bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling and simulation of the human δ opioid receptor
Authors: Aburi Mahalaxmi , Smith Paul E. 
Published: July 2004

AbstractA model for the human δ opioid receptor has been generated via sequence alignment, structure building using the crystal structure of bovine rhodopsin as a template, and refinement by molecular dynamics simulation. The model building suggested that, in addition to the previously postulated interaction between D128 and Y308, an internal salt bridge also exists between residues D128 and R192, both of which are conserved in all the opioid receptors. The model and salt bridge were then shown to be stable during a 20‐nsec simulation in a lipid bilayer. It is therefore proposed that both of these interactions play a role in stabilizing the inactive state of the receptor. The model is also used in an effort to rationalize many of the mutational studies performed on δ opioid receptors, and to suggest a plausible explanation for the differences between known δ opioid agonists and antagonists.
A mobile loop order–disorder transition modulates the speed of chaperonin cycling
Authors: Shewmaker Frank , Kerner Michael J. , Hayer‐Hartl Manajit , Klein Gracjana , Georgopoulos Costa , Landry Samuel J. 
Published: July 2004

AbstractMolecular machines order and disorder polypeptides as they form and dissolve large intermolecular interfaces, but the biological significance of coupled ordering and binding has been established in few, if any, macromolecular systems. The ordering and binding of GroES co‐chaperonin mobile loops accompany an ATP‐dependent conformational change in the GroEL chaperonin that promotes client protein folding. Following ATP hydrolysis, disordering of the mobile loops accompanies co‐chaperonin dissociation, reversal of the GroEL conformational change, and release of the client protein. “High‐affinity” GroEL mutants were identified by their compatibility with “low‐affinity” co‐chaperonin mutants and incompatibility with high‐affinity co‐chaperonin mutants. Analysis of binding kinetics using the intrinsic fluorescence of tryptophan‐containing co‐chaperonin variants revealed that excessive affinity causes the chaperonin to stall in a conformation that forms in the presence of ATP. Destabilizing the β‐hairpins formed by the mobile loops restores the normal rate of dissociation. Thus, the free energy of mobile‐loop ordering and disordering acts like the inertia of an engine's flywheel by modulating the speed of chaperonin conformational changes.
Our experience with 23 consecutive patients on gemcitabine/carboplatin chemotherapy for treatment of metastasized transitional cell carcinoma of the urothelium
Authors: HOSCHKE BERND , MAY MATTHIAS , SEEHAFER MATTHIAS , HELKE CHRISTIAN 
Published: July 2004

Abstract  Aim:  To evaluate the activity and toxicity of gemcitabine plus carboplatin in patients with metastatic transitional cell carcinoma (TCC) of the urothelium.Methods:  Twenty‐three consecutive patients (from February 1999 to January 2002) with metastatic TCC and no prior chemotherapy were referred to our institution. Each patient was treated with gemcitabine (1000 mg/m2) on Days 1 and 8 and carboplatin (area under curve, 4.5) on Day 1. Cycles were repeated every 21 days until tumor progression or severe toxicity was seen, or for a maximum of six cycles. Median age of the patients was 68 years (range 47–82). The median Eastern Cooperative Oncology Group (ECOG) performance score was one and the median creatinine clearance rate was 56 mL/min (range 31–94).Results:  The overall response rate was 60.8%, with five of the 23 patients achieving a complete response, and nine showing a partial response. Median time to tumor progression (TTP) was 7.8 months, with a median survival of 15.4 months and a 1‐year survival probability of 56%. Most of the complications from toxicity were hematological.Conclusions:  Gemcitabine plus carboplatin is active in the treatment of metastatic urothelial cancer in those patients new to chemotherapy and has an acceptable safety profile. The potential clinical benefit of this novel combination in the treatment of transitional cell carcinoma warrants further testing in Phase III studies.
Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer
Authors: ONOZAWA MIZUKI , KAWAI KOJI , YAMAMOTO TAKAHIRO , HINOTSU SHIRO , TSUKAMOTO SADAMU , HATTORI KAZUNORI , MIYANAGA NAOTO , SHIMAZUI TORU , AKAZA HIDEYUKI 
Published: July 2004

Abstract  Background:  Since the advent of cisplatin‐based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND.Methods:  Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non‐seminoma in 16 cases. All of the patients with non‐seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs.Results:  Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non‐seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non‐seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha‐fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm.Conclusions:  Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.
Histopathological aspects of transitional cell carcinoma of the bladder: Analysis of 20 years experience
Authors: SCIARRA ALESSANDRO , DE MATTEIS ANNA , MARIOTTI GIANNA , VORIA GIUSEPPE , LUCERA ROSSANA , DI SILVERIO FRANCO 
Published: July 2004

Abstract  Background:  In this study we used histopathological examinations performed over a 20‐year period to describe the characteristics of newly diagnosed transitional cell carcinoma (TCC) of the bladder in relation to patient age, and to verify changes in the TCC over different periods of observation or in relation to patient age.Methods:  We reviewed all histopathological examinations performed from January 1979 to December 1998 in patients undergoing surgery who were newly diagnosed with TCC of the bladder. All examinations were performed by the same pathologist and reviewed by two pathologists. In each case analyzed, we evaluated T classification of the tumor, histological grade, size, localization, growth type, multiplicity and carcinoma in situ (CIS).Results:  The study population included 3113 men and 620 women. The mean patient age was 66.31 ± 10.84 years. A high percentage of Ta (52.2%) and T1 (27.7%) tumors were found. The number of cases observed and, in particular, the percentage of Ta tumors increased significantly and progressively from the first (1979–1983 = 376 cases; Ta = 37.8%) to the last (1994–1998 = 1732 cases; Ta = 56.3%) period of observation (P < 0.001). A significant difference in the distribution of histological grade and T classification in the different age decades was apparent (P < 0.001); in particular, for G1 and Ta tumors there was a trend to decrease, whereas for G3, T1 and T2 tumors there was a tendency to increase with age decades.Conclusion:  In our analysis, age of patient and the period of examination significantly influenced different pathological characteristics of newly diagnosed TCC of the bladder.
Health‐related quality of life after chemotherapy for advanced germ cell tumors: A comparison of standard‐dose and high‐dose chemotherapy
Authors: MIYAKE HIDEAKI , MURAMAKI MOTOTSUGU , ETO HIROSHI , KAMIDONO SADAO , HARA ISAO 
Published: July 2004

Abstract  Background:  The objective of this study was to evaluate the health‐related quality of life (HRQoL) in patients with germ cell tumors who received standard‐dose chemotherapy or high‐dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT), and to compare the HRQoL of these patients with patients who had undergone surveillance therapy only.Methods:  Among the 102 patients included in this study, 38 underwent standard‐dose cisplatin‐based combination chemotherapy alone, 24 received high‐dose chemotherapy with PBSCT following standard‐dose chemotherapy, and 40 underwent surveillance monitoring. HRQoL was evaluated using the SF‐36 survey, which contains 36 questions that assess eight quality‐of‐life aspects, including physical functioning, role‐physical functioning, bodily pain, general health, vitality, social functioning, role‐emotional functioning and mental health.Results:  The follow‐up period of the surveillance group was significantly longer than that of the remaining two groups receiving chemotherapy; however, scale scores were not affected by the duration of follow up in either group. No significant difference was observed in any scale scores between the patients undergoing chemotherapy and those in the surveillance group. In comparison with the general population in the USA, social functioning in both the chemotherapy and surveillance groups was significantly lower, whereas vitality in these two groups was significantly higher. Patients undergoing standard‐dose chemotherapy alone had a significantly higher score for mental health than those undergoing high‐dose chemotherapy. However, there were no significant differences in the remaining seven scores, irrespective of the type of chemotherapy.Conclusions:  Seven of the eight scale scores of HRQoL were favorable in patients who received chemotherapy or surveillance, and no significant difference was observed between these two groups. Moreover, with the exception of the mental health score, HRQoL was not significantly affected by the type of chemotherapy. Therefore, patients who received chemotherapy, including high‐dose chemotherapy with PBSCT, seem to be generally satisfied with their overall HRQoL.
Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high‐risk urothelial cancer
Authors: SUZUKI SHIN , SHINOHARA NOBUO , HARABAYASHI TORU , SATO SOSHU , ABE TAKASHIGE , KOYANAGI TOMOHIKO 
Published: July 2004

Abstract  Background:  The objective of this study was to retrospectively investigate the effectiveness of adjuvant combination chemotherapy for locally advanced urothelial cancer.Methods:  Between 1987 and 1998, 56 patients with locally advanced bladder (n = 27) or upper urinary tract (n = 29) cancer (pathological stage T3, T4 or N1, N2 and M0) were treated by radical cystectomy or radical nephroureterectomy and regional lymphadenectomy. Thirty‐one patients had lymph node‐positive disease and 25 patients did not. Twenty patients underwent adjuvant chemotherapy and 36 patients were observed after surgery. Cox proportional hazards models were used to determine the impact of numerous clinicopathological findings on survival. A subgroup analysis of patients with lymph node‐positive disease was conducted to evaluate disease‐free survival and overall survival rates.Results:  In this series, the median follow‐up period was 39 months (range, 4–163) after surgery. Disease‐free and overall survival rates of all 56 patients were 45% and 58%, respectively, at 3 years. Only lymph node status was significantly associated with disease‐free and overall survival in the multivariate analyses. In a subgroup analysis of patients with lymph node‐positive disease, 16 patients who underwent adjuvant chemotherapy had superior disease‐free survival compared to 15 patients with no adjuvant chemotherapy (P = 0.0376).Conclusion:  These findings show that the prognosis of advanced urothelial cancer is significantly associated with nodal status. Furthermore, adjuvant combination chemotherapy has a positive impact on survival in patients with lymph node‐positive disease.
Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy
Authors: UEMURA HIROJI , NAKAMURA MASAFUMI , HASUMI HISASHI , SUGIURA SHINPEI , FUJINAMI KIYOSHI , MIYOSHI YASUHIDE , YAO MASAHIRO , KUBOTA YOSHINOBU 
Published: July 2004

Abstract  Background:  The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies.Methods:  Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies.Results:  Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty‐six men with one negative re‐biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer‐detected group and the no‐cancer‐detected group (P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut‐off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re‐biopsies showed that cancer‐detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant).Conclusions:  A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer.
Single‐blind, randomized controlled study of the clinical and urodynamic effects of an α‐blocker (naftopidil) and phytotherapy (eviprostat) in the treatment of benign prostatic hyperplasia
Authors: YAMANISHI TOMONORI , YASUDA KOSAKU , KAMAI TAKAO , TSUJII TOSHIHIKO , SAKAKIBARA RYUJI , UCHIYAMA TOMOYUKI , YOSHIDA KEN‐ICHIRO 
Published: July 2004

Abstract  Aim:  The aim of our study was to examine the efficacy of naftopidil in terms of the international prostate symptom score (IPSS) and urodynamic parameters in the treatment of benign prostatic hyperplasia (BPH). Eviprostat was used as a control to study the efficacy of naftopidil.Methods:  Forty‐nine patients with BPH (mean age 67.9 ± 7.8 years) were involved in the study. Patients were randomly assigned either to the naftopidil group, which was treated with the α‐blocker naftopidil (50–75 mg daily, 36 patients), or the eviprostat group, which was treated with phytotherapy (six tablets of eviprostat daily, 13 patients).Results:  The mean total IPSS, the total storage and voiding symptom scores, and the quality of life score decreased significantly (P < 0.0001 for each variable) in the naftopidil group, but not in the eviprostat group. In the naftopidil group, analyses showed significant increases in average and maximum flow rate and bladder capacity at first desire to void (P < 0.001, P = 0.001 and P = 0.024, respectively), and significant decreases in the postvoid residual, the percent of residual and the Abrams–Griffiths number (P = 0.009, P = 0.008 and P = 0.042, respectively). However, in the eviprostat group, no significant changes were noted in terms of these symptomatic and urodynamic parameters. In the pressure/flow study, an improvement in the International Continence Society nomogram grade was noted in 29% of the naftopidil group, but in only 16% of the eviprostat group. Among the 14 patients in the naftopidil group, detrusor overactivity disappeared in 21% and cystometric capacity increased in 36%, but no improvement in detrusor overactivity was noted in the eviprostat group.Conclusions:  Naftopidil appears to have been effective in this short‐term treatment of BPH.
Clinical study of bladder cancer: Proteinuria as a predictor of recurrence and efficacy of intravesical bacille Calmette–Guerin therapy
Authors: SATOH AKINORI , HANAWA YASUMASA , NAKAMURA SO 
Published: July 2004

Abstract  Aim:  We studied the clinical characteristics of bladder cancer, with special attention to the clinical and pathological variables that affect tumor stage, relapse and efficacy of intravesical therapy.Methods:  We reviewed the medical records of 152 patients of the Saiseikai Central Hospital who had been diagnosed as having bladder cancer between 1981 and 2001.Results:  The age of the patients ranged from 24 to 88 years, with a median of 63.5 years. The median follow up was 52.4 months (range, 0.5–259.5 months). There was no difference in the incidence of gross hematuria as a presenting symptom among the patients with invasive cancer, superficial cancer and carcinoma in situ (CIS). However, the incidence of urinary frequency and painful urination did differ significantly between patients. Although patients with invasive cancer had a longer time to hospital visit than those with superficial cancer, this time difference was not statistically significant. Presence of proteinuria, multifocality and intravesical bacille Calmette–Guerin (BCG) therapy were the significant predictors of relapse after transurethral resection (TUR). Presence of proteinuria was shown to adversely affect the efficacy of intravesical BCG therapy. In the BCG‐treated group, 3‐year relapse‐free survival was 78.4% for patients without proteinuria and 40.0% for those with proteinuria; this difference was statistically significant (P = 0.0277).Conclusions:  Time to hospital visit did not influence the pathological stage of cancer in patients included in the present study. Presence of proteinuria, multifocality and BCG therapy were the significant predictors of relapse after TUR. Presence of proteinuria was shown to adversely affect the efficacy of intravesical BCG therapy. Proteinuria might be helpful in predicting tumor relapse and efficacy of intravesical BCG therapy in clinical settings, along with other markers.
Complications of laparoscopic radical cystectomy during the initial experience
Authors: HEMAL ASHOK K , KUMAR RAJEEV , SETH AMLESH , GUPTA NARMADA P 
Published: July 2004

Abstract  Aim:  Radical cystectomy is the standard of care for patients with muscle invasive bladder cancer. While open radical cystectomy is now a standard procedure, laparoscopic radical cystectomy is still in its infancy. We performed this surgery laparoscopically in 11 patients and review the procedure specific complications.Methods:  Beginning in February 1999, 11 patients underwent laparoscopic radical cystectomy at the Department of Urology, All India Institute of Medical Sciences, New Dehli. Urinary diversion was performed by an open‐hand sewn ileal conduit.Results:  There were three intraoperative complications specifically related to the laparoscopic radical cystectomy. These included injury to the external iliac vein in one patient and a small rectal tear in two. All were repaired with laparoscopic free hand suturing with normal postoperative recovery. Other laparoscopy‐related complications were subcutaneous emphysema in one patient and hypercarbia necessitating conversion to open surgery in a patient who, four weeks after surgery, died of multiple organ failure. One patient had margins positive and received cisplatinum‐based chemotherapy. All patients had normal renal function and preserved upper tracts with no evidence of metastasis at a mean of 18.4 months follow up (range 1–48 months).Conclusions:  Though there were three complications specific to the laparoscopic radical cystectomy, none necessitated a conversion to open surgery or hampered the overall outcome. Absence of local recurrence or metastatic disease at four years of follow up suggests that the procedure is oncologically valid. Laparoscopic radical cystectomy is a new procedure and it is important to critically analyze the complications in order to reduce their occurrence and allow the development of a better technique.
Determining the contribution of asphyxia to brain damage in the neonate
Authors: Low James A. 
Published: July 2004

AbstractStudies in the research laboratory have demonstrated the complex relationship between fetal and newborn asphyxia and brain damage, a balance between the degree, duration and nature of the asphyxia and the quality of the cardiovascular compensatory response. Clinical studies would support the contention that the human fetus and newborn behave in a similar manner. An accurate diagnosis of asphyxia requires a blood gas and acid base assessment. The clinical classification of fetal asphyxia is based on a measure of metabolic acidosis to confirm that fetal asphyxia has occurred and the expression of neonatal encephalopathy and other organ system complications to express the severity of the asphyxia. The prevalence of fetal asphyxia at delivery is at term, 25 per 1000 live births of whom 15% are moderate or severe; and in the preterm, 73 per 1000 live births of whom 50% are moderate or severe. It remains to be determined how often the asphyxia recognized at delivery may have been present before the onset of labor. There is a growing body of indirect and direct evidence to support the contention that antepartum fetal asphyxia is important in the occurrence of brain damage. Although much of the brain damage observed in the newborn reflects events that occurred before delivery, newborn asphyxia and hypotension, particularly in the preterm newborn, may contribute to the brain damage accounting for deficits in surviving children
Surgical repair of genital fistulae
Authors: Naru Tahira , Rizvi Javed H. , Talati Jamsheer 
Published: July 2004

AbstractObjective:  Genital fistula is one of the serious childbirth injuries that can occur among women in the developing countries. Complex fistulae still represent a challenging management problem. We report our experience of managing genital fistulae at the Aga Khan University Hospital (AKUH), Karachi, Pakistan.Methods:  Eighty‐seven women with genital fistulae were managed between January 1988 and December 2002. Sixty‐eight cases were urogenital and 19 were rectovaginal fistulae. Three women had concomitant urogenital and rectovaginal fistulae. The position of patients for surgery and the route of repair were individualized according to the appropriate access to the fistulae.Results:  Of the 68 cases of urogenital fistulae, 54 were successfully repaired at first attempt. Three patients were cured at second repair. A success rate of 83.8% was achieved. Four patient with ureterosigmoid anastomosis and seven patients who were lost to follow‐up, were considered as failures. All of the 19 rectovaginal fistulae (100%) closed after single repair.Conclusion:  With an experienced uro‐gynecologic team using conventional approach and meticulous repair, a high percentage of patients with genital fistulae can be rendered dry and continent.