Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML

Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.     

Juvenile myasthenia gravis

Juvenile myasthenia gravis shares a similar pathophysiologic origin with adult myasthenia gravis, but there are important differences, mostly relating to epidemiology, presentation, and therapeutic decision making. Gender ratios and the proportion of seropositive patients differ in the pre‐ and postpubertal age groups. The diagnostic evaluation is similar to that in adults, although special techniques are sometimes necessary to perform single‐fiber electromyography in younger patients. Therapeutic decisions in affected children and adolescents are complicated by the greater long‐term consequences of using steroids, and thus other interventions, such as intravenous immunoglobulin (IVIg) and plasmapheresis, may play a greater therapeutic role in this population than in adults. Steroid‐sparing agents may contribute to the management of refractory cases, but they should be used with caution due to the risk of malignancy. Muscle Nerve, 2008     

Treatment of myofascial trigger points in patients with chronic shoulder pain: a randomized,controlled trial

Background  

Shoulder pain is a common musculoskeletal problem that is often chronic or recurrent. Myofascial trigger points (MTrPs) cause shoulder pain and are prevalent in patients with shoulder pain. However, few studies have focused on MTrP therapy. The aim of this study was to assess the effectiveness of multimodal treatment of MTrPs in patients with chronic shoulder pain.     

Nonanemic Patients Do Not Benefit from Autologous Blood Donation Before Total Hip Replacement

To avoid the potential risks of allogeneic transfusion during total hip arthroplasty (THA), the use of preoperative autologous blood donation (PABD) has been utilized. We performed a retrospective chart review of 283 patients undergoing THA that either donated 1 U of autologous blood (188 patients) or did not donate autologous blood before surgery (95 patients) in order to investigate the difference in postoperative transfusion rate (autologous and allogeneic), the incidence of allogeneic transfusion, and the difference in cost of each protocol. In addition, the study compared transfusion rates in patients with and without preoperative anemia (hemoglobin (Hb) ≤ 12.5 g/dL). At 0.75 transfusions per patient versus 0.22 transfusions per patient, the PABD patients had a significantly higher overall transfusion rate. PABD significantly reduced the need for allogeneic blood in anemic patients (Hb ≤ 12.5 g/dL) from 52.6% to 11.8%. PABD did not have the same affect in nonanemic patients (allogeneic transfusion rate 5.7% versus 4.0%). The study demonstrated that nonanemic patients undergoing THA do not benefit from PABD, but it is effective for anemic patients.     

Tumor necrosis factor alpha-induced endothelial tissue factor is located on the cell surface rather than in the subendothelial matrix

Because there is no consensus regarding the precise distribution of induced endothelial tissue factor (TF), we studied TF activity in and on tumor necrosis factor alpha-stimulated cultured human umbilical vein endothelial cells (ECs) and their underlying matrix. TF was mainly expressed on the cell surface. Only small traces were found on the apical surface suggesting that TF is predominantly located on the basolateral side of the cell membrane. The presence of TF on the cell surface was confirmed by flow cytometry. Subendothelial TF activity appeared to be dependent upon the procedure used to remove the stimulated EC monolayer. Whereas ammonium hydroxide or hypotonic lysis resulted in relatively high levels of matrix-associated TF, virtually no TF was found on the matrix after mild enzymatic detachment of stimulated ECs. Cell removal with EDTA resulted in intermediate levels of matrix-associated TF. Neither the enzymatic treatment nor EDTA degraded or removed this TF activity. Similar patterns were observed for matrix-associated TF antigen and EC surface markers. Electron microscopic analysis showed cell fragments on the matrix after monolayer lysis. The findings strongly suggest that induced endothelial TF associated with the subendothelial matrix actually represents TF on EC remnants.     

Autoantibody against erythrocyte protein 4.1 in a patient with autoimmune hemolytic anemia

We observed the presence of a new autoantibody, anti-erythrocyte protein 4.1, in a patient with autoimmune hemolytic anemia (AIHA). Western blotting analysis revealed that IgG from the patient's plasma reacted with erythrocyte protein 4.1. However, among other patients with hemolytic diseases (six having AIHA and three each having either hereditary spherocytosis, elliptocytosis, or lead poisoning) as well as among control subjects, no antibody activity to protein 4.1 was observed. In addition to the anti-protein 4.1 antibody, two different kinds of anti-erythrocyte antibodies were detected by conventional serological studies in this patient. One of them was an anti-Ena-like antibody in the eluate from the patient's erythrocytes, while another was the anti-S-specific antibody in the plasma. An elution study and an absorption study using S antigen-positive erythrocytes demonstrated that the anti-protein 4.1 antibody differed from both the anti-Ena-like antibody and the anti-S antibody. Familial analysis of the patient revealed the same antibody in her brother, who did not have hemolytic anemia. These results demonstrate that anti-protein 4.1 antibody is considered to be included in the spectrum of anti-cytoskeleton autoantibodies, which have been observed in patients having increased cell lysis as well as in healthy subjects.     

Peroxidase-H2O2-halide system: Cytotoxic effect on mammalian tumor cells

Myeloperoxidase, H2O2, and a halide constitute a potent antimicrobial system. A cytotoxic effect of this system on a line of mouse ascitic lymphoma cells (LSTRA) is demonstrated here using four different assay systems: 51Cr release, trypan blue exclusion, inhibition of glucose C-1 oxidation, and loss of oncogenicity for mice. Deletion of each component of the system, preheating the peroxidase, or addition of azide, cyanide, or catalase abolished the cytotoxicity. Myeloperoxidase was effective with either chloride or iodide as the halide, while lastoperoxidase was effective with iodide but not chloride. The iodinated thyroid hormones, triiodothyronine and thyroxine, could substitute for the halide, and H2O2 could be replaced by a peroxide- generating enzyme system such as glucose and glucose oxidase or by H2O2 producing bacteria such as pneumococci or streptococci. The possibility is raised that the peroxidases of inflammatory cells and certain biologic fluids may affect tumor initiation or growth in vivo.