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Biomedical subjects

J Duffy

Publications and source records attributed to J Duffy.

At least 19 recordsLinked to original sources
PubMed2006

Effects of elevated temperature and nickel pollution on the immune status of Japanese medaka.

Changes in a host's environment (i.e. physical or chemical) can alter normal immune function. In aquatic organisms, exposure to stress can result in significant changes in innate immunity. In the natural environment, fish are exposed to multiple stressors simultaneously. Temperature change and/or chemical exposure as individual environmental stressors have been shown in various fish species to alter all aspects of the immune response. These same stressors have also been shown to alter plasma steroid levels in exposed fish. For this study, the effects of elevated temperature and nickel pollution on specific immune parameters of Japanese medaka (Oryzias latipes) were determined. Fish were exposed for 1, 7 or 14d to either: waterborne nickel (Ni) at the nominal concentration of 125ppb; a 5 degrees C (+/-0.5 degrees C) rapid increase in water temperature; or, both potential stressors in combination. Medaka maintained at room temperature (25 degrees C+/-1 degrees C) served as the controls. Altered function of the innate and adaptive arms of the immune response was evaluated by assessing kidney macrophage-mediated superoxide (O(2)(-)) production and splenic T-cell proliferation, respectively. Plasma cortisol levels were analysed in the same fish as a marker of the physiological stress response. While kidney cell number was unaffected by exposure of fish to either stressor alone or both factors in combination, spleen cellularity was decreased (compared to control fish) in medaka exposed for 1d to thermal stress in combination with Ni, and to a lesser extent to thermal stress alone. T-lymphocyte proliferation by medaka splenocytes was not affected by any exposure paradigm. Unstimulated intracellular O(2)(-) production by kidney phagocytes was significantly elevated (compared to control) in medaka exposed for 1d to either thermal stress alone or temperature change in combination with Ni; by 7d, only the stressor combination significantly increased baseline O(2)(-) production. Resting levels of extracellular O(2)(-) production was significantly reduced in fish maintained for 1d at the elevated temperature. Effects on phorbol 12-myristate 13 acetate (PMA)-stimulated intracellular and extracellular O(2)(-) production were less dramatic than those observed for resting phagocytes. Exposure of medaka to elevated temperature for 14d tended (p<0.06) to reduce PMA-stimulated intracellular O(2)(-) production (compared to the time-matched control). Although exposure of fish for 14d to elevated temperature only slightly reduced stimulated extracellular O(2)(-) production, exposure for the same duration to Ni alone significantly depressed oxyradical production by kidney phagocytes (compared to the time-matched controls). Decreased plasma cortisol levels were observed in fish exposed for 7d to either an elevated water temperature or Ni (compared to the time-matched control); by 14d of exposure, no significant treatment-induced effects on cortisol levels were observed. These findings add to the growing body of literature seeking to determine what effects, if any, exposure to multiple aquatic pollution-induced effects have upon fish health and the health of impacted ecosystems.

Animals↗
PubMed2006

Severe pulmonary disease due to multisystemic eosinophilic epitheliotropic disease in a horse.

Multisystemic eosinophilic epitheliotropic disease was diagnosed histologically in a 17-year-old Quarter Horse intact mare that was presented with a chronic history of respiratory distress. At necropsy, the lungs were poorly collapsed and the pulmonary parenchyma contained innumerable, discrete, spherical nodules in a miliary pattern. A few similar nodules were scattered in the liver and the renal lymph nodes. Histologically, these nodules consisted of fibrosing eosinophilic granulomas. Based on histologic findings and the absence of an etiologic agent, a diagnosis of multisystemic eosinophilic epitheliotropic disease was made.

Animals↗
PubMed2005

Predictors of operative death after oesophagectomy for carcinoma.

BACKGROUND: Oesophagectomy for carcinoma provides a chance of cure but carries significant risk. This study defined risk factors for death after oesophageal resection for malignant disease. METHODS: Between 1990 and 2003, 773 oesophagectomies for oesophageal cancer were performed. Continuous variables were categorized into quartiles for analysis. Predictors of operative mortality were identified by univariate and multiple logistic regression analysis. RESULTS: The operative mortality rate was 4.8 per cent (37 of 773). In univariate analysis, advanced age, reduced forced expiratory volume in 1 s (FEV1), reduced forced vital capacity, presence of diabetes and tumour located in the upper third of the oesophagus were associated with a higher mortality rate. Multivariate analysis identified age (highest relative to lowest quartile, odds ratio (OR) 4.87 (95 per cent confidence interval (c.i.) 1.35 to 17.55); P = 0.009), tumour position (upper third relative to other locations, OR 4.23 (95 per cent c.i. 1.06 to 16.86); P = 0.041) and FEV1 (lowest relative to highest quartile, OR 4.72 (95 per cent c.i. 1.01 to 21.99); P = 0.018) as independent predictors of death. CONCLUSION: Advanced age, impaired preoperative respiratory function and a tumour high in the oesophagus are associated with a significantly increased risk of death after oesophagectomy for carcinoma.

Adult↗
PubMed2004

New approaches to enhance the accuracy of the diagnosis of reflux disease.

The accuracy of symptoms in diagnosing gastro-oesophageal reflux disease (GORD) is complicated by the lack of a gold standard test. Statistical techniques such as latent class and Bayesian analyses can estimate accuracy of symptoms without a gold standard. Both techniques require three independent diagnostic tests. Latent class analysis makes no assumptions about the performance of the tests. Bayesian analysis is useful when the accuracy of the other tests is known. These statistical techniques should be used in the future to validate GORD symptom questionnaires comparing them with endoscopy, oesophageal pH monitoring, and response to proton pump inhibitor therapy. Studies that evaluate GORD symptoms are usually done in secondary care. The prevalence of GORD in primary care will be lower and this reduces the positive predictive value of symptoms. There will be some bias in the type of patient referred for diagnosis and this usually decreases the specificity of symptom diagnosis.

Bayes Theorem↗
PubMed2003

Progressive nonfluent aphasia and subsequent aphasic dementia associated with atypical progressive supranuclear palsy pathology.

We describe a right-handed man who developed progressive nonfluent aphasia and apraxia of speech beginning at age 71. By age 74 he had behavioral changes, aphasic dementia, as well as mild parkinsonism; extraocular movements were normal except for mild limitation of upgaze. Serial neuropsychometric testing and single photon emission computed tomography (SPECT) scans showed progressive changes reflecting left>right cerebral hemisphere dysfunction. Neuropathologic examination revealed findings characteristic of progressive supranuclear palsy (PSP) except that the cortical pathology was more widespread than is typical of PSP. We conclude that the clinical manifestations in this case were more similar to the syndrome of progressive nonfluent aphasia with subsequent aphasic dementia and mild parkinsonism, rather than those of PSP. Hence, PSP can present clinically as an atypical dementing syndrome dominated by progressive aphasia/apraxia of speech.

Aged↗
PubMed2001

Rigorous new approach to constructing a gold standard for validating new diagnostic criteria, as exemplified by the eosinophilia-myalgia syndrome.

BACKGROUND: Constructing diagnostic criteria, a common problem in clinical medicine, is particularly difficult for diseases that lack a pathognomonic "gold standard." To develop an improved strategy for constructing such criteria, we used the eosinophilia-myalgia syndrome as an example. The goal, for research classifications, was to construct validated clinically sensible criteria and to develop improved methods that can be used for other disorders. METHODS: Using a "pattern-based" approach with data from several separate sources, a committee of investigators first prepared and informally tested criteria for the diagnosis of eosinophilia-myalgia syndrome. A gold standard challenge set of reports of cases and noncases was independently generated and separately validated by an external panel of clinical experts. The criteria were then tested using the gold standard set, and interobserver variability and diagnostic accuracy were determined. RESULTS: Interobserver variability showed the following mean proportionate agreements: 98.7% for the presence of specific criteria elements, 99% to 100% for diagnosis, and 97% to 98% for diagnostic pattern. kappa Values were correspondingly high. Diagnostic accuracy showed sensitivity at 88%, specificity at 97%, and overall accuracy at 92%. CONCLUSIONS: The proposed criteria are accurate and reproducible, and can be used in future clinical investigations of the eosinophilia-myalgia syndrome. The new strategy and methods developed for this challenge can be valuable for solving analogous problems in constructing criteria for other clinical disorders.

Diagnostic Techniques and Procedures↗
PubMed2001

Antibiotic use in Ontario facilities that provide chronic care.

OBJECTIVE: To determine the incidence and variability of antibiotic use in facilities which provide chronic care and to determine how often clinical criteria for infection are met when antibiotics are prescribed in these facilities. DESIGN: A prospective, 12-month, observational cohort study. SETTING: Twenty-two facilities which provide chronic care in southwestern Ontario. PARTICIPANTS: Patients who were treated with systemic antibiotics over the study period. MEASUREMENTS: Characteristics of antibiotic prescriptions (name, dose, duration, and indication) and clinical features of randomly selected patients who were treated with antibiotics. RESULTS: A total of 9,373 courses of antibiotics were prescribed for 2,408 patients (66% of all patients in study facilities). The incidence of antibiotic prescriptions in the facilities ranged from 2.9 to 13.9 antibiotic courses per 1,000 patient-days. Thirty-six percent of antibiotics were prescribed for respiratory tract infections, 33% for urinary infections, and 13% for skin and soft tissue infections. Standardized surveillance definitions of infection were met in 49% of the 1,602 randomly selected patients who were prescribed antibiotics. Diagnostic criteria for respiratory, urinary, and skin infection were met in 58%, 28%, and 65% of prescriptions, respectively. One third of antibiotic prescriptions for a urinary indication were for asymptomatic bacteriuria. Adverse reactions were noted in 6% of prescriptions for respiratory and urinary infections and 4% of prescriptions for skin infection. CONCLUSIONS: Antibiotic use is frequent and highly variable amongst patients who receive chronic care. Reducing antibiotic prescriptions for asymptomatic bacteriuria represents an important way to optimize antibiotic use in this population.

Aged↗
PubMed2001

Life-sustaining treatment and assisted death choices in depressed older patients.

OBJECTIVES: The major purpose of this study was to examine the effect of depressed mood in older, medically ill, hospitalized patients on their preferences regarding life-sustaining treatments, physician-assisted suicide (PAS), and euthanasia and to determine the degree to which financial constraints affected their choices. DESIGN: Cross-sectional study. SETTING: General medical hospital. PARTICIPANTS: One hundred fifty-eight medically hospitalized, nondemented patients age 60 or older, mean age 74.1 (range 60-94). The sample was divided, based on Center for Epidemiologic Studies-Depression (CES-D) scores, into a depressed group (n = 71) and a nondepressed control group. MEASUREMENTS: Subjects underwent a structured interview evaluating their life-sustaining treatment choices and whether they would accept or refuse PAS or euthanasia under a variety of hypothetical conditions. These choices were reevaluated with the introduction of financial impact. In addition, assessment included measures of depression, suicide, cognition, social support, functioning, and religiosity. RESULTS: Depression was found to be highly associated with acceptance of PAS and euthanasia in most hypothetical clinical scenarios in addition to patients' current condition. Compared with nondepressed people, depressed respondents were 13 times as likely to accept PAS when considering their current condition (95% confidence interval [CI] 1.68-110.98), and over twice as likely to accept PAS when facing a hypothetical terminal illness or coma. Depression alone was weakly associated with life-sustaining treatment choices but, when financial impact was introduced, significantly more depressed subjects refused treatment options they had previously desired than did nondepressed subjects. The presence of suicidal ideation, even passive ideation, was strongly predictive of life-sustaining treatment refusals and increased interest in PAS and euthanasia. Depression's effect on acceptance of PAS was confirmed by logistic regression, which also showed that religious coping was significantly correlated with less interest in PAS in two hypothetical scenarios. CONCLUSION. Depressed subjects and even subjects with subtle, passive suicidal ideation were markedly more interested in PAS and euthanasia than nondepressed subjects in hypothetical situations. Depressed subjects were also particularly vulnerable to rejecting treatments if financial consequences might have resulted.

Activities of Daily Living↗
PubMed2001

Concurrent opioid dependence and mental health problems: a review of the issues for general practice.

The literature is reviewed on the issue of concurrent opioid dependence and mental health problems within the general practice setting. People with such problems have poorer personal, clinical and social outcomes than people with either mental health or drug and alcohol (D&A) problems alone. Mental health and drug services operate from different policy systems and are generally not co-ordinated with each other, leaving the onus on the patient to move effectively through health systems. The common statement that GPs are ideal health professionals to manage concurrent problems is contrasted with the evident barriers in general practice such as lack of time, knowledge, skills and confidence. Models for managing concurrent problems tend towards shared care. However, these models either have received mixed evidence (e.g. consultant-liaison psychiatry) or are amenable to development but remain untested (e.g. co-ordinated care, community health centre programs). The Enhanced Primary Care items introduced in 1999/2000 may provide an incentive for GPs to participate in shared care arrangements with other health professionals. However, there is a need for mechanisms to increase the links between GPs and other health services.

Australia↗
PubMed2001

The dimensions of service quality for hospitals: development and use of the KQCAH scale.

Using a combination of qualitative and quantitative research methodologies, this study identifies the dimensions of hospital service quality, operationalizes the dimensions, and develops an instrument to measure patient satisfaction. This instrument, the Key Quality Characteristics Assessment for Hospitals (KQCAH) scale, was developed using input from 12 hospital administrators, over 100 hospital employees, and 23 recent patients and family members.

Attitude of Health Personnel↗
PubMed2000

Genetic modification of survival in tissue-specific knockout mice with mitochondrial cardiomyopathy.

We recently described a mouse model that reproduces important pathophysiological features of mitochondrial DNA (mtDNA) mutation diseases. The gene for mouse mitochondrial transcription factor A, Tfam (also called mtTFA), a nucleus-encoded key regulator of mtDNA expression, was targeted with loxP sites (Tfam(loxP)) and disrupted in vivo by transgenic expression of cre-recombinase from the muscle creatinine kinase (Ckmm) promoter. This promoter is active from embryonic day 13, and the knockouts had normal respiratory chain function in the heart at birth and developed mitochondrial cardiomyopathy postnatally. In this paper, we describe a heart-knockout strain obtained by mating Tfam(loxP) mice to animals expressing cre-recombinase from the alpha-myosin heavy chain (Myhca) promoter. This promoter is active from embryonic day 8, and the knockouts had onset of mitochondrial cardiomyopathy during embryogenesis. The age of onset of cardiac respiratory chain dysfunction can thus be controlled by temporal regulation of cre-recombinase expression. Further characterization demonstrated that approximately 75% of the knockouts died in the neonatal period, whereas, surprisingly, approximately 25% survived for several months before dying from dilated cardiomyopathy with atrioventricular heart conduction blocks. Modifying gene(s) affect the life span of the knockouts, because approximately 95% of the knockout offspring from an intercross of the longer-living knockouts survived the neonatal period. Thus, the tissue-specific knockouts we describe here not only reproduce important pathophysiological features of mitochondrial cardiomyopathy but also provide a powerful system by which to identify modifying genes of potential therapeutic value.

Animals↗
PubMed2000

Apathy in neurologic disorders.

Recent research has greatly increased our understanding of the clinical phenomenology and etiology of apathy as a distinct clinical symptom and syndrome. Several rating scales have been developed that assist in making a diagnosis of apathy. Apathy has received increasing attention as an important source of functional disability that should be considered when assessing and treating patients with neurologic disease.

Affect↗
PubMed2000

Antiphospholipid syndrome and perioperative hemostatic management of cardiac valvular surgery.

Hemostatic aspects of antiphospholipid syndrome (APS) present unique challenges to clinicians and laboratory personnel alike, particularly in the perioperative period. These challenges are especially evident in patients requiring cardiac valve replacement surgery. However, the literature outlining the optimal approach in such patients is limited. We present the case of a 25-year-old woman with severe aortic regurgitation as a result of APS with particular reference to the precautions necessary during perioperative care. Particularly important are the prevention of thrombotic or hemorrhagic complications, management of associated thrombocytopenia, and laboratory methods of perioperative anticoagulation monitoring in the setting of prolonged clotting times.

Adult↗