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Biomedical subjects

W Gordon

Publications and source records attributed to W Gordon.

At least 37 records · Page 2Linked to original sources

Concurrent chemotherapy/radiotherapy for limited small-cell lung carcinoma: a Southwest Oncology Group Study.

The Southwest Oncology Group (SWOG) has conducted a phase II study to explore the efficacy and toxicity of initial, concurrent use of radiation therapy with cisplatin, etoposide (VP-16), and vincristine in limited-stage small-cell carcinoma of the lung. Two courses of cisplatin, VP-16, and vincristine chemotherapy were given with concurrent radiotherapy (XRT) to the primary tumor to a total dose of 4,500 cGy. Elective brain XRT was given to all patients concurrent with a third course of cisplatin/VP-16 therapy. Consolidation chemotherapy consisting of vincristine, methotrexate, and VP-16 alternating with Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide, was given for 12 weeks following the initial induction chemotherapy/XRT program. Patients with a complete response had all therapy discontinued. Among 154 eligible patients treated, the complete response rate was 56%, with a partial response rate of 27%. The median survival is 17.5 months with an estimated 30% survival rate at 4 years from initiation of treatment. Combined modality toxicities were acceptable with the predominant toxicity being moderate to severe leukopenia and mild radiation esophagitis. The results of this treatment program appear superior to any previously reported by our group and compare favorably to those in the literature at large.

Adult↗

Medicaid versus state funding of community residences: impact on daily life of people with mental retardation.

The unintended effects on quality of life that flow from decisions regarding funding sources used to support community-based residential programs were documented. Results show that community residence program structures play an important role in determining quality of life after deinstitutionalization. Clients living under program structures flowing from the Medicaid ICF/MR funding source were less active and involved in life than were clients living in programs funded by non-Medicaid state sources. We hypothesized that the reason for this differential outcome was the result of Medicaid funding regulations and their interpretation, which create an institutional-like set of program structures leading to restrictive care patterns.

Activities of Daily Living↗

A chimeric mouse-human antibody that retains specificity for HIV gp120 and mediates the lysis of HIV-infected cells.

Murine mAb BAT123, which was made against the envelope glycoprotein gp120 of HTLV-IIIB strain of HIV type 1 (HIV-1), is capable of neutralizing HTLV-IIIB in vitro. It also inhibits the fusion between uninfected CD4+ cells and HIV-1-infected cells to form syncytia. As a step to explore the potential utility of the anti-HIV antibody in vivo, we have constructed a mouse-human chimeric antibody by rDNA techniques. The chimeric antibody, which bears the variable domains of mouse antibody BAT123 and constant domains Cr1 and C kappa of human Ig retains the Ag specificity of BAT123 as determined by its reactivity with HIV-1-infected H9 cells, gp120 in Western blot analysis, and the oligopeptide recognized by BAT123. The antiviral activities of the chimeric antibody in neutralizing HIV-1 infection as well as inhibiting the syncytia formation are also found identical to those of the parent murine antibody. Moreover, in the presence of human blood mononuclear cells, the chimeric antibody but not BAT123 (mouse IgG1) induces antibody-dependent cellular cytotoxicity. The findings point to the potential usefulness of the chimeric antibody in treating patients infected with HIV-1.

Amino Acid Sequence↗

Pre-clinical studies on boron neutron capture therapy.

The present report provides an overview of the multidisciplinary research effort on BNCT that currently is in progress at The Ohio State University. Areas under investigation include the preparation of boron containing monoclonal antibodies, the synthesis of boron containing derivatives of promazines and phathalocyanines, the development of a rat model for the treatment of glioblastoma by means of BNCT, the design of an accelerator-based neutron irradiation facility, and 10B concentration measurements using alpha track autoradiographic methods. Progress in each of these areas is described and the direction of future research is indicated.

Animals↗

Generation and characterization of monoclonal antibodies to the putative CD4-binding domain of human immunodeficiency virus type 1 gp120.

A panel of seven monoclonal antibodies against the relatively conserved CD4-binding domain on human immunodeficiency virus type 1 (HIV-1) gp120 was generated by immunizing mice with purified gp120. These monoclonal antibodies reacted specifically with gp120 in an enzyme-linked immunosorbent assay and Western blots (immunoblots). By using synthetic peptides as antigens in the immunosorbent assay, the epitopes of these seven monoclonal antibodies were mapped to amino acid residues 423 to 437 of gp120. Further studies with radioimmunoprecipitation assays showed that they cross-reacted with both gp120 and gp160 of diverse HIV-1 isolates (HTLV-IIIB, HTLV-IIIRF, HTLV-IIIAL, and HTLV-IIIWMJ). They also bound specifically to H9 cells infected with HTLV-IIIB, HTLV-IIIRF, HTLV-IIIAL, HTLV-IIIZ84, and HTLV-IIIZ34 in indirect immunofluorescence studies. In addition, they blocked effectively the binding of HIV-1 to CD4+ C8166 cells. Despite the similarity of these properties, the monoclonal antibodies differed in neutralizing activity against HTLV-IIIB, HTLV-IIIRF, and HTLV-IIIAL, as demonstrated in both syncytium-forming assays and infectivity assays. Our findings suggest that these group-specific monoclonal antibodies to the putative CD4-binding domain on gp120 are potential candidates for development of therapeutic agents against acquired immunodeficiency disease syndrome.

Animals↗

First year after stroke: tracking cognitive and affective deficits.

A total of 58 cerebrovascular accident (CVA) rehabilitation inpatients with lateralized brain damage were assessed at two time points (T1 = admission to rehabilitation facility, about 7 weeks post-CVA, and T2 = 10 months post-CVA) in the following domains: hemispatial neglect, reaction time, depression, and affect comprehension. Performance was compared with 22 age-matched control subjects. Repeated measures ANOVAs were performed with patients subdivided into groups by laterality of lesion and visual field status (a strong predictor of psychometric performance, particularly in the hemispatial-neglect domain). During this initial year after stroke onset, significant improvements were observed in hemispatial neglect and affect comprehension in the two right-brain-damaged groups, but not the left-brain-damaged group. There was also a trend for improvement in observer rating of depression in all three groups. However, there was poor resolution of reaction time and self-reported depression in all three groups. These findings suggest that these latter domains should be targeted for more aggressive therapeutic intervention. An important component of such intervention, in addition to direct treatment of deficits, should be education of both patient and family as to the nature of deficits, expectations regarding resolution, and appropriate attributions of changed behavior after stroke.

Affect↗

Concurrent chemotherapy and radiation therapy for limited unresectable non-small cell carcinoma of the lung. A phase I study.

We treated nine patients diagnosed as inoperable, but localized non-small cell lung cancer with aggressive high-dose radiation therapy and two cycles of concomitant cisplatin and 5-fluorouracil (5-FU) to determine the feasibility of this approach for this disease. This combined modality program was well tolerated by seven of our nine patients. One who had a poor initial performance status died of sepsis. Another could not tolerate the nausea and vomiting. Only one patient has suffered a local failure inside the irradiated areas. Eight have died, and 5 of 9 survived at least 1 year. The survival is at least consistent with that associated with radiation therapy alone.

Adult↗

A surface mold using iridium-192 seeds.

A radioactive mold for treating skin was constructed by embedding ribbons of iridium-192 seeds in bolus material. The mold was designed to match the treatment area outlined on the patient's skin. Computer-assisted pre-planning was performed to optimize the seed strength, number of seeds, and spacing of ribbons. An outline of the treatment area was transferred to the surface of a uniform slab of tissue-equivalent bolus material 1.3 to 1.4 cm thick and planned locations for the ribbons were marked. Seeds were loaded into the bolus material at a depth to place the sources approximately 1.0 cm from the skin. The resulting mold was flexible enough to conform to the patient's skin and the seeds were so tightly confined within the bolus that there was no possibility of loss. Isodose distributions for the mold on a flat surface agreed well with preplans. A velcro strap and neck collar were used to attach the mold to the anterior portion of the patient's neck. For situations in which radioactive surface applicators are desirable, the use of iridium-192 seeds offers uniform dose within a highly individualized treatment area.

Brachytherapy↗

Concurrent chemotherapy and radiotherapy for limited small-cell carcinoma of the lung: a Southwest Oncology Group Study.

This pilot study in limited-stage small-cell carcinoma of the lung using concurrent cisplatin (Platinol) and etoposide (VePesid) chemotherapy with radiotherapy has yielded a high complete response rate in 23 of 40 patients evaluable for response. Five of these responders have survived greater than 2 years off all therapy with a stable, high performance status. Median survival of all patients is 18 months. Toxicity has been acceptable, the most common being neutropenia. Radiation toxicities include 17 of 40 patients experiencing mild to moderate esophagitis, with one severe toxicity; and three of 40 patients developing mild to moderate radiation pneumonitis. The high complete remission observed with this program and the long tumor-free interval seen off maintenance therapy deserve further exploration. Toxicities appear only moderately greater than with other programs currently utilized.

Antineoplastic Combined Chemotherapy Protocols↗

The impact of deinstitutionalization on activities and skills of severely/profoundly mentally retarded multiply-handicapped adults.

This study evaluated the change in activity patterns and skills of severely/profoundly mentally retarded, multiply-handicapped residents as they moved from large total care institutions to community living. Twenty-seven individuals were evaluated just before leaving the institution, 3 months post-exit, and 9 months post-exit. In comparison to a nondisabled reference group, residents were less active, mobile, social, and independent both in the institution and community. Residents did show, however, significant changes toward the nondisabled pattern of daily living after moving to the community. Clients improved in 4 of 16 skill areas within 3 months after entering the community: expressive communication, eating, serving meals and washing dishes, and meal preparation.

Activities of Daily Living↗

Dyskeratosis congenita. Haematologic, cytogenetic, and dermatologic studies.

In a family of 5 boys and 6 girls, 3 brothers have clinical dyskeratosis congenita. Teeth from 2 of the patients were taurodent , and mineral density of the enamel was significantly different from normal. The haematopoietic marrow was hypocellular and there was striking prominence of plasma cells having normal morphology; no granulomata were demonstrated. The decreased erythroid precursors in the marrow correlated with quantitatively reduced erythropoiesis demonstrated on ferrokinetic studies. Recurrent infections occurred but could not be related to neutropenia, and granulocytes and monocytes retained normal function. No abnormality was demonstrated in humoral or cellular immune mechanisms. While superficially similar, dyskeratosis congenita and Fanconi's anaemia are genetically distinct, being X-linked in the former and inherited as an autosomal recessive in the latter.

Adolescent↗

Decrease of lactoferrin concentration in the tears of myotonic muscular dystrophy patients.

Tears from myotonic muscular dystrophy (MMD) patients and normal controls were analyzed for their tear proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Lactoferrin comprised about 18% of the total tear protein in MMD patients as opposed to about 27% in normals. The albumin content relative to total protein in MMD tears was about 25% while the same value for normals is 13%. The lactoferrin/albumin ratio, was about 0.8 for MMD patients and about 2.1 for normals.

Erythrocyte Membrane↗

Pyoderma gangrenosum, vesicovaginal fistula and endometriosis. A case report.

A 47-year-old multiparous woman presented with endometriosis, true urinary incontinence, and the mucosal and skin lesions of pyoderma gangrenosum. The subsequent investigations, treatment and course are discussed, as well as the possible causal interrelationship between the above three conditions.

Endometriosis↗

Radiation therapy in the management of patients with mesothelioma.

The results of radiation therapy in the management of 27 patients with malignant mesothelioma were reviewed. Eight patients were treated with a curative intent combining attempted surgical excision of tumor (thoracic in 6 and peritoneal in 2), aggressive radiation therapy, and combination chemotherapy using an adriamycin-containing regimen. One patient achieved a 2-year disease-free interval followed by recurrence of tumor above the thoracic irradiation field. This patient was retreated with localized irradiation and is disease-free after 5 years of initial diagnosis. One patient has persistent abdominal disease at 18 months; the other 6 patients suffered local recurrence within 8-13 months of initiation of treatment. Radiation therapy was used in 19 other patients who received 29 courses for palliation of dyspnea, superior vena cava syndrome, dysphagia, or neurological symptoms of brain metastasis. A palliation index was used to determine the effectiveness of irradiation and revealed that relief of symptoms was complete or substantial in 5 treatment courses, moderately effective in 6 courses and inadequate in 18 treatment courses. Adequate palliation strongly correlated with a dose at or above 4,000 rad in 4 weeks. The management of patients with mesothelioma requires new and innovative approaches to increase the effectiveness of radiation therapy and minimize the significant potential combined toxicity of pulmonary irradiation and adriamycin.

Adult↗