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Biomedical subjects

J Sanders

Publications and source records attributed to J Sanders.

At least 127 records · Page 7Linked to original sources

Acute megakaryoblastic leukemia in children: treatment with bone marrow transplantation.

Seven children underwent BMT for acute megakaryoblastic leukemia (AMKL). They were assessed for clinical, hematologic, and cytogenetic findings as well as response to treatment. The diagnosis of AMKL was established by cytochemistry, immunophenotyping and/or platelet-peroxidase reactivity. Patients had received various prior chemotherapies. One was in first remission, another in second remission and five were in relapse at the time of admission for transplant. Marrow donors included an HLA identical sibling (one), phenotypically HLA identical unrelated (two) and partially HLA identical family members (four). Five patients achieved engraftment, one rejected the graft and died on day 20 after a second unrelated transplant and one died from infection on day 5. Two patients relapsed within the first month after transplant and died of recurrent leukemia. Another died of a second malignancy on day 2232. Two patients survive disease-free more than 3.8 and 4.3 years after transplant.

Bone Marrow Transplantation↗

Parasitological, clinical and haematological response of children with Plasmodium falciparum to 4-aminoquinolines and to pyrimethamine-sulfadoxine with quinine in western Kenya.

Children with Plasmodium falciparum infections in Western Province, Kenya, were studied in 1987 for their parasitological, clinical and haematological response to chloroquine, to amodiaquine and to pyrimethamine-sulfadoxine plus quinine. Ninety-eight children under 5 years of age were treated in 1 of 2 hospitals. Of the 56 patients treated with chloroquine base 25 mg/kg, 91% had resistant infections, with 36% having no significant decrease in parasitaemia (RIII resistance); however, 69% responded clinically within a week. Of the 27 patients treated with amodiaquine base 25 mg/kg, 67% had resistant infections, with 7% RIII resistant; 81% responded clinically. The parasites cleared in all 15 children given pyrimethamine-sulfadoxine plus 3 days of quinine. Only when parasites cleared did patients have improved haemoglobins and haematocrits. This study shows that parasitaemia in children hospitalized in western Kenya responds poorly to 4-aminoquinolines, although the patients improve clinically, at least during the first 7 days. Young children may need to clear parasites to avoid the risk of severe anemia and the need for blood transfusions.

Amodiaquine↗

Successful allogeneic bone marrow transplantation in a 6.5-year-old male for severe aplastic anemia complicating orthotopic liver transplantation for fulminant non-A-non-B hepatitis.

We report the case of a 6.5-year-old male who received an unrelated orthotopic liver transplant for hepatic failure and encephalopathy following non-A-non-B hepatitis and subsequently developed severe aplastic anemia. For treatment of his aplastic anemia, he received a successful marrow transplant from his 9-year-old genotypically HLA-identical sister following conditioning with cyclophosphamide 200 mg/kg and anti-thymocyte globulin 90 mg/kg. Significant veno-occlusive disease of the liver and graft-versus-host disease did not occur. The patient remains alive without clinical chronic active hepatitis or need for blood product therapy. His hematocrit is 36%, white blood cell count 9.7 x 10(3)/mm3, and platelet count 1.7 x 10(5)/mm3 almost 2 years after marrow transplantation.

Anemia, Aplastic↗

Expression of embryonic globins by erythroid cells in juvenile chronic myelocytic leukemia.

Juvenile chronic myelocytic leukemia (JCML) is a rare hematopoietic neoplasia of early childhood with distinct hematologic and biochemical features. We studied the biologic properties and the globin synthetic profiles of JCML erythroid cells both in vivo and in vitro from a total of 24 patients. In these cases we observed the exuberant colony-forming unit-macrophage (CFU-M) colony growth, as reported previously. Furthermore, in contrast to previous reports, we found significant erythroid colony growth in most of our cases (average: 1,182 burst-forming unit-erythroid [BFUe] per 10(5) plated cells, range: 40 to 6,927). This growth was by and large erythropoietin-dependent and was not greatly influenced by other added cytokines. By several criteria all erythroid colony growth detected in vitro was derived from JCML progenitors. The globin synthetic profile of JCML erythroid cells showed high levels of fetal hemoglobin both in vivo and in vitro (gamma/gamma + beta: 53% to 94% in reticulocytes, 62% to 98% in BFUe-derived cells). In addition (in seven cases studied) we detected embryonic globins (epsilon and zeta) at the protein and messenger RNA level, a novel finding for primary leukemic cells. We speculate that the transformed erythroid cells in JCML harbor a trans environment supporting expression of developmentally earlier genes (fetal, embryonic). However, in contrast to other acute or subacute leukemias, JCML erythroid cells also have the ability to reach full maturation to the red cell level, thus allowing detection of this primitive program in vivo.

Bone Marrow↗

Temporary clipping in aneurysm surgery: technique and results.

The use of temporary clipping has become an established tool in the armamentarium of the aneurysm surgeon. Our experience with 62 consecutive patients is presented, detailing operative protocols and results. Twenty-two had unruptured aneurysms (35%), 15 were grade I (24%), 16 grade II (25%), five grade III (8%), and four grade IV (7%). The aneurysms were mainly located in the middle cerebral artery (29 patients) and the anterior communicating artery (13 patients). Eleven of our 62 patients (17%) developed a new, persistent postoperative deficit. However, in only one case (2%) was temporary clipping felt to be implicated in the development of the deficit. In three other patients (5%), the effect of temporary clipping, although unlikely, could not be excluded. Overall, 92% of our patients with temporary clipping had good to excellent outcome, with 3% mortality and 5% morbidity. We believe that temporary clipping is a safe procedure that contributes significantly to a better outcome.

Adult↗

Value of day 100 screening studies for predicting the development of chronic graft-versus-host disease after allogeneic bone marrow transplantation.

We prospectively evaluated 169 patients with a number of screening studies performed between 71 to 121 days after allogeneic marrow transplantation to detect the development of chronic graft-versus-host disease (GVHD). Group 1 patients (n = 78) were asymptomatic and had normal physical examinations at the time of screening and, with a minimum of 8 years follow-up, have not developed chronic GVHD. Group 2 patients (n = 38) had signs and symptoms of chronic GVHD at time of testing. Group 3 patients (n = 53) were similar to those in group 1 in having no clinically evident GVHD at the time of testing, but later developed clinical chronic GVHD. Using time to an event analysis, we compared patients in groups 1 and 3 to determine which of 17 clinical and laboratory factors evaluated at screening accurately predicted the development of subsequent chronic GVHD. Multivariate analyses showed several factors to have independent predictive value. In the first model, results of oral biopsies were excluded since these were done only in one half of the patients. Predictive factors in this analysis included: (1) histologic findings of GVHD on skin biopsy, relative risk 3.23 (95% confidence interval 1.75 to 5.94), P = .0002; and (2) history of grade II through IV acute GVHD, relative risk 3.12 (95% confidence interval 1.72 to 5.64), P = .0002. When oral biopsy results were included in the second model, independent risk factors included: (1) histologic findings of GVHD on skin biopsy, relative risk 5.96 (95% confidence interval 1.95 to 18.19), P = .0017; and (2) low numbers of immunoglobulin A (IgA)-bearing plasma cells detected by direct immunofluorescence in salivary gland areas on oral biopsy, relative risk 11.53 (95% confidence interval 2.51 to 52.03), P = .0017. Our study demonstrates the value of day 100 screening studies for predicting subsequent development of clinical chronic GVHD.

Adolescent↗

The alternative splicing product alpha Ains-crystallin is structurally equivalent to alpha A and alpha B subunits in the rat alpha-crystallin aggregate.

In rodents and some other unrelated mammals, alternative splicing of the alpha A-crystallin gene transcript results in the synthesis of the elongated alpha Ains-crystallin chain. This polypeptide is identical to the normal alpha A-crystallin chain of 173 residues, but contains an additional sequence of 23 amino acid residues inserted between positions 63 and 64. To determine the effects of this insert peptide, the structure of the rat alpha-crystallin aggregate and its subunits alpha A-, alpha Ains- and alpha B-crystallin was studied using fluorescence spectra, partial urea dissociation, and lactoperoxidase-catalysed iodination of surface residues. The data suggest that all alpha-crystallin subunits occupy equivalent positions in the protein aggregate, and that the insert peptide merely elongates the connecting peptide between the putative amino- and carboxyl-terminal domain of the alpha A-crystallin subunit.

Amino Acid Sequence↗

Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia.

To determine the incidence of secondary cancers after bone marrow transplantation, we reviewed the records of all patients at our center who received allogeneic, syngeneic, or autologous transplants for leukemia (n = 1926) or aplastic anemia (n = 320). Thirty-five patients were given a diagnosis of secondary cancer between 1.5 months and 13.9 years (median, 1.0 year) after transplantation. Sixteen patients had non-Hodgkin's lymphomas, 6 had leukemias, and 13 had solid tumors (including 3 each with glioblastoma, melanoma, and squamous-cell carcinoma). There were 1.2 secondary cancers per 100 exposure-years during the first year after transplantation (95 percent confidence interval, 0.7 to 2.0). The rate declined to 0.4 (95 percent confidence interval, 0.2 to 0.7) after one year. The age-adjusted incidence of secondary cancer was 6.69 times higher than that of primary cancer in the general population. In a multivariate model, the predictors (and relative risks) of any type of secondary cancer were acute graft-versus-host disease treated with either antithymocyte globulin (relative risk, 4.2) or an anti-CD3 monoclonal antibody (13.6) and total-body irradiation (3.9). Two additional factors were associated with secondary non-Hodgkin's lymphomas: T-lymphocyte depletion of donor marrow (12.4) and HLA mismatch (3.8). We conclude that recipients of bone marrow transplantation have a low but significant risk of a secondary cancer, particularly non-Hodgkin's lymphoma.

Adolescent↗

Evaluation of staging workup in malignant melanoma.

To evaluate the role of staging workup in primary and recurrent malignant melanoma, we reviewed the results in 115 patients with primary melanoma and in 28 patients with recurrent disease who underwent evaluation with chest roentgenograms, radionuclide bone and liver scans, and either a radionuclide brain scan or computed tomography of the brain. Upper gastrointestinal tract series with small-bowel follow-through were obtained in 42 patients. Metastatic disease was documented in nine of 143 chest roentgenograms, seven of 137 liver-spleen scans, three of 141 bone scans, two of 85 brain scans, two of 43 brain computed tomographic scans, and two of 42 upper gastrointestinal tract series. All documented metastasis was in stage II and recurrent melanoma. Postoperatively determined serum lactate dehydrogenase levels showed greater than 300 U/L in all patients with documented metastasis except in two with bone and one with brain metastases. We conclude that, in view of low yield, there is no role for routine metastatic workup to detect silent metastasis in malignant melanoma. Elevated postoperative serum lactate dehydrogenase levels indicate need for metastatic workup.

Alkaline Phosphatase↗

The myelin proteins of the shark brain are similar to the myelin proteins of the mammalian peripheral nervous system.

The two major structural proteins in the shark CNS are similar to the structural proteins, Po and myelin basic protein (MBP), found in the mammalian peripheral nervous system (PNS). Shark Po is 46% similar to its mammalian counterpart. The extracellular domain of shark Po also appears to be organized as an immunoglobulin-like domain that mediates homotypic interactions. The intracellular domain of shark Po also is very basic and may play a role in myelin condensation analogous to that of MBP. Shark MBP is 44% similar to mammalian MBP. Both MBPs show conserved interspersed regions and are present in multiple forms that arise by alternative splicing of a single transcript. These structural analyses indicate that the complexities seen in mammalian myelin arose early during vertebrate evolution.

Amino Acid Sequence↗

Detection of bovine respiratory syncytial virus using a heterologous antigen-capture enzyme immunoassay.

Based on the marked antigenic similarities that exist between antigens of the human and bovine strains of respiratory syncytial virus (RSV), an enzyme immunoassay (EIA) designed to detect human RSV was used to detect bovine RSV. The commercial test kit (RSV EIA) consists of a solid phase (beads) coated with a capture antiserum prepared against the Long strain of human RSV. The RSV EIA test was compared with the method of inoculation of cell cultures and fluorescent antibody (FA) staining of lung tissue for the detection of bovine RSV. Using a cell culture-propagated stock of strain 375 of bovine RSV, the threshold of sensitivity of the EIA test for the cattle strain of RSV was determined to be less than or equal to 10(2.3) CCID50/ml. In addition, RSV EIA detected the bovine RSV in nasal samples obtained from 3 experimentally inoculated cattle. The RSV EIA exhibited a sensitivity of greater than or equal to 80% during the period that shedding of infectious virus took place. All of the bovine RSV FA-positive lung samples (n = 37) were positive by the RSV EIA. Twenty-six of the remaining 214 bovine RSV FA-negative lung samples were positive by the RSV EIA. The RSV EIA was also used to test 137 nasal swabs obtained from cases of bovine respiratory disease. Of these, 38 tested positive by RSV EIA. All samples that tested positive by EIA were confirmed by blocking assays using hyperimmune serum anti-bovine RSV and a pool of monoclonal antibodies specific for that virus.

Animals↗