bluuebunny/crossref_metadata_2025 huggingface dataset:
Patent Ductus Arteriosus and Respiratory Outcome in Premature Infants
Authors: Bancalari Eduardo , Claure Nelson , Gonzalez Alvaro
Published: October 2005

A persistent ductus arteriosus is a common event in preterm infants. The systemic-to-pulmonary shunting that occurs as the pulmonary vascular resistance decreases after birth can have significant cardiovascular and respiratory consequences. Acute pulmonary effects include pulmonary edema and hemorrhage, worsened lung mechanics and deterioration in gas exchange with hypoxemia and hypercapnia. The increased pulmonary blood flow can also produce damage to the capillary endothelium and trigger an inflammatory cascade. This, plus the need for longer and more aggressive mechanical ventilation, can explain the association between patent ductus arteriosus and an increased risk for bronchopulmonary dysplasia in extremely premature infants.
The Clever Fetus: Responding to Inflammation to Minimize Lung Injury
Authors: Kramer Boris W. , Jobe Alan H.
Published: October 2005

Clinical and experimental information indicate that fetal exposure to inflammation can induce lung maturation. This inflammation may be chronic and indolent. We present clinical and experimental information that challenge assumptions about chorioamnionitis associated infection/inflammatory exposures to the fetus. We question the assumption that the fetal compartment is sterile, and that delivery is inevitable if chronic infection/inflammation is present. We demonstrate that the preterm fetus can develop a brisk and adequate inflammatory response, and the fetus also can quickly modulate and downregulate inflammation to prevent injury. The fetus at risk of early preterm delivery may be exposed to both chorioamnionitis and glucocorticoids. Both exposures can either increase or decrease fetal inflammatory responses depending on the timing of the exposures. The immunomodulatory ability of the fetus to fetal exposures remains an unexplored research field.
Methylxanthine Therapy for Apnea of Prematurity: Evaluation of Treatment Benefits and Risks at Age 5 Years in the International Caffeine for Apnea of Prematurity (CAP) Trial
Authors: Schmidt Barbara
Published: October 2005

Methylxanthine therapy reduces the frequency of apnea and the need for mechanical ventilation. Recent research has raised concerns about the safety of methylxanthines in very preterm infants. Possible adverse effects include poor growth, worsening of hypoxic-ischemic brain damage and abnormal childhood behavior. Over 2,000 infants with birth weights 500–1,250 g have been randomized in the international placebo-controlled Caffeine for Apnea of Prematurity (CAP) trial to examine the long-term efficacy and safety of methylxanthine therapy for the management of apnea of prematurity. Additional therapies such as continuous positive airway pressure were used as necessary to control apneic attacks. At 18 months we measure the combined rate of death or survival with one or more of the following impairments: cerebral palsy, cognitive deficit, blindness and deafness. This outcome was chosen because of the need to evaluate the impact of common neonatal therapies beyond discharge from the intensive care unit. However, several potential long-term consequences of methylxanthine therapy may not become apparent until the study cohort reaches pre-school age. We will therefore extend the follow-up to age 5 years. The main outcome at 5 years will be a composite of death or survival with severe disability in at least one of six domains: cognition, neuromotor function, vision, hearing, behavior, and general health. Once this project is completed, caffeine will be one of the most rigorously evaluated neonatal therapies.
Dysregulation of Expression of Immunoregulatory and Cytokine Genes and Its Association with the Immaturity in Neonatal Phagocytic and Cellular Immunity
Authors: Satwani Prakash , Morris Erin , van de Ven Carmella , Cairo Mitchell S.
Published: October 2005

Background: Innate and adaptive immunity is comprised of cellular and humoral factors that provide rapid protection against microbial invasion. However, immaturity of innate and adaptive immune responses in the perinatal period predisposes the neonate to increased infectious morbidity and mortality from a variety of organisms. Objectives: To elucidate dysregulation of expression of various immunoregulatory and cytokine genes and its association with the immaturity in neonatal phagocytic cellular immunity. Methods: Comparison of protein production and mRNA of granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-12, IL-15 and IL-18 in adult peripheral blood (APB) mononuclear cells (MNC) and cord blood (CB) MNC was studied. Effects of hematopoietic growth factors (HGFs, GM-CSF, M-CSF, G-CSF, IL-11) were studied in vivo in rats as well as randomized controlled studies conducted in neonates. Oligonucleotide microarrays were used to study gene expression patterns of activated CB and APB monocytes and dendritic cells. Results and Conclusions: We demonstrated dysregulation of various immunoregulatory and cytokine genes in CB MNC. This dysregulation may in part explain the immaturity of neonatal cell-mediated immunity. There are probably various dysregulated cytokines yet to be discovered. Biological agents such as IL-2, IL-12, IL-11 and/or IL-18 alone or in combination with HGFs should be considered for future studies to identify new approaches to enhance neonatal host defense, and thereby decrease the incidence of neonatal sepsis and the consequent high risk of morbidity and mortality.
Oxidative Stress in the Newborn – A 30-Year Perspective
Authors: Saugstad Ola Didrik
Published: October 2005

In this review the development of the concept ‘hypoxia-reoxygenation injury’ is outlined. An update of some important factors and mechanisms related to oxidative stress injury in newborn infants is presented, including the metabolism of glutathione, the role of antioxidants, iron and nitric oxide, and how these may influence health and disease in the newborn and contribute to ‘oxygen radical disease of the newborn’. New insight into how hyperoxia and hypoxia may induce changes leading to retinopathy of prematurity by vascular endothelial growth factor acting in concert with insulin-like growth factor is briefly summarized. Inflammation and oxidative stress seem to be two sides of the same coin in newborn babies both contributing to injury partly through similar mechanisms.
Non-Invasive Diagnostic Tests for Bladder Cancer: A Review of the Literature
Authors: Bassi PierFrancesco , De Marco Vincenzo , De Lisa Antonello , Mancini Mariangela , Pinto Francesco , Bertoloni Rossella , Longo Fabrizio
Published: October 2005

Transitional cell carcinoma of the bladder is the second most common malignancy of the genitourinary tract. Cystoscopy and urine cytology are the traditional most used techniques for diagnosis and surveillance of superficial bladder cancer. Urine cytology is specific for diagnosis of bladder cancer but sensitivity results not high, particularly in low-grade disease. Voided urine can be easily obtained and therefore additional diagnostic urine tests would be ideal for screening or follow-up of transitional cell carcinoma. A number of studies have focused on the evaluation of urinary markers that hold promise as non-invasive adjuncts to conventional diagnostic or surveillance techniques. In this review we discuss several new urinary markers (test for bladder tumor antigen, NMP22®, fibrin degradation products, telomerase, fluorescence in situ hybridization test, flow cytometry) and their role in detection and follow-up of bladder cancer. Most of these markers have higher sensitivity than urine cytology, but voided urine cytology has the highest specificity.
Intermittent Androgen Castration: A Biological Reality during Intermittent Treatment in Metastatic Prostate Cancer?
Authors: Mottet N. , Lucas C. , Sene E. , Avances C. , Maubach L. , Wolff J.M.
Published: October 2005

Introduction: To assess the effects of intermittent maximal androgen blockade (IMAB) on testosterone (T) levels during on- and off-treatment periods. Materials and Methods: A total of 51 patients with metastatic prostate cancer underwent a 6-months period of continuous maximal androgen blockade (MAB) consisting of leuprorelin (3.75 mg at monthly intervals) plus flutamide (250 mg t.i.d.) followed by IMAB. During each cycle, the cut-off prostate-specific antigen (PSA) levels to stop and resume treatment were 4 and 10 ng/ml, respectively. IMAB continued until progression under treatment occurred. Monthly PSA and T measurements were performed in central laboratories. Results: From the 51 patients included (mean age 67.6 years), 27, 16, 12, 8 and 5 underwent a second, third, fourth, fifth and sixth cycle, respectively (mean follow up: 17 months). Before treatment, 4 patients had a T lower than normal laboratory value but these recovered all to a normal T value at the end of the first cycle. During the 6 cycles, only 8 patients did not recover a normal T at least once during the off-treatment periods (OTP). The mean T values at the end of each OTP did not change during these 6 cycles (Anova test, p = 0.621) with a mean stable recovery delay of 32–43 days (Anova test, p = 0.722). Conclusion: IMAB protocol with an initial 6-month treatment period can result in an intermittent castration with the recovery of normal T levels in most patients during six consecutive cycles of treatment.
Incidentally Detected Prostate Cancer in Cystoprostatectomy Specimens
Authors: Kouriefs C. , Fazili T. , Masood S. , Naseem M.S. , Mufti G.R.
Published: October 2005

Objectives: Bladder and prostate cancers occur with increasing prevalence in the ageing population. Our study aims to quantify the incidence of prostate cancer in patients undergoing cystoprostatectomy for bladder cancer and assess the impact of that incidental prostate cancer on oncological outcome. Methods and Materials: We retrospectively reviewed the pathology reports of 128 men who underwent cystoprostatectomy for bladder cancer. Results: Twenty-three men (18%) were found to have incidental prostate cancer. All incidental prostate cancers were organ confined and 91% were well or moderately differentiated. At a mean follow-up of 55 months the prostate cancer-free survival was 96%. Conclusion: The incidence of prostate cancer in cystoprostatectomy specimens is high. When the prostate is removed completely the presence of incidental prostate cancer does not influence the overall oncological outcome.
Diethylstilboestrol versus Bicalutamide in Hormone Refractory Prostate Carcinoma: A Prospective Randomized Trial
Authors: Manikandan Ramaswamy , Srirangam Shalom J. , Pearson Evelyn , Brown Stephen C.W. , O’Reilly Patrick , Collins Gerald N.
Published: October 2005

Objective: To compare the efficacy of diethylstilboestrol (DES) with bicalutamide in the treatment of hormone refractory prostate cancer in relation to its effect on prostate-specific antigen (PSA) and survival. Methods: Patients on LHRH analogues for prostate carcinoma with evidence of biochemical or clinical progression were randomized into one of the treatment arms (n = 58). The first group (group A, n = 26) received 1 mg of DES with 75 mg of aspirin per day in addition to the primary hormonal treatment. The second group (group B, n = 32) received bicalutamide at a dose of 50 mg/day in addition to the primary treatment. Patients were followed up every 3 months with their PSA being checked and were also monitored for any clinical progression and adverse effects as a result of treatment. Any adverse event occurring after patients were started on treatment was attributed to the drug and patients were clinically assessed at each visit. Failure of treatment was defined as a 50% or greater increase in PSA after commencing treatment. Once randomized, all patients were followed up for survival regardless of failure of second-line hormonal manipulation. Results: The mean age of the patients was 76.7 years (60–88, SD 7.4) in group A and 76 years (67–86, SD 6.9) in group B. Twelve patients in each group had metastatic disease. The median follow-up periods for both groups were 24 months (range 6–48 in group A, range 3–54 in group B). 65% of the patients in group A (17/26) and 43.5% (14/32) in group B had a fall in their PSA levels (p = 0.08, Fisher’s exact test) with 23% (6/26) and 31% (10/32) having a >50% response respectively (p = 0.34, Fisher’s exact test). Mean PSA nadir in those who responded were 20.6 ng/ml (range 1.6–59.4) and 7.41 ng/ml (range 0.1–42.6) in groups A and B respectively. The median duration of response was 9 months (3–18 months) for group A and 12 months (3–18 months) for group B. Seven patients in group A and 6 in group B experienced adverse events. Three of the 7 in the group A experienced cardiovascular related adverse effects (1 congestive cardiac failure, 1 pulmonary embolism and 1 stroke). At the end of the study period, 14 (54%) of group A patients were alive and 12 (46%) were dead. In group B, 15 (47%) were alive, 16 (50%) were dead and 1 (3%) lost to follow-up. At the completion of the study, 3 patients in each group were still on treatment. Conclusion: Low-dose DES and 50 mg of bicalutamide per day are equally effective in hormone refractory prostate carcinoma with respect to biochemical response, although DES has more severe adverse effects. This is a small sample and larger multicentre trials are needed to give us a definite conclusion.
Predictive Value of the International Prostate Symptom Score for Positive Prostate Needle Biopsy in the Low-Intermediate Prostate-Specific Antigen Range
Authors: Kefi Aykut , Irer Bora , Ozdemir Ismail , Tuna Burcin , Goktay Yigit , Yorukoğlu Kutsal , Esen Adil
Published: October 2005

Purpose: Serum prostate-specific antigen (PSA) has a restricted predictive value for prostate cancer in the low-intermediate PSA range (2.5–10 ng/ml). Our aim was to determine the predictive value of the International Prostate Symptom Score (IPSS) for positive prostate needle biopsy (PNB) in patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy with a low-intermediate PSA level. Patients and Methods: Between 2001 and 2004, the data of 389 consecutive patients applying for any urologic complaint to our department and who underwent TRUS-guided prostate biopsy due to an elevated serum PSA and/or abnormal digital rectal examination (DRE) were retrospectively analyzed. A total of 158 eligible patients with a low-intermediate PSA level were included in the study. The patient’s age, PSA, free PSA, free/total PSA, prostate volume, PSA density (PSAD), pre-biopsy IPSS were compared in the positive and negative biopsy groups. Results: Fifty-eight of 158 patients (37%) who underwent TRUS-guided prostate biopsy had positive PNBs. Forty-eight patients (30%) had abnormal DREs. In the positive PNB group, the mean age was older and PSAD was higher, but the means of the prostate volumes and total IPSS were lower (p < 0.05). Multivariate analysis demonstrated that age and IPSS were independent predictors of a positive PNB (p < 0.05). The odds ratio of mild IPSS for positive PNB controlled for age was 3.0 (95% CI 1.5–6.7). Receiver-operating characteristics analysis revealed a mild IPSS (AUC = 0.640) and was a considerable predictor for positive PNB as well as PSAD (AUC = 0.648). The sensitivity and specificity of IPSS with a cutoff value of 7.5 points were 31 and 87% for prediction of prostate cancer detection. Conclusion: In the low-intermediate PSA range, mild IPSS may be a predictive factor for positive PNB with a similar specificity of PSAD.
Assessment of Obstruction in Adult Ureterocele by Means of Color Doppler Duplex Sonography
Authors: Zougkas K. , Kalafatis P. , Ioannidis St. , Katsikas V. , Radopoulos D.
Published: October 2005

Aim: The purpose of this study is to present a method for identifying a ureteral obstruction in unilateral orthotopic ureterocele by means of conventional sonography and color Doppler duplex sonography. We focus on the measurement of the ureterocele dimensions, the degree of dilation it causes to the ipsilateral upper urinary tract, the registration of urine out-flow from the ureteral orifice into the bladder and its spectral analysis. Material and Method: Over 2 years at our institutions, 8 adult patients (7 women, 1 man) were diagnosed as having a single system orthotopic ureterocele. Four of them presented with lumbar pain, dysuria and recurrent urinary tract infections, while the remainder were asymptomatic and diagnosed accidentally. The diagnosis was based on serial sonography of the upper and lower urinary tract confirmed by intravenous pyelography and cystoscopy. We also performed color Doppler duplex sonographic evaluation of the urine jets ejected from both ureteral orifices into the bladder. Using the flow spectral study we analyzed the waveforms and measured their duration and flow rate. The study was completed with a comparative analysis of the data obtained from both ureteral orifices. Results: Cystic dilation of the lower ureteric extremity into the bladder was presented in all cases. Upper urinary tract dilation, of various grades, was present in 4 of 8 patients. Differences in urine jets between those derived from the ureterocele and those from the healthy contralateral ureteral orifice were significant in those patients with dilation of the upper urinary tract. The differences concerned mainly the frequency and symmetry of the jets as well as the pattern, duration and velocity of their waves. The 4 above-mentioned patients, with dilated upper urinary tracts and waveforms differentiated from the contralateral ones, were characterized as obstructive. On the other hand, the remaining 4 patients with subclinical ureterocele showed insignificant differences in urine jets and waveforms, and were found to be non-obstructive. Conclusion: Conventional sonography of the urinary tract in combination with color Doppler duplex sonography of the ureteral jets can be used in an attempt to diagnose and evaluate a unilateral orthotopic (single system) ureterocele and assess the necessity of intervention to identify the obstruction.
Effectiveness of Urethral Injection of Botulinum A Toxin in the Treatment of Voiding Dysfunction after Radical Hysterectomy
Authors: Kuo Hann-Chorng
Published: October 2005

Objective: After radical hysterectomy for cervical cancer patients may have difficulty in urination due to detrusor underactivity and a non-relaxing urethral sphincter. This study evaluated the effectiveness of urethral injection of botulinum A toxin in treating voiding dysfunction in these patients. Methods: Thirty patients with difficult urination after radical hysterectomy due to cervical cancer were enrolled to receive urethral injection of 100 units of botulinum A toxin (n = 20) or medical treatment as controls (n = 10). The clinical results and urodynamic parameters at baseline and after treatment were compared in the study group, and the quality of life (QOL) index was compared between the study and control groups. Results: After urethral injection of botulinum A toxin, 8 patients had excellent results (40%) and 8 had improved results (40%) in the study group. Both voiding pressure (115.2 ± 63.7 vs. 90.2 ± 49.5 ml, p = 0.025) and post-void residual volume (330.9 ± 124.9 vs. 183.9 ± 183.4 ml, p = 0.011) improved significantly after treatment. The obstructive symptom score was significantly reduced (17.5 ± 4.7 vs. 5.7 ± 2.3 points, p = 0.000) and the QOL index also improved (4.5 ± 2.7 vs. 2.3 ± 2.3 points, p = 0.000) after treatment. The success rate was 80% in the study group. There were no significant changes in obstructive symptom scores or the QOL index in the control group. The maximal effect appeared about 1 week after treatment. The duration of the therapeutic effect ranged from 3 to 9 months. Mild stress urinary incontinence and nocturnal enuresis were noted in 7 patients (35%). Conclusion: Urethral injection of botulinum A toxin can be effectively used to treat patients with detrusor underactivity and non-relaxing urethral sphincter after radical hysterectomy with few adverse effects.
Increased Expression of EZH2, a Polycomb Group Protein, in Bladder Carcinoma
Authors: Arisan Serdar , Buyuktuncer Elif Damla , Palavan-Unsal Narcin , Çaşkurlu Turhan , Çakir Omer Onur , Ergenekon Erbil
Published: October 2005

Introduction: Recent experiments have demonstrated that polycomb group gene enhancer zeste homolog 2 (EZH2) is highly expressed in many cancer types. Therefore, we aim to demonstrate EZH2 gene expression in transitional cell bladder cancer. Patients and Methods: The reverse transcriptase-polymerase chain reaction (RT-PCR) was used for detection of EZH2 mRNA levels in healthy and cancerous human bladder specimens. Also, expression of the particular protein was determined by Western blotting and immunohistochemistry to confirm RT-PCR results. Results: Gradually increased expression of EZH2 was detected by mRNA and protein levels in highly advanced bladder cancer specimens. In contrast, 100% of control subjects were negative for EZH2 expression. The expression of EZH2 was more frequent in G3 (92%) than G1-G2 (62–63%) and more frequent in T1-2 (72–85%) than Ta (56%). Western blot analysis results confirm the RT-PCR results. Conclusions: EZH2 overexpression precedes high frequencies of proliferation and the gradual advance of bladder cancer. These observations suggest that deregulated expression of EZH2 is associated with bladder carcinoma.
Expression and Functional Influence of Cellular Retinoic Acid-Binding Protein II in Renal Cell Carcinoma
Authors: Goelden Ulrike , Pfoertner Susanne , Hansen Wiebke , Toepfer Tanja , von Knobloch Rolf , Hofmann Rainer , Buer Jan , Schrader Andres Jan
Published: October 2005

Introduction: Retinoic acid (RA) and its derivates possess antiproliferative and tumor-suppressive abilities and are successfully used in the treatment of various malignancies. However, in metastatic renal cell carcinoma (RCC), its application did not meet first expectations. As the exact mechanisms of RA action and especially the role of the cellular retinoic acid-binding proteins (CRABP) still remain unclear, we studied the expression of CRABP-II and its potential influence on RA response in RCC. Materials and Methods: We used the real-time RT-PCR methodology to investigate CRABP-II expression in 12 RCC samples and corresponding normal kidney tissue. Moreover, CRABP-II was cloned and overexpressed in CAKI-2 RCC cells. CRABP-II (un)transfected CAKI-2 cells were stimulated with all-trans RA (ATRA) and 9-cis RA, and their antiproliferative effects were evaluated using 3H-thymidine-proliferation assays. Results: Using RPS9 and RPLP0 to normalize its expression, the median tumor/kidney ratio for CRABP-II expression was 0.16 and 0.12, respectively. Using proliferation assays, CRABP-II overexpressing CAKI-2 cells did not exhibit a significant change in RA sensitivity, but appeared to be less sensitive toward RA-stimulation compared to CAKI-2 cells expressing naturally low levels of CRABP-II (maximum difference, 59% at 3 µM ATRA). Conclusions: We were able to demonstrate a downregulation of CRABP-II expression in primary RCC tumor samples compared to the corresponding normal kidney tissue. However, CRABP-II overexpression in CAKI-2 RCC cells did not significantly influence RA associated antiproliferative actions. Further experiments are necessary to define the exact role of CRABP-II and its downregulation in RCC including its influence and dependence on other molecules involved in RA signalling and metabolism.
Free Insulin-Like Growth Factor-1 Levels in Bladder Growth following Spinal Cord Injury Experimentally
Authors: Serel T. Ahmet , Uysal Eda , Kutluhan Süleyman , Soyupek Sedat , Kılıç Sahir , Hoşcan M. Burak
Published: October 2005

Introduction: To determine the levels of spinal cord injury (SCI) on free insulin-like growth factor-1 (IGF-1) content in the bladder and the possible role of free IGF-1 in growth in hypertrophic bladders in an experimental model. Materials and Methods: The contents of free IGF-1 and protein in paraplegic and non-paraplegic rats which was induced experimentally by SCI were measured. The wet weights of the bladders were also determined. The results gained were compared. Results: The mean bladder free IGF-1 level in paraplegic rats was significantly higher than the corresponding bladder free IGF-1 level in sham-operated bladder (p < 0.05). Mean wet weight bladder in paraplegic rats was significantly higher than the sham-operated rats (p < 0.05). Paraplegic bladder had a significantly higher mean protein content than the sham-operated bladder (p < 0.05). Serum free IGF-1 levels in the two groups were not different. Conclusion: Our pilot study reveals that free IGF-1 may be effective in SCI.
Extramedullary Hematopoiesis in Chronic Myelofibrosis Encasing the Pelvicaliceal System and Perirenal Spaces: CT Findings
Authors: La Fianza Alfredo , Torretta Lorella , Spinazzola Angelo
Published: October 2005

We examined a 46-year-old male patient with idiopathic myelofibrosis diagnosed 28 months earlier. After chemotherapy and irradiation, CT showed nonnodular, soft tissue masses in the renal hilum, pelvicaliceal system, perirenal and periureteral spaces. Ultrasound-guided biopsy showed extramedullary hematopoiesis (EMH). The mass, which caused delayed nephrographic enhancement, without hydroureteronephrosis, was the only site of EMH. We report the CT findings of this uncommon EMH localization.
Giant Cystine Stone in an Infant Bladder with No Evidence of Cystinuria – Valence of Possible Pathomechanisms
Authors: Schwentner Christian , Oswald Josef , Lunacek Andreas , Bartsch Georg , Radmayr Christian
Published: October 2005

Bladder calculi account for approximately 5% of all urinary calculi. Children are at high risk in endemic areas whereas otherwise the entity is rare. Diet, voiding dysfunction and uncorrected anatomical abnormalities predispose to bladder stone formation. We report the case of a 2-year-old girl with a giant cystine bladder stone without relevant cystinuria and a small left kidney. Suprapubic cystolithotomy was performed for stone removal. We discuss possible associations of cystine calculi with unilateral genitourinary pathologies in the absence of persistent excess cystinuria.
Does the Prostate Really Need Androgens to Grow? Transurethral Resection of the Prostate in a Male-to-Female Transsexual 25 Years after Sex-Changing Operation
Authors: Casella R. , Bubendorf L. , Schaefer D.J. , Bachmann A. , Gasser T.C. , Sulser T.
Published: October 2005

We present the case of a male-to-female transsexual presenting with obstructive voiding symptoms due to benign prostatic hyperplasia 25 years after sex-changing operation and under continuous estrogen therapy.
Chronological Trend of Calorie Intake and the Incidence of Epithelial Neoplasms of the Large Intestine during the Past 30 Years in Japan
Authors: Kanazawa Kyotaro , Negishi Seiichi , Kishi Koichiro , Sawabe Motoji , Arai Tomio
Published: October 2005

Objectives: The authors tried to elucidate the effects of food intake on the incidences of colorectal cancer and adenoma. Materials and Methods: Large intestines obtained from a series of consecutive autopsies performed at the Tokyo Metropolitan Geriatric Hospital were scrutinized to detect colorectal neoplasms. Chronological trends and age-dependent incidences of adenoma and overt lethal cancer were checked, while cancer in adenoma were included in the category of adenoma. Data on food consumption were obtained from the ‘The National Nutrition Survey in Japan’ (Ministry of Health, Labor and Welfare of Japan). Results: There were 405 cancers and 12,883 adenomas in the 7,091 large intestines examined. The incidences of cancer and adenoma increased with age; overt lethal cancer was found in 5.79% and adenoma in 56.79% of the general population ≧60 years in Tokyo. Calorie intake steeply increased since 1964, the year of the Olympic Games in Tokyo, until the early 1970s. Subsequently, it has continuously declined down to the level of the late 1940s, although the ingredients have changed tremendously. Chronological trends of the incidences of colorectal cancer and adenoma showed similar patterns as calorie intake, but, the influence of calorie intake on the incidences of cancer or adenoma was manifested 18 and 24 years later, respectively. Conclusions: (1) During the last 30 years, the incidences of colorectal cancer and adenoma were 5.79 and 56.79%, respectively, in individuals aged ≧60 years in Japan. (2) The chronological trends of both lesions showed a pattern similar to that of calorie intake, but, as the trend of cancer incidence preceded the course of adenoma by 6 years, adenoma is not the sole precursor lesion of overt lethal cancer.
Epidemiological Evaluation of Stroke in Babol, Northern Iran (2001–2003)
Authors: Ahangar Alijan Ahmadi , Ashraf Vaghefi Seyed Behnam , Ramaezani Mirsaid
Published: October 2005

This retrospective descriptive analytical study was performed on 250 patients (130 males and 120 females) diagnosed to have stroke in the Department of Neurology, Babol, Iran, from April 2001 to April 2003.The risk factors for stroke were recorded. The frequencies of hypertension, diabetes mellitus, cardiac diseases and hyperlipidemia were 54, 24, 43.2 and 26%, respectively. All these epidemiological factors were associated with stroke (p < 0.05). The incidence of stroke was 50/100,000 population during 2 years. It happened more often in females than males, and ischemic stroke (67%) was twice as frequent than hemorrhagic stroke (33%). The mortality rate was 32%. The most common epidemiological risk factors for stroke in our region were hypertension, cardiac diseases and diabetes mellitus.
Cerebral Syncope: Insights from Valsalva Maneuver
Authors: Chuang Yu-Ming , Hu Han-Haw , Pan Po-Jung
Published: October 2005

Background and Purpose: Cerebral syncope refers to a loss of consciousness associated with cerebral vasoconstriction in the absence of systemic hypotension. The diagnosis of cerebral syncope could be established by the head-up tilt test (HUT) and transcranial Doppler ultrasonography. Valsalva maneuver (VM) permitted assessment of cerebral autoregulatory function by provoking blood pressure (BP) changes. To develop a path-physiological approach for vasomotor reactivity of cerebral syncope, the authors combined these maneuvers (HUT/transcranial Doppler/VM). Methods: Using transcranial Doppler ultrasonography, we simultaneously recorded systemic arterial BP in the radial artery and flow velocities in both middle cerebral arteries (MCAFV) in 10 cerebral syncope patients (4 males and 6 females, 35.24 ± 4.5 years old) during the Valsalva maneuver. Results: The characteristic changes in BP (phases I–IV) were seen in all subjects, accompanying distinct changes in cerebral blood flow velocity. The BP/heart rate responding to VM was within normal limit in all subjects. There was no orthostatic hypotension. Instead, BP increased during the tilting test in 2 subjects (20.00%). The MCAFV dropped 25.4 ± 2.3% from baseline. Abnormal flattening of MCAFV during late phase II (IIb), the paradoxical drop of flow velocity despite restoration of BP, was noted in 9 subjects (90.00%). Conclusion: During VM there are complex changes in relevant cardiovascular and cerebrovascular variables within a short time span. The paradoxical drop of MCAFV during phase IIb was the result of complex parameters. Among them, a failure in cerebrovascular resistance reduction and even paradoxical vasoconstriction might further compromise cerebral perfusion pressure and lead to syncope.
Artistic Creativity, Style and Brain Disorders
Authors: Bogousslavsky Julien
Published: October 2005

The production of novel, motivated or useful material defines creativity, which appears to be one of the higher, specific, human brain functions. While creativity can express itself in virtually any domain, art might particularly well illustrate how creativity may be modulated by the normal or pathological brain. Evidence emphasizes global brain functioning in artistic creativity and output, but critical steps which link perception processing to execution of a work, such as extraction-abstraction, as well as major developments of non-esthetic values attached to art also underline complex activation and inhibition processes mainly localized in the frontal lobe. Neurological diseases in artists provide a unique opportunity to study brain-creativity relationships, in particular through the stylistic changes which may develop after brain lesion.
Glucocorticoid Metabolism in the Human Fetal Lung: Implications for Lung Development and the Pulmonary Surfactant System
Authors: Garbrecht Mark R. , Klein Jonathan M. , Schmidt Thomas J. , Snyder Jeanne M.
Published: October 2005

It has been nearly 35 years since Liggins and Howie first reported the benefits of antenatal glucocorticoid (GC) treatment to promote the maturation of the human fetal lung, and nearly that long since Pasqualini and colleagues demonstrated that the human fetal lung actively metabolizes GCs. Since that time, our understanding of the effects of GCs on fetal lung maturation and pulmonary surfactant production has increased dramatically. Similarly, characterization of the enzymes involved in GC metabolism has greatly expanded our understanding of GC signaling in target tissues. In man, the biologically active GC (cortisol) and the biologically inactive GC (cortisone) are interconverted by the tissue-specific expression of the type 1 and type 2 11β-hydroxysteroid dehydrogenase enzymes (HSD1 and HSD2). Much of the research on GC metabolism in peripheral target tissues has focused on the role of HSD1 in amplifying the effects of GCs in liver and adipose tissue or on the role of HSD2 in blocking the effects of GCs in the kidney and placenta. In contrast, the role of GC metabolism in modulating the effects of GCs on fetal lung maturation and the pulmonary surfactant system in humans is less understood. The goal of this review article is to present a brief overview of the role of GCs in human fetal lung maturation and pulmonary surfactant production, and to familiarize the reader with the biochemistry of the metabolism of natural and synthetic GCs by the HSD enzymes. In addition, we will review data concerning the expression and activity of the HSD enzymes in the human fetal lung and contrast this to what is known about the HSD enzymes in the fetal rodent lung. Although rodents, rabbits, sheep, and several primates have been invaluable model systems for the study of fetal lung development, we have chosen to largely focus this review on human lung, since there are significant differences in GC metabolism between humans and other species.
The North American Survey of Placement and Adjustment Strategies for Deep Brain Stimulation
Authors: Ondo William G. , Bronte-Stewart Helen
Published: October 2005

Background: Deep brain stimulation (DBS) is gaining wide acceptance as treatment for Parkinson’s disease (PD), essential tremor, and dystonia. Methods: A 40-item questionnaire commissioned by the DBS Study Group was sent to 46 centers that had performed at least 25 DBS implantations. These centers were identified through the DBS Study Group, other professional societies, and with the assistance of the Medtronic Corporation. The results were then tabulated and descriptive analyses were performed. Results: Thirty-six of 47 centers (77%) responded, they had implanted 4,553 patients. The timing for bilaterally implanted patients varied, as 13 sites almost always implanted simultaneously whereas 14 sites almost never implanted simultaneously. Stereotactic frames included Leksell (n = 19), CRW (n = 15) and Compass (n = 2). Post-placement imaging was routinely performed by almost all centers and included MRI (n = 23), CT (n = 4), CT/MRI variably (n = 5), and ventriculography (n = 1). Two centers used more than one electrode per side. The 34 centers that used a single electrode averaged 2.3 ± 1.4 passes per electrode (range: 1–18 passes). Most centers used macro-stimulation to confirm placement by assessing the intra-operative clinical response (n = 34), and to assess for adverse events (n = 26) at high voltages, averaging 6.7 ± 2.3 V (range: 4–10). The initial activation averaged 18 ± 12 days after electrode placement (average range: 11 ± 10 to 28 ± 18 days, absolute range: 1–90 days). Most sites had several programmers; however, the primary programmers were neurology staff (n = 15), the neurologist (n = 13), neurosurgery staff (n = 6), the neurosurgeon (n = 2), or a physiatrist (n = 1). Twelve centers automatically reduced PD medications on the day of initial activation, 9 centers reduced them variably, and 16 centers initially did not reduce them. Eventually, 80.4% of patients were reported to have some dose reduction, and 47.1% had a greater than 50% reduction of PD medications. Conclusions: Strategies regarding DBS placement and adjustment vary in North America.
Gamma Knife Radiosurgery for Trigeminal Neuralgia: The Washington University Initial Experience
Authors: Drzymala Robert E. , Malyapa Robert S. , Dowling Joshua L. , Rich Keith M. , Simpson Joseph R. , Mansur David B.
Published: October 2005

Seventy-three patients were evaluated for the changes in pain relief, numbness and paresthesias after Gamma Knife radiosurgery to a maximum dose of 76–87 Gy for trigeminal neuralgia. Patients experienced pain relief as follows: 59% attained complete pain relief without prior surgery (33% with prior surgery); 25% achieved ≧50% pain reduction (28% with prior surgery); 11% of surgery patients obtained minor pain relief, and 16% of patients without surgery had no relief (28% with prior surgery). Level of pain decreased rapidly within 6 weeks after radiosurgery. Numbness/paresthesias developed slowly over the first 12–15 months. Bothersome levels were experienced by 15% of the patients without prior surgery (22% with prior surgery). Comparison of the occurrence of numbness/paresthesias, with respect to prior surgery, was not statistically significant. Only 2% of all patients had persistently bothersome side effects. In conclusion, radiosurgery is an effective treatment of trigeminal neuralgia, especially for those patients not having prior surgery.
Implantation of a Closed-Loop Stimulation in the Management of Medically Refractory Focal Epilepsy
Authors: Fountas Kostas N. , Smith Joseph R. , Murro Anthony M. , Politsky Jeffrey , Park Yong D. , Jenkins Patrick D.
Published: October 2005

Open-loop stimulation studies have shown varying control of seizures with stimulation of different anatomical targets. A recent multi-institutional clinical study utilizing an external closed-loop stimulation system had promising results. A novel implantable closed-loop Responsive Neurostimulation System (RNS) (Neuropace, Inc., Mountainview, Calif., USA) consisting of a cranially implanted pulse generator, one or two quadripolar subdural strip or depth leads and a programmer is under testing in a prospective clinical trial. The RNS pulse generator continuously analyzes the patient’s electrocortigrams (ECoGs) and automatically triggers electrical stimulation when specific ECoG characteristics programmed by the clinician, as indicative of electrographic seizures or precursor of epileptiform activities, are detected. The pulse generator then stores diagnostic information detailing detections and stimulations, including multichannel stored ECoGs. The RNS programmer communicates transcutaneously with the implanted pulse generator when initiated by a clinician. The RNS programmer can download diagnostics and store ECoGs for review. The RNS programmer can then be used to program detection and stimulation parameters. In our current communication, we describe the selection criteria for implanting this system, the preparation of the surgical candidates as well as the surgical technique. We also present our preliminary results with 8 patients who had an RNS implanted. Seven patients (87.5%) had more than 45% decrease in their seizure frequency. The mean follow-up time in our series was 9.2 months. The implantation of a closed-loop stimulation system, in our experience, represents a safe and relatively simple surgical procedure. However, the efficacy of this new treatment modality remains to be determined in further multi-institutional, prospective clinical studies.
Association of Angiotensinogen Gene Polymorphisms with Essential Hypertension in African-Americans and Caucasians
Authors: Markovic Daniela , Tang Xiagna , Guruju Mallikarjunrao , Levenstien Mark A. , Hoh Josephine , Kumar Ashok , Ott Jurg
Published: October 2005

Obective: Molecular variants of angiotensinogen (AGT) have been linked to essential hypertension, and promoter variants have been shown to alter the transcription rate of AGT in vitro. We employed a case-control study to determine whether single nucleotide polymorphisms (SNPs) in the promoter region of AGT were associated with hypertension in African-Americans and Caucasians. Methods: The frequencies of the variants at base positions –6, –20, –217, –793, and –776, both alone and in combination (haplotypes), were compared between cases and controls in samples stratified based on race and sex. A logistic regression model was applied to test whether AGT genotypes were significant predictors of the disease while adjusting for race, sex, and age. Results: Subjects with the AA or AG genotype at locus –793 were significantly more likely to have the disease (OR = 1.88, 95% CI = 1.12–3.15). Additionally, the differences in haplotype frequency distributions between cases and controls were significant at the 7% level for all four subgroups (stratified by race and sex) after adjusting for multiple testing. Based on the odds ratios for each individual haplotype, the haplotype AAAAT (nucleotide sequences at base positions –6, –20, –217, –793, –776) in African-American males, African-American females, and Caucasian females may confer susceptibility to the disease in these population subsets. Conclusion: Overall, the present report provides statistical evidence for the association of AGT with essential hypertension.
Spectrum of the Posterior Inferior Cerebellar Artery Territory Infarcts
Authors: Kumral Emre , Kısabay Ayşın , Ataç Ceyla , Çallı Cem , Yünten Nilgün
Published: October 2005

Background and Purpose: The clinical, etiological and stroke mechanisms are defined well before but the detailed clinical and etiologic mechanisms regarding to all clinical spectrum of posterior inferior cerebellar artery (PICA) infarcts were not systematically studied by diffusion-weighted imaging (DWI). Methods: Seventy-four patients with PICA territory ischemic lesion proved by DWI with decreased apparent diffusion coefficient and FLAIR (fluid attenuation inversion recovery) included in our Registry, corresponding to 2% of 3,650 patients with ischemic stroke, were studied. The presence of steno-occlusive lesions in the posterior circulation were sought by magnetic resonance angiography, and reviewed with a three-dimensional rotating cineangiographic method. Results: We found six subgroups of PICA territory infarcts according clinico-topographical relationship: (1) 9 patients with lesion in the territory lateral branch of PICA; (2) 23 patients with an infarct in the territory of medial branch of PICA; (3) 9 patients with a lesion involving both medial and lateral branches of the PICA; (4) 9 patients with cortical infarcts at the boundary zones either between medial and lateral branches of the PICA or between PICA and m/l superior cerebellar artery (SCA); (5) 10 patients with a lesion at the deep boundary zones either between medial and lateral PICA, or between PICA and medial/lateral SCA; (6)14 patients with concomitant multiple lesions in the PICA and in other vertebrobasilar artery territories. The main cause of PICA infarcts was extracranial large-artery disease in 30 patients (41%) patients, cardioembolism and in situ branch disease in 15 patients (20%) each. Conclusions: Multiple PICA territory lesions on DWI were not uncommon and could be caused by multiple emboli originating from break-up of atherosclerotic plaque in the subclavian/innominate-vertebral arterial system. DWI findings of single or multiple small lesions could account for some cases with transient and subtle cerebellar symptoms which have been considered before as ‘vertebrobasilar insufficiency’ without morphologic lesion. Different clinical-DWI correlations allow us to determine better definition of the topographical and etiological spectrum of acute PICA territory lesions, which was previously defined by pathological and conventional MRI studies.
Comparison of Five MR Sequences for the Detection of Acute Intracranial Hemorrhage
Authors: Oppenheim Catherine , Touzé Emmanuel , Hernalsteen Danielle , Peeters André , Lamy Catherine , Mas Jean-Louis , Meder Jean-François , Cosnard Guy
Published: October 2005

Purpose: To evaluate the respective value of 5 MR sequences to distinguish between stroke patients with and without acute intracerebral hemorrhage (ICH). Methods: MR images obtained ≤6 h after stroke onset of 86 patients (43 ICH, 43 non-ICH) were reviewed by 3 observers who looked for signs of acute ICH on each image set [T1 and T2 gradient echo (GRE), FLAIR, T2-EPI and DWI], presented separately. Results: For the identification of ICH, intraobserver and interobserver concordance were at least ĸ = 0.95 for all sequences. Of all interpretations, 7 (0.4%) were erroneous, with sensitivity and specificity of FLAIR, T2-EPI and DWI reaching 100%; GRE sensitivity and specificity were 100% and 95–97.5%, respectively; T1 sensitivity and specificity were 97.3–100% and 97.4–100%, respectively. All 4 patients misclassified on one pulse sequence were correctly classified on all the other sequences. Conclusion: In the setting of acute stroke, each of the 5 studied sequences enables ICH and non-ICH patients to be distinguished with high sensitivity and specificity.
Bladder Storage and Emptying Disorder Frequencies in Hemorrhagic and Ischemic Stroke Patients with Bladder Dysfunction
Authors: Ersoz Murat , Tunc Hakan , Akyuz Mufit , Ozel Sumru
Published: October 2005

Background: Bladder dysfunction is common in stroke patients and it has a considerable impact on their lives. The objective of this study was to investigate the frequencies of urine storage and emptying disorders in hemorrhagic and ischemic stroke patients with persistent bladder dysfunction. Methods: A total of 48 stroke patients who underwent urodynamic tests because of persistent bladder dysfunction were evaluated retrospectively. Urine storage and emptying disorder frequencies were determined and compared in hemorrhagic and ischemic stroke subgroups. Results:Storage disorder frequencies were 73.3 and 63.6% in hemorrhagic and ischemic stroke groups, respectively (p > 0.05), while emptying disorder frequencies were 13.3 and 51.5% (p < 0.02). Conclusions: Evaluation of the stroke type may be helpful in the determination of the type of urinary dysfunction and in choosing the appropriate bladder management strategy, but further studies with larger sample sizes are needed.