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Biomedical subjects

B L Zidar

Publications and source records attributed to B L Zidar.

11 recordsLinked to original sources

A phase II evaluation of ifosfamide and mesna in unresectable diffuse malignant mesothelioma. A Southwest Oncology Group study.

BACKGROUND: Malignant mesothelioma is a highly treatment-resistant neoplasm. This study represents an attempt to define an effective form of systemic therapy. METHODS: Twenty-six patients with unresectable diffuse malignant mesothelioma were enrolled in Southwest Oncology Group (SWOG) study 8731 and treated with ifosfamide, 2 g/m2 intravenously for 4 days, and mesna 2 g/m2 intravenously for 5 days, every 3 weeks. Patients were either previously untreated with chemotherapy or had at most one prior systemic treatment. RESULTS: Two patients, or 8% (95% confidence interval, 1-25%), achieved partial response, with response durations of 4 and 6 months. One additional patient met criteria for tumor size reduction but not duration criteria. Thirteen (50%) patients had stable disease of 4 months' median duration (range, 1-13 months). The median survival of the entire group was 6.5 months. The dose-limiting toxicity was granulocytopenia (11 patients, < or = 250/microliters). CONCLUSIONS: Ifosfamide/mesna has modest activity in malignant mesothelioma. It could be tested using alternate dosage schedules and in combination with other agents in treating this highly resistant neoplasm.

Adult

Mucin-positive epithelial mesothelioma.

Mucin-positive epithelial mesothelioma is a rare, frequently unrecognized entity that should not be misinterpreted as metastatic adenocarcinoma, as each is associated with differing treatment and prognosis. Presented herein is a case of an acidic and neutral mucin-positive papillary mesothelioma of the right pleura, with cytologic, histologic, histochemical, immunohistochemical, and ultrastructural evaluation.

Adenocarcinoma

Clinical and pathologic features of primary gastric rhabdomyosarcoma.

The authors report a case of a collision tumor composed of a primary gastric rhabdomyosarcoma intermingled with an adjacent infiltrating gastric adenocarcinoma. Only eight cases of gastric rhabdomyosarcoma have been reported previously and little information is recorded about the behavior of this tumor. Gastric rhabdomyosarcoma has several distinctive clinical features. It is a highly aggressive tumor (median survival, 2.5 months) occurring in both children and adults and frequently presents as metastatic disease to lung or cervical lymph node. The initial diagnosis is often difficult to establish, especially on biopsy material. In several instances, the correct diagnosis was established only at autopsy. The authors' patient was correctly diagnosed during life and received considerable benefit from cyclophosphamide, doxorubicin, and vincristine (CAV) therapy and survived for 26 months after diagnosis. Two of the previously reported eight cases of primary gastric rhabdomyosarcoma and this case have adjacent admixed glandular gastric adenocarcinomas. Since three of the nine known cases of primary gastric rhabdomyosarcoma have an adjacent admixed gastric adenocarcinoma, there appears to be a greater than chance association between these two tumors.

Adenocarcinoma

ViVACCy--a drug schedule based on G2 blockade and prolonged infusion of multiple tubulin-binding agents. A pilot study.

A drug schedule has been devised based on a strategy of G2 blockade followed by prolonged infusion of tubulin-binding agents. The regimen consists of doxorubicin 32 mg/m2 i.v. and cyclophosphamide 320 mg/m2 i.v. on day 1 followed by vinblastine (0.3 to 1.2 mg/m2/day), cisplatin (3 to 12 mg/m2/day), and vincristine (0.04 to 0.16 mg/m2/day) by continuous intravenous infusion on days 5 to 12. Courses are repeated every 28 days. Eighteen patients with advanced solid tumors received 37 courses of chemotherapy in a pilot study to determine safe drug concentrations for the three-drug infusion for 7 days. Dose limiting toxicity was myelosuppression. Patients who received prior mitomycin-C experienced more profound thrombocytopenia than those who did not. Nonhematologic toxicities included mild nausea, vomiting, and transient elevations of serum alkaline phosphatase and serum creatinine. One patient with squamous cell carcinoma of the esophagus who erroneously received vincristine 0.8 mg/m2 instead of 0.08 mg/m2 for 4 1/2 days developed transient myalgia, ileus, and a transient peripheral neuropathy; the patient achieved a sustained complete remission for 15 months and died of unrelated causes. Minor responses and stable disease were seen in two patients with renal cell carcinoma (1 and 2.5 months), three patients with colorectal carcinoma (1.5, 2, and 4 months), and one patient with squamous cell carcinoma of the tongue (2 months). The ViVACCy drug regimen can be given without undue toxicity and may be active in solid tumors.

Adult

Normal pressure hydrocephalus in a patient with systemic lupus erythematosus.

We describe a patient who had concomitant systemic lupus erythematosus (SLE) and a normal pressure hydrocephalus. She improved only after appropriate therapy for each. Although 6 patients with arthritis and normal pressure hydrocephalus have been described, this is the first report of it occurring in a patient with SLE. It has been emphasized that normal pressure hydrocephalus can easily be overlooked in elderly patients with arthritic conditions. Since neuropsychiatric symptoms are likelier to occur in patients with SLE than in other rheumatologic conditions, the diagnosis of normal pressure hydrocephalus may be delayed or overlooked. Because normal pressure hydrocephalus is a potentially reversible cause of neurologic dysfunction, it should be considered in appropriate populations.

Aged

Serum colony-stimulating and colony-inhibitory activity in response to neutropenia.

Since sera from most species contain both colony-stimulating and column-inhibitory factors, the net CSA results from a balance between these opposing substances. Studies were performed to determine whether the increased CSA noted during neutropenia or endotoxemia is due to an increase in CSF or to a decline in serum inhibitors. Rats were treated with cyclophosphamide, total body irradiation, or endotoxin and bled during the peak CSA response. By separation studies using Sephadex G150, it was shown that serum levels of high-molecular-weight inhibitors were unchanged from control values. Minimal CSA was detected in normal serum fractions; increased activity was found in fractions from neutropenic animals. During a postcyclophosphamide rebound neutrophilia, serum CSA was undetectable; inhibitor levels were similar to those measured in untreated controls. These observations show that the increased serum CSA seen with neutropenia is due to a true increase in CSF and not to a decline in circulating inhibitors.

Agranulocytosis

Observations on the anemia and neutropenia of human copper deficiency.

Following extensive bowel resection, a young woman experienced severe malnutrition; subsequent administration of parenteral nutrition precipitated the copper deficiency syndrome. This consisted of hypocupremia, subnormal ceruloplasmin levels, anemia, and severe neutropenia. The bone marrow was megaloblastic, vacuolated, and sideroblastic; granulocytic maturation was not observed beyond the myelocyte stage. Copper sulfate therapy was followed by a marked reticulocytosis, increase in hematocrit, and recovery of neutrophils. Additional studies indicated that both serum and urinary erythropoietin values were low; serum activity increased after copper supplementation. Abnormal granulopoiesis was demonstrated using the in vitro granulocyte colony assay. The patient's granulcoytic stem cells were normal on two occasions; however, mixing studies showed that culture of the patient's copper-deficient marrow with her copper-deficient serum yielded significantly reduced numbers of granulocyte colonies. Thus, copper appears to be a necessary element for normal hematopoiesis; lack of this trace element may result in ineffective erythropoiesis and granulopoiesis.

Adult

Hairy cell leukaemia: seven cases with probable B-lymphocytic origin.

Mononuclear cells from seven patients with hairy cells leukaemia were examined for features suggestive of either a lymphocytic or monocytic origin. Immunofluorescent staining of both methanol fixed and incubated cells, using monospecific antisera, revealed a predominant cell-associated immunoglobulin in each case. Three were positive for mu and kappa chains, two for gamma and kappa chains, one for delta and kappa chain determinants and one reacted only with antigamma chain serum. Formation of EAC rosettes, a feature of both B lymphocytes and monocytes, was variable. T cells, as judged by E rosettes, were not elevated in any patient. Phytohaemagglutinin reactivity was normal in six and depressed in one case. With the exception of minimal activity in assays for glass adherence and latex particle phagocytosis, none of the cells showed features typical of monocytes. Hairy cells were negative by peroxidase stain and lacked the electron microscopic characteristics of monocytes. They did not react in either rosette or phagocytic assays with anti-A or anti-D coated erythrocytes nor did they elaborate granulocyte colony stimulating factor, a monocyte-derived in vitro granulopoietin. Although unequivocal classification of these abnormal cells is not possible, the data storngly suggests that this represents a variant of a B lymphocytic neoplasm.

Adult

Acute myeloblastic leukemia and hypercalcemia. A case of probable ectopic parathyroid hormone production.

We studied a patient with acute myeloblastic leukemia, hypercalcemia, hypophosphatemia and inappropriately elevated serum parathyroid hormone levels to define the mechanism of the hypercalcemia. On six occasions during two years, hypercalcemia occurred in conjunction with relapses of leukmia. Each time, serum calcium decreased to normal levels in parallel with reduction of the leukemic mass. During two periods of hypercalcemia, immunoreactive parathyroid hormone values were abnormally high. In addition, hormone was detected in vitro after short-term incubation of the leukemic cells (after 24 hours, the patient's cells produced 129 pg of PTH per milliliter, whereas myeloblasts from a normocalcemic patient with leukemia produced only 33 pg). In freeze-thawing experiments, 39 pg of parathyroid hormone was released form 1 x 108 of the patient's myeloblasts; no hormone was released from the normocalcemia cells. These findings suggest that the hypercalcemia resulted from ectopic parathyroid hormone production by leukemic cells.

Adult

Diphenylhydantoin-induced serum sickness with fibrin-platelet thrombi in lymph node microvasculature.

In this 16 year old boy a syndrome, characterized by high fever, generalized lymphadenopathy, splenomegaly, diffuse skin rash, facial and periorbital edema, neutropenia, thrombocytopenia, elevated serum glutamic oxaloacetic transaminase (SGOT) levels and transient electrocardiographic changes, appeared 2 weeks after the institution of diphenylhydantoin therapy. Lymph node biopsy, performed at the height of the illness, revealed widespread subendothelial fibrin exudation and fibrin-platelet thrombi in the lymph node microvasculature, a finding most consistent with thrombotic thrombocytopenic purpura. Although many types of abnormal lymph node histology have been described with diphenylhydantoin, this appears to be the first instance of this histologic picture. This syndrome may be related to a serum sickness-like illness which triggered an episode of localized coagulopathy.

Acute Disease