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Biomedical subjects

J Quinn

Publications and source records attributed to J Quinn.

At least 19 recordsLinked to original sources
PubMed2007

Plasmablastic lymphoma presenting as a paravertebral mass in a patient with Crohn's disease after immunosuppressive therapy.

The case of a 32-year-old man with a paravertebral mass and skin nodules, occurring against a background of immunosuppressive therapy for Crohn's disease, is presented. The tumours showed morphological and immunophenotypical features of plasmablastic lymphoma. To our knowledge, this is the first reported case of plasmablastic lymphoma presenting in this location, and also after immunosuppression with infliximab treatment for Crohn's disease.

Adult↗
PubMed2006

Treatment of refractory fludarabine induced autoimmune haemolytic with the anti-CD20 monoclonal antibody rituximab.

A patient with cold-type autoimmune haemolytic anaemia for 8 years developed progressive B cell chronic lymphocytic leukaemia (CLL). Despite the risk of fludarabine induced exacerbation of haemolysis, he was given aggressive anti-CLL therapy with six courses of FCR (fludarabine 25 mg/m2 D1-3, cyclophosphamide 250 mg/m2 D2-4 and rituximab 375 mg/m2 D1) every 4 weeks. This resulted in a marked acute increase in haemolysis shortly after completing each course of fludarabine. However, haemolysis had settled to its baseline level by the time of subsequent courses of FCR. FCR resulted in complete clinical remission of CLL but residual haemolysis persisted. The patient was then given four weekly infusions of single agent rituximab, resulting in ongoing remission of haemolysis. In this patient, rituximab appears to have controlled fludarabine induced exacerbation of autoimmune haemolysis. In addition, subsequent single agent rituximab therapy resulted in prolonged remission of cold-type autoimmune haemolytic anaemia. It remains to be seen if the addition of rituximab will allow other patients with a positive direct Coomb's test and/or autoimmune haemolysis to receive fludarabine containing chemotherapy without undue risk of life-threatening haemolytic anaemia.

Adult↗
PubMed2005

CML clonal evolution with resistance to single agent imatinib therapy.

We describe a 58-year-old male diagnosed with chronic myeloid leukaemia (CML) who failed to have a cytogenetic response to interferon-alpha and hydroxyurea. On subsequent therapy with imatinib mesylate he failed to have any cytogenetic response but also developed a complex clonal evolution with an additional Philadelphia (Ph) chromosome and trisomy 8 respectively in two Ph-positive subclones. The addition of cytosine arabinoside to imatinib resulted in reversion to single Ph-chromosome positivity with the disappearance of the previous additional clonal abnormalities. The case demonstrates the efficacy of combined treatment with imatinib and cytarabine in the management of CML resistant to single agent imatinib.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Asynchronous regional brain volume losses in presymptomatic to moderate AD.

To determine if rates and locations of brain volume loss associated with AD are phase-specific, occurring prior to clinical onset and at later stages, we performed longitudinal volumetric MRI analysis on 155 subjects enrolled in a prospective study of aging and dementia. Subjects were divided by Clinical Dementia Rating (CDR) scale into stages of Normal (CDR 0 --> 0), Very Mild (CDR 0 --> 0.5 and 0.5 --> 0.5), Mild (CDR 0.5 --> 1.0 and 1.0 --> 1.0) and Moderate (CDR 1.0 --> 2.0 and 2.0 --> 2.0) dementia. Rates of volume change in CSF spaces, lobar and medial temporal lobe regions were analyzed for group differences across stages. Annual rates of ventricular volume change differed between non-demented and very mild group (p<0.01). In later severity stages, ventricular, temporal, basal ganglia-thalamic region and total volumes show change. Rates of volume loss increase as dementia progresses, but not uniformly in all regions. These regional and phase-specific volume changes form targets for monitoring disease-modifying therapies at clinically relevant, defined stages of dementia.

Aged↗
PubMed2004

Confirmation and refinement of an 'at-risk' haplotype for schizophrenia suggests the EST cluster, Hs.97362, as a potential susceptibility gene at the Neuregulin-1 locus.

Two recent association studies have implicated the neuregulin-1 gene (NRG1) at chromosome 8p21-22 as a susceptibility gene for schizophrenia. Stefansson et al identified three 'at-risk' haplotypes (HapA, B and C) which spanned the NRG1 locus and shared a common core haplotype. Subsequently, they demonstrated evidence that the core haplotype was associated with schizophrenia in an independent Scottish sample. To confirm and refine this haplotype we investigated the NRG1 locus in an independent Irish case-control sample. We did not find the core haplotype to be associated in our sample. However, we identified a refined 2-marker haplotype (HapB(IRE)) that shared common alleles with one of the Icelandic 'at-risk' haplotypes and is in significant excess in the Irish cases (19.4%) vs controls (12.3%) (P=0.013). This refined 'at-risk' haplotype is also in significant excess in the Scottish case sample (17.0% vs 13.5%; P=0.036). Interestingly, this refined 'at-risk' haplotype is positioned close to an EST cluster of unknown function (Hs.97362) within intron 1 of NRG1.

Genetic Predisposition to Disease↗
PubMed2004

Evaluation of 5-day therapy with telithromycin, a novel ketolide antibacterial, for the treatment of tonsillopharyngitis.

A pooled analysis of two double-blind, multicentre, Phase III studies compared oral telithromycin 800 mg once-daily for 5 days with penicillin V 500 mg three-times-daily or clarithromycin 250 mg twice-daily for 10 days in the treatment of Streptococcus pyogenes (group A beta-haemolytic streptococcus; GABHS) tonsillopharyngitis. Patients aged > or = 13 years with acute GABHS tonsillopharyngitis were randomised to receive telithromycin (n = 430), penicillin (n = 197) or clarithromycin (n = 231). Clinical isolates of S. pyogenes (n = 590) obtained from throat swab samples on study entry were tested for their in-vitro susceptibility to telithromycin, clarithromycin and azithromycin. Telithromycin demonstrated in-vitro activity against the clinical isolates of S. pyogenes (MIC50/90 0.03/0.06 mg/L) higher than clarithromycin or azithromycin (MIC50/90 0.06/0.06 mg/L and 0.12/0.25 mg/L, respectively), including erythromycin-resistant strains. At the post-therapy/test of cure (TOC) visit (days 16-23), satisfactory bacteriological outcome was demonstrated for 88.3% (234/265) and 88.6% (225/254) of telithromycin- and comparator-treated patients, respectively (per-protocol population). Overall, GABHS eradication rates were 88.7% (235/265) for telithromycin and 89.0% (226/254) for comparators. The clinical cure rates at the post-therapy/TOC visit were 93.6% (248/265) and 90.9% (220/242) for telithromycin and pooled comparators, respectively. Telithromycin was generally well-tolerated. Most adverse events considered to be possibly related to study medication were gastrointestinal and of mild intensity. Discontinuations as a result of adverse events were few in both treatment groups. In conclusion, telithromycin 800 mg once-daily for 5 days was as effective as penicillin V or clarithromycin for 10 days in the treatment of GABHS tonsillopharyngitis.

Adolescent↗
PubMed2004

Detection of Pneumocystis jiroveci in respiratory specimens by four staining methods.

We examined four staining methods on replicate smears of 313 respiratory specimens submitted for Pneumocystis jiroveci examination. The sensitivity and specificity of Calcofluor white stain (CW) were 73.8 and 99.6%, respectively. The sensitivity and specificity of Grocott-Gomori methenamine silver stain (GMS) were 79.4 and 99.2%, respectively. The sensitivity and specificity of Diff-Quik stain were 49.2 and 99.6%, respectively. The sensitivity and specificity of Merifluor Pneumocystis stain were 90.8 and 81.9%, respectively. Only CW and GMS had positive and negative predictive values of >90%.

Bronchoalveolar Lavage Fluid↗
PubMed2003

Natural history of cognitive decline in the old old.

OBJECTIVE: To prospectively examine the occurrence and outcome of cognitive decline in healthy, community-dwelling elders. METHODS: Ninety-five elders (mean age 84 years) who at entry had no cognitive impairment were followed for up to 13 years. Cognitive decline was defined as obtaining either a Clinical Dementia Rating (CDR) = 0.5 or Mini-Mental State Examination (MMSE) score < 24 on two examinations. RESULTS: Three outcomes of aging were determined: intact cognition, persistent cognitive decline without progression to dementia, and dementia. Whereas 49% remained cognitively intact, 51% developed cognitive decline. Mean follow-up to first CDR 0.5 was 3.8 years and age at conversion was 90.0 years. Those who remained cognitively intact had better memory at entry and were less likely to have APOE4 than those who developed cognitive decline. Of the 48 participants with cognitive decline, 27 (56%) developed dementia (CDR > or =1) a mean of 2.8 years later. Participants with cognitive decline who progressed to dementia had poorer confrontation naming at the time of their first CDR 0.5 than those with persistent cognitive decline who did not progress during follow-up. CONCLUSION: The old old are at high risk for developing cognitive decline but many will not progress to dementia in the next 2 to 3 years or even beyond. These findings are important for understanding the prognosis of cognitive decline and for the design of treatment trials for AD. APOE genotype is a risk factor for cognitive decline.

Aged↗
PubMed2003

The family and compliance in schizophrenia: the influence of clinical variables, relatives' knowledge and expressed emotion.

BACKGROUND: . A variety of factors are related to compliance with medication in schizophrenia, but little attention has been paid to the role of families. Carers' knowledge or expressed emotion (EE) may be related to compliance. The aim of the present study was to evaluate the relevance of these two factors, as well as their relationships with other variables for the prediction of compliance. METHOD: A sample of patient-carer pairs (N = 79) involved in a family intervention for schizophrenia trial was recruited. Compliance, symptoms, social functioning and attitudes to their carers were assessed in patients. Carers' EE, knowledge and psychopathology were also evaluated. RESULTS: A number of factors were related to compliance, including carers' EE and patients' psychotic symptoms, which contributed independently to not taking medication. Carers' knowledge about schizophrenia and other groups of symptoms was not related to compliance. CONCLUSIONS: EE may be an important factor to account for in the understanding of patients' compliance and the direction of the relationship between EE and compliance should be the subject of further study.

Adolescent↗
PubMed2003

The Family Questionnaire (FQ): a scale for measuring symptom appraisal in relatives of schizophrenic patients.

OBJECTIVE: This study examined the psychometric properties of the Family Questionnaire (FQ): a self-report measure of relatives' perceptions of the behaviours and symptoms of schizophrenic patients in terms of three dimensions: the frequency of symptoms, the relatives' concern (primary appraisal) and their ability to cope (secondary appraisal) with the symptoms. METHOD: Factor analysis of the FQ, test-retest and inter-rater reliability, and measures of validity were examined. RESULTS: Factor analysis supported the validity of five subscales labelled negative symptoms, antisocial behaviours, interpersonal problems, affective symptoms and psychotic symptoms. Test-retest reliability for all scales was good and the prediction that there would be limited correspondence between two different relatives' scores was supported for the subscales of negative symptoms and affective symptoms. Concurrent measures of relatives' distress, burden and patients' symptomatology indicated that the FQ showed acceptable validity. In particular, the study showed that high expressed emotion relatives have higher scores on the appraisal dimensions of some subscales. CONCLUSION: The study provides evidence that the FQ is a useful tool for measuring relatives' perceptions of schizophrenic illness, particularly within the context of family interventions where it may be utilized to help to understand the factors mediating relatives' burden and distress.

Adaptation, Psychological↗
PubMed2002

A videotaped CIBIC for dementia patients: validity and reliability in a simulated clinical trial.

BACKGROUND: The global impression of a clinician is an Food and Drug Administration--mandated primary outcome measure for clinical trials in dementia. Reliability and validity of these measures are not well established. METHODS: A videotaped version of the Clinician's Interview Based Impression of Change (CIBIC) was evaluated. Raters were informed that the videotaped interviews were taken at baseline and 6 to 12 months later, when in fact half of the interviews were shown in reverse order. Ratings on "true order" interviews were compared with ratings on "reverse order" interviews. In addition, ratings by neurologists experienced in dementia were compared with those of less experienced raters. RESULTS: Inter-rater reliability of the neurologists was poor when measured by absolute agreement on a 7-point scale (kappa = 0.18). With a less stringent 3-point scale (better, worse, or unchanged), inter-rater reliability was significantly better for the true order videos (kappa = 0.51) than for the reversed order videos (kappa = 0.12). Validity also was reduced in the reverse order group: neurologists rated 90% of subjects correctly in the "true order" group and 63% correctly in the "reversed order" group. The inter-rater reliability of the neurologists was greater than the less experienced raters, but the validity of the neurologists' ratings was only marginally better. CONCLUSIONS: The reliability and validity of the videotape CIBIC are reasonable when patients follow the expected course of gradual decline, but are poor when patients appear to improve. These findings suggest that global assessments should be modified as outcome measures in clinical trials with patients with dementia.

Aged↗
PubMed2001

The challenge of effectively addressing tobacco control within a health promoting NHS Trust.

As part of its participation in the international network of health promoting hospitals (HPH), South Tyneside Health Care NHS Trust has initiated a series of sub-projects that are informed by the contemporary evidence-base and the principles of the HPH programme. This paper concerns the first of these sub-projects, whose aim is to establish an equitable and effective Trust-wide system to address smoking in South Tyneside. The ambition is to build a framework for, and foster a culture within which, individuals will be treated considerately, whilst managing "unhealthy" behaviour in such a way as to have a long-term positive impact within the organisation and the surrounding community. This paper will briefly outline the key activities underway, and the manner in which it is hoped this approach to undertaking a HPH sub-project will contribute to sustainable local health improvement, while also supporting the Trust's broader transformation into a truly health promoting organisation.

Community Health Planning↗
PubMed2001

Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults.

AIM: To estimate the effectiveness of triple combination therapy in antiretroviral-naive adults. METHODS: A systematic overview of results from clinical trials involving triple combination therapy with dual nucleoside reverse transcriptase inhibitors (NRTI) and: a protease inhibitor (PI triple); a non-nucleoside reverse transcriptase inhibitor (NNRTI triple); or a third NRTI (triple NUC). Data from 23 clinical trials involving 31 independent treatment groups, 19 unique antiretroviral regimens, and 3257 enrolled patients were included in this study. RESULTS: Median log(10) baseline plasma HIV RNA and CD4 cell count over all trials averaged 4.69 (49,329 copies/ml) and 375 x 10(6) cells/l, respectively. The overall estimated percentage of patients with plasma HIV RNA < or = 400 copies/ml at 24 weeks was 64% [95% confidence interval (CI), 60 to 67%]. The percentages of patients with plasma HIV RNA < or = 50 copies/ml at 48 weeks by drug class were: PI triple, 46% (95% CI, 41 to 52%); NNRTI triple, 51% (95% CI, 43 to 59%); triple NUC, 45% (95% CI, 36 to 54%). The CD4 cell count increase over all trials at 24 and 48 weeks averaged +123 x 10(6) cells/l (95% CI, 111 x 10(6) to 135 x 10(6) cells/l) and +160 x 10(6) cells/l (95% CI, 146 x 10(6) to 175 x 10(6) cells/l), respectively and did not differ between drug classes. In multivariable regression analysis, neither baseline plasma HIV RNA level and CD4 cell count nor treatment regimen predicted plasma HIV RNA < or = 50 copies/ml at week 48. However, pill count was significantly negatively associated with plasma HIV RNA < or = 50 copies/ml at week 48 (P = 0.0085). CONCLUSIONS: The results suggest that three drug regimens containing two NRTI with a PI, a NNRTI, or a third NRTI may provide comparable activity, and practical issues such as daily pill burden should be considered when choosing a treatment regimen.

CD4 Lymphocyte Count↗
PubMed2001

Relationship of the factor structure of psychopathology in schizophrenia to the timing of initial intervention with antipsychotics.

Timing of intervention with antipsychotic medication may influence long-term outcome in schizophrenia in a manner that is poorly understood. This study evaluated psychopathology, its factor structure, and cognitive dysfunction in older patients with chronic schizophrenia in relation to the intervals from onset of psychosis to initiation of treatment with antipsychotics, and from initiation of antipsychotic treatment to current assessments. The subjects were 129 patients with schizophrenia, many of whom became ill in the preneuroleptic era. Their current psychopathology was assessed using the Positive and Negative Syndrome Scale, and its factor structure examined using principal component analysis. Current general and executive cognitive function was evaluated using the Mini-Mental State Examination and the Executive Interview, respectively. Using multiple regression modelling, increasing duration of initially unmedicated psychosis, but not the much longer duration of subsequently treated illness, was the primary predictor of psychomotor poverty (negative symptoms) but not of reality distortion or disorganisation over the three domains of psychopathology resolved; duration of initially unmedicated psychosis marginally predicted the severity of general, but not of executive, cognitive dysfunction. Delayed intervention with antipsychotics appears associated with poorer long-term course in terms of increased severity of psychopathology in the psychomotor poverty domain.

Aged↗
PubMed2001

Vulnerability to involuntary movements over a lifetime trajectory of schizophrenia approaches 100%, in association with executive (frontal) dysfunction.

This study assessed the prevalence of involuntary movements among older inpatients with severe schizophrenia, many of whom had experienced a lifetime of illness and its treatment, and examined their neuropsychological correlates. The subjects of this study were 128 inpatients with a DSM-IV diagnosis of schizophrenia. They were assessed using the Abnormal Involuntary Movement Scale, the Mini-Mental State Examination for general cognitive impairment and the Executive Interview for executive dyscontrol; additionally, their medical records were reviewed in detail for treatment histories. Prevalence of involuntary movements was examined and their clinical correlates determined in relation to topography of movement disorder using logistic regression. In schizophrenia, prevalence of involuntary movements was: age <65years, 63%; 65-75years, 80%; >75years, 93%. The primary correlate both of overall and of orofacial movements was poor executive function, whereas the primary correlate of limb-trunkal movements was poor general cognitive function. On approaching the limits of human longevity following a lifetime trajectory of illness and its treatment, essentially 'all' patients with schizophrenia appear inherently vulnerable to the emergence of involuntary movements in topographically specific association with cognitive deficits.

Adult↗
PubMed2001

Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine.

PURPOSE: To assess thiopurine S-methyltransferase (TPMT) phenotype and genotype in patients who were intolerant to treatment with mercaptopurine (MP) or azathioprine (AZA), and to evaluate their clinical management. PATIENTS AND METHODS: TPMT phenotype and thiopurine metabolism were assessed in all patients referred between 1994 and 1999 for evaluation of excessive toxicity while receiving MP or AZA. TPMT activity was measured by radiochemical analysis, TPMT genotype was determined by mutation-specific polymerase chain reaction restriction fragment length polymorphism analyses for the TPMT*2, *3A, *3B, and *3C alleles, and thiopurine metabolites were measured by high-performance liquid chromatography. RESULTS: Of 23 patients evaluated, six had TPMT deficiency (activity < 5 U/mL of packed RBCs [pRBCs]; homozygous mutant), nine had intermediate TPMT activity (5 to 13 U/mL of pRBCs; heterozygotes), and eight had high TPMT activity (> 13.5 U/mL of pRBCs; homozygous wildtype). The 65.2% frequency of TPMT-deficient and heterozygous individuals among these toxic patients is significantly greater than the expected 10% frequency in the general population (P <.001, chi(2)). TPMT phenotype and genotype were concordant in all TPMT-deficient and all homozygous-wildtype patients, whereas five patients with heterozygous phenotypes did not have a TPMT mutation detected. Before thiopurine dosage adjustments, TPMT-deficient patients experienced more frequent hospitalization, more platelet transfusions, and more missed doses of chemotherapy. Hematologic toxicity occurred in more than 90% of patients, whereas hepatotoxicity occurred in six patients (26%). Both patients who presented with only hepatic toxicity had a homozygous-wildtype TPMT phenotype. After adjustment of thiopurine dosages, the TPMT-deficient and heterozygous patients tolerated therapy without acute toxicity. CONCLUSION: There is a significant (> six-fold) overrepresentation of TPMT deficiency or heterozygosity among patients developing dose-limiting hematopoietic toxicity from therapy containing thiopurines. However, with appropriate dosage adjustments, TPMT-deficient and heterozygous patients can be treated with thiopurines, without acute dose-limiting toxicity.

Adolescent↗
PubMed2001

Beta-amyloid plaques induce neuritic dystrophy of nitric oxide-producing neurons in a transgenic mouse model of Alzheimer's disease.

A causative role for nitric oxide has been postulated in a number of neurodegenerative diseases. Using histochemical and immunohistochemical methods, we examined the effect of beta-amyloid plaques on nitric oxide-producing cells in transgenic mice which overexpress a mutant human amyloid precursor protein (APP). In 14-month-old animals, nitric oxide synthase (NOS)-positive dystrophic neurites were observed frequently in the cerebral cortex and hippocampus of all of 16 plaque-bearing transgenic animals and in none of 16 wild-type animals. Double labeling of NOS and beta-amyloid revealed that 90% of beta-amyloid plaques were associated with NOS-containing dystrophic neurites. In 7-month-old animals, beta-amyloid plaques were very rare, but those present were frequently associated with NOS-positive neuritic dystrophy. We conclude that beta-amyloid plaques induce neuritic dystrophy in cortical neurons containing NOS in this model of AD, and hypothesize that this finding may be relevant to the mechanism of beta-amyloid neurotoxicity in human AD.

Alzheimer Disease↗