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71.
Resistance to multiple hormones in patients with pseudohypoparathyroidism. Association with deficient activity of guanine nucleotide regulatory protein 总被引:14,自引:0,他引:14
M A Levine R W Downs A M Moses N A Breslau S J Marx R D Lasker R E Rizzoli G D Aurbach A M Spiegel 《The American journal of medicine》1983,74(4):545-556
Pseudohypoparathyroidism type I is characterized by resistance (defined as a deficient urinary cAMP response) to parathyroid hormone and, in most cases, hypocalcemia and hyperphosphatemia. Many patients with pseudohypoparathyroidism type I snow a peculiar somatic phenotype termed Albright's hereditary osteodystrophy, but patients without this feature who show identical parathyroid hormone resistance have been described. Parathyroid hormone resistance in pseudohypoparathyroidism type I has been attributed to a defective parathyroid hormone receptor-adenylate cyclase complex. Recent studies have demonstrated deficient activity of the guanine nucleotide regulatory protein (G unit) of adenylate cyclase in many patients with Pseudohypoparathyroidism. Since the G unit is common to all tissues, as opposed to hormone receptors, which are tissue specific, a defective G unit should lead to resistance to multiple hormones that act by stimulating adenylate cyclase. To test this hypothesis, we studied erythrocyte G unit activity and clinical endocrine function in 29 patients with pseudohypoparathyroidism type I. Thirteen patients had deficient erythrocyte G unit activity (43 ± 9 percent of control [mean ± 1 SD]); 16 patients had normal G unit activity (92 ± 8 percent of control) (p < 0.001). Patients with deficient erythrocyte G unit activity had significantly greater (p < 0.001) basal and thyrotropin-releasing hormonestimulated thyrotropin levels than patients with normal erythrocyte G unit activity or normal control subjects (15.0 ± 6.5 and 54.3 ±22.7; 4.5 ± 2.0 and 19.5 ± 6.6; 2.0 ± 1.1 and 16.5 ± 6.7 μU/ml, respectively). In the absence of goiter or antithyroid antibody, an elevated thyrotropin level in patients with deficient erythrocyte G unit activity is consistent with thyroid resistance to thyrotropin. Furthermore, patients with deficient erythrocyte G unit activity had significantly lower (p < 0.02) integrated plasma cAMP increases to glucagon stimulation than either patients with normal erythrocyte G unit activity or normal subjects (5.1 ± 2.2 versus 8.6 ± 3.9 versus 8.6 ± 3.6 μ M × minutes), consistent with impaired hepatic cyclase responsiveness to glucagon. Clinical evidence of gonadal dysfunction was common in patients with deficient erythrocyte G unit activity, but was not observed in patients with normal erythrocyte G unit activity. These observations suggest that patients with Pseudohypoparathyroidism and deficient erythrocyte G unit activity have a disorder that is generalized to cyclase-dependent tissues, and not limited to parathyroid hormone-sensitive tissues. Moreover, it appears that patients with pseudohypoparathyroidism and normal erythrocyte G unit activity may have a defect limited to parathyroid hormone-sensitive tissues. These data support the hypothesis that a deficiency of G units is the basis for multiple hormone resistance in pseudohypoparathyroidism. 相似文献
72.
Barnett S. Kramer Philip A. Pizzo Kathleen J. Robichaud Frank Witesbsky Robert Wesley 《The American journal of medicine》1982,72(4):561-568
Blood and surveillance body cultures are frequently used to monitor potential infectious complications in febrile cancer patients. However, such cultures are costly and their value unclear when patients are already being treated with antibiotics. We prospectively studied all patients who became febrile (oral temperature > 38 °C three times over a 24-hour period or > 38.5 °C once) and granulocytopenic (less than 500 polymorphonuclear leukocytes per mm3) during a four-year period, and evaluated the value of clinical assessment and microbiologic surveillance in patient management. Two hundred and seventy-one patients who experienced 652 episodes were entered into study. All patients had routine examination, chest radiograph, and surveillance cultures of nose, throat, urine, stool and at least two preantibtotic blood cultures. According to their initial evaluation, patients were classified as having an infectious etiology for their fever or as having unexplained fever, and were treated accordingly with specific or empiric antibiotic therapy. Patients remained on study until their polymorphonuclear leukocytes were greater than 500 per mm3, during which time they had weekly surveillance cultures and daily blood cultures when febrile. Although 62 percent of the patients who became septic were colonized with the infecting organism(s), these cultures were not helpful in initial diagnosis or antibiotic management. Similarly, routine surveillance cultures were not useful in guiding or altering subsequent therapy in patients already receiving antibiotics. Although initially negative, blood cultures became positive in 11 patients who had received antibiotics for a median of 12 days (range three to 37 days). As a result of these blood cultures obtained at follow-up, modification of the antimicrobial regimen was made in seven patients, and six patients survived the episode. The mortality rate for patients in whom positive blood cultures developed while receiving antibiotics was 54 percent compared with a 15 percent mortality rate for patients prior to starting antibiotics (p = 0.01). Although routine body surveillance cultures are costly, insensitive, and unlikely to influence antimicrobial management, serial blood cultures, even in patients receiving antibiotic therapy, can specifically influence therapy and outcome, and may be justifiable for patients receiving maximum supportive care. 相似文献
73.
Raphael Dolin Arnold G. Levy Richard G. Wyatt Thomas S. Thornhill Jerry D. Gardner 《The American journal of medicine》1975,59(6):761-768
Peroral jejunal biopsies were performed in seven normal volunteer subjects prior to, 48 hours after and two weeks after the administration of the Hawaii agent of viral gastroenteritis. Light and electron microscopic examination revealed an intact mucosa with blunted villi, shortened and distorted microvilli, swollen mitochondria and intercellular edema. These histologic changes were seen only in acutely ill volunteer subjects and were absent two weeks after illness in three of four who were previously ill. This reversible lesion was similar to, but not identical with, that previously described in viral gastroenteritis induced by the Norwalk agent.Serum antibody increases in response to the Hawaii agent as measured by immune electron microscopy were present in three of four ill volunteer subjects and in none of three who remained well. 相似文献
74.
75.
Barry J. Maron William C. Roberts Jesse E. Edwards Hugh A. McAllister Daniel D. Foley Stephen E. Epstein 《The American journal of cardiology》1978,41(5):803-810
Sudden death is a recognized complication in symptomatic patients with hypertrophic cardiomyopathy. However, its occurrence in patients with no or transient previous cardiac symptoms presents a particularly challenging diagnostic and therapeutic dilemma. Therefore, 26 patients with hypertrophic cardiomyopathy whose death was the first definitive manifestation of cardiac disease were evaluated. Their ages ranged from 8 to 49 years (mean 18) and 23 were less than 25 years of age; 19 were male and 7 female. Of the 26 patients, 13 died during or immediately after moderate or severe physical exertion. Of 12 patients with previous cardiac catheterization, 6 had no or a small left ventricular outflow tract gradient under basal conditions and 6 had an outflow gradient of 50 mm Hg or greater. Left ventricular end-diastolic pressure was elevated in nine patients, and the ventricular septum was moderately to severely thickened (17 mm or more) in all patients. The electrocardiogram was abnormal in all 19 patients studied before death. Thus, sudden death may be the first definitive manifestation of cardiac disease in some patients with hypertrophic cardiomyopathy. Although the effects of patient selection in this study group cannot be excluded, sudden death was common in children and young adults and was often related to physical exertion; each patient showed a distinctly abnormal electrocardiogram and moderate to severe ventricular septal thickening. 相似文献
76.
Haralampos M. Moutsopoulos Jacob Karsh Robert O. Wolf Thomas M. Tarpley Anthony Tylenda Nicholas M. Papadopoulos 《The American journal of medicine》1980,69(1):39-42
Lysozyme and total protein concentrations in parotid saliva were measured in 17 patients with primary Sjögren's syndrome, in six patients with Sjögren's syndrome secondary to hyperlipoproteinemia and in 14 age- and sex-matched healthy control subjects. Increased lysozyme concentrations were found only in patients with primary Sjögren's syndrome and correlated well with the presence of parotid gland enlargement. The total protein concentration in the saliva of patients with Sjogren's syndrome was not different from that of the control subjects. Parotid saliva lysozyme determination may be useful as an early adjunctive diagnostic test of primary Sjögren's syndrome. 相似文献
77.
M Peters-Golden R A Wise M C Hochberg M B Stevens F M Wigley 《The American journal of medicine》1984,77(6):1027-1034
In order to determine the predictive value of lung function studies for subsequent prognosis in systemic sclerosis, 71 patients with systemic sclerosis were followed up for a mean of five years after pulmonary function testing. A carbon monoxide diffusing capacity less than or equal to 40 percent of the predicted reference value was associated with only a 9 percent five-year cumulative survival rate compared with a 75 percent cumulative five-year survival in patients with a carbon monoxide diffusing capacity greater than 40 percent of predicted. An obstructive ventilatory defect was also associated with increased mortality, and all six patients with obstruction and a diffusing capacity less than 70 percent of the predicted died during the study period. Male gender, independent of abnormalities of pulmonary function, was also associated with a poor prognosis. Although it is not clear whether a severely impaired diffusing capacity is indicative of interstitial pulmonary fibrosis or pulmonary vasculopathy or is a marker of generalized vascular disease, a severely depressed carbon monoxide diffusing capacity is an important predictor of mortality in patients with systemic sclerosis. 相似文献
78.
Attention is called to the development of coronary heart disease in two patients several years after they received mediastinal irradiation for Hodgkin's disease. One patient, a 33 year old man, died suddenly eight years after irradiation; necropsy disclosed marked narrowing of all three major coronary arteries. In addition to severe intima fibrous thickening, there also was considerable adventitial scarring of the coronary arteries. This type of coronary sclerosis is different from that seen in the usual patient with coronary heart disease. The second patient, a 42 year old man, had an acute myocardial infarction on two occasions, the first six years after mediastinal irradiation. Observations in previously described patients with coronary heart disease almost surely induced by therapeutic irradiation for Hodgkin's disease are reviewed. 相似文献
79.
80.
Vincent J. Vigorita G.William Moore Grover M. Hutchins 《The American journal of cardiology》1980,46(4):535-542
The relation between the severity and duration of diabetes mellitus and the severity of ischemic heart disease is uncertain. The clinical findings and the findings at autopsy were studied in 185 patients with diabetes mellitus of adult onset who ranged in age from 37 to 91 years and had a clinical diagnosis of diabetes established for a few days to 50 years before death. No statistically significant association was demonstrated either by simple correlation or by multivariate regression analysis between the clinically diagnosed severity or duration of diabetes and either the overall coronary disease, the number of diseased vessels or the number of myocardial infarctions. The presence of other expected correlations in the multivariate analysis suggested that the results of this study were not spurious. However, comparison with 185 age- and sex-matched control patients revealed that on the average, diabetic patients have more overall coronary disease (p < 0.002), more diffuseness of coronary disease (p < 0.005), more coronary collateralizatlon (p < 0.001), more vessels involved by atherosclerosis (p < 0.001) and more myocardial infarcts (p < 0.001). The results suggest that although diabetes mellitus of adult onset is a condition in which the larger coronary arteries are subject to more atherosclerosis than are those in nondiabetic subjects, the progression of the atherosclerotic disease is unrelated to the duration or severity of the diabetes mellitus. 相似文献