Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: long-term results of a randomized trial in allogeneic marrow recipients with leukemia. Nordic Bone Marrow Transplantation Group.
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Leukemic patients receiving marrow from HLA-identical sibling donors were randomized to treatment with either busulfan 16 mg/kg (n = 88) or total body irradiation ([TBI] n = 79) in addition to cyclophosphamide 120 mg/kg. The patients were observed for a period of 5 to 9 years. Busulfan-treated patients had an increased risk of veno-occlusive disease (VOD) of the liver (12% v 1%, P =.01) and hemorrhagic cystitis (32% v 10%, P =.003). Acute graft-versus-host disease (GVHD) was similar in the two groups, but the 7-year cumulative incidence of chronic GVHD was 59% in the busulfan-treated group versus 47% in the TBI group (P =.05). Death from GVHD was more common in the busulfan group (22% v 3%, P <.001). Obstructive bronchiolitis occurred in 26% of the busulfan patients but in only 5% of the TBI patients (P <.01). Complete alopecia developed in 8 busulfan patients and partial alopecia in 17, versus five with partial alopecia in the TBI group (P <.001). Cataracts occurred in 5 busulfan-treated patients and 16 TBI patients (P =.02). The incidence of relapse after 7 years was 29% in both groups. Seven-year transplant-related mortality (TRM) in patients with early disease was 21% in the busulfan group and 12% in the TBI group. In patients with more advanced disease, the corresponding figures were 64% and 22%, respectively (P =.004). Leukemia-free survival (LFS) in patients with early disease was 68% in busulfan-treated patients and 66% in TBI patients. However, 7-year LFS in patients with more advanced disease was 17% in the busulfan group versus 49% in the TBI group (P <.01). In patients with chronic myeloid leukemia (CML) in first chronic phase, 7-year LFS was 72% and 83% in the two groups, respectively. (+info)
The changing elderly population and future health care needs.
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The impending growth of the elderly population requires both fiscal and substantive changes in Medicare and Medicaid that are responsive to cost issues and to changing patterns of need. More emphasis is required on chronic disease management, on meaningful integration between acute and long-term care services, and on improved coordination between Medicare and Medicaid initiatives. This paper reviews various trends, including the growth in managed-care approaches, experience with social health maintenance organizations and Program of All-Inclusive Care for the Elderly demonstrations, and the need for a coherent long-term care policy. Such policies, however, transcend health care and require a broad range of community initiatives. (+info)
Endothelin B receptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction.
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OBJECTIVES: This study was designed to assess the functional importance of endothelin (ET)B receptors in patients with left ventricular systolic dysfunction (LVSD) by comparing the hemodynamic effects of ET-1, a nonselective ET(A) and ET(B) agonist, with ET-3, a selective ET(B) receptor agonist. BACKGROUND: Knowledge of the functional importance of ET(B) receptors in mediating vasoconstriction in chronic heart failure will help determine whether antagonists at both ET(A) and ET(B) receptors are required to fully prevent vasoconstriction to endogenously produced ET-1. METHODS: We infused ET-1 (5 and 15 pmol/min) and ET-3 (5 and 15 pmol/min) into two separate groups of eight patients with LVSD with similar baseline hemodynamic indices. Hemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. RESULTS: Endothelin-1 infusion led to systemic vasoconstriction, with a rise in mean arterial pressure (mean +/- SEM 100 +/- 3 to 105 +/- 3 mm Hg, p < 0.02) and systemic vascular resistance (1,727 +/- 142 to 2,055 +/- 164 dyn/s/cm(-5), p < 0.001) and a fall in cardiac index (2.44 +/- 0.21 to 2.22 +/- 0.20 liters/min/m , p < 0.01). Endothelin-3 infusion also led to systemic vasoconstriction, with a rise in mean arterial pressure (99 +/- 6 to 105 +/- 6 mm Hg, p < 0.01) and systemic vascular resistance (1,639 +/- 210 to 1,918 +/- 245 dyn/s/cm(-5), p < 0.01) and a fall in cardiac index (2.66 +/- 0.28 to 2.42 +/- 0.24 liters/min/m2, p < 0.05). Pulmonary hemodynamic measurements did not change significantly in either group. CONCLUSIONS: Both ET-1 and ET-3 infusions led to systemic vasoconstriction; the hemodynamic changes observed were of a similar magnitude at the same molar concentration. This suggests that ET(B) receptors are functionally important in mediating vasoconstriction, at least in the systemic circulation, in patients with LVSD. (+info)
Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance.
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OBJECTIVES: The purpose of the study was to investigate if apoptosis occurs in skeletal muscle myocytes and its relation to exercise intolerance in patients with chronic heart failure (CHF). BACKGROUND: Intrinsic abnormalities of skeletal muscle frequently limit exercise tolerance in CHF patients. Recently, apoptosis has been detected in cardiac myocytes of patients with CHF, suggesting that apoptosis may contribute to the reduced contractile force. The presence and regulation of apoptosis in skeletal myocytes of patients with CHF remains to be defined. METHODS: Skeletal muscle biopsies (m. vastus lateralis) of 34 CHF patients (New York Heart Association functional class II-III) and eight age-matched healthy control subjects were analyzed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling for the presence of apoptosis, and by immunohistochemistry and videodensitometrical quantification for inducible nitric oxide synthase (iNOS) and Bcl-2 expression. Maximal oxygen consumption (VO2max) was determined by ergospirometry. RESULTS: Apoptosis was detected in 16/34 (47%) patients with CHF and in none of the healthy subjects. Patients with apoptosis-positive skeletal muscle myocytes exhibited a significantly lower VO2max (12.0 +/- 3.7 vs. 18.2 +/- 4.4 ml/kg/min; p = 0.0005), a higher iNOS expression (6.8 +/- 3.6 vs. 3.7 +/- 2.6% iNOS-positive stained tissue area; p = 0.015) and a lower Bcl-2 expression (1.0 +/- 0.3 vs. 1.4 +/- 0.4% Bcl-2-positive tissue area; p = 0.03) as compared with patients with apoptosis-negative biopsies. CONCLUSIONS: These results indicate that apoptosis is frequently found in skeletal muscle obtained from CHF patients, which is associated with significant impairment of functional work capacity. In skeletal muscle of these patients, iNOS and Bcl-2 are possibly involved in the regulation of apoptosis. (+info)
Amiodarone versus propafenone for conversion of chronic atrial fibrillation: results of a randomized, controlled study.
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OBJECTIVES: The purpose of this study was to investigate the efficacy and safety of amiodarone and propafenone in the conversion of chronic atrial fibrillation in a prospective, randomized, placebo-controlled study. BACKGROUND: The effectiveness of amiodarone and propafenone in the treatment of patients with chronic atrial fibrillation has not been adequately studied. METHODS: One hundred one patients (48 men, mean age 64 +/- 9 years) with atrial fibrillation lasting >3 weeks participated in the study. Thirty-four patients received amiodarone (300 mg intravenously over 1 h, followed by 20 mg/kg over the next 24 h plus 600 mg orally, in three doses, for 1 week, then 400 mg/day orally, for three weeks), 32 received propafenone (2 mg/kg intravenously over 15 min, followed by 10 mg/kg over 24 h and then 450 mg/day orally, for one month) and the remaining 35 served as control subjects. All patients received digoxin and anticoagulant treatment as indicated (International Normalized Ratio 2 to 3). RESULTS: Conversion to sinus rhythm was achieved in 16 (47.05%) patients who received amiodarone, in 13 (40.62%) who received propafenone and in none of the control subjects (p < 0.001 for both groups vs. control subjects). Those who converted had smaller atria than those who did not and atrial fibrillation of shorter duration in both the amiodarone and propafenone groups. Treatment was discontinued in one patient of the propafenone group because of significant QRS widening. CONCLUSIONS: Amiodarone and propafenone appear to be safe and equally effective in the termination of chronic atrial fibrillation. Left atrial diameter and arrhythmia duration are independent predictors of conversion. (+info)
Spontaneous late improvement of myocardial viability in the chronic infarct zone is possible, depending on persistent TIMI 3 flow and a low grade stenosis of the infarct artery.
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OBJECTIVE: In the chronic phase of myocardial infarction, the relation between myocardial recovery and infarct related artery status remains unclear. The spontaneous changes in rest-redistribution thallium defect size were prospectively studied over six months in 52 patients with chronic Q wave myocardial infarction. DESIGN: Changes in rest thallium defect size, thallium uptake in the infarct area, and radionuclide left ventricular ejection fraction were compared to the quantitative coronary angiogram data. Two groups of patients were considered: patients with a percentage of stenosis below 100% (group 1, n = 31); and patients with an occluded artery (group 2, n = 21). RESULTS: In the overall population, the mean (SD) defect size decreased from 28.2 (17.2)% to 24.9 (19.3)% of the whole myocardium (p = 0.01), while, in this area, the thallium uptake increased from 62.9 (13.7)% to 66. 9 (15.6)% (p < 0.001). At the time of inclusion, the defect size, thallium uptake, and ejection fraction were similar in both groups. In group 1 patients only, the reduction in defect size correlated with the improvement in ejection fraction (r = 0.41, p = 0.02) and was related to the percentage of coronary artery stenosis. TIMI 3 patients reduced the defect size while other patients increased this defect (-5.1 (7.0)% v +11.0 (14.4)%, p < 0.001). In contrast, no significant relations were found in group 2 patients. CONCLUSION: Late spontaneous recovery in thallium defect can occur in patients with a patent infarct related artery, depending on the TIMI flow grade and a low grade stenosis of the infarct related artery, and is associated with functional improvement. (+info)
Inhibition of inducible nitric oxide synthase exacerbates chronic cerebral toxoplasmosis in Toxoplasma gondii-susceptible C57BL/6 mice but does not reactivate the latent disease in T. gondii-resistant BALB/c mice.
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Infection of C57BL/6 mice with Toxoplasma gondii leads to progressive and ultimately fatal chronic Toxoplasma encephalitis (TE). Genetic deletion or inhibition of inducible nitric oxide synthase (iNOS) from the beginning of infection increased the number of T. gondii cysts in the brain and markedly reduced the time-to-death in this mouse strain. In the present study, we addressed whether iNOS also contributes to the control of intracerebral parasites in a clinically stable latent infection that develops in T. gondii-resistant BALB/c mice after resolution of the acute phase of TE. iNOS was expressed in the inflammatory cerebral infiltrates of latently infected BALB/c mice, but the number of iNOS+ cells was significantly lower than in the brains of chronically infected T. gondii-susceptible C57BL/6 mice. In BALB/c mice with latent TE (> 30 days of infection), treatment with the iNOS inhibitors L-N6-iminoethyl-lysine or L-nitroarginine-methylester for < or = 40 days did not result in an increase of the intracerebral parasitic load and a reactivation of the disease, despite the presence of iNOS-suppressive inhibitor levels in the brain. However, L-nitroarginine-methylester treatment had remarkably toxic effects and induced a severe wasting syndrome with high mortality. In contrast to BALB/c mice, L-N6-iminoethyl-lysine treatment rapidly exacerbated the already established chronic TE of C57BL/6 mice. Thus, the containment of latent toxoplasms in T. gondii-resistant BALB/c mice is independent of iNOS, whereas the temporary control of intracerebral parasites in T. gondii-susceptible C57BL/6 mice with chronic TE requires iNOS activity. (+info)
Mortality in relation to smoking: 20 years' observations on male British doctors.
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In 1951 the British Medical Association forwarded to all British doctors a questionnaire about their smoking habits, and 34440 men replied. With few exceptions, all men who replied in 1951 have been followed for 20 years. The certified causes of all 10 072 deaths and subsequent changes in smoking habits were recorded. The ratio of the death rate among cigarette smokers to that among lifelong non-smokers of comparable age was, for men under 70 years, about 2:1, while for men over 70 years it was about 1-5:1. These ratios suggest that between a half and a third of all cigarette smokers will die because of their smoking, if the excess death rates are actually caused by smoking. To investigate whether this is the case, the relation of many different causes of death to age and tobacco consumption were examined, as were the effects of giving up smoking. Smoking caused death chiefly by heart disease among middle-aged men (and, with a less extreme relative risk, among old men,) lung cancer, chronic obstructive lung disease, and various vascular diseases. The distinctive features of this study were the completeness of follow-up, the accuracy of death certification, and the fact that the study population as a whole reduced its cigarette consumption substantially during the period of observation. As a result lung cancer grew relatively less common as the study progressed, but other cancers did not, thus illustrating in an unusual way the causal nature of the association between smoking and lung cancer. (+info)