bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes and pregnancy: women’s opinions about the care provided during the childbearing year
Authors: Anderberg Eva , Berntorp Kerstin , Crang‐Svalenius Elizabeth 
Published: January 2009

Background:  The extended programmes for pregnant women with diabetes, needed to improve pregnancy outcome, might negatively influence the experience of expecting a baby.Aim:  To investigate opinions about care during pregnancy, childbirth and the postnatal period among women with diabetes mellitus (DM) and gestational DM (GDM).Method:  A four‐part questionnaire was constructed, covering the childbearing year, with a focus on treatment and information. A total of 156 women were asked to participate (53 DM, 103 GDM), three refused. The questionnaire was anonymous.Results:  The reply frequency was 94%. Of all answers, 95% fell in neutral‐satisfied range (Lickert scale 2–5). Three answering patterns deviated positively (care on Specialist Antenatal Clinic, accessibility, and participation–responsibility–respect). Four patterns deviated negatively (information flow, preparation, postpartum care and postpartum check‐up). Increased supervision caused problems with time for the family and at work. Comments showed focus on diabetes, forcing the healthy pregnancy aspects into the background. The answers concerning treatment indicated satisfaction (4 + 5 Lickert scale). Women with GDM felt badly prepared before the glucose tolerance test. It was doubtful whether they had been able to make an informed choice about participating. Lack of knowledge among staff was pointed out. Need for more written material was expressed.Conclusion:  Satisfaction with care was shown. A discussion about the implication of informed choice with both staff and mothers are needed. Sharper implementation of the diabetes‐care‐chain was also an area for improvement.
The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC
Authors: Liptrott NJ , Penny M , Bray PG , Sathish J , Khoo SH , Back DJ , Owen A 
Published: January 2009

Mandarin translation of abstractBackground and purpose:  The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on the expression of CYPs, transporters and chemokine receptors in PBMC.Experimental approach:  Human PBMC were incubated with cytokines for 48 h. ATP‐binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5 expression were measured by quantitative polymerase chain reaction and flow cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent probes.Key results:  We show here functional activity of CYP3A4 and CYP2B6 in PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein expression of all proteins. For example, interleukin‐2 (IL‐2) had a marked impact on ABCB1 mRNA (% control 4745 ± 11961) and protein (% control 200 ± 57). Increases in drug efflux transporter expression, in response to cytokines, resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for IL‐2 and interferon‐γ (IFNγ) respectively] and saquinavir (decrease of 28% and 30% for IL‐2 and IFNγ respectively). The degree to which drug transporter and chemokine receptor expression changed in response to cytokines was positively correlated (e.g. ABCB1 and CXCR4, r2 = 0.545).Conclusions and implications:  These data have important implications for diseases in which cytokines are dysregulated and for which pharmacological intervention targets immune cells. Mandarin translation of abstract
BGC20‐1531, a novel, potent and selective prostanoid EP4receptor antagonist: a putative new treatment for migraine headache
Authors: Maubach KA , Davis RJ , Clark DE , Fenton G , Lockey PM , Clark KL , Oxford AW , Hagan RM , Routledge C , Coleman RA 
Published: January 2009

Background and purpose: Prostanoid EP4receptor antagonists may have therapeutic utility in the treatment of migraine since EP4receptors have been shown to be involved in prostaglandin (PG)E2‐induced cerebral vascular dilatation, which may be an important contributor to migraine pain. This study reports the pharmacological characterization of BGC20‐1531, a novel EP4receptor antagonist.Experimental approach: BGC20‐1531 was characterized in radioligand binding andin vitrofunctional assays employing recombinant and native EP4receptors. Changes in canine carotid haemodynamics were used to assess the pharmacodynamic profile of BGC20‐1531in vivo.Key results: BGC20‐1531 exhibited high affinity at recombinant human EP4receptors expressed in cell lines (pKB7.6) and native EP4receptors in human cerebral and meningeal artery (pKB7.6–7.8) but showed no appreciable affinity at a wide range of other receptors (including other prostanoid receptors), channels, transporters and enzymes (pKi < 5). BGC20‐1531 competitively antagonized PGE2‐induced vasodilatation of human middle cerebral (pKB7.8) and meningeal (pKB7.6) arteriesin vitro, but had no effect on responses induced by PGE2on coronary, pulmonary or renal arteriesin vitro. BGC20‐1531 (1–10 mg·kg−1i.v.) caused a dose‐dependent antagonism of the PGE2‐induced increase in canine carotid blood flowin vivo.Conclusions and implications: BGC20‐1531 is a potent and selective antagonist at EP4receptorsin vitroandin vivo, with the potential to alleviate the symptoms of migraine that result from cerebral vasodilatation. BGC20‐1531 is currently in clinical development for the treatment of migraine headache.
Discovery of the hepatitis C virus
Authors: Houghton Michael 
Published: January 2009

AbstractAfter nearly 6 years of intensive investigations between 1982 and 1988 in my laboratory at Chiron corporation, in which numerous molecular biological methods were used to investigate the viral aetiology of parenterally transmitted non‐A, non‐B viral hepatitis (NANBH), a single cDNA clone (5‐1‐1) was isolated that was shown to be derived from a new flavi‐like virus, termed the hepatitis C virus (HCV). After screening hundreds of millions of bacterial cDNA clones derived from different liver and plasma samples obtained from experimentally infected chimpanzees, a single HCV clone was eventually isolated using a novel, blind immunoscreening method in which antibodies derived from a clinically diagnosed NANBH patient were used to identify a cDNA clone encoding an immunodominant epitope within HCV nonstructural protein 4. Its viral origin was demonstrated by its specific hybridization to a large single‐stranded RNA molecule of ∼10 000 nucleotides found only in NANBH‐infected samples that shared distant sequence identity with flaviviruses. Further, HCV clone 5‐1‐1 was shown to be extrachromosomal and to encode an antigen eliciting antibody seroconversion only in NANBH‐infected chimpanzees and humans. Subsequent work demonstrated that HCV was the principal cause of parenterally transmitted NANBH around the world, with an estimated 170 million global carriers and that blood screening tests detecting circulating HCV antibodies and viral RNA could effectively eradicate the transmission of transfusion‐associated NANBH. Key viral‐encoded enzymes essential to its life cycle are now the targets of vigorous, ongoing drug development activities, and the feasibility of successful vaccination strategies has been demonstrated using the valuable chimpanzee model, without which any progress on HCV would not have been possible. My colleagues and coworkers who made essential contributions to the discovery of HCV were George Kuo, who had his own laboratory at Chiron and who provided intellectual and practical input, Dan Bradley of the Centers for Disease Control and Prevention, who provided a large supply of well‐characterized chimpanzee samples and knowledge of the NANBH field, and Qui‐Lim Choo, in my own laboratory, who provided many years of outstandingly dedicated and precise molecular biology expertise.
HBeAg‐negative chronic hepatitis B: why do I treat my patients with nucleos(t)ide analogues
Authors: Lampertico Pietro , Colombo Massimo 
Published: January 2009

AbstractAntiviral therapy is aimed to persistently suppress hepatitis B virus (HBV) to prevent liver complications and improve survival and long‐term administration of nucleos(t)ide analogues represents an attractive treatment strategy.Five oral analogues are available, and all inhibit viral replication in most patients during the first year of therapy. By converse, long‐term monotherapy is associated to high rates of resistance with lamivudine, and intermediate rates with Adefovir and Telbivudine. Third‐generation analogues such as Entecavir and Tenofovir may efficiently inhibits viral replication in most patient for many years as they couple potency and high genetic barrier. In patients developing drug‐resistance, specific rescue protocols based upon ‘early add‐on’ have been developed to rapidly and efficiently control viral replication. In cirrhotics, long‐term effective analog‐based therapy prevented clinical decompensation for many years, but not liver cancer development. Long‐term administration of NUCs, either as a monotherapy or as a sequential combination, inhibits HBV replication in most HBeAg‐negative patients for at least 5 years, preventing clinical decompensation in cirrhotics.
Hepatitis B and pregnancy: an underestimated issue
Authors: Jonas Maureen M. 
Published: January 2009

AbstractHepatitis B infection during pregnancy presents a unique set of management issues. Aspects of care that must be considered include maternal and fetal effects of hepatitis B, effects of pregnancy itself on the course of hepatitis B infection and its complications, treatment of hepatitis B during pregnancy and prevention of perinatal infection. There are insufficient studies to date regarding these concerns; most are from the Far East, and many have important limitations, but some have yielded valuable data. Pregnant women with acute hepatitis B virus (HBV) infection typically have a course not very different from that in the general adult population, but the risk of transmission of HBV to neonates increases the later in gestation the acute infection occurs. Chronic HBV infection is usually mild in pregnant women, but may flare shortly after delivery. The risk of perinatal transmission is highest in women with high levels of viraemia; this may be a factor in the small but reproducible failure rate of current immunoprophylaxis strategies. Obstetrical policies must be assessed with respect to detection of maternal infection and liver disease, as well as with respect to perinatal transmission risk. In addition to the usual issues of drug efficacy and safety in the affected individuals, effects on the developing fetus must be considered. This paper reviews the current experience in each of these areas, and highlights the need for further investigation into this critical but often underestimated topic.
The global burden of hepatitis C
Authors: Lavanchy Daniel 
Published: January 2009

AbstractHepatitis C is of concern both to industrialized and developing countries. Preliminary unpublished estimates of the global burden of disease (GBD) attributable to HCV‐related chronic liver disease seem to be substantial. Therefore, the reduction of global mortality and morbidity related to chronic hepatitis C should be a concern to public health authorities, and primary, secondary and tertiary prevention activities should be implemented and monitored in each country, with precise targets set to be reached. In order to decide on national health policies, there is a need to estimate the burden of disease, globally, regionally and nationally. To evaluate the GBD, three components have to be assessed: 1) The global, regional and national burden of morbidity and mortality associated with HCV infection, based on prevalence, incidence, transmission and economics; 2) The natural history of HCV infection, including ‘healthy individuals’; and 3) The areas for which more research is needed. A working group was created to assist the World Health organization (WHO) in estimating the GBD associated with HCV infection.
Management and prevention of drug resistance in chronic hepatitis B
Authors: Zoulim Fabien , Durantel David , Deny Paul 
Published: January 2009

AbstractThe management of hepatitis B virus resistance to antivirals has evolved rapidly in recent years. The definition of resistance is now well established, with the importance of partial response and the improvement of assays to detect genotypic resistance and virological breakthrough. Data on phenotypic resistance have allowed to define the cross‐resistance profile for the main resistant mutants, providing a rationale for treatment adaptation. Clinical studies have shown that an early treatment intervention in case of a virological breakthrough or a partial response with the addition of a second drug having a complementary cross‐resistance profile allows one to maintain the majority of patients in clinical remission. The prevention of resistance should rely on the use of the most potent antivirals with a high genetic barrier to resistance as a first‐line therapy. The future perspectives are to design strategies to hasten the HBsAg clearance, which should become a new treatment endpoint, to prevent drug resistance and to decrease the incidence of complications of chronic hepatitis B.
Hepatitis B and hepatitis C in 2009
Authors: Marcellin Patrick 
Published: January 2009

AbstractHepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most frequent viral infections in humans, and represent a major global public health problem. HBV‐ and HCV‐related chronic hepatitis are the main causes of cirrhosis and hepatocellular carcinoma (HCC) that are responsible for a high rate of morbidity and mortality. End‐stage HBV‐ and HCV‐related liver disease and HCC are the main causes of liver transplantation. In the last few years, knowledge of the epidemiology and the natural history of HBV and HCV infection has markedly improved. Furthermore, considerable progress has been made in the efficacy of therapy. New drugs and new therapeutic strategies that are currently under evaluation could further improve the efficacy of therapy in the near future.
Visual fields at school‐age in children treated with vigabatrin in infancy
Authors: Gaily Eija , Jonsson Henna , Lappi Marjatta 
Published: January 2009

SummaryPurpose:  The use of vigabatrin (VGB) as an antiepileptic drug (AED) has been limited by evidence showing that it causes vigabatrin‐attributed visual field loss (VAVFL) in at least 20–40% of patients exposed at school age or later. VGB is an effective drug for infantile spasms, but there are no reports on later visual field testing after such treatment. Our aim was to investigate the risk of VAVFL in school‐age children who had received VGB in infancy.Methods:  Visual fields of 16 children treated with VGB for infantile spasms were examined by Goldmann kinetic perimetry at age 6–12 years. Normal fields were defined as the temporal meridian extending to more than 70°, and mild VAVFL between 50 and 70°. Abnormal findings were always confirmed by repeating the test. Exposure data were collected from hospital charts.Results:  Vigabatrin was started at a mean age of 7.6 (range, 3.2–20.3) months. The mean duration of therapy was 21.0 (9.3–29.8) months and cumulative dose 655 g (209–1,109 g). Eight children were never treated with other AEDs, five received only adrenocorticotropic hormone (ACTH) in addition to VGB, and three children had been treated with other AEDs. Fifteen children had normal visual fields. Mild VAVFL was observed in one child (6%) who had been treated with VGB for 19 months and who received a cumulative dose of 572 g.Conclusions:  The risk of VAVFL may be lower in children who are treated with VGB in infancy compared to patients who receive VGB at a later age.
Glutamine induces epileptiform discharges in superficial layers of the medial entorhinal cortex from pilocarpine‐treated chronic epileptic rats in vitro
Authors: Sandow Nora , Zahn Robert K. , Gabriel Siegrun , Heinemann Uwe , Lehmann Thomas‐Nicolas 
Published: January 2009

SummaryPurpose:  Glutamine (GLN) is a precursor for synthesis of glutamate and γ‐aminobutyric acid (GABA) and has been found in the cerebrospinal fluid (CSF) at mean concentrations of 0.6 mM. Experiments on slices are usually performed in artificial CSF (aCSF) kept free of amino acids. Therefore, the role of glutamine, particularly in tissue of epileptic animals, remains elusive.Methods:  Using extracellular recordings we studied effects of GLN on field potentials and stimulus‐evoked field responses in the medial entorhinal cortex (MEC) of combined entorhinal cortex hippocampal slices from pilocarpine‐treated chronic epileptic rats and age‐matched saline‐injected control rats.Results:  In presence of GLN (0.5 and 2 mM) recurrent epileptiform discharges (REDs) were observed in slices from epileptic rats (64% and 80%, respectively), but not in slices from control rats. REDs were restricted to the superficial MEC, suppressed by the α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazol‐propionate (AMPA)/kainate receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (30 μM), attenuated by the inhibitor of neuronal glutamine transporters methylamino‐isobutyric acid (10 mM), and apparently augmented and prolonged by the GABAA receptor antagonist bicuculline‐methiodide (5 μM). In contrast, amplitudes of stimulus evoked nonsynaptic and synaptic field responses increased in slices from control rats (+23% and +12% of the reference values) and insignificantly less or not in those of epileptic rats (+6.5% and −0.25%, respectively). Notably, stimulus‐evoked slow negative transients confined to slices of epileptic animals were reduced in amplitude (−18%).Discussion:  In combined entorhinal hippocampal slices from chronic epileptic animals, GLN induces glutamatergic REDs via neuronal uptake in superficial layers of the MEC where inhibitory function seemed to be partially preserved.
Oral automatisms induced by stimulation of the mesial frontal cortex
Authors: Unnwongse Kanjana , Lachhwani Deepak , Tang‐Wai Richard , Matley Kirk , O’Connor Timothy , Nair Dileep , Bingaman William , Wyllie Elaine , Diehl Beate 
Published: January 2009

SummaryExtraoperative electrical stimulation is frequently used to identify eloquent areas in patients with pharmacoresistant epilepsy who undergo subdural grid evaluation for epilepsy surgery. Oral automatisms elicited by cortical stimulation have been described in the mesial temporal lobe, but also in the mesial frontal lobe, particularly the cingulate gyrus. However oral automatisms attributed to stimulation in the superior frontal gyrus without afterdischarges have never been reported. Herein we present two patients with right frontal lobe epilepsy with oral automatisms induced by electrical stimulation of the right mesial superior frontal gyrus.
A substantial number of Rasmussen syndrome patients have increased IgG, CD4+ T cells, TNFα, and Granzyme B in CSF
Authors: Takahashi Yukitoshi , Mine Jyun , Kubota Yuko , Yamazaki Etsuko , Fujiwara Tateki 
Published: January 2009

SummaryPurpose:  We studied the immunologic molecules in cerebrospinal fluid (CSF) and discussed their evolutional changes in pediatric patients with Rasmussen syndrome (RS).Methods:  CSF samples collected from 27 patients with RS (average onset age, 7.5 ± 5.6 years) were studied. Cell count, protein, glucose, albumin, chloride, and immunoglobulin G (IgG) levels were measured by conventional methods. Surface markers of lymphocytes in CSF were examined by a cell sorter. Granzyme B, interferon γ (IFNγ), interleukin 4 (IL‐4), tumor necrosis factor α (TNFα), and IL‐12 in CSF were quantitated by enzyme‐linked immunosorbent assay (ELISA). Autoantibodies against GluR ε2 (NR2B) were examined by immunoblot.Results:  The data of the first CSF examination showed that IgG levels (Mann‐Whitney U test, p < 0.01), CD4+ T cells (p = 0.02), TNFα levels (p < 0.01), and Granzyme B levels (p < 0.01) were elevated compared with disease controls. White blood cell count, IFNγ level, IL‐12 level, and Granzyme B level were elevated, especially in the early stage of disease. CD4+ T cells, CD8+ cells, CD3+ T cells, IgG levels, and TNFα levels were elevated at all stages of disease evolution. Protein levels and albumin levels were elevated in the progressed stage. Autoantibodies against GluR ε2 (NR2B) (IgG) were found in 50% of patients in the early stage, and the positive rate was low at the progressed stage.Discussion:  The present findings suggest that complex pathophysiologic mechanisms involving CD4+ T cells and CD8+ T cells change evolutionally during the progression of RS. A crucial cytotoxic process occurs in the early stage, and declines in the progressed stage.
Facial emotion recognition impairment in chronic temporal lobe epilepsy
Authors: Meletti Stefano , Benuzzi Francesca , Cantalupo Gaetano , Rubboli Guido , Tassinari Carlo Alberto , Nichelli Paolo 
Published: January 2009

SummaryPurpose:  To evaluate facial emotion recognition (FER) in a cohort of 176 patients with chronic temporal lobe epilepsy (TLE).Methods:  FER was tested by matching facial expressions with the verbal labels for the following basic emotions: happiness, sadness, fear, disgust, and anger. Emotion recognition performances were analyzed in medial (n = 140) and lateral (n = 36) TLE groups. Fifty healthy subjects served as controls. The clinical and neuroradiologic variables potentially affecting the ability to recognize facial expressions were taken into account.Results:  The medial TLE (MTLE) group showed impaired FER (86% correct recognition) compared to both the lateral TLE patients (FER = 93.5%) and the controls (FER = 96.4%), with 42% of MTLE patients recording rates of FER that were lower [by at least 2 standard deviations (SDs)] than the control mean. The MTLE group was impaired compared to the healthy controls in the recognition of all basic facial expressions except happiness. The patients with bilateral MTLE were the most severely impaired, followed by the right and then the left MTLE patients. FER was not affected by type of lesion, number of antiepileptic drugs (AEDs), aura semiology, or gender. Conversely, the early onset of seizures/epilepsy was related to FER deficits. These deficits were already established in young adulthood, with no evidence of progression in older MTLE patients.Conclusion:  These results on a large cohort of TLE patients demonstrate that emotion recognition deficits are common in MTLE patients and widespread across negative emotions. We confirm that early onset seizures with right or bilateral medial temporal dysfunction lead to severe deficits in recognizing facial expressions of emotions.