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Biomedical subjects

H O Douglass

Publications and source records attributed to H O Douglass.

At least 19 recordsLinked to original sources

Selectivity of the micro-leukocyte adherence inhibition assay in pancreatic cancer.

A modified leukocyte adherence inhibition assay was performed on white blood cells from patients with ductal pancreatic cancer, other malignancies, benign gastrointestinal diseases including pancreatitis, and healthy controls, using four different ductal pancreatic cancer membrane preparations and similar preparations from gastric and colorectal cancers. A mean adherence index of less than or equal to 0.2 was evidence that the leukocytes "recognized" the antigen(s). In 9 of 10 patients with localized pancreatic cancer, 13 of 15 leukocyte populations "recognized" the pancreatic cancer antigen(s) and not other tested antigen(s). Leukocytes from only 11 of 18 patients (17 of 29 assays) with metastatic pancreatic cancer "recognized" the pancreatic tumor antigen (and no other antigen). The inability to recognize the pancreatic tumor antigen(s) was not related to nutritional, biochemical or therapeutic status of the patient, but was related to the demonstration of a response to skin test antigens. In contrast, 3 of 35 leukocyte populations in 2 of 31 patients with malignancies other than pancreatic, 1 of 28 with benign gastrointestinal disease, and one of 38 healthy control populations "recognized" the antigen. The LAI is worthy of further study in the differential diagnosis of pancreatic cancer.

Adenocarcinoma

Gastrointestinal carcinoids: extrahepatic metastases and symptomatology following resection.

Of 49 patients with midgut and hindgut carcinoids, second primary distinct carcinomas occurred in 12. The most aggressive carcinoids were the 24 that arose in the distal small bowel and cecum. Of the patients affected, 15 had lymph node metastases and eight had liver metastases at the time of diagnosis. That only five patients were completely relieved of symptoms following resection was partially explained by autopsy findings in 15 patients, six of whom had metastatic extra-abdominal carcinoid without liver metastases (most commonly, bone metastases).

Adolescent

Comparison of intramural 5-fluorouracil and more conventional routes of drug administration on concentrations in gastric regional lymph nodes: a potential for trans-endoscopic adjuvant chemotherapy.

Intramural injection of 20 muCi (2-14C) 5-fluorouacil (5-FU) into the gastric submucosa of dogs and baboons was employed to evaluate the kinetics of 5-FU distribution following this route of administration and to compare these results with those following intraluminal, intravenous, and local intraarterial injections. Measurements of radioactivity taken over a six-hour period after injections demonstrated that the greatest concentration of isotope in samples of gastric wall and perigastric lymph nodes was found after administration of the drug directly into the stomach wall. Clinical application of intramural injections of 5-FU into the stomach wall under direct gastroscopic visual control, may be worthy of trial in patients with gastric cancer.

Animals

Lymphocytic infiltration in murine tumors.

Histologic grading of the histiolymphocytic reaction in nodules of T241 or B16 murine tumors in 94 C57BL/6J mice was performed at various time intervals post-inoculation. The infiltrate occurring in the first four days was generally sparse and no significant difference was observed between two different dose control inocula, suggesting a weak primary localization. Comparison between control inocula, and challenge inocula in mice harboring the same tumor for 10 days, showed a somewhat denser infiltrate initially in the challenge inocula. Despite the immunogenicity of these tumors, as shown by concomitant immunity, lymphocytic infiltration was generally sparse, consistent with an hypothesis of deficient localization of immunocompetent cells at tumor sites.

Animals

Phase II evaluation of diglycoaldehyde, VP-16-213, and the combination of methyl-CCNU and beta-2'-deoxythioguanosine in previously treated patients with colorectal cancer: an Eastern Cooperative Oncology Group study (EST-1275).

The Eastern Cooperative Oncology Group assessed the activity of diglycoaldehyde (DGA), VP-16-213, and the combination of methyl-CCNU and beta-2'-deoxythioguanosine in previously treated patients with advanced colorectal cancer. Objective responses were seen in two of 40 evaluable patients receiving methyl-CCNU and beta-2'-deoxythioguanosine and in one of 35 patients receiving DGA. None of 33 patients responded to VP-16-213, but one death related to sepsis and bone marrow failure occurred. Survival of patients whose previous chemotherapy included a nitrosourea was markedly shortened compared to those who had not been exposed to nitrosoureas. With the possible exception of DGA, further treatment of patients with colorectal cancer with these therapies is not warranted.

Aldehydes

Randomized phase II clinical trial of adriamycin, methotrexate, and actinomycin-D in advanced measurable pancreatic carcinoma: a Gastrointestinal Tumor Study Group Report.

Sixty-six patients with advanced pancreatic carcinoma were randomized to receive single agent chemotherapy with either adriamycin, methotrexate, or actinomycin-D using conventional dose, route and schedule of administration. All patients had measurable lesions which were used to objective assessment of response. For adriamycin, 2 of 25 patients (8%) evidenced a partial response (2 of 15 (13%) previously untreated patients). One of 25 patients treated with methotrexate and one of 28 received actinomycin-D responded. The duration of responses ranged from 43-64 days for those patients with no chemotherapy prior to study entry. The median survival of patients who received adriamycin as initial treatment was 12 weeks compared to 8 weeks for methotrexate and 6 weeks for actinomycin-D therapy.

Adult

Chemotherapy of advanced measurable colon and rectal carcinoma with oral 5-fluorouracil, alone or in combination with cyclophosphamide or 6-thioguanine, with intravenous 5-fluorouracil or beta-2'-deoxythioguanosine or with oral 3(4-methyl-cyclohexyl)-1(2-chlorethyl)-1-nitrosourea: a Phase II-III study of the Eastern Cooperative Oncology Group (EST 4273).

In a randomized multi-institutional trial of the Eastern Cooperative Oncology Group, 316 patients with advanced measurable colorectal adenocarcinoma were treated with a weekly schedule of 5-fluorouracil given orally and intravenously with oral-5-fluorouracil in combination with cyclophosphamide or 6-thioguanine, or with oral Methyl CCNU administered once every eight weeks. On failure or progression, 133 protocol patients crossed-over to a secondary therapy, while 116 other patients previously treated with 5-fluorouracil off protocol were randomized to treatment with Methyl CCNU or B-2'-deoxythioguanosine. Response rates among patients who had received no prior chemotherapy were 18% to oral 5-FU, 15% to intravenous 5-FU and to MeCCNU, 12% to 5-FU and 6-thioguanine and 5% to cyclophosphamide and 5-FU, with little activity (3% response rate) in crossover or previously treated patients. Treatment with 5-FU, particularly oral 5-FU was associated with the least drug-related toxicity. Hematologic toxicity was greatest with Methyl CCNU, but was no more frequent in previously treated than in untreated patients. A tendency toward cumulative bone marrow depression was noted. 5-FU was effective only in ambulatory patients, whereas responses among non-ambulatory patients were seen only in the group treated with Methyl-CCNU.

Adenocarcinoma

Lung resection for metastatic osteogenic sarcoma.

Osteogenic sarcoma, excluding the paraosteal osteosarcoma, has a grave prognosis, half of the patients dying within 1 year following ablative surgery of the primary lesion. Once pulmonary metastasis is detected, most patients do not survive more than 3 years. Various attempts by investigators to prolong patient survival, including surgery, chemotherapy, immunotherapy, radiation therapy, and combined modalities, have met with some success. This report is a summary of 13 patients who underwent lung resections and received adjuvant chemo- and/or immunotherapy for metastatic osteogenic sarcoma in our intstitute in the past 7 years.

Adolescent

Identification of a macromolecule containing an anticarcinoembryonic antigen-reactive substance and immunoglobulin M in human pancreatic cancer.

Ascitic fluid from a patient with carcinoma of the pancreas was fractionated by ammonium sulfate precipitation. The fraction precipitated between 25 and 50% saturation of ammonium sulfate was sequentially chromatographed on Sephadex G-200 and Sepharose 6B. A macromolecular fraction (greater than 10(6) daltons) obtained was found to react with both antihuman IgM and antiserum to carcinoembryonic antigen (CEA). This fraction was further purified by adsorption with protein A-Sepharose CL-4B and chromatography on DEAE-Sephacel. The purified macromolecular fraction had a sedimentation value of 28S as determined by ultracentrifugation. Upon dissociation of the purified macromolecule at pH 2.3 and purification of the dissociated components on Sepharose CL-2B and BioGel A 1.5M, a 19S protein and a 5S protein were recovered. The 19S protein showed a complete line of identity with a reference human IgM when reacted with antihuman IgM in gel diffusion, whereas the 5S protein showed a partial immunologic identity with colon CEA against anti-CEA. These results indicated the existence of an IgM-containing macromolecular complex with an anti-CEA cross-reactive substance in the extracellular fluid of human pancreatic cancer.

Ammonium Sulfate

Elemental diet as an adjuvant for patients with locally advanced gastrointestinal cancer receiving radiation therapy: a prospectively randomized study.

Thirty patients with locally advanced, nonresectable, nonmetastatic cancer in the peripancreatic region, stomach and colorectum-anus, to be treated with radiation therapy with or without adjuvant chemotherapy, were randomized to receive standard diet and either usual between-meal feedings or 300 calories tid of a high nitrogen elemental diet. Although weight loss associated with radiation therapy was not significantly reduced in those receiving the nutritional supplement, delayed hypersensitivity skin test responses tended to improve in patients receiving the elemental dietary supplement and to deteriorate in controls. Planned radiation therapy was completed in all nutritionally supported patients. One control patient expired shortly after treatment was halted abruptly, and three other control patients required rescue by total parenteral nutrition.

Energy Intake

cis-Dichlorodiammineplatinum (II) in advanced osteogenic sarcoma.

Eight patients with advanced metastatic osteogenic sarcoma were treated with cis-dichlorodiammineplatinum(II) (DDP). Prior to DDP, seven patients had amputations and all had received adjuvant adriamycin (ADR) therapy. In addition, prior to DDP, six patients had received high-dose methotrexate. There was one complete response (pulmonary metastases) and four partial responses (three metastases in the lungs and one in the bone). One additional patient, with local recurrence of osteogenic sarcoma of the mandible following initial resection and adjuvant ADR, was retreated with surgery and DDP and is disease-free for greater than 3 years. The cumulative dose ranged from 300 to 660 mg/m2. Toxicity included irreversible kidney damage in two patients, transient severe hematologic suppression in two patients, and nausea and vomiting in all patients. DDP is a new effective agent in the treatment of osteogenic sarcoma.

Adolescent