PURPOSE: Evaluate response, duration of response, and toxicity of paclitaxel in combination with other drugs known to be effective in non-Hodgkin's lymphoma (NHL). METHODS: Thirty-eight patients with relapsed/refractory NHL who had been exposed to doxorubicin as well as the cytarabine-cisplatin combinations received Mesna 1.33 gm/M2/D daily days 1, 2, 3 i.v. over 1 hour; ifosfamide 1.33 gm/M2/D daily days 1, 2, 3 i.v. over 1 hour (same bag); Novantrone 8 mg/M2/D i.v. day 1; and Taxol 27.5 mg/M2/D daily days 1, 2, 3, 4 by continuous 24-hour intravenous infusion. Premedication for Taxol included dexamethasone, diphenhydramine, and cimetidine on day 1. RESULTS: Of 35 evaluable patients, 9 (26%) achieved a complete response and 7 (20%) a partial response for a total response rate of 46%. The median failure-free and overall survival times were 2 and 10 months, respectively. Major toxicity was hematologic with a median absolute neutrophil nadir of 196/mm3. Only 10% of the cycles were associated with a grade 3-4 infection. CONCLUSION: MINT is an active and safe regimen for relapsed/refractory NHL that have failed both an Adriamycin-containing regimen and a cytarabine/cisplatin-containing regimen.

Adult↗

PubMed1999

Interleukin-10 levels are often elevated in serum of adults with Hodgkin's disease and are associated with inferior failure-free survival.

BACKGROUND: Interleukin-10 (IL-10) is a pleiotropic cytokine that protects B- or T-lymphocytes and hemopoietic progenitors from apoptosis induced by doxorubicin, glucocorticoids, or deprivation of growth factors. IL-10 is also immunosupressive, and tumor cells secreting IL-10 can grow in syngeneic or allogeneic hosts, and can inhibit the generation of tumor-specific cytotoxic T cells. Hodgkin-Reed-Sternberg cells are derived from follicular center B cells and they may be latently infected by EBV. When this occurs they often express IL-10. Based on these considerations we investigated the relationship between pretreatment serum IL-10 levels and failure-free survival (FFS) in Hodgkin's disease (HD). PATIENTS AND METHODS: Untreated patients, older than 16 years, with biopsy-proven HD, were included if treated with ABVD or equivalent regimens, and if pretreatment serum was available. IL-10 levels were determined with a capture enzyme-linked immunoassay specific for cellular IL-10. RESULTS: Among healthy adult volunteers serum IL-10 levels ranged from 4.8-9.8 pg/ml (mean 7.1, standard deviation 1.5 pg/ml). Therefore levels > or = 10 pg/ml were considered elevated. We identified 101 patients with available serum. Their median age was 32 years, and 60% had B-symptoms. Ann Arbor stage was I in 4, II in 21, III in 35, and IV in 41 patients. Histology was nodular sclerosis in 74, mixed cellularity in 12, lymphocyte predominance in six, lymphocyte depletion in one, and unclassified in eight patients. Pretreatment serum IL-10 levels were elevated in 51 patients, and were higher in those with serum albumin < 3.5 g/dl, B symptoms, serum beta 2-microglobulin > or = 2.5 mg/l, anemia, and AAS III or IV. After a median follow-up of 32 months for survivors, 20 patients have progressed, and the three-year FFS of those with high vs. normal serum IL-10 was 60% +/- 9 vs. 91 +/- 9% (50% vs. 50% of the population; P = 0.004 by log-rank). Among patients with Ann Arbor stage III or IV the three-year FFS for those with high vs. normal serum IL-10 (58 vs. 42% of the population) was 57 +/- 9% vs. 92 +/- 6% (P = 0.008 by log-rank). Multivariate analysis using Cox's proportional hazards model confirmed that IL-10 was an independent variable associated with inferior FFS in this population. CONCLUSIONS: Elevation of serum IL-10 levels is frequent and is associated with inferior FFS in adults with ABVD-treated HD. This observation should be verified in other patient populations. In addition, the source and the role of IL-10 in the biology of HD should be further investigated.

Adolescent↗

PubMed1999

Mandatory reporting of intimate partner violence to police: views of physicians in California.

OBJECTIVES: This study examined physicians' perspectives on mandatory reporting of intimate partner violence to police. METHODS: We surveyed a stratified random sample of California physicians practicing emergency, family, and internal medicine and obstetrics/gynecology. RESULTS: An estimated 59% of California primary care and emergency physicians (n = 508, 71% response rate) reported that they might not comply with the reporting law if a patient objects. Primary care physicians reported lower compliance. Most physicians agreed that the legislation has potential risks, raises ethical concerns, and may provide benefits. CONCLUSIONS: Physicians' stated noncompliance and perceived negative consequences raise the possibility that California's mandatory reporting law is problematic and ineffective.

Adult↗

PubMed1999

Intensive dose ifosfamide and etoposide with G-CSF for stem cell mobilization in patients with non-Hodgkin's lymphoma.

We studied 36 patients with non-Hodgkin's lymphoma to evaluate the stem cell yield following recovery from intensive dose ifosfamide and etoposide given as mobilization chemotherapy. We also assessed the toxicity of the regimen and engraftment kinetics. All patients had intermediate grade lymphoma and had either failed to achieve a complete remission to induction chemotherapy or had relapsed. Patients received ifosfamide 10 g/m2 IV total dose given over 72 hours, etoposide 150 mg/m2 IV every 12 hours for 6 doses and G-CSF 10 microg/kg/d. Thirty-four patients went on to receive high-dose chemotherapy with BEAM or with CVP and BEAM. A median of 2 (1-10) apheresis was required to reach the target CD34+ count of >4 x 10(6)/kg. A median of 13.1 CD34+ cells/kg (4.1-148) was obtained. Toxicity was limited to mucositis in 3 patients, transient confusion and transient rise in liver function tests in 3 and 2 patients respectively. The median time to engraftment was 10 days (8-17) for all the patients undergoing high-dose chemotherapy. The regimen of intensive dose ifosfamide and etoposide along with G-CSF is well tolerated and in this group of patients has lead to successful stem cell harvests and sustained engraftment.

Adult↗

PubMed1999

California's mandatory reporting of domestic violence injuries: does the law go too far or not far enough?

Explore the source record for details and available documents.

Adult↗

PubMed1998

Hodgkin's disease: correlation of clinical characteristics with probabilities for negative lymphangiogram vs. negative laparotomy findings in patients with Stage I supradiaphragmatic presentations vs. those in patients with Stage II.

PURPOSE: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. METHODS AND MATERIALS: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. RESULTS: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms, nodular sclerosis histology, age <40 years, and <4 involved sites, whereas negative laparotomy findings correlated strongly with a combination of <4 involved sites and mediastinal disease. Predicted probabilities again depended on the ratios of favorable to unfavorable characteristics. CONCLUSION: This study demonstrated that probabilities for negative abdominal findings for patients with supradiaphragmatic presentations of NS and MC Hodgkin's disease depended on: 1) whether the disease presented as Stage I or as Stage II; 2) whether staging was limited to a lymphangiogram or whether it included a laparotomy; and 3) or whether the clinical features associated with the presenting stage and methods of staging were favorable or unfavorable.

Abdomen↗

PubMed1998

Protein tyrosine kinase activity in T lymphocytes from patients with systemic lupus erythematosus.

We have recently observed an abnormal pattern of protein tyrosine phosphoryl-ation in resting T lymphocytes obtained from peripheral blood of patients with systemic lupus erythematosus (SLE). To examine whether these findings may be related to dysregulated protein tyrosine kinase (PTK) function, we tested the relative amount and enzyme activity of the main PTKs involved in the earliest signalling steps triggered via the CD3 pathway. Cell lysates from peripheral blood T cells in SLE patients showed lower amounts of p59(fyn) and p56(lck) as shown by immunoblot. In contrast, the amount of ZAP-70, a PTK of the syk family, was comparable in both groups. However, p59(fyn) immuno-precipitates obtained from unstimulated peripheral blood SLE T cells showed enhanced PTK activity as compared to controls, whereas the PTK activity of p56(lck) and ZAP-70 molecules was comparable in both groups. The unchecked activity of the TCR/CD3-associated src kinase p59(fyn) may alter the balance needed for regulated T cell responses in SLE patients.

Adult↗

PubMed1998

Mesenteric venous thrombosis after appendicectomy in a child: clinical case and review of the literature.

Mesenteric venous thrombosis (MVT) after appendicectomy has not been reported in the pediatric literature. This complication is associated with significant morbidity and mortality rates in adults. The report of this case attempts to analyze the features found in an appendicectomized child documented by radiological examination and surgery before and after starting heparin therapy. Anticoagulation treatment should be started as soon as possible and continued for a long time to decrease the risk of relapse.

Appendectomy↗

PubMed1998

Alternating triple therapy for the treatment of intermediate grade and immunoblastic lymphoma.

BACKGROUND: CHOP is currently considered the gold standard of treatment for intermediate grade lymphomas. We designed a new regimen known as 'ATT' (alternating triple therapy) which uses three non-cross resistant combinations in alternating sequence for nine cycles. MATERIALS AND METHODS: This is a phase II clinical trial with comparison to CHOP/CMED historical controls using prognostic factors. The tumor score system was used to evaluate the results of this trial. Two hundred sixty-eight eligible patients who had one or more of the following adverse features: bulky disease, elevated LDH or > 1 extranodal site were analyzed. Outcome measures consist of survival and failure free survival. RESULTS: At a median follow-up of 32 months, there was no statistically significant difference in survival for those with favorable prognostic factors (tumor score < or = 2). However, there was a statistically significant difference in favor of ATT for those with unfavorable tumor scores. When we examined the failure-free survival of those with unfavorable tumor scores, we again observed a superiority for the ATT regimen over CHOP/CMED but the opposite was true for those with favorable tumor scores. We also found a statistically significant difference in favor of the ATT regimen when compared with CHOP/CMED for patients < or = 60 years old with a tumor score > or = 3, while no advantage was found for those > 60 years. CONCLUSIONS: ATT appears more effective but only for patients < 60 years old with unfavorable tumor scores. In those older than 60 years with favorable tumor score, CHOP/CMED appears superior. ATT might be an adequate regimen for young patients with poor prognostic features while CHOP/CMED might be a better choice for those with good prognosis irrespective of age. For those > 60 years with unfavorable tumor scores neither ATT or CHOP/CMED were adequate treatment. Because of the phase II nature of this study, these conclusions should be considered as hypotheses which require prospective testing.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Paclitaxel plus high-dose cyclophosphamide with G-CSF support in patients with relapsed and refractory aggressive non-Hodgkin's lymphoma.

Based on the single-agent activity of both paclitaxel and cyclophosphamide in the treatment of non-Hodgkin's lymphoma (NHL), we conducted a phase II study to evaluate the efficacy of the combination of the two drugs in patients with refractory and relapsed aggressive NHL. All patients received 900 mg/m2 bolus of cyclophosphamide intravenously daily for 3 consecutive days with a concurrent infusion of 150 mg/m2 of paclitaxel over 72 h (50 mg/m2/d). 24 h after the completion of chemotherapy, patients received subcutaneous injections of 5 microg/kg of granulocyte-colony stimulating factor (G-CSF) daily until white cell count recovery. Treatment was repeated every 3 weeks. Patients who had at least a partial response (PR) after two courses continued to receive a maximum of four courses. Patients with responding disease were allowed to undergo high-dose chemotherapy followed by stem-cell/bone marrow transplantation if they were eligible. Of the 77 patients who were eligible for the study, 74 (96%) were evaluable for toxicity and treatment response. The overall response rate was 45% (95% CI 33-57%). Patients who received treatment after their disease relapsed from a complete response (CR) had an 81% response rate (38% CRs), whereas those with primary refractory disease had a 22% response rate. Toxicities of > grade 2 included alopecia (100%) and stomatitis (25%). Neutropenic fever of grade > 2 occurred after 18% of the courses, and platelet count of < or = 20 x 10(9)/l developed after 20% of the courses. Thus, the combination of paclitaxel plus high-dose cyclophosphamide is an effective new regimen in the treatment of refractory and relapsed NHL.

Adult↗

PubMed1998

Injury-control education in six U.S. medical schools.

PURPOSE: To assess knowledge, attitudes, and formal instruction related to injury control among fourth-year medical students. Injury is the leading cause of death among Americans aged 1 to 44 years. METHOD: The authors conducted a cross-sectional survey of fourth-year students at six U.S. medical schools, four of which maintain federally funded injury prevention research centers. Main outcome measures included injury-related knowledge scores, three attitude measures, and self-reported exposures to injury prevention education. RESULTS: Six hundred and thirty-five fourth-year medical students (73% of those eligible) participated. The responding students were, on average, unable to correctly answer half of the questions testing injury-related knowledge. They rated medical problems more important and more preventable than injury problems, and they felt more comfortable asking their patients about risk factors for medical problems. These findings may be explained, in part, by the students' reported minimal exposure to injury control education in medical school. The students encountered the topic more frequently on rotations in pediatrics (84%), family medicine (73%), and preventive medicine (66%) than on rotations in emergency medicine (47%), internal medicine (41%), or obstetrics and gynecology (34%). Injury control was encountered least often on rotations in psychiatry (23%) and surgery (14%). CONCLUSIONS: These findings suggest that injury control is given limited coverage in the curricula of U.S. medical schools. As a result, students have little understanding of the principles and benefits of injury control.

Cross-Sectional Studies↗