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Biomedical subjects

W S Hwang

Publications and source records attributed to W S Hwang.

At least 19 recordsLinked to original sources

Allogeneic bone marrow transplantation for fourteen patients with severe aplastic anemia.

BACKGROUND: Bone marrow transplantation (BMT) is the best curative approach for younger patients with severe aplastic anemia (SAA). Major obstacles to success of allogeneic BMT include graft-versus-host disease (GVHD), graft rejection and treatment related toxicities. Experience with 14 SAA patients who received BMT is reported here. METHODS: From December 1986 to May 1995, 14 patients with SAA were treated with BMT; 13 were allogeneic, and 1 was syngeneic. There were nine males and five females whose average age was 24.7 years (range 15-36 years). The median pretransplant disease duration was 93 days (range 7-610 days). Five patients were nontransfused before BMT. The pretransplant conditioning regimen consisted of 200 mg/kg cyclophosphamide (CY) intravenously, divided over four consecutive days, followed by 300 cGy total-body irradiation (TBI) on the day before BMT. Two untransfused, one transfused patient and one syngeneic transplant received CY only as preconditioning. For GVHD prophylaxis, the 13 patients were given a combination of cyclosporine and a short course of methotrexate. RESULTS: Of the 14 patients, 11 were still alive 10 to 90 months later, with functional engraftment; the median survival of 39 months. There were three deaths including one with primary graft failure with intracranial hemorrhage, and two with delayed graft rejection and sepsis. The patient who received syngeneic BMT developed late graft failure six months post-transplant, but was successfully treated with a second BMT. Acute GVHD occurred among 5 of the 13 engrafted patients, only one of whom was Grade III clinically. Chronic GVHD was observed in 2 out of 10 evaluable patients. CONCLUSIONS: The combination of CY and TBI is an effective, well-tolerated conditioning regimen for BMT in patients with SAA. The acute GVHD rate was low in our patients receiving cyclosporine. BMT is the treatment-of-choice for patients under the age of 40 with SAA, for those with human leucocyte antigen (HLA)-identical siblings or an identical twin and particularly for those patients who have not received transfusion.

Adolescent

Familial adenomatous polyposis and lung cancer.

A 43-year-old man presented with a lung nodule 19 years after undergoing a total colectomy for familial adenomatous polyposis (FAP). There had been no evidence of malignant transformation in the colectomy specimen, and current gastrointestinal investigation did not reveal evidence of tumor. Pathological analysis of the lung nodule demonstrated adenocarcinoma of the lung of the fetal type. This is the first reported case of a lung neoplasm in a patient with FAP. The development of an unusual lung tumor in a patient with FAP, a condition associated with other extracolonic tumors, suggests that there may be an association between the two conditions.

Adenocarcinoma, Papillary

Generation of lymphokine-activated killer (LAK) cell activity from malignant peritoneal effusions.

A generation of lymphokine-activated killer (LAK) cell activities from malignant peritoneal effusions was investigated in 10 patients with abdominal carcinomatosis. Five of the 10 patients were victims of colorectal cancers, three of gastric cancers, and one each of ovarian cancer and cholangiocarcinoma. Lymphocytes, the so-called effusion associated lymphocytes (EALs), were isolated from malignant peritoneal effusions by density gradient centrifugation and the plastic adherence method. These isolated EALs were subsequently cultured in the presence of recombinant interleukin-2(rIL-2), 3,000 I.U./ml, for 30 days. Natural killer (NK) cell activities and LAK cell activities of the freshly isolated and cultured EALs were examined at 0, 7, 14, and 30 days of culture by means of a standard 51Cr-release assay using K-562, HL-60, and autologous tumor cells as target cells. The NK cell activities of the freshly isolated EALs were not detected in any of the 10 patients. The LAK activities, however, could be generated in all of them, and the activities were maximal at 7 days. The longer the EALs remained in the culture, the weaker were the LAK cell activities. As far as cell growth was concerned, EALs proliferated well as long as the rIL-2 were present in the culture. Phenotypic analysis of the freshly isolated EALs revealed the presence of NK cells (22%, CD16+CD56+), T helper/inducer (18%, CD4+), T cytotoxic/suppressor (50%, CD8+), and B cells (8%, CD19+). After being cultured with rIL-2, the B lymphocytes gradually disappeared, and the T lymphocytes predominated with an increase in the percentage of T helper/inducer cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascitic Fluid

Primary non-Hodgkin's lymphoma of the mediastinum: a clinicopathological report of six cases.

BACKGROUND: Primary mediastinal non-Hodgkin's lymphoma [NHL] predominates in young adult with diffuse large B-cell histologic characteristics, and favorable prognosis. Six patients with this disease were diagnosed and treated at the Tri-Service General hospital during the period of 1986 to 1991. METHODS: Pathology data were reviewed. All cases were classified according to the International Working Formulation. All specimens were studied immunohistologic for immunoglobulin kappa and lambda light chains, common leukocyte antigen (CLA), B cell marker (L26) and T cell marker (MT1 & UCHL1). All patients were treated with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) and adjuvant radiotherapy. RESULTS: Most of the patients were young adults with bulky disease in the anterior mediastinum. All presented with symptoms attributed to a rapidly growing mass. Four patients had superior vena cava syndromes. The histologic types were B-cell type lymphoma, including immunoblastic cell in two, and diffuse large cleaved cells in four patients. Three were in stage II and the others were in stage IV. Complete response was achieved in four patients and partial response in two, with an overall response rate of 100%. CONCLUSIONS: The results suggest that primary non-Hodgkin's non-lymphoblastic lymphoma commonly occurs in young adults and had an associated aggressive clinical course. In view of these results, observation have also suggested that intensive chemotherapy and bone marrow transplantation are needed for patients who relapse or fail to get complete remission.

Adult

Combination chemoimmunotherapy with interferon-alpha and cisplatin in patients with advanced non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) has a relatively low response rate to systemic chemotherapy. Recently, several investigations have shown that interferon may augment the cytotoxic effect of chemotherapeutic agents and may improve the result of chemotherapy in treating cancers. METHODS: An open-label noncomparative phase II study investigated the efficacy and safety of combined chemoimmunotherapy for NSCLC using IFN-alpha, given by intramuscular injection with 9 million units thrice a week for a maximum of 26 weeks, and cisplatin by intravenous infusion, 100 mg/m2, every 4 weeks for a maximum of 6 cycles. Ten patients, with histology-confirmed NSCLC at stage IV of their diseases were enrolled. They included 5 men and 5 women, with an average age of 53.7 year. Five of them had adenocarcinoma; the other five had squamous cell carcinoma. RESULTS: Five patients, including two patients with squamous cell carcinoma and three with adenocarcinoma, obtained a partial response (response rate 50%). The time needed to achieve a sustained response ranged from 5 to 13 weeks with a median of 8 weeks. The response duration ranged from 14 to 37 weeks with a median of 20 weeks. The overall survival time for the ten patients ranged from 2 to 20 months with a median of 8 months. All 10 patients needed dose modifications of IFN-alpha and/or cisplatin because of myelosuppression and/or impaired renal function. Other frequently encountered side effects included gastrointestinal disturbances and a flu-like syndrome, but these were well tolerated. CONCLUSIONS: These preliminary results indicate that chemoimmunotherapy with IFN-alpha and cisplatin can be an effective alternative therapy for patients with advanced NSCLC, but there are significant side effects.

Adenocarcinoma

Single pass sequencing of a unidirectional human fetal heart cDNA library to discover novel genes of the cardiovascular system.

A human fetal heart cDNA library was constructed in the lambda gt22A expression vector. Polymerase chain reaction (PCR) was used to amplify the cDNA inserts. PCR products were purified and used in cycle sequencing reactions in the presence of a fluorescein-conjugated primer and electrophoresed on a Pharmacia A.L.F. Sequencer. Partial cDNA sequences, or expressed sequence tags (ESTs) were searched against the Genbank and EMBL databases to identify novel genes expressed in the human cardiovascular system.

Base Sequence

Diffuse-variant tenosynovial giant cell tumor: a rare and aggressive lesion.

The diffuse-variant tenosynovial giant cell tumor is rare. Although it shares histologic features with the exclusively intra-articular pigmented villonodular synovitis and local tenosynovial giant cell tumor, its behavior differs dramatically, being locally very aggressive. We report a case of a diffuse-variant aggressive tenosynovial giant cell tumor that, although diploid by flow cytometry, demonstrated trisomy 7 and 5 as well as clonal rearrangements involving chromosomes 1, 3, and 15. These cytogenetic abnormalities may be markers for aggressive behavior and useful for directing treatment.

Adult

Fine-needle aspiration of histiocytic necrotizing lymphadenitis (Kikuchi's disease).

Fine-needle aspiration (FNA) of the lymph node was done in five patients with histiocytic necrotizing lymphadenitis (Kikuchi's disease). In four patients, the aspirates were found to have many small and large atypical lymphocytes, some reactive, phagocytic histiocytes, and intense extracellular debris. Neutrophils, plasma cells, or multinucleated giant cells were not seen. These cytologic findings were considered diagnostic for Kikuchi's disease. In one patient, the aspirate did not show significant histiocytosis or tissue necrosis and was considered nondiagnostic. In patients with both typical clinical features and characteristic cytologic findings in the lymph node aspirates, FNA of the lymph node alone will suffice for diagnosis. In those patients with typical clinical features but nondiagnostic findings in the FNA aspirates, the diagnosis of Kikuchi's disease may have to be established either on repeated nodal FNA or on lymph node biopsy.

Adolescent

Ultrastructural changes of articular cartilage chondrocytes associated with freeze-thawing.

In an attempt to justify the use of cryopreserved versus fresh articular cartilage (AC) allografts, we used transmission electron microscopy (TEM) to study the ultrastructure of fresh versus frozen-thawed AC with or without a dimethyl sulfoxide (DMSO) treatment. AC explants were cut aseptically from the femoral condyles of healthy, mature rabbits when they were killed. Half of all explants were incubated in Ham's F-12 medium, supplemented with antibiotics and with or without 7.5% DMSO, frozen to -80 degrees C, stored for 24 h, and thawed rapidly. These, and the control explants, were fixed with glutaraldehyde, paraformaldehyde, and acrolein in cacodylate buffer. Sections were stained for acid phosphatase (APase), postfixed with osmium, embedded, and examined under TEM. The typical organization of the matrix and the cells was noted in control sections. The chondrocytes contained intact nuclei, organelles, and discrete plasma membrane. Although some endoplasmic reticula and nuclear membrane appeared intact, distinct ultrastructural changes were observed in frozen-thawed samples treated with DMSO. These changes included condensation of chromatin, large lipid droplets, partly disrupted plasma membrane, and pericellular precipitation of APase-positive crystalites. In sections not treated with DMSO, the cytoplasm was extensively vacuolated and no distinct organelles could be detected in the chondrocytes. Little difference was noted between the matrix organization of fresh or frozen-thawed samples. Our results suggest that distinct ultrastructural changes occur in the chondrocytes following freeze-thawing of intact AC and that DMSO pretreatment may contribute to improvement in the cryopreservation of AC.

Acid Phosphatase

Prediction of chemotherapy response in human leukemia using in vitro chemosensitivity test.

We performed the dye exclusion assay (DEA) and the MTT dye reduction assay to determine the drug sensitivity of acute leukemia using short-term microplate cultures. The in vitro results were compared with the clinical response of 31 patients with acute leukemia treated by combination chemotherapy. The true-positive rates of the DEA and MTT assays were 86.7 and 91.3%, respectively; the true-negative rates were 33.3 and 77.8%, respectively; and the predictive accuracy was 62.5 and 87.5%, respectively. The DEA and MTT assays gave comparable results in drug sensitivity testing of leukemic blast cells. Our data suggest that MTT assay is the more suitable for assessing chemosensitivity in acute leukemia.

Adult

Treating carcinomatous pleural effusion by intrapleural injection of OK-432 in patients with non-small-cell lung cancer.

The effect of intrapleural injection of OK-432, a streptococcal preparation, for management of carcinomatous pleural effusion was investigated in patients with non-small cell lung cancer (NSCLC). Ten patients, including 5 men and 5 women with performance status 2-3(ECOG) and average age of 66.4 years, received OK-432 for different times after the tumor burden in effusion was relieved with adequate drainage. The response rate was 100% in terms of decreased reaccumulation of pleural fluid, improvement of general status, and disappearance of tumor cells in the fluid. The adverse effects of this treatment were mild-including fever, chills, chest pain and nausea-and all were tolerable to patients. Median survival time was 4.5 months after treatment. This preliminary report indicates that intrapleural injection of OK-432 is an effective alternate method for management of carcinomatous pleural effusion to improve the quality of life for terminally ill cancer patients.

Adenocarcinoma

Intrathoracic extraskeletal Ewing's sarcoma: a case report and review of literature.

Extraskeletal Ewing's sarcoma (EES) is a rare tumor of soft tissue. As an uncommon clinical entity with histologic features similar to those of other small round-cell tumors, EES occasionally produces difficulty in diagnosis. Hence, diagnosis should be confirmed by histochemical, immunohistochemical and clinical findings. Here, we describe a man aged 29 years who had intrathoracic mass was diagnosed as EES after incisional biopsy of the tumor. The presence of glycogen in the tumor cells was demonstrated by periodic acid-Schiff (PAS) stain but immunoreactivity for cytokeratin, epithelial membrane antigen, leukocyte common antigen, desmin, actin and neuron-specific enolase were absent; vimentin was present. The patient was successfully treated with VIP regimen (etoposide, ifosfamide and cisplatin) followed by local irradiation. He remained alive without recurrence after one year. A review of the literature and recent advances in the treatment of EES are reported.

Adult

Captopril-induced agranulocytosis: a case report.

Captopril 12.5 mg twice daily was initially administered given to a woman with chronic renal failure and hypertension. Three weeks later, she developed chills, high fever and sore throat. Hemogram showed severe neutropenia; the white cell count showed 600/cu mm; bone marrow aspirate and biopsy revealed a paucity of myeloid series. Antineutrophil antibody was not detected in the serum. The neutrophil counts returned to normal after captopril was discontinued two weeks later. We recommend that the peripheral white blood cell count in patients whom captopril is prescribed must be carefully monitored in the first three months, particularly in those with impaired renal function.

Aged

A new variant of lethal neonatal short-limbed platyspondylic dwarfism.

This article describes an unusual skeletal dysplasia in a male fetus diagnosed by ultrasound at 18 weeks of gestation. The clinical and radiologic findings resemble thanatophoric dysplasia. Histologic examination revealed abnormalities in the resting cartilage, physeal growth plate, and bone. The resting cartilage contained peculiar large chondrocytes with huge lacunae. The growth plate revealed absence of column formation and hypertrophic vacuolated chondrocytes extending far into the metaphyseal bone trabeculae. The bone was hypercellular with absence of lamellar bone. The cortical bone was scanty and woven. The histopathologic features are, therefore, unique and differ from all other well-recognized varieties of short-limbed platyspondylic dwarfism.

Bone and Bones

Primary colorectal lymphoma in Taiwan.

BACKGROUND: Sixteen patients with primary lymphoma of the colon and rectum were studied. METHODS: The median age of these patients was 34 years, and 13 were men. These patients often experienced abdominal pain, diarrhea, a palpable abdominal mass, weight loss, bloody stools, and tumor of the cecum. Intermediate or high-grade lymphomas occurred in 14 patients, and 5 patients had T-cell lesions. The diagnoses were established by using laparotomy in 14 patients and colonoscopic biopsy in 2 patients. Fourteen patients had surgical resections followed by chemotherapy: cyclophosphamide, doxorubicin, vincristine, and prednisolone in 10; cyclophosphamide, vincristine, and prednisolone (COP) in 2; and cyclophosphamide, vincristine, methotrexate, and prednisolone in 1 patient. Two patients underwent biopsy alone followed by chemotherapy with COP in one and chemotherapy with prednisolone in the other. RESULTS: The median follow-up time was 38 months (range, 2-82 months). Eight patients are alive with no evidence of disease (range, 10-82+ months). Six patients died of disease from 2 to 44 months after diagnosis. One patient who had no evidence of lymphoma died of esophageal carcinoma at 61 months. The median survival time was 59 months. CONCLUSIONS: The authors' experience with colorectal lymphoma in Taiwan is different from that reported from Japan and other countries. The patients of this study were significantly younger and many had T-cell lesions. Despite the frequently poor histologic types, surgical resection and adjuvant chemotherapy can result in long-term, disease-free survival in many patients with primary colorectal lymphoma.

Adolescent

Collagen fibril structure of normal, aging, and osteoarthritic cartilage.

The collagen architecture in normal, aging, and osteoarthritic articular cartilage was studied optically using a new silver staining technique based on specimens from 50 autopsy cases, four amputated limbs, and six osteoarthritic knees. In the normal articular cartilage, the collagen fibrils in the superficial zone were compactly arranged into layers of decussating flat ribbons mostly parallel to the artificial split lines. The fibrils showed a tendency to condense into vertical arcade columns undergirded by tangential bundles in the intermediate zone. In the deep zone, the fibrils formed a random meshwork with a slight preponderance of vertical fibrils in the perilacunar region. Three types of early degradative lesions involving the collagen network were identified. Type I lesions consisted of focal superficial disruptions related to age and friction. Type II lesions consisted of focal disruptions of tangential fibrils in the intermediate zone leading to cyst formation, probably representing a form of local stress failure. Type III lesions were found in the patella and consisted of marked swelling of the superficial zone, the cause of which was unknown. Lesions of varying severity were seen within each of the three types; the morphological changes of the more severe lesions overlapped with those of clinically overt osteoarthritis.

Adolescent

Localization and therapy of human cervical tumor xenografts with radiolabeled monoclonal antibody 1H10.

Murine IgG3 monoclonal antibody (Mab) 1H10, which recognizes a tumor-associated antigen expressed on the surface of more than 40% of human cervical carcinoma tissues, was used for in vivo localization and therapy of cervical tumor xenografts. A human cervical carcinoma cell line, CaSki, was used as our experimental tumor system. Mab 1H10 antigen expression on the surface of CaSki cells was found to be cell-cycle independent. The ability of Mab 1H10 F(ab')2 to bind to CaSki tumor xenografts was verified by direct immunohistochemical staining of thin tumor sections with a Mab 1H10-peroxidase conjugate. Radioimmunoscintigraphy of nude mice bearing CaSki tumors after iv administration of [131I]1H10 F(ab')2 showed clear tumor images 48 hr after Mab injection. Radiolabeled Mab 1H10 F(ab')2 was found to specifically localize in solid CaSki tumors 96 hr after antibody injection. Radioactivity in tumor tissue was 4 times higher than that in kidney tissue and over 6 times higher than that in liver tissue. Mab 1H10 F(ab')2 binding to xenografted CaSki tumors was 17 times greater than a control IgG3 F(ab')2 after 96 hr. Therapy of athymic mice bearing established CaSki tumors with three iv injections of 100 microCi [131I]1H10 F(ab')2 resulted in extensive tumor necrosis and significant suppression (p < 0.05) of tumor growth compared to that in control mice. These results indicate that Mab 1H10 F(ab')2 may be clinically useful for detection or treatment of cervical cancer.

Animals

Myeloblastic leukemoid reaction in paroxysmal nocturnal hemoglobinuria associated with myelodysplasia.

Paroxysmal nocturnal hemoglobinuria (PNH) has been observed to evolve into myelofibrosis and acute myeloid leukemia. Myeloblastic leukemoid reaction has not been described in PNH. We described a patient with PNH with myelodysplasia and septicemia. The marrow aspirates showed a picture of myeloblastosis which subsided when sepsis was controlled. The myeloblastic leukemoid reaction in our patient related to overwhelming sepsis, splenectomy and overt hemolysis.

Bone Marrow