B-cell function in patients with chronic lymphocytic leukemia

Summary Using a reverse hemolytic protein A plaque assay, spontaneous and pokeweed mitogen (PWM)-induced immunoglobulin (Ig) secretion was determined in peripheral blood from 22 patients with B₁-chronic lymphocytic leukemia (CLL), one patient with B₂-CLL, and one patient with suppressor T-CLL. Diagnoses were established by cytological and histological criteria as well as several marker analyses. Lymphocytes from B₁- and B₂-CLL patients were unable to secrete Ig either spontaneously or after PWM stimulation. In T-CLL lymphocytes, spontaneous Ig secretion was suppressed very probably by the OKT-8-positive leukemic population, since, after cultivation with PWM, a normal Ig secretion could be demonstrated which was paralleled by a decrease in the OKT-8-positive cells. Cocultivation experiments with freshly isolated, unseparated lymphocytes from normal subjects and lymphocytes from patients were of no informational value, since isolated normal B-cells alone already showed a high rate of Ig secretion. However, coculture experiments with separated subpopulations after PWM stimulation revealed an intrinsic B-cell defect in lymphocytes from B₁-CLL patients, whereas their T-lymphocytes were found to be normal helper cells.

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Abbreviations CLL Chronic lymphocytic leukemia - PWM Pokeweed mitogen - ISC Immunoglobulin-secreting cells - Ig Immunoglobulin(s) Supported by the Deutsche Forschungsgemeinschaft (Ru 215/2)     

Behavioral effects of hashish in mice

The acute and subchronic effects of hashish extract (20 mg ⁹-THC/kg) on the social interactions between two drug-treated residents and an untreated intruder male were investigated. In this analysis 28 different behavioral elements were recorded.A single drug application suppressed all categories of behavior, except submissive behavior and flight, in dominant and subordinate residents. Treated animals were less active than controls and immobility was very frequent. An elevated total activity, due to an increase in non-social activities, was observed in the untreated intruder males of this group. Social investigation as well as submissive behavior and flight were reduced in these animals.On introduction of an untreated male after the fourth drug treatment of the residents, the drugged males showed tolerance to the sedative and most of the other behavioral effects of the drug, and intruder males behaved quite normally.The formation of a dominant-subordinate relation within the group was influenced neither by a single nor by repeated drug treatment.The acute and subchronic effects of hashish extract on social, especially aggressive behavior of males are compared to those described in previous papers and the variation in the results of the different studies is discussed.     

Cauda equina syndrome secondary to lumbar disc herniation: a meta-analysis of surgical outcomes

STUDY DESIGN: A meta-analysis of surgical outcomes of cauda equina syndrome secondary to lumbar disc herniation. OBJECTIVES: To determine the relationship between time to decompression after onset of cauda equina syndrome and clinical outcome, and to identify preoperative variables that were associated with outcomes. SUMMARY OF BACKGROUND DATA: The timing of surgical decompression for cauda equina syndrome is controversial. Although most surgeons recommend emergent decompression, results in certain studies show that delayed surgery may provide a satisfactory outcome. METHODS: A meta-analysis was performed to determine the correlation between timing of decompression and clinical outcome. One hundred four citations were reviewed, and 42 met the inclusion criteria. Preoperative and postoperative data were recorded. Length of time to surgery was broken down into five groups: less than 24 hours, 24-48 hours, 2-10 days, 11 days to 1 month, and more than 1 month. Logistic regression was used to determine the association between preoperative variables and postoperative outcomes. RESULTS: Outcomes were analyzed in 322 patients. Preoperative chronic back pain was associated with poorer outcomes in urinary and rectal function, and preoperative rectal dysfunction was associated with worsened outcome in urinary continence. In addition, increasing age was associated with poorer postoperative sexual function. No significant improvement in surgical outcome was identified with intervention less than 24 hours from the onset of cauda equina syndrome compared with patients treated within 24-48 hours. Similarly, no difference in outcome occurred in patients treated more than 48 hours after the onset of symptoms. Significant differences, however, were found in resolution of sensory and motor deficits as well as urinary and rectal function in patients treated within 48 hours compared with those treated more than 48 hours after onset of symptoms. CONCLUSIONS: There was a significant advantage to treating patients within 48 hours versus more than 48 hours after the onset of cauda equina syndrome. A significant improvement in sensory and motor deficits as well as urinary and rectal function occurred in patients who underwent decompression within 48 hours versus after 48 hours.     

Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin's disease: a report from the German Hodgkin's Lymphoma Study Group.

PURPOSE: To assess the incidence and outcome of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients with Hodgkin's disease (HD). PATIENTS AND METHODS: Between 1981 and 1998, the GHSG conducted three trial generations for early, intermediate, and advanced HD involving a total of 5,411 patients (called HD1 through HD9). RESULTS: A total of 46 patients with secondary AML/MDS were identified. The median age at diagnosis of leukemia was 47 years (range, 22 to 79 years). Primary therapy was as follows: radiotherapy alone (n = 4); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; n = 1); cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/ABVD or similar (n = 30); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) baseline (n = 2); and BEACOPP escalated (n = 9). Twelve patients developed AML/MDS after salvage therapy, including four patients who developed AML/MDS after high-dose chemotherapy with autologous stem-cell transplantation. Thirty-six of the secondary malignancies were AML, and 10 malignancies were MDS. After a median observation time of 55 months, incidence of secondary AML/MDS was 1%. Treatment for secondary AML/MDS was as follows: cytarabine (Ara-C)-containing regimens (6-thioguanin, cytarabine, daunorubicin [TAD]/high-dose cytarabine, mitoxantrone [HAM], HAM, Ida-Ara-C (idarubicin + Ara-C), Ida-Flag (idarubicin, fludarabin, Ara-C, G-CSF), and idarubicin, cytarabine, etoposide [ICE]+HAM; n = 11), TAD-chemotherapy (n = 5), other regimens (n = 3), no treatment or supportive care (n = 24), palliative oral chemotherapy (n = 3), and allogeneic stem cell transplantation (n = 9). After 24 months of observation, no difference in freedom from treatment failure and overall survival (2% and 8%, respectively) was observed in patients who developed AML or MDS. CONCLUSION: The prognosis of patients with secondary AML/MDS after primary HD is poor. Thus, emphasis should be made to improve initial treatment in an attempt to prevent this complication.     

Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG).

BACKGROUND: We designed a dose- and time-intensified high-dose sequential chemotherapy regimen for patients with relapsed and refractory Hodgkin lymphoma (HD). PATIENTS AND METHODS: Eligibility criteria included age 18-65 years, histologically proven primary progressive (PD) or relapsed HD. Treatment consisted of two cycles DHAP (dexamethasone, high-dose cytarabine, cisplatinum); patients with chemosensitive disease received cyclophosphamide followed by peripheral blood stem cell harvest; methotrexate plus vincristine, etoposide and BEAM plus peripheral blood stem cell transplantation (PBSCT). RESULTS: A total of 102 patients (median age 34 years, range 18-64) were enrolled. The response rate was 80% (72% complete response, 8% partial response). With a median follow-up of 30 months (range 3-61 months), freedom from second failure (FF2F) and overall survival (OS) were 59% and 78% for all patients, respectively. FF2F and OS for patients with early relapse were 62% and 81%, for late relapse 65% and 81%; for PD 41% and 48%, and for multiple relapse 39% and 48%, respectively. In multivariate analysis response after DHAP (P <0.0001) and duration of first remission (PD and multiple relapse versus early and late relapse; P=0.0127) were prognostic factors for FF2F. Response after DHAP (P <0.0081), duration of first remission (P=0.0017) and anemia (P=0.019) were significant for OS. CONCLUSION: Based on the promising results of this study, a prospective randomized European intergroup study was started comparing this intensified regimen with two courses of DHAP followed by BEAM (HD-R2 protocol).