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[Development of a new technique to detect the laterality of microscopic hematuria by means of gas cystoscopy].

BACKGROUND: We developed a new technique to determine the laterality of microscopic hematuria by means of gas cystoscopy. METHODS: An originally designed catheter system consisted of two catheters. On the tip of an inner catheter, a urine dipstick for blood was attached, with a cap on the tip of an outer catheter to keep the dipstick dry. In order to react a dipstick with the urine coming out from a ureteral orifice in the bladder, CO2 was insufflated into the bladder through a cystoscope (gas cystoscopy). The laterality of microscopic hematuria was determined in the bladder, based on the color reaction on the dipstick. RESULT: This technique was performed successfully in 14 (88%) of 16 cases with microscopic hematuria. The laterality of microscopic hematuria was determined to be ipsilateral in 6 patients, which coincided with the side of a urological upper urinary tract disorder. In contract, bilateral microscopic hematuria was confirmed in 8 patients with glomerular disorders. CONCLUSION: The diagnostic process in patients with microscopic hematuria remains unsolved for urologists and nephrologists. This technique may provide a new approach in diagnosing microscopic hematuria.

Adult↗

Gains of 1q21-q22 and 13q12-q14 are potential indicators for resistance to cisplatin-based chemotherapy in ovarian cancer patients.

The mechanism of drug resistance in ovarian cancer is multifactorial, and accumulation of multiple genetic changes may lead to the drug-resistant phenotype. In our attempt to find characteristic genetic changes in drug-resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers using the comparative genomic hybridization method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy and 14 tumors from patients who had complete response to the chemotherapy. We found gains in chromosomal regions 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators, and regulators of the apoptotic pathway are located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance to cisplatin-based chemotherapy in ovarian cancer patients based on the comparative genomic hybridization analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients before cisplatin-based chemotherapy.

Antineoplastic Agents↗

[Development of blood examination method of serum amyloid A and LDL complex, and clinical application to prediction of cardiovascular event].

In recent years, it has been reported that the acute-phase proteins C-reactive protein(CRP) and serum amyloid A(SAA), the sera levels of which are elevated in inflammation, are also elevated in coronary artery disease such as acute myocardial infarction. Also, high-sensitivity CRP assay is thought to be useful in predicting the prognosis of coronary heart disease. While investigating complexes of acute-phase proteins and low-density lipoprotein(LDL), we found a complex of LDL and SAA(SAA/LDL complex). The SAA/LDL complex in blood are formed from LDL and HDL by an oxidation reaction. Therefore, we developed an ELISA using anti-human SAA antibody and anti-human apoB, and determined a new method for measuring SAA/LDL complex in sera. We evaluated SAA/LDL complex as a new marker for prediction of prognosis in addition to the ordinary markers in consecutive 140 patients with stable coronary heart disease who had at least 1 coronary artery stenosis more than 50% in diameter at the diagnostic coronary angiography. Of these 140 patients, 2 developed fatal myocardial infarction, 2 cerebral infarction, and 17 angina pectoris requiring coronary revascularization therapy during 1 year and 6 months after blood examinations. The SAA/LDL complex value in this EVENT group of 21 patients was significantly higher than that in the control group of 119 individuals. High-sensitivity CRP (hs-CRP) assay and SAA measurement showed no significant difference between the 2 groups. The SAA/LDL complex reflects intravascular inflammation directly and can be a new marker more sensitive than hs-CRP or SAA for prediction of prognosis in patients with stable coronary artery disease.

Acute-Phase Proteins↗

Characterization of the glomerular endothelial cell in culture.

Because of difficulties associated with the culture, cloning and propagation of glomerular endothelial cells (GENs), the biological properties of these cells remain largely unknown. We modified the methods established by Ballermann to propagate GENs from adult bovine kidney. We found that the addition of insulin, transferrin and selenium into the standard culture media was an important step in promoting the propagation of the first clone from a single cell and in maintaining the viability of the cells. These cells expressed factor VIII-related antigen and took up acetylated-LDL, but did not contain the Weibel-Palade body, unlike endothelial cells derived from large vessels. Furthermore, GENs were compared with aortic endothelial cells (AECs) to investigate the differences in culture conditions. Compared with AECs, GENs required a higher concentration of serum and the supplementation of growth factor to maintain their biological activity. In addition, GENs were very susceptible to trypsinization and produced prostaglandin E2 as a major cyclooxygenase product, whereas AECs produced PGI2. These findings suggest that GENs will be easily obtained from adult bovine kidney in culture and provide useful information on the functional properties of these cells under physiological and pathophysiological conditions.

Animals↗

Expression of heat shock protein 70 in grossly resected esophageal squamous cell carcinoma.

BACKGROUND: The aim of the present study was to use immunohistochemical methods to clarify the clinical implication of heat shock protein (HSP) 70 expression in esophageal squamous cell carcinoma and to investigate the function of HSP70 as a chaperone for p53. METHODS: Seventy-one patients with esophageal squamous cell carcinoma were admitted in the present study. Expression of HSP70 was analyzed by immunohistochemistry and correlated with TNM classification, vessel invasion, p53 expression, and clinical outcome after operation. RESULTS: Overexpression of HSP70 was related to sex (p < 0.05), tumor configuration (p < 0.05), lymph node metastasis (p < 0.01), and lymphatic vessel invasion (p < 0.05). Expression of p53 and HSP70 were not correlated with each other (p = 0.824). Esophageal squamous cell carcinoma with HSP70 expression exhibited a significantly better prognosis compared with HSP70-negative esophageal squamous cell carcinoma in univariate analysis (p < 0.05), but no significance was found in multivariate analysis. CONCLUSIONS: We suggest that HSP70 expression might be of use to assess the progression, lymph node metastasis, and lymphatic vessel invasion of esophageal squamous cell carcinoma. Inasmuch as both lymph node metastasis and HSP70 expression are prognostic variables in esophageal squamous cell carcinoma, examination of HSP70 expression may be of use to assess clinical outcome after operation.

Adult↗

Measurement of cystatin-C and creatinine in urine.

BACKGROUND: The concentration of serum cystatin-C (Cys-C) is highly correlated with creatinine (Cr), and is mainly determined by glomerular filtration; thus, Cys-C may be an index of the glomerular filtration rate (GFR). However, the kinetics of urinary Cys-C and Cr excretions are unclear. Thus, we investigated the kinetics of urinary Cys-C and Cr excretions, and examined whether the urinary Cys-C concentration can be used as a marker of renal function. METHODS: The urinary excretion of Cys-C and Cr was evaluated in 1670 healthy subjects and 217 patients with proteinuria. We also investigated the urinary Cys-C concentration in 52 patients with chronic renal failure. RESULTS: There was a good correlation between the urinary concentrations of Cys-C and Cr in the healthy group. This relation was also observed in patients showing persistent proteinuria without tubular cell damage. The mean urinary Cr concentration increased with age, and it was affected by the muscle mass. In contrast, the urinary Cys-C concentration was not affected by the muscle mass, and the concentration remained constant for all ages. We further found that the ratio of Cys-C to Cr (CCR) is a good index of the state of Cys-C reabsorption in the proximal tubules. CONCLUSIONS: The urinary CCR can be a marker of renal tubular dysfunction. In addition, when CCR was in the normal range, the urinary Cys-C concentration accurately reflected the glomerular filtration function.

Adolescent↗

Silent cerebral infarction in hemodialysis patients.

BACKGROUND: Cerebrovascular diseases are very common in hemodialysis (HD) patients. Silent cerebral infarction (SCI) has not been investigated in HD patients although it may be a significant risk factor for cerebrovascular diseases. HYPOTHESIS: Chronic renal failure may be an independent risk factor for SCI and cerebrovascular diseases. METHODS: Cranial magnetic resonance imaging (MRI) was performed on 123 HD patients without symptomatic cerebrovascular disease and on 52 control subjects. We investigated the prevalence of SCI and performed cross-sectional study using multiple logistic analysis to assess the relationship between SCI and the risk factors. RESULTS: The prevalence of SCI was significantly higher in HD patients than in the healthy control group (60 patients (48.8%) vs. 5 patients (9.6%), chi(2) = 22.4, p < 0.0001). Multiple logistic regression analysis with all subjects showed that independent risk factors of SCI were chronic renal failure, hypertension, smoking and age (R(2) = 0.468, p < 0.0001). In only the HD patient group, age and smoking were shown to be independent risk factors of SCI (R(2) = 0.378, p < 0.0001) while HD duration and hypertension were not. CONCLUSIONS: The findings of the present study indicate that chronic renal failure maintained by hemodialysis increases the prevalence of SCI and that age and smoking habits are also significantly associated with SCI in HD patients.

Age Factors↗

[Difference of optic disc topography between a low-tension group and a high-tension group in normal-tension glaucoma patients].

PURPOSE: Glaucomatous visual field loss and optic disc damage differ by intraocular pressure (IOP) levels. In this study, we compared the optic disc topography in the high-tension group and the low-tension group in normal-tension glaucoma (NTG). METHOD: We selected NTG patients with mean deviation (MD) > or = -10.00 dB and the highest recorded IOP of < 14 mmHg or > or = 17 mmHg without glaucoma treatment. We classified NTG eyes into the following two groups: 1) a low-tension group with the highest recorded IOP of < 14 mmHg, 2) a high-tension group with the highest recorded IOP of > or = 17 mmHg. The optic disc parameters in the low-tension group eyes were compared with those in the high-tension group eyes using a Heidelberg Retina Tomograph. RESULTS: Nineteen eyes of nineteen patients were selected for each group. The cup/disc area ratio in the global sector, and the rim volume in the nasal sector of the low-tension group had deteriorated more than in the high-tension group. CONCLUSIONS: The disc topography is different between the low-tension group and the high-tension group in the nasal sector, suggesting that different pathogenetic mechanisms exist in the optic disc damage in NTG.

Aged↗

[Study of chromogenic substrate on protein C activity assay--in patients treated with warfarin].

Protein C is an anticoagulant protein that circulates in blood as a zymogen of a serine protease. Recently the exogenous Protein C activator has been obtained from the venom of Agkistrodon Contortrix Contortrix. We also reported a functional assay method which activates Protein C with PROTAC and then measure the amidolytic activity with chromogenic substrate (S-2366) by COBAS FARA. At present, S-2366 (Glu-Pro-Arg-pNA), CBS 65-25 (Lys-Pro-Arg-pNA) and SPECTROZYME PCa (Lys-Pro-Arg-pNA) are used as the chromogenic substrate for activated Protein C. We studied which substrate is more suitable for amidolytic activity assay for Protein C by PROTAC in 99 patients under long-term Warfarin therapy and 29 as normal subjects. Our results indicate that SPECTROZYME PCa and CBS 65-25 are unsuitable for Protein C activity assay with PROTAC. Because change of absorbance was detected in Protein C deficient plasma and we couldn't gain good correlation between amidolytic activity of activated Protein C measured with these chromogenic substrates and antigenicity of Protein C by EIA. On the other hand, S-2366 is the most specific for activated Protein C and we also obtained good correlation against Protein C antigen.

Chromogenic Compounds↗

Gianturco-Rösch Z stents in tracheobronchial stenoses.

PURPOSE: To evaluate expandable metallic Gianturco-Rösch Z (GRZ) stents for treatment of benign and malignant tracheobronchial stenoses. PATIENTS AND METHODS: Six patients, ages 45-73 years, were treated for severe dyspnea with placement of GRZ stents. Three patients had benign tracheal lesions (one tracheomalacia, two postoperative) and received uncovered GRZ stents. Three patients had malignant stenoses at the level of the carina; one received an uncovered stent and the other two received silicone-covered GRZ stents. RESULTS: Two patients with benign lesions responded well to stent placement. One was asymptomatic for a year and then was lost to follow-up; the other improved substantially but died of end-stage lung disease 5 months after stent placement. A third patient with a benign high tracheal lesion did poorly; symptoms recurred secondary to inferior migration of a stent, which was removed surgically at 4 months. All patients with malignant lesions improved symptomatically after stent placement and remained without significant dyspnea until death (from 1 to 6 months). CONCLUSION: Expandable GRZ stents are promising devices for treatment of benign lesions and offer effective palliation of malignant tracheobronchial stenoses.

Aged↗

Assessment of pancreatic CT enhancement using a high concentration of contrast material.

OBJECTIVE: To evaluate the usefulness of pancreatic enhancement using a high concentration of contrast material in CT. METHODS: We performed abdominal CT on 125 patients after dividing them at random into five groups with two different concentrations, two different injection rates and three different injection doses: group A: 100 ml, 300 mgI/mL, 3 mL/sec; group B: 2 mL/kg, 300 mgI/mL, 3 mL/sec; group C: 1.5 mL/kg, 370 mgI/mL, 3 mL/sec; group D: 2 mL/kg, 300 mgI/mL, 5 mL/ sec; and group E: 1.5 mL/kg, 370 mgI/mL, 5 mL/sec. Among these five groups, the two groups given a concentration of 370 mgI/mL received a dose of 1.5 mL/body weight. RESULTS: The peak enhancement value of the pancreas was significantly greater in group E than in groups A and B. However, no statistically significant differences were found among the other groups. CONCLUSION: The fast injection rate using the high concentration of contrast medium provided greater enhancement of the pancreas than the slow injection rate using the routine concentration of contrast medium, and pancreatic CT enhancement depended more on the dose of iodine per second than on that of total iodine.

Adult↗

[In vitro activity of fluconazole, a novel bistriazole antifungal agent].

Fluconazole is a novel triazole antifungal agent with excellent activities against a broad range of medically important fungi. The in vitro antifungal activities of fluconazole especially against Candida albicans were examined and the results summarized as follows: 1. Fluconazole was proved to exhibit the highest antifungal activity in synthetic amino-acid medium, fungal (SAAMF), well buffered in a physiologically neutral range. 2. In a exposed time-killing test performed using SAAMF (pH 7.4), the growth inhibition by fluconazole was enhanced in proportion to an increase of fluconazole concentration and 99% inhibition was observed at a concentration of 1 microgram/ml though further increases of concentration up to 80 micrograms/ml failed to demonstrate complete inhibition. 3. Activities of fluconazole against medically important various yeasts were determined by a broth dilution method in SAAMF using the viable counts technique. Among 9 species tested, C. albicans and Candida kefyr were the most sensitive to fluconazole with a IC99 range from 0.20 microgram/ml to 0.39 microgram/ml. On the contrary, Candida glabrata, Cryptococcus neoformans and Trichosporon cutaneum were the least sensitive with a IC99 range from 3.13 micrograms/ml to 12.5 micrograms/ml. 4. Growth inhibition activities of fluconazole against 4 species of Aspergillus were measured on the basis of mycelial protein content. IC50 and IC90 of fluconazole against Aspergillus fumigatus were distributed in the range of 23.9-43.5 micrograms/ml and 50- greater than 100 micrograms/ml, respectively. 5. The anti-Candida activity of fluconazole was little affected by serum concentrations. Fluconazole at a concentration of 0.20 microgram/ml inhibited significantly the mycelial-phase growth and germ tube elongation of C. albicans in a medium supplemented with serum. 6. The germ tube formation and elongation of C. albicans cells engulfed by murine peritoneal exudative cells were significantly affected in a medium containing 1 microgram fluconazole per ml.

Animals↗

[Rastelli operation for congenital heart disease complicated with peripheral pulmonary artery stenosis].

Peripheral pulmonary artery stenosis following the occlusion of ductus arteriosus is not rare in patients with pulmonary atresia. It is also seen after the creation of Blalock-Taussig shunt for various types of cyanotic congenital heart disease. Although pericardial patch enlargement for the pulmonary artery stenosis has been done at corrective surgery, the results were unsatisfactory because of restenosis. So, we proposed and performed a new method of pulmonary artery plasty using large rectangular heterogeneous pericardium, by which pulmonary artery could be widely enlarged from the pulmonary trunk to periphery of the stenosis. A 3-year-old female (case 1) was diagnosed with pulmonary atresia, ventricular septal defect, patent ductus arteriosus and coronary anomaly associated with left pulmonary artery stenosis. She previously received left Blalock-Taussig shunt. Another patient was a 4-year-old male (case 2) diagnosed with double-outlet right ventricle, pulmonary stenosis and patent ductus arteriosus. He also received right Blalock-Taussig shunt and had left pulmonary artery stenosis. Both patients received Rastelli operation with pulmonary artery plasty simultaneously. Rastelli operation was performed using composite graft consisted of valved heterogeneous pericardial roll and knitted Dacron graft. Post operative courses were uneventful and they were doing well one year after operation. We consider that the pulmonary artery plasty with rectangular heterogeneous pericardial patch is an effective surgical procedure to avoid restenosis compared with conventional pericardial patch enlargement or balloon pulmonary artery plasty.

Blood Vessel Prosthesis↗

Clinical features of relative focal hyperfusion in patients with intracerebral hemorrhage detected by contrast-enhanced xenon CT.

BACKGROUND AND PURPOSE: The prevalence and clinical features of relative focal hyperperfusion were investigated in 165 consecutive patients with intracerebral hemorrhage. METHODS: Contrast-enhanced xenon CT was used to observe regional cerebral blood flow in all patients (86 men and 79 women ranging in age from 25 to 89 years; mean age, 66 years). The clinical data of patients with and without relative focal hyperperfusion were compared to define distinguishing characteristics. RESULTS: Relative focal hyperperfusion was observed in 24 (23.5%) of 102 patients in the acute stage but in no patient in the subacute or chronic stages. Relative focal hyperperfusion was associated significantly more often with putaminal and subcortical hemorrhage than with thalamic and cerebellar hemorrhage. We found that patients with relative focal hyperperfusion had a lower mean age than those without it; a male dominance; and a more common history of intracerebral hemorrhage. CONCLUSION: Relative focal hyperperfusion occurs in the acute stage after intracerebral hemorrhage and does not persist for more than 30 days. The most common locations are the putamen and subcortical areas. Risk factors include male sex and previous bleeding in the same area.

Adult↗

Complications of laparoscopic surgery in neonates and small infants.

PURPOSE: The difficulty of performing laparoscopic surgery in small infants remains a common complaint of pediatric surgeons. The aim of this study was to evaluate the complications of laparoscopic surgery in small infants weighing less than 5 kg. METHODS: Since 1997, 154 infants weighing less than 5 kg underwent laparoscopic surgery (group S). During that same period, 96 infants weighing less than 10 kg (group M) and 335 children weighing more than 10 kg (group L) also underwent laparoscopic surgery. Intra- and postoperative complications were evaluated and compared between the 3 groups, especially in the 60 cases that underwent Nissen fundoplication. P < .05 was considered a significant difference. RESULTS: Complications such as gastrointestinal perforation and wound infection were observed in 15 (9.7%), 15 (15.6%), and 32 (9.6%) infants of groups S, M, and L, respectively. There were no significant differences in complication rates among the 3 groups. However, in Nissen fundoplication, 5 of 15 patients in group S had complications, thereby significantly increasing the complication rate as compared with group L (1 of 23, P = .04). Major complications in group S were gastrointestinal perforation and vagal nerve injury. CONCLUSIONS: Laparoscopic surgery is feasible even in small infants. However, in Nissen fundoplication, special attention is necessary to avoid severe intraoperative complications.

Adolescent↗

Possible harmful effects on central nervous system cells in the use of physiological saline as an irrigant during neurosurgical procedures.

BACKGROUND: Physiologic saline is routinely used as an irrigant in neurosurgery especially in Japan. Cerebrospinal fluid (CSF) differs from physiologic saline in its concentration of inorganic salts, osmolality, and pH and is completely different insofar as it contains glucose, protein, cholesterol, and other lipids. The present study was designed to compare the possible functional and morphologic deleterious influence of these differences on cultured rat neural cells using saline (S), Ringer's solution with glucose (Lactec G, LG; Otsuka Pharmaceutical Co.; Tokyo, Japan) and without glucose (Lactec, L; Otsuka Pharmaceutical Co.), and an artificial CSF (ACSF). METHODS: Primary cultured rat neurons and astrocytes were divided into five groups according to the medium used, the four experimental groups (ACSF, L, LG, and S) and one control group (C). At various time points up to 24 hours, the rhodamine 123 uptake by neuronal or astrocytic cellular mitochondria was evaluated as cell function assessment. Morphologic assessment for both neuron and astrocyte culture was carried out with scanning electron microscopy (SEM) at the 24-hour time point. RESULTS: SEM showed little difference between the C and ACSF groups, whereas morphologic deterioration was particularly severe in the S group for both neurons and astrocytes. In the case of neuronal mitochondrial activity, the L and S groups demonstrated respectively severe and some deterioration, particularly in the mitochondria of the neuronal processes. The deleterious effects in mitochondrial activity of the S group were even more apparent in the astrocytic cells. CONCLUSION: These results suggest that physiologic saline, when used as an irrigant in neurologic surgery, might in some circumstances cause damage to exposed and compromised neural cells.

Animals↗

ras gene alterations in invasive and non-invasive rat bladder carcinomas induced by N-methyl-N-nitrosourea.

We have established a reliable method to induce invasive and non-invasive carcinomas in the heterotopically transplanted urinary bladder of rats by repeated injection of N-methyl-N-nitrosourea (MNU), and examined the alterations of the ras oncogenes and ras oncogene product (p21) in the induced tumours. The incidence of muscle-invasive carcinomas was proportional to the total dose of MNU. When 5, 6 or 12 doses of MNU were used, muscle invasive carcinomas developed in 22, 58 or 45% of animals, respectively, after a mean observation period, respectively, of 54 +/- 9, 45 +/- 13 and 38 +/- 3 weeks. Whereas activated H-ras gene was detected in only one non-invasive carcinoma by DNA transfection assay, seven of 18 non-invasive and invasive carcinomas showed activated ras p21 when examined by immunoblot analysis. Amplification or rearrangement of myc or epidermal growth factor (EGF) receptor gene was not observed. The results indicate that alterations of ras gene may be involved in the development of rat bladder carcinomas but not of invasiveness.

Animals↗

Recurrence of renal cell carcinoma more than 5 years after nephrectomy.

OBJECTIVES: We evaluated clinical features and predictive factors for the recurrence of renal cell carcinoma (RCC) developing more than 5 years after nephrectomy. METHODS: We retrospectively reviewed 239 patients with RCC who underwent surgery for the primary lesion. To identify factors that affected recurrence more than 5 years after nephrectomy (delayed recurrence) and its clinical outcomes, we performed a multivariate analysis using Cox's proportional hazards model and a survival study. RESULTS: Recurrence developing within 5 years after nephrectomy (early recurrence) was found in 57 patients and delayed recurrence in 11 patients. The multivariate analysis revealed no clinical and pathologic features influencing delayed recurrence in 114 patients who survived more than 5 years after nephrectomy without having early recurrence. The patients with delayed recurrence showed better clinical outcomes than those with early recurrence when the rate was determined from the time of recurrence. CONCLUSIONS: Although delayed recurrence is not a rare event for patients with RCC, no clinical and pathologic factors at the time of the initial treatment can predict the recurrence. Patients who are free of recurrence for more than 5 years after surgery for a primary lesion should be carefully followed up for delayed recurrence.

Adult↗