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PubMed2005

A prognostic role of mean 24-h pulse pressure level for cardiovascular events in type 2 diabetic subjects under 60 years of age.

OBJECTIVE: To assess the prognostic role of ambulatory 24-h pulse pressure (PP) on various vascular events in relatively young type 2 diabetic subjects under 60 years of age. RESEARCH DESIGN AND METHODS: In this prospective study, 237 type 2 diabetic subjects without any history of vascular complications were analyzed. After excluding 9 dropout subjects, 228 subjects (mean age, 46 years; 69% men; mean follow-up period, 100 months) entered the study. RESULTS: Distribution of 24-h PP for all subjects showed left skewed data, indicating that there may be a diabetic subgroup that had a wide PP. Therefore, further analysis was performed by stratifying the diabetic subjects by quartile of 24-h PP. Outcomes for the widest quartile (n = 58; cut point = 53.3 mmHg) was then compared with those from the other narrower quartiles (n = 170). In the diabetic subjects with a wide PP, cardiovascular events occurred more frequently than those in the diabetic subjects with a narrow one (20.7 vs. 4.1%; P < 0.001), resulting in the significant difference in the cumulative incidence of cardiovascular events (P < 0.001, log-rank test), but not cerebrovascular events, between the two subgroups. The Cox model revealed that a wide 24-h PP at baseline independently predicted subsequent cardiovascular events but not cerebrovascular events. By contrast, only duration of diabetes was the risk factor for cerebrovascular events. CONCLUSIONS: This study showed that a wide 24-h PP is predictive for cardiovascular events in relatively young diabetic subjects.

Adolescent↗
PubMed2005

[Development of the Dementia Quality of Life Instrument-Japanese version].

AIM: The aim of this study was to develop the Dementia Quality of Life Instrument-Japanese version (DQoL-Japanese Version). METHODS: The subjects were 72 elderly patients, 19 men and 53 women (Vascular Dementia: 66, Senile dementia Alzheimer type 6) using day care and day services who had obtained approval for participation in the investigation. The interview survey was conducted from October 2002 to January 2003. RESULTS: In the subscales of the DQoL-Japanese Version, "negative feelings" scored the highest and "affirmative feelings" the lowest. There was a significant correlation coefficient between the test and those of a conducted 2 weeks later, ranging from 0.730 to 0.857 (p<0.05). The internal consistency reliability for the five scales ranges from alpha=0.66 to 0.864. There was a significant correlation coefficient between the Geriatric Depression Scale (GDS) and DQOL sub-scales such as "self esteem," "positive affect", "negative feelings" and "feeling of belonging". On the other hand, there was no significant relationship between the GDS and "aesthetics" of the DQoL-Japanese Version. CONCLUSIONS: It was suggested that the DQoL-Japanese Version DQoL is useful to measure subjective QOL of elderly patients with dementia. The subjects who understood the questions of the DQoL-Japanese Version and were able to be interviewed, had a Mini-Mental State score of 13 points or more. It was clarified that DQoL-Japanese Version was reliable and showed evidence of validity as well as the original DQOL.

Dementia↗
PubMed1992

Zinc iodide-osmium tetroxide impregnation of the "tubulo-vesicular system" in Tomes' process of the rat incisor ameloblast.

Zinc iodide-osmium tetroxide (ZIO) is a nonspecific but selective impregnation method that visualizes a tubulo-vesicular system in cells. The detailed structure and three-dimensional distribution of this ZIO-impregnated system was studied in the Tomes' process of secretory ameloblasts in the rat incisor. The ZIO-impregnated system consisted of an extensive array of smooth membrane-bound thick and thin tubules and vesicles. The interconnected thick and thin tubules formed a complex "core network" in the central cytoplasm of Tomes' process that enmeshed and often surrounded individual secretory granules. From the core network, radial branches extended toward the smooth cell membrane of the interdigitating portion of Tomes' process. Although the core network and branches frequently appeared connected to the secretory granules and the cell membrane, stereo-pair electron microscopy failed to show conclusive evidence of such continuity. However, many coated vesiclelike structures were attached to the core network and its branches. No special relationship was found between interrod and rod secretory sites and the tubulo-vesicular network. In thick sections, the ZIO-impregnated tubulo-vesicular network occupied a considerable volume of cytoplasm. The vinblastine-labile nature of this network as demonstrated previously (Nanci et al., 1987) indicated that the system undergoes rapid and extensive turnover. Considering the dynamic nature and sheer volume of the tubulo-vesicular system, we propose that it be regarded as a major cell organelle.

Ameloblasts↗
PubMed1998

A new in-vitro drug sensitivity test (collagen-gel droplet embedded-culture drug sensitivity test) in carcinomas of pancreas and biliary tract: possible clinical utility.

The collagen-gel droplet embedded-culture drug sensitivity test (CD-DST), a chemosensitivity test, evaluate the efficacy of anticancer drugs and to was used clinically to thus plan rational postoperative chemotherapy for patients with pancreatic and biliary tract carcinomas. The CD-DST solves some problems inherent in other conventional assays. This method: (1) allows evaluation of four chemotherapeutic agents, using small quantities of cells (1 x 10(5) cells), (2) shows high primary culture success rates, (3) maintains the original growth characteristics of the cultured cells, (4) eliminates the effects of fibroblasts by employing image analysis, and (5) permits evaluation using physiologic drug concentrations. Primary cultures of tumor cell samples from all 25 patients with pancreatic or biliary tract carcinomas studied were successful. Against pancreatic carcinomas, the efficacy rates, assessed by CD-DST, of four anticancer drugs evaluated were: 25.0% for mitomycin (MMC), followed by 23.5% for adriamycin, 18.8% for 5-fluorouracil (5-FU), and 11.8% for cisplatin (CDDP). Against biliary tract carcinomas, the rates were highest for 5-FU and MMC (50.0%) and lowest for CDDP (25.0%). The efficacy rates for all four anticancer drugs evaluated were higher against biliary tract carcinomas than against pancreatic carcinomas. Tumor cultures from 10 of 17 patients with pancreatic cancer and 3 of 8 patients with biliary tract cancer showed no sensitivity to any of the drugs tested. The in-vitro results with CD-DST suggest the risk of administering non-selective postoperative chemotherapy to patients with pancreatic and biliary tract carcinomas, and emphasize the importance of carefully selecting effective chemotherapeutic agents based on adequate chemosensitivity testing.

Antineoplastic Agents↗
PubMed2005

Osteoarthritis development in novel experimental mouse models induced by knee joint instability.

OBJECTIVE: Although osteoarthritis (OA) is induced by accumulated mechanical stress to joints, little is known about the underlying molecular mechanism. To apply approaches from mouse genomics, this study created experimental mouse OA models by producing instability in the knee joints. METHODS: The models were of four types: severe, moderate, mild, and medial, depending on the severity and direction of instability imposed by combinations of ligament transection and menisectomy. OA development was evaluated by X-ray and histology by Safranin-O staining, and quantified using our original gradings. Expressions of type II, IX and X collagens and matrix metalloproteinase (MMP)-2, -3, -9 and -13 were further examined by immunohistochemistry and in situ hybridization (ISH). RESULTS: The severe, moderate and mild models exhibited OA development in the posterior tibial cartilage. The severe model showed cartilage destruction at 2 weeks and osteophyte formation at 4-8 weeks after surgery; however, the mild model showed only a partial cartilage destruction at 8 weeks. The grading confirmed that the OA disorders progressed depending on the severity of joint instability. In the medial model, the OA development in the medial tibial cartilage was similar to that in the posterior cartilage of the mild model. Among the collagens and MMPs, type X collagen and MMP-13 were markedly induced and colocalized in the early stage OA cartilage. CONCLUSION: We established four types of mouse models exhibiting various speeds of OA progression. By applying a mouse genomics approach to the models, molecular backgrounds in various stages of OA development can be clarified.

Animals↗
PubMed2007

Comparative evaluation of central muscarinic receptor binding activity by oxybutynin, tolterodine and darifenacin used to treat overactive bladder.

PURPOSE: We characterized muscarinic receptor binding in the mouse cerebral cortex after oral administration of anticholinergic agents used to treat overactive bladder. MATERIALS AND METHODS: Muscarinic receptors in the mouse cerebral cortex and bladder after oral administration of anticholinergic agents were measured using [(3)H]N-methylscopolamine. RESULTS: In vitro binding affinities of tolterodine and its metabolite 5-hydroxymethyl metabolite in the mouse cerebral cortex and bladder were considerably greater than those of oxybutynin and darifenacin. Also, muscarinic receptor binding affinity of oxybutynin and its metabolite N-desethyl-oxybutynin in the cerebral cortex compared with that in the bladder was 2 to 3 times higher, whereas that of tolterodine and 5-hydroxymethyl metabolite was approximately 2 times lower. Oral administration of oxybutynin (76.1 micromol/kg), tolterodine (6.31 micromol/kg) and darifenacin (59.1 micromol/kg) showed binding activity that was approximately equal to that of bladder muscarinic receptors. Oral administration of oxybutynin (76.1 micromol/kg) showed significant binding of cerebral cortical muscarinic receptors in mice, as indicated by about a 2-fold increase in K(d) values for specific [(3)H]N-methylscopolamine binding 0.5 and 2 hours later. On the other hand, tolterodine and darifenacin given at oral doses that would exert a similar extent of bladder receptor binding activity as oxybutynin showed only a low level of binding activity of central muscarinic receptors in mice. CONCLUSIONS: Significant binding of brain muscarinic receptors in mice was observed by the oral administration of oxybutynin but not tolterodine and darifenacin.

Animals↗
PubMed2006

Increased basal platelet activity, plasma adiponectin levels, and diabetes mellitus are associated with poor platelet responsiveness to in vitro effect of aspirin.

INTRODUCTION: Aspirin is one of the most effective antiplatelet agents and is now commonly used to prevent vascular events. In some patients, however, recurrent vascular events have been demonstrated despite aspirin therapy. Our objective was to characterize individuals showing poor response to in vitro effect of aspirin, using PFA-100. METHODS: One hundred sixty-eight healthy male subjects were analyzed. We assessed platelet function tests, including PFA-100, whole blood aggregation, and optical platelet aggregation. Also measured were hemostatic and other parameters including von Willebrand factor (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), soluble vascular adhesion molecule-1 (sVCAM-1), high sensitive C-reactive protein (hs-CRP), and adiponectin. Poor responders were defined as having a collagen/epinephrine-induced closure time (CEPI-CT) under 250 s with PFA-100 when incubated with 10 microM aspirin, whereas good responders were defined as having a CEPI-CT of more than 250 s. RESULTS AND CONCLUSIONS: PFA-100 tests revealed that 40 subjects (24%) were poor responders (PR) and 128 (76%) were good responders (GR). Poor responsiveness was significantly associated with (1) higher basal platelet activities in PFA-100, as well as in whole blood aggregation and aggregometer;(2) increased level of adiponectin (8.8+/-4.1 micro g/mL [PR] vs 7.3+/-2.9 micro g/mL [GR], p=0.010);and (3) the presence of diabetes mellitus (17.5% [PR] vs 4.7% [GR], p=0.009). Importantly, whereas 24% of the subjects showed insufficient inhibition in PFA-100 when incubated with 10 microM aspirin, almost all subjects showed maximum inhibition with 30 microM aspirin. These observations suggest that higher doses of aspirin might overcome aspirin resistance.

Adiponectin↗
PubMed1998

Inhibitory effects of the herbal medicine Sho-saiko-to (TJ-9) on cell proliferation and procollagen gene expressions in cultured rat hepatic stellate cells.

BACKGROUND/AIMS: It is of extreme importance to prevent liver fibrosis and subsequent progression to liver cirrhosis. The aim of our study was to elucidate in vitro whether Sho-saiko-to exerted inhibitory effects on hepatic stellate cells. METHODS: Hepatic stellate cells were isolated from male Wistar rats. Water-soluble ingredients of Sho-saiko-to were obtained at concentrations of 10, 100, 250, 500 and 1000 microg/ml. Morphological transformation was observed under a phase-contrast microscope. Flow cytometric analysis was performed on day 4 after culture to evaluate the potential to proliferate of the stellate cells by analyzing cell cycles. Northern blot analysis was carried out on day 3 after culture to determine the expressions of type I and type III procollagen mRNAs. RESULTS: (i) Sho-saiko-to 500 and 1000 microg/ml inhibited morphological transformation of the stellate cells to myofibroblast-like cells. (ii) Sho-saiko-to 500 and 1000 microg/ml significantly (p<0.0001) accumulated the cells in the G0/G1 phase (118.8+/-0.7%, 119.2+/-0.5%, respectively as compared with control) and significantly (p<0.0001) decreased cell numbers subsequently in G2/M phase (47.5+/-8.1%, 48.9+/-2.0%, respectively). (iii) Sho-saiko-to 500 and 1000 microg/ml also significantly (p<0.05 or p<0.0001) suppressed procollagen mRNA expression of type I to 51.5+/-6.4%, 34.9+/-3.7%, respectively, and type III to 51.3+/-12.3%, 46.7+/-11.4%, respectively. CONCLUSIONS: We have clarified the inhibitory effects of Sho-saiko-to on hepatic stellate cells in vitro. Sho-saiko-to could be a potent inhibitor in the pathogenesis of liver fibrosis.

Adipocytes↗
PubMed2005

Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis.

BACKGROUND & AIMS: Basic fibroblast growth factor (bFGF) is a promising therapeutic agent for various diseases. It remains unclear, however, whether bFGF is effective for the treatment of inflammatory bowel disease. The aim of this study was to examine the efficacy of bFGF on 2 experimental murine colitis models and to investigate its molecular mechanisms. METHODS: We evaluated the effects of human recombinant bFGF (hrbFGF) on mice with dextran sulfate sodium (DSS)-induced colitis and mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis as well as normal mice. Body weight, survival rate, and histologic findings of the colonic tissues were examined. Gene expression of tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-2, transforming growth factor (TGF)-beta, mucin 2 (MUC2), intestinal trefoil factor (ITF), and vascular endothelial growth factor (VEGF) in the colonic tissues was determined. The proliferation activity of hrbFGF on the colonic epithelium was evaluated by immunohistochemistry. RESULTS: Rectal administration of hrbFGF ameliorated DSS-induced colitis in a dose-dependent manner. Gene expression of TNF-alpha was significantly reduced in the colonic tissues of mice with DSS-induced colitis treated with hrbFGF, whereas MUC2 and ITF messenger RNA expression was up-regulated. Rectal administration of hrbFGF significantly improved the survival rate of mice with TNBS-induced colitis and partially ameliorated colitis. hrbFGF significantly increased the number of Ki-67-positive cells in the colonic epithelium of normal mice, and up-regulated the gene expression of COX-2, TGF-beta, MUC2, ITF, and VEGF in the colonic tissues. CONCLUSIONS: Rectal administration of bFGF might be a promising option for the treatment of inflammatory bowel disease.

Administration, Rectal↗
PubMed2000

Screening for prostate cancer using prostate-specific antigen alone as a first-line checkup parameter: results of the health checkup system.

BACKGROUND: The incidence of prostate cancer in Japan is not very high but it is the most increasing malignant tumor form. To decrease the mortality from cancer, detection of early cancer and early treatment are most effective. As a primary screening for prostate cancer, measurement of serum prostate-specific antigen(PSA) added to the health checkup system has not been assessed. METHODS: Among males who received a health checkup during a 30-month period, serum PSA levels were measured in males who desired prostate cancer screening. The cut-off value for PSA was 4.0 ng/ml. Males with serum PSA levels exceeding this value were referred for further screening by digital rectal examination (DRE) and transrectal ultrasonography (TRUS). In secondary screening, in all males with PSA levels of 10.0 ng/ml or more and in males in whom PSA levels were within the gray zone (4.0-10.0 ng/ml) and either DRE or TRUS showed abnormal findings, systematic prostate sextant needle biopsy was performed. RESULTS: Of 24528 males who received a health checkup, 1125 (4.6%) underwent prostate cancer screening. In 60 (5.3%) of these males, PSA levels exceeded the cut-off value. In 34 of 50 males who received further screening, prostate biopsy was performed. Seventeen males were diagnosed as having prostate cancer. Detection rates of prostate cancer were 1.53% (17/1125) in males overall and 2.1% (17/819) in males > or =50 years old. In 16 of 17 males, clinically localized cancer was suggested. In 12 of these patients, radical prostatectomy was performed. No lymph node metastasis was detected in any patient. CONCLUSIONS: These results suggest that prostate cancer screening using PSA as a primary screening parameter during general health checkups is very useful for efficiently detecting early-stage prostate cancer.

Aged↗
PubMed2006

Population pharmacokinetics of darbepoetin alfa in haemodialysis and peritoneal dialysis patients after intravenous administration.

AIMS: To characterize the pharmacokinetics of darbepoetin alfa and covariate relationships in haemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Data were collected from 131 (63 HD and 68 PD) patients who received darbepoetin alfa intravenously. A total of 917 serum concentrations were available. The data were analysed by nonlinear mixed effect modelling using NONMEM with a model including endogenous erythropoietin production. In addition, the final model was evaluated using bootstrap resampling. RESULTS: The selected basic model was a two-compartment model with a combination of additive and the constant coefficient of variation error models. The significant covariates were weight (WT) for clearance (CL) and the volume of central compartment (V(1)), and the dialysis technique (DIA) for V(1). The typical values of CL and V(1) were 0.0807 l h(-1) and 2.51 l, respectively. V(1) in PD patients was 17% higher than in HD patients. With the introduction of WT in CL and WT and DIA in V(1), interindividual variability decreased from 27.1% to 20.6% in CL and from 29.1% to 21.8% in V(1). The mean parameter estimates from the bootstrap datasets were similar to those from the original dataset. Evaluation by bootstrapping showed that the final model was stable. CONCLUSIONS: The results of the present analysis suggest no dosage regimen change is warranted for darbepoetin alfa in HD and PD patients over the range of distribution of covariates included in this study.

Adult↗
PubMed1995

The forms and the levels of fecal PMN-elastase in patients with colorectal diseases.

OBJECTIVES: To compare the form of polymorphonuclear leukocyte (PMN)-elastase in feces with that in plasma and to investigate the usefulness of measuring fecal PMN-elastase levels in patients with colorectal diseases. METHODS: We examined PMN-elastase complexed with alpha 1-antitrypsin (alpha 1-AT), chymotrypsin, and alpha 2-macroglobulin by ELISA in feces and plasma. Fecal levels of total PMN-elastase were determined in patients with colonic polyp (N = 19), colonic cancer (N = 20), ulcerative colitis (UC; N = 36), colonic Crohn's disease (CD; N = 26), and in control subjects (N = 20). RESULTS: Most PMN-elastase was not complexed with alpha 1-AT, chymotrypsin, or alpha 2-macroglobulin in feces, whereas most plasma PMN-elastase was complexed with alpha 1-AT. Fecal concentrations and daily fecal excretion of PMN-elastase were significantly increased in patients with active UC (medians 54.8 micrograms/g, 15.14 mg/day) and active CD (41.5 micrograms/g, 10.24 mg/day) compared to those values in control subjects (0.6 micrograms/g, 0.11 mg/day) and in patients with colonic cancer (2.5 micrograms/g, 0.33 mg/day). In inactive UC and CD, these values (3.4 micrograms/g, 0.52 mg/day and 5.2 micrograms/g, 0.59 mg/day, respectively) were significantly lower than in active UC and CD, respectively. In UC, all patients whose rectal biopsies showed infiltration of PMN had high fecal PMN-elastase levels. CONCLUSIONS: Our results suggest that the measurement of fecal PMN-elastase concentrations are useful for monitoring the disease activity of UC and CD, especially when evaluating whether intestinal inflammation has disappeared completely.

Adult↗
PubMed1993

Aggressive pulmonary metastasectomy for soft tissue sarcomas.

BACKGROUND: To evaluate the efficacy of aggressive pulmonary metastasectomy for treating soft tissue sarcomas, the clinical data on the surgical management of 23 patients with extensive pulmonary metastases from soft tissue sarcomas were reviewed. METHODS: Between January 1973 and April 1991, 9 male patients and 14 female patients were treated. Their ages ranged from 13-68 years (median, 42 years). Twenty-one patients (91%) had bilateral and multiple metastases, and two patients had solitary metastasis. The number of resected metastatic nodules ranged from 1-110 (mean, 30.5). As an initial surgical approach, median sternotomy was used on 18 patients and lateral thoracotomy on 5 patients. Eleven patients underwent two or more explorations for recurrent metastases using lateral thoracotomy. The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was adopted in 10 patients since 1986. RESULTS: The actuarial 2-year and 5-year survival rates after the first pulmonary resection were 49.7% and 24.8%, respectively. Histologic type (alveolar soft part sarcoma versus synovial sarcoma, P < 0.025), histologic grade (G1 and G2 versus G3, P < 0.01), and metastatic localization (subpleural versus extrapleural, P < 0.005) were the most significant prognostic factors for aggressive pulmonary metastasectomy of soft tissue sarcomas. Application of laser surgery, absence of local recurrences, and absence of extrapulmonary metastases before pulmonary resection also correlated with better prognosis with borderline significance. CONCLUSIONS: Aggressive pulmonary metastasectomy for soft tissue sarcomas is a recommended procedure, even in the case of extensive metastases. The combination of median sternotomy and Nd:YAG laser-assisted surgery is a useful technique, especially in bilateral multiple pulmonary metastases.

Adolescent↗
PubMed2006

Long-term functional outcome of colonic J-pouch reconstruction after low anterior resection for rectal cancer.

PURPOSE: To evaluate the long-term functional outcome of colonic J-pouch reconstruction after low anterior resection (LAR) for rectal cancer in a prospective study. METHODS: We compared the functional outcome of 46 patients who underwent J-pouch reconstruction (J-group) and 49 patients who underwent straight anastomosis (S-group) after LAR for rectal cancer. We evaluated clinical function using a 17-item questionnaire about different aspects of bowel function. Physiologic reservoir function was evaluated by manovolumetry. RESULTS: Among the patients with an ultralow anastomosis (<or=4 cm from the anal verge), those in the J-group had fewer bowel movements during the day and at night, and less urgency, soiling, protective pad use, incontinence, and dissatisfaction with bowel function than those in the S-group. Among the patients with a low anastomosis (5-8 cm from the verge), those in the J-group had fewer bowel movements at night, and less urgency and soiling than those in the S-group. Moreover, reservoir function (reflected by the maximum tolerable volume, threshold volume, and compliance) was better in the J-group than in the S-group in both the ultralow and low anastomosis groups. CONCLUSION: J-pouch reconstruction after low anterior resection creates a better stool reservoir than straight anastomosis, especially when the anastomosis is less than 4 cm from the anal verge, resulting in a better quality of life 3 years after rectal cancer resection.

Adult↗
PubMed2002

Tympanometric findings in patients with enlarged vestibular aqueducts.

OBJECTIVES: The purpose of this study was to study systematically some relationships between the resonance frequency of the middle-ear transmission system and the volume of the endolymphatic duct and sac in patients with an enlarged vestibular aqueduct (EVA). STUDY DESIGN: Prospective study. METHODS: Thirteen patients (24 ears) with EVA, 17 subjects (29 ears) with normal hearing, and 17 patients (21 ears) with sensorineural hearing loss without EVA served as experimental subjects. Standard pure-tone audiometry, standard clinical tympanometry (using a 226-Hz probe tone), and multifrequency tympanometry were performed on each ear. Magnetic resonance imaging was used to determine the area of the cochlear modiolus and the volume of the endolymphatic duct and sac. RESULTS: The audiometric configurations for most patients sloped downward from the low to the high frequencies. A significant air-bone gap was computed at each of these test frequencies. Multifrequency tympanometry yielded resonance frequencies for the patients with EVA that was significantly lower than those measured for the control subjects. In general, for patients with EVA, the resonance frequency of the middle ear system decreased as the volume of the endolymphatic duct and sac increased. This inverse relation was significant (correlation coefficient = -0.483, P =.0157). However, there was no correlation between resonance frequency and the degree of cochlea modiolar deficiency. CONCLUSIONS: Clinically, our findings suggest that EVA probably should be included in the differential diagnosis for a patient who presents with a moderate to severe mixed hearing loss, a normal tympanogram at 226 Hz, and a resonance frequency that is abnormally low.

Acoustic Impedance Tests↗
PubMed1995

Proliferating cell nuclear antigen cyclin in human transitional cell carcinoma.

OBJECTIVES: To confirm the value of the proliferating cell nuclear antigen (PCNA) labelling index in relation to histological grade, stage and prognosis. MATERIALS AND METHODS: Tissue specimens from 56 patients (49 men, 7 women; mean age 65 years [range 34-86]) with newly diagnosed transitional cell carcinoma of the urinary bladder were stained by an avidin-biotin peroxidase method using an anti-PCNA monoclonal antibody. Immunohistochemical analysis was performed on ethanol-fixed, paraffin-embedded tissue sections obtained by endoscopic biopsy or transurethral resection (TUR). The PCNA labelling index was determined by counting the number of PCNA-labelled cells in the tissue sections. RESULTS: Grade 1 tumours averaged 5.1 +/- 3.0% labelling versus 10.9 +/- 5.2% in grade 2 tumours, and grade 3 tumours had a PCNA labelling index of 21.8 +/- 10.4%. The average labelling indices for superficial tumour (37 patients) and invasive tumour (19 patients) were 7.5 +/- 5.3% and 20.8 +/- 10.0%, respectively. A distant metastatic bladder tumour showed an average labelling index of 42.3%. To analyse survival, tumours with PCNA indices above and below the median level (12%) were compared. Those patients with an index of < 12% (the mean of all of the PCNA values) had a worse prognosis than those with an index of > 12%. The mean PCNA labelling indices in recurrent and non-recurrent tumours were 6.4 +/- 0.7% and 8.2 +/- 1.7%, respectively, statistically not significant. CONCLUSION: The higher PCNA labelling index may indicate biological malignancy. These results suggest that measurement of the PCNA labelling index in bladder cancer may prove to be an objective and quantitative assay of biological aggressiveness and provide significant prognostic information, though it does not help to select patients at high risk of recurrence in superficial tumours.

Adult↗
PubMed2007

Recurrent renal hyperparathyroidism caused by parathyromatosis.

BACKGROUND: Parathyromatosis is defined as multiple foci of benign hyperfunctioning parathyroid tissue in the neck or mediastinum. Parathyromatosis is a problematic cause of recurrent hyperparathyroidism (HPT). In renal HPT, the stimuli of the parathyroid cells persist after parathyroidectomy (PTx), and for this reason, parathyromatosis might be important in renal HPT. METHODS: Between July 1973 and December 2005, 1,932 patients underwent PTx for advanced renal HPT in our department. We evaluated the frequency, clinical findings and the prognosis of this kind of parathyroid disorder. RESULTS: After total PTx with forearm autograft for renal HPT, which was performed initially in our department, the risk for developing parathyromatosis was 0.11% (2/1837); after sub-total PTx, it was 5% (1/20). The risk for developing parathyromatosis was lower after total PTx with forearm autograft than after sub-total PTx (P < 0.05). In patients who developed persistent or recurrent HPT and were referred to our department for neck re-operation, parathyromatosis occurred in 12.1% (7/58); in those originally operated on at our hospital, the corresponding figure was 7.1% (3/42). This difference was not significant (P = 0.42). Only in 4 of 10 patients was parathyromatosis suggested before re-operation. However, in spite of several re-operations, high parathyroid hormone (PTH) levels persisted in 6 of 10 patients with parathyromatosis. CONCLUSION: Parathyromatosis is a non-negligible cause of recurrent renal HPT in patients who require neck re-exploration. Parathyromatosis is difficult to diagnose pre-operatively and completely controlled by re-operation. Parathyromatosis should be kept in mind when performing neck re-exploration for recurrent renal HPT.

Adult↗
PubMed2000

Immunohistochemical localisation of protein tyrosine kinase receptors Tie-1 and Tie-2 in synovial tissue of rheumatoid arthritis: correlation with angiogenesis and synovial proliferation.

OBJECTIVE: To investigate the involvement of Tie-1 and Tie-2, receptor tyrosine kinases required for angiogenesis, in synovial proliferation and angiogenesis of rheumatoid arthritis (RA). METHODS: Synovial tissues from 10 patients with RA and three control subjects were analysed by double immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Expression of Tie-1 and Tie-2 was seen in all synovia, but predominantly in papillary projected portions. In synovial lining cells, Tie-2 was expressed mainly in the basal layer and frequently colocalised with vimentin and proliferating cell nuclear antigen (PCNA), whereas Tie-1 was also expressed in the superficial layer. In stromal cells, Tie-2 immunoreactivity was restricted to vimentin positive fibroblast-but not macrophage derived cells, whereas Tie-1 expression was not dependent on the phenotype. Tie receptors were also highly expressed in the endothelium and surrounding pericytes of capillaries scattered over the papillary proliferated synovium without notable difference in the expression of the two receptors. Furthermore, Tie positive vessels often overexpressed PCNA. In normal synovia, expression of Tie receptors was restricted to the capillary endothelium. RT-PCR confirmed the expression of Tie-1 and Tie-2 in RA synovial tissues and also in the cultured synoviocytes. CONCLUSION: The results suggest the possible involvement of overexpressed Tie-1 and Tie-2 in synovial lining and stromal cells in the pathophysiology of RA synovitis, probably through distinct mechanisms. Furthermore, expression of Tie receptors in actively growing vasculature may reflect the direct involvement of these receptors in angiogenesis and subsequent vascularisation.

Adult↗