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Biomedical subjects

G M Schmidt

Publications and source records attributed to G M Schmidt.

At least 55 records · Page 3Linked to original sources

Bone marrow transplantation for acute nonlymphoblastic leukemia during first complete remission. An analysis of prognostic factors.

Sixty-nine patients with acute nonlymphocytic leukemia in first remission received total-body irradiation and chemotherapy followed by allogeneic bone marrow transplantation from histocompatible sibling donors. Patient age was between 1 and 41 years: 20 patients 1-19 years (group 1); 27 patients 20-29 years (group 2); and 22 patients 30-41 years (group 3). Two pretransplant radiochemotherapy regimens were employed: The first 45 patients received total-body irradiation (in a single dose) with cytosine arabinoside and cyclophosphamide; the next 24 patients received total-body irradiation (in a fractionated schedule) with cyclophosphamide alone. For all patients, actuarial disease-free survival is 51% (37 of 69 patients are alive and in continuous remission between 5 months and 9.3 years, median 3.7 years). For group 1 actuarial survival is 56%, group 2 48%, and group 3 48%. When analyzed for pretransplant factors that might predict disease-free survival after bone marrow transplantation neither patient age, white cell count at the time of diagnosis, FAB leukemic subtype, length of time before achieving remission, nor length of time between remission and bone marrow transplantation were established as prognostic.

Acute Disease↗

Bone marrow transplantation for myelodysplastic and myeloproliferative syndromes.

Twenty patients (age range, 4 to 48 years; median age, 36 years) with de novo or drug-induced myelodysplastic syndromes or myeloproliferative disorders were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Four preparative regimens were used; three regimens consisted of combined total body irradiation (TBI) and chemotherapy and one of combination chemotherapy only. One patient received marrow from his identical twin brother, whereas the other 19 patients were grafted with marrow from histocompatible siblings. In 19 patients the abnormal clone was at least temporarily ablated, while in one patient the congenital myelodysplasia persisted. Eight patients are alive and well for +108 to +3,359 days post-transplantation. Nine patients died of transplant-related complications (six of interstitial pneumonia, two of gastrointestinal bleeding, and one of fungal sepsis) and three patients died with persisting or recurring disease. One patient with a late recurrence has undergone a second successful bone marrow transplant procedure. Outcome of BMT was not related to French-American-British (FAB) type, marrow fibrosis, cytogenetic abnormalities, or preparation regimen. Marrow transplantation as a means of providing long-term disease-free survival and possible cure should be considered in patients if a suitable donor is available.

Adolescent↗

Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

We report the treatment outcome of allogeneic bone marrow transplantation in ten patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Six patients are alive and well for 6 to 30 months (median 19 months) after transplantation. Four patients died with transplant related complications. In view of the poor prognosis associated with this disease, marrow ablation followed by allogeneic or syngeneic marrow grafting may be the preferred treatment modality if a suitable marrow donor is available.

Acute Disease↗

Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies.

In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16-213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.

Acute Disease↗

Unsuccessful treatment of disseminated protothecosis in a dog.

Systemic protothecosis was diagnosed in a 7-year-old dog that had only ocular manifestations. During the 3-month course of disease, a variety of drugs was administered, including amphotericin B, gentamicin, and ketoconazole. The ocular signs initially abated, but subsequently worsened during this period. The dog was found dead 3 months after initial examination, and systemic protothecosis was confirmed at necropsy.

Amphotericin B↗

Rhegmatogenous retinal detachment in Labrador retrievers. I. Development of retinal tears and detachment.

We used clinical and pathologic methods to examine ten Labrador retrievers with ocular and skeletal abnormalities. The major ocular findings were axial myopia; cataract; vitreous abnormalities, including liquefaction, detachment, and vitreoretinal traction; retinal tears; rhegmatogenous retinal detachment; and proliferative vitreoretinopathy. The appendicular skeleton showed retarded bone growth, bone dysplasia, and degenerative arthropathy. Vitreoretinal traction appeared to be the cause of the retinal tears because (1) formed vitreous was always attached near the anterior edge of the tear, and (2) vitreous traction caused a retinal ridge adjacent to a retinal tear in a dog that had not yet developed retinal detachment. The pathogenetic sequence of spontaneous vitreous abnormalities, retinal tears, and retinal detachment observed in these dogs has not previously been described in animals, to the best of our knowledge, and mimicked human rhegmatogenous retinal detachment, particularly those associated with giant retinal tears.

Animals↗

Rhegmatogenous retinal detachment in Labrador retrievers. II. Proliferative vitreoretinopathy.

We observed proliferative vitreoretinopathy in Labrador retrievers with spontaneous rhegmatogenous retinal detachment. Cellular membranes and their associated connective tissue matrix were prominent on the surfaces of the detached formed vitreous and on the retina. Membrane contraction folded the underlying vitreous and retina and exerted traction on the structures to which they attached. Proliferation occurred in the retinal pigment epithelium under the detached retina and in the nonpigmented ciliary epithelium when it became detached. Retinal pigment epithelial cells, nonpigmented ciliary epithelial cells, macrophages, and glial cells appeared to contribute to the membranes. Our findings suggested a sequence that began with vitreous abnormalities and ended with fibrocellular membranes on the surfaces of the vitreous and the totally detached retina. Because a similar sequence can develop in humans, these dogs may be useful in future studies of proliferative vitreoretinopathy.

Animals↗

Onchocerca cervicalis in horses: dermal histopathology.

A histopathological study of ventral midline skin from midwestern U.S. horses with and without onchocerciasis due to Onchocerca cervicalis found perivascular mononuclear dermatitis as the most consistent difference between the two groups. Seasonal variation in parasite numbers or cellular influxes was not observed. Eosinophilic dermatitis was observed in horses with onchocerciasis and dermatitides of unknown etiology.

Animals↗

Immunoglobulin levels in tears and aqueous humor of horses before and after diethylcarbamazine (DEC) therapy.

A quantitative investigation of equine tear and aqueous humor immunoglobulins was done using normal horses and ponies as well as horses and ponies infected with Onchocerca cervicalis. The equine immunoglobulin isotypes IgGa, IgM, IgA and IgG(T) were quantitated by either single radial immunodiffusion (SRID) or radioimmunoassay (RIA). Tear immunoglobulin levels for IgGa (128 +/- 151 micrograms/ml), IgA (1,664 +/- 1,038 micrograms/ml) and IgM (106 +/- 74 micrograms/ml) were measured, while IgG(T) was not detectable. In horses with ocular inflammation the IgGa was 18-fold higher in the tears, 2,269 +/- 3,077 micrograms/ml. Aqueous humor obtained by paracentesis of the normal equine eye under anaesthesia, resulted in values for IgGa (45.2 +/- 20.0 micrograms/ml), IgG(T) (5.2 +/- 2.0 micrograms/ml), IgM (1.3 +/- 4.8 micrograms/ml) and IgA (0.8 +/- 1.0 micrograms/ml). A pooled sample of normal aqueous fluid obtained from over 100 horses at an equine abbatoir in Indiana gave values of 1,150 micrograms/ml for IgGa, 65 micrograms/ml for IgG(T), 2.5 micrograms/ml for IgA and 3.0 micrograms/ml for IgM. In animals infected with 0. cervicalis and treated with Diethylcarbamazine (DEC), there was a marked elevation of IgGa and IgG(T) in the tears and aqueous humor while IgA and IgG(T) were also elevated slightly in the aqueous. The findings of elevated immunoglobulin isotypes in the aqueous humor may not be related to the DEC treatment and 0. cervicalis infections but rather to repeated paracentesis and the development of acute inflammation of the equine eye as a result of the trauma of paracentesis. The elevations in equine immunoglobulin isotypes in the tears after DEC treatment are not subject to the same caveat. The preferential elevation in IgGa and IgG(T) in the tears precedes the development of corneal opacities observed in the same horses. The concentration of specific antimicrofilarial antibody in these tears remains to be determined but may well account for a major share of the total immunoglobulins detected.

Animals↗

Equine onchocerciasis: lesions in the nuchal ligament of midwestern U.S. horses.

Nuchal ligaments from midwestern U.S. horses infected with adult Onchocerca sp. were studied. The prevalence of Onchocerca sp. infection in horses increased with age. Ten percent of horses less than one year old were infected, 28% of horses one to five years old, 48% of horses six to 15 years old, and 90% of horses over 16 years old. Lesions in Onchocerca sp.-infected nuchal ligaments varied with age of the horse. Horses less than five years old had few or no lesions, whereas most horses six to 15 years old had focal mineralization and granuloma formation around adult worms. In infected nuchal ligaments of horses over 16 years old, mineralization was much greater and fewer normal parasites were found. Our data suggest that infection by viable parasites is terminated naturally.

Age Factors↗

Evaluation of platelet surface antigens: localization of the PlA1 alloantigen.

An approach is described for localizing antigenic determinants to specific platelet proteins. Platelets are solubilized, electrophoresed and transferred to nitrocellulose paper where they are immobilized. After incubation with radiolabelled specific antibody, the antigenic determinants are localized by radioautography. Purified proteins ranging in size from 50000 to 540000 could be studied in this manner and still retain their antigenicity. Solubilized immobilized platelet proteins were reacted with serum IgG from two patients with post-transfusion purpura known to have anti-PlA1 antibodies. The radioactivity was associated with a major protein band with an apparent molecular weight of 100000 daltons. However, when purified anti-PlA1 antibody eluted from PlA1 (+) platelets was used, at least six additional minor bands were noted with molecular weights ranging from about 86000 to 175000. No radioactive bands were noted using PlA1 negative platelets or reduced PlA1 (+) platelet proteins. Reaction of the antibody from one patient wih proteins from thrombasthenic platelets resulted in a marked reduction in the intensity of all radioactive bands. In addition, a new high molecular weight band was noted which was not present in reactions containing PlA1 (+) platelets. These data suggest that the PlA1 antigen is primarily but not entirely localized to glycoprotein IIIa. This approach is relatively simple, requires only minimal amounts of antibody and should be generally useful in the study of cellular antigens and other complex mixtures of proteins.

Antigens, Surface↗

Equine ocular onchocerciasis: histopathologic study.

Equine eyes (368) were examined clinically and histologically for abnormalities associated with the presence of ocular microfilariae of naturally occurring Onchocerca sp infection. Forty of the eyes had microfilariae in the conjunctiva, but distinguishing clinical abnormalities were not associated with their presence. In 1 horse with ocular microfilariae that was treated with diethylcarbamazine daily for 2 weeks, ocular tissue samples were obtained before, during, and after the horse was treated, and the samples were compared histologically. During treatment of the horse, microfilariae apparently moved from the conjunctival stroma into the perilimbal corneal stroma; inflammatory cells were more abundant in the perilimbal tissues. The tissue samples obtained before and after the treatment appeared similar.

Age Factors↗

Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia.

Thirty-three patients with acute leukemia (15 with lymphoblastic leukemia and 18 with myeloblastic leukemia) were entered into a program of high-dose radiochemotherapy followed by allogeneic bone-marrow transplantation. These patients were in various clinical stages of disease. Of 10 in complete hematologic remission at the time of transplantation, seven were alive without maintenance therapy at the time of evaluation, eight to 35 months after grafting; one was in relapse. Of 11 who received transplants during partial remission, six were in remission without further treatment eight to 33 months after transplantation. In 12 the disease was refractory to chemotherapy when preparation for transplantation was started, and only one of them was alive and free of disease after 10 months. Recurrent leukemia, graft-versus-host disease, viral pneumonia, and early therapy-related toxicity were the major causes of failure. High-dose chemotherapy and total-body irradiation followed by allogeneic marrow transplantation performed during complete or partial remission can produce long-term remission of acute leukemia.

Acute Disease↗