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Biomedical subjects

J R Sullivan

Publications and source records attributed to J R Sullivan.

At least 19 recordsLinked to original sources

Metabolism and disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin in ring-necked pheasant hens, chicks, and eggs.

The T 1/2 for whole-body elimination of [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) derived radioactivity in ring-necked pheasant hatchlings was 13 d, whereas in adult hen pheasants that were not producing eggs it was 378 d. All TCDD-derived radioactivity in hen tissues was from the parent compound. The oral bioavailability of TCDD in the adult hen pheasant varied with the environmental matrix, with 30% of the dose absorbed from a suspension of earthworms, 33% absorbed from a soil suspension, 41% absorbed from a suspension of paper mill sludge, and 58% absorbed from a suspension of crickets. A cumulative dose of 1.0 micrograms TCDD/kg body weight, administered as weekly doses of 0.1 micrograms/kg for 10 wk, did not adversely affect hen condition or egg production. Under these exposure conditions, hens translocated about 1% of their cumulative TCDD dose to each of the first 15 eggs laid. All of the TCDD-derived radioactivity in the eggs was the parent compound and was confined entirely to the yolk; no TCDD was detected in egg albumin. We conclude that TCDD was more persistent in pheasant hens than in chicks and that egg laying was an important route of elimination in the hen.

Administration, Oral

Toxicity and reproductive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in ring-necked pheasant hens.

Hen pheasants (Phasianus colchicus) injected with graded single doses of TCDD (6.25, 25, or 100 micrograms/kg) exhibited delayed-onset body weight loss and mortality--classic signs of the wasting syndrome. The lowest single dose of TCDD to produce this effect was 25 micrograms/kg. When hen pheasants were treated weekly with far lower doses of TCDD (0.01-1.0 microgram/kg/wk) for 10 wk, signs of the wasting syndrome and mortality were also produced. The lowest cumulative TCDD dose required to produce the response, using a weekly dosing regimen, was 10 micrograms/kg. Furthermore, using this dosing regimen, egg production by hens treated with a cumulative TCDD dose of 10 micrograms/kg was reduced, as was hatchability of their eggs. We conclude that hen pheasants are responsive to the overt toxic effects of TCDD and that the lowest cumulative dose of TCDD that produces overt signs of toxicity, 10 micrograms/kg, also reduces egg production and egg hatchability.

Animals

Phase I clinical trial of drug-monoclonal antibody conjugates in patients with advanced colorectal carcinoma: a preliminary report.

Melphalan (MEL), an alkylating agent, has been modified to a derivative, N-acetylmelphalan (N-AcMEL), which can be conjugated to anticolon cancer monoclonal antibodies (MoAbs 30.6, I-1, and JGT) and used for immunochemotherapy. The final immunoconjugates possess potent cytotoxicity and specificity in preclinical studies. In a phase I clinical study, N-AcMEL-MoAb conjugates were administered via the hepatic artery to 10 patients, nine of whom had disseminated colorectal cancer (including the liver) and one of whom had Dukes' C colon cancer that had been resected. The selection of MoAb was based on the immunoperoxidase staining of the primary colon cancer tissue. Thus far doses of 1000 mg/m2 MoAb conjugated to 20 mg/m2 of N-AcMEL have been administered with no significant side effects, whereas MEL unconjugated to monoclonal antibodies would have caused myelosuppression in a proportion of patients at the same dosage. Serum antimouse antibody responses were noted in all of the patients; febrile reactions were noted with higher doses but were easily controlled with antipyretics, antihistamines and, if necessary, steroids. Serum sickness developed in one patient who was given a second course of treatment in the presence of human antimouse antibody, but the episode was self-limiting. Eight of the 10 patients had evaluable disease. Subjective improvement was noted in almost all of the patients examined, and 33%, or 3 of 9, of the treatments (nine courses of treatment in eight patients with evaluable disease; one of the patients had two courses of treatment) led to antitumor responses (minor response) by objective assessment with computed tomography of the liver. It is important to note that treatment with N-AcMEL-MoAb conjugates was safe at a dose of 20 mg/m2 of N-AcMEL, whereas the efficacy of such a form of treatment remains to be determined.

Adult

Heterogeneity of the human transferrin receptor and use of anti-transferrin receptor antibodies to detect tumours in vivo.

The human transferrin receptor (TFR) which is present on dividing cells, many tumours and erythroid precursors is readily identified using specific monoclonal antibodies. A new anti-human TFR monoclonal antibody, HuLy-m9, is described and its distribution on cell lines, normal and tumour tissue was examined and compared with two other anti-TFR monoclonal antibodies, namely, OKT9 and 5E9. The three antibodies were shown to recognise different epitopes on the surface of the TFR and have different reactivities with in vitro cell lines. Peptide map analyses of the TFR recognised by each monoclonal antibody from the same cell line were identical; however, differences were observed between cell lines. 131I-radiolabelled HuLy-m9 was used to successfully localise a nasopharyngeal carcinoma in vivo.

Antibodies, Monoclonal

Visualization of metastases from colon carcinoma using an iodine 131-radiolabeled monoclonal antibody.

A murine monoclonal antibody that reacts with human colonic cancer (250-30.6) was labeled with radioactive iodine (131I) and the antibody was injected intravenously into 15 patients with known metastases originating from carcinoma of the colon (10 cases), malignant melanoma (1), breast (1), pancreas (1), hepatocellular carcinoma (1), and adenocarcinoma of unknown origin (1). Of the patients with metastatic colon carcinoma, there were 19 known deposits as judged by the techniques of clinical examination, x-rays, and scans obtained using sulpha-colloid. Of these 19 deposits, 17 (90%) were found using the 131I-labeled monoclonal antibody. In one case, the primary tumor, previously undiagnosed, was found. In only 1 of the 10 patients was tumor not found and this was due to the subsequent finding that the undifferentiated tumor did not react with antibody. Of the five patients who did not have carcinoma of the colon, three had negative scans, but two were positive. Thus, the technique of immunoscintography can readily detect both primary and metastatic tumors.

Adenocarcinoma

Ciramadol. A new analgesic.

Ciramadol (WY 15705), a new analgesic and narcotic antagonist was studied on oral-dose form in 16 patients (15 of whom were suffering from malignant disease) to evaluate the analgesic dose and toxicity. Patients with mild or moderate pain experienced effective relief with doses of from 20 mg to 60 mg (mean dose, 47 mg). In patients with moderate to severe pain, effective pain control was not achieved (mean dose, 82 mg). There was no consistent effect on blood pressure level, heart rate, or respiratory rate. Mild or moderate sedation occurred in eight patients. Nausea and vomiting occurred in two patients.

Adult

Two cases of carcinoma of the lung characterized by a bone marrow agar culture pattern resembling acute myeloid leukemia.

In vitro agar culture patterns of bone marrow cells in acute myeloid leukemia may show several growth patterns, including cultures where no colonies or clusters develop, cultures with varying numbers of clusters and no colonies, or colony and cluster formation with an extremely high ratio of clusters to colonies. Twelve cases of carcinoma of the lung are described, of which two show an in vitro growth pattern of cluster formation alone, characteristic of that seen in acute myeloid leukemia. The remaining ten patients showed slightly reduced colony numbers compared to normal.

Bone Marrow

Toxic rash associated with high dose methotrexate therapy.

Fifteen rashes were observed in thirteen patients in association with high dose methotrexate therapy. The lack of recurrence of the rash with further treatment courses and the association of the rash with other toxic manifestations and with larger doses of methotrexate suggests a toxic mechanism. Rashes have frequently been reported in association with dose methotrexate therapy (Van Scott, Auerbach & Weinstein, 1964; Leone, Albala & Rege, 1968; Mitchell et al., 1968; Capizzi et al., 1970; Jaffe et al., 1973; Rosen, Suwansirikul & Kwon, 1974; Pratt et al., 1975; Jaffe & Traggis, 1975; Ensminger & Frei, 1977; Stoller et al., 1977). They include perifolliculitis, transient erythema progressing to maculopapular eruptions, occasionally desquamating, sloughing over pressure areas, reactions confined to radiation portals, exacerbation of acne, photosensitivity and rarely urticaria. Relatively few reports sufficiently document the incidence or types of rash. It has been suggested that the rash is allergic in nature (Mitchell et al., 1968) or a toxic phenomenon (Djerassi et al., 1972; Djerassi & Kim, 1976), possibly related to drug effects on small vessels (Van Scott, 1963).

Erythema

Results of treatment of head and neck carcinoma with high dose methotrexate.

Forty four patients with squamous cell carcinoma of the head and neck from a variety of primary sites were treated with high dose methotrexate with folinic acid rescue from 1975 to 1977. The overall response rate was 66%. Response duration was short with a mean of 16 weeks. The usefulness of this technique in the treatment of head and neck cancer is discussed.

Carcinoma, Squamous Cell

Complications of tumour overkill when associated with high dose methotrexate therapy.

Three patients, in whom tumour overkill by cytotoxic treatment, including high dose methotrexate with folinic acid rescue, resulted in the 'phosphate shower syndrome' (hyper-uricaemia, hyperkalaemia and hyperphosphataemia with hypocalcaemia and tetany, with metabolic acidosis and acute renal impairment) are described. Severe methotrexate toxicity occurred in two of these patients. High dose methotrexate would appear contra-indicated in situations where massive tumour lysis is possible.

Adolescent

Primary lymphoma of lung.

Five cases of primary lymphocytic lymphoma of the lung are described. One patient died 14 years after diagnosis, with spread of the tumour to the opposite lung. The remaining four patients were alive and well 18 months to 25 years after diagnosis. The pathological features of these five cases are described and the nature, diagnosis, therapy, and prognosis are considered in relation to experience in the literature. The tumor is rare. It is important because of its good prognosis and diagnostic difficulty.

Adult

Some uses of the continuous flow blood separator in the myeloproliferative syndrome.

A continuous flow blood separator was used for leucapheresis in two patients with chronic myeloid leukaemia, complicated by pregnancy and leukastasis respectively, and for thrombocytopheresis in a patient with megakaryocytic myelosis. The cases described, outline some of the clinical uses of this machine in the myeloproliferative syndrome.

Adult

Immunization with influenza vaccine in patients with haematological malignant disease.

Fifty-eight patients with a variety of haematological lymphoproliferative or myeloproliferative disorders were given bivalent subunit influenza virus vaccine, and their antibody responses after vaccination were compared with those of a normal control group. Although geometric mean titres of the patient group showed lower initial antibody levels, smaller increments, and lower final titres, after vaccination 83% of this group achieved satisfactory antibody levels to the A/Pt Chalmers strain, and 57% to the B/Hong Kong strain. The lowest antibody levels and smallest responses occurred in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and multiple myeloma. Four of seven patients who showed low antibody levels, and no response to the first injection, responded to a second dose.

Adult