Biomedical subjects
Publications and source records attributed to R Segal.
The Ottawa Regional Cancer Centre offers an Oncology Rehabilitation Program to patients with cancer. Between January 1997 and December 1998, 254 patients with cancer participated in the program. This paper describes the program and its participants. The program's strengths, limitations and future directions are also discussed.
Differences in QT dispersion (a predictor for sudden death) were observed in a subgroup of patients in the ELITE heart failure study of losartan compared with captopril, and may explain improved survival with losartan.
BACKGROUND: Cancer patients with single tumors live longer today due to earlier detection and improved treatment methods. For this reason, the authors see more patients who develop a second primary tumor. The etiology of the second tumor can be the same as the first, whether treatment-induced or unknown. The prognoses of these patients usually depend on the behavior of the second tumor. METHODS: The authors investigated the lymphocyte subset in 88 of the more than 750 patients listed in the tumor registry at their treatment center who had at least one carcinoma of the breast or colon and a second primary of the same or another site. Mononuclear cells were obtained from heparinized blood by the standard fractionation Hypaque gradient centrifugation technique. Helper and suppressor cells were identified by using three murine monoclonal antibodies: CD3 for mature T lymphocytes, CD4 for helper inducer cells, and CD8 for suppressor cytotoxic cells. T-cell subset distribution was evaluated with flow cytometry. RESULTS: Most values of CD3, CD4, and CD4/CD8 were lower in patients than in healthy controls. The values of CD4 and CD4/CD8 were lower in patients who had a second tumor in the colon rather than in the breast. CONCLUSIONS: As tumors in patients with a second primary sometimes recur or the patient develops a third primary, the authors are prospectively following their patients to see whether those with immunosuppression have a greater tendency to develop recurrent disease or a third primary.
OBJECTIVES: Intermittent androgen suppression (IAS) has been suggested as a means of attenuating the androgen deprivation syndrome in men with incurable prostate cancer. Laboratory data suggest that intermittent therapy may prolong the duration of androgen dependence. METHODS: Since October 1993, 54 patients have entered a Phase II protocol consisting of 8 months of total androgen blockade (TAB) using leuprolide (Lupron) depot and nilutamide (Anandron) followed by an off-treatment interval of variable length. Eleven patients had biopsy-proven local failure after radiotherapy, 4 had biochemical failure, 24 had distant metastases (fewer than six axial sites on bone scan), 11 had combined local and distant failure, and 4 were treated as primary management for nodal disease. Mean prostate-specific antigen (PSA) at entry was 37 ng/mL (range 3.8 to 196). After 8 months of TAB, hormonal therapy was discontinued for those patients whose PSA was less than 4.0 ng/mL and stable or decreasing and was resumed (cycle 2) when PSA increased to greater than 10 ng/mL. RESULTS: As of April 1 998, mean follow-up was 33 months (range 14 to 53). Patients have completed at least one, and up to five treatment cycles. The mean time to nadir PSA in cycle 1 was 20 weeks, and the mean time off was 35 weeks (31 weeks for those with metastatic disease versus 39 for local or biochemical failure). In cycle 2, the mean time to PSA nadir was 17 weeks, and the mean time off was 30 weeks (28 weeks for metastatic disease and 38 weeks for local or biochemical failure). In cycle 3, the time to PSA nadir was 19 weeks. Full testosterone data are available for 40 patients in cycle 1. Normal levels were achieved during the off-treatment interval in 73% by a mean of 18 weeks (median 9). Testosterone normalization in cycle 2 was achieved in 71% at a mean time of 17 weeks (median 14). CONCLUSIONS: TAB can be used intermittently, and appears to be more appropriate for patients with local or biochemical failure. Testosterone recovery is not universal in the off-treatment intervals. IAS needs to be investigated in a randomized trial to determine the effect on overall survival and quality of life.
BACKGROUND: In the Evaluation of Losartan in the Elderly (ELITE) heart failure study, a survival benefit (primarily because of a reduction in sudden deaths) was observed in symptomatic patients treated with losartan compared with captopril. METHODS AND RESULTS: The Losartan Heart Failure Survival Study--ELITE II (currently ongoing) is a double-blind, randomized clinical trial being conducted in 45 countries at 288 sites. ELITE II formally tests the hypotheses that losartan, compared with captopril, will reduce all-cause mortality (primary end point) and sudden cardiac death and/or resuscitated cardiac arrest (secondary end point). In addition, all-cause mortality and/or hospitalizations and cardiovascular mortality and/or hospitalizations will be evaluated. The trial has 90% power to detect a 25% treatment difference in all-cause mortality (event driven, 510 deaths). Substudies are examining quality of life, health care resource utilization, and mechanisms related to the reduction in sudden death. During recruitment (June 1997 to May 1998), 3,152 patients aged 60 years or older (mean age, 71.6 years), with New York Heart Association classes II (51%), III (44%), and IV (5%), and left ventricular ejection fraction of 40% or less (mean, 31%) were randomized to receive either 12.5 mg of losartan, titrated as tolerated to 50 mg once daily, or 12.5 mg of captopril, titrated as tolerated to 50 mg thrice daily. Randomization was stratified by clinical site and for baseline beta-blocker use. CONCLUSION: The ELITE II study will further define the role of losartan in the treatment of patients with symptomatic heart failure relative to the angiotensin-converting enzyme inhibitor captopril, an agent from a class currently considered standard treatment for this disease.
Anthracyclines and cisplatin have been shown separately to have modest activity in prostate cancer. The synergism between anthracyclines and cisplatin, with the lack of overlapping toxicities, led to the conduct of this phase II trial of the combination of epirubicin and cisplatin in hormone-refractory metastatic prostate cancer. Twenty-one evaluable patients with hormone-refractory metastatic prostate cancer received epirubicin 100 mg/m2 followed by cisplatin 80 mg/m2 with prehydration and mannitol diuresis. Epirubicin and cisplatin produced a biochemical response (>50% decrease in tumor marker) in 32% of patients, symptomatic improvement in 38%, and a response in measurable and evaluable disease sites in 14%. Toxicities were mainly hematologic, with 77% and 41% >grade 2 neutropenia and thrombocytopenia, respectively. Greater than grade 2 toxicities were: cardiac (three), renal secondary to sepsis (one), nausea and vomiting (two), weakness (one), mucositis (one), and diarrhea (one). The combination of epirubicin and cisplatin was associated with manageable toxicities in this elderly population; however, antitumor activity was marginal in this disease. Participation in clinical trials should continue to be offered to patients with hormone-refractory metastatic prostate cancer.
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Explore the source record for details and available documents.
The Losartan Heart Failure ELITE Study recently found that in patients with symptomatic heart failure and a left ventricular ejection fraction of </=0.40, losartan compared to captopril improved survival with better tolerability. The objective of this study was to perform an economic evaluation of losartan versus captopril based on the results of the Losartan Heart Failure ELITE Study. The Losartan Heart Failure ELITE Study was a multinational, double-blind, randomized 48-week study comparing the safety and efficacy of losartan to captopril in angiotensin-converting enzyme-inhibitor-naive patients >/=65 years with symptomatic heart failure. Data on health care resource utilization were collected as part of the trial. We conducted a cost-effectiveness analysis to estimate the lifetime benefits of treatment and the associated costs. We observed no differences between treatments in the number of hospitalizations, hospital days, and emergency room visits per patient over the trial period. We estimated the total cost of losartan to be USD 54 (95% CI: USD -1,717, USD 1,755) less per patient than captopril over this time frame. We also estimated that over the projected remaining lifetime of the study population, losartan compared to captopril would increase survival by 0.20 years (undiscounted) at an average cost of USD 769 (discounted) more per patient. This cost increase translated into a cost-effectiveness ratio of USD 4,047 per year of life gained for losartan relative to captopril. In patients with symptomatic heart failure, losartan compared to captopril increased survival with better tolerability at a cost well within the range accepted as cost-effective.
The objective of this work was to determine markers of endothelial cell activation in valves from patients with antiphospholipid syndrome (APS) and heart valve involvement, in order to establish a role for endothelial cells in the pathogenesis of the valvular disease. Sixteen valves from ten patients with APS, obtained from autopsies or removed during valve replacement, were studied. Two groups of valves were used as controls. One group included seven normal valves from patients who died from non-cardiac diseases. The other group of valves were obtained from patients with bacterial endocarditis during autopsies or valve replacement operations. Immunoperoxidase and immunofluorescence stainings with antibodies to human immunoglobulins, endothelial cells, alpha3beta1 integrin, collagen IV, laminin and fibronectin were employed. Three histopathological patterns were apparent: normal valves, valves with verrucous endocarditis and valves with fibrocalcific changes. In all the valves with verrucous endocarditis the following findings were observed: (1) increased expression of the alpha3beta1 integrin on the endothelial cells, (2) increased amount of collagen IV, laminin and fibronectin, (3) proliferation of blood vessels and (4) linear subendothelial deposition of immunoglobulins and complement. The valves with fibrocalcific changes were deformed and showed a thick layer of collagen IV, laminin and fibronectin, yet in two valves the indothelial cells showed an expression of the alpha3beta1 integrin. The control valves did not express the integrin and had only a thin subendothelial band of collagen IV. In valves from patients with APS, 1 markers of endothelial cell activation are upregulated while the inflammatory exudate is scant. There is also a prominent deposition of immunoglobulins in the valves from patients with APS, suggesting a possible association between the deposition of the antibodies and the activation of the endothelial cells in APS.
The drug use process suffers from problems related to quality and cost that have not responded well to administrative or educational interventions. In many cases, attempts to improve the quality of physician prescribing have been clumsy, often based on intuition. This article begins by describing the drug use process and the role of prescribing in that process. In the following section, we describe what is known about how physicians make drug choice decisions. The paper concludes with suggestions, based on evidence, about the design of strategies for influencing prescribing.
OBJECTIVE: Primary generalized osteoarthritis (OA), the most prevalent joint disease, is usually symmetric. Sporadic case reports mention decreased OA manifestations in limbs in which there are neurologic deficits, but no systematic research has been published. The aim of the present study was to examine these observations in a planned and controlled survey in a group of patients with OA. METHODS: Seventy-five geriatric patients with a history of stroke and hemiparalysis were studied clinically and radiographically (hand radiographs; graded according to a modified Altman method) for the presence and the degree of OA in the hands. Detailed clinical and radiologic scores were calculated for each hand. Demographic, occupational, and neurologic data were collected. Patients with other joint or neurologic conditions were excluded. A group of 55 elderly patients without stroke were similarly studied (controls). Scores in the paralyzed hand were compared with those in the nonparalyzed hand in the stroke patients and subgroups (by Student's paired t-test and Wilcoxon test). Scores in the dominant hands were compared with those in the nondominant hands in stroke patients and control subjects (by Student's paired t-test and Mann-Whitney test). Correlation between the degree of neurologic damage and OA asymmetry (Pearson's correlation coefficient) was also sought. RESULTS: Paralyzed hands showed significantly fewer OA changes than nonparalyzed hands, both clinically and radiologically. This trend, accentuated in patients with more severe paralysis, disappeared in those with mild residual paresis. Asymmetry of OA was more pronounced in patients with flaccid, compared with spastic, paralysis. The degree of paralysis and loss of muscle strength correlated with the degree of OA asymmetry. Women had significantly higher OA scores than men. In the control group, dominant hands had higher OA scores, but this finding was concealed among hemiparalyzed patients. Lifetime gross occupational load and present grip strength did not correlate with the degree of OA. CONCLUSION: In elderly patients, hemiparalysis reduces ipsilateral hand expression of OA, while OA is accentuated (or increased) in the dominant hand of patients without paralysis. This first systematic study confirms the findings of previous case reports and lends support to the role of biomechanical factors in the development of OA.
A novel serum 21 kDa haptoglobin-related protein (Hpr) was investigated in patients with malignant lymphoma, to evaluate its correlation with clinical and histologic features at presentation and its possible role as a tumor marker for patient outcome. One hundred fifty eight serum samples were taken from 88 patients with non-Hodgkin's lymphoma (n=58) and Hodgkin's disease (n=30) at presentation and in the course of follow-up. Sera from 61 healthy volunteers served as normal controls. Serum Hpr levels in the lymphoma patients (median 430x10 u/ml, range 0-4000x10 ) were significantly higher than in the control group (median 68x10 u/ml, range 0-180x10 )(p=0.0001). Higher median Hpr values were detected in patients with advanced disease (p=0.013), "B" symptoms (p=0.029) and in males (p=0.053). There was also a significant correlation between Hpr and erythrocyte sedimentation rate (p=0.028). Serial determinations showed a significant decrease of the initial Hpr values obtained after treatment in 41 patients, 38 of whom achieved complete remission. In the follow-up period additional Hpr measurements were taken from 17 patients. Three of them eventually relapsed, and showed increased Hpr levels at the time of relapse. Hpr levels remained low in 11 of 14 patients who maintained complete remission, and increased in three. In conclusion, serum Hpr is a new serum tumor marker of potential use in the clinical setting of lymphoma.
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This report describes the development and validation of an instrument to assess the attributions human immunodeficiency virus (HIV)-infected persons who are currently taking antiretrovirals make about the effects of these medications. The specific limitations in functioning that the subjects attributed to the effects of medication were assessed. The scores on a ten-item instrument were found to have high internal consistency reliability and to be related to beliefs about the benefits and barriers to taking antiretrovirals. The attribution that the use of antiretrovirals had contributed to an increase in depressive symptoms was related to reports of having temporarily discontinued use of antiretrovirals during the preceding month. The summated score on the Medication Attribution Scale (MAS) and other subscale scores were not found to predict self-reported intentional alterations of treatment regimens. Multiple regression analyses indicated that negative attributions about the effects of medications contributed to the amount of variance in quality of life explained over and above that explained by perceived health status and level of symptomology.
The proportion of patients with intractable pain successfully managed with spinal cord stimulation (SCS) remains disputed. We analyze 27 consecutive patients with intractable pain treated with SCS using identical hardware (Itrel II System; Medtronic Neurological, Inc Minneapolis, MN, USA) by a single satisfactory diagnosis 1992 through 1995. A rigid selection protocol was used: 1. A satisfactory diagnosis of the pathologic process resulting in pain was made. 2. A corrective surgical procedure was judged not feasible by surgeons experienced in the particular pathology, e.g., vascular peripheral nerve, spine. 3. Lack of satisfactory response to noninterventional pain management modalities by an interdisciplinary pain clinic. 4. Independent psychological evaluation, including a structured interview was performed by a psychologist specialized in chronic pain management. In the last eight cases, a battery of self-report tests designed to assess psychosocial and behavioral consequences of the chronic pain problem were administered as well. All cases were of nonmalignant pain, except for one patient. Thirteen cases were diagnosed with failed back surgery syndrome (FBSS), one older patient with lumbosacral radiculopathy who refused decompression, one cervical radiculopathy and Klippel-Feil syndrome, six with reflex sympathetic dystrophy (RSD), two with peripheral vascular ischemic disease, one with post-thoracotomy pain syndrome, one with leg pain following resection of angiolipoma, one with traumatic superficial peroneal neuropathy, and one with Pancoast's tumor. Fifteen patients were female and twelve were male. All were Caucasian. Their ages ranged from 27 to 84 years (mean:48). The average follow-up was 21 months (range: 48-6). All patients underwent a three day trial screening with Pisces-Quad/Resume epidural leads connected to a temporary external stimulator. An Itrel II System pulse-generator was internalized in each of the 24 patients who had successful trial (three cervical and twenty-one thoracic-lumbar). There was no morbidity. Pain reduction was sustained in 22 out of the 24 patients who continue to use the stimulator. The same number would choose to receive in an electrical stimulator again. Normalization or improvement in Quantitative Sudomotor Axon Reflex Test (Q-SART) and Thermography was documented in the patients with RSD. We conclude that rigid selection protocol can maximize the proportion of patients with intractable pain who are successfully treated with SCS. Strict neurosurgical technique eliminates infection risk. Hardware selection minimizes incidence of malfunction.
OBJECTIVE AND IMPORTANCE: We present a very unusual case of diffuse spread of Wegener's granulomatosis causing hydrocephalus. CLINICAL PRESENTATION: A 53-year-old man presented in 1985 with bilateral middle ear infections requiring myringotomies. During the next 18 months, he went on to develop a left Bell's palsy. The patient then began to develop recurrent occipital headaches along with left sixth and seventh nerve palsies and a green nasal discharge requiring hospitalization. Workup included magnetic resonance imaging showing pronounced enhancement of the tentorium and meninges in the occipital region with normal ventricle size. An x-ray of the chest showed multiple pulmonary nodules. A regimen of prednisone and cyclophosphamide was initiated. The patient did well for 2 years until he again developed middle ear infections and headache. Serial lumbar punctures showed increased pressures. A circulating antineutrophil cytoplasmic antibody was positive. Cyclophosphamide was administered, with acetazolamide added for treatment of the elevated intracranial pressure. The patient stabilized for another 2 years but then presented in 1994 with recurrent headache, bilateral papilledema, and mild left arm and right leg weakness. A lumbar puncture was performed with an opening pressure of 52 cm H2O. Computed tomography of the head revealed moderate enlargement of the lateral third and fourth ventricles, consistent with communicating hydrocephalus. INTERVENTION: A right frontal ventriculoperitoneal shunt was placed. A leptomeningeal biopsy performed at the side of catheter placement (far away from any meningeal enhancement revealed by magnetic resonance imaging) showed chronic meningitis and multinucleated giant cells. Cyclophosphamide therapy was begun again. The patient has not experienced recurrence of headache, cranial nerve deficits, or papilledema for more than 3 years. CONCLUSION: This is the first reported case of diffuse involvement of the meninges from Wegener's granulomatosis. Fortunately, this patient responded well to shunting and sustained medical management. Although rare, Wegener's granulomatosis should be included in the differential diagnosis of chronic aseptic meningitis, communicating hydrocephalus, and papilledema.