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Biomedical subjects

S Sorensen

Publications and source records attributed to S Sorensen.

At least 37 records · Page 2Linked to original sources

Salvage therapy for relapsed or refractory non-Hodgkin's lymphoma utilizing autologous bone marrow transplantation.

PURPOSE: Our objective was to evaluate the impact of high-dose therapy and autologous bone marrow transplantation as salvage treatment for recurrent non-Hodgkin's lymphoma in a defined group of patients from the Nebraska Lymphoma Study Group. DESIGN: Patients treated initially by oncologists from the Nebraska Lymphoma Study Group between January 1983 and July 1987 who subsequently underwent autologous bone marrow transplantation for recurrent or refractory disease were evaluated for treatment outcome. PATIENTS: Twenty-five patients with relapsed or refractory non-Hodgkin's lymphoma underwent high-dose therapy and autologous stem cell infusion in the time period reviewed. An initial doxorubicin (Adriamycin)-containing chemotherapy regimen had failed in all patients. The most favorable subgroup included 17 patients who were less then 60 years of age and had received no chemotherapy beyond their initial doxorubicin-containing regimen when referred for bone marrow transplantation. RESULTS: The complete response rate to the high-dose therapy was 52%, with an actuarial five-year disease-free survival of all patients treated of 40%. The overall survival at five years was 46%. CONCLUSIONS: High-dose chemo-radiotherapy, followed by infusion of autologous hematopoietic stem cells, can effectively function as salvage therapy in a significant number of patients in whom primary chemotherapy regimens for non-Hodgkin's lymphoma fail. This treatment approach appears to offer superior results when compared with the reported outcome for patients treated with salvage chemotherapy administered at conventional doses.

Adolescent↗

Clinical significance of immunophenotype in diffuse aggressive non-Hodgkin's lymphoma.

We performed a prospective study of the clinical significance of immunophenotype in 110 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by oncologists in the Nebraska Lymphoma Study Group between October 1982 and May 1986. All patients were immunophenotyped from biopsies performed before therapy was administered. The patients were treated with a uniform protocol of radiotherapy for minimal nonbulky, stage I or II disease (seven patients) or a single, six-drug chemotherapy regimen cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone (CAP-BOP) in patients with more extensive disease (103 patients). Ninety-one patients (83%) had B-cell lymphoma and 19 patients (17%) had T-cell lymphoma. The histologic diagnosis of diffuse mixed-cell lymphoma was significantly associated with T-cell immunophenotype (45% v 5%; P less than .001), and the diagnosis of diffuse large-cell lymphoma was significantly associated with B-cell immunophenotype (40% v 5%; P = .006). However, no significant difference in frequency of prognostic variables such as age, stage, systemic symptoms, tumor bulk, serum lactic dehydrogenase, or performance status was found between the B-cell and T-cell groups. Patients with B-cell NHL had a slightly higher complete remission rate (74% v 53%; P = NS), similar durability of complete remission (75% v 70% at 3 years; P = NS), and a slightly but not significantly better overall survival (50% v 41% at 3 years; P = NS). The slight advantage in response rate and survival for B-cell patients was related to a very poor outcome for patients with stage IV T-cell NHL. For patients with stage I to III disease, neither the complete remission rate (B-cell, 82% v T-cell, 91%; P = NS) nor overall survival (3-year survival for B cell, 58% v T cell, 73%; P = NS) were significantly different. However, with stage IV disease B-cell patients fared far better than those with T-cell NHL for both complete remission rate (67% v 0%; P = .002) and overall survival (3-year survival, 44% v 0%; P = .002). Immunophenotyping intermediate- and high-grade NHL allowed identification of a subgroup of patients who had a very poor prognosis with this treatment approach and for whom alternate therapy might be considered.

Antigens, CD↗

ChlVPP--an effective and well-tolerated alternative to MOPP therapy for Hodgkin's disease.

The substitution of chlorambucil for nitrogen mustard and vinblastine for vincristine has been suggested to be an equally effective and well-tolerated variation of the MOPP regimen (mechlorethamine, vincristine, procarbazine, and prednisone). We treated 76 patients with advanced (i.e., Stage III, IV, or II with bulky mediastinal mass) or recurrent Hodgkin's disease with chlorambucil 6 mg/m2, procarbazine 100 mg/m2, and prednisone 40 mg p.o. daily, all on days 1-14; plus vinblastine 6 mg/m2 i.v. on day 1 and 8 of each 28-day cycle (ChlVPP). There was no maximum dose of the myelosuppressive agents. Patients who had not previously been irradiated received from 2,300 to 4,100 cGY to sites of previously bulky diseases after completing 6 cycles of ChlVPP. ChlVPP was easy to administer (i.e., 87% of patients without previous chemotherapy received greater than or equal to 80% of the planned doses of myelosuppressive drugs) and was generally well tolerated, with only occasional vomiting from procarbazine and phlebitis from vinblastine. In patients without previous chemotherapy, 49 (76%) achieved a complete remission (CR) and 7 (11%) a stable partial remission (i.e., residual, stable radiographic abnormality). With a maximum follow-up of 4 years, only one CR has relapsed for an actuarial CR durability of 97%. ChlVPP with consolidative radiation therapy to sites of bulky disease is effective in advanced Hodgkin's disease and, compared with most other available regimens, is extremely well tolerated.

Adolescent↗

The importance of age in survival of patients treated with chemotherapy for aggressive non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) is a malignancy that occurs frequently in the elderly with a median age greater than 60 years. However, most chemotherapy trials have included predominantly patients less than 60 years of age. We treated 157 patients with diffuse aggressive NHL between September 1982 and May 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), procarbazine, bleomycin, vincristine, and prednisone (CAP/BOP). There were no treatment exclusions for age. Patients in this study ranged in age from 15 to 91 years (median, 63) with 112 patients greater than or equal to 60 years of age. The overall complete remission (CR) rate was 65% with no significant difference for age less than 60 (76%) v age greater than or equal to 60 (61%) (P = .18). With a median 36-month follow-up (range, 22 to 65 months), the overall 5-year survival was 42%. The patients less than 60 years old had a 62% 5-year survival in contrast to a 34% 5-year survival in those patients greater than or equal to age 60 (P = .01). The deaths attributed to tumor or treatment-related toxicity were similar above and below age 60. The difference in survival was due to other causes of death not obviously related to the lymphoma or its therapy-occurring in 22% of patients greater than or equal to 60 years of age but only 2% of patients less than 60 years (P = .005). Our data supports the position that aggressive NHL in elderly patients is not significantly less responsive than in younger patients; however, the inclusion of older patients in clinical trials will decrease the overall survival secondary to deaths due to apparently unrelated causes.

Adolescent↗

Pulmonary emboli in patients receiving chemotherapy for non-Hodgkin's lymphoma.

Combination chemotherapy has dramatically improved the prognosis of patients with intermediate and high grade histologic subtypes of non-Hodgkin's lymphomas. Treatment-related complications, however, are considerable, and a common problem encountered is respiratory distress or respiratory insufficiency. Usually these difficulties have been attributed to infectious etiologies or to chemotherapy-induced interstitial fibrosis, most often involving bleomycin. We describe five patients presenting with respiratory problems several weeks after the initiation of chemotherapy. These patients, who represent 3 percent of all patients treated with a single bleomycin-containing regimen for intermediate or high grade non-Hodgkin's lymphoma, were all initially thought to have chemotherapy-induced interstitial fibrosis but were found on subsequent evaluation to have pulmonary emboli. Of the three patients in whom pulmonary emboli were diagnosed antemortem, two had symptoms suggestive of pulmonary emboli and all were successfully treated and remained well and free of lymphoma for over 24 months. Two additional patients were diagnosed at autopsy. We suggest that pulmonary emboli may contribute significantly to the morbidity and mortality of patients undergoing chemotherapy for non-Hodgkin's lymphoma and recommend that patients presenting with respiratory difficulties be evaluated for pulmonary emboli.

Aged↗

Chemotherapy for diffuse large-cell lymphoma--rapidly responding patients have more durable remissions.

Fifty-one patients with diffuse large-cell lymphoma (DLCL) were treated with a six-drug combination chemotherapy regimen including cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone. The patients were restaged after three cycles of therapy, and restaging was repeated at 2-month intervals in patients who had persistent disease. Responding patients received two cycles of therapy after documentation of complete remission (CR). With all patients considered evaluable, 73% of the patients achieved a CR. Twenty-six of the 37 CRs (70%) achieved remission in the first three treatment cycles. The durability of remission in the rapidly responding patients was significantly better than for patients who required five cycles to achieve CR (80% v 40% at 2 years, P = .02) despite the latter patients having received two more cycles of therapy. Rapidly responding patients with DLCL do not require prolonged therapy and have a better prognosis than patients achieving a CR more slowly.

Actuarial Analysis↗

The normal right ventricular response to supine exercise.

Nine normal, healthy young males performed graded, maximal supine bicycle exercise with monitoring of hemodynamic and gated blood pool parameters. Right ventricular ejection fraction (RVEF) was greater than 0.45 in all acquisitions at rest (mean +/- SD = 0.53 +/- 0.05) and increased greater than 0.05 in all subjects with maximal exercise (mean +/- SD = 0.69 +/- 0.06 at stage 4). There was a very close correspondence between RV and LV stroke counts from the radionuclide angiograms at rest and all exercise levels in all patients. Cardiac output changes by radionuclide data from the RV correlated closely with those obtained by the Fick technique. Multivariate analysis of RVEF vs pulmonary artery pressure, total pulmonary resistance, and heart rate showed that RVEF was inversely related to total pulmonary resistance in these patients (n = 43 acquisitions, r = 0.61, RVEF = 0.75 -- 0.001 TPR in dynes-sec/cm5 Sy.x = 0.07) and positively related to heart rate (n = 43, 4 = 0.78, RVEF = 0.34 + 0.0025 x HR Sy.x = 0.05). RVEF was not significantly related to the other hemodynamic parameters. These results suggest that in normal subjects RV systolic function is afterload-dependent and that total pulmonary resistance may be a suitable afterload index. The results emphasize that heart rate must be considered when comparing RVEF changes.

Adult↗

Ethanol-induced depressions in cerebellar and hippocampal neurons of mice selectively bred for differences in ethanol sensitivity: an electrophysiological study.

The recently discovered profound differential sensitivity of cerebellar Purkinje (P) cells in long-sleep (LS) verus short-sleep (SS) mice to the depressant effects of locally applied ethanol was extended in this study. First, the sensitivity of Purkinje neurons from HS mice (an outbred stock of mice from which the LS and SS lines were derived), was found to be almost exactly intermediate between the values for the long-sleep and short-sleep animals. Second, no differential sensitivity in long-sleep versus short-sleep hippocampal pyramidal neurons was observed. This was true using both spontaneous and evoked activity. Third, no differential sensitivity of P cells was seen in long- versus short-sleep mice with local application of halothane. Taken together with previous reports, these data strongly suggest that whatever genetically determined central nervous alterations result in the differential soporific effects of ethanol in the two (LS and SS) mouse lines, such alterations are brain region- and depressant drug-specific rather than generalized.

Action Potentials↗

Electrophysiological correlates of ethanol-induced sedation in differentially sensitive lines of mice.

Acute electrophysiological effects of ethanol were studied in two lines of mice that differ markedly in their response to the soporific effects of systemic alcohol administration. Cerebellar Purkinje neurons from the genetic line that had long sleep times were one to two orders of magnitude more sensitive to the depressant effects of locally administered ethanol than those from the line that had short sleep times. The data suggest that there are genetically determined specificities in the acute effects of ethanol on central neurons and that such specificities might be used to determine which regions of the cerebellum participate in differences in behavioral responses to this substance.

Action Potentials↗

Giant-cell arteritis, temporal arteritis and polymyalgia rheumatica. A retrospective study of 63 patients.

The initial clinical symptoms, the course of the disease, and the effect of corticosteroid treatment have been analyzed in a retrospective study of 63 patients with temporal arteritis or polymyalgia rheumatica. The relationship between the physical examination of the temporal regions, the ophthalmological examination, and biopsy from the temporal artery with respect to the diagnostic value were examined. Histological examination of biopsy specimens from the temporal artery in 58 patients revealed arteritis in 46. Half of the patients had only local symptoms from the temporal regions; one fourth presented such symptoms as well as myalgias, and one fourth had myalgias only. Patients presenting local symptoms of temporal arteritis as well as of myalgias had always had myalgias as the initial symptom and developed local symptoms of temporal arteritis 1-24 months later. Permanent reduction of vision occurred in 20% of the patients. Symptoms of generalized arteritis were observed in several patients. The overlapping of the clinical symptoms, the positive biopsy findings in patients with polymyalgia rheumatica as the only local symptom and the identical reaction to corticosteroid treatment support the conception of temporal arteritis and polymyalgia rheumatica as two manifestations of the same disease. The physical and the ophthalmological examinations were of limited diagnostic value. Positive biopsy findings were seen in 25 patients with noraml palpatory findings, and in 46 patients without eye symptoms the ophthalmoscopic examination revealed no signs of arteritis. If the first biopsy from the temporal artery is negative, biopsy from the contralateral temporal artery should be performed. Correctly timed corticosteroid treatment in adequate doses can prevent reduction of vision in giant-cell arteritis. The treatment is a long-term therapy, its average duration in the present study being more than two years.

Adrenal Cortex Hormones↗