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J Schwade

Publications and source records attributed to J Schwade.

12 recordsLinked to original sources
PubMed2001

What's in a shape? Children represent shape variability differently than adults when naming objects.

Children and adults often generalize a word to objects of the same shape. However, the shape properties on which generalization is based are unknown. We investigated the degree to which two shape dimensions were represented categorically by children and adults when learning names for objects. Multidimensional scaling techniques were used to establish the perceptual similarity of two sets of objects in Experiment 1. In Experiments 2 and 3, children (from 2;8 to 4;5 years of age) and adults participated in two tasks in which they learned a novel name for an exemplar. We then examined how often the novel name was generalized to different objects and to line drawings of the objects. In one task, participants generalized the names from memory; in a second task the exemplar was in front of the participant during generalization. Adults accepted names more often to objects that fell "within" the proposed shape boundaries than to objects that fell "across" the boundaries. Children, however, were just as likely to generalize names to novel objects that fell within as to objects that crossed the boundaries.

Adolescent↗
PubMed2000

Radical prostatectomy: geographic and demographic variation.

OBJECTIVES: Previous reports have documented a geographic variation in the use of radical prostatectomy. We examined whether this phenomenon can be explained by factors other than geography alone. METHODS: This study was based on the data from nine geographic regions of the Surveillance, Epidemiology, and End Results (SEER) program for the years 1983 through 1994. Patients with localized or regional prostate cancer were included in the analysis. Logistic regression analysis was used to investigate the influence of geographic and demographic factors on the use of radical prostatectomy. The squared multiple correlation coefficient R(2) was used to measure the proportion of variation in the selection of radical prostatectomy explained by each factor of interest. RESULTS: As previously reported, the use of radical prostatectomy was significantly associated with geographic location; the degree of geographic variation varied as a function of age and was most dramatic in the youngest (younger than 45 years) and the oldest (75 years or older) groups. Overall, however, geography explained less than 2% of the total variation in the use of radical prostatectomy. Age was the most important factor that influenced the use of radical prostatectomy. CONCLUSIONS: Geography explains only a small proportion of the variation in the use of radical prostatectomy. In fact, of the factors examined, only age appeared to meaningfully explain the variation in the use of radical prostatectomy. Overall, our ability to explain the variation in the use of radical prostatectomy remains meager, and new factors must be identified if we are to better understand how patients and physicians make clinical decisions.

Adult↗
PubMed1995

Five-chlorodeoxycytidine and biomodulators of its metabolism result in fifty to eighty percent cures of advanced EMT-6 tumors when used with fractionated radiation.

PURPOSE: To extend our findings in previous radiation and biochemical studies with five rodent tumors, in which we used one and occasionally two or three irradiations. The extent of control of the EMT-6 mammary adenocarcinoma was determined using fractionated radiation (12 irradiations) over a 3-week period using the radiosensitizer 5-chloro-2'-deoxycytidine (CldC) and biomodulators of its metabolism: N-(Phosphonacetyl)-L-aspartate (PALA), tetrahydrouridine and 5-fluoro-2'-deoxycytidine (FdC). METHODS AND MATERIALS: Mammary adenocarcinoma EMT-6 tumors implanted 1 week prior to therapy in BALB/c mice were subjected to single daily doses of focused radiation, not exceeding a total of 60 Gy, on days 2-5 of each week. N-(Phosphonacetyl)-L-aspartate (PALA) was administered on the first day of therapy. Five-fluoro-2'-deoxycytidine and CldC were administered in the morning and afternoon, respectively, of the next 2 days, and CldC was administered on the fourth day. Tetrahydrouridine was always coadministered with FdC or CldC. Drug and radiation treatments overlapped for 3 weeks. RESULTS: Fifty to 80% cures (usually 70%) were obtained with no apparent morbidity and the same moderate weight loss that occurs with radiation alone. Neither tumor regrowth delay nor cures were obtained with drugs or radiation alone. An apparent threefold dose increase effect was obtained with the end point: "days to reach 4 times initial tumor volume." Increasing the radiation dose threefold (without drugs) resulted in four out of five deaths; increasing the dose twofold (without drugs) resulted in extensive weight loss and hair loss in the entire ventral area and no cures. Increasing the dose of drugs or radiation 1.5-fold, in the complete protocol, did not result in increased morbidity. Comparative studies with Iododeoxyuridine demonstrate the heightened efficacy of CldC. CONCLUSIONS: One cannot achieve the same results obtained with CldC and the modulators by merely increasing the dose of radiation. There is a significant window of safety in this approach. The evidence we have obtained with EMT-6, the fifth rodent tumor we have studied with CldC, as well as the demonstrated and proposed reasons for its superior efficacy over 5-Iododeoxyuridine (and 5-Bromodeoxyuridine), drugs in current use, indicate that CldC will allow more aggressive treatment of human tumors with radiation than is now feasible.

Adenocarcinoma↗
PubMed1994

Phase I trial of low dose N-phosphonacetyl-L-aspartic acid and high dose 5-fluorouracil administered concomitantly with radiation therapy for unresectable localized adenocarcinoma of the pancreas.

BACKGROUND: Preclinical and clinical data suggest that N-phosphonacetyl-L-aspartic acid (PALA) can augment the cytotoxic effects of 5-fluorouracil (5-FU). In addition, the combination of 5-FU and radiation therapy has been used with success in prolonging survival and providing palliation of symptoms in patients with advanced unresectable pancreatic carcinoma. This Phase I study was undertaken to determine the feasibility and evaluate the qualitative and quantitative toxicities of PALA and escalating doses of 5-FU administered concomitantly with radiation therapy in patients with locally advanced nonmetastatic pancreatic adenocarcinoma. METHODS: Ten previously untreated patients with advanced nonmetastatic adenocarcinoma of the pancreas were treated with 250 mg/m2 of PALA given as an intravenous bolus followed 24 hours later by 5-FU, which was given by continuous 24-hour infusion every week. The 5-FU doses were assigned according to a Phase I drug escalation (1000 mg/m2, 1300 mg/m2, and 1700 mg/m2). Radiation therapy was delivered concurrently with chemotherapy at a dose of 180 cGy per fraction (900 cGy per week) over 6 1/2 weeks. PALA and 5-FU were continued weekly after the end of radiation therapy, with disease assessments made every 8 weeks. Chemotherapy was continued until the disease progressed. RESULTS: All 10 patients were evaluable. The maximum tolerated dose (MTD) of 5-FU was 1300 mg/m2. Two of the four patients treated at the 1700 mg/m2 dose level experienced dose-limiting toxicities, nausea/vomiting and mucositis, respectively. Toxicities were mild to moderate at the 1000 mg/m2 and 1300 mg/m2 dose levels. Two patients treated with 5-FU at the 1300 mg/m2 dose level had complete responses, and one patient treated at the 1700 mg/m2 dose level had a partial response. The median survival was 12.5 months, and four patients survived more than 1 year. CONCLUSIONS: PALA and 5-FU administered concomitantly with radiation therapy is an active regimen in locally advanced, unresectable pancreatic cancer. Dose-limiting toxicities are nausea/vomiting and mucositis. The MTD of 5-FU is 1300 mg/m2. The regimen is well tolerated and administered in an outpatient setting.

Adenocarcinoma↗
PubMed1992

5-chlorodeoxycytidine, a radiosensitizer effective against RIF-1 and Lewis lung carcinoma, is also effective against a DMBA-induced mammary adenocarcinoma and the EMT-6 tumor in BALB/c mice.

5-Chlorodeoxycytidine (CldC), coadministered with modulators of pyrimidine metabolism, is an effective radiosensitizer of murine tumors. Past studies that utilized RIF-1 tumors in C3H mice and Lewis lung carcinoma (LLC) in BDF1 mice have been extended with an emphasis on using multiple cycles of drug administration followed by irradiation of LLC and the use of two additional tumor models. Four of seven cures of BDF1 mice bearing LLC were obtained with three doses of 20 Gy irradiation, in which the first and third dose were preceded by a "Standard Protocol" that includes N-(phosphonacetyl)-L-aspartic acid (PALA), 5-fluorodeoxycytidine (FdC), tetrahydrouridine, and the radiosensitizer, 5-chlorodeoxycytidine. No cures were obtained in groups of mice receiving radiation alone or drugs alone, and there were no "no takes" in untreated control groups (six mice/group). Extensive tumor inhibition, exceeding that obtained with drugs or radiation alone, was obtained with two cycles of drugs and radiation combined when a dimethybenzanthracene-induced mammary adenocarcinoma was used in BALB/c mice. With the EMT-6 tumor in BALB/c mice, doses of 10 and 20 Gy were administered 9 and 16 days after tumor implantation, each preceded with the Standard Protocol; this resulted in a tumor growth delay of 24 days. No tumor growth delay occurred with drugs or radiation alone. The omission of PALA, FdC or CldC from the Standard Protocol resulted in loss of tumor control, which was obtained with the complete protocol. The fact that 5-chlorodeoxycytidine is an effective radiosensitizer in four rodent tumor systems is compelling evidence that it has potential as a radiosensitizer of human tumors, especially in view of its tumor selectivity and its resistance to catabolism when used with modulators of its metabolism, and in view of the high levels of the key enzymes in human tumors, which can convert 5-chlorodeoxycytidine to 5-chlorodeoxyuridine triphosphate, the proximate radiosensitizer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Preclinical evaluation of submillimeter diameter microwave interstitial hyperthermia applicators.

Ultra miniature coaxial cable has been used, with microscopic techniques, to fabricate interstitial hyperthermia applicators having diameters of 0.20 mm, 0.33 mm, and 0.58 mm; commercial applicators have a diameter of 1.1 mm. Animal studies with the 0.33 mm diameter applicators have shown that they produce less local tissue trauma than the larger-diameter devices. All of these applicators operate at 915 MHz and have similar heating patterns because they use the conventional monopole design and the catheters have been approximately scaled to the dimensions of each size applicator. We have measured the heating (SAR) patterns of these applicators in tissue-simulating phantoms, both singly and in arrays, using a miniature electric field probe. As an intermediate step to patient trials, we have examined the ability of these applicators to provide effective heating of perfused tissue, using pig thigh and liver as models. Test results suggest that the durability and power handling capabilities of our submillimeter applicators are adequate for use in patients. These new applicators should be useful in the percutaneous treatment of deep-seated tumors and in intraoperative treatments. The applicators also permit intraluminal or intravascular access to tumors.

Animals↗
PubMed1984

A Phase I study of intermittent intravenous bromodeoxyuridine (BUdR) with conventional fractionated irradiation.

A Phase I trial of intravenous bromodeoxyuridine (BUdR) and conventional fractionated radiation therapy was performed in 14 patients with glioblastoma multiforme and 7 patients with other poorly radioresponsive tumors. The BUdR was given as a constant intravenous infusion for 12 hr/day for up to 14 days. Thirteen patients received a second 14 day infusion following a 10 to 14 day interruption for bone marrow recovery. Local toxicity (within the radiation field) was minor, with 7 of the 21 patients requiring a brief treatment break for moist skin desquamation. There was no significant CNS toxicity noted clinically nor by autopsy examination. Additionally, no significant enhancement of radiation injury was noted to bowel or liver. However, one patient treated for multiple pulmonary metastases experienced a clinical and radiographic pattern consistent with radiation pneumonitis. Dose-dependent systemic toxicity occurred in bone marrow and skin. Moderate myelosuppression, especially thrombocytopenia, was found following a 14 day cycle of BUdR at and above 650 mg/m2/12 hr infusion. Approximately one-third of patients developed a maculo-papular erythematous rash to the scalp, neck and upper chest. In two patients, the rash became generalized with evidence of epidermolysis on skin biopsy. Pharmacology studies revealed steady-state arterial plasma levels of 2 X 10(-6) M/1 during the 12 hr infusion of 650 to 700 mg/m2. Radiosensitization was measured by a change in the D0 of radiation survival curves of human bone marrow CFUc prior to and following the 14 day infusion in 4 patients. A trend of increasing radiosensitization was noted in most patients as the infusion rate of BUdR was increased from 500 to 870 mg/m2/12 hr. We conclude that the maximum tolerable dose of BUdR is 650 to 700 mg/m2/12 hrs when given as a 2 week intermittent intravenous infusion. Local toxicity is acceptable. The major systemic toxicities are myelosuppression and a maculopapular skin rash.

Adult↗
PubMed1982

Effects of cranial radiation on hypothalamic-adenohypophyseal function: abnormal growth hormone secretory dynamics.

The function of the hypothalamic-adenohypophyseal unit was tested in 2 groups of rhesus monkeys before and at periodic intervals after the administration of 2400 and 4000 rads cranial radiation. This therapy was given in 10 fractions over a 2-week period. Plasma TSH, basally and after TRH administration, and LH and FSH, before and after gonadotropin-releasing hormone stimulation, were normal up to 1 yr after radiation. Plasma GH at the basal state and after arginine and L-dopa stimulation was also normal. An insulin tolerance test, however, demonstrated a blunted GH response at a dose (0.1 U/kg) that caused brisk stimulation of GH secretion in normal control monkeys. A larger dose of insulin (0.2 U/kg) resulted in ample secretion of GH in these animals, suggesting decreased hypothalamic sensitivity to insulin in treated animals. The measurement of GH every 20 min for 24 h in animals treated with 4000 rads showed a dramatically altered secretory pattern of GH 1 yr after radiation. GH secretory spikes were markedly decreased in both frequency and amplitude, suggesting a reduction in the normal daily production of GH.

Animals↗
PubMed1977

A comparison of the response to arm and leg work in patients with ischemic heart disease.

An exercise test based on arm work was evaluated in a series of 33 male patients, mean age 52 years, with ischemic heart disease. The responses to arm exercise on a modified table-mounted bicycle ergometer and to standard bicycle exercise were compared. Twenty six of 33 patients (79 per cent) had identical end-points with both tests. Three patients had an ischemic response, i.e., significant ST abnormality and/or angina pectoris during leg work only, and four patients during arm work only. 41 per cent of the peakload during leg exercise. Mean values were 181 and 439 kpm./min. (p less than 0.001). Comparison of individual data on peak load demonstrated only a weak correlation between arm and leg work capacity (r = 0.37, p less than 0.05). Peak heart rate was slightly higher during leg work, 129 compared to 122 beats/min. (p less than 0.05) but the mean heart rate-systolic blood pressure products were not significantly different. A subgroup of seven patients had a history of angina pectoris preferentially precipitated by arm work but their physiological responses did not differ significantly from those of patients without a history of arm work sensitivity. The data indicate that arm work is a satisfactory alternate diagnostic test method with respect to myocardial ischemia, but measurements of physical work capacity defined as aerobic capacity, cannot be based on arm work.

Adult↗