[A case of pleural sarcoidosis in which vats lung biopsy, obtained pleural and pulmonary lesions].

Here we report a case that was diagnosed as sarcoidosis but required differential diagnosis from pneumoconiosis. A 51-year-old asymptomatic man, who showed signs of bilateral hilar lymphadenopathy (BHL) on a chest X-ray taken during a medical check, was given a diagnosis of sarcoidosis, based on the results of mediastinoscopic mediastinal lymph node biopsy. Because of the presence of large and small nodular lesions adjacent to the pleura extending from the bilateral upper lobes into the lung field, and continuous bead-like, small nodular lesions in the right interlobar pleura, pleural sarcoidosis was suspected and thoracoscopy was performed. Macroscopically, multiple grayish-white nodules with distinct margins, up to 1cm in diameter surrounded by a proliferation of capillaries were found in the pleura, particularly in the upper lobes. Lesions were also scattered over the interlobar pleura and diaphragmatic surface. Histopathologically, several non-caseous epithelioid cell granulomas and silicotic nodule-like lesions of hyaline degeneration were found; therefore, pneumoconiosis, or more specifically chronic berylliosis, was suspected. Despite these symptoms, the patient did not have a history of exposure, and the results of the lymphocyte stimulation test using beryllium were negative in blood and bronchoalveolar lavage fluid. The patient was given a diagnosis of pleural sarcoidosis and has been observed without treatment.

Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2).

Ascorbic acid (vitamin C) is a cofactor required in catecholamine synthesis for conversion of dopamine to norepinephrine by dopamine beta-hydroxylase. Mutant mice lacking the plasma membrane ascorbic acid transporter (SVCT2) have severely reduced tissue levels of ascorbic acid and die after birth. We therefore investigated whether these mice might have impaired synthesis of catecholamines. Levels of catecholamines in brain were unaffected by SVCT2 deficiency. In heart, the only evidence for impaired dopamine beta-hydroxylase activity was a twofold increase in tissue dopamine. An influence of the deficiency on tissue catecholamines was most prominent in the adrenals where norepinephrine was decreased by 50% and epinephrine, by 81%. On the ultrastructural level, adrenal chromaffin cells in SVCT2 null mice showed depletion of catecholamine storage vesicles, increased amounts of rough endoplasmic reticulum, signs of apoptosis, and increased glycogen storage. Decreased plasma levels of corticosterone indicated additional effects of the deficiency on adrenal cortical function. These data show that deranged catecholamine system function in SVCT2 null mice is largely restricted to the adrenal medulla and cannot account for the lethality in these animals. The data, however, establish a crucial role for ascorbic acid in adrenal chromaffin cell function.

Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glucose elevation in response to high-intensity exercise.

Classic congenital hyperplasia (CAH) is characterized by impaired adrenocortical function with a decrease in cortisol and aldosterone secretion and an increase in androgen secretion. Adrenomedullary function is also compromised due to developmental defects in the formation of the adrenal medulla, leading to decreased production of epinephrine. To examine the response to a natural stressful stimulus in patients with classic CAH, we studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with CAH and nine healthy controls matched for gender, age, and percent body fat. The same relative workload was applied, based on individual maximal aerobic capacity, and all patients received their usual glucocorticoid and mineralocorticoid replacement. When compared with their normal counterparts, patients with CAH had significantly lower epinephrine levels both at baseline and at peak exercise (P < 0.01), whereas norepinephrine levels did not differ. Blood glucose concentrations were similar at baseline, but the normal exercise-induced rise observed in the healthy controls was significantly blunted in the CAH patients (P < 0.01). Peak heart rate was also lower in CAH patients than healthy controls (P < 0.05). As expected, the normal exercise-induced increase in cortisol was not observed in patients with CAH. No significant differences were found in serum levels of insulin, glucagon, GH, lactate and free fatty acids, blood pressure, or ability to sustain exercise between the two groups. Patients with CAH replaced with glucocorticoids have decreased adrenomedullary reserve and impaired exercise-induced changes in glucose but normal short-term high-intensity exercise performance. Whether the combination of epinephrine and cortisol deficiency poses a risk for hypoglycemia and/or decreased endurance during long-term physical stress has to be determined.

[A case report of tuberculous pleuritis diagnosed by thoracoscopy using fiberoptic bronchoscope].

A 27-year-old male visited the outpatient clinic of our hospital with the chief complaints of fever, right chest pain and shortness of breath. He was admitted to our hospital for detailed examination of the right hydrothorax. The pleural effusion obtained by thoracocentesis was exudative and negative for Mycobacterium tuberculosis. Since the titer of adenosine deaminase in the pleural effusion was abnormally high, antitubercular therapy was started under suspicion of tuberculous pleuritis. Thereafter, the patient's subjective symptoms and blood parameters improved. Necrotic tissues were obtained by pleural biopsy using the Cope needle. In order to make a definitive diagnosis, pleural biopsy was performed thoracoscopically. White tubercular lesions with a smooth surface were sparsely distributed on the pleura. Histopathologically, these lesions were characterized by central areas of caseous necrosis surrounded by epithelial cells and Langhans' giant cells. Therefore, they were considered to be granulomatous lesions. The patient was given a diagnosis of idiopathic tuberculous pleuritis, and was treated with four antitubercular drugs in combination. His clinical signs subsided, and he was discharged. This case indicates that the examination of the inside of the pleural cavity with a flexible bronchoscope, instead of thoracoscope, under local anesthesia is useful to diagnose patients having tuberculous pleuritis.

[A clinical study of tuberculous pleurisy].

A clinical study of 38 patients (28 men and 10 women) with tuberculous pleurisy was conducted. The age of these patients ranged from 19 to 92 years, with an average age of 48.9 years. In 30 patients, the chief complaint was fever, and other common complaints included chest pain, dyspnea, and coughing. Bacillus tuberculosis was found in the pleural fluid of 7.9% of the patients. Tuberculous pleurisy was diagnosed histologically, based on pleural biopsy, in 23.7% of the patients. The diagnosis rate of pleural biopsy was 47.4%. There were no significant differences in results of blood and pleural fluid tests between idiopathic pleurisy and concomitant pleurisy, but the tuberculin skin test was positive in only 50% of the patients with concomitant pleurisy. The tendency was that the longer the time period between symptom onset and first examination, the greater the pleural fluid retention. The diagnosis rate of pleural biopsy was influenced by the severity of pleural fluid retention. A thoracic cavity drain was inserted for continuous drainage in 15 patients, and every patient underwent INH + RFP-based chemotherapy. Tuberculous pleurisy is an important disease among patients with pleural fluid retention, thus clinicians need to know how to treat this disease.

[The platelet-sparing effect of carboplatin and docetaxel combination chemotherapy for lung cancer].

Paclitaxel and carboplatin chemotherapy is reported to be a platelet-sparing drug combination. The objective of this study was to elucidate whether docetaxel with carboplatin has a similar platelet-sparing effect. This study investigated the time-course of the changes in the platelet count and the circulating concentration of thrombopoietin (TPO), a platelet growth factor, during combination chemotherapy consisting of carboplatin and docetaxel. Eleven patients with advanced lung cancer were enrolled; 8 receiving carboplatin and docetaxel (docetaxel group), and 3 receiving carboplatin and irinotecan (irinotecan group). The time-course profiles of the platelet count and the circulating TPO concentration were determined and compared between the two groups. The platelet count decreased significantly only in the irinotecan group, and on day 15 after therapy the thrombocytopenia was pronounced in comparison with that in the docetaxel group. The circulating TPO concentration remained almost constant in the irinotecan group, with no significant increases, while that in the docetaxel group was increased significantly on day 4 (p < 0.05), day 8 (p < 0.05), and day 15 (p < 0.01) after therapy. There was also a significant difference between the docetaxel group and irinotecan group with respect to circulating TPO concentration (p < 0.05). These results suggest that docetaxel might also have a platelet-sparing effect on the anti-platelet activity of carboplatin, mediated by levels of circulating TPO concentration.

[A phase I study of gemcitabine and irinotecan as second line treatment for advanced non-small cell lung cancer].

A phase I study was conducted to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of gemcitabine and irinotecan combination therapy as second line treatment in patients with advanced non-small cell lung cancer (NSCLC). Twelve patients with measurable NSCLC (age range 46-74 years; 7 males, 5 females; performance status 0 = 4, 1 = 8) who progressed or failed first-line chemotherapy were enrolled. Prior chemotherapy was platinum-based without gemcitabine or irinotecan. Gemcitabine was administered at a fixed dose of 1,000 mg/m2 after irinotecan administration, and irinotecan was administered at doses from 50 to 125 mg/m2 with an increment of 25 mg/m2, both on day 1 and 8. Chemotherapy was repeated every 3 weeks. Grade 3/4 leukopenia occurred in three patients (25%), neutropenia in four (33%), anemia in one (8%), and thrombocytopenia in one (8%). Grade 3 nausea and vomiting was observed in three (25%), grade 2 diarrhea in one (8%), and liver dysfunction in one (8%). Other toxicities were mild. Two of the three patients at level 4 (irinotecan 125 mg/m2) experienced dose limiting toxicity: one patient experienced grade 4 leukopenia and neutropenia, and the other experienced treatment delay of more than 2 weeks. The objective response rate was 16.6% (2/12). The maximum tolerated dose in this combination therapy was gemcitabine 1,000 mg/m2 and irinotecan 125 mg/m2. The dose level of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 on day 1 and 8 of a 3-week cycle is recommended for a phase II study.

First case report of acquired pure red cell aplasia associated with micafungin.

A 70-year-old Japanese man with chronic kidney disease under treatment with oral prednisolone for organizing pneumonia developed pulmonary aspergilloma. The patient was started on micafungin (MCFG), with no addition of any other new drug. About 5 weeks later, aggravation of his normocytic anemia associated with a low reticulocyte count was observed. Bone marrow puncture and biopsy revealed intense hypoplasia of the erythroblasts. As there was no evidence of malignancy, human parvovirus B19 infection, autoimmune diseases or hemorrhage, the patient was diagnosed as having acquired pure red cell aplasia (PRCA). The anemia improved along with an increase of the reticulocyte count to the normal level within 12 weeks of discontinuation of the MCFG therapy. The patient showed no evidence subsequently of any recurrence of the normocytic normochromic anemia or relapse of the PRCA. This is the first reported case of PRCA associated with MCFG.

Type 1 Diabetes Mellitus Associated with Pegylated Interferon-α Plus Ribavirin Treatment for Chronic Hepatitis C: Case Report and Literature Review.

Combined pegylated interferon (PEG-IFN)+ribavirin (RBV) therapy has been used as a primary treatment for chronic hepatitis C. However, IFN-induced autoimmune disease, including type 1 diabetes mellitus, has been highlighted as one of the problems with this therapy. Here we report the case of a patient who developed type 1 diabetes mellitus during combined PEG-IFN+RBV therapy for hepatitis C but who showed no exacerbation of diabetes despite continued use of IFN. A 63-year-old man with chronic hepatitis C and a nonresponder to previous IFNα treatments, was admitted to our hospital because of excessive thirst, polydipsia, and polyuria 24 weeks after the start of PEG-IFNα+RBV therapy. High levels of blood glucose and glycosylated hemoglobin and low levels of C-peptide and immunoreactive insulin were observed. The serum antiglutamic acid decarboxylase antibody titer was 27,700 U/mL. We diagnosed IFN-induced type 1 diabetes mellitus; however PEG-IFNα+RBV therapy was continued for 48 weeks. Serum HCV remains negative five years after this treatment. Intensive insulin therapy was started immediately after the diagnosis of type 1 diabetes. Although the patient initially required 22 U/day of insulin, the dosage could be gradually reduced after completion of PEG-IFNα+RBV therapy and blood glucose remained well controlled. Prediction of onset of type 1 diabetes mellitus on the basis of baseline measurement of pancreas-associated autoantibodies is difficult. Therefore, it would be advisable to consider the possibility of onset of type 1 diabetes mellitus in all patients receiving IFN+RBV therapy.

Prevalence of adrenal masses in Japanese patients with type 2 diabetes mellitus.

INTRODUCTION: To date, there have been no reports on the prevalence of adrenal masses in type 2 diabetic patients. The present study aimed to evaluate the prevalence of adrenal incidentaloma in type 2 diabetic patients in Japan. SUBJECTS: We retrospectively evaluated the presence of adrenal masses using abdominal CT scans in 304 type 2 diabetic patients. In those with adrenal masses, we examined the hormone production capacity of the adrenal mass. RESULTS: Fourteen patients (4.6%) had an adrenal mass. Hormonal analysis identified one case as having subclinical Cushing's syndrome, two with primary aldosteronism. Eleven cases had non-functioning masses. DISCUSSION: The reported prevalence of adrenal incidentaloma in normal subjects is 0.6-4.0% in abdominal CT scan series. Our results show a relatively high prevalence of adrenal tumors in diabetic patients. On the other hand, the frequency of functional adenoma in diabetic patients is 21.4%, which is similar to that of normal subjects. CONCLUSION: Although further studies are needed to evaluate the prevalence of adrenal tumors in diabetic patients, our data suggest that evaluation of the presence of adrenal masses may be needed in patients with type 2 diabetes mellitus.