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Biomedical subjects

N K Cheung

Publications and source records attributed to N K Cheung.

At least 163 records · Page 9Linked to original sources
PubMed1986

Diagnostic imaging of human neuroblastoma with radiolabeled antibody.

In a previous study, the authors showed that iodine-131 labeled monoclonal antibody (Mab 3F8) could be used to image human neuroblastoma xenografts in mice with excellent tumor-to-tissue ratios. In this study they report their experience with six patients scanned with radiolabeled 3F8. There was strong accumulation of the labeled antibody in viable tumor, but no significant uptake was noted in normal brain, liver, spleen, or adrenal glands. Tumor-to-nontumor activity ratios varied but were approximately 10:1-20:1. This ratio yields good contrast for visualization. Time-activity curves show that radioactivity levels in normal tissue have a half-time of about 40 hours, whereas tumor tissues show a half-time of about 60 hours. Significant gastric secretion of free iodine demonstrated that the Mab was being deiodinated. Calculated radiation doses indicate that tumors receive at least ten times the dose to other tissues. The results indicate that Mab 3F8 has clinical potential for both imaging and therapy of human neuroblastomas.

Adolescent↗
PubMed1986

Detection of neuroblastoma cells in bone marrow using GD2 specific monoclonal antibodies.

Three murine monoclonal antibodies (Mab) against a cell surface antigen, the disialoganglioside GD2, were investigated for detecting bone marrow metastasis in patients with neuroblastoma (NB) by indirect immunofluorescence (IF). As few as 0.01% NB cells could be detected. No Mab reactivity was found in 60 non-NB marrows. Thirty-five marrows from patients with stage III and stage IV NB at diagnosis were examined during the course of their disease. Tumor involvement was found in 74% by Mab, 55% by the two-layer soft agar clonogenic assay (CA), and 27% by conventional histochemical stains. All marrows containing NB histologically were positive for tumor by Mab; 71% were also positive by CA. Of histologically negative marrows, 63% were Mab positive, the majority (78%) of which were also positive by CA. All Mab nonreactive samples were negative histologically and by CA. We conclude that these antibodies are highly sensitive and specific in detecting NB metastasis in bone marrow.

Animals↗
PubMed1986

Antibody response to Escherichia coli L-asparaginase. Prognostic significance and clinical utility of antibody measurement.

By using a modification of the microtiter solid-phase radioimmunoassay, we have measured Escherichia coli L-asparaginase (L-ASP) specific IgG, IgG4, and IgE antibodies in children who received L-ASP as part of their chemotherapy for leukemia and lymphoma. In 13 children with acute lymphoblastic leukemia induced with vincristine, prednisone, and L-ASP (10,000 IU/M2 i.v. each week for 3 weeks), seven developed high titer specific IgG antibodies. Four of the seven relapsed at the time of their peaking IgG response (6-10 months). None of the six with low or absent L-ASP antibody response have relapsed (followed for 20-35 months). In six children with allergic reactions to L-ASP reinduction, all had high titers of L-ASP specific IgG4 (greater than or equal to 20 U/ml) at the time of their reaction. In 16 other children with low L-ASP IgG4 (less than 13 U/ml), none demonstrated allergic reactions to rechallenge. Specific IgE was not consistently detectable in either group. In 21 patients with leukemia or lymphoma on L-ASP with cyclophosphamide-containing regimens, none developed significant IgG antibody response, compared with seven of 13 not receiving cyclophosphamide (p less than 0.001). We conclude: (a) development of L-ASP antibodies may have prognostic significance; (b) the detection of specific IgG4 can predict L-ASP allergy; and (c) cyclophosphamide-containing regimens reduce antibody formation to L-ASP and may allow repetitive (without anaphylaxis) and more effective (avoiding neutralizing antibodies) use of L-ASP.

Adolescent↗
PubMed1986

Surgical endoscopy training in a university program.

Recent directives from the American Board of Surgery requires that applicants become familiar with a variety of endoscopic procedures. The purpose of this report is to review the VA Medical Center's two and a half year experience following the establishment of a surgical endoscopy unit. During the first year, July 1982-June 1983, 212 procedures were performed. These included 64 Colonoscopies (C), 98 Gastroscopies (G), 42 Flexible Sigmoidoscopies (S) and 8 Choledochoscopies (CD). The following year 564 procedures were performed (C-201, G-269, S-86, CD-8). Over the last 6 months 210 procedures were performed (C-98, G-86, S-22, CD-4). Senior surgical residents in their fourth or fifth year of training spent 4 months in the endoscopy service as part of their surgical oncology rotation. Technical and diagnostic competency was achieved in 2 to 4 months. This review indicates that the volume of cases, currently averaging 45 per month, is adequate to train surgical residents and support an independent endoscopy service. The establishment of the unit has also been associated with the development of screening programs for colon and esophageal cancers as well as broader applications of some of the newer indications of fiberoptic endoscopy. Future plans include introduction of variceal sclerotherapy and ERCP.

Endoscopy↗
PubMed1985

Preoperative intra-arterial infusion chemotherapy for advanced squamous cell carcinoma of the mouth and oropharynx.

Twelve patients with advanced locoregional (Stage III and IV) squamous cell carcinoma of the oral cavity and oropharynx underwent treatment with cisplatin, vinblastine, bleomycin, and 5-fluorouracil, given by intra-arterial infusion, as primary adjuvant therapy, in preparation for radiation therapy and surgery. Responses were observed during or immediately after infusion therapy in 8 of 12 (67%) of patients (1 complete response, 7 partial responses). Infusion chemotherapy was followed by radiation therapy alone in five patients and by radiation and surgery in six patients. The protocol was initiated in August 1981, and six patients are now free of their primary cancer, at 21 to 36 months, whereas six have died with disease. Arterial infusion of a combination of effective antineoplastic agents is a promising method for the preparation of selected patients for radiation therapy and surgery, as it is less likely to produce serious systemic toxicity and it requires a shorter period than systemic neoadjuvant chemotherapy.

Aged↗
PubMed1985

Ganglioside GD2 specificity of monoclonal antibodies to human neuroblastoma cell.

Four monoclonal antibodies (3F8, 3A7, 3G6, and 2F7) against human neuroblastoma cells have been suggested to react with surface glycolipids of these cells. In this report these monoclonal antibodies were shown to be specific to the disialoganglioside GD2 using a thin-layer chromatography (TLC)-immunostaining method. When mixed human brain gangliosides were developed by TLC in two different solvent systems and incubated with each of the monoclonal antibodies, only GD2 was stained. These antibodies also reacted with highly purified GD2 on the plate. These findings suggest that GD2 provides an antigenic site on the surface of human neuroblastoma cells.

Animals↗
PubMed1985

Underestimation of specific immunoglobulin E by microtiter plate enzyme-linked immunosorbent assays.

We developed an ELISA by use of monoclonal anti-IgE to measure allergen-specific IgE. We measured perennial ryegrass (PRG) specific immunoglobulin E (sIgE) with conventional single incubations and with the recently reported transfer method to decrease interference in the assay. Paired sera in 10 patients before and during immunotherapy with PRG extract were analyzed for PRG sIgE with single serum incubations and with the sum of five serial serum incubations. A standardized reference serum and patient sera were incubated 12 hours and then transferred to a second well, incubated 12 hours more, and transferred again. The process was repeated until five pairs of wells had been incubated with each serum dilution. Color was developed, and optical density was measured. PRG sIgE was calculated by interpolation from the reference curve. Evidence of interference was inferred when less PRG sIgE was detected by single incubation than by transfer. Inhibition of 71.3% occurred in the sera drawn during immunotherapy. Inhibition of 32.9% was found before immunotherapy. Also, a late peaking of the well-to-well curve of optical density was observed in nine of 10 sera drawn during immunotherapy (the exception had not reached full strength), whereas all of the sera drawn before immunotherapy had normal curves. This suggests that sIgE determinations performed in microtiter plate format with single incubations will usually underestimate the sIgE level. This drawback needs to be kept in mind by the clinician interpreting the results of these assays.

Enzyme-Linked Immunosorbent Assay↗
PubMed1985

Eradication of neuroblastoma cells in vitro by monoclonal antibody and human complement: method for purging autologous bone marrow.

We describe an in vitro method which is useful for purging autologous bone marrow of neuroblastoma cells. The method utilizes a single murine monoclonal antibody 3G6 (an immunoglobulin MK) which we have previously developed against the ganglioside GD2; undiluted human complement; and unfractionated whole bone marrow at 1 X 10(7) nucleated cells/ml. Tumor cell clonogenic assays, Hoechst 33342 fluorescent nuclear stain, and trypan blue viability stain methods were used to assay cytotoxicity. This complement-mediated cytotoxicity technique killed 99.9-100% of neuroblastoma cell lines NMB-7, LAN-1, LAN-5, and IMR-6, while normal marrow precursor cells were not detectably damaged. The presence of normal bone marrow did not inhibit the human complement-mediated cytotoxicity. Applying the cytotoxicity method to whole unseparated bone marrow demonstrated killing of seeded neuroblastoma cells, with no gross hemolysis or cell clumping. The method did not require expensive special equipment, use of animal complement sera, or prior fractionation of the bone marrow. The average marrow nucleated cell recovery was 95%. These studies indicate that in vitro purging of autologous marrow infiltrated with neuroblastoma with monoclonal antibody 3G6 and human complement is both technically feasible and effective in eradicating residual tumor while preserving bone marrow stem cells.

Animals↗
PubMed1985

Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells.

Using a somatic cell hybridization technique, four murine monoclonal antibodies (three immunoglobulin M and one immunoglobulin G3) were produced against a human neuroblastoma cell surface glycolipid antigen. They reacted strongly with all human neuroblastoma tumor-containing specimens and six of eight human neuroblastoma cell lines. More than 98% of each neuroblastoma cell population possessed this surface antigen, and in the presence of complement, 100% of them were killed. While melanoma and osteogenic sarcoma carried this antigen, leukemia and most Ewing's and Wilms' tumors did not. There was no cross-reaction with 30 normal or remission bone marrow samples and none with normal human tissues other than neurons in vitro. This antigen was neuraminidase sensitive, separable on thin-layer chromatogram, and did not modulate after combining with the monoclonal antibodies. These antibodies could detect less than 0.1% tumor cells deliberately seeded in the bone marrow samples. Because of their unique properties, these monoclonal antibodies may have diagnostic and therapeutic potentials.

Animals↗
PubMed1985

Oropharyngeal Candida prophylaxis in pediatric bone marrow transplant patients.

The effect of a multi-agent regimen on oropharyngeal candidiasis (OPC) prophylaxis in 16 consecutive pediatric bone marrow transplant patients was assessed. The multi-agent regimen consisted of: 1) debriding all mucous membrane surfaces within the oropharyngeal cavity with povidone-iodine 4 times a day, 2) swabbing all mucous membrane surfaces within the oropharyngeal cavity with nystatin 4 times a day, and 3) Ketoconazole given daily by mouth. Multi-agent regimen therapy was initiated on the day marrow ablative therapy began, and was terminated when the patient's absolute neutrophil count recovered to above 500/mm3. Baseline oropharyngeal fungal cultures indicated that 8 out of 16 (50%) of the patients were Candida carriers. Subsequent surveillance cultures indicated that 13 out of 16 (81.3%) of the patients had negative oropharyngeal fungal cultures during the entire period they were on the multi-agent regimen. The remaining three patients had negative oropharyngeal fungal cultures by the end of the experimental period. None of the patients developed Candida esophagitis or sepsis. The above regimen is an effective and non-toxic method to prevent oropharyngeal candidiasis in pediatric BMT patients.

Adolescent↗
PubMed1984

Multimodality preoperative treatment for advanced cancer of the head and neck.

Neoadjuvant induction chemotherapy with cisplatin, methotrexate, and bleomycin appears to improve the results of treatment of advanced stage IV head and neck cancer, compared with results in historical control subjects. Patients treated with induction chemotherapy and radiation therapy had a 29 percent overall survival rate at 3 years, which represents approximately a twofold improvement in the survival rate. Patients who were treated with chemotherapy and radiation therapy followed by surgery had more than a threefold increase in the survival rate (49 percent at 3 years), compared with historical data from our institution and elsewhere for such patients [9-11]. Distant metastases developed in 25 percent of the patients, and it thus appears that long-term, effective consolidation and maintenance chemotherapy [12,13] need to be developed for patients who receive combination therapy before surgery for head and neck cancer.

Actuarial Analysis↗
PubMed1984

Incidence of acute graft-versus-host disease with and without methotrexate prophylaxis in allogeneic bone marrow transplant patients.

Methotrexate has been used as the mainstay therapy to prevent or ameliorate graft-versus-host disease (GVHD) in allogeneic bone marrow transplantation. We began a nonrandomized study in which methotrexate was not given routinely. Fifty-five patients underwent transplant for acute leukemia (44 patients), aplastic anemia (6 patients), and other malignancies (5 patients). Methotrexate was given to 34 patients (MTX +) and was withheld in 21 patients (MTX -). Median (range) age of patients was 12 (0.8-43) years in the MTX + group, and 16 (3-45) years in the MTX- group. Mean days (+/- SEM) to engraftment (neutrophils greater than 500/microL, and platelets greater than 20,000/microL untransfused) occurred earlier in the MTX- patients (19.6 +/- 1.4 v 24.9 +/- 1.8 days for granulocytes, and 19.3 +/- 1.5 v 27.4 +/- 2.8 days for platelets, P less than .05). There were no statistically significant differences between the patient groups for the incidence or severity of GVHD (10/34 in the MTX + group had grade O-l GVHD compared to 9/21 in the MTX- group). The interstitial pneumonitis occurred at a significantly increased rate in patients who received methotrexate (15/34) compared to those patients who did not (3/21) (P = .02). However, there was also a significant relationship between the interstitial pneumonitis and the preparative regimen: if the preparative regimen contained 1,000 rad single fraction total body irradiation, 8/14 patients were affected compared to 5/22 patients affected when 1,200 rad fractionated total body irradiation was used (P = .03). Because methotrexate significantly retards hematopoietic reconstitution, randomized trials for GVHD prevention are recommended.

Acute Disease↗
PubMed1984

Von Haberer-Finney gastrectomy revisited.

Von Haberer and Finney independently introduced end-to-side gastroduodenostomy for gastrointestinal reconstruction. Clinical appraisal of this procedure with hemigastrectomy is the basis of this report. From 1967 to 1982, 113 duodenal ulcer patients underwent the operation. Indications were intractability in 58 patients, hemorrhage in 36, perforation in two, and obstruction in 17. Truncal vagotomy was performed on all patients except in five with intractability, 19 with hemorrhage, two with perforation, and 17 with obstruction. There were three postoperative deaths (2.7%). Nine patients were lost to follow-up, seven of whom were operated upon 5 or more years previously. Thus far, there has been no clinical evidence of recurrent ulcers or of dumping. Five patients, all chronic alcoholics, were below normal weight. The Von Haberer-Finney gastrectomy has certain distinct advantages: 1) direct inspection of the interior of the descending duodenum is possible during duodenotomy; 2) anatomic continuity of the gastrointestinal tract is established; 3) duodenal stump perforation does not occur because the duodenum can be decompressed via a nasogastric tube passed through the anastomosis; 4) afferent loop syndrome cannot occur; and 5) iron deficiency anemia is less likely because the duodenum is not bypassed.

Adolescent↗
PubMed1983

Reduction of interference by specific IgG with a modified microtiter solid-phase radioimmunoassay to measure honeybee venom IgE.

By means of monoclonal mouse anti-human IgE antibody, the microtiter solid-phase radioimmunoassay (MSPRIA) was modified to measure honeybee venom (HBV) IgE. HBV IgG was measured by MSPRIA(G) using affinity column purified goat anti-human IgG antibody and correlated with results obtained with staphylococcal protein A-SPRIA. Nonlinear specific IgE dilution curves were associated with high HBV IgG content. By serial transfer and assay of the supernatant, the interference of IgE by specific IgG could be reduced. The degree of interference was correlated with the specific IgG content. The principle of serial supernatant transfer and assay was applied to the standardization of reference HBV IgE serum, and the quantitation of HBV IgE contents in patients and controls. HBV IgE levels in patients allergic to honeybee stings correlated with the skin-test endpoint titrations. While 75% of the allergic patients were skin-test positive, 83% of them were IgE positive by the MSPRIA and 67% were IgE positive by the RAST.

Antibodies, Anti-Idiotypic↗
PubMed1983

Platelet-associated immunoglobulin G in childhood idiopathic thrombocytopenic purpura.

Platelet-associated IgG was studied in children with acute and chronic ITP and in patients with thrombocytopenic SLE, using the microtiter solid-phase radioimmunoassay. Of the children with acute ITP, 85% had elevated PAIgG levels. The degree of elevation of PAIgG at onset of disease did not correlate with the development of chronicity. Of the children with acute ITP, clinically and hematologically indistinguishable from the rest, 15% had normal PAIgG values. All of 22 children with chronic ITP had elevated PAIgG values. Although there was good correlation between the platelet count and the PAIgG value in children with chronic ITP, the association was not as striking in those with acute ITP; thus, factors in addition to the level of PAIgG may contribute to the thrombocytopenia in the latter group. Patients with SLE and thrombocytopenia had higher values of PAIgG than would be predicted from the platelet count; the PAIgG value is probably not the only factor determining the degree of immune thrombocytopenia.

Acute Disease↗