1,25-dihydroxyvitamin D suppresses circulating levels of parathyroid hormone in a patient with primary hyperparathyroidism and coexistent sarcoidosis

CONTEXT: PTH is excessively secreted to develop hypercalcemia and accelerate bone turnover in patients with primary hyperparathyroidism. PTH stimulates the production of 1,25-dihydroxyvitamin D [1,25(OH)2D] that in turn suppresses the synthesis of PTH in parathyroid cells. OBJECTIVE: The objective of the study was to clarify whether 1,25(OH)2D indeed inhibits circulating levels of PTH and influences bone turnover, even in a patient with primary hyperparathyroidism. DESIGN, SETTING, AND PATIENT: We evaluated PTH levels in a patient with primary hyperparathyroidism and coexistent sarcoidosis whose serum 1,25(OH)2D levels were independent of PTH. INTERVENTIONS AND MAIN OUTCOME MEASURES: The present case was treated with prednisolone before and after surgical resection of parathyroid adenoma, and Ca-regulating hormones and bone markers were measured. RESULTS: Serum Ca and PTH levels significantly decreased after parathyroid surgery, whereas serum 1,25(OH)2D levels remained high. Prednisolone administration promptly decreased serum 1,25(OH)2D levels and reciprocally increased PTH levels despite consistent serum Ca levels either before or after surgery. PTH levels were negatively correlated with serum 1,25(OH)2D levels before and after surgery. Urine N-telopeptides, serum osteocalcin, and bone-type alkaline phosphatase all decreased to physiological ranges after parathyroid surgery. CONCLUSIONS: These results suggest that 1,25(OH)2D indeed inhibits the production of PTH not to exacerbate hypercalcemia in a patient with primary hyperparathyroidism. Furthermore, PTH but not 1,25(OH)2D may primarily be involved in the stimulation of bone turnover.     

Increased macrophage colony-stimulating factor levels in patients with Graves’ disease

Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves’ disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P < 0.05) and control subjects (P < 0.0001). Serum M-CSF concentrations correlated closely with T3 levels in patients (r = 0.51, P < 0.005). Serial measurement of five individual patients revealed that serum concentrations of M-CSF were significantly decreased (P < 0.05), reaching normal control values upon attainment of euthyroidism. Furthermore, oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P < 0.05). The close correlation between serum M-CSF and serum thyroid hormone levels suggests that high circulating levels of thyroid hormones may directly or indirectly potentiate the production of M-CSF in patients with GD.     

Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory

Background:  Autoreactive T cells that proliferate in response to autoantigens are found in both autoimmune diseases and controls but have important qualitative differences in relative activation states, costimulation signal requirements and pathogenetic significance.
Methods:  To understand the differences between autoreactive T cells in PBC versus controls, we have developed autoreactive T-cell clones (TCC) from patients with PBC and healthy controls, and have used a peptide corresponding to the CD4 major autoantigen (Ag) to define the relative proliferative response. Peripheral blood mononuclear cells (PBMC) from PBC respond to the Ag in a costimulation-independent manner, but PBMC from controls respond to the Ag in a costimulation-dependent manner. Next, we established nine autoreactive TCC from patients with PBC and eight from healthy controls.
Results:  Among 17 TCC, eight were the costimulation-dependent type and nine were independent. In addition, costimulation-dependent autoreactive TCC became anergic after stimulation in the presence of APC that did not provide costimulatory signals. Finally, we observed that anergic TCC exhibit regulatory functions.
Conclusions:  In the case of regulatory dendritic cells, we could not induce TCC anergy. On the other hand, when using peptide analog in a costimulation-deficient manner, we could induce TCC anergy, even though these TCC were costimulation independent.     

Regional myocardial perfusion and metabolism assessed by positron emission tomography in children with Kawasaki disease and significance of abnormal Q waves and their disappearance

To clarify the significance of newly appearing abnormal Q waves and their disappearance in patients with Kawasaki disease, regional myocardial perfusion and glucose metabolism at rest in the fasting condition were assessed by positron emission tomography (PET) with ¹³N-ammonia and ¹⁸F-fluorodeoxyglucose (FDG), and regional wall motion by left ventriculography in regions with persistent and transient abnormal Q waves in 14 patients. PET identified 3 groups of abnormal myocardial segments: segments with hypoperfusion without increased FDG uptake, those with hypoperfusion and increased FDG uptake, and those with normal perfusion and increased FDG uptake. Almost all the segments with persistent or transient abnormal Q waves had abnormal PET findings. PET demonstrated evidence of metabolic activity in 57% of segments with persistent abnormal Q waves and 67% of those with transient abnormal Q waves. Regional wall motion, scored from 0 (normal) to 4 (dyskinesia), was not significantly different between segments with persistent and transient abnormal Q waves (2.3 ± 1.3 vs 2.2 ± 1.2). The persistence of abnormal Q waves on serial electrocardiograms was significantly shorter in metabolically active than in inactive segments (19 ± 17 vs 92 ± 27 months). In conclusion, in patients with Kawasaki disease, the new appearance of abnormal Q waves is a reliable clue to the presence of ischemic myocardial injury and a high proportion of them are associated with metabolically active myocardial regions. The disappearance of abnormal Q waves does not necessarily mean the normalization of regional myocardial perfusion, metabolism or function, and their early disappearance may imply “viability” in the associated myocardial region.     

Measurement of Intrahepatic Pressure as an Index of Hepatic Sinusoidal Pressure

Intrahepatic pressure was measured in 148 patients with liver disease (32 outpatients, 116 inpatients) and 13 controls with almost normal liver histology (inpatients), with a 23-gauge needle (inner diameter 0.38 mm). Intrahepatic pressure was significantly elevated in the group order of chronic active hepatitis without bridging necrosis (n = 17, 9.2 +/- 3.0 mm Hg), chronic active hepatitis with bridging necrosis (n = 24, 12.3 +/- 5.7), and posthepatitic liver cirrhosis (n = 65, 18.8 +/- 4.2), compared with controls (n = 13, 6.8 +/- 2.7), whereas it was not elevated in the group of idiopathic portal hypertension (n = 9, 7.8 +/- 2.5 mm Hg), acute hepatitis (n = 10, 8.4 +/- 2.6 mm Hg), and chronic persistent hepatitis (n = 23, 7.9 +/- 2.7 mm Hg), compared with controls. As complications, four patients had abdominal discomfort continuing for more than a day; however, patients were allowed to walk after they had rested on their beds for 30 min. In 37 patients (27 with cirrhosis, seven idiopathic portal hypertension, and three others), portal vein and/or hepatic vein catheterization was performed during the same procedure of intrahepatic pressure measurement. Intrahepatic pressure showed significant correlations with corrected wedged hepatic vein pressure (r = 0.91), portohepatic gradient (r = 0.69), wedged hepatic vein pressure (r = 0.79), and portal vein pressure (r = 0.68). Slopes were 0.97, 0.83, 0.66, and 0.65, respectively. In conclusion, intrahepatic pressure reflects hepatic sinusoidal pressure (corrected wedged hepatic vein pressure), and intrahepatic pressure starts to elevate at the stage of chronic active hepatitis.     

A case of hypersensitivity pneumonitis caused by Humicola fuscoatra

A 51-year-old housewife with hypersensitivity pneumonitis caused by Humicola fuscoatra is reported. The diagnosis was made by an inhalation challenge with H. fuscoatra antigen. She was admitted for diagnosis and treatment of a fever and productive cough. Auscultation of her lungs revealed inspiratory fine crackles. Her chest CT showed diffuse miliary nodules in a centri-lobular distribution with patchy ground glass opacities. Findings of transbronchial lung biopsy and BAL fluid were compatible with a hypersensitivity pneumonitis. Her symptoms worsened on returning home, which suggested the existence of some aetiological agent in the subject's house. H. fuscoatra, Penicillium decumbens and Aspergillus versicolor were isolated from a number of rooms. High titres of serum anti H. fuscoatra, P. decumbens and A. versicolor were detected. Inhalation challenge tests with both P. decumbens and A. versicolor antigen were negative, in contrast to that with H. fuscoatra which was positive. Based on these results, we advised the patient to cleanse her entire house. Since cleaning, her symptoms have not worsened upon returning home. This is the first report of hypersensitivity pneumonitis caused by H. fuscoatra antigen.     

Effects of intra- and extrahepatic portal systemic shunts on insulin metabolism

To study the effects of intra- and extrahepatic portal-systemic shunts on insulin degradation, 11 patients with liver cirrhosis and 7 noncirrhotic patients with liver disease were studied with percutaneous transhepatic catheterization. Insulin levels in portal and peripheral blood were measured simultaneously for 1-2 hr after intravenous administration of glucose. The degrees of intra- and extrahepatic portal-systemic shunting were measured with this technique using 131I-macroaggregated albumin and 99mTc-macroaggregated albumin. The amount of insulin secreted and insulin degraded were assessed from the areas under blood concentration curves for portal and peripheral blood. Insulin degradation was significantly reduced in cirrhotics compared to noncirrhotics with liver disease, although there was no difference in the amount of insulin secreted between these two groups. It was also correlated significantly with the degree of intrahepatic shunting but not with the degree of extrahepatic shunting. These results suggest that intrahepatic shunting plays an important role in the reduction of insulin degradation in cirrhosis.     

Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis

BACKGROUND/AIMS: The presence of antibodies to the 210-kDa glycoprotein of the nuclear pore complex (gp210) is highly indicative of primary biliary cirrhosis (PBC). However, the significance of anti-gp210 antibody titers for monitoring PBC remains unresolved. METHODS: We used an ELISA with a gp210 C-terminal peptide as an antigen to assess serum antibody titers in 71 patients with PBC. RESULTS: Patients were classified into three groups: Group A in whom anti-gp210 titers were sustained at a high level, Group B in whom anti-gp210 status changed from positive to negative under ursodeoxycholic acid (UDCA) therapy, Group C in whom anti-gp210 antibodies were negative at the time of diagnosis. The rate of progression to end-stage hepatic failure was significantly higher in group A (60%) as compared to groups B (0%) and C (4.2%). The sustained antibody response to gp210 was closely associated with the severity of interface hepatitis. The significance of anti-gp210 antibody was confirmed by National Hospital Organization Study Group for Liver Disease in Japan. CONCLUSIONS: The serial quantitation of serum anti-gp210-C-terminal peptide antibodies is useful for monitoring the effect of UDCA and for the early identification of patients at high risk for end-stage hepatic failure.