Stop-flow in mediastinum and thorax for resistant lymphoma

BACKGROUND/AIMS: Management of patients with heavily pretreated malignant lymphoma failing frontline treatment and salvage high-dose chemotherapy and autologous peripheral stem cell rescue, is problematic. A pilot study was conducted to evaluate isolated thoracic perfusion of drugs by means of stopflow technique. METHODOLOGY: Six patients were enrolled in the study; diagnoses included 4 advanced Hodgkin's disease, 1 primary mediastinal B-cell lymphoma, and 1 anaplastic large cell lymphoma. Patients were aged 18-37 years; 4 presented with bulky mediastinum. They had never achieved a complete response since all had progressed from front-line treatment, and 3 had even failed salvage high-dose chemotherapy with autologous peripheral stem cell rescue. Cisplatin (100 mg/m2) and melphalan (35 mg/m2) were used. Carmustine (100 mg/m2) were added to these 2 drugs and cytarabine (2000 mg/m2) in patients not previously treated by carmustine, etoposide, cytarabine, and melphalan. Epidoxorubicin (70 mg/m2) was added in patients who previously received a suboptimal dosage of antracycline. Drugs were delivered monthly via aortic perfusion performed by means of Aigner's stop-flow technique. RESULTS: Overall 13 cycles of perfusional chemotherapy were administered with a median number of 2 cycles. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery. After 1 month, 6 (100%) objective responses after isolated thoracic perfusion were recorded, 3 (50%) of which were complete. Tolerance to therapy was excellent. Hematological toxicity was mild and transfusional support was needed only in one course. At the last follow-up, 2 patients are alive (1 complete response and 1 very good partial response, maintained). CONCLUSIONS: This new therapeutical approach seems very active in recurrent/refractory malignant lymphoma and may play an important role in this setting.     

Drug susceptibility of Mycobacterium tuberculosis in HIV-infected and -uninfected Ethiopians and its impact on outcome after 24 months of follow-up.

From a prospective cohort study on tuberculosis/human immunodeficiency virus (TB/HIV) interaction in Addis Ababa, Ethiopia, drug susceptibility results were available for 94 TB patients (46% HIV-infected). Resistance to one or more drug(s) was detected in 21 (22.3%) and multidrug resistance in five (5.3%) patients. Occurrence of resistance was not related to HIV status or outcome after 24 months of follow-up. However, among HIV-infected TB patients who died during follow-up, survival time in those with a resistant Mycobacterium tuberculosis strain was significantly shorter compared to those with a sensitive strain (6 vs. 13 months). Early detection of drug resistance and timely treatment change can therefore have a positive impact on survival in HIV-infected TB patients.     

Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide

Inducible heme oxygenase (HO-1) has recently been recognized as an antioxidant and cytoprotective gene. By use of Western blotting, cell viability analysis, and antisense technique, the present study investigates the involvement of HO-1 in endothelial protection induced by the clinically used nitric oxide (NO) donor molsidomine (specifically, its active metabolite 3-morpholinosydnonimine [SIN-1]) and the second messenger cGMP. In bovine pulmonary artery endothelial cells, SIN-1 and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) at 1 to 100 micromol/L induced the synthesis of HO-1 protein in a concentration-dependent fashion up to 3-fold over basal levels. HO-1 induction by SIN-1 was inhibited in the presence of the NO scavenger phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide and the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazole[4, 3-a]quinoxalin-1-one. 8-Bromo-cGMP (1 to 100 micromol/L) and dibutyryl cGMP (1 to 100 micromol/L) as well as the activator of particulate guanylyl cyclase atrial natriuretic peptide (1 to 100 nmol/L) produced increases in HO-1 protein similar to those produced by SIN-1. SIN-1 and 8-bromo-cGMP increased heme oxygenase activity (bilirubin formation). Cytoprotection by NO donors was abrogated in the presence of the heme oxygenase inhibitor tin protoporphyrin IX. Pretreatment of cells with a phosphorothioate-linked HO-1 antisense oligonucleotide prevented protection by SIN-1 or 8-bromo-cGMP against tumor necrosis factor-alpha cytotoxicity, whereas sense and scrambled HO-1 were without effect under these conditions. Our results show for the first time that HO-1 is a cGMP-sensitive endothelial gene and establish conclusively a causal relationship between HO-1 induction and endothelial protection by the NO/cGMP system. By targeting cytoprotective HO-1, NO donors may therefore be expected to induce antioxidant, antiatherogenic, and anti-inflammatory effects.     

Impact of the earthquake of September 26, 1997 in Umbria, Italy on the socioenvironmental and psychophysical conditions of an elderly population

The consequences of natural disasters on the social and health status of older people have not been deeply considered. The aim of this study was to evaluate the socioenvironmental and psychophysical conditions of an elderly population after a devastating earthquake. A randomly selected group of 332 older people (> or =64 years) was selected among 1548 eligible subjects living in the city of Nocera Umbra four months after an earthquake of 5.6 magnitude on the Richter scale. Three geriatricians evaluated the study subjects by means of a structured interview, and standardized scales, which considered physical and mental status, mood and anxiety, and self-perception of well-being, as well as the characteristics of family composition and social interactions. Of the study subjects, 11.1% lived alone, and 33.4% with the spouse only. Most were self-sufficient in the basic activities of daily life. Musculoskeletal diseases and hypertension were the most frequently observed pathologies in this geriatric population. In addition, 47.9% of the subjects lived in temporary houses; this group more frequently suffered from hypertension, and had a higher score of comorbidity as measured by Cumulative Illness Rating Scale (CIRS) compared to people who remained at home. People living in the pre-fabricated huts also showed a higher score on the Geriatric Depression Scale and the Hamilton scale for anxiety, and complained more often of their health status, evaluated as self-perception of well-being, when compared to the home dwellers. Although all the studied subjects suffered from the discomforts caused by the earthquake, the precariousness of living in temporary houses, whose structural characteristics do not take the needs of elderly subjects into account, could justify the higher distress experienced by persons housed in the huts. These observations suggest that, after natural disasters, emergency programs should be more adapted to elderly people, whose needs and expectations are often different from those of young adults.     

Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMV-specific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R⁺) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D⁺/R⁻). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (P < 0.05). During the antiviral prophylaxis, all 20 D⁺/R⁻ KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results.     

Assessment of condylar volume and ramus height in JIA patients with unilateral and bilateral TMJ involvement: retrospective case-control study

The objectives of the study are to analyze volumetric differences of condylar volumes in patients with unilateral and bilateral JIA and to compare results     

Defaulters from antiretroviral treatment in Jimma University Specialized Hospital, Southwest Ethiopia

Objective To determine the prevalence of and factors associated with defaulting from antiretroviral treatment (ART) in Jimma, Ethiopia. Methods Unmatched case control study: cases were individuals who had missed two or more clinical appointments (i.e. had not been seen for the last 2 months) between January 2005 and February 2007; controls were individuals who had been on ART at least for 1 year and were rated as excellent adherers by the providers. Data were collected from patient records, and by telephone call and home visit to identify the reason for defaulting. Results Of 1270 patients who started ART, 915 (72.0%) were active ART users and 355 (28.0%) had missed two or more clinical appointments. The latter comprised 173 (13.6%) defaulters, 101 (8.0%) who transferred out, 75 (5.9%) who died, and 6 (0.5%) who restarted ART. Reasons for defaulting were unclear in most cases. Reasons given were loss of hope in medication, lack of food, mental illness, holy water, no money for transport, and other illnesses. Tracing was not successful because of incorrect address on the register in 61.6% of the cases. Taking hard drugs (cocaine, cannabis and IV drugs), excessive alcohol consumption, being bedridden, living outside Jimma town and having an HIV negative or unknown HIV status partner were associated with defaulting ART. Conclusion A significant proportion of patients defaulted from ART treatment. ART clinics should ensure that patients’ addresses are correct and complete. Programmatic and counseling efforts to decrease ART defaulting should address illicit drug and excessive alcohol use, decentralise ART services, institute home‐based treatment options for seriously ill and bedridden patients, and address patients concerns.     

IL-4 in vitro production is upregulated in Alzheimer's disease patients treated with acetylcholinesterase inhibitors

Cytokines appear to be involved in the pathogenesis of Alzheimer's Disease (AD). Their modulation by treatment has been investigated only in a few studies. The aim of our study was to evaluate the effect of acetylcholinesterase inhibitors (AChEI) on Interleukin-4 (IL-4) production in AD patients. IL-4 levels were measured by ELISA on peripheral blood mononuclear cell cultures in the presence or absence of Concanavalin A or Phytohaemagglutinin. Linear regression analysis shows that patients who have been treated, have higher levels of IL-4 independently from age, gender and comorbidity. The increased production of IL-4 in AChEI treated patients might represent an additional mechanism through which AChEI act on AD progression.