bluuebunny/crossref_metadata_2025 huggingface dataset:
The contribution of small cryptic plasmids to the antibiotic resistance of enteropathogenic Escherichia coli E2348/69
Authors: Handford Cynthia L. , Stang Charma T. , Raivio Tracy L. , Dennis Jonathan J.
Published: November 2009

Two uncharacterized small cryptic plasmids (SCPs) were isolated from enteropathogenic Escherichia coli strain E2348/69. Genomic DNA sequence analysis of both SCPs indicated that the smaller plasmid, p5217, encoded several mobilization genes, whereas the larger plasmid, p6148, encoded several putative antibiotic resistance determinants. Complementation analysis showed that p6148 encodes functional streptomycin resistance genes but, owing to the presence of several frameshift mutations, a nonfunctional sulfonamide resistance determinant. A plasmid similar to p6148 has previously been shown to confer a slight growth advantage on E. coli. However, we were unable to observe any significant growth advantage in different E. coli strains transformed with p6148. The p6148 DNA sequence is homologous in sequence and arrangement to DNA from other plasmid families, including large conjugative plasmids and SXT integrative and conjugative elements. This study suggests that gene clusters of the sul2–strAB antibiotic resistance genes are widespread and highly transferable, owing to their presence in a wide variety of mobile genetic elements.
Phosphatidylcholine in membrane ofEscherichia colichanges bacterial antigenicity
Authors: Chen Fan , Zhao Qiong , Cai Xueli , Lv Luchao , Lin Wen , Yu Xuejin , Li Changyu , Li Yang , Xiong Min , Wang Xing-Guo
Published: November 2009

This study reports that Escherichia coli phosphatidylcholine-positive (PC+) strain Top10/ptac66 (PC+PE+), in which borrelial PC synthase (PCS) directly condenses exogenous choline with CDP-diacylglycerol (CDP-DAG) to form PC, displayed not only stronger resistance to antimicrobial peptides cecropin P1 and indolicidin, but also decreased ability to attract macrophages to the abdominal cavity of infected mice in the 36 h following infection, compared with the control strainTop10/ptac85 (PC–PE+). Rabbit sera raised against the PC+strains Top10/ptac66 (PC+ PE+) and AD93/ptac67 (PC+PE–) recognized a different set of periplasmic proteins and lipopolysaccharides,compared with those detected by antisera to the PC–strains Top10/ptac85 and AD93 (PC–PE–) . Electron microscopy also showed that the morphology of cell wall of Top10/ptac66 was different from that of the control strain Top10/ptac85. Enhancement of bacterial resistance to antimicrobe peptides, alteration of bacterial antigenicity and evasion of macrophage attacks in mice suggest that PC in the bacterial membrane may play a role in bacterial evasion of the innate or adaptive immune response of the host.
Expression of the atf1+ gene is upregulated in fission yeast under nitrosative and nutritional stresses
Authors: Song S.-H. , Kim B.-M. , Lim C.-J. , Song Y.S. , Park E.-H.
Published: November 2009

This work was designed to assess regulation of the atf1+ gene in the fission yeast Schizosaccharomyces pombe under nitrosative and nutritional stresses, using the atf1+–lacZ fusion gene and RT–PCR. Nitric oxide (NO)-generating sodium nitroprusside (SNP; 10 µmol/L) and nitrogen depletion significantly enhanced synthesis of β-galactosidase from the atf1+–lacZ fusion gene in S. pombe Pap1-positive KP1 cells, but not in S. pombe Pap1-negative TP108-3C cells. SNP (10 µmol/L) and nitrogen depletion also caused a significant increase in atf1+ mRNA levels in Pap1-positive cells, but not in Pap1-negative cells. Depletion of glucose marginally increased synthesis of β-galactosidase from the fusion gene in S. pombe Pap1-positive cells. Taken together, the S. pombe atf1+ gene is upregulated by nitrosative and nutritional stresses on a transcriptional level, possibly via the mediation of Pap1.
Role of YiaX2 in l-ascorbate transport in Klebsiella pneumoniae 13882
Authors: Campos Evangelina , Aguilera Laura , Giménez Rosa , Aguilar Juan , Baldoma Laura , Badia Josefa
Published: November 2009

The yiaK–S operon is required for aerobic growth on l-ascorbate in several Enterobacteriaceae. Here we present evidence that the yiaX2 gene belonging to the yiaK–S operon of Klebsiella pneumoniae 13882, which encodes a protein similar to the putative transporters classified as the major facilitator superfamily, is involved in the uptake of l-ascorbate. Concentration kinetic analysis yielded an apparent Km of YiaX2 for l-ascorbate of 161.38 ±8.28 µmol·L–1 and a Vmax of 3.81 ± 0.60 nmol·mg–1·min–1. This carrier uses the energy from electrochemical gradients, since it was inhibited by carbonyl cyanide m-chlorophenylhydrazone, a hydrophobic proton conductor that dissipates proton motive force.
Juvenile Idiopathic Arthritis: Classification, Clinical Presentation and Current Treatments
Authors: Dannecker Günther E. , Quartier Pierre
Published: November 2009

Background: The term juvenile idiopathic arthritis (JIA) describes a clinically heterogeneous group of arthritides. The onset in all subgroups is before 16 years of age, but each group presents with different clinical signs and symptoms. The cause of the disease is unknown, but both genetic and environmental factors are believed to be involved. Management of the disease has greatly improved in recent years due to advances in pharmacologic treatment options (especially with new biologic agents) and the prognosis for patients is better than ever before. However, none of the available drugs has a curative potential. This review provides an overview on the classification and the clinical symptoms of the defined subgroups of JIA as well as pharmacotherapies for it. Conclusions: Treatment of children with JIA is challenging and complex. Since lengthy therapy might be necessary, a multidisciplinary pediatric rheumatology team is crucial for optimal treatment. Although a cure is unknown at this time, adequate treatment aims to preserve function of the joints as well as normal childhood development.
Natural History of Growth and Body Composition in Juvenile Idiopathic Arthritis
Authors: Bechtold S. , Roth J.
Published: November 2009

Background: In patients with juvenile idiopathic arthritis (JIA), growth impairment and altered body composition, including disturbed skeletal development, are well-known long-term complications. Data on longitudinal growth in patients with systemic and polyarticular JIA reveal growth impairment in the active phases of the disease. With reduction in disease activity and lower glucocorticoid (GC) doses, some patients experience ‘catch-up’ growth; however, many have only a slight improvement in height standard deviation during puberty or after cessation of GC treatment. The consequence is a final height below the 3rd percentile and below the genetic height potential. Although few studies have specifically addressed body composition in children with JIA, studies on the development of bone mass have described notable deficits in both GC-treated and GC-naïve children. In recent years, the deficits in bone mass have been related, in part, to the deficits in muscle mass, which are prevalent in these patients. Conclusions: The major goal for physicians caring for patients with JIA is optimal disease control while maintaining normal growth. Early recognition of patients who develop prolonged growth disturbances and altered body composition is important as these abnormalities contribute to long-term morbidity and need to be addressed both diagnostically and therapeutically when treating children with JIA.
Adult Outcomes of Patients with Juvenile Idiopathic Arthritis
Authors: Minden Kirsten
Published: November 2009

Background: Knowledge of the long-term outcomes of patients with juvenile idiopathic arthritis (JIA) has evolved during the past decade. Recent studies, using standardized classification criteria, new and reliable outcome measures and improved methods of statistical analyses, show that outcomes are still less than ideal. Approximately half of all young adults with JIA have ongoing active disease and over one third experience detectable degrees of disability and organ damage. These patients also show a distinctive pattern of growth disturbances. Most patients with general growth failure have systemic or polyarticular disease: significant short stature (final height standard deviation score <–2) has been noted in 41% of patients with systemic JIA and in 11% of patients with polyarticular JIA. In contrast, localized growth disturbances can be seen in patients with oligoarthritis. Conclusions: Despite its name, JIA can be a lifelong disorder. With early and more widespread use of biological and other innovative therapies, however, outcomes for patients with JIA should improve further.
Mechanisms of Impaired Growth: Effect of Steroids on Bone and Cartilage
Authors: Olney Robert C.
Published: November 2009

Background: Long-term treatment with high-dose glucocorticoids (GCs) has profound effects on bone metabolism and linear growth. Bone metabolism is a balance between bone resorption by osteoclasts and new bone formation by osteoblasts. Systemically, GC treatment reduces circulating levels of estrogen and modestly increases parathyroid hormone levels. At the local level, GCs decrease insulin-like growth factor I (IGF-I) production, induce IGF-I resistance and increase nuclear factor κB ligand production by osteoblasts. These alterations inhibit new bone formation and stimulate bone resorption, with a net loss of bone over time. Clinically, this results in decreased bone mineral density, osteoporosis and increased risk for fracture. Local effects of GCs at the growth plate include reduction of IGF-I production, inducing IGF-I resistance and reducing production of C-type natriuretic peptide, which results in a reduction of chondrocyte proliferation, matrix synthesis and hypertrophy. These reductions in chondrocyte function result in decreased linear growth. Conclusions: The effects of GCs on bone metabolism and linear growth are sensitive and specific and represent an evolutionary adaptation to redirect resources during times of physiologic stress. Since many of these effects result from alterations in IGF-I production, growth hormone therapy is a potential approach to ameliorate these problems.
Mechanisms of Muscle Atrophy Induced by Glucocorticoids
Authors: Schakman O. , Gilson H. , Kalista S. , Thissen J.P.
Published: November 2009

Background: Many pathological states characterized by muscle atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoid (GC) levels, suggesting that GC could trigger the muscle atrophy observed in these conditions. GC-induced muscle atrophy results from decreased protein synthesis and increased protein degradation. The inhibitory effect of GCs on protein synthesis is thought to result mainly from the inhibition of the p70 ribosomal S6 protein kinase. The stimulatory effect of GCs on muscle proteolysis results from the activation of two major cellular proteolytic systems: ubiquitin proteasome and lysosomal systems. The decrease in muscle production of insulin-like growth factor I (IGF-I), a muscle anabolic growth factor, could contribute to GC-induced muscle atrophy. By activating the phosphatidylinositol-3-kinase/Akt pathway, IGF-I overrides GC action to stunt muscle atrophy. Evidence also indicates that increased production of myostatin, a catabolic growth factor, could play a critical role in GC-induced muscle atrophy. Conclusions: Recent progress in understanding the role of growth factors in GC-induced muscle atrophy allows investigation into new therapies to minimize this myopathy.
Promoting Growth in Chronic Inflammatory Disease: Lessons from Studies of the Growth Plate
Authors: Ahmed S.F. , Sävendahl L.
Published: November 2009

Background: Growth disorders are commonly observed in children with chronic inflammatory disease. It is likely that these disorders are mediated by a combination of factors, including the disease process and its treatment (with drugs such as glucocorticoids [GCs]). These factors affect the growth hormone-insulin-like growth factor I (IGF-I) axis, which is crucial for promoting linear growth at the level of the growth plate. Recent advances in our knowledge of the effects of GCs and proinflammatory cytokines on the growth plate have led to an improved understanding of the biological rationale for the use of growth-promoting therapy in children with chronic inflammatory disease and concurrent growth retardation. Conclusions: Both GCs and proinflammatory cytokines can adversely affect a number of components of growth plate chondrogenesis, and these effects can be ameliorated by raising local IGF-I exposure. However, this intervention does not lead to complete normalization of the growth plate. In children with chronic inflammation, the cornerstone of improving growth remains the judicious use of GCs while ensuring effective control of the disease process.
Can Growth Hormone Counteract the Catabolic Effects of Steroids?
Authors: Mauras Nelly
Published: November 2009

Background: Chronic administration of glucocorticosteroids (GCs) can have significant catabolic effects in vivo in a host of metabolic systems, including amino acid metabolism, skeletal muscle, bone and linear growth. GCs inhibit protein synthesis and increase protein breakdown at the skeletal muscle and whole-body level and impair growth hormone (GH) secretion and action. Conversely, GH and insulin-like growth factor I (IGF-I) are potent protein-anabolic and growth-promoting agents in vitro and in vivo. This review summarizes both the catabolic effects of GCs and the anabolic and metabolic effects of GH and IGF-I. Conclusions: Both GH and IGF-I may decrease the catabolic effects of chronic steroid use in humans, particularly by enhancing lean body mass accrual and, in children, by increasing linear growth.
Surgical Management of Brain Cavernomas in Children
Authors: Alexiou George A. , Mpairamidis Evriviadis , Sfakianos George , Prodromou Neofytos
Published: November 2009

Background: Cavernous hemangiomas are benign vascular hamartomas caused by developmental malformations of the vascular bed. They can be found in 0.3–0.7% of the population, whereas one fourth of these lesions occur in children. Methods: In the present study, we report on 16 cases of cavernomas surgically treated in our institute. From each patient’s file, the age, sex, lesion location, symptoms and follow-up were analyzed. Results: The most commonly presenting symptom was epilepsy. Radiological signs of acute hemorrhage were observed in 3 cases. Three children had multiple cavernomas. The parietal lobe was the most common site of occurrence, whereas only 2 cavernomas were infratentorial. There was no operative mortality. Postoperatively, there was no additional neurological deficit, and all patients gradually improved. In a case of pontine cavernoma, there was a need for reoperation due to rebleeding. Conclusion: With the improvement of microsurgical techniques and modern neuroimaging, nearly all cavernomas can be safely removed. Total resection is associated with patients’ clinical improvement and seizure control.
Chiari Drop Attacks: Surgical Decompression and the Role of Tilt Table Testing
Authors: Straus David , Foster Kimberly , Zimmerman Frank , Frim David
Published: November 2009

Background: Chiari I malformation (CM1) is characterized by impaired CSF flow through the foramen magnum. Dysfunctional autonomic cardiovascular regulation may result in syncope. Syncope may be the primary presenting symptom of CM1: a syndrome termed Chiari drop attack. It has been postulated that Chiari drop attack is secondary to dysautonomia caused by hindbrain compression. There has been recent debate regarding the association between CM1, dysautonomia and Chiari drop attack. Methods: We selected patients with Chiari drop attacks who had negative workups for cardiac syncope, followed by tilt table testing and subsequent surgical decompression. We report test results and clinical outcomes following CM1 decompression. Results: Ten patients met the inclusion criteria: 5 patients had positive and 5 negative tilt table tests. Following decompression, 7 had symptomatic improvement or resolution and 3 failed to improve. The sensitivity and specificity of the tilt table test for detecting clinical improvement with surgical decompression was 43 and 33%, respectively. Tilt table testing had 40% accuracy in predicting clinical response to decompression. Conclusions: In this short series, surgical decompression of CM1 has a high success rate (70%) for patients with Chiari drop attacks. Tilt table testing has poor predictive value in judging the clinical response to surgical decompression and is not a useful test to guide surgical decision- making.
Clinicopathological Analyses of Fifty Supracricoid Laryngectomized Specimens: Evidence Base Supporting Minimal Margins
Authors: Nakayama Meijin , Holsinger Christopher , Okamoto Makito , Seino Yutomo , Miyamoto Shunsuke , Takeda Masahiko , Yokobori Satoru , Masaki Takashi , Hayashi Seiichi
Published: November 2009

Objectives: Supracricoid laryngectomy (SCL) is a reliable laryngeal preservation surgery. However, close surgical margins are often inevitable. Based on clinicopathological analyses of supracricoid laryngectomized specimens, we evaluated the evidence base supporting minimal margins. Methods: The distance between tumor edge and resected margin was measured macro- and microscopically at the anterior, posterior, superior and inferior edges, using 50 surgical specimens. The margins were correlated with pathological T staging and the prognoses. Results: The anterior and posterior margins were the shortest, and the superior margin was the longest. The inferior margin was the only edge at which a positive margin was encountered. Cancer extending 10 mm below the glottal free edge significantly decreased the inferior margin. Conclusions: The surgical potential of SCL with cricohyoidoepiglottopexy was confirmed to be able to cope with tumor extensions showing margins of a few millimeters at the anterior, posterior and superior ends. Accurate assessment and management at the inferior margin is the key to stable local control.
Response of Coronary Heart Disease Risk Factors to Changes in Body Fat during Diet-Induced Weight Reduction in Japanese Obese Men: A Pilot Study
Authors: Ohkawara Kazunori , Nakata Yoshio , Numao Shigeharu , Sasai Hiroyuki , Katayama Yasutomi , Matsuo Tomoaki , Okura Tomohiro , Tanaka Kiyoji
Published: November 2009

Objective: Serial measurements were used to examine the response of coronary heart disease (CHD) risk factors to regional fat changes during weight reduction. Methods: Nine Japanese obese men participated in a diet-induced weight loss program. Regional fat masses, abdominal visceral fat area (VFA), subcutaneous fat area (SFA) and CHD risk factors, including total (TC), high (HDLC)- and low-density lipoprotein cholesterol (LDLC), triglycerides (TG), fasting plasma glucose, immunoreactive insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and glycosylated hemoglobin A1c (HbA1c) were assessed at baseline and after 1, 2 and 3 months. Results: Meanweight reduction during the study was –11.9 ± 4.2 kg, which was associated with a gradual, significant decrease (p < 0.05) in arm, leg and trunk fat masses, VFA and SFA. The levels of TC, LDLC and TG decreased significantly within 1 month and remained at these values, whereas HDLC, HOMA-IR, and HbA1c did not change. There was no significant correlation between changes in regional fat masses and CHD risk factors in any period studied. Conclusions: CHD risk factors do not necessarily respond in the same manner as changes in body fat during diet-induced moderate weight reduction.
Exclusive Olive Oil Consumption Is Associated with Lower Likelihood of Developing Left Ventricular Systolic Dysfunction in Acute Coronary Syndrome Patients: The Hellenic Heart Failure Study
Authors: Chrysohoou Christina , Kastorini Christina-Maria , Panagiotakos Demosthenes , Aggelopoulos Panagiotis , Tsiachris Dimitris , Pitsavos Christos , Stefanadis Christodoulos
Published: November 2009

Background/Aims: The aim of the present work was to evaluate the association between exclusive olive oil consumption and the development of left ventricular systolic dysfunction (LVSD) in patients with a previous acute coronary syndrome (ACS). Methods: From 2006 to 2007, 651 consecutive ACS patients were enrolled. In 288 males (64 ± 13 years) and 75 females (71 ± 11 years), LVSD (ejection fraction <40%) developed after the cardiac event, and 221 males (62 ± 11 years) and 69 females (66 ± 11 years) were without LVSD (ejection fraction >50%). Detailed information regarding their clinical characteristics, anthropometric data, physical activity, smoking and dietary habits (including lipids use) were recorded. Results: 70% of the LVSD patients and 76% of the non-LVSD patients reported exclusive olive oil consumption. Multi-adjusted analysis revealed that exclusive olive oil consumption in post-ACS patients with a first cardiac episode was associated with a 65% (95% confidence interval 0.14–0.87) lower likelihood of developing LVSD after adjusting for various confounders. No significant association was observed among participants with a previous history of ACS. Conclusions: Exclusive, long-term olive oil consumption seems to offer significant protection against the development of LVSD in post-ACS patients.
Comparison of Sleep EEG Profiles of Patients Suffering from Restless Legs Syndrome, Restless Legs Syndrome and Depressive Symptoms, and Major Depressive Disorders
Authors: Brand Serge , Lehtinen Antreas , Hatzinger Martin , Holsboer-Trachsler Edith
Published: November 2009

Background: Depressive disorders and restless legs syndrome (RLS) demand particular attention because sleepiness, daytime fatigue and loss of interest are symptoms attributable to both depressive disorders and RLS. Moreover, a high comorbidity rate is observed. The aim of the present study was to compare polysomnographic data of patients suffering from RLS, RLS and depressive symptoms, and major depressive disorders (MDD). Methods: Sleep EEG recordings of patients suffering from RLS (n = 25), RLS and depressive symptoms (n = 38), as well as MDD (n = 15) were compared. Results: Compared to patients with MDD, both groups with RLS had statistically decreased values of sleep continuity, including sleep efficiency, sleep onset latency and wakening after sleep onset. Patients with RLS or RLS and depressive symptoms had also decreased slow-wave sleep compared to patients with MDD. Conclusions: Objective sleep assessment supports previous findings: RLS is a disorder seriously affecting sleep, even compared to MDD. Concomitant symptoms of depression do not seem to additionally deteriorate sleep, though they trigger differences in treatment.
Plasma β-Carotene Is Not a Suitable Biomarker of Fruit and Vegetable Intake in German Subjects with a Long-Term High Consumption of Fruits and Vegetables
Authors: Garcia A.L. , Mohan R. , Koebnick C. , Bub A. , Heuer T. , Strassner C. , Groeneveld M.J. , Katz N. , Elmadfa I. , Leitzmann C. , Hoffmann I.
Published: November 2009

Background/Objective: β-Carotene is often used as a marker for the amount of fruit and vegetables consumed, but little is known about plasma β-carotene concentrations in subjects whose habitual (long-term) diets are characterized by different amounts of foods of plant origin. We compared dietary β-carotene intake and plasma concentrations in women on habitual diets differing in the consumed amounts of foods of plant origin. Methods: A comparison of dietary β-carotene intakes and plasma β-carotene concentrations in women adhering to an average Western diet (n = 172), wholesome nutrition (following preventive recommendations) (n = 238) or a raw food diet (n = 104). Results: Dietary β-carotene intake was 5.5, 9.3, 14.7 mg/day for women adhering to an average Western diet, wholesome nutrition and raw food diet, respectively (p < 0.001). Corresponding multivariate adjusted plasma β-carotene concentrations were 1.07, 1.65, and 1.16 µmol/l, respectively (p < 0.001). Comparable dietary β-carotene intake resulted in lower multivariate adjusted plasma β-carotene in women adhering to a raw food diet and average Western diet compared to those on wholesome nutrition (p < 0.001 for all intake groups up to 20 mg/day). The amount of fruit and vegetable intake did not predict plasma β-carotene levels in women consuming a raw food diet. Conclusions: Plasma β-carotene concentrations differed among the diet groups, with highest plasma levels in women adhering to wholesome nutrition. Plasma β-carotene concentrations may not reflect β-carotene intake and the amount of fruit and vegetables consumed.
Family History of Diabetes and Prevalence of the Metabolic Syndrome in U.S. Adults without Diabetes: 6-Year Results from the National Health and Nutrition Examination Survey (1999–2004)
Authors: Ghosh A. , Liu T. , Khoury M.J. , Valdez R.
Published: November 2009

Background/Aims: Type 2 diabetes and cardiovascular disease share risk factors. The influence of family history of diabetes on the odds of having metabolic syndrome has not been estimated for the U.S. population. Our objective was to quantify this association in a national sample of U.S. adults without diabetes. Methods: The sample included 4,937 individuals from the National Health and Nutrition Examination Survey (NHANES) (1999–2004). Familial risk of diabetes was classified in 3 strata according to the combination of relatives affected. Metabolic syndrome was defined according to guidelines issued by 4 groups or organizations. The prevalence and odds of this syndrome were compared among familial risk strata after controlling for relevant risk factors. Results: Overall, depending on the definition and after controlling for key variables, people with a moderate familial risk of diabetes, and people with a high familial risk of diabetes were between 1.4 and 1.6, and 1.6 and 1.8 times as likely, respectively, to have metabolic syndrome compared to people with average familial risk. Conclusion: In a nationally representative sample of U.S. adults without diabetes, family history of diabetes shows a significant, independent association with metabolic syndrome and its traits. This association supports the idea that shared genes and environment contribute to the expression of complex traits such as diabetes and the metabolic syndrome.
Homocysteine May Contribute to Pathogenesis of RNA Damage in Brains with Alzheimer’s Disease
Authors: Isobe Chiaki , Abe Takashi , Terayama Yasuo
Published: November 2009

Background: The pathogenesis of Alzheimer’s disease (AD) is related to homocysteine (HC), but the details are unknown. Objective: We aimed to measure the cerebrospinal fluid (CSF) concentrations of 8-hydroxyguanosine (8-OHG), considering RNA oxidative damage marker, free HC and total HC in the CSF of patients with AD and in normal control subjects. Method and Patients: Subjects were 18 untreated patients with AD (M/F = 7/11) and 15 age-matched controls (M/F = 9/6), with a mean age ± SD of 67.4 ± 5.0 years for patients and of 65.7 ± 9.2 years for controls. The concentrations of free HC, total HC and 8-OHG in the CSF of AD patients were measured by high-performance liquid chromatography using an electrochemical detector. The control subjects were neurologically normal patients who underwent lumbar spinal anesthesia for minor surgery. Results: Total HC and 8-OHG concentrations were significantly increased, and there was a significant positive correlation between total HC and 8-OHG concentrations. However, the concentration of 8-OHG in the CSF showed no correlation with 8-OHG in serum and was not significantly altered in AD patients. Conclusion: These results suggest that total HC and 8-OHG are positively correlated and may be related to AD pathogenesis due to RNA-associated oxidative damage linked to total HC.
Role of the Perifornical Hypothalamic Monoamine Neurotransmitter Systems in Anorectic Effects of Endotoxin
Authors: Adamson Trinka W. , Corll Connie , Svec Frank , Porter Johnny
Published: November 2009

The cachexia-anorexia syndrome, in which patients suffering from chronic illness lack the desire to eat and experience weight loss, creates a serious clinical problem when patients are attempting to overcome the disease process. Endotoxin (ET) has many actions in the brain and peripheral injections can affect regulation of monoamines in brain areas as diverse as the olfactory lobes and the locus coeruleus. Certainly, ET is involved in the febrile process and it plays a prominent role in the regulation of food intake and maintenance of body weight during chronic illnesses. Monoamine neurotransmitters in specific regions of the hypothalamus also participate in the regulation of food intake and body weight and have been well characterized. In this regard, the hypothalamic perifornical nucleus (PFN) is of interest to our lab due to its role in drug-induced anorexia caused by amphetamines. It is also the most sensitive site in the hypothalamic monoaminergic system that involves dopamine (DA) and epinephrine (EPI). DA antagonist, stereotaxically placed in this site, can stimulate feeding, and specific injections of DA or EPI can result in a 70–90% decrease in food intake, even in food-deprived animals. We have shown in our studies that ET in a dose (0.2 mg/kg of lipopolysaccharide) that does not induce noticeable ambulatory (lack of movement) effects (related to malaise) can cause a significant decrease in food intake in lean Zucker rats. We hypothesize that exogenous ET causes an increase in the extracellular concentrations of monoamines in the perifornical hypothalamus, which in turn can mediate the decrease in food intake. Microdialysis was utilized to measure extracellular concentrations of EPI, norepinephrine, 5-hydroxyindoleacetic acid, DA, and serotonin or 5-hydroxytryptamine. These measurements were taken at a post-ET time period that coincides with an ET-induced decrease (4×) in food intake. Extracellular DA and EPI both significantly increased in the PFN in response to injection of ET. Increases in extracellular DA were dose related and were significant (p < 0.05) compared to zero baseline and saline at both doses of ET. No statistically significant differences were found in 5-hydroxyindoleacetic acid, norepinephrine, and serotonin in microdialysates of this part of the hypothalamus. The present data suggest that catecholamines, namely DA and EPI which are known to decrease food intake, in the PFN may be involved in the regulation of decreases in food intake caused by peripherally administered ET. This does not rule out a role for locally produced inflammatory molecules in the brain in this process.
Evaluation of Biological Aging Process – A Population-Based Study of Healthy People in China
Authors: Bai Xiaojuan , Han Lulu , Liu Qiang , Shan Haiyan , Lin Hongli , Sun Xuefeng , Chen Xiang-mei
Published: November 2009

Background: Although there have been cross-sectional and longitudinal studies examining biological age (BA) with chronological age (CA)-related changes in physical, physiological, biochemical, and hormonal variables, few studies have performed echocardiographic evaluation of the cardiovascular system and inflammatory biomarkers. Furthermore, little is known about biomarkers of aging and BA score (BAS) for healthy people in China. Objectives: The purpose of this study was to identify the biomarkers of healthy aging and to establish BAS for healthy people in China. Methods: We examined 2,876 men and women aged 30–98 years old in three Chinese cities, and 852 healthy subjects were assessed with 108 physical, morphological, physiological and biochemical variables. After excluding binary variables, variables that had a correlation coefficient with CA of ≤0.25 and redundant variables, eight variables including CA, arterial pulse pressure (PP), intima-media thickness (IMT), end diastolic velocity (EDV), ratio of peak velocity of early filling to atrial filling (E/A), mitral valve annulus lateral wall of peak velocity of early filling (MVEL), cystatin C (CYSC), and fibrinogen (FIB) were selected as candidate biomarkers of aging based on a factor-weighted BAS composite for predicting BA. Results: The BAS equation was 0.248 (CA) + 0.195 (IMT) – 0.196 (EDV) – 0.167 (E/A) – 0.166 (MVEL) + 0.188 (PP) + 0.182 (FIB) + 0.193 (CYSC). Individual BAS were significantly correlated with CA (r = 0.893, p < 0.001). Biological aging rate predicted by BAS was accelerated with increases in CA, and peaked when healthy men and women reached ≧75 years of age. Conclusions: Our data suggest that BAS is superior to CA in assessing the rate of aging in healthy Chinese people. The cardiovascular variables play a crucial role in the evaluation of biological aging. Biological aging rate appears to be age specific.
Cardiac Tachyarrhythmia in the Fetus: Diagnosis, Treatment and Prognosis
Authors: Stewart P.A. , Wladimiroff J.W.
Published: November 2009

Real-time directed M-mode echocardiography permits analysis of atrial and ventricular mechanical systole and allows inference of the type of arrhythmia present. Accurate diagnosis in cases of fetal tachyarrhythmia is of vital importance when therapy is considered, and in planning further management and delivery of an affected infant. Fetal tachyarrhythmia may be life-threatening especially when fetal hydrops is present and aggressive therapy is mandatory in these cases with digoxin being the drug of choice. In our series the incidence (8.3%) of congenital heart disease was as expected, but the incidence (54%) of atrial flutter was surprisingly high. The prognosis was dependent on the presence or absence of fetal hydrops and was not influenced by the type of arrhythmia or gestational age.
Ultrasound Diagnosis of Intrauterine Growth Retardation
Authors: Warsof Steven L. , Sayegh Sue Kelly
Published: November 2009

Intrauterine growth retardation is associated with increased perinatal morbidity and mortality. Assuming an accurately dated pregnancy, ultrasonic estimations of fetal weight can be used to predict intrauterine growth retardation. Antenatal detection of this condition will have an impact on management and ideally may improve outcome.
Vehicular Trauma in Pregnancy: An Algorithm for Diagnosis and Fetal Therapy
Authors: Schoenfeld Alex , Ziv Elan , Neri Alex , Stein Leonard B. , Ovadia Jardena
Published: November 2009

The incidence of motor vehicle accidents resulting in trauma in pregnant women is increasing. The best chance for fetal survival is to ensure maternal survival, so awareness of the types of injuries and their presentation after vehicular trauma is of the utmost importance. An algorithm for the approach to diagnosis and fetal therapy based upon obstetrics and trauma care parameters is hereby presented to the trauma team.
Sacrococcygeal Teratoma
Authors: Pringle Kevin C. , Weiner Carl P. , Soper Robert T. , Kealey Patrick
Published: November 2009

The definition, natural history and prognosis of sacrococcygeal teratoma (SCT) are reviewed. Two cases of SCT are presented in detail. Both were diagnosed well before delivery and required intensive perinatal management. Both babies survived intact after removal of 30–50% of total body mass. Case selection for antenatal therapy remains a problem. Prospects for antenatal therapy are reviewed.
Experience with 8 Cases of Prenatally Diagnosed Sacrococcygeal Teratomas
Authors: Holzgreve W. , Miny P. , Anderson R. , Golbus M.S.
Published: November 2009

Based on an analysis of eight prenatal diagnoses of sacrococcygeal teratomas and a review of the literature on this condition, sacrococcygeal teratoma can be accurately diagnosed which is related to significant fetal wastage as well as neonatal morbidity and mortality. These tumors are usually benign and the long-term morbidity, but not the overall survival rate, appears to be related to the American Academy of Pediatrics Surgical Section type of tumor. α-Fetoprotein can be normal or elevated and acetylcholinesterase in amniotic fluid can be present in spite of the polyhydramnios, but sonography can distinguish these lesions from neural tube defects. Nonimmune hydrops is an ominous sign, particularly in cases detected early in pregnancy. Timing and method of delivery are important considerations for neonatal survival with these lesions. However, normal survival with minimal morbidity is possible even in the largest of sacrococcygeal teratomas.
Psychological Implications of Fetal Diagnosis and Therapy
Authors: Thomassen-Brepols L.J.
Published: November 2009

Virtually nothing is known about the psychological implications of fetal diagnosis and therapy. This paper discusses some of the possible implications in light of the known psychological responses to fetal diagnosis by amniocentesis and genetic pregnancy termination. These are discussed against the background of the meaning of a pregnancy to the couple, the impact of the changes forced upon a couple by the discovery of a defect, and the likely approaches to decision making when the available options are presented.
Some Aspects of Fetal Biology
Authors: Forestier F.
Published: November 2009

Fetal blood sampling under ultrasound control is rapidly expanding the study of human fetal biology. Pure fetal blood is required for prenatal diagnosis, establishment of reference ranges for biologic measurements and assessment of fetal welfare. Hematological, biochemical and immunological parameters were selected on blood of normal fetuses sampled between the 18th and 36th week of gestation. They were referred to us for various prenatal diagnosis (mainly toxoplasmosis) but were well and confirmed healthy at birth. These data indicate a slower metabolism in fetuses compared to their mother, a lower level of energy requirement and a relative liver immaturity. An important point concerns the evolution of some parameters all along the pregnancy. The correlation observed between the different biological levels either in cord or maternal sera (or between both) paves the way for future studies concerning fetal metabolism. These normal values of fetal biology will improve our knowledge of physiology and help to determine the specific values of a test in fetal pathology.
Measurement of the Fetal Urine Production Rate Using Real-Time Ultrasound in Fetuses with Bilateral Hydronephrosis
Authors: Yamaguchi Yoshiyuki , Shimokawa Hiroshi , Hori Eiichi , Matsumoto Naomichi , Nakano Hitoo , Suita Sachiyo , Kukita Joji
Published: November 2009

The fetal urine production rate (FUPR) in 147 normal fetuses after 27 weeks of gestation and 5 with bilateral hydronephrosis was measured using real-time ultrasound. Later, the correlation between FUPR and renal function was evaluated postnatally. In the normal fetuses, FUPR (mean ± 2 SD) increased gradually from 1.9 ± 1.6 at 27–28 weeks of gestation to 7.5 ± 4.5 ml/l0 min at 37–38 weeks of gestation. In the 5 cases with bilateral hydronephrosis, FUPR was within normal ranges and increased with advances in gestation. Intrauterine intervention was not performed in any of the cases, and, at present, renal insufficiency is nil.
Prenatal Diagnosis of Fetal Brain Tumors
Authors: Alvarez Manuel , Chitkara Usha , Lynch Lauren , Mehalek Karen E. , Heller Debra , Berkowitz Richard L.
Published: November 2009

Two cases of congenital brain tumors were detected during routine antepartum sonography at the Mount Sinai Medical Center Perinatal Ultrasound Unit. In both cases, diagnosis was made during the third trimester at 31 and 33 weeks, respectively. In one of these patients, no intracranial abnormalities were noted on a sonogram performed in conjunction with genetic amniocentesis at 18 weeks gestation. The histologic diagnosis of both tumors was glioblastoma multiforme grade III. Previous reports describing the prenatal sonographic diagnosis of intracranial tumors have been in cases with fetal intracranial teratomas.
An Immunological Approach to the Treatment of Inherited Life-Threatening Bone Marrow Defects
Authors: Brent Leslie
Published: November 2009

The evidence that the human fetus at 15–22 weeks gestation is still immunoincompetent when judged by the generation of cytotoxic T cell responses is briefly reviewed. It suggests that it might be possible to induce immunological tolerance in the human fetus by the inoculation of allogeneic cells, thus offering a potential treatment for fetuses that have been shown to suffer from life-threatening inherited bone marrow disorders. Adult bone marrow or fetal liver thus transplanted could be expected to establish cellular chimerism and ameliorate the symptoms of the disease. Graft-versus-host disease (GVHD), brought about by mature lymphocytes present in adult bone marrow, poses the main threat. Rodent experiments have shown that GVHD can be avoided if T cell-depleted bone marrow is used in the induction of tolerance. This report summarises experiments in cynomolgus monkeys designed to test this approach rigorously by the inoculation of T-depleted paternal bone marrow cells into fetuses of different ages. Although it has become clear that tolerance can be induced there have been many in utero deaths, at least some of them from GVHD. Those fetuses that went to term were not chimeric. The possible reasons for these disappointing results are discussed.
Interest of Biology in the Management of Pregnancies where a Fetal Malformation Has Been Detected by Ultrasonography
Authors: Boue A. , Muller F. , Briard M.L. , Boue J.
Published: November 2009

The results of two French collaborative studies are reported with respect to chromosomal and biochemical analyses following the ultrasonographic detection of a fetal anomaly. Overall, chromosomal anomalies were observed in 14.8%, ranging from 8.6% in isolated single malformations to 40.5% in multiple fetal malformations associated with intrauterine growth retardation. Acetylcholinesterase (AChE) electrophoresis was performed on the amniotic fluid of 64 cases of ultrasonographically diagnosed isolated hydrocephalus. 8 cases of previously unsuspected open neural tube defects were diagnosed by AChE. Digestive microvillar enzyme assays were useful in the precise diagnosis of suspected gastrointestinal anomaly. The correlation of the results of ultrasonography and chromosomal and biochemical analyses is the basis for the diagnosis and the prognosis of pregnancy.
Fetal Umbilical Cord Catheterization under Ultrasound Guidance
Authors: Lémery D. , Urbain M.-F. , Micorek J.-C. , Jacquetin B.
Published: November 2009

Since 1984 we have performed 30 intrauterine exchange transfusions (IUET) under ultrasound guidance. In 4 pregnancies with anterior placenta, we performed 9 umbilical cord catheterizations in 11 IUET: the first with material for epidural analgesia and the others with a central venous catheter. The latest one was performed at 34 weeks, the earliest at 27 weeks and repeated up to 4 times. Every catheterization did not last more than 5 min and we did not find any infection, hematoma or placental or cord injury. All 4 pregnancies were delivered at 34–36 weeks and the babies are alive and healthy (the oldest is 4 years old). This technique, when possible, is a good alternative to long procedures with risk of fetal movements, and limits the risk of hematoma.
Human Fetal Behavior and Blood Flow in Term Pregnancies: A Review
Authors: van Eyck Jim , Wladimiroff Juriy W.
Published: November 2009

A review is presented of the latest data on the relationship between the blood flow velocity waveform in the lower thoracic part of the fetal descending aorta, internal carotid and umbilical artery and fetal behavioral states, in particular state IF and 2F [1], in the normal-growing and growth-retarded fetus at term. Fetal neurological development, expressed by the emergence of fetal behavior and eventually resulting in well-distinguishable fetal behavioral states, is clearly associated with specific hemodynamic adaptations. The asymmetrically growth-retarded human fetus is capable of modifying this relationship. In the analysis of blood flow velocity waveforms for clinical purposes, fetal behavioral states and fetal heart rate have to be taken into account for a proper interpretation of recorded data.
Assessment of Fetal Blood Volume for Computer-Assisted Management of in utero Transfusion
Authors: Mandelbrot L. , Daffos F. , Forestier F. , MacAleese J. , Descombey D.
Published: November 2009

We performed 41 intravascular ultrasound-guided fetal transfusions in a total of 20 pregnancies with erythroblastosis fetalis or alloimmune thrombocytopenia. On the basis of this experience, we developed a computer-assisted procedure for determining the volume to be transfused, which provides an adequate final concentration. Fetal weight was estimated using ultrasound measurements. Fetoplacental blood volume was estimated from the regression line: fetoplacental volume (ml) = 1.046 + fetal weight (g) × 0.14. The volume to be transfused was calculated using the simple dilution formula:Vtransfused = Vfetoplacental·(Cfinal –– Cinitial)/Ctransfused
Abdominal Wall Defects and Obstructive Uropathies
Authors: Pringle K.C.
Published: November 2009

Gastroschisis and omphalocele (exomphalos) are embryologically distinct, and for this reason each has its own distinct constellation of associated anomalies. The perinatal management of both gastroschisis and omphalocele addresses the controversy as to the best mode of delivery that has been expressed in the literature with regard to gastroschisis and has exercised many of those involved in antenatal diagnosis in the case of omphalocele. The post-delivery management of both of these defects is briefly discussed. Controversies surrounding the aetiology of renal dysplasia and whether urinary tract obstruction is a cause of dysplasia or an anomaly associated with dysplasia are also discussed. The options for therapy and the indications for an in utero shunting procedure are outlined as well as the controversy centred around the utility of an in utero shunt. The need for a prospective randomised trial is emphasised, together with the difficulty that is raised by the need to choose a limited number of prospective indices on which treatment decisions in such a trial must be based. The need for a long-term follow-up of all patients entered in such a trial is emphasised.
Perinatal Cerebral Asphyxia: Pharmacological Intervention
Authors: Gunn A.J. , Williams C.E. , Bennet L. , Cook C.J. , Gluckman P.D.
Published: November 2009

Perinatal asphyxia is associated with an increased risk of cerebral palsy and significant mortality. We investigated the use of flunarizine, a calcium antagonist and MK-801, an excitatory amino acid antagonist, in preventing the sequelae of severe hypoxic/ischemic insults. Flunarizine was neuroprotective in the infant rat subjected to unilateral carotid ligation and 2 h of hypoxia. Preliminary analysis of experiments in a novel model of cerebral ischemia in the fetal sheep suggests that prophylactic treatment with flunarizine greatly modified the outcome after 30 min of total ischemia. Treatment with MK-801 prevented post-ischemic seizures. The background to these developments is outlined and future prospects considered.
Allogeneic Fetal Bone Cranioplasty in Macaca mulatta
Authors: Bacher John D. , Michejda Maria
Published: November 2009

Teratogen-induced herniation of the occipital lobes (encephalocele) associated with cranium bifidum in monkey fetuses (Macaca mulatta) were repaired by amputation and cranioplasty in utero or postnatally. Fetal allogeneic cranial bone which had been fresh frozen was used in conjunction with a bone paste to provide a protective covering of the neural tissue following repair of the encephalocele. The bone graft in those animals treated in utero or 1–2 weeks post-partum developed a strong union with the calvarium, provided good protection for the underlying dura and neural tissue, had a smooth surface, and provided good cosmetic-reconstructive results. In contrast, when the cranioplasty procedure was performed on infant monkeys at 2–3 months of age the bone graft was rejected.