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K Shigehara,
N Shijubo, M Ohmichi,
K Kamiguchi,
R Takahashi,
S Morita-Ichimura,
T Ohchi,
T Tatsuno,
Y Hiraga,
S Abe,
N Sato
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ABSTRACT: In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.
Clinical & Experimental Immunology 05/2003; 132(1):152-7. · 3.36 Impact Factor
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K Shigehara,
N Shijubo, M Ohmichi,
R Takahashi,
S Kon,
H Okamura,
M Kurimoto,
Y Hiraga,
T Tatsuno,
S Abe,
N Sato
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ABSTRACT: Sarcoidosis is a systemic chronic granulomatous disease of unknown cause. Recent investigations revealed that the cytokine profile in inflamed lesions of sarcoidosis is Th1 dominant. To obtain better immunopathologic understanding of sarcoidosis, we examined the expression of IL-12 and IL-18 and their roles in IFN-gamma production in pulmonary sarcoidosis. Sarcoid cases had significantly elevated levels of IL-12 (p40 and p70) and IL-18 in bronchoalveolar lavage (BAL) fluids compared with healthy subjects. IL-12 p70 and IL-18 were immunohistochemically expressed in the epithelioid cells and giant cells of sarcoid granulomas. Significant induction of IFN-gamma, IL-12 p70, and IL-18 was observed from sarcoid BAL fluid cells with LPS stimulation, whereas LPS tended to induce only IL-12 p70 in BAL fluid cells from healthy subjects. Sarcoid cases had significantly greater IFN-gamma induction with LPS stimulation than healthy subjects did. IL-18 mRNA expression was observed in freshly isolated sarcoid BAL fluid cells as well as in LPS-stimulated sarcoid BAL fluid cells, but IFN-gamma and IL-12 mRNA expression was observed only in LPS-stimulated BAL fluid cells. Treatment with anti-IL-12- and anti-IL-18-neutralizing Abs significantly inhibited IFN-gamma production from LPS-stimulated BAL fluid cells of sarcoid cases. Coadministration of rIL-12 or rIL-18 induced greater IFN-gamma production in sarcoid BAL fluid cells than in normal BAL fluid cells. We concluded that bioactive IL-12 and IL-18 were produced in sarcoid BAL fluid cells and synergistically induced IFN-gamma production, indicating important cytokines in the Th1 response of sarcoidosis.
The Journal of Immunology 02/2001; 166(1):642-9. · 5.79 Impact Factor
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ABSTRACT: IL-18, identified as an IFN-gamma-inducing factor, is a proinflammatory cytokine that plays an important role in TH1 cell activation. Recently, it was reported that histamine induced IL-18 and that IL-18 might act as a coinducer of TH1 and TH2 cytokines.
The aim was to evaluate the contribution of IL-18 to asthma exacerbation.
Serum IL-18, soluble IL-2 receptor, eosinophil cationic protein, and plasma IFN-gamma levels, as well as peak expiratory flow were measured in patients with stable asthma (n = 28), acute mild or moderate asthma (n = 23), or pulmonary sarcoidosis (n = 35) and in healthy subjects (n = 26). We compared the serum IL-18 levels between patients with acute asthma and those in remission and examined the time course in acute exacerbation after asthma therapy.
Significantly higher serum IL-18 levels were found in patients with acute asthma (215 +/- 33 pg/mL, mean +/- SE; P = .02) and pulmonary sarcoidosis (239 +/- 27 pg/mL, P = .008) than in control subjects (127 +/- 11 pg/mL), but the plasma IFN-gamma level was significantly elevated in only pulmonary sarcoidosis (P < .001). In pulmonary sarcoidosis the IL-18 values significantly correlated with the IFN-gamma levels (r = 0.61, P < .001), but in acute asthma they did not. The IL-18 levels during acute asthma exacerbation were significantly higher (P = .01) than on remission days. In acute asthma, circulating IL-18 levels significantly correlated with serum soluble IL-2 receptor levels (r = 0.77, P < .0001) but not with serum eosinophil cationic protein levels. The IL-18 level had a tendency to inversely correlate with peak expiratory flow. The elevated IL-18 levels in acute asthma quickly decreased on day 3 (P = .02) and day 7 (P = .002) after therapy.
It was suggested that IL-18 may play a potential role to activate immunologic responses and may reflect disease activity in mild and moderate asthma exacerbation.
Journal of Allergy and Clinical Immunology 02/2001; 107(2):331-6. · 11.00 Impact Factor
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K Shigehara,
N Shijubo, M Ohmichi,
G Yamada,
R Takahashi,
H Okamura,
M Kurimoto,
Y Hiraga,
T Tatsuno,
S Abe,
N Sato
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ABSTRACT: Interleukin-18 (IL-18) has recently been identified as an interferon-gamma (IFN-gamma)-inducing factor, and it plays an important role in T helper 1 (Th1) response. We measured the serum levels of IL-18 and IFN- gamma in 37 patients with pulmonary sarcoidosis and 25 healthy control subjects. We also measured the levels of IL-18 and IFN-gamma in 10-fold concentrated bronchoalveolar lavage (BAL) fluids of 19 patients with pulmonary sarcoidosis and 9 healthy control subjects (all lifelong nonsmokers). The levels of serum IL-18 and IFN-gamma were significantly increased in patients with sarcoidosis. The levels of BAL fluid IL-18 were significantly elevated in patients with sarcoidosis, however, the IFN-gamma levels of the patients and control subjects were all below sensitivity. Serum IL-18 levels significantly correlated with serum IFN-gamma levels and lysozyme activity. The patients positive for gallium-67 ((67)Ga) scan had significantly elevated serum IL-18 levels as compared with those of the negative patients. BAL fluid IL-18 levels significantly correlated with serum IL-18 levels in patients with sarcoidosis, and there was a significant correlation between IL-18 levels and lymphocyte proportions in sarcoid BAL fluids. In patients with sarcoidosis, IL-18 seems to induce IFN-gamma production and IL-18 levels in sera may reflect disease activity of sarcoidosis.
American Journal of Respiratory and Critical Care Medicine 12/2000; 162(5):1979-82. · 11.08 Impact Factor
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N Shijubo,
Y Itoh,
K Shigehara,
T Yamaguchi,
K Itoh,
Y Shibuya,
R Takahashi,
T Ohchi, M Ohmichi,
Y Hiraga,
S Abe
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ABSTRACT: Sarcoidosis is a systemic granulomatous disorder with a high rate of spontaneous regression. Clara cell 10-kDa protein (CC10), the predominant product of nonciliated bronchiolar epithelial cells, is a potent immunoregulatory and anti-inflammatory agent. CC10 levels were measured in sera and bronchoalveolar lavage (BAL) fluids from 31 sarcoidosis patients (nine progressive disease and 22 regressive disease) and their relevance to spontaneous regression investigated. The inhibitory effects of recombinant CC10 on interferon gamma (IFN-gamma) production were examined using lipopolysaccharide (LPS)-stimulated sarcoid BAL fluid cells, and the blocking effects of monoclonal antibody TY-5, directed against CC10, on CC10 function were also tested. Serum and BAL fluid CC10 levels in the regressive disease group were significantly higher than those in the progressive disease group (serum, p<0.05; BAL fluid, p<0.005) and healthy subjects (serum, p<0.0001; BAL fluid, p<0.005). CC10 inhibited, in part, IFN-gamma production from LPS-stimulated sarcoid BAL fluid cells (CC10 inhibition: 1,000 ng x mL(-1), 30%; 100 ng x mL(-1), 14%). TY-5 restored IFN-gamma production by blocking CC10 function. Sarcoidosis patients with regressive disease showed increased Clara cell 10-kDa protein levels in their sera and bronchoalveolar lavage fluids. Clara cell 10-kDa protein may be a regulator of the inflammatory process in sarcoidosis.
European Respiratory Journal 10/2000; 16(3):414-9. · 5.89 Impact Factor
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ABSTRACT: The frequency and clinical picture of sarcoidosis are different in Finland and Hokkaido, Japan. The aim of this study was to compare the normalisation rate of chest radiographic changes in patients with biopsy-proven sarcoidosis.
The chest radiographs of 437 Finnish and 457 Japanese patients were used and, for the purpose of this study, double-checked in order to make sure that the interpretations were identical. On a yearly basis the radiographs were classified as normalised, improved, unchanged or deteriorated.
Normalisation of chest radiographs occurred in 73% of the Japanese and 40% of the Finnish patients. The difference between the two series was significant (p < 0.001). Gender, young age, presence or absence of symptoms or extrapulmonary lesions at diagnosis or treatment with corticosteroids did not influence the difference between the two series. Of the 191 Finnish and 309 Japanese patients with initial stage I disease a normal chest radiograph was obtained in 47% of the Finnish and 76% of the Japanese patients (p < 0.001), despite the fact that the Finnish series included patients with erythema nodosum, who had a 59% normalisation rate. Of the 186 Finnish and 125 Japanese patients with initial stage II disease, normalisation of the chest radiographs was seen in 36% of the Finnish and in 73% of the Japanese patients (p < 0.001). No difference in normalisation rate was seen between stage III patients.
The prognosis of pulmonary sarcoidosis in Japanese patients in Hokkaido is significantly better than that in Finland defined as normalisation rate of the chest radiographs.
Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 07/2000; 17(2):158-66. · 1.27 Impact Factor
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K Shigehara,
N Shijubo, M Ohmichi,
S Kon,
Y Shibuya,
R Takahashi,
S Morita-Ichimura,
T Tatsuno,
Y Hiraga,
S Abe,
N Sato
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ABSTRACT: Active sarcoidosis is considered to be a Th1 dominant condition. We examined whether Th1 cytokines are highly expressed at inflammed lesions of Japanese patients with sarcoidosis.
To investigate the mRNA expression of Th1 cytokines and IL-12 in sarcoid BAL cells, we used semiquantitative reverse transcription--polymerase chain reaction method.
The mRNA expressions of Th1 cytokines (IFN-gamma and IL-2) in active sarcoid BAL cells were significantly elevated as compared with those in healthy volunteers. The proportion of positive IL-4 mRNA expression in sarcoid BAL cells was not significantly higher than that in healthy volunteers. Further, there was no significant difference in IFN-gamma mRNA levels between the groups positive and negative for IL-4 mRNA expression. Although the proportion of positive expression of IL-12 mRNA in active sarcoid BAL cells was not significantly higher than that in healthy volunteers, the group positive for IL-12 mRNA expression had significantly elevated levels of IFN-gamma mRNA than did the negative group.
These results may indicate that IL-12 induces IFN-gamma expression and subsequent Th1 dominant condition in Japanese patients with sarcoidosis.
Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 07/2000; 17(2):151-7. · 1.27 Impact Factor
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ABSTRACT: Lupus pernio, an uncommon skin condition due to sarcoidosis in Japan, is a chronically persistent, violaceous skin lesion primarily involving the nose, cheek, ears, and fingers. It has often been associated with chronic fibrotic non-resolving pulmonary sarcoidosis. We reported a case of sarcoidosis associated with lupus pernio and primary pulmonary cavitation as a rare manifestation in the lung. A 44-year-old man visited our hospital in January 1986 because of a 3-year history of swollen and violaceous cheeks (lupus pernio) and an 8-year history of erythema in both upper and lower limbs. The biopsy specimen obtained from the skin lesion revealed epithelioid cell granulomas without any evidence of Mycobacterium or fungal growth. Serum ACE (45.4 U/ml) was elevated. Chest X-ray films and computed tomographic (CT) scans showed bilateral hilar lymphadenopathy, nodules, multiple small opacities, and reticulo-linear opacities. Gallium scintigraphy demonstrated abnormal uptake in the mediastinal and hilar lymph nodes and lung fields. The patient had not received corticosteroids. Chest X-ray films and CT scans in July 1989 showed increased opacities and cavitation. Because pyogenic bacteria and acid-fast bacilli were not detected by repeated sputum examinations or bronchial washing, we concluded that the cavitary lesions were manifestations of primary pulmonary cavitation due to sarcoidosis. Prednisolone (40 mg daily) was prescribed and the dosage was gradually tapered. The lung lesions gradually resolved and have not recurred.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 05/2000; 38(4):307-11.
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ABSTRACT: Thromboxane (TX) A2 is an important bronchoconstrictor in the pathogenesis of asthma. Seratrodast, known as AA-2414, is a new oral TXA2 receptor antagonist which is currently prescribed in asthma therapy in Japan. However its clinical effects have been very different in individual subjects. To assess whether the clinical efficacy of TXA2 antagonist is predictable on the basis of urinary arachidonic acid metabolites in urine of patients with asthma, an open and multicentre trial was conducted. Fifty adult asthmatic subjects (women/men = 28/22) were enrolled [resting mean forced expiratory volume in 1 sec (FEV1)% was 82%; range, 50-96%]. Urinary levels of 11-dehydro-TXB2, leukotriene (LT) E4, 2,3-dinor-6-keto-prostaglandin F1alpha and creatinine in 3-h urine collected in the morning at the start of seratrodast (80 mg day(-1), once a day at evening for 4 weeks) were measured. Responders were defined by improvements of asthma symptoms score and peak expiratory flow rate (PEFR). Of the 50 subjects, 45 completed this study. Eighteen patients were responders and the other 27 were nonresponders. There were no significant differences between the two groups in patients' characteristics, baseline lung functions, treatments and baseline urinary eicosanoids. The 11-dehydro-TXB2/LTE4 ratio of responders was significantly higher (P = 0.0091) than that of non-responders (mean +/- SE, 7.49+/-0.71 vs. 5.09+/-0.67). Eleven patients out of 18 responders agreed to continue this drug for 6 months, the 11-dehydro-TXB2/LTE4 ratio decreased during this period, but not significantly. Our data demonstrated that responders and non-responders to TXA2 receptor antagonist existed in patients with asthma, and it suggests that the ratio of urinary eicosanoids might be a possible predictor of the effects of TXA2 receptor antagonist.
Respiratory Medicine 01/2000; 93(12):891-7. · 2.47 Impact Factor
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ABSTRACT: Two or more cases of sarcoidosis in one family is not unusual. To compare the frequencies of familial sarcoidosis in Finland and Hokkaido, Japan, and to analyse the type of associations reported, we collected data on all patients visiting hospitals for sarcoidosis in 1984 in Finland (1378 patients) and Hokkaido (208 patients), including information about familial sarcoidosis. We also analysed the familial cases seen among 571 sarcoidosis patients diagnosed at the Mjölbolsta hospital in Finland from 1955 to 1987 and among 686 Japanese patients seen in Sapporo from 1964 to 1988. In 1984, 50 sarcoidosis patients visiting Finnish hospitals and nine sarcoidosis patients in Hokkaido reported as familial cases. Of the sarcoidosis patients seen in Finland at the Mjolbolsta hospital in 1955-1987, 27 had a family member with the same disease, while this number was 20 in the Sapporo hospital in 1964-1988. Those surveys give a prevalence of familial sarcoidosis in Finland of 3.6-4.7% and in Hokkaido of 2.9-4.3%. Among familial cases, the dominating relationships were sister-brother and mother-child relationships.
Respiratory Medicine 07/1999; 93(6):408-12. · 2.47 Impact Factor
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ABSTRACT: The efficacy and safety of intravenous ciprofloxacin 200 mg every 8 or 12 h and 300 mg every 12 h in treatment lasting 3-14 days were investigated in patients with lower respiratory tract bacterial infections. Patients presented with pneumonia, bronchiectasis with infection, previous pulmonary tuberculosis with infection and diffuse panbronchiolitis. Clinical efficacy was seen in six of eight patients, with apparent recovery in terms of chest radiographs, fever reduction and laboratory findings. Pharmacokinetic analysis in one patient treated with intravenous ciprofloxacin 300 mg showed that at 0.5 h after the first dose, ciprofloxacin serum and sputum concentrations were equivalent (2.45 micrograms/ml and 2.25 micrograms/ml, respectively). Adverse events were recorded in only two patients and involved a slight elevation in liver function tests and eosinophilia. This study indicates that intravenous ciprofloxacin is useful in the treatment of lower respiratory tract infections.
The Journal of international medical research 02/1999; 27(6):297-304. · 0.90 Impact Factor
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ABSTRACT: A previously healthy 26-year-old woman presented with a fever and coughing on October 1, 1995. Despite treatment with beta-lactam antibiotics at another hospital, she had a high fever, coughing, and dyspnea. A chest roentgenogram showed diffuse infiltrates in both lung fields. On October 9, she was transferred to our hospital. On admission, a chest X-ray film showed marked diffusely infiltrates in both lung fields and a effusion in the left lung. Arterial blood gas analysis after inhalation of 4 liters per minute of oxygen via a nasal cannula revealed a PaO2 of 39.0 torr. Despite treatment with various antibiotics, including minocyclin and gamma-globulin, her respiratory condition rapidly deteriorated. She was mechanically ventilated by with intermittent mandatory ventilation and positive end-experiatory pressure, and received antibiotics and methylprednisolone pulse therapy. He chest X-ray and arterial blood gase findings, gradually improved. The passive hemagglutination titer for Mycoplasma rose from 1:4 on October 9, to 1:2,560 on the 14th hospital day. Acute respiratory failure due to Mycoplasma pneumoniae pneumonia was diagnosed. A chest X-ray film obtained 2 months after admission showed linear-reticular shadows in both lung fields and pulmonary-function tests revealed abnormally low vital capacity and diffusing capacity. Examination of a specimen obtained by transbronchial lung biopsy revealed focal intraalveolar exudate with fibrin and macrophages. Very mild interstitial thickening was also noted. The lymphocyte stimulation responses to PPD, PHA, and Con A were low early in the illness and became normal after recovery. Several reports have said that an enhanced pulmonary cellular immune response may be responsible for the development of severe Mycoplasma pneumoniae, resulting in a temporary decrease in the cell-mediated immune response. This case supports that hypothesis. We believe that in severe cases, steroid therapy including pulse therapy should be started as soon as possible.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 05/1998; 36(4):374-80.
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ABSTRACT: A 54-year-old man who worked as a farmer was admitted to the hospital in August 1989 because of bilateral hilar adenopathy that was detected during a mass screening. Laboratory examination showed a high serum lysozyme level and the PPD skin test was negative. Examination of a specimen obtained by transbronchial lung biopsy revealed non-caseous epithelioid cell granuloma. Sarcoidosis was diagnosed. The patient was not treated, and the bilateral hilar adenopathy had lessened by 1992. The patient was readmitted to our hospital because of right hilar and upper mediastinal enlargement seen on a chest radiograph in April 1994. Computed tomography and magnet resonance imaging disclosed an anterior mediastinal tumor in contact with the right upper lobe, the left inominate vein, and the pericardium. Bronchoscopy showed no abnormality in the right upper-lobe bronchus. Examination of a specimen obtained from the B3b bronchus showed no evidence of malignant cells. Examination of a tumor specimen obtained by transdermal biopsy showed squamous cell carcinoma. After the patient underwent combination chemotherapy, the tumor ws resected, along with the right upper lobe, the left inominate vein, and the pericardium, which were difficult to separate from the tumor. Postoperative pathological examination showed that squamous cell carcinoma was intermingled with normal thymus tissue. We believe that squamous cell carcinoma originated in the thymus. Non-caseous epithelioid cell granulomas were also found in the resected right upper lobe and in a mediastinal lymph node. The patient was discharged after post-operative irradiation of the mediastinum. Thymic carcinoma is rare, and sarcoidosis in a patient with thymic carcinoma is very rare. T lymphocytes are very important in the pathogenesis of sarcoidosis, and the thymus is involved in the growth and differentiation of T lymphocytes. The occurrence of these two diseases in one patient is interesting, but the relationship is not clear.
Nihon Kyōbu Shikkan Gakkai zasshi 06/1997; 35(5):571-6.
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ABSTRACT: We compared the clinical picture of sarcoidosis in patients diagnosed at Mjölbolsta hospital in Finland in 1955-1987 with those diagnosed in Sapporo in 1964-1988. The female:male ratios showed a slight female predominance. The mean age (SD) at diagnosis was 41.5 (13.0) years at Mjölbolsta and 30.0 (15.4) years in Sapporo. In both series, half of the patients had been detected at mass x-ray surveys. The presenting symptoms varied considerably among the symptomatic patients. At Mjölbolsta hospital, 189 patients (33%) had cough, 21% fever, 21% general malaise, 18% dyspnoea, 18% erythema nodosum, 16% joint pain and only 27 patients (5%) had eye symptoms. In Sapporo, 245 patients (41%) had eye symptoms, 18 (4%) had enlarged peripheral lymph nodes, 14 (3%) had cough, 10 (2%) had fever. Erythema nodosum did not occur as a presenting symptom in Sapporo. The chest radiographs showed bilateral hilar lymphadenopathy (BHL, stage I) in 48% of the Mjölbolsta patients and in 57% of the Sapporo patients. Stage II lesions were seen in 39% and 20%, and stage III lesions in 12% and 5% respectively. Only 1% had a normal chest radiograph at Mjölbolsta hospital as compared with 18% in Sapporo. The Sapporo patients were more obstructive but the proportion of smokers was also higher. No difference in diffusion capacity was seen.
Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 10/1996; 13(2):159-66. · 1.27 Impact Factor
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A Saito,
Y Kawakami,
E Yamaguchi,
H Koba,
S Abe, M Ohmichi,
Y Hiraga,
K Kikuchi,
Y Ohsaki,
H Matsumoto, [......],
T Ito,
T Bando,
K Takeuchi,
H Hirano,
Y Tanifuji,
Y Tanno,
K Shirato,
M Takahashi,
M Sakamoto,
M Nakashima
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ABSTRACT: To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against chronic lower respiratory tract infections, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as a control drug. RIPM-AC was orally administered at 200 mg, and CTM-HE at 400 mg, t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 202, of which 151 cases (RIPM-AC group: 75, CTM-HE group: 76) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent+good) were 85.3% (64/75) in the RIPM-AC group and 80.3% (61/76) in the CTM-HE group. There was no significant difference between the two groups, hence the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 50.0% (13/26) in the RIPM-AC group and 75.0% (18/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 10 cases (11.0%) of the RIPM-AC group and 10 cases (10.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 8 cases(9.5%) of the RIPM-AC group and in 14 cases (16.7%) of the CTM-HE group. There were no significant differences between the two groups in the incidence of side effects and abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 73 cases (80.2%) and CTM-HE in 71 cases (77.2%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 79.5% (62/78) in the RIPM-AC group and 76.9% (60/78) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of chronic lower respiratory tract infections.
The Japanese journal of antibiotics 04/1996; 49(3):219-49.
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A Saito,
M Sakamoto, M Ohmichi,
Y Hiraga,
K Kikuchi,
Y Ohsaki,
N Sasaki,
H Matsumoto,
T Suda,
M Tsuzino, [......],
H Kobayashi,
S Chiba,
T Ito,
K Moriya,
T Bando,
K Takeuchi,
Y Tanifuji,
K Shirato,
Y Tanno,
M Nakashima
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ABSTRACT: To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against bacterial pneumonia, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as the control drug. Both RIPM-AC and CTM-HE were orally administered at 200 mg t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 208, of which 152 cases (RIPM-AC group: 73, CTM-HE group: 79) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent + good) were 91.8% (67/73) in the RIPM-AC group and 94.9% (75/79) in the CMT-HE group. There was no significant difference between the two groups, and the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 84.6% (22/26) in the RIPM-AC group and 91.7% (22/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 9 cases (9.6%) of the RIPM-AC group and 5 cases (4.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 23 cases (26.7%) of the RIPM-AC group and 15 cases (15.6%) of the CTM-HE group. There was no significant differences between the two groups in the incidence of side effects nor of abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 64 cases (68.1%) and CTM-HE in 82 cases (80.4%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 86.5% (64/74) in the RIPM-AC group and 92.5% (74/80) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of bacterial pneumonia.
The Japanese journal of antibiotics 03/1996; 49(2):144-74.
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ABSTRACT: The efficacy, safety and usefulness were evaluated for a combined antibiotic tazobactam/piperacillin (TAZ/PIPC) consisting of a new beta-lactamase inhibitor, tazobactam (TAZ), and a broad spectrum penicillin antibiotic, piperacillin (PIPC), in chronic respiratory tract infections with PIPC as the control in a multi-institutional comparative study. The drugs used were a preparation containing 0.5 g of TAZ and 2.0 g of PIPC per vial (TAZ/PIPC group) and a preparation containing 2.0 g of (PIPC group). The drugs were intravenously injected one vial at a time twice a day for 14 days as a rule. The following results were obtained: 1. Clinical effect There was no significant difference between TAZ/PIPC (86% or 76/88) and PIPC (81% or 69/85). 2. Bacteriological effect There was no significant difference between TAZ/PIPC (93% or 42/45) and PIPC (88% or 36/41) in terms of bacterial eradication rates. In 34 patients with beta-lactamase-producing pyogenic bacteria, there was no significant difference between TAZ/PIPC (77% or 10/13) and PIPC (88% or 15/17). 3. Degrees of improvement in clinical symptoms, signs and laboratory findings The TAZ/PIPC group was likely to show reductions in fever and the amount of sputum soon after administration. 4. Side effects Incidences of side effects were 7% (7/96) in the TAZ/PIPC group and 3% (3/89) in the PIPC group, showing no significant difference between the two groups. The main symptoms were allergic reaction and gastrointestinal symptoms. 5. Abnormal clinical laboratory test values The incidence was 17% (15/89) in the TAZ/PIPC group and 21% (18/87) in the PIPC group. The main symptoms were eosinophilia and hepatic dysfunction, and most of these symptoms were mild. 6. Usefulness The usefulness rates in the TAZ/PIPC group were 80% (71/89) and 78% (66/85) in the PIPC group, showing no significant difference. Thus, TAZ/PIPC exhibited excellent clinical effects and presented no troubles with safety. When comprehensively evaluated, TAZ/PIPC appears to be a very useful drug for the treatment of chronic respiratory tract infections.
The Japanese journal of antibiotics 05/1995; 48(4):482-513.
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ABSTRACT: We investigated phenotypic surface markers of peripheral blood lymphocytes including expression of gamma delta T cell receptor (TCR gamma delta) in 185 patients with sarcoidosis and 42 normal subjects. The proportion of TCR gamma delta+ lymphocytes in peripheral blood of patients with sarcoidosis (5.5 +/- 5.4%) was significantly higher than in normal subjects (3.6 +/- 2.2%; p < 0.05). A number of patients with sarcoidosis had prominently increased levels of circulating TCR gamma delta+ lymphocytes. Successive measurements of circulating TCR gamma delta+ lymphocytes demonstrated the persistence of increased levels of circulating TCR gamma delta+ lymphocytes. We divided the patients with sarcoidosis into two groups, one with high, the other with low TCR gamma delta+ expression. Compared with the low-value group, the high-value group had significantly decreased levels of circulating CD4+ lymphocytes, decreased incidence of a positive tuberculin reaction, and higher levels of serum angiotensin-converting enzyme and lysozyme, suggesting that these two groups may differ in their immunological response and disease activity of sarcoidosis. Measurement of TCR gamma delta+ expression in the circulation seems to be useful for estimating the disease activity of sarcoidosis.
Respiration 02/1995; 62(2):84-8. · 2.26 Impact Factor
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ABSTRACT: The efficacy of transbronchial lung biopsy (TBLB) for the diagnosis of sarcoidosis was compared to that of scalene node biopsy (SNB). We performed both TBLB and SNB or in 336 consecutive patients with clinical features of sarcoidosis. In 270 out of 336 patients epithelioid cell granuloma was found. The frequency of granuloma in specimens obtained by TBLB was higher than that of SNB at any radiographic stage. In stage 0 and stage I diseases however, the frequency of epithelioid cell granuloma in the specimens was increased by examining both of TBLB and SNB. We concluded that SNB was useful in consecutive patients with sarcoidosis in whom the epithelioid cell granuloma could not be confirmed by TBLB.
Nippon rinsho. Japanese journal of clinical medicine 07/1994; 52(6):1539-43.
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ABSTRACT: Ga-67 scintigraphy was useful in evaluating the extent and relative activity of pulmonary sarcoidosis. It is also helpful detecting the involved lesions in sarcoidosis. The Ga-67 SPECT image was more excellent than planar image, because the SPECT image was able to distinguish abnormal intrapulmonary accumulation, especially, the hilar and mediastinal lymph node accumulation from normal accumulation; sternum, vertebrae, etc, which usually overlap on the planar image. Ga-67 SPECT imaging may also be useful in the diagnosis of myocardial sarcoidosis and in the evaluation of lesions, size and response to corticosteroid therapy. Several data, however, suggest that prediction of the clinical course or the prognosis of patients with pulmonary sarcoidosis is not possible by the degree of pulmonary Ga-67 accumulation.
Nippon rinsho. Japanese journal of clinical medicine 07/1994; 52(6):1516-20.
