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Biomedical subjects

M N Silverstein

Publications and source records attributed to M N Silverstein.

At least 37 records · Page 2Linked to original sources
PubMed1994

Trends in the incidence of polycythemia vera among Olmsted County, Minnesota residents, 1935-1989.

To investigate the suggestion that the incidence of polycythemia vera has increased in recent decades, we ascertained secular trends in the incidence of polycythemia vera in Olmsted County, Minnesota, over the 55-year period, 1935-1989. The inpatient and outpatient medical records of all potential cases of polycythemia vera in Olmsted County residents were reviewed and the diagnostic criteria of the Polycythemia Vera Study Group were applied. We found no indication of an increase in the age- and sex-adjusted incidence of polycythemia vera, which averaged 1.9 per 100,000 person-years (95% C.I., 1.4-2.5) over the study period. Incidence rates increased with age, and age-adjusted incidence rates were greater for men (2.8 per 100,000 person-years; 95% C.I., 1.8-3.9) than for women (1.3 per 100,000 person-years; 95% C.I., 0.7-1.9), with the highest incidence rate (23.5 per 100,000 person-years) among men aged 70-79 years. Survival was reduced in this inception cohort of 50 cases, compared to that expected for individuals of like age and sex (P < 0.0001); median survival following diagnosis was 7.2 years.

Adult↗
PubMed1992

Idiopathic myelofibrosis with myeloid metaplasia involving the renal pelves, ureters and bladder.

Myeloid metaplasia associated with idiopathic myelofibrosis most commonly involves the reticuloendothelial organs, such as the spleen, liver and retroperitoneal lymph nodes. We report on a patient with myeloid metaplasia (extramedullary hematopoiesis) of the renal pelves, ureters and bladder. The pathogenesis, clinical characteristics, treatment and prognosis of this condition are discussed.

Adult↗
PubMed1992

Pernicious anaemia as a risk factor for osteoporosis.

1. If gastric acid is necessary for the absorption of dietary calcium, the total absence of gastric acid secretion that occurs in pernicious anaemia could result in bone loss. To investigate this, we measured calcium absorption and bone density in 21 postmenopausal women (ages 51-76 years) with pernicious anaemia and in 24 normal postmenopausal women (ages 51-79 years). 2. Relative to the normal women, in the women with pernicious anaemia the bone mineral density of the lumbar spine was decreased by 16% (P less than 0.001). 3. After adjustment for age and body weight, lumbar spine bone mineral density correlated with the serum concentration of group 1 pepsinogens (a group of proteins produced by the gastric fundus) (r = 0.61, P less than 0.01). 4. Despite achlorhydria, the women with pernicious anaemia had normal true fractional calcium absorption and normal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. 5. We conclude that gastric acid is not required for the absorption of dietary calcium. Thus, the loss of cancellous bone must be caused by some mechanism yet to be identified.

Achlorhydria↗
PubMed1991

Essential thrombocythemia in young adults.

Essential thrombocythemia is typically a disorder of adults in the sixth or seventh decade of life and is characterized by frequent thrombohemorrhagic complications. In young patients, the optimal management of complications is controversial. We studied 56 young adults (33 female and 23 male patients) with a diagnosis of essential thrombocythemia. The mean duration of follow-up was 4.68 years. The mean platelet count at diagnosis was 1,328,000/mm3. Platelet aggregation studies in 21 patients demonstrated hypoaggregation to epinephrine; spontaneous platelet aggregation was present in 4. At diagnosis, 39 patients were asymptomatic, and thrombocytosis was discovered incidentally. Throughout follow-up (up to 20 years), 24 patients remained asymptomatic. Thrombotic complications developed in 24 patients; they were life-threatening in only 3. The most common vaso-occlusive symptoms were migraine headache (in 12 patients) and erythromelalgia (in 3). Minor hemorrhagic complications occurred in six patients, and none was life-threatening. Serious complications (one cerebral and two myocardial infarctions) occurred in three patients, all of whom recovered. Two deaths occurred, neither of which was attributable to essential thrombocythemia. The treatment regimens used were chemotherapy in 9 patients, antiaggregating agents in 7, radioactive phosphorus in 1, the newer platelet-lowering agent anagrelide in 10, and only observation in 29. No treatment-related acute leukemias developed. This series of young patients with essential thrombocythemia, the largest to date, demonstrates a low incidence of life-threatening complications and a favorable long-term prognosis. Therapeutic recommendations should remain conservative, and potential leukemogens should be avoided unless serious complications develop. Anagrelide may be useful in young patients with thrombocythemia who are symptomatic.

Adolescent↗
PubMed1990

Two families with hemoglobin Sogn, beta(A11)14 Leu----Arg, in Minnesota and Indiana: hematologic, functional, and biosynthetic features.

Sogn hemoglobinopathy was identified in a young American woman and in a young American man of apparently unrelated families of Norwegian ancestry. Both persons were asymptomatic and without clinical or hematologic manifestations. Hemoglobin Sogn, beta(A11)14 Leu----Arg, is an unstable hemoglobin that may easily be mistaken for hemoglobin S, G, or D by alkaline hemoglobin electrophoresis. These are the first known instances of hemoglobin Sogn outside of Norway. Oxygen affinity is normal. Sogn hemoglobinopathy is an incidental finding that has no adverse implication for the health of heterozygotes.

Adult↗
PubMed1988

Anagrelide: a new drug for treating thrombocytosis.

Anagrelide is a member of the imidazo (2,1-b) quinazolin-2-one series of compounds, with a powerful antiaggregating effect on platelets. During studies in humans, anagrelide in small doses has produced thrombocytopenia. We therefore evaluated it in the treatment of thrombocytosis, and to date, platelet levels in 15 of 17 patients with primary thrombocythemia, 2 patients with polycythemia vera and thrombocytosis, and 1 patient with chronic granulocytic leukemia and thrombocytosis have been well controlled with the use of this agent. Induction doses of 1.0 to 1.5 mg given orally every six hours have produced a decrease in the platelet count, starting on day 5 and reaching a normal level by day 12. Side effects of anagrelide have been minimal. Maintenance therapy with 1.5 to 4.0 mg a day has continued to control the platelet count in patients for up to 28 months. This new agent appears promising in the treatment of thrombocytosis in patients with chronic myeloproliferative disease.

Adult↗
PubMed1988

Chemotherapy followed by consolidation radiation therapy for the treatment of clinical stage II aggressive histologic type non-Hodgkin's lymphoma.

Sixty-three eligible patients with Ann Arbor clinical Stage II or IIE aggressive histologic type non-Hodgkin's lymphomas received combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [COPA]) as the primary treatment technique. Moderate-dose radiation therapy (2500 to 3000 cGy in 2 to 3 weeks) was given to anatomic areas involved initially by lymphoma in patients demonstrated to be in complete remission after chemotherapy. Fifty-seven percent of the patients were free of lymphoma clinically after induction chemotherapy. The minimum patient follow-up from the start of chemotherapy is 3.7 years, and the median follow-up for patients still alive is 4.7 years. The progression-free survival is projected to be 62% at 4 years, and 86% of the patients achieving a complete response are projected to be in continuous remission at 4 years from the completion of all therapy. There were no treatment-related fatalities. This treatment sequence has produced durable tumor control in the majority of patients with acceptable toxicity. The need for consolidation radiation therapy is being studied currently in a controlled clinical trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Relative and absolute polycythemia. How to tell them apart.

Relative and absolute polycythemia can be differentiated by measuring red cell mass and plasma volume. Often no treatment is recommended for patients with relative polycythemia unless directed toward vascular complications; phlebotomy is definitely contraindicated. For patients with polycythemia vera, however, phlebotomy is used routinely to decrease blood viscosity, while myelosuppression is reserved for patients who are not relieved by phlebotomy alone. Secondary polycythemia is controlled by correcting the cause or by circumspect use of phlebotomy if the cause cannot be remedied.

Diagnosis, Differential↗
PubMed1987

Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma.

Three hundred thirty-two eligible patients with advanced (Ann Arbor stage III or IV) non-Hodgkin's lymphoma of aggressive histologic subtype (Rappaport classification diffuse histiocytic [DH], diffuse poorly differentiated lymphocytic [DPDL], diffuse mixed [DM], or diffuse undifferentiated [DU]) were randomly assigned to receive induction chemotherapy with one of three intensive regimens in a clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) between 1978 and 1983. Chemotherapy regimens consisted of cyclophosphamide, vincristine, prednisone, and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (COPA) administered in 3-week cycles; cyclophosphamide plus doxorubicin plus prednisone beginning day 1, with vincristine plus bleomycin day 15 of each 3-week cycle (COPA + Bleo); or cyclophosphamide plus doxorubicin plus procarbazine beginning day 1, and bleomycin plus vincristine plus prednisone beginning day 15 of each 4-week cycle (CAP-BOP). The median patient follow-up from study entry for patients still alive is 5 years. The three regimens were not significantly different with respect to complete response (CR) rates (43% to 46%), time to progression of malignant disease (median, 1.0 to 1.7 years), or survival (5-year survival, 34% to 45%), although duration of complete remission appeared to be shorter in patients receiving COPA (P = .03). COPA + Bleo and CAP-BOP were significantly more toxic than the COPA regimen. This study did not demonstrate any substantial therapeutic advantage associated with the addition of a fifth or sixth chemotherapy drug, or with treatment administered on a more frequent administration schedule, compared with the COPA regimen in this population of patients with advanced diffuse non-Hodgkin's lymphoma. The relatively small proportion of long-term disease-free survivors treated with COPA underscores the need for prospective clinical trials of new and more effective treatments for patients with these potentially curable tumors.

Adult↗
PubMed1987

Contribution of prednisone to the effectiveness of hexamethylmelamine in multiple myeloma.

The Eastern Cooperative Oncology Group evaluated hexamethylmelamine in 89 patients with advanced refractory or relapsing multiple myeloma. Hexamethylmelamine was initially used as a single agent administered orally at 200 mg/m2/day for the first 3 weeks of each 4-week cycle. When this regimen proved to be ineffective, it was modified first by increasing the dose of hexamethylmelamine to 280 mg/m2/day and subsequently by adding prednisone at 75 mg for the first 7 days of each 28-day cycle. None of the 39 patients receiving hexamethylmelamine without prednisone had an objective response, while two patients had minimal objective improvement (25%-50% decrease in M protein with symptomatic improvement). Only 14% of these patients had objective or symptomatic response or both. In contrast, patients treated with hexamethylmelamine plus prednisone had a 22% objective response rate, with another 14% showing lesser degrees of objective improvement. Fifty-one percent of the patients treated with this regimen had either objective or symptomatic improvement or both. Severe (grade 3) toxicity was seen in nearly two-thirds of the patients on the higher-dose hexamethylmelamine regimens compared with 37% of the patients receiving low-dose hexamethylmelamine; however, in most instances this represented rapidly reversible cytopenias. Because all but one of the patients responding to hexamethylmelamine plus prednisone had experienced previous treatment failure on regimens containing prednisone in similar dose and schedules, it is unlikely that the responses are due to prednisone alone. Instead, this study suggests that the activity of hexamethylmelamine in multiple myeloma is dependent on the concomitant administration of prednisone and that the combination regimen appears to be synergistic.

Adult↗
PubMed1985

Deletions of chromosome 13 in malignant hematologic disorders.

Thirteen patients with a hematologic disorder and an interstitial deletion of part of a chromosome #13 were evaluated to determine if any specific clinical manifestations are associated with these cytogenetic anomalies. Our results suggest that these anomalies occur in approximately 1.7% of patients with a chromosomally abnormal clone and a hematologic disorder. They may occur as the sole chromosome anomaly (8 of our patients) or with other abnormalities (5 of our patients). The breakpoints are not always the same, but band 13q14 always seems to be lost. At the time of chromosome analysis, 5 patients had a history of myelofibrosis or agnogenic myeloid metaplasia, 2 had acute nonlymphocytic leukemia, 2 had a myelodysplastic syndrome, one had polycythemia vera, one had sideroblastic anemia, one had acute lymphocytic leukemia, and one had an undifferentiated myeloproliferative disorder.

Adult↗
PubMed1984

High-dose cyclophosphamide. An effective treatment for advanced refractory multiple myeloma.

The Eastern Cooperative Oncology Group evaluated cyclophosphamide 600 mg/m2 intravenously daily X 4 (total dose each cycle 2400 mg/m2) as an aggressive approach to the treatment of patients with advanced multiple myeloma. The overall objective response rate is 43%. This includes a 38% response rate for all previously treated patients and a 29% response rate for patients refractory to prior therapy with cyclophosphamide. The objective response duration was 3 months and the survival of responding patients 9 months. A subjective response rate of 63% was observed, characterized by effective pain relief and improved performance. Sixty-nine percent of patients experienced leukocyte cell nadirs less than 500/mm2 with a mean time to marrow recovery of 17 days. Thrombocytopenia was less severe but required platelet transfusion in 43% of patients. Bone marrow toxicity was encountered in all patients, and death in aplasia is a significant risk. Strict adherence to entry criteria, and a systematic plan for hospitalization for antibiotic and blood component support is required for treatment with this regimen.

Alopecia↗
PubMed1983

Sequential cyclophosphamide-prednisone and vincristine-bleomycin (CPOB). An effective, schedule-dependent treatment for advanced diffuse histiocytic lymphoma.

In an Eastern Cooperative Oncology Group non-Hodgkin's lymphoma clinical trial, 90 patients with Stage III or IV diffuse histiocytic lymphoma (DHL) were treated with one of four chemotherapy regimens. All patients were previously untreated with chemotherapy, and careful restaging was required to document responses. Each treatment included cyclophosphamide, vincristine and prednisone (COP) plus Adriamycin (COPA), BCNU (BCVP) or bleomycin (COPB and CPOB). The two bleomycin-containing regimens differed only in the schedule of drug administration. CPOB-treated patients received cyclophosphamide on day 1, prednisone on days 1 to 5 and vincristine and bleomycin on day 15 of each 21-day cycle. COPB-treated patients received the same four drugs in the same dosage; however, the schedule was changed so that vincristine and bleomycin were given on day 1. Treatment of responders was continued for 8 cycles. Those with a complete response (CR) were randomized to maintenance therapy with BCVP or no treatment. Treatment with CPOB yielded a CR rate of 55% compared to 25% for COPB (P = 0.07). In contrast to COPB, treatment with CPOB was associated with a significantly longer median duration of CR (26.5 versus 5.7 months; P less than 0.05) and median survival (27.7 versus 11.2 months; P less than 0.02). The CR rate was 31% for BCVP and 45% for COPA, and the median survivals were 10.7 months and 14.4 months, respectively. One half of the CPOB-treated patients who achieved CR remained alive in continuous CR after 30 to 72 months. No advantage for maintenance therapy was observed. Myelotoxicity was greater with CPOB than COPB, but comparable to COPA. This trial demonstrated that the results of treatment of DHL with COP plus bleomycin were strikingly dependent upon the schedule of administration of bleomycin and vincristine. Bleomycin effectively combined with COP, as in CPOB, yielded results comparable to those obtained when Adriamycin was added to COP. CPOB appears to be an effective treatment for DHL that should be considered as an alternative to other regimens, particularly for patients who cannot receive Adriamycin.

Antineoplastic Agents↗
PubMed1981

Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy.

In studies to determine the optimal treatment for polycythemia vera, 431 previously untreated patients whose disease met established diagnostic criteria were entered into a prospective, randomized controlled trial between 1967 and 1974. Three treatment regimens were used: phlebotomy alone, chlorambucil supplemented by phlebotomy, or radioactive phosphorus supplemented by phlebotomy. Despite minor differences in age and sex, the three groups were comparable in initial hematocrit, white-cell and platelet counts, and disease-related symptoms. The median duration of follow-up is now more than 6 1/2 years. As of February 15, 1980, there were no statistically significant differences in survival among the groups. However, the risk of acute leukemia in patients given chlorambucil was 2.3 times that in patients given radioactive phosphorus and 13 times that in patients treated with phlebotomy alone. The increased incidence of leukemia during chlorambucil treatment is statistically significant (P less than or equal to 0.002); accordingly, the Polycythemia Vera Study Group has discontinued the use of chlorambucil in the treatment of polycythemia vera.

Acute Disease↗