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Biomedical subjects

J Doherty

Publications and source records attributed to J Doherty.

At least 19 recordsLinked to original sources
PubMed2005

Implications for anaesthesia in a patient established on clozapine treatment.

Clozapine is an atypical antipsychotic agent with a novel pharmacological profile and multiple clinical properties. Because of its side effects, it is recommended in treatment of severe resistant schizophrenia for which purpose it is remarkably effective. Little is known about the safety profile of clozapine during pregnancy and labour and because it is now used more commonly to manage schizophrenia, it is important that we as anaesthetists are aware of its many interactions and potential side effects. We present a case of a successful emergency caesarean section in a schizophrenic patient on clozapine treatment.

Adult↗
PubMed2003

[A guideline for guidelines--methodological report and use of the guideline women's information].

UNLABELLED: Information and education is needed to empower autonomy and self-determination of patients (informed consent). Furthermore reliable and accurate medical information is necessary for patients who want to take an active part in medical decision-making. The aim of this work is to define the requirements helping to assure the development of good qualified information material relevant for women and female patients as "a guideline on women information". An example of its use is given by embeding this guideline in the guideline for early detection of breast cancer in Germany by defining the specific elements required for developing qualified information on this issue for women. METHODS: A systematic, stepwise methodological process according to a level two guideline of the German Association of the Scientific Medical Societies (AWMF) and the Agency for Quality in Medicine (AZQ) was performed with the following elements: 1. Establishing an expert panel, 2. Generating the guideline statements by a formal, consensus based nominal group process, 3. External review process and finding supportive partners for the guideline on women information, 4. Using the guideline for guidelines: implementing the concept in the guideline of early detection of breast cancer in Germany. RESULTS: The "guideline women information" comprises nine elements of quality assuring requirements for the development of gender-specific information material and eleven specific elements which directly relate to the guideline statements on early detection of breast cancer. After external review 30 organisations gave their written support for future implementation of the guideline. The "guideline women information" was integrated as a tool for quality assurance of lay information into the "guideline for early detection of breast cancer in Germany". CONCLUSION: The "guideline women information" is a systematically developed, consensus-based recommendation to improve the development of qualified lay information at the point of its process by defining gender-specific aspects required for good lay information and its evaluation. As a guideline for guidelines its use is demonstrated by integrating this guideline into the "guideline for early detection of breast cancer in Germany" to ensure the development of qualified guideline compliant information.

Breast Neoplasms↗
PubMed2003

Physician diagnosed asthma, respiratory symptoms, and associations with workplace tasks among radiographers in Ontario, Canada.

BACKGROUND: Medical radiation technologists (MRTs) or radiographers have potential exposure to chemicals including sensitisers and irritants such as glutaraldehyde, formaldehyde, sulphur dioxide, and acetic acid. AIMS: To determine the prevalence of asthma and work related respiratory symptoms among MRTs compared with physiotherapists, and to identify work related factors in the darkroom environment that are associated with these outcomes. METHODS: As part of a two component study, we undertook a questionnaire mail survey of the members of the professional associations of MRTs and physiotherapists in Ontario, Canada, to ascertain the prevalence of physician diagnosed asthma, and the prevalence in the past 12 months of three or more of the nine respiratory symptoms (previously validated by Venables et al to be sensitive and specific for the presence of self reported asthma). Information on exposure factors during the past 12 months, such as ventilation conditions, processor leaks, cleanup activities, and use of personal protective equipment was also collected. RESULTS: The survey response rate was 63.9% among MRTs and 63.1% among physiotherapists. Most analyses were confined to 1110 MRTs and 1523 physiotherapists who never smoked. The prevalence of new onset asthma (since starting in the profession) was greater among never smoking MRTs than physiotherapists (6.4% v 3.95%), and this differed across gender: it was 30% greater among females but fivefold greater among males. Compared with physiotherapists, the prevalence of reporting three or more respiratory symptoms, two or more work related, and three or more work related respiratory symptoms in the past 12 months was more frequent among MRTs, with odds ratios (ORs) (and 95% confidence intervals) adjusted for age, gender, and childhood asthma, of 1.9 (1.5 to 2.3), 3.7 (2.6 to 5.3), and 3.2 (2.0 to 5.0), respectively. Analyses examining latex glove use indicated that this was not likely to account for these differences. Among MRTs, respiratory symptoms were associated with a number of workplace and exposure factors likely to generate aerosol or chemical exposures such as processors not having local ventilation, adjusted OR 2.0 (1.4 to 3.0); leaking processor in which clean up was delayed, 2.4 (1.6 to 3.5); floor drain clogged, 2.0 (1.2 to 3.2); freeing a film jam, 2.9 (1.8 to 4.8); unblocking a blocked processor drain, 2.4 (1.6 to 3.7); and cleaning up processor chemical spill, 2.8 (1.9 to 4.2). These outcomes were not associated with routine tasks unlikely to generate exposures, such as working outside primary workplace, loading film into processor, routine cleaning of processors, or removing processed film. Males reported that they carried out a number of tasks potentially associated with irritant exposures more frequently than females, consistent with the marked increase in risk for new onset asthma. CONCLUSIONS: These findings suggest an increase of work related asthma and respiratory symptoms shown to denote asthma among MRTs, which is consistent with previous surveys. The mechanism is not known but appears to be linked with workplace factors and may involve a role for irritant exposures.

Adult↗
PubMed2002

Weight loss and malnutrition in patients with chronic graft-versus-host disease.

It is well known that weight loss occurs in patients with chronic graft-versus-host disease. However, the severity and frequency of weight loss in this population have not been adequately described. Recent data suggest that a body-mass index (BMI) below 21.9 is an independent risk factor for mortality. In our analysis we have shown that out of 93 patients with cGVHD, 43% are malnourished as evidenced by a BMI less than 21.9 and 14% are severely malnourished (BMI less than 18.5). In addition, there is a clear trend showing that patients with active, ongoing cGVHD have lower BMIs (P = 0.02). Furthermore, we show that many symptoms thought to contribute to weight loss in patients with cGVHD, such as odynophagia and oral sensitivity, are not related to weight loss in our population. We conclude that, in all likelihood, unknown causes still exist that are responsible for weight loss in this group of patients. Elevated resting energy expenditure and elevated serum tumor necrosis factor-alpha are potential contributors to weight loss that will be tested in future studies. We also conclude that treating cGVHD aggressively may help reverse weight loss and malnutrition, which may be independent risk factors for mortality in this population.

Adolescent↗
PubMed2001

Reduced excitatory drive onto interneurons in the dentate gyrus after status epilepticus.

Impaired GABAergic inhibition may contribute to the development of hyperexcitability in epilepsy. We used the pilocarpine model of epilepsy to demonstrate that regulation of excitatory synaptic drive onto GABAergic interneurons is impaired during epileptogenesis. Synaptic input from granule cells (GCs), perforant path, and CA3 inputs onto hilar border interneurons of the dentate gyrus were examined in rat hippocampal slices during the latent period (1-8 d) after induction of status epilepticus (SE). Short-term depression (STD) of GC inputs to interneurons induced by brief (500-800 msec), repetitive (5-20 Hz) stimulation, as well as paired-pulse depression at both GC and CA3 inputs to interneurons, were significantly (p < 0.05) enhanced in SE-experienced rats. In contrast, we found no significant differences between SE-experienced and age-matched control rats in the properties of minimal EPSCs evoked at low frequency (0.3 Hz). Consistent with reduced GABAergic inhibition onto granule cells, paired-pulse depression of perforant path-evoked granule cell population spikes was lost in SE-experienced rats. Enhanced STD was partially mediated by group II metabotropic glutamate receptors, because the selective antagonist, 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid, attenuated STD in SE-experienced rats but had no effect on STD of GC inputs in the normal adult rat. The group II mGluR agonist, (2S',1R',2R',3R')-2-(2,3-dicarboxylcyclopropyl) glycine (1 micrometer), produced a greater depression of GC input to hilar border interneurons in SE-experienced rats than in controls. These results indicate that, in the SE-experienced rat, excitatory drive to hilar border inhibitory interneurons is weakened through a use-dependent mechanism involving group II metabotropic glutamate receptors.

Action Potentials↗
PubMed2001

Development of a prognostic model for grading chronic graft-versus-host disease.

The disease-specific survival (DSS) of 151 patients with chronic graft-versus-host disease (cGVHD) was studied in an attempt to stratify patients into risk groups and to form a basis for a new grading of cGVHD. The data included the outcome and 23 variables at the diagnosis of cGVHD and at the primary treatment failure (PTF). Eighty-nine patients (58%) failed primary therapy for cGVHD. Nonrelapse mortality was 44% after a median follow-up of 7.8 years. The probability of DSS at 10 years after diagnosis of cGVHD (DSS1) and after PTF (DSS2) was 51% (95% confidence interval [CI] = 39%, 60%) and 38% (95% CI = 28%, 49%), respectively. According to multivariate analysis, extensive skin involvement (ESI) more than 50% of body surface area; hazard ratio (HR) of 7.0 (95% CI = 3.6-13.4), thrombocytopenia (TP) (< 100 000/microL; HR, 3.6; 95% CI = 1.9-6.8), and progressive-type onset (PTO) (HR, 1.7; 95% CI = 0.9-3.0) significantly influenced DSS1. These 3 factors and Karnofsky Performance Score of less than 50% at PTF were significant predictors for DSS2. The DSS1 at 10 years for patients with prognostic factor score (PFS) at diagnosis of 0 (none), 1.9 and below [corrected] (ESI only or TP and/or PTO), above 1.9 and not above 3.5 [corrected] (ESI plus either TP or PTO), and more than 3.5 (all 3 factors) was 82%, 68%, 34%, and 3% (P =.05, <.001, <.001), respectively. The DSS2 at 5 years for patients with PFS at PTF of 0, 2 or less, 2 to 3.5, and more than 3.5 were 91%, 71%, 22%, and 4% (P =.2,.005, and <.001), respectively. It was concluded that these prognostic models might be useful in grouping the patients with similar outcome.

Actuarial Analysis↗
PubMed2000

Evoked epileptiform discharges in the rat anterior piriform cortex: generation and local propagation.

The purpose of this study was to identify cellular and synaptic properties of neurons in a small region within the anterior piriform cortex (aPC), termed the area tempestas (AT), responsible for triggering forebrain seizures in rats. Using a brain slice preparation, we performed whole-cell patch recordings from neurons in the regions overlapping the functionally defined AT. Local electrical stimulation activated synaptic inputs to neurons in these regions, collectively termed the deep aPC (daPC). Synaptic inputs were blocked by selective ionotropic glutamate receptor antagonists. Excitatory bursts were evoked from 59% of daPC neurons as the stimulus intensity was raised above a precise threshold. Secondary bursts (6-15 Hz) occurred in 34% of daPC neurons. Evoked bursts were synaptically driven, as they were blocked by TTX (1 microM) or 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX, 1 microM), but not by inclusion of cesium and N-(2, 6-dimethylphenylcarbamoylmethyl) triethylammonium (QX-314) in the internal patch solution. Neither augmentation of excitatory nor suppression of inhibitory transmission were required to evoke bursts from daPC neurons. However, bicuculline (20 microM) lowered the threshold intensity for evoking discharges and increased the incidence and duration of evoked bursts, indicating active inhibitory control of daPC neurons. Stimulation in the daPC evoked epileptiform field potentials from layer II of the adjacent PC and bursts from layer II pyramidal neurons. This work demonstrates that synaptically dependent excitatory burst discharges can be evoked from daPC neurons without altering the balance between synaptic excitation and inhibition. Stimuli that trigger bursts in daPC neurons also generate epileptiform activity in layer II pyramidal cells, indicating that propagation of excitatory activity triggered from the daPC to the pyramidal neurons of the aPC can contribute to the initiation of seizures induced by disinhibition of the AT in vivo.

Animals↗
PubMed1999

Middle T antigen activation of signal transduction pathways does not overcome p53-mediated growth arrest.

Polyomavirus middle T antigen does not overcome p53-mediated G(1) arrest in mouse embryo fibroblasts. Middle T antigen still associates with the signaling molecules phosphatidylinositol 3-kinase and SHC and activates the transcriptional activity of c-Myc and AP1 in p53-arrested cells. Examination of cell cycle regulatory proteins indicated that p53 does not interfere with these mitogenic signals but acts later in the G(1) phase of the cell cycle.

Activating Transcription Factor 4↗
PubMed1999

Health expenditure and finance: who gets what?

The methods used in South Africa's first comprehensive review of health finance and expenditure are outlined. Special measures were adopted to make the process acceptable to all concerned during a period of profound political transition. The estimation of indicators of access to public sector resources for districts sorted by per capita income allowed the health care problems of disadvantaged communities to be highlighted.

Costs and Cost Analysis↗
PubMed1999

Using administrative data to compare the relative effectiveness of amlodipine vs nifedipine CC.

OBJECTIVE: To describe an approach for using claims data to compare the effectiveness of 2 similar drugs used for similar indications within a health maintenance organization. STUDY DESIGN: A database study comparing the effectiveness of amlodipine and nifedipine CC in the initial treatment of hypertension. PATIENTS AND METHODS: The claims records of Pennsylvania Medicaid patients between 18 and 64 years of age with continuous eligibility in 1994 were studied. Pharmacy, hospital, and outpatient claims data were merged, and adult patients receiving the target drugs for the specified indication were identified. The effectiveness of the 2 agents used were compared based on the concept that a change in dispensed medication suggested either an adverse event or lack of effectiveness. Adherence rates, adverse events, and pharmacy and nonpharmacy costs associated with the 2 agents were also compared. RESULTS: Patients receiving amlodipine and nifedipine CC as initial treatment for hypertension had similar demographic characteristics and numbers of comorbid conditions. More patients started on nifedipine CC switched to another calcium channel blocker (15.8% for nifedipine CC vs 10.3% for amlodipine). More patients started on amlodipine switched to another class of antihypertensive agent (13.2% for amlodipine vs 7.3% for nifedipine CC). Patients in both groups received adjunctive antihypertensive drugs at a similar frequency (35% for nifedipine CC vs 42%, for amlodipine). Rates of adherence were similar. In adherent patients, there was no difference in rates of reported adverse events. The nonpharmacy costs were similar between groups. Patients in the amlodipine group also had a trend toward higher overall pharmacy charges (all medications) and higher charges for antihypertensive medications other than the study drugs ($302 vs $188, P = .054). CONCLUSIONS: Claims data are often the best available evidence for comparing the effectiveness of pharmaceuticals in real clinical practice. While these comparisons have inherent limitations, the accuracy of the assessment can be maximized by limiting the assessment to agents with the same specific indications. Other important elements include comparison of crossover rates to other pharmaceuticals in the same class; rates of addition of other pharmaceuticals in the same class, adherence, adverse events, and overall healthcare charges.

Adult↗
PubMed1998

Differential regulation of synaptic inputs to dentate hilar border interneurons by metabotropic glutamate receptors.

Regulation of synaptic transmission by metabotropic glutamate receptors (mGluRs) was examined at two excitatory inputs to interneurons with cell bodies at the granule cell-hilus border in hippocampal slices taken from neonatal rats. Subgroup-selective mGluR agonists altered the reliability, or probability of transmitter release, of evoked minimal excitatory synaptic inputs and decreased the amplitudes of excitatory postsynaptic currents (EPSCs) evoked with conventional stimulation. The group II-selective agonist, (2S,1R',2R',3R')-2-(2, 3-dicarboxylcyclopropyl) glycine (DCG-IV; 1 microM), reversibly depressed the reliability of EPSCs evoked by stimulation of the dentate granule cell layer. However, DCG-IV had no significant effect on EPSCs evoked by CA3 stimulation in the majority (82%) of hilar border interneurons. Both the group III-selective agonist, -(+)-2-amino-4-phosphonobutyric acid (-AP4; 3 microM), and the group I-selective agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG; 20 microM) reversibly depressed synaptic input to interneurons from both CA3 and the granule cell layer. We conclude that multiple pharmacologically distinct mGluRs presynaptically regulate synaptic transmission at two excitatory inputs to hilar border interneurons. Further, the degree of mGluR-meditated depression of excitatory drive is greater at synapses from dentate granule cells onto interneurons than at synapses from CA3 pyramidal cells.

Animals↗
PubMed1998

The cost implications of participatory research. Experience of a health services review in a rural region in South Africa

OBJECTIVES: The study objectives were to estimate the total costs incurred by a comprehensive review of primary health care services in a rural region in South Africa, and to determine which of these costs were incurred because of the participatory research techniques employed by the review. DESIGN: The costing study estimated the direct and indirect costs of each component of the review in order to determine total costs. Costs that were linked to participatory research activities were aggregated separately. SETTING: The review that was costed was conducted in an area that included the former 'homeland' KaNgwane and the adjacent areas of 'white' South Africa, in part of what is now known as Mpumalanga Province. SUBJECTS: Not relevant. OUTCOME MEASURES: Direct, indirect, total, research and participation costs were used as outcome measures. RESULTS: Expenditure generated by participatory research techniques was estimated to be almost 14% of the total (direct and indirect) costs. CONCLUSIONS: Despite these costs, participatory research techniques are invaluable in terms of the many benefits they have for a research project. However, because of these costs, it is important that the financing of participatory research should be carefully planned. Projects must budget for the direct costs of participatory techniques, participating organisations and individuals must be committed to bearing the indirect costs of participation, and, increasingly, funders must consider funding these indirect costs. This is important in the South African situation, where public health research relies increasingly on the participation of relevant stakeholders.

Journal Article↗
PubMed1998

Evaluation of rural ambulance services.

The evaluation of ambulance services in a rural area of South Africa is described. The approach is affordable and could be applied in other countries. As well as providing valuable information it involves health workers in planning, motivates them to improve service delivery, and lends support to their requests for increased resources.

Ambulances↗