Chronic gamma-irradiation results in increased cell killing and chromosomal aberration with specific breakpoints in fibroblast cell strains derived from non-Hodgkin's lymphoma patients.

Cultured skin fibroblast cells from 6 patients with non-Hodgkin's lymphoma (NHL) and 2 clinically normal subjects were compared for cell survival and chromosomal aberration after chronic gamma-irradiation. Fibroblasts from an ataxia telangiectasia (AT) homozygote and an AT heterozygote were used as positive controls. Following irradiation, fibroblasts from all 6 NHL patients showed an increase in both cell death and chromosomal aberration (breaks and rearrangements) compared to the normal subjects. The difference in the frequency of chromosomal aberration between the normals and the NHL patients remained virtually unchanged over a period of 24-72 h post irradiation incubation of the cells. Cell cycle analysis by flow cytometry carried out in 1 normal and 1 NHL fibroblast cell strain showed that more cells representing the NHL patient were in G2/M phase compared to the normal at various times of cytogenetic analysis. While the AT homozygote appeared to be the most radiosensitive, the AT heterozygote showed a slightly higher incidence of cell death and chromosomal aberration than the normals. The cellular and chromosomal radiosensitivity of fibroblast cell lines from the NHL patients differed slightly from that of the AT heterozygote but clearly occupied an intermediate position between the AT homozygote and the normal subjects. Cells from 3 of the NHL patients showed radiation-induced specific chromosomal breaks involving chromosomes 1, 2, 6, 8, 10 and 11 which correspond to known fragile sites. Such breakpoints associated with increased radiosensitivity may be indicative of predisposition to malignancy in the patients studied.     

Post-irradiation DNA synthesis inhibition and G2 phase delay in radiosensitive body cells from non-Hodgkin's lymphoma patients: an indication of cell cycle defects

In the present study, both post-irradiation DNA synthesis and G₁ phase accumulation were analyzed in lymphoblastoid cell lines (LCLs) and fibroblast cell strains derived from (Saudi) patients with non-Hodgkin's lymphoma (NHL), ataxia telangiectasia (AT), AT heterozygotes and normal subjects. A comparison of the percent DNA synthesis inhibition (assayed by ³H-thymidine uptake 30 min after irradiation), and a 24 h post-irradiation G₂ phase accumulation determined by flow cytometry placed the AT heterozygotes and the NHL patients in an intermediate position between the normal subjects (with maximum DNA synthesis inhibition and minimum G₂ phase accumulation) and the AT homozygotes (with minimum DNA synthesis inhibition and maximum G₂ accumulation). The similarity between AT heterozygotes and the NHL patients with respect to the two parameters studied after irradiation was statistically significant. The data indicating a moderate abnormality in the control of cell cycle progression after irradiation in the LCLs and fibroblasts from NHL patients may explain the enhanced cellular and chromosomal radiosensitivity in these patients reported by us earlier. In addition to demonstrating a link between cell cyle abnormality and radiosensitivity as a possible basis for cancer susceptibility, particularly in the NHL patients, the present studies emphasized the usefulness of the assay for 24 h post-irradiation G₂ phase accumulation developed by Lavin et al. (1992) in characterizing AT heterozygote-like cell cycle anomally in cancer patients irrespective of whether they carried the AT gene or any other affecting the cell cycle.     

Frequency and distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced structural chromosome aberrations in fibroblasts from sarcoma and non-Hodgkin's lymphoma patients

The frequency and distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced structural aberrations, i.e., chromatid and chromosome gaps, breaks, and exchanges, were studied in fibroblasts from 16 patients with sarcoma, 15 with non-Hodgkin's lymphoma (NHL), and 14 controls. The mean frequencies of aberrant cells, and gap, break, and gap + break events per 100 cells were 22.9, 5.1, 28.6, and 33.7 in the sarcoma group; 19.1, 5.0, 22.5, and 27.5 in the NHL group; and 23.5, 6.1, 33.5, and 39.6 in the control group. None of the differences between the groups were statistically significant. The distribution of MNNG-induced aberrations was non-random (P less than 0.001) in all 3 groups. Eight, 11, and 17 chromosome bands in the sarcoma, NHL, and control groups, respectively, were particularly break-prone. Only 2 hot spots in the sarcoma group (1p32, 11q23), and 3 in the NHL group (1p36, 3q25, 6p21), coincided with the 25 and 60 bands known to be involved in primary rearrangements in sarcomas and NHL. We conclude that neither the frequency nor the distribution of MNNG-induced chromosomal aberrations indicates any latent chromosomal instability in sarcoma and NHL patients.     

CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV.     

MACOP-B chemotherapy for the treatment of high grade and intermediate grade non Hodgkin's lymphoma.

Between Nov. 1985 and Nov. 1988, sixty-three patients with high grade malignant (hg) and intermediate grade malignant (img) Non Hodgkin's Lymphoma (NHL) were treated with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin). Thirty-seven patients received MACOP-B as an upfront treatment modality, whereas twenty-six patients had relapsed disease and received MACOP-B as a salvage protocol. Four weeks after termination of therapy, 75% of patients with de novo NHL and 72% of the patients with relapsed NHL were in complete remission (CR). In the group of newly diagnosed NHL, 22% achieved partial remission (PR) and 3% no change (NC), whereas in the group with relapsed disease 14% had PR and 14% had progressive disease (PD). At a medium follow-up of 12 months (range 1 month to 33 months), 74% of patients with de novo NHL continued to be in CR whereas the continuous CR rate in patients with relapsed disease was 35%. Overall survival after 30 months of observation for the patient group with de novo NHL was 75% and 40% for patients with relapsed NHL. The mean duration for completion of the projected 12 chemotherapy cycles, given in weekly intervals, was 12.9 and 13.5 weeks in upfront or salvage therapy, respectively. With low incidence of major toxicities, application of drugs on an outpatient basis, and high efficacy, MACOP-B shows substantial advantages for therapy of de novo and relapsed NHL.     

Renal Involvement in Non-Hodgkin Lymphoma: Proven by Renal Biopsy

Aims

To determine the spectrum of renal lesions in patients with kidney involvement in non-Hodgkin''s lymphoma (NHL) by renal biopsy.

Methods

The clinical features and histological findings at the time of the renal biopsy were assessed for each patient.

Results

We identified 20 patients with NHL and renal involvement, and the diagnosis of NHL was established following the kidney biopsy in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n = 4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T-cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had impaired renal function. The pathological findings included (1) membranoproliferative glomerulonephritis-like pattern in seven patients; (2) crescent glomerulonephritis in four; (3) minimal-change disease in three, and glomeruli without specific pathological abnormalities in three; (4) intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one; and (7) lymphoma infiltration of the kidney in eight patients.

Conclusion

A wide spectrum of renal lesions can be observed in patients with NHL, and NHL may be first proven by renal biopsies for evaluation of kidney injury or proteinuria. Renal biopsy is necessary to establish the underlying cause of renal involvement in NHL.     

TGF-beta1 gene polymorphisms influence the course of the disease in non-Hodgkin's lymphoma patients

Non-Hodgkin's lymphomas (NHL) constitute a heterogenous group of mainly B-cell lymphoproliferative diseases with different patterns of clinical behaviour. Biological mechanisms leading to development of NHL are not clearly understood. Transforming growth factor-beta1 (TGF-beta1) influences B cell growth and development. The present study aimed to determine whether there is an association between the polymorphic features located within the TGF-beta1 gene in NHL patients and progression of the disease. Two single nucleotide polymorphisms at positions 869 T/C (Leu10Pro) and 915 G/C (Arg25Pro) in the precursor region of the TGF-beta1 gene were determined in 55 NHL patients and 50 healthy individuals by PCR-SSP technique using commercial primers. In univariate analysis the presence of TGF-beta1 high producer genotypes (T/T G/G or T/C G/G) was found to significantly associate with an increased number of extranodal sites (11/30 vs 3/25, p=0.035 for two or more extranodal sites in patients having or lacking the TGF-beta1 high producer genotype, respectively). TGF-beta1 high producer genotype together with other clinical and biological factors (patient sex and age, stage and aggressiveness of the disease, presence of B symptoms, serum LDH level) were subjected to multivariate logistic regression analyses for the number of extranodal sites. Multivariate analysis confirmed the role of TGF-beta1 high producer genotype as a risk factor of NHL manifestation in two or more extranodal sites (OR=7.217, p=0.043) in addition to histological aggressiveness of the disease (OR=4.302, p=0.057). TGF-beta1 gene polymorphisms were found to associate with the course of the disease in NHL patients. TGF-beta1 high producer genotype appeared as an independent risk factor of extranodal manifestation of the disease.     

Cytogenetic investigations in three cell types of a Saudi family with ataxia telangiectasia

Summary Chromosomal analyses were performed on lymphocytes, fibroblasts and lymphoblastoid cell lines derived from a Saudi family with ataxia telangiectasia (AT). The three siblings of a consanguineous marriage were all affected. The lymphocytes of the AT homozygotes (probands) showed an increase of 2- to 6-fold and 4- to 8-fold respectively, in the frequency of spontaneous and X-ray-induced chromosomal aberrations compared with controls, while the parents (obligate heterozygotes) of the patients showed no notable difference. The unirradiated lymphocytes from the oldest AT sibling, an 11-year-old boy (AT1), showed specific rearrangements involving chromosomes 7 and 14 [t(7;14)(q35;q12)] and 12 and 14 [t(12;14)(q23;q12)] in two different clones. The most severely affected sibling was a 9-year-old girl (AT2) who presented with a clone showing a novel rearrangement involving chromosomes 14 and 17, namely: del(14) (q31q32) and dup(17)(q21–q24). The lymphocytes from the third sibling, a 2-year-old boy (AT3), showed a t(2;14)(p24;q12). In addition, an inv(14)(q12q32) was observed in all three AT patients, while inv(7)(p14q35) was found only in patients 2 and 3. The lymphocytes from the AT parents and controls showed normal karyotypes. The breakpoints involving chromosomes 2,12 and 17, observed in our studies, have rarely been reported in other series of AT patients. No non-random chromosomal rearrangements were observed either in the skin fibroblasts or in the lymphoblastoid cell lines derived from the AT patients, although all cell lines showed an increase in both spontaneous and radiation-induced chromosomal breaks per cell. The present study constitutes the first report on a cytogenetic analysis of a Saudi family with three AT siblings.     

Previous Exposure to Statin May Reduce the Risk of Subsequent Non-Hodgkin Lymphoma: A Nationwide Population-Based Case-Control Study

Background

The purpose of this study was to investigate the association between previous exposure to statins and the risk of non-Hodgkin lymphoma (NHL).

Methods

This nationwide population-based case–control study was conducted using the National Health Insurance Research Database of Taiwan. The NHL group consisted of the patients with a first-time diagnosis of NHL between 2005 and 2008. The cases of the control group were pair-matched to the NHL group according to sex, year of birth and date of NHL diagnosis (index date). The statin administration data from both groups were retrospectively collected from the index date to January 1, 1996. The cumulative defined daily dose (cDDD) was estimated to evaluate the statin exposure. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression.

Results

The study population was composed of 1715 NHL patients and 16942 control subjects. The analysis revealed that previous statin administration was associated with a reduced risk of subsequent NHL with an adjusted OR of 0.52 (95% CI, 0.43–0.62). Additionally, there was a dose-response relationship between statin administration and the risk of NHL. The adjusted ORs were 0.63 (95% CI, 0.46–0.86), 0.58 (95% CI, 0.42–0.79), 0.51 (95% CI, 0.38–0.67), and 0.36 (95% CI, 0.24–0.53) for the subjects with statin administrations of fewer than 28, 28 to 90, 91 to 365, and more than 365 cDDDs, respectively, relative to the subjects without any statin administration.

Conclusions

The results of this study suggest that previous statin administration is associated with a lower risk of subsequent NHL. As statins are widely used medications, the magnitude of the risk reduction may have a substantial influence on public health. Further studies to confirm our findings are warranted.     

Cancer/testis antigens expression and autologous serological response in a set of Brazilian non-Hodgkin’s lymphoma patients

Background

Based on their tumor-associated expression pattern, cancer/testis antigens (CTAs) are considered potential targets for cancer immunotherapy. We aim to evaluate the expression of CTAs in non-Hodgkin??s lymphoma (NHL) samples and the ability of these patients to elicit spontaneous humoral immune response against CTAs.

Methods

Expression of MAGE-A family, CT7/MAGE-C1, CT10/MAGE-C2, GAGE and NY-ESO-1 was analyzed by immunohistochemistry in a tissue microarray generated from 106 NHL archival cases. The humoral response against 19 CTAs was tested in 97 untreated NHL serum samples using ELISA technique.

Results

11.3?% of NHL tumor samples expressed at least 1 CTA. MAGE-A family (6.6?%), GAGE (5.7?%) and NY-ESO-1(4.7?%) were the most frequently expressed antigens. We found no statistically significant correlation between CTA positivity and clinical parameters such as NHL histological subtype, Ann Arbor stage, international prognostic index score, response to treatment and overall survival. Humoral response against at least 1 CTA was observed in 16.5?% of NHL serum samples. However, overall seroreactivity was low, and strong titers (>1:1000) were observed in only two diffuse large B-cell lymphomas patients against CT45.

Conclusion

Our findings are in agreement with most of published studies in this field to date and suggest an overall low expression of CTAs in NHL patients. However, as many new CTAs have been described recently and some of them are found to be highly expressed in NHL cell lines and tumor samples, further studies exploring the expression of different panels of CTAs are needed to evaluate their role as candidates for immunotherapy in NHL patients.     

Frequency and distribution of mitomycin C-induced structural chromosome aberrations in lymphocytes from non-Hodgkin lymphoma patients

Lymphocytes from 15 untreated patients with non-Hodgkin lymphoma (NHL) and 15 controls were exposed to 0.08 micrograms/ml mitomycin C, and the frequency and distribution of structural chromosome aberrations (chromatid and chromosome gaps, breaks, and exchanges) were analyzed in 100 mitoses per subject. The mean frequencies of aberrant cells, and gap, break, and gap + break events were 8.7, 0.9, 9.7, and 10.6 in the NHL group and 11.6, 1.1, 12.7, and 13.8 in the control group. None of the differences between the two groups was significant (P greater than 0.05). The distribution of breakpoints was nonrandom (P less than 0.001) in both groups, with a particularly marked excess of breaks in 9q11. The other breakage-prone bands were 1q11 and 1q21 in the NHL group and 1p11, 1q11, 2q31, and 16q11 in the control group. None of these hot spots coincided with any of the 60 bands known to be involved in primary chromosome abnormalities in NHL.     

Blood concentrations of tumor necrosis factor-alpha in malignant lymphomas and their decrease as a predictor of disease control in response to low-dose subcutaneous immunotherapy with interleukin-2

Tumor necrosis factor-alpha (TNF-alpha), a cytokine provided by both immunomodulating and inflammatory activities, has been described to be abnormally increased in the blood of patients affected by malignant lymphomas, particularly NHL. However, the biological and clinical significance of TNF-alpha secretion in malignant lymphomas is still controversial. The present study was carried out to further define TNF-alpha secretion in untreated malignant lymphomas and during low-dose IL-2 immunotherapy. The study included 80 malignant lymphoma patients, 54 of whom were affected by HD and the other 26 by NHL. The mean TNF-alpha serum concentrations observed in untreated lymphoma patients were significantly higher than those seen in the healthy controls, without significant differences between HD and NHL. Moreover, both HD and NHL lymphoma patients at clinical stage III-IV showed significantly higher mean TNF-alpha levels than those at clinical stage I-II. Finally, patients with systemic symptoms had higher mean TNF-alpha concentrations than those without any systemic symptoms, even though statistical significance was observed only for NHL patients. In a second study we have evaluated changes in TNF-alpha levels in seven evaluable lymphoma patients (NHL: 6; HD: 1)--who did not respond to conventional therapies--during subcutaneous low-dose IL-2 (3 MIU/day, 6 days/week for 4 weeks). Long-term stable disease was achieved in four patients with NHL, whereas the other three progressed. In patients with stable disease the mean TNF-alpha concentrations significantly decreased during treatment, whereas they increased in progressing patients. This study, by showing an abnormally enhanced TNF-alpha secretion in both NHL and HD patients with advanced disease and systemic symptoms and a decrease in its levels in patients who achieved disease control on IL-2 immunotherapy, appears to confirm the unfavorable prognostic significance of enhanced TNF-alpha levels in malignant lymphomas.     

Diagnostic and prognostic value of immunohistological bone marrow examination: results in 212 patients with lymphoproliferative disorders

Cryostat sections of 246 consecutive bone marrow biopsies from 212 patients with lymphoproliferative disease were investigated using a panel of monoclonal antibodies (MOAb's) and an immunoperoxidase technique. Bone marrow involvement was demonstrated by immunohistological examination in 121/160 patients (76%) with non-Hodgkin lymphomas (NHL) and 16/23 patients (70%) with plasma cell malignancies; the definite immunological diagnosis could be performed in 77% and 88%, respectively. Reactivity with the MoAb Ki-67 correlated with clinical parameters: in all cases exhibiting more than 5% positive cells an unfavourable course was seen, independent of the histological subtype. Another MoAb of potential prognostic relevance is KiM 4 b, which reacts with follicular dendritic cells (FDC). Besides the presence of FDC in germinal center tumors (CB/CC and CC-NHL) we found FDC in a minority of cases with B-CLL (5/44) and IC lymphoma (4/18). In the latter group 3/4 patients showed a favourable clinical course (vs 2/14 without FDC). The MoAb Tü 1 could discriminate between the lymphoplasmocytoid (11/12 positive) and the lymphoplasmocytic (0/6 positive) subtype of IC lymphoma and has proven of diagnostic importance. Expression of IL-2 receptors, detected by MoAb anti-Tac (CD 25), was demonstrated on leukemic cells from patients with hairy cell leukemia (100%), B-CLL (82%), IC (61%), CC (50%) and CB/CC lymphoma (50%). A considerable number of reactive T-lymphocytes (5%-60% of tissue cells) were identified among the neoplastic B cells with a predominance of CD4+ cells in most cases with NHL, whereas the CD4+/CD8+ ratio was significantly lower in myelomas and non-infiltrated bone marrows. The potential meaning of these findings is discussed. The immunohistological bone marrow analysis represents an important additional method in the diagnostic procedures of lymphoproliferative diseases involving the bone.     

Combined cytomorphologic and immunophenotypic analysis in the diagnostic workup of lymphomatous effusions

OBJECTIVE: To analyze the results of cytomorphology and immunophenotyping in 54 patients with lymphomatous effusions. STUDY DESIGN: We report the results of cytomorphology and immunophenotyping in 54 patients with lymphomatous effusions. Twenty-three of the 54 had a previous diagnosis of NHL. In the remaining 31 patients, lymphomatous involvement was clinically suspected. RESULTS: Thirty-three lymphomatous effusions were positive for involvement by NHL. Twenty-one of these 33 patients (64%) had a previous diagnosis of NHL. Of the remaining 12 patients with newly diagnosed NHL, 11 had high grade lymphoma, and one had follicular center lymphoma. Twenty effusions were considered to be reactive; only two of these patients had NHL. One effusion revealed involvement by a previously unknown carcinoma. We observed seven false negative results if only one of both methods was considered. A high grade NHL was not diagnosed by immunophenotyping in one case, and six cases of low grade NHL could not be detected by cytomorphology. The combined strategy of cytomorphology and immunophenotyping had a sensitivity of 100% and specificity of 100% in our study, confirmed by follow-up studies. CONCLUSION: Both methods have shown difficulties in the examination of lymphomatous effusions. Cytomorphology has problems distinguishing reactive effusions from low grade NHL. The detection of high grade NHL by immunophenotyping is difficult. However, both methods together offer the advantage of dual staining ability and are most helpful in distinguishing clonal lymphomatous from reactive effusions.     

Rate of Primary Refractory Disease in B and T-Cell Non-Hodgkin’s Lymphoma: Correlation with Long-Term Survival

Background

Primary refractory disease is a main challenge in the management of non-Hodgkin’s Lymphoma (NHL). This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients.

Methods

Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%), intensive therapy with autograft (16.9%), or other therapies (19.9%). Among B-cell NHL, 1,356 (47.8%) received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months.

Results

Overall, 690 (22.2%) patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001). Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001). Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001).

Conclusion

Chemosensitivity to primary treatment is crucial for the long-term survival in NHL. This supports the necessity of studies aimed to early identify refractory disease and to develop different treatment strategies for responsive and refractory patients.     

Membrane-bound/soluble IL-2 receptor (IL-2R) and levels of IL-1α, IL-2, and IL-6 in the serum and in the PBMC culture supernatants from 17 patients with hematological malignancies

The present study investigated the peripheral blood mononuclear cells (PBMC) blastic responses to PHA, PHA plus recombinant IL-2 (rIL-2) and rIL-2 alone; the expression of membrane-bound IL-2R on PHA-stimulated PBMC; and the levels of IL-1α, IL-2, IL-6, and sIL-2R in serum and in culture supernatants from PHA-stimulated PBMC in 17 patients with hematological malignancies (mean age 58.5 yr, range 22–82): 6 with non-Hodgkin’s lymphoma (NHL), 4 with Hodgkin’s lymphoma (HL), 5 with Hairy cell leukemia, 1 with chronic myelogenous leukemia, and 1 with chronic lymphocytic leukemia. The patients with HL and NHL with active disease (AD) were separated from those in clinical remission. The patients with AD were studied at diagnosis (obviously before therapy) and the patients in clinical remission were out of therapy since at least 6 mo. The lymphocyte blastogenic response to PHA was significantly lower in patients with HL and NHL with AD than in the control group. The response to rIL-2 alone was in the same range in the control group and in HL and NHL AD patients. By adding rIL-2 to PHA there was an increase of the blastogenic response of the same patients. The percentage of CD25 expressed on PHA-stimulated lymphocytes from patients with HL and NHL AD and from normal subjects is in the same range. Serum levels of IL-2, IL-6, and sIL-2R were significantly higher in HL and NHL AD patients than in controls as well as in all other hematological malignancies. Supernatants derived from PHA-stimulated PBMC were assessed for the presence of cytokines and sIL-2R by ELISA. The levels of IL-2, IL-6, and sIL-2R were significantly lower in HL and NHL AD patients than in controls as well as in all other hematological malignancies.     

Effect of Autogenic Training on General Improvement in Patients with Irritable Bowel Syndrome: A Randomized Controlled Trial

Autogenic training (AT) is a useful and comprehensive relaxation technique. However, no studies have investigated the effects of AT on irritable bowel syndrome (IBS). In this study we tested the hypothesis that AT improves symptoms of IBS. Twenty-one patients with IBS were randomly assigned to AT (n = 11, 5 male, 6 female) or control therapy (n = 10, 5 male, 5 female). AT patients were trained intensively, while the control therapy consisted of discussions about patients’ meal habits and life styles. All patients answered a question related to adequate relief (AR) of IBS symptoms and four questionnaires: Self-induced IBS Questionnaire (SIBSQ), Self-reported Depression Scale (SDS), State-Trait Anxiety Inventory (STAI), and Medical Outcome Short Form 36 Health Survey (SF-36). The proportion of AR in the last AT session in the AT group (9/11, 81.8%) was significantly higher than that in the controls (3/10, 30.0%, Chi-square test, p = 0.048). Two subscales of the SF-36, i.e., social functioning and bodily pain, were significantly improved in the AT group (p < 0.05) as compared to the control group. Role emotional (p = 0.051) and general health (p = 0.068) showed a tendency for improvement in the AT group. AT may be useful in the treatment of IBS by enhancing self-control.     

Differences between patients with non-Hodgkin's lymphomas in a cohort of HIV/AIDS patients in Puerto Rico.

The close association between AIDS and non-Hodgkin's lymphoma (NHL) is well known. Few studies are available that evaluate the profile of NHL in a cohort of HIV-infected patients who reside in Puerto Rico. The present study was performed in a cohort of 2,843 HIV-infected patients followed in the Retrovirus Research Center at Bayamón, Puerto Rico, evaluated between January 1992 until December 2000. NHL prevalence was determined and differences between AIDS defining and non-AIDS defining NHL were evaluated with the Fisher and ANOVA test. NHL prevalence was 0.9%. Nine (33%) were AIDS-defining (AIDS-d) NHL and 18 (67%) were non-AIDS-d NHL. Both groups were similar in gender distribution and mean diagnosis age. The median CD4+ T cell count at diagnosis was below 150/mm3 in both groups. Injecting drug use was higher in AIDS-d NHL patients and Homo-Bisexual contact was higher in non-AIDS-d NHL patients. Death rate in the first year after the NHL was 67% in the AIDS-d group and 56% in the non-AIDS-d group. AIDS-d NHL incidence decreased after the implementation of combined antiretroviral therapy in the cohort, a finding not seen in the non-AIDS-d NHL. In summary the study detected low NHL prevalence, with high degree of immunological damage at the time of the lymphoma diagnosis. Conversely dissimilar response to the antiretroviral therapies was also perceived in the incidence of the two NHL groups.     

Bodychecking Rules and Concussion in Elite Hockey

Athletes participating in contact sports such as ice hockey are exposed to a high risk of suffering a concussion. We determined whether recent rule changes regulating contact to the head introduced in 2010–11 and 2011–12 have been effective in reducing the incidence of concussion in the National Hockey League (NHL). A league with a longstanding ban on hits contacting the head, the Ontario Hockey League (OHL), was also studied. A retrospective study of NHL and OHL games for the 2009–10 to 2011–12 seasons was performed using official game records and team injury reports in addition to other media sources. Concussion incidence over the 3 seasons analyzed was 5.23 per 100 NHL regular season games and 5.05 per 100 OHL regular season games (IRR 1.04; 95% CI 1.01, 1.50). When injuries described as concussion-like or suspicious of concussion were included, incidences rose to 8.8 and 7.1 per 100 games respectively (IRR 1.23; 95% CI 0.81, 1.32). The number of NHL concussions or suspected concussions was lower in 2009–10 than in 2010–11 (IRR 0.61; 95% CI 0.45, 0.83), but did not increase from 2010–11 to 2011–12 (IRR 1.05; 95% CI 0.80, 1.38). 64.2% of NHL concussions were caused by bodychecking, and only 28.4% of concussions and 36.8% of suspected concussions were caused by illegal incidents. We conclude that rules regulating bodychecking to the head did not reduce the number of players suffering concussions during NHL regular season play and that further changes or stricter enforcement of existing rules may be required to minimize the risk of players suffering these injuries.