Biomedical subjects
Publications and source records attributed to J Redmond.
Six patients developed metastatic merkel-cell carcinoma and were treated with a combination chemotherapy frequently used for small-cell lung cancer. Five of six patients had a complete response for a median of 3.5 months. Overall survival from initiation of chemotherapy was a median of 6.5 months. Two patients died from major complications of therapy.
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Our patient had stage IIIAI Hodgkin's disease with synchronous myelofibrosis and myeloid metaplasia. A slowly progressive myeloproliferative disease developed over 9 1/2 years and terminated in a painful osteolytic bone disease, spinal extradural granulocytic sarcoma and acute megakaryocytic leukemia. It is likely that this was a result of the myeloproliferative disease rather than a late complication from combination chemotherapy. Our case demonstrates the importance of a curative approach to Hodgkin's disease even in the face of a coexistent disease with a long or unknown natural history.
Small cell lung cancer is an aggressive neoplasm; metastases are detected in two-thirds of patients at diagnosis with use of conventional staging, which includes bilateral bone marrow biopsy, bone scintigraphy, and computed tomography (CT) of the head and abdomen. In 25 patients, small cell lung cancer was staged prospectively with both conventional staging and a magnetic resonance (MR) imaging protocol that included 1.5-T MR imaging of the pelvis, abdomen, spine, and brain. According to conventional staging, 14 patients had extensive disease and 11 patients had limited disease; according to staging with MR, 19 patients had extensive disease and six had limited disease. All metastatic disease sites seen with conventional staging were identified on MR images. MR images showed additional metastatic involvement in bone (four patients) and liver (three patients) not detected at conventional staging. A low-attenuation hepatic lesion on a CT scan was identified as a hemangioma on MR images. These preliminary data suggest that small cell lung cancer may be accurately staged with use of a single MR imaging study.
The conventional estimation of motor, sensory, and mixed nerve conduction velocities reflects activity in the fastest conducting, heavily myelinated nerve fibers that are only a small proportion of the total. Unmyelinated and thinly myelinated fibers are not evaluated by this technique and numerically represent the largest group of fibers in human cutaneous nerves. The availability of new quantitative techniques to study this aspect of sensory function is an important addition to standard electrodiagnosis. Patient understanding and cooperation is essential because subjective responses are evaluated. We evaluated a reference range for 20 healthy subjects as well as variability on repeated testing. Vibration and thermal thresholds were measured bilaterally at several sites. Measurements were repeated at intervals ranging from two days to three months. There was no side difference but substantial site differences were noted for all measurements. Intraindividual variation was substantial but within the expected range for a psychophysiologic test. Close correlation was noted between various measurements at same and different sites, indicating a great degree of interindividual variation. The Marstock method is recommended for routine clinical use.
Diffuse well-differentiated lymphocytic lymphoma (D-WDLL) and chronic lymphocytic lymphoma (CLL) represent closely related neoplasms which may have indolent courses. Dating back more than one century, reports of associated second primary malignancies continue to intrigue clinicians. A case of synchronous D-WDLL and gastric adenocarcinoma, presenting as splenomegaly and iron deficiency anemia, is presented. The case and literature are reviewed.
A case of acute, transient agranulocytosis and thrombocytopenia associated with ingestion of dipyrone is reported. This once widely used analgesic, which is now banned in the United States, was obtained by the patient as "aspirin" while traveling in Mexico. Studies of the effects of this patient's serum on purified CD34+ marrow cells, which were highly enriched for hematopoietic progenitors, showed not only a drug-dependent suppression of the in vitro growth of myeloid progenitors, as has been reported previously, but also a drug-dependent suppression of primitive multipotential progenitors (CFU-Mix) and erythroid progenitors (BFU-E). These findings indicate that autoimmune, antibody-hapten interactions which have been reported to occur in dipyrone- and aminopyrine-induced agranulocytosis are not restricted to the neutrophil lineage.
Patients with chronic disabling low-back pain have poor prospects of returning to work. The authors tested a treatment program of functional restoration with behavioral support through 1 year prospective observation of patients disabled for an average of 19 months without evidence of surgically correctable disease. Ninety patients were studied: 59 program graduates, five program dropouts, 17 patients denied program authorization by their insurance carriers, and six crossover patients. Three patients were admitted but refused to participate in the treatment program. Initial demographic, physical, and self-assessment attributes were similar for all four groups. At year's end, 81% of program graduates, 40% of the dropouts, and 29% of those denied the program had returned to work. All six crossover patients were working 6 months after treatment. Program graduates showed significant improvements in self-assessed pain, disability, and depression, and in physical capacities after 3 weeks of treatment. These improvements were maintained through the year except for partial decreases in frequent lifting, cycling endurance, and isokinetic trunk extension strength. Functional restoration with behavioral support is an effective treatment for patients with chronic, disabling low-back pain, as measured by self-assessments, physical capacities, and return to work.
We have previously reported an algorithm that invokes several imaging modalities in the early detection of metastatic and benign disease of the spine in patients with cancer (J Clin Oncol 4:576, 1986). The development of new lesions (shown by Tc99m bone scans) in cancer patients with normal neurological examinations is further evaluated with plain radiographs, spinal computed tomography (CT), and CT myelography (CT-M). Of 60 patients in the original study, 28% were diagnosed as having only benign disease and the remainder had spinal metastases. Thecal sac impingement was seen in 47% of patients with metastatic disease and disruption of the posterior vertebral cortex was noted in all patients with epidural compression. We now report the 2-year follow-up of 55 of these patients. Without treatment, the 17 patients diagnosed with benign disease have shown no evidence of local failure in the spine and median survival is greater than 27 months. Thirty-eight patients diagnosed with spinal metastases had a median survival time of 16.9 months. Radiation therapy directed by CT-M findings provided pain relief in 78% of patients with back pain and metastatic disease. No patient, including 19 with thecal sac impingement, developed clinical myelopathy. These results demonstrate the usefulness of an imaging algorithm for the early identification and distinction of spinal metastatic disease and benign disease in patients with cancer.
Rat mast cells with the properties of mucosal mast cells (MMC) proliferate in cultures of haemopoietic tissue in the presence of conditioned medium (CM) from antigen- or mitogen-activated T lymphocytes. The present study shows that recombinant rat interleukin-3 (rIL-3) both stimulated the development of MMC from bone marrow (BM) precursors and maintained the proliferation of rat MMC lines in an identical manner to that of CM. The content per cell of the MMC granule-specific proteinase RMCPII was similar in both IL-3- and CM-stimulated cultures. Passage of CM through DEAE-cellulose separated two active peaks that stimulated autologous MMC proliferation. The biochemical properties of peak 1 were similar to those of murine IL-3 and stimulated multi-potential stem cell development in soft agar cultures of BM cells from rats treated with 5-fluorouracil (which enriches for haemopoietic stem cells). RIL-3 was also active in this assay whereas peak 2 was not, demonstrating that peak 1 contained IL-3 activity. The presence of MMC in the majority of multi-potential colonies in the soft agar cultures confirmed the early stem cell origin of the MMC lineage. The cultured BM-derived mast cells in the rat are analogues of the MMC subset that is most readily observed proliferating in the gastrointestinal tract in response to helminth parasite infection. The demonstration that IL-3 is responsible for the development and proliferation of MMC should lead to a better understanding of the functional roles of these cells.
A 60-year-old man with postpolycythemic myeloid metaplasia developed acute neutrophilic dermatosis (Sweet's syndrome), which responded to systemic steroid therapy. Six months later he developed acute myelogenous blast crisis refractory to leukemic induction therapy.
The authors reviewed 1373 consecutive cases of patients with oral head and neck cancer or lung cancer and identified 25 patients with multiple primary neoplasia (MPN). All 25 MPN cases had squamous carcinoma of the head and neck; however, only 40% (N = 10) had squamous carcinoma of the lung. The histologic types of non-squamous lung carcinoma were: adenocarcinoma 36% (N = 9), small cell carcinoma 20% (N = 5), and large cell undifferentiated carcinoma 4% (N = 1). Of 927 cases of MPN of the head and neck and lung reported in the English language literature, only 100 cases (10.78%) demonstrated a histologic discrepancy between the primary tumors. Recent reports demonstrate a histologic shift toward non-squamous lung carcinoma in MPN that is similar to our data, and that corresponds to the increase in non-squamous carcinomas recently seen in lung cancer in general. Possible implications of these findings are discussed.
A cell-free, water-soluble cytotoxin from an ovine strain of Pasteurella haemolytica biotype A serotype 1 killed sheep bronchoalveolar macrophages at 37 degrees C, but not at 4 degrees C or 22 degrees C. The cytotoxin was stable over the pH range 2-12, resistant to heat at 60 degrees C but inactivated at 100 degrees C or by autoclaving. Trypsin also destroyed the cytotoxin, which is therefore thought to contain a protein component essential for biological activity. A preliminary purification of the crude cytotoxin using gel-filtration column chromatography resulted in the isolation of a biologically active fraction which resolved as a single protein band and one carbohydrate band on non-dissociating polyacrylamide gels. However, this fraction resolved into approximately 16 component bands on a sodium dodecyl sulphate polyacrylamide gel.
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New lesions were shown by Tc99m bone scans to have developed in sixty patients with known metastatic cancer or high-risk primary cancer and normal neurologic examinations; they were further evaluated with plain radiographs, spinal computed tomography (CT), and CT myelography (CT-M) according to an algorithm. Three groups were identified based on plain radiographs: group 1 (normal radiograph), group 2 (compression fracture as indicated by radiograph), group 3 (evidence of metastasis as indicated by radiograph). In group 1 (n = 18), spinal CT revealed that 33% of the patients had benign disease and 67%, metastases; epidural compression was seen in 25% of the patients with metastasis as indicated by CT-M. In group 2 (n = 26), CT-M disclosed that 38% had a benign compression fracture and 62% had metastases and that 63% of the patients with metastases had an epidural compression. In group 3 (n = 16), spinal CT revealed that 15 patients had metastases (one patient had benign disease). Epidural cord compression was seen in 47% of the patients with metastatic disease. In all groups, the presence of cortical bone discontinuity around the neural canal (seen in 31 patients) was highly associated with epidural compression (seen in 20 patients). Our approach allowed the early and accurate diagnosis of spinal metastasis and epidural tumor as well as the diagnosis of benign disease and was useful in planning optimal local therapy.
Fifty-six patients with advanced non-Hodgkin's lymphoma (NHL) were entered into a phase II study of prednimustine, an ester of chlorambucil and prednisolone. All patients were refractory to extensive prior combination chemotherapy. Therapy with prednimustine, 100 mg/m2/day orally, was given for three consecutive days every 2 weeks. The overall response rate in 43 evaluable patients was 30% (13/43), with 9% (4/43) achieving complete response (CR) and 21% (9/43) achieving partial response (PR). In the favorable histology subgroup (23 patients), the response rate was 39% (9/23), with 4% (1/23) achieving CR and 35% (8/23) achieving PR. In the unfavorable histology subgroup (20 patients), responses were seen in 20% (4/20) with 15% (3/20) achieving CR, all in heavily pretreated diffuse histiocytic lymphoma. Toxicity of this regimen was mild, with leukopenia below 3,000/mm3 in 22% and thrombocytopenia below 90,000/mm3 in 16% of patients. A positive correlation was observed between response and hematologic toxicity, indicating the potential for a dose-escalation schedule in future trials. These data confirm activity of prednimustine in NHL refractory to standard treatment. In view of its relatively mild toxicity, we conclude that prednimustine is an appropriate agent to test in combination chemotherapy regimens in this group of lymphomas.
Two patients with poor-prognosis leukemia were treated with high-dose cytosine arabinoside (Ara-C), 3 g/m2, for induction. Both patients developed serious jaundice in the second posttreatment week. Clinically, the jaundice was characterized by conjugated hyperbilirubinemia, normal amino transferase levels, significant elevation of alkaline phosphatase, and no evidence of obstruction. Microscopic examination of the liver showed only passive congestion with blood, and no bile lakes or plugs. This was believed to be most consistent with drug-induced intrahepatic cholestasis, possibly as a result of injury to the hepatocyte transport system.