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Biomedical subjects

P Carey

Publications and source records attributed to P Carey.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders.

BACKGROUND: A large proportion of patients with anxiety disorders fail to respond to first-line medication interventions, despite evidence of the effectiveness of these agents. OBJECTIVES: To assess the effects of medication versus placebo augmentation in the treatment of patients with anxiety disorders who have failed to respond adequately to first-line drug therapies. SEARCH STRATEGY: The Cochrane Depression, Anxiety & Neurosis Group (CCDAN) specialised registers (CCDANCTR-Studies and CCDANCTR-References) were searched on 3/8/2005, MEDLINE (January 1966 to July 2005) and PsycINFO (1966 to 2005, Part A). Unpublished trials were identified through the Controlled Trials database and the National Institute of Health's Computer Retrieval of Information on Scientific Projects (CRISP) service (1972 to 2005). Additional studies in any language were sought in reference lists of retrieved articles. SELECTION CRITERIA: All randomised controlled trials (RCTs) of the medication augmentation of pharmacotherapy for treatment resistant anxiety disorders. DATA COLLECTION AND ANALYSIS: Two raters independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary statistics were stratified by class of augmentation agent and anxiety disorder. Overall effect estimates were calculated using a random-effects model, heterogeneity was assessed and subgroup/sensitivity analyses were undertaken. MAIN RESULTS: Twenty eight short-term (average of seven weeks) randomised controlled trials (740 participants) were included in the review, 20 of which investigated augmentation of medication for treatment-resistant obsessive compulsive disorder (OCD). Summary statistics for responder status from nine trials demonstrate overall superiority of a variety of medication agents to placebo (relative risk of non-response (RR) 3.16, 95% CI 1.08 to 9.23). Similarly, symptom severity was significantly reduced in the medication groups, relative to placebo (number of trials (N) = 14, standardised mean difference (SMD) -0.87, 95% CI -1.37 to -0.36). There is no evidence of a difference between medication and placebo in total dropout rate, or in the number of dropouts due to adverse events. AUTHORS' CONCLUSIONS: Medication augmentation can be an effective and well-tolerated short-term treatment strategy for non-responders to first-line pharmacotherapy of anxiety disorders. However, any conclusions must be tentative in view of methodological and clinical heterogeneity, and the fact that much of the relevant database is based on antipsychotic augmentation trials in OCD patients resistant to serotonin reuptake inhibitors (SRIs). Additional data are needed to address several areas, including the efficacy of augmentation over the longer-term, and the value of medication augmentation in comparison to other strategies (e.g. switching medication, adding psychotherapy).

Anti-Anxiety Agents↗
PubMed2006

A comparison of the effects of citalopram and moclobemide on resting brain perfusion in social anxiety disorder.

INTRODUCTION: The serotonin specific reuptake inhibitor (SSRI) citalopram and the reversible mono-amine oxidase-A inhibitor (RIMA) moclobemide have both been used successfully for the treatment of social anxiety disorder (SAD). In this study we investigate the effects of these compounds on resting brain function using single photon emission computed tomography (SPECT). METHODS: Subjects meeting DSM-IV criteria for SAD underwent regional cerebral blood flow (rCBF) SPECT using Tc-HMPAO at baseline and after 8 weeks of treatment with either citalopram or moclobemide. Using statistical parametric mapping brain SPECT studies were analysed to determine the effects of treatment on rCBF, to compare the effects of citalopram and moclobemide, and to detect correlations between changes in rCBF and clinical response. RESULTS: Subjects received citalopram (n=17) or moclobemide (n=14) as therapy. Subjects in both treatment groups demonstrated a significant improvement of SAD symptoms as measured by the Liebowitz Social Anxiety Scale total score. All subjects demonstrated a decrease in rCBF in the insulae post therapy. Subjects receiving citalopram had decreased superior cingulate rCBF after therapy compared to those receiving moclobemide. CONCLUSION: Both SSRI's and RIMA's decreased rCBF in the insulae during treatment of SAD; an effect that may be consistent with the role of these regions in processing internal somatic cues evoked by emotional stimuli. Citalopram had a greater effect on superior cingulate perfusion, an effect that is consistent with evidence of high levels of 5-HT transporters in this region.

Adult↗
PubMed2003

Dehydrated hereditary stomatocytosis with transient perinatal ascites.

The case is reported of a mother and baby with dehydrated hereditary stomatocytosis and perinatal ascites, an autosomal dominant condition not previously reported in Britain. Recognition is important for the management of pregnancy and for avoidance of splenectomy which, if performed, can predispose the patient to fatal thromboembolic events.

Adult↗
PubMed2002

Epstein-Barr virus (types 1 and 2) in the tear film in Sjogren's syndrome and HIV infection.

Evidence of Epstein-Barr virus (EBV) shedding in the saliva and tear film has been sought to explain the pathogenesis of the oral and ocular features of Sjogren's syndrome. Patients with human immunodeficiency virus (HIV) infection are purported to have a higher incidence of keratoconjunctivitis sicca. Twenty patients with definite Sjogren's syndrome (primary and secondary), 19 with HIV infection, and 15 normal controls were recruited and studied. Human herpes viruses (EBV 1 and 2, CMV, HZV, and HSV-1) in tear film were detected by polymerase chain reaction of DNA extracted from Schirmer strips. HSV-1, VZV, and CMV were not detected in any tear samples. EBV-1 DNA was found in the tear film of 4 patients with Sjogren's syndrome, which was not significantly different from the control group (P = 0.18). Twelve patients with HIV infection had evidence of EBV-1 in their tears, which was significantly different from controls (P = 0.0002) and patients with Sjogren's syndrome (P = 0.014). EBV-2 was found in 3 patients with HIV and in 1 patient with secondary Sjogren's syndrome, and was always found as a co-infection with EBV-1 (P = 0.01). This represents the first report examining EBV types 1 and 2 in the tear film and also EBV in the tear film of patients with HIV. Shedding of EBV in the tear film was not related to the presence of keratoconjunctivitis sicca in Sjogren's syndrome. EBV-2 co-infection with EBV-1 has not been previously reported in the tear film. EBV infection is abnormally regulated in Sjogren's syndrome and HIV, and it is likely that the presence of EBV in the tear film is related to the patients' altered immune status.

Adolescent↗
PubMed2001

A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.

The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.

Acute Disease↗
PubMed2001

Intravenous apomorphine therapy in Parkinson's disease: clinical and pharmacokinetic observations.

Six patients with Parkinson's disease and refractory motor fluctuations, with severe subcutaneous (s.c.) nodule formation as a result of long-term s.c. apomorphine infusions, were switched to intravenous (i.v.) therapy via a long-term in-dwelling venous catheter. Five patients were followed-up for a mean of 7 months (range 0.5-18 months). All patients had plasma apomorphine concentrations measured at baseline during s.c. infusions and three had follow-up measurements when stabilized on i.v. therapy, to test the hypothesis that motor fluctuations in these patients are largely due to impaired absorption of apomorphine. The mean i.v. rate of 9.0 mg/h (range 5-14 mg) and 24-h dose of 256.7 mg (range 90-456 mg) of apomorphine were not significantly reduced compared with the s.c. route (9.24 mg/h and 243.4 mg). However, additional oral anti-parkinsonian medication was reduced by a mean of 59%, and 'off' time was virtually eliminated (mean reduction from 5.4 to 0.5 h per day, P< 0.05). There was also a significant reduction in dyskinesias and markedly improved quality of life. Pharmacokinetic analysis demonstrated more reliable and smoother delivery of apomorphine via the i.v. route, although 'off' periods were not always explained by low plasma apomorphine concentrations. Complication rates were high and included three unforeseen hazardous intravascular thrombotic complications, secondary to apomorphine crystal accumulation, necessitating cardiothoracic surgery. We conclude that i.v. apomorphine therapy holds promise as a more effective way of controlling motor fluctuations than the s.c. route. However, further preclinical research is required before i.v. Britaject apomorphine can be recommended for routine clinical practice. Even when stable plasma apomorphine concentrations were achieved, motor fluctuations could not be totally eradicated, suggesting that postsynaptic receptor changes may also play a role in the refractory 'off' periods in these patients.

Aged↗
PubMed2001

Influence of prior exposure to zidovudine on stavudine phosphorylation in vivo and ex vivo.

Intracellular phosphorylation of stavudine (d4T) and zidovudine (ZDV) was investigated in peripheral blood mononuclear cells (PBMCs) isolated from ZDV-naive and ZDV-experienced human immunodeficiency virus (HIV)-positive patients. An in vivo study measured the amount of d4T triphosphate (d4TTP), while an ex vivo study assessed the capacity of cells to phosphorylate added d4T. Endogenous dTTP was also measured. d4TTP and dTTP were determined in vivo using a reverse transcriptase chain termination assay. In ex vivo studies, d4T (1 microM) was incubated in resting and phytohemagglutinin-stimulated (10 microg ml(-1); 72 h) PBMCs for 24 h. After washing and methanol extraction, radiolabeled anabolites were detected by high-performance liquid chromatography. d4TTP reached its highest level 2 to 4 h after dosing (0.21 +/- 0.14 pmol/10(6) cells; n = 27 [mean +/- standard deviation]). Comparison of ZDV-naive and ZDV-experienced individuals showed no significant difference in levels of d4TTP (ZDV naive, 0.23 +/- 0.17 pmol/10(6) cells [n = 7] versus ZDV experienced, 0.20 +/- 0.14 pmol/10(6) cells [n = 20]; P = 0.473) or the d4TTP/dTTP ratio (0.14 +/- 0.12 [n = 7] and 0.10 +/- 0.08 [n = 20], respectively; p = 0.391). Ex vivo data demonstrated no significant difference in the formation of d4TTP or total d4T phosphates in naive and experienced patients (0.086 +/- 0.055 pmol/10(6) cells in ZDV-naive patients [n = 17] versus 0.081 +/- 0.038 pmol/10(6) cells in ZDV-experienced patients [n = 22]; P = 0.767). The ability of HIV-infected patients to phosphorylate d4T in vivo and ex vivo was unchanged with increasing exposure to ZDV.

Anti-HIV Agents↗
PubMed2001

Takayasu arteritis and atherosclerosis: illustrating the consequences of endothelial damage.

The excess of cardiovascular morbidity associated with chronic vasculitic disease has become a focus of considerable research, particularly regarding the link between endothelial damage and the development of atherosclerosis. We describe a case of Takayasu arteritis treated sub-optimally by today's standards, giving rise to an 11 year history of progressive, stepwise decline associated with cerebrovascular events and leading to early death. Postmortem findings presented a picture of chronic atherosclerotic disease but in a distribution consistent with lesions of Takayasu arteritis.

Aorta↗
PubMed2000

Post-transfusion HIV infection despite donor screening: a report of three cases.

In August 1996, a blood donation was collected which subsequently infected three patients post-transfusion with HIV 1. The donation itself was originally screened as negative for anti-HIV 1/2 using a sensitive EIA method, but subsequently was shown to contain p24 Ag and HIV RNA by an amplification technique. The proposed introduction of nucleic acid testing of all blood donations in the UK for hepatitis C, hepatitis B and HIV may further reduce the remote risk of further episodes of post-transfusion infection. The infection in the index recipient was detected on routine pre-transplant virological screening but proved difficult to confirm, at a time when she had recently received myeloablative treatment for a haematological malignancy which impaired the immune response. There is a need for continued vigilance in such patients to exclude post-transfusion infection, at a time when natural immunological responses have been impaired by their disease or treatment.

Aged↗
PubMed2000

Peripheral neuropathy: zalcitabine reassessed.

Given that the long-term medical management of HIV infection necessitates making best use of all available antiretrovirals, it is somewhat surprising that the nucleoside analogue reverse transcriptase inhibitor (NRTI) zalcitabine is less commonly used. This may be due to the potential for peripheral neuropathy (PN) which has been associated with the use of this drug. The perception that zalcitabine is poorly tolerated appears to have arisen largely from the results of early monotherapy trials in patients with AIDS and low CD4 cell counts. In contrast, results of more recent studies show that PN is relatively infrequent when zalcitabine is used in combination with other antiretrovirals in current treatment settings.

Anti-HIV Agents↗
PubMed1999

GaIN (Georgia Interactive Network for Medical Information) study on health professionals' search requests and continuing education needs.

Health sciences librarians are being called upon to be more proactive in their institutions' continuing education efforts. In an effort to identify whether search requests indicated CE needs, a study was conducted by a group of members of GaIN (Georgia Interactive Network for Medical Information). MEDLINE requests from health care professionals for subject specific clinical topics were collected during a six-month period via a standard search request form created for the study. Copies of all completed requests were collected and broad ICD-9 codes assigned to the search topics. Institutional reports were generated for each participating library to share with hospital CE coordinators. They were also compiled for the group as a whole, and reflected the "hottest" topics requested during the study period for physicians and for non-physicians (nurses, allied health, administrators). A survey to hospital librarians and CE educators showed some value in the reports, but greater potential for further collaboration between librarians and CE coordinators.

Allied Health Personnel↗
PubMed1996

Memory for conversation.

Memory for conversation is treated as a source of coherence in social encounters and its connections with social competence are tested in a study of problem-solving conversations. As predicted, accurate recall is found to correlate positively with social competence and negatively with social anxiety. Partners have better memory for their own contributions than for each other's, and this difference is exacerbated by topic importance. Differences in recall are also found for differing amounts of involvement in the conversations. Results are explained in terms of resource allocation during conversation.

Analysis of Variance↗
PubMed1995

Toxoplasmosis masking non-Hodgkin's lymphoma: a case report.

A 39-year-old female with persistent cervical lymphadenopathy is reported. Initial investigations resulted in a diagnosis of toxoplasmosis, but subsequently the patient proved to have high grade immunoblastic non-Hodgkin's lymphoma. This paper highlights the difficulties in accurately diagnosing some cases of either toxoplasmosis or lymphoma, and briefly mentions some of the ongoing technical advances which will increase diagnostic specificity and sensitivity by early detection of genetic mutations.

Adult↗