Involvement of dendritic cells in sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown aetiology. It has been suggested that T helper type 1 (Th1) polarisation is associated with the pathophysiology of sarcoidosis, but the mechanism of skewing towards Th1 has not been elucidated. Dendritic cells (DCs) are known to regulate immune responses. This study was performed to determine whether DCs are involved in the aetiology of sarcoidosis. METHODS: The numbers of peripheral blood DCs in 24 patients with sarcoidosis were analysed and biopsy specimens from four patients were stained immunohistochemically using monoclonal antibodies. RESULTS: The numbers of both myeloid and lymphoid DC subsets were significantly decreased in the blood and mature DCs were found in the granulomas of patients with sarcoidosis. A number of interferon-gamma (IFN-gamma) producing T cells were also detected in the sarcoid granuloma, as well as many interleukin (IL)-4 producing T cells. Double staining of the biopsy specimen using anti-fascin and anti-CD3 antibodies showed an anatomical interaction between DCs and T cells. CONCLUSIONS: These findings suggest that the blood DC subsets may migrate into the affected tissues, contributing to the formation of the granulomas in sarcoidosis. It is hypothesised that the migrating DCs may regulate the T cell response in sarcoidosis, at least in the granulomatous lesions.

Results of surgery for bronchogenic carcinoma located in the aortic window.

Because of its critical location, lung cancer located in the aortic window can cause complications affecting the pulmonary artery trunk, aortic arch and esophagus. The results of surgical treatment are poor; however, there are few long-term survivors. In an attempt to define the indications for extended surgery, we evaluated eleven patients with non-small cell lung cancer. The tumors were classified according to their clinical extent of invasion as Type A (invading the anterior mediastinum including the central part of the pulmonary artery), Type B (invading upwardly to the mediastinum through the aortic window) or Type C (invading the posterior mediastinum including the thoracic aorta or esophagus). In the five patients with type A invasion, no metastases to the upper mediastinal lymph nodes other than the subaortic lymph nodes were found. The three patients with type B invasion had many metastases to the upper mediastinal lymph nodes. There were no metastases in the upper mediastinum in any of these patients with type C invasion, but metastases were found in a lower mediastinal lymph node #9, and a carinal lymph node. Each group clearly demonstrated a different site of mediastinal lymph nodes metastasis. The long term result was good in Type A invasion, in contrast to Type B or C invasion. Our classification may be useful for planning one's surgical approach to advanced lung cancer of the aortic window.

[Bronchogenic carcinoma located in the aortic window].

In the patients with invasion to the aortic window, we performed operation via median sternotomy combined with anteroaxillar thoracotomy. In such patients with T4 invasion, conventional pneumonectomy could not be performed because of the extensive invasion near the main pulmonary artery trunk. In these patients in this study, complete resection of the involved pulmonary artery could be performed using a vascular clamp without CP bypass. Operative technique was as follows: first, the pericardium was opened and taping of the aorta was applied. When the uninvolved part of the intrapericardial pulmonary artery was long enough to cut, we could use a stapling device, but the stapling device could not be used in many cases because the length of the uninvolved segment was too short to cut the left pulmonary artery. In order to carry out complete resection, it was necessary to clamp the central part of the main pulmonary artery diagonally from the left lower side to the right upper side. The pulmonary arterial stump was closed with continuous 4-0 monofilament mattress and over and over suture. We recommend an aggressive surgical approach for the tumor with invasion to the aortic window, because the prognosis is dismal in nonresected locally advanced lung cancer.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1994). III. Secular changes in susceptibility].

Susceptibilities of Enterococcus faecalis, Staphylococcus aureus, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa and Serratia spp. isolated from patients with urinary tract infections (UTIs) in 10 hospitals during June 1994 to May 1995 to various antimicrobial agents were compared with those in the same period of previous years according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. No remarkable changes were found in susceptibilities of Citrobacter spp., Enterobacter spp. and Serratia spp. The susceptibilities of E. faecalis to amikacin and quinolones were better than those in 1993. As for S. aureus, susceptible strains to all drugs increased in uncomplicated UTIs. Against E. coli in 1993, the antimicrobial activities of piperacillin, cefotiam and aminoglycosides have decreased, however, in 1994, these activities have turned to the better state. As for Klebsiella spp. susceptible strains to ABPC decreased. The susceptibilities of P. mirabilis to all drugs except minocycline were good. Against P. aeruginosa in 1993, the activities of aminoglycosides have decreased, but, in 1994, these activities have turned to the better state. These data should be considered in clinical treatment of various urinary tract infections.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1994). I. Susceptibility distribution].

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 567 bacterial strains isolated from patients with urinary tract infections in 10 hospitals during the period of June 1994 to May 1995. Of the above total bacterial isolates, Gram-positive bacteria accounted for 26.8% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 73.2% and most of them were Escherichia coli. 1. Enterococcus faecalis. Ampicillin (ABPC) and imipenem (IPM) showed the highest activities against E. faecalis isolated from patients with urinary tract infections. The MIC90s of them were 1 microgram/ml. Vancomycin (VCM) was also active with the MIC90 of 2 micrograms/ml. Piperacillin (PIPC) and biapenem (BIPM) were also active with the MIC90s of 4 micrograms/ml and 8 micrograms/ml, respectively. The others were not so active with the MIC90s of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA. VCM showed the highest activities against S. aureus isolated from patients with urinary tract infections. Its MIC90 was 1 microgram/ml against both S. aureus and MRSA. Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The others except minocycline (MINO) were not so active with the MIC90s of 64 micrograms/ml or above. 3. Staphylococcus epidermidis. MINO showed the strongest activity against S. epidermidis isolated from patients with urinary tract infections. Its MIC90 was 0.25 microgram/ml. ABK was also active with the MIC90 of 1 microgram/ml. Cephems were active with the MIC90s of 2 approximately 16 micrograms/ml, but penicillins and quinolones were not so active with the MIC90s and 64 approximately 128 micrograms/ml. 4. Citrobacter freundii. Gentamicin (GM) showed the highest activities against C. freundii isolated from patients with urinary tract infections. Its MIC90 was 1 microgram/ml. IPM was also active with the MIC90 of 2 micrograms/ml. Cefpirome (CPR) and cefozopran (CZOP) were also active with the MIC90s of 4 micrograms/ml and 8 micrograms/ml. The others were not so active with the MIC90s of 32 micrograms/ml or above. 5. Enterobacter cloacae. IPM showed the highest activities against E. cloacae. Its MIC90 was 0.5 microgram/ml. GM and amikacin (AMK), ciprofloxacin (CPFX) and tosulfloxacin (TFLX) were also active with the MIC90s of 4 micrograms/ml. Penicillins and cephems except latamoxef (LMOX), cefmenoxime (CMX), CPR and CZOP showed lower activities with the MIC90s of 256 micrograms/ml or above. 6. Escherichia coli. Most of antimicrobial agents were active against E. coli. CPR, CZOP, IPM, carumonam (CRMN), CPFX and TFLX showed the highest activities against E. coli. The MIC90s of them were 0.125 microgram/ml or below. Cefotiam (CTM), flomoxef (FMOX) CMX, ceftazidime (CAZ), and LMOX were also active with the MIC90s of 0.25 microgram/ml. Penicillins were not so active with the MIC90s of 128 micrograms/ml or above. 7. Klebsiella pneumoniae. CRMN showed the highest activities against K. pneumoniae. Its MIC90 was < or = 0.125 microgram/ml. CZOP was also active with the MIC90 of 0.25 microgram/ml. Penicillins were not so active with the MIC90s of 128 micrograms/ml or above. 8. Proteus mirabilis. P. mirabilis was susceptible to a majority of drugs. CMX, CAZ, LMOX, CRP, cefpodoxime (CPDX), CRMN, CPFX and TFLX showed the highest activities against P. mirabilis isolated from patients with urinary tract infections. The MIC90s of them were 0.125 microgram/ml or below. MINO was not so active with the MIC90 of 128 micrograms/ml. 9. Pseudomonas aeruginosa. Most of the agents were not so active against P. aeruginosa. IPM showed MIC90 of 8 micrograms/ml. The others were not so active with the MIC90s of 16 micrograms/ml or above. CPFX showed MIC50 of 0.5 microgram/ml.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1994). II. Background of patients].

Clinical background was investigated on 628 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during period from June, 1994 to May, 1995. 1. Distributions of sex, age and urinary tract infections Among over sixties males, the majority was taken by complicated urinary tract infections. Among females, the uncomplicated urinary tract infections was most frequent without a relation of age. As for over 40 females, the increase of complicated UTI was admitted. 2. Distribution of sex, age and pathogens isolated from UTIs In uncomplicated UTIs, Escherichia coli was most frequently isolated without a relation of age, and next Enterococcus faecalis and CNS. In complicated UTIs without indwelling catheter, E. coli, Pseudomonas aeruginosa and E. faecalis were isolated the most frequent. In complicated UTIs with indwelling catheter, P. aeruginosa was most frequently isolated, and next E. faecalis and Staphylococcus aureus. 3. Administration of antimicrobial agents and pathogens isolated from UTIs In uncomplicated UTIs, pathogens, after administration of antibiotics, isolated from patients have obviously decreased from 216 to 32 isolates. And also, pathogens of complicated UTIs without indwelling catheter, have decreased from 127 to 50 isolates. However, in complicated UTIs with indwelling catheter, pathogens after or before administration of antibiotics, were not revealed an obvious change. 4. Pathogens and UTIs with or without factor and operation In uncomplicated UTIs with or without factor and operation, E. coli was mainly detected. In complicated UTIs without indwelling catheter and with factor and operation E. faecalis was mainly detected, and next E. coli, S. aureus and P. aeruginosa. Without factor and operation, E. coli was mainly detected. In complicated UTIs with indwelling catheter and with factor and operation, P. aeruginosa, E. faecalis and S. aureus were mainly detected at 23.5%, 15.0%, 15.0%, respectively. Without factor and operation, Proteus spp. 22%, and next E. faecalis and P. aeruginosa 10% and 12%, were detected, respectively. The distribution of pathogens, in the case of Proteus spp. and P. aeruginosa has been obviously varied by the influence of factor and operation.

Percutaneous and endobronchial high dose rate brachytherapy for lung cancer.

Endobronchial and percutaneous high dose rate (HDR) brachytherapy was performed with a microSelectron HDR using iridium-192 as a radiation source. As spontaneous pain was uncontrollable by external beam radiation (EBR), chemotherapy, hyperthermia or a combination of these treatment methods, three patients with lung cancer infiltration into the chest wall underwent percutaneous HDR brachytherapy for palliation of severe pain. Selectron needles were inserted under CT guidance and the irradiation dose was set to 10 or 12 Gy at the point 1 cm from the center of the radiation source. A total of 2-4 selectron needles was introduced by means of a template. Irradiation was performed once a week for 1-2 weeks depending on the degree of alleviation of spontaneous pain. In all 3 cases, alleviation of spontaneous pain occured within 7 days after the completion of HDR brachytherapy, and the mean pain score decreased from a value of 2 to 1 within 2 weeks. After discharge from the hospital, the pain score remained between 1-4 in all 3 patients. One problem in percutaneous brachytherapy is the possible hindrance of multiple selectron needle insertion through the template by the ribs depending on the location of the lesion. Six patients aged 51-75 years were subjected to endobronchial HDR brachytherapy. Two of these patients had postoperative recurrence of lung cancer, and 3 patients received concomitant chemotherapy. Brachytherapy was performed 3.4 months (average) after the administartion of 40-70 Gy of EBR. Endobronchial irradiation was performed at a dose of 7 Gy, measured at 1 cm from the center of the radiation source, once a week over a 3 week period for a total of 21 Gy. With the exception of 2 patients who died due to systemic exacerbation, local control of the illness has been good. In endobronchial HDR brachytherapy, it is important to develop a system for altering radiation dose in response to changes in the caliber of the tracheobronchial tree and the degree of the tumor invasion under the bronchial mucosa.

[A case of AIDS patient who was hard to diagnose from an initial symptom of interstitial pneumonitis].

A thirty-six year old male was admitted to the hospital because of fever and dyspnea. On the eighth day the patient turned out to be HIV positive. Although aggressive therapy was performed, the patient died of HIV related disease such as Pneumocystis carinii pneumonitis and CMV infection which led to multiple organ failure seventeen days after admission. We reported a case of AIDS patient who was hard to diagnose from an initial symptom of interstitial pneumonitis.

[Neoadjuvant chemotherapy effective for small cell lung cancer in a nephrectomized patient].

A 67-year-old man, who was nephrectomized due to renal cell cancer 4 years ago, was admitted to examine a mass shadow in the right middle lung field. He was diagnosed as small cell lung cancer with TBLB. Because of impaired renal function, he was treated with CBDCA (300 mg/m2, day 1), THP (30 mg/m2, day 1) and oral etoposide (25 mg/body, for 21 days) without any renal complications. After 3 courses of chemotherapy, the lung CT showed scar lesion despite the disappearance on the chest X-ray, and a right lower lobectomy was performed. Malignant cells remained in the scar lesion, but not in the lymph nodes. These findings suggested the effectiveness of neoadjuvant chemotherapy. This newly-designed chemotherapy procedure is necessary for patients with renal complications.

Results of chemo-radiotherapy and prognostic factors of small cell lung cancer.

We studied the therapeutic results and prognostic factors in 63 cases of small cell lung cancer (SCLC) experienced in our hospital over the past eight years. In the group initially treated with combination chemotherapy using COMP-VAD, the survival period was significantly prolonged. Use of adjuvant radiotherapy from the beginning had no effect on improvement in the survival period, but the period until local recurrences tended to be prolonged. Prognostic factors influencing survival were analyzed by the log rank test and generalized Wilcoxon test and multivariate analysis by the proportional hazard model of Cox. Statistical significance using univariate analysis was found for six factors (PS, clinical stage, LDH, albumin, treatment protocols, treatment response). The strong prognostic factors determined by multivariate analysis were, in the order of importance, chemotherapy protocol, initial PS, and treatment response.