Biomedical subjects

M Dooley

Publications and source records attributed to M Dooley.

At least 19 recordsLinked to original sources

PubMed2000

Stability studies on the cathepsin L proteinase of the helminth parasite, Fasciola hepatica.

Fasciola hepatica, the liver fluke, secretes a cathepsin L cysteine proteinase. The enzyme is active over the pH range 5-9 and is remarkably stable at 37 degrees C, pH 7.0, in contrast to mammalian cathepsin Ls that are active in the acidic pH range and are inactivated within 15 min at neutral pH. The liver fluke proteinase is also very tolerant of organic solvents, particularly dimethylformamide. However, it is completely inactivated by 1 mM Hg(2+) and adversely affected by other heavy metals and divalent cations. Addition of glycerol and EDTA enhanced the liver fluke enzyme's stability at 50 degrees C, while glucose and glycerol protected the enzyme from inactivation by repeated freeze-thawing. The high stability of liver fluke cathepsin L suggests that it may have potential for use in bioindustrial applications.

Journal Article↗

PubMed2000

Donepezil: a review of its use in Alzheimer's disease.

Donepezil (E-2020) is a reversible, noncompetitive, piperidine-type cholinesterase inhibitor. It is selective for acetylcholinesterase rather than butyrylcholinesterase. Donepezil 5 and 10 mg/day significantly improved cognition and global clinical function compared with placebo in well designed short term trials (14 to 30 weeks) in 161 to 818 patients with mild to moderate Alzheimer's disease. Beneficial effects on cognition were observed from week 3 of treatment. Donepezil 10 mg/day significantly delayed the deterioration in activities of daily living (ADL) [by 55 weeks] compared with placebo in a retrospective analysis of 1 trial, and in the largest trial significantly improved patients' abilities to perform complex tasks. However, no significant improvement in function was observed with donepezil 5 mg/day in another trial. In the 2 trials of longest duration donepezil (5 and 10 mg) significantly delayed symptomatic progression of the disease. While there was no evidence for a positive effect of donepezil on patients' quality of life, there are no validated measures of this parameter specific to patients with Alzheimer's disease. Donepezil (5 and 10 mg) significantly reduced caregiver burden. Long term efficacy data suggest that improvements in cognition, global function or ADL are maintained for about 21 to 81 weeks with donepezil (10 mg/day in most patients). Donepezil is generally well tolerated with the majority of adverse events being mild and transient. Predictably, most events were cholinergic in nature and generally related to the gastrointestinal and nervous systems. The incidence of these events was significantly higher with donepezil 10 mg than with placebo in short term clinical trials; however, this may have been due to the 7-day dose increase schedule used in these studies and can be minimised by increasing the dose after a longer (6-week) period. The incidence of serious adverse events was generally similar between donepezil 5 and 10 mg (4 to 10%) and placebo (5 to 9%) in short term trials. 26% of patients receiving donepezil (5 and 10 mg) reported serious events over a 98-week period in a long term trial. Importantly, there was no evidence of hepatotoxicity with this drug. Conclusions. Donepezil (5 and 10 mg) is an agent with a simple once-daily dosage schedule which improves cognition and global clinical function in the short (up to 24 weeks) and long term (up to about 1 year) in patients with mild to moderate Alzheimer's disease. Improvements in ADL were also observed with donepezil 10 mg/day. Adverse events associated with donepezil are mainly cholinergic. Donepezil has been extensively studied and should be considered as a first-line treatment in patients with mild to moderate Alzheimer's disease.

Aged↗

PubMed2000

Iomeprol: a review of its use as a contrast medium.

UNLABELLED: Iomeprol is a nonionic, monomeric iodinated contrast medium. Unlike the older ionic agents, iomeprol has low chemotoxicity, osmolality and viscosity and high water solubility. Compared with other nonionic contrast media, the osmolality and viscosity are lower and the water solubility is reported to be higher with iomeprol. Most radiographs (about 67 to 100%) obtained with iomeprol (containing 150 to 400 mg/ml of iodine) were of good or excellent quality in noncomparative and comparative trials recruiting 40 to 6127 patients undergoing various radiographic procedures. As expected, the diagnostic efficacy of iomeprol did not differ significantly from that of other nonionic agents (iopamidol, iopromide, iohexol and iotrolan). Iomeprol (containing 150 to 400 mg/ml of iodine) was well tolerated in clinical trials. Most adverse events were transient and of mild to moderate intensity and were similar to those observed with other contrast media. The overall incidence of adverse events ranged from 3 to 49.7% and mainly included localised pain (< or =6%) and heat sensations (8 to 45%), taste disturbances (3 to 27%) and various pseudoallergic reactions (< or =20% for each type of event). The incidence of heat or pain and taste disturbances with iomeprol was similar to that observed with iopromide and iopamidol. Pain (but not heat sensations) was reported significantly less frequently and taste disturbances reported significantly more frequently with iomeprol than with iohexol in a comparative trial. Pseudoallergic reactions (such as nausea, vomiting, skin reactions, dizziness, headache) were significantly less common with iomeprol than with ioxaglate and occurred at a similar frequency to that with iopromide and iopamidol. Cardiovascular events were rarely observed with iomeprol. Currently available iomeprol solutions contain a range of iodine concentrations (150 to 400 mg/ml) and are approved for a wide variety of diagnostic procedures. Iomeprol solutions are chemically stable which negates the need for chelating agents. Formulations of this agent are therefore the first not to contain edetic acid (EDTA). CONCLUSIONS: Iomeprol shows equivalent diagnostic efficacy, and a similar adverse event profile, to that of other nonionic contrast media. The availability of a range of iodine concentrations enables iomeprol to be used in a variety of diagnostic procedures. Iomeprol, like others in its class, is suitable for use in diagnostic imaging.

Contrast Media↗

PubMed2000

Zaleplon: a review of its use in the treatment of insomnia.

Zaleplon is a pyrazolopyrimidine hypnotic agent which is indicated for the short term (2 to 4 weeks) management of insomnia. Zaleplon 5 and 10 mg at bedtime (usual recommended doses) significantly reduced sleep latency compared with placebo in clinical trials in nonelderly and elderly patients with insomnia. In general, sleep maintenance (sleep duration and number of awakenings) and sleep quality were not significantly different from placebo with zaleplon 5 and 10 mg/night. Zaleplon 20 mg/night significantly improved sleep latency and duration in nonelderly patients, but effects on number of awakenings were inconsistent and sleep quality generally did not improve. The relative hypnotic efficacy of zaleplon compared with that of triazolam and zolpidem is not yet clearly established. Tolerance to the hypnotic effects of zaleplon generally did not occur during 5 weeks' treatment, or during long term treatment (6 or 12 months) according to a small number of studies presented as abstracts. Zaleplon was well tolerated in clinical trials. The most common event was headache but the incidence was similar to that observed with placebo. Zaleplon 5 and 10 mg did not impair psychomotor function or memory even immediately after the dose in studies in volunteers or patients with insomnia. Zaleplon 20 mg, however, impaired psychomotor function and memory immediately after the dose but next-day effects were not observed. The psychomotor profile of zaleplon appears to be better than that of comparator agents. Rebound insomnia was not observed after sudden discontinuation of up to 12 months' treatment with zaleplon 5 and 10 mg/night and up to 4 weeks' treatment with zaleplon 20 mg/night. In addition, the potential for withdrawal syndrome with zaleplon appears to be low according to limited data. In conclusion, zaleplon 5, 10 and 20 mg administered at bedtime, or later if patients have difficulty sleeping, is an effective and well tolerated hypnotic agent. There was no evidence of next-day residual effects with the 5 and 10 mg dosages, and the incidence of withdrawal effects with zaleplon 5, 10 and 20 mg did not differ significantly to that observed with placebo. In addition, tolerance to the effects of zaleplon is unlikely to develop when administered for the recommended treatment period. The comparative efficacy and tolerability of zaleplon with other short acting nonbenzodiazepine hypnotics is difficult to establish. However, on the basis of current efficacy evidence and the lower incidence of residual effects with zaleplon 5 and 10 mg relative to comparator agents, this drug represents a useful option in the management of patients with insomnia who have difficulties initiating sleep.

Acetamides↗

PubMed2000

Levetiracetam. A review of its adjunctive use in the management of partial onset seizures.

UNLABELLED: Levetiracetam, the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is approved for use as adjunctive therapy in adult patients with partial onset seizures. Oral levetiracetam 1000, 2000 and 3000 mg/day administered as adjunctive therapy for up to 18 weeks significantly increased responder rates and reduced seizure frequency compared with placebo in 3 well designed pivotal trials in adults with treatment-refractory partial seizures with or without secondary generalisation. Levetiracetam 3000 mg/day also significantly increased the number of seizure-free patients, but the effects of levetiracetam 1000 and 2000 mg/day on this end-point were unclear. Effects on seizure severity were not assessed in these trials. Although not yet approved as monotherapy or for use in paediatric patients, efficacy was observed with levetiracetam 3000 mg/day as monotherapy in adult patients with refractory partial seizures with or without secondary generalisation and with the 10 to 40 mg/kg/day dosage as adjunctive therapy in children with refractory partial seizures. However, these data are limited. Oral levetiracetam 1000, 2000 and 3000 mg/day as adjunctive therapy is generally well tolerated with an overall incidence of adverse events similar to that observed with placebo. The most commonly reported events in individual clinical trials were CNS-related and included somnolence, asthenia, headache and dizziness. Levetiracetam administered as adjunctive therapy does not appear to interact with other anticonvulsant drugs, and no clinically relevant interactions were observed between levetiracetam and digoxin, warfarin or probenecid; oral contraceptive protective efficacy was also not affected by levetiracetam. CONCLUSIONS: Levetiracetam is a new anticonvulsant agent with a favourable tolerability profile and a low potential for drug interactions. It has shown efficacy as adjunctive therapy in patients with treatment-refractory partial onset seizures with or without secondary generalisation in clinical trials. Direct comparative trials with other anticonvulsant agents are not yet available, but placebo-controlled clinical evidence to date suggests that levetiracetam (1000, 2000 and 3000 mg/day) is a useful option as adjunctive therapy in patients with this subtype of epilepsy.

Administration, Oral↗

PubMed1999

Structure-activity studies of conantokins as human N-methyl-D-aspartate receptor modulators.

The activities of conantokin-G (con-G), conantokin-T (con-T), and several novel analogues have been studied using polyamine enhancement of [3H]MK-801 binding to human glutamate-N-methyl-D-aspartate (NMDA) receptors, and their structures have been examined using CD and 1H NMR spectroscopy. The potencies of con-G[A7], con-G, and con-T as noncompetitive inhibitors of spermine-enhanced [3H]MK-801 binding to NMDA receptor obtained from human brain tissue are similar to those obtained using rat brain tissue. The secondary structure and activity of con-G are found to be highly sensitive to amino acid substitution and modification. NMR chemical shift data indicate that con-G, con-G[D8, D17], and con-G[A7] have similar conformations in the presence of Ca2+. This consists of a helix for residues 2-16, which is kinked in the vicinity of Gla10. This is confirmed by 3D structure calculations on con-G[A7]. Restraining this helix in a linear form (i.e., con-G[A7,E10-K13]) results in a minor reduction in potency. Incorporation of a 7-10 salt-bridge replacement (con-G[K7-E10]) prevents helix formation in aqueous solution and produces a peptide with low potency. Peptides with the Leu5-Tyr5 substitution also have low potencies (con-G[Y5,A7] and con-G[Y5,K7]) indicating that Leu5 in con-G is important for full antagonist behavior. We have also shown that the Gla-Ala7 substitution increases potency, whereas the Gla-Lys7 substitution has no effect. Con-G and con-G[K7] both exhibit selectivity between NMDA subtypes from mid-frontal and superior temporal gyri, but not between sensorimotor and mid-frontal gyri. Asn8 and/or Asn17 appear to be important for the ability of con-G to function as an inhibitor of polyamine-stimulated [3H]MK-801 binding, but not in maintaining secondary structure. The presence of Ca2+ does not increase the potencies of con-G and con-T for NMDA receptors but does stabilize the helical structures of con-G, con-G[D8,D17], and, to a lesser extent, con-G[A7]. The NMR data support the existence of at least two independent Ca2+-chelating sites in con-G, one involving Gla7 and possibly Gla3 and the other likely to involve Gla10 and/or Gla14.

Amino Acid Sequence↗

PubMed1999

Demograghic and socio-economic determinants of community and hospital services costs for people with HIV/AIDS in London.

We examined the influence of demographic, social and economic background of people with HIV/AIDS in London on total community and hospital services costs. This was a retrospective study of community and hospital service use, needs and costs based on structured questionnaires administered by trained interviewers and costing information obtained from the service purchasers and providers, based on two Genito-urinary Medicine clinics in London: the Jefferiss Wing at St. Mary's Hospital and Patric Clements at the Central Middlesex Hospital, London, England. The subjects were 225 HIV infected patients (105 asymptomatic, 59 symptomatic non-AIDS and 61 AIDS). We found that over and above well established determinants of health care costs for HIV infected people such as disease stage and transmission category, social and economic factors such as employment and support of a living-in partner significantly reduced community services costs. Private health insurance had a similar effect, though only a small proportion of HIV people had such cover. The cost of community services for HIV infected non-European Union nationals, mainly of African origin, was one quarter that for the European Union nationals. Community services costs were highest for heterosexually infected women and lowest for heterosexually infected men after adjusting for other factors. Hospital services costs were significantly higher for HIV infected people lacking educational qualifications and employment. We conclude that access to community care for HIV infected non-EU nationals appears to be very poor as the cost of their community services was one quarter that for the EU nationals after adjusting for the effects of transmission category, disease stage, living with a partner, employment and having a private health insurance. Additional incentives for informal care for HIV infected people could be a cost-effective way to improve their community health service provisions.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Ibandronate.

Ibandronate (ibandronic acid) is a third generation bisphosphonate which inhibits hone resorption in human and animal studies. It also inhibits bone formation only at high doses (10 microg/kg/day) in animal studies. In animal models, ibandronate was more potent than etidronate, clodronate, pamidronate and alendronate and equivalent in potency or more potent than risedronate in inhibiting induced hypercalcaemia and bone resorption. In clinical studies, single-dose ibandronate (0.2 to 6 mg intravenously) significantly reduced albumin-corrected serum calcium levels and urinary markers of bone resorption in patients with hypercalcaemia of malignancy, and in those with bone metastases. Serum calcium levels were normalised in 50 and 67% of ibandronate 2 mg recipients and in about 76% of 4 mg recipients. In postmenopausal women with osteoporosis or osteopenia. ibandronate (0.5 to 5 mg/day orally or 0.5 to 2 mg every 3 months intravenously) dose-dependently increased bone mineral density, with parallel reductions in the biochemical markers of bone turnover. In preliminary studies in patients with Paget's disease a single intravenous ibandronate dose (2mg) decreased serum alkaline phosphatase levels and urinary markers of bone turnover. Adverse events associated with the use of ibandronate in the management of hypercalcaemia of malignancy include increased body temperature, hypocalcaemia and hypophosphataemia. Less commonly, flu-like symptoms and gastrointestinal intolerance may occur.

Animals↗

PubMed1999

Lamifiban.

Lamifiban is an intravenously administered, selective, reversible, nonpeptide glycoprotein IIb/IIIa receptor antagonist which inhibits platelet aggregation and thrombus formation by preventing the binding of fibrinogen to platelets. In trials in patients with non-Q wave myocardial infarction (MI) or unstable angina pectoris (PARAGON A and the Canadian Lamifiban Study), the incidence of clinical events at 30 days in patients receiving lamifiban (1 to 5 microg/min) was not significantly different from that in patients receiving aspirin plus heparin or aspirin alone. In PARAGON A, the incidence of clinical events at 6 months was significantly lower after lamifiban (with or without heparin) and aspirin therapy than after standard heparin and aspirin therapy. A large phase III trial (PARAGON B) is under way comparing lamifiban plus aspirin and heparin with standard aspirin and heparin therapy in patients with non-Q wave MI or unstable angina pectoris. In clinical trials, the most common adverse events associated with lamifiban were bleeding complications which were increased by the concomitant administration of heparin.

Acetates↗

PubMed1999

Sibrafiban.

Sibrafiban is the orally administered, nonpeptide, double-prodrug of Ro 44-3888 which is a selective glycoprotein IIb/IIIa receptor antagonist. It is currently undergoing clinical trials for secondary prevention of cardiac events in patients stabilised after acute coronary syndromes. In a phase II dose-finding study (TIMI 12) in patients stabilised after a myocardial infarction (MI) or an episode of unstable angina, there was a dose-dependent inhibition of platelet aggregation which correlated closely with the plasma concentration of the total active drug. An ongoing phase III study (SYMPHONY) compares the effects of sibrafiban on cardiac events with that of aspirin in patients stabilised after a Q wave MI or an episode of unstable angina. This large trial uses twice daily dosage regimens to produce the plasma concentrations which were associated with less bleeding in the earlier dose-ranging trial. A long term (minimum duration 12 months) phase III study (2nd SYMPHONY) is under way to compare the effects of sibrafiban on cardiac events with those of aspirin in patients stabilised after an MI or an episode of unstable angina. The most common adverse events associated with sibrafiban include bleeding, with minor haemorrhages occurring more often than with aspirin.

Animals↗

PubMed1999

Capecitabine.

Capecitabine is an orally administered fluoropyrimidine carbamate used for the treatment of paclitaxel- or anthracycline-refractory breast cancer. Capecitabine is metabolised via a 3-step process to the active agent fluorouracil. The final step of this process occurs preferentially in malignant tissue. In patients with paclitaxel-refractory breast cancer receiving capecitabine (2510 mg/m2/day for 2 weeks of a 3-week cycle) the objective tumour response rate was 20%. Disease progression occurred in 34% of patients and 40% had stable disease. In this trial, the median duration of response was 241 days. Disease progression or death occurred in 83% of patients, and median time to progression was 93 days. Median survival time was 384 days. In previously untreated patients with breast cancer, the response rate was higher and time to disease progression was longer after oral capecitabine (2510 mg/m2/day for 2 weeks of a 3-week cycle) than after intravenous cyclophosphamide, methotrexate and fluorouracil therapy. In clinical trials, generally gastrointestinal or haematological adverse events were reported most frequently. Other commonly reported events included hand-and-foot syndrome, fatigue, hyperbilirubinaemia, dermatitis and anorexia.

Animals↗

PubMed1999

Rizatriptan: a review of its efficacy in the management of migraine.

UNLABELLED: Rizatriptan is an orally active serotonin 5-HT1 receptor agonist selective for the 5-HT(1B/1D) subtypes. The efficacy of oral rizatriptan (5 or 10 mg) has been demonstrated in large (n = 309 to 1746) well designed comparative trials with placebo and oral sumatriptan. Two hours postdose, rizatriptan 5 or 10 mg was more effective than placebo at producing pain relief or a pain free status, relieving migraine-associated symptoms and normalising functional ability. In general, rizatriptan 10 mg appeared to be more effective than rizatriptan 5 mg. However, recurrence rates with rizatriptan 5 and 10 mg appeared to be similar to those with placebo. Patients were significantly more likely to achieve pain relief within 2 hours after receiving rizatriptan 5 mg than sumatriptan 25 mg and after rizatriptan 10 mg than sumatriptan 50 mg. This was also observed with rizatriptan 10 mg compared with sumatriptan 100 mg according to an age-adjusted and a prespecified per-protocol analysis. In general, rizatriptan was better than sumatriptan at relieving migraine-associated symptoms, particularly nausea, and in normalising functional ability depending on which doses were compared. The incidence of headache recurrence, time to onset of recurrence and the need for escape medication in nonresponders appeared to be similar between rizatriptan and sumatriptan. Over the 24 hours after the dose, rizatriptan 10 mg improved the quality of life of patients with migraine compared with placebo. Rizatriptan 10 mg also significantly improved work function compared with placebo and with sumatriptan 50 mg. Rizatriptan appears to be well tolerated with most adverse events being mild and transient. The most commonly experienced events included general digestive complaints, general neurological complaints, dizziness, somnolence, asthenia/fatigue and pain and pressure sensations. In clinical trials, the overall incidence of adverse events with rizatriptan 5 or 10 mg was similar to that with sumatriptan 25 or 50 mg but lower than that with sumatriptan 100 mg. Chest pain was reported by 1 to 3% of rizatriptan recipients and by 3 to 6% of patients receiving sumatriptan (25, 50 or 100 mg); clinically significant effects on ECG parameters, heart rate or blood pressure were not observed with rizatriptan. CONCLUSIONS: Rizatriptan produces pain relief and a pain free status, relieves associated symptoms of migraine, normalises functional ability and improves patient quality of life. Rizatriptan 10 mg appears to be more effective than rizatriptan 5 mg. In comparison with oral sumatriptan, rizatriptan may provide better relief from pain and nausea, with some evidence of a faster onset of action. Thus, rizatriptan 5 or 10 mg is likely to establish a place as an effective and well tolerated agent for the management of acute migraine.

Administration, Oral↗

PubMed1998

Determinants of antepartum human immunodeficiency virus testing in a non-Medicaid obstetric population.

OBJECTIVE: To determine voluntary human immunodeficiency virus (HIV) testing rates and factors influencing testing in a private obstetric practice. METHODS: Antepartum patients were offered HIV testing after completing a self-assessment questionnaire. Perceived risks and demographics were correlated with testing rates. RESULTS: Overall, 348/600 (58%) women consented to HIV testing. In a univariate analysis, patients with "any" perceived risk(s) were more likely to be tested. Single women and those with an at-risk partner(s) or a history of sexually transmitted disease (STD) were more likely to desire testing. These factors remained independently associated with voluntary testing in a multivariate regression model. No patients tested positive for HIV. CONCLUSIONS: In our private obstetric practice, 26% of women perceived themselves at risk for HIV infection, and testing rates depended on the various risks identified. A history of STDs or an at-risk sexual partner were stronger predictors of voluntary testing than was marital status. Focused HIV counseling among pregnant women at relatively low risk for infection may be possible.

Blood Transfusion↗

PubMed1998

Pramipexole. A review of its use in the management of early and advanced Parkinson's disease.

UNLABELLED: Pramipexole is an orally active non-ergoline dopamine agonist with selective activity at dopamine receptors belonging to the D2 receptor subfamily (D2, D3, D4 receptor subtypes) and with preferential affinity for the D3 receptor subtype. It is approved as monotherapy in early Parkinson's disease and as adjunctive therapy to levodopa in patients with advanced disease experiencing motor effects because of diminished response to levodopa. The potential neuroprotective effects of pramipexole have been shown in animal and in vitro studies. Data from relatively long term (10- or 31-week) studies suggest that pramipexole monotherapy (0.375 to 6.0 mg/day) can improve activities of daily living and motor symptoms in patients with early Parkinson's disease. Pramipexole (0.375 to 4.5 mg/day for 31 or 36 weeks), as an adjunct to levodopa in advanced disease, improved activities of daily living and motor symptoms, reduced the duration and severity of 'off' periods and allowed a reduction in levodopa dosage. Mentation, behaviour and mood [Unified Parkinson's Disease Rating Scale (UPDRS) part I], and timed walking test were not significantly improved. The extent of disability improved according to the UPDRS parts II and III but, when assessed by secondary efficacy parameters, it is unclear whether disability or the severity of disease improved. No significant differences were observed in patients randomised to pramipexole or bromocriptine according to a secondary hypothesis in a prospective study in which both drugs were better than placebo. Some quality-of-life measures improved with active treatment relative to placebo. Further studies comparing pramipexole with other dopamine agonists and levodopa in patients with early and advanced Parkinson's disease would be useful. In pramipexole recipients with early disease, the most commonly experienced adverse events were nausea, dizziness, somnolence, insomnia, constipation, asthenia and hallucinations. The most commonly reported adverse events in pramipexole recipients with advanced disease were orthostatic hypotension, dyskinesias, extrapyramidal syndrome (defined as a worsening of the Parkinson's disease), dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia and urinary frequency. The incidence of some adverse events did not greatly differ between pramipexole and placebo recipients. CONCLUSIONS: Pramipexole is effective as adjunctive therapy to levodopa in patients with advanced Parkinson's disease. However, the potential beneficial effects of pramipexole on disease progression need to be confirmed in clinical studies. The efficacy of pramipexole monotherapy in patients with early disease has also been demonstrated, although the use of dopamine agonists in early Parkinson's disease remains controversial.

Antiparkinson Agents↗

PubMed1998

Fixed combination verapamil SR/trandolapril.

Verapamil sustained-release (SR)/trandolapril is a combination of a phenylalkylamine calcium antagonist and an angiotensin converting enzyme inhibitor for the management of essential hypertension. Verapamil SR/trandolapril does not adversely influence glucose, insulin or lipid parameters in patients with mild to moderate essential hypertension and type 2 (non-insulin-dependent) diabetes mellitus with or without elevated cholesterol and/or triglyceride levels. Verapamil SR/trandolapril reduces proteinuria to a greater extent than the individual components in patients with diabetic or non-diabetic proteinuria. The antihypertensive efficacy of once daily verapamil SR/trandolapril (180/1 or 180/2 mg) for 8 weeks or 6 months is similar to that of atenolol/chlorthalidone (100/25 mg) and lisinopril/hydrochlorothiazide (20/12.5 mg), and was at least as good as that of metoprolol/hydrochlorothiazide (100/12.5 mg) in a small trial. The reduction in sitting or supine diastolic and systolic blood pressure is greater after verapamil SR/trandolapril (180/2 to 240/4 mg) than after monotherapy with verapamil SR (180 and 240 mg/day) or trandolapril (2 to 8 mg/day). Fewer cardiac events occurred after verapamil SR/trandolapril (240/1 to 360/2 mg/day) than after trandolapril (1 to 2 mg/day) in postmyocardial infarction patients with congestive heart failure. The incidence of adverse events after verapamil SR/trandolapril is similar to that of comparator drugs and the individual components of the combination.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Urapidil. A reappraisal of its use in the management of hypertension.

UNLABELLED: Urapidil is a peripheral postsynaptic alpha 1-adrenoceptor antagonist with central agonistic action at serotonin 5-HT1A receptors. It reduces blood pressure by decreasing peripheral vascular resistance. Oral urapidil decreases blood pressure in patients with mild to moderate essential hypertension and associated risk factors such as hyperlipidaemia or type 2 (non-insulin-dependent) diabetes mellitus with no effect on heart rate. The antihypertensive efficacy of urapidil is similar to that of most comparators in patients with mild to moderate essential or secondary hypertension and no concomitant risk factors. However, the antihypertensive efficacy of urapidil was lower than that of hydrochlorothiazide in a well designed trial. Lipid levels and glucose metabolism are not adversely affected and may improve with urapidil in patients with lipid or glucose abnormalities. Urapidil can be safely combined with other antihypertensive agents such as hydrochlorothiazide and nifedipine and improves blood pressure control in previous nonresponders to monotherapy. Intravenous urapidil reduces blood pressure in patients with pre-eclampsia or hypertension in pregnancy and in patients with hypertensive crises or peri- or postoperative hypertension. The decrease in blood pressure is similar to that observed after nifedipine, enalaprilat, sodium nitroprusside and dihydralazine, greater than that of ketanserin according to 1 larger study, and greater than that of sublingual nitroglycerin in 1 trial in patients with nonsurgical hypertensive crises and pulmonary oedema. However, more patients responded to treatment with urapidil than with enalaprilat or nifedipine. Heart rate is less likely to be altered by urapidil than with some comparator drugs. Urapidil appears to be well tolerated, with most adverse events being mild and transient. The incidence of adverse events with urapidil is similar to that with prazosin, metoprolol, atenolol, sodium nitroprusside and hydrochlorothiazide and less than that with nifedipine and clonidine. Urapidil may not be as well tolerated as captopril and, in 1 study, more urapidil than nitrendipine recipients discontinued treatment because of adverse events. CONCLUSIONS: urapidil reduces blood pressure without altering heart rate. The oral formulation is an effective choice in patients with hypertension and concomitant dyslipidaemia or type 2 diabetes mellitus, in whom the drug does not adversely affect and may improve lipid profiles and glucose metabolism. The intravenous formulation is effective in controlling various hypertensive crises and hypertension associated with pregnancy or surgery and is similar to or better than other first-line agents used in these conditions. Thus, urapidil may be a useful alternative to currently available antihypertensive agents.

Antihypertensive Agents↗

PubMed1996

Community service needs of people with HIV infection in London.

The objectives of this study were to describe the expressed needs for community services of HIV-infected individuals by disease stage, gender and transmission category and the barriers which prevent the receipt of such services. Structured interviewer-administered questionnaires concerning a 6-month retrospective period were used to obtain information on need for community services and problems which prevented the receipt of services. The study sample included 70 homosexual men with asymptomatic HIV disease, 42 homosexual men with symptomatic non-AIDS, 53 homosexual men with AIDS, 23 heterosexual men, 29 heterosexual women, 9 male and 9 female injecting drug users. The main outcome measures were the extent to which needs for community services were met and person/service combinations for which problems or barriers prevented the receipt of community services. On average, subjects expressed a need for 10 categories of community services over the 6-month period: homosexuals expressed a mean of 10, heterosexuals 10, injecting drug users 11, subjects with asymptomatic HIV infection 9, subjects with symptomatic non-AIDS 11, subjects with AIDS 13, men 9 and women 14. A total of 58% of community service needs were always met, 6% were rarely not met, 16% were sometimes not met, 6% were often not met and 14% were not met at all. The extent to which subjects felt that their needs were met was similar for the different study groups, but the needs of women were met somewhat less frequently than those of men. Similarly, people with AIDS felt that their needs were met slightly less often. Reported levels of unmet need were high for a wide range of services. The most common reason subjects gave for not having received a community service for which they expressed a need was ignorance of where or how to obtain the service. This was mentioned in one-third of all such cases. Anxieties over the competence with which a service would be rendered was mentioned in 13% of cases and long waiting times in 11%. The frequencies of unmet need for many community services were high and often seemed to arise either from a lack of awareness on the part of subjects on how and where services could be obtained or from doubts about the relevance of services offered. Both of these barriers should be surmountable through the provision of better information to patients, extending user involvement in service development and the better co-ordination of service delivery through care management approaches.

Adult↗

PubMed1996

The economic costs of caring for people with HIV infection and AIDS in England and Wales.

The objectives of this study were firstly to estimate total lifetime care costs for an individual with HIV/AIDS, and secondly to estimate the total costs of caring people with HIV infection and AIDS in England and Wales between 1992 and 1997 inclusive. Questionnaires and monthly diaries were used to collate data on healthcare utilisation from patients with HIV infection over a 6-month period. These data were then used to estimate the annual total direct costs of care (stratified by disease stage), total lifetime costs of care, and present and future total national care costs for England and Wales. Costing data were obtained from providers of services throughout Greater London. In total, 235 patients with HIV infection were recruited from 2 clinics in Greater London. All costs were calculated in 1992-93 pounds sterling (pound; 1 pound = $US1.58, December 1995). Annual care costs were estimated at 4515 pounds ($US7134) for a person with asymptomatic HIV disease, 8836 pounds ($US13,961) for a person with symptomatic non-AIDS and 15 268 pounds ($US24,123) for a person with AIDS. Lifetime care costs were estimated at 84,522 pounds ($US133,545) per patient. The total costs of care for England and Wales were forecast to increase from 116,627,400 pounds ($US184,271,300) in 1992 to 162,638,100 pounds ($US256,968,200) in 1997. In conclusion, our study further emphasises the continued shift in hospital services from the inpatient sector to the outpatient sector. The importance of community care and informal care, in terms of the associated direct economic costs, is also highlighted. This emphasises the need for close collaboration between different agencies and strategic coordination of services. Finally, the study forecasts an increase in care costs in England and Wales during the 1990s.

Acquired Immunodeficiency Syndrome↗