bluuebunny/crossref_metadata_2025 huggingface dataset:
Bevacizumab reverses need for liver transplantation in hereditary hemorrhagic telangiectasia
Authors: Mitchell Andrew , Adams Leon A. , MacQuillan Gerry , Tibballs Jon , vanden Driesen Rohan , Delriviere Luc
Published: January 2008

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by mucocutaneous and visceral telangiectasia. Hepatic involvement with vascular malformations may lead to portal hypertension, biliary ischemia, and high-output cardiac failure. Liver transplantation is indicated for life-threatening disease but carries significant risk from surgery and chronic immunosuppression. We report a case of a 47-year-old woman with HHT successfully treated with the vascular endothelial growth factor (VEGF) antibody bevacizumab. The patient was referred for consideration of liver transplantation because of hepatic HHT leading to high-output cardiac failure, diuretic resistant ascites, cholestasis, and malnutrition. As she was considered a high-risk candidate for transplantation, she underwent 6 courses of bevacizumab (5 mg/kg) over 12 weeks. A dramatic improvement in her clinical state was observed after 3 months with reversal of cholestasis, resolution of cardiac failure and ascites, and improvement in nutritional status with a 10% dry weight increase. Treatment induced a marked reduction in liver vascularity and halving of her liver volume from 4807 to 2269 mL over 6 months. This was associated with normalization of her cardiac output from 10.2 to 5.1 L/minute. Correspondingly, she ceased diuretic medications, returned to full-time work, and was delisted as a transplant candidate. She remains well 6 months after completing treatment. In conclusion, antagonism of VEGF receptors led to a dramatic regression of hepatic vascular malformations and reversal of high-output cardiac failure and complications of portal hypertension in this patient with HHT. Bevacizumab may potentially alleviate the need for liver transplantation in this group of patients. Liver Transpl 14:210–213. 2008. © 2008 AASLD.
Proton‐Conducting Properties of Acid‐Doped Poly(glycidyl methacrylate)‐1,2,4‐Triazole Systems
Authors: Çelik Sevim Ünügür , Akbey Ümit , Bozkurt Ayhan , Graf Robert , Spiess Hans W.
Published: January 2008

1,2,4‐triazole‐functional PGMA polymers have been synthesized and their anhydrous proton‐conducting properties were investigated after doping with phosphoric acid and triflic acid. PGMA was prepared by solution polymerization and then modified with 1H‐1,2,4‐triazole (Tri) and 3‐amino‐1,2,4‐triazole (ATri). FT‐IR, 13C NMR and elemental analysis verify the high immobilization of the triazoles in the polymer chain. Phosphoric‐acid‐doped polymers showed lower Tg and higher proton conductivities. PGMA‐Tri 4 H3PO4 showed a maximum water‐free proton conductivity of approximately 10−2 S · cm−1 while that of PGMA‐ATri 2 H3PO4 was 10−3 S · cm−1. The structure and dynamics of the polymers were explored by 1H MAS and 13C CP‐MAS solid‐state NMR.

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Separation properties in neighbourhood and quasi‐apartness spaces
Authors: Havea Robin , Ishihara Hajime , Vîţă Luminiţa
Published: January 2008

We investigate separation properties for neighbourhood spaces in some details within a framework of constructive mathematics, and define corresponding separation properties for quasi‐apartness spaces. We also deal with separation properties for spaces with inequality. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A localic theory of lower and upper integrals
Authors: Vickers Steven
Published: January 2008

An account of lower and upper integration is given. It is constructive in the sense of geometric logic. If the integrand takes its values in the non‐negative lower reals, then its lower integral with respect to a valuation is a lower real. If the integrand takes its values in the non‐negative upper reals, then its upper integral with respect to a covaluation and with domain of integration bounded by a compact subspace is an upper real. Spaces of valuations and of covaluations are defined.

Riemann and Choquet integrals can be calculated in terms of these lower and upper integrals. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The natural numbers in constructive set theory
Authors: Rathjen Michael
Published: January 2008

Constructive set theory started with Myhill's seminal 1975 article [8]. This paper will be concerned with axiomatizations of the natural numbers in constructive set theory discerned in [3], clarifying the deductive relationships between these axiomatizations and the strength of various weak constructive set theories. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
1H–1H scalar coupling across two stacked aromatic rings: DFT calculations and experimental proof
Authors: Bifulco Giuseppe , Mangoni Alfonso
Published: January 2008

1H–1H scalar coupling across two stacked (parallel and eclipsed) aromatic rings has been revealed through the 1D and 2D 1H NMR analysis of a [2,2]paracyclophane and rationalized by means of density functional theory (DFT) calculation of the J values. Copyright © 2008 John Wiley & Sons, Ltd.
1H and 13C NMR data of benzylsulfonic acids—model compounds for lignosulfonate
Authors: Lutnaes Bjart F. , Myrvold Bernt O. , Lauten Rolf A. , Endeshaw Molla M.
Published: January 2008

Although there has been a major progress in the analysis of native lignin using NMR in the recent years, not much attention has been paid to lignosulfonates. Lignosulfonates are more difficult to analyse because of solubility issues and a more complex structure owing to chemical modification during the pulping process. A large database of NMR data is available for the building blocks of native lignin, but no data are available for the corresponding sulfonated compounds. We have prepared 15 monomeric and seven dimeric sulfonated model compounds characterised by NMR. These include models for end groups, as well as β‐β, β‐5, 5‐5 and β‐O‐5 linkages in lignosulfonates, and will be important for further structural investigation on lignosulfonate. Copyright © 2008 John Wiley & Sons, Ltd.
Drug‐screening platform based on the contractility of tissue‐engineered muscle
Authors: Vandenburgh Herman , Shansky Janet , Benesch‐Lee Frank , Barbata Victoria , Reid Jonathan , Thorrez Lieven , Valentini Robert , Crawford Gregory
Published: January 2008

A tissue‐based approach to in vitro drug screening allows for determination of the cumulative positive and negative effects of a drug at the tissue rather than the cellular or subcellular level. Skeletal muscle myoblasts were tissue‐engineered into three‐dimensional muscle with parallel myofibers generating directed forces. When grown attached to two flexible microposts (μposts) acting as artificial tendons in a 96‐well plate format, the miniature bioartificial muscles (mBAMs) generated tetanic (active) forces upon electrical stimulation measured with a novel image‐based motion detection system. mBAM myofiber hypertrophy and active force increased in response to insulin‐like growth factor 1. In contrast, mBAM deterioration and weakness was observed with a cholesterol‐lowering statin. The results described in this study demonstrate the integration of tissue engineering and biomechanical testing into a single platform for the screening of compounds affecting muscle strength. Muscle Nerve, 2007
Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: Frequency, extent, and specificity
Authors: Kuwabara Satoshi , Sonoo Masahiro , Komori Tetsuo , Shimizu Toshio , Hirashima Fumiko , Inaba Akira , Misawa Sonoko , Hatanaka Yuki ,   Tokyo Metropolitan Neuromuscular Electrodiagnosis Study Group
Published: January 2008

Previous studies suggest that in amyotrophic lateral sclerosis (ALS) the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) are more severely involved than abductor digiti minimi (ADM). To elucidate the pattern, frequency, extent, and specificity of such dissociated muscle atrophy in ALS, compound muscle action potentials recorded from APB, FDI, and ADM were analyzed in 77 ALS patients, 171 normal controls, and 196 disease controls. Compared with normal controls, ALS patients had a reduced APB/ADM amplitude ratio (P < 0.001) and FDI/ADM ratio (P < 0.001), whereas patients with other anterior horn diseases showed similar APB/ADM and FDI/ADM ratios to normal values. Decreased APB/ADM ratio was found in 41% of ALS patients, 5% of normal controls, and 4% of disease controls. Prominent muscle atrophy in APB and FDI, with relatively preserved ADM, appears to be specific to ALS. Dissociated hand muscle atrophy presumably reflects part of the pathophysiology and supports the diagnosis of ALS. Muscle Nerve, 2008
Antibodies to myelin‐associated glycoprotein (anti‐Mag) in IgM amyloidosis may influence expression of neuropathy in rare patients
Authors: Garces‐Sanchez Mercedes , Dyck Peter J. , Kyle Robert A. , Zeldenrust Steven , Wu Yanhong , Ladha Shafeeq S. , Klein Christopher J.
Published: January 2008

We have examined whether antibodies to myelin‐associated glycoprotein (anti‐MAG) influence neuropathy occurrence and phenotype in primary (AL IgM) amyloidosis. Anti‐MAG and the cross‐reacted sulfoglucuronyl paragloboside antibodies (SGPG) were studied in 46 patients with IgM amyloidosis (21 with polyneuropathy), and 21 matched IgM MGUS (monoclonal gammopathies of undetermined significance) controls without neuropathy. We assessed the occurrence, phenotype of neuropathy, and attributes of nerve conduction and their relation to antibody activity. Twenty of 46 patients with IgM amyloidosis (7 with and 13 without polyneuropathy) had elevation of anti‐MAG or SGPG by enzyme‐linked immunosorbent assay (ELISA). Two of the polyneuropathy patients with IgM amyloidosis had antibodies to MAG based on Western blot (WB) positivity. One of these patients, with the highest anti‐MAG titer, had a painful sensory ataxia, with prominent demyelination, and amyloid deposition in sural nerve. The other anti‐MAG WB‐positive amyloid patient had an axonal neuropathy and dysautonomia. Low levels of anti‐MAG antibodies were found in 12 of 21 IgM MGUS controls without neuropathy (mean follow‐up, 11 years). We conclude that finding serum anti‐MAG antibodies does not exclude the diagnosis of primary amyloidosis. They do not appear to affect the occurrence or expression of polyneuropathy, except possibly in occasional cases with WB positivity. Muscle Nerve, 2007
Stimulus pulse‐width influences H‐reflex recruitment but not Hmax/Mmax ratio
Authors: Lagerquist Olle , Collins David F.
Published: January 2008

It has been proposed that pulse‐widths of 0.5–1.0 ms should be used to evoke H‐reflexes in humans; however, the influence of pulse‐width on H‐reflex recruitment over a range of stimulus intensities has not been well characterized. We constructed soleus H‐reflex vs. M‐wave recruitment curves using 50, 200, 500, and 1000 μs pulses in 12 subjects. In contrast to previous findings, changing the pulse‐width did not significantly alter maximal H‐reflex (Hmax) or M‐wave (Mmax) amplitudes or Hmax/Mmax ratios. In fact, the 1000 μs pulses resulted in larger H‐reflexes when the M‐wave was 5% Mmax; smaller M‐waves at Hmax; and lower H‐reflex thresholds compared with 50 μs pulses. These differences reflect a leftward shift in the H‐reflex vs. M‐wave recruitment curve when using wide vs. narrow pulses and, combined with no change in the Hmax/Mmax ratios, suggest that factors other than antidromic collision in motor axons limit Hmax. These results support the idea that 1000 μs pulses should be used to evoke H‐reflexes and suggest that wider pulses may be beneficial to generate contractions with a greater reflex contribution when using neuromuscular stimulation for rehabilitation. Muscle Nerve, 2007
Inclusion body myositis functional rating scale: A reliable and valid measure of disease severity
Authors: Jackson C.E. , Barohn R.J. , Gronseth G. , Pandya S. , Herbelin L. ,   The Muscle Study Group (MSG)
Published: January 2008

We developed a disease‐specific, 10‐point functional rating scale for patients with inclusion body myositis (IBMFRS). The IBMFRS was utilized as a secondary outcome measure in a multicenter pilot trial of the clinical safety and tolerability of high‐dose beta interferon‐1a. In this trial, 28 IBM patients completed the IBMFRS at baseline and monthly for 6 months. The IBMFRS showed statistically significant correlations (P < 0.001) with maximal voluntary isometric contraction, manual muscle testing, handgrip dynamometry, and the amyotrophic lateral sclerosis (ALS) functional rating scale (ALSPRS). Compared to these other outcome measures, the IBMFRS was also the most sensitive measure of change over the course of the study. Muscle Nerve, 2008
Reliability of quantifying foot and ankle muscle strength in very young children
Authors: Rose Kristy J. , Burns Joshua , Ryan Monique M. , Ouvrier Robert A. , North Kathryn N.
Published: January 2008

Preschool‐age children with neuromuscular disorders are often excluded from clinical trials due to the lack of reliable and objective strength measures. We evaluated the reliability of measuring foot and ankle muscle strength in 60 healthy children age 2–4 years. The strength of foot inversion and eversion, ankle plantarflexion, and dorsiflexion was measured using a hand‐held dynamometer. Intrarater and interrater reliability of two assessors was determined for each muscle group using intraclass correlation coefficients (ICCs), 95% confidence intervals (CIs), and standard error of measurement (SEM). For all muscle groups intrarater (ICC2,2 = 0.85‐0.94, 95% CI = 0.75–0.96, SEM = 1.5–4.7 N) and interrater (ICC2,1 = 0.88–0.96, 95% CI = 0.81–0.98, SEM = 1.2–4.6 N) reliability was high for all children. As expected, reliability was generally highest in 3‐ and 4‐year‐old children and lowest in 2‐year‐old children. Hand‐held dynamometry can reliably measure foot and ankle strength in very young children and may help aid in diagnosis and in characterizing disease progression in disorders affecting the foot and ankle. Muscle Nerve, 2008
Gene and protein expression associated with protein synthesis and breakdown in paraplegic skeletal muscle
Authors: Drummond Micah J. , Glynn Erin L. , Lujan Heidi L. , Dicarlo Stephen E. , Rasmussen Blake B.
Published: January 2008

Spinal cord injury reduces the rate of skeletal muscle protein synthesis and increases protein breakdown, resulting in rapid muscle loss. The purpose of this study was to determine whether long‐term paraplegia would eventually result in a downregulation of muscle mRNA and protein expression associated with both protein synthesis and breakdown. After 10 weeks of spinal cord transection, soleus muscle from 12 rats (6 sham‐control, 6 paraplegic) was studied for mRNAs and proteins associated with protein synthesis and breakdown using real‐time polymerase chain reaction and immunoblotting techniques. Protein kinase B (PKB/Akt), ribosomal S6 kinase 1 (S6K1), and myogenin mRNA were downregulated, whereas muscle ring finger 1 (MuRF1) and phospho‐forkhead transcription factor 4 (FoxO4) protein were increased in paraplegic rats. We conclude that gene and protein expression of pathways associated with protein synthesis are reduced, whereas some markers of protein breakdown remain elevated following chronic paraplegia. Clinical interventions designed to increase muscle protein synthesis may be helpful in preventing excessive muscle loss during long‐term paraplegia. Muscle Nerve, 2008
An FPTAS for a supply scheduling problem with non‐monotone cost functions
Authors: Ng Chi To , Kovalyov Mikhail Yakovlevich , Cheng Tai Chiu Edwin
Published: January 2008

Chauhan et al. Oper Res Lett 33 (2005), 249–254 presented a fully polynomial time approximation scheme (FPTAS) for a supply scheduling problem, which is to minimize a total cost associated with the sizes of deliveries from several providers to one manufacturer. The cost functions are assumed non‐decreasing and their arguments are assumed continuously divisible. In this note, we give a motivation for considering the case of non‐monotone cost functions with continuously divisible or discrete arguments. For this more general case, we suggest a modification of the FPTAS in [Chauhan et al., Oper Res Lett 33 (2005), 249–254]. We also suggest a different FPTAS to handle concave cost functions. © 2008 Wiley Periodicals, Inc. Naval Research Logistics, 2008
Analysis of ellagic acid in pomegranate rinds by capillary electrophoresis and high‐performance liquid chromatography
Authors: Zhou Benhong , Wu Zhenhua , Li Xiaojun , Zhang Jie , Hu Xianming
Published: January 2008

Two novel methods for the analysis of ellagic acid in pomegranate (Punica granatum) rinds are proposed. Capillary electrophoresis (CE) was performed in a bare fused‐silica capillary using a buffer solution of tri(hydroxymethyl)aminomethane:potassium dihydrogen phosphate (pH 8.4) with an applied voltage of 20 kV and UV detection at 254 nm. HPLC analysis was performed with a Zobax SB C18 column and a mobile phase consisting of methanol:ethyl acetate:potassium dihydrogen phosphate: phosphoric acid at a flow rate of 1.0 mL/min. Under optimised conditions, the HPLC retention and the CE migration times for ellagic acid were 10.32 and 12.23 min, respectively. Calibration curves of peak area vs. concentration gave correlation coefficients of 0.9999 for HPLC and 0.9990 for CE. The detection limits for HPLC and CE were 2.8 and 2.2 µg/mL, respectively. Average recoveries were 98.32 ± 1.2% for HPLC and 96.52 ± 2.8% for CE. Both methods were shown to be suitable for the determination of ellagic acid in pomegranate rinds extraction; however, the CE method required less solvent and gave better column efficiency, whilst the HPLC provided superior precision. Copyright © 2008 John Wiley & Sons, Ltd.
Birth after pre‐implantation genetic diagnosis (PGD) of spinocerebellar ataxia 2 (Sca2)
Authors: Moutou Céline , Nicod Jean‐Christophe , Gardes Nathalie , Viville Stéphane
Published: January 2008

Background

Spinocerebellar ataxia 2 (SCA2) is an autosomal‐dominant neurodegenerative disease caused by an extended polyglutamine sequence in the ATXN2 protein. We describe the development of a new single‐cell multiplex PCR protocol for pre‐implantation genetic diagnosis (PGD) of SCA2 and its successful clinical application.

Methods

Three duplex tests have been developed, one, which combines the detection of the CAG repeats in addition to the D12S821 microsatellite, another, the amplification of the CAG repeats and the D12S1333 microsatellite and the last, the combination of both microsatellites D12S821 and D12S1333.

Results

PCR conditions were established using 226 single lymphoblasts or patient lymphocysts. Amplification was obtained in an average of 99.6%, a complete genotype in 86%, a conclusive result in 96% and an allelic drop‐out (ADO) rate of 10.7% was observed. PGD for SCA2 was performed for a couple with a paternal risk of transmitting the pathology. Two cycles were done from which 18 embryos were biopsied, 8 were diagnosed as unaffected, 9 as affected and 1 gave no results. In both cycles 2 embryos were transferred, with no pregnancy at the first attempt, and a twin pregnancy at the second attempt. The patient delivered one girl and one boy at 36 weeks and 3 days. Copyright © 2008 John Wiley & Sons, Ltd.
Outcome following prenatal diagnosis of complete atrioventricular septal defect
Authors: Rasiah S. V. , Ewer A. K. , Miller P. , Wright J. G. , Tonks A. , Kilby M. D.
Published: January 2008

Objective

To identify in a case cohort study, overall outcome following prenatal diagnosis of complete AVSD (cAVSD) in a tertiary referral fetal cardiology center.

Method

We retrospectively reviewed all pregnancies from 1997 to 2004 in which the fetus was identified on ultrasound examination as having a cAVSD.

Results

A prenatal diagnosis of cAVSD was made using fetal echocardiography in 99 fetuses. The median (range) gestational age at diagnosis was 23 weeks (17–37). In 41 cases, cAVSD was the sole cardiac lesion. The remaining 58 fetuses had associated additional intracardiac malformations. Prenatal karyotype was obtained in 43 fetuses and was abnormal in 23. Extracardiac anomalies were also identified in 25 fetuses. Following prenatal counseling, 35 couples chose termination. Of the 64 continuing pregnancies, 12 were stillbirths and 4 were lost to follow‐up. Of the 48 live births, 16 were neonatal deaths without surgery while 32 babies underwent surgery and 19 have survived to date (follow‐up between 2 years 10 months to 9 years 10 months).

Conclusion

At the time of prenatal diagnosis at a regional fetal medicine center, the overall survival rate for fetuses with cAVSD is 32% (excluding termination and those lost to follow‐up). This information has important implication for parents of fetuses with cAVSD and when undergoing prenatal counseling. Copyright © 2008 John Wiley & Sons, Ltd.
SAFE—The Special Non‐invasive Advances in Fetal and Neonatal Evaluation Network: aims and achievements
Authors: Chitty Lyn S. , van der Schoot C. Ellen , Hahn Sinuhe , Avent Neil D.
Published: January 2008

In this short review, the objectives and work of SAFE—the Special Non‐invasive Advances in Fetal and Neonatal Evaluation Network, a European Union Framework VI network of excellence is described. We demonstrate how this network facilitates the implementation of non‐invasive prenatal diagnosis (NIPD) for single gene disorders, fetal rhesus typing, aneuploidy and pregnancy complications. Copyright © 2008 John Wiley & Sons, Ltd.
OEIS sequence—a rare congenital anomaly with prenatal evaluation and postnatal outcome in six cases
Authors: Tiblad Eleonor , Wilson R. Douglas , Carr Michael , Flake Alan W. , Hedrick Holly , Johnson Mark P. , Bebbington Michael W. , Mann Stephanie , Adzick N. Scott
Published: January 2008

Objective

To describe the outcome of children prenatally diagnosed with omphalocele, exstrophy of the cloaca, imperforate anus and spinal defects (OEIS).

Method

A retrospective study identified six fetuses diagnosed with OEIS from 2001 to 2007 and data were collected from pre‐ and postnatal charts.

Results

Prenatal findings included an infraumbilical wall defect, omphalocele, no visible bladder and spinal defects. Abnormalities of the upper urinary tract were seen in all cases and ambiguous genitalia in four. Four women continued the pregnancy after prenatal counseling and these fetuses were liveborn at a mean gestational age of 36 weeks. Postnatal evaluation confirmed the prenatal findings in the neonates. The children have required multiple surgeries. Common complications are recurrent urinary tract infections and failure to thrive. Neurodevelopment and motor function are normal in all children, except for one child with lower extremity paralysis and global developmental delay.

Conclusion

Prenatal diagnosis of OEIS is reliable and no significant differences in pre‐ and postnatal findings in the children were found. Correct diagnosis of abnormalities of external and internal genitalia remains a challenge and abnormalities of the upper urinary tract are common. Postnatal survival is good but associated with considerable morbidity and psychosocial consequences. Copyright © 2008 John Wiley & Sons, Ltd.
When to biopsy a foot ulcer? Seven cases of malignant melanoma presenting as foot ulcers
Authors: Kong M‐F , Jogia R , Jackson S , Quinn M , McNally P , Davies M
Published: January 2008

Over the last four years we have diagnosed seven cases of malignant melanoma which were referred to our diabetes foot ulcer clinic. In five of our patients who had diabetes the lesion was initially misdiagnosed as a neuropathic foot ulcer. Acral melanoma is frequently misdiagnosed due to its less common location and because it does not fit the ‘ changing mole’ pattern. It has been mistaken for plantar warts, fungal infections, hyperkeratotic lesions and non‐healing ulcers. Early detection of malignant melanoma greatly enhances the prognosis but primary melanoma of the foot has been associated with a poorer survival rate.

In the light of our cases we advocate a high index of suspicion for an alternative aetiology such as melanoma in cases where the ulcer looks atypical and refuses to heal with conventional treatment, if the ulcer is in an unusual anatomical site or when one cannot easily postulate a cause for development of the ulcer for any other reason. If the ulcer looks ‘ suspicious' and atypical, a dermatology opinion should be sought early and a biopsy should be considered. Copyright © 2008 John Wiley & Sons.
Diabetic mastopathy
Authors: Ghosh S , Collier A , Simpson C , Malik I , Milne A
Published: January 2008

Diabetic mastopathy can be a source of diagnostic confusion for clinicians. It may present with clinical features similar to breast cancer, and fine needle aspirate, core biopsy and mammography maybe unhelpful in excluding malignant disease. Surgical biopsy reveals characteristic features. As the lesion can recur, follow up is necessary. Copyright © 2008 John Wiley & Sons.
The management of type 2 diabetes care: the challenge within primary care
Authors: Mold F , While A , Forbes A
Published: January 2008

Managing type 2 diabetes in primary care poses many challenges for health professionals in preventing and managing complications. These challenges are greatly amplified in those environments with high levels of deprivation and ethnic diversity.

A retrospective structured audit of patient electronic medical records, with systematic extraction of clinical data, was undertaken in three general practices in an ethnically diverse outer London primary care trust. The records of 646 patients were analysed.

Patients from minority ethnic groups were significantly more likely to have poor glycaemic control (p<0.05), and a higher proportion of patients with poor control were aged under 60 (p<0.05). Asian patients showed much higher levels of overall body mass index (BMI) risk, with all Asian patients (100%, n=85) having a sub‐optimal BMI compared to other patient groups (p<0.001). Younger age (50 years and under) was associated with less frequent contact (p<0.05). Patients managed solely in general practice had significantly better glycaemic control than those in shared care schemes (p<0.01). Feedback from practices found that diabetes support services were limited and, as such, influenced health professionals' ability to provide some on‐going care in terms of dietary advice and insulin initiation.

The audit findings suggest that there are some significant relationships between diabetes outcomes, patient characteristics and the care process. It may be possible to develop interventions suitable for metropolitan primary care and which reflect the diversity of population needs. Copyright © 2008 John Wiley & Sons.
Unique proteomic features induced by a potential antiglioma agent, Nordy (dl‐nordihydroguaiaretic acid), in glioma cells
Authors: Bian Xiu‐Wu , Xu Jian‐Ping , Ping Yi‐Fang , Wang Yan , Chen Jian‐Hong , Xu Cheng‐Ping , Wu Yu‐Zhang , Wu Jun , Zhou Xiang‐Dong , Chen Yi‐Sheng , Shi Jing‐Quan , Wang Ji Ming
Published: January 2008

Nordy is a chirally synthesized compound of a natural lipoxygenase inhibitor nordihydroguaiaretic acid. In this study, we found that Nordy inhibited the growth of human glioma cell lines in vitro and their tumorigenicity in mice. In addition, Nordy promoted differentiation of highly malignant human glioma cells. Investigation into the mechanistic basis of Nordy activities revealed that it altered the pattern of protein expression profiles in tumor cells. By using 2‐DE, we found that in human glioma cell lines, at least six proteins were down‐regulated after Nordy treatment, while four proteins were elevated in the same cells. Among the six down‐regulated proteins, microsequencing with MALDI TOF MS confirmed the identity of five: proliferation‐associated gene A (PAG‐A), alternative splicing factor‐3 (ASF‐3), β‐galactoside binding lectin, eukaryotic translation initiation factor 5A (eIF‐5A), and coffilin‐1 (nonmuscle). Four up‐regulated proteins were GST‐π, glyceraldehyde‐3‐phosphate dehydrogenase, α‐enolase, and cyclophilin. All these proteins have been reported to participate in key cellular functions including proliferation, metabolism, differentiation, apoptosis, and gene transcription. Our results suggest that Nordy may constitute a promising drug lead for the development of novel antitumor agents targeting proteins that control tumor cell function at multiple levels.
Differential expression of proteins in response to the interaction between the pathogen Fusarium graminearum and its host, Hordeum vulgare
Authors: Geddes Jennifer , Eudes François , Laroche André , Selinger L. Brent
Published: January 2008

Using proteomic techniques, a study aimed at isolating and identifying proteins associated with resistance to fusarium head blight (FHB) was conducted on six barley genotypes of varying resistance. At anthesis, barley spikelets were point inoculated with Fusarium graminearum macroconidial suspensions or mock inoculum. In total, 43 acidic protein spots out of 600 were detected 3 days postinoculation to be differentially expressed due to FHB and were identified. Identification of proteins responsive to FHB included those associated with oxidative burst and oxidative stress response, such as malate dehydrogenase and peroxidases, and pathogenesis‐related (PR). An increase in abundance of PR‐3 or PR‐5 could be associated with the resistant genotypes CI4196, Svansota, and Harbin, as well as the intermediate resistant genotype CDC Bold. On the contrary, the susceptible genotype Stander showed a decrease in abundance of these acidic PR‐proteins. In the susceptible and intermediate resistant genotypes Stander and CDC Bold, as well as CI4196, the increased abundance of proteins associated with an oxidative response might have prepared the terrain for saprophytic fungal invasion. On the contrary, in the resistant sources Harbin and Svansota we did not observed change in abundance of these proteins. Not a single significant change in acidic protein abundance could be detected in Chevron. Three distinct response patterns are reported from these six barley genotypes.
Arginine‐rich cell penetrating peptides: Design, structure–activity, and applications to alter pre‐mRNA splicing by steric‐block oligonucleotides
Authors: Abes R. , Arzumanov A. , Moulton H. , Abes S. , Ivanova G. , Gait M. J. , Iversen P. , Lebleu B.
Published: January 2008

Rerouting the splicing machinery with steric‐block oligonucleotides (ON) might lead to new therapeutic strategies in the treatment of diseases such as β‐thalassemia, Duchenne muscular dystrophy, or cancers. Interfering with splicing requires the sequence‐specific and stable hybridization of RNase H‐incompetent ON as peptide nucleic acids (PNA) or phosphorodiamidate morpholino oligomers (PMO). Unfortunately, these uncharged DNA mimics are poorly taken up by most cell types and conventional delivery strategies that rely on electrostatic interaction do not apply. Likewise, conjugation to cell penetrating peptides (CPPs) as Tat, Arg9, Lys8, or Pen leads to poor splicing correction efficiency at low concentration essentially because PNA– and PMO–CPP conjugates remain entrapped within endocytotic vesicles. Recently, we have designed an arginine‐rich peptide (R‐Ahx‐R)4 (with Ahx for aminohexanoic acid) and an arginine‐tailed Penetratin derivative which allow sequence‐specific and efficient splicing correction at low concentration in the absence of endosomolytic agents. Both CPPs are undergoing structure–activity relationship studies for further optimization as steric‐block ON delivery vectors. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Prior neonatal isolation reduces induction of NGF mRNA and decreases GDNF mRNA in the hippocampus of juvenile and adult rodents subjected to immobilization stress
Authors: Kawano Ki‐Ichiro , Morinobu Shigeru , Sawada Takuya , Tsuji Seiichi , Erabi Kaori , Fuchikami Manabu , Kozuru Toshiro , Yamawaki Shigeto , Hisaoka Kazue , Takebayashi Minoru
Published: January 2008

Numerous studies have demonstrated that early adverse experiences are associated with the development of susceptibility to stress later in life. Although it is known that early experience of adversity, such as neonatal isolation, maternal separation, and low maternal care, enhances the activity of the hypothalamo‐pituitary‐adrenalaxis in rodents, the detailed mechanism underlying stress susceptibility induced by early adversity remains to be elucidated. Since neurotrophins have been shown to have a neuroprotective effect, we examined the influence of repeated neonatal isolation on expression of nerve growth factor (NGF), glia cell‐derived neurotrophic factor (GDNF), and neurotrophin‐3 mRNA in the hippocampus of juvenile and adult rats subsequently exposed immobilization stress, using real‐time quantitative PCR and in situ hybridization. Neonatal isolation did not affect the basal hippocampal expression of these neurotrophin mRNAs in either juvenile or adult rats not subsequently exposed to immobilization. Similarly, there was a significant interaction between neonatal isolation and immobilization that affected the expression of NGF and GDNF mRNAs. Neonatal isolation attenuated the induction of NGF mRNA in both groups of rats and decreased GDNF mRNA in juvenile rats in response to immobilization. The decreased induction of NGF mRNA and reduced GDNF mRNA in response to immobilization was found in the CA3 pyramidal cell layer and dentate gyrus granular cell layer in the hippocampus of adult rats that had been subjected to neonatal isolation. These findings suggest that susceptibility to stress arising from prior neonatal isolation might be a result of decreased neuroprotective support through NGF and GDNF. Synapse 62:259–267, 2008. © 2008 Wiley‐Liss, Inc.
Age‐ and Sex‐Related Incidence of Surgically Treated Primary Hyperparathyroidism
Authors: Miller Barbra S. , Dimick Justin , Wainess Reid , Burney Richard E.
Published: January 2008

Background

Primary hyperparathyroidism (1° HPT) is reported most often in women over the age of 50. Beyond that, little is known about the epidemiology of this condition, and no studies have specifically examined the age and gender distribution of patients with 1° HPT.

Methods

We analyzed patients from the Nationwide Inpatient Sample (NIS), a 20% random sample of all hospital stays from 2000–2004, and also from the University of Michigan endocrine surgery database from 1999–2005. Surgically treated 1° HPT was used as a surrogate marker for 1° HPT. An age‐ and sex‐based frequency distribution was computed for each dataset.

Results

A total of 7,513 females and 2,677 males who underwent surgery for 1° HPT in the 5‐year period 2000 through 2004 were reported in the NIS. At the University of Michigan from 1999 through 2005, 790 females and 276 males underwent parathyroidectomy for 1° HPT. In both datasets, the frequency of 1° HPT began to rise slowly in both sexes at age 11 and increased more rapidly among females than males beginning at age 21–25 (NIS) and 26–30 (UM). Incidence curves for both women and men in both databases were similar in shape and unipolar in configuration. Peak incidence was at age 56–60 (NIS) and 61–65 (UM) in females and age 56–60 in males (both datasets). The female:male ratio was noted to rise steadily among the NIS patients until perimenopausal age, after which it became stable for the next 20 years before decreasing again. No change in the female:male ratio over time was seen among the UM patients.

Conclusions

Primary HPT occurs more frequently in females than in males at all ages. The incidence increases steadily after age 25 in both sexes. The female:male ratio does not change during the peri‐ and postmenopausal years. This information should stimulate new hypotheses to explain the difference in the incidence of 1°HPT between men and women.
Midcycle pericoital intravaginal bee honey and royal jelly for male factor infertility
Authors: Abdelhafiz Ahmed T. , Muhamad Jehan A.
Published: January 2008

Objective

To evaluate the efficacy of pericoital intravaginal applications of a mixture of Egyptian bee honey and royal jelly (H/RJ) in the midcycle for the treatment of infertility due to asthenozoospermia.

Methods

Sohag University Hospital and Asyut Gynecology and Infertility Clinic conducted a crossover study of 99 couples affected by asthenozoospermia. One group used midcycle pericoital vaginal applications of H/RJ and the other underwent a standard intrauterine insemination (IUI) procedure, for 3 cycles or until conception occurred for both groups. After a washout period of 2 months, the couples for whom no pregnancy occurred were crossed over.

Results

A total of 553 cycles were analyzed. There were 23 (8.1%) and 7 (2.6%) pregnancies per cycle, respectively, in the H/RJ and the IUI groups, and the difference was statistically significant (P < 0.001).

Conclusion

Using H/RJ intravaginally might be a simple and reasonably effective method of treating asthenozoospermia.
Pinch-induced behavioral inhibition (‘clipnosis’) in domestic cats
Authors: Pozza Megan E. , Stella Judi L. , Chappuis-Gagnon Anne-Claire , Wagner Susan O. , Buffington C.A. Tony
Published: January 2008

Research has documented immobilization of rodents, rabbits, guinea pigs and dogs by mechanical means, typically using neck clips or inversion (‘animal hypnosis’). In contrast, only a few studies of mechanical immobilization of cats are available, although some success has been reported in the literature. Domestic cats may be effectively immobilized by clips placed along the animal's dorsum. We use the term ‘pinch-induced behavioral inhibition’ (PIBI) for this behavior because it describes both the method and the response, while avoiding the more anthropomorphic term ‘hypnosis’. We investigated the effectiveness of PIBI and its neurological and habituation effects in healthy cats and cats with idiopathic cystitis (IC). Although not all cats were susceptible to PIBI and effectiveness varied among individuals, PIBI was useful for gentle restraint in most cats.
Gender differences in then-3 fatty acid content of tissues
Authors: Childs Caroline E. , Romeu-Nadal Meritxell , Burdge Graham C. , Calder Philip C.
Published: January 2008

Dietaryn-3 PUFA have many beneficial effects on cell and tissue function and on human health. In mammals then-3 essential fatty acid α-linolenic acid (ALNA) can be converted into longer-chain (LC)n-3 PUFA such as EPA and DHA via a series of desaturase and elongase enzymes that are mainly active in the liver. Human studies have identified that males and females appear to differ in their ability to synthesise EPA and DHA from ALNA, with associated differences in circulating concentrations. Based on studies of women using the contraceptive pill or hormone-replacement therapy and of trans-sexual subjects it is suggested that sex hormones play a role in these differences. The rat has been used to investigate gender differences inn-3 PUFA status since this model allows greater dietary control than is possible in human subjects. Like human subjects, female rats have higher plasma DHA concentrations than males. Rats also respond to increased dietary ALNA in a way that is comparable with available human data. The concentrations of LCn-3 PUFA in rat plasma and tissues are positively associated with circulating concentrations of oestradiol and progesterone and negatively associated with circulating concentrations of testosterone. These findings suggest that sex hormones act to modify plasma and tissuen-3 PUFA content, possibly by altering the expression of desaturase and elongase enzymes in the liver, which is currently under investigation.
Effects of exercise and restrained eating behaviour on appetite control
Authors: Martins Catia , Robertson M. Denise , Morgan Linda M.
Published: January 2008

Obesity is a global epidemic; increased consumption of energy-dense food and reduced physical activity levels are likely to be the main drivers. Previous cross-sectional research has shown that sedentary males, unlike their active counterparts, are unable to compensate for previous energy intake (EI). Using a longitudinal design a 6-week exercise intervention was found to improve short-term appetite control, leading to a more ‘sensitive’ eating behaviour in response to previous EI, both acutely at a test meal and for the next 24 h. Although the mechanisms whereby acute and chronic exercise improves short-term appetite remain unknown, post-ingestive satiety peptides are likely to be involved. Acute exercise was found to increase postprandial levels of polypeptide YY, glucagon-like peptide-1 and pancreatic polypeptide but to have no impact on ghrelin, suggesting that exercise can trigger physiological changes in satiety hormone secretion that could help in appetite control and weight maintenance. In the context of an increased availability of highly-palatable food, dietary restraint may be increasingly important. Although restraint has been associated with abnormal eating behaviour, in the laboratory no counter-regulation was found in restrained eaters when presented with a buffet meal 60 min after a high-energy preload or when a pasta-meal was presented 3 h after preloading. Although restraint was not found to impact on polypeptide YY or TAG, lower postprandial glucose and insulin plasma levels were observed in restrained eaters, together with increased feelings of fullness. In conclusion, short-term appetite control seems to be favourably modified by exercise, while the impact of restraint on appetite seems to be more complex.
Effects of dietary polyphenols on gene expression in human vascular endothelial cells
Authors: Nicholson Sonja K. , Tucker Gregory A. , Brameld John M.
Published: January 2008

Previous studies have shown that consumption of fruit and vegetables plays a role in preventing the onset of CVD. These beneficial effects have been linked to the presence of polyphenolic compounds in plant-derived foods and their antioxidant capacity. It has been hypothesised that polyphenols may also have a direct effect on vascular endothelial cell growth and the expression of genes involved in angiogenesis and other roles of the endothelium. Previous studies in this area have tended to use concentrations of polyphenols that are supraphysiological (1–100 μm). The effects of more physiological concentrations (0·1 μm) of various individual polyphenols on gene expression were therefore investigated in cultured human umbilical vein endothelial cells (HUVEC) using both microarray and quantitative RT–PCR methodologies. Treatment of HUVEC with ferulic acid, quercetin or resveratrol (0·1 μm) resulted in changes to gene expression that for the three treatments amounted to significant (>2-fold) down-regulation of the expression of 363 genes and significant (>2-fold) up-regulation of 233 genes of the 10 000 genes present on the microarray. The majority of these genes were affected by resveratrol. Quantitative RT–PCR studies indicated that resveratrol (0·1 μm) significantly increased the expression of the gene encoding endothelial NO synthase (eNOS), which synthesises the vasodilator molecule NO, and both resveratrol and quercetin decreased expression of the potent vasoconstrictor, endothelin-1 (ET-1), while ferulic acid had no effect. The effects of resveratrol (0·1 μm) were also investigated when HUVEC were under oxidative stress following treatment with H2O2 (0–50 μm), which dose-dependently increased expression of eNOS and ET-1. Resveratrol stimulated eNOS mRNA in the absence of H2O2 and still allowed the increase with H2O2, but the effects were not additive. In contrast, resveratrol blocked the stimulatory effect of H2O2 on ET-1 expression. Hence, resveratrol has potent effects at a physiological concentration (0·1 μm) that would be expected to result in vasodilation and therefore help reduce blood pressure and the risk of CVD.
Chromium and polyphenols from cinnamon improve insulin sensitivity
Authors: Anderson Richard A.
Published: January 2008

Naturally-occurring compounds that have been shown to improve insulin sensitivity include Cr and polyphenols found in cinnamon (Cinnamomon cassia). These compounds also have similar effects on insulin signalling and glucose control. The signs of Cr deficiency are similar to those for the metabolic syndrome and supplemental Cr has been shown to improve all these signs in human subjects. In a double-blind placebo-controlled study it has been demonstrated that glucose, insulin, cholesterol and HbA1c are all improved in patients with type 2 diabetes following Cr supplementation. It has also been shown that cinnamon polyphenols improve insulin sensitivity in in vitro, animal and human studies. Cinnamon reduces mean fasting serum glucose (18–29%), TAG (23–30%), total cholesterol (12–26%) and LDL-cholesterol (7–27%) in subjects with type 2 diabetes after 40 d of daily consumption of 1–6 g cinnamon. Subjects with the metabolic syndrome who consume an aqueous extract of cinnamon have been shown to have improved fasting blood glucose, systolic blood pressure, percentage body fat and increased lean body mass compared with the placebo group. Studies utilizing an aqueous extract of cinnamon, high in type A polyphenols, have also demonstrated improvements in fasting glucose, glucose tolerance and insulin sensitivity in women with insulin resistance associated with the polycystic ovary syndrome. For both supplemental Cr and cinnamon not all studies have reported beneficial effects and the responses are related to the duration of the study, form of Cr or cinnamon used and the extent of obesity and glucose intolerance of the subjects.
Diabetic threesome (hyperglycaemia, renal function and nutrition) and advanced glycation end products: evidence for the multiple-hit agent?
Authors: Kaňková Kateřina
Published: January 2008

Complex chemical processes termed non-enzymic glycation that operatein vivoand similar chemical interactions between sugars and proteins that occur during thermal processing of food (known as the Maillard reaction) are one of the interesting examples of a potentially-harmful interaction between nutrition and disease. Non-enzymic glycation comprises a series of reactions between sugars, α-oxoaldehydes and other sugar derivatives and amino groups of amino acids, peptides and proteins leading to the formation of heterogeneous moieties collectively termed advanced glycation end products (AGE). AGE possess a wide range of chemical and biological properties and play a role in diabetes-related pathology as well as in several other diseases. Diabetes is, nevertheless, of particular interest for several reasons: (1) chronic hyperglycaemia provides the substrates for extracellular glycation as well as intracellular glycation; (2) hyperglycaemia-induced oxidative stress accelerates AGE formation in the process of glycoxidation; (3) AGE-modified proteins are subject to rapid intracellular proteolytic degradation releasing free AGE adducts into the circulation where they can bind to several pro-inflammatory receptors, especially receptor of AGE; (4) kidneys, which are principally involved in the excretion of free AGE adducts, might be damaged by diabetic nephropathy, which further enhances AGE toxicity because of diminished AGE clearance. Increased dietary intake of AGE in highly-processed foods may represent an additional exogenous metabolic burden in addition to AGE already present endogenously in subjects with diabetes. Finally, inter-individual genetic and functional variability in genes encoding enzymes and receptors involved in either the formation or the degradation of AGE could have important pathogenic, nutrigenomic and nutrigenetic consequences.