Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid cell-specific monoclonal antibodies

Second or third chemotherapy-induced remissions in acute myelogenous leukemia (AML) are limited by early relapse of the leukemia. We developed monoclonal antibodies (MoAbs) that are cytotoxic to myeloid leukemia cells to treat bone marrow from these patients ex vivo for autologous transplantation. In this pilot study, bone marrow was harvested from ten patients with AML in remission, treated with one or two complement-fixing MoAbs, PM-81 and AML-2-23, which react with myeloid differentiation antigens, incubated with rabbit complement, and cryopreserved. These MoAbs were chosen because they have broad reactivity with AML cells but not with pluripotent progenitor cells. At the time of transplant, 6 patients were in second complete remission, 1 each was in third complete or partial remission, and 2 were in early first relapse. The patients were treated with cyclophosphamide (60 mg/kg a day for 2 days) and total body irradiation (200 cGy twice a day for 3 days) and given infusions of MoAb-treated bone marrow. Full bone marrow reconstitution was observed in eight patients; two patients did not recover platelets. Seven of the ten patients are surviving and disease-free at 21.0, 15.0, 13.0, 10.0, 6.0, 3.0, and 2.0 months posttransplant. Treating bone marrow with MoAbs to myeloid differentiation antigens does not interfere with pluripotential stem cell engraftment. Longer follow-up and a controlled study are necessary to prove that the apparent efficacy of this therapeutic approach in some patients is attributable to MoAb-mediated killing of leukemia cells.     

Prevalence of rheumatoid arthritis in Tucumán,Argentina

OBJECTIVE: To ascertain the prevalence of rheumatoid arthritis (RA) in Tucumán, Argentina. METHODS: The study was conducted between January 1, 1998, and December 31, 1999, in Tucumán province in northwest Argentina. Outpatient and hospitalization medical records for all patients with RA aged > or = 16 years were reviewed. Diagnosis was by 1987 American College of Rheumatology (ACR) criteria for RA and the population data were based on the 1991 national census. Prevalence rates, with 95% CI, were calculated using the number of San Miguel de Tucumán residents who fulfilled the 1987 ACR criteria for RA as numerator, and the city population aged > or = 16 as denominator. Crude and age-specific prevalence rates were calculated as number of cases/1,000 inhabitants. RESULTS: We identified 695 cases of RA. Sex-specific and overall prevalence rates (per 1,000) were 1.97 (95% CI 1.8-2) for all, 0.6 (95% CI 0.49-0.73) for men, 3.2 (95% CI 2.9-3.5) for women. CONCLUSION: Prevalence of RA is low in residents of Tucumán, Argentina, and comparable with rates observed in epidemiological surveys from Southern European countries.     

The concerted mechanism of photo-induced biprotonic transfer in 7-azaindole dimers: a model for the secondary evolution of the classic C2h dimer and comparison of four mechanisms

A mechanism is proposed for the formation in gas phase, during a short time, of the delicately symmetrical coplanar C(2h) classic 7-azaindole (7AI) doubly hydrogen-bonded dimer. Of the five card-pack or otherwise random geometry structures most likely to be formed in the supersonic jet expansion molecular beam, none would be an obvious precursor to the C(2h) dimer. One unstable dimer with dipole-dipole, van der Waals, and plane-to-plane hydrogen bonding is shown to be capable of unhinging about the hydrogen-bond pair as an axis, from 0 degrees to 90 degrees to 180 degrees, yielding a deep minimum for the C(2h) structure with its delicate geometry and symmetry. This relaxation mechanism is feasible in the 3-micros interval between the nozzle escape and the first laser pulse interception of the molecular beam. In the second part of the paper four published mechanisms are compared for concerted vs. two-step biprotonic phototransfer for the 7AI dimers. The dependence of the latter two models on H-atom instead of proton-transfer as an intermediate step negates the mechanism in a singlet (pi,pi*) electronic state by the valency repulsion, in the 3-electron orbital that would be generated. The concerted mechanism for biprotonic phototransfer is reaffirmed by the analysis of the quantum mechanical conditions set on the biprotonic transfer in the photo-excited molecular 7AI pair.     

Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir

Registration studies show entecavir (ETV) to be effective and safe in NUC‐naïve patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naïve HBeAg‐positive and HBeAg‐negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty‐nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log₁₀ IU/mL. Ninety‐two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti‐HBe positive; 14% became HBsAg negative and 13% anti‐HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off‐treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off‐treatment, 3 of them showed HBeAg reversion and 4 lost anti‐HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.     

Immunoproteomic Analysis To Identify Shiga Toxin-Producing Escherichia coli Outer Membrane Proteins Expressed during Human Infection

Shiga-toxin producing Escherichia coli (STEC) is the etiologic agent of acute diarrhea, dysentery, and hemolytic-uremic syndrome (HUS). There is no approved vaccine for STEC infection in humans, and antibiotic use is contraindicated, as it promotes Shiga toxin production. In order to identify STEC-associated antigens and immunogenic proteins, outer membrane proteins (OMPs) were extracted from STEC O26:H11, O103, O113:H21, and O157:H7 strains, and commensal E. coli strain HS was used as a control. SDS-PAGE, two-dimensional-PAGE analysis, Western blot assays using sera from pediatric HUS patients and controls, and matrix-assisted laser desorption ionization–tandem time of flight analyses were used to identify 12 immunogenic OMPs, some of which were not reactive with control sera. Importantly, seven of these proteins have not been previously reported to be immunogenic in STEC strains. Among these seven proteins, OmpT and Cah displayed IgG and IgA reactivity with sera from HUS patients. Genes encoding these two proteins were present in a majority of STEC strains. Knowledge of the antigens produced during infection of the host and the immune response to those antigens will be important for future vaccine development.     

A multicentre observational study of the effectiveness,safety and economic impact of nivolumab on non-small-cell lung cancer in real clinical practice

International Journal of Clinical Pharmacy - Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective...     

Use of amplified Mycobacterium tuberculosis direct test in respiratory samples from HIV-infected patients in Brazil

OBJECTIVE:

To compare the accuracy of the amplified Mycobacterium tuberculosis direct (AMTD) test with reference methods for the laboratory diagnosis of tuberculosis in HIV-infected patients.

METHODS:

This was a study of diagnostic accuracy comparing AMTD test results with those obtained by culture on Löwenstein-Jensen (LJ) medium and by the BACTEC Mycobacteria Growth Indicator Tube 960 (BACTEC MGIT 960) system in respiratory samples analyzed at the Bioassay and Bacteriology Laboratory of the Oswaldo Cruz Foundation Evandro Chagas Clinical Research Institute in the city of Rio de Janeiro, Brazil.

RESULTS:

We analyzed respiratory samples collected from 118 patients, of whom 88 (74.4%) were male. The mean age was 36.6 ± 10.6 years. Using the AMTD test, the BACTEC MGIT 960 system, and LJ culture, we identified M. tuberculosis complex in 31.0%, 29.7%, and 27.1% of the samples, respectively. In comparison with LJ culture, the AMTD test had a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 89.4%, 75.7%, and 95.0%, respectively, for LJ culture, whereas, in comparison with the BACTEC MGIT 960 system, it showed values of 88.6%, 92.4%, 83.8%, and 94.8%, respectively.

CONCLUSIONS:

The AMTD test showed good sensitivity and specificity in the population studied, enabling the laboratory detection of M. tuberculosis complex in paucibacillary respiratory specimens.     

High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma

The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated.