bluuebunny/crossref_metadata_2025 huggingface dataset:
Cystatin‐C and beta trace protein as markers of renal function in pregnancy
Authors: Akbari Ayub , Lepage Nathalie , Keely Erin , Clark Heather D. , Jaffey James , MacKinnon Martin , Filler Guido
Published: April 2005

Objective  To assess the validity of Cystatin‐C (Cys‐C) and beta trace protein (BTP) as clinical markers of glomerular filtration rate (GFR) in pregnant women.

Design  Prospective cross sectional study.

Setting  Obstetric unit of a tertiary care hospital.

Population  One hundred and thirty‐seven normal pregnant women and 13 women postpartum.

Methods  Twenty‐four hour creatinine clearance (CrCl), serum creatinine, Cys‐C and BTP concentrations were measured on normal pregnant women in the first trimester (n= 5), second trimester (n= 68) and third trimester (n= 64) and in 13 women postpartum. Data are given as median (2.5th centile, 97.5th centile).

Main outcome measures  Serum concentrations of Cys‐C and BTP compared with creatinine clearance and serum creatinine.

Results  The median serum creatinine throughout gestation was 53 μmol/L (39, 71), and median CrCl was 143 mL/minute (91 to 216). Postpartum, creatinine rose to 74 μmol/L (58, 86) and CrCl decreased to 104 mL/minute (71, 159). For Cys‐C, the median concentration was 0.70 mg/L (0.46, 1.32), and 0.54 mg/L (0.36, 0.96) for BTP. Comparing the second and third trimesters, there was no significant difference between CrCl (median 145 vs 141 mL/minute) and BTP concentrations (median 0.51 vs 0.55 mg/L), while median Cys‐C was significantly higher in the third trimester (0.61 vs 0.88 mg/L; P < 0.001). Unlike creatinine and BTP, Cys‐C levels decreased to 0.72 mg/L (0.57, 0.95) postpartum. The only significant relationship of either of these markers to the standard used for GFR was between Cys‐C and CrCl in the third trimester, and the correlation was weak (r= 0.27 for 1/Cys‐C vs CrCl).

Conclusion  These data demonstrate that despite claims to the contrary, Cys‐C is a poor marker of GFR during pregnancy. Similarly, BTP shows little promise.
DNA identification of fetal cells isolated from cervical mucus: potential for early non‐invasive prenatal diagnosis
Authors: Katz‐Jaffe Mandy G. , Mantzaris Debbie , Cram David S.
Published: April 2005

Objectives To develop a reliable method to isolate fetal cells for genetic diagnosis.

Design Aspiration of cervical mucus from pregnant women in the first trimester.

Setting Pregnant women were recruited before an elective termination of pregnancy.

Population Sixty pregnant women (7–10 weeks of gestation).

Methods Fetal cells were isolated from aspirated cervical mucus of pregnant women using a combination of enzymatic digestion, fluorescent immunohistochemistry, micromanipulation and single‐cell DNA allelic profiling.

Main outcome measures The isolation and identification of fetal cells.

Results The transformation of the tenacious cervical mucus into a single‐cell suspension enabled the isolation and identification of fetal cells by fluorescent immunohistochemistry. Confirmation of fetal origin was accomplished by single‐cell DNA allelic profiling alongside known maternal cells.

Conclusions This novel non‐invasive method is rapid and efficient with results attainable within 24 hours as early as seven weeks of gestation. The technique would offer earlier reassurance and the option of first trimester therapeutic abortions to both high and low risk pregnant women.
Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double‐blinded, placebo‐controlled trial
Authors: Impey Lawrence , Pandit Meghana
Published: April 2005

Background  External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non‐cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re‐attempted after a failed attempt.

Objective  To determine whether tocolysis should be used if ECV is being re‐attempted after a failed attempt.

Design  Randomised, double‐blinded, placebo‐controlled trial.

Setting  UK teaching hospital.

Population  One hundred and twenty‐four women with a breech presentation at term who had undergone an unsuccessful attempt at ECV.

Methods  Relative risks with 95% confidence intervals for categorical variables and a t test for continuous variables. Analysis was by intention to treat.

Main outcome measures  Incidence of cephalic presentation at delivery. Secondary outcomes were caesarean section and measures of neonatal and maternal morbidity.

Results  The use of tocolysis for a repeat attempt at ECV significantly increases the incidence of cephalic presentation at delivery (RR 3.21; 95% CI 1.23–8.39) and reduces the incidence of caesarean section (RR 0.33; 95% CI 0.14–0.80). The effects were most marked in multiparous women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64–53.62). Maternal and neonatal morbidity remain unchanged.

Conclusions  The use of tocolysis increases the success rate of repeat ECV and reduces the incidence of caesarean section. A policy of only using tocolysis where an initial attempt has failed leads to a relatively high success rate with minimum usage of tocolysis.
Prenatal diagnosis and obstetric outcomes in triplet pregnancies in relation to chorionicity
Authors: Geipel Annegret , Berg Christoph , Katalinic Alexander , Plath Hanno , Hansmann Manfred , Germer Ute , Gembruch Ulrich
Published: April 2005

Objective  This study describes the frequency, pregnancy complications and outcomes of non‐trichorionic triplet pregnancies.

Design  A retrospective observational study.

Setting  Two tertiary level referral centres of Obstetrics and Prenatal Medicine, Germany.

Population  All women booked to receive targeted ultrasound screening between January 1998 and June 2003. The mixed low and high risk population included 36,430 women with ultrasound examinations between 11 and 24 weeks of gestation. Of those with available outcome, 176 were triplet pregnancies with three viable fetuses.

Methods  Analysis of ultrasound data and perinatal outcome in triplet gestations who had first and second trimester targeted ultrasound examination. Pregnancies with monochorionic or dichorionic placentation were identified and pregnancy outcome was compared to trichorionic triplets.

Main outcome measures  Intrauterine fetal death, fetal growth restriction (FGR), mean discordance and survival rate in non‐trichorionic versus trichorionic triplets.

Results  Triplets were trichorionic in 81.8% and had a monochorionic or dichorionic placentation in the remaining 18.2%. The rate of monochorionicity and dichorionicity was significantly higher after spontaneous conception than after assisted reproductive technologies (44.8%vs 12.9%, P < 0.001). In non‐reduced monochorionic and dichorionic triplets compared with non‐reduced trichorionic triplets, there was a higher rate of intrauterine fetal death (8.8%vs 1.5%, P < 0.01), FGR (33.3%vs 25.5%), mean discordance (20.5%vs 12.7%, P < 0.01), discordance >30% (26.3%vs 2.9%, P < 0.01) and delivery <32 weeks of gestations (47.4%vs 32.2%). There was a lower survival rate in non‐trichorionic triplets (84.2%) than in trichorionic ones (91.7%).

Conclusion  Triplet pregnancies with a monochorionic or dichorionic placentation are at significantly higher risk of adverse pregnancy outcome compared with trichorionic pregnancies. First trimester evaluation of chorionicity is strongly emphasised.
Erythrokeratodermia variabilis (EKV) – eine Störung der epidermalen Expression von Gap‐Junction‐Proteinen
Authors: Ständer Sonja , Stadelmann Antje , Traub Otto , Traupe Heiko , Metze Dieter
Published: April 2005

Die Erythrokeratodermia variabilis (EKV) ist eine seltene autosomal‐dominant vererbte Genodermatose mit einer epidermalen Verhornungsstörung. Das klinische Bild der EKV wird von zwei Morphen geprägt: transiente, schnell wandernde Erytheme und persistierende braune Hyperkeratosen. Vor kurzem wurde der zugrunde liegende Gendefekt der EKV auf dem kurzen Arm von Chromosom 1 lokalisiert, der für das Gap‐Junction‐Protein Connexin 31 kodiert. Wir stellen einen 48jährigen Patienten vor, bei dem seit dem dreißigsten Lebensjahr großflächige, scharf begrenzte, randständig schuppende Erytheme an den Extremitäten, Gesäß und Rumpf auftreten. Histologisch fand sich eine orthokeratotische Hyperkeratose mit fokaler Parakeratose bei Akanthose der Epidermis. Immunhistochemisch konnte eine vermindert Expression des Gap‐Junction‐Proteins Connexin 31 sowie vermehrte Expression von Connexin 43 dargestellt werden. Ultrastrukturell zeigten sich erweiterte Interzellularräume in der oberen Epidermis mit unauffälligen Desmosomen, Adherensjunktionen und regulären Gap Junctions.

In der Epidermis wird u. a. die Zellproliferation und ‐differenzierung über die Gap Junctions reguliert. Die Mutation im Connexin 31 wird daher als ursächlich für das klinische Bild der EKV angesehen. Die Überexpression von Connexin 43, die hier erstmals beschrieben wird, entsteht möglicherweise reaktiv als Folge der CX31‐Mutation und kompensiert vorübergehend den Defekt.
MAGNETIC RESONANCE IMAGING FINDINGS IN SPINAL CORD INFARCTION IN THREE SMALL BREED DOGS
Authors: Grünenfelder Fredrik I. , Weishaupt Dominik , Green Ron , Steffen Frank
Published: April 2005

Fibrocartilaginous embolization (FCE) of the spinal cord is a common disease in large breed dogs. There are only a few reports about this entity in small breed dogs and it has never been reported in chondrodystrophic breed. For definitive diagnosis histopathologic examination is necessary. Magnetic resonance imaging (MRI) as a potential diagnostic tool for intravitam diagnosis of FCE has been mentioned before, but results have not been reported so far. This report describes the neurological findings and MRI results in three small breed dogs, including a Pekingese dog, with FCE of the spinal cord. The disease was suspected in two animals based upon clinical and MRI‐appearance and confirmed in the third by histopathological examination. In all three cases, similar focal intramedullary lesions, consisting of hyperintensive signals on T2‐weighted images, were detected. Based on these findings, high‐field MRI may be used as an antemortem tool for the diagnosis of FCE. It is also shown that FCE can occur in chondrodystrophic dogs.
ENDOSCOPIC RETROGRADE CHOLANGIO‐PANCREATOGRAPHY IN HEALTHY BEAGLES
Authors: Spillmann Thomas , Happonen Irmeli , Kähkönen Tuomo , Fyhr Thomas , Westermarck Elias
Published: April 2005

Endoscopic retrograde cholangiography and pancreatography was performed in seven healthy Beagles to assess the common bile duct and the accessory pancreatic duct after retrograde filling with an iodine contrast medium. All dogs had a major and a minor duodenal papilla. One Beagle had additionally an accessory papilla. The diameter of the contrast filled ducts was measured at three defined measure points (MP1–3) in ventrodorsal radiographs and left lateral radiographs. In ventrodorsal radiographs of endoscopic retrograde cholangiography the common bile duct had a straight craniomedial course. The mean duct diameter was from proximal to distal 3.04±1.89 mm at MP1, 2.38±1.23 mm at MP2, and 2.11±0.84 mm at MP3. In ventrodorsal radiographs of endoscopic retrograde pancreatography, the left and right branch of the accessory pancreatic duct united in the pancreatic body. The mean diameter of the right branch was 0.88±0.14 mm at MP1, 0.72±0.2 mm at MP2 and 0.61±0.11 mm at MP3. The left branch had a diameter of 0.93±0.28 mm at MP1, 0.86±0.21 at MP2, and 0.6±0.07 mm at MP3. The mean length was 81.6±14.3 mm for the right and 107.0±24.9 mm for the left branch. In left lateral radiographs of endoscopic retrograde pancreatography, it was not possible to differentiate the left from the right branch. Both branches ran nearly parallel and showed similar diameters but slight differences in length. The study proves that endosopic retrograde cholangio‐pancreatography is possible in dogs. Radiographs taken from dogs in dorsal recumbency allow an objective assessment of the common bile duct and the accessory pancreatic duct.
TRANS‐SPLENIC PORTAL SCINTIGRAPHY IN NORMAL DOGS
Authors: Cole Robert C , Morandi Federica , Avenell James , Daniel Gregory B
Published: April 2005

The purpose of this study was to (1) establish a technique for ultrasound‐guided trans‐splenic portal scintigraphy (TSPS) using99mTcO4−, (2) evaluate portal vein morphology, (3) compare the radiation exposures for TSPS vs. per‐rectal portal scintigraphy (PRPS), and (4) compare the quality of numerical data from the TSPS vs. PRPS. Eight juvenile dogs underwent PRPS and TSPS (minimum of 48 h between studies) after initial screening tests. PRPS was done according to established protocol using 425±36 MBq (mean±SD) of99mTcO4−. TSPS was done with the dogs in right lateral recumbency over the gamma camera.99mTcO4−(57±13.9 MBq) was injected into the spleen 1–2 s following initiation of the dynamic acquisition. The frame rate was 4 frames/s for 5 min. There was significantly lower radioactivity of99mTcO4−given and significantly higher total counts recorded in the liver and heart during the TSPS compared with PRPS. The total counts for the TSPS and PRPS were 7120±4386 and 830±523, respectively. Percent absorption from the spleen was 52.5±19.1% compared with 9.2±5.7% for the colon. Calculated transit time for the TSPS studies was 7±2.3 s. In TSPS studies, the splenic and portal veins were clearly identified. Radiation exposure levels of the dogs were significantly lower following TSPS than after PRPS. TSPS appears superior to PRPS as a method to image the portal venous system representing a valid alternative diagnostic test for animals with suspected portosystemic shunts.
USE OF99MTCO TRANS‐SPLENIC PORTAL SCINTIGRAPHY FOR DIAGNOSIS OF PORTOSYSTEMIC SHUNTS IN 28 DOGS
Authors: Morandi Federica , Cole Robert C. , Tobias Karen M. , Berry Clifford R. , Avenell James , Daniel Gregory B.
Published: April 2005

Ultrasound‐guided percutaneous trans‐splenic portal scintigraphy (TSPS) using99mTcOhas been used to image the portal venous system in normal dogs. Compared with per‐rectal portal scintigraphy, it provides higher count density, consistent nuclear venograms of the splenic and portal vein, and significantly decreased radiation exposures. This paper describes the use of TSPS for the diagnosis of portosystemic shunts in 28 dogs. TSPS was performed injecting 70±28 MBq of99mTcO(mean±SD) into the splenic parenchyma with ultrasound guidance. A dynamic acquisition at a frame rate of four frames/s for 5 min was initiated after placement of the needle and approximately 2 s prior to injection. All dogs had diagnoses confirmed via exploratory laparotomy or ultrasonographic identification of the shunting vessel(s). Three studies (10.7%) were nondiagnostic because of intraperitoneal rather than intrasplenic injection of the radionuclide. Three pathways were recognized on the scintigraphic images: (1) portoazygos shunts—the99mTcObolus traveled dorsally, running parallel to the spine and entering the heart craniodorsally; (2) single portocaval or splenocaval shunts—the99mTcObolus ran from the area of the portal vein/splenic vein junction in a linear fashion toward the caudal vena cava entering the heart caudally; (3) internal thoracic shunt—the99mTcObolus traveled ventrally along the thorax and abdomen entering the cranial aspect of the heart. Single and multiple shunts were easily distinguished. There were no distinguishing features between single intra and extrahepatic portocaval shunts.
A Homolog of
Drosophila grainy head
Is Essential for Epidermal Integrity in Mice
Authors: Ting Stephen B. , Caddy Jacinta , Hislop Nikki , Wilanowski Tomasz , Auden Alana , Zhao Lin-lin , Ellis Sarah , Kaur Pritinder , Uchida Yoshikazu , Holleran Walter M. , Elias Peter M. , Cunningham John M. , Jane Stephen M.
Published: April 2005

The
Drosophila
cuticle is essential for maintaining the surface barrier defenses of the fly. Integral to cuticle resilience is the transcription factor
grainy head
, which regulates production of the enzyme required for covalent cross-linking of the cuticular structural components. We report that formation and maintenance of the epidermal barrier in mice are dependent on a mammalian homolog of
grainy head, Grainy head-like 3
. Mice lacking this factor display defective skin barrier function and deficient wound repair, accompanied by reduced expression of transglutaminase 1, the key enzyme involved in cross-linking the structural components of the superficial epidermis. These findings suggest that the functional mechanisms involving protein cross-linking that maintain the epidermal barrier and induce tissue repair are conserved across 700 million years of evolution.
An Epidermal Barrier Wound Repair Pathway in
Drosophila
Is Mediated by
grainy head
Authors: Mace Kimberly A. , Pearson Joseph C. , McGinnis William
Published: April 2005

We used wounded
Drosophila
embryos to define an evolutionarily conserved pathway for repairing the epidermal surface barrier. This pathway includes a wound response enhancer from the
Ddc
gene that requires
grainy head
(
grh
) function and binding sites for the Grh transcription factor. At the signaling level, tyrosine kinase and extracellular signal-regulated kinase (ERK) activities are induced in epidermal cells near wounds, and activated ERK is required for a robust wound response. The conservation of this Grh-dependent pathway suggests that the repair of insect cuticle and mammal skin is controlled by an ancient, shared control system for constructing and healing the animal body surface barrier.
Representation of Visual Gravitational Motion in the Human Vestibular Cortex
Authors: Indovina Iole , Maffei Vincenzo , Bosco Gianfranco , Zago Myrka , Macaluso Emiliano , Lacquaniti Francesco
Published: April 2005

How do we perceive the visual motion of objects that are accelerated by gravity? We propose that, because vision is poorly sensitive to accelerations, an internal model that calculates the effects of gravity is derived from graviceptive information, is stored in the vestibular cortex, and is activated by visual motion that appears to be coherent with natural gravity. The acceleration of visual targets was manipulated while brain activity was measured using functional magnetic resonance imaging. In agreement with the internal model hypothesis, we found that the vestibular network was selectively engaged when acceleration was consistent with natural gravity. These findings demonstrate that predictive mechanisms of physical laws of motion are represented in the human brain.
Atomic-Scale Visualization of Inertial Dynamics
Authors: Lindenberg A. M. , Larsson J. , Sokolowski-Tinten K. , Gaffney K. J. , Blome C. , Synnergren O. , Sheppard J. , Caleman C. , MacPhee A. G. , Weinstein D. , Lowney D. P. , Allison T. K. , Matthews T. , Falcone R. W. , Cavalieri A. L. , Fritz D. M. , Lee S. H. , Bucksbaum P. H. , Reis D. A. , Rudati J. , Fuoss P. H. , Kao C. C. , Siddons D. P. , Pahl R. , Als-Nielsen J. , Duesterer S. , Ischebeck R. , Schlarb H. , Schulte-Schrepping H. , Tschentscher Th. , Schneider J. , von der Linde D. , Hignette O. , Sette F. , Chapman H. N. , Lee R. W. , Hansen T. N. , Techert S. , Wark J. S. , Bergh M. , Huldt G. , van der Spoel D. , Timneanu N. , Hajdu J. , Akre R. A. , Bong E. , Krejcik P. , Arthur J. , Brennan S. , Luening K. , Hastings J. B.
Published: April 2005

The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface. Our measurements point toward analogies between this nonequilibrium phase transition and the short-time dynamics intrinsic to equilibrium liquids.
Hypoxia, Global Warming, and Terrestrial Late Permian Extinctions
Authors: Huey Raymond B. , Ward Peter D.
Published: April 2005

A catastrophic extinction occurred at the end of the Permian Period. However, baseline extinction rates appear to have been elevated even before the final catastrophe, suggesting sustained environmental degradation. For terrestrial vertebrates during the Late Permian, the combination of a drop in atmospheric oxygen plus climate warming would have induced hypoxic stress and consequently compressed altitudinal ranges to near sea level. Our simulations suggest that the magnitude of altitudinal compression would have forced extinctions by reducing habitat diversity, fragmenting and isolating populations, and inducing a species-area effect. It also might have delayed ecosystem recovery after the mass extinction.
Reconstitution of Circadian Oscillation of Cyanobacterial KaiC Phosphorylation in Vitro
Authors: Nakajima Masato , Imai Keiko , Ito Hiroshi , Nishiwaki Taeko , Murayama Yoriko , Iwasaki Hideo , Oyama Tokitaka , Kondo Takao
Published: April 2005

Kai proteins globally regulate circadian gene expression of cyanobacteria. The KaiC phosphorylation cycle, which persists even without transcription or translation, is assumed to be a basic timing process of the circadian clock. We have reconstituted the self-sustainable oscillation of KaiC phosphorylation in vitro by incubating KaiC with KaiA, KaiB, and adenosine triphosphate. The period of the in vitro oscillation was stable despite temperature change (temperature compensation), and the circadian periods observed in vivo in KaiC mutant strains were consistent with those measured in vitro. The enigma of the circadian clock can now be studied in vitro by examining the interactions between three Kai proteins.
Corticotropin-releasing factor receptor subtypes mediating nutritional suppression of estrous behavior in Syrian hamsters
Authors: Seymour Patricia L. , Dettloff Samantha L. , Jones Juli E. , Wade George N.
Published: April 2005

Caloric deprivation inhibits reproduction, including copulatory behaviors, in female mammals. Decreases in metabolic fuel availability are detected in the hindbrain, and this information is relayed to the forebrain circuits controlling estrous behavior by neuropeptide Y (NPY) projections. In the forebrain, the nutritional inhibition of estrous behavior appears to be mediated by corticotropin-releasing factor (CRF) or urocortin-signaling systems. Intracerebroventricular (ICV) infusion of the CRF antagonist, astressin, prevents the suppression of lordosis by food deprivation and by NPY treatment in Syrian hamsters. These experiments sought to determine which CRF receptor type(s) is involved. ICV infusion of the CRF receptor subtype CRFR2-selective agonists urocortin 2 and 3 (UCN2, UCN3) inhibited sexual receptivity in hormone-primed, ovariectomized hamsters. Furthermore, the CRFR2-selective antagonist, astressin 2B, prevented the inhibition of estrous behavior by UCN2 and by NPY, consistent with a role for CRFR2. On the other hand, astressin 2B did not prevent the inhibition of behavior induced by 48-h food deprivation or ICV administration of CRF, a mixed CRFR1 and CRFR2 agonist, suggesting that activation of CRFR1 signaling is sufficient to inhibit sexual receptivity in hamsters. Although administration of CRFR1-selective antagonists (NBI-27914 and CP-154,526) failed to reverse the inhibition of receptivity by CRF treatment, we could not confirm their biological effectiveness in hamsters. The most parsimonious interpretation of these findings is that, although NPY inhibits estrous behavior via downstream CRFR2 signaling, food deprivation may exert its inhibition via both CRFR1 and CRFR2 and that redundant neuropeptide systems may be involved.
Motor Neuron Firing Dysfunction in Spastic Patients With Primary Lateral Sclerosis
Authors: Floeter Mary Kay , Zhai Ping , Saigal Rajiv , Kim Yongkyun , Statland Jeffrey
Published: April 2005

Patients with corticospinal tract dysfunction have slow voluntary movements with brisk stretch reflexes and spasticity. Previous studies reported reduced firing rates of motor units during voluntary contraction. To assess whether this firing behavior occurs because motor neurons do not respond normally to excitatory inputs, we studied motor units in patients with primary lateral sclerosis, a degenerative syndrome of progressive spasticity. Firing rates were measured from motor units in the wrist extensor muscles at varying levels of voluntary contraction ≤10% maximal force. At each force level, the firing rate was measured with and without added muscle vibration, a maneuver that repetitively activates muscle spindles. In motor units from age-matched control subjects, the firing rate increased with successively stronger contractions as well as with the addition of vibration at each force level. In patients with primary lateral sclerosis, motor-unit firing rates remained stable, or in some cases declined, with progressively stronger contractions or with muscle vibration. We conclude that excitatory inputs produce a blunted response in motor neurons in patients with primary lateral sclerosis compared with age-matched controls. The potential explanations include abnormal activation of voltage-activated channels that produce stable membrane plateaus at low voltages, abnormal recruitment of the motor pool, or tonic inhibition of motor neurons.
Array lessons from the heart: focus on the genome and transcriptome of cardiomyopathies
Authors: Sanoudou Despina , Vafiadaki Elizabeth , Arvanitis Demetrios A. , Kranias Evangelia , Kontrogianni-Konstantopoulos Aikaterini
Published: April 2005

Our understanding of the cardiovascular system has evolved through the years by extensive studies emphasizing the identification of the molecular and physiological mechanisms involved in its normal function and disease pathogenesis. Major discoveries have been made along the way. However, the majority of this work has focused on specific genes or pathways rather than integrative approaches. In cardiomyopathies alone, over 30 different loci have shown mutations with varying inheritance patterns, yet mostly coding for structural proteins. The emergence of microarrays in the early 1990s paved the way to a new era of cardiovascular research. Microarrays dramatically accelerated the rhythm of discoveries by giving us the ability to simultaneously study thousands of genes in a single experiment. In the field of cardiovascular research, microarrays are having a significant contribution, with the majority of work focusing on end-stage cardiomyopathies that lead to heart failure. Novel molecular mechanisms have been identified, known pathways are seen under new light, disease subgroups begin to emerge, and the effects of various drugs are molecularly dissected. This cross-study data comparison concludes that consistent energy metabolism gene expression changes occur across dilated, hypertrophic, and ischemic cardiomyopathies, while Ca2+ homeostasis changes are prominent in the first two cardiomyopathies, and structural gene expression changes accompany mostly the dilated form. Gene expression changes are further correlated to disease genetics. The future of microarrays in the cardiomyopathy field is discussed with an emphasis on optimum experimental design and on applications in diagnosis, prognosis, and drug discovery.
The World’s Most Influential Prison: Success or Failure?
Authors: Johnston Norman
Published: April 2005

This article traces both the history and worldwide influence of a system of complete separation of prisoners from each other during their entire sentence and the unique architecture developed and instituted on a large scale at Eastern State Penitentiary in Philadelphia in 1829. Although not followed in other U.S. prison systems, the so-called Pennsylvania System was adopted, along with the architecture, in most of Europe, South America, and large parts of Asia until early in the 20th century. This article considers the successes and failures of the system and assesses its place in the history of corrections.
Ending the Culture of Street Crime
Authors:   The Lifers Public Safety Steering Committee of the State Correctional Institution
Published: April 2005

This article explores the problem of crime and violence, offering a new way to look at what motivates certain individuals who habitually engage in criminal activity. Explaining the concept of the existence of a pervasive culture of crime is the primary focus of this article. It also seeks to provide a multidirectional strategy for ending that culture, which includes the utilization of former members of the culture as part of the solution.
Bioavailability of Azacitidine Subcutaneous Versus Intravenous in Patients With the Myelodysplastic Syndromes
Authors: Marcucci Guido , Silverman Lewis , Eller Mark , Lintz Linda , Beach C. L.
Published: April 2005

The primary objectives of this study were to characterize the absolute bioavailability of azacitidine after subcutaneous (SC) administration and to compare the single‐dose pharmacokinetics of azacitidine following SC and intravenous (IV) administration. Six patients with myelodysplastic syndromes were randomly assigned according to a crossover design to treatment A, consisting of azacitidine administered as a single 75‐mg/m2 SC dose, or treatment B, consisting of azacitidine administered as a single 75‐mg/m2 IV infusion dose over 10 minutes. A minimum of 7 days and a maximum of 28 days were permitted between treatments. The study demonstrated good bioavailability of a SC azacitidine dose compared to an IV infusion treatment. The exposure profiles following SC drug administration illustrate measurable azacitidine levels with bioavailability (AUC) values within 89% of those measured following IV administration (range, 70%‐112%). The median IV half‐life was 0.36 ± 0.02 hours compared to 0.69 ± 0.14 hours for SC administration. Regardless of the route of administration, a single dose of azacitidine, 75 mg/m2, was generally well tolerated.
Single‐ and Multiple‐Dose Pharmacokinetics of Levovirin Valinate Hydrochloride (R1518) in Healthy Volunteers
Authors: Huang Yue , Ostrowitzki Susanne , Hill George , Navarro Mercidita , Berger Nancy , Kopeck Paul , Mau Cheng I. , Alfredson Tom , Lal Ritu
Published: April 2005

R1518 is a valine ester prodrug of levovirin as an investigational new drug for the treatment of hepatitis C virus. Two phase 1, single‐ and multiple‐dose studies were conducted to investigate the pharmacokinetics of R1518 in healthy volunteers. After oral dosing, R1518 was rapidly and exclusively converted to levovirin. Levovirin plasma concentrations peaked at 2 hours, with T1/2 ranging from 6 to 8 hours. The T1/2 of R1518 was less than 1 hour, with relative exposures (R1518/levovirin) less than 6%. A high‐fat meal did not affect the pharmacokinetics. The female groups in both studies had higher plasma levels than males did due to age and renal function difference. An accumulation ratio of 1.3 to 1.5 was observed with the twice‐daily regimen. About 75% to 90% of the levovirin equivalent dose was recovered in urine. Increase in exposure was slightly disproportionate to increase in dose. Significantly improved oral absorption of levovirin was achieved following administration of R1518.
Racist Extremism in Central and Eastern Europe
Authors: Mudde Cas
Published: April 2005

Based in part on the results of a unique, comparative research project, the aim of this article is threefold: (1) to provide a comparative summary of racist extremism in Central and Eastern Europe (CEE); (2) to compare the situation of racist extremism in CEE to that in Western Europe; and (3) to come to some further insights about racist extremism in the region. It concludes, in contrast to many of the alarming statements on the topic, that CEE is neither a hotbed of racist extremism nor a safe haven for racist extremists. In fact, if one compares the state of racist extremism in CEE to that in Western Europe, the differences seem less striking than is often assumed. Yet while the impact of racist extremism in CEE might not be as great as is often assumed, a lot remains to be done, particularly now that these countries are or will soon be members of the European Union.
The neuronal ceroid lipofuscinosis Cln8 gene expression is developmentally regulated in mouse brain and up-regulated in the hippocampal kindling model of epilepsy
Authors: Lonka Liina , Aalto Antti , Kopra Outi , Kuronen Mervi , Kokaia Zaal , Saarma Mart , Lehesjoki Anna-Elina
Published: April 2005

Background

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by accumulation of autofluorescent material in many tissues, especially in neurons. Mutations in the CLN8 gene, encoding an endoplasmic reticulum (ER) transmembrane protein of unknown function, underlie NCL phenotypes in humans and mice. The human phenotype is characterized by epilepsy, progressive psychomotor deterioration and visual loss, while motor neuron degeneration (mnd) mice with a Cln8 mutation show progressive motor neuron dysfunction and retinal degeneration.

Results

We investigated spatial and temporal expression of Cln8 messenger ribonucleic acid (mRNA) using in situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR) and northern blotting. Cln8 is ubiquitously expressed at low levels in embryonic and adult tissues. In prenatal embryos Cln8 is most prominently expressed in the developing gastrointestinal tract, dorsal root ganglia (DRG) and brain. In postnatal brain the highest expression is in the cortex and hippocampus. Expression of Cln8 mRNA in the central nervous system (CNS) was also analyzed in the hippocampal electrical kindling model of epilepsy, in which Cln8 expression was rapidly up-regulated in hippocampal pyramidal and granular neurons.

Conclusion

Expression of Cln8 in the developing and mature brain suggests roles for Cln8 in maturation, differentiation and supporting the survival of different neuronal populations. The relevance of Cln8 up-regulation in hippocampal neurons of kindled mice should be further explored.
Risk factors for delirium in acutely admitted elderly patients: a prospective cohort study
Authors: Korevaar Johanna C , van Munster Barbara C , de Rooij Sophia E
Published: April 2005

Background

Delirium is a neuropsychiatric syndrome frequently observed in elderly hospitalised patients and can be found in any medical condition. Due to the severe consequences, early recognition of delirium is important in order to start treatment in time. Despite the high incidence rate, the occurrence of delirium is not always identified as such. Knowledge of potential risk factors is important. The aim of the current study is to determine factors associated with the occurrence of a prevalent delirium among elderly patients acutely admitted to an internal medicine ward.

Methods

All consecutive patients of 65 years and over acutely admitted to the Department of Internal Medicine of the Academic Medical Centre, Amsterdam, a university hospital, were asked to participate. The presence of delirium was determined within 48 hrs after admission by an experienced geriatrician.

Results

In total, 126 patients were included, 29% had a prevalent delirium after acute admission. Compared to patients without delirium, patients with delirium were older, more often were cognitively and physically impaired, more often were admitted due to water and electrolyte disturbances, and were less often admitted due to malignancy or gastrointestinal bleeding. Independent risk factors for having a prevalent delirium after acute admission were premorbid cognitive impairment, functional impairment, an elevated urea nitrogen level, and the number of leucocytes.

Conclusions

In this study, the most important independent risk factors for a prevalent delirium after acute admission were cognitive and physical impairment, and a high serum urea nitrogen concentration. These observations might contribute to an earlier identification and treatment of delirium in acutely admitted elderly patients.
Difficulties in assessing cytomegalovirus-associated gastric perforation in an HIV-infected patient
Authors: Mégarbane Bruno , Résière Dabor , Ferrand Jacqueline , Raskine Laurent , Vahedi Kouroche , Baud Frédéric J
Published: April 2005

Background

Active Cytomegalovirus (CMV) infection is a common complication in advanced symptomatic Human Immunodeficiency Virus (HIV) infection. CMV-induced intestinal perforations are hard to diagnose and may be observed throughout the gastrointestinal tract. Isolated stomach perforation is exceptional.

Case presentation

A 47-year-old man was admitted to our intensive care unit with multiorgan failure. Gastrointestinal endoscopic examination showed erythematous gastritis but normal duodenum and colon. CMV blood culture was positive. Histologic examination of a gastric biopsy showed inflammatory infiltrate and immunostaining typical intranuclear CMV inclusion bodies. Concomitant abdominal CT scan disclosed large peripancreatic hypodensities without pneumoperitoneum. The patient died despite supportive therapies and ganciclovir infusion. Postmortem examination showed a 4-cm gastric perforation adhering to the transverse colon and liver, with a thick necrotic inflammatory coating around the pancreas. The whole GI tract, except the stomach, was normal. As other causes, especially Helicobacter pylori infection could be ruled out, a causal relationship between CMV and gastric disease was assumed.

Conclusion

CMV may be responsible for gastric perforations, with difficulties in assessing the diagnosis. Early diagnosis based on cautious endoscopy and histopathologic examination is needed to make a favorable outcome possible.
Validation of multi-stage telephone-based identification of cognitive impairment and dementia
Authors: Crooks Valerie C , Clark Linda , Petitti Diana B , Chui Helena , Chiu Vicki
Published: April 2005

Background

Many types of research on dementia and cognitive impairment require large sample sizes. Detailed in-person assessment using batteries of neuropyschologic testing is expensive. This study evaluates whether a brief telephone cognitive assessment strategy can reliably classify cognitive status when compared to an in-person "gold-standard" clinical assessment.

Methods

The gold standard assessment of cognitive status was conducted at the University of Southern California Alzheimer Disease Research Center (USC ADRC). It involved an examination of patients with a memory complaint by a neurologist or psychiatrist specializing in cognitive disorders and administration of a battery of neuropsychologic tests. The method being evaluated was a multi-staged assessment using the Telephone Interview of Cognitive Status-modified (TICSm) with patients and the Telephone Dementia Questionnaire (TDQ) with a proxy. Elderly male and female patients who had received the gold standard in-person assessment were asked to also undergo the telephone assessment. The unweighted kappa statistic was calculated to compare the gold standard and the multistage telephone assessment methods. Sensitivity for classification with dementia and specificity for classification as normal were also calculated.

Results

Of 50 patients who underwent the gold standard assessment and were referred for telephone assessment, 38 (76%) completed the TICS. The mean age was 78.1 years and 26 (68%) were female. When comparing the gold standard assessment and the telephone method for classifying subjects as having dementia or no dementia, the sensitivity of the telephone method was 0.83 (95% confidence interval 0.36, 1.00), the specificity was 1.00 (95% confidence interval 0.89,1.00). Kappa was 0.89 (95% confidence interval 0.69, 1.000). Considering a gold-standard assessment of age-associated memory impairment as cognitive impairment, the sensitivity of the telephone approach is 0.38 (95% confidence interval 0.09, 0.76) specificity 0.96 (CI 0.45, 0.89) and kappa 0.61 (CI 0.37, 0.85).

Conclusion

Use of a telephone interview to identify people with dementia or cognitive impairment is a promising and relatively inexpensive strategy for identifying potential participants in intervention and clinical research studies and for classifying subjects in epidemiologic studies.
Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents
Authors: Díaz-Montero C Marcela , McIntyre Bradley W
Published: April 2005

Background

Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis) in human osteosarcoma would result in resistance to chemotherapy.

Methods

Osteosarcoma cell lines (SAOS-2 and TE-85) obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI) staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining.

Results

Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended). Moreover, suspended anoikis resistant TE-85 cells (TE-85ar) retained their sensitivity to chemotherapy as well.

Conclusion

Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.
Ultrasound image attributes of human ovarian dominant follicles during natural and oral contraceptive cycles
Authors: Birtch Rebecca L , Baerwald Angela R , Olatunbosun Olufemi A , Pierson Roger A
Published: April 2005

Background

Computer-assisted analyses were used to examine ultrasound image attributes of human dominant ovarian follicles that developed during natural and oral contraceptive (OC) cycles. We hypothesized that image attributes of natural cycle follicles would quantitatively differ from those in OC cycles and that OC cycle follicles would possess image attributes indicative of atresia.

Methods

Dominant ovarian follicles of 18 clinically normal women were compared using transvaginal ultrasonography for the 7 days before ovulation during a natural cycle (n = 9) or the 7 days before peak estradiol in women using OC (n = 11). Follicles were analyzed using region and line techniques designed to compare the image attributes numerical pixel value (NPV), pixel heterogeneity (PH) and area under the curve (AUC).

Results

NPV was higher in OC cycle follicles with region analysis and tended to be higher with line analysis (p = 0.005 and p = 0.06, respectively). No differences were observed in two other image attributes (AUC and PH), measured with either technique, between natural and OC cycle follicles.

Conclusion

The increased NPV value of OC cycle follicles and lack of differences in PH and AUC values between natural cycle and OC cycle follicles did not support the hypothesis that OC cycle follicles would show ultrasonographically detectable signs of atresia. Image attributes observed in OC cycle follicles were not clearly indicative of atresia nor were they large enough to preclude preovulatory physiologic status in OC cycle follicles.
Diets and selected lifestyle practices of self-defined adult vegetarians from a population-based sample suggest they are more 'health conscious'
Authors: Bedford Jennifer L , Barr Susan I
Published: April 2005

Background

Few population-based studies of vegetarians have been published. Thus we compared self-reported vegetarians to non-vegetarians in a representative sample of British Columbia (BC) adults, weighted to reflect the BC population.

Methods

Questionnaires, 24-hr recalls and anthropometric measures were completed during in-person interviews with 1817 community-dwelling residents, 19–84 years, recruited using a population-based health registry. Vegetarian status was self-defined. ANOVA with age as a covariate was used to analyze continuous variables, and chi-square was used for categorical variables. Supplement intakes were compared using the Mann-Whitney test.

Results

Approximately 6% (n = 106) stated that they were vegetarian, and most did not adhere rigidly to a flesh-free diet. Vegetarians were more likely female (71% vs. 49%), single, of low-income status, and tended to be younger. Female vegetarians had lower BMI than non-vegetarians (23.1 ± 0.7 (mean ± SE) vs. 25.7 ± 0.2 kg/m2), and also had lower waist circumference (75.0 ± 1.5 vs. 79.8 ± 0.5 cm). Male vegetarians and non-vegetarians had similar BMI (25.9 ± 0.8 vs. 26.7 ± 0.2 kg/m2) and waist circumference (92.5 ± 2.3 vs. 91.7 ± 0.4 cm). Female vegetarians were more physically active (69% vs. 42% active ≥4/wk) while male vegetarians were more likely to use nutritive supplements (71% vs. 51%). Energy intakes were similar, but vegetarians reported higher % energy as carbohydrate (56% vs. 50%), and lower % protein (men only; 13% vs. 17%) or % fat (women only; 27% vs. 33%). Vegetarians had higher fiber, magnesium and potassium intakes. For several other nutrients, differences by vegetarian status differed by gender. The prevalence of inadequate magnesium intake (% below Estimated Average Requirement) was lower in vegetarians than non-vegetarians (15% vs. 34%). Female vegetarians also had a lower prevalence of inadequate thiamin, folate, vitamin B6 and C intakes. Vegetarians were more likely than non-vegetarians to consider various health conditions and food/nutrition concerns when choosing foods.

Conclusion

In this population-based study, evidence was obtained to indicate that vegetarians appear more 'health conscious' than non-vegetarians, although specific differences were not always consistent by gender. Additional population-based studies are required to determine if the observed gender differences exist in other populations.