Biomedical subjects

S Stewart

Publications and source records attributed to S Stewart.

At least 91 records · Page 5Linked to original sources

PubMed1999

Effects of a multidisciplinary, home-based intervention on unplanned readmissions and survival among patients with chronic congestive heart failure: a randomised controlled study.

BACKGROUND: Hospital admissions among patients with congestive heart failure (CHF) are a major contributor to health-care costs. Previous investigations suggest that the therapeutic efficacy of pharmacotherapy in CHF may be improved by strategies incorporating home visits to identify and address factors precipitating deterioration and resultant readmission. METHODS: Chronic CHF patients discharged home after acute hospital admission were randomly assigned usual care (n=100) or a multidisciplinary, home-based intervention (n=100), consisting of a home visit by a cardiac nurse 7-14 days after discharge. The primary endpoint of the study was frequency of unplanned readmission plus out-of-hospital death within 6 months. FINDINGS: During 6 months' follow-up there were 129 primary endpoint events in the usual-care group and 77 in the intervention group (p=0.02). More intervention-group than usual-care patients remained event-free (38 vs 51; p=0.04). Overall, there were fewer unplanned readmissions (68 vs 118; p=0.03) and associated days in hospital (460 vs 1173; p=0.02) among intervention-group patients. Hospital-based costs were Australian $490,300 for the intervention group and A$922,600 for the usual-care group (p=0.16); the mean cost of the intervention was A$350 per patient, and other community-based costs were similar for both groups. INTERPRETATION: A home-based intervention has the potential to decrease the rate of unplanned readmissions and associated health-care costs, prolong event-free and total survival, and improve quality of life among patients with chronic CHF.

Aged↗

PubMed1999

Hemodynamic effects of basal and stimulated release of endogenous nitric oxide in isolated human lungs.

Background-We compared the hemodynamic responses to inhibition or stimulation of endothelial nitric oxide (NO) release of isolated explanted lungs from transplantation recipients with pulmonary hypertension and in normotensive unallocated donor lungs. Methods and Results-Lungs from 10 patients with severe pulmonary hypertension (SPH) and from 16 patients with severe chronic obstructive lung disease (COLD) were studied. Fourteen normotensive lungs were studied as controls. The lungs were perfused at a constant flow. In protocol 1 N(G)-nitro-L-arginine methyl ester caused a similar rise in baseline pulmonary artery pressure (PAP) that was similar in SPH (+17.1+/-4.2 mm Hg; n=5), COLD (+15.5+/-4.8 mm Hg; n=8), and control lungs (+14.5+/-1.5 mm Hg; n=7). Arterial occlusion demonstrated that most of the changes with N(G)-nitro-L-arginine methyl ester were precapillary. The response to sodium nitroprusside (10(-8) to 10(-4) mol/L) was similar in all groups. In protocol 2, the lungs were preconstricted, and acetylcholine (10(-9) to 10(-5) mol/L) caused a lesser fall in PAP in both COLD and SPH lungs compared with control (-41.9+/-8.6%, -55. 7+/-7.6%, and -73.2+/-2.5%, respectively; P<0.05), whereas sodium nitroprusside (10(-5) mol/L) decreased PAP to initial levels in all lungs. Conclusions-Stimulated release of NO is impaired in arteries of lungs with plexogenic or hypoxemic pulmonary hypertension. In contrast, basal release of NO appears to be maintained.

Acetylcholine↗

PubMed1999

Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector.

The bacterial pathogen Yersinia uses a type III secretion system to inject several virulence factors into target cells. One of the Yersinia virulence factors, YopJ, was shown to bind directly to the superfamily of MAPK (mitogen-activated protein kinase) kinases (MKKs) blocking both phosphorylation and subsequent activation of the MKKs. These results explain the diverse activities of YopJ in inhibiting the extracellular signal-regulated kinase, c-Jun amino-terminal kinase, p38, and nuclear factor kappa B signaling pathways, preventing cytokine synthesis and promoting apoptosis. YopJ-related proteins that are found in a number of bacterial pathogens of animals and plants may function to block MKKs so that host signaling responses can be modulated upon infection.

Bacterial Proteins↗

PubMed1999

Using problem-based learning as part of general dental practice vocational training.

The use of problem-based learning as part of a vocational training scheme for vocational dental practitioners is described and evaluated. Problem-based learning is currently viewed as an effective means of delivering medical education and has been adopted as a principal style of education by many undergraduate medical and dental schools around the world.

Education, Dental↗

PubMed1999

Prolonged beneficial effects of a home-based intervention on unplanned readmissions and mortality among patients with congestive heart failure.

BACKGROUND: A single home-based intervention (HBI) applied immediately after hospital discharge in a cohort of "high-risk" patients with congestive heart failure has been shown to decrease numbers of unplanned readmissions plus out-of-hospital deaths during a period of 6 months. The duration of this beneficial effect remains uncertain. METHODS: Hospitalized patients with congestive heart failure who had been randomly assigned to receive either usual care (n=48) or HBI 1 week after discharge (n=49) were subject to an extended follow-up of 18 months. The primary end point of the study was frequency of unplanned readmissions plus out-of-hospital deaths. Secondary end points included total hospital stay, frequency of multiple readmissions, cost of hospital-based care, and total mortality. RESULTS: During 18-month follow-up, HBI patients had fewer unplanned readmissions (64 vs 125; P=.02) and out-of-hospital deaths (2 vs 9; P=.02), representing 1.4+/-1.3 vs 2.7+/-2.8 events per HBI and usual-care patient, respectively (P=.03). The HBI patients also had fewer days of hospitalization (2.5+/-2.7 vs 4.5+/-4.8 per patient; P=.004) and, once readmitted, were less likely to experience 4 or more readmissions (3/31 vs 12/38; P=.03). Hospital-based costs were significantly lower among HBI patients (Aust $5100 vs Aust $10600 per patient; P=.02). Unplanned readmission was positively correlated with 14 days or more of unplanned readmission in the 6 months before study entry (odds ratio [OR], 5.4; P=.006). Positive correlates of death were (1) non-English speaking (OR, 4.9; P=.008), (2) 14 days or more of unplanned readmission in the 6 months before study entry (OR, 4.9; P=.008), and (3) left ventricular ejection fraction of 40% or less (OR, 3.0; P=.03); conversely, assignment to HBI was a negative correlate (OR, 0.3; P=.02). CONCLUSIONS: In this controlled study, among a cohort of high-risk patients with congestive heart failure, beneficial effects of a postdischarge HBI were sustained for at least 18 months, with a significant reduction in unplanned readmissions, total hospital stay, hospital-based costs, and mortality.

Adult↗

PubMed1999

Metastatic breast cancer diagnosed during a work-up for urinary incontinence: a case report.

Breast cancer is the most commonly diagnosed cancer among women in the USA and the second leading cause of cancer deaths in women. Breast cancer metastases to the bladder are unusual but have been reported occasionally in the literature. The majority of the reports describe bladder metastases presenting with symptomatology or occurring in the context of disseminated disease. We present the case of an 87-year-old woman with a history of breast cancer and negative routine work-up for metastatic disease. She was referred to the urogynecology division in our institution because of complaints of urinary incontinence and urinary urgency. A urethrocystoscopy revealed suspicious bladder mucosal lesions that were biopsied. The pathology findings, when compared to the original cancer specimens, were consistent with metastatic disease. This case suggests that in patients with a history of breast cancer, even subtle urinary symptoms should be thoroughly evaluated.

Aged↗

PubMed1999

Intravenous ganciclovir prophylaxis for cytomegalovirus in heart, heart-lung, and lung transplant recipients.

Cytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart-lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody-negative heart-lung transplant patients receiving organs from CMV antibody-positive donors (CMV-mismatched patients) that in 1986 we adopted the policy of not transplanting CMV-positive organs into CMV-negative heart-lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV-mismatched heart recipients and CMV antibody-positive heart-lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P = 0.0006) and CMV disease (17 % vs 74 %, P = 0.0004) among CMV antibody-positive heart-lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart-lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups.

Adolescent↗

PubMed1999

Eosinophilic alveolitis in BAL after lung transplantation.

Lung transplantation has become a therapeutic option for patients with end stage lung disease. However, outcome after transplantation is complicated by episodes of rejection and infections. Bronchoalveolar lavage is a valuable tool in monitoring patients after transplantation, since it allows the detection of pathogens. A marker specifically indicating rejection from changes in BAL fluid has not been found yet. Especially changes in differential cell count, like lymphocytosis or an increase in polymorphnuclear granulocytes, are unspecific. The role of high eosinophil levels in BAL has not been elucidated yet. We analyzed 25 BAL samples and clinical data of 4 patients who underwent lung transplantation and presented with recurrent episodes of eosinophilic alveolitis in BAL. All patients demonstrated a deterioration of clinical condition, lung function, and blood gas analysis during times of eosinophilia in BAL, compared to previous examinations. In all cases, eosinophilia in BAL was accompanied by rejection. All patients were finally treated with high doses of steroids, resulting in improvement of all parameters. Eosinophilia was not associated with significant changes in the IL-5 concentration in BAL or the pattern of IL-5 expression in BAL cells. In conclusion, eosinophilic alveolitis may indicate acute rejection in patients after lung transplantation, if other causes of eosinophilia are excluded.

Bronchoalveolar Lavage Fluid↗

PubMed1999

Pegylated liposomal adriamycin: a review of current and future applications.

Anthracyclines such as adriamycin have a broad spectrum of activity in human tumours, but are limited, to an extent, by their non-selective delivery to a host of normal tissues and hence, subsequent toxicity. The development of liposomes has offered a drug delivery system with significant potential to target tumours whilst sparing normal tissues. A significant breakthrough has been achieved by coating the liposome with polyethylene glycol (pegylation), and thus altering the pharmacokinetics of the drug considerably. In this review, the authors discuss the promising data now emerging with pegylated liposomal adriamycin, and also describe possible future applications.

Journal Article↗

PubMed1999

Social class, race/ethnicity, and incidence of breast, cervix, colon, lung, and prostate cancer among Asian, Black, Hispanic, and White residents of the San Francisco Bay Area, 1988-92 (United States).

BACKGROUND: To date only eight US studies have simultaneously examined cancer incidence in relation to social class and race/ethnicity; all but one included only black and white Americans. To address gaps in knowledge we thus investigated socioeconomic gradients in cancer incidence among four mutually exclusive US racial/ethnic groups-- Asian and Pacific Islander, black, Hispanic, and white-- for five major cancer sites: breast, cervix, colon, lung, and prostate cancer. METHODS: We generated age-adjusted cancer incidence rates stratified by socioeconomic position using: (a) geocoded cancer registry records, (b) census population counts, and (c) 1990 census block-group socioeconomic measures. Cases (n = 70,899) were diagnosed between 1988 and 1992 and lived in seven counties located in California's San Francisco Bay Area. RESULTS: Incidence rates varied as much if not more by socioeconomic position than by race/ethnicity, and for each site the magnitude - and in some cases direction - of the socioeconomic gradient differed by race/ethnicity and, where applicable, by gender. Breast cancer incidence increased with affluence only among Hispanic women. Incidence of cervical cancer increased with socioeconomic deprivation among all four racial/ethnic groups, with trends strongest among white women. Lung cancer incidence increased with socioeconomic deprivation among all but Hispanics, for whom incidence increased with affluence. Colon and prostate cancer incidence were inconsistently associated with socioeconomic position. CONCLUSIONS: These complex patterns defy easy generalization and illustrate why US cancer data should be stratified by socioeconomic position, along with race/ethnicity and gender, so as to improve cancer surveillance, research, and control.

Adolescent↗

PubMed1999

Randomized, trough blood cyclosporine concentration-controlled trial to compare the pharmacodynamics of Sandimmune and Neoral in de novo lung transplant recipients.

The greater and more consistent absorption of cyclosporine from the microemulsion formulation (Neoral; Novartis Pharmaceuticals Ltd., Frimley, UK) when compared with that from the original form (Sandimmune; Novartis Pharmaceuticals Ltd., Frimley, UK) results in greater systemic exposure. Lung transplant recipients could particularly benefit from this enhanced exposure, but not at the expense of excessive cyclosporine toxicity. We compared the pharmacodynamics of Neoral and Sandimmune over the first postoperative year in 50 lung transplant recipients. Twenty-eight patients were randomly selected to receive Neoral and 22 to receive Sandimmune. Nine patients with cystic fibrosis (CF) were randomly selected independently (5, Neoral; 4, Sandimmune). Patients were maintained on similar trough blood cyclosporine concentrations (C0) throughout the 12-month follow-up. A limited blood sampling strategy was adopted to compare the pharmacokinetics of the two formulations at the end of weeks 1 to 4, and of weeks 13, 26, 39, 52. The influence of any difference between the pharmacokinetics of Neoral and Sandimmune on either efficacy or toxicity of the drug was investigated during the follow-up period. Patients in the Neoral and the Sandimmune groups were matched demographically. There were no differences in dose-normalized blood cyclosporine concentrations measured predose (C0) or 6 hours postdose between the two groups. However, the measurement at 2 hours postdose (C2) and the total AUC0-6 were significantly greater in the Neoral group in both CF and non-CF patients at all visits (p < 0.001). Non-CF patients required 9% lower doses of Neoral to achieve comparable C0 measurements to those patients receiving Sandimmune. However, patients with CF required 2 to 3 times the dose of both Neoral and Sandimmune to achieve the same C0 as non-CF patients. The linear rejection rate in the Sandimmune group was 1.87 episodes per patient year, which was similar to the rejection rate of 1.97 episodes per patient year in the Neoral group. Serial lung function, blood biochemistry and hematology, mortality and the incidence of severe renal dysfunction, hypertension, infection, seizures, and new-onset diabetes were all similar in the two groups. Despite equivalent C0, those in the Neoral group were consistently exposed to greater blood cyclosporine concentrations during the dosing interval than those in the Sandimmune group. This did not increase the incidence of serious cyclosporine-associated side effects or influence the rate of acute rejection either. When data from the Neoral and Sandimmune groups were combined, measurements of C0 but not C2 or C6 were associated with the risk of acute lung allograft rejection.

Adult↗

PubMed1999

Uncovering a multitude of sins: medication management in the home post acute hospitalisation among the chronically ill.

BACKGROUND: Sub-optimal use of prescribed medication is often associated with unplanned hospitalisation among the chronically ill. AIMS: To examine the extent of sub-optimal use of prescribed medication in a 'high risk' patient cohort recently discharged from acute hospital care. METHODS: Chronically ill patients discharged from acute hospital care (n = 342) were studied. At one week post discharge a home visit was performed by a nurse and a pharmacist during which medication management (including compliance and medication-related knowledge) was assessed. RESULTS: During the majority of home visits at least one medication-related problem was detected: approximately half of the cohort subject to a 'reliable' pill-count were found to be mal-compliant and almost all demonstrated inadequate medication-related knowledge. Mal-compliance was correlated with > or = five prescribed medications (Odds ratio [OR] 2.6: p < 0.002). Comparatively, lower medication-related knowledge was correlated with age > 75 years (OR 2.2: p < 0.001), exacerbation of a pre-existing chronic illness (OR 2.7: p = 0.044) and < or = six years formal education (OR 1.9: p = 0.004). Neither were modulated by extent of in-hospital counselling. Other previously unknown problems detected during the home visit included hoarding of previously prescribed medication (35%) and reducing medication intake to minimise costs (21%). CONCLUSIONS: Management of prescribed medications among chronically ill patients recently discharged from acute hospital care is often sub-optimal. Assessment of medication management in the home provides an invaluable opportunity to detect and address problems likely to result in poorer health outcomes.

Aged↗

PubMed1999

Is health-related quality of life among older, chronically ill patients associated with unplanned readmission to hospital?

BACKGROUND: Assessment of health-related quality of life (HRQL) is being used increasingly to assess the impact of treatment. AIMS: To determine if HRQL, assessed shortly after acute hospitalisation, is associated with readmission to hospital. METHODS: In a prospective, longitudinal study, 163 chronically ill, medical and surgical patients (mean age 67.0+/-16.3 years) discharged to home following acute hospitalisation were studied. HRQL was assessed at one month post-hospital discharge using the MOS 36-Item Short-Form Health Survey (SF-36). Patients were followed-up for six months thereafter to determine subsequent incidence of unplanned readmission. RESULTS: HRQL as measured by the eight health dimensions of the SF-36, for the entire cohort, was lower relative to age and gender matched norms for the local population (p<0.01). During study follow-up, 47 (35%) patients had an unplanned readmission and one patient died. Patients who had an unplanned readmission demonstrated both significantly lower physical (32.2+/-9.8 vs 38.6+/-10.1: p<0.001) and mental (45.1+/-12.7 vs 49.9+/-12.3: p=0.03) health component scores in comparison to the remainder of the cohort. On multivariate analysis, independent correlates of unplanned readmission were: 1) presence of formal home assistance (OR 6.4: p<0.01), 2) > or =five prescribed medications (OR 2.4: p=0.04), 3) > or =two admissions in the six months before follow-up (OR 4.3: p<0.01) and 4) an SF-36 physical component score of < or =40 (OR 2.2: p=0.05). CONCLUSIONS: In this cohort of predominantly older and chronically ill patients recently discharged from acute hospital care, relatively lower SF-36 physical health component scores were independently associated with an increased risk of subsequent unplanned readmission.

Aged↗

PubMed1999

Ablation of ventricular tachycardia with a saline-cooled radiofrequency catheter: anatomic and histologic characteristics of the lesions in humans.

INTRODUCTION: In animal models, active cooling of the electrode during radiofrequency (RF) ablation allows creation of larger lesions, presumably by increasing the power that can be delivered without coagulum formation. These RF lesions have not been characterized in human myocardium in regions of infarction and scarring. METHODS AND RESULTS: Cooled-tip RF catheter ablation of ventricular tachycardias (VTs) was performed in two patients who had severe congestive heart failure and subsequently underwent cardiac transplantation. The first patient had four different monomorphic VTs. RF applications along the inferoseptal margin of a scarred region abolished all inducible VTs. The second patient had sarcoidosis involving the myocardium and four different inducible VTs. RF current applied at an inferobasal VT exit and at the right and left septa failed to abolish the VTs. The explanted hearts were examined at the time of cardiac transplantation 18 and 21 days later, respectively. Lesions extended to depths up to 7 mm, reaching clusters of myocardial cells deep to regions of fibrosis. Microscopically, the ablation sites contained coagulation necrosis with hemorrhage, surrounded by a rim of granulation tissue. CONCLUSION: Saline-irrigated RF catheter ablation produces relatively large lesions capable of penetrating deep into scarred myocardium.

Adult↗

PubMed1999

Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization.

Genetic screens for modifiers of activated Ras phenotypes have identified a novel protein, kinase suppressor of Ras (KSR), which shares significant sequence homology with Raf family protein kinases. Studies using Drosophila melanogaster and Caenorhabditis elegans predict that KSR positively regulates Ras signaling; however, the function of mammalian KSR is not well understood. We show here that two predicted kinase-dead mutants of KSR retain the ability to complement ksr-1 loss-of-function alleles in C. elegans, suggesting that KSR may have physiological, kinase-independent functions. Furthermore, we observe that murine KSR forms a multimolecular signaling complex in human embryonic kidney 293T cells composed of HSP90, HSP70, HSP68, p50(CDC37), MEK1, MEK2, 14-3-3, and several other, unidentified proteins. Treatment of cells with geldanamycin, an inhibitor of HSP90, decreases the half-life of KSR, suggesting that HSPs may serve to stabilize KSR. Both nematode and mammalian KSRs are capable of binding to MEKs, and three-point mutants of KSR, corresponding to C. elegans loss-of-function alleles, are specifically compromised in MEK binding. KSR did not alter MEK activity or activation. However, KSR-MEK binding shifts the apparent molecular mass of MEK from 44 to >700 kDa, and this results in the appearance of MEK in membrane-associated fractions. Together, these results suggest that KSR may act as a scaffolding protein for the Ras-mitogen-activated protein kinase pathway.

14-3-3 Proteins↗

PubMed1999

Metastatic endometrial stromal sarcoma masquerading as pulmonary lymphangioleiomyomatosis.

A 39 year old female presented with bilateral pneumothoraces and interstitial shadowing on chest x ray. A diagnosis of lymphangioleiomyomatosis was made following an open lung biopsy. Over the next eight years she developed respiratory failure leading to single lung transplantation but she died in the immediate postoperative period. Necropsy examination and review of the previous open lung biopsy revealed multiple pulmonary metastases from a low grade endometrial stromal sarcoma of the uterus. This case high-lights the importance of an accurate diagnosis before transplantation.

Adult↗

PubMed1999

Effects of pattern, spatial frequency, number, and rate of stimulus presentation on the accuracy of detection.

Brief trains of pulsed stimuli were used to assess whether magnocellular or parvocellular visual pathways could be differentiated perceptually. Trains of either one to four sine-wave, square-wave, or checkerboard gratings were presented at three temporal and two spatial frequencies to six observers. The task of the observer was to report the perceived number of stimuli (gratings) in a train. The difference between actual number and perceived number of gratings was recorded as an error score. It was found that neither the pattern nor the spatial frequency of the gratings significantly affected perceptual accuracy. On the other hand, the number of gratings in a train and the interstimulus interval between gratings produced significant differences. Perceptual accuracy was greater when lower numbers of gratings in a train were presented with longer interstimulus intervals. The observers typically reported fewer stimuli than were presented. The source of the discrepancy is discussed in terms of a light adaptive process initiated in the retina.

Adolescent↗

PubMed1999

Cancer screening practices among primary care physicians serving Chinese Americans in San Francisco.

Previous research has reported a lack of regular cancer screening among Chinese Americans. The overall objectives of this study were to use a mail survey of primary care physicians who served Chinese Americans in San Francisco to investigate: a) the attitudes, beliefs, and practices regarding breast, cervical, and colon cancer screening and b) factors influencing the use of these cancer screening tests. The sampling frame for our mail survey consisted of: a) primary care physicians affiliated with the Chinese Community Health Plan and b) primary care physicians with a Chinese surname listed in the Yellow Pages of the 1995 San Francisco Telephone Directory. A 5-minute, self-administered questionnaire was developed and mailed to 80 physicians, and 51 primary care physicians completed the survey. A majority reported performing regular clinical breast examinations (84%) and teaching their patients to do self-breast examinations (84%). However, the rate of performing Pap smears was only 61% and the rate of ordering annual mammograms for patients aged 50 and older was 63%. The rates of ordering annual fecal occult blood testing and sigmoidoscopy at regular intervals of three to five years among patients aged 50 and older were 69% and 20%, respectively. Barriers (patient-specific, provider-specific, and practice logistics) to using cancer screening tests were identified. The data presented in this study provide a basis for developing interventions to increase performance of regular cancer screening among primary care physicians serving Chinese Americans. Cancer screening rates may be improved by targeting the barriers to screening identified among these physicians. Strategies to help physicians overcome these barriers are discussed.

Asian↗