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Biomedical subjects

M Liepman

Publications and source records attributed to M Liepman.

18 recordsLinked to original sources

Interdigitating reticulum-cell sarcoma of the intestine: a case report and review of the literature.

Dendritic cells are immune accessory cells which are widely distributed in many tissues. Those which are present within lymphoid follicle centers are classified as follicular dendritic cells. Those which are found outside germinal centers may be referred to as interdigitating reticulum cells, or Langerhans cells when they occur in the skin. Abnormal proliferations of dendritic cells are best known as the group of disorders comprising Langerhans-cell histiocytosis, which occurs primarily in children and teenagers. There are increasing reports of malignant proliferations of both types of dendritic cells in adults. However, there is only one previous description of the cytologic features of a dendritic cell sarcoma based on imprint cytology of a resected jejunal mass. The current report provides a detailed description of the cytologic features of a fine-needle aspirate of a recurrence of an interdigitating reticulum-cell sarcoma of the cecum.

Aged

Preirradiation chemotherapy of supratentorial malignant primary brain tumors with intracarotid cis-platinum (CDDP) and i.v. BCNU. A phase II trial.

Thirty patients with histologically verified malignant supratentorial gliomas were treated with a preirradiation chemotherapy protocol consisting of two courses of intracarotid (i.c.) CDDP, 90 mg/m2, followed by i.v. BCNU, 200 mg/m2. Side effects from therapy were mild and self-limiting; no irreversible retinal or neurologic toxicity could be attributed to i.c. chemotherapy. Of the 27 patients who completed the chemotherapy portion of the protocol, tumor size on postchemotherapy computed tomography (CT) was decreased by greater than 50% in 13% as compared to the postoperative CT scan; in only 4% was the CT scan unequivocally increased in size. Twenty-five (83%) patients completed the entire protocol. Median time to tumor progression and survival in patients who completed the protocol was 53 (range of 13-130+) and 61 (range of 29-130+) weeks, respectively. Twenty-four percent of patients still have not demonstrated tumor progression at intervals greater than 1 year after diagnosis as judged by clinical and radiographic criteria. Tumor recurrences were always contiguous to the original tumor bed. We conclude that preirradiation chemotherapy may be administered safely and with low morbidity. Further study to determine an optimal timing between chemotherapy and radiation therapy is warranted.

Adult

Safety and efficacy of long-term oral anticoagulation in cancer patients.

The course of long-term oral anticoagulation in 25 patients (186 patient-months) with cancer managed in an outpatient anticoagulation clinic was analyzed to determine the frequency of complications. Major and minor hemorrhagic complications occurred in 10.7% and 32% of treatment courses, respectively, for an incidence of 1.6% and 4.8%, respectively, per patient-month. Recurrent thromboembolism occurred in 14% of treatment courses. These results are better than previous reports in the literature, but worse than our overall anticoagulation clinic experience. Patients with cancer requiring anticoagulation are at a higher risk of hemorrhagic and thrombotic complications. Accordingly, we recommend that such patients be monitored closely, preferably by physicians experienced with such therapy, as in an anticoagulation clinic, to avoid an excessive degree of morbidity.

Adult

Evidence for two isozymes of leukocyte alkaline phosphatase in leukemic leukocytes.

Leukocyte alkaline phosphatase (LAP) is a granulocyte enzyme whose level of expression is markedly altered in various disease states. We have characterized LAP from normal cells and leukemic cells with a high level of LAP activity in order to determine whether increased enzyme levels are caused by increased levels of the same enzyme or induction of a different alkaline phosphatase. Leukocyte alkaline phosphatase was purified from normal granulocytes and from leukemic cells of a patient with chronic granulocytic leukemia (CGL) in blast phase with an elevated LAP level. LAP was partially purified utilizing diethylaminoethyl (DEAE)-cellulose ion exchange chromatography, gel filtration, and preparative electrophoresis. The sample prepared from normal granulocytes contained a single protein with LAP activity having a molecular weight of 61,000 as determined by SDS gel electrophoresis. The sample from the CGL blast-phase cells, however, demonstrated two proteins with alkaline phosphatase activity, one with a molecular weight of 61,000 (LAPs) and one with a molecular weight of 45,000 (LAPf). Differential heat inactivation and distinct isoelectric points of the two isozymes suggest that they are different proteins. We interpret our data to suggest two closely related LAP alleles whose expression is controlled independently. This may represent either genetic heterogeneity or induction of "tumor marker" gene expression.

Alkaline Phosphatase

Dendritic cell phenotype in localized malignant histiocytosis of the small intestine.

We studied a unique case of a localized non-Hodgkin's lymphoma of the pleomorphic large-cell type arising in the small intestine to determine its phenotype. Immunohistochemical staining for S100 protein, lysozyme, alpha 1-antitrypsin, and Leu-M1 was performed. Many lymphoma cells were positive for S100 protein and were negative with the other antibodies. These findings indicate a probable dendritic cell origin for this lymphoma similar to that seen in histiocytosis X and some cases of malignant histiocytosis, but apparently quite distinct from the S100 protein-negative, lysozyme-positive, alpha 1-antitrypsin-positive cells seen within the mononuclear phagocytic system.

Adult

Altered isozyme patterns of leucocyte alkaline phosphatase in disease states.

Leucocyte alkaline phosphatase (LAP) is a granulocyte enzyme whose concentration varies in disease states. In order to determine whether the pattern of expression is altered in leukaemic granulocytes, we have analysed the LAP isozyme pattern of a series of normal subjects and patients with various haematological diseases. Electrophoretic patterns of partially purified LAP samples were determined by polyacrylamide gel electrophoresis in the presence of Triton X-100. These patterns were reproducible on repeated samples from the same patient. Presence of the LAPf and LAPs isozymes were determined after staining with the dye Fast Blue BB. Granulocytes were obtained from 15 normal subjects. Thirteen of these samples had only the LAPs isozyme. The other two had LAPs, plus a small amount (less than or equal to 10% of total) of LAPf activity. Eight patients with stable phase chronic myelogenous leukaemia (CML) had only small amounts of the normal LAPs isozyme and no evidence of LAPf . Of 11 patients with CGL who clinically had blast crisis. 10 had both LAPs and LAPf . The eleventh patient who was Ph1 negative had only LAPs. Three of five patients with polycythaemia vera had only the LAPs isozyme while two had both isozymes. Six patients with non-malignant leucocytosis had only LAPs. We interpret this data to indicate that the increased levels of LAP activity in some CGL blast crisis patients are primarily related to synthesis of the LAPf isozyme.

Alkaline Phosphatase

Leukocyte alkaline phosphatase: another organ-specific alkaline phosphatase.

We have used enzyme specific inhibitors and heat inactivation to distinguish Leukocyte alkaline phosphate (LAP) from other organ-specific alkaline phosphatases as well as to compare LAP from normal granulocytes and leukemic cells with elevated LAP. The heat inactivation and inhibition curves of LAP are quite different from those of other organ-specific alkaline phosphatases. The inhibition curves and heat inactivation characteristics of LAP from normal granulocytes and that obtained from chronic granulocytic leukemia (CGL) blast phase cells with elevated LAP are identical. These data suggest that LAP is distinct from other organ-specific alkaline phosphatases, particularly placental alkaline phosphatase. We also conclude that the LAP present in cells with elevated levels is very similar or identical to that of normal granulocytes.

Alkaline Phosphatase

Phase I evaluation of semustine in a weekly schedule.

A phase I study of weekly semustine was conducted in 32 patients with advanced cancer. Doses were escalated from 18 to 36 mg/m2/week. At a dose of 36 mg/m2/week, 43% of the patients developed platelet counts less than 100,000/mm3 after a median of 20 weeks on study, and 25% developed wbc counts less than 3000/mm3 after a median of 16 weeks on study. Drug-related nausea was reported by only one patient and was the only subjective toxic effect reported. Tumor regressions were noted in patients with adenocarcinoma of the colon, melanoma, and mixed adenocarcinoma and squamous cell lung cancer. A reasonable starting dose for phase II studies is 36 mg/m2/week, with dose adjustments based on platelet and wbc counts.

Dose-Response Relationship, Drug

Totally implanted system for intravenous chemotherapy in patients with cancer.

A totally implanted system for improved central venous access has been investigated in 20 patients with cancer (six with solid tumors, four with leukemia, and 10 with lymphomas) who were treated with aggressive chemotherapy regimens and who lacked peripheral venous sites. The system is implanted using local anesthesia and consists of a subcutaneous injection port connected to a Silastic catheter threaded through the subclavian vein into the superior vena cava. Injections and continuous infusions (for up to three weeks) of virtually all classes of antineoplastic agents, antibiotics, blood components, and intravenous solutions were administered through the system. The system was filled with heparinized saline and not otherwise flushed between uses. The system has remained functional for periods exceeding 450 days (mean 235 days). There was no significant local irritation and no system became infected. None of 18 large-bore catheters (0.63 mm lumen) became occluded (seven to 300 days), whereas five of six small-bore catheters (0.38 mm lumen) became occluded (90 to 420 days). Three of the occluded systems were replaced. Acceptance has been excellent, and patients have had no impediment to normal activities. This system appears to be an alternate means of safe and reliable central venous access with improved convenience and cosmetic acceptability.

Antineoplastic Agents

Totally implanted venous and arterial access system to replace external catheters in cancer treatment.

A totally implanted venous and arterial access system was tested in 30 cancer patients. The device, an injection port (Infuse-A-Port, Infusaid Corp., Sharon, Mass.), consisted of a 3.5 by 1.5 cm conical chamber with a self-sealing silicone rubber septum connected to a Silastic catheter. Ten patents had the injection port operatively placed for arterial access. A total of 39 bolus injections and 18 continuous infusions lasting an average 5.4 +/- 3.4 days were administered through the port. The total time of arterial access ranged from 70 to 370 days. No special program of heparinization was required to maintain patency. The injection port was used for central venous access in 20 patients. The first six patients had a small lumen catheter of 0.38 mm internal diameter, and five had occlusion between 142 and 447 days. Subsequently, 19 ports with a larger catheter lumen of 0.63 mm were used. These ports functioned for an average of 274 +/- 110 days (23 to 382 days). There were 380 single bolus injections and 64 continuous infusions. A variety of anticancer agents as well as whole blood, blood products, and antibiotics were administered with the device without difficulty. Patient acceptance was excellent.

Adult

Splenomegaly without an apparent cause.

Twenty-eight patients undergoing splenectomy for splenomegaly of unclear causation are presented. The cause of splenomegaly was determined at splenectomy in seven patients, none of whom had lymphoma. In three additional patients, disease associated with splenomegaly developed in the follow-up period after splenectomy. During the entire follow-up period, only one instance of lymphoma has developed. Especially in young patients who have a history of recent infection, a delay in performing splenectomy for splenomegaly is indicated.

Adolescent

The treatment of chronic lymphocytic leukemia with COP chemotherapy.

Since single drug therapy of chronic lymphocytic leukemia (CLL) has not resulted in prolonged remissions of advanced disease, we initiated a program of combination chemotherapy, COP (cycloposphamide, vincristine sulfate, prednisone) for CLL patients with increasing adenopathy, spenomegaly, and/or signs of marrow failure defined as either anemia or thrombocytopenia. Thirty-six patients received COP either as initial therapy or following progression of disease on single agent therapy. The response rate was 72% with 26 patients responding (16 complete remissions, and 10 good partial remissions). The responses lasted from 8 to 50+ months. Sixteen of the responding patients remain in remission, 2 have active disease and 8 have died. Median survival has not yet been reached but the two-year survival from initiation of COP of the responding patients (complete and good partial response) is 90%. Ten patients had either poor partial or no response with median survival of 18 months. The median survival of the entire group of 36 patients is 35 months. COP is an effective and well tolerated therapy for advanced chronic lymphocytic leukemia.

Cyclophosphamide

Attitudes toward risk factor behavior of relatives of cancer patients.

BACKGROUND: Targeted health promotion requires an identifiable subpopulation which is accessible, at increased risk, receptive to input, and receptive to change. Relatives of recently diagnosed cancer patients may meet these criteria and have not previously been investigated as recipients of preventive education regarding smoking and diet. METHODS: This study investigates these factors, beliefs regarding perceived susceptibility to cancer, and attitudes toward behavior change in 101 relatives of 50 patients with smoking-related cancers, breast cancer, and other diet-related cancers. Congruence of attitudes between patients and relatives, another possible factor in changing health behaviors, also was assessed. RESULTS: Access to relatives of patients was very high, as was their willingness to discuss these issues (99% of relatives contacted participated in the survey). Relatives' ratings of relevant risk factors were generally higher than those of patients; ratings of their own vulnerability were moderate. Within diagnostic groups, there was high concordance of belief between patients and relatives for certain types of risk, such as heredity for breast cancer (r = 0.81) and smoking for smoking-related cancers (r = 0.52), but not for dietary factors. CONCLUSIONS: The high level of access suggests that relatives may be receptive to discussing issues of behavior risk and change. They are at least as aware as patients of cancer risk factors. Spontaneous behavior change was very low. They may therefore be good candidates for targeted health promotion regarding cancer risk.

Adult