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Biomedical subjects

J Horton

Publications and source records attributed to J Horton.

At least 73 records · Page 4Linked to original sources
PubMed1996

Metastatic Adenoid Cystic Carcinoma of Salivary Glands: Case Reports and Review of the Literature.

BACKGROUND: Adenoid cystic carcinoma is an uncommon tumor of the salivary gland. Little has been published on the chemotherapy of this neoplasm. METHODS: The literature on this disease is reviewed, and data from seven unpublished cases are presented. RESULTS: Four patients received cyclophosphamide. One responded, and another had pain relief. The literature review did not identify any single drug or combination that might be regarded as the treatment of choice. CONCLUSIONS: Systematic, multi-institutional studies are required to determine appropriate systemic treatment for metastatic adenoid cystic carcinoma of salivary gland origin.

Journal Article↗
PubMed1996

Age and the Risk of Breast Cancer Recurrence.

BACKGROUND: Various parameters assist in the definition of prognosis and in the choice of therapy for breast cancer. This study evaluates the effects of prognostic factors on disease outcome in elderly women. METHODS: A retrospective cohort analysis was performed on 1,267 consecutive patients with locoregional breast cancer, including 374 patients 65 years of age or older, who were referred to a university cancer center over an eight-year period. Information on prognostic factors, disease outcome, and survival was analyzed. RESULTS: Women 65 years of age or older were more likely to have early-stage cancers, lower histologic grade, higher hormone receptor levels, and lower S-phase fractions. They experienced a longer time to disease recurrence and overall longer survival than their younger counterparts. CONCLUSIONS: Advancing age should not be considered an unfavorable risk factor for breast cancer. Prognosis and treatment should be based on disease stage and histologic and biologic parameters rather than patient age.

Journal Article↗
PubMed1996

Selective inhibitors of plasma kallikrein.

Based on a tetrapeptide fragment [Pro387-Ser390] of HK we have developed a series of potent low molecular weight (5-600 Da) inhibitors of PK which are stable to the enzyme. These inhibitors show good selectivity for PK versus tissue kallikrein, thrombin and plasmin. Such inhibitors will help define the role of PK and kinins in human physiology and pathophysiology. They may also find clinical use in the treatment of diseases where kinins are important mediators.

Amino Acid Sequence↗
PubMed1996

Continuous infusion etoposide in advanced AIDS-related kaposi sarcoma.

We conducted a preliminary phase II clinical trial to determine the toxicity, response, and survival rate of 72-hour continuous infusion etoposide administered to patients with AIDS-related Kaposi sarcoma. Nine patients with biopsy proven and measurable disease AIDS-related Kaposi sarcoma were treated with a continuous infusion of etoposide at a dose of 100 mg/m2 per day for 3 days every 3 weeks. All patients were evaluated for toxicity, response, and survival employing the NCI Common Toxicity Criteria, and both the Eastern Cooperative Oncology Group (ECOG) and AIDS Clinical Trials Group (ACTG) response criteria. All patients enrolled had at least two on-study poor risk factors by ACTG staging criteria. A total of 17 cycles of therapy were administered. Thirty-five percent of cycles were associated with grade 3 or greater leukopenia. Infectious complications were common, and there was one toxic death. Two partial responses (22%) by ACTG criteria were observed (95% confidence interval, 0% to 51%). In the absence of objective responses using more strict solid tumor response criteria and toxicity encountered we believe further evaluation of a 72-hour continuous infusion schedule of etoposide in patients with advanced AIDS and poor risk Kaposi's sarcoma is not warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Expression and regulation of superoxide dismutase activity in human skin fibroblasts from donors of different ages.

We have determined the activities, protein, and mRNA abundances as well as the level of transcriptional activation of two intracellular forms of the free radical metabolizing enzyme superoxide dismutase in 29 human skin fibroblast lines established from donors of different ages. SOD-1 (a copper and zinc containing form of SOD) and SOD-2 (a manganese containing form of the enzyme) activities were both observed to be significantly lower in cell lines derived from fetal skin than in lines established from postnatal skin (ages 17-94 years). The percent of total activity contributed by SOD-1 decreased in an age-associated manner from approximately 50% in the fetal lines to less than 20% in lines established from old tissue donors. All of the cell lines were screened to exclude the possibility that they contained a polymorphism known to influence SOD-2 activity. Northern blot analysis revealed three SOD-1 mRNA transcripts that were 0.5, 0.7, and 1.9 kb in length. Although SOD-1 protein abundance was lower in fetal lines than in lines derived from postnatal donors, SOD-1 mRNA abundance did not differ between fetal cells and cell lines derived from young donors. SOD-2 protein abundance and mRNA abundance were both significantly lower in fetal lines than in postnatal lines. No postnatal age-dependent differences were observed in any of the SOD-2 parameters examined. Nuclear run-on analysis revealed that fetal cell lines exhibited a lower level of transcriptional initiation for SOD-1 than postnatal lines. The transcription of SOD-2 was readily detected in postnatal lines, but undetectable in fetal lines. These results are consistent with multiple levels of control for SOD-1 expression and with a strong transcriptional influence on SOD-2 expression.

Adolescent↗
PubMed1995

Neurocysticercosis: optimal dose treatment with albendazole.

Albendazole has been used successfully in the treatment of cerebral cysticercosis for several years. The published dosage schedule has varied from 15 mg/kg/day for 8 days to up to 30 days. Fifty three patients with neurocysticercosis received 8, 15 or 30 days treatment with 800 mg of albendazole daily. The present study demonstrates the effectiveness in clinical and radiological terms of albendazole 800 mg/day for 8 days for the majority of patients affected with cystic or encephalitic parenchymatous cysticercosis. There was no apparent advantage of continuation of treatment for 15 or 30 days in this series. The routine use of high dose steroids limited the effects of parasite destruction. No toxicity attributable to albendazole was encountered.

Adult↗
PubMed1995

Middle cerebral artery blood flow velocity and stable xenon-enhanced computed tomographic blood flow during balloon test occlusion of the internal carotid artery.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography has been reported to reflect changes in cerebral blood flow (CBF) with the use of radioactive tracer techniques, which are weighted to measure primarily cortical structures. We tested the hypothesis that changes in transcranial Doppler ultrasonography would reflect changes in CBF in the middle cerebral artery vascular territory with the use of stable xenon-enhanced CT to assess CBF during carotid occlusion. METHODS: Thirty-one conscious patients underwent balloon test occlusion of the internal carotid artery and transcranial Doppler ultrasonography and xenon-enhanced CT assessment of blood flow velocity and CBF, respectively, of the middle cerebral artery and its distribution during balloon test occlusion. RESULTS: A significant correlation was seen between the change in CBF and the change in blood flow velocity for both brain levels at which CBF was determined (P < .0001). The average change in blood flow velocity was -13.4%, and the change in CBF was -15.1% and -17.7% at the two anatomic levels examined. CONCLUSIONS: The data indicate that changes in blood flow velocity generally reflect changes in CBF throughout the middle cerebral artery vascular territory with abrupt occlusion of the internal carotid artery in unanesthetized humans.

Adult↗
PubMed1995

Diagnosis and Management of Thyroid Cancer.

Thyroid carcinoma, which comprises the majority of endocrine malignancies, has a substantial annual morbidity and mortality based on age and other predisposing factors. Diagnosis of a growing thyroid nodule can be difficult, but ultrasonography, radionuclide scanning, and fine needle aspiration allow the majority of nodules to be properly characterized. Treatment of differentiated thyroid carcinoma remains controversial. Surgical resection continues to be the most important modality with long survival if the tumor is resected early. Newer imaging techniques have improved the diagnosis of locally recurrent or metastatic disease. Radioactive iodine ablation is indicated for patients with "high-risk" tumors or advanced age. Few patients respond to cytotoxic chemotherapy. In the past decade, advances in the screening and diagnosis of medullary thyroid carcinoma have led to earlier detection with improvement in survival.

Journal Article↗
PubMed1994

Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrome.

OBJECTIVE: To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS). DESIGN: A prospective, double-blind, placebo-controlled, randomized, parallel, multicenter pilot clinical trial. PATIENTS: A total of 51 patients with sepsis-induced ARDS were entered into the study within 18 hours of developing sepsis or sepsis syndrome. INTERVENTION: Patients were randomized into four treatment groups in a 2:1:2:1 ratio, as follows: 12 hours of surfactant per day, 12 hours of 0.6% saline per day, 24 hours of surfactant per day, and 24 hours of 0.6% saline per day. Surfactant or saline was aerosolized continuously for up to 5 days using an in-line nebulizer that aerosolized only during inspiration. MAIN OUTCOME MEASURES: Ventilatory data, arterial blood gases, and hemodynamic parameters were measured at baseline, every 4 or 8 hours during the 5 days of treatment, 24 hours after treatment, and 30 days after treatment, at which time mortality was also assessed. Safety was evaluated throughout the 30 days of the study. RESULTS: Surfactant was administered safely in ventilated patients when given continuously throughout the 5 days using the nebulizer system. Although there were no differences in any physiological parameters between the treatment groups, there was a dose-dependent trend in reduction of mortality from 47% in the combined placebo group to 41% and 35% in the groups treated with 12 hours and 24 hours of surfactant per day, respectively. CONCLUSIONS: Aerosolized surfactant was well tolerated when administered on a continuous basis for up to 5 days; however, at the doses given, it did not result in significant improvements in patients with sepsis-induced ARDS.

APACHE↗
PubMed1994

Hormonal treatment for metastatic breast cancer. An Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen.

BACKGROUND: Tamoxifen and aminoglutethimide are two hormone therapies reported to be effective palliative approaches for patients with metastatic breast cancer. The current trial was designed to evaluate their relative therapeutic effectiveness. METHODS: Two hundred forty-nine postmenopausal women with advanced breast cancer were randomized in an Eastern Cooperative Oncology Group (ECOG) Phase III study to treatment with adrenalectomy, aminoglutethimide, or tamoxifen with crossover to alternate therapy if disease progressed. Adrenalectomy was dropped as a treatment after 2 years because of low patient accrual. RESULTS: There were 216 evaluable patients entered in the study with 108 initially randomized to aminoglutethimide and 108 to receive tamoxifen therapy. The overall response rate for aminoglutethimide was 45%, and for tamoxifen it was 27%. One institution had a response rate of 60% with aminoglutethimide and only 4% with tamoxifen, whereas all of the other institutions combined had a response rate of 41% with aminoglutethimide and 34% with tamoxifen. Eighty-seven evaluable patients crossed over to the other drug (44 to aminoglutethimide and 43 to tamoxifen). There was a 36% response rate to aminoglutethimide and 19% to tamoxifen, with stable disease in 36% of both groups. The overall survival rates were identical. Toxicity was greater with aminoglutethimide (dermatitis) but was not life-threatening. Glucocorticoid support with either dexamethasone or hydrocortisone was acceptable. CONCLUSIONS: Both aminoglutethimide and tamoxifen produced responses in postmenopausal patients with breast cancer, and a significant number of crossover responses were observed. Of interest in this randomized study was the observation that one institution had a markedly different response rate on induction, reinforcing the need for multi-institution trials in Phase III studies.

Adrenalectomy↗
PubMed1994

Continuous infusion bleomycin in AIDS-related Kaposi's sarcoma.

PURPOSE: To determine the toxicity, response, and survival rate of 72-hour continuous infusion bleomycin administered to patients with AIDS-related Kaposi's sarcoma. PATIENTS AND METHODS: Seventeen patients with biopsy-proven and measurable-disease AIDS-related Kaposi's sarcoma were treated with a continuous infusion of bleomycin at a dose of 20 mg/m2/d for 3 days every 3 weeks. All patients were evaluated for toxicity, response, and survival using the National Cancer Institute common toxicity criteria, and both the Eastern Cooperative Oncology Group (ECOG) and AIDS Clinical Trials Group (ACTG) response criteria. Fourteen of 17 patients (82%) enrolled had at least two on-study poor-risk factors by ACTG staging criteria. RESULTS: A total of 59 cycles of therapy were administered. Only one cycle (2%) was complicated by an absolute neutrophil count less than 500, and there were no episodes of febrile neutropenia. Fifty-four percent of cycles were associated with fever during the infusion, and five cycles (8%) were complicated by grade 3 rash. There were no other clinically significant (> or = grade 3) toxicities. There were seven partial remissions (41%) by ECOG criteria (95% confidence interval, 18% to 64%) and 11 partial remissions (65%) by ACTG criteria (95% confidence interval, 42% to 88%). Three of five (60%) previously treated patients had a partial remission with this schedule of bleomycin. The median survival duration was 7 months, with a range of 2.5 to 25 months. CONCLUSION: This continuous infusion schedule of bleomycin is active in patients with advanced-stage AIDS-related Kaposi's sarcoma and has acceptable toxicity. This regimen should be further evaluated in patients with earlier stage Kaposi's sarcoma and as salvage therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Effects of estrogen on response to edetic acid infusion in postmenopausal osteoporotic women.

We and others have hypothesized that estrogen helps preserve bone mass by affecting the PTH/vitamin D regulation of skeletal metabolism. To evaluate this theory, we tested the effect of estrogen administration on parathyroid sensitivity to hypocalcemic challenge. Subjects were postmenopausal osteoporotic women recruited from a tertiary care clinic (9 untreated and 12 receiving hormone replacement therapy at the time of the investigation). After baseline serum and urine testing, edetic acid (50 mg/kg) was infused over a 2-h period. Serum and urine samples were obtained over 5 h and 24 h after beginning the infusion. Serum ionized calcium dropped equally in both groups of women. There were overall group differences in PTH-(1-84) secretion (P < 0.02), with a greater peak (P < 0.04) and a longer period of elevation (P < 0.01) in the untreated than in the hormone-treated osteoporotic women. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] and phosphorus as well as urinary phosphate and cAMP responded similarly in the two groups of women. Estrogenized osteoporotic women demonstrate a smaller PTH increment to hypocalcemia, indicating that the parathyroid has reduced sensitivity under the influence of estrogen. Despite the smaller PTH increase in estrogenized individuals, renal responses to PTH were the same as those in untreated osteoporotic women, implying an estrogen-mediated increase in the sensitivity of the kidney to PTH.

Administration, Oral↗
PubMed1994

Cleavage of human kininogen fragments at Met-Lys by human tissue kallikrein.

1. Tissue kallikrein (TK) cleaves low molecular weight kininogen (LK) at two sites to release kallidin: site I (between Arg389 and Ser390) is a typical cleavage point for a trypsin-like enzyme whereas site II (between Met379 and Lys380) is unusual and unique to TK. In order to learn more about the structural requirements and mechanism of cleavage at site II, we studied the hydrolysis by TK of several synthetic LK fragments varying in length between 4 and 22 residues and containing either site II only or both sites I and II. 2. Blocking site I cleavage in LK fragments by substituting DArg for LArg at position 389 or omitting site I from the sequence still allowed cleavage to proceed at site II. Replacement or deletion of selected amino acid residues in these fragments demonstrated that the presence of Arg381 was essential for site II cleavage to occur whereas Pro383, Phe385 and Ser386 could be replaced with Ala without affecting binding or cleavage by TK. Ki values towards TK were determined for all LK fragments in order to compare their binding affinities to the enzyme. Short peptides containing site II only exhibited high Ki values (> or = 100 microM) whereas longer fragments containing both sites I and II had Ki values of 2-7 microM. 3. In order to bring sites I and II into close proximity spatially and thus facilitating efficient cleavage in the enzyme-substrate complex, we prepared several cyclic analogs of the longer LK fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗