five patients were hospitalized, two for preplanned hospitalizations, the others for one asthma attack, one worsening of low back pain, and one angina attack, none attributed to treatment by the GP. None of the AE was life-threatening. Identified risk factors for AE were age and previous medical history, especially of gastrointestinal disorders. CONCLUSIONS: Good quality large scale studies with little or no loss to follow-up can be done in a general practice setting. At the dose used, ketoprofen was generally well tolerated, and used at a lower dose than prescribed, it was not associated with severe or new side-effects. The results of this study could justify its use in self-medication in these indications.
The occurrence of psychosis is frequent during the evolution of Parkinson's disease. The reduction of therapeutics or the use of classical neuroleptics may improve the symptoms, but usually worsens parkinsonism. Clozapine is an atypical neuroleptic with only few extrapyramidal effects, which has been proposed at low dose in this indication since 1985. A review of the literature, about more than 200 patients shows good results in approximately 90% without worsening of extrapyramidal symptoms. Some patients even noted an improvement of their motor state while treated by clozapine alone or as dopatherapy was secondarily increased. More controversial results were obtained in demented or depressed patients. Sedation is one of the most frequently encountered side-effect but rarely necessitates the withdrawal of clozapine. Even if the risk of agranulocytosis is slight, regular blood cell counts must be done.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A patient presented with paroxysmal hypertension and typical clinical features of phaeochromocytoma, but with a normal adrenal computed tomographic scan and much higher plasma noradrenaline than adrenaline concentrations. Urinary vanillylmandelic acid concentrations were only moderately elevated. This syndrome probably arose as a consequence of an interaction between the monoamine oxidase inhibitor selegiline, the sympathomimetic agent ephedrine, and a tricyclic antidepressant. The mechanism of the interaction is thought to be related to increased sympathetic release of noradrenaline by ephedrine, inhibition of catabolism by selegiline, and inhibition of reuptake of noradrenaline by the tricyclic. Although newer selective monoamine oxidase inhibitors are considered to be safer than earlier non-selective inhibitors, they can also contribute to drug interactions mimicking phaeochromocytoma.
Although smooth muscle tone is a key determinant of mechanical properties of arteries in animal experiments, it has not yet been studied in humans because of technical limitations. To assess the influence of tone on arterial properties in humans and to emphasize the interest of calculation at specific stress, we used echo tracking and photoplethysmographic measurement of arterial pressure to study radial arterial mechanics during a cold pressor test (CPT) in 12 healthy volunteers (28 +/- 2 yr). During CPT, mean arterial pressure rose from 83 +/- 3 to 106 +/- 5 mmHg (P < 0.05), internal diameter decreased from 2.75 +/- 0.15 to 2.54 +/- 0.14 mm (P < 0.05), and wall thickness increased from 0.576 +/- 0.027 to 0.634 +/- 0.029 mm (P < 0.05). At a specific pressure (105 mmHg), midwall stress and incremental modulus decreased whereas arterial compliance increased. The incremental modulus of elasticity and compliance were fitted as functions of pressure and of midwall stress. CPT decreased the modulus about equally at all wall stresses measured. The modulus decreased and the compliance increased at every level of pressure measured. At all levels of midwall stress, the compliance was decreased. Thus acute sympathetic stimulation induced by CPT decreases the wall stiffness of human arteries in vivo. This may be explained by an unloading of stiffer wall components during active arterial constriction.