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Biomedical subjects

J F Wilson

Publications and source records attributed to J F Wilson.

At least 181 records · Page 10Linked to original sources

Comparison of nonisotopic and radioimmunoassay techniques for digoxin: a study based on external quality assurance measurements.

A comparison of the precision and accuracy of three nonisotopic and of radioimmunoassay (RIA) techniques for digoxin was made using data from 141 samples of spiked human serum assayed between 1984 and 1987 by members of the Heathcontrol external quality assurance scheme. There were significant differences between techniques in the number of observations rejected as outliers greater than 3 SD from the sample mean, the percentages of rejected measurements being Abbott TDX 1.4, RIA 3.3, Ames TDA 4.2, and Syva EMIT 6.3. Ames TDA and Syva EMIT were shown to have a significantly lower precision than the other techniques in measurements of digoxin concentrations less than 1 nmol/L. A significant 4% negative bias was observed for Ames TDA measurements of digoxin concentrations between 1 and 2.6 nmol/L. A concentration-related bias was demonstrated for Abbott TDX measurements that varied from 14% overestimates at concentrations less than 1 nmol/L to 6.7% underestimates of digoxin at concentrations greater than 2.6 nmol/L.

Digoxin↗

Ion and ion channel involvement in alpha-melanocyte-stimulating hormone secretion from superfused slices of rat hypothalamus.

Release of alpha-melanocyte-stimulating hormone (alpha-MSH) from 250 micron frontal slices of rat hypothalamus superfused at 37 degrees C with oxygenated artificial cerebrospinal fluid (ACSF) was quantified in freeze-dried samples of ACSF by radioimmunoassay. Significant reproducible increases in alpha-MSH release were caused by 40-70 mM K+ in ACSF, maximum release being caused by 50 mM K+. Fifty mM K+-stimulated alpha-MSH release was abolished in the absence of Ca2+ from ACSF and by the presence of 10(-6) M tetrodotoxin. Tetrapentylammonium ions, 10(-4) M and 10(-3) M, stimulated dose-dependent increases in alpha-MSH release. The data support a putative neurotransmitter/neuromodulator role for alpha-MSH in the CNS.

Animals↗

Dopaminergic inhibition of alpha-melanocyte-stimulating hormone release from superfused slices of the rat hypothalamus.

The dopamine agonist apomorphine (10(-6) M) significantly reduced the 50 mM K+-stimulated, Ca2+-dependent release of immunoreactive alpha-melanocyte-stimulating hormone (alpha-MSH) from superfused slices of rat hypothalamus but did not alter baseline peptide release. Flupenthixol (10(-6) M), a dopamine receptor antagonist, significantly increased both basal and 50 mM K+-stimulated alpha-MSH release, possibly via blockade of inhibition caused by endogenous dopamine release. The latter increases were Ca2+-dependent and were inhibited by 10(-6) M apomorphine.

Animals↗

Nonfunctioning islet cell carcinoma of the pancreas. Complete response to continuous 5-fluorouracil infusion.

An unresectable, intraabdominal recurrence of a nonfunctioning islet cell carcinoma of the pancreas developed in a 56-year-old man 9 years after he achieved complete remission from extensive radiotherapy. Chronic renal failure secondary to radiation nephritis precluded the use of streptozotocin. 5-fluorouracil (5-FU) (300 mg/m2 per day) was given as a continuous, systemic infusion through a chronic indwelling central venous catheter for 1 year's duration. Treatment resulted in the prompt disappearance of all signs and symptoms of cancer, and computed tomography (CT) of the abdomen documented complete response. The patient continues in complete clinical remission 16 months after 5-FU was stopped. Continuous 5-FU infusion may be a potentially efficacious and less toxic alternative to streptozotocin in the treatment of islet cell carcinoma. Further clinical evaluation will be necessary to define its overall role in the management of these patients.

Adenoma, Islet Cell↗

Mammary carcinoma developing after radiotherapy and chemotherapy for Hodgkin's disease.

Two patients developed breast cancer after treatment of Hodgkin's disease. Both had received mediastinal irradiation 13 to 15 years, respectively, before the diagnosis of breast carcinoma. One patient had synchronous bilateral breast cancer when the diagnosis was made. Discussed is the risk of mammary carcinoma as a second malignant neoplasm in patients treated for Hodgkin's disease.

Adult↗

Low permeability of the blood-brain barrier to nanomolar concentrations of immunoreactive alpha-melanotropin.

The permeability of the blood-brain barrier (BBB) to immunoreactive alpha-melanotropin (alpha-MSH) was quantified in rats pretreated with monosodium L-glutamic acid to deplete their CNS stores of endogenous alpha-MSH. The methodology, suitable for poorly permeable substances, monitored blood and brain tissue concentrations of alpha-MSH over 15 min following intravenous injection of 30 nmol synthetic alpha-MSH. Rate constants for entry of alpha-MSH into brain tissue were estimated from separate non-linear least-squares fits of connecting two- and one-compartment open models to plasma and extravascular brain tissue concentration data, respectively. Comparisons were made to rate constants measured similarly for 14C-inulin. The BBB had a low permeability to immunoreactive alpha-MSH, consistent with peptide penetrating the barrier by passive diffusion dependent upon the lipid solubility of the molecule.

Animals↗

Application of the avidin-biotin immunohistochemical method for the diagnosis of alveolar hydatid disease from tissue sections.

The avidin-biotin immunohistochemical (ABC) method was applied to the diagnosis of alveolar hydatid disease in patients from the hyperendemic region of western Alaska. The test was specific for larval cestodes of the genus Echinococcus, and exhibited high sensitivity. A negative reaction was obtained in all cases in which spontaneous death of the larval cestode had occurred. Results were inconsistent in sections of lesions from patients who had received long-term therapy with mebendazole, because of the persistence of antigens for a considerable time following the death of the parasite.

Animals↗

Phase I-II study of prophylactic hepatic irradiation with local irradiation and systemic chemotherapy for adenocarcinoma of the pancreas.

Although the addition of 5-FU to radiation therapy for locally advanced adenocarcinoma of the pancreas improved short-term survival (GITSG), there were no differences in patterns of failure. Hepatic metastases were equally common in both groups. Therefore, a pilot study of prophylactic hepatic irradiation was developed. Between March 1983 and May 1985, 16 patients were entered in a Phase I/II study of prophylactic hepatic irradiation with local irradiation and systemic chemotherapy for adenocarcinoma of the pancreas at the Medical College of Wisconsin Affiliated Hospitals. Megavoltage radiation (1.8 Gy/fraction) was given to the pancreas with a minimal margin (2 cm) around the tumor, localized by surgical clips or CT scan with a total dose of 61.2 Gy over 7 weeks. Prophylactic hepatic irradiation was added to the fourth week of irradiation to a total dose of 23.4 Gy over 21/2 weeks. 5-Fluorouracil, 500 mg/M2/day was given at Day 1, 2, 3, 29, 30, and 31 of radiotherapy, then a weekly maintenance for 1 year. Fifteen patients were evaluable: One patient refused chemotherapy. The follow-up period was 14 to 50 months (median 26 months). The most common side effect was nausea. Maintenance 5-FU was discontinued in one patient because of GI bleeding. Three-quarters of the patients developed temporary elevations of hepatic enzymes. No severe or life-threatening complications were observed. One, 2-, 3-, and 4-year disease-free survivals are 66.7%, 46.7%, 20% and 13.3%, respectively. Patterns of failure revealed that only two patients had hepatic metastasis as the first site of failure, five patients died of abdominal carcinomatosis, and three patients failed in the pancreas. Two patients died without evidence of cancer. Two patients are alive and well beyond 4 years after the diagnosis. This study confirms that such aggressive combined modality treatment is well tolerated and suggests that the frequency of hepatic metastasis can be reduced.

Adenocarcinoma↗

Evaluation of chromatographic and kit immunoassay techniques for the measurement of theophylline in serum: a study based on external quality assurance measurements.

The accuracy and precision of assay techniques used to measure theophylline concentrations in human serum were compared using data from 96 samples from the Heathcontrol external quality assurance scheme. Abbott TDX had the highest precision, with a mean coefficient of variation (CV) of measurements of 6.4%, and Ames Fluorostat was most accurate, with a mean bias of +0.1%. Differences between the better techniques, however, were not significant. The Beckman ICS assay gave the lowest precision (CV 9.3%) and, in addition, produced the highest proportion (7.5%) of rejected observations greater than 3 standard deviations from the sample mean. The least accurate method was radioimmunoassay, with a -9.9% bias. Measurements from two samples spiked with paraxanthine demonstrated that 76% of laboratories using high-pressure liquid chromatography (HPLC) were unable to distinguish between paraxanthine and theophylline. The +4% bias observed at low concentrations and the high variability (CV 8.3%) of measurements made by HPLC were thus attributed to interference by paraxanthine present in the sample matrix. Discriminant analysis of a range of HPLC column and mobile phase parameters indicated that separation of theophylline and paraxanthine was achieved by the use of lower flow rates with mobile phases of solvent mixtures with lower proton donator selectivity.

Chromatography, High Pressure Liquid↗

Head and neck tumors: dosimetric considerations of mixed-energy photon beam therapy.

The goal of sophisticated treatment planning in radiation therapy is to maximize dose to the tumor or target volume, while the integral dose is minimized, to reduce normal tissue morbidity. In the head and neck regions, the anatomic irregularities of individual patients and the critical structures that limit the administration of dose within the irradiated volumes often complicate the optimization of dosimetry. The availability of dual-energy accelerators that deliver beams of low- and high-energy photons allows the convenient administration of mixed-energy photon irradiation and facilitates the development of optimal treatment strategies for selected lesions. Highly lateralized carcinomas of the upper aerodigestive tract, in which sparing of contralateral cervicofascial tissue is desirable, are particularly well suited for this technique. Treatment plans that make use of irradiation with conventional single-energy beams and mixed-energy photon therapy are compared for representative lesions of the head and neck.

Carcinoma, Squamous Cell↗

Risk factors for infection with Echinococcus multilocularis in Alaska.

We studied 19 Eskimo patients with alveolar hydatid disease from the north-western coast of Alaska for risk factors for infection with Echinococcus multilocularis. Each case-patient was matched by age and sex with 2 unrelated controls who had no clinical or serologic evidence of infection with E. multilocularis and who resided in three villages endemic for alveolar hydatid disease. Behaviors thought to increase exposure to E. multilocularis and the chronologic occurrence of these behaviors in the participant's life were assessed by a standardized questionnaire. Case-patients were more likely than controls to have owned dogs for their entire lives (odds ratio 6.00, P less than 0.05), tethered their dogs near the house (odds ratio 8.50, P less than 0.05), and lived in houses built directly on the tundra rather than on gravel or a permanent foundation (odds ratio 11.00, P less than 0.01). Case-patients were not more likely to have owned sled dogs, trapped or skinned foxes, or engaged in other outdoor activities away from home. These findings suggest that controlling the parasite in the domestic dog population, as well as controlling the dog population itself, are important aspects of preventing alveolar hydatid disease in the northwestern Native Alaskan population.

Adolescent↗

Esthesioneuroblastoma masquerading as extramedullary plasmacytoma.

Nine years after biopsy and radiation therapy for an extramedullary plasmacytoma of the nasal cavity, a 64-year-old man developed locally recurrent tumor. Repeat biopsy revealed tumor identical in hematoxylin and eosin stain (H & E) appearance to that found originally, leading to the diagnosis of recurrent extramedullary plasmacytoma. Neither the original tumor or its recurrence demonstrated features characteristic of esthesioneuroblastoma (e.g., nests, rosettes, ganglion cells, or fibrillary background). However, Gremilus staining and neuron specific enolase tests (immunoperoxidase method), done strictly as a teaching exercise, were strongly positive and eventually resulted in an altered diagnosis to esthesioneuroblastoma. This case underscores the difficulty that may be encountered in distinguishing these two pathologic entities of the nasal cavity solely on the basis of H & E staining. In view of differences in staging, evaluation, prognosis, and management, accurate differentiation of these two relatively uncommon tumors of the nasal cavity is of immediate clinical importance. These observations suggest that care should be taken to exclude the possibility of esthesioneuroblastoma before making the histologic diagnosis of extramedullary plasmacytoma of the nasal cavity.

Diagnosis, Differential↗

Severe reduction in food intake by pregnant rats resembles a learned food aversion.

To assess the effects of sucrose, low levels of dietary protein, and pregnancy on food intake, sixty-four female rats were assigned to eight groups in a 2 X 2 X 2 design. Food, water, and sucrose intake and rats' weights were measured daily. Pregnant rats offered sucrose with low protein (8%) diets did not maintain adequate weight gain during pregnancy; 25% of these subjects perished during the last days of pregnancy. These results have implications for human populations that have high birth rates and diets that are deficient in protein. A hormonal mechanism which regulates appetite or taste preferences during pregnancy is postulated and a "learned food aversion" interpretation is given for the data.

Animals↗

Objective response of malignant carcinoid to radiation therapy.

In a retrospective review, we were able to identify records for 18 patients who were treated for malignant carcinoid in our Departments of Radiation Oncology from 1974-1985. At postmortem examination, one was found not to have malignant carcinoid. In 4 cases irradiation was administered postoperatively to patients whose subsequent courses did not permit assessment of objective response. Using standard criteria for objective response, an objective response rate of 54% was observed in the 13 cases whose records were adequate to make this assessment. Of the 7 responses, 3 were complete within the treated field as judged by clinical findings (2 patients) or postmortem examination (1 patient). Of the 6 nonresponders, 2 interrupted treatment prematurely, 2 were treated to a planned dose of only 2000 and 2500 cGy, and 2 were treated palliatively to limited ports which included only partial volumes of tumor. We conclude that radiation therapy is an effective treatment modality with a high rate of objective response in the management of those patients with malignant carcinoid tumors who require non-surgical, anti-neoplastic therapy.

Carcinoid Tumor↗