Chronic necrotizing pulmonary aspergillosis in pneumoconiosis: clinical and radiologic findings in 10 patients.

STUDY OBJECTIVE: To characterize clinical, radiographic, and CT findings of chronic necrotizing pulmonary aspergillosis (CNPA) in patients with pneumoconiosis. METHODS: We studied 10 patients with pneumoconiosis who were seen at Asahi Rosai Hospital and received a clinical diagnosis of CNPA during a 15-year period, and detailed the long-term clinical and radiologic courses of four cases. RESULTS: All patients were men, ranging in age from 48 to 77 years (mean, 60.1 years). Their occupational histories included pottery making (n = 9) and coal mining (n = 1). Chest radiographic findings by the International Labor Organization profusion grading system were greater than category 2. All patients were symptomatic, with a productive cough, hemoptysis, and dyspnea. Serum findings were positive for the Aspergillus antibody in seven patients. The radiologic findings consisted of parenchymal infiltrates and cavities mostly containing mycetoma, which generally involved the upper lobes. The disease progressed slowly; in one patient, broad destruction of the lung was observed after > 10 years without antifungal administration. Most of the patients experienced clinical and radiologic improvement after receiving antifungal therapy, by oral, inhaled, or intracavitary administration. CONCLUSIONS: Chronic persistent or progressive upper-lobe infiltrates and cavities in patients with pneumoconiosis should raise the possibility of CNPA. Early diagnosis and initiation of effective therapy are recommended to achieve a better outcome.     

Association of Ob-R gene polymorphism and insulin resistance in Japanese men

Leptin and its receptors are known to play a role in glucose metabolism. We succeeded in cloning human Ob-R cDNA and revealed 7 single nucleotide polymorphisms (SNPs) (Lys109Arg, Arg223Gln, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the coding region of Ob-Rb. Although these 7 SNPs were not associated with an obese phenotype, several studies have reported that some of them were associated with impaired glucose metabolism. To clarify whether the Arg223Gln and A3057G (Pro1019Pro) polymorphisms influence glucose metabolism in Japanese, 696 Japanese men were genotyped. Individually, the Arg223Gln and the A3057G polymorphisms were not associated with the glucose metabolic parameters. No associations were found between haplotype and clinical parameters. However, in 327 subjects with normal glucose tolerance (NGT), the subjects with Arg/Gln or Gln/Gln + A/A haplotype showed significantly higher serum insulin levels and homeostasis model assessment (HOMA) index than those with Arg/Arg + A/A haplotype and Arg/Gln or Gln/Gln + A/G or G/G haplotype. The subjects with Arg/Gln or Gln/Gln + A/A haplotype showed a significantly lower fasting glucose to insulin (GI) ratio than those with Arg/Arg + A/A haplotype. These results suggest that the Ob-R gene may serve as a modifier gene for insulin resistance in Japanese men.     

Detection and partial sequencing of hepatitis C virus RNA in the liver.

To detect hepatitis C virus RNA, total RNA was extracted from liver tissue, reverse transcribed to complementary DNA, and amplified by polymerase chain reaction. The reaction products were analyzed by ethidium bromide staining in acrylamide gel and hybridization with a radiolabeled probe. Hepatitis C virus RNA was thereby detected in 17 of 27 (63%) liver tissue specimens obtained from patients with non-A, non-B chronic liver diseases. Of these 27 patients, viral RNA was detected in 12 of 17 (71%) liver tissues from anti-hepatitis C virus-positive patients and in 5 of 10 (50%) liver tissues from anti-hepatitis C virus-negative patients. Direct sequencing of amplified complementary DNA (35 nucleotides) of the 17 RNA-positive samples showed only 66% to 77% homology to the reported hepatitis C virus complementary DNA sequence. These results indicate that the majority of anti-hepatitis C virus-positive patients are currently infected with hepatitis C virus, and some of the anti-hepatitis C virus-negative patients with non-A, non-B hepatitis are harboring hepatitis C virus in the liver. Detection of hepatitis C virus RNA appears to provide a useful indicator in the study of hepatitis C virus infection.     

Optimal therapeutic range for oral anticoagulants in Japanese patients with prosthetic heart valves: a preliminary report from a single institution using conversion from thrombotest to PT-INR

The thrombotest (TT) technique has been widely used in Japan for monitoring oral anticoagulant therapy (OAT). The therapeutic range was originally recommended to be 10%–25%. However, the International Committee for Standardization in Hematology/International Committee on Thrombosis and Hemostasis (ICSH/ICTH) recommended using the international normalized ratio of prothrombin time (PT-INR) for monitoring OAT. It is necessary to use a universal standard measure for monitoring OAT in accordance with the ICSH/ISTH recommendation. We simultaneously measured TT and PT in blood samples from 1 157 patients on long-term warfarin therapy, and studied the correlation between TT and PT-INR. An excellent linear correlation was obtained between TT-INR and PT-INR with the regression equation PT-INR = 1.0420 TT-INR − 0.0987 (r = 0.905, P < 0.001). We also examined the correlation between the incidence of thromboembolism in 170 patients receiving warfarin therapy after prosthetic valve replacement; 50.5% received concomitant antiplatelet therapy. Thromboembolism occurred in 9 of 170 patients during a mean follow-up period of 2.44 years. The average TT values in patients with and without thromboembolism were 26.4% (PT-INR: 1.53) and 21.1% (1.73), respectively (P < 0.01). The incidence of thromboembolism did not differ significantly between patients on warfarin alone (average TT: 22.2%) and those on warfarin and antiplatelet agent (average TT: 20.9%). Our results suggest that the incidence of thromboembolism is low in Japan despite a less intensive regimen having been adopted. Received: June 22, 2000 / Accepted: October 4, 2000     

Estrogen and non-feminizing estrogen for Alzheimer's disease

The preventive effect of estrogen on Alzheimer's disease (AD) has become clearer with many epidemiological reports. However, the therapeutic effects of estrogen have been controversial until now. In our trials, estrogen treatment showed a beneficial therapeutic effect for women with mild to moderate AD. Improvement of cognitive function was recognized during the third week from the beginning of administration and maintained as long as estrogen treatment continued. The longer the duration of HRT, the more HRT is useful for the prevention and therapy of AD. However, in most cases, administration of estrogen is discontinued because of the adverse effects on the uterus and breast. J 861 is a derivative of estradiol-17alpha, which has little effect on the sexual organs. The effects of estradiol-17beta (E2) and J 861 on neuronal function and vascular factors were investigated. J 861 was suggested to prevent both the intracellular calcium increase and peroxidation induced by amyloid beta (Abeta), more effectively than E2. The effect of J 861 may be related with both the direct non-genomic and the ER-mediated systems. J 861 showed neurotrophic effects like E2. J 861 inhibited the adhesion of monocytes to vascular endothelium, more effectively than E2. Also, J 861 suppressed the expression of adhesive factors, such as E-selectin and intercellular cell adhesion molecule-1 (ICAM-1), more effectively than E2.