Evaluation of community-acquired pneumonia guidelines of Japanese Respiratory Society: differentiation of atypical pneumonia and bacterial pneumonia]

To evaluate the usefulness of differentiation of atypical pneumonia and bacterial pneumonia in the community-acquired pneumonia guidelines of the Japanese Respiratory Society, we investigated 124 cases of three atypical pneumonias (Mycoplasma pneumonia, 62 cases; Chlamydia pneumoniae pneumonia, 46 cases; Chlamydia psittaci pneumonia, 13 cases) and 403 cases of bacterial pneumonia at our hospital over seven years. Overall, the sensitivity and specificity of the criteria in the guideline were 70.4% and 91.8%, respectively. High accordance was recognized in patients under 60 years old with atypical pneumonia. Items in the criteria that included subjective factors were considered inassessable. We found that the differentiation of pneumonias in the guideline is useful for the diagnosis of atypical pneumonia among younger patients, but it should be concise and objective. We therefore propose that the criteria would be more effective if they consisted of only 4 items: age under 60 years, no underlying disorders, presence of stubborn dry cough, and normal peripheral white blood cell count.     

A case of rapid development of arc welder's lung during the course of a year]

A 57-year-old man who had worked as a welder for about 40 years was admitted to our hospital. Every year he had had medical examinations in his workplace. On March 17, 1999, there was no finding of pneumoconiosis, but he had worked in a tunnel on a special arc welding project from December 20, 1999 to January 10, 2000. On admission, chest radiography revealed reticular shadows in the middle and lower lung fields. CT scans showed ground-glass opacities in both lungs. Serum iron was high (231 micrograms/dl) and serum ferritin was extremely high (2,309 ng/ml). Many iron particles were detected in the alveoli of the transbronchial biopsy specimen, and also in the sputum. A pathological diagnosis of siderosis was therefore made, and, considering the patient's occupation, the condition was termed arc welder's lung. This rapidly developing case was characterized by reticular shadows on chest radiography.     

Cardiac angiotensin II type 2 receptor activates the kinin/NO system and inhibits fibrosis

We have previously demonstrated that stimulation of the angiotensin (Ang) II type 2 receptor in vascular smooth muscle cells caused bradykinin production by activating kininogenase in transgenic mice. The aim of this study was to determine whether overexpression of AT2 receptors in cardiomyocytes attenuates Ang II-induced cardiomyocyte hypertrophy or interstitial fibrosis through a kinin/nitric oxide (NO)-dependent mechanism in mice. Ang II (1.4 mg/kg per day) or vehicle was subcutaneously infused into transgenic mice and wild-type mice for 14 days. The amount of cardiac AT2 receptor relative to AT1 receptor in transgenic mice was 22% to 37%. Ang II caused similar elevations in systolic blood pressure (by approximately 45 mm Hg) in transgenic mice and wild-type mice. Myocyte hypertrophy assessed by an increase in myocyte cross-sectional area, left ventricular mass, and atrial natriuretic peptide mRNA levels were similar in transgenic and wild-type mice. Ang II induced prominent perivascular fibrosis of the intramuscular coronary arteries, the extent of which was significantly less in transgenic mice than in wild-type mice. Inhibition of perivascular fibrosis in transgenic mice was abolished by cotreatment with HOE140, a bradykinin B2 receptor antagonist, or L-NAME, an inhibitor of NO synthase. Cardiac kininogenase activity was markedly increased (approximately 2.6-fold, P<0.001) after Ang II infusion in transgenic mice but not in wild-type mice. Immunohistochemistry indicated that both bradykinin B2 receptors and endothelial NO synthase were expressed in the vascular endothelium, whereas only B2 receptors were present in fibroblasts. These results suggest that stimulation of AT2 receptors present in cardiomyocytes attenuates perivascular fibrosis by a kinin/NO-dependent mechanism. However, the effect on the development of cardiomyocyte hypertrophy was not detected in this experimental setting.     

Increased bone resorption may play a crucial role in the occurrence of osteopenia in patients with type 2 diabetes: Possible involvement of accelerated polyol pathway in its pathogenesis

In order to investigate the underlying mechanism of alterations in bone mineral metabolism in patients with type 2 diabetes, we determined circulating levels of bone functional markers along with urinary excretion of sorbitol (SOR) and bone mineral density (BMD), and also examined their mutual interrelationship. A total of 151 male type 2 diabetic patients were examined in this study. Forty-eight age-matched male healthy subjects were also studied as the controls. A significant reduction of serum intact osteocalcin (i-OC) was found in the diabetic groups (p<0.01). On the other hand, circulating levels of tartrate resistant acid phosphatase (TRAP) in the diabetic patients were significantly higher than those in the controls (p<0.01). Interestingly, a significantly negative relationship was observed between BMD and serum TRAP (p<0.01), although no significant relationship was noted between BMD and serum i-OC in diabetic patients. Urinary excretion of SOR was significantly elevated in the diabetic patients when compared with the controls (p<0.01). In addition, a significantly positive correlation was observed between serum TRAP and urinary SOR (p<0.01), but not between serum i-OC and urinary SOR. Elevated serum TRAP in diabetes was reduced after the administration of aldose reductase inhibitor (p<0.05). It seems most likely that the increase in osteoclastic function probably due to accelerated polyol pathway plays a crucial role in the pathogenesis of decreased bone mineral content in male patients with type 2 diabetes.     

An autopsy case of Aspergillus pneumonia after inhalation of a great deal of dust in a mushroom factory]

A man in his forties with alcoholic liver injury was referred to our hospital because of progressive dyspnea and diffuse infiltrative shadows in both lung fields. Two weeks before admission he had carried a lot of rotten Enoki mushrooms in his factory, and then inhaled a great deal of airborne dust. Serological examination showed extremely elevated beta-D-glucan and positive Aspergillus antigen. Culture of dust collected from the floor of the factory proved to be positive for Aspergillus fumigatus. Aspergillus pneumonia was diagnosed and treatment with anti-fungal drugs was started. In spite of intensive treatment he died of respiratory failure. The autopsy disclosed multiple abscess formation containing hyphae of Aspergillus fumigatus and granulomatous reaction with multinuclear giant cells. However, there was no Aspergillus invasion in other organs. This was a rare case of invasive pulmonary aspergillosis that developed after inhalation of organic dust in a non-immunocompromised host.     

Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast

It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the intratumoral concentration of sex steroids has not been examined in DCIS. Therefore, in this study, we first examined the intratumoral concentrations of estradiol and 5alpha-dihydrotestosterone (DHT) using liquid chromatography/electrospray tandem mass spectrometry in DCIS. Intratumoral concentrations of both estradiol and DHT were threefold higher in DCIS than non-neoplastic breast tissues and estrogen-producing enzymes (aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1)), and androgen-producing enzymes (17betaHSD5 and 5alpha-reductase type 1 (5alphaRed1)) were abundantly expressed in DCIS by real-time PCR and immunohistochemical analyses. The intratumoral concentration of DHT was significantly lower in IDC than DCIS, while the expression of aromatase mRNA in carcinoma cells and intratumoral stromal cells was significantly higher in IDC than those in DCIS. Immunohistochemistry for sex steroid-producing enzymes in DCIS demonstrated that 5alphaRed1 immunoreactivity was positively correlated with Ki-67 labeling index and histological grade and was also associated with an increased risk of recurrence in patients with DCIS examined. Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids. Therefore, estradiol and DHT may play important roles in the development of DCIS of the human breast.     

A technique for diagnosis of accessory pathway using the H-H and A-A intervals of the first entrained cycle during ventricular overdrive pacing

Although advancement of succeeding atrial activation by a ventricular extrastimulus (VES) on His refractoriness during supraventricular tachycardia (SVT) has been used as evidence of an accessory pathway (AP), the sensitivity of this method is suboptimal. This study was designed to compare the His-His (H-H) and atrial-atrial (A-A) intervals of the first entrained cycle during ventricular overdrive pacing (VOD) for the diagnosis of AP, in comparison to the conventional VES method. In 55 patients with SVT, a VES was elicited on His refractoriness during SVT. VOD was subsequently performed at cycle lengths 30 to 40 ms shorter than SVT cycle lengths. When the A-A interval became equal to the pacing cycle length after some beats of VOD, the cycle was considered the first entrained cycle and the H-H interval preceding the A-A interval was measured. VES advanced the next atrial activation in 16 patients (52%) with an AP, but in no patient without an AP. The H-H interval of the first entrained cycle was longer than the pacing cycle length by > or =15 ms in all patients with an AP, but was equal to the pacing cycle length in all patients without an AP. The criterion of H-H greater than A-A by > or =15 ms for the first entrained cycle provided higher diagnostic yield for AP compared with the VES method(100% vs 52%, p <0.001). In conclusion, this new criterion reliably diagnoses the presence of an AP in patients with SVT, with higher sensitivity compared with the VES method.