Biomedical subjects

Caroline M Perry

Publications and source records attributed to Caroline M Perry.

25 records · Page 2Linked to original sources

PubMed2002

Biapenem.

Biapenem is a new parenteral carbapenem antibacterial agent with a broad spectrum of in vitro antibacterial activity encompassing many Gram-negative and Gram-positive aerobic and anaerobic bacteria, including species producing beta-lactamases. Biapenem is more stable than imipenem, meropenem and panipenem to hydrolysis by human renal dihydropeptidase-I (DHP-I), and therefore does not require the coadministration of a DHP-I inhibitor. After intravenous administration, biapenem is widely distributed and penetrates well into various tissues (e.g. lung tissue) and body fluids (e.g. sputum, pleural effusion, abdominal cavity fluid). In randomised, nonblind or double-blind clinical trials, biapenem showed good clinical and bacteriological efficacy (similar to that of imipenem/ cilastatin) in the treatment of adult patients with intra-abdominal infections, lower respiratory infections or complicated urinary tract infections. Biapenem is generally well tolerated. The most common adverse events in clinical trials were skin eruptions/rashes, nausea and diarrhoea.

Adult↗

PubMed2002

Danaparoid: a review of its use in thromboembolic and coagulation disorders.

UNLABELLED: Danaparoid (danaparoid sodium) is a low molecular weight heparinoid which has undergone clinical study for use as continued anticoagulant therapy in patients with heparin-induced thrombocytopenia (HIT), for the prophylaxis and treatment of deep vein thrombosis (DVT), and for the treatment of disseminated intravascular coagulation (DIC). A nonblind study in patients with HIT has reported that complete clinical resolution is significantly more likely in patients receiving danaparoid than in patients receiving dextran 70. In addition, retrospective analyses and noncomparative data support the use of danaparoid for continued anticoagulant therapy in patients with HIT. Studies in patients undergoing hip surgery have shown that danaparoid significantly reduces the incidence of postoperative DVT compared with aspirin, warfarin, dextran 70 and heparin-dihydroergotamine, while additional data suggest no difference between danaparoid, enoxaparin and dalteparin. In patients undergoing abdominal or thoracic surgery for removal of a malignancy, danaparoid reduced the incidence of postoperative DVT compared with placebo, but showed no significant difference when compared with unfractionated heparin (UFH). Two studies have compared danaparoid with UFH in the prophylaxis of DVT following acute ischaemic stroke; twice daily danaparoid was significantly superior to UFH whereas there was no significant difference between a once-daily dosage and UFH. Danaparoid did not differ from UFH in terms of efficacy in the treatment of existing DVT. In all comparative studies examining the efficacy of danaparoid in the prophylaxis or treatment of DVT (versus warfarin, dextran 70, enoxaparin, dalteparin, aspirin, heparin-dihydroergotamine, UFH and placebo), the incidence of haemorrhagic complications did not differ between treatment groups. In patients with DIC, 61.9% of those patients receiving danaparoid experienced either disappearance or reduction of symptoms of DIC whereas 62% of those receiving UFH showed either no change or aggravation of their symptoms. There was no significant difference between treatment groups in tolerability or overall improvement of DIC. CONCLUSIONS: Danaparoid is an effective anticoagulant agent which has undergone clinical evaluation in a wide range of disease indications. Current guidelines support the use of danaparoid in prophylaxis of DVT following ischaemic stroke, and in patients who develop HIT. Danaparoid has shown efficacy in DIC, and for DVT prophylaxis in patients undergoing hip surgery although further data are required to establish the role of danaparoid in these indications. In particular, double-blind trials comparing danaparoid with such recommended therapies as the low molecular weight heparins will provide more definitive data on the place of danaparoid in the clinical management of these conditions and ultimately lead to improved patient outcomes.

Anticoagulants↗

PubMed2002

Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension.

In well designed studies in patients with mild to moderate hypertension, combinations of the sustained-release (SR) formulation of the nondihydropyridine calcium channel antagonist verapamil 120 to 240 mg/day and the ACE inhibitor trandolapril 0.5 to 8 mg/day were significantly more effective in reducing sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline than placebo. In most randomised studies, combinations of verapamil SR 120 to 240 mg/day and trandolapril 0.5 to 8 mg/day were significantly more effective in lowering sitting DBP and SBP than the corresponding monotherapies administered at the same dosage. Trandolapril/verapamil SR 2/180 mg/day provided significantly more effective 24-hour ambulatory blood pressure (BP) control than of the corresponding monotherapies. Moreover, trandolapril/verapamil SR reduced BP in patients inadequately controlled with either of the corresponding monotherapies. The antihypertensive efficacy of trandolapril/verapamil SR 2/180 mg/day was generally similar to that of other combinations of antihypertensive agents (metoprolol/hydrochlorothiazide, atenolol/chlorthalidone, lisinopril/hydrochlorothiazide, enalapril/hydrochlorothiazide) in patients with hypertension, including those with type 2 diabetes mellitus. Trandolapril/verapamil SR reduced BP in patients with hypertension and type 2 diabetes or primary renal disease, Black patients and elderly patients. Trandolapril/verapamil SR was more effective than the individual components administered as monotherapy in reducing proteinuria in patients with type 2 diabetes or primary renal disease. Trandolapril/verapamil SR had a neutral or beneficial effect on metabolic parameters (glucose, insulin, lipids) in patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR preserved left ventricular function in patients with heart failure. Fewer cardiac events occurred after therapy with trandolapril/verapamil SR than after trandolapril alone in post-myocardial infarction patients with congestive heart failure. The incidence of adverse events in recipients of trandolapril/verapamil SR was similar to that of the individual components, and that of other combination therapies. In placebo-controlled trials conducted in the US, headache, upper respiratory tract infections, cough, constipation, atrioventricular block (first degree) and dizziness were the most commonly reported adverse events in recipients of combinations of verapamil SR (120 to 240 mg/day) and trandolapril (0.5 to 8 mg/day). In conclusion, the fixed-dose combination of trandolapril/verapamil SR is an effective treatment for patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR tended to be more effective than monotherapy with either verapamil SR or trandolapril, and generally showed antihypertensive efficacy similar to that of other combination antihypertensive therapies. Current data support the use of trandolapril/verapamil SR as an alternative treatment when monotherapy with either agent is not effective. Data from large clinical trials currently being conducted will assist in fully defining the role of trandolapril/verapamil SR as a cardio- and renoprotective agent.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Spotlight on amisulpride in schizophrenia.

UNLABELLED: Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D(2)/D(3) autoreceptors. At higher doses, amisulpride antagonises postsynaptic D(2) and D(3) receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms. Amisulpride 400 to 800 mg/day was more effective than haloperidol, risperidone and flupenthixol in controlling affective symptoms in these patients. In randomised, double-blind trials involving patients with predominantly negative symptoms of schizophrenia, amisulpride 50 to 300 mg/day was more effective than placebo. Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia. Long-term treatment with amisulpride was associated with improvements in quality of life and social functioning. Amisulpride is generally well tolerated. In well-controlled trials, the neurological tolerability profile (including ratings on extrapyramidal symptom scales) of amisulpride 400 to 1200 mg/day was superior to that of the conventional antipsychotics (haloperidol or flupenthixol), but was similar to that of the atypical antipsychotic risperidone. At low dosages of amisulpride (< or = 300 mg/day), the incidence of adverse events (including extrapyramidal symptoms) reported with amisulpride was similar to that with placebo. CONCLUSION: In comparative trials, amisulpride 400 to 1200 mg/day showed efficacy in reducing overall symptomatology and positive symptoms similar to that of conventional antipsychotics and newer atypical antipsychotics in patients with acute exacerbations of schizophrenia. Moreover, its effective alleviation of negative and affective symptoms, its lower association with extrapyramidal symptoms and loss of cognitive function than conventional antipsychotics and its long-term efficacy justifies consideration of the use of higher dosages of amisulpride in this group of patients. Consequently, the dosage of amisulpride that is recommended in patients with acute exacerbations of schizophrenia is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia. Amisulpride is a first-line treatment option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.

Amisulpride↗

PubMed2002

Infliximab: an updated review of its use in Crohn's disease and rheumatoid arthritis.

Infliximab is a chimeric monoclonal antibody that binds to tumour necrosis factor-alpha (TNFalpha) and neutralises its effects. TNFalpha plays an important role in the development of both Crohn's disease and rheumatoid arthritis. In a large, double-blind, randomised study involving patients with active, refractory Crohn's disease, significantly more recipients of intravenous infliximab, compared with placebo, achieved a clinical response after 4 weeks' follow-up. Moreover, infliximab administration was associated with a rapid improvement in endoscopic and histological findings in clinical trials involving patients with active, refractory Crohn's disease. The results of the A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen (ACCENT) I study showed that maintenance infliximab therapy prolonged response and remission in patients with moderate to severe Crohn's disease. In patients with enterocutaneous fistulae associated with Crohn's disease who were involved in a double-blind, randomised study, significantly more patients who received multiple infusions of infliximab, compared with placebo, experienced a > or=50% reduction from baseline in the number of draining fistulae at > or =2 consecutive study visits. In patients with active rheumatoid arthritis refractory to treatment with methotrexate who were enrolled in a large, double-blind, randomised study [the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) study], American College of Rheumatology (ACR) 20, 50 and 70% response rates were seen in significantly more patients who received multiple infusions of infliximab plus methotrexate, compared with methotrexate plus placebo, after 30 and 54 weeks' treatment. Moreover, the ACR 20% response rate was maintained after 102 weeks' treatment. In addition, significantly less radiographic progression was seen in infliximab plus methotrexate, compared with methotrexate plus placebo, recipients after 54 weeks' treatment. Infliximab therapy was also associated with improvements in health-related quality of life in patients with Crohn's disease or rheumatoid arthritis. Infliximab was generally well tolerated in clinical trials with the most common adverse events including upper respiratory tract infection, headache, nausea, coughing, sinusitis and diarrhoea. Infliximab therapy may be associated with an increased risk of reactivation of tuberculosis in patients with latent disease. In conclusion, infliximab is an important treatment option in patients with active Crohn's disease who have not responded to conventional therapy and in patients with Crohn's disease who have fistulae. Moreover, infliximab plus methotrexate is effective in patients with active rheumatoid arthritis who have not responded adequately to traditional disease-modifying antirheumatic drugs, in terms of reducing symptoms and signs, improving physical function and delaying the progression of structural damage.

Antibodies, Monoclonal↗

PubMed2002

Spotlight on peginterferon-alpha-2a (40KD) in chronic hepatitis C.

Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a that has been developed to improve on the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. Peginterferon-alpha-2a (40KD) is produced by the covalent attachment of recombinant interferon-alpha-2a to a branched mobile 40KD polyethylene glycol moiety, which shields the interferon-alpha-2a molecule from enzymatic degradation, reduces systemic clearance and enables once-weekly administration. Peginterferon-alpha-2a (40KD) was significantly more effective than interferon-alpha-2a in interferon-alpha therapy-naive adults with chronic hepatitis C in three nonblind, randomised, multicentre trials. Virological responses (intention-to-treat results) were achieved in 44 to 69% of patients with or without cirrhosis after 48 weeks of treatment with peginterferon-alpha-2a (40KD) 180 microg/week; sustained virological responses 24 weeks after the end of treatment occurred in 30 to 39% of patients. Virological responses at the end of treatment and at long-term follow-up were significantly higher than those achieved with interferon-alpha-2a. Peginterferon-alpha-2a (40KD) was significantly more effective than interferon-alpha in patients with or without cirrhosis infected with HCV genotype 1. Sustained biochemical responses achieved with peginterferon-alpha-2a (40KD) 180 microg/week ranged from 34 to 45% and were significantly higher than with interferon-alpha-2a. Recipients of peginterferon-alpha-2a (40KD) also experienced histological improvements; 24 weeks after discontinuation of treatment with peginterferon-alpha-2a (40KD) 180 microg/week, 54% to 63% of patients had a >/=2-point improvement in histological activity index score. Peginterferon-alpha-2a (40KD) produced histological responses in patients (with or without cirrhosis) with or without a sustained virological response. Peginterferon-alpha-2a (40KD) produced better results than interferon-alpha-2a alone or interferon-alpha-2b plus oral ribavirin on various measures of quality of life in patients with chronic hepatitis C. The tolerability profile of peginterferon-alpha-2a (40KD) is broadly similar to that of interferon-alpha-2a in patients with chronic hepatitis C with or without cirrhosis. Headache, fatigue and myalgia are among the most common adverse events. In conclusion, peginterferon-alpha-2a (40KD) administered once weekly produces significantly higher sustained responses, without compromising tolerability, than interferon-alpha-2a administered thrice weekly in noncirrhotic or cirrhotic patients with chronic hepatitis C, including those infected with HCV genotype 1 - a group in whom interferon-alpha treatment has usually been unsuccessful. Peginterferon-alpha-2a (40KD) is a valuable new treatment option and appears poised to play an important role in the first-line treatment of patients with chronic hepatitis C, including difficult-to-treat patients such as those with compensated cirrhosis and/or those infected with HCV genotype 1.

Antiviral Agents↗

PubMed2002

Zidovudine: a review of its use in the management of vertically-acquired pediatric HIV infection.

UNLABELLED: Zidovudine is a thymidine analog that, after intracellular phosphorylation to zidovudine triphosphate metabolite, inhibits HIV-specific reverse transcriptase and terminates proviral DNA. Zidovudine administered to mildly symptomatic women with HIV infection in the antepartum (100mg orally 5 times/day), intrapartum (2 mg/kg intravenously over 1 hour then 1 mg/kg/h) and then to the neonate for 6 weeks (2 mg/kg), significantly reduced the rate of vertical HIV transmission by about two thirds, in the absence of breast-feeding (The Pediatric AIDS Clinical Trials Group 076 trial, standard protocol). Shorter zidovudine regimens, reduced the risk of transmission of HIV by 50% in a non-breast-feeding population and by about 37% in breast-feeding populations. Zidovudine (standard protocol) in combination with lamivudine was superior to zidovudine alone. A short oral zidovudine regimen was not as effective as a two-dose oral nevirapine regime, although the combination of short-course zidovudine plus lamivudine was as effective. Suppression of viral replication in neonates, infants and children has been achieved with zidovudine when used in triple-therapy regimens that include other antiviral drugs. Results from a trial of treatment-naive children indicate that the antiviral efficacy of combinations of zidovudine and lamivudine or abacavir, given with the protease inhibitor nelfinavir, is superior to treatment with this combination minus nelfinavir. When zidovudine was used in other highly active antiretroviral therapy regimens significant improvements in surrogate markers were consistently seen. Changing to ritonavir-containing regimens was superior to changing to treatment with two new nucleoside reverse transcriptase inhibitors. Short- and long-term (up to 5.6 years) outcomes from clinical trials showed that prenatal and neonatal exposure to zidovudine was generally well tolerated with the exception of mild anemia that resolved spontaneously after treatment cessation. Zidovudine was generally well tolerated as monotherapy in clinical trials of pediatric patients with HIV infection, and adverse events were similar to those reported in adults, with anemia and neutropenia being the most common. CONCLUSION: Zidovudine, as monotherapy or in combination with other antiretroviral agents, remains a first-choice therapy for the prophylaxis of mother-to-child HIV transmission as shown by substantial reductions in transmission rates. Where feasible, the optimal strategy to prevent vertical transmission is to combine drug therapy with Cesarean section delivery and no breast-feeding. In addition, zidovudine in combination with another nucleoside analogue and a protease inhibitor is a first- or second-choice therapy for the treatment of pediatric HIV infection as significant and sustained reductions in viral load have been shown in both plasma and cerebrospinal fluid.

Adolescent↗