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BACKGROUND: Intra-operative cell salvage is not routinely used during cesarean delivery because it is not cost-effective for patients at low risk of hemorrhage and there are theoretical concerns about amniotic fluid embolism. Some guidelines recommend using leukocyte depletion filters to decrease the risk of amniotic fluid embolism before re-infusing salvaged blood, but these filters are not available in Japan. We compared the efficacy and safety of leukocyte depletion and micro-aggregate filters in combination with intra-operative cell salvage during cesarean delivery.METHODS: Blood was collected in a Cell Saver 5 reservoir during cesarean delivery. Four samples were collected: pre-wash, post-wash, post-filtration with a leukocyte depletion filter and post-filtration with a micro-aggregate filter. Each sample was analyzed for amniotic fluid markers of zinc coproporphyrin-1 and sialyl-Tn, for fetal hemoglobin, and the sample underwent pathological examination for white blood cells and squamous cells. Post-filtration samples were compared using paired t-tests with P

Recently, a high rate of endometrial cancer has been reported in women with hereditary non-polyposis colorectal cancer (HNPCC), suggesting a relationship between familial endometrial cancers and HNPCC. Familial endometrial cancers constitute only about 0.5% of all endometrial carcinomas and it is essential to examine family histories in detail. A mutational analysis of three DNA mismatch repair (MMR) genes (hMLH1, hMSH2 and hMSH6) in patients with endometrial cancer who meet our criteria for familial predisposition to HNPCC-associated endometrial cancers was performed. Mutations were detected in 18 of the 120 patients (15.0%). Most HNPCC-related endometrial cancers do not meet the New Amsterdam Criteria for HNPCC. These clinical criteria may identify only some HNPCC-associated endometrial cancers. Establishing the correct family history for endometrial cancer patients is important for diagnosing familial endometrial carcinomas. An analysis of MMR genes may be useful for patients with endometrial cancer showing familial aggregation. In addition, gynecologists must be accurately informed, and it is important to perform large-scale, multicenter studies both nationwide and internationally. (Cancer Sci 2008; 99: 1715–1719)

The aim was to assess whether hepatocyte growth factor (HGF) and interleukin (IL)-6 in combination with prostate volume are able to accurately detect prostate cancer in patients with gray-zone prostate-specific antigen (PSA) levels. A total of 159 patients with PSA levels of

Anastomotic leakage is major complication of colorectal surgery. Total parenteral nutrition (TPN) and fasting are conservative treatments for leakage in the absence of peritonitis in Japan. Elemental diet (ED) jelly is a completely digested formula and is easily absorbed without secretion of digestive juices. The purpose of this study was to assess the safety of ED jelly in management of anastomotic leakage.Six hundred and two patients who underwent elective surgery for left side colorectal cancer from January 2008 to December 2011 were included in the study. Pelvic drainage was performed for all patients. Sixty-three (10.5%) patients were diagnosed with an anastomotic leakage, and of these, 31 (5.2%) without diverting stoma were enrolled in this study.Sixteen patients received TPN (TPN group) and 15 patients received ED jelly (ED group). The duration of intravenous infusion was significantly shorter in the ED group than in the TPN group (15 days versus 25 days, P= 0.008). In the TPN group, catheter infection was occurred in 2 patients who required re-insertion of the catheter.Conservative management of anastomotic leakage after colorectal surgery with ED jelly appears to be a safe and useful approach.

We performed a multicenter study in Japan to assess the efficacy and safety of immunosuppressive therapy with high-dose mizoribine (MZR; 6 mg/kg) combined with basiliximab (Bas), cyclosporine (CyA), and a corticosteroid in 90 patients. MZR was adjusted to maintain a target trough level of 1 to 2 μg/mL. CyA was started at 7 mg/kg to maintain blood levels in the target therapeutic range of 200 ng/mL (trough [C0]), 1200 ng/mL (2-hour post-dose [C2]), and 6000 ng · h/mL (area under the curve 0–9 ). Bas (20 mg/body weight) was administered on the day of transplantation and on postoperative day 4. Rejection was diagnosed by episode and protocol biopsies. Cytomegalovirus (CMV) antigenemia (direct immunological staining of leukocytes using peroxidase-labeled monoclonal antibody [C7-HRP]) levels were measured every 2 weeks for 6 months. At 12 months, all patients and grafts were surviving except for one death from infection: the 1-year patient and graft survival rate was 98.9%. The acute rejection rate was 21.1%. The mean serum creatinine level at 1 year was 1.51 ± 0.61 mg/dL. The incidence of CMV disease was 0% with 28.9%, CMV antigenemia and 5.6%, ganoyclovir treatment. The incidence of BK virus disease was 2.2%. The mean serum uric acid level was 7.15 ± 1.79 mg/dL at 1 month and 7.06 ± 1.78 mg/dL at 3 months. We observed that a high-dose MZR regimen in combination with CyA, Bas, and corticosteroid was safe and effective to reduce the frequency of CMV and BK virus-related events in renal transplant recipients.

Objective Osteoclasts may be involved in the process of rheumatoid bone destruction. To test this hypothesis, we developed an in vitro model of bone destruction by osteoclast-like cells derived from cultured rheumatoid synovial tissue without using any inducers. Methods Synovial tissues were obtained from rheumatoid arthritis and osteoarthritis patients and tissue pieces of about 2 mm(3) that contained synovial lining were cultured. Multinucleated cells derived from cultured synovial tissues were studied cytochemically and morphologically for osteoclast-specific markers. Results Fibroblast-like and macrophage-like cells from the tissue pieces proliferated in the coexistence of lymphocytes. After 14 days of culture, multinucleated cells with tartrate-resistant acid phosphatase activity appeared. These cells expressed vacuolar H(+)-ATPase, the vitronectin receptor and cathepsin K. Although binding of (125)I-labelled salmon calcitonin was very low, the cells contained ringed structures of F-actin and showed strong bone-resorbing activity on ivory slices. Proliferation of macrophage-like cells and formation of multinucleated cells continued during 6 months of culture in the presence of fibroblast-like cells. The bone-resorbing activity of multinucleated cells derived from rheumatoid synovial tissue was much higher than that of cells from osteoarthritis synovial tissue, and was related to the disease activity of rheumatoid arthritis. Conclusion Our culture system reproduced in vitro the process of bone destruction by rheumatoid synovium, including the proliferation and fusion of precursor cells, polarization, activation and bone tissue resorption. This system may provide a tool for understanding the mechanisms of bone destruction in rheumatoid arthritis and for the development of new therapies to prevent bone destruction.

Objectives. We investigated the prevalence of the metabolic syndrome (MS) in kidney transplantation patients and assessed its development based on plasma adiponectin levels and the results of an oral glucose tolerance test (OGTT). Methods. We performed a cross-sectional study of 94 recipients with stable graft function who underwent kidney transplantation between January 1999 and October 2008. The presence of MS was determined using National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria with body mass index (BMI) used in place of waist circumference. In addition, we measured plasma adiponectin level and performed a 75-g oral GTT. Results. Fourteen (14.9 %) recipients suffered from MS for a mean period of 46.7 months (range, 1-106) after transplantation. BMI at the time of transplantation was significantly greater in the MS group (23.4 ± 3.24 vs 20.1 ± 2.50; P

In the present single center study, we analyzed 277 kidney transplant patients (procedures performed between February 1984 and February 2006) to determine the impact of long-term dialysis on kidney transplant outcomes. Forty-four had been treated prior to renal transplantation with dialysis for more than 10 years (range, 10.0-32.5 years, average, 16.6 years; Group I), while the remaining 233 recipients showed an average end-stage renal disease period of 2.8 years (range, 0-9.8 years; Group II). There were no significant differences in patient survivals between the 2 groups: 97.3% vs 97.4% at 1 year; 85.7% vs 92.4% at 5 years; 85.7% vs 90.7% at 10 years (P = .2347). Five Group I patients died: 2 from infections, 2 from liver dysfunction, and 1 from cerebral bleeding. These causes of death were similar to those among Group II patients. Graft survival was not significantly different between the 2 groups: 95% vs 88.8% at 1 year; 75.5% vs 76.5% at 5 years; 75.5% vs 65.5% at 10 years (P = .6264). Our results suggested that dialysis treatment for more than 10 years did not have negative effects on posttransplantation patient and graft survival.

Head rotation can cause occlusion of the vertebral artery most commonly at the atlas loop, and repetitive compression from head turning induces vertebral artery dissection (VAD). Although ultrasound examinations are useful in diagnosis, dissected lesions unaccompanied by hemodynamic changes can be overlooked. Because the narrowed, dissected vessel in the atlas loop may cause rotational occlusion, we confirmed whether adding submaximal head rotation to a cervical ultrasound examination would facilitate the detection of VAD in the atlas loop.We investigated 7 patients who developed infarction in the posterior circulation and were clinically suspected of VAD. Using a 7.5-MHz linear probe, we recorded the waveform of the vertebral artery at the C4-C6 level and diagnosed rotational vertebral artery occlusion (RVAO) when head rotation induced the disappearance of end-diastolic flow.All 3 patients with VAD in the atlas loop demonstrated RVAO of the dissected vertebral arteries in the acute stroke phase. RVAO was not observed in the dissected vertebral arteries excepting the atlas loop, nor in the nondissected vertebral arteries of any patients.For posterior circulation stroke patients, adding submaximal head rotation to the cervical ultrasound examination facilitated the detection of VAD in the atlas loop.

Donation after cardiac death (DCD) has the potential to significantly increase the number of organ donors. In this study, we investigate the influence of several donor parameters on the early graft function in kidney transplantation from DCD donors. We performed 58 kidney transplantations from DCD donors. Recipients were divided into 2 groups according to their graft function: normal graft function (NGF), patients who became be free of hemodialysis within 14 days post-transplantation) and delayed graft function (DGF) group, patients who required hemodialysis for longer than 15 days after transplantation). We compared donor age, sex, cause of death, warm and total ischemic time, duration of anuria (urine volume10 mL/h), and low blood pressure (systolic blood pressure60 mm Hg), usage of catecholamine and vasopressin, serum creatinine on the day of admission and graft retrieval, serum sodium concentration, and body temperature between 2 groups. The number of recipients in NGF and DGF group was 41 and 17. Univariate analysis revealed that duration of anuria (24 vs ≥ 24 hours) and usage of catecholamine significantly influenced graft function. Duration of anuria was an independent risk factor for early graft function by multivariate analysis. In cadaveric kidney transplantation from DCD donors, there was a trend to poorer early graft function with donors who suffered from anuria for longer than 24 hours before kidney retrieval.

Adiponectin and leptin, polypeptide hormones produced by adipocytes, have recently been reported to be associated with prostate cancer risk, though, the relationship remains poorly understood. We examined the association of adiponectin and leptin levels in serum with prostate cancer risk after adjustments for age, obesity-related factors, and prostate cancer risk.Fifty-four prostate cancer patients and 70 control subjects provided blood sampled between 2008 and 2009. Using those, we determined serum adiponectin and leptin levels, and evaluated their relationships with prostate cancer risk after adjustments for age, obesity-related factors (body weight, body mass index, waist circumference), and prostate volume. Adipokine densities were calculated by dividing serum level with prostate volume.There were no differences for median serum adiponectin and leptin levels between the prostate cancer and benign control groups (P=0.22 and 0.78, respectively). Patients with levels of both adipokines in the highest quartile after adjustment for age had significantly higher risks of prostate cancer (adiponectin: odds ratio [OR] 2.79, P=0.014; leptin: OR 2.72, P=0.027). Patients with an adiponectin level greater than the median after adjustment for body weight also had a significantly elevated risk of prostate cancer (OR 2.22, P=0.031), whereas, those with a leptin level significantly greater than the median had a significantly lower risk (OR 0.46, P=0.027). Furthermore, median adiponectin density was significantly higher in the prostate cancer group than the benign group (P=0.0033).Serum adiponectin and leptin levels are useful markers for prostate cancer risk after adjustments for age, obesity-related factors, and prostate volume.

A recent report noted that cyclosporine (CsA) inhibits replication of the hepatitis C virus (HCV) in vitro. Thus, CsA may be a superior immunosuppressant for renal transplant recipients infected with HCV. In the present retrospective study, we assessed whether CsA reduced the clinical impact of HCV infection among those patients. A total of 405 renal transplants were performed between 1973 and 2005, of whom we studied 189 who received CsA-based immunosuppression (CsA group) vs 108 who received an azathioprine-based regimen (AZA group). There were 44 HCVAb carriers and 145 noncarriers in the CsA group, and 41 carriers and 67 noncarriers in the AZA group. Our results showed that patient survival rate was significantly worse among HCVAb carriers than among noncarriers, as the overall survival rates were 82.9% and 90.9%, respectively, after 10 years and 71.5% and 85.7%, respectively, after 20 years (P = .0003). Patient survival rates were also significantly worse in HCVAb carriers than in noncarriers in both groups, which were 83.2% and 95.0%, respectively, after 10 years, and 74.7% and 88.8%, respectively, after 20 years (P = .0147) in the CsA group, and 82.9% and 83.6%, respectively, after 10 years and 70.7% and 80.6%, respectively, after 20 years (P = .0171) in the AZA group. Conversely, no significant difference was seen in patient survival rate for HCVAb carriers between the two groups (83.2% vs 82.9% at 10 years, and 74.7% vs 70.7% at 20 years, P = .8195). Our results confirmed that HCV infection has a negative impact on the long-term survival of renal transplant patients who receive either a CsA-based or an AZA-based regimen, suggesting that CsA does not have a positive impact on HCV carriers.

A 39-year-old man who had a subdiaphragmatic bronchogenic cyst in the left crus of diaphragm received surgical treatment. The cyst was located in the retroperitoneum just below the diaphragm and was adhered to the left crus of diaphragm and unconnected with any other structures. The surgically resected cyst was 50 x 25 x 22 mm diameter and the wall was thin and contained white turbid mucus. Histologically, the cyst consisted of ciliated epithelium, mucus glands, smooth muscle, cartilage and this evidence established the final diagnosis of bronchogenic cyst. The post operative course was uneventful and the patient was discharged 10 days after operation. This is the 4th reported case of a subdiaphragmatic bronchogenic cyst in the Japanese literature.

We experienced 3 cases of video-assisted thoracoscopic surgery for spontaneous hemopneumothorax. All the patients had received emergent operations because of massive intrathoracic bleeding. At the operation, a 3 cm-minithoracotomy and 2 trocar ports were fashioned. In the head up position, massive blood clots in the apex in the thoracic cavity was removed by using grasping forceps and the source of bleeding point was detected easily. The bleeding was successfully stopped. It was difficult to remove massive blood clots from trocar port by suction, however it was easy to remove massive blood clots from a 3 cm-minithoracotomy window by using a large grasping forceps. Post operative course was satisfactory and the all patients discharged within 2 weeks after admission. We concluded that the spontaneous hemopneumothorax may be a good indication for video-assisted thoracoscopic surgery.

We investigated the antiemetic effect, safety and usefulness of granisetron hydrochloride tablets on nausea and vomiting induced by oral anticancer drugs used in chemotherapy for gastric cancer and colorectal cancer. In the present trial, oral administration of granisetron hydrochloride was performed during 5 days after nausea or vomiting. 1) Clinically, the effective rate of granisetron hydrochloride (the percentage of cases in which the drug was assessed as "Remarkably effective" or "Effective") was more than 75% on each day of administration. There were no adverse events or abnormal laboratory tests. 2) In terms of usefulness, granisetron hydrochloride was rated "Extremely useful" or "Useful" in 17 out of 23 cases (78.2%). The above results have shown that granisetron hydrochloride tablets, administrated orally once daily at a dose of 2 mg, have an excellent antiemetic effect, and that this is a safe and useful drug.

The aim of this study is to evaluate the effect of adjuvant hepatic arterial infusion chemotherapy (HAIC) following liver resection on the frequency of residual liver recurrence and overall survival.During 1992 to 1997, 84 patients with liver metastasis from colorectal cancer resected curatively had undergone adjuvant HAIC. The regimen of the HAIC is 1,500 mg of 5-FU by 24-hr continuous infusion once a week for eight weeks. 37 cases in the HAIC group, including patients given more than 7 g of 5-FU, were compared with the control group.The cumulative 5-year liver recurrence-free ratios were 72.6% in the HAIC group and 29.8% in the control group (p = 0.0005). The cumulative 5-year survival ratios were 61.4% in the HAIC group and 28.0% in the control group (p = 0.0069). Multivariate analysis revealed that more than 5 mm of surgical margin and adjuvant HAIC significantly decreased the risk of recurrences in residual liver.Adjuvant HAIC is an effective procedure to prevent recurrence in residual liver and improve the prognosis of patients with liver metastasis from colorectal cancer.

We report a rare case with multiple renal infarction associated with lupus anticoagulant and SLE. A 20-year old woman presented with remitent fever, butterfly rash and, abdominal pain. Laboratory findings showed leukopenia, positive antinuclear and anti-DNA antibodies, and biological false positive for syphilis. Despite a therapy with prednisolone 25 mg/day, the patient showed hypocomplementemia, high titer of anti-DNA antibody and a development of proteinuria and an elevation of serum creatinine. Renal biopsy revealed no abnormalities. She presented abdominal pain with an elevation of serum LDH. Abdominal dynamic computed tomography demonstrated multiple perfusion defects in both kidneys indicating multiple renal infarction. Brain MRI showed multiple micro infarction in the anterior lobes. She was treated with 80 mg of aspirin and have been in remission for two years. Although there have been reported 18 cases with renal infarction associated with antiphospholipid syndrome, this is the first report in Japan. Renal infarction should be differentiated from renal involvement in patients with SLE who have antiphospholipid antibodies.

Rheumatoid factors (RFs) in sera from rheumatoid arthritis (RA) patients bind better to agalactosyl IgG [gal(-) IgG] than to native IgG. Recently, a novel lectin-enzyme immunoassay (LEIA) which can detect all isotypes of the immunoglobulins was developed in Japan. Since RFs are also detectable in Sjögren's syndrome (SS), we determined anti-gal(-) IgG antibodies and RF isotypes in sera from primary or secondary SS and RA patients to elucidate the clinical significance of these antibody profiles.A series of 128 patients with primary SS (35 pts.), RA (57 pts.), or secondary SS [n = 36 pts., the SS being associated with RA (RA-SS) in 12 pts., systemic lupus erythematosus (SLE-SS) in 17 pts., and mixed connective tissue disease (MCTD-SS) in 7 pts.] and 38 healthy females were examined. Anti-gal(-) IgG antibodies were measured with a LEIA kit (ED055) using human gal(-) IgG as antigen. IgG-, IgA- and IgM-RF were determined with an enzyme-linked immunosorbent assay kit using human IgG-Fc as antigen. RFs were also examined by a conventional assay (laser nephelometry; LN-RF).Serum anti-gal(-) IgG antibody titers were higher in RA than in primary SS, SLE-SS or MCTD-SS, but the incidence of the antibodies did not differ between RA and primary SS. In both RA and primary SS, the antibodies were positive in half of the LN-RF-negative patients, and were also detected in almost all of those patients who had at least one of the RF isotypes. LN-RF, IgG-RF, IgA-RF and IgM-RF were present more frequently and their titers were higher in RA than in primary SS, but IgA-RF levels were similar in both groups. In RA-SS, all of the antibody titers were notably higher than in RA or primary SS. In RA and primary SS, IgA-RF and IgM-RF were common RF isotypes, and anti-gal(-) IgG antibody levels correlated well with LN-RF, IgA-RF and IgM-RF levels. These antibody profiles did not relate to any of the clinical parameters in RA, but all the antibody titers correlated with anti-SS-A/Ro antibody levels in primary SS.The anti-gal(-) IgG antibodies are not specific for RA; they are also frequent in SS. Our LEIA for antibodies is a very sensitive method to detect all RF isotypes in both RA and SS. Most of the antibody profiles are common to both diseases, although antibody titers are higher in RA, especially in RA-SS.

Three young women were admitted to our hospital because of severe anemia and fever of unknown origin. The patients had a long history of frequent hospitalizations and operations. During hospitalization, the patients complained of hematemesis, hematuria and fever, which were sometimes discrepant with their physical and laboratory findings. After the careful observation, the patients were diagnosed as Munchausen syndrome because of either discovery of the tools used to make their symptoms or the patient's confession that these symptoms were made by herself. The patients with Munchausen syndrome sometimes show various symptoms and signs of multisystem inflammatory diseases, which mimick the clinical feature of connective tissue diseases. It is important for rheumatologists to be aware of the existence of Munchausen syndrome among the differential diagnosis of connective tissue diseases.

Plasmin and matrix metalloproteinase-3 (MMP-3) have been linked to articular destruction in rheumatoid arthritis (RA). We compared circulating levels of plasmin-mediated fibrin degradation product (FDP D-dimer) and MMP-3 with traditional parameters of disease activity in RA to determine their clinical utility.Serum levels of MMP-3 and D-dimer were determined by enzyme-linked immunoassays in 60 patients with RA. Twenty healthy females and 21 patients with systemic lupus erythematosus (SLE) served as controls.MMP-3 (436.8 +/- 474.2 ng/ml) and D-dimer levels (351.2 +/- 296.3 ng/ml) were markedly elevated in the sera from RA patients as compared with healthy controls (43.9 +/- 15.2 ng/ml and 63.0 +/- 64.1 ng/ml, p0.0001, respectively). Both levels strongly correlated with each other (r = 0.627, p0.0001) and were closely associated with various clinical parameters for the disease activity of RA, including the erythrocyte sedimentation rate (ESR) and the Lansbury's activity index (p0.0001). MMP-3 levels were more highly correlated with articular parameters such as the swollen and painful joint counts (r = 0.454, p = 0.0002), whereas D-dimer levels correlated well with C-reactive protein (CRP) levels (r = 0.581, p0.0001). In SLE patients, MMP-3 (239.1 +/- 199.6 ng/ml, p0.0001) and D-dimer levels (86.9 +/- 85.2 ng/ml, p = 0.0278) were also higher than in healthy controls. Both levels correlated with each other (r = 0.612, p = 0.0025), and were associated with ESR and CRP levels, as was observed in RA patients, but not with most of the other clinical indicators for SLE.Serum levels of MMP-3 and D-dimer are clinically useful indicators for disease activity in RA. Our results further support the hypothesis that MMP-3 and plasmin may interact in the inflammatory synovial tissues, and thus augment the articular destruction seen in RA. In SLE patients, however, MMP-3 producing cells could be different from in RA patients, and further studies will be required to clarify the pathogenetic mechanism underlying the raised serum levels of MMP-3 and/or D-dimer.

To clarify whether immunoglobulin A (IgA) antiphospholipid antibodies (aPL) are an independent risk factor for specific manifestations of collagen vascular diseases.We determined IgG, IgM, and IgA anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC) in 77 patients with various collagen diseases. Fifty-four patients who had positive results for either or both antibody classes were compared to 23 patients with systemic lupus erythematosus who had none of these antibodies. The association between the antibodies and clinical manifestations (thrombosis, fetal loss, thrombocytopenia, biological false positive test for syphilis, cutaneous manifestations, central nervous system involvement, and renal involvement) was analyzed.Of 54 patients with aPL, 33 showed significantly high levels of IgA aCL. Among them, IgA aCL coexisted with other aCL isotypes or LAC in 24 patients. The 9 patients with IgA aCL alone frequently had vasculitis associated manifestations, although thrombotic events and recurrent fetal loss were rare. Multivariate linear regression analysis showed that IgA aCL were independently associated with thrombocytopenia, skin ulcers, chilblain lupus, and vasculitis. There was also an association between IgM aCL and skin ulcers or chilblain lupus.Clinical manifestations of patients with IgA aCL differ from those of patients with IgG aCL. Determination of all 3 aCL isotypes and LAC is important to assess the risk of specific clinical manifestations in patients with aPL.

Lymph node metastasis is the most important prognostic factor in colon cancer. However, more accurate screening for metastasis than that afforded by conventional pathology remains elusive. We have employed a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for a matrix metalloproteinase (MMP), 'matrilysin', because this gene is epithelial-specific and consistently expressed in colorectal cancer cells. The sensitivity of this assay was examined with the matrilysin-producing rectal cancer cell line 'CaR-1'. Matrilysin mRNA was detected in this system when more than 10(4) matrilysin-positive cells existed in a lymph node of ordinary size. Fourteen of 15 (93%) primary colon cancers and none of the surrounding normal tissues expressed matrilysin. All 10 histologically-positive lymph nodes were positive for matrilysin, while of 60 histologically-negative lymph nodes, eight were positive for matrilysin. When the additional sequential sectioning and histological re-examination was performed on five of these eight 'matrilysin-positive, but histologically-negative' lymph nodes, micrometastases were detected in three. Only one of the lymph nodes that were histologically-positive, but negative by matrilysin assay was from a patient with colon cancer in which matrilysin was not detected. In conclusion, RT-PCR assay for matrilysin is a sensitive method for detecting occult metastases in patients with colon cancer, and may complement histologic examination.

We studied the efficacy of oral pilocarpine hydrochloride (9 mg/day, three times daily) on sicca symptoms in 21 patients with Sjögren's syndrome (SS) of the patients, 19 continued the treatment for at least one month, and subjective improvement of dry mouth and dry eye was observed in 10 patients (53%) and 5 patients (26%), respectively. As adverse effects, diaphoresis was most frequently recognized, but it was generally mild and tolerable. In the four patients who have been taking pilocarpine for 12 months, any severe side effects have not been observed. Since the incidences of clinical improvement of sicca symptoms and adverse effects were comparable with the other studies reported from US or Europe, our treatment protocol using pilocarpine hydrochloride (9 mg/day) was considered as appropriate for Japanese SS patients.

Imipenem/cilastatin sodium (IPM/CS) was administered to 102 patients with respiratory tract infections and lung cancer. Patients with other serious diseases were excluded and a total of 73 patients were enrolled. They were divided into 12 patients who underwent surgery (operated group) and 61 who did not (non-operated group); the latter group included 28 patients treated with anticancer agents or radiation therapy (treated group) and 33 untreated patients (untreated group). IPM/CS was effective in 75% of the patients, both with and without surgery. The drug was effective in 81% of the treated group, although many of the patients had Stage III or more advanced cancer, as well as bronchial occlusion. IPM/CS was also effective in 69% of the untreated group, although many of the patients have serious infections and a PS (Performance Status) of 3 or greater. Thus, IPM/CS treatment achieved good results. Bacteriological studies showed that 3 out of 4 strains in the operated group and 16 out of 18 in the non-operated group were eliminated. Safety was evaluated in all patients. Two patients (2%) experienced side effects and two others (2%) showed abnormal clinical findings, but the symptoms were mild and resolved after discontinuation or completion of therapy. In conclusion, IPM/CS was very effective for treating respiratory infections in patients with lung cancer.

The effects of the genotypes of CYP2E1, ALDH2, ADH upon the blood ethanol and acetaldehyde levels were investigated. The predicting 95% confidence bounds determined on regression analysis of the data suggested that after venous injection of ethanol, the blood ethanol and acetaldehyde concentrations in a volunteer normal homozygous for ALDH2 (ALDH2*1/1) were significantly lower than that heterozygous (ALDH2*1/2). And the blood ethanol and acetaldehyde concentrations in a volunteer with C2 allele (C1/C2) were significantly lower than that in (C1/1). However, there were no significant differences in the blood ethanol and acetaldehyde concentrations between volunteers with ADH2*1/1 and ALDH2*1/2. It is possible that the ALDH2*1 and C2 alleles may correspond to the lower blood ethanol and acetaldehyde concentrations after intravenous administrations of 0.2 g /kg of ethanol.

To clarify possible associations of decay-accelerating factor (DAF, CD55), expressed on circulating lymphocyte subsets and other hematologic cells, with corresponding cytopenias observed in primary Sjögren's syndrome (SS).DAF expression on peripheral blood (PB) cells was determined in 21 patients with SS and 11 healthy controls by single or 2 color flow cytometry.In the PB from SS patients, anemia, monocytopenia, neutropenia, and lymphocytopenia were observed. Compared to the controls, the percentages of DAF-negative cells were higher in CD4+ and CD8+ T cell subsets from SS patients, but the expression of DAF was similar in the other PB cells, including CD19+ B cells, CD56+ NK cells, monocytes, granulocytes, and erythrocytes. The percentages of DAF-negative cells among the CD4+ and CD8+ cells were positively correlated in SS patients, but the numbers of cells in both subsets were decreased in those patients being treated with prednisolone. However, these proportional changes are thought to reflect a decrease in the numbers of DAF-positive CD4+ and CD8+ cells, because the absolute numbers of circulating DAF-positive CD4+ and CD8+ cells, but not DAF-negative cells, were significantly decreased in SS patients. In addition, DAF-negative cells were detectable in both CD45RA+ (naive) and CD45RO+ (memory) T cells from healthy individuals, and the expression of DAF was remarkably increased in both subsets after in-vitro activation with concanavalin-A.DAF-negative cells are proportionally increased among circulating CD4+ and CD8+ T cells in SS patients, although such changes are due to decreased numbers of DAF-positive cells within each subset. When considering previous observations, the DAF-negative CD4+ and CD8+ cells probably belong to activated T cell subsets in both SS patients and controls. However, the patterns of DAF expression seemed to be different between activated T cells recognized in the PB, and those induced by in vitro-stimulation.

We evaluated the incidence of synchronous or metachronous multiple primary cancer, hereditary or familial cancer, and the familial aggregation of cancer in 142 patients who were treated for endometrial cancer at Tsukuba University Hospital in the period 1977 to 1995. Synchronous multiple primary cancers were identified in 6 of the 142 patients (4.2%). Eleven patients (7.7%) had a history of extraendometrial cancer. Patients with endometrial cancer had a significantly high incidence of a history of breast cancer. Endometrial cancer was diagnosed in two patients who were screened before menopause. Four patients with endometrial cancer (2.8%) subsequently developed extraendometrial forms of cancer. One patient (0.7%) was considered to have a hereditary form of cancer, and 5 patients (3.5%) had familial forms of cancer. A total of 86 cases of cancer were found among 53 kindred (37.3%). More detailed studies are needed to elucidate the aggregation of cancers in the families of patients with endometrial cancer in Japan. Patients with a history of breast cancer should be screened for the presence of endometrial cancer.

The glutathione S-transferase (GST) pi has been studied in association with the mechanisms of multidrug resistance and as a marker for malignant tumors. In this study, specimens from 92 cases of cervical neoplasms and 10 cases of normal squamous epithelium adhering to myoma were stained immunohistochemically with a rabbit polyclonal antibody to GST-pi. In 6 cases of normal squamous epithelium, the intermediate layer was positively stained with the GST-pi antibody. In all 20 cases of dysplasia, the cells with koilocytotic atypia were stained positively. In all 10 cases of carcinoma in situ and all 16 cases of stage Ia squamous cell carcinoma, various intensities of GST-pi staining were demonstrated. Forty-six specimens of stage Ib or more squamous cell carcinoma were positive for GST-pi binding except only one case. In general, squamous cell carcinoma of the uterine cervix is resistant to chemotherapeutic agents. GST-pi is most frequently stained in cervical squamous cell carcinoma as compared with ovarian or endometrial carcinoma. In conclusion, these results suggest that GST-pi may be a marker for cervical squamous cell carcinoma.

In a study to evaluate the usefulness of DMARDs combination therapy for RA, AF and MTX were concurrently given to RA patients who had responded poorly to over three months of monotherapy of either AF or MTX. The study was composed of two stages. In the first stage, patients were concurrently given AF and MTX for six months in order to evaluate the efficacy of combination therapy. In the second stage, patients who had responded to the earlier combination therapy were again put on monotherapy of the additive DMARD. Safety evaluation was conducted with 126 patients, and both efficacy and utility were evaluated in 100 patients. Lansbury index for RA significantly improved in both groups of patients starting with the AF and followed by the MTX combination (Group I) and those who started with MTX alone followed by the AF combination (Group II). The ratio of patients who achieved slight improvement or better in the overall improvement rating was significantly higher in Group I at 74.6%, vs. 51.1% in Group II patients. Ten patients (16.9%) and 2 patients (4.9%) were switched to their additive DMARD monotherapy of MTX and AF respectively, having responded to the combination therapy in stage I with slight improvement or a better rating. Adverse events were observed in 44 patients (34.9%), but the combination therapy neither increased the incidence of adverse events nor caused new adverse events. Combination therapy of AF and MTX appeared to be useful both in terms of efficacy and safety for patients who have experienced the dwindling effect of monotherapy.

We determined fluctuations in circulating lymphocyte subsets induced by methylprednisolone pulse therapy (MPT) and the continuous administration of prednisolone (PSL) in 17 patients with autoimmune or systemic rheumatic disease. Two-color flow cytometry, using monoclonal antibodies to various lymphocyte subsets, was performed to identify a possible association between the clinical efficacy of treatment and modulative effects on each subset. Both MPT and continuous oral PSL showed suppressive effects on most of the lymphocyte subsets: CD4+, CD45RA or CD45RA+CD4+, CD8+, CD11b.CD8+, CD5+ B, and CD57+ or CD57 CD16+ cells. Modulation of lymphocyte subsets were more profound with MPT than with continuous oral PSL. The results are relevant to the different degrees of immuno-suppression effected by the two treatment modalities. We found that the number of CD45RA.CD4+ cells after MPT treatment correlated with the clinical efficacy of the treatment: the less CD45RA.CD4+ cell numbers decreased after MPT treatment, the greater was the clinical efficacy of the treatment. The results probably are associated with a rapid recovery of the subset after MPT treatment in the responders. Thus, the sequential monitoring of circulating lymphocyte subsets is useful in predicting the clinical effects of MPT treatment.

Left lateral chest radiographs with normal studies were evaluated in 100 Japanese (50 females and 50 males) to compare the radiolucency of the retrosternal space (RSS) with that of the retrocardiac space (RCS) and to measure the RSS. In 56 (56%) cases, the RSS was equally radiolucent to the RCS. In 40 (40%) cases, the RSS was less radiolucent than the RCS (33 of 50 females and 7 of 50 males). The difference between the sexes was statistically significant (p = 0.0001). The RSS was more radiolucent than the RCS in only 4 (4%) males. Frontal chest radiographs of 50 females were classified into one of three groups (Small, Medium, or Large) depending on the size of soft tissue opacity of the breast. The differences between the radiolucency of the RSS and RCS were statistically significant between the Small and Medium and the Small and Large groups (both p0.0001). The strength of the relationship between the radiolucency and body-to-fat ratio was statistically significant (p = 0.0028). Results of data comparison between females and males remained significant when adjusted for differences in body-to-fat ratio (p0.0001). The distance on the chest radiograph from the sternum to the most anterior aortic border (the distance of RSS) could be measured on only 37 (37%) lateral chest radiographs, and the averages and standard deviations were as follows: 2.2 +/- 0.5 in all cases, 2.0 +/- 0.5 in females, and 2.4 +/- 0.5 in males. The difference between the sexes was statistically significant (p0.05). In conclusion, an RSS that is more opaque (less radiolucent) than the RCS is a frequent normal finding because of the opacity of the breast and fat tissue, especially in females, and the length of the RSS is shorter in females than in males.

Abnormalities of prostanoid metabolism, which may affect renal function, were studied in lupus nephritis. The subjects were 31 patients with lupus nephritis, ten with non-renal SLE, and four with renal, non-SLE collagen disease. Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-PGF1α,2,3-dinor-6-keto-PGF1α and PGE2, and plasma level of 11-dehydro-TXB2were determined. The effects of four days' dosing of a selective thromboxane A2(TXA2) synthetase inhibitor, DP-1904 (DP), on pros tanoid metabolism, were also studied.Urinary excretion of TXB2, which reflects the renal production of TXA2, was signifi cantly increased in the patients with lupus nephritis as compared with non-renal SLE (p < 0.05). The urinary TXB2/6-keto-PGF1α ratio was also increased in lupus nephritis as compared with non-renal SLE or healthy controls (p < 0.01), indicating a prostanoid imbal ance, which may lead to impaired renal function and subsequent pathology. The urinary TXB2/6-keto-PGF1αratio in these lupus nephritis patients showed negative correlations with Ccr and positive correlations with anti-DNA antibody titer (p < 0.001).DP was administered orally (400 mg/day, given in two divided doses) for four days to eight lupus nephritis patients. The urinary excretion of TXB2and urinary TXB2/6-keto- PGF1α ratio were decreased after one to two days of treatment in all patients. An increase in creatinine clearance used as a measure of renal function was observed in four of eight patients. Furthermore, no side effects were elicited during the four days of treatment.The conclusions reached were that the abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function through hemodynamic mediation, and that the deviated metabolism was reversible and, at least partially, corrected by a TXA2syn thetase inhibitor.

The object of the present study was to confirm the HLA-DRB1 matching effect on rejection crisis, its severity, and kidney graft survival based on genotyping. Ninety-four renal allografts were included in this study. DNA typing of HLA-DRB1 was performed by the polymerase chain reaction sequence-specific oligonucleotide method. The incidence of acute rejection within 6 months following transplantation, the frequency of OKT3 administration for steroid-resistant rejection, histopathological findings, and graft survival rate were compared between the DRB1-matched (n = 23) and DRB1-mismatched (n = 71) groups. Four acute rejections occurred in the DRB1-matched group (incidence; 17%) and 40 in the DRB1-mismatched group (56%). In the DRB1-matched group, the incidence of acute rejection was significantly less frequent than that of the DRB1-mismatched group (P0.005). In the DRB1-matched group, only one patient received OKT3 administration (4%), in contrast to 16 of 71 patients in the DRB1-mismatched group (23%). The use of OKT3 was significantly less frequent in the DRB1-matched group (P0.05). Histopathological findings from biopsy specimens showed no constant distribution of pathological grades of acute rejection according to DRB1 matching in the present study. The graft survival rate in the two groups did not differ significantly, but the graft survival rate in the DRB1-mismatched group had a tendency to decrease as the grafts survived longer. In conclusion, the results of the present study confirm that HLA-DRB1 matching has marked beneficial effects on kidney transplants through reduction of the acute rejection rate and decrease of the severity of rejection, and suggest that improvement of graft survival will be obtained through kidney allocation to a DRB1-matched recipient.

We describe here an experience of successful treatment of systemic sclerosis (SSc) complicated with various gastrointestinal (GI) problems including pneumoperitoneum, pneumatosis cystoides intestinalis and malabsorption syndrome. A 35-year-old female had developed selerodactyly since February, 1990. She had been treated under the diagnosis of SSc at other hospital. She had required several hospitalizations because of nausea, vomitting and abdominal distension, but her GI symptoms had gradually deteriorated. In April 1993, she was referred to our hospital and admitted for the treatment of her GI problems. On admission, she had systemic cutaneous sclerosis and marked abdominal distension without peritoneal signs was recognized. Chest and abdominal roentgenograms demonstrated massive free air under the diaphragm, marked dilation of small and large bowels, and multiple intestinal cysts (pneumatosis cystoides intestinalis ; PCI). We treated her GI problems with various modalities combined with medications, oxygen breathing, intravenous hyperalimentation and hyperbaric oxygen therapy. Pneumoperitoneum and PCI had disappeared after 8 courses of hyperbaric oxygen therapy and her GI symptoms had been well controled by intravenous hyper alimentation. Thereafter, she has been on intermittent parenteral nutrition through subcutaneous port inplantation. During the courses of this treatment, she developed an episode of Wernicke-Kolsakoff (W-K) syndrome which was considered to associate with malabsorption syndrome. The W-K syndrome had recovered by intravenous administration of vitamin B1.

In 118 patients with common epithelial ovarian tumors (carcinomas and tumors of borderline malignancy) treated at Tsukuba University Hospital and Tsukuba-Gakuen Hospital, family histories of ovarian and breast cancer were obtained from medical records or in interviews, and familial aggregation of these cancers was examined. 1. A positive family history was found in 10 patients (8.5%). The high incidences of familial ovarian cancer and ovarian cancer in patients who were previously affected with breast cancer were statistically significant. 2. Patients with serous adenocarcinoma showed a significantly greater rate of positive family history than those with mucinous adenocarcinoma. 3. No significant correlation was seen between the clinical stage and a positive family history. 4. Every patient except one with a positive family history had onset of ovarian cancer after menopause. The age at onset for familial ovarian cancer cases was younger than that for the patients' relatives who were affected previously. 5. There were 14 healthy women considered to be at high risk for ovarian cancer among 5 familial ovarian and 2 familial ovarian and breast cancer aggregations. These preliminary findings suggest that screening for early ovarian cancer should be conducted in high risk relatives of familial cancer patients and women affected with breast cancer previously. More detailed studies are needed to define the occurrence of familial or hereditary ovarian and breast cancers in Japan.

To clarify the pathological role of the apoptosis-related molecules expressed on peripheral blood (PB) lymphocyte subsets in primary Sjögren's syndrome (SS).The levels of apoptosis-regulating proteins, Fas and bcl-2, were determined in the PB lymphocyte subsets from 21 patients with SS and 14 healthy controls by 2-color flow cytometry.In the PB from SS patients, lymphocytopenia, especially CD4+ cell-lymphocytopenia, was prominent. As observed in previous studies, the percentages of CD4+ CD45RA+ cells were lower in the SS patients than in the controls, while activated (DR+) cells were increased in CD4+ cells from the patients. Fas+ cells were also increased in the patients' CD4+ cells and CD8+ cells, but not in their B cells or natural killer cells. Furthermore, we observed several positive correlations among the percentages of activated cells (DR+ cells or CD45RA-cells) and Fas+ cells recognized in the CD4+ and/or CD8+ cells from the patients. On the other hand, intra-cellular bcl-2 proteins measured as mean fluorescence intensity were significantly diminished in the CD4+ cells, CD8+ cells, CD19+ cells, CD45RO+ cells and Fas+ cells from 14 SS patients compared with 12 healthy controls. In addition, the numbers and/or percentages of CD4+ cells and Fas+ cells positively correlated with their expression of bcl-2 in SS patients.The abnormal balance between Fas and bcl-2 expression detected in the PB lymphocyte subsets from SS patients relates, at least partially, to the lymphocytopenia observed in the patients.

Although the incidence of pulmonary tuberculosis had been rapidly decreased in Japan, it is pointed out that the rate of decrease in annual incidence became smaller in recent years. This slowing down of the rate of decrease is considered to be resulted from an increase in number of individuals who are more susceptible to tuberculous infection; such as the elderly, young people who are not exposed to TB bacilli previously and therefore not immunized, patients with malignant disease or with organ transplantation and HIV-infected persons. Pulmonary tuberculosis still remained as a pulmonary infectious disease of highly ranked importance. Especially, miliary tuberculosis is life-threatening and occasionally fatal unless early intensive antituberculosis chemotherapy was started on the basis of a rapid and definite diagnosis. We made a retrospective survey to clarify the characteristic clinical features of miliary tuberculosis. For this purpose, we compared the characteristics and clinical features of 10 patients with miliary tuberculosis and those of 18 patients with severe pulmonary tuberculosis, not due to hematogenous dissemination. The mean ages of miliary tuberculosis group and that of severe pulmonary tuberculosis group were 62.6 and 63.8 years old, respectively, with no significant difference. Nine out of ten patients with miliary tuberculosis had fever as one of initial symptoms, whereas, all the patients with severe pulmonary tuberculosis had cough and sputa but they seldom developed fever (high fever) at the initial stage of their diseases. Duration from onset of symptom to the admission was 1.2 months on average in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical effectiveness of erythromycin for patients with diffuse panbronchiolitis (DPB) was previously recognized. However, it remains unknown what kind of airway lesions change with the clinical effectiveness induced by erythromycin. We performed the present study to clarify this unknown. We devised a method for scoring findings on high-resolution computed tomography (HRCT) to aid in the objective evaluation of the airway lesions in patients with DPB. The 18 patients with DPB were treated with oral erythromycin, 600 mg/d. All patients were evaluated by pulmonary function tests and HRCT before and after 3 months of therapy. Characteristic HRCT findings in patients with DPB pretherapy were small nodules, airway ectasia, periairway thickening, and mucus plugging. After erythromycin therapy, there was significant reduction in scores for the extent of small nodular opacities, the severity of periairway thickening, and the extent of mucus plugging with a corresponding significant improvement in results of the pulmonary function test parameters. The present study demonstrated reversible airway lesions in patients with DPB in response to erythromycin therapy.

Concentrations of thrombomodulin in blood plasma were measured by a one-step sandwich enzyme immunoassay (EIA). The concentrations in normal healthy subjects were 9.9 +/- 2.9 ng/ml. The concentrations were found to be significantly higher in patients with SLE, RA and other collagen diseases in their active stages than at their non-active stages. The concentrations increased in patients with DIC, and significantly higher levels were observed when DIC was complicated by multiple organ failure. These findings indicate that plasma concentrations of thrombomodulin may be a useful parameter for vascular injuries caused by inflammatory processes or coagulation/fibrinolysis reactions.

Peripheral blood stem cell (PBSC) transplantation (PBSCT) following high-dose chemotherapy is considered to be an effective and curative strategy for patients with certain malignancies. Optimal conditions for collection of PBSC and successful PBSCT, however, are still controversial. We performed 57 leukaphereses after 19 courses of chemotherapy for mobilization of PBSC (semi-high-dose VP-16 alone; 500 mg/m2/day for 3 or 4 days, 13 courses, or conventional chemotherapy; six courses) combined with subsequent G-CSF administration in 13 patients with malignancies (six with lymphoma, five with leukemia, and two with germ cell tumors). Total numbers of the CD34+ cells and CFU-GM obtained by multiple leukaphereses after one course of mobilization therapy were 0.63-168.74 x 10(6)/kg (mean 33.94) and 0.15-56.0 x 10(5)/kg (mean 8.22), respectively. We demonstrated that many cellular components of peripheral blood (PB) on the day of PBSC harvest, especially CD34+ cell, total leukocyte, myelocyte and monocyte counts, were correlated with the numbers of CFU-GM obtained in each leukapheresis. A daily increase of leukocyte counts was another useful indicator for the day of PBSC harvest. We also found that the time when total leukocyte counts in PB recovered to more than 5000/microliters or when CD34+ cells within PB mononuclear cells exceeded 1% was optimal for PBSC harvest. Our results confirmed that the semi-high-dose regimen with VP-16 combined with G-CSF is a safe method which has both antitumor effects and mobilization ability of PBSC in patients with hematological malignancies. PBSCT following various high-dose chemotherapy regimens with or without total body irradiation was also performed in 11 of the 13 patients, and rapid hematologic recovery was observed in all of the patients.

Recently, the roles of inflammatory processes in the pathogenesis of asthma have been emphasized. To elucidate the roles of T lymphocytes in local inflammatory sites in asthma, we examined T cell phenotypes with flow cytometry and carried out cytokine message amplification phenotyping (MAPPing) of bronchoalveolar lavage (BAL) cells taken from patients with steady-state asthma (n = 11). The percentage of CD4+ T cells in total lymphocytes correlated significantly (r = 0.784, p0.005) with that of lymphocytes in total CD45+ BAL cells. The positivities of T cell activation markers (CD25, HLA-DR) in CD4+ T cells were inversely correlated with the ratio of CD3+ T cells to total CD45+ BAL cells (CD25, r = 0.648, p = -0.059, HLA-DR, r = -0.741, p0.05). Most CD4+ T cells were of the CD45 RO+ "memory" phenotype. With cytokine MAPPing, IL-2 or IFN gamma were detected in only 2 of 11 patients, but IL4 or IL-5 were detected in 8 patients. These results suggest that non-activated TH2 type memory CD4+ T cells accumulate in local inflammatory sites of the bronchi of patients with steady-state asthma, and that these cells releases cytokines (IL-4, IL-5) when activated by some stimuli, which can lead to an asthma attack.

In the present study, we used the envelope method to divide patients with respiratory infections into two groups: a monotherapy group given imipenem/cilastatin sodium (IPM/CS) and a combination therapy group given imipenem/cilastatin sodium plus amikacin sulfate (AMK). We then compared the clinical efficacy and safety between groups. 1. Safety was evaluated in 83 patients in the IPM/CS group and 88 in the IPM/CS + AMK group while clinical efficacy was evaluated in 77 and 80 patients in the respective groups. 2. The overall efficacy rate was 84.4% in the IPM/CS group. Among the main infections, the efficacy rates were 82.7% in 52 cases of pneumonia (including lung abscess), 100% in cases of infected bronchiectasis, 66.7% in six cases of secondary infection of chronic respiratory disease, and 100% in four cases of chronic bronchitis. The overall efficacy rate was 83.8% in the IPM/CS + AMK group. Among the main infections, the efficacy rates were 88.1% in 59 cases of pneumonia (including lung abscess), 83.3% in 12 cases of infected bronchiectasis, and 60.0% in five cases of secondary infection of chronic respiratory disease. No significant differences in efficacies were seen between groups. 3. In the IPM/CS group, the efficacy rates were 92.3% for patients without prior antibiotic therapy in the IPM/CS group and 68.0% for those with prior therapy; in the IPM/CS + AMK group, the respective rates were 83.7% and 83.9%. In the IPM/CS group, there was a significant difference in the responses of patients with and without prior antibiotic therapy (P0.05). 4. Side effects were observed in six patients in the IPM/CS group (7.2%) and two patients in the IPM/CS + AMK group (2.3%). Abnormal laboratory test results were noted in 5 patients in the IPM/CS group (6.0%) and in 10 in the IPM/CS + f1p4group (11.4%). There was no significant difference in the incidence of side effects between groups and no severe adverse reactions in either group. These results indicate that IPM/CS alone produces of good response in moderate to severe respiratory infections while IPM/CS combined with AMK is useful in intractable respiratory infections.

In 34 hospitals in Kyushu area, the clinical effects and safety of fluconazole (FLCZ) against pulmonary mycosis were studied. To a total of 108 patients with respiratory diseases was FLCZ administered. The results were as follows. 1. Sixty-six cases were evaluable for the clinical efficacy of FLCZ. In 8 cases of pulmonary cryptococcosis, the clinical efficacy rate was 100% (8/8). In 58 cases of pulmonary aspergillosis, it was 43.1% (25/38). Overall, the clinical efficacy rate was 50% (33/66). 2. Fungi were eliminated in 3 of 6 cases in which Cryptococcus was detected, and were eliminated in 8 and reduced in 4 of 30 cases in which Aspergillus spp. including A. fumigatus were detected. 3. Side effects were observed in 5 of 87 cases (5.7%), none of them was serious, however. Abnormal results of laboratory tests that might be related to the FLCZ administration were observed in 5 cases (5.7%). 4. From these results, fluconazole appears to be a potent antifungal agent for treatment of pulmonary mycosis.