Biomedical subjects
Publications and source records attributed to R Saral.
Neurologic abnormalities are known to occur in a significant number of patients with Waldenström's macroglobulinemia. We have described such a patient whose initial presenting symptom was sudden hearing loss. She had no progression of the hearing deficit with long-term anticoagulant therapy.
Observations of 20 consecutive bone marrow transplantation recipients disclosed two distinctive categories of pulmonary interstitial changes. Interstitial infiltrates occurring less than 14 days after transplantation were observed in 13 of 20 patients and are believed to represent pulmonary edema. A late pulmonary interstitial process, which appears more than 30 days following transplantation (median 57 days), was encountered in 10 of 14 patients with successful grafts; the late changes represent interstitial pneumonia, a common cause of morbidity and mortality following bone marrow transplantation. It is probably attributable to a combination of factors including the preparatory chemotherapy and radiotherapy, and delayed immunologic reconstitution following transplantation.
Of 89 consecutive patients undergoing treatment for hematologic malignancies or undergoing allogeneic bone marrow transplantation, 60 were colonized with Candida albicans and 25 with C. tropicalis. However, of the 18 disseminated infections caused by Candida species, 15 infections in 14 patients were caused by C. tropicalis and only three infections in three patients by C. albicans. The setting in which the infection occurred, skin lesions, polyarthralgias, or polymyalgias, and the unexplained deterioration of renal function were features suggestive of the diagnosis. Defervescence occurred in 10 of the 14 treated patients with C. tropicalis infections in 1 to 6 d (mean, 2.5 d) after initiation of therapy, even though all continued to be granulocytopenic. Resolution occurred in eight of the 15 C. tropicalis infections. In one case outcome was indeterminate, four patients died due to the infection, and two died from other causes but with the infection unresolved.
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Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus.
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Sequential chemotherapeutic regimens, primarily used in the treatment of hematopoietic malignancies, and employing ara-C as a basic antineoplastic agent induce mucosal alterations in the entire gastrointestinal tract. These are characterized by surface and glandular epithelial atypia, immaturity, and necrosis. Glandular regeneration is characteristically delayed leading to a state of intestinal aproliferative cytopenia. Other toxic intestinal changes include telangiectasia of blood vessels and the formation of intramural hematomas. Intestinal infections develop frequently and are complicated by peritonitis, liver abscesses, pneumatosis cystoides in testinalis and sepsis. These intestinal lesions are accompanied by a predictable clinical syndrome which begins concomitantly with ara-C infusions and is characterized by diarrhea, ileus, abdominal pain, hematemesis and melena, severe hypokalemia, hypocalcemia and a protein-losing enteropathy. Additional toxic manifestations induced by ara-C include transient weight gains, fever elevations and severe bone marrow depression. The genesis of the intestinal lesions is linked to the three day dose schedule of ara-C infusions which insures both arrest of the cycling intestinal cells in the S-phase and a high cytotoxic index. The severity of these lesions is markedly augmented by prior treatment with ara-C and cyclophosphamide which causes synchronization and probable recruitment of intestinal stem cells, respectively.
Massive bleeding owing to cyclophosphamide-induced hemorrhagic cystitis was not affected by intravesical instillation of 4 per cent formalin or 1 per cent silver nitrate. After initiation of a continuous systemic infusion of vasopressin hematuria and transfusion requirements diminished markedly. Adverse reactions were mild. Intravenous vasopressin was a safe and effective means to control temporarily life-threatening hemorrhagic cystitis.
A 22-yr-old man with acute myelocytic leukemia received a bone marrow transplant from a genotypically HLA-identical female sibling after cyclophosphamide preparation. He remained in complete remission for 18 mo, when he developed a chloroma in the perineum. The chloroma was treated with local radiotherapy. The chloroma recurred 8 mo later and was treated with radiotherapy followed by combination chemotherapy. At 34 mo after transplant, marrow relapse and chloroma were documented. The first chloroma contained host cells by fluorescent Y-chromatin body analyses of interphase nuclei. All metaphase cells and karyotypes from peripheral blood and marrow samples showed no evidence of host cells from 3 wk after transplant through the time of marrow relapse. Data from autosomal and sex chromosome studies indicate that the marrow relapse occurred in cells of donor origin. A new consistent chromosome abnormality [45, X, -X, t(8;21) (q22; q22)] was observed in a majority of donor cells. The patient received a second bone marrow transplant from the same donor after preparation with busulfan and cyclophosphamide and attained a complete remission with full hematologic engraftment.
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