Relationship between respiratory symptoms and cough receptor sensitivity.

The relationship was studied between preschool and current respiratory symptoms and cough receptor sensitivity in children. Forty six white children aged 7 years were investigated. They were divided into three groups: (i) healthy children; (ii) children with a history of idiopathic cough; and (iii) children with a history of wheezing. Cough receptor sensitivity was assessed by the inhalation of serially increasing concentrations of nebulised citric acid. The concentration which first induced a cough was the cough threshold and was taken as a measure of cough receptor sensitivity. The cough threshold was unrelated to respiratory symptoms, bronchial responsiveness, parental smoking, and atopic status. A wide variation in cough threshold was seen. Although these results suggest that idiopathic cough is unrelated to cough receptor sensitivity as assessed by the citric acid cough threshold, it is unclear whether threshold measurements are an accurate reflection of receptor sensitivity.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

Case report 487

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official nor as reflecting the views of the United States Air Force     

Adenylate cyclase activity as a predictor of thyroid tumor aggressiveness

Prior studies in our laboratory have shown that human thyroid neoplasms have a greater adenylate cyclase activity in response to thyroid stimulating hormone (TSH) than does the adjacent histologically normal thyroid tissue. However, there is little information relating activity of the TSH receptor-adenylate cyclase system to the type of thyroid neoplasm. Thyroid tissue from 67 patients was divided by clinical and histological criteria into 6 categories: normal (59), benign tumors (20), stage 1 carcinoma—intrathyroidal involvement only (25), stage 2 carcinomaregional lymph node involvement (6), stage 3 and 4 carcinoma—tissue invasion or distant metastasis (11), and medullary carcinoma (3). Adenylate cyclase activity in an 8,000 x g thyroid membrane preparation was determined in the basal state and when maximally stimulated with 300 mU/ml TSH. The cyclase responsiveness was the ratio of TSH stimulated adenylate cyclase activity compared to basal adenylate cyclase activity. The cyclase responsiveness by category is: normal, 2.8±0.2 (mean ± SEM); benign, 17.9±2.4; stage 1 carcinoma, 9.2±1.9; stage 2 carcinoma, 4.0±1.0; stage 3 and 4 carcinoma, 1.6±0.4; and medullary carcinoma, 1.05±0.04 (for the neoplasms,p <0.02 by ANOVA). Tumor stage was the only correlate with this trend as other prognostic risk factors (age, sex, a history of neck irradiation, or papillary versus follicular histology) showed no difference in cyclase responsiveness. These studies demonstrate a consistent inverse correlation between adenylate cyclase responsiveness and tumor stage or aggressiveness. Cyclase responsiveness appears to have clinical application for predicting which thyroid tumors will behave aggressively.

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Resumen Estudios previos en nuestro laboratorio han demostrado que los neoplasmas tiroideos humanos poseen una mayor actividad de adenilato ciclasa en respuesta a la administración de hormona estimulante de la tiroides (TSH) que el tejido tiroideo histológicamente normal adyacente. Sin embargo, existe muy poca información sobre la relation de la actividad del sistema receptor de TSH-adenilato ciclasa y el tipo del neoplasma tiroideo. Tejido tiroideo proveniente de 67 pacientes fue dividido mediante criterios chlínicos e histológicos en 6 categorias: normal (59), tumores benignos (20), extensión intratiroidea solamente en estado 1 (25), carcinoma-extensión ganglionar regional en estado 2 (6), carcinoma-invasión tisular o metástasis distantes en estados 3 y 4 (11), y carcinoma medular (3). La actividad de la adenilato ciclasa en una preparación de membrana tiroidea de 8,000 × g fue determinada en el estado basai y en estado de maxima estimulación con 300 mU/ml TSH. El grado de respuesta de la ciclasa fue la tasa de actividad de la adenilato ciclasa estimulada por TSH comparada con la actividad basai de la adenilato ciclasa. El grado de respuesta por categorías fue: normal, 2.8±0.2; tumor benigno, 17.9±2.4; carcinoma estado 1, 9.2±1.9; carcinoma estado 2, 4.0±1.0; carcinoma estados 3 y 4, 1.6±0.4; y carcinoma medular, 1.05±0.04 (para los neoplasmas,p < 0.02 por ANOVA). El estado del tumor apareció como el único factor de correlatión con esta gradación, ya que otros factures de pronóstico (edad, sexo, historia de irradiación cervical, histología papilar versus folicular) no demostraron diferencia en cuanto al grado de respuesta de la ciclasa. Estos estudios demuestran una consistente relación inversa entre el grado de respuesta de la adenilato ciclasa y el estado o agresividad tumoral. El grado de respuesta de la ciclasa parece tener aplicación clínica para predecir qué tumores tiroideos se habrán de comportar en forma agresiva.

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Résumé Les études antérieures provenant de nos laboratoires ont démontré une augmentation de l'activité enzymatique de l'adénylate-cyclase en réponse à la thyroïd stimulating hormone (TSH) dans le tissu thyroïdien humain tumoral, par rapport au tissu thyroïdien adjacent normal. Cependant il existe peu de données concernant l'activité du système récepteur TSH/adénylatecyclase par rapport au type de tumeur de la thyroïde. Les tissus thyroïdiens provenant de 67 patients différents ont été repartis en 6 groupes selon des critères cliniques et histologiques: normal (59), tumeur bénigne (20), cancer stade 1 (intrathyroïdien uniquement) (25), cancer stade 2 (envahissement ganglionnaire régional) (6), cancer stade 3 et 4 (envahissement tissulaire avoisinant ou métastases à distance (11), et cancer médullaire (3). A partir d'une préparation de membrane thyroïdienne centrifugée à 8,000 × g, l'activité de l'adénylate-cyclase a été déterminée en l'état basai et après stimulation maximale par 300 mU/ml de TSH. La réponse enzymatique a été mesurée comme étant le rapport de l'activité stimulée par la TSH/activité basale. Les résultats selon les 6 groupes étaient (moyen±ET): tissu normal, 2.8±0.2; tumeur bénigne, 17.9±2.4; cancer stade 1, 9.2±1.9; cancer stade 2, 4.0±1.0; cancers stade 3 et 4, 1.6±0.4; et cancer médullaire, 1.05±0.04 (p < 0.02 par l'analyse de variance pour les néoplasies). Le stade tumoral était la seule variable corrélée avec l'activité enzymatique. L'activité enzymatique n'était pas corrélée avec l'âge, le sexe, les antécédents d'irradiation cervicale antérieure ou l'histologie (papillaire vs. folliculaire). Ces études montrent un rapport inversement proportionnel entre l'activité d'adénylate-cyclase et le degré d'agressivité tumorale ou le stade. La réponse d l'adénylate-cyclase paraît avoir une application clinique: prévoir quelles tumeurs thyroïdiennes auront une évolution agressive.

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Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.

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Supported in part by the Medical Research Service of the Veterans Administration.