Improved percent-predicted peak VO2 is associated with lower risk of hospitalization in patients with coronary heart disease. Analysis from the FRIEND registry.

BACKGROUND: Normal standards for peak oxygen consumption (VO2peak) are controversial because they tend to be population and protocol specific. This study was undertaken to examine the association between percentage of age-predicted VO2peak and all-cause hospital readmission in cardiac outpatients who were referred to an exercise-based secondary prevention program. METHODS: Hospital readmission was assessed in 1283 male patients with coronary heart disease (CHD) three years after enrolment, and related to the age-predicted VO2peak derived from the Fitness Registry and the Importance of Exercise: A National Data Base equation (FRIEND%PRED). VO2peak was estimated using a moderate perceptually regulated 1-km treadmill-walking test. Readmission was also assessed during the fourth-to-sixth years as function of improvement in FRIEND%PRED in 845 patients who were re-evaluated 3 years after baseline. RESULTS: During the 3-years after baseline, readmission rate was lower across increasing tertiles of FRIEND%PRED. Compared to the lowest tertile, the adjusted hazard ratios (HRs) for the second and third tertile were 0.98 (95% CI 0.76-1.27, p = 0.90) and 0.71 (0.53-0.95, p = 0.002). The rate of readmission from the fourth-to-sixth years after baseline was lower across tertiles of improved FRIEND%PRED, with adjusted HRs 0.78 (0.60-1.03, p = 0.08) and 0.58 (0.42-0.75, p < 0.0001) for the intermediate and high tertiles vs the lowest tertile. After adjustment for confounders, every 1 unit % increase in FRIEND%PRED was associated with a 3% reduction in risk of readmission (HR 0.97, 0.95-0.98, p < 0.0001). CONCLUSIONS: Age-predicted VO2peak estimated by a moderate treadmill-walk predicts hospital readmission in outpatients with CHD undergoing secondary prevention.

Urinary excretion of low molecular weight proteins in patients with pure monoclonal light chain proteinuria.

BACKGROUND: Because urinary low molecular weight protein (LMWP) measurement shows changes in renal integrity at an early stage, beta2-microglobulin (B2m), retinol-binding protein (RBP) and alpha1-microglobulin (A1m) were evaluated in 24-hour urine collection of 65 patients with pure monoclonal light chain (MLC) proteinuria and in 47 patients with different kidney diseases (DKDs) for comparison. METHODS AND RESULTS: Albumin, kappa, lambda, A1m and B2m were measured by immunonephelometry. RBP was determined by ELISA. The mean values of LMWP quantitation were significant for origin of the disease (MLC and DKD) (p<0.05) and renal failure (RF) (p<0.001) (MANOVA). Tukey HSD test only showed significant differences for LMWP between MLC patients with RF and DKD patients without RF. The mean value of A1m was different between patients with and without RF in each group (p<0.05 for MLC, and p<0.01 for DKD). In the group without RF, the frequency of A1m excretion above 12 mg/L differed between MLC patients and DKD patients (p<0.01). CONCLUSION: A tubular dysfunction occurred in a great number of patients excreting pure MLC even in those with well-preserved renal function, as it did in patients with DKDs. In patients with MLC without RF, A1m might be measured for the early recognition of tubular involvement.

Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

Thin layer gel filtration immunofixation: identification of abnormal molecular weight immunoglobulins or related fragments.

A simple procedure is described to identify immunoglobulin (Ig) fragments without isolation from biological fluids. It involves an initial separation based on molecular weight (MW) by thin layer gel filtration (TLG) followed by immunofixation (IF) in cellulose acetate strips with monovalent antisera. TLG-IF permits detection of differences about 10,000 Da MW and specific immunological typing, making it a useful tool in the accurate identification of protein fragments.

Immunofixation on cellulose acetate: an improved screening method for monoclonal immunoglobulins.

A rapid, simple and economical method is described for typing monoclonal immunoglobulins. It is a modification of the immunofixation electrophoresis method and cellulose acetate has been used as a supporing medium. It involves an initial electrophoretic separation followed by an antigen (Ag)-antibody (Ab) reaction 'in situ'. Eight samples can be typed on each 5.7 cm x 10.5 cm strip and only 20 microliter of commercial antiserum are required (about 2.5 microliter per sample). The method permits detection of monoclonal proteins at concentrations as low as 100 ng/microliter in only 60 min.

Two different Fc gamma receptor-dependent cytotoxic mechanisms triggered by monoclonal immunoglobulins.

It is known that the receptors for the Fc portion of IgG molecules (Fc gamma R) are widely distributed in cells of the immune system. The expression of Fc gamma R enables monocytes and neutrophils to destroy antibody-coated target cells through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. In addition, the interaction of immune complexes or aggregated IgG with monocytes or neutrophils led to the lysis of nonsensitized target cells in a process known as nonspecific cytotoxicity (NSC). Despite that ADCC and NSC are both triggered through Fc gamma R, the cytolytic mechanism involved in each reaction is different. In this paper we analyze the ability of human monoclonal IgG1, IgG2, IgG3 and IgG4 to induce ADCC and NSC. Our results demonstrate that each IgG subclass is able to induce both, NSC and ADCC, mediated by monocytes or neutrophils, indicating that there is no correlation between IgG subclass specificity and the ability to activate both mechanisms.

Loss of hepatitis A virus (HAV) antibodies after peripheral stem cell transplantation (PSCT).

The majority of patients with hepatitis A have a benign course, but some may develop fulminant hepatitis and hematological complications. Peripheral stem cell transplantation (PSCT) is associated with loss of immunity. There are no data regarding loss of HAV antibodies (anti-HAV) after PSCT. We retrospectively evaluated the persistence of anti-HAV in a nonvaccinated population that underwent PSCT. Serum detection of anti-HAV was determined before and after PSCT using a qualitative commercially available enzyme immunoassay. From January 1997 to March 2001, 136 (68%) of 201 patients tested (+) for anti-HAV prior to PSCT. Subsequent investigation of anti-HAV was possible in 36 of these patients at a median of 12 months after PSCT. The median age of patients was 47 years old; they had diagnoses of hematological malignancies (33) and solid tumors (three), and underwent autologous (31) and allogenic (five) PSCT. A total of 31 (86%) of 36 patients remained anti-HAV (+) and five (14%) became (-) after PSCT. The variables age, sex, diagnosis, type of PSCT, time of testing, and number of CD34 cells infused were not predictors of loss of anti-HAV. In conclusion, 14% of 36 nonvaccinated anti-HAV (+) patients lost their antibodies at a median of 12 months after PSCT.

Isolation and amino terminal sequence of beta-trace, a novel protein from human cerebrospinal fluid.

beta-Trace, a 23.5 kDa glycoprotein of unknown biological functions, is present in all body fluids tested. It is found in higher concentration in human seminal fluid and cerebrospinal fluid (CSF) than in serum. A one-step procedure for the isolation of beta-trace from pooled CSF is described, by affinity chromatography using a specific antibody made against beta-trace. Amino terminal sequence analysis yields the sequence A P E A Q V S V Q P N F Q Q D K F L G with no homology to known proteins, indicating that beta-trace is a novel CSF protein.

[Plasma clearance of alpha 1-antitrypsin. A simple method for the study of intestinal protein loss]. / Depuración plasmática de alfa-1-antitripsina. Método simple para el estudio de la perdida proteica intestinal.

We tried to evaluate the value of the alpha-1-antitrypsin clearance in order to search for the protein loss through the digestive tract. Twenty-two patients were studied, 11 with protein losing enteropathy and 11 normal controls. Alpha-1-antitrypsin concentration was determined in serum and feces to obtain the clearance of such protein. The values were always abnormal in patients with protein losing enteropathy, and normal in control patients. We consider this method simple and safe for the evaluation of intestinal protein loss, besides having the advantage of not using radioactive material.

Endovascular stent treatment for symptomatic benign iliofemoral venous occlusive disease: long-term results 1987-2009.

Venous stenting has been shown to effectively treat iliofemoral venous obstruction with good short- and mid-term results. The aim of this study was to investigate long-term clinical outcome and stent patency. Twenty patients were treated with venous stenting for benign disease at our institution between 1987 and 2005. Fifteen of 20 patients (15 female, mean age at time of stent implantation 38 years [range 18-66]) returned for a clinical visit, a plain X-ray of the stent, and a Duplex ultrasound. Four patients were lost to follow-up, and one patient died 277 months after stent placement although a good clinical result was documented 267 months after stent placement. Mean follow-up after stent placement was 167.8 months (13.9 years) (range 71 (6 years) to 267 months [22 years]). No patient needed an additional venous intervention after stent implantation. No significant difference between the circumference of the thigh on the stented side (mean 55.1 cm [range 47.0-70.0]) compared with the contralateral thigh (mean 54.9 cm [range 47.0-70.0]) (p=0.684) was seen. There was a nonsignificant trend toward higher flow velocities within the stent (mean 30.8 cm/s [range 10.0-48.0]) and the corresponding vein segment on the contralateral side (mean 25.2 cm/s [range 12.0-47.0]) (p=0.065). Stent integrity was confirmed in 14 of 15 cases. Only one stent showed a fracture, as documented on x-ray, without any impairment of flow. Venous stenting using Wallstents showed excellent long-term clinical outcome and primary patency rate.

Preferential association of kappa IIIb light chains with monoclonal human IgM kappa autoantibodies.

The predominance of the relatively uncommon V region subgroup isotype kappa III among the light chains of human monoclonal (IgM kappa) anti-IgG antibodies, (i.e., rheumatoid factors), was further documented through sequence analyses of ten such autoantibodies isolated from IgM-anti-IgG cold-insoluble immune complexes (mixed cryoglobulins). The amino-terminal sequence of all ten kappa-chains was characteristic for kappa III proteins and virtually identical to that of a prototype kappa III light chain. Similar sequence identity was found for kappa-chains isolated from three IgM kappa autoantibodies that formed cold-insoluble immune complexes with low-density lipoprotein (LDL). The thirteen light chains were found to be virtually identical in sequence for the first framework region (FR); ten of these proteins sequenced through the first complementarity-determining region (CDR) and into the second FR were markedly similar. The second CDR of five proteins was almost identical in sequence to that of the prototype kappa III-chain. Concordance was also demonstrated between the structural classification of the light chains as kappa III and their immunochemical classification as members of this V region subgroup. Serologic analyses of light chains isolated from seven IgM kappa autoantibodies (six anti-IgG, one anti-LDL) and of one intact IgM kappa anti-LDL antibody showed that each had antigenic determinants common to kappa II proteins. These light chains also expressed the antigenic determinant(s) of a V-region sub-subgroup of kappa III proteins designated kappa IIIb. Our studies confirm the preferential association of kappa III (and kappa IIIb) light chains with IgM kappa anti-IgG antibodies and demonstrate a similar association for IgM kappa anti-LDL antibodies. The finding that these and other types of IgM kappa autoantibodies, e.g., cold agglutinins, have remarkably similar light chains suggests an inherent restriction in the immune response to self-antigens.

IgG1-kappa biclonal gammopathy associated with multiple myeloma suggests a regulatory mechanism.

Multiclonal gammopathies associated with multiple myeloma may result either from a neoplastic transformation of a cell clone undergoing immunoglobulin class switching or from independent transforming events yielding proliferation of unrelated plasma cell clones. The simultaneous presence of more than one neoplastic clone may possess regulatory implications in terms of cell proliferation, clonal expansion, secretion of M-components or response to chemotherapy. We report a patient, diagnosed with multiple myeloma stage IIIa, who presented with two well-defined homogeneous IgG1-kappa components in the serum (designated WER-1 and WER-2) with striking differences in their plasma concentration and response to the classic melphalan/prednisone treatment. Immunochemical characterization and amino terminal sequence analysis of both the heavy and light chains of each M-component undoubtedly determined their biclonal origin. WER-1 was identified as IgG1(VHII)-kappaI while WER-2 was classified as IgG1(VHIII)-kappaIII. The plateau phase was characterized by very low or undetectable levels of WER-2, a high, almost constant, concentration of WER-1 and the absence of Bence Jones proteinuria, whereas these parameters were completely reversed during the escape phase with levels resembling those observed at the time of diagnosis. The statistically significant negative correlation between the biclonal components and the different susceptibility to the treatment clearly suggests regulatory interactions between the clones WER-1 and WER-2.

Immunocompetence and prognosis in children with acute lymphoblastic leukemia: combination of two different maintenance therapies.

Intensive chemotherapy in patients with leukemia produced immunosuppression. The level of immunocompetence correlates with prognosis. The immunological function of 29 children with acute lymphoblastic leukemia (ALL) in complete remission and on 2 different maintenance therapies was evaluated and compared with 16 normal children (Group A). Sixteen children (Group B) with ALL received 6 mercaptopurine (6MP) daily and methotrexate (MTX) twice a week, and 13 children (Group C) received 6MP and MTX weekly for maintenance. There was depression of both cellular immunity, measured by the number of T cells and skin tests, and humoral immunity, measured by number of B cells, primary antibody production to typhoid vaccine, and levels of immunoglobulins. However, continuous maintenance therapy (Group B) produced significantly more severe immunosuppression of cellular immunity than the intermittent therapy (Group C). Humoral immunity was equally depressed in both groups of leukemia patients, but was less altered than cellular immunity. Concomitantly, patients with intermittent maintenance chemotherapy had less hematologic depression, fewer episodes of infection, and fewer died in complete remission. Patients of both groups with higher levels of immunocompetence had better prognosis with longer duration of complete remission than patients with severe immunosuppression. Out of 6 patients with "favorable immunocompetence" only 1 relapsed at 7 months and the other 5 remain in complete remission from 8 to 31 months. Among 23 leukemic patients with "unfavorable immunocompetence," 15 relapsed and 8 remain in complete remission from 9 to 26 months.

Comparison of two combination chemotherapy regimens for multiple myeloma: methyl-CCNU, cyclophosphamide, and prednisone versus melphalan and prednisone.

Of 139 evaluable and previously untreated patients with multiple myeloma, 67 received methyl-CCNU-cyclophosphamide-prednisone (group A) and 72 received melphalan-prednisone (group B); 48% and 33% respectively had good responses and the overall response rates (good plus partial) were 75% and 65% for groups A and B respectively. The survival curves for both groups of patients were similar, with a median survival of 32 months. At 36 months, 70% of those patients who obtained good response were alive, 29% of those with partial response were alive, and 13% of those with no response were alive. The clinical staging system described by Durie and Salmon shows a good prognosis for stage I patients, with 80% remaining alive at 48 months, while the survival curves for stage II and III patients were similar, with 33% and 28% respectively remaining alive at 48 months. The combination of methyl-CCNU-cyclophosphamide-prednisone is not more effective in terms of response rate or duration of survival than melphalan-prednisone.