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Cryptococcus neoformans is an opportunistic fungal infectious pathogen in immunocompromised patients with acquired immunodeficiency syndrome and hematological malignancies. Recently, innate immune cells, such as NK, NKT and γ δ T cells, have been found critical for determining the quality of acquired immunity by affecting the direction of Th1-Th2 balance. Th1-type immune response is important for the host defense against C. neoformans, and innate immunity may involve this process. In the present review, the accumulated knowledge including our own data on the role of innate immune lymphocytes in the host defense to this fungal pathogen are summarized, focusing on NKT and γ δ T cells. [ABSTRACT FROM AUTHOR]

A 25-year-old woman with a history of B-cell acute lymphoblastic leukemia over ten years ago was referred to our hospital with a chief complaint of leukoblastosis. She was participating in a JPLSG (Japanese Pediatric Leukemia/Lymphoma Study Group) clinical study at that time. We diagnosed ALL relapse by multi-color flow cytometric analysis of bone marrow samples at admission, with reference to previous JPLSG data. Because her leukemic cells were resistant to conventional cytotoxic agents, she proceeded to lymphocyte apheresis for chimeric antigen receptor T-cell (CAR-T, Tisagenlecleucel [Tisa-cel]). She received two cycles of inotuzumab ozogamicin as a bridging therapy to Tisa-cel, resulting in a hematological complete remission (minimal residual disease measured by polymerase chain reaction [PCR-MRD] was positive at 1.0×10 -4 ). She was finally administered Tisa-cel and achieved MRD negativity. She is currently in complete remission with careful MRD monitoring. This strategy of sequential bi-targeted therapy combining antibody conjugates and CAR-T cells provides tumor control in deeper remission and minimal damage to organ function through reduced use of cytotoxic anti-tumor agents. Therefore, we believe that this therapeutic strategy is an effective and rational treatment for adolescent and young adult ALL patients.

Acquired hemophilia A (AHA) is a rare disease characteized by bleeding symptoms caused by decreased factor VIII activity due to the appearance of inhibitors to factor VIII triggered by malignancy or collagen disease. An 86-year-old woman developed purpura on her extremities after the first dose of the BNT162b2 mRNA COVID-19 vaccine. This symptom subsided after a few days. After the second dose of the BNT162b2 mRNA COVID-19 vaccine, purpura appeared again, and the patient was referred to our hospital Her APTT was remarkably prolonged to 110 seconds, and a cross-mixing test revealed an inhibitor pattern. Since FVIII activity was <1% and FVIII inhibitor was 51.6 BU, she was diagnosed with AHA. Prednisolone therapy was started, and coagulative complete remission was achieved. Because acquired hemophilia can develop after mRNA COVID-19 vaccination, as in this case, it is critical to monitor the appearance of bleeding symptom.

The gene mutation occurring with transformation in lymphoplasmacytic lymphoma (LPL) /Waldenström macroglobulinemia (WM) has not been fully elucidated. Herein, we report a 61-year-old man with LPL/WM. In this case, the MYD88 gene mutation appeared with transformation to diffuse large B-cell lymphoma (DLBCL). Bone marrow biopsy revealed the involvement of CD20 positive small plasmacytoid lymphocytes, indicating LPL/WM. However, the samples taken from both the cervical lymph node and the pleural effusion provided a pathological diagnosis of DLBCL. All samples showed the same patterns of surface antigen expressions and immunoglobulin gene rearrangements. Therefore, these lymphomas had identical clonality and were regarded as transformation from LPL/WM to DLBCL. The MYD88 L265P mutation has recently been identified in most LPL/WM cases. The gene analysis in this case demonstrated that the MYD88 L265P mutation was detectable in only the pleural effusion sample (DLBCL cells), not in the lymphoma cells of the bone marrow (LPL/WM cells). Thus, it was concluded that LPL/WM had transformed into DLBCL with the MYD88 L265P mutation in this patient.

A 67-year-old man was admitted with a 1-month history of spontaneous hematoma in his right back and severe anemia. He had suffered from rashes with blisters involving both legs for 10 years, which had shown worsening and extended to his entire body concurrently with the hematoma. APTT was markedly prolonged to 119 seconds, and Factor VIII:C and FVIII inhibitor levels were less than 1% and 153.1 BU/ml, respectively, confirming the diagnosis of acquired hemophilia A (AHA). Skin biopsy revealed his rashes to be caused by autoimmune bullous disease (ABD), and laboratory and physical findings showed that he also had autoimmune hypothyroidism (Hashimoto's disease). Recombinant FVIIa was effective for management of his bleeding; in addition, FVIII inhibitor reduction and FVIII:C recovery, in parallel with improvement of the skin lesions, were achieved by administering prednisolone and cyclophosphamide. To our knowledge, this is the first report of AHA associated with ABD and Hashimoto's disease.

The rare central nervous system (CNS) infiltration of Waldenström macroglobulinemia (WM) is known as Bing-Neel syndrome (BNS). Furthermore, the transformation of WM into diffuse large B-cell lymphoma (DLBCL) is also unusual. Herein, we report a 69-year-old male with DLBCL transformed from BNS. In November 2008, the patient visited a prior hospital because of anemia and was diagnosed with WM. After receiving chemotherapy (R-CHOP), his serum immunoglobulin M (IgM) level decreased and then remained at approximately 2000 mg/dl for 3 years. In November 2011, he complained of visual impairment and photophobia in his left eye. Magnetic resonance imaging showed enlargement of the left optic nerve and cerebrospinal fluid examination indicated CNS infiltration of WM cells. Consequently, he was diagnosed with BNS. He thus received CNS targeted chemotherapy (R-MPV) and achieved a partial response. In May 2014, IgM was elevated and swelling of systemic lymph nodes was detected. Inguinal lymph node biopsy yielded a pathological diagnosis of DLBCL and the clonality of tumor cells between WM and DLBCL was confirmed by the allele-specific oligonucleotide polymerase chain reaction (ASO-PCR).

A 61-year-old woman who had received treatment for tuberculous pleurisy for 2 months visited our outpatient clinic. Chest computed tomography (CT) showed the presence of a lens-shaped pleural mass with pulmonary infiltration, despite the decreased pleural effusion. Two weeks later, chest CT showed an increase in the size of the mass and expansion of the intrapulmonary shadow. Percutaneous CT-guided lung biopsy was performed, and histopathological examination revealed granulomatous inflammation without caseous necrosis or acid-fast bacilli. Sputum culture was negative for acid-fast bacilli. Anti-tuberculosis medication was continued, and the lesions eventually resolved. These lesions were diagnosed as pleural tuberculomas, and the intrapulmonary infiltration was considered to be due to the paradoxical worsening of the patient's condition.

This review discusses the clinicoradiological diagnosis of pulmonary tuberculosis. To make a differential diagnosis between pneumonia and mycobacterial infections, it is very important to analyze the radiological findings of inflammatory lung diseases based on normal anatomical structures. If clinicoradiological analyses could make these differentiations, the appropriate treatment strategy for respiratory infections could be established. To accomplish this, exact orientations of pulmonary lobulus, acinus, and miliary nodule are very important. Then, through analyzing chest CT findings and distribution patterns based on normal anatomical structures, estimation of Mycobacterium tuberculosis infection could be possible. To differentiate infections caused by Mycobacterium tuberculosis from other respiratory diseases, several important criteria have been demonstrated. In addition, activity of pulmonary tuberculosis as well as smear-positivity could be analyzed radiologically. The HRCT patterns described allow classification of disseminated tuberculosis according to the mechanism of spread (haematogenous and/or bronchogenic).

Diabetes mellitus (DM) is a risk factor of tuberculosis (TB). We studied the clinical presentation of pulmonary TB among patients with DM in comparison with patients without DM who were admitted into the hospital of the University of the Ryukyus from 2006 to 2010. The clinical data were collected from medical records retrospectively. Ten cases (25%) of hospitalized patients with pulmonary TB had DM. The DM group showed lower Body Mass Index and higher incidence of chronic heart failure and chronic renal failure. The DM group also were more likely to have cavitary lesion, had longer period of hospitalization, and higher mortality. Their causes of deaths were mainly the co-morbidities and associated complications. Further studies are warranted in order to fully elucidate the relationships between pulmonary TB and DM.

Recently, the clinical importance of non-tuberculous mycobacteria(especially, Mycobacterium avium complex [MAC] respiratory infection) has been increasing. In addition, an official ATS/IDSA statement about diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases has been published in February, 2007. In this review article, clinical features and radiological findings of pulmonary MAC diseases mainly i) primarily fibrocavitary disease, and ii) nodular/bronchiectatic disease are described. Primarily fibrocavitary disease is characterized by cavitary lesions in upper lung fields in elderly subjects, smoking patients, or patients with pneumoconiosis. Nodular/bronchiectatic disease is characterized by centrilobular nodules and diffuse bronchiectases in the right middle lobe and the left lingula in middle-aged women. In addition, diagnosis and treatment for pulmonary diseases caused by MAC are also described.

A 55-year-old man who had a living kidney transplant 3 months previously was admitted complaining of 4 days of non-productive cough and fever. Because of his low oxygen saturation (SpO2 83% on room air), ground-glass opacities in both lung fields, and marked elevation of beta-D-glucan, a diagnosis of Pneumocystis jirovecii pneumonia (PCP) was considered. The diagnosis of PCP was confirmed by bronchoalveolar lavage. Subsequently, his oxygenation level decreased even after the administration of trimethoprim-sulfamethoxazole, therefore we concurrently administered 60 mg of prednisolone. His clinical symptoms and radiographic findings gradually improved. However, his respiratory condition and radiographic findings exacerbated again after the tapering of prednisolone. His condition improved after the prednisolone dose was returned to 30 mg per day. This case suggested that, in the treatment of PCP in patients without human immunodeficiency virus (HIV) infection, reduction of steroids may cause exacerbation of PCP, similar to immune reconstitution inflammatory syndrome which occurs in HIV patients.

Background: The A-DROP is a predicting pneumonia severity index which is adopted in the Japanese Respiratory Society (JRS) guidelines. For community-acquired pneumonia, we made a modified A-DROP, adding two new index items to the current A-DROP. Then, we retrospectively compared the modified A-DROP with the current A-DROP regarding 30-day mortality., Methods and Results: We analyzed consecutive 227 patients hospitalized with community-acquired pneumonia (mean age 79.0 years). The added index items were respiratory rate > or = 30/min and the presence or absence of underlying diseases. There were 16 fatalities (7.0%). In the extremely severe group, the sensitivities of the 30-day death and odds ratios were 19.9% and 9.5 in the current A-DROP, but 75.0% and 14.1 for the modified A-DROP, respectively. In addition, regarding the receiver-operating characteristic (ROC) area under the curve for the 30-day death ratio, the current A-DROP and modified A-DROP were 0.807 and 0.840, respectively., Conclusions: The modified A-DROP improved the ability to predict outcomes compared with the current A-DROP.

The prevalence of primary intestinal tuberculosis is increasing with social change and medical progress. However, it remains unknown whether or not primary intestinal tuberculosis exists without the involvement of other internal organs. This review verifies hypotheses about infectious courses of intestinal tuberculosis. We also evaluate the significance of bowel infection. As a result, we found some patients with intestinal tuberculosis who do not have tuberculosis lesions in other internal or external organs, and the tubercle bacillus, which is ordinarily transmitted with airborne droplet nuclei, might cause oral transmission by several factors.

Noninvasive positive pressure ventilation (NPPV) is respiratory therapy designed to assist ventilation without endotracheal intubation. It has been reported that NPPV is useful for respiratory failures due to various conditions. Recently, the critical care ventilator has been developed to cover either invasive or noninvasive mechanical ventilation. In the present report, we describe 3 successfully treated cases of acute exacerbation of bronchial asthma using NPPV by critical care ventilator. In all cases, the ventilator was immediately synchronized with spontaneous breathing, patients were able to avoid endotracheal intubation, and weaned from the ventilator soon. In conclusion, NPPV using a critical care ventilator was considered to be a useful treatment.

A 28-year-old woman was admitted to our hospital complaining of a 7-day chilly sensation with fever. She was given a diagnosis of pneumococcal pneumonia because of infiltration on chest radiography, sputum gram staining and testing positive for a pneumococcal urinary antigen. A 10-day course of antibiotics showed improvements in symptoms and infiltration. However, her X-ray film revealed severe volume loss in the right lung. Organizing pneumonia was diagnosed with lymphocytosis in BALF and Masson bodies upon TBLB examination. Administration of prednisolone obtained rapid improvement of the volume loss. This case was interesting, showing an organizing tendency in the acute-stage pneumococcal pneumonia.

A 79-year-old woman with colon cancer and multiple liver metastases was admitted to our hospital for systemic chemotherapy. She underwent first cycle of modified FOLFOX6 chemotherapy. She was confused on treatment day 5. Blood test revealed her serum ammonia level to be 121 microg/dl. We diagnosed 5-fluorouracil (5FU)-induced hyperammonemia. Conservative treatment resulted in improvement of metal status. The reason for hyperammonemia after administration of 5FU was the excess production of ammonium from metabolites of 5FU.

A 56-year-old man, having no particular past history, was admitted to our hospital, with a 9-month history of painful ulcerated lesion of the tongue and a 6-month history of productive cough. A physical examination revealed swelling of his cervical lymph nodes, and a chest roentgenogram on admission showed cavities in the both upper lung fields and nodular shadows over the both lung fields. He was initially suspected of having both cancer of the tongue and pulmonary tuberculosis, but finally diagnosed as secondary tuberculosis of the tongue due to sputum smear-positive pulmonary tuberculosis by biopsy of the tongue and sputum examination. He was treated with isoniazid, rifampicin, ethambutol and pyrazinamide, and his pain and ulcerated lesion of the tongue rapidly improved. Due to our search for recent 16 cases of tuberculosis of the tongue in Japan, we found that the patients of tuberculosis of the tongue were more likely to have concurrently sputum smear-positive pulmonary tuberculosis. In some cases, the delay in diagnosis was seen. These cases suggest that refractory ulcerated cases of the tongue should be subjected to the biopsy and examination for acid fast bacilli of the tongue with suspicion of tuberculosis of the tongue, and then a chest roentgenogram with suspicion of pulmonary tuberculosis.

A 39-year old woman presented with cough. Computed tomography showed a mass in the lower lobe of the right lung. Although bronchofiberscope was performed, accurate diagnosis of the tumor was not obtained. Based on the characteristics of the tumor from the results of chest MRI and PET-CT, a diagnosis of bronchogenic cyst with infection was suspected. Therefore, surgical resection was performed, revealing an intrapulmonary bronchogenic cyst and another tumor of the pleura on the vertebral body. Pathological findings demonstrated that the wall of the intrapulmonary tumor was covered with many ciliated epithelia and bronchial cartilages, suggesting a diagnosis of bronchogenic cyst. The tumor on the pleura was also diagnosed to be bronchogenic cyst based on pathological findings. Therefore, we diagnosed both intrapulmonary and pleural cysts.

Fifteen cases of legionella pneumonia experienced in our department or associated hospital were included in this study. Each case was classified with the A-DROP system of the Japanese Respiratory Society Guidelines, and guidelines from the Infectious Diseases Society of America (IDSA) (1998) and then we compared the severity of the cases of pneumonia. Although 10 cases were classified as intermediate, 3 as severe, and 2 as extremely severe with the A-DROP system, most cases were classified as severe according to the IDSA guidelines. Among 5 fatal cases, three were ranked as intermediate with the A-DROP system. However all the fatal cases were ranked as severe in the IDSA guidelines. This study suggested that the A-DROP system might underestimate the severity of pneumonia in cases with legionella pneumonia.

Mycobacterium avium complex (MAC) causes respiratory tract infections and develops granulomatous lesions in the alveolar areas and bronchioles in humans. In contrast with the above, the intestinal tract is the primary infection site of immunocompromised hosts, such as patients with acquired immune deficiency syndrome (AIDS), or animals, such as pigs. Recent studies have revealed that hosts with hereditary dysfunction of mediators in the Th-1 cascade as well as hosts with a high titer of auto-antibodies against interferon-gamma are susceptible to MAC, and such hosts facilitate dissemination of MAC. However, their disseminated lesions are formed mainly in the lung or in soft tissues, and the mechanism of development of MAC in such host may be different from that of AIDS-related MAC infection. In this review, we specifically discuss the development mechanism of disseminated MAC disease in recently-identified several pathological conditions.

A 58-year-old man with cough and bloody sputum was admitted because of right lung tumor and thrombocytopenia. Idiopathic thrombocytopenic purpura (ITP) was diagnosed. For treatment of ITP, he was treated with platelet transfusions, intravenous gamma-globulin and oral prednisolone. However, the platelet count did not completely improved. Since a relationship between ITP and Helicobacter pylori (HP) infection has been reported, and result of urease test was positive, the patient was treated by HP eradication therapy. After the eradication therapy, the platelet count improved to the normal range. The diagnosis of squamous cell carcinoma of the lung was confirmed by a cervical lymph node biopsy. As a result of improvement in platelet count, we were able to perform the chemotherapy of lung cancer.

A 20-year-old man visited a clinic with high fever and a dyspnea. The chest X-ray film and CT showed multiple patchy ground glass opacities in all lung fields with thickened interlobular septa and bilateral pleural effusions. Examination of bronchoalveolar lavage fluid led to a diagnosis of acute eosinophilic pneumonia. The patient was a current smoker and he had changed the brand of cigarette he smoked from one with a filter to another brand without filter, one week before disease onset. His symptoms improved after the administration of methylprednisolone. This case suggested that the presence of a filter or a difference in ingredients, or both, between brands of cigarette might contribute to the development of acute eosinophilic pneumonia.

Primary extranodal involvement of Hodgkin lymphoma (HL) is rare. We report two HL patients presenting with exclusive or predominant lung involvement. In both cases, the results of transbronchial and/or CT-guided lung needle biopsy were indicative of granulomatous disease. Eventually, lymph node biopsy specimens revealed HL with nodular sclerosis type and lymphocyte-rich type, respectively. There were no specific symptoms, laboratory and imaging findings for pulmonary HL. A histological examination was required to confirm the diagnosis. Lung biopsy techniques such as transbronchial or percutaneous biopsy may be insufficient to allow diagnosis of HL. Pulmonary HL should be included in the differential diagnosis of lung involvement, even when the pathological evaluation of nonspecific inflammation was made from the biopsied specimens.

Recently, the clinical importance of nontuberculous mycobacteria (especially, Mycobacterium avium complex [MAC] respiratory infection) has been increasing. In addition, an official ATS/IDSA statement about diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases has been published in February, 2007. In this review article, essence of this official statement will be introduced. In MAC respiratory infection, (i) primarily fibrocavitary disease, (ii) nodular/bronchiectatic disease, and (iii) hypersensitivity-like disease are identified, and (i) and (ii) are clinically important. Primarily fibrocavitary disease is characterized by cavitary lesions in upper lung fields in elderly subjects, smoking patients, or patients with pneumoconiosis. Nodular/bronchiectatic disease is characterized by centrilobular nodules and diffuse bronchiectases in the right middle lobe and the left lingula in middle-aged women. In addition, disseminated MAC disease in patients with acquired immunodeficiency syndrome should be considered. Further studies concerning transmission route as well as mechanism of MAC disease should be performed.

Mycobacterium avium complex (MAC) infection has been giving major impact on human health. MAC infection is also one of zoonosis transmittable from environmental reservoirs to domestic animal such as pig, and from wildlife to human. Although the relationship between pig MAC infection and human MAC infection has been suggested, it has not been clarified about difference of pathogens, differences in the pathogenesis of the disease, and differences in pathological findings between them. As one of zoonosis, hog farms suffer from the epidemic in pig population and it may causes huge economical loss. At the same time, from pig to human transmission of MAC has been worried. Therefore, the control of MAC infection among hog farms is a very important issue both for pig industries and for human public health. We have demonstrated that the specific MAC strains can spread through pig market in the main island of Okinawa. In pig MAC infection, pathogens are infected orally, and granulomatous lesions are formed in abdominal lymph nodes. Subsequently, it spreads lymphogenously or hematogenously and forms disseminated disease. Pathologically, calcified lesion was formed within several months. These findings are quite different from human MAC disease, in which the infection was caused by inhalation, and form granulomatous lesions in lungs, and rarely cause lymph node swellings. Since the pathogenesis of human MAC respiratory infection has not been well clarified, it may be very important to examine the mechanism of pig MAC infection to find out some clues to explain the mechanism of human MAC infection.

An 80-year-old man was admitted to our hospital for treatment of recurrent esophageal cancer in December, 2004. He was diagnosed as having esophageal cancer of stage IVa (T2N4M0) in October, 2002, and he received chemoradiotherapy (nedaplatin (CDGP)/5-fluorouracil (5-FU) total 6 course+60 Gy). Afterwards, lymph nodes recurred, and two courses of CDGP/vindesine were given. Then, the primary lesion showed a complete response (CR), and lymph nodes a partial response (PR). In December, 2004, paraesophageal lymph nodes were enlarged to the size of 7 cm. On admission, because of renal disturbance and dementia with advanced age, we chose chemotherapy with TS-1 (100 mg/body/day, three weeks of administration, then two weeks of withdrawal). He had adverse effects of hematotoxicity of grade 3, and non-hematotoxicity of grade 1. He received 6 courses of this regimen and eventually showed CR. Serum SCC was decreased from 4.7 ng/mL to 0.9 ng/mL. At present,the lesions have not recurred during the follow-up for 18 months.

The history of influenza pandemics was reviewed and clinical manifestations of pneumonia associated with influenza virus infections are described and several typical cases are presented. Several types of pneumonia associated with the influenza virus infection have been reported: 1) influenza complicated by secondary bacterial pneumonia, 2) primary influenza virus pneumonia, 3) combined influenza virus and bacterial pneumonia. Secondary bacterial pneumonia often produces a syndrome that is clinically distinguishable from that of primary viral pneumonia. In primary influenza virus pneumonia, chest roentgenography revealed bilateral infiltrations but no consolidation. Histologically, diffuse alveolar damage and hemorrhagic bronchiolitis were frequently observed in primary influenza virus pneumonia, in which case the prognosis was the worst. Although rare, the possibility of cryptogenic organizing pneumonia associated with influenza virus infection should be recognized. H. influenzae, S. pneumoniae, or S. aureus were frequently associated with influenza viral infection, and treatment against these bacteria should be considered.

This review discusses the clinicoradiological findings of pulmonary tuberculosis as well as non-tuberculous mycobacteria. To make a differential diagnosis between pneumonia and mycobacterial infections, it is very important to analyze the radiological findings of inflammatory lung diseases based on normal anatomical structures. If clinicoradiological analyses could make these differentiations, the appropriate treatment strategy for respiratory infections could be established. To accomplish this, exact orientations of pulmonary lobulus, acinus, and respiratory bronchioles is very important. Then, through analyzing chest CT findings and distribution patterns based on normal anatomical structures. estimation of causative pathogens could be possible. To differentiate infections caused by Mycobacterium tuberculosis from non-tuberculous mycobacteria, several important criteria have been demonstrated. Briefly, in MAC respiratory infection, right middle lobe and left lingula are frequently involved and centrilobular nodules and diffuse bronchiectases are characteristic radiological findings.

We report a case of multisystem Langerhans cell histiocytosis (LCH) with lung, bone and pituitary involvement. A 20-year-old man developed thirst, polydipsia and polyuria in 1983. He had right femur pain from 1988 and osseous LCH was diagnosed based on the operated specimen in 1989. From July 1990, he had right chest pain on coughing and dyspnea and was admitted in November 1990. LCH involving the lungs was diagnosed by CT images and diabetes insipidus was also detected. Steroid therapy was started from 1991, but he discontinued it in 1998. Though he stopped smoking, his clinical symptoms worsened and he experienced bilateral pneumothoraces in 2002 and since then he has been receiving home oxygen therapy. Pulmonary LCH is thought to have a good prognosis, but in recent studies, its survival rate appears low. We report a case of multisystem LCH with lung deterioration over about 15 years.

Endogenous endophthalmitis (EBE) is intraocular infection usually associated by bcteremia. Although, EBE is an uncommon disease, visually prognosis is very poor. Immune suppressive disease, such as diabetes or malignancy is a predisposing factor of EBE. Although, in east Asia, including Japan, gram negative organisms reported as common pathogen causing EBE, we here repot a case of group B streptococcus EBE. A 53- year old man, who has history of diabetes mellitus, was admitted to our hospital with compliant of sudden visual loss and pain at his right eye. His visual acuity was no hand perception in the right. In auscultation, there were coarse crackles at his left lung. Axial magnetic resonance imaging of eye showed exophthalmos of right eye and cellulites. Chest radiography revealed infiltration at the left middle lung field. EBE and pneumonia due to GBS were diagnosed and he was treated with intravenous cefotaxim. Despite of administration of antibiotics and vitreous surgery, deterioration of his visual activity was observed. Therefore antibiotics were changed to intravenous vancomicin and topical levofloxacin and amykacin were added also. But he finally lost his visual acuity of right eye.

Purpose: To obtain baseline, medical students are recommended to make two-step tuberculin skin tests when they are in good physical health, as the baseline information to detect later tuberculosis infection. We investigated a method to obtain appropriate baseline data, because the accurate method of this test was not yet established., Subjects and Methods: The subjects were the tuberculin skin test results of 1066 medical students who were subjected to different methods of tuberculin skin test (58% tested once, 37% tested twice, and 5% tested three times). We retrospectively made multi-dimensional analysis about these data., Results: (i) In the first tuberculin skin test, 20% of the results were negative. (ii) When repeated with intervals between one to four years, the diameters of erythema gradually increased due to the effect of prior tests. (iii) The difference in size of erythema between the first tuberculin skin test and the repeated tests was less than 10 mm. (iv) When two-step tuberculin skin test was repeated, significant increase in the diameters of erythema were demonstrated in the second test (P = 0.0048). (v) Regarding booster phenomenon, it apparently lasted for one year, and it also remained after two years or over. CONSIDERATION: Thus, repeated tuberculin skin tests performed in good physical health was difficult to interpret measuring the diameters of erythema to detect tuberculosis infection. Thus, the diagnostic value of a tuberculin skin test was reduced while it requires unnecessary time and expenditure for its implementation., Conclusion: It seems to be appropriate for medical students to make a two-step tuberculin skin tests, soon after their enrollment, and the results should be used as a baseline to detect possible later tuberculosis infection.

We report 2 cases of pulmonary aspergillosis treated successfully by combining micafungin and traconazole. Case 1: A 51-year-old man with hemoptysis and dyspnea on effort treated for pulmonary tuberculosis and aspergillosis was found on chest CT on admission to have a fungus ball in the left upper lobe and increasing consolidation around the cavity of both lung fields. Bronchoscopy proved positive for aspergillus PCR in bronchial lavage. He was diagnosed with chronic necrotizing pulmonary aspergillosis, based on clinical and radiological findings and the positive reaction for aspergillus PCR. He was treated with micafungin alone at first, this proved ineffective, so itraconazole was added, resulting in improvement. Case 2: A 24-year-old woman with stabilized Hodgkin's disease (mixed). She had suffered from a cough and back pain, and chest CT showed increasing consolidation inside and around a giant bulla. She was diagnosed with chronic necrotizing pulmonary aspergillosis, based on isolation for Aspergillus sp. in sputum culture and a positive reaction for Aspergillus antigen in bronchial lavage and Aspergillus antibody in serum. She was treated with the combined micafungin and itraconazole, which rapidly improved symptoms and radiological findings. Pulmonary aspergillosis therapy is often difficult, because delivery of the drug to the infection site is limited and drug tolerance is poor. We found that combination micafungin and itraconazole therapy is tolerable and effective in these cases.

This study was designed to evaluate peak inspiratory flow (PIF) and peak expiratory flow (PEF) in 24 patients with mild asthma. After inhalation of a beta2-stimulant (beta2), PIF significantly increased from 173.0 +/- 67.0 (range 70-300 L/min) to 194.0 +/- 66.7 after 1 minute, and to 199.3 +/- 63.0 after 15 minutes (p < 0.0025, and p < 0.008, respectively). PEF also significantly increased. The previous inhalation of beta2 improved the efficacy of inhalation of dry powder. This evidence should be considered in performing patient education for effective methods of inhalation.

A 51-year-old man complaining of cough and bloody sputum, was admitted to our hospital because of antibiotic-resistant chronic pneumonia in the right upper lobe. Initially, bronchoscopic examination and sputum culture revealed no evidence of malignancy or any specific infection, either pathologically or microbiologically. However, pathological examination of a solid body expectorated with sputum revealed typical sulfur granules, indicating pulmonary actinomycosis. Two actinomyceses named Actinomyces odontolyticus and Actinomyces meyeri were detected later. Pulmonary infection caused by these types of actinomyceses is rare, and the diagnostic procedure seemed to be unusual.

This study was designed to evaluate the effect of discontinuing oral beta2-stimulant in patients with asthma who were being treated with multiple medications. Thirty-two asthmatics controlled under multiple medications who had a stable PEF were entered. Patient symptoms, PEF, FEV10, V75,V50, and V25 were evaluated before and after discontinuing beta2-stimulant. Results showed that after discontinuing beta2-stimulant, there was little change in symptoms, PEF, or FEV10, and only two patients had to be re-medicated with oral beta2-stimulant. However, deterioration of V50 and V25 were clearly observed, suggesting that oral beta2-stimulant had an affect on dilatation of the small airway. Based on our data, we should regard that when discontinuing oral beta2-stimulant from combined use, the lung function reflecting the small airway decreases even if no change of symptoms is observed.

Inhaled beta(2)-agonists (long-acting as well as short acting) are used world-wide for the relief of asthma symptoms. However, there are few reports which have evaluated the additive effect of short-acting beta(2)-agonists to long-acting beta(2)-agonists on airway resistance measured by a plethysmography. This study was designed to evaluate the additive effect of inhaled short-acting beta(2)-agonists (protecarol) to long-acting beta(2)-agonists (salmeterol) on airway resistance in normal healthy volunteers (S+P group). In addition, to compare the effects of beta(2)-agonists which have different types of intrinsic activities, acute effect of inhaled procaterol adding to procaterol was also evaluated (P+P group). Seven healthy volunteers (all male and all non-smokers) were entered in this study. Pulmonary function was measured by a body plethysmography. Forced expiratory volume per 1 second (FEV1), the maximum flow rate at 25% (V(.) 25), the maximum flow rate at 50% of forced vital capacity (V(.) 50), and airway resistance were measured before and after inhalation of salmeterol (1 dry powder, 50 microg) or procaterol (2 puffs, 20 microg). Sixty minutes after inhalation of salmeterol, or 15 minutes after inhalation of procaterol, inhalation of procaterol (2 puffs, 20 microg) was added, and then pulmonary function was monitored. FEV1, V(.) 25, and V(.) 50 were significantly increased after inhalation of salmeterol as well as procaterol. In addition, airway resistance decreased significantly after inhalation of salmeterol as well as procaterol. In the S+P group, additional decrease of airway resistance after inhalation of procaterol was relatively small compared with the P+P group. In conclusion, although additional bronchodilatoric effects were observed in the S+P and P+P group, the effects seemed to be different based on the intrinsic activity of each beta(2)-agonist.

It has been suggested that the Arg 16/Gly 16 allele at codon 16 of beta 2-adrenoceptor polymorphism plays a role in down-regulating the stimulus of bronchodilatation caused by beta 2-agonists. This study was designed to evaluate the difference of bronchodilator responsiveness to beta 2-agonist (procaterol) and anti-cholinergic drug (oxitropium) between those who have Arg 16/Gly 16 allele (hetero type) and those who have Gly 16/Gly 16 allele (variant type) at codon 16 of in healthy women. Airway resistance and other pulmonary function tests were measured by a body plethysmography before and 5, 10, 15, 20, and 30 minutes after inhalation of procaterol or inhalation of procaterol and oxitropium. In healthy women inhaled procaterol, percent changes of respiratory airway resistance compared with values before inhalation were -2.8 after 5 minutes, -7.5 after 10 minutes, -11.2 after 15 minutes, -15.4 after 20 minutes, and -12.6 after 30 minutes. In healthy women inhaled porcaterol and oxitropium, percent changes of respiratory airway resistance compared with values before inhalation were -14.5 after 5 minutes, -18.9 after 10 minutes, -17.0 after 15 minutes, -20.8 after 20 minutes, and -20.4 after 30 minutes. Patterns of decrease of respiratory airway resistance differed between women who have Arg 16/Gly 16 allele (hetero type) and those who have Gly 16/Gly 16 allele (variant type). In women who have Gly 16/Gly 16 allele (variant type), although acute decrease of respiratory airway resistance was observed, the duration of bronchodilator effect by inhaled procaterol and oxitropium was shorter than those observed in Arg 16/Gly 16 allele (hetero type). The present study showed inhalation of procaterol and oxitropium had a differential bronchodilator effect in healthy women, depending on their genotype of beta 2-adrenoceptor polymorphism at codon 16.

The history of influenza pandemics was reviewed and clinical manifestations of pneumonia associated with influenza virus infections are described. Several types of pneumonia associated with the influenza virus infection have been reported: 1) influenza complicated by secondary bacterial pneumonia, 2) primary influenza virus pneumonia, 3) combined influenza virus and bacterial pneumonia. Secondary bacterial pneumonia often produces a syndrome that is clinically distinguishable from that of primary viral pneumonia. In primary influenza virus pneumonia, chest roentgenography revealed bilateral infiltrations but no consolidation. Histologically, diffuse alveolar damage and hemorrhagic bronchiolitis were frequently observed in primary influenza virus pneumonia, in which case the prognosis was the worst. Although rare, the possibility of bronchiolitis obliterans organizing pneumonia associated with influenza virus infection should be recognized. H. influenzae, S. pneumoniae, or S. aureus were frequently associated with influenza viral infection, and treatment against these bacteria should be considered.

Although rates of emphysematous change in smokers have been reported previously, the precise effects of smoking on emphysematous change have not been established because the study subjects of previous reports were heterogeneous. This study was designed to determine the incidence of emphysematous change identified by LMCT imaging in public-school teachers. We reviewed 1776 consecutive subjects (ages from 31 to 61 years) who had undergone LMCT scanning during health care examinations. In addition, their replies to questionnaires about smoking were obtained. Emphysematous change was found by LMCT imaging in 22 male smokers. In these 22 smokers, the scores of emphysematous change according to Goddard's method was well correlated with smoking history. According to the questionnaires, the smoking rates of male and female teachers were 56.7% and 4%, respectively. Eighty-five percent of the teachers worked in offices separated from smokers. Most smokers wished to quit smoking and most teachers knew the risk of nicotine as well as the rate of smoking among high school students. However, knowledge of the relationships between smoking and lung cancer, myocardial infarction, and subarachnoid hemorrhage were not adequate. Our present study clearly demonstrated the incidence of emphysematous change in school teachers. In addition, early exposure to information about the risks of smoking is believed to be important for students, but school teachers did not have enough of such information.

A 46-year-old woman was admitted to our hospital because of fever, cough and headache in December 2001. Although she had been treated for nasal obstruction and epistaxis by an otorhinolaryngologist in our hospital since 1996, no accurate diagnosis had been made despite repeated biopsies of the nasal mucosa. A chest CT taken in 1999 showed ground-glass opacities in both upper lobes. On admission, chest radiography and CT showed mass shadows without cavitation, corresponding to the lesions causing the ground-glass opacities. In addition, paranasal sinus MRI showed a deformity of the nasal septum accompanied by a space-occupying lesion, suggesting Wegener's granulomatosis. However, the cytoplasmic-antineutrophil cytoplasmic antibody (c-ANCA) test was negative. To achieve a definitive diagnosis, we performed an open lung biopsy. The specimen, obtained from the right upper lobe, showed the typical findings of a Wegener's granulomatosis including necrotizing vasculitis. Oral prednisolone treatment initiated at 20 mg daily, combined with oral cyclophosphamide at 50 mg daily markedly improved not only the clinical symptoms, but also the mass shadows in the left upper lobe. Patients with the limited form of Wegener's granulomatosis are occasionally seronegative and respond well to therapy. However, the natural course and the changes in chest radiographs are not understood well in such cases. In this paper, we report a case of the limited form of Wegener's granulomatosis that progressed slowly over a period of 6 years.

This study is designed to evaluate radiological, clinical, and pathological findings of Mycobacterium avium complex (MAC) respiratory infection. Two-hundreds of non-tuberculous mycobacteria obtained from upper respiratory tract were collected. Among them, 88 cases were selected according to the strict diagnostic criteria of MAC and chest CT findings were evaluated in 67 cases. In addition, successive chest CT findings were evaluated in 25 cases with MAC respiratory infection. Furthermore, pathological findings were evaluated in 9 surgically-resected lung specimens. Fever, hemoptysis, and dyspnea were more frequently observed in smear-positive patients than in smear-negative, culture-positive patients. Centrilobular nodules and bronchiectasis are frequent observations in patients with MAC. In addition, cavity formation was more frequently observed in smear-positive patients compared with smear negative-cases. Since the score of bronchiectasis in the second CT was significantly higher than in the first CT, progression of bronchiectasis appeared to be caused by MAC infection. Pathologically, extensive granuloma formation throughout the airways was clearly demonstrated. Immunohistochemical staining demonstrated: 1) epithelioid cells and giant cells; and 2) myofibroblasts extensively infiltrating the cavity wall. When granuloma was initially formed, no myofibroblasts were found, but as caseous necrosis appeared, the thin epithelioid cell layer was detected and the outer myofibroblast layer gradually became thick. In the cavitary wall, the layer of epithelioid cells and multinucleated giant cells surrounded necrosis, and was associated with the outer layer of myofibroblasts. In addition, the anti-TGF-beta 1 antibody stained the cytoplasm of epithelioid cells and multinucleated giant cells, preceding the advent of myofibroblasts.