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Biomedical subjects

G Higgins

Publications and source records attributed to G Higgins.

At least 73 records · Page 4Linked to original sources

Clinical trials with diglycoaldehyde (NSC-118994): review and reasons for withdrawal from clinical trial.

All Phase II studies with diglycoaldehyde with leukemia and solid tumors have been reviewed. The dose schedules employed ranged from 1.5 to 2.0 g/m2/day for 3 to 5 days. The most common side effects have been gastrointestinal (nausea and vomiting), which occurred in 22% of the patients. Renal toxicity (rise in BUN, creatinine, and urinary proteins) was seem in 17% of the patients treated. Other infrequent toxicities include hypocalcemia (9%) and local complications such as phlebitis. Leukopenia, thrombocytopenia, positive Coombs' test and impairment in coagulation profile were also reported. In contrast to the hints of therapeutic efficacy described during Phase I trials, in phase II trials no activity was noted among 96 patients with solid tumors and only minimal antileukemic action among 49 other patients. These disappointing Phase II trials coupled with prominent toxicities have prompted the decision to terminate further clinical testing. This report summarizes all clinical observations as an example of circumstances which curtail clinical testing of anticancer drugs.

Aldehydes↗

The origin and extent of direct amygdala projections to the region of the dorsal motor nucleus of the vagus and the nucleus of the solitary tract.

The site of origin of a direct projection from the amygdala to autonomic regulatory nuclei in the dorsomedial medulla has been precisely localized and delimited in the rabbit by means of the retrograde axonal transport of horseradish peroxidase. Labeled cells in the amygdala were found to be confined within regions of the ipsilateral central nucleus. Many labeled cells were also observed to extend beyond the central nucleus into closely related regions of the substantia innominata and bed nucleus of the stria terminalis.

Amygdala↗

Response to pneumococcal polysaccharide vaccine in patients with untreated Hodgkin's disease. Children's Cancer Study Group Report.

Patients with Hodgkin's disease (HD) have a high risk of overwhelming pneumococcal infections after splenectomy. Previous studies have shown that HD patients given polyvalent pneumococcal polysaccharide (PPS) vaccine after immunosuppressive therapy have a suboptimum antibody response. This study shows significant antibody response in HD patients to PPS vaccine given before radiation and chemotherapy. The same response was obtained whether the vaccine was given before or after splenectomy.

Adolescent↗

Use of hypnosis for multiple symptoms in an adolescent girl with leukemia.

An adolescent girl with chronic myelogenous leukemia was treated with hypnosis for several disease- and treatment-related problems during the last 4 months of her life. Data were collected before and after hypnosis on the nature and intensity of the patient's acute pain and anxiety during bone marrow aspirations, chronic headache and backache, nausea and vomiting during chemotherapy, anorexia, and the discomfort associated with spiking temperatures. Comparisons of baseline and posthypnosis reports suggest that hypnosis was successfully used for acute and chronic pain, anxiety, unpleasant body sensations and, possibly, nausea and vomiting. The hypnotic techniques used, the limitations of hypnosis and clinical issues in this case are presented and discussed.

Anorexia↗

Plasma and tumor ACTH in carcinoma of the lung.

Plasma and tissue contents of immunoreactive ACTH were determined in 100 patients undergoing surgical resection for lung cancer. ACTH was detectable (greater than 1 ng ACTH equivalent/g wet weight) tissue in 47 of 49 specimens of epidermoid carcinoma, in 15 of 17 specimens of adenocarcinoma and in 7 of 8 specimens of large cell carcinoma; the median concentrations in these three tumor types were 8, 3 and 9 ng/g, respectively. Patients with oat cell carcinoma were not considered candidates for curative resection and are not included in this series. ACTH was not detectable in 36 specimens of apparently normal lung tissue from the same lobe but distant from the tumor and ranged up to 6 ng/g in 14 other specimens. One-half of patients with epidermoid carcinoma but only one-quarter of those with adenocarcinoma had preoperative plasma levels exceeding 250 ng/L plasma. About 75% of patients survived for at least one year whether preoperative plasma levels were greater than 400 ng/L or less than 200 ng/L. In only 4 of 21 patients with preoperative levels greater than 300 ng/L did the plasma fall by at least one-half in the immediate postoperative period. It is concluded that measurement of preoperative and postoperative plasma immunoreactive ACTH does not have a prognostic value for remission or long term survival in lung cancer, probably because it is unlikely that the tumor per se is the sole source accounting for the elevated levels generally observed in this condition.

Adenocarcinoma↗

Improved remission induction rate with D-ZAPO but unimproved remission duration with addition of immunotherapy to chemotherapy in previously untreated children with ANLL.

In 163 children with acute nonlymphocytic leukemia (ANLL), a D-ZAPO induction program consisting of daunomycin, 5-azacytidine, cytosine arabinoside, prednisone, and vincristine resulted in a remission rate of 71.8%. Immunologic therapy was employed during maintenance with the aim of prolonging remission and improving survival. The administration of immunotherapy consisting of a mixture of bacillus Calmette-Guérin (BCG) and allogenic acute myelomonocytic leukemic cells injected intradermally on day 14 of each of the first three monthly cycles of 6-thioguanine for ten days, 5-azacytidine and cytosine arabinoside for four days, and vincristine for one day did not improve remission duration or survival compared to that due to chemotherapy alone. Important prognostic factors identified in this study included a remission induction rate significantly better for females than males (P = 0.04), for children between the ages of 5 and 10 years compared to those greater than this age group (P = 0.01), and a prolonged remission duration (P = 0.04), and survival (P less than 0.01) for patients with initial white blood counts of less than 20 x 10(9)/liter.

Adolescent↗

Evaluation of cyclocytidine in children with advanced acute leukemia and solid tumors.

Cyclocytidine, a slow-release form of cytosine arabinoside, was evaluated in 69 children with advanced acute leukemia and solid tumors. One child with acute lymphocytic leukemia attained a complete remission. This child had received intrathecal cytosine arabinoside prior to the cyclocytidine. Eighteen of the 31 patients with acute lymphocytic leukemia/acute undifferentiated leukemia who did not respond received two or more courses of the drug. There were no responses in 15 children with acute myelogenous leukemia, in 11 children with neuroblastoma, or in 11 children with various solid tumors of childhood. A dose of 600 ng/m2/day for 10 consecutive days is tolerated in children.

Adolescent↗

Avian antigen-binding cells. I. Characterization of antigen-binding T cells from bursectiomized chickens by autoradiography.

Antigen-binding cells (ABC) from spleens of HGG-immunized, bursectomized agammaglobulinemic (Bx) chickens were detected by direct autoradiography with 125I-HGG and by sandwich autoradiography with HGG plus 125I-goat-anti-HGG. The specificity of antigen binding was demonstrated by 1) inhibition of binding of 125I-HGG by preincubation with unlabeled HGG and 2) a specific increase in ABC after immunization. The ABC from Bx chickens were not B cells, as shown by the virtual absence of immunoglobulin-bearing cells in this population and by the lack of inhibition of antigen binding by anti-immunoglobulin sera. The ABC were not macrophages and did not bind HGG via Fc receptors because their frequency was unchanged after passage over nylon wool or incubation with antigen-antibody complexes. The temperature dependence and azide stabilization of the ABC were characteristic of antigen-binding T cells. Therefore, T cells capable of binding soluble antigen were demonstrated in Bx chicken spleen, which is free of contamination by B cells and passively adsorbed antibody.

Animals↗

Avian antigen-binding cells. II. Enrichment of antigen-binding B and T cells.

Antigen-binding B and T cells from chicken spleens were selected on plates of antigen-derived gelatin. Hapten-specific B cells from DNP-immune normal chicken spleens were selected on DNP-gelatin. As much as 165-fold functional enrichment of precursors of anti-DNP antibody-producing cells, as measured in an adoptive transfer system, was achieved. However, the enrichment of DNP-binding cells assessed by rosette formation and autoradiography was no more than 25-fold. HGG-specific T cells from bursectomized agammaglobulinemic chickens immunized with deaggregated HGG were selected on HGG-gelatin. In the fraction adherent to HGG-gelatin, at least a 20-fold enrichment of suppressors of the antibody response to TNP-HGG, as measured by adoptive transfer, was accomplished. In contrast, no more than 6-fold enrichment of HGG-binding cells was detected by autoradiography. Antigen-specific depletion and enrichment of suppressor T cells and of HGG-binding cells occurred in parallel, suggesting that suppressor cells can bind soluble antigen and can be isolated on antigen coupled to a solid support.

Animals↗

L-asparaginase reinduction and maintenance therapy in previously treated acute lymphocytic leukemia.

Four patients with acute lymphocytic leukemia previously treated with conventional chemotherapy received intramuscular L-asparaginase in combination with other chemotherapy for reinduction and maintenance therapy. These patients received the L-asparaginase for 8, 14, 27, and 34+ months without demonstrating any significant adverse effects. Only 1 of the 4 was clearly resistant to the other chemo-therapy, and 3 of 4 had recurrence of their disease while receiving L-asparaginase. L-asparaginase can be added to reinduction and maintenance regimens of patients resistant to other chemotherapy and is well tolerated for long periods when given intramuscularly weekly with other immunosuppressant agents.

Adolescent↗