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Biomedical subjects

S Groshen

Publications and source records attributed to S Groshen.

At least 127 records · Page 7Linked to original sources
PubMed1990

Bone marrow transplantation with interleukin-2-activated bone marrow followed by interleukin-2 therapy for acute myeloid leukemia in mice.

We have investigated approaches to induce graft-versus-leukemia (GVL) effect in autologous bone marrow transplantation (ABMT) without graft-versus-host disease to improve survival and cure in leukemia. The present study shows that bone marrow transplantation (BMT) using syngeneic bone marrow activated with interleukin-2 (ABM) for 24 hours in vitro, followed by interleukin-2 (IL-2) therapy, was superior to BMT with fresh, syngeneic bone marrow (FBM) in terms of survival and cure in mice with acute myeloid leukemia (P less than .001) and led to normal hematopoietic reconstitution. Addition of IL-2 therapy after BMT with FBM did not improve the results over BMT with FBM alone (P = .98). These results suggest that the GVL effect of ABMT can be enhanced by using ABM for BMT followed by IL-2 therapy without compromising engraftment.

Animals↗
PubMed1990

Correlation of anti-emetic efficacy and plasma levels of ondansetron.

Intravenous ondansetron was administered at doses from 0.01 to 0.48 mg/kg every 4 h for three doses to patients receiving cisplatin 60-120 mg/m2 for the first time. Plasma samples were collected from 28 patients at baseline and at suitable times post-dose for pharmacokinetic analysis, and were assayed for ondansetron by high-pressure liquid chromatography. Plasma trough level was defined as the level before the third dose and 4 h area-under-the-curve (AUC4) was calculated with the linear trapezoidal method. Despite wide inter-patient variation, a correlation was seen between both trough level (r = 0.737, P less than 0.0001) and AUC4 (r = 0.903, P less than 0.001) related to dose. Trough level was also predictive of AUC4 (r = 0.824, P less than 0.0001). Frequency of complete protection (no emetic episodes) was equivalent throughout the AUC4 range, suggesting anti-emetic activity even at low AUC4. However, a trend toward better protection against failure (5 or more episodes) was seen when higher values of AUC4 were achieved, suggesting more consistent anti-emetic activity at moderate to high AUC4.

Adult↗
PubMed1990

Factors influencing survival and prognosis in early breast carcinoma (T1N0M0-T1N1M0). Assessment of 644 patients with median follow-up of 18 years.

That there is probably a significant proportion of "cured" patients, particularly in the T1N0 group, is an important observation when one considers the proper role of adjuvant therapy, especially for patients with stage I disease. Analysis of this series indicates that patients with T1N0 disease can be subdivided into different prognostic groups. Factors associated with an especially favorable prognosis in T1N0 cases are a primary tumor size of 1 cm or less; special tumor type such as tubular, medullary, papillary, or colloid carcinoma; and low-grade tumor. Relatively unfavorable tumor characteristics are size greater than 1.0 cm (especially the group 1.7 to 2.0 cm), the presence of lymphatic tumor emboli in the breast, blood vessel invasion, high-grade tumor or poor differentiation, and intense peritumoral lymphoplasmacytic reaction. The T1N0 patients whose tumors manifest the latter features may have longer disease-free survival as a result of adjuvant therapy. On the other hand, women in the T1N0 group with an especially favorable prognosis usually can be spared adjuvant therapy.

Breast Neoplasms↗
PubMed1990

Phase I study of combination recombinant interleukin-2 and interferon gamma in patients with advanced malignancies.

A phase I trial of interleukin-2 and interferon gamma combination treatment in patients with advanced malignancies was performed based on preclinical in vitro and in vivo data which demonstrated synergistic antitumor effect. The toxicities, immune parameters, and tumor responses are described. The clinical and biologic maximal tolerated doses were extrapolated from these data.

Adolescent↗
PubMed1990

Evidence that appearance of thymulin in plasma follows lymphoid chimerism and precedes development of immunity in patients with lethal combined immunodeficiency transplanted with T cell-depleted haploidentical marrow.

Thymulin, a peptide secreted by human thymic epithelial cells, circulates in peripheral blood. Levels of plasma thymulin (FTS-Zn) activity were analyzed in 21 patients with lethal combined immunodeficiency disorders who were treated with transplantation of HLA-haplotype-mismatched parental bone marrow depleted of T cells by differential agglutination with soybean agglutinin and E-rosetting (SBA-E-BMT). Among these 21 infants, 15 were patients with severe combined immunodeficiency (SCID) and 6 had combined immunodeficiency (CID) with Omenn's syndrome or CID with T cell predominance (CIDTP). In contrast to normal infants who possess high levels of plasma thymulin activity, 20 of the 21 patients demonstrated undetectable or low plasma thymulin levels for their age at admission prior to transplantation. Following SBA-E-BMT, however, thymulin became detectable in the plasma of 17 of 18 evaluable patients and reached normal or near-normal levels between 21 and 125 days posttransplant. In patients in whom the timing of engraftment could be established by emergence of donor lymphocytes, thymulin appeared in the plasma at approximately the same time as lymphoid chimerism was detected, and in all patients who were engrafted and immunologically reconstituted, the increment in thymulin levels preceded development of immune functions. These studies support the concept that normal marrow-derived cells in the graft can provide a stimulus necessary for induction of thymic epithelial secretory function in patients with thymic dysplasia. Further, immunologic reconstitution in these patients was not seen following SBA-E-BMT unless and until recovery of thymus function had been observed.

Bone Marrow Transplantation↗
PubMed1989

Subject-reported compliance in a chemoprevention trial for familial adenomatous polyposis.

A high level of compliance with an assigned treatment regimen is fundamental to accurate assessment of treatment effectiveness in any clinical trial. If compliance is poor, an effective treatment may be confounded by inadequate delivery of the regimen. Although much research has focused on broad aspects of compliance dealing with clinical therapeutic situations, there was a need for further research dealing specifically with adherence issues in a long-term chemoprevention trial since subject motivation in the latter is likely to differ from that of the former. Examining subject-reported compliance over the first 2-year treatment periods of a long-term chemoprevention trial for familial adenomatous polyposis, it was found that (1) compliance decreased over time, (2) fiber compliance was lower than vitamin compliance, and (3) four explanatory variables which may be amenable to individualized study-team interventions emerged as useful prognosticators of fiber compliance.

Activities of Daily Living↗
PubMed1989

Nonmammary malignant neoplasms in patients with stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. A long-term follow-up study.

We have recently updated the follow-up of 644 women with pathologically determined Stage I (T1N0M0) (474 patients) and Stage II (T1N1M0) (170 patients) breast carcinoma treated by modified or radical mastectomy from 1964 through 1970 at Memorial Sloan-Kettering Cancer Center. Median follow-up was 18.2 years with over 90% of surviving patients followed for 15.7 years. Recurrences occurred in 166 (26%) with 148 (23%) dead of disease and 18 (3%) alive with recurrence when last seen. A nonmammary malignant neoplasm (NMMN) was confirmed in 86 (13%) of the 644 patients. Of these, 55/86 (64%) were diagnosed after and 27 (32%) were diagnosed before the breast carcinoma. Four patients (5%) had a NMMN before and after the breast carcinoma. The most frequent sites of prior carcinoma were the cervix (n = 8), colon-rectum (n = 7), and oropharynx (n = 5), whereas the more common locations of subsequent NMMN were the ovary (n = 11), colon-rectum (n = 10), lung (n = 9), stomach (n = 6), and lymphoma-leukemia (n = 5). There was not a statistically significant difference in the frequency of subsequent NMMN when patients who received adjuvant radiation were compared with those who received adjuvant thiotepa or no adjuvant therapy. There was no excess of lymphoma or of other NMMN in the treated region or of contralateral breast carcinoma among adjuvant radiation treated patients. The overall hazard rate for subsequent NMMN was 7/1.000 women at risk per year. The risk was fairly stable over the first 15 years of follow-up but rose to 12/1,000 in the 15-20-year period. The observed frequency and time distribution of NMMN were very similar to the expected frequency determined by comparison with a population of age-matched women. Most fatal NMMN arose in the ovaries, stomach, women. Most fatal NMMN arose in the ovaries, stomach, pancreas, and lungs. There were 35 deaths due to NMMN detected subsequent to the diagnosis of breast carcinoma (15% of all cancer deaths and 64% of 55 subsequent NMMN). In this series, subsequent NMMN were as frequent as contralateral breast carcinoma, and they were responsible for seven times more deaths. Hence, an important goal of any follow-up program for breast cancer patients should be the early detection and treatment of NMMN.

Breast Neoplasms↗
PubMed1989

Relationship between menarcheal age and adult height.

Many factors contribute to the attainment of adult height, including genetic and environmental variables. To assess the relationship between menarcheal age and adult height, measured adult height and recalled menarcheal age were compared by regression analysis in 425 women. The overall regression equation, Height = 158.14 + .4321 (Age) - .1667 (Age - 13)2, was significant (P less than .003), as was the coefficient for the quadratic term (P not equal to .014). After exclusion of those in whom menarche occurred after age 16, the overall linear regression equation for the remaining 416 patients, Height = 153.95 + .7353 (Age), was still significant (P not equal to .001), but the coefficient for the quadratic term was not. These data suggest that menarcheal age significantly correlates with adult height as an independent variable.

Adult↗
PubMed1989

Controlling delayed vomiting: double-blind, randomized trial comparing placebo, dexamethasone alone, and metoclopramide plus dexamethasone in patients receiving cisplatin.

The majority of patients receiving cisplatin at a dose of 120 mg/m2 experience delayed nausea and vomiting occurring between 24 and 120 hours after chemotherapy administration. Ninety-one patients who were receiving cisplatin (120 mg/m2) as initial chemotherapy were entered into this double-blind trial. All patients received intravenous (IV) metoclopramide, dexamethasone, and lorazepam for the control of acute emesis during the period from 0 to 24 hours after cisplatin. Patients were then randomized to one of three treatment regimens: placebo; oral dexamethasone, 8 mg twice daily for two days, then 4 mg twice daily for two days; or the combination of oral metoclopramide, 0.5 mg/kg four times daily for four days, plus oral dexamethasone administered as above. Forty-eight percent of individuals who received the two-drug combination of metoclopramide plus dexamethasone experienced delayed vomiting as opposed to 65% who were administered dexamethasone alone and 89% who received placebo (P = .006). Scores assessing the severity of delayed nausea and vomiting were consistently worse in individuals receiving placebo. The incidences of sleepiness, restlessness, heartburn, hiccoughs, loose bowel movements, insomnia, and acute dystonic reactions did not differ significantly among the three regimens and were mild and self-limited. The two-drug combination of oral metoclopramide plus dexamethasone is well tolerated, safe, and more effective than dexamethasone alone or placebo in controlling delayed vomiting following cisplatin.

Adult↗
PubMed1989

A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma.

This study was undertaken to investigate the long-term survival and the probability of "cure" in a group of 644 patients treated by mastectomy for T1 breast carcinoma. After a median follow-up of 18.2 years, 23% were dead of recurrent breast carcinoma, 3% were alive with recurrent disease, and 74% had not experienced a recurrence. The probability of recurrence was directly related to the initial extent of the disease. Overall, 16% of recurrences and 25% of deaths due to disease occurred in the second decade of follow-up. The proportion of recurrences detected in the second decade was inversely related to the stage of the primary tumor at diagnosis. When stratified by tumor size, T1N0M0 patients with tumors 1.0 cm or less in diameter had a significantly better 20-year recurrence-free survival (86%) than did T1N0M0 patients with tumors 1.1 to 2.0 cm (69%). When observed and expected survival curves were compared by the method of Brinkley and Haybittle, it appeared that 80% of T1N0M0 patients with tumors 1 cm or less might be cured at 20 years, whereas for those in the 1.1- to 2-cm group, the proportion cured was indeterminate, but might be as high as 70%. A potentially cured group could not be identified among T1N1M0 patients, but an estimated 52% of these patients did not have a recurrence within the nearly 20-year follow-up period. These data are important when one considers the proper role of adjuvant therapy for stage I disease. Patients with tumors larger than 1 cm and those with axillary lymph node metastases may have an improved recurrence-free survival as a result of systemic adjuvant treatment, while women in the T1N0M0 group with an especially favorable recurrence-free survival, particularly those with tumors 1 cm in diameter or smaller, might be spared adjuvant therapy.

Breast Neoplasms↗
PubMed1989

Pathological prognostic factors in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma: a study of 644 patients with median follow-up of 18 years.

Prognostic factors have been examined in 644 patients with tumor-node-metastasis (TNM) stage T1 breast carcinoma treated by mastectomy and followed for a median of 18.2 years. Overall, 148 patients (23%) died of recurrent breast carcinoma. Eighteen (3%) were alive with recurrent disease and 478 (74%) were alive or died of other causes without recurrence. Unfavorable clinicopathologic features were larger tumor size (1.1 to 2.0 cm v less than or equal to 1 cm), perimenopausal menstrual status, the number of axillary lymph node metastases, poorly differentiated grade, presence of lymphatic tumor emboli (LI) in breast tissue near the primary tumor, blood vessel invasion (BVI), and an intense lymphoplasmacytic reaction around the tumor. Median survival after recurrence for the entire series was 2 years. This was not significantly influenced by tumor size, the number of axillary nodal metastases, the type of treatment for recurrence, or the interval to recurrence. The proportions surviving 5 and 10 years after recurrence were 17% and 5%, respectively. Among T1N0M0 cases, the chance of a local recurrence was 2.8% within 20 years. Median survival of T1N0M0 cases after local recurrence (4.5 years) was significantly longer than after systemic recurrence (1.5 years). A similar trend (3.7 v 2.0 years), not statistically significant, was seen in T1N1M0 patients, who had a 6.5% chance of local recurrence within 20 years. Median survival following systemic recurrence detected 10 or more years after diagnosis in T1N0M0 and in T1N1M0 patients was significantly longer than the median survival for systemic recurrences found in the first decade of follow-up. This difference did not apply following local recurrence in either T1N0M0 or T1N1M0 cases. It is evident that patients with T1 breast carcinoma can be subdivided into differing prognostic groups and this must be taken into account when considering the role of adjuvant chemotherapy for stage I disease. Systemic adjuvant treatment may prove to be beneficial for patients with unfavorable prognostic factors, while women with an especially low risk for recurrence (eg, T1N0M0 tumor 1.0 cm or less) might be spared such treatment.

Breast Neoplasms↗
PubMed1989

Contralateral breast carcinoma: an assessment of risk and prognosis in stage I (T1N0M0) and stage II (T1N1M0) patients with 20-year follow-up.

Among 644 patients with a small (T1) primary breast carcinoma who were followed up for a median of 18.2 years, subsequent contralateral breast carcinomas were detected in 57 of 610 women (9%) who had a contralateral breast at risk. The average annual hazard rate for contralateral carcinomas was 8/1000 patients at risk per year without significant fluctuations throughout the 20 years of follow-up. Recurrences were caused by 9 of 57 (16%) subsequent contralateral carcinomas, and 4 of the 57 patients (7%) died of recurrent contralateral carcinomas. Contralateral carcinomas were responsible for 5.1% (9 of 176) of all recurrences of breast carcinomas and 2.6% (4 of 153) of breast carcinoma deaths. Surveillance of the contralateral breast must continue throughout a patient's lifetime. Detection and treatment of subsequent lesions at an early stage is a beneficial result of follow-up, especially in women whose first carcinoma is likely to have been cured.

Age Factors↗
PubMed1988

Blood transfusion and lung cancer recurrence.

Recent reports have suggested that perioperative blood transfusions may adversely affect prognosis after resection of non-small cell lung cancer (NSCLC). To determine the impact of perioperative transfusion on the recurrence-free interval, the status of 352 patients who underwent pulmonary resection for pathologic Stages I and II NSCLC was investigated. Transfused patients were significantly older than untransfused patients (P = 0.0009) but were not significantly different in sex distribution (P = 0.12) or tumor stage (P = 0.09). Recurrence was not significantly different in transfused patients when compared with patients who received no blood (P = 0.23) even when stratified for stage (Stage I, P = 0.58; Stage II, P = 0.14). Furthermore, the number of units transfused was not associated with time to tumor recurrence (P = 0.58). Contrary to other reports, these results do not support the contention that perioperative blood transfusion is significantly associated with decreased recurrence-free survival.

Aged↗
PubMed1988

Ornithine decarboxylase levels in the rectal mucosa of patients with colonic neoplasia.

Ornithine decarboxylase (ODC) activity in biopsy specimens of normal-appearing rectal mucosa was measured in 15 control patients, 5 patients with colon adenomas, and 11 patients with colon cancer. While women had significantly higher ODC activity than men, ODC activity was increased regardless of gender in the rectal mucosal biopsies of patients with benign or malignant colonic neoplasia compared with those of controls. The positive predictive value of ODC activity for remote colonic neoplasia was 61% for women and 91% for men. The results provide a rationale for long-term studies of ODC activity in rectal mucosa as a biological marker of high risk for large bowel neoplasia.

Adenoma↗
PubMed1988

Control of chemotherapy-induced diarrhea with the synthetic enkephalin BW942C: a randomized trial with placebo in patients receiving cisplatin.

Diarrhea commonly occurs following the administration of cisplatin. BW942C, a pentapeptide, is a synthetic enkephalin shown to control castor oil-induced and traveler's diarrhea. To assess the safety and efficacy of BW942C in controlling diarrhea caused by cisplatin, 30 adults with lung cancer who had already experienced diarrhea (three or more loose bowel movements) during the 24-hour period following a prior cisplatin administration were randomized to receive either BW942C or placebo during the next cisplatin course. All patients received a concomitant antiemetic regimen including metoclopramide, dexamethasone, and lorazepam during all courses. Patients administered BW942C experienced less diarrhea (27% v 67%, P = .02). Twenty-seven percent of patients given the pentapeptide had loose bowel movements as opposed to 93% who received placebo (P = .0002). There were no significant differences in the incidence and degree of vomiting and other treatment-related side effects observed between the placebo and treatment groups. We conclude that oral BW942C is more effective than placebo in controlling diarrhea following cisplatin chemotherapy.

Adult↗
PubMed1987

Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia.

Ninety-seven children with either acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) received HLA-identical bone marrow transplants from sibling donors, after preparation with 1320 cGy of hyperfractionated total-body irradiation and high-dose cyclophosphamide. Kaplan-Meier product-limit estimates (means +/- SE) of disease-free survival at five years among patients with ALL in second remission, third remission, and fourth remission or relapse were 64 +/- 9, 42 +/- 14, and 23 +/- 11 percent, respectively, with probabilities of relapse of 13 +/- 7, 25 +/- 13, and 64 +/- 16 percent. Among patients with AML in first remission, second remission, and third remission or relapse, five-year disease-free survival estimates were 66 +/- 10, 75 +/- 15, and 33 +/- 19 percent, with respective relapse probabilities of 0, 13 +/- 12, and 67 +/- 19 percent. The most frequent cause of death in patients in early remission (ALL in second or third remission or AML in first or second remission) was bacterial sepsis, fungal sepsis, or both, most often in the presence of acute or chronic graft-versus-host disease. Among patients with ALL who received transplants while in second remission, the duration of the initial remission had no effect on the probability of relapse after transplantation. The only pretransplantation factor that significantly affected outcome was the disease status at the time of transplantation; patients in early remission had better disease-free survival. We conclude that transplantation after preparation with hyperfractionated total-body irradiation and cyclophosphamide is an effective mode of therapy in children with refractory forms of acute leukemia.

Bone Marrow Transplantation↗