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Biomedical subjects

D Goldstein

Publications and source records attributed to D Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1999

Lone atrial fibrillation: prognostic differences between paroxysmal and chronic forms after 10 years of follow-up.

BACKGROUND: Lone atrial fibrillation (LAF) is defined by the presence of atrial fibrillation unassociated with other evidence of organic heart disease. There are conflicting data concerning the prognostic importance, rate of embolic complications, and survival in subjects affected by this arrhythmia. METHODS AND RESULTS: One hundred forty-five patients younger than 50 years at the time of the first diagnosis were identified; 96 had paroxysmal and 49 had chronic LAF. They were followed up with clinical and echocardiographic controls, and we recorded every thromboembolic complication and death. During the follow-up (10 +/- 8 years) among patients with paroxysmal LAF, 1 (1%) had an ischemic stroke, 2 a transient ischemic attack, and 1 a myocardial infarction. In the group with chronic LAF, 1 patient had moderate heart failure, 2 myocardial infarction, and 1 transient ischemic attack. In this group, 8 embolic complications in 7 (16.3%) patients were observed. One patient with intestinal embolism died during surgery; 2 (6.1%) patients died suddenly. CONCLUSIONS: The prognosis of young patients with paroxysmal LAF appears to be excellent, whereas patients with chronic LAF are at increased risk of embolic complications and higher mortality rates. Our results suggest that LAF is not always a benign disorder, as suggested by previous studies. Subgroups with substantially increased risk for thromboembolic events caused by LAF should be better identified.

Adult↗
PubMed1999

Attitudes and information needs of Chinese migrant cancer patients and their relatives.

BACKGROUND: The information needs of ethnic minorities often differ from that of the dominant culture, leading to dissatisfaction among both patients and health professionals. AIMS: This research project aims to identify attitudes towards cancer and associated information and communication needs of Chinese patients and their relatives in Sydney, thereby providing a framework for the provision of culturally appropriate cancer care for Chinese-Australians. METHODS: A qualitative data collection strategy was selected as the most appropriate method, because no validated measures are available and no previous research has examined attitudes and needs of Chinese-Australian cancer patients. Patients were recruited from three major teaching hospitals in Sydney and from a Chinese cancer support organisation. Sampling was discontinued when informational redundancy was achieved. Four focus groups and 26 individual telephone interviews were conducted with a total of 36 cancer patients and 12 relatives born in China, Singapore and Malaysia. RESULTS: While individual differences were observed, a majority view was expressed on a range of issues. Non-disclosure of a poor prognosis was favoured, and the role of the family in liaising between health professionals and the patient was emphasised. Patients preferred a confident and clear diagnosis and treatment recommendation. Most patients wished to incorporate Chinese culture-specific treatments into their care. The need for interpreters and psychological and spiritual support was emphasised. CONCLUSIONS: Providing information in a culturally sensitive manner will assist doctors in providing optimum care and support for ethnic minority groups in this country.

Attitude to Health↗
PubMed1999

Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer.

PURPOSE: To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. RESULTS: A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P =.025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P <.001), nausea or vomiting (P =.003), and fever without documented infection (P =.007), and less hospitalization for febrile neutropenia than did CMFP (P =.001). Alopecia, peripheral neuropathy, and myalgia or arthralgia were more severe with paclitaxel (all P <.0001). Overall, quality of life was similar for both treatments (P > = .07). CONCLUSION: Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP.

Adult↗
PubMed1999

Mortality and cause of death in patients with chronic non-rheumatic atrial fibrillation after a two-year follow-up.

BACKGROUND: Non-rheumatic atrial fibrillation (NRAF) is a very common arrhythmia but its role in the prognosis and cardiovascular mortality is controversial. In particular, cause and predictors of death are not completely known. METHODS: We analyzed the cause of death and the possible predictors of cardiovascular mortality in 664 outpatients (mean age 72 +/- 9 years old) enrolled in the "Trieste Area Study on Non-Rheumatic Atrial Fibrillation" (TASAF), a prospective community study, after a follow-up of 27 +/- 9 months. The mean duration of the arrhythmia at enrollment was 59 months (range 1-360 months). Only 42 patients (6.3%) were on anticoagulants by general practitioners and 205 (30.8%) were on antiplatelet drugs. RESULTS: Of these patients, 110 (16.5%) died: 28 (25.5%) due to a cerebral or peripheral thromboembolism, 10 (8.2%) of sudden death, 46 (42.7%) of expected cardiac death and 25 (22.7%) of non-cardiac causes. In one patient, the cause of death was uncertain. Sixty-nine patients underwent postmortem examination. In univariate analysis, left ventricular dysfunction (p = 0.03) and an enlarged left atrium (p = 0.03) proved to be directly related to increased cardiovascular mortality. Both in univariate and Cox proportional hazards model analysis, aging (odds ratio 1.09, IC 95% 1.05-1.12, p = 0.00001), history of heart failure (odds ratio 1.27, IC 95% 1.01-1.60, p = 0.036), cardiomegaly (odds ratio 1.35, IC 95% 1.01-1.81, p = 0.040), diabetes mellitus (odds ratio 1.35, IC 95% 0.99-1.84, p = 0.058) and previous myocardial infarction (odds ratio 1.56, IC 95% 1.20-2.03, p = 0.0007) were all independent risk factors for cardiovascular mortality. A history of cerebral or systemic embolism (23 versus 12%, p = 0.09) and, above all, one or more recurrences before enrollment (11 versus 2.3%, p = 0.04), were associated with embolic mortality. CONCLUSIONS: Patients with NRAF have an increased risk of cardiovascular death. Aging, the presence of diabetes, cardiomegaly on chest x-ray, heart failure and a previous myocardial infarction were independent risk factors for cardiovascular mortality. A history of embolism at enrollment significantly conditioned the embolic mortality rate but above all, embolic events during follow-up determined a very high percentage of total deaths (25.5% of all causes). A proper anticoagulant therapy should strongly be advised to all patients with no contraindications.

Aged↗
PubMed1999

Novel antipsychotics: comparison of weight gain liabilities.

BACKGROUND: We performed a retrospective analysis of 122 clinical records of 92 male patients with DSM-III-R schizophrenia to examine the relative weight gain liabilities of clozapine, risperidone, olanzapine, and sertindole compared with haloperidol. We hypothesized that the unique pharmacodynamic profiles of these agents would contribute to different amounts and patterns of weight gain. METHOD: Data were analyzed to determine differences in weight gain during treatment among patients receiving 5 different drug treatments (clozapine [N = 20], olanzapine [N = 13], risperidone [N = 38], haloperidol [N = 43], and sertindole [N = 8]). Measures of maximal weight gain, final weight, and duration to maximal weight gain were calculated. RESULTS: Repeated measures analyses of variance controlling for age, treatment duration, and initial weight revealed statistically significant differences between groups on all 3 measures. Clozapine and olanzapine had the greatest maximal weight gain liability (F = 4.13, df = 4,23; p = .01). Weight gain with clozapine, but not olanzapine or risperidone, appears to persist (as reflected by final weight) despite behavioral interventions (e.g., nutritional consultation, suggested exercise regimen; F = 5.69, df = 4,23; p = .003). Clozapine- and olanzapine-treated subjects appeared to gain weight over a prolonged period of time, whereas risperidone-and sertindole-treated subjects had a more limited period of weight gain (F = 2.95, df = 4,25; p = .04). CONCLUSION: Clozapine and olanzapine caused the most weight gain, risperidone was intermediate, and sertindole had less associated weight gain than haloperidol. The relative receptor affinities of the novel antipsychotics for histamine H1 appear to be the most robust correlate of these clinical findings.

Adult↗
PubMed1999

[Prevalence of medical complaints in the community-dwelling elderly receiving regular medication].

We assessed the prevalence of self-reported medical complaints among the community-dwelling elderly receiving regular medication, and determined associations between health and sociodemographic variables, and the prevalence of complaints. The study included 170 patients, 60-90 years of age, living at home. Participants were recruited from the 3 main primary care clinics in Rishon LeZion. All were receiving chronic medication and were followed-up utilizing a long-term medication card. Data were gathered in interviews held in patients' homes using a structured questionnaire which included sociodemographics, diseases and medication, mental state assessment by Katzman's score, and a list of 15 medical complaints common among the aged. Relations to age, gender, education, living arrangements, number of diseases and number of medications per patient were determined. Mean age of participants was 73.2 +/- 6.0 years and they suffered an average of 4.07 +/- 2.16 diseases and took 5.10 +/- 2.83 types of drugs. The most prevalent complaints were: weakness and fatigue (65.0%), agitation and restlessness (56.4%), dry mouth (45.6%), constipation (43.6%) and dizziness (43.2%). The number of diseases, gender, education and age had the strongest associations with the prevalence of specific complaints, as well as their total number. The association between number of medications and mean number of complaints was of borderline significance.

Aged↗
PubMed1998

Requirement for Rho-mediated myosin light chain phosphorylation in thrombin-stimulated cell rounding and its dissociation from mitogenesis.

Thrombin treatment causes a dose-dependent rounding of 1321N1 astrocytoma cells. This cytoskeletal response is rapid, peaking 2 h after thrombin stimulation, and reverses by 50% after 24 h. The thrombin receptor peptide SFLLRNP also induces cell rounding, whereas other G protein-linked receptor agonists such as carbachol, lysophosphatidic acid, or bradykinin fail to do so. Results of studies using pharmacological inhibitors do not support a requirement for phosphatidylinositol 3-kinase, mitogen-activated protein kinase, or Ca2+ mobilization in this response. Inhibition of protein kinase C or tyrosine kinase produces minimal blockade. Pertussis toxin treatment is also without effect. However, thrombin-induced rounding is fully blocked by the C3 toxin from Clostridium botulinum, which specifically ADP-ribosylates and inactivates the small G protein Rho. Thrombin also leads to a rapid, 2.4-fold increase in 32P incorporation into myosin light chain while carbachol does not. Myosin phosphorylation, like cell rounding is inhibited by inactivation of Rho with C3 exoenzyme, suggesting that myosin phosphorylation is necessary for this cytoskeletal response. This is supported by the observation that thrombin-induced rounding is also blocked by the myosin light chain kinase inhibitor KT5926. However, treatment with KT5926 fails to inhibit mitogenesis. Thus, cell rounding is not prerequisite to thrombin-induced DNA synthesis. We conclude that stimulation of the heterotrimeric G protein-coupled thrombin receptor in 1321N1 cells activates Rho-dependent pathways for both DNA synthesis and cell rounding, the cytoskeletal response being mediated in part through increases in myosin phosphorylation.

Astrocytoma↗
PubMed1998

Vitamin E and oxidative stress in the heart of the cardiomyopathic syrian hamster.

Myocardial deterioration is relentlessly progressive in almost all patients who develop overt symptoms. Many dilated cardiomyopathies are associated with a marked increase in cardiac sympathetic tone which may be toxic to myocytes. Microvascular spasm, leading to diffuse, focal reperfusion injury, also appears to be an important mechanism of cardiomyocyte loss in many models of dilated cardiomyopathy. Free radicals may mediate both catecholamine-induced damage and reperfusion injury. We hypothesized that myocardial antioxidant reserve may be significantly reduced in dilated cardiomyopathy and that alpha-tocopheryl acetate may be of benefit. The enzymes superoxide dismutase, catalase and glutathione peroxidase were measured in the myocardial tissue of control and cardiomyopathic hamsters in early (25-50 days) and late (275-320 days) stages of the cardiomyopathy. In another study, myocardial glutathione peroxidase activity and protein oxidation was measured in control and late stage cardiomyopathic hamsters receiving alpha-tocopheryl (70 mg/kg/day) or vehicle for 1 month. There were no significant differences in glutathione peroxidase activity between control and cardiomyopathic hamsters in the early stage of the cardiomyopathy. Superoxide dismutase and catalase activities did not change with aging; however, glutathione peroxidase decreased over 30%, alpha-tocopherol was reduced by approximately 50% and protein oxidation increased more than 2-fold in the hearts of late stage cardiomyopathic hamsters. Alpha-tocopheryl acetate administration restored alpha-tocopherol levels, glutathione peroxidase activity and protein oxidation to normal. We conclude that the decompensating heart has significantly limited antioxidant reserve and that this reserve is sensitive to the intake of antioxidant supplements.

Animals↗
PubMed1998

Administration of imiquimod, an interferon inducer, in asymptomatic human immunodeficiency virus-infected persons to determine safety and biologic response modification.

A phase I study to determine safety, maximum tolerated dose, and biologic response during multiple once-a-week administration of oral imiquimod, an immune response modifier, was conducted in 12 adults with early human immunodeficiency virus (HIV) infection. All completed the dose-escalation phase of weekly dosing at 100-mg increments and received at least one maintenance dose, 100 mg below the patient's toxic dose, for 12 weeks. Dose-limiting toxicity occurred in 3 patients at 200-mg, 5 at 300-mg, and 3 at 400-mg dose levels. One tolerated the 500-mg dose without dose-limiting toxicity. Dose-limiting toxicities included fatigue, fever, malaise, increased transaminases, hypotension, vomiting, and depression. Seven of 12 completed 12 weeks of maintenance. At > or = 200 mg of imiquimod, all patients had biologic responses, measured by elevations in serum interferon, beta2-microglobulin, and neopterin levels. Imiquimod induced pronounced levels of circulating interferon in asymptomatic HIV-infected persons, with variable effect on virus load.

Administration, Oral↗
PubMed1998

A phase II study of liposomal doxorubicin in the treatment of HIV-related Kaposi's sarcoma.

OBJECTIVES: To evaluate the toxicity and clinical efficacy of liposomal encapsulated doxorubicin (DOX-SL) in the treatment of HIV-related Kaposi's sarcoma (KS). METHODS: DOX-SL 20-40mg/m2 was administered by intravenous infusion over 30-60 minutes every two weeks. Toxicity was assessed in all patients and response assessed in patients who completed two or more cycles of therapy. RESULTS: Twenty-five patients with KS were enrolled. Nine had received previous KS chemotherapy but only one prior anthracycline therapy. Eighteen patients had CD4 counts < 50/mm3. Eight had pulmonary and/or visceral KS. A total of 191 cycles were given, median 6, range 1-33. Twenty patients completed two or more cycles and were considered evaluable for efficacy. A defined response occurred in 11 patients, nine achieving a partial response and two a complete response. The median duration of response was 120 days and the median time to disease progression was 187 days. Acute toxicity was minimal, except in one patient who had generalised erythema, hypotension and diaphoresis within ten minutes of starting DOX-SL infusion. Grade 3 or 4 neutropenia occurred in 13.6 and 3.7% of cycles respectively. Neutropenic sepsis secondary to drug therapy was not reported. Alopecia and gastrointestinal symptoms were mild and infrequent. No cardiac toxicity was seen. Nine/25 patients developed HIV-associated illnesses while on study (three Pneumocystis carinii pneumonia, two systemic Cytomegalovirus infection, three cryptosporidiosis, one Mycobacterium avium intracellulare--(MAC) infection). Median survival in the evaluable patients was 219 days. CONCLUSIONS: DOX-SL is an effective and well tolerated palliative therapy in AIDS-related KS.

Adult↗
PubMed1998

Long term follow-up of CEOP in the treatment of HIV related non-Hodgkin's lymphoma (NHL).

BACKGROUND: The development of non-Hodgkin's lymphoma (NHL) in AIDS conveys a poor prognosis with less than 10% of patients surviving beyond two years. These tumours are generally aggressive and often require systemic chemotherapy to bring about effective palliation. AIMS: To report on the long term follow-up of patients with HIV related NHL treated with CEOP chemotherapy. METHODS: This is a retrospective analysis of a group of 18 patients treated at two institutions between October 1990 and 1992 with modified CEOP chemotherapy. Doses were calculated using cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, vincristine 2 mg and prednisone 75-100 mg x five days, however initial doses of cyclophosphamide and epirubicin were modified to 50-75% of calculated dose. RESULTS: Seventeen of the 18 patients were male, one female; age range 26-79 (median 36 years); seven with immunoblastic, three Burkitt's, one Ki-1 (anaplastic), six diffuse large cell, and one mixed large and small cell. Eight patients (44%) achieved a complete remission, with seven patients (39%) achieving a partial remission, for an overall response rate of 83% (95% CI = 59-96%). Survival ranged from three-35 months (median nine months). Interestingly, four patients (22%) survived more than two years (median 31 months), three remaining in complete remission at the time of death. Generally therapy was well tolerated and toxicity was manageable. CONCLUSIONS: CEOP is an effective, tolerable and safe regimen and our long term follow-up suggests that there is a small sub-population of patients with HIV and lymphoma who may have a better prognosis and as such would clearly benefit from systemic chemotherapy as a means of prolonging survival and not simply palliation.

Adult↗