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Pulmonary dendritic cells (DCs) are key regulators of immune responses. An increased accumulation of DCs was reported in the lungs of patients with idiopathic interstitial pneumonia (IIP).This study aimed to investigate the number of pulmonary DCs in patients with collagen vascular disease associated interstitial lung diseases (CVD-ILDs).Lung tissue samples obtained from 27 patients with IIP and 39 patients with CVD-ILD were detected using monoclonal antibodies against CD1a, CD1c, CD83, Langerin and DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN).No significant differences in the number or distribution of DCs were observed between patients with IIP and CVD-ILDs. When DC marker expression was analyzed according to pathological subgroup, patients with idiopathic usual interstitial pneumonia (UIP) showed increased DC-SIGN staining when compared with CVD-UIP (p0.05).Both mature and immature DCs accumulate in CVD-ILDs. The number of DCs expressing DC-SIGN in CVD-UIP was decreased compared with that in idiopathic UIP. The variation in accumulated DC-SIGN-positive cells might help to explain the differences in the development and maintenance of lung inflammation between idiopathic UIP and CVD-UIP.

Although serum Krebs von den Lungen-6 (KL-6) levels are reported to increase in pulmonary tuberculosis (PTB) patients according to disease activity, the relationship between serum KL-6 levels and prognosis remains unclear. In this study, we prospectively examined serum KL-6 levels in 188 PTB patients and assessed 60-day mortality. Univariate and multivariate logistic regression analysis demonstrated that serum KL-6 levels were not significantly associated with prognosis. For receiver operating characteristic analysis, the area under the curve had low accuracy for predicting mortality. These findings indicate that serum KL-6 levels do not perform adequately for use as a prognostic marker in patients with PTB.

Systolic anterior motion of the anterior mitral leaflet and asymmetric septal hypertrophy (ASH) are characteristic features of hypertrophic obstructive cardiomyopathy (HOCM) on an echocardiogram. Among 9,670 patients over 60 years old examined by echocardiography from January, 1984 to October, 1990, 55 patients showed systolic anterior motion of the anterior mitral leaflet and/or the chordae tendinae (SAM). We investigated clinical features and morphological features of the left ventricle on an echocardiogram in the 55 patients with SAM. They were classified into three groups according to the degree of SAM. Thirty eight cases (group I) had no mitral and/or chordal-septal contact, 10 (group II) had brief contact (less than 30% on the echocardiographic systole) and 7 (group III) had prolonged contact (greater than or equal to 30%). Ages ranged from 60 to 99 with a mean age of 78.2 years. There were 19 males and 36 females and there was a predominance of females in each group. Thirty five cases had hypertension and 34 left ventricular hypertrophy on electrocardiograms. One case of group I, 3 of group II and 7 of group III had a clinical diagnosis of HOCM. In comparison with each group, the incidence of LVH (SV1 + RV5 greater than or equal to 35 mm) was 52% in group I, 90% in group II and 83% in group III and that of LVH (SV1 + RV5 greater than or equal to 70 mm) was 29%, 20% and 67%, respectively. On echocardiographic examination, the diastolic descent rate of the anterior mitral leaflet in the 3 groups was 36.1 +/- 13.1 mm/sec, 19.4 +/- 13.1 mm/sec and 10.7 +/- 11.8 mm/sec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Desquamative interstitial pneumonia (DIP) is a rare pattern of diffuse parenchymal lung disease known to overlap with respiratory bronchiolitis-interstitial lung disease (RB-ILD). The aim was to review biopsy-proven cases of DIP to investigate further the clinical, imaging and histological features of this disease.Twenty patients fulfilled the pathological criteria: 19 men and one woman with a mean age of 54 years. Clinical features, bronchoalveolar lavage (BAL) data, radiological findings, pathological findings other than criteria, effect of therapy and outcome were examined. The BAL data for 17 cases revealed marked eosinophilia (mean 18%) and moderate neutrophilia (mean 11%). Computed tomography in 17 patients showed peripheral involvement in all cases with a clear margin in 64% and thin-walled cysts in 35% of cases. Additional pathological features were a distinct lobular distribution (70%) and architectural destruction (70%) with cyst formation (55%). Eighteen of the 19 patients (95%) improved under steroid pulse and/or oral therapy. Sixteen subjects (80%) are alive, three died of other diseases and one died of DIP 74 months after the diagnosis. Percent vital capacity increased significantly and new thin-walled cysts appeared in one case.BAL eosinophilia, lobular distribution and architectural destruction with cyst formation are characteristic features of DIP.

There is sparse epidemiologic information regarding the role of dietary factors in the development of idiopathic pulmonary fibrosis (IPF).To examine the relationship between specific types of fatty acids and selected foods high in fat and IPF in Japan.Included were 104 cases agedor = 40 years who had been diagnosed in the last 2 years in accordance with the most recent criteria. Controls agedor = 40 years consisted of 56 hospitalised patients diagnosed as having acute bacterial pneumonia and four out-patients with common cold.Intake of saturated fatty acids, mono-unsaturated fatty acids, n-6 polyunsaturated fatty acids and meat was independently associated with an increased risk of IPF. Specifically, the multivariate OR for comparison of the highest with the lowest quartile of intake of saturated fatty acids was 6.26 (95%CI 1.79-24.96, P for trend = 0.01) and for meat it was 7.19 (95%CI 2.15-27.07, P for trend = 0.02). Intake of cholesterol, n-3 polyunsaturated fatty acids, fish, eggs and dairy products was not related to the risk.These findings suggest that consumption of saturated fatty acids and meat may increase the risk of IPF.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to enhance the symptoms of food-dependent exercise-induced anaphylaxis (1, 2). We report a rare case of wheat-induced anaphylaxis not related to exercise in which oral challenges with wheat and gluten-induced whole blood histamine release were enhanced by NSAIDs. A 59-year-old man was admitted to our hospital for investigation of recurrent food-induced anaphylaxis. He first developed urticaria after eating noodles at age 58. Since then he frequently had urticaria andoccasionally experienced anaphylaxis, including dyspnoea, wheezing, angioedema, and loss of consciousness after ingesting wheat, including noodles, bread, breaded cutlets, and tempura (Japanese deep-fried foods). It was determined that he had these episodes of anaphylaxis without exercise. Total IgE was 160 IU/ml. Skin-prick testing and specific IgEwere positive for wheat and gluten, the major allergen in wheat-induced allergy. To determine an elimination diet and to instruct the patient, open oral challenges were performed. Oral challenges with bread, noodles, cutlets, and tempura were all negative. However, when 30 mg of diclofenac sodium, an NSAID, was taken just before the challenge, he developed urticaria 1 h after eating noodles or tempura.He developed no symptoms after taking diclofenac sodium only. To clarify the effect of NSAIDs on wheat-induced anaphylaxis, we measured histamine release after in vitro exposure to gluten with or without tolmetin sodium, an NSAID, in this patient and a normal control subject. Heparinized whole blood samples were taken and incubated with gluten at concentrations ranging from 2.5 to 2500 lg/ml and with tolmetin sodium at concentrations ranging from 0.125 to 12.5 mg/ml for 30 min at 37 C. After centrifugation, histamine was measured in the cell-free supernatants by radioimmunoassay. Histamine release was found to be positive with gluten at the concentration of 2500 lg/ml in the patient. With tolmetin sodium at concentrations of 0.125 and 1.25 mg/ml, gluten-induced histamine release was not affected. However, tolmetin sodium at the concentration of 12.5 mg/ml enhanced the gluten-induced histamine release at all concentraions of gluten. Interestingly, tolmetin sodium enhanced histamine release even in the absence of gluten in the control subject as well as in the patient. Histamine release was not found in other conditions in the control subject. At follow-up 1 year after the discharge, he remained asymptomatic after strict elimination of wheat. The results of our in vitro study indicate that the induction of positive oral challenges with wheat after pretreatment with an NSAID is, at least partly, because of enhancement of histamine release. To our knowledge, this is the first report of wheatinduced anaphylaxis not related to exercise confirming thatNSAIDs enhance type I allergic reactions. Previous studies demonstrated that NSAIDs enhance in vitro histamine release induced by IgEor nonIgE-mediated mechanisms (3). In our study, histamine release was induced by tolmetin sodium even in the absence of allergen. In this regard, we speculate that the extent of enhancement of histamine releasemaydependon the type anddose of the NSAIDs as our patient developed no symptoms after taking diclofenac sodium only. We found that enhancement of the allergic symptoms induced by NSAIDs is not a specific phenomenon in fooddependent exercise-induced anaphylaxis, but can occur in other type I allergic diseases. Furthermore, pretreatment with NSAIDs under controlled conditions is useful for confirming the diagnosis of food-induced allergy when food challenge tests fail to induce positive reactions.

The relationships between immunological reactivity and bronchial responsiveness to allergen and non-specific bronchial responsiveness are unclear in occupational asthma caused by low molecular weight substances.We assessed the above relationships in green tea-induced asthma, an occupational asthma of green tea factory workers, in which epigallocatechin gallate (EGCg), a low molecular weight component of green tea leaves, is the causative agent.Subjects consisted of 21 patients suspected of having green tea-induced asthma, on whom skin test and inhalation challenge with EGCg were performed. The skin sensitivity or end-point titration to EGCg as a measure of immunological reactivity, together with the provocative concentrations causing a 20% or greater fall in forced expiratory volume in 1 s (PC20) of EGCg and methacholine, were determined.We found that 11 patients had green tea-induced asthma, with immediate asthmatic reactions in eight and dual asthmatic reactions in three. We also found that 11 of 13 patients (85%) with immunological reactivity and bronchial hyper-responsiveness to methacholine experienced an asthmatic reaction and that no subject without immunological reactivity reacted. There were significant correlations among skin sensitivity, EGCg PC20 and methacholine PC20. Multiple linear regression analysis showed the relationship: log (EGCg PC20)=0.42 log (skin sensitivity)+1.17 log (methacholine PC20)+0.93 (r=0.796, P0.05).It is concluded that bronchial responsiveness to EGCg can be highly satisfactorily predicted by skin sensitivity to EGCg and bronchial responsiveness to methacholine.

Eosinophilic tracheobronchitis with cough hypersensitivity, abbreviated as atopic cough, is an important cause of chronic cough. The reason for the absence of airway hyper-responsiveness is unknown, differing from asthma, a Th2 cytokine-mediated disorder.To compare the type 1 helper T cell (Th1)/Th2 balance in the peripheral blood from subjects with atopic cough and atopic asthma, we assessed the intracellular cytokine production at the single-cell level.Thirty-six subjects (10 patients with atopic cough, 18 with atopic asthma, and eight control subjects) were included. Intracellular IL-4 and IFN-gamma were detected in CD4+ T cells by flow cytometry.A significantly lower ratio of IFN-gamma-/IL-4-producing CD4+ T cells after phorbol 12-myristate acetate/ionomycin stimulation was found in patients with atopic cough and atopic asthma compared with normal subjects. In comparison between atopic patients, the ratio of IFN-gamma-/IL-4-producing cells was significantly higher in atopic cough than in atopic asthma. However, the proportion of IL-4-producing CD4+ T cells was significantly higher in patients with atopic asthma than in normal control subjects and no significant difference was detected between patients with atopic cough and normal subjects. No significant difference in the proportion of IFN-gamma-producing cells was found between the subjects. Overall, the total IgE levels were positively correlated to the IL-4-producing cells and inversely correlated to the ratio of IFN-gamma-/IL-4-producing cells.These results show the lower degree of Th2 cytokine predominance in atopic cough compared with atopic asthma and suggest the relation between the Th1/Th2 balance and atopic status.

A 59-year-old man was admitted to our hospital because of dyspnea. Chest radiography showed infiltration and consolidation in both lung fields. He was clinically diagnosed as having idiopathic interstitial pneumonia (IIP), and histological examination of a thoracoscopic lung biopsy specimen showed nonspecific interstitial pneumonia (NSIP) group 1. Corticosteroid therapy had previously been effective, but about 1 year later the disease recurred. The patient's clinical condition was very similar to the first episode, and is improving in response to the same treatment again. Although it is generally accepted that patients with IIP diagnosed histologically as NSIP have a good prognosis, it should be remembered that recurrence is possible, even in patients with group 1.

The aim of the present retrospective study was to clarify the histopathologic substrates of left ventricular myocardium with transient asynergy due to acute ischemic insult in man. Three patients who had had prolonged chest pain, new abnormal Q waves and new ST segment elevation were studied. There was no significant elevation of serum creatine phosphokinase activity in two of the three patients. Echocardiograms on admission or the next day showed severe hypokinetic or akinetic motion and thinning of the anteroseptal and apical portions of the left ventricle and regional dilatation of the same portions. Disappearance of the abnormal Q waves, ST segment elevation resolution, and early T wave inversion were observed later. Complete improvement of the echocardiographic abnormalities was confirmed after a few weeks in all patients. Manifest ischemic lesions of subendocardial scars of the anteroseptal region of the left ventricle were detected in only one of the three cases by gross examination. However, on microscopic examination, islands of necrotic myocytes were interspersed with islands of viable cells throughout the jeopardized region in one case, although the scattered necrotic foci were restricted to the subendocardium and the trabeculae. Normal myocardium and subendocardial scars were observed in the other two cases. In conclusion, left ventricular myocardium with transient asynergy. detected clinically during acute ischemic attack, consists of normal myocardium or small ischemic lesions primarily in the subendocardium.

A 45-year-old man was admitted with a severe dry cough and fever. He had been given 100 mg/day of minocycline and other drugs for 9 days to treat hematopyuria. Chest X-ray film showed multiple nodular shadows with diffuse reticular shadows. After all the drugs were discontinued, the fever and the shadows improved, but the severe dry cough persisted. The day 4 bronchofiberscopic findings included multiple white plaques in the tracheobronchial mucosa. Punch biopsy specimens obtained from the white plaques revealed severe eosinophil infiltration, and the eosinophil count in the bronchoalveolar lavage fluid had increased (differential count 23%). After three days of 125 mg/day of methylprednisolone sodium succinate injection therapy, the severe cough, the X-ray shadows and the white plaques disappeared. With a positive result in the lymphocyte migration inhibition test, the patient's condition was diagnosed as minocycline-induced eosinophilic pneumonia.

Substantial evidence obtained through polymerase chain reaction techniques strongly supports that reactivation of latently infected herpes simplex virus (HSV) in geniculate ganglia is the main cause of Bell's palsy. However, serum antibody titers to HSV rarely increase in patients with this disease. This discrepancy may result from the difficulty in detecting a small increase in antibody titers by conventional serological analysis. To detect such a small increase in antibody titer, we defined the significant increase in IgG antibody titers more precisely, and examined the association of HSV or varicella-zoster virus (VZV) with Bell's palsy. From 40 patients with Bell's palsy, paired sera were obtained within the 4th disease day and 2 weeks later. IgG antibodies to HSV, VZV, cytomegalovirus (CMV), or measles virus (MsV) were measured with solid-phase enzyme immunoassay (EIA). IgM antibodies were measured with captured EIA. Each antibody titer was expressed as an EIA-value, which was quantitatively measured by using a calibration curve prepared from the samples containing known titers to the virus in proportion to the logarithm of its titer. An EIA-value ratio (EVR) between paired sera and a corrected EVR was calculated according to the formulae: EVR = [EIA-value in the second serum]/[EIA-value in the first serum]; corrected EVR = [EVR to HSV, VZV or CMV]/[EVR to MsV]. The association with a virus was determined to be positive when the corrected EVR of the virus was beyond the normal range (the logarithmical mean +/- 3 SD of corrected EVRs among 24 healthy controls) while the corrected EVR of the other viruses were within it. Using the corrected EVR, 6 patients were positive: 4 for HSV, 2 for VZV. On the other hand, the conventional serological analysis, which confirms positivity by a 4-fold increase in IgG antibody titer or a demonstration of IgM antibody, disclosed only 2 positive patients (1 for HSV, 1 for VZV). EIA is a very sensitive method of detecting antibodies. Corrected EVRs can exclude a decrease in antibody titers induced by corticosteroids, which are generally used for therapy of Bell's palsy. Moreover, the normal range of corrected EVRs can be defined more precisely than in conventional serological analyses. Our results indicate that some sensitive analysis, such as the corrected EVR method, may make it possible to serologically detect the causative virus of Bell's palsy.

We performed clinicopathologic study of 56 aged patients with calcified aortic valve stenosis and investigated the indications for percutaneous aortic balloon valvuloplasty.The patients were 24 men and 32 women with a mean age of 81.9 years, who were classified into the following 3 types by etiology: 33 patients (58.9%) had senile aortic stenosis, 10 patients (17.9%) had bicuspid aortic stenosis, and 13 patients (23.2%) had rheumatic aortic stenosis. The sites of calcification were divided into the following 3 categories: cusp bases (base type), free edges (edge type), and both bases and edges (mixed type).Among the 33 patients with senile aortic stenosis, 10 (30.3%) had calcification of base type, 2 (6.1%) of edge type and 21 (63.6%) of mixed type. Among the 10 patients with bicuspid aortic stenosis, one (10%) had calcification of base type and 9 (90%) of mixed type. Among the 13 patients with rheumatic aortic stenosis, 3 (23.1%) had calcification of edge type and 10 (76.9%) of mixed type. In addition, 2 or 3 commissures were fused in patients with rheumatic aortic stenosis. The cusps of the aortic valves in the bicuspid type were the most severely thickened among the 3 groups. Soft X-ray imaging showed the aortic valves of rheumatic aortic stenosis were the most severely calcified (calcification score: 2.4), followed by those of bicuspid aortic stenosis (1.9) and senile aortic stenosis (1.6).Percutaneous aortic balloon valvuloplasty is most suitable in patients with calcified senile aortic stenosis because of the milder calcification, compared with those of the other 2 types.

We report a rare case of tracheobronchomegaly with crescent-type tracheobronchomalacia. A 77-year-old man with a chronic cough was referred to our hospital because of fever and dyspnea. Radiographic examination showed enlargement of the trachea and main bronchi. On chest radiography, the transverse diameter of the trachea was 31 mm, and consolidation shadows were seen in both upper lung fields. Tracheobronchomegaly with pneumonia was diagnosed. The pneumonia was improved by administration of PAPM/BP. On bronchoscopic examination, the trachea and main bronchi were extremely dilated on inspiration, and were collapsed on expiration. The biopsy specimen from the bronchial mucosa showed non-specific chronic inflammation.

We explored the prognosis for 123 patients with either idiopathic interstitial pneumonia (IIP) or bronchiolitis obliterans organizing pneumonia (BOOP). All patients underwent either open lung biopsy or thoracoscopic lung biopsy procedures. The histopathologic diagnosis of IIP included patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and desquamative interstitial pneumonia with respiratory bronchiolitis-associated interstitial lung disease. The prognosis was poorest for patients with a histologic diagnosis of UIP, and excellent for those who received a diagnosis of BOOP. Although the prognosis is generally considered to be good for patients with NSIP, some NSIP patients in our study died. Histopathologic diagnosis based on surgical lung biopsy is useful in evaluating the prognosis for patients with IIP.

A 66-year-old man was referred to our hospital because of cough. Chest X-ray films showed complete atelectasis of the left lung. Serum CYFRA was elevated. Bronchoscopic examination disclosed a white polypoid lesion occluding the left main bronchus. A biopsy specimen from the lesion revealed numerous aspergillus hyphae. Oral itraconazole (100 mg) and weekly endobronchial instillation of fluconazole were administered. Three months later, on the 12th bronchoscopic examination, the tumor occluding the left main bronchus was detected after the removal of aspergillus, and the biopsy findings yielded a diagnosis of squamous cell carcinoma. Aspergillosis complicated by lung cancer without cavity formation is very rare, and compounded the difficulty of diagnosing lung cancer in this case.

A 68-year-old man was hospitalized on March 4, 1998 for disturbances in consciousness. In 1995, he had received proximal subtotal gastrectomy and reconstructive surgery of the jejunal interposition for gastric cancer. Thereafter he had been taking enough food without the habit of taking liquor. In October 1997, his short term memory was becoming gradually worse. On February 12, 1998, he suffered from numbness in the feet, and then dysphagia, unsteady gait, and diplopia developed gradually. On February 26, brain MRI showed no abnormalities. On March 3, he had a fever of 38.5 degrees C and his consciousness became unclear. Neurological examination revealed semi-coma, total ophthalmoplegia, and absence of doll's eye movement. Deep tendon reflexes were absent. The serum thiamine level was 9 ng/ml (normal range: 20-50). Brain MRI demonstrated symmetrical high intensity lesions in the periaqueductal area of the midbrain, dorsomedial nuclei of bilateral thalami, and vestibular nuclei. About 30 seconds after intravenous infusion of thiamine, his consciousness improved dramatically, but returned to semi-coma after about two minutes. Wernicke-Korsakoff syndrome usually occurs acutely. In the present case, however, the disease showed slow onset, chronic progression, and then rapid worsening after fever. Reconstructive surgery of the jejunal interposition might have caused the slow onset of Wernicke-Korsakoff syndrome, and fever might have facilitated the rapid progression of the disease. An immediate high concentration of thiamine modifies the kinetics of acetylcholine receptor ion channels, thereby maintaining wakefulness, and the level of consciousness may change dramatically.

An autopsy case of MND with dementia, 67 years old, man, was reported. The behavioral disturbance appeared at 61 years old, and was followed by the upper limb weakness and respiratory failure. He had remained on a respirator for 56 months. The total duration of the disease was 74 months, which was far longer than mean duration of the cases previously reported, 25-30 months. The pathological findings were about essentially identical to those mentioned before, such as cortical alterations in temporal and frontal lobes, neuronal loss with gliosis in amygdaloid body and substantia nigra, and loss of lower motoneurons in anterior horn of spinal cord and in the several motor cranial nerve nuclei. There were several Bunina bodies in the remnant lower motoneurons, but no changes in the pyramidal tracts or loss of Betz cells in the precentral gyrus. Intracytoplasmic ubiquitin-immunopositive inclusions in the granule cells of hippocampal dentate gyrus were also encountered, but the number of which did not increased, compared to the preceding data. There may be frequently little correlation between the disease duration and the number of such inclusions. The regional alteration in the intermediate zone between subiculum and entorhinal cortex was revealed also at the level of the splenium of corpus callosum. It has been reported that such parahippocampal lesion may initiate at the anterior part of temporal lobe and become undiscernible at more posterior level than the lateral geniculate body. The formation of such parahippocampal lesion may be concerning with the length of disease duration. In addition, there were numerous senile plaques, diffuse or neuritic type only in the parietal lobe cortex without any other changes.

A 62-year-old man with a medical history that included artificial pneumothorax therapy at the age of 18 was admitted to our hospital because of persistent cough. Chest computed tomographic scans disclosed atelectasis in the right lung and pyothorax surrounded by calcifications. Radiographic examination failed to disclose any tumors. After admission, high grade fever developed due to aggravated pyothorax infection. Because antibiotic therapy and drainage failed, open window thoracostomy was performed. Tumors were found along the wall of the pyothorax cavity, and examination of resected specimens yielded a diagnosis of non-Hodgkin's lymphoma, diffuse large cell type (B-cell lineage). It was difficult to close the pyothorax cavity due to infection and lymphoma. Therefore, with the thoracic window open, the patient was given combination chemotherapy including CHOP (6 courses) and DeVIC (7 courses). He died of disseminated intravascular coagulation 17 months after thoracostomy. In patients with pyothorax associated lymphoma, chemotherapy is sometimes difficult to perform because of persistent pyothorax infection. Although edema and ascites due to protein loss from the tumor complicated the treatment of our patient, we concluded that open window thoracostomy is effective in managing pyothorax prior to and during chemotherapy.

A 65-year-old man was admitted to our hospital because of thirstyness and left lower abdominal pain. On admission, he was found to have urolithiasis, renal insufficiency (BUN: 73 mg/dl, Crt: 4.4 mg/dl), and hypercalcemia (13.2 mg/dl). Chest X-ray films and computed tomograms showed enlargement and calcification of the hilar lymph nodes, and thickened interlobar fissures in both lungs. Levels of angiotensin converting enzyme (30.2 IU/l) and 1.25 (OH)2VitD3 (66.4 pg/ml) were elevated. Histologic examination of the specimen obtained from transbronchial lung biopsy showed non-caseous epithelioid cell granulomas. Because the level of parathyroid hormone was normal and no malignancies were detected, a diagnosis of sarcoidosis was made. Treatment with extracorporeal shock wave lithotripsy, transurethral lithotomy, saline infusion, and prednisolone (30 mg/day) alleviated the urolithiasis, renal insufficiency, and hypercalcemia. After discharge, the patient was followed up and given prednisolone therapy. About 1 month after the prednisolone dose had been tapered to 15 mg/day, the patient experienced dyspnea and facial and pedal edema. Because congestive heart failure was diagnosed, he was re-admitted to our hospital for a second time. Although he was then placed on intensive therapy, he died of ventricular tachycardia associated with sarcoidosis of the heart.

We describe a 57-year-old man with interstitial pneumonia associated with systemic sclerosis. About 3 years prior to the appearance of distinctive signs of systemic sclerosis, he was admitted to our hospital with a chronic dry cough. A chest roentgenogram on admission revealed reticulonodular shadows in both lung fields. There were no abnormal laboratory findings. Open lung biopsy specimens revealed patterns indicative of usual interstitial pneumonia, and myxomatous connective tissue within the lumen of the airways. Skin biopsy specimens showed heightened levels of collagen in the dermis, a finding consistent with systemic sclerosis. The patient was given a diagnosis of lung involvement preceding systemic sclerosis despite the absence of concurrent skin symptoms.

Pharmacist's instruction is provided to asthmatic patients who received an inhaled steroid in Hamamatsu University Hospital. We studied influences of pharmacist's instruction on the repeutic effects of an inhaled steroid, beclomethasone dipropionate (BDP). In 29 patients who had been treated with inhaled BDP under the physician's instruction for more than 3 months, we examined drug compliance, correctness of inhalation procedure and treatment score, symptom score, peak expiratory flow (PEF) values, and compared these before and after the instruction. The instruction was repeatedly provided at an interval of about one month. Patients who followed the indicated regimen were 55.2 and 93.1% before and after the instruction, respectively. An appropriate inhalation maneuver was respectively. An appropriate inhalation maneuver was performed in 24.1 and 93.1% of patients before and after the instruction, respectively. PEF values increased by 12.9 +/- 9.3% (mean +/- standard deviation, p0.01) after the instruction. In conclusion, pharmacist's repeated instruction enhanced the therapeutic effects of inhaled BDP in patients with asthma.

We examined sympathetic and parasympathetic function in 17 chronic alcoholics. The subjects were divided into 4 groups; (1) alcoholics without neurologic deficits, (2) alcoholics with mild neuropathy, (3) alcoholics with prominent neuropathy, (4) patients with alcoholic neuropathy but long abstinence. We measured pulsatile arterial pressure (AP) noninvasively and heart rate (HR) was calculated from the AP signals. The sweat response on the palm and sole were measured by ventilated capsular method, while the cutaneous blood flow response by laser Doppler flowmetry. The AP, HR, sweating and cutaneous blood flow response to the Valsalva maneuver were evaluated. In alcoholics with minimal and prominent neuropathy, a pressor (overshooting) in phase IV of the Valsalva maneuver were decreased significantly. The HR response (reflex bradycardia) in phase IV of the Valsalva maneuver was significantly decreased only in alcoholics with prominent neuropathy. The alcoholics with no or minimal neuropathy showed exaggerated sweat responses on the palm and sole. In prominent alcoholic neuropathy, the sweat response was greater on the palm, but diminished on the sole. In no or minimal neuropathy, magnitude of the blood flow response was markedly reduced on both sites. The low resting blood flow levels may contribute to the diminished response. We also evaluated pupillary light reflex and response to methacholine in 7 alcoholics with neuropathy by a portable infrared pupillometer system that can be used with personal computers. Maximum constriction velocity of the pupillary light reflex in patients with alcoholic neuropathy was slower than that in the controls. Reflex amplitude was smaller in the alcoholics than that in the control. However, local administration of methacholine did not change pupillary size and light reflex in the alcoholics same as the controls. The data suggest that preceding sympathetic hyperfunction related with distressed autonomic center is existing with sympathetic hypofunction involved from the sympathetic fibers, target organs and higher center.

Some patients with chronic idiopathic interstitial pneumonia (IIP) experience acute exacerbations (AE). Because the precise mechanisms of AE in patients with IIP remain unclear, the treatment for AE is not established and the efficacy of steroids is controversial. Consequently, it is difficult to predict outcomes in patients with AE of IIP. We therefore studied the relationship between clinical findings, efficacy of treatment, and clinical outcome in patients with AE of IIP. Thirty-two patients were enrolled, and were divided into two groups: 10 who were alive more than one year after the onset of the AE survivors, 8 men and 2 women, and 22 who died within one year of the AE (non-survivors, 17 men and 5 women). Survivors were significantly younger than non-survivors (59.7 +/- 9.9 vs 67.5 +/- 8.2 years, respectively, p0.05). The values of PaCO2 measured before the AE were higher in survivors than in non-survivors (43.0 +/- 3.7 vs 38.4 +/- 4.0 torr, respectively, p0.05). At the onset of the AE the levels of C-reactive protein in serum were higher in survivors than in non-survivors (13.9 +/- 7.9 vs 7.3 +/- 5.8 mg/dl, respectively, p0.05). Chest X-ray films showed progression of ground-glass shadows in both groups when the AE occurred; the radiographic findings did not differ markedly between groups. Of the 22 non-survivors, 7 had received medication before the AE; none of the survivors had received medication before the AE. At the time of the AE all patients were treated with steroid pulse therapy, and the dose of methylprednisolone used, did not differ significantly between groups. These data suggest that three factors are closely related to responsiveness to steroid therapy and to clinical outcomes after AE in patients with IIP: 1) age at the onset on IIP, 2) respiratory status before the AE, and 3) disease activity as reflected by inflammatory reactions.

We report on a patient of Ki-1 lymphoma-associated hypereosinophilic syndrome and eosinophilic polymyositis. A 22-year-old male was admitted to a hospital because of anterior chest pain, when he had a white cell count of 12,000 with 33% of eosinophils. He first noticed muscle weakness in the right shoulder at age 23 years. At the age of 25, he experienced marked muscle weakness in his arms and neck, which brought him to our hospital. Neurological examination on admission revealed moderate muscle atrophy and weakness in the neck flexors and both upper extremities, and marked muscle hypertrophy in the sternocleidomastoideus and trapezius muscles. Laboratory studies showed a white blood cell count of 17,700 with 56% of eosinophils. His serum creatine kinase (CK) level was elevated to 347 units. A muscle biopsy specimen showing active myositis infiltrated by eosinophils confirmed the diagnosis of eosinophilic myositis. Although eosinophilia and serum CK activity decreased markedly with corticosteroid treatment, his muscle weakness was unchanged. At the age of 27 years, lymphadenopathy developed. Immunocytochemical examination on a biopsied neck lymph node indicated Ki-1 lymphoma with positive Ki-1, CD45 and epithelial membrane antibodies. In spite of chemotherapy and local irradiation treatment, he died four months after the emergence of Ki-1 lymphoma. We discussed the relationship between hypereosinophilic syndrome, eosinophilic polymyositis and Ki-1 lymphoma on pathogenetic mechanism.

We studied clinicopathological characteristics of interstitial pneumonia associated with amyopathic dermatomyositis. The subjects comprised two men and three women, and their mean age was 58.2 years. All subjects had cruptions specific for dermatomyositis, but had no signs of myositis. They all presented with acutely or subacutely developed coughing and dyspnea. Results of tests for anti-Jo-1 antibody were negative in all cases. Chest X-ray films showed infiltrations or streaky shadows, or both in the middle and lower lung fields. Analysis of bronchoalveolar lavage fluid revealed abnormally high percentages of lymphocytes and neutrophils. In one patients a specimen obtained by open lung biopsy showed homogeneous cell infiltrations in alveolar septa and regional alveolar damage. That patient was successfully treated with cyclosporin and corticosteroids in early phase of the disease. The other four patients received immunosuppressive agents after respiratory failure developed. All four died despite having received high-dose corticosteroid and immunosuppressive therapy. Examination of autopsy specimens showed diffuse alveolar damage.

A 52-year-old man with an 8-year history of rheumatoid arthritis was admitted to the hospital because of coughing and purulent sputum. A chest X-ray film obtained on admission showed small nodular shadows without overinflation in both lower lung fields, and a high-resolution CT scan showed many micronodular shadows in the centrilobular regions. Follicular bronchiolitis was diagnosed from the results of an open-lung biopsy, and prednisolone therapy was started at a dosage of 40 mg/day. Sinusitis developed 4 years later. Five years after the start of steroid therapy, dilation of bronchi and thickening of bronchial walls appeared on a CT scan, which also showed areas of low attenuation that were presumed to be bronchiolitis obliterans. These findings suggest that the pattern of airway disease can vary during the course of rheumatoid arthritis.

Severe mitral regurgitation (MR) due to abnormal chordae tendineae as a primary cause is rare. This clinicopathologic study included four such cases which occurred among 6,500 consecutive autopsies on persons older than 60 years. This paper describes three of these cases. Case 1 was a 76-year-old woman with congestive heart failure, MR and atrial fibrillation. She died of acute myocardial infarction. The heart weighed 360 g. Mitral regurgitation was caused by a thick and long abnormal chorda originating from the posteromedial papillary muscle and protruding into the atrial surface of the middle scallop of the posterior mitral leaflet associated with prolapsed anterior mitral leaflet. Case 2 was an 81-year-old woman with MR and congestive heart failure. She died of acute myocardial infarction. The heart weighed 480 g. There were abnormal chordae tendineae with very few branches at the posterior commissure. Parts of both mitral leaflets on the sides of posterior commissure were also prolapsed. Case 3 was a 91-year-old man with MR and atrial fibrillation. He died of congestive heart failure. The heart weighed 530 g. Abnormal chordae tendineae with reticular structures originated from the anterolateral papillary muscle and protruded into the anterior mitral leaflet, which induced severe MR. These cases had abnormally protruding chordae tendineae, abnormal branching, and abnormal structures of the chordae tendineae, respectively. These abnormal chordae tendineae were considered to be congenital anomalies. Clinically all patients had a holosystolic murmur (Levine III-IV degrees), refractory congestive heart failure and atrial fibrillation. The etiology of the MR in these three patients was suspected to be ruptured chordae tendineae demonstrated on echocardiograms. These patients had heavy hearts (mean 457 g) with enlarged left atria and thickened mitral valves, which corresponded to the appearance of severe MR.

The beneficial effect of plasma exchange, plasmapheresis or immunoadsorption therapy on Fisher's syndrome, suggested previously, has not been proved since no controlled studies have been conducted. In order to assess the effect of any treatment on Fisher's syndrome, simple and reasonable grading scales for evaluating the major neurological signs are needed. We tried immunoadsorption therapy in four patients with Fisher's syndrome, whose sera had anti-GQ1b antibodies. The clinical course was observed, with assessment of the severity of the major neurological signs based on grading scores; ranging from 0 to 30 for external ophthalmoplegia, from 0 to 10 for ataxia, and from 0 to 16 for areflexia. Tryptophan- or phenylalanine-linked polyvinyl alcohol gel column (TR-350, PH-350) was used as an adsorbent. In a patient who had IgG anti-GQ1b antibody and another patient who had both IgG and IgM anti-GQ1b antibodies, we compared the effectiveness of TR-350 and PH-350 to remove the anti-GQ1b antibody during the therapy. Two patients underwent immunoadsorption therapy at the height of clinical manifestations: in one patient, the therapy was discontinued because of critical hypotension and arrhythmia; the other was given only three sessions of therapy. The other two patients received six or seven sessions during the early recovering stage. All patients recovered without major neurological sequelae. Since ataxia was improved earlier than external ophthalmoplegia, the duration of hospitalization and the time of return to social life depended upon the recovery of external ophthalmoplegia. Analysis of the time course of external ophthalmoplegia score indicated that the improving period and the 50%-recovery day came earlier in the patients who were given a sufficient number of sessions than those who received an insufficient number of sessions. The treatment with TR-350 reduced the IgG anti-GQ1b antibody titer more than that with PH-350, but reduced the IgM anti-GQ1b antibody titer similarly. Immunoadsorption therapy using TR-350 has a probable beneficial effect on Fisher's syndrome even though it is carried out after the height of illness. The evaluation method for the severity of external ophthalmoplegia that we used in the present study is useful for assessing the effect of therapy on Fisher's syndrome.

We studied the clinical and immunological characteristics of patients with bronchiolar diseases associated with collagen vascular disease (15 patients with rheumatoid arthritis and 1 primary Sjögren's syndrome). Histological examinations showed that 9 patients had follicular bronchiolitis and 7 had bronchiolitis obliterans. Follicular bronchiolitis was characterized by hyperplasia of bronchus-associated lymphoid tissue, and immunohistochemical studies revealed that the pattern of distribution of T cells and B cells in bronchus-associated lymphoid tissue from patients with follicular bronchiolitis was similar to that in diffuse panbronchiolitis, which may be used as a representative model of chronic respiratory infection. In addition, bacterial cultures of sputum samples were positive in 44% of patients with follicular bronchiolitis and in 71% of patients with bronchiolitis obliterans. These results suggest that antigen stimulation is involved in the development of bronchiolar diseases associated with collagen vascular disease.

An autopsy case of meningeal spreading of glioblastoma multiforme (GBM) probably originating in the cervical cord was reported. In contrast to autopsy findings, main symptoms were similar to subacute meningitis, and any signs of myelopathy could not be detected during the clinical course. The patient was a 22-year-old man who was hospitalized because of a 2-week history of progressive headache following cough and slight fever. Vomiting and somnolence, developing 5 days before admission, were improved the day after a lumbar puncture performed at another hospital. On admission, meningeal signs, mild right abducens palsy, and depressed deep tendon reflexes were detected. There was no muscle weakness, sensory loss, or Babinski sign. Lumbar puncture yielded CSF with an opening pressure of 280 mmH2O, 21 mononuclear cells/mm3, a protein level of 645 mg/dl, and a glucose level of 7 mg/dl. Cytology for malignancy and multiple cultures were negative. Brain CT scan showed mild hydrocephalus and swelling of the brainstem and cerebellum. Intravenous administration of antimicrobial drugs was started and ventriculoperitoneal shunt surgery was performed. During the third hospital week, however, meningeal signs progressed and somnolence reappeared, followed by progressive multiple cranial neuropathy and polyradiculopathy characterized by flaccid tetraparesis, muscle atrophy, and sensory impairment without a level. Babinski sign could not be detected. MRI revealed an intramedullary lesion in the lower cervical cord, swelling of the brainstem, cerebellum, spinal cord and nerve roots, and a diffuse or nodular thickning of leptomeninges. Repeated CSF cytology disclosed atypical cells. Examinations for extraneural malignancies were negative. During the 9th hospital week, flaccid tetraplegia progressed and stupor developed, and the patient died 2 weeks later. The pathological study was limited to the brain. The brain showed a diffuse opalescent thickening of the leptomeninges, especially over the ventral aspect of the brainstem and cerebellum, where the blood vesseles and cranial nerves were obscured. Histological examination revealed the appearance of GBM. The malignant cells filled the subarachnoid space, and to a variable extent penetrated the brainstem and cerebellum along perivascular spaces. Hypertrophied optic tracts and trigeminal nerves were also infiltrated by the cells. However, there were no mass lesions assumed to be primary ones anywhere in the cerebral parenchyma. Therefore, it was thought that GBM primarily growing in cervical cord metastasized to intracranial subarachnoid space by way of the cerebrospinal fluid pathway. Spinal cord GBM usually presents signs of myelopathy from the early stage. The present case was characterized by no signs of myelopathy during the clinical course. It is speculated that the intramedullary GBM, originating near the surface of cervical cord, had been rapidly disseminated into the subarachnoid space up to the intracranial cavity before myelopathy appeared, and caused cranial and spinal nerve roots dysfunction, which covered signs of myelopathy. Cord GBM should be always considered as a differential diagnesis in a case of subacute meningitis.

Vancomycin hydrochloride (VCM) is one of the most useful drugs in treating methicillin-resistant Staphylococcus aureus (MRSA) infections. Intravenous administration of the drug is, however, not appropriate in patients with impaired renal or liver function. Thus, we studied the effect of inhaled VCM on MRSA. Fifty-one patients with MRSA in their sputum (35 men and 16 women 21, in the "infected" group and 30 in the "colonized" group, mean age 76.4 years) were studied. MRSA was eliminated in 84.3% of the patients (43 of 51 patients), and the average time required for elimination was 14.7 days. MRSA colonization or infection recurred in 46.5% of the patients (20 of 43 patients), and the duration from elimination until recurrence of MRSA averaged 28 days. Eight patients in whom MRSA was not eliminated by inhaled VCM were not clinically distinguishable from other patients, but their performance status was worse. Two hours after VCM was inhaled, serum VCM concentrations were unmeasurable in 7 patients. The VCM level in sputum peaked at 262.5 micrograms/g just after inhalation, and then gradually decreased. No side effects of this treatment were observed. These results suggest that inhaled VCM can be used to eliminate MRSA.

BACKGROUND--The migration and proliferation of fibroblasts may be important in the pathogenesis of pulmonary fibrosis. Considerable data are available on the proliferation of fibroblasts, but very few on their migration. METHODS--The migratory activity of fibroblasts obtained from lung biopsy specimens from 11 patients with idiopathic pulmonary fibrosis (IPF) was studied using a 96-well chemotaxis chamber. Fibroblasts from eight normal controls, seven patients with interstitial fibrosis associated with a collagen vascular disease (IP-CVD), and 13 patients with sarcoidosis were also examined. Migratory activity was tested in a serum-free medium in the presence and absence of platelet derived growth factor (PDGF), 30 ng/ml, as a chemoattractant. RESULTS--Migration of fibroblasts from patients with IPF was enhanced in serum-free maintenance medium alone (mean (SD) controls v IPF: 183 (86) v 689 (491) cells/field), and was also enhanced when cells were stimulated by PDGF (controls v IPF: 829 (222) v 1928 (600) cells/field). Fibroblasts from tissues with dense fibrosis had a greater capacity for migration than those from an earlier stage of fibrosis. No correlation was found between migratory activity and proliferative capacity of the individual cells. CONCLUSIONS--The fact that fibroblasts from fibrotic lungs migrate faster than those from controls suggests that migration is related to the initiation of the pulmonary fibrotic process. These in vitro studies suggest that fibroblasts derived from the lungs of patients with pulmonary fibrosis have a migratory phenotype. Such a change in fibroblast phenotype, if it occurred in vivo, may be important in the context of the pathogenesis of pulmonary fibrosis.

A very small number of patients with asthma show symptomatic improvement after administration of aspirin and other cyclooxygenase inhibitors. The clinical features of such patients with so-called aspirin-relieved asthma are similar to those with aspirin-induced asthma, but the pathogenesis is unclear.We encountered one confirmed aspirin-relieved asthma patient and investigated the effects of cyclooxygenase and lipoxygenase inhibitors on his condition.Our patient showed a marked improvement of the forced expiratory volume in one second (FEV1) after administration of aspirin and three other cyclooxygenase inhibitors (indomethacin, mefenamic acid, and ketoprofen). A 5-lipoxygenase inhibitor (AA861, Takeda, Japan), however, evoked acute asthma, and repeated administration of this drug resulted in some desensitization, but not complete tolerance.These results suggest an altered balance of arachidonic acid metabolism may play a critical role in the pathophysiology of aspirin-relieved asthma.

The efficacy and safety of video thoracoscopic lung biopsy (VTLB) and of open lung biopsy (OLB) were compared in patients with diffuse lung diseases. Thirty-three patients who had undergone VTLB were retrospectively studied and compared with 67 patients who had undergone OLB. There were no significant differences in age (52.8 +/- 10.9 vs 53.4 +/- 10.3), in the number of biopsies per patient (2.6 +/- 0.6 vs 2.7 +/- 0.6), or in the rate of diagnosis (94% vs 93%) between the two groups. However, the rate of diagnosis was low when the number of VTLB or OLB performed per patient was low. The patients undergoing VTLB had significantly shorter operative times (VTLB, 100.2 +/- 27.2 min. vs OLB, 119.8 +/- 42.6 min; p0.01) and less blood loss (VTLB, 4.7 +/- 14.6 ml vs OLB, 65.7 +/- 77.0 ml; p0.001). Complications occurred in 3 of the 33 who underwent VTLB, and in 18 of the 67 who underwent OLB. These results indicate that VTLB is an effective and safe alternative in the diagnosis of diffuse lung diseases.

Urinary excretion of leukotrienes is greater in patients with aspirin-induced asthma (AIA) than in other patients with asthma in remission, and is greater still during an aspirin-induced attack. We therefore hypothesized that increased phospholipase A2 (PLA2) activity leads to increased leukotriene synthesis when non-steroidal antiinflammatory drugs inhibit cyclooxygenase in patients with AIA, and that PLA2 activity increases further during an aspirin induced attack. To test this hypothesis, we measured the serum PLA2 activity in adult asthmatic patients, and compared the activity in those with AIA to the activity in those without AIA. The subjects were 43 patients with asthma in remission, 17 with AIA and 26 without AIA. Serum PLA2 activity was also measured before and after intravenous administration of lysine-aspirin in three patients with AIA and in one without AIA. Serum PLA2 activity was measured by radioimmunoassay. Serum PLA2 activity in patients with AIA, in those without AIA, and in healthy controls was 300.9 +/- 52.9, 294.4 +/- 65.3 and 171.7 +/- 41.8 pmol/ml/min, respectively. Serum PLA2 activity in asthmatic patients was significantly higher than in healthy controls (p0.01), but there was no difference between patients with and without AIA. Intravenous lysine-aspirin provoked asthmatic attacks in three patients with AIA. However, intravenous lysine-aspirin did not significantly change serum PLA2 activity in the three patients with AIA or in the patient without AIA. These results indicate that although PLA2 may be involved in the pathogenesis of bronchial asthma, it is not specific to AIA. Thus, the pathophysiology of AIA remains unclear and further investigation is needed.

Muramyl dipeptide (MDP), derived from the major constituent of bacterial cell walls, can augment host defense mechanisms, and romurtide [MDP-Lys (L18)], a synthetic MDP derivative, is thought to be more potent than other MDP derivatives. Therefore, we evaluated whether romurtide can bolster the immune defense mechanisms of the lung. We compared the functions of peripheral blood leukocytes with those of broncho alveolar lavage fluid cells (BALF cell) in DA rats and in patients with lung cancer who were treated with radiation. The results indicate that romurtide can increase the antibacterial activity of BALF cells preferentially and that this adjuvant therapy can help to prevent respiratory infections.

T lymphocytes in bronchoalveolar lavage (BAL) fluid from patients with sarcoidosis are activated. They are thought to recognize as yet unknown antigens and to play an important role in the pathogenesis of the disease. We studied the use of the T cell receptor V beta gene of lymphocytes obtained by BAL and lymphocytes obtained from peripheral blood of 11 patients with sarcoidosis and 9 normal controls, using the reverse transcriptase-polymerase chain reaction. As compared to the normal controls, V beta 2 and V beta 6 genes were predominantly expressed (15% of the sum of all V beta transcripts) on lymphocytes obtained from BAL fluid in 4 and 7 of 11 patients with sarcoidosis, respectively, but no specific V beta gene was predominantly expressed on lymphocytes obtained from peripheral blood. These results imply that those lymphocytes that are obtained from BAL fluid and that express V beta 2 and V beta 6 genes are involved in the pathogenesis of sarcoidosis.

T lymphocytes in bronchoalveolar lavage (BAL) from idiopathic interstitial pneumonia (IIP) patients are considered to recognize unknown antigens, such as dust, fume, virus or degenerated autoantigens. To analyse the nature of these T lymphocytes, we investigated T cell receptor (TCR) V beta gene usage (22 kinds) in BAL Lymphocytes and Peripheral blood lymphocytes from 10 11P patients and 9 normal controls, using reverse transcriptase-polymerase chain reaction method. In BAL lymphocytes, predominant usage of V beta genes (15% of the sum of all V beta transcripts) was recognized in 7 of 10 IIP patients, which appeared to vary in individuals (Case 1: V beta 14, case 2: V beta 3, V beta 5.1, case 5: V beta 2, case 6: V beta 6, case 7: V beta 8, case 8: V beta 7, V beta 20, case 9: V beta 6), whereas no predominant V beta usage was demonstrated in normal controls. It remains to be elucidated whether the BAL lymphocytes expressing predominant V beta genes are involved in the activation of alveolar macrophages, fibroblasts, thereby inducing the production of autoantibodies.

A 76-year-old man was admitted to our hospital in December of 1990, for investigation of progressive dyspnea on exertion over the previous 3 months. Physical examination revealed cyanosis, but no edema. Cardiomegaly was seen on chest X-ray, and findings compatible with right-sided congestive heart failure were revealed by ECG and echocardiography. Lung perfusion scintigrams showed multiple defects in both lungs, but no abnormal findings were detected on a ventilation study. Venograms of the lower extremities disclosed thrombosis of the right femoral vein. Therefore, a diagnosis of recurrent pulmonary thromboembolism was made. Furthermore, lupus anticoagulant and IgG-class anticardiolipin antibody were noted in the serum. The patient was treated with intravenous heparin, long-term warfarin, and transvenous placement of a Greenfield filter in the inferior vena cava. The clinical symptoms and signs improved, and no recurrence has been seen during the 13 months since the onset. On discharge, both antiphospholipid antibodies were negative. This case of primary antiphospholipid syndrome without autoimmune disease, with transiently positive antibodies only in the exacerbation phase, is discussed herein.

A 41-year-old male developed acute interstitial pneumonia after inhalation of Blasticidin S, an antibiotic effective against rice blast disease. He presented with diarrhea, followed by dry cough, dyspnea and fever. A chest roentgenogram showed bilateral diffuse ground glass appearance, superimposed by patchy shadows. Arterial blood gas analysis revealed severe hypoxemia. Bronchoalveolar lavage fluid specimen showed moderate increase in total cell count, lymphocytes, neutrophils and eosinophils with marked elevation of CD4/8 ratio. Antibiotic therapy with minocycline failed to improve his condition, and methylprednisolone pulse therapy followed by methylprednisolone (48 mg) resulted in clinical remission with resolution of the chest roentgenogram findings. Blasticidin S should be kept in mind as a causative agent of acute interstitial pneumonia.

We evaluated autonomic function in alcoholic neuropathy by non-invasive hemodynamic studies using servo-plethysmo-manometry and laser Doppler flowmetry. In 16 alcoholics compared with 17 age-matched healthy controls, the extent of AP responses to phase IV of the Valsalva maneuver, cold pressor test and isometric exercise decreased significantly, indicating sympathetic hypofunction. Five patients had paradoxical depressor response to cold pressor test, which was reproducible by submersion of the hand in warm water. The data suggest involvement of the higher autonomic center. Reflex bradycardia in phase IV of the Valsalva maneuver and the variation coefficient of R-R intervals in the electrocardiogram were lower, indicating parasympathetic hypofunction. Cutaneous blood flow response in the foot upon local warming and submersion of the hand in cold water was significantly impaired, but that in the contralateral hand was not. Abnormalities in the autonomic function tests may result from a toxic effect of ethanol on the peripheral and central autonomic nervous system and the cardiovascular system. The results indicate not only parasympathetic (vagal) but sympathetic dysfunction mediating cardiovascular regulation in patients with alcoholic neuropathy.

To clarify the pathogenesis of idiopathic interstitial pneumonia (IIP), we compared the data of interstitial pneumonia (IP) associated with collagen vascular disease (CVD) with those of idiopathic pulmonary fibrosis (IPF). These disorders are found to have similar clinical, radiographic, and morphological findings, and lung function. However, the in vitro behavior of fibroblasts from CVD-IP and IPF, and the detection of soluble ICAM-1 were different. Further, in the T cell receptor repertoire, the predominance of different genes was found in bronchoalveolar lavage cells from CVD and IPF. These differences could partly explain the variability of IP pattern seen in CVD. In summary, our results indicate the possibility that CVD-IF and IPF result from different mechanisms although they share the same spectrum of pulmonary changes.

We report two cases of idiopathic interstitial pneumonia (IIP) with acute deterioration after bronchoalveolar lavage (BAL). Case 1 was a 54-year-old woman, and case 2 was a 75-year-old man. Both were diagnosed as having IIP, and hospitalized with complaints of high fever and dyspnea. After BAL, the degree of dyspnea increased. White blood cell count and lactate dehydrogenase were elevated, and PaO2 was decreased. Chest X-ray revealed consolidation of the upper lung fields and reticulo-granular shadows spreading through both lungs. BAL fluid examination showed an elevated neutrophil fraction (case 1: 6.5%, case 2: 35.2%), suggesting respiratory tract infection although bacteria could not be detected. Case 1 died of respiratory failure despite corticosteroid therapy. Autopsy revealed diffuse alveolar damage with focal pneumonia in the right S6 corresponding to the upper lobe consolidation. Case 2 improved after antibiotic therapy. These findings suggest that aspiration of infected fluid during BAL can cause acute exacerbation of IIP. It is important to recognize that the BAL procedure can induce an acute exacerbation of IIP.

Recently, we have reported that a nebulized solution of sodium cromoglycate (SCG) (Intal), a well known antiallergic agent, has an acute bronchodilator effect in patients with aspirin-induced asthma (AIA). Amlexanox is an antiallergic agent, with a structure similar to that of SCG. Therefore, we investigated the acute bronchodilator effect of amlexanox administered orally to adult asthmatics, focusing on a comparison between AIA and non-AIA patients. Fifteen patients participated, 8 having AIA and 7 non-AIA. After performing spirometry during remission, they were administered either amlexanox or placebo using a randomized double-blind protocol. Spirometry was then performed at 30, 60, 90 min, 2 h, and 3 h after administration. The placebo used was lactose. In the AIA group, FEV1 was significantly improved after administration of amlexanox. However, FEV1 was significantly decreased after placebo administration. On the other hand, in the non-AIA group, FEV1 was not changed after administration of either of the drugs. From these results, we conclude that amlexanox has an acute bronchodilator effect only in AIA patients.

We present a 36-year-old male who developed pulmonary infarction secondary to antithrombin III variant. He was admitted to our hospital with progressive chest pain and hemosputum. The presence of multiple defects on 99mTc perfusion scan indicated the diagnosis of pulmonary infarction. He had a past history of pulmonary infarction 4 years before this episode as well as a family history of recurrent thromboembolic disease. Through coagulation studies revealed that the concentration of antithrombin III antigen and progressive antithrombin activity were within normal limits, while heparin cofactor activity was decreased markedly. Of 5 people in his family, 4 proved to have low heparin cofactor activity. These data suggest that functional abnormality of antithrombin III seems to be closely associated with pulmonary infarction.

We report a case of asthma that was relieved by aspirin and other cyclooxygenase inhibitors. The patient, a 51-year-old man, was admitted to our hospital because of an asthmatic attack. Onset of asthma had occurred at the age of 40 years, after a flu-like infection, and was preceded for several years by perennial rhinitis and loss of the sense of smell. The course was perennial, and unrelated to the seasons. These clinical features resembled those of aspirin-induced asthma (AIA). Therefore, suspecting AIA, we performed a aspirin-DL-lysine iv challenge test. After aspirin-DL-lysine injection, FEV1 was increased by about 30% and nasal obstruction was improved. Other cyclooxygenase inhibitors (indomethacin, mefenamic acid, ketoprofen) also improved FEV1 by more than 30%. Hydrocortisone sodium succinate (HCs) improved FEV1 about 20%. Lipoxygenase inhibitor (AA861) produced an evident attack, but continued administration did not result in complete tolerance. On the other hand, seven other AIA patients showed no reaction to AA861. DSCG had an acute bronchodilative effect similar to that of AIA. Paraben and chloramphenicol sodium succinate (CMs) produced an asthmatic attack. The present patient showed a marked improvement in response to cyclooxygenase inhibitors and HCs, in contrast to the situation in AIA, and developed an evident asthmatic attack in response to lipoxygenase inhibitor. He showed marked improvement in the response to DSCG and developed an asthmatic attack in response to paraben and CMs, as in AIA. Our results suggest an abnormality of Arachidonic acid metabolism not only in AIA but also in asthma relieved by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium cromoglycate (SCG) (Intal) is a well-known anti-allergic agent which protects against allergen- and exercise-induced bronchospasms. The effect has been recognized non-acute, unlike that of bronchodilators. However, we have found that some patients with aspirin-intolerant asthma (AIA) show significant improvement soon after a single inhalation of SCG nebulized solution. In this study, we investigated the acute bronchodilator effect of SCG given by nebulizer in adult asthmatics, especially compairing AIA with non-AIA (aspirin-tolerant asthma) patients. Twenty patients with AIA and 11 with non-AIA participated in the study. After performing spirometry on remission, they inhaled either SCG via a nebulizer or 4 ml of placebo in a randomized double-blind fashion. After inhalation, spirometry was performed every ten minutes for one hour. The placebo used was a saline solution of the same osmolarity as that of the SCG nebulized solution. Placebo inhalation provoked asthmatic attacks in five of the patients with AIA and one with non-AIA, but SCG did not. In the AIA group, twelve out of the twenty patients also had improved nasal symptoms soon after inhalation of SCG. Forced expiratory volume in one second (FEV1) was significantly improved 10 minutes after inhalation of SCG. Fifty minutes after SCG inhalation, the percent degree of FEV1 improvement was approximately 17%. However, FEV1 was significantly decreased by approximately 14% after inhalation of placebo. In the non-AIA group, FEV1 was not increased after inhalation of SCG. V25 was not changed after inhalation of SCG in AIA and non-AIA groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A 12-year-old boy was admitted to our hospital in May 1990. Since two years previously, he became restless and could not adapt himself to his new school mates and teacher. He came to refuse going to school, and his intellectual performance rapidly deteriorated, thereafter. During the following two years, he gradually became mutic and incontinent with dystonic involuntary movements, and was admitted to our hospital. Examination revealed melanoderma, mutism, dementia and grossly normal visual and auditory system except for bilateral optic atrophy. Volitional movements were severely limited because of marked truncal and extreme dystonia and spastic paresis. Urinary 17-KS and 17-OHCS were decreased. Serum cortisol did not increase normally on rapid ACTH test. Very-long-chain fatty acids in serum were increased. Serial CTs and MRI demonstrated marked ventricular dilatation and diffuse white-matter lesions involving the frontal lobes, corpus callosum, internal capsules, and less markedly parieto-occipital regions with slight calcification in the optic radiations. Those in the frontal lobes had been visualised in CTs taken 18 months after the onset. School refusal, the initial symptoms of the patient, is one of serious socioeducational problems in Japan. While the majority of children with school refusal might be of non-organic affections, those with apparent mental deterioration and behavioral abnormalities should undergo non-invasive CT or MRI evaluation during the early stage of the disorder. And if diffuse white matter lesions is suggested even in the frontal lobe, the possibility of adrenoleuko-dystrophy should be considered.