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Biomedical subjects

J Horton

Publications and source records attributed to J Horton.

At least 19 recordsLinked to original sources
PubMed1992

Reduced intracellular drug accumulation in the absence of P-glycoprotein (mdr1) overexpression in mitoxantrone-resistant human MCF-7 breast cancer cells.

A mitoxantrone-resistant human MCF-7 breast cancer subline (MCF/MX) which is approximately 4000-fold resistant to mitoxantrone was isolated by serial passage of the parental wild-type MCF-7 cells (MCF/WT) in stepwise increasing concentrations of drug. MCF/MX cells were also approximately 10-fold cross-resistant to doxorubicin and etoposide but were not cross-resistant to vinblastine. Intracellular accumulation of radiolabeled mitoxantrone was markedly reduced in MCF/MX cells relative to that in the drug-sensitive MCF/WT cells. This decrease in intracellular drug accumulation into MCF/MX cells was associated with enhanced drug efflux, which was reversed when cells were incubated in the presence of sodium azide and 2, 4-dinitrophenol, suggesting an energy-dependent process. Incubation of MCF/MX cells with verapamil did not affect either the accumulation of mitoxantrone or the level of resistance in these cells. Furthermore, RNase protection and Western blot analyses failed to detect the expression of the mdr1 RNA or P-glycoprotein, a drug efflux pump known to be associated with the development of multidrug resistance in vitro. However, a polyclonal antibody directed against a synthetic peptide corresponding to the putative ATP binding domain of P-glycoprotein reacted with two (M(r) 42,000 and 85,000) membrane proteins from MCF/MX cells which were not found in MCF/WT. Functional assays and Western blot analysis for topoisomerase II revealed no differences in topoisomerase II activity or protein levels in MCF/MX cells. Thus, resistance in this cell line is apparently associated with enhanced drug efflux involving a pathway distinct from the mdr1-encoded multidrug transporter P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Does extent of surgery influence outcome for astrocytoma with atypical or anaplastic foci (AAF)? A report from three Radiation Therapy Oncology Group (RTOG) trials.

103 patients with the diagnosis of AAF were identified from the RT/BCNU arms of 3 RTOG malignant glioma trials. Pre-treatment tumor size was less than 5 cm for 48% and greater than or equal to 5 cm for 52%, and tumor sites were frontal lobe in 55%, temporal in 25%, and parietal in 16%. Surgery consisted of biopsy for 30%, partial resection for 56%, and total resection for 14%. Extent of surgery correlated with age, with 81% of patients less than 40 undergoing partial/total resection vs. 60% of those over 40 (P = 0.019). The median survival time (MST) of patients undergoing partial/total resection was 49 mo., vs. 18 mo. for those biopsied only (P = 0.002). Patients with frontal location had longer MST than those with non-frontal lesions (MST: 49 vs. 25 mo., P = 0.047), while no survival difference was apparent by univariate analysis of tumor size. Multivariate analysis demonstrated that only younger age, frontal location, and smaller tumor size correlated significantly with extended survival. Extent of surgery was not predictive. The close correlation between young age and extensive surgery obscures the survival advantage for greater surgery seen with univariate analysis. Smaller tumor size and frontal location favorably influence outcome even when adjusted by age.

Adult↗
PubMed1992

A comparison of scaphoid-trapezium-trapezoid fusion and four-bone tendon weave for scapholunate dissociation.

The contact characteristics of the radiocarpal joint (area, pressure, and ratios of scapholunate area, pressure and force transmitted) were determined with the use of pressure-sensitive film in seven normal wrists after ligament sectioning to create scapholunate instability, with reconstruction involving a scaphoid-trapezium-trapezoid fusion, and with reconstruction involving a four-bone tendon weave procedure. The results demonstrated that the scaphoid-trapezium-trapezoid fusion significantly altered the contact characteristics of the wrist, transferring load, pressure, and area to the radioscaphoid joint, thereby unloading the lunate. In contrast, the tendon weave reconstruction produced characteristics similar to those of the normal joint.

Arthrodesis↗
PubMed1992

Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group.

A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2 was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2 (regimens A and B) or 75 mg/m2 (regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2 orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0-1, 2-3) and largest tumor diameter at entry (greater than 2- less than or equal to 10 cm, greater than 10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (less than or equal to 1 year, greater than 1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61% response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age less than 60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation.

Altretamine↗
PubMed1991

Long-term survival in treated anaplastic astrocytomas. A report of combined RTOG/ECOG studies.

This report evaluates the long-term survival of patients with histologically confirmed anaplastic astrocytoma on several combined RTOG (Radiation Therapy Oncology Group) studies. Included in this analysis are the following studies: RTOG/ECOG (Eastern Cooperative Oncology Group) 74-01, RTOG 76-11, and RTOG 79-18, with the various treatment arms separated into radiation therapy (RT) only (47 patients) radiation therapy and chemotherapy (Chemo) (78 patients) and radiation therapy, chemotherapy, and misonidazole (Mizo) (24 patients). Pretreatment characteristics of age, prior surgery, performance status, and neurological function classification are identified. Median survival for patients treated with RT only is 3.0 years. Median survival for patients treated with RT + Chemo is 2.3 years, and for patients treated with RT + Chemo/Miso is 1.2 years. Five-year survival rates are 35% for patients treated with RT only, 29% for patients treated with RT + Chemo, and 24% for patients treated with RT + Chemo/Miso. Age and performance status have been identified in previous studies as important prognostic variables and are confirmed in this analysis. Patients treated with misonidazole had a significantly worse prognosis after adjustment for differences in prognostic factors. Addition of chemotherapy did not improve survival except in less favorable prognostic categories. In general, more aggressive treatment regimens are associated with decreased survival compared to conventional postoperative irradiation.

Adolescent↗
PubMed1991

Treatment of advanced refractory lymphomas with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (the BBVDD regimen). An ECOG pilot study.

Forty-four patients with relapsed, refractory malignant lymphomas (12 Hodgkin's disease, 32 non-Hodgkin's lymphoma) were treated with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (BBVDD regimen). Patients had failed at least one, and frequently two, chemotherapy regimens before admission to the study. Of the patients with Hodgkin's disease, 2 (17%) achieved complete response (CR), and 3 (25%) attained a partial response (PR) for an overall response rate (CR + PR) of 42%. Among the patients with non-Hodgkin's lymphoma there were 6 CR (19%) and 12 PR (37%), for an overall response rate of 56%. Median durations of response ranged from 2.5 months for nodular non-Hodgkin's lymphoma in PR to 28.5 + months for Hodgkin's disease in CR. In these heavily pretreated patients, the incidence of toxic effects was grade 3 (48%), grade 4 (23%), grade 5 (2%). The one death (grade 5 toxicity) was attributed to pulmonary impairment due to bleomycin. BBVDD is a moderately effective regimen for the palliation of patients with refractory lymphomas and merits further study.

Ambulatory Care↗
PubMed1991

Eastern Cooperative Oncology Group study 1879: mitotane and adriamycin in patients with advanced adrenocortical carcinoma.

From November 1979 to July 1986, 52 patients (27 women and 25 men; median age 52 years) with advanced adrenocortical carcinoma entered a prospective, nonrandomized study evaluating moderate-dose mitotane and doxorubicin hydrochloride (Adriamycin). Thirty-two tumors (62%) were well differentiated and evidence of hormone production was present in 24 patients (46%). Patients with well-differentiated or functional tumors received mitotane, 6 gm daily; patients for whom mitotane failed or those with poorly differentiated, non-hormone-producing tumors received Adriamycin, 60 mg/m2 every 3 weeks. Initially, 36 patients were treated with mitotane and 16 patients with Adriamycin. Eight patients (22%) responded to mitotane and three (19%) responded to Adriamycin. No response was noted in the 15 patients for whom mitotane failed and who then received Adriamycin. Severe toxicity occurred in 36% of patients who received mitotane and in 26% who received Adriamycin. Overall median survival after onset of treatment was 14 months. We conclude that mitotane or Adriamycin used initially can induce tumor regression in about 22% and 19% of selected patients, respectively. However, Adriamycin is ineffective as second-line chemotherapy for patients with well-differentiated or functioning tumors for whom mitotane is ineffective.

Adrenal Cortex Neoplasms↗
PubMed1991

Clinical evaluation of albendazole and praziquantel in the treatment of cerebral cysticercosis.

One hundred consecutive patients presenting with symptoms and signs of neurocysticercosis, confirmed by neuroimaging techniques were randomly assigned to treatment with either praziquantel 50 mg/kg/day for 15 days or albendazole 15 mg/kg/day for 30 days. All patients were treated also with steroids for 42 days. Follow-up was for 90 days for response to treatment and for at least 1 year for recurrence. Although similar numbers of patients showed no improvement in neuroimaging criteria at 3 months, the response to albendazole was more pronounced with larger numbers showing marked improvement or disappearance of lesions. Similar findings were apparent, with resolution of the presenting neurological signs and symptoms being more frequent, in the albendazole group. Electroencephalographic changes were also normalized. The use of steroids eliminated the frequently observed headache that has been seen during the first few days of treatment and permitted severe cases to be treated. Both albendazole and praziquantel appear to be effective at the doses used, with albendazole showing a slightly better overall response.

Adult↗
PubMed1989

Microdosimetry of a 42 MeV therapy neutron beam.

Radiation quality of fast neutron therapy beams can change with depth. For a neutron beam generated by p----Be, the primary effect is a "hardening" of the neutron beam produced by the scattering of slow neutron components. A 42 MeV neutron therapy beam was investigated using microdosimetric techniques. We report measurements of dose mean and saturation-corrected lineal energy in water phantom at build-up depth, 5, 15, and 30 cm, and show representative logarithmic dose distributions in lineal energy. RBE is also calculated using assumptions based on the Theory of Dual Radiation Action and presented as a function of dose and depth.

Humans↗
PubMed1989

Radiation Therapy Oncology Group (RTOG) survival data on anaplastic astrocytomas of the brain: does a more aggressive form of treatment adversely impact survival?

The RTOG has sponsored several studies for malignant gliomas of the brain that have included tumors classified as either glioblastoma multiforme (GBM) or anaplastic-atypical astrocytoma (AAF) under the Nelson schema. Glioblastoma multiforme, the more aggressive histology, has done poorly under all forms of treatment having a typical median survival of 8-11 months. The less common and less aggressive anaplastic-atypical astrocytoma seems to show a survival that worsens with treatment more aggressive than standard radiotherapy. All patients in this report have had their tumors centrally reviewed by a RTOG neuropathologist and have had the diagnosis of anaplastic-atypical astrocytoma confirmed. We compare three patient groups: standard photon radiotherapy from the 60 and 70 Gy arms of RTOG 74-01/ECOG 1374 and from the 65 Gy control arm of RTOG 76-11; radiation therapy and chemotherapy from RTOG 74-01/ECOG 1374 (60 Gy + BCNU and 60 Gy + MeCCNU + DTIC) and from RTOG 79-18 (60 Gy + BCNU); and photon irradiation plus a neutron boost from RTOG 76-11 and RTOG 80-07. There are 47 analyzable cases treated with photons alone, 78 analyzable cases treated with photons + chemotherapy, and 38 analyzable cases treated with photons + neutron boost. Median survival for the three groups of patients is, respectively, 3.0 years, 2.3 years, and 1.7 years. Actuarial survival curves are presented for each subgroup of patients and then for the patient subgroups further broken down by major prognostic variables--age and Karnofsky performance status. In each "better prognostic category," the median survival decreased as the "aggressiveness" of the treatment increased. The implications of these findings for future clinical trials is discussed.

Adolescent↗
PubMed1989

Topical and systemic antibiotics in the prevention of wound infection.

We evaluated under controlled conditions the efficacy of topical and systemic antibiotics, alone and in combination, in the prevention of wound infection and measured serum and tissue antibiotic levels in the wound and distant tissue after administration of antibiotics topically, systemically, and in combination. Adult Sprague-Dawley rats were contaminated on the dorsal paravertebral muscles with a preset standardized inoculum of Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis. A second-generation cephalosporin was used; systemic administration was given intramuscularly and topically in powder form. Wound infection was confirmed by the recovery of the organism by culture. Prophylactic antibiotics were effective in preventing wound infection in all groups. Topical antibiotic and a combination (topical/systemic) antibiotic were significantly more effective than was systemic antibiotic alone in preventing wound infection. Adequate levels of antibiotic were achieved in serum and tissue with both topical and systemic antibiotics. Wound tissue concentration of antibiotic was significantly higher when topical antibiotic was used.

Administration, Topical↗
PubMed1989

Dimethyl-prostaglandin E2 prevents stress ulceration with minimal complications.

Gastric mucosal damage produced by topical application of necrotizing agents is diminished by topical or systemic pretreatment with a variety of E and F prostaglandins. The rat restraint model of gastric mucosal injury is more analogous to clinical stress ulceration than are models using intragastric application of toxic solutions; however, previous use of prostaglandin E1 in the restraint model resulted in a prohibitive incidence of GI morbidity. The current study used the restraint model of stress ulceration to compare the effects of a more potent prostaglandin analogue, 16,16-dimethyl prostaglandin E2, with hyperosmolar glucose and antacids. All three agents afforded significant protection from grossly apparent mucosal lesions, alone and in combination. Although other physiologic effects of each agent differed, the only effect which correlated with prevention of mucosal lesions was suppression of gastric acidity. Since effective doses of cytoprotective prostaglandins did not produce notable morbidity in comparison with other agents, they may prove to be a useful adjunct to stress ulcer prophylaxis in clinical settings.

16,16-Dimethylprostaglandin E2↗
PubMed1989

The cardiocirculatory and metabolic effects of endotoxin challenge after canine resuscitated hemorrhagic shock.

Although adequate volume resuscitation has decreased mortality from hemorrhagic shock, recovery in many patients is complicated by sepsis. To determine whether a subject debilitated by hemorrhagic shock would exhibit greater cardiocirculatory dysfunction when challenged with sepsis, ten dogs (Group I) were hemorrhaged to a mean arterial blood pressure of 30 mm Hg. After 2 hours of hypotension, shed blood and lactated Ringer's solution (50 ml/kg) were given, and the dogs were observed for 3 to 6 days. Ten dogs were sham hemorrhage and served as controls (Group II). On the experimental day, all cardiovascular and hemodynamic parameters were measured in both groups of animals before endotoxin challenge. There was no significant difference in cardiac output, stroke volume, stroke work, +dP/dt max, myocardial blood flow, myocardial oxygen metabolism, or acid-base balance in the two groups. Compared to sham-hemorrhaged dogs, resuscitated shock dogs had a significantly lower mean arterial blood pressure (127 +/- 7 vs. 110 +/- 6 mm Hg; p less than 0.05), and heart rate was significantly higher (86 +/- 6 vs. 109 +/- 7 beats/minute; p less than 0.05). Furthermore, maximal rate of left ventricular pressure fall (-dP/dT max) was significantly lower in the animals previously hemorrhaged, suggesting a persistent defect in left ventricular relaxation. Blood glucose and insulin levels were significantly elevated in the resuscitated shocked dogs, likely due to increased circulating catecholamine concentrations and enhanced glycogenolysis. Endotoxin shock caused significant hypotension, acidosis, and impaired regional perfusion in all dogs. In addition, cardiac output, stroke volume, dP/dT, and left ventricular end-diastolic pressure fell and hyperglycemia and hyperinsulinemia occurred in all dogs after endotoxin injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Do hospital personnel in hyperendemic areas require immunization against hepatitis B virus (HBV) infection? Is vertical transmission of HBV infection common in this group?

Medical personnel working in contact with blood and blood-contaminated body fluids are often considered to be a high-risk group for hepatitis B virus (HBV) infection and, as a result, it is recommended that they should be vaccinated against this infection. To find out if this is necessary in a country hyperendemic for HBV infection and to see if parents transmit the infection to their offspring, a total of 336 volunteer hospital employees, and 103 children of 47 of them, were tested for HBsAg, anti-HBc, anti-HBs, HBeAg and anti-HBe using the radioimmunoassay technique. Of these, 242 (72%) were found to have evidence of past or present HBV infection and only 94 (28%) had no such evidence. The infection prevalence in the 47 parents was 68% comparable to that of the total sample. Only 9 of their 103 children were positive for HBV markers. All tested parents of these positive children were either negative for all markers or positive for anti-HBs. The HBV infection prevalence among this hospital population is not different from that of the general Ethiopian population, and vertical transmission appears unlikely in this group. Therefore, mass vaccination of hospital staff in hyperendemic areas is unnecessary.

Adult↗
PubMed1988

Tamoxifen in advanced prostate cancer: an ECOG pilot study.

A group of 19 patients with advanced (Stage D) prostate cancer were treated with one of three dose levels of the anti-estrogen tamoxifen, 10 mg (3 patients), 20 mg (8 patients), or 30 mg (8 patients) daily. Five patients had received no prior systemic therapy. The treatment was tolerated well, but no objective responses occurred.

Cerebral Cortex↗