Forensic issues in suicide due to acid ingestion in a case of major depressive disorder.

Although rare, suicide using caustic substances in psychiatric practice is not infrequent. Such circumstances involve important forensic and psychiatric issues. In this case report, death due to sulfuric acid ingestion in a patient with major depressive disorder is reported. The legal issues concerning suicide in a patient with mental illness, autopsy findings, forensic issues, and pathophysiology concerning death by acid ingestion have been discussed.

Colony-stimulating activity of fetal liver cells: synergistic role of stem cell factor in bone marrow recovery from aplastic anemia.

Previously, we and others have shown that fetal liver infusion (FLI) leads to autologous hematopoietic improvement in 40-54% of patients with aplastic anemia. However, whether this recovery was spontaneous or the effect of the infused liver cells was not clear. To dissect the role of FLI in autologous hematopoietic recovery, the colony-supporting potential of fetal liver-conditioned medium (FLCM) was evaluated in bone marrow (BM) cells of normal adult and aplastic anemia patients. In both cases, each sample of FLCM supported the growth of colony-forming cells in semi solid culture medium. The FLCM was assayed for the presence of four principal colony-stimulating cytokines, namely stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and erythropoietin (Epo). While GM-CSF, IL-3, and Epo were present in insignificant amounts or were altogether absent, 50-635 pg/ml of SCF was found in 8 of the 13 FLCM samples tested. Preliminary results of bioneutralization assay indicated the possible role of SCF, secreted by the FL cells, in colony-supporting activity of aplastic anemia and normal BM cells. Overall, our in vitro study implicates the paracrine role of infused FL cells in regenerating autologous hematopoiesis in aplastic anemia patients.

High dose chemotherapy followed by autologous haemopoietic stem cell transplant in multiple myeloma.

BACKGROUND: High dose chemotherapy followed by autologous stem cell transplant is currently used for the treatment of patients with advanced multiple myeloma. However, there are no reports of the results of this treatment modality in Indian patients. METHODS: Fifty patients with advanced multiple myeloma underwent treatment with high dose melphalan followed by autologous stem cell transplant (bone marrow: 7; peripheral blood stem cells: 43). The patients' ages ranged from 26 to 65 years (median: 52 years) and 35 were men. All patients had received chemotherapy initially with a mean of 9.4 cycles (range: 1-36). Thirty patients had evidence of chemosensitive disease at the time of transplant. The mean interval from diagnosis to transplant was 17.5 months (range: 3-129 months) and the median number of mononuclear cells infused was 4.86 x 10(8) per kg (range: 2-10.48). RESULTS: Post-transplant, 43 of 50 patients engrafted. The median number of days to engraftment (absolute neutrophil count > 500/cmm) was 12 (range: 9-24) and to achieve platelet transfusion independence (> 20,000/cmm) was 13 (range: 8-36). Seven patients died prior to engraftment. Grade III-IV oral mucositis was the major non-haematological toxicity. Excluding the 4 patients who had complete response prior to the transplant and continued in the same status post-transplant, 31/46 patients (67%) responded; complete response was achieved in 25 (54%) and partial response in 6 (13%). Patients with chemosensitive disease had higher rates of complete response; 20 of 26 patients with partial response at transplant achieved complete response compared to 5 of 20 patients with persistent/refractory disease (p < 0.01). Currently, 34 of 50 (68%) patients are alive, 17 (34%) disease-free, 6 with disease are on salvage therapy, 11 (22%) with positive monoclonal protein but asymptomatic are under observation. Nine (18%) patients have died; 8 due to progressive disease and 1 of an unrelated cause. The median follow up for the entire group is 26 months (range: 1-144 months). The Kaplan-Meier probability of overall and progression-free survival for the whole group at 30 months is 62% +/- 8.11% (SE) and 42% +/- 9.54% (SE), respectively. A haemoglobin level < or = 10 g/dl (p < 0.003) affected the survival adversely. Chemosensitive disease (p < 0.008) at transplant and complete response post-transplant (p < 0.0001) were associated with significantly longer survival. CONCLUSION: High dose melphalan followed by autologous stem cell transplantation is an effective treatment for patients with advanced multiple myeloma and achievement of complete response is associated with improved survival.

Redefining 'self': the role of microflora (commensals) mismatch in the development of GvHD after allogeneic stem cell transplantation and some possible remedies.

The discovery of human leukocyte antigen (HLA) molecules and their role in allorecognition has facilitated the initiation of allogeneic stem cell transplantation in human beings. HLA mismatch to a large extent explains the phenomenon of graft rejection and graft versus host disease (GvHD). Incidence of GvHD even in syngeneic transplants suggests a role for extra genetic factors in the causation of GvHD. We hereby propose a hypothesis that the definition of 'self' (in the immunological sense) should be broadened to include both genetically determined molecules (e.g. HLA) and the microbial flora that colonize an individual. This hypothesis explains several observations about GvHD which can not fully be accounted for by the HLA mismatch theory and gives some clues towards circumventing GvHD.

Autologous bone marrow/stem cell transplantation: initial experience at a north Indian referral centre.

BACKGROUND: High-dose chemotherapy and/or radiation therapy rescued by autologous bone marrow or peripheral blood stem cells is being increasingly used for the treatment of haematological and solid malignancies. While few centres in India use this modality of therapy, the worldwide experience is encouraging. We, therefore, analysed the results of our initial experience with this therapeutic modality. METHODS: Forty-two patients [multiple myeloma (17), Hodgkin's disease (4), non-Hodgkin's lymphoma (3), chronic myeloid leukaemia (2), acute myeloid leukaemia (2), acute lymphoblastic leukaemia (2), epithelial ovarian cancer (6), breast cancer (4), primitive neuroectodermal tumour and testicular germ cell tumour (1 each)] underwent high-dose chemotherapy followed by either autologous bone marrow transplant (n = 9), peripheral blood stem cell transplant (n = 30) or both (n = 3). The indications for transplant included either advanced stage at diagnosis, other adverse prognostic indicators during the course of their disease, or relapse. The data were analysed retrospectively in December 1998 using hospital records. Follow up data of all the patients were available. RESULTS: Thirty-four of the 42 patients (81%) showed stable engraftment. Eight patients (19%) died in the early post-transplant period (day 5 to day 52 post-transplant). Seven patients died due to neutropenic infections and one due to acute renal failure. Of the 34 surviving patients, 20 were alive at the time of analysis and 14 had died. All but one death in this group were due to progressive primary malignancy. The median overall survival for all patients was 17 months and for the 34 engrafted patients it was 27 months. An analysis of factors affecting survival revealed that patients with chemosensitive disease had a longer overall survival (20.9 v. 6.1 months, p = 0.04) compared to those with chemoresistant disease. CONCLUSION: Autologous bone marrow or peripheral stem cell transplantation is a feasible procedure in India with an acceptable morbidity and mortality. It should be offered more frequently to properly selected patients.

Blood stem cell transplantation: current concepts.

Mobilized peripheral blood haematopoietic progenitor cells are increasingly being used as against bone marrow (BM) transplants, following high dose chemotherapy and/or radiotherapy for the management of chemosensitive malignancies. Rapid haematopoietic reconstitution as evidenced by reduced duration of neutropaenia, fewer donor platelet infusions, shorter hospital stay and reduced cost of treatment are the advantages of this procedure. Reduced tumour cell contamination of mobilized blood compared to bone marrow however, has not been substantiated. Mobilization of lymphokine activated killer cells (LAK), use of blood stem cells (BSC) for allogeneic transplants and ex vivo expansion of the mobilized cells are emerging as the future areas for research. Addition of interleukin-3 (IL-3), stem cell factor (c-kit ligand) and PIXY-321 appear to open-up new vistas by enforcing trilineage and multilineage haematopoietic reconstitution.

Storage of haemopoietic stem cells for autologous bone marrow transplantation.

For reinfusing autologous bone marrow cells after high-dose chemotherapy and/or radiotherapy it is necessary that an effective technique for their storage is available. The traditional method uses 10% dimethyl sulphoxide as cryoprotectant, a rate-controlled computerized freezer programmed to cool the cells at a constant rate of 1 degrees C per minute and liquid nitrogen as the storage system. The method is time-consuming, expensive and requires technical expertise. Moreover, it is often associated with varying levels of clinical toxicity following infusion of the preserved cells. Processing the harvest to reduce the initial volume and the mature cells has been shown to be beneficial in reducing the volume of the cryoprotectant and the incidence of toxicity. An alternative, cost-effective method using a cryoprotectant mixture of 5% dimethyl sulphoxide, 6% hydroxyethyl starch and 4% albumin has been found to be effective even when the cells are stored at -80 degrees C without rate-controlled freezing. However, its efficacy needs to be evaluated for extended periods. The current use of purging and cell sorting methods seems to be promising.

Orbital granulocytic sarcomas (myeloid sarcomas) in acute nonlymphocytic leukemia.

In a series of 89 patients with acute leukemia, orbital granulocytic sarcomas were observed in 7. All these patients had acute nonlymphocytic leukemia, and they were all children. The orbital involvement usually was bilateral, and the patients had proptosis, conjunctival hemorrhage, and chemosis. Morphologic, cytochemical, and immunophenotypic analyses did not show a predilection for any particular myeloid cell type. Two patients had biphenotypic leukemias with myeloid components. The ocular manifestations responded well to chemotherapy irrespective of the hematologic response.