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S Dubrey

Publications and source records attributed to S Dubrey.

At least 19 recordsLinked to original sources
PubMed1998

Dose-intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients.

AL (amyloid light-chain) amyloidosis is an uncommon plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure and death in a median of 13 months. Autologous stem-cell transplantation is effective therapy for multiple myeloma and therefore, we evaluated its efficacy for AL amyloidosis. Patients with adequate cardiac, pulmonary, and renal function had stem cells mobilized with granulocyte-colony stimulating factor and were treated with dose-intensive intravenous melphalan (200 mg/m2). Response to therapy was determined by survival and improvement of performance status, complete response or persistence of the clonal plasma cell disorder, and change in the function of organs involved with amyloid at baseline. We enrolled 25 patients with a median age of 48 years (range, 29-60), all of whom had biopsy-proven amyloidosis with clonal plasma cell disorders. Twenty-two (88%) were Southwest Oncology Group performance status 1 or 2 within a year of diagnosis, and 16 (64%) had received no prior therapy. Predominant amyloid-related organ involvement was cardiac (n = 8), renal (n = 7), hepatic (n = 6), neuropathic (n = 3), and lymphatic (n = 1). Fifteen patients had one or two organ systems involved, whereas 10 had three or more involved. With a median follow-up of 24 months (12-38), 17 of 25 patients (68%) are alive, and the median survival has not been reached. Thirteen of 21 patients (62%) evaluated 3 months posttransplant had complete responses of their clonal plasma cell disorders. Currently, two thirds of the surviving patients (11 of 17) have experienced improvements of amyloid-related organ involvement in all systems, whereas 4 of 17 have stable disease. The improvement in the median performance status of the 17 survivors at follow-up (0 [range, 0-3]) is statistically significant versus baseline (2 [range, 1-3]; P < . 01). Significant negative prognostic factors with respect to overall survival include amyloid involvement of more than two major organ systems and predominant cardiac involvement. Three patients have experienced relapses of the clonal plasma cell disorder at 12 and 24 months. Dose-intensive therapy should currently be considered as the preferred therapy for patients with AL amyloidosis who meet functional criteria for autologous transplantation.

Adult↗
PubMed1996

Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: one-year follow-up in five patients.

The morbidity and lethality of AL amyloidosis is caused by the deposition of lg light chains as fibrillar amyloid protein in vital organs, disrupting their function, and not by the generally low burden of clonal plasma cells that produce the paraproteins. Survival of patients with AL amyloidosis is no more than 1 to 2 years from the time of diagnosis with current management approaches. Clearly, more effective therapies are needed for this rapidly lethal disease. Five patients were treated with dose-intensive melphalan and blood stem cell support and followed for a period of 1 year. Patients were diagnosed with AL amyloidosis by tissue biopsy and categorized by performance status and organ involvement. Their plasma cell dyscrasias were evaluated with immunofixation electrophoresis of serum and urine specimens, quantitative serum lgs, and immunohistochemical staining of bone marrow biopsy specimens. After treatment with dose-intensive intravenous melphalan followed by infusion of autologous growth-factor-mobilized blood stem cells, clinical evaluations and plasma cell studies were repeated at 3 and 12 months. Three men and 2 women aged 38 to 53 years were treated. Median performance status (SWOG) was 2 (1 to 3), and clinical presentations included nephrotic syndrome (n = 1), symptomatic cardiomyopathy (n = 1), gastrointestinal involvement with polyneuropathy (n = 2), and hepatomegaly (n = 1). With a median follow-up of 13 months (12 to 17 months), all five patients are well and have shown stable or improved performance status and clinical remission of organ-related dysfunction, including a 50% reduction in daily proteinuria with no change in creatinine, reversal of symptoms of cardiomyopathy and reductions of posterior wall and septal thickening, reversal of polyneuropathy and gastric atony, and resolution of hepatomegaly by computed tomographic scan. In 3 of the 5 patients (60%) at 12 months after treatment, plasma cell dyscrasias could not be detected. Dose-intensive chemotherapy with intravenous melphalan and growth-factor-mobilized blood stem cell support is feasible therapy for patients with AL amyloidosis, even when there is clinical evidence of cardiac involvement. At least some patients with AL amyloidosis achieve complete remission of their plasma cell dyscrasia, improvement in performance status, and clinical remission of organ-specific disease after this form of treatment.

Adult↗
PubMed1996

Resolution of heart failure in patients with AL amyloidosis.

BACKGROUND: Patients with AL amyloidosis and congestive heart failure have a very poor prognosis. To date, the recovery of these patients has not been described in detail. OBJECTIVE: To determine the frequency and characteristics regression of disease in patients with congestive heart failure due to AL amyloidosis. DESIGN: Review of patients with systemic AL amyloidosis. SETTING: An international referral center for amyloidosis in the United States. PATIENTS: 140 patients with congestive heart failure due to Al amyloidosis who were seen between 1983 and 1994. MEASUREMENTS: Functional status, Doppler echocardiography, and objective measurements of disease activity. RESULTS: 3 of 140 patients (2.1%) had marked resolution of congestive heart failure and evidence for remission of disease activity. All 3 had been treated with melphalan. CONCLUSIONS: Melphalan appears to have had a favorable effect in 3 patients with AL amyloidosis and heart failure. The abolition of light chains that was seen in these 3 patients suggests that light-chain toxicity may play a role in the genesis of heart failure in patients with AL amyloidosis.

Amyloidosis↗
PubMed1995

Doppler determined aortic acceleration after dipyridamole in the prediction of coronary artery disease.

Change in the acceleration of aortic blood flow with stress testing is reported to reflect the presence of myocardial ischaemia. We studied its clinical usefulness when compared with dipyridamole thallium scintigraphy in 101 patients, of whom 64 had coronary angiography. Maximum aortic acceleration increased after dipyridamole (P < 0.0001), although no correlation existed between the aortic acceleration and evidence of thallium perfusion abnormalities. For the patients who had angiography, the increase in aortic acceleration was similar for those with no significant coronary stenoses, single vessel or multi-vessel disease. Compared with coronary angiography, Doppler measurement of maximum aortic acceleration had a sensitivity of 92% and a specificity of 37% for the detection of coronary artery disease. When patients with previous myocardial infarction or left ventricular dysfunction were excluded, there was still no relationship between the maximum aortic acceleration and the presence of coronary artery disease. We conclude that changes in the acceleration of aortic blood flow after dipyridamole stressing do not predict the presence or severity of coronary artery disease as measured from perfusion defects at thallium scintigraphy or by coronary angiography. We have observed a wide variability of aortic maximum acceleration in the evaluation of myocardial ischaemia, which we feel introduces serious limitations to its use in routine clinical practice.

Acceleration↗
PubMed1995

Atrial thrombi occurring during sinus rhythm in cardiac amyloidosis: evidence for atrial electromechanical dissociation.

Thrombus formation in the left atrium is rare in patients in sinus rhythm. In three patients with extensive cardiac amyloidosis transthoracic echocardiography showed large atrial thrombi in or protruding into the body of the left atrium during sinus rhythm. Doppler studies showed no A wave on mitral inflow. Severe atrial and ventricular infiltration by amyloid may have resulted in mechanical atrial standstill with resultant thrombus formation. These findings suggest that patients with severe cardiac amyloidosis may require anticoagulation when atrial function is impaired.

Adult↗
PubMed1994

Emerging patterns of heart disease in HIV infected homosexual subjects with and without opportunistic infections; a prospective colour flow Doppler echocardiographic study.

We studied 124 homosexual men aged 36.7 +/- 7.6 years (range 23-57) using Doppler echocardiography. One hundred and one patients (Group A) had had acquired immunodeficiency syndrome for 1.6 +/- 1.0 years and 23 patients (Group B) had had HIV infection without opportunistic infections for 3.2 +/- 2.3 years. Doppler echocardiography was normal in 31% of Group A patients and in 61% of Group B. Pericardial effusion was found in 44 Group A patients (44%) and two Group B patients (9%). In Group A, left ventricular dilatation and/or dysfunction were found in 20 patients (20%), aortic root dilatation and regurgitation in eight patients (8%) and an intracardiac echogenic mass in seven patients (7%); in Group B one patient (4%) had an intracardiac mass. Forty-four (44%) Group A patients had cardiac presentations, and of these 22 had cardiomegaly with clinical signs of heart failure; 10 patients had tachyarrhythmias compared to only two in Group B. Although the CD4 lymphocyte count (%) was significantly lower in Group A than in Group B (5.4 +/- 6.1 vs 13.3 +/- 7.3, P < 0.001), the presence of pericardial effusion, left ventricular dysfunction, right-sided cardiac enlargement or the duration of HIV infection, did not relate to the CD4 level in either group. Although often not diagnosed clinically, cardiac involvement in patients with AIDS is a clinical reality, with pericardial effusion, cardiomyopathy and left ventricular dysfunction appearing to have a high prevalence in male homosexual patients with AIDS. These clinical and echocardiographic findings are associated with clinically apparent intercurrent opportunistic infections, rather than the HIV virus per se, or the severity of infection as reflected by the CD4 count.

AIDS-Related Opportunistic Infections↗
PubMed1994

Muscular false tendons, aberrant left ventricular papillary musculature, and severe electrocardiographic repolarisation abnormalities: a new syndrome.

Three patients (age 18-39 years; two men) with normal exercise capacity, normal left ventricular function, large muscular false tendons within the left ventricle, and anomalously placed papillary muscles associated with giant T wave inversion on the electrocardiogram are described. The absence of adverse cardiovascular events at long-term follow up (mean 13 years) indicates that this is a benign unrecognised syndrome.

Adult↗
PubMed1994

Exercise electrocardiography and aortic Doppler velocimetry in asymptomatic identical twins discordant for type 1 (insulin dependent) diabetes.

OBJECTIVE: To determine the influence of insulin dependent diabetes on the prevalence of myocardial ischaemia and on global left ventricular systolic performance. DESIGN: Stress treadmill electrocardiograms and simultaneous Doppler measurement of aortic maximum acceleration were obtained during exercise on symptom free subjects. The electrocardiograms were scored blindly according to the Minnesota code. PARTICIPANTS: 39 identical twin pairs (22 male) discordant for insulin dependent diabetes and 39 non-diabetic controls of similar age and sex were examined. The twins and controls had a mean age of 37 (range 25-69) with a mean (SD) duration of diabetes in the diabetic twin of 17 (7) years. Those selected were normotensive and had no renal impairment. RESULTS: Systolic blood pressure was significantly higher in the diabetic twins than in their non-diabetic cotwins both at rest (p < 0.05) and at peak exercise (p < 0.01). Electrocardiographic evidence of ischaemia was not correlated within twin pairs and was found in similar numbers of diabetic twins, their non-diabetic cotwins, and control subjects. Abnormal electrocardiograms were found in a similar number of diabetic twins (23%), non-diabetic cotwins (18%), and controls (15%). There was a significant correlation in Doppler measurements of global left ventricular systolic function within the identical twins; no significant difference was found for these Doppler measurements in the diabetic twins, non-diabetic cotwins, or controls. CONCLUSION: Exercise characteristics and cardiac function seem to be subject to shared genetic or shared environmental influences or both, whereas electrocardiographic features of ischaemia seem to be environmentally determined. In a selected cohort of diabetic identical twins without evidence of nephropathy there was no evidence that diabetes influenced the prevalence of myocardial ischaemia or global left ventricular systolic function.

Adult↗
PubMed1994

Defrosting insulin: a case report.

We report a case where a patient used microwave radiation to thaw his frozen insulin resulting in marked deterioration in his diabetic control. The consequences of this action were examined using high-performance liquid chromatography.

Adult↗