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Biomedical subjects

J H Lipton

Publications and source records attributed to J H Lipton.

At least 55 records · Page 3Linked to original sources

Ocular masquerade syndrome in lymphoid blast crisis of chronic myeloid leukemia.

A 56-year-old woman presented with CML in lymphoid blast crisis. Complete remission with no suggestion of CML was achieved with chemotherapy. Twenty-six months later, an isolated ocular anterior chamber relapse of acute leukemia presenting as uveitis (ocular masquerade syndrome) was diagnosed and treated with radiotherapy. Ten months later, a second ocular relapse in the same location was diagnosed and treated with radiotherapy. Two months later, a systemic relapse into second chronic phase was diagnosed and is currently being treated with alpha interferon. Only one previous case of leukemic hypopyon in CML has been reported. This is also the first case of isolated ocular blast crisis relapse in CML to be described.

Blast Crisis↗

Determination of IL6, IL1, and IL4 in the plasma of patients with multiple myeloma.

Interleukin 6 (IL6) plasma levels were measured in 63 patients with multiple myeloma and 8 individuals with benign monoclonal gammopathy. 15 of these 71 samples showed by an enzyme linked immunosorbent assay (ELISA) detectable levels that ranged from 5 to 107 pg of IL6/ml. The IL6 levels of patients with multiple myeloma did not differ significantly from those of normal individuals (N = 25, range 5-27 pg IL6/ml) (Student's t-test, p = 0.295). The samples were negative for IL4; 3 were found positive for IL1 beta. A correlation between IL6, IL4 and IL1 beta levels and disease status was not observed for this group of patients.

Enzyme-Linked Immunosorbent Assay↗

Allogeneic bone marrow transplantation from a related donor undergoing long-term immunosuppressive and cytotoxic therapy.

We report the case of a patient with acute myeloid leukemia in second remission who received an allogeneic bone marrow transplant from an immunosuppressed HLA-identical sibling donor. The donor was receiving prednisone, azathioprine and cyclosporine for a cadaveric renal allograft. Bone marrow growth in culture from the donor was normal. Engraftment was within normal limits. Moderate acute graft-versus-host disease (GVHD) developed. We suggest that transplants from immunosuppressed donors are feasible and that this does not preclude the development of GVHD.

Antineoplastic Agents↗

Pregnancy after BMT: three case reports.

A case of successful pregnancy after BMT in a 24-year-old woman with ALL, conditioned with CY, L-asparaginase, methylprednisolone and total body irradiation (TBI) is reported. A second case of two spontaneously aborted pregnancies in a woman transplanted for ALL at the age of 29 years using CY and TBI conditioning and a third case, this time a successful pregnancy in a woman transplanted for AML at age 27 years using CY and TBI conditioning are also described. There are now 6 successful live births after TBI reports of, versus 16 following regimens in which no TBI is used. This is the first report of a successful pregnancy reported in a female transplanted when older than 25 years using any TBI-containing regimen.

Adult↗

Treatment of adults with severe aplastic anemia: primary therapy with antithymocyte globulin (ATG) and rescue of ATG failures with bone marrow transplantation.

PURPOSE: To evaluate a policy of immunosuppression with antithymocyte globulin (ATG) as primary therapy for adults with severe aplastic anemia (SAA) regardless of the availability of an HLA-identical bone marrow donor. PATIENTS AND METHODS: Thirty-one consecutive adults with SAA who satisfied the age criteria for allogeneic bone marrow transplantation (BMT) (age less than 51 years) were treated with ATG 20 mg/kg/day for 10 days along with high-dose corticosteroids. Patients with an HLA-identical donor received a transplant if they did not respond to ATG or if they developed life-threatening complications during or soon after ATG administration. Eight patients with no response to ATG were also treated with oral cyclosporine 12.5 mg/kg/day. RESULTS: Eleven patients had a complete and five a partial response to ATG; two patients improved with cyclosporine treatment, resulting in an overall response rate of 58% to immunosuppression. Nine of 14 patients with donors received a BMT: seven because they did not respond to ATG and two because of serious infections. Seven grafts were obtained from related and two from unrelated donors. There was no significant difference in survival between those with and without a related HLA-identical donor (log-rank p value = 0.969). At a median follow-up of 58 months, 26 of 31 are alive with an actuarial survival of 80% at 5 years. Two patients died of infection, two died from complications of BMT, and one remains transfusion-dependent. One patient died of refractory leukemia at 30 months; one patient relapsed with hypoplasia 95 months after initial therapy with ATG. He showed a complete response to treatment with cyclosporine. No other late hematologic events have occurred. CONCLUSIONS: This treatment approach resulted in the restoration of hematopoiesis and independence from transfusion in 80% of patients with SAA entered into the study. The efficacy of allogeneic BMT in salvaging cases in which ATG failed does not appear to be compromised. Follow-up for the development of clonal hematologic disorders remains an important part of this treatment policy.

Adolescent↗

High-dose cytosine arabinoside remission induction for acute myelogenous leukemia: comparison of two regimens of remission maintenance.

We report a single institution sequential trial of two maintenance treatment regimens for patients with acute myelogenous leukemia (AML). A total of 175 consecutive patients with AML received initial remission induction therapy with high-dose cytosine arabinoside (ara-C) and glucocorticoids. For the initial 63 patients (group A), the control population, planned maintenance treatment was with conventional-dose ara-C given over 4 days for up to 18 months. The subsequent 107 patients (group B) had planned maintenance therapy of up to 6 courses of daunorubicin, ara-C and prednisone and daily cis-retinoic acid for up to two years. The presenting features of group A and B patients were similar as were the response to remission induction, 60 and 52%, respectively. Severe neurological toxicity was encountered once after high-dose ara-C; no drug-related deaths occurred during maintenance treatment. Median duration of remission for group B patients was 9.9 months compared with 5.5 for group A (p = 0.0685). Median survival duration for the two groups was similar, 9.1 months for group A and 10.4 for group B. Survival of patients in group B who attained a complete remission was significantly better than that of patients in group A (p = 0.0439). The studies confirm our initial experience with remission induction using single agent high-dose ara-C and suggest a positive role for maintenance therapy in AML.

Acute Disease↗

Drug-induced fatal aplastic anemia following cataract surgery.

Aplastic anemia attributed to medications used in ophthalmology is rare. We report a fatal case that developed in a 73-year-old woman 7 weeks after cataract extraction performed under local anesthesia. Postoperative medications included a chloramphenicol-containing ointment, flurbiprofen sodium drops, prednisone acetate drops and orally given acetazolamide. It was felt that the aplastic anemia was related to therapy with chloramphenicol or acetazolamide or both. We recommend that the course of prophylactic antibacterial therapy after intraocular surgery be kept short, regardless of the preparation used. We urge caution in the choice and use of drugs known to be associated with aplastic anemia and recommend close monitoring of the hemogram.

Acetazolamide↗

Dermatomyositis and granulomatous myopathy associated with sarcoidosis.

A previously healthy, 21-year-old female presented with acute dermatomyositis. Chest X-ray revealed bilateral hilar adenopathy, and mediastinal lymph node biopsy demonstrated noncaseating granulomata compatible with sarcoidosis. The patient improved spontaneously. The significance of bilateral hilar adenopathy in association with dermatomyositis and implications for management are discussed.

Adult↗

Fat embolization and pulmonary infiltrates after bone marrow transplantation.

Pulmonary interstitial infiltrates developed in a 22-year-old female after bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in second remission. She was receiving prednisone for graft versus host disease (GvH). There was some evidence of cardiac failure, but the primary diagnosis was that of cytomegalovirus (CMV) pneumonia, which resolved. Recurrent infiltrates were associated with the appearance of fat emboli in the pulmonary capillaries. There was little histological evidence of CMV pneumonitis, although other tests confirmed persistent infection. The patient recovered after further treatment directed at CMV infection and cardiac failure with a modest reduction in steroid dose. Most previous descriptions of pulmonary fat embolization (PFE) in immunocompromised patients have been derived from autopsy studies, and the majority of patients have received steroid therapy. The present case illustrates that PFE may complicate or contribute to the picture of interstitial pneumonitis (IPN) in the BMT recipient and that this syndrome may be reversible.

Adult↗

Miliary pattern as presentation of leiomyomatosis of the lung.

A 30-year-old woman presented with progressive dyspnea on exertion and a rapidly-growing uterine mass. Chest x-ray examination revealed a miliary interstitial nodular pattern in both lung fields. Transbronchial biopsy yielded lung tissue containing multiple nodules of smooth muscle, consistent with benign metastasizing leiomyoma. Subsequent hysterectomy revealed an atypical cellular leiomyoma. We wish to emphasize the need for chest x-ray examination in the workup of uterine tumors in women of reproductive age.

Adult↗

Q fever inflammatory pseudotumor of the lung.

A 36-year-old man presented with malaise, myalgia, fever, and weight loss. Liver function tests were moderately abnormal and chest x-ray film revealed an irregular mass in the right lower lobe. Bronchoscopy with cytology was not helpful. Serology revealed markedly elevated titers to Q fever. The mass was presumed to represent the presence of a Q fever pseudotumor. The patient responded to therapy with resolution of symptoms and chest x-ray film and decrease in titers to Q fever.

Adult↗

Calcium uptake by isolated rat intestinal cells.

Intestinal cells were isolated by a combination of mechanical and enzymatic means, and their calcium uptake was assayed by a rapid filtration procedure. Calcium uptake was a time- and concentration-dependent process that was markedly elevated at 25 and 37 degrees C, as compared to 0 degree C. Cells isolated from rat duodenum exhibited higher uptakes than cells from jejunum, which in turn took up more calcium than cells from the ileum. Duodenal cells from vitamin D-deficient animals took up less calcium than cells from vitamin D-replete cells. In vivo vitamin D repletion with 1,25-dihydroxyvitamin D3 raised calcium uptake by duodenal cells from treated animals toward that of cells from replete rats. Furthermore, calcium uptake by duodenal cells from vitamin D-deficient animals approximated that of ileal cells from replete rats. These findings with isolated cells parallel prior findings of tissue calcium transport and suggest that cellular calcium uptake may be related to the saturable component of intestinal calcium absorption. Isolated intestinal cells may therefore constitute one experimental model for the study of transcellular calcium transport.

Animals↗

Characterization of macrophage- and granulocyte-inducing proteins for normal and leukemic myeloid cells produced by the Krebs ascites tumor.

Medium from serum-free cultures of Krebs ascites tumor cells contains two macrophage and granulocyte inducing (MGI) activities that can act on the myeloid precursors of these hematopoietic cells. One activity, MGI-1, induced the formation of macrophage and granulocyte colonies from normal myeloid precursors. The second activity, MGI-2, induced macrophage and granulocyte differentiation in myeloid leukemic cells that no longer required MGI-1 for colony formation. The medium contained one species of MGI-1 and two species of MGI-2. One species of MGI-2, MGI-2A, copurified through five stages of purification with MGI-1, but separated from the other MGI-2 species, MGI-2B, at an early stage in purification. MGI-1, MGI-2A and MGI-2B were purified 1490, 1140 and 678-fold, respectively. When bands with biological activity gel from non-denaturing polyacrylamide gels were run on SDS-polyacrylamide gel electrophoresis, MGI-1 and MGI-2A activities were associated with similar Mr and each activity showed two bands, one of 23 000 and the other 25 000. MGI-2B activity showed one band with a Mr of 45 000. Secretion did not appear to involve glycosylation, none of the species bound to concanavalin A, soybean agglutinin, or wheat germ agglutinin agarose columns and they did not appear to contain carbohydrates. The assays for MGI-1 and MGI-2 activities were not affected by adding protease inhibitors. But MGI-2 was more readily destroyed by treatment with proteases and was more labile at high temperature and low pH than MGI-1. It is suggested that the level of cellular proteases may play a role in regulating the relative amounts of MGI-1 and MGI-2 that are present in vivo.

Animals↗

Separation of different molecular forms of macrophage- and granulocyte-inducing proteins for normal and leukemic myeloid cells.

It is shown that serum of mice treated with endotoxin (ES) contains three separable and functionally distinct forms of macrophage- and granulocyte-inducing (MGI) proteins. One form (MGI-1M) induced the formation of macrophage colonies from normal bone-marrow cells and showed on gel filtration an apparent molecular weight of 300,000; a second form (MGI-1G) induced the formation of granulocyte colonies from normal bone-marrow cells and had an apparent molecular weight of 45-100,000; and the third form (MGI-2) induced the normal differentiation of MGI+D+ myeloid leukemic cells to macrophages and granulocytes and had an apparent molecular weight of 28,000. Studies on the time course of the decrease of these three activities in ES have indicated that MGI-2 was more readily inactivated in vivo than MGI-1M and MGI-1G. The MGI-1M in ES isolated after gel filtration was completely neutralized by an antiserum to MGI-1 from mouse L-cells, whereas the isolated MGI-1G and MGI-2 were not affected by this antiserum. Gel filtration under dissociating conditions (6 M guanidinium chloride) resulted in a reduction of the apparent molecular weights of MGI-1M from 300,000 to 42,000, and of MGI-1G from 45-100,000 to 28,000, while it produced no change in the 28,000 apparent molecular weight of MGI-2. Similar studies with conditioned medium produced in vitro from mouse lung and peritoneal macrophages showed that in these conditioned media, MGI-1 (both G and M) in the native form had an apparent molecular weight of 41,000 and MGI-2 of 24,000, and that both MGI-1 and 2 had an apparent molecular weight of 24,000 under dissociating conditions. The results indicate that MGI-1 exists in serum in vivo and in these conditioned media as aggregated proteins, whereas MGI-2 does not, and that macrophages and lung tissue are not the only source of the MGI proteins found in ES. It is suggested that all three forms of MGI activity are derived from one precursor protein; that only the MGI-2 form assayed on leukemic cells should be used for treatment based on the induction of normal cell differentiation in myeloid leukemia; and that MGI-2 may serve as a survey mechanism for inducing differentiation in myeloid leukemic cells that have lost their responsiveness to the MGI-1 molecules that control the viability, proliferation and differentiation of normal myeloblasts.

Animals↗