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Biomedical subjects

A Gottlieb

Publications and source records attributed to A Gottlieb.

At least 19 recordsLinked to original sources

Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD.

BACKGROUND AND METHODS: MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) has been the standard treatment for Hodgkin's disease for almost 20 years. In a randomized, multicenter trial, we compared three regimens of primary systemic therapy for newly diagnosed advanced Hodgkin's disease in Stages IIIA2, IIIB, and IVA or IVB: (1) MOPP alone given for 6 to 8 cycles, (2) MOPP alternating with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for 12 cycles, and (3) ABVD alone for 6 to 8 cycles. Patients in a first relapse after radiation therapy were eligible. No additional radiation therapy was given. Patients who did not have a complete response or who had a relapse with either MOPP alone or ABVD alone were switched to the opposite regimen. RESULTS: Of 361 eligible patients, 123 received MOPP, 123 received MOPP alternating with ABVD, and 115 received ABVD alone. The patients were stratified according to age, stage, previous radiation, histologic features, and performance status. The overall response rate was 93 percent, with complete responses in 77 percent: 67 percent in the MOPP group, 82 percent in the ABVD group, and 83 percent in the MOPP-ABVD group (P = 0.006 for the comparison of MOPP with the other two regimens, both of which contained doxorubicin). The rates of failure-free survival at five years were 50 percent for MOPP, 61 percent for ABVD, and 65 percent for MOPP-ABVD. Age, stage (III vs. IV), and regimen influenced failure-free survival significantly. Overall survival at five years was 66 percent for MOPP, 73 percent for ABVD, and 75 percent for MOPP-ABVD (P = 0.28 for the comparison of MOPP with the doxorubicin regimens). MOPP had more severe toxic effects on bone marrow than ABVD and was associated with greater reductions in the prescribed dose. CONCLUSIONS: In this trial, ABVD therapy for 6 to 8 months was as effective as 12 months of MOPP alternating with ABVD, and both were superior to MOPP alone in the treatment of advanced Hodgkin's disease. ABVD was less myelotoxic than MOPP or ABVD alternating with MOPP.

Adult

Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma.

BACKGROUND: In 1984, the Eastern Cooperative Oncology Group began a randomized controlled clinical trial of patients with advanced (stage III or IV) diffuse mixed or diffuse large-cell lymphoma to determine whether complete-remission rates, survival, and toxicity differed when patients were treated with a chemotherapeutic regimen containing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), as compared with a regimen containing bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, and leucovorin (m-BACOD). METHODS: From July 1984 through January 1988, 392 patients were enrolled, 325 of whom (83 percent) were eligible for the analysis and capable of being evaluated. The extent of disease was defined according to standard staging techniques, including bilateral bone-core biopsies in 88 percent of patients. Randomization was stratified according to age (< 60 or > or = 60 years), performance status (0, 1, or other), stage (III or IV), and histologic presentation (diffuse mixed or diffuse large-cell lymphoma). RESULTS: After a median follow-up of four years, there were no significant differences in rates of complete remission, time to treatment failure, disease-free survival, or overall survival in the patients treated with CHOP as compared with those treated with m-BACOD. However, there was more severe and life-threatening pulmonary, infectious, and hematologic toxicity associated with the m-BACOD regimen. In an attempt to measure the importance of dose intensity in the 325 patients who could be analyzed, we retrospectively calculated dose intensity (measured in milligrams per square meter of body-surface area per week) and normalized dose intensity (defined as a percentage of the prescribed dose) for all drugs. The median normalized dose intensity for both cyclophosphamide and doxorubicin was found to be greater in the patients treated with CHOP than in those treated with m-BACOD. CONCLUSIONS: For patients with stage III or IV diffuse mixed or diffuse large-cell lymphoma, CHOP is superior to m-BACOD, but the role of dose intensity is not yet clear.

Age Factors

Phase II trial of ifosfamide/mesna and mitoxantrone in previously treated patients with non-Hodgkin's lymphoma: cancer and leukemia group B study 8753.

Ifosfamide (2.0 g/m2 intravenously/day x 3) with mesna (400 mg/m2 intravenously q 4 h daily x 3) was combined with mitoxantrone (14 mg/m2 intravenously x 1) and given on a 3 week schedule to patients with previously treated non-Hodgkin's lymphoma. In 45 eligible/evaluable patients, a 47% response rate (95% confidence interval: 32%, 62%) was achieved of which 25% were complete responses and 22% were partial responses. Median duration of remission was 10 months with 42% of patients in remission at 18 months. Hematologic toxicity (granulocytopenia) was the dose-limiting toxicity with severe or life-threatening granulocytopenia in 98% of patients at full protocol doses. Nausea/vomiting was seen in 73% of patients but was usually mild/moderate. Three patients had significant hematuria secondary to ifosfamide. Two patients had severe changes in the left ventricular ejection fraction (LVEF) secondary to mitoxantrone; and one patient had acute neurologic dysfunction secondary to ifosfamide. Ifosfamide/mesna can be safely combined with mitoxantrone at full doses in previously treated patients with non-Hodgkin's lymphoma. This combination should be considered for other trials in lymphoma.

Adult

The selective use of AMSA following high-dose cytarabine in patients with acute myeloid leukaemia in relapse: a Leukemia Intergroup study.

This clinical trial was designed to evaluate the role of high-dose cytarabine (ara-C) in the treatment of adults with acute myeloid leukaemia (AML) in first relapse. We also tested the hypothesis that the selective use of AMSA (100 mg/m2/d on days 7, 8 and 9) would increase the complete remission (CR) rate when leukaemia cells remained in the bone marrow immediately following 6 d of Ara-C (2-3 g/m2/12 h) alone. Of 155 patients evaluable for response, 115 (74%) experienced marked cytoreduction by day 6 and received no further induction chemotherapy; 53 (45%) of these patients achieved CR after one course and 45 (38%) had resistant disease. The 36 patients (23%) with inadequate cytoreduction after the 6 d of ara-C alone were randomly assigned either to no further chemotherapy (21 patients) or to 3 d of AMSA (15 patients). The CR rates after one course were 14% and 53%, respectively (P = 0.01), and the fractions with resistant disease were 76% and 40%, respectively. The fractional reduction of leukaemia cells in the day 6 bone marrow aspirate specimen (P < 0.0001) and the reduction in the leukaemia cell mass measured in the day 6 marrow biopsy (P = 0.001) were the strongest predictors for achieving CR versus having residual disease in univariate analyses. The median duration of remission was 5 months, but seven patients (10%) remain in CR after 30-92 + months. Among the 140 patients who received only the 6 d of ara-C, the pretreatment albumin (P = 0.002) and lactate dehydrogenase (P = 0.01) levels were the strongest predictors of response in univariate analyses, but only the albumin remained significant (P = 0.01) in a stepwise logistic regression analysis. Those patients with albumin > 4.0 mg/dl and LDH < 125% of normal had a 71% CR rate, and only 16% had resistant disease. Thus, pretreatment characteristics and rapid cytoreductin in the day 6 bone marrow sample identified a favourable subset of patients with AML in first relapse, some of whom responded quite well to 6 d of ara-C alone and have had long disease-free remissions.

Acute Disease

Phase I-II trial of high-dose melphalan in previously untreated stage III multiple myeloma: Cancer and Leukemia Group B study 8512.

To study the efficiency of high-dose melphalan in previously untreated patients with advanced myeloma, we performed a Phase I-II trial. Twenty-eight patients were treated at dose level of 60-140 mg/m2. Each patient was first treated with a priming dose of cyclophosphamide (300 mg) followed by high-dose melphalen 1 week later. One course of therapy was given. Patients were then followed without further therapy until relapse. Clinical and laboratory features of the 28 patients in this study included: median age 63, performance status 0-2, hypercalcemia 21%, bone pain 82%, paraprotein types: IgG 76%, Iga 20%, and paraproteinuria 71%. Because none of the patients achieved complete remission (CR) at 60 mg/m2, despite life-threatening toxicity in all patients, the dose level was rapidly increased to 140 mg/m2, a dose previously reported to induce a high percentage of CR. At this dose, CR was achieved in only 1 of 11 patients (9%). This patient had multiple plasmacytomas without generalized bone marrow involvement. One additional patient at 100 mg/m2 achieved CR. Of the whole group, 12 achieved PR. Durations of remissions were generally short: CR 6.3 and 18+ months and PR 2.3-18 month, median 6.9 months. Life-threatening myelosuppression was universal with prolonged pancytopenia. Treatment-related deaths from sepsis were observed in 29% of patients. The median survival of the entire group was 15.6 months. Older patients in this trial did not tolerate high-dose melphalen therapy well; this resulted in a high proportion of toxic deaths and poor overall survival.

Adult

Effects of a peer-counseled AIDS education program on knowledge, attitudes, and satisfaction of adolescents.

Education programs for adolescents regarding acquired immunodeficiency syndrome (AIDS) have been advocated by many professionals to help minimize the risk of infection in this population. This study compares a peer-led vs. an adult-led AIDS education program on the knowledge, attitudes, and satisfaction of the adolescents with their education. Eighty-two male and female adolescents, ranging in age from 12 to 18 years, were randomly assigned to a peer (n = 27), adult (n = 28), and control (n = 27) group. Intervention consisted of receiving didactic information and viewing a videotape about AIDS transmission and prevention. All subjects completed the AIDS Knowledge Questionnaire-Revised, AIDS Attitude Survey, and a measure of consumer satisfaction. Statistical analyses revealed a significant effect for knowledge and attitudes toward practicing personal preventive behaviors and the seriousness of AIDS; both peer- and adult-led groups were superior to controls (p less than 0.05). With the exception of satisfaction with providers, no other significant effects were found across the intervention groups. Satisfaction with providers showed an effect for sex (p less than 0.05). Female adolescents reported more satisfaction with presenters than male adolescents did. Although both adult and peer counselors were equally effective in promoting knowledge gains and appropriate attitude changes, more questions were asked of the peer counselors. These data suggest that when education is presented by peer counselors, adolescents may be more likely to see AIDS as a personal danger and that peer counselors should be considered when designing comprehensive AIDS education programs.

Acquired Immunodeficiency Syndrome

The incidence of narcotic-induced emesis.

Epidemiologic studies of the incidence of emesis induced by narcotic analgesics are lacking. The histories of 260 cancer patients receiving oral narcotic analgesics prescribed at the Pain Clinic of our Institute from December 1988 to December 1989 were reviewed. Of the 260 patients, 120 were women, median age 61 (range 30-90) yr and 140 were men, median age 62 (range 30-82) yr. Nausea and vomiting associated with assumption of the various narcotics were buprenorphine 8.3% and 22.7%, morphine 18.3% and 28%, codeine 16.2% and 29.7%, and oxycodone 10% and 40%, respectively. Since the use of narcotic analgesics can effectively relieve pain and improve quality of life in cancer patients, it is important to be aware of the incidence of narcotic-induced emesis in order to use appropriate prophylactic antiemetic therapy.

Adult

Lichenoid histopathologic changes in patients with clinical diagnoses of exfoliative dermatitis.

Among 30 patients who received a clinical diagnosis of exfoliative dermatitis and were biopsied between 1982 and 1990, nine showed microscopic features of lichenoid dermatitis. Clinical information was available in eight of these cases. Possible etiologic factors included lymphoma, herpes simplex infection, connective tissue disease, and (in five cases) reactions to drugs. In each instance, microscopic features included a superficial perivascular lymphocytic infiltrate involving the dermal-epidermal interface, vacuolar alteration of the basilar layer, and individually necrotic keratinocytes at all levels of the epidermis. Such microscopic changes are not usually described in connection with exfoliative dermatitis, with the possible exception of those cases related to lichen planus or lupus erythematosus. Disseminated lichenoid drug eruption is one possible interpretation of the drug-induced cases. Erythema multiforme is another condition that has similar microscopic features and has been associated with drugs (many of which also cause exfoliative dermatitis), infectious agents, neoplasms, and connective tissue diseases. Lichenoid dermatitis can become generalized and clinically mimic and exfoliative dermatitis. Many, but not all, of these eruptions may be triggered by drugs.

Adult

The treatment of patients with newly diagnosed poor prognosis acute myelogenous leukaemia: response to treatment and treatment failure.

The failure of poor prognosis patients with newly diagnosed AML to enter remission is usually due to two phenomena: a high mortality rate and resistance of the leukaemia to chemotherapy. We conducted a pilot study of a regimen designed to overcome these two types of treatment failure. Patients were carefully selected for therapy on the basis of their likelihood of surviving. Chemotherapy consisted of high dose cytosine arabinoside (HDaraC) with the doses modified on the basis of patient age so as to reduce the risk of toxicity. Finally, daunorubicin was administered only to those patients for whom HDaraC was not likely to produce sufficient antileukaemia effects to produce a remission. The median patient age was 67 years and 69/88 (78%) patients had a history of preleukaemia and/or toxic exposure. Only 11/84 (13%) patients died during remission induction therapy and 40/84 (48%) entered CR. Patients with only one risk factor had a higher CR rate than those with more than one risk factor (56% v. 30%, P = 0.02) and also had longer durations (222 d v. 113.5 d, P = 0.035). Two types of resistance to chemotherapy were observed: 'classical resistance' (the failure of chemotherapy to produce substantial killing of leukaemia cells) and the rapid regrowth of leukaemia cells subsequent to a level of cytoreduction which otherwise would have been sufficient to produce a CR.

Aged

A comparison of three clinic-based AIDS education programs on female adolescents' knowledge, attitudes, and behavior.

Health providers are becoming increasingly aware that adolescents are a population at risk for acquired immune deficiency syndrome (AIDS) and have identified education as essential for prevention. This study evaluates three clinic-based programs designed to determine the effects of education on knowledge and attitudes regarding AIDS and condom acquisition. Seventy-five sexually active females attending adolescent health clinics were randomly assigned to one of three groups: 1) controls (C) receiving no education; 2) education (E) alone consisting of a brief lecture on AIDS: and 3) enhanced education (EE) where the lecture was provided as well as a videotape describing the importance of condom use. All participants completed the AIDS Knowledge Questionnaire-Revised, the AIDS Attitude Survey, a self-report measure of condom use and received a coupon that could be exchanged for free condoms from the hospital pharmacy. A significant effect was found for knowledge, where both E and EE were superior to controls (p less than .001). No statistical differences were noted across groups regarding attitudes or condom acquisition. However, all adolescents in the EE group who reported prior condom use obtained condoms from the pharmacy as compared to the other groups (p less than .05). Our results suggest that educating adolescents in medical settings can improve their knowledge about AIDS. Didactic lectures in combination with videotape presentations on condom use appeared to be the best format for reinforcing an adolescent's existing behavior.

Acquired Immunodeficiency Syndrome

MDR1 transcript levels as an indication of resistant disease in acute myelogenous leukaemia.

The expression of the MDR1 gene was studied by Northern blot analysis in leukaemic cell specimens obtained from 74 patients with acute myelogenous leukaemia (AML). No relationship was found between MDR1 RNA levels and FAB type of leukaemia or patient age. Transcript levels tended to be highest in the leukaemic cells of patients with a history of toxic exposure or preleukaemia compared with 'standard risk' patients at diagnosis but the differences were not significant (P = 0.07). Patients whose leukaemic cells contained high MDR1 transcript levels were difficult to induce into remission and, if remission was induced, the remissions were short. Hence high levels of MDR1 expression may explain, at least in part, the ineffectiveness of anthracycline antibiotic containing treatment regimens in some patients with AML.

Adolescent

Postsecondary experiences of young adults with severe physical disabilities.

A need exists for follow-up information to determine how well the educational system is meeting the needs of young adults with severe physical disabilities. This study of the postsecondary experiences of 106 graduates of a special school for youth with severe physical disabilities examined the educational, employment, and community adjustment outcomes of these students. Findings suggest that young adults with physical disabilities should cultivate personal and family networks, continue their education, and use vocational rehabilitation agencies. Access to transportation was also found to be a key element in achieving employment and independence.

Adult

Disodium clodronate in the treatment of pain due to bone metastases.

Disodium clodronate (dichloromethylene bisphosphonate) a drug belonging to the class of bisphosphonates, inhibits osteoclastic bone resorption and therefore it may be used in the palliative treatment of patients affected by osteolytic bone metastases. The authors have evaluated the activity and tolerability of disodium clodronate in providing pain relief and improving the quality of life in patients with bone metastases, who were not improved by radiotherapy or chemotherapy. Out of 37 patients, 32 could be evaluated for pain relief. Of these, 62.5% had their pains improved by disodium clodronate administration without regard to the type of ongoing analgesic therapy, which had no implications on the outcome of the treatment.

Adult

Sodium naproxen versus sodium diclofenac in cancer pain control.

In a single-blind random study, simultaneously carried out by five Pain Therapy and Palliative Care Centres, the analgesic power and side-effects of sodium naproxen (CAS 26159-34-2) and sodium diclofenac (CAS 15307-86-5) by mouth were compared in a group of 100 advanced cancer patients. The patients complained of somatic and/or visceral pain and were treated with non-steroid anti-inflammatories as required. The dose administered amounted to 550 mg every 12 h for sodium naproxen and to 100 mg every 12 h for sodium diclofenac. The study stressed the similar analgesic effect of the two drugs--pain intensity and duration decreased by half in the first week of treatment--and a comparatively low morbidity rate.

Aged

Adolescents and AIDS. Female's attitudes and behaviors toward condom purchase and use.

Condom use has been advocated as a method to prevent human immunodeficiency virus (HIV) transmission. Although condoms are not uniformly popular with adolescent males, adolescent females' beliefs about condom use are unclear. To assess the specific health attitudes and behaviors as they relate to condom purchase by adolescents, we surveyed 99 adolescent females between 12 and 19 years of age (50 black, 49 white) who were attending a comprehensive adolescent health clinic. The respondents were from low to middle socioeconomic backgrounds and 85% were sexually active. A 41-item survey was developed and focused on four areas: comfort or embarrassment with menses (EM), basic knowledge of acquired immunodeficiency syndrome (AIDS) (KA); comfort in discussing contraception with partner (CC) and risk of contracting AIDS (AR). Chi-square analyses of the four factors determined that decreased EM was related to increased age (p less than 0.05), sexual activity (p less than 0.05), and CC (p less than 0.05). Older adolescents also demonstrated greater CC (p less than 0.05). Increased KA was related to contraceptive use (p less than 0.02) as well as CC (p less than 0.02). Descriptive analyses showed that 62% of the sample reported that a fear of AIDS had influenced their contraceptive behavior, but only 17% of the females reported purchasing or using a condom to prevent AIDS transmission. These findings suggest that although adolescent females have an awareness about AIDS, their behavior remains unchanged.

Acquired Immunodeficiency Syndrome

The role of prostacyclin in the mesenteric traction syndrome during anesthesia for abdominal aortic reconstructive surgery.

Mesenteric traction syndrome consists of sudden tachycardia, hypotension, and cutaneous hyperemia, and frequently occurs during mesenteric traction in patients undergoing abdominal aortic aneurysm (AAA) reconstructive surgery. The etiology and clinical impact of this phenomenon are unknown, but the symptoms suggest a release of vasoactive materials from the mesenteric vascular bed. Thirty-one patients who underwent AAA surgery were studied. Mesenteric traction was accompanied by a decrease in systolic (p = 0.005) and diastolic (p less than 0.05) blood pressures, and in systemic vascular resistance (p less than 0.005), and was accompanied by an increase in heart rate (HR) (p less than 0.005), and cardiac output (p = 0.01). These hemodynamic changes coincided with an increase (p less than 0.001) in plasma concentrations of 6-keto-prostaglandin F1 (6-K-PGF1). No apparent change was found in prostaglandin E2, thromboxane B2, and histamine concentrations. The concentration of 6-K-PGF1 was correlated with diastolic blood pressure (r = -0.52, p less than 0.005) and HR (r = 0.65, p less than 0.001). Cutaneous hyperemia was observed in 58% of the patients. In an additional six patients, who had taken aspirin daily before AAA surgery, no significant changes were observed in the hemodynamic measurements or 6-K-PGF1 concentrations. These data suggest that mesenteric traction syndrome may be mediated at least in part by a selective release of prostacyclin.

6-Ketoprostaglandin F1 alpha