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Biomedical subjects

A M Yeager

Publications and source records attributed to A M Yeager.

At least 73 records · Page 4Linked to original sources
PubMed1988

Cytomegalovirus infection after autologous bone marrow transplantation with comparison to infection after allogeneic bone marrow transplantation.

Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P = .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P = .02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P less than .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v 23%, P less than .001).

Bone Marrow Transplantation↗
PubMed1988

Separation of rat bone marrow cells by counterflow centrifugal elutriation: a model for studying the effects of lymphocyte depletion.

We have developed a simple three flow-rate, fixed rotor speed, counterflow centrifugal elutriation (CCE) procedure that permits the isolation of an engraftable lymphocyte-depleted (greater than 98%) fraction from ACI rat bone marrow. The different cell fractions were characterized by morphology, alloreactivity in mixed lymphocyte culture and limiting dilution analysis, colony-forming capacity, and their capacity to reconstitute hematopoiesis and effect a graft-versus-host reaction in lethally irradiated allogeneic hosts. After CCE fractionation of ACI rat marrow, transplantation of the lymphocyte-depleted marrow fraction resulted in sustained engraftment without evidence of clinical or histologic acute graft-versus-host disease (GVHD). CCE fractionation of rat bone marrow may be a useful preclinical model for studying lympho-hematopoietic and immune reconstitution after transplantation with lymphocyte-depleted donor marrow, as well as for studying the role of lymphocyte subpopulations on engraftment, acute GVHD, and leukemia relapse in syngeneic and allogeneic bone marrow transplantation.

Animals↗
PubMed1987

Allogeneic, syngeneic, and autologous bone marrow transplantation in the acute leukemias--Baltimore experience.

In presentation of our data in context of other clinical series, we have identified a few bone marrow transplant preparative regimens that appear to have a superior advantage over others as far as their antileukemic effects are concerned. So far, the delayed and late effects of the treatment appear to be quite acceptable considering the ultimate fatal outcome in the acute leukemias, in particular those in their second remission. GvHD and viral infections account for about two-thirds of the mortalities in series where leukemic relapse is very low. It is hoped that solutions or at least partial solutions will not only improve the overall therapeutic results, but will allow us to extend the procedure to older patients. It is suggested that the need for unrelated HLA "matched" donors may be supplanted by the use of autologous bone marrow transplants, particularly in the older patients.

Acute Disease↗
PubMed1987

Pneumatosis intestinalis in children after allogeneic bone marrow transplantation.

Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or high-grade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT.

Acute Disease↗
PubMed1987

Simultaneous determination of psychosine and cerebrosides.

A new method was developed for the simultaneous determination of psychosine and cerebrosides in tissues. Total lipids extracted from the tissues were treated with [3H]acetic anhydride in toluene-methanol. Known amounts of nonradioactive N-acetylpsychosine were added to the reaction product and then subjected to mild alkaline methanolysis. After the product was washed, it was fractionated by silica gel column chromatography and the fraction containing glycolipids was benzoylated. The benzoylated product was finally fractionated on TLC. The amounts of benzoylated derivatives of nonhydroxy- and hydroxycerebrosides and N-acetylpsychosine were determined using a scanning densitometer. The amounts of psychosine in tissues were calculated from the radioactivity in the spot of N-acetylpsychosine and the recovery of added carrier N-acetylpsychosine. This method allowed us to determine 5 to 1000 pmol of psychosine and 1 to 20 nmol of cerebrosides in peripheral nerves and other tissues of the twitcher mouse as well as transfected Schwann cells derived from the sciatic nerves.

Animals↗
PubMed1987

Hematopoietic cell transplantation in murine globoid cell leukodystrophy (the twitcher mouse): effects on levels of galactosylceramidase, psychosine, and galactocerebrosides.

Hematopoietic cell transplantation (HCT) prolongs survival in the twitcher mouse, an authentic animal model of human globoid cell leukodystrophy (Krabbe disease; galactosylceramidase deficiency), but the effects of HCT on levels of galactosylceramidase, psychosine, and cerebrosides in the tissues of twitcher mice have not been previously studied. Galactosylceramidase was less than 8% of control activity in tissues of untreated twitcher mice but reached normal values in brain and spleen and 20-30% of control in kidney of 100-day-old twitchers that received HCT at age 10 days. Using a recently developed method for the simultaneous determination of psychosine and cerebrosides, we measured the tissue levels of these lipids in the above animals. The levels of psychosine in brain, sciatic nerve, and kidney of untreated twitcher mice were 44, 200, and 12 times control values, respectively, in 30-day-old animals and 69, 500, and 14 times control levels in 40-day-old mice. On the other hand, levels of cerebroside were approximately 35% of control values in sciatic nerve, remained about the same in the brain, and were elevated 10-fold in the kidney of twitcher mice. After HCT, psychosine levels in the brains of 30-day-old twitchers were lowered to 30-35% of values in untreated twitchers, and the levels remained in that range during the post-HCT period. Similarly, brain cerebroside levels remained low in HCT-treated twitcher mice. Although psychosine levels in sciatic nerves of HCT-treated twitcher mice increased more slowly than in the nerves of untreated twitchers, the levels in 100-day-old HCT-treated twitcher mice had reached the same high values as those seen in untreated 40-day-old twitchers. It is not known whether the extremely high levels of psychosine in sciatic nerves ultimately contribute to the death of twitcher mice after HCT.

Aging↗
PubMed1987

Allogeneic, syngeneic and autologous marrow transplantation in the acute leukemias and lymphomas--Baltimore experiences.

Allogeneic bone marrow transplants (BMT) in acute lymphoblastic leukemia following cyclophosphamide (Cy) and total body irradiation (TBI) has resulted in disease-free survival (DFS) for CR1, CR2, and CR3 of 10/18 (56%), 16/30 (53%) and 4/17 (24%), respectively. Median follow-up of survivors was 25-43 months. One relapse was seen in CR1, 1 in CR2, and 6 in CR3. Allogeneic BMT in acute nonlymphoblastic leukemia (ANLL) following busulfan (Bu) resulted in DFS for CR1, CR2 + CR3 + early relapse of 21/47 (45%) and 13/41 (32%), respectively. Median DFS of survivors of all groups together was 36 months. DFS of all patients 20 years or less was 15/27 (56%) and 19/61 (31%) for ages 21-46. Three relapses of 47 (6%) were seen in CR1 and 6/41 (15%) in subsequent remission and early relapse. BMT of autologous BMT with 4-hydroperoxy-cyclophosphamide (4-HC) purged marrow in ANLL in CR1 (5), CR2 (32) and CR3 (9) following Bu + Cy resulted in DFS of 19/46 (41%) for 1-67 months (median 15 months). Twenty patients with prior risk non-Hodgkin's lymphoma received 4-HC-purged marrow following Cy + TBI. DFS was 10/20 (50%) for 1.4-9.5 years (median 2.9 years).

Acute Disease↗
PubMed1987

Treatment of poor prognosis non-Hodgkin's lymphoma using cyclophosphamide and total body irradiation regimens with autologous bone marrow rescue.

Twenty patients with poor prognosis non-Hodgkin's lymphoma received regimens which employed cyclophosphamide and total body irradiation followed by autologous bone marrow rescue. There were two toxic deaths. All 10 patients with residual disease prior to treatment achieved a complete remission. Ten patients survive disease free from 1.4 to 9.5 years and median survival exceeds 2.9 years. The actuarial 3-year disease-free survival is 50%. Treatment with cyclophosphamide and total body irradiation followed by autologous bone marrow infusion is an effective salvage regimen for poor prognosis lymphoma. Durable long-term remissions can be achieved.

Adolescent↗
PubMed1986

Autologous bone marrow transplantation in patients with acute nonlymphocytic leukemia, using ex vivo marrow treatment with 4-hydroperoxycyclophosphamide.

We studied 25 patients with acute nonlymphocytic leukemia in second remission (20 patients) or third remission (5 patients) in whom autologous bone marrow transplantation was performed with use of marrow incubated ex vivo with the alkylating agent 4-hydroperoxycyclophosphamide. Patients received intensive cytoreductive therapy with busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, followed by an infusion of marrow that had been collected in remission, treated with 4-hydroperoxycyclophosphamide, and cryopreserved. Four patients died from bacterial or fungal sepsis within the first month after transplantation, and one patient with persistent marrow hypoplasia died from gram-negative sepsis 155 days after infusion with autologous marrow. In the remaining patients, peripheral-blood levels of neutrophils in excess of 0.5 X 10(9) per liter and platelet counts over 50 X 10(9) per liter were attained at median intervals of 29 and 57 days after transplantation, respectively. Nine patients had leukemic relapses at 73 to 316 days (median, 182 days) after infusion of autologous marrow, for an actuarial relapse rate of 46 percent. Eleven patients (eight in second remission and three in third) remained in remission at a median of more than 400 days (range, greater than 230 to greater than 1653 days) after transplantation. The observed disease-free survival after transplantation with autologous marrow treated with 4-hydroperoxycyclophosphamide compares favorably with the results of syngeneic or allogeneic transplantation in similar groups of patients.

Acute Disease↗
PubMed1986

Nerve conduction studies in the Twitcher mouse (murine globoid cell leukodystrophy).

Progression of the neuropathy in the Twitcher mouse (twi-C57BL/6J), an animal model of globoid cell leukodystrophy, was assessed with serial motor nerve conduction studies from just after birth until near death (day 45) and after hematopoietic cell transplantation (HCT). Under ether anesthesia, the tibial nerve was stimulated percutaneously at the sacral notch and at the ankle, and recordings were made from plantar foot muscles. Motor conduction velocity (MCV), distal latency, amplitude, duration and number of phases of compound muscle action potentials on proximal (pCMAP) and distal (dCMAP) stimulation were measured. In 15-19 day-old Twitcher, despite the absence of motor signs, MCV was significantly reduced, 12.8 +/- 2.8 (10) m/s (M +/- SD, No. of recordings), compared with unaffected siblings, 18.1 +/- 2.6 (21) m/s (P less than 0.01). The ratio of pCMAP to dCMAP amplitudes was reduced in the Twitcher, 0.39 +/- 0.13 (10), compared with controls 0.72 +/- 0.17 (21) and the ratio of pCMAP to dCMAP phases was increased (2.8 +/- 0.8 (10) vs 1.0 +/- 0.2 (21), P less than 0.01 for all). As neurologic signs progressed by 35-39 days, MCV became slower, 5.8 +/- 1.0 (11) m/s, pCMAP and dCMAP became smaller, but the ratio of pCMAP to dCMAP amplitudes in the Twitcher (0.55 +/- 0.36, 11) was similar to controls (0.71 +/- 1.0, 20) as was the ratio of pCMAP to dCMAP phases (1.0 +/- 0.4 vs 1.0 +/- 0.1). These results suggest that there is diffuse non-uniform slowing of nerve conduction with block especially in proximal nerve fibers initially. With HCT, mean MCV remained slow (6.7 +/- 1.2 (18) m/s, vs 34.5 +/- 3.9 (12) m/s) but motor function persisted.

Age Factors↗
PubMed1986

Computed tomography of gastrointestinal inflammation after bone marrow transplantation.

Overwhelming secretory diarrhea can be a major complication after bone marrow transplantation, associated usually with acute graft-versus-host disease (AGVHD). Radiographic evaluation may be hampered by nausea, vomiting, or debilitation. Computed tomography (CT) in seven such patients demonstrated diffuse wall thickening in the small intestine, colon, and/or mesentery. In two cases, prolonged adherence of oral contrast material to the luminal surface resulted in bizarre patterns of coating. In two others, a layer of low attenuation within the thickened wall produced a target appearance consistent with submucosal edema or hemorrhage. Small bowel dilatation and fold enlargement was the only finding in one patient. The role that superinfection of the gastrointestinal tract with opportunistic organisms can play in this immunocompromised group of patients is less well established. In this group of patients, the findings were due to AGVHD in two, AGVHD and viral enteritis in two, and viral enteritis alone in three. CT may be an alternative to routine contrast studies in assessing the extent of gastrointestinal tract involvement after bone marrow transplantation. Neither contrast studies nor CT were able to differentiate between AGVHD and viral enteritis.

Adolescent↗
PubMed1985

A therapeutic trial of amniotic epithelial cell implantation in patients with lysosomal storage diseases.

To determine whether allografts of normal amniotic epithelium might provide a nonimmunogenic cellular source of exogenous lysosomal enzymes, subcutaneous implants of amniotic epithelium were performed in six children with clinically advanced storage diseases. The clinical and the biochemical status of each patient was observed for several weeks after amniotic epithelial cell implantation (AECI). Serial studies of blood samples from each patient in the post-AECI period did not demonstrate any increase in levels of deficient lysosomal hydrolase. In two patients, quantitative urinary excretion of substrate was also studied and did not show consistent alterations after AECI. No patient had objective improvement in clinical or neurodevelopmental status following AECI. Two patients died with progressive disease at 2 1/2 and 3 1/2 mo after AECI; no residual amniotic epithelium was found at postmortem examination. Four patients are alive with progressive disease at 6-14 mo after AECI. We conclude that allografts of normal human amnion do not provide sufficient replacement hydrolases for clinical or biochemical improvement in lysosomal storage diseases.

Amidohydrolases↗
PubMed1984

Prolonged survival and remyelination after hematopoietic cell transplantation in the twitcher mouse.

The twitcher mouse is an animal model of galactosylceramidase deficiency (Krabbe's disease), a human sphingolipidosis. The effects of hematopoietic cell transplantation as potential enzyme replacement therapy were examined in the twitcher mouse. Survival in twitcher mice with transplants was significantly prolonged and was associated with gradual repair of demyelination in peripheral nerves. In contrast, there was no improvement in the neurodegenerative process in the central nervous system after transplantation. These observations indicate that cellular transplantation may effectively provide in vivo enzyme replacement for the peripheral manifestations of genetic storage diseases. Strategies to perturb the blood-brain barrier may be necessary for enzyme replacement to be therapeutic in diseases with central nervous system manifestations.

Animals↗
PubMed1984

Bone marrow transplant in adrenoleukodystrophy.

An allogeneic bone marrow transplant (BMT) from a normal HLA identical sibling donor was performed in a 13-year-old boy with rapidly progressive adrenoleukodystrophy (ALD). Engraftment and complete hematologic recovery occurred within 4 weeks, but neurologic deterioration continued. The patient died of an adenovirus infection 141 days after BMT. ALD is characterized by abnormally high plasma levels of very long chain fatty acids (VLCFA) as a result of impaired capacity to degrade them. Ten days after BMT, the white blood cell VLCFA levels and enzyme activity became normal; after 3 months, there was progressive reduction of plasma VLCFA to levels only slightly above normal.

Adolescent↗
PubMed1983

Hemoglobin Cheverly: an unstable hemoglobin associated with chronic mild anemia.

The evaluation of a family with chronic mild anemia led to the identification of a new unstable hemoglobin (Hemoglobin Cheverly). Modest anemia and reticulocytosis, normal to slightly increased mean corpuscular volume (MCV), and normal mean corpuscular hemoglobin concentration (MCHC) were present in the affected family members. Electrophoresis of blood samples on cellulose acetate and on citrate agar revealed normal patterns. Globin chain analysis and isoelectric focusing data were also normal. After incubation for 3 h at 41 degrees C, Heinz bodies were detected in 95-100% of erythrocytes from affected individuals. Positive heat and isopropanol tests confirmed the initial observation of the Heinz body preparation and indicated that an unstable hemoglobin was present. Structural analysis showed an amino acid substitution of Phe-Ser at position 45 (CD4) in the beta chain. Hemoglobin Cheverly has a reduced affinity for oxygen and a reduced Bohr effect, properties that can be rationalized on the basis of the x-ray crystallographic structure of normal hemoglobin. Despite structural and functional similarities between Hb Cheverly and Hb Hammersmith, beta 42 (CD1) Phe-Ser, the clinical manifestations of Hb Cheverly are mild in contrast to the severe disease observed with Hb Hammersmith. Reasons for the apparently silent clinical expression of Hb Cheverly are not known. We discuss the implications of unstable hemoglobins in the evaluation of chronic anemia in pediatric patients.

Anemia↗
PubMed1983

The effects of 5-fluorouracil on hematopoiesis: studies of murine megakaryocyte-CFC, granulocyte-macrophage-CFC, and peripheral blood cell levels.

the effect of 5-fluorouracil (5-FU) on megakaryocytopoiesis in mice was studied with assays of megakaryocyte colony-forming cells (Meg-CFC) in bone marrow and spleen and simultaneous determinations of peripheral blood counts, after a single intraperitoneal dose (150 mg/kg) of 5-FU. Although only moderate thrombocytopenia (platelet count 40% of control values) occurred at 7 days following administration of 5-FU, sustained rebound thrombocytosis (platelets 200-250% of control values) was observed from days 11 to 17. No rebound leukocytosis was detected despite comparable initial leukopenia. Megakaryocyte colony-forming cells (Meg-CFC) in bone marrow and spleen were decreased for 2 and 5 days, respectively, after administration of 5-FU. Subsequently, there was a prolonged rebound increase in the total number of Meg-CFC in the spleen from days 11 to 17 after 5-FU, a phenomenon which did not occur with Meg-CFC derived from the bone marrow. Granulocyte-macrophage colony-forming cells (GM-CFC) in bone marrow and spleen exhibited alterations which were similar to those of Meg-CFC, indicating similar sensitivities of GM-CFC and Meg-CFC to 5-FU. Normal feedback mechanisms which control platelet levels are perturbed for almost 3 wk after administration of 5-FU. The simultaneous occurrence of maximal thrombocytosis and increased splenic Meg-CFC suggests that increased platelet production after 5-FU is associated with concomitant stimulation of the megakaryocyte progenitor compartment in the mouse spleen. However, the concurrence of thrombocytosis and increased splenic Meg-CFC indicates that elevated levels of Meg-CFC did not initiate the period of thrombocytosis.

Animals↗