bluuebunny/crossref_metadata_2025 huggingface dataset:
Helicobacter pylori-induced H,K-ATPase α-subunit gene repression is mediated by NF-κB p50 homodimer promoter binding
Authors: Saha Arindam , Hammond Charles E. , Trojanowska Maria , Smolka Adam J.
Published: January 2008

Infection of human gastric body mucosa by the gram-negative, microaerophilic bacterium Helicobacter pylori induces an inflammatory response and a transitory hypochlorhydria that progresses in ∼2% of patients to atrophic gastritis, dysplasia, and gastric adenocarcinoma. We have previously shown that H. pylori infection of cultured gastric epithelial cells (AGS) represses the activity of the transfected α-subunit (HKα) promoter of H,K-ATPase, the parietal cell enzyme mediating acid secretion. However, the mechanistic details of H. pylori-mediated repression of HKα and ensuing hypochlorhydria are unknown. H. pylori is known to upregulate the transcription factor NF-κB through the ERK1/2 MAPK pathway. We identified NF-κB-binding regions in the HKα promoter and found that H. pylori inoculation of AGS cells increased NF-κB p50 binding to the transfected HKα promoter and repressed its transcriptional activity. Immunoblot and DNA-protein interaction studies showed that although active phosphorylated NF-κB p65 is present in H. pylori-infected AGS cells, an NF-κB p50/p65 heterodimeric complex fails to bind to the HKα promoter. Point mutations at −159 and −161 bp in the HKα promoter NF-κB binding sequence prevented binding of NF-κB p50 and prevented H. pylori repression of point-mutated HKα promoter activity in transfected AGS cells. Small interfering RNA-mediated knockdown of NF-κB p50 in H. pylori-infected AGS cells also abrogated H. pylori-induced HKα repression, whereas NF-κB p65 knockdown did not. We conclude that H. pylori inhibits HKα gene expression by ERK1/2-mediated NF-κB p50 homodimer binding to the HKα promoter. This study identifies a novel pathogen-dependent mechanism of H,K-ATPase inhibition and contributes to understanding of H. pylori pathophysiology.
Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats
Authors: Hayashi Yujiro , Tsuji Shingo , Tsujii Masahiko , Nishida Tsutomu , Ishii Shuji , Iijima Hideki , Nakamura Toru , Eguchi Hiroshi , Miyoshi Eiji , Hayashi Norio , Kawano Sunao
Published: January 2008

Mesenchymal stem cells (MSCs), a subpopulation of adult somatic stem cells, are an attractive stem cell source in regenerative medicine because of their multipotentiality. We examined the effects of MSC transplantation on gastric ulcer healing. Putative MSCs, isolated from bone marrow aspirates of male rats by dish adherence and expanded in culture, were characterized by flow cytometry and reverse transcription-polymerase chain reaction. Gastric ulcers were induced by serosal application of acetic acid on the anterior wall of the stomach in female rats. Either MSCs (labeled with PKH67; 1×107 cells) or vehicle was injected into the gastric wall surrounding the ulcer. The healing process of the ulcer and the influence of anti-vascular endothelial growth factor (VEGF) antibody were examined. CD29-positive, CD90-positive, CD34-negative, and CD45-negative MSCs expressed mRNAs for VEGF and hepatocyte growth factor (HGF). The MSCs were transplantable to the gastric tissue surrounding the ulcer, where a majority of the engrafted cells were positive for vimentin. The transplantation significantly accelerated gastric ulcer healing compared with controls. The engrafted MSCs also expressed VEGF and HGF. Administration of anti-VEGF neutralizing antibody dose dependently reduced the MSC-induced promotion of ulcer healing. In conclusion, MSC transplantation accelerated gastric ulcer healing, possibly through the induction of angiogenesis in the gastric mucosa via the secretion of VEGF. The beneficial effects of MSCs might be mediated not only by their differentiation into gastric interstitial cells, but also by their ability to supply angiogenic factors.
d-Glucose modulates synaptic transmission from the central terminals of vagal afferent fibers
Authors: Wan Shuxia , Browning Kirsteen N.
Published: January 2008

Experimental evidence suggests that glucose modulates gastric functions via vagally mediated effects. It is unclear whether glucose affects only peripheral vagal nerve activity or whether glucose also modulates vagal circuitry at the level of the brain stem. This study used whole cell patch-clamp recordings from neurons of the nucleus of the tractus solitarius (NTS) to assess whether acute variations in glucose modulates vagal brain stem neurocircuitry. Increasing d-glucose concentration induced a postsynaptic response in 40% of neurons; neither the response type (inward vs. outward current) nor response magnitude was altered in the presence of tetrodotoxin suggesting direct effects on the NTS neuronal membrane. In contrast, reducing d-glucose concentration induced a postsynaptic response (inward or outward current) in 54% of NTS neurons; tetrodotoxin abolished these responses, suggesting indirect sites of action. The frequency, but not amplitude, of spontaneous and miniature excitatory postsynaptic currents (EPSCs) was correlated with d-glucose concentration in 79% of neurons tested ( n = 48). Prior surgical afferent rhizotomy abolished the ability of d-glucose to modulate spontaneous EPSC frequency, suggesting presynaptic actions at vagal afferent nerve terminals to modulate glutamatergic synaptic transmission. In experiments in which EPSCs were evoked via electrical stimulation of the tractus solitarius, EPSC amplitude correlated with d-glucose concentration. These effects were not mimicked by l-glucose, suggesting the involvement of glucose metabolism, not uptake, in the nerve terminal. These data suggest that the synaptic connections between vagal afferent nerve terminals and NTS neurons are a strong candidate for consideration as one of the sites where glucose-evoked changes in vagovagal reflexes occurs.
Effects of ω-hydroxylase product on distal human pulmonary arteries
Authors: Morin Caroline , Guibert Christelle , Sirois Marco , Echave Vincent , Gomes Marcio M. , Rousseau Eric
Published: January 2008

The aim of the present study was to provide a mechanistic insight into how 20-hydroxyeicosatetraenoic acid (20-HETE) relaxes distal human pulmonary arteries (HPAs). This compound is produced by ω-hydroxylase from free arachidonic acid. Tension measurements, performed on either fresh or 1 day-cultured pulmonary arteries, revealed that the contractile responses to 1 μM 5-hydroxytryptamine were largely relaxed by 20-HETE in a concentration-dependent manner (0.01–10 μM). Iberiotoxin pretreatments (10 nM) partially decreased 20-HETE-induced relaxations. However, 10 μM indomethacin and 3 μM SC-560 pretreatments significantly reduced the relaxations to 20-HETE in these tissues. The relaxing responses induced by the eicosanoid were likely related to a reduced Ca2+ sensitivity of the myofilaments since free Ca2+ concentration ([Ca2+])-response curves performed on β-escin-permeabilized cultured explants were shifted toward higher [Ca2+]. 20-HETE also abolished the tonic responses induced by phorbol-ester-dibutyrate (a PKC-sensitizing agent). Western blot analyses, using two specific primary antibodies against the PKC-potentiated inhibitory protein CPI-17 and its PKC-dependent phosphorylated isoform pCPI-17, confirmed that 20-HETE interferes with this intracellular process. We also investigated the effect of 20-HETE on the activation of Rho-kinase pathway-induced Ca2+ sensitivity. The data demonstrated that 20-HETE decreased U-46619-induced Ca2+ sensitivity on arteries. Hence, this observation was correlated with an increased staining of p116Rip, a RhoA-binding protein. Together, these results strongly suggest that the 20-hydroxyarachidonic acid derivative is a potent modulator of tone in HPAs in vitro.
Skeletal muscle contractile protein function is preserved in human heart failure
Authors: Okada Yoko , Toth Michael J. , VanBuren Peter
Published: January 2008

Skeletal muscle weakness is a common finding in patients with chronic heart failure (CHF). This functional deficit cannot be accounted for by muscle atrophy alone, suggesting that the syndrome of heart failure induces a myopathy in the skeletal musculature. To determine whether decrements in muscle performance are related to alterations in contractile protein function, biopsies were obtained from the vastus lateralis muscle of four CHF patients and four control patients. CHF patients exhibited reduced peak aerobic capacity and knee extensor muscle strength. Decrements in whole muscle strength persisted after statistical control for muscle size. Thin filaments and myosin were isolated from biopsies and mechanically assessed using the in vitro motility assay. Isolated skeletal muscle thin-filament function, however, did not differ between CHF patients and controls with respect to unloaded shortening velocity, calcium sensitivity, or maximal force. Similarly, no difference in maximal force or unloaded shortening velocity of isolated myosin was observed between CHF patients and controls. From these results, we conclude that skeletal contractile protein function is unaltered in CHF patients. Other factors, such as a decrease in total muscle myosin content, are likely contributors to the skeletal muscle strength deficit of heart failure.
Advances in Chemotherapy against Advanced or Metastatic Colorectal Cancer
Authors: Omura Kenji
Published: January 2008

In the early 1990s, some prospective controlled trials revealed the superiority of chemotherapy for survival compared with best supportive care for advanced or metastatic colorectal carcinoma. Until recently, 5-fluorouracil (5-FU) and leucovorin (LV) were the standard therapies against advanced or metastatic colorectal cancer. Theoretically, LV should increase the antitumor activity of 5-FU, although this effect of LV addition has been controversial. A meta-analysis which analyzed 21 randomized controlled trials revealed that a combination of 5-FU and LV doubled the response rate compared with 5-FU alone (from 11 to 21%) and prolonged the median survival time by about 1 month (from 10.5 to 11.7 months). Chemotherapy against advanced or metastatic colorectal cancer has steadily advanced after the introduction of triplet regimens containing 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) and (trans-R,R-1,2-diamine cyclohexane)oxalatoplatinum(II) (L-OHP). For LV/5-FU/CPT-11, the regimen in which 5-FU is administered with continuous infusion (FOLFIRI) is preferred compared with the 5-FU bolus infusion. According to the results of the randomized controlled trial comparing FOLFIRI followed by FOLFOX6 and the reverse sequence, FOLFOX6 followed by FOFIRI, in the treatment of advanced colorectal cancer, FOLFIRI and FOLFOX are now considered to have almost the same efficacy in the treatment of advanced or metastatic colorectal cancer. FOLFIRI followed by FOLFOX or FOLFOX followed by FOLFIRI provide a median survival time of about 21 months in advanced or metastatic colorectal cancer. Both an anti-vascular endothelial growth factor monoclonal antibody, bevacizumab, and an anti- epidermal growth factor receptor monoclonal antibody, cetuximab, should prolong the survival of advanced or metastatic colorectal cancer by 2–3 months in combination with FOLFIRI or FOLFOX. However, from the viewpoint of medical economics, because of the high acquisition costs in relation to clinical benefits, antibodies are unlikely to represent a cost-utility solution. New agents, including macromolecule agents, small-molecule agents and vaccines, will be introduced alongside chemotherapy against colorectal cancer. Subsequently, clinical researchers will have to consider the cost-utility of these agents.
Palliative Radiation Therapy for Advanced Gastrointestinal Cancer
Authors: Murakami Naoya , Nakagawa Keiichi , Yamashita Hideomi , Nagawa Hirokazu
Published: January 2008

Patients with locally advanced disease can have significant local symptoms. The most common symptoms from local extension are pain, bleeding (hematemesis, melena) and obstruction (dysphagia, vomiting). These can cause a significant impact on a patient’s quality of life. Radiation therapy is used to control these symptoms with modern 3-dimensional conformal techniques or brachytherapy. The aim of this study was therefore to review the outcome of palliative radiation therapy in patients with symptomatic locally advanced or recurrent gastrointestinal cancer.
Sonic Hedgehog and Bone Morphogenetic Protein-4 Signaling Pathway Involved in Epithelial Cell Renewal along the Radial Axis of the Intestine
Authors: Ishizuya-Oka Atsuko , Hasebe Takashi
Published: January 2008

The organogenesis of the digestive tract proceeds according to the positional information along the cephalo-caudal, dorsal-ventral and left-right axes of the embryonic body and the radial axis of the tract during development. Among them the radial axis, which corresponds to the crypt-villus axis in the adult small intestine, is essential for a rapid cell renewal of the epithelium throughout adulthood and is important from the clinical viewpoint. All of the adult intestinal epithelial cells originate from multipotent stem cells localized in the basal region of the crypt. Descendants of the stem cells, as they migrate up or down along the crypt-villus axis, actively proliferate, differentiate and finally undergo apoptosis. Recently, there has been a growing body of evidence that the Wnt and Notch signaling pathways are involved in cell proliferation and cell fate determination, respectively, during the epithelial cell renewal. However, the molecular mechanisms by which the radial axis is established and/or is maintained to enable the epithelial cell renewal have not yet been fully understood, and their clarification is urgently needed for stem cell therapies. In the amphibian intestine during metamorphosis, stem cells analogous to the mammalian ones appear and newly form the epithelium that undergoes the cell renewal along the radial axis by the inductive action of thyroid hormone. Thus, this animal model provides us with a good opportunity to clarify the molecular mechanisms of radial axis formation. By using the Xenopus laevis intestine, we found that sonic hedgehog (Shh), which is secreted by the stem cells, induces bone morphogenetic protein-4 (BMP-4) in subepithelial fibroblasts and that both Shh and BMP-4 are involved in the development of the cell-renewable epithelium. In this review, we highlight the molecular aspects of the cell renewal of the adult intestinal epithelium and propose important roles of the Shh/BMP-4 signaling pathway in the establishment and/or maintenance of the radial axis common to the human intestine.
Real-Time Assessment of Gastroduodenal Motility by Ultrasonography
Authors: Haruma Ken , Kusunoki Hiroaki , Manabe Noriaki , Kamada Tomoari , Sato Motonori , Ishii Manabu , Shiotani Akiko , Hata Jiro
Published: January 2008

Functional dyspepsia (FD) is a clinical syndrome involving upper abdominal symptoms, the causes of which cannot be identified by conventional diagnostic evaluation. Many pathophysiological factors, such as gastric acid, gastroduodenal motility, gastric accommodation, sensory disturbance, stress and Helicobacter pylori infection, may play a role in the pathogenesis of FD. Dysmotility of the upper gastrointestinal tract has been implicated in the symptoms of FD. In previous studies, antral hypomotility and delayed gastric emptying have been reported as major pathogenetic factors in patients with FD. Although a number of methods have been applied to evaluate gastroduodenal motility in humans, many of them have technical limitations and are too expensive or complex to use in daily clinical practice. Recent technical developments enable one to evaluate gastroduodenal motility by using ultrasonography. Ultrasonography is a simple, noninvasive modality for the assessment of gastric emptying and antral motility in either a liquid or solid meal, along with the examination of duodenogastric reflux.
The Importance of Palliative Care in Urology
Authors: Brierly Robert D. , O’Brien Tim S.
Published: January 2008

Introduction: The aim of this study was to identify patients with advanced urological cancer who may benefit from specialist palliative care and to quantify the number of these patients, characterize their problems and to see if their needs were being met. Methods: The study was divided into two parts over 4-month periods centred on a hospital trust in the UK with a catchment population of 850,000. Urology in-patients were observed prospectively and out-patients were observed retrospectively. Patients were included if they had unresectable, locally advanced or metastatic urological cancer. Patients with prostate cancer were included if they had advanced disease with hormone relapse, defined as three successive rises in PSA. Results: 881 admissions to the urology ward were reviewed. A total of 24 patients with terminal malignancy had 27 admissions. Two patients died during their admission. The average length of stay was 16.6 days. Only 5 patients underwent surgical intervention. The majority of patients had general systemic symptoms of advanced malignancy. 2,482 out-patient visits were reviewed where 69 patients with terminal malignancy received 82 outpatient consultations, representing approximately 10% of all cancer visits. Seventy-five percent of the patients had specific problems or were generally unwell as a result of their disease and would have benefited from specialist palliative care. The remaining 25% were well at the time of their visit, but potential psychosocial problems arising from coping with advancing terminal disease were not addressed. Conclusion: Patients requiring palliative care place a heavy burden on in- and out-patient services. There is a case for a palliative care physician to be closely involved in urological cancer teams. Urologists need to be trained in palliative care, as this comprises a significant volume of their work.
Modified Transurethral Incision of the Bladder Neck Treating Primary Bladder Neck Obstruction in Young Men: A Method to Improve Voiding Function and to Preserve Antegrade Ejaculation
Authors: Yang Stephen Shei-Dei , Tsai Yao-Chou , Chen Jen-Jih , Peng Chung-Hsin , Hsieh Jui-Hsiang , Wang Chung Cheng
Published: January 2008

Objectives: To evaluate the voiding function, ejaculation status and sexual function after the novel modification of transurethral incision of the bladder neck (TIBN) treating young men with primary bladder neck obstruction (PBNO). Methods: Using a videourodynamic study, PBNO was diagnosed in 33 young men 27–50 years of age who presented with chronic lower urinary tract symptoms and low urinary flow. TIBN was performed in all patients, with the modification of preserving a portion of the supramontanal tissue during the procedure. International Prostate Symptom Score (I-PSS), quality of life, uroflowmetry, postvoid residual urine, the status of ejaculation and sexual function using the 5-item version of the International Index of Erectile Function (IIEF-5) were assessed before, 3 and 24 months after treatment. Results: Follow-up data were available in 32 (97%) and 26 (79%) patients at 3 and 24 months postoperatively, respectively. During the 2-year follow-up, mean I-PSS decreased from 20.7 to 5.9 (p < 0.01). Mean quality of life decreased from 4.2 to 2.3 (p < 0.01). Mean maximum flow increased from 10.7 to 19.2 ml/s (p < 0.01). Mean postvoiding residual urine decreased from 107 to 48 ml (p < 0.01). All patients had antegrade ejaculation postoperatively. Mean IIEF scores did not change significantly (22.6 ± 2.6 vs. 20.7 ± 4.3, p = 0.08). Successful overall outcome was achieved in 22 (84.6%) of 26 patients. Conclusions: Applying thismodified TIBN to treat the sexually active young men with PBNO had the advantage of improving voiding function and preserving both antegrade ejaculation and sexual function.
Clinical and Radiological Features of Adrenal Cysts
Authors: Erbil Yeşim , Salmaslıoğlu Artür , Barbaros Umut , Bozbora Alp , Mete Özgür , Aral Ferihan , Özarmağan Selçuk
Published: January 2008

Adrenal cysts are very rare lesions, usually asymptomatic or without characteristic symptoms. They are classified as pseudocysts, endothelial cysts, epithelial cysts or parasitic cysts. Although pseudocysts are reported to be the most common clinically recognized adrenal cysts in surgical series, endothelial cysts are more common in autopsy series. We studied 15 consecutive patients with adrenal cysts who underwent surgical resection at our institution from 1990 to 2005. Of 15 patients with adrenal cysts, 10 had pseudocysts, 3 epithelial cysts, 1 an endothelial cyst and 1 a parasitic cyst. In conclusion, a better understanding of cystic adrenal masses is necessary to recognize true adrenal cysts and differentiating them from adrenal carcinoma or adenoma by demonstrating the foci of cystic or degenerative changes.
Does Position Affect Uroflowmetry Parameters in Women?
Authors: Gupta Narmada P. , Kumar Atul , Kumar Rajeev
Published: January 2008

Purpose: To investigate the effect of position on voiding using uroflowmetric variables and postvoid residual urine volume assessment in healthy normal women. Materials and Methods: 67 healthy females volunteered to participate in this study. Their mean age was 32 years. Each female attended the urodynamic suite on 2 separate days. They performed 2 voids, 1 in a sitting and another in a squatting posture each day. Maximum flow rate (Qmax), average flow rate (Qave), voided volume and corresponding postvoid residual urine (PVR) were compared for each position using paired Student’s t test. Results: The mean Qmax values obtained for sitting and squatting postures were 18.4 ± 3.2 and 24.8 ± 4.9 ml/s, respectively, and corresponding Qave values were 9.2 ± 1.9 and 12.3 ± 3.3 ml/s, respectively. Mean PVR values for sitting and squatting were 51.8 ± 22.2 and 21.6 ± 12.7 ml, respectively. Conclusion: The posture adopted for micturition affects uroflowmetric variables. The squatting posture is associated with a significantly higher maximum flow rate and a lower postvoid residue. Therefore, when low urine flow rates or high residual urine volumes are encountered during urodynamic study, the patients should be asked whether they normally micturate in a sitting or squatting position. If the former position is used, repeat studies with the patients squatting should be considered before accepting an abnormal test result as indicative of lower-urinary-tract dysfunction.
Cadaveric Fascia Lata versus Intravaginal Slingplasty for the Pubovaginal Sling: Surgical Outcome, Overall Success and Patient Satisfaction Rates
Authors: Basok Erem Kaan , Yildirim Asif , Atsu Necmettin , Basaran Adnan , Tokuc Resit
Published: January 2008

Background: A wide variety of surgical procedures has been used to treat female stress urinary incontinence (SUI). The purpose of this study was to compare cadaveric fascia lata (CFL) sling with intravaginal slingplasty (IVS) in the surgical treatment of SUI. Methods: One hundred and thirty-nine women with SUI were randomly assigned to either CFL sling (n = 67) or IVS (n = 72). Concomitant urinary urge incontinence was present in 49 patients (73%) in the CFL sling and 44 patients (61%) in the IVS group. Daily mean pad usage was 4.1 ± 3.5 in the CFL sling and 2.9 ± 1.7 in the IVS group. The objective cure rate was evaluated by the pad test, and patient satisfaction rate was assessed by a subjective questionnaire. Results: The surgical results of both procedures with a follow-up 12 months were documented. The overall success rate was 79% in the CFL sling and 70.8% in the IVS (p = 0.261). In contrast patient satisfaction rates were 82 and 87.5%, respectively (p = 0.210). Comparison of the CFL sling with IVS showed persistent urinary urge incontinence in 67 and 25% (p = 0.0001) and de novo urinary urge incontinence in 22 and 6.9%, respectively (p = 0.009). The groups did not differ significantly with respect to intraoperative and postoperative complications. Conclusions: There is no statistical difference in the overall success, satisfaction and complication rates in either group. In our series, both procedures were found to be effective, durable and significantly improved quality of life in patients with SUI but long-term results are awaited.
Overactive Bladder in Children Should Be Strictly Differentiated from Monosymptomatic Nocturnal Enuresis
Authors: Kajiwara Mitsuru , Kato Masao , Mutaguchi Kazuaki , Usui Tsuguru
Published: January 2008

Introduction: To elucidate the prevalence of concomitant overactive bladder in children with a chief compliant of primary enuresis, and to evaluate the pathogenetic difference between monosymptomatic and non-monosymptomatic enuresis. Materials and Methods: All patients had evidence of primary enuresis. Neurogenic bladder was excluded. Urinary symptoms were evaluated by taking a history from the affected children and parents, and using a questionnaire and bladder diary. Voiding cystourethrography was performed for non-responders to exclude urinary abnormalities. Results: Eighty-eight patients (9.8 ± 3.1 years old) were enrolled. Initial assessment demonstrated that 24% had undervalued overactive bladders and 9% had constipation. Voiding cystourethrography was performed in 25%, demonstrating mechanical urethral obstructions in 8% and vesicoureteral reflux in 4.5%. Constipation, a history of urinary tract infections, mechanical obstructions and vesicoureteral reflux were strongly associated with non-monosymptomatic enuresis. Conclusions: Patients with non-monosymptomatic enuresis had a different clinical background, therapeutic response and pathogenetic abnormalities. In children an overactive bladder should be strictly differentiated from monosymptomatic enuresis.
Effect of Laparoscopic Hysterectomy on the Vascularization of the Lower Urinary Tract
Authors: Liu Cheng-Min , Tsai Eing-Mei , Hsu Shih-Cheng , Wu Chin-Hu , Wang Chiu-Lin , Long Cheng-Yu
Published: January 2008

Introduction: The aim of this prospective study was to evaluate the changes in the vascularization of the lower urinary tract following laparoscopic hysterectomy (LH). Methods: Seventy women undergoing LH not under the indication of a uterine myoma were included. All subjects underwent urinalysis, pelvic examination, and introital color Doppler ultrasonography and completed a urinary questionnaire before and 6 months after LH. One-hour pad tests and urodynamic studies were performed in clinically incontinent women pre- and postoperatively. Results: Evaluation of the Doppler velocimetric parameters of bladder neck and periurethral vessels before and after LH, including number of vessels, pulsatility index, systolic peak, and minimum diastole, revealed no statistically significant differences (p > 0.05). In addition, the prevalence of stress urinary incontinence (SUI) decreased significantly from 37.1% (n = 26) preoperatively to 17.1% (n = 12) postoperatively (p < 0.01). A total of 19 patients reported no further SUI following LH. Their urinary leakages on the pad tests had all <10 g before surgery. When we analyzed the data of the women reporting no further SUI (n = 19) and de novo SUI (n = 5) following LH, the changes in the pulsatility index also showed no significant difference from the pre-LH values (p > 0.05). Conclusions: The results of our study suggest that LH has little impact on the blood flow of bladder neck and urethra. Although some women experienced relief of the symptoms of mild or de novo SUI after LH, this being unrelated to changes in the vascularization of the lower urinary tract.
Intravesical Bacillus Calmette-Guérin Therapy for T1 Superficial Bladder Cancer
Authors: Demkow Tomasz , Alter Andrzej , Wiechno Paweł
Published: January 2008

Introduction: The management of transitional bladder cancer, which invades the lamina propria (pT1) and has a marked propensity for recurrence and progression, is controversial. Without adjuvant treatment the recurrence rate can be up to 80% and progression up to 50%. We retrospectively analyzed the incidence of recurrence and progression of pT1 transitional bladder cancer (grade 1–3) after complete transurethral resection of a bladder tumor (TURBT) and adjuvant immunotherapy with bacillus Calmette-Guérin (BCG). Materials and Methods: 77 patients with stage pT1 transitional cell carcinoma underwent TURBT of all visible tumors and adjuvant BCG intravesical instillations. Before BCG therapy, 12 patients presented with stage pT1 G1 tumors, 50 presented with pT1, and 15 with pT1 G3 tumors. Results: 51 patients (66.2%) were disease-free throughout the BCG instillation and follow-up period (median of 45 months); 8 patients (10.4%) experienced recurrence during the BCG instillations, but were disease-free following the last instillation; 16 patients (20.8%) experienced recurrence at a median of 17 months, and 2 patients (2.6%) with pT1 G3 died because of progression. Conclusions: Adjuvant intravesical BCG therapy following TURBT appears to be an effective primary treatment for patients with pT1 transitional cell carcinoma.
Comparative Study of Graft Nephrectomy in Pre-Cyclosporine and Cyclosporine Era
Authors: Adhikary Samiran Das , Viswaroop Sistla Bobby , Kekre Nitin Sudhakar , Gopalakrishnan Ganesh
Published: January 2008

Objective: To assess the incidence and identify the indications for graft nephrectomy (GN) in the cyclosporine (CSA) era as compared to GN in the pre-CSA era. Materials and Methods: This is a retrospective study of 1,866 renal transplants done from 1971 to 1999. 675 were transplanted in the pre-CSA era (group 1) and 1,191 in the CSA era (group 2). The published series on experience with GN in the pre-CSA era was compared with that in the CSA era. GN done within 6 months of transplant was defined as early GN and those done after 6 months were included under late GN. The incidence, indication and the implications of GN were studied and compared with our experience in the pre-CSA era. Results were analyzed using the χ2 test. Results: Of the 675 transplants in group 1, thirty-one had GN compared to 15 of 1,191 in group 2. There was a significant decrease in GN in the CSA era. Of the 31 in group 1, thirty had early GN as compared to 6 of 15 in group 2 (p = 0.003). On the contrary, late GN was significantly higher in group 2 (9/15) as compared to group 1 (1/31). Acute rejections and graft infections were the predominant causes of graft loss in group 1, while late graft loss due to symptomatic chronic rejection was the commonest cause in group 2. Morbidity was equal in both groups while mortality was significantly higher in group 1. Conclusion: CSA has significantly reduced the need for GN. By reducing hyper, acute, and irreversible acute rejection, the need for early GN has also been reduced significantly. Though there is an increased incidence of chronic allograft nephropathy, late GN is indicated only when there is refractory hematuria, intractable proteinuria and graft sepsis. With better immunosuppression, graft loss secondary to infection has decreased and mortality due to GN has been minimized.
Verapamil Attenuates Renal Tubular Apoptosis in Response to Partial Unilateral Ureteral Obstruction
Authors: Topcu Sukru Oguzkan , Erbagci Ahmet , Erturhan Sakip , Yagci Faruk , Ucak Ramazan
Published: January 2008

Introduction: Partial unilateral ureteral obstruction (PUUO) is the type of obstruction that is most often encountered in pediatric clinical practice. The majority of our knowledge on PUUO has been derived from experimental studies and the effects of PUUO on the kidney have still been a source of continual investigation. Material and Methods: In the present study, renal expression of p53, Fas and PCNA were examined in rabbits with long-term (4 weeks) partial obstruction. Additionally, the effect of calcium channel blocker on pronounced apoptotic changes were evaluated. Results: Immunohistochemistry results revealed that PUUO for 4 weeks caused an upregulation of p53 to 55.2 ± 2% and Fas to 30.1 ± 1.1%, whereas verapamil challenge attenuated the expression of these two apoptotic markers (p53: 15.9 ± 1.8%; Fas: 18.2 ± 1.4%, p < 0.05). Importantly, PCNA activity was also increased in response to PUUO. However, verapamil treatment after onset of obstruction caused a markedly decrease in the expression of PCNA (42.9 ± 10.8% vs. 9.6 ± 2.1%, PUUO, PUUO + verapamil; respectively, p < 0.05). Conclusion: The expression of p53, Fas and PCNA molecules is associated with long-term partial ureteral obstruction, whereas verapamil seems to be a protective agent against apoptotic changes.
Cell Proliferation and DNA Content in Rat Urothelial Lesions after Repeat Intravesical Instillations of Mitomycin C and Bacillus Calmette-Guérin
Authors: Oliveira P. , Palmeira C. , Colaço A. , De la Cruz P L.F. , Lopes C.
Published: January 2008

Aim: To study cell proliferation and DNA content in urothelial lesions identified after repeated intravesical instillations of mitomycin C (MMC) and bacillus Calmette-Guérin (BCG) in normal rat urothelium. Material and Methods: A total of 45 rats were divided into nine equal groups: those intravesically instilled with MMC; those receiving BCG intravesically, and a control group intravesically instilled with a physiological solution of sodium chloride (SF). Animals were killed 1, 4 or 8 weeks after the last intravesical instillation. An immunohistochemical streptavidin-biotin-peroxidase technique was performed to investigate Ki-67 expression and the DNA ploidy status was measured using static cytometry. Results: In urothelium exposed to MMC lesions such as simple hyperplasia, dysplasia, carcinoma in situ(CIS), and squamous cell metaplasia were identified. The proliferation index presented values of 11.73, 22.43 and 31.46% in hyperplasias, dysplasias, and CIS, respectively (p < 0.05). The frequency of abnormal DNA content amongst those animals exhibiting simple hyperplasias 25% were aneuploid, in the dysplasia 85.2% were aneuploid (p = 0.041). CIS were all multiploid, and squamous cell metaplasias were all diploid. Animals treated with BCG and SF presented no urothelial lesions and a diploid DNA content. Conclusions: The aneuploid and multiploid DNA content and proliferation index observed in urothelial lesions identified after repeated intravesical instillations of MMC reflect a high degree of genomic instability in such lesions which in itself may lead to rapid regeneration of new phenotypes.
Hemangioma of the Prostatic Urethra: Holmium Laser Treatment
Authors: Ponce de León Javier , Arce Jacobo , Gausa Luís , Villavicencio Humberto
Published: January 2008

Urethral hemangiomas are benign vascular tumors that are found in perimontanal prostatic localization and less frequently in the urethra. Although different urethral procedures have been postulated for its treatment, the best results are achieved using lasers. A patient who underwent endoscopic holmium laser treatment for such hemangiomas is presented. Total disappearance of the lesions without any complications was achieved.
Cutaneous Metastases in Renal Cell Carcinoma
Authors: Bujons A. , Pascual X. , Martínez R. , Rodríguez O. , Palou J. , Villavicencio H.
Published: January 2008

Cutaneous metastases from a renal cell carcinoma are rarely diagnosed during life. We report a case of renal carcinoma metastatic to the skin that occurred 18 months after kidney removal. The cutaneous metastasis was excised. Cutaneous metastases from urological tumors are uncommon and occur in 1% of the patients, and their clinical appearance may mimic other common dermatological disorders affecting patients with advanced malignancies.
Sex Chromosomes and Sex Determination in Lepidoptera
Authors: Traut W. , Sahara K. , Marec F.
Published: January 2008

The speciose insect order Lepidoptera (moths and butterflies) and their closest relatives, Trichoptera (caddis flies), share a female-heterogametic sex chromosome system. Originally a Z/ZZ (female/male) system, it evolved by chromosome rearrangement to a WZ/ZZ (female/male) system in the most species-rich branch of Lepidoptera, a monophyletic group consisting of Ditrysia and Tischeriina, which together comprise more than 98% of all species. Further sporadic rearrangements created multi-sex chromosome systems; sporadic losses of the W changed the system formally back to Z/ZZ in some species. Primary sex determination depends on a Z-counting mechanism in Z/ZZ species, but on a female-determining gene, Fem, in the W chromosome of the silkworm. The molecular mechanism is unknown in both cases. The silkworm shares the last step, dsx, of the hierarchical sex-determining pathway with Drosophila and other insects investigated, but probably not the intermediate steps between the primary signal and dsx. The W chromosome is heterochromatic in most species. It contains few genes and is flooded with interspersed repetitive elements. In interphase nuclei of females it is readily discernible as a heterochromatic body which grows with increasing degree of polyploidy in somatic cells. It is used as a marker for the genetic sex in studies of intersexes and Wolbachia infections. The sex chromosome system is being exploited in economically important species. Special strains have been devised for mass rearing of male-only broods in the silkworm for higher silk production and in pest species for the release of sterile males in pest management programs.
Small Supernumerary Marker Chromosomes (sSMC) in Patients with a 45,X/46,X,+mar Karyotype – 17 New Cases and a Review of the Literature
Authors: Liehr T. , Mrasek K. , Hinreiner S. , Reich D. , Ewers E. , Bartels I. , Seidel J. , Emmanuil N. , Petesen M. , Polityko A. , Dufke A. , Iourov I. , Trifonov V. , Vermeesch J. , Weise A.
Published: January 2008

Small supernumerary marker chromosomes (sSMC) can appear in a numerically normal ‘basic karyotype’, but also in a numerically abnormal one like a Turner syndrome karyotype (= sSMCT). Here we present 17 new cases with such a mos 45,X/46,X,+mar karyotype. Moreover we reviewed all 512 cytogenetically similar cases available from the literature and supply for the first time data on occurrence, shapes and subgroups of this rare cytogenetic entity. sSMCT are very rare in the common population (1:100,000) – however, they can be observed with a 45- and even 60-times higher frequency in infertile and (develop)mentally retarded patients, respectively. Even though sSMCT derive from one of the gonosomes in >99% of the cases, there are also exceptional reports on sSMCT derived from one of the autosomes. The majority of sSMCT(X) form ring chromosomes, while most sSMCT(Y) are inverted duplicated/isodicentric chromosomes. Although >500 sSMCT are reported, a detailed characterization of the chromosomal breakpoints is only given for a minority. Thus, more cases with detailed (molecular) cytogenetic marker chromosome characterization are needed to provide information on formation and effects of an sSMCT.
EuroGentest: DNA-Based Testing for Heritable Disorders in Europe
Authors: Javaher Poupak , Kääriäinen Helena , Kristoffersson Ulf , Nippert Irmgard , Sequeiros Jorge , Zimmern Ron , Schmidtke Jörg
Published: January 2008

Objectives: Regarding the recent attention to develop policies regarding the provision of clinical genetic testing services, access to, acceptance, utilisation and regulation of genetic services was investigated in selected European countries as well as one non-European country. Methods: Data were collected on the basis of relevant international reports and sources accessible via the internet, from self- designed, internationally administered surveys and with the help of a panel of experts from European countries participating in several workshops as well as from National European Societies of Human Genetics. Results: A selection of divergent health care systems was reviewed and compared (e.g. Finland, Germany, Portugal, Sweden, UK, France, Italy, Spain, Czech Republic, Lithuania and Serbia/Montenegro). For the evaluation of clinical validity and utility of genetic testing, background information was provided focussing on DNA-based testing for heritable disorders with a strong genetic component (usually due to the action of a single gene). Conclusions: There is great heterogeneity in genetic testing services among the countries surveyed. It is premature to mandate that genetic testing provided by clinical services meets professional standards regarding clinical validity and utility, because there is to date no consensus within the scientific community and among health care providers to what extent clinical validity and utility can and need to be assessed. Points to consider in the process of developing such standards are proposed.
Vacuum Assisted Closure Device Improves the Take of Mesh Grafts in Chronic Leg Ulcer Patients
Authors: Körber A. , Franckson T. , Grabbe S. , Dissemond J.
Published: January 2008

Background: Vacuum assisted closure (VAC) is established in the management of acute and chronic wounds. In recent years, few data have been published concerning VAC therapy after skin graft transplantation. Objectives: The aim of this study was to determine whether postoperative VAC helps assist closure of mesh grafts in chronic leg ulcer patients. Patients/Methods: We report a consecutive case series of 54 patients with chronic leg ulcers who received a total of 74 mesh grafts. A postoperative VAC therapy was performed in 28 mesh grafts, and 46 mesh grafts were treated with standard gauze therapy. Results: In the VAC group, 92.9% of grafts showed complete healing, compared to 67.4% in the control group without postoperative VAC therapy. Differential analysis revealed a negative correlation of the take rate in patients over 70 years of age or in patients suffering from diabetes mellitus or dermatoliposclerosis. Particularly patients with diabetes mellitus and of greater age exhibited improved take rates, both 100%, in the VAC group compared to 50 and 62%, respectively. Conclusion: The results of our retrospective study demonstrate for the first time the significant benefit of VAC therapy after skin grafting in chronic leg ulcer patients as evaluated in a clinical trial.
Childhood Craniopharyngioma
Authors: Müller Hermann L.
Published: January 2008

Background: Craniopharyngioma are embryogenic malformations of the sellar area. With an overall incidence of 0.5–2 new cases per million population per year, 30–50% of all cases occur in childhood. Overall survival rates are high. However, quality of life (QoL) is substantially reduced in many survivors due to sequelae such as extreme obesity caused by hypothalamic lesions. Methods: Based on retrospective analysis of 306 patients with childhood craniopharyngioma (HIT ENDO), we found that QoL was negatively related to hypothalamic involvement, tumor size and the number of neurosurgical interventions. Results: Irradiation had no significant impact on long-term QoL. The prospective surveillance of 98 patients in KRANIOPHARYNGEOM 2000 revealed frequent and early events in terms of tumor relapse after apparently complete resection (EFS: 0.60 ± 0.09 at 3 years) and tumor progression after incomplete resection (EFS: 0.22 ± 0.09). Conclusion: We conclude that radical surgery in patients with hypothalamic involvement has a major negative impact on long-term QoL. Innovative treatment strategies are warranted to improve QoL in these patients at risk. Accordingly, the appropriate time point of irradiation after incomplete resection will be analyzed in KRANIOPHARYNGEOM 2007.
Metabolic Control and Growth during Exclusive Growth Hormone Treatment in X-Linked Hypophosphatemic Rickets
Authors: Mäkitie Outi , Toiviainen-Salo Sanna , Marttinen Eino , Kaitila Ilkka , Sochett Etienne , Sipilä Ilkka
Published: January 2008

Background: GH may improve phosphate balance and height in X-linked hypophosphatemic rickets (XLH). This study evaluated the impact of exclusive rhGH therapy on phosphate homeostasis and growth. Methods: Ten children (median age 12.2 years) with XLH were included in a 12-month trial with GH. Conventional treatment was discontinued 1 month prior GH (0.033 mg/kg/day); 1α-hydroxyvitamin D was added at 6 months and oral phosphate at 12 months, when GH was discontinued. Patients were followed 1–3 monthly until 18 months for clinical, biochemical and radiographic parameters. Results: Serum phosphate Z-score increased significantly from baseline at 6 months (p = 0.005) and 9 months (p = 0.009) but returned to baseline by 12 months. Serum 1,25-dihydroxyvitamin D also increased significantly. Parathyroid function normalized. The median height Z-score was –2.2 (–2.7 to +0.4) at GH onset and –1.7 (–2.3 to +0.3) at 12 months. One patient showed a significant increase in radiographic rickets activity and 3 patients aggravation of lower limb deformity; the others showed no changes or improvement in these parameters. Conclusions: GH treatment improved serum phosphate and 1,25-dihydroxyvitamin D, normalized parathyroid function and improved longitudinal growth in XLH. It may however aggravate pre-existing skeletal deformities.
Incidence of Classical 21-Hydroxylase Deficiency and Distribution of CYP21A2 Mutations in Estonia
Authors: Liivak Kaur , Tobi Simon , Schlecht Helene , Tillmann Vallo
Published: January 2008

Aims: To determine the incidence of classical 21-hydroxylase deficiency (21-OHD) in Estonia from 1978 to 2004, and describe their phenotype and genotype. Methods: All Estonian endocrinologists informed us about their patients with 21-OHD. The diagnosis was confirmed in 20 patients, who were all screened for 8 common mutations of the CYP21A2 gene. Results: The 27-year period incidence was 1:25,500. The incidence from 1992 was 1:16,100, which more accurately reflects the real situation in Estonia. The salt-wasting form (SW) was diagnosed in 14 (7 males) and the simple virilizing form in 6 patients (1 male). The median age at diagnosis of the SW form was 30 days in males and 2 days in females. The investigation of 34 unrelated alleles showed that a common deletion/conversion was the most frequent mutation in our group (7/34). Six other mutations were present: p.Ile172Asn (5/34), 8-bp deletion (3/34), intron-2 splice mutation (3/34), p.Arg356Trp (3/34), p.Gln318X (3/34) and a small conversion (2/34). Mutations in 8 alleles remained uncertain. Conclusions: The incidence of classical 21-OHD in Estonia in 1992–2004 was 1:16,100. The genotype of our patients is similar to those from other Caucasian populations. The relatively late age at diagnosis and the skewed female:male ratio supports the need for newborn screening for 21-OHD.
Evaluation of the Pituitary Function with Insulin Tolerance (Hypoglycaemia) Testing: Are There Any Differences Using Insulin Lispro Compared to Regular Insulin?
Authors: Yuen Kevin C.J. , Amin Rakesh , Cook Marie B. , Rhoads Sharon A. , Cook David M.
Published: January 2008

Background/Aim: The insulin tolerance test (ITT) remains the gold standard for evaluating the pituitary function, but has potential risks when hypoglycaemia is induced. There are scarce data using short-acting insulin analogs for ITTs. This pilot study compares the effects of insulin lispro (LPI) with regular insulin (RGI) during an ITT. Methods: Patients with suspected hypopituitarism (n = 103) randomly received either LPI (n = 51) or RGI (n = 52). Results: All patients reported signs and symptoms when hypoglycaemia was induced. In the LPI group, hypoglycaemia occurred sooner (23.6 ± 1.6 vs. 28.3 ± 1.4 min, p < 0.05), and duration of hypoglycaemia (25.0 ± 1.7 vs. 31.9 ± 1.9 min, p < 0.05) and time for blood glucose levels to return to a ‘safe’ level (>3.3 mmol/l; 56.5 ± 2.3 vs. 76.0 ± 2.1 min, p < 0.001) were shorter as compared with the RGI group. No differences in peak growth hormone and cortisol levels were observed between the two groups. Conclusions: Our data suggest that despite inducing similar symptomatology, LPI exerted a quicker onset and a shorter duration of hypoglycaemia as compared with RGI. Thus, using LPI might reduce the potential risks associated with an ITT by shortening the hypoglycaemic phase of the test.