bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrence in Supratentorial Anaplastic Ependymoma
Authors: Kumar Raj , Singhal Namit , Jaiswal Shishir K. , Mahapatra A.K.
Published: September 2007

Aim: To study the outcome and recurrence in supratentorial anaplastic ependymoma. Methods: Sixteen cases of supratentorial anaplastic ependymoma were reviewed. The average age of presentation was 8.2 years ranging from 1 to 16 years of age. The mean duration between the onset of first symptoms to time of presentation was 4.2 months. Follow-up ranged from 5 to 58 months with a mean of 16.8 months. Results: Gross total excision of tumor was achieved in 14 cases, as judged on the basis of intraoperative impression and confirmed with postoperative contrast MR or CT scan. There were 2 unfortunate deaths in the series, one as result of disseminated intravascular coagulation in view of massive blood loss and the other child had evidence of central transtentorial herniation preoperatively which failed to recover. Postoperative cranial radiotherapy was offered to all the 14 remaining cases. Twelve of 14 cases showed evidence of recurrence at follow-up. Recurrence occurred as early at 6 months and as late as 58 months. Only 2 children were recurrence free at follow-up of 6 months and 14 months, respectively. Two operated and irradiated cases of differentiated ependymomas (grade II) developed anaplastic recurrence at follow-up of 5 years and 9 years, respectively, suggesting a malignant transformation of tumor at follow-up. Four out of 12 cases were reoperated for their recurrence in view of localized nature of recurrence and good Karnofsky’s performance status. Conclusion: It is obvious that anaplastic ependymomas of the supratentorial compartment are aggressive tumors with high rates of recurrence even after gross total excision and irradiation. Gross total excision and postoperative irradiation are not effective in preventing early recurrence in anaplastic ependymomas, and other factors affecting the outcome need to be analyzed.
Glioblastoma Multiforme following Cranial Irradiation and Chemotherapy for Acute Lymphocytic Leukaemia
Authors: Menon R. , Muzumdar D. , Shah A. , Goel A.
Published: September 2007

The most common secondary neoplasms which occur following cranial radiation therapy are sarcoma and meningioma. The occurrence of glioblastoma multiforme following radiation and chemotherapy in acute lymphocytic leukaemia (ALL) is rare. We report 3 cases of glioblastoma multiforme in children developing 11–72 months following completion of chemotherapy/radiotherapy for ALL. The exact cause for the development of glioblastoma multiforme following therapy for ALL is not clear. A genetic predisposition may be essential for the occurrence of such a highly malignant primary brain tumour in leukaemia patients, irrespective of radiation and/or chemotherapy. The pathogenesis and surgical management are discussed, and the literature on the subject is reviewed.
Surgical Management of Chiari Malformation: Analysis of 128 Cases
Authors: Guo Fuyou , Wang Meiyun , Long Jiang , Wang Huaili , Sun Hongwei , Yang Bo , Song Laijun
Published: September 2007

Objective: A variety of surgical interventions have been recommended for patients with Chiari malformations (CMs). In this study, we have evaluated the intraoperative findings and clinical outcome in different-aged patients with CMs undergoing posterior fossa decompression. Methods: Sixteen pediatric and 112 adult cases with CMs underwent suboccipital craniectomy and wide duraplasty as well as autogenous bone grafting in selected cases. The clinical outcome was assessed by evaluation of postoperative signs and symptoms and magnetic resonance imaging of the craniocervical junction. Results: The most striking intraoperative finding was the presence of a very thin membrane over the opening of the central canal; the occurrence of this membrane in pediatric patients was significantly higher than that in adults (94 and 43%, respectively; p < 0.05, Fisher’s exact probability test). During the immediate postoperative period, 81% of pediatric CMs and 90% of adult CMs showed improved symptomatology and magnetic resonance imaging revealed favorable findings comprising syrinx collapse or reduction of the syrinx diameter in 14 (88%) pediatric and 92 (82%) adult CMs. During discharge from hospital, 103 (90%) patients with CMs type I and 11 (85%) with CMs type II achieved good results. However, there was a statistically significant difference in the occurrence of poor results between patients treated with bony fusion and those without fusion (24 vs. 6%;p < 0.05, Fisher’s exact probability test). The incidence of vertebral instability was markedly augmented in pediatric CMs in comparison to adult CMs (19 vs. 2%; p < 0.01, Fisher’s exact probability test). Conclusions: Suboccipital decompression and duraplasty with autogenous bone grafts in selected cases are effective treatments for most patients with CMs. A higher incidence of a special membrane over the obex and atlantoaxial instability were closely associated with childhood CMs.
CSF Fistula through the Umbilicus following a Shunt Surgery: A Case Report and Literature Review
Authors: Mohindra Sandeep , Singla Navneet , Gupta Rahul , Gupta Sunil Kumar
Published: September 2007

Background: Ventriculoperitoneal shunting is among the commonest neurosurgical operations. Shunt catheters within the peritoneal cavity have migrated through and perforated almost all the intra-abdominal hollow viscera. Case Description: A unique case of an infant is presented, in whom CSF leaked via a fistulous opening through the umbilicus. The embryological aspect of this anomalous communication is described, along with all the 7 cases previously reported with their pathophysiological causes. Conclusions: The CSF fistula through the umbilicus may be due to varying pathological causes. The present paper describes an altogether new pathological cause behind such a complication, with a re-visit to all other described causes. The present description of a patent intercoelomic communication, an embryological remnant, puts a new light on this 3-decade-old complication.
Ependymoma of the Cauda Equina Starting with Communicating Hydrocephalus: A Case Report
Authors: Tzekov Christo , Naydenov Emanuil , Kalev Ognian
Published: September 2007

The presence of concomitant hydrocephalus in cases with spinal cord tumors is relatively rare. Here, we describe a case of myxopapillary ependymoma of the cauda equina starting with communicating hydrocephalus in a 14-year-old boy. The patient presented to the clinic without underlying causes of hydrocephalus on the neuroimaging data. After ventriculoperitoneal shunt placement, despite the numerous malfunction incidents, the patient was doing well. Eight years later, he developed progressive weakness and coldness of the lower limbs. Multiple cystic lesions in the cervicothoracic area were found on magnetic resonance imaging. Decompressive hemilaminectomy of the cervicothoracic region was performed with temporary improvement of the patient’s condition. Because of persisting complaints, the sacral area of the spine was also observed and neuroimaging data for a tumoral lesion in the cauda equina region were found. The lesion was surgically removed and the histological result was myxopapillary ependymoma. Therefore, cases presenting with internal hydrocephalus without clear-cut intracranial etiology should have detailed neuroimaging of the whole central nervous system.
Schwannoma of the Cervical Vagus Nerve
Authors: Singh Devender , Pinjala R.K.
Published: September 2007

Nerve sheath tumors arising from the cervical vagus nerve are extremely rare and difficult to diagnose. We report a 14-year-old boy who presented with a several month history of an asymptomatic right cervical swelling. Ultrasound and fine needle aspiration cytology revealed a vascular lesion. He was meticulously evaluated with CT scan and digital subtraction angiography. Surgical excision of the lesion was carried out and histological examination revealed a schwannoma. Schwannoma is a relatively rare tumor and even rarer in children. The incidence of such tumors and the management of our patients are discussed.
Giant Malignant Nerve Sheath Tumor of Lumbosacral Plexus with Intraspinal Extension in a Child with Neurofibromatosis Type 1
Authors: Pratap Akshay , Nepal Pravin , Agrawal Amit , Singh Mahi Pal , Pandey Sagar Raj
Published: September 2007

Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in young adults and are one of the most frequent non-rhabdomyosarcomatous soft tissue tumors in pediatric age. These tumors usually occur in young adults from a previously recognized neurofibroma, neurofibromatosis type 1 (NF1), with a noted change in size and pain. This child reached the age of 10 without the presence of the more commonly seen manifestations of NF1. Pseudoarthrosis in children has a high rate of association with NF1, and in this case diagnosis of NF1 was supported by development of MPNST in a pre-existing plexiform neurofibroma.
Intramedullary Spinal Epidermoid Associated with an Intramedullary Lipoma
Authors: Bayar M. Akif , Gokcek Cevdet , Erdem Yavuz , Kilic Celal , Celik Haydar , Edebali Nurullah , Yasitli Ugur , Tekiner Ayhan
Published: September 2007

True intramedullary epidermoids and true intramedullary lipomas of the spinal cord are very rare lesions. To our knowledge, there has been no reported case associated with an intramedullary spinal lipoma. This is the first reported case with the association of these two lesions. In this report a 3-year-old boy with intramedullary spinal lipoma is presented. We discuss the frequency, clinical features, MRI characteristics and limits of surgical treatment of these tumors and review the associated literature.
Chiari Malformation Type III Treated with Primary Closure
Authors: Singh Jaggi Ramandeep , Premsagar Ishwar Chandra
Published: September 2007

Chiari malformations represent various clinical and anatomic processes that entail varying degrees of involvement of the rhombencephalon (hindbrain). The type III Chiari malformation is distinctly rare. Chiari described only one case of his type III deformity, which is indicative of its rarity. We report a case of Chiari malformation type III, a female child who presented to us at the age of 1 month with a swelling at the back of the neck since birth. MRI revealed a Chiari type III malformation with a high cervical meningoencephalocele along with herniation of cerebellar tissue through the bony defect in the posterior elements of the C2 vertebra. At surgery, the meningoencephalocele was excised along with the gliotic cerebellar tissue, and a posterior fossa decompression along with augmentation duraplasty was done. The postoperative period was uneventful. The case and relevant literature is reviewed.
Inflicted Traumatic Brain Injury: Advances in Evaluation and Collaborative Diagnosis
Authors: Glick Jill C. , Staley Kelley
Published: September 2007

The determination that a traumatic brain injury is not accidental requires data collection from multiple domains: historical, clinical, laboratory, radiographic, environmental and psychosocial. These essential, yet disparate, types of information must be synthesized in a collaborative and interdisciplinary process to formulate a medical opinion with regard to the cause of an injury, and the final opinion has tremendous consequences for children and families. Medically directed child protection teams have emerged as the standard of care in many children’s hospitals and child abuse pediatrics is now a recognized medical subspecialty with board certification available in the next several years. Not only do the child and family benefit from this coordinated effort, but there are also great benefits for the members of the child protection team: more clearly defined responsibilities, redirected focus on treatment for the surgeon, and increased confidence that the opinion is based upon consensus and current scientific knowledge. By this process and its division of labor, the child abuse pediatrician assumes responsibility for ensuring that a final medical opinion is arrived at, and then advocates for appropriate disposition for the child. The child abuse pediatrician is responsible for establishing institutional standards for family evaluation, collecting all necessary medical data and directing a consensus-based decision making process that is based upon current medical knowledge, medical literature and experience. The child abuse pediatrician also assumes the role of primary communication conduit for investigational agencies and the courts. The neurosurgeon is a key member of the child protection team and relies on the team to obtain necessary historical information to address consistency of the mechanism with the sustained injuries and has an integral role in determining the team’s final opinion. An interdisciplinary response to inflicted traumatic brain injury is the cornerstone for establishing a rigorous standard of care; it also fosters education across medical subspecialties where controversy has been a significant part of the landscape. Valid and useful clinical research that describes head injury as accidental or inflicted can only be performed in the context of an interdisciplinary, medically directed child protection team that strives for objectivity and precision in the determination of the manner of an injury.
Giant Colloid Cyst in a Child
Authors: Kasliwal Manish K. , Kiran Sai , Agrawal Deepak , Sharma Bhawani Shankar
Published: September 2007

We describe a case of a giant third ventricular colloid cyst occurring in a 10-year-old child with unusual imaging features and discuss the causes for these imaging findings.
Complete Remission of a Metastatic Pancreatic Carcinoma after Modified G-FLIP Therapy
Authors: Alldinger Ingo , Tsamaloukas Antonis G. , Germing Ulrich , Hosch Stefan B. , Knoefel Wolfram T.
Published: September 2007

This is a report about a patient who had a complete remission of a metastatic pancreatic adenocarcinoma after a modified G-FLIP therapy administered in an outpatient setting. The patient underwent surgery and the complete remission could be proven histologically. The administered chemotherapy was very effective and is even more attractive since it could be administered without admission to hospital.
Sectionectomy Is Suitable for Patients with T2 Hepatocellular Carcinoma according to the Modified International Union against Cancer TNM Classification
Authors: Ariizumi Shun-Ichi , Katagiri Satoshi , Katsuragawa Hideo , Kotera Yoshihito , Yamamoto Masakazu
Published: September 2007

Background/Aims: The effectiveness of systematized hepatectomy in the modified International Union Against Cancer (UICC) staging classification for hepatocellular carcinoma (HCC) has not been clarified in detail. Methods: We retrospectively studied 406 patients with UICC T1 HCC and 124 patients with T2 HCC who underwent initial curative hepatectomy from 1994 through 2003. Outcomes after sectionectomy or larger resection and segmentectomy or smaller resection for patients with T1 HCC and T2 HCC were examined. Results: The overall recurrence-free survival rate and survival rate of sectionectomy or larger resection at 5 years (45 and 79%, respectively) did not significantly differ from those of segmentectomy or smaller resection (38 and 81%, respectively) in patients with T1 HCC. However, in patients with T2 HCC, the 5-year recurrence-free survival rate and survival rate after sectionectomy or larger resection (37 and 71%, respectively) were significantly different from those after segmentectomy or smaller resection (6%: p < 0.0001, and 35%: p = 0.0027, respectively). Multivariate analysis showed sectionectomy or larger resection to be a significant independent prognostic factor for recurrence-free survival and survival in patients with T2 HCC. Conclusions: Sectionectomy or larger resection prevents intrahepatic recurrence of HCC and prolongs survival in patients with T2 HCC.
Red Hot Chilli Consumption Is Harmful in Patients Operated for Anal Fissure – A Randomized, Double-Blind, Controlled Study
Authors: Gupta Pravin J.
Published: September 2007

Aims: This study was aimed to determine whether there was any relationship between consumption of chillies and postoperative symptoms after closed anal sphincterotomy in patients with chronic anal fissure. Materials and Methods: Patients were randomly assigned to receive analgesics and fiber supplement alone (control patients) or consumption of 1.5 g chilli powder twice daily along with identical fiber and analgesics (chilli group). The evaluation of symptoms (pain, anal burning, and pruritus) during the postoperative period was assessed by means of patients’ self-questionnaires. The amount of analgesic tablets consumed and the frequency of stool during the study period were also noted. Results: 28 patients were recruited in each arm. Postoperative symptoms were higher in the group consuming chillies during the first postoperative week. The global scores for postoperative pain (7.60 in chilli group and 2.95 in control group, p < 0.001) and for anal burning (8.85 for the chilli group vs. 4.21 for the control group, p < 0.0001) were significant. Conclusion: This study shows that consumption of red chillies after anal fissure surgery should be forbidden to avoid postoperative symptoms.
Long-Term Results of Percutaneous Radiofrequency Ablation of Unresectable Colorectal Hepatic Metastases: Final Outcomes
Authors: Suppiah A. , White T.J. , Roy-Choudhury S.H. , Breen D.J. , Cast J. , Maraveyas A. , Hartley J.E. , Monson J.R.T.
Published: September 2007

Introduction: Percutaneous radiofrequency ablation (PcRFA) provides alternative means of treating patients with unresectable colorectal liver metastases. We previously reported our initial experience in 30 patients treated with PcRFA. We present the final long-term results in these 30 patients. Methods: The final outcome of the 30 patients treated with PcRFA is reported, 30 months following the initial results published in 2004. Results: Thirty patients (21 males and 9 females), median age 74.5 (44–85) years, underwent PcRFA for 57 lesions in 60 sessions. The final results in this cohort of patients are reported: 28 dead and 2 lost to follow-up. Median follow-up was 22 (3–53) months. Median size was 31 (8–70) mm. Nineteen lesions required repeat PcRFA. Median ablation time per lesion was 12 (4.5–36) min. Eleven patients received chemotherapy pre-PcRFA and 15 received chemotherapy post-PcRFA. Three patients went on to have limited hepatectomies. Complications occurred in 3 (5%) and median hospital stay was 1 (1–7) day. The median hepatic disease-free survival was 12 (95% CI 6.1–17.9) months and actuarial survival was 23.2 (95% CI 18.5–27.8) months. Conclusion: PcRFA is safe and associated with increased disease-free and overall survival in patients with unresectable colorectal hepatic metastases.
Intestinal Toxicity Induced by 5-Fluorouracil in Pigs: A New Preclinical Model
Authors: Manzano M. , Bueno P. , Rueda R. , Ramirez-Tortosa C.L. , Prieto P.A. , Lopez-Pedrosa J.M.
Published: September 2007

Background: The goal of this study was to develop an animal model of intestinal injury induced by 5-fluorouracil (5-FU) in pigs. Methods: Six domestic pigs were used as control (healthy group) and another 6 malnourished pigs orally received 5-FU (treated group). After 4 weeks of treatment, pigs were sacrificed and jejunum, ileum and colon were isolated for histological, immunological and biochemical analyses. Results: 5-FU caused a decrease in the intestinal mass. Disaccharidase, and phosphate alkaline activities, and glutathione redox cycle were disrupted by 5-FU. Histopathological alterations in the crypts and villous were greater in the small intestine than in the colon. 5-FU decreased the number of peripheral and intestinal leukocytes, promoting an increase in T-cytotoxic cells and a decrease in T-helper and B cells. Conclusion: This pig model of intestinal dysfunction closely mimics the common side effects of cancer chemotherapy in humans, and provides a useful tool for evaluating novel antimucotoxic agents.
Successful Preoperative Chemotherapy with S-1 plus Low-Dose Cisplatin for Advanced Gastric Cancer with Synchronous Liver Metastases: Report of 2 Cases
Authors: Takahashi Naoto , Nimura Hiroshi , Aoki Hiroaki , Koyama Tomoki , Mitsumori Norio , Aiba Keisuke , Kashiwagi Hideyuki , Yanaga Katsuhiko
Published: September 2007

We report 2 cases of advanced gastric cancer with synchronous liver metastases who were successfully downstaged using S-1 plus low-dose cisplatin chemotherapy followed by surgical resection. S-1 was administered orally (80 mg/m2/day) twice daily for 14 consecutive days, and cisplatin (15 mg/m2) was infused over 1 h on days 1 and 8. Successful downstaging of the hepatic metastases was confirmed by imaging analyses; however, neither patient showed a complete response of the primary lesion in the stomach. Toxicities, according to the WHO criteria, were mild. The patients underwent surgical resection within 4 weeks after the last chemotherapy. Postoperatively, they were discharged without complications and received adjuvant chemotherapy. Both patients remained alive and well at 17 and 12 months after surgery, respectively, without recurrence. These cases provide further evidence that S-1 plus low-dose cisplatin chemotherapy enables downstaging of advanced gastric cancer and a subsequent potentially curative resection without serious complications.
Diagnosis, Management and Clinical Outcome of Bone Metastases in Breast Cancer Patients: Results from a Prospective, Multicenter Study
Authors: Cazzaniga Marina E. , Dogliotti Luigi , Cascinu Stefano , Barni Sandro , Labianca Roberto , Chiara Silvana , Conte Pier Franco , Gasparini Giampietro , Pasetto Lara , Torri Valter
Published: September 2007

Background: Little information is available about the management and clinical outcome of bone metastases (BM) in breast cancer patients. Methods: We prospectively studied 459 breast cancer patients with first diagnosis of BM for at least 2 years to collect information about diagnosis, management and clinical outcome. Results: Two hundred and forty-eight patients (54%) had only BM, 86 (18.7%) had concomitant nonskeletal BM and 125 (27.2%) had previous nonskeletal BM. At enrolment, skeletal-related events were present in 132 patients (28.8%). Cancer treatments consisted of hormones (227/459, 49.5%) or chemotherapy (192/459, 41.8%). Age (≤70) and nonskeletal BM are inversely correlated with the use of chemotherapy or endocrine treatment (p < 0.0001). Bisphosphonates were used in 67.5% of the cases, alone (62.3%) or combined with other drugs. After a median follow-up of 28 months (range 2–43), 272 patients developed new metastases (59.2%), progression occurred mainly in nonskeletal sites (107/459, 23.3%), except for BM patients, who progressed prevalently at bone (69/248, 27.8%). New skeletal-related events were observed in 122 patients (26.6%). The 2-year probability for disease progression control and survival was 0.19 (95% CI 0.15–0.24) and 0.64 (95% CI 0.58–0.69), respectively. The 2-year probability for death according to the presence of nonskeletal metastases and the time of appearance (previous or concomitant to BM) was 0.74 (95% CI 0.67–0.79) for BM, 0.38 (95% CI 0.25–0.51) for previous nonskeletal BM and 0.56 (95% CI 0.46–0.66) for concomitant nonskeletal BM (p < 0.0001). Conclusions: Clinical outcome is significantly different according to the metastatic sites.
Antioxidant Activity in the Newborn Brain: A Luciferase Mouse Model
Authors: Dohlen Gaute , Odland Hans Henrik , Carlsen Harald , Blomhoff Rune , Thaulow Erik , Saugstad Ola Didrik
Published: September 2007

Introduction: Oxidative stress in the newborn period may cause cell injury and inflammation if the antioxidant capacity is insufficient. To monitor antioxidant and inflammatory activity we examined by in vivo imaging various strains of luciferase reporter mice whose light-emitting properties were regulated by response elements or complete promoters related to oxidative stress and/or inflammation. The aim of this study is to present a model that can monitor genetic activity in vivo during pregnancy and the first 10 days of life. Methods: One mouse strain reports the activity of nuclear factor-ĸB (NF-ĸB) activity, a transcription factor essential for modulating inflammation, apoptosis, differentiation and cell growth. A second mouse strain reports on superoxide dismutase 1-promoter activity. A third strain reports the promoter activity of γ-glutamylcysteine synthetase, the rate limiting enzyme in glutathione production, and the last strain reports on antioxidant responsive element (ARE)/electrophil responsive element. Wild-type female mice mated with NF-ĸB mice were imaged through pregnancy to monitor intrauterine NF-ĸB activation. Results: Intrauterine NF-ĸB activity increased dramatically from day 17 towards labor. During the first 4 days of life luminescence measured was intense in all mice with distinct strain differences. All strains had high luminescence levels at day 1 and a considerably lower level at day 10. Conclusion: This model allows investigation of the transcriptional regulation of key proteins related to oxidative stress and inflammation in pregnancy and the first days of life. With very little stress to the newborn animals genetic activity can be monitored day by day.
Lidocaine Attenuates Lipopolysaccharide-Induced Acute Lung Injury through Inhibiting NF-κB Activation
Authors: Feng Guang , Liu Su , Wang Guang-Lei , Liu Gong-Jian
Published: September 2007

Background and Objectives: Lidocaine has been reported to attenuate the inflammatory response in addition to its anesthetic activity, but the mechanisms are poorly understood. The objective of this study is to determine if lidocaine prior to endotoxemia diminishes pulmonary dysfunction by blocking the NF-ĸB activation. Methods: Rats were assigned to: (1) control (0.9% sodium chloride); (2) lipopolysaccharides (LPS); (3) LPS + lidocaine 1 mg/kg; (4) LPS + lidocaine 2 mg/kg, and (5) LPS + lidocaine 4 mg/kg. The LPS and LPS + lidocaine 4 mg/kg groups were subjected to 1-, 3-, 6- and 12-hour time points. To investigate the activation of NF-ĸB, the expression of NF-ĸB in the nuclear and IĸBα in the cytosol extracts were analyzed by Western blot. The concentration of TNF-α and IL-6 in serum was detected by ELISA. The pathologic changes of the lung were observed using HE staining. Results: After i.p. injection of LPS, the expression of NF-ĸB in the nuclear extracts was significantly increased and IĸBα in the cytosol extracts was markedly decreased. The concentration of TNF-α and IL-6 in serum was increased. Pathological examination showed that the normal structure of the lung was destroyed badly. However, lidocaine reversed the above results. Conclusion: Lidocaine attenuates LPS-induced lung injury via mechanisms involving inhibiting NF-ĸB activation and cytokine release, which implies that lidocaine may be a potential anti-inflammatory agent in endotoxemia.
Neurohumoral Activity, Heart Failure and Prognosis in Patients with End-Stage Renal Disease Treated by Hemodialysis
Authors: Spinar J. , Ludka O. , Dusek L. , Vitovcova L. , Sobotova D. , Spinarova L. , Tomandl J. , Vitovec J.
Published: September 2007

Background: Chronic renal failure treated by regular hemodialysis is frequently accompanied by chronic heart failure; the mortality of both is high. Aim: To evaluate the role of markers of neurohumoral activation for the prognosis of patients treated with regular dialysis. Patients: 99 patients with end-stage renal disease were followed up for 3 years. Methods: Clinical evaluation, echocardiography, biochemistry including NT-proBNP and big endothelin (Big-ET). Results: The incidence of heart failure was 97% and the 3-year mortality was 50%. The sensitivity of NT-proBNP and Big-ET level for the prediction of death was 0.712 and 0.824, respectively, and specificity 0.642 and 0.695, respectively. The cut-off points were NT-proBNP ≧2,000 pg/ml and Big-ET ≧1.55 pmol/l. Neither NT-proBNP nor Big-ET could be incorporated in the multivariate model for overall survival, which means that although both parameters significantly influenced overall survival as single risk factors, they were not effective in competition with the other significant predictors. Conclusion: Overall survival seems to be influenced namely by age, hemoglobin, left atrium diameter or pulmonary congestion class on chest X-ray, while probability of early risk was associated with Big-ET, history of diabetes mellitus, C-reactive protein, uric acid and hemoglobin. The only intersection of the models is hemoglobin as a thoroughly significant predictor.
Urinary Excretion of Monocyte Chemoattractant Protein-1: A Biomarker of Active Tubulointerstitial Damage in Patients with Glomerulopathies
Authors: Dantas Márcio , Almeida Romão Elen , Silva Costa Roberto , dos Reis Marlene Antônia , Vieira Neto Osvaldo Merege , Ribeiro Richard Augusto , Ravinal Roberto Cuan , Rodrigues Júnior Antônio Luiz , Coimbra Terezila Machado
Published: September 2007

Background/Aims: The urinary concentration of the monocyte chemoattractant protein-1 (uMCP-1) chemokine is increased in several proteinuric and/or inflammatory renal diseases. In the present study, we evaluated the association between uMCP-1 and renal function, proteinuria, glomerular and interstitial macrophage infiltration, and renal fibrosis in patients with primary and secondary glomerulopathies diagnosed by renal biopsy. Methods: Thirty-seven patients aged 32.6 ± 7.7 years were studied. uMCP-1 was determined by ELISA. Renal macrophage expression (CD68 positive cells) is reported as number of macrophages/104 µm2 of the cortical tubulointerstitial (TI) area or of glomerular capillary tuft area. Cortical interstitial fibrosis was quantitated by PicroSirius red staining under polarized light by a computerized manner. Results: The uMCP-1 ratio (pg/ml/urinary creatinine mg/ml) was positively correlated (Spearman coefficient) with proteinuria (r = 0.4629; p < 0.005) and number of macrophages in the cortical TI area (r = 0.64; p = 0.0005), and negatively correlated with creatinine clearance (r = –0.4877; p < 0.001). The uMCP-1 ratio was not significantly correlated with number of macrophages/glomerular capillary tuft area (r = 0.27; p = 0.19) or with percent cortical interstitial fibrosis (r = 0.08; p = 0.62). Conclusions: The uMCP-1 excretion is a biomarker of the inflammatory activity of the TI area, and does not reflect chronic interstitial damage.
Change in Salt Intake Affects Blood Pressure of Chimpanzees
Authors: Elliott Paul , Walker Lesley L. , Little Mark P. , Blair-West John R. , Shade Robert E. , Lee D. Rick , Rouquet Pierre , Leroy Eric , Jeunemaitre Xavier , Ardaillou Raymond , Paillard Francoise , Meneton Pierre , Denton Derek A.
Published: September 2007

Background—

Addition of up to 15.0 g/d salt to the diet of chimpanzees caused large rises in blood pressure, which reversed when the added salt was removed. Effects of more modest alterations to sodium intakes in chimpanzees, akin to current efforts to lower sodium intakes in the human population, are unknown.

Methods and Results—

Sodium intakes were altered among 17 chimpanzees in Franceville, Gabon, and 110 chimpanzees in Bastrop, Tex. In Gabon, chimpanzees had a biscuit diet of constant nutrient composition except that the sodium content was changed episodically over 3 years from 75 to 35 to 120 mmol/d. In Bastrop, animals were divided into 2 groups; 1 group continued on the standard diet of 250 mmol/d sodium for 2 years, and sodium intake was halved for the other group. Lower sodium intake was associated with lower systolic, diastolic, and mean arterial blood pressures in Gabon (2-tailed
P
<0.001, unadjusted and adjusted for age, sex, and baseline weight) and Bastrop (
P
<0.01, unadjusted;
P
=0.08 to 0.10, adjusted), with no threshold down to 35 mmol/d sodium. For systolic pressure, estimates were −12.7 mm Hg (95% confidence interval, −16.9 to −8.5, adjusted) per 100 mmol/d lower sodium in Gabon and −10.9 mm Hg (95% confidence interval, −18.9 to −2.9, unadjusted) and −5.7 mm Hg (95% confidence interval, −12.2 to 0.7, adjusted) for sodium intake lower by 122 mmol/d in Bastrop. Baseline systolic pressures higher by 10 mm Hg were associated with larger falls in systolic pressure by 4.3/2.9 mm Hg in Gabon/Bastrop per 100 mmol/d lower sodium.

Conclusions—

These findings from an essentially single-variable experiment in the species closest to
Homo sapiens
with high intakes of calcium and potassium support intensified public health efforts to lower sodium intake in the human population.
Bone Morphogenic Protein Antagonists Are Coexpressed With Bone Morphogenic Protein 4 in Endothelial Cells Exposed to Unstable Flow In Vitro in Mouse Aortas and in Human Coronary Arteries
Authors: Chang Kyunghwa , Weiss Daiana , Suo Jin , Vega J. David , Giddens Don , Taylor W. Robert , Jo Hanjoong
Published: September 2007

Background—

Exposure to disturbed flow, including oscillatory shear stress, stimulates endothelial cells (ECs) to produce bone morphogenic protein (BMP) 4, which in turn activates inflammation, a critical atherogenic step. BMP activity is regulated by the level of BMP antagonists. Until now it was not known whether shear also regulates the expression of BMP antagonists and whether they play a role in EC pathophysiology.

Methods and Results—

BMP antagonists follistatin, noggin, and matrix Gla protein were expressed in cultured bovine and human arterial ECs. Surprisingly, oscillatory shear stress increased expression of the BMP antagonists in ECs, whereas unidirectional laminar shear decreased such expression. Immunohistochemical studies with mouse aortas showed data consistent with in vitro findings: Only ECs in the lesser curvature exposed to disturbed flow, but not those in the greater curvature and straight arterial regions exposed to undisturbed flow, showed coexpression of BMP4 and the BMP antagonists. Similarly, in human coronary arteries, expression of BMP4 and BMP antagonists in ECs positively correlated with the severity of atherosclerosis. Monocyte adhesion induced by oscillatory shear stress was inhibited by knockdown of BMP4 or treatment with recombinant follistatin or noggin, whereas it was increased by knockdown of follistatin and/or noggin.

Conclusions—

The present results suggest that ECs coexpress BMP antagonists along with BMP4 in an attempt to minimize the inflammatory response by oscillatory shear stress as part of a negative feedback mechanism. The balance between the agonist, BMP4, and its antagonists may play an important role in the overall control of inflammation and atherosclerosis.
Atrium-Selective Sodium Channel Block as a Strategy for Suppression of Atrial Fibrillation
Authors: Burashnikov Alexander , Di Diego José M. , Zygmunt Andrew C. , Belardinelli Luiz , Antzelevitch Charles
Published: September 2007

Background—

The development of selective atrial antiarrhythmic agents is a current strategy for suppression of atrial fibrillation (AF).

Methods and Results—

Whole-cell patch clamp techniques were used to evaluate inactivation of peak sodium channel current (
I
Na
) in myocytes isolated from canine atria and ventricles. The electrophysiological effects of therapeutic concentrations of ranolazine (1 to 10 μmol/L) and lidocaine (2.1 to 21 μmol/L) were evaluated in canine isolated coronary-perfused atrial and ventricular preparations. Half-inactivation voltage of
I
Na
was ≈15 mV more negative in atrial versus ventricular cells under control conditions; this difference increased after exposure to ranolazine. Ranolazine produced a marked use-dependent depression of sodium channel parameters, including the maximum rate of rise of the action potential upstroke, conduction velocity, and diastolic threshold of excitation, and induced postrepolarization refractoriness in atria but not in ventricles. Lidocaine also preferentially suppressed these parameters in atria versus ventricles, but to a much lesser extent than ranolazine. Ranolazine produced a prolongation of action potential duration (APD
90
) in atria, no effect on APD
90
in ventricular myocardium, and an abbreviation of APD
90
in Purkinje fibers. Lidocaine abbreviated both atrial and ventricular APD
90
. Ranolazine was more effective than lidocaine in terminating persistent AF and in preventing the induction of AF.

Conclusions—

Our study demonstrates important differences in the inactivation characteristics of atrial versus ventricular sodium channels and a striking atrial selectivity for the action of ranolazine to produce use-dependent block of sodium channels, leading to suppression of AF. Our results point to atrium-selective sodium channel block as a novel strategy for the management of AF.
Parental Occurrence of Premature Cardiovascular Disease Predicts Increased Coronary Artery and Abdominal Aortic Calcification in the Framingham Offspring and Third Generation Cohorts
Authors: Parikh Nisha I. , Hwang Shih-Jen , Larson Martin G. , Cupples L. Adrienne , Fox Caroline S. , Manders Emily S. , Murabito Joanne M. , Massaro Joseph M. , Hoffmann Udo , O’Donnell Christopher J.
Published: September 2007

Background—

Parental premature cardiovascular disease (CVD) is a risk factor for coronary heart disease (CHD). We related validated parental premature CVD with the subclinical measures of coronary artery (CAC) and abdominal aortic (AAC) calcification in the community.

Methods and Results—

We studied 2 generations of Framingham Heart Study subjects who underwent multidetector computed tomography measurements of CAC and AAC and who had 2 parents in the study. Subjects included 797 Framingham Offspring (mean age, 63 years; 56% women) and 1238 Third Generation (Gen3) (mean age, 46 years; 47% women) participants free of CVD. Generalized estimating equations adjusted for major CVD risk factors were used to relate validated parental premature CVD and CHD to CAC and AAC, defined by >90th percentile age- and sex-specific cut points from a healthy subsample. Parental premature CVD was associated with CAC among Gen3 (odds ratio=2.17 [1.41 to 3.33];
P
<0.001) and nonsignificantly among Offspring (odds ratio=1.42 [0.91 to 2.22];
P
=0.12). Parental premature CHD was associated with CAC among Gen3 (odds ratio=2.22 [1.22 to 4.01]) but not Offspring. Parental premature CVD was not associated with AAC in either cohort. Parental premature CHD was associated with AAC among Gen3 (odds ratio=1.65 [0.99 to 2.75];
P
=0.05) but not among Offspring. The magnitude of risk conferred was greater for paternal than maternal premature CVD.

Conclusions—

Parental premature CVD is associated with CAC, and premature CHD is associated with AAC, after adjustment for risk factors, particularly in younger middle-aged adults. Risk conferred by parental premature CVD on vascular calcification may be mediated through novel mechanisms not accounted for by classic CVD risk factors known to cause atherosclerosis.
Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension
Authors: Lewis Gregory D. , Shah Ravi , Shahzad Khurram , Camuso Janice M. , Pappagianopoulos Paul P. , Hung Judy , Tawakol Ahmed , Gerszten Robert E. , Systrom David M. , Bloch Kenneth D. , Semigran Marc J.
Published: September 2007

Background—

Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension (PH) have reduced exercise capacity and increased mortality compared with HF patients without PH. We tested the hypothesis that sildenafil, an effective therapy for pulmonary arterial hypertension, would lower pulmonary vascular resistance and improve exercise capacity in patients with HF complicated by PH.

Methods and Results—

Thirty-four patients with symptomatic HF and PH were randomized to 12 weeks of treatment with sildenafil (25 to 75 mg orally 3 times daily) or placebo. Patients underwent cardiopulmonary exercise testing before and after treatment. The change in peak V̇
o
2
from baseline, the primary end point, was greater in the sildenafil group (1.8±0.7 mL · kg
−1
· min
−1
) than in the placebo group (−0.27 mL · kg
−1
· min
−1
;
P
=0.02). Sildenafil reduced pulmonary vascular resistance and increased cardiac output with exercise (
P
<0.05 versus placebo for both) without altering pulmonary capillary wedge or mean arterial pressure, heart rate, or systemic vascular resistance. The ability of sildenafil treatment to augment peak V̇
o
2
correlated directly with baseline resting pulmonary vascular resistance (
r
=0.74,
P
=0.002) and indirectly with baseline resting right ventricular ejection fraction (
r
=−0.64,
P
=0.01). Sildenafil treatment also was associated with improvement in 6-minute walk distance (29 m versus placebo;
P
=0.047) and Minnesota Living With Heart Failure score (−14 versus placebo;
P
=0.01). Subjects in the sildenafil group experienced fewer hospitalizations for HF and a higher incidence of headache than those in the placebo group without incurring excess serious adverse events.

Conclusions—

Phosphodiesterase 5 inhibition with sildenafil improves exercise capacity and quality of life in patients with systolic HF with secondary PH.
Peroxisome Proliferator-Activated Receptor-γ Is Involved in the Control of Renin Gene Expression
Authors: Todorov Vladimir T. , Desch Michael , Schmitt-Nilson Nina , Todorova Anelia , Kurtz Armin
Published: September 2007

Based on the presence of a functional retinoic acid receptor/retinoid X receptor transcription factor binding sequence (hormone-responsive element) in the renin gene enhancer and on the fact that the peroxisome proliferator-activated receptors (PPARs) bind to DNA as heterodimers with retinoid X receptors, we speculated that PPARs are involved in the regulation of renin gene expression. To test this hypothesis, we used the human renin-producing cell line CaLu-6. Endogenous or pharmacological PPARγ agonists (unsaturated fatty acids and thiazolidinediones, respectively) stimulated renin gene expression. Surprisingly, we found that PPARγ targets a palindromic repeat with a 3-bp spacer (Pal3) in the proximal human renin promoter. Thus, renin is the first gene described with a functional Pal3 sequence. PPARγ agonists also stimulated renin gene expression in cultured native juxtaglomerular cells, which are the main source of renin in vivo. In summary, PPARγ was identified as a novel intracellular mediator involved in the upregulation of renin transcription.
Rho Kinase Activation and Gene Expression Related to Vascular Remodeling in Normotensive Rats With High Angiotensin I–Converting Enzyme Levels
Authors: Rivera Paulina , Ocaranza María Paz , Lavandero Sergio , Jalil Jorge E.
Published: September 2007

The RhoA/Rho kinase (ROCK) pathway is a new mechanism of remodeling and vasoconstriction. Few data are available regarding ROCK activation when angiotensin I–converting enzyme is high and blood pressure is normal. We hypothesized that ROCK is activated in the vascular wall in normotensive rats with genetically high angiotensin I–converting enzyme levels, and it causes increased vascular expression of genes promoting vascular remodeling and also oxidative stress. Aortic ROCK activation, mRNA and protein levels (of monocyte chemoattractant protein-1, transforming growth factor [TGF]-β
1
, and plasminogen activator inhibitor-1 [PAI-1]), NADPH oxidase activity, and O
2
·−
production were measured in normotensive rats with genetically high (Brown Norway [BN]) and low (Lewis) angiotensin-I–converting enzyme levels and in BN rats treated with the ROCK antagonist fasudil (100 mg/kg per day) for 7 days. ROCK activation was 12-fold higher in BN versus Lewis rats (
P
<0.05) and was reduced with fasudil by 100% (
P
<0.05). Aortic TGF-β1, PAI-1, and monocyte chemoattractant protein-1 mRNA levels were higher in BN versus Lewis rats by 300%, 180%, and 1000%, respectively (
P
<0.05). Aortic TGF-β1, PAI-1, and monocyte chemoattractant protein-1 protein levels were higher in BN versus Lewis rats (
P
<0,05). Fasudil reduced TGF-β1 and PAI-1 mRNA and TGF-β1, PAI-1, and monocyte chemoattractant protein-1 protein aortic levels to those observed in Lewis rats. Aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity and
.
O
2
−
production were increased by 88% and 300%, respectively, in BN rats (
P
<0.05) and normalized by fasudil. In conclusion, ROCK is significantly activated in the aortic wall in normotensive rats with genetically high angiotensin-I–converting enzyme and angiotensin II, and it causes activation of genes that promote vascular remodeling and also increases vascular oxidative stress.
Expression and Function of the Calcium-Sensing Receptor in Juxtaglomerular Cells
Authors: Ortiz-Capisano M. Cecilia , Ortiz Pablo A. , Garvin Jeffrey L. , Harding Pamela , Beierwaltes William H.
Published: September 2007

Calcium-sensing receptors sense and translate micromolar changes of extracellular calcium into changes in intracellular calcium. Renin, a component of the renin-angiotensin system, is synthesized by, stored in, and released from the juxtaglomerular cells through a cAMP-dependent pathway. Increased intracellular calcium inhibits the adenylyl cyclase isoform type V, cAMP formation, and renin release from juxtaglomerular cells. We hypothesized that calcium-sensing receptors are expressed in juxtaglomerular cells and mediate changes in intracellular calcium and renin release. To test this we used primary cultures of isolated mouse juxtaglomerular cells in which we ran RT-PCR, Western blots, and immunofluorescence. RT-PCR showed a positive band at the expected 151 bp consistent with calcium-sensing receptor. Western blots showed a 130- to 150-kDa band confirming the calcium-sensing receptor in juxtaglomerular cells. Immunofluorescence and confocal microscopy using 2 different antibodies against the calcium-sensing receptor in juxtaglomerular cells showed positive fluorescence in the juxtaglomerular cells, which also had positive labeling for renin. To test whether calcium-sensing receptors regulate renin release, juxtaglomerular cells were incubated with a calcium-sensing receptor agonist, the calcimimetic cinacalcet-HCl, at concentrations of 50 and 1000 nmol/L in 0.25 mmol/L of calcium medium. Cinacalcet-HCl decreased juxtaglomerular cell cAMP formation to 47.3±6.8% and 44.2±9.7% of basal, respectively (
P
<0.001), and decreased renin release from 541.9±86.2 to 364.6±64.1 (
P
<0.05) and 279.6±56.9 (
P
<0.005) ng of angiotensin I per milliliter per hour per milligram of protein, respectively. We conclude that juxtaglomerular cells express the calcium-sensing receptor and that their activation leads to inhibition of adenylyl cyclase-V activity, decreasing cAMP formation and suppressing renin release.