Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation

Allogeneic bone marrow transplantation (BMT) is the only curative therapy available for patients with myelodysplastic syndrome (MDS). In an attempt to identify prognostic factors influencing outcome, we collected data retrospectively on 60 consecutive adult patients who had undergone BMT at our center for primary MDS or acute myelogenous leukemia evolving from preexisting primary MDS (sAML). Patients were divided into subgroups according to cytogenetic abnormalities based on a recently described International MDS Workshop categorization system. The 7-year actuarial event-free survival (EFS), relapse rate, and nonrelapse mortality (NRM) for all patients were 29% (95% confidence interval [CI], 16% to 43%), 42% (CI, 24% to 67%), and 50% (CI, 37% to 64%), respectively. The EFS for the good-, intermediate-, and poor-risk cytogenetic subgroups were 51% (CI, 30% to 69%), 40% (CI, 16% to 63%), and 6% (CI, 0% to 24%), respectively (P = .003). The corresponding actuarial relapse rates were 19% (CI, 6% to 49%), 12% (CI, 2% to 61%), and 82% (CI, 48% to 99%), respectively (P = . 002) with no difference in NRM between the subgroups. Univariate analysis showed cytogenetic category, French-American-British (FAB) subtype, and graft-versus-host disease (GVHD) prophylaxis used to be predictive of relapse and EFS. In multivariate analysis, only the cytogenetic category was predictive of EFS, with the relative risk of treatment failure for the good-, intermediate-, and poor-risk cytogenetic subgroups being 1.0, 1.5, and 3.5, respectively (P = . 004). For adults with primary MDS and sAML, even after BMT, poor-risk cytogenetics are predictive of an unfavorable outcome; novel treatment strategies will be required to improve results with allogeneic BMT in this patient population.     

Outpatient parenteral anti-infective therapy for skin and soft-tissue infections

Skin and soft tissue infections (SSIs) are one of the many infectious diseases that can be treated by outpatient parenteral anti-infective therapy (OPAT). Determining whether a patient with SSIs is treated topically, orally, or parenterally depends on the severity of infection and host factors. The decision to hospitalize, initiate, or transition to OPAT with SSIs depends on the medical assessment and consideration of available resources for OPAT. Anti-infective selection depends on the clinical presentation, likely organisms, pharmacodynamics, pharmacokinetics, and drug stability.     

Symptomatic intraarticular ganglia of the cruciate ligaments of the knee

This case report draws attention to the clinical presentation, differential diagnosis, and recommended diagnostic modality and treatment of symptomatic ganglia of the anterior and posterior cruciate ligaments. One patient presented with a recurrent inability to fully extend the left knee. Another patient presented with pain and soreness over the lateral aspect of the knee, including the lateral joint line. The diagnosis of ganglia of the cruciate ligaments was made after clinical, radiographic, and magnetic resonance examination. Both patients were treated successfully with resection of their ganglia using arthroscopic techniques.     

Management of extremity soft-tissue sarcomas

Management of extremity soft-tissue sarcomas requires accurate clinical staging, pathologic diagnosis, surgical resection with a wide margin, and adjuvant radiation therapy for high-grade lesions. Brachytherapy offers a clean benefit in local control for large (> 5 cm) high-grade sarcomas. The role of radiation therapy for small high-grade and all low-grade soft-tissue sarcomas still is being evaluated. Survival is function of histologic grade, age of patient, size and location of the tumor, metastases, and adequacy of the surgical resection. Efficacy of chemotherapy has yet to be proven.     

Parameters Controlling Tensile and Compressive Strength of Artificially Cemented Sand

The enhancement of local soils with cement for the construction of stabilized pavement bases, canal lining, and support layer for shallow foundations shows great economical and environmental advantages, avoiding the use of borrow materials from elsewhere, as well as the need of a spoil area. The present research aims to quantify the influence of the amount of cement, the porosity, and the voids/cement ratio in the assessment of unconfined compressive strength (qu) and splitting tensile strength (qt) of an artificially cemented sand, as well as in the evaluation of qt/qu relationship. A program of splitting tensile tests and unconfined compression tests considering three distinct voids ratio and seven cement contents, varying from 1 to 12%, was carried out in the present study. The results show that a power function adapts well qt and qu values with increasing cement content and with reducing porosity of the compacted mixture. The voids/cement ratio is demonstrated to be an appropriate parameter to assess both qt and qu of the sand-cement mixture studied. Finally, the qt/qu relationship is unique for the sand-cement studied, being independent of the voids/cement ratio.     

Existing antilisterial immunity does not inhibit the development of a Listeria monocytogenes-specific primary cytotoxic T-lymphocyte response

Chloroplast and cytoplasmic signal recognition particles (cpSRP and cySRP) each contain a similar subunit, SRP54. The chloroplast homologue binds to cpSRP43, which is absent from cytosolic SRP, and cySRP54 binds to SRP-RNA, which appears to be absent from cpSRP. In the presence of cpSRP43, cpSRP54 posttranslationally forms a soluble targeting intermediate, transit complex, with the major light harvesting protein of the thylakoid membrane. In contrast, cySRP54 functions cotranslationally. In this study we investigated whether cytosolic and chloroplast forms of SRP54 were interchangeable in three types of functional assays: complementation of an Escherichia coli SRP54 mutant, formation of the transit complex, and heterologous binding between the SRP54 subunits, cpSRP43, and SRP-RNA. In no cases were the 54-kDa subunits able to substitute for each other suggesting that the two proteins are fundamentally different.     

Sib-pair analysis detects elevated Lp(a) levels and large variation of Lp(a) concentration in subjects with familial defective ApoB

Whether or not Lp(a) plasma levels are affected by the apoB R3500Q mutation, which causes Familial Defective apoB (FDB), is still a matter of debate. We have analyzed 300 family members of 13 unrelated Dutch index patients for the apoB mutation and the apolipoprotein(a) [apo(a)] genotype. Total cholesterol, LDL-cholesterol, and lipoprotein(a) [Lp(a)] concentrations were determined in 85 FDB heterozygotes and 106 non-FDB relatives. Mean LDL levels were significantly elevated in FDB subjects compared to non-FDB relatives (P < 0.001). Median Lp(a) levels were not different between FDB subjects and their non-FDB relatives. In contrast, sib-pair analysis demonstrated a significant effect of the FDB status on Lp(a) levels. In sib pairs identical by descent for apo(a) alleles but discordant for the FDB mutation (n = 11) each sib with FDB had a higher Lp(a) level than the corresponding non-FDB sib. Further, all possible sib pairs (n = 105) were grouped into three categories according to the absence/presence of the apoB R3500Q mutation in one or both subjects of a sib pair. The variability of differences in Lp(a) levels within the sib pairs increased with the number (0, 1, and 2) of FDB subjects present in the sib pair. This suggests that the FDB status increases Lp(a) level and variability, and that apoB may be a variability gene for Lp(a) levels in plasma.     

Antileukemia activity of a natural killer cell line against human leukemias

We describe here the in vitro and in vivo antileukemia activity of a recently described natural killer (NK) cell line (NK-92), which has features of human activated NK cells. The cytotoxic activity of rhIL2-dependent cultured NK-92 cells against primary patient-derived leukemic target cells [12 acute myelogenous leukemias (AMLs), 7 T acute lymphoblastic leukemias (T-ALLs), 14 B-lineage-ALLs, and 13 chronic myelogenous leukemias (CMLs)], human leukemic cell lines (K562, KG1, HL60, Raji, NALM6, TALL-104, CEM-S, and CEM-T) and normal bone marrow cells was measured in 51Cr-release assay (CRA). The patient-derived leukemias could be subdivided into three groups based on their sensitivity to NK-92 cells: insensitive (< or =19% lysis), sensitive (20-49% lysis), and highly sensitive (> or =50% lysis) at an E:T ratio of 9:1. Of 46 patient-derived samples, 24 (52.2%) were sensitive or highly sensitive to NK-92-mediated in vitro cytotoxicity (6 of 12 AMLs, 7 of 7 T-ALLs, 5 of 14 B-lineage-ALLs, and 6 of 13 CMLs). NK-92 cells were highly cytotoxic against all of the eight leukemic cell lines tested in a standard 4-h CRA. Normal human bone marrow hematopoietic cells derived from 18 normal donors were insensitive to NK-92-mediated cytolysis. In comparison with human lymphokine-activated killer cells, normal NK cells, and T cells, NK-92 cells displayed more powerful antileukemia activity against a patient-derived T-ALL as well as K562 and HL60 cells, both in in vitro CRA and in a xenografted human leukemia SCID mouse model. The NK-92 cells did not induce the development of leukemia in SCID mice after i.v., i.p., or s.c. inoculation. In adoptive transfer experiments, SCID mice receiving i.p. inoculations of human leukemias derived from a T-ALL (TA27) and an AML (MA26) that were highly sensitive to the cytolysis of NK-92 cells in vitro, as well as a pre-B-ALL (BA31) that was insensitive to the in vitro cytolysis of NK-92 cells, were treated by administration of NK-92 cells with or without rhIL2 (2 x 10(7) NK-92 cells i.p.; one dose or five doses). Survival times of SCID mice bearing the sensitive TA27 and MA26 leukemias were significantly prolonged by adoptive cell therapy with NK-92 cells. Some of the animals who received five doses of NK-92 cells with or without rhIL2 administration were still alive without any signs of leukemia development 6 months after leukemia inoculation. In contrast, survival of mice bearing the insensitive BA31 leukemia were not affected by this treatment. This in vitro and in vivo antileukemia effect of NK-92 cells suggests that cytotoxic NK cells of this type may have potential as effectors of leukemia control.