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Biomedical subjects

J S Stewart

Publications and source records attributed to J S Stewart.

At least 19 recordsLinked to original sources
PubMed1991

Unilateral olfactory deprivation: effects on succinate dehydrogenase histochemistry and [3H]leucine incorporation in the olfactory mucosa.

Surgically closing one external naris reduces airflow through one half of the nasal cavity, decreasing the access of odors to the receptor sheet. In rats, unilateral naris occlusion performed near birth results in large reductions in the size of the olfactory bulb, the primary central relay, when examined 30 days later. Previous research has demonstrated that there is a rapid reduction in [3H]2-deoxyglucose (2-DG) and [3H]leucine uptake in the bulb within hours after naris closure. The present study examined whether similar rapid changes could be observed in the sensory periphery. Pups occluded on P1 and examined on P3 with succinate dehydrogenase histochemistry exhibited reduced staining on the closed side of the nasal cavity, suggesting occlusion results in reductions in mucosal metabolism. Larger differences in staining were observed in pups examined at P6. [3H]Leucine incorporation was quite similar on both sides of the nasal septum as late as 30 days post occlusion, suggesting less dramatic changes in protein synthesis. The results suggest that naris closure does indeed have rapid effects on mucosal function, but indicate that the changes are different than those observed in the bulb.

Animals↗
PubMed1991

Treating the vaginal vault in carcinoma of the endometrium using the Buchler afterloading system.

The advent of high-dose-rate afterloading intracavitary radiotherapy has implications for both staff safety and the possibility of convenient, outpatient-based treatment for the patient. We have carried out a retrospective analysis of its use with high-activity iridium 192 and the Buchler machine to treat the vaginal valut in patients with adenocarcinoma of the endometrium, most of whom also received external-beam radiotherapy to the pelvis. We have compared the survival, complication and local control rates with a comparable group of historical controls treated with low-dose-rate intracavitary caesium ovoids. Complication rates, which included vaginal stenosis not volunteered by the patient, were 16% (95% confidence intervals 6-26%) in the study group and 28% (95% confidence intervals 17-41%) in the control group, with no serious complications requiring surgery. The actuarial survival was 92% at 5 years in the study group, and 94% at 5 years in the control group. Local control was 94% at 5 years in the control group and 98% at 5 years in the study group. The authors suggest that the use of high-dose-rate intracavitary radiotherapy, with the Buchler afterloading system, for vaginal vault irradiation in carcinoma of the endometrium is a convenient, safe and quick method, which does not necessitate admission or sedation of the patient. In addition it provides complete radiation protection for staff.

Adenocarcinoma↗
PubMed1990

Olfactory bulb and sensory epithelium in goldfish: morphological alterations accompanying growth.

Considerable growth of both the body and the brain occurs throughout the lifespan in goldfish. In the present study growth-related changes in the goldfish olfactory system were examined using quantitative morphometric techniques as well as [3H]thymidine autoradiography. While the two olfactory structures examined, the bulb and the rosette, grow in proportion to the rest of the animal, each structure shows evidence of differential maturation. Examination of olfactory bulb laminar volumes suggest that bulbs expand primarily by generating neuropil rather than by adding new cells. This interpretation was supported by the findings that olfactory bulb granule cells decrease in density and increase in soma size as animals grow. Additionally, virtually no [3H]thymidine-labeled cells were found in the granule cell zone. Olfactory rosettes grow by adding new lamellae to the structure's medial aspect as well as by increasing the length of existing lamellae. These findings were supported by examining [3H]thymidine-labeled cells, which were differentially distributed across the rosette, with significantly more labeled cells found medially vs laterally. Results are discussed in terms of their implications for the system's functioning during growth.

Animals↗
PubMed1990

Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody.

Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment.

Antibodies, Anti-Idiotypic↗
PubMed1990

Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer.

From March 1987 to March 1988, a phase I to II study was carried out in 25 patients with ovarian cancer. They received escalating doses of intraperitoneally (IP) administered yttrium-90 (Y-90)-labeled monoclonal antibody, HMFG1, against a tumor cell-surface antigen. Myelosuppression prevented an escalation of the administered Y-90 activity above 25 mCi. Y-90-labeled antibody was absorbed from the peritoneal cavity into the circulation. Maximum blood Y-90 activity was observed 40 hours after the IP injection with a mean of 21% of the injected activity (range, 14.2% to 26.4%) in the circulation. The radiation dose the bone marrow received from circulating Y-90-labeled antibody (the blood radiation dose) was calculated by applying the Medical Internal Radiation Dose (MIRD) formulation to the measured Y-90 activity in patients blood. Myelosuppression occurred following calculated blood radiation doses to bone marrow of only 10 to 30 cGy. The excessive myelosuppression following such modest radiation doses from circulating Y-90-labeled antibody could be explained by the uptake of Y-90 by bone. In an attempt to reduce bone absorption of Y-90, seven patients received an intravenous (IV) infusion of EDTA (Sinclair Pharmaceuticals Ltd, Godalming, United Kingdom). This increased the urinary excretion of Y-90 from a mean of 11.1% to 32.3% of the injected activity (P = .0001). Fourteen patients had assessable tumor at laparoscopy. Tumor regression was observed in one patient, and palliation of ascites in a further patient.

Adult↗
PubMed1990

Postnatal ossification centers of the atlas and axis in miniature schnauzers.

Postnatal ossification of the atlas and axis was studied in Miniature Schnauzers by examining alizarin-stained bone clearings, cleaned dry bones, radiographs, histologic sections, and arterially perfused bone clearings. Sixty-two pups (1 day to 16 weeks old) and 4 adults were examined. In 1-day-old pups, the atlas consisted of 3 separate ossification centers: a left and right neural arch center and midventrally, the intercentrum 1, which formed the body of the atlas. The axis contained 4 separate ossification centers: a left and right neural arch center; centrum 2 in the main part of the axis body; and centrum 1, which formed the caudal part of the dens and the cranial part of the axis body. By 6 weeks of age, the epiphysis on the caudal end of the axis body had begun to ossify. At this time, the intercentrum 2, which developed as a cuboidal ossification center intercalated between centrum 1 and centrum 2 in the middle of the cranial half of the axis body, also began to ossify. The centrum of the proatlas, which formed the apex of the dens, was first seen ossified in a 9-week-old pup. These 10 ossification centers were seen as constant and separate elements. In all dogs, the dens developed from 2 separate ossification centers: the centrum of the proatlas formed the cranial one-quarter, and centrum 1 formed the caudal three-quarters. Dens dysplasia is unlikely to be a result of failure of development of one of the ossification centers for the dens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Intraperitoneally administered 90Y-labelled monoclonal antibodies as a third line of treatment in ovarian cancer. A phase 1-2 trial: problems encountered and possible solutions.

A phase 1-2 trial of 90Y-labelled monoclonal antibody, HMFG1 administered intraperitoneally to 30 patients with ovarian carcinoma is presented. The problems encountered with myelotoxicity are described, and the steps which have so far been taken to overcome this and to increase the dose of 90Y to an estimated tumouricidal level. Bone deposition of free 90Y limits the dose which can be administered without severe bone marrow toxicity. The intravenous use of a chelating agent, Ledclair (EDTA) has allowed the dose to be increased from 18 to 30 mCi without causing severe myelotoxicity. 90Y-DTPA MAb is an unstable immunoconjugate in vivo and in vitro. The use of a more stable linkage such as a macrocycle should enable the administered dose to be increased without increasing the amount of free 90Y which becomes available to be deposited in bone. This would be expected to reduce toxicity and increase therapeutic efficacy.

Antibodies, Monoclonal↗
PubMed1989

Malignant ascites: review of the literature, and an update on monoclonal antibody-targeted therapy.

Malignant ascites presents a difficult clinical problem, causing discomfort and distress to patients in the later stages of disease. Repeated attempts at palliation are often unsuccessful. In this article, conventional forms of therapy for malignant ascites are reviewed and their limitations outlined. Furthermore, we present data on a new form of therapy: antibody guided irradiation. Pilot studies have produced encouraging results in the management of malignant serous effusions, and further randomised studies are currently in progress.

Antibodies, Monoclonal↗
PubMed1989

Intraperitoneal radioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies.

Thirty-six patients with ovarian cancer were treated with intraperitoneal I-131 labeled monoclonal antibodies to tumor associated antigens. The activity of I-131 administered was increased from 20 mCi to 158 mCi and the pharmacokinetics and toxicity evaluated. Five patients who had developed HAMA (Human Antimouse Antibodies) were retreated, and the pharmacokinetics and toxicity of the first and second treatment compared. Patients receiving their first therapy (HAMA negative), had a maximum of 25% (range 19.8-39.8%) of the injected activity in their circulation. This was accompanied by severe marrow suppression at I-131 activities over 120 mCi. The 5 HAMA positive patients had only 5% injected activity in the systemic circulation (range 3.8-6%), with rapid urinary excretion and neglible marrow suppression. In 31 patients with assessable disease there were no responses in 8 patients with gross disease (nodules greater than 2 cms), partial responses in 2 out of 15 patients with nodules less than 2 cms, and complete responses in 3 out of 6 patients with microscopic disease. The non specific radiation dose to the peritoneal cavity was estimated to be less than 500 cGy by lithium fluoride TLD, and could not be expected to account for the responses seen.

Animals↗
PubMed1989

Intraperitoneal radioimmunotherapy for ovarian cancer.

Twenty-eight patients with assessable residual ovarian cancer after cytoreductive surgery and chemotherapy received intraperitoneal I-131 labelled monoclonal antibodies. There was no response in eight patients with tumour nodules greater than 2 cm, a partial response in two of the 15 patients with tumour nodules less than 2 cm, and a complete response in three of the other five patients with positive peritoneal washings. A further six patients received Y-90 labelled monoclonal antibodies for residual ovarian cancer. There was no response in one patient with nodules greater than 2 cm, and a partial response in one of the other five patients with tumour nodules less than 2 cm. The non-specific radiation dose in the peritoneal cavity from the infused isotope was measured by lithium fluoride thermoluminescent dosimetry (TLD). The radiation dose received by the peritoneal serosa was less than 500 cGy and was not sufficient to account for the observed tumour response. Significant bone marrow suppression was observed with I-131 activities greater than 120 mCi and with Y-90 activities greater than 13 mCi. The haemopoietic bone marrow is the dose-limiting organ in patients receiving radioimmunotherapy.

Adult↗
PubMed1989

Knemidokoptes mutans (Acari: Knemidocoptidae) in a great-horned owl (Bubo virginianus).

A routine examination of a captive juvenile great-horned owl (Bubo virginianus) revealed bilateral proliferative papillary hyperkeratosis on the feet. Microscopic examination of skin scrapings produced numerous mites identified as Knemidokoptes mutans. This is the first record of this parasite in a great-horned owl. A single dose of ivermectin (200 micrograms/kg) was effective in treatment of this infection.

Animals↗
PubMed1988

Intraperitoneal 131I- and 90Y-labelled monoclonal antibodies for ovarian cancer: pharmacokinetics and normal tissue dosimetry.

The pharmacokinetics of intraperitoneal (i.p.) radiolabelled monoclonal antibody (MAb) was studied in 35 patients receiving 40 i.p. injections. Eleven patients received 131I-labelled MAb, 24 received 90Y-labelled MAb, and 5 patients received a second 131I MAb treatment after having developed human anti-mouse antibodies (HAMA). All patients had blood and urine isotope activity monitored for 5 days after MAb injection. The radiation dose to bone marrow from the vascular compartment in the marrow was calculated by applying the MIRD formula to the measured blood activity. In HAMA-negative patients, peak blood isotope activity was observed at 40 hr post injection with a mean of 26% and 21% of the injected 131I and 90Y activity respectively. Sixty-five percent of the injected 131I activity, but only 12% of the administered 90Y, was excreted in the urine. Myelosuppression limited the administered 131I and 90Y activities to below 160 and 20 mCi respectively. In patients receiving 131I labelled MAbs, the marrow is irradiated by MAb within its circulation, producing myelosuppression that can be predicted by applying the MIRD formula to the blood isotope activity. This is not true for 90Y-labelled MAbs, where bone absorption of yttrium (which cannot be measured in patients) is the dominant radiation source for bone-marrow irradiation. Patients with HAMA present clear 131I MAb rapidly with a decreased radiation dose to marrow and reduced myelosuppression. Giving patients intravenous antimouse immunoglobulin to clear 131I-labelled MAb absorbed from the peritoneal cavity could decrease the toxicity observed in these patients. Patients receiving 90Y DTPA-chelated MAbs are unlikely to benefit, as catabolized yttrium is not excreted, and is concentrated in liver, spleen and bone. On the other hand, the use of i.v. chelating agents as EDTA may scavenge non-protein-bound 90Y with increased excretion in the urine and less myelosuppression.

Antibodies, Monoclonal↗
PubMed1987

Fast neutron therapy for soft tissue sarcoma.

Seventy-nine patients with soft tissue sarcoma were treated with fast neutron therapy at the Hammersmith Hospital, MRC Cyclotron Unit. Sixty-six of these, treated between 1971 and 1983 were assessable. The histology was reviewed and graded in 82% of cases and tumors divided into groups according to maximum diameter. In sixteen patients, who were irradiated following complete macroscopic removal of tumor, there was 94% local control and 86% survived 5 years. Of the 50 patients who had gross tumors present 62% were greater than 10 cm in diameter, and 20 were recurrent after previous radiotherapy or surgery or both. Sixty-eight per cent of gross tumors completely regressed and local control was 52%. The main cause of death was metastatic spread, and median survival was 63 months for Grade 1 patients, 9 months for Grade 2, and 7 months for Grade 3. Thus, there was a significant advantage to patients with Grade 1 tumor but little difference between Grades 2 and 3. Twenty-seven patients experienced late complications of treatment, 67% of which involved the skin predominantly and were related to the low energy of neutrons used. Seventeen of the 27 had received previous radiotherapy. Neutron therapy given in this dose and fractionation produced a higher local control rate than photon therapy, but complications were more frequent. Since these mainly involved the skin a lower level of complications may be anticipated using higher energy neutrons which will have a more even distribution of dose and lower skin dosage. Forty-eight per cent of patients developed metastatic disease, indicating the need for effective systemic therapy, especially in Grades 2 and 3 tumors.

Fast Neutrons↗