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Biomedical subjects

C A Kelly

Publications and source records attributed to C A Kelly.

At least 37 records · Page 2Linked to original sources
PubMed2001

Interstitial lung disease in patients with rheumatoid arthritis: a comparison with cryptogenic fibrosing alveolitis.

OBJECTIVES: There is a lack of information on the natural history of patients with rheumatoid arthritis (RA) and associated interstitial lung disease (ILD). However, cryptogenic fibrosing alveolitis (CFA) is known to have a poor long-term prognosis. As part of a longitudinal prospective study, we compared baseline characteristics in 18 patients with RA-ILD and 18 patients with CFA matched for age, sex and symptoms. We wished to establish whether there were significant baseline differences in clinical, physiological or radiological parameters. METHODS: A diagnosis of ILD was confirmed by high-resolution computed tomography (HRCT) and supported by clinical and physiological findings in all patients. A number of clinical, immunological, physiological and radiological parameters were compared between the two groups. The median age in each group was 77 yr and 10 patients in each group were male. RESULTS: Twelve of the RA patients had smoked in excess of 10 pack yr as compared with nine patients with CFA (not significant). Clubbing was found in five patients with RA-ILD and in 14 with CFA (P=0.008). Pulmonary function tests showed no significant differences between the groups in forced expiratory volume in 1s, vital capacity or gas transfer factor. HRCT showed more ground glass shadowing and peripheral disease in RA patients, but more established basal disease in those with CFA. Additionally, HRCT evidence of honeycombing was associated with an absence of rheumatoid factor and a low gas transfer factor. CONCLUSIONS: Clubbing is more common in patients with CFA, while RA-ILD patients have a higher prevalence of rheumatoid factor. Together with the differences in baseline HRCT, these variables in two groups of patients with similar physiological impairment at baseline may be important predictors of outcome in the longer term.

Aged↗
PubMed2000

Tuning charge recombination rate constants through inner-sphere coordination in a copper(I) donor-acceptor compound.

The coordination compounds [Cu(bpy-MV2+)(PPh3)2](PF6)3, where bpy-MV2+ is the 1-(4-(4'-methyl-2,2'-bipyridin-4-yl)butyl)-1'-methyl-4, 4'-bipyridinediium(2+) cation, and [Cu(dmb)(PPh3)2](PF6), where dmb is 4,4'-dimethyl-2,2'-bipyridine, have been prepared and characterized. Visible light (417 nm) excitation of [Cu(bpy-MV2+)(PPh3)2]3+ at room temperature leads to rapid intramolecular electron transfer, kcs > 1 x 10(8) s-1, to form a charge-separated state with an electron localized on the pendant viologen group and a copper(II) metal center, abbreviated [CuII-bpy-MV.+]. This state recombines to ground-state products with first-order rate constants that can be tuned with solvent over a approximately 10(7)-10(5) s-1 range. The activation parameters were determined from temperature-dependent electron-transfer data with Arrhenius analysis. A model is proposed wherein a solvent molecule is coordinated to Cu(II) in the charge-separated state, [(S)CuII-bpy-MV.+]. Visible light excitation of [Cu(dmb)(PPh3)2](PF6) in argon-saturated dichloromethane produces long-lived photoluminescent excited states, tau = 80 ns, that are dynamically quenched by the addition of Lewis basic solvents. The measured quenching constants each correlate well with the lifetime of the charge-separated state measured after excitation of [Cu(bpy-MV2+)(PPh3)2]3+ in the corresponding solvent.

Journal Article↗
PubMed2000

Dementia: the cost of care for behaviourally disturbed patients living in the community.

OBJECTIVE: To determine the cost of care of people with dementia and behavioural disturbances living in the community, which is currently unknown. DESIGN, SETTING & PATIENTS: This is a study of 12 randomly selected subjects attending a continuing care dementia day facility for people with behavioural disturbances. MEASURES: Hours of care received from different sources were recorded and costed. RESULTS: The total mean direct costs to the public services was pound400 per person per week. Caregiver's time costed at professional rates were pound1208 per person per week. CONCLUSIONS: Unpaid caregivers supported by publicly funded agencies provide a less expensive service compared to specialised institutional care.

Aged↗
PubMed2000

Thioridazine for dementia.

BACKGROUND: Neuroleptic drugs are controversial treatments in dementia, with evidence accumulating that they may hasten clinical decline. Despite these concerns, they are commonly prescribed for elderly and demented patients. Thioridazine, a phenothiazine neuroleptic, is one of the most commonly prescribed. It has often been a preferred agent because it is thought to produce relatively less frequent motor side effects. The drug has significant sedative effects, and it is thought that these are the main mechanism of action in calming and controlling the patient. However, pharmacologically, it also has marked anticholinergic properties that could potentially have a detrimental effect on cognitive function. OBJECTIVES: To determine the evidence on which the use of thioridazine in dementia is based in terms of: 1) efficacy in controlling symptoms 2) cognitive outcome for the patient 3) safety SEARCH STRATEGY: The Cochrane Controlled Trials Register and other electronic databases were searched using the terms 'thioridazine', 'melleril', 'dementia' and 'old age'. In addition, Novartis, the pharmaceutical company that developed and markets thioridazine, was approached and asked to release any published or unpublished data they had on file. SELECTION CRITERIA: Unconfounded, single-blind or double-blind, randomised trials were identified in which treatment with thioridazine was administered for more than one dose and compared to an alternative intervention in patients with dementia of any aetiology. Trials in which allocation to treatment or comparator were not truly random, or in which treatment allocation was not concealed were reviewed but are not included in the data analysis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers (VC, CAK and RJH). For continuous and ordinal variables, the main outcome measures of interest were the final assessment score and the change in score from baseline to the final assessment. The assessment scores were provided by behavioural rating scales, clinical global impression scales, functional assessment scales, psychometric test scores, and frequency and severity of adverse events. Data were pooled where appropriate or possible, and the Peto odds ratio (95%CI) or the weighted mean difference (95%CI) estimated. Where possible, intention to treat data were used. MAIN RESULTS: The meta-analysis showed that, compared with placebo, thioridazine reduced anxiety symptoms as evidenced by changes on the Hamilton Anxiety Scale. However, there was no significant effect on clinical global change, and a non-significant trend for higher adverse effects with thioridazine. Compared to diazepam, thioridazine was superior in terms of some anxiety symptoms, with similar adverse effects. Global clinical evaluation scales mostly did not favour either treatment. Compared to chlormethiazole, thioridazine was significantly inferior when assessed on some items of the CAPE and the Crichton Geriatric Behavioural Rating Scales. Thioridazine was also associated with significantly more dizziness. No superiority for thioridazine was shown in comparisons with etoperidone, loxapine or zuclopenthixol. REVIEWER'S CONCLUSIONS: Very limited data are available to support the use of thioridazine in the treatment of dementia. If thioridazine were not currently in widespread clinical use, there would be inadequate evidence to support its introduction. The only positive effect of thioridazine when compared to placebo is the reduction of anxiety. When compared to placebo, other neuroleptics, and other sedatives it has equal or higher rates of adverse effects. Clinicians should be aware that there is no evidence to support the use of thioridazine in dementia, and its use may expose patients to excess side effects.

Antipsychotic Agents↗
PubMed2000

The QUASIMEME laboratory performance study of polycyclic aromatic hydrocarbons (PAHs): assessment for the period 1996-1999. Quality Assurance of Information in Marine Environmental Monitoring in Europe.

The results of the laboratory performance studies held during the period 1996-99 and involving the determination of PAHs in sediments and biota have been assessed. Overall 67% of the data submitted met the QUASIMEME criterion for satisfactory performance, although differences in performance were apparent between the two main analytical techniques employed: gas chromatography and high-performance liquid chromatography. Further development of PAH methodology utilising coupled gas chromatography mass spectrometry is encouraged as the most appropriate means of meeting the future requirements for the determination of a wider range of PAH analytes. More reference materials are also urgently required for use in marine monitoring programmes, and they need to be certified for a wider range of PAHs than hitherto, including both parent PAHs and their alkylated derivatives.

Certification↗
PubMed2000

Association of antibiotic utilization measures and control of multiple-drug resistance in Klebsiella pneumoniae.

OBJECTIVE: To study the association of antibiotic-utilization measures and control of multidrug-resistant (MDR) Klebsiella pneumoniae after emergence in two hospitals in our medical center. DESIGN AND SETTING: Rates of MDR K. pneumoniae at two hospitals were compared before and after acute interventions, including emphasis on Contact Precautions and education in antibiotic utilization. Antipseudomonal beta-lactam antibiotic use was measured before and after the interventions at both hospitals. Pulsed-field gel electrophoresis of whole cell DNA was used as a marker of strain identity. RESULTS: Clonal strain dissemination was the major mechanism of emergence at hospital A; emergence was polyclonal at hospital B. Antibiotic-utilization interventions at both institutions included physician education regarding the association of ceftazidime use and MDR K. pneumoniae. At hospital A, ceftazidime use decreased from 4,301 g in the preintervention period, to 1,248 g in the postintervention period. Piperacillin-tazobactam use increased from 12,455 g to 17,464 g. Ceftazidime resistance in K. pneumoniae decreased from 110 (22%) of 503 isolates to 61 (15%) of 407 isolates (P<.05); piperacillin-tazobactam resistance decreased from 181 (36%) of 503 to 77 (19%) of 407 isolates (P<.05). At hospital B, ceftazidime use decreased from 6,533 g in the preintervention period to 4,792 g in the postintervention period. Piperacillin-tazobactam use increased from 58,691 g to 67,027 g. Ceftazidime resistance in K. pneumoniae decreased from 42 (10%) of 415 isolates to 19 (5%) of 383 isolates (P<.05). Piperacillin-tazobactam resistance decreased from 91 (22%) of 415 isolates to 54 (14%) of 383 isolates (P<.05). Follow-up data showed continued decrease in piperacillin-tazobactam resistance despite increased use at both hospitals. CONCLUSIONS: Antibiotic-use measures may be particularly important for control of MDR K. pneumoniae, whether emergence is clonal or polyclonal.

Anti-Bacterial Agents↗
PubMed2000

Ten year follow up of pulmonary function in patients with primary Sjögren's syndrome.

OBJECTIVES: To follow up a previous report on the lung function of patients with primary Sjögren's syndrome (SS), and describe the findings having followed up this cohort for a median duration of 10 years (range 8-12 years). METHODS: 30 patients fulfilling Fox's criteria for definite or probable primary SS were assessed within six months of diagnosis and after a median duration of four and then 10 years by a clinical examination, chest radiograph, and lung function studies (FEV(1), FVC, TLCO, and KCO). RESULTS: At baseline, symptomatic dyspnoea was a common finding, reported by 13/30 patients, of whom two had evidence of fibrosing alveolitis on plain chest radiograph. Five patients had a carbon monoxide transfer factor (TLCO) more than two standardised residuals below the predicted value. After four years' follow up two further patients developed radiological fibrotic changes and there were significant reductions in TLCO (p<0.02) and transfer coefficient (KCO) (p<0.02) compared with the baseline measurements. At 10 years' follow up four patients had died and four were lost to follow up. One patient with fibrosing alveolitis had died from chest disease. There were no further cases of pulmonary fibrosis identified on plain chest radiograph. The lung function studies showed no further deterioration from the results found at year four with significant improvements in both TLCO (p<0.001) and KCO (p<0.001). Those patients who were anti-Ro antibody positive had significantly lower transfer factors than patients with primary SS without this serological marker (p<0.02). CONCLUSION: This long term follow up of lung disease in primary SS is reassuring, and suggests that most patients do not develop progressive lung disease. Pulmonary disease occurs predominantly in anti-Ro antibody positive patients and presents early in the course of the disease.

Adult↗
PubMed1999

Primary Sjögren's syndrome in the North East of England: a long-term follow-up study.

OBJECTIVE: Although primary Sjogren's syndrome is often a benign condition, characterized by lymphocytic infiltration of salivary and lacrimal glands, some patients develop systemic features. We have previously found that anti-Ro antibodies identified patients with more systemic disease, with increased incidence of parotid swelling, lymphadenopathy and lymphoma. METHODS: We have followed up a cohort of 100 patients over 10 yr, to establish whether the phenotypic expression of disease changed, and whether the different autoantibody patterns expressed at presentation could be used to predict outcome. RESULTS: While seronegative patients (ANA, RF, Ro and La negative) remained polysymptomatic, they did not develop systemic complications or serological changes. Thirty-nine per cent of ANA- or RF-positive patients who were negative for Ro and La were given revised diagnoses over the follow-up period, including rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disease and scleroderma. Parotid swelling and lymphadenopathy were more common in Ro/La-positive patients, where the relative risk of developing non-Hodgkin's lymphoma was 49.7. CONCLUSION: Both HLA B8 and DR3 were present in 79% of Ro/La-positive patients, but were found together in only 4% of seronegative patients, supporting the view that these clinical subgroups of primary Sjogren's syndrome are both serologically and immunogenetically distinct. Patients who are initially autoantibody (including Ro and La) negative do not evolve into 'systemic' Sjogren's syndrome or other connective tissue diseases.

Adolescent↗
PubMed1998

Selective serotonin reuptake inhibitors and hyponatraemia: review and proposed mechanisms in the elderly.

The association between selective serotonin reuptake inhibitors (SSRIs) and hyponatraemia has been well documented, the elderly appearing to be at greatest risk. An analysis of data of hyponatraemia in the elderly using SSRIs from all published cases and from the Committee on Safety of Medicines found that the mean time to detection was about 3 weeks after commencing SSRIs. A wide range of time to detection (1-253 days) and non-specific symptoms suggest hyponatraemia is detected by chance rather than being specifically looked for. In the elderly there are physiological changes, a high prevalence of medical illnesses and concomitant drug use, which may precipitate hyponatraemia. Together with a risk of altered water regulation in psychiatric illness this may account for the particular susceptibility of the elderly to hyponatraemia whilst using SSRIs.

Aged↗
PubMed1996

Dose to contralateral breast: a comparison of four primary breast irradiation techniques.

PURPOSE: Contralateral breast dose from primary breast irradiation has been implicated in the risk of second breast malignancies. It has been previously shown that the use of half-beam blocking can increase the opposite breast dose by a factor of five. This study evaluates four different breast treatment techniques to compare the radiation dose to the contralateral breast. METHODS AND MATERIALS: Dose measurements were made using thermoluminescent dosimeters (TLD) capsules, which were placed in the Rando phantom in the following locations in the contralateral breast: seven along the central axis plane, on at 5 cm superior to, and one 5 cm inferior to the central axis plane. One TLD capsule was placed in the midcenter of the treated breast. The following radiation techniques were used: (a) half-beam with a custom block (HB+CB), (b) half-beam using asymmetric collimator jaw (HB/AJ), (c) half-beam using asymmetric collimator jaw with custom block (H/AJ+CB), and (d) isocentric technique with nondivergent posterior borders [Joint Center for Radiation Therapy (JCRT) techique]. For each technique, isodose distributions for the Rando phantom were optimized using (a) 15 degree medial and lateral compensating wedges, and (b) a single 30 degree lateral compensating wedge. The phantom was treated with 6 MV photons. Each technique was repeated six times, and the TLD readings were averaged. RESULTS: The custom cerrobend half-beam block technique gives the highest contralateral breast dose, regardless of wedge. The remaining techniques give results in a similar range, with the asymmetric jaw with no medial wedge technique giving the lowest total dose (p = not significant). The use of a medial wedge increases the opposite breast dose for all techniques. The asymmetric half-beam technique gives significantly less dose than the cerrobend half-beam technique, due to decreased transmission through the asymmetric collimators. The asymmetric jaw vs JCRT technique results in similar contralateral breast dose. CONCLUSIONS: As expected, dose to the contralateral breast increases with the use of a medial wedge. Cerrobend half-beam blocking gives the highest opposite breast dose. The lowest contralateral breast dose is with the asymmetric jaw with no medial wedge and no block. The asymmetric jaw technique with block yields equivalent contralateral breast doses to the JCRT technique.

Breast↗
PubMed1996

Whipple's disease presenting with lung involvement.

A 31 year old man presented with nonspecific symptoms and a chest radiograph showing several pulmonary nodules which rapidly enlarged. Bronchoscopic examination showed endobronchial lesions, histological examination of which led to the diagnosis of Whipple's disease. The patient made a gradual recovery with prolonged antibiotic therapy and the pulmonary lesions reduced in size. This is the first reported case of Whipple's disease presenting with large pulmonary nodules and endobronchial lesions and is notable for the absence of gastrointestinal features.

Adult↗
PubMed1996

Clearance rate of serum-free and total PSA following radical retropubic prostatectomy.

BACKGROUND: Our objective was to determine the clearance rate of free and total serum PSA following radical retropubic prostatectomy. METHODS: Sera were obtained from 10 men with localized prostate cancer prior to and 1, 4, 8, 24, 48, and 72 hr after radical prostatectomy. No patient received any postoperative blood transfusion. Free and total PSA were measured using the Hybritech Tandem-R (total PSA) and radioimmunometric free PSA assay. Postsurgery serum-free and total PSA concentrations were modeled using a "two-compartment" pharmacokinetic model. RESULTS: The pharmacokinetic model with an initial constant "infusion" suggests that, following release from the prostate, both free and total PSA are taken up into a second compartment for metabolism. The movement of PSA between these compartments was accurately modeled. Following surgery, there is a shift of both free and total PSA best modeled as a constant infusion into the serum at a rate of 1.97 and 1.60 ng/ml, respectively, for a period of approximately 1 hr. Following this initial constant infusion, the half-life estimations for free and total PSA are initially 1.2 and 0.75 hr, respectively, which then increase to 22 and 33 hr, respectively. CONCLUSIONS: Serum free and total PSA are cleared from the circulation following a "two-compartment" model with an initial constant "infusion." The constant "infusion" is most likely a consequence of surgical manipulation. The initial half-life estimates are < 2 hr for both free and total PSA, and later increase to 22 and 33 hr, respectively.

Aged↗
PubMed1995

Association of HLA-DR4, protease inhibitor phenotypes and keratoconjunctivitis sicca with pulmonary abnormalities in rheumatoid arthritis.

One-hundred rheumatoid arthritis (RA) patients were assessed for the association of HLA-DR4, protease inhibitor (Pi) phenotype and keratoconjunctivitis sicca (KCS) with a variety of clinical features, airflow obstruction and bronchial reactivity. Spirometry, lung volume and gas transfer factor measurements were performed to detect airflow obstruction. Bronchial reactivity to inhaled methacholine was assessed by measuring the provocative dose of methacholine causing a 20% fall in FEV1 from the baseline (PD20). Sixty-two patients were HLA-DR4 positive, 87 had Pi MM and 13 MS phenotypes and 37 had positive Schirmer's tear tests. Patients with KCS had a significantly increased history of wheeze (11/37 vs 7/63, P = 0.03, relative risk (RR) 1.8 [95% CI 1.04, 3.1]), those with HLA-DR4 had a significantly decreased atopy on skin-prick testing [3/62 vs 7/38, were significantly higher in the Pi MS group compared to Pi MM group. There was no significant association of HLA-DR4, Pi phenotype and KCS with bronchial reactivity. We conclude that there is no overall significant association of HLA-DR4, Pi phenotype and KCS with airflow obstruction and bronchial reactivity in RA.

Adult↗
PubMed1995

High resolution computed tomography of the lung in lifelong non-smoking patients with rheumatoid arthritis.

OBJECTIVES: To define pulmonary involvement on high resolution computed tomography (HRCT) of the thorax in lifelong non-smoking rheumatoid arthritis patients and to relate the results to pulmonary function, bronchial reactivity, and a variety of clinical and serological factors. METHODS: Twenty lifelong non-smoking RA patients (mean age 59 years (range 44-72; 18 females) were studied. Detailed medical and drug histories were taken. Protease inhibitor phenotype (Pi) and HLA-DR4 status were assessed. Schirmer's tear tests were performed to detect keratoconjunctivitis sicca (KCS). Spirometry, flow volume loops, and gas transfer factor measurement were recorded. The degree of bronchial reactivity (PC20 FEV1) was measured by a methacholine inhalation test. Chest and hand radiographs and HRCT of the lung were performed in all patients. RESULTS: Thirteen patients were HLA-DR4 positive. Eighteen had the Pi MM and two the Pi MS phenotype. Eight patients had evidence of KCS on Schirmer's tear testing. Ten patients achieved PC20 FEV1 in the methacholine inhalation test. All the patients had normal chest radiographs and all showed evidence of erosive arthropathy on hand radiographs. Five patients (25%) showed basal bronchiectasis and one mild interstitial lung disease on HRCT. All five patients with bronchiectasis had the Pi MM phenotype, four had HLA-DR4, four had KCS and three achieved PC20 FEV1; these values were not significantly different (p > 0.05) from those in patients without bronchiectasis. CONCLUSION: Using the highly sensitive technique of HRCT, we found evidence to suggest that the incidence of bronchiectasis in lifelong non-smoking RA patients may be much higher than previously reported.

Adult↗
PubMed1994

A single isocenter three-field breast irradiation technique using an empiric simulation and asymmetric collimator.

The treatment of abutting fields presents multiple difficulties, including problems of field overlaps or gaps, complexity of simulation, and the difficulties of daily setup and variation. Multiple techniques have been described for the treatment of the breast/chest wall and supraclavicular nodes using tangents and a matched supraclavicular field. The techniques described have used collimator angles, couch angles, and/or corner blocks in an attempt to match these fields with no overlap or gap. Some of these techniques required complex calculations or treatment devices to achieve a geometric match between fields. We describe a technique for treatment of breast and supraclavicular nodes that uses a single isocenter and requires asymmetric collimator jaws to give half-blocked fields. The simulation and setup are done empirically, with no complex calculations required. The daily setup and treatment can be done rapidly and reliably, with no extra equipment required. Custom blocks may be used to conform to the chest wall contour and decrease the amount of lung in the treatment fields.

Breast Neoplasms↗