bluuebunny/crossref_metadata_2025 huggingface dataset:
What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson's disease with dementia
Authors: Minett Thaís S. C. , Thomas Alan , Wilkinson Lucy M. , Daniel Sarah L. , Sanders Jonathan , Richardson Jonathan , Littlewood Elizabeth , Myint Pat , Newby Jane , McKeith Ian G.
Published: November 2003

Background

This open label study was designed to assess the effects of donepezil treatment, its withdrawal and subsequent recommencement on cognitive functioning, behaviour and parkinsonian symptoms in patients with probable dementia with Lewy bodies (DLB) and with Parkinson's disease who subsequently developed dementia (PDD).

Methods

Eight patients with DLB and 11 with PDD were treated with up to 10mg of donepezil daily for 20 weeks followed by a 6‐week withdrawal period. The primary outcome measures were the Mini‐Mental State Examination (MMSE), the total Neuropsychiatric Inventory (NPI) and the Unified Parkinson's Disease Rating Scale III. Testing was conducted before dosing, at week 20, at a withdrawal visit and 3 months after recommencement on donepezil.

Results

Patients with DLB and PDD showed a significant improvement in cognition with treatment, loss of this improvement on withdrawal and restoration of treatment gains on recommencement. Both groups also demonstrated favourable, behavioural changes with treatment, PDD patients in particular deteriorating significantly after withdrawal. The only NPI symptom domain that showed a consistent significant response to both treatment (positive) and withdrawal (negative) was hallucinations. The medication was well tolerated and parkinsonian features did not alter significantly over the testing sessions.

Conclusions

Our results suggest that treatment with donepezil improves cognition and hallucinations without increasing parkinsonian symptoms, and its sudden withdrawal is usually detrimental, producing acute cognitive and behavioural decline. Although recommencement on donepezil appears to reverse this deterioration we do not advise its abrupt discontinuation in this population. Copyright © 2003 John Wiley & Sons, Ltd.
Role of behavioural disturbance in the loss of autonomy for activities of daily living in Alzheimer patients
Authors: Lechowski L. , Dieudonné B. , Tortrat D. , Teillet L. , Robert P. H. , Benoit M. , Forette B. , Vellas B.
Published: November 2003

Background

Cognitive impairment is associated with functional impairment in patients with Alzheimer's disease (AD). Behavioural disturbance is very common in these patients. Nevertheless, there has been very little research into the relations between behavioural disturbance and functional status in AD. The purpose of this study is to investigate the relationship between behavioural disturbance and functional status after taking account of cognitive impairment.

Material and methods

579 patients were prospectively evaluated at 16 French hospitals, all referents for AD, and were diagnosed with possible or probable AD. These patients were assessed with NeuroPsychiatric Inventory (NPI), cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS‐cog), Clinical Dementia Rating scale (CDR) and Instrumental Activities of Daily Living scale (IADL).

Results

The number of men with available data for IADL total score was too small to make any analysis. ‘Group A’ gathered 256 women for whom the relation between autonomy for Activities of Daily Living (ADL) and the other variables were determined. ‘Group B’, pooled 85 women for whom relations found were verified. Linear regression was used for the analysis. With age, cognitive impairment allows us to explain best (38%) the loss of autonomy for ADL.

Conclusion

The role of behavioural disturbances in the loss of autonomy for ADL was not determinant in our study, whereas cognitive impairment and age were better able to determine the loss of autonomy for ADL. Further study is needed to explain the decline of functional status in AD patients. Copyright © 2003 John Wiley & Sons, Ltd.
The breast cancer low‐penetrance allele 1100delC in the CHEK2 gene is not present in Spanish familial breast cancer population
Authors: Osorio Ana , Rodríguez‐López Raquel , Díez Orland , de la Hoya Miguel , Ignacio Martínez José , Vega Ana , Esteban‐Cardeñosa Eva , Alonso Carmen , Caldés Trinidad , Benítez Javier
Published: November 2003

Searching for low‐penetrance genes involved in breast cancer susceptibility has been a field of interest in the last few years. Recently, the CHEK 2 gene, involved in DNA damage and replication checkpoints, has been pointed out as a good candidate; moreover, a specific variant in this gene,1100delC, has been found to increase breast cancer susceptibility among familial breast cancer cases not attributable to mutations in BRCA1 or BRCA2 genes. In our present study, we evaluated the role of the 1100delC variant as a susceptibility allele in breast cancer in the Spanish population. However, our results suggest that this variant is absent or very infrequent in our population, making its screening irrelevant from the practical point of view. © 2003 Wiley‐Liss, Inc.
Interactions between N–acetylcysteine and sodium selenite in modulating the clastogenicity of urethane and 2–acetylaminofluorene in mice
Authors: Balansky Roumen M. , De Flora Silvio
Published: November 2003

Combined treatment with different agents represents a promising approach in cancer chemoprevention. Therefore, it is useful to assess in preclinical models the efficacy of combinations that are selected by taking into account mechanistic considerations. We designed 2 studies evaluating the interaction between N–acetylcysteine (NAC) and sodium selenite (Se), both given with the drinking water to Balb/c mice, in modulating clastogenic effects in bone marrow polychromatic erythrocytes. In a first study, a single i.p. injection of urethane considerably enhanced the frequency of micronucleated cells. While NAC produced a significant inhibition, Se further enhanced urethane clastogenicity. When given in combination at the same doses, NAC prevented the adverse effect of Se. In a second study, a single i.p. injection of 2–acetylaminofluorene enhanced the frequency of micronucleated cells. Se did not reduce this effect to a significant extent, while NAC produced a dose–dependent inhibition. When tested at the lower dose in combination with Se, the protective effect of NAC was unchanged. Especially in association with Se, NAC also prevented the toxicity of 2–acetylaminofluorene by normalizing the ratio of polychromatic to normochromatic erythrocytes. In conclusion, NAC attenuated the clastogenicity of both urethane and 2–acetylaminofluorene and the toxicity of this aromatic amine. In addition, NAC prevented the clastogenic and toxic effects resulting from the interaction of Se with urethane. Together with the findings of previous studies, it appears that, besides its intrinsic protective properties in carcinogenesis, NAC is capable of attenuating the adverse effects of several cytotoxic drugs and chemopreventive agents. © 2003 Wiley‐Liss, Inc.
Evaluation of dietary, medical and lifestyle risk factors for incident kidney cancer in postmenopausal women
Authors: Nicodemus Kristin K. , Sweeney Carol , Folsom Aaron R.
Published: November 2003

Kidney cancer incidence rates in the United States have been increasing and are not fully accounted for by better diagnostic techniques. Risk factors in women are incompletely described. A total of 34,637 Iowan women initially free of cancer completed a mailed questionnaire in 1986. Kidney cancer incidence was identified over 15 years of follow‐up (n= 124) through linkage to a statewide cancer registry. Adjusted for age and other risk factors, kidney cancer was associated positively with maximum adult weight (pfor trend = 0.02) and current waist‐to‐hip ratio (pfor trend = 0.002). Compared to nondrinkers, consumers of alcohol of 3.0 or more grams per day had a relative risk (RR) of 0.52 (95% CI = 0.29–0.92). Total vitamin C intake was associated positively with risk of kidney cancer (pfor trend = 0.04), whereas total vitamin E intake was associated negatively with risk (pfor trend = 0.002). The few women who used copper supplements had a 6.52‐fold increase in risk of kidney cancer (95% CI = 1.95–21.8). Compared to never users, women who were former users of estrogen had an increased risk of kidney cancer (RR = 1.62; 95% CI = 1.11–2.36), but current users of estrogen were not at a higher risk. Women who were nulliparous or had more than 2 live births were also at increased risk of kidney cancer compared with women who had 1 or 2 live births. In conclusion, in these postmenopausal women, overweight, particularly central adiposity, was an important risk factor for kidney cancer. Potential risk factors that warrant further exploration were low intake of alcohol and vitamin E, higher intake of vitamin C, nulli‐ or multiparity and use of copper supplements. © 2003 Wiley‐Liss, Inc.
Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas
Authors: Tiemersma Edine W. , Bunschoten Annelies , Kok Frans J. , Glatt Hansruedi , de Boer Sybrand Y. , Kampman Ellen
Published: November 2003

Cigarette smoke contains polycyclic hydrocarbons and arylamines that may both be activated by sulfotransferase, encoded by SULT1A1. A genetic polymorphism leads to an Arg213His substitution, thereby decreasing enzyme activity and stability and might thus modify the association between smoking and colorectal adenomas. We investigated this in a Dutch case‐control study. Additionally, we evaluated potential roles of epoxide hydrolase (EPHX), N‐acetyltransferases (NAT1 and NAT2) and glutathione S‐transferases (GSTM1 and GSTT1). The data analysis included 431 adenoma cases and 432 polyp‐free controls (54% women; mean age, 54.6 years) enrolled at endoscopy in 8 Dutch hospitals between 1997 and 2000. All participants provided data on smoking habits and blood for DNA isolation. Genotyping was performed using appropriate polymerase chain reaction‐restriction fragment length polymorphism procedures. Multivariate models included age, sex, endoscopy indication, consumption of snacks and alcohol and, if appropriate, daily smoking dose or smoking duration. Smoking increased colorectal adenoma risk, most importantly by duration. Smoking for more than 25 years more than doubled adenoma risk (OR = 2.4, 95% CI = 1.4–4.1) compared to never smoking. Combinations of SULT1A1 fast sulfation (*1/*1) and of NAT2 slow acetylation with smoking resulted in a 4 times higher risk of adenomas compared to never smokers with other inherited gene variants, although there was no statistically significant effect modification. We found no clear effects of the other genetic polymorphisms on the association between smoking and adenomas. We conclude that smoking increases risk of colorectal adenomas and that SULT1A1 and NAT2 only modestly modify this association. © 2003 Wiley‐Liss, Inc.
Protective effect of green tea against prostate cancer: A case‐control study in southeast China
Authors: Jian Le , Xie Li Ping , Lee Andy H. , Binns Colin W.
Published: November 2003

To investigate whether green tea consumption has an etiological association with prostate cancer, a case‐control study was conducted in Hangzhou, southeast China during 2001–2002. The cases were 130 incident patients with histologically confirmed adenocarcinoma of the prostate. The controls were 274 hospital inpatients without prostate cancer or any other malignant diseases, and matched to the age of cases. Information on duration, quantity and frequency of usual tea consumption, as well as the number of new batches brewed per day, were collected by face‐to‐face interview using a structured questionnaire. The risk of prostate cancer for tea consumption was assessed using multivariate logistic regression adjusting for age, locality, education, income, body mass index, physical activity, alcohol consumption, tobacco smoking, total fat intake, marital status, age at marriage, number of children, history of vasectomy and family history of prostate cancer. Among the cases, 55.4% were tea drinkers compared to 79.9% for the controls. Almost all the tea consumed was green tea. The prostate cancer risk declined with increasing frequency, duration and quantity of green tea consumption. The adjusted odds ratio (OR), relative to non‐tea drinkers, were 0.28 (95% CI = 0.17–0.47) for tea drinking, 0.12 (95% CI = 0.06–0.26) for drinking tea over 40 years, 0.09 (95% CI = 0.04–0.21) for those consuming more than 1.5 kg of tea leaves yearly, and 0.27 (95% CI = 0.15–0.48) for those drinking more than 3 cups (1 litre) daily. The dose response relationships were also significant, suggesting that green tea is protective against prostate cancer. © 2003 Wiley‐Liss, Inc.
Retargeting of adenoviral infection to melanoma: Combining genetic ablation of native tropism with a recombinant bispecific single‐chain diabody (scDb) adapter that binds to fiber knob and HMWMAA
Authors: Nettelbeck Dirk M. , Rivera Angel A. , Kupsch Jörg , Dieckmann Detlef , Douglas Joanne T. , Kontermann Roland E. , Alemany Ramon , Curiel David T.
Published: November 2003

Gene therapy is an emerging and promising modality for the treatment of malignant melanoma and other neoplasms for which conventional therapies are inadequate. Various therapeutic genes have shown promise for tumor cell killing. However, successful gene therapy depends on the development of efficient and targeted gene transfer vectors. Here we describe a novel strategy for targeting of adenovirus‐mediated gene transfer to melanoma cells. This strategy combines genetic ablation of native adenoviral tropism with redirected viral binding to melanoma cells via a bispecific adapter molecule, a bacterially expressed single‐chain diabody, scDb MelAd, that binds to both the adenoviral fiber protein and to the high molecular weight melanoma‐associated antigen (HMWMAA). This antigen is widely and specifically expressed on the surface of melanoma cells and its expression is associated with tumor development and progression. Our results showed specific and strong binding of the anti‐HMWMAA scFv RAFT3 and the bispecific adapter scDb MelAd to melanoma cells. In adenoviral infection experiments, we demonstrated i) substantially (>50‐fold) reduced infectivity of capsid mutant adenoviruses, ii) restored (up to 367‐fold increase), CAR‐independent and HMWMAA‐mediated infectivity of these mutant viruses by scDb MelAd specifically in melanoma cells, and iii) higher levels of transgene expression in melanoma cells by fiber mutant virus complexed with scDbMelAd, relative to a vector with wild‐type fibers. We confirmed the utility of this targeting strategy with human primary melanoma cells that represent clinically relevant substrates. These experiments established that the retargeting strategy mediates up to 54‐fold increased adenoviral gene transfer to CAR‐negative melanoma cells compared to the vector with native tropism. Hence, the HMWMAA‐targeted adenoviral vector lacking native tropism exhibits both enhanced specificity and augmented infectivity of gene transfer to melanoma cells, suggesting that it is feasible to use this vector to improve gene therapy for malignant melanoma. © 2004 Wiley‐Liss, Inc.
Osteogenic differentiation of cultured rat and human bone marrow cells on the surface of zinc‐releasing calcium phosphate ceramics
Authors: Ikeuchi Masako , Ito Atsuo , Dohi Yoshiko , Ohgushi Hajime , Shimaoka Hideki , Yonemasu Kunio , Tateishi Tetsuya
Published: November 2003

Rat and human bone marrow cells (BMCs) were cultured on a composite ceramic of zinc‐containing β‐tricalcium phosphate and hydroxyapatite (ZnTCP/HAP) with a (Ca+Zn)/P molar ratio of 1.60 and varying zinc contents. After a 2‐week culture of the BMCs in the presence of β‐glycerophosphate and dexamethasone, many macroscopic mineralized areas with high alkaline phosphatase (ALP) activity were seen on the ZnTCP/HAP ceramic disks. The ALP activity increased with increasing zinc content in the ceramics. The highest ALP activity was observed when the BMCs were cultured on the ceramics with 1.26 wt % zinc, and the ceramics released zinc ions at concentrations from 2.2 to 7.2 μg/mL into the culture medium. Zinc ions were incorporated into mineralized areas produced by BMCs. BMCs also were directly cultured onto the culture dish surface, and the addition of 100 μM of free ZnCl2 (6.5 μg/mL) to the culture medium significantly increased the ALP activity of the BMCs relative to the culture medium without the ZnCl2addition. The maximum zinc concentration required to enhance mineralization was higher in human BMCs than in rat BMCs. The present study demonstrates the superiority of ZnTCP/HAP ceramics over TCP/HAP in supporting the osteogenic differentiation of BMCs, and thus these ceramics are safe and useful in clinical settings, such as for bone reconstructive surgery. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1115–1122, 2003
Novel associated hydrogels for nucleus pulposus replacement
Authors: Thomas Jonathan , Lowman Anthony , Marcolongo Michele
Published: November 2003

Hydrogels of poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) blends may provide a material suitable for replacement of the nucleus pulposus of the intervertebral disc. This research examined the stability of these hydrogels under simulated physiological conditions. Polymer dissolution and stability were characterized over 120 days immersion, chemical surface analysis over 56 days immersion, and tensile mechanical behavior over 56 days immersion. Rubber elasticity theory was used by combining mechanical results with swelling data to calculate network characteristics such as the molecular weight between physical crosslinks and density of crosslinks. Properties were examined as a function of PVA/PVP composition as well as PVA molecular weight and PVP molecular weight. Results indicated that PVA/PVP blends prepared with moderate amounts of PVP (0.5–5%) resulted in a polymer network stabilized through interchain hydrogen bonding between hydroxyl groups on PVA chains and carbonyl groups on PVP chains. Most notably, a significant decrease in percentage of polymer mass loss was seen for blends prepared with 143K molecular weight PVA. Surface chemical analysis revealed that PVP unincorporated in the network structure suffered significant dissolution out of the polymer network and into solution. The molecular weight of PVA and PVP were shown to have a significant influence on the blends' network properties. Gels prepared with lower molecular weight PVA resulted in a more stable blend containing a higher density of crosslinks. However, blends prepared with a higher molecular weight PVA showed superior polymer network stability in dissolution studies. The blend that had the best combination of network stability under physiological conditions and a relatively tight, stable, and crosslinked network was prepared with 99% PVA (143K) and 1% PVP (40K). This material is proposed as an implant material for replacement of the degenerated nucleus pulposus. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1329–1337, 2003
Thermally reversible polymer gel for chondrocyte culture
Authors: Au Angela , Ha Jinny , Polotsky Anna , Krzyminski Karol , Gutowska Anna , Hungerford David S. , Frondoza Carmelita G.
Published: November 2003

We have evaluated a biomaterial to serve as a scaffold for the propagation and amplification of chondrocytes that promotes the original cellular phenotype of these cells. The goal of the present study was to investigate the use of thermally reversible polymer gels poly(NiPAAm‐co‐AAc), as a biocompatible supporting scaffold for the propagation of chondrocytic cells. The polymer gels at temperatures above its lower critical solution temperature whereas liquefying at temperatures below its lower critical solution temperature of 34.5°C. Hence, the polymer, in its gelled form, has the ability to hold cells in situ, forming a matrix similar to the natural cellular environment or the extracellular matrix that comprises cartilage. We tested the hypothesis that the polymer gel promotes cell viability and function. Human osteoblast‐like cells, nasal chondrocytes, and articular chondrocytes (1 × 105/150 μL) were resuspended in enriched Dulbecco's minimal essential media and were plated onto control (without gel) and gel containing 24‐well plates. The plates were reincubated at 37°C, 5% CO2 for the time point of interest. Additional media was added to the plates and exchanged as needed. After cell culture, cells were retrieved, enumerated, and cell viability was determined. Other aliquots of the cells were stained for morphological analysis whereas expression of chondrocyte markers including collagen type II and aggrecan were determined using reverse transcriptase–polymerase chain reaction. The polymer gel was not cytotoxic because the cell number retrieved from three‐dimensional culture gel was found to be one to two times higher than that retrieved from monolayer culture. Chondrocytes propagated in the thermo‐reversible polymers expressed enhanced or maintained expression of collagen type II and aggrecan. Collagen type I expression was decreased or unaltered. The N‐isopropylacrylamide and acrylic acid copolymer gel has potential use as a cell culture substrate and as a cell delivery vehicle. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1310–1319, 2003
In vitro evaluation of degradation and cytotoxicity of a novel composite as a bone substitute
Authors: Liu Bai‐Shuan , Yao Chun‐Hsu , Chen Yueh‐Sheng , Hsu Shan‐Hui
Published: November 2003

The purpose of this study was to prepare and evaluate in vitro the feasibility and cytocompatibility of a novel composite (GGT) as a large defect bone substitute. The composite is tricalcium phosphate ceramic particles combined with genipin crosslinked gelatin. After soaking the GGT composites in Ringer solutions at 37°C for 7, 14, 28, 42, 56, and 84 days, the in vitro biologic degradation rate and biocompatibility were determined. Substances released from soaked GGT composites were analyzed with an ultraviolet visible light spectrophotometer. In addition, the solution soaking the GGT was co‐cultured with osteoblasts to determine whether or not the released substances from GGT could facilitate the growth of bone cells. After they had been cultured for 2 days, the osteoblasts were tested for differentiation and proliferation by alkaline phosphatase (ALP) activity and a MTT assay. Results indicate that the concentration of the genipin solution is a critical factor in deciding the crosslinking degree of the GGT composite. Complete crosslinking reaction in the GGT composite occurred when 0.5 wt % of genipin had been added. Cytotoxic testing revealed that 80 ppm of the genipin in the culture medium served as the level over which cytotoxicity to osteoblasts could be produced. In addition, we found that gelatin and calcium continuously were released from the GGT composite in the soaking solution, which promoted differentiation and proliferation of the osteoblasts. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1163–1169, 2003
Fabrication and in vitro testing of polymeric delivery system for condensed DNA
Authors: Huang Yen‐Chen , Connell Maureen , Park Youmie , Mooney David J. , Rice Kevin G.
Published: November 2003

Polyethylenimine (PEI) was combined with plasmid DNA and freeze dried following the addition of sucrose as a lyoprotectant and pore‐forming agent. Freeze‐dried PEI DNA condensates were dry mixed with granular polylactideglycolic acid (PLGA) then compression molded and sponged to encapsulated PEI DNA. A measurement of the elastic modulus indicated that 91 wt% sucrose substituted for 95 wt% sodium chloride as a porogen, resulting in PLGA sponges with a mechanical modulus of 100 kPa. The PEI DNA was retained (80%) within PLGA sponges prepared with sucrose during the leaching and subsequent 2‐week release studies, whereas sodium chloride PLGA sponges caused the premature release (100%) of PEI DNA within 2 days. In vitro gene transfer studies with PEI DNA PLGA sponges established that adherent and infiltrating fibroblasts expressed reporter gene for 15 days compared with the short, 3‐day expression mediated by direct gene of PEI DNA on cells in culture. The results demonstrate an approach to encapsulate condensed DNA in a PLGA sponge for the purpose of retaining DNA within the matrices and creating efficient gene transfer during tissue engineering. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1384–1392, 2003
Use of vascular endothelial cell growth factor gene transfer to enhance implantable sensor function in vivo
Authors: Klueh U. , Dorsky D. I. , Kreutzer D. L.
Published: November 2003

In the current study, we developed and validated a simple, rapid and safe in vivo model to test gene transfer and sensor function in vivo. Using the model, we tested the specific hypothesis that in vivo gene transfer of angiogenic factors at sites of biosensor implantation would induce neovascularization surrounding the sensor and thereby enhance biosensor function in vivo. As the in vivo site for testing of our gene transfer cell and biosensor function systems, the developing chorioallantoic membrane (CAM) of the embryo was utilized. Vascular endothelial cell growth factor (VEGF) was used as a prototype for angiogenic factor gene transfer. A helper‐independent retroviral vector derived from Rous sarcoma virus (RSV), designated RCAS, was used for gene transfer of the murine VEGF (mVEGF) gene (mVEGF:RCAS) into the DF‐1 chicken cell line (designated mVEGF:DF‐1). Initially, the ability of VEGF:DF‐1 cells to produce VEGF and RCAS viral vectors containing the mVEGF gene (mVEGF:RCAS) was validated in vitro and in vivo, as was the ability of the mVEGF:DF‐1 cells to induce neovascularization in the ex ova CAM model. Using the system, we determined the ability of mVEGF:DF‐1 cells to enhance acetaminophen senor function in vivo, by inducing neovascularization at sites of sensor implantation in the ex ova CAM model. For these studies, acetaminophen sensors were placed on 8‐day‐old ex ova CAMs, followed by addition of media or cells (mVEGF:DF‐1 cells or GFP:DF‐1 cells) at the sites of biosensor implantation on the CAM. At 4 to 10 days after sensor placement, the biosensor function was determined by measuring sensor response to an intravenous injection of acetaminophen. Sensors implanted on CAMs with buffer or control cells (GFP:DF‐1 cells) displayed no induced neovascularization around the sensor and had minimal/baseline sensor responses to intravenous acetaminophen injection (media, 133.33 ± 27.64 nA; GFP:DF‐1, 187.50 ± 55.43 nA). Alternatively, the sensors implanted with mVEGF:DF‐1 cells displayed massive neovascularization and equally massive sensor response to intravenous injection of acetaminophen (VEGF:DF‐1, 1387.50 ± 276.42 nA). These data clearly demonstrate that enhancing vessel density (i.e., neovascularization) around an implanted sensor dramatically enhances sensor function in vivo. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1072–1086, 2003
Activation of calcineurin expression in ischemia‐reperfused rat heart and in human ischemic myocardium
Authors: Lakshmikuttyamma Ashakumary , Selvakumar Ponniah , Kakkar Rakesh , Kanthan Rani , Wang Rui , Sharma Rajendra K.
Published: November 2003

Calcineurin (CaN) has been reported as a critical mediator for cardiac hypertrophy and cardiac myocyte apoptosis. In the present study, we investigated the activity and expression of CaN and the effect of calpain in rat heart after ischemia and reperfusion. Rat ischemic heart showed significant increase in CaN activity. Western blot analysis of normal rat heart extract with a polyclonal antibody raised against bovine CaN indicated a prominent immunoreactive band of 60 kDa (CaN A). In ischemic‐reperfused hearts, the expression of CaN A was significantly low and immunoreactivity was observed in proteolytic bands of 46 kDa. This may be due to the proteolytic degradation of CaN A in ischemic tissues by m‐calpain. We also noticed in vitro proteolysis of bovine cardiac CaN A by m‐calpain. Immunohistochemical studies showed strong staining of immunoreactivity in rat hearts that had gone under 30 min ischemia followed by 30 min reperfusion similar to that found in human ischemic heart. Ischemia is associated with multiple alterations in the extracellular and intracellular signaling of cardiomyocytes and may act as an inducer of apoptosis. The increase in CaN activity and strong immunostaining observed in ischemic/perfused rat heart may be due to the calpain‐mediated proteolysis of this phosphatase. © 2003 Wiley‐Liss, Inc.
Bcl‐2 prevents hypoxia/reoxygenation‐induced cell death through suppressed generation of reactive oxygen species and upregulation of Bcl‐2 proteins
Authors: Saitoh Yasukazu , Ouchida Rika , Miwa Nobuhiko
Published: November 2003

The function of bcl‐2 in preventing cell death is well known, but the mechanisms whereby bcl‐2 functions are not well characterized. One mechanism whereby bcl‐2 is thought to function is by alleviating the effects of oxidative stress upon the cell. To examine whether Bcl‐2 can protect cells against oxidative injury resulting from post‐hypoxic reoxygenation (H/R), we subjected rat fibroblasts Rat‐1 and their bcl‐2 transfectants b5 to hypoxia (5% CO2, 95% N2) followed by reoxygenation (5% CO2, 95% air). The bcl‐2 transfectants exhibited the cell viability superior to that of their parent non‐transfectants upon treatment with reoxygenation after 24‐, 48‐, or 72‐h hypoxia, but not upon normoxic serum‐deprivation or upon serum‐supplied hypoxic treatment alone. Thus bcl‐2 transfection can prevent cell death of some types, which occurred during H/R but yet not appreciably until termination of hypoxia. The time‐sequential events of H/R‐induced cell death were shown to be executed via (1) reactive oxygen species (ROS) production at 1–12 h after H/R, (2) activation of caspases‐1 and ‐3, at 1–3 h and 3–6 h after H/R, respectively, and (3) loss of mitochondrial membrane potential (ΔΨ) at 3–12 h after H/R. These cell death‐associated events were prevented entirely except caspase‐1 activation by bcl‐2 transfection, and were preceded by Bcl‐2 upregulation which was executed as early as at 0–1 h after H/R for the bcl‐2 transfectants but not their non‐transfected counterpart cells. Thus upregulation of Bcl‐2 proteins may play a role in prevention of H/R‐induced diminishment of cell viability, but may be executed not yet during hypoxia itself and be actually operated as promptly as ready to go immediately after beginning of H/R, resulting in cytoproteciton through blockage of either ROS generation, caspase‐3 activation, or ΔΨ decline. © 2003 Wiley‐Liss, Inc.
Relationships between coping style and PAI profiles in a community sample1
Authors: Deisinger Julie A. , Cassisi Jeffrey E. , Whitaker Sandra L.
Published: November 2003

Relationships between coping style and psychological functioning were examined in a heterogeneous community sample (N = 168). Psychological functioning was categorized with the Personality Assessment Inventory (PAI; Morey, 1991). Subjects were assigned to PAI configurai profile clusters, using T‐scores from PAI clinical scales. Three PAI clusters were prominent in this sample: normal, anxious, and eccentric. Multivariate analysis of covariance revealed that these clusters differed significantly in coping style, as measured by the dispositional format of the COPE Inventory (Carver, Scheier, & Weintraub, 1989). Normals coped through avoidance significantly less than anxious or eccentric subjects. Also, normals engaged in seeking social support and venting more than eccentric but less than anxious subjects. Gender differences also were noted, with women more likely to cope by seeking social support and men more likely to cope through hedonistic escapism. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
Comparing two self‐report measures of coping— the Sense of Coherence Scale and the Defense Style Questionnaire1
Authors: Sammallahti Pirkko R. , Holi Matti J. , Komulainen Erkki J. , Aalberg Veikko A.
Published: November 2003

Antonovsky's Sense of Coherence Scale (SOC) and Bond's Defense Style Questionnaire (DSQ) were compared in a sample of 334 community controls and 122 psychiatric outpatients. The major question was, whether the two coping inventories with different theoretical backgrounds—stress research vs. psychoanalysis—tap similar phenomena. The affinity of the two coping measures was evident: in multiple regression analysis defenses explained 68% of the variance in sense of coherence. Not surprisingly, the SOC scale—emerging out of the salutogenic orientation—showed more expertise in measuring how people manage when they do well, whereas the DSQ—with its theoretical roots deep in psychopathology—was most sensitive to how people manage when they do rather poorly. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
Red flags and religious coping: Identifying some religious warning signs among people in crisis1
Authors: Pargament Kenneth I. , Zinnbauer Brian J. , Scott Allie B. , Butter Eric M. , Zerowin Jill , Stanik Patricia
Published: November 2003

This study attempts to identify some of the signs of ineffective religious involvement in coping. Drawing from a process/integration model of efficacious coping, three broad types of religious warning signs were defined and 11 subscales were developed. These subscales were administered to a group of Roman Catholic church members and two groups of college undergraduates who had experienced different types of negative life events in the past two years. Statistical analyses were conducted to determine the relationship between these subscales and measures of general mental health and event specific outcome. The theoretical and practical implications of these results are considered. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
Use of the Coping Inventory for Stressful Situations in a clinically depressed sample: Factor structure, personality correlates, and prediction of distress1
Authors: McWilliams Lachlan A. , Cox Brian J. , Enns Murray W.
Published: November 2003

The Coping Inventory for Stressful Situations (CISS; Endler & Parker, 1990) is a self‐report measure of Emotion‐, Task‐, and Avoidance‐oriented coping. The psychometric properties of the CISS were evaluated in a large sample of outpatients with major depressive disorder (N = 298). The CISS scales demonstrated good reliability and support for their factorial validity was obtained. Relationships between the CISS scales and the broad personality domains from the five‐factor model of personality, as well as two measures of emotional distress, were examined. Less‐adaptive coping strategies (i.e., Emotion‐oriented coping) were associated with less‐adaptive personality traits (i.e., Neuroticism) and with psychological distress (i.e., Depression), whereas the reverse was found regarding adaptive coping strategies (i.e., Task‐orientated coping). The incremental validity of the CISS was demonstrated by multiple‐regression analyses that found two CISS scales accounted for significant variance in psychological distress beyond that contributed by the demographic and personality variables. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
A posteriori error approximation in EFG method
Authors: Gavete L. , Gavete M. L. , Alonso B. , Martín A. J.
Published: November 2003

Recently, considerable effort has been devoted to the development of the so‐called meshless methods. Meshless methods still require considerable improvement before they equal the prominence of finite elements in computer science and engineering. One of the paths in the evolution of meshless methods has been the development of the element free Galerkin (EFG) method. In the EFG method, it is obviously important that the ‘a posteriori error’ should be approximated.

An ‘a posteriori error’ approximation based on the moving least‐squares method is proposed, using the solution, computed from the EFG method. The error approximation procedure proposed in this paper is simple to construct and requires, at most, nearest neighbour information from the EFG solution. The formulation is based on employing different moving least‐squares approximations. Different selection strategies of the moving least‐squares approximations have been used and compared, to obtain optimum values of the parameters involved in the approximation of the error.

The performance of the developed approximation of the error is illustrated by analysing different examples for two‐dimensional (2D) potential and elasticity problems, using regular and irregular clouds of points. The implemented procedure of error approximation allows the global energy norm error to be estimated and also provides a good evaluation of local errors. Copyright © 2003 John Wiley & Sons, Ltd.
A method for structural dynamic contact problems with friction and wear
Authors: Strömberg Niclas
Published: November 2003

A method for structural dynamic contact problems with friction and wear is suggested. The method is obtained by including wear in the non‐smooth contact dynamics method of Moreau. A comparison of the method to the discrete energy‐momentum method of Simo and Tarnow is also outlined briefly. The fully discrete equations are treated using the augmented Lagrangian approach, where a non‐smooth Newton method is used as the equation solver. Two two‐dimensional examples are solved by the method. It is investigated how solutions of contact, friction and wear are influenced by inertia. It is shown that the quasi‐static assumption might be questionable for solving contact problems with friction and wear. Copyright © 2003 John Wiley & Sons, Ltd.
Treatment satisfaction and metabolic outcome in patients with type 2 diabetes starting insulin: one‐to‐one vs group therapy
Authors: Erskine PJ , Idris I , Daly H , Scott AR
Published: November 2003

The UK Prospective Diabetes Study (UKPDS) confirmed that intensive therapy resulting in optimal glycaemic control (HbA1C7%) reduces the risk of microvascular complications in patients with type 2 diabetes. The understanding that type 2 diabetes is a progressive disease has resulted in many patients being converted from tablets to insulin following secondary failure of hypoglycaemic agents. Recognising the need for early intervention, increasing numbers of patients are being referred from primary care for initiation of insulin therapy. To cope with this increase in demand, group education insulin starter groups were introduced at our centre in 1999.

The aim of this study was to retrospectively compare the one‐year outcome in terms of metabolic and treatment satisfaction parameters for all patients with type 2 diabetes who were converted to insulin conventionally in a one‐to‐one setting with a diabetes specialist nurse (1997–1998) or via group education insulin starter groups (1999–2000).

Records of consecutive patients with type 2 diabetes, converted to insulin during 1997–1998 (conventional one‐to‐one group) and 1999–2000 (insulin starter group) were audited for baseline parameters and one‐year follow‐up outcomes. Treatment satisfaction was measured using the Diabetes Treatment Satisfaction Questionnaire (DTSQ).

Both conventional one‐to‐one (n=64) and insulin starter group (n=69) therapy were equally matched for age, duration of diabetes and initial weight. Initial glycaemic control was significantly higher with one‐to‐one teaching compared with group therapy (fructosamine 479±99µmol/L vs 439±82µmol/L respectively, p=0.01). At one year, glycaemic control was similar for both groups (one‐to‐one 381±72µmol/L vs insulin starter group 397±76µmol/L, p=NS). Similar numbers of patients in both groups achieved target glycaemic control of <350µmol/L fructosamine. General treatment satisfaction in the insulin starter group setting (30.4±7) was significantly greater than one‐to‐one teaching (26.9±8, p=0.001), out of a maximum score of 36, measured using the DTSQ.

In conclusion, conversion to insulin can be successfully achieved through group sessions, with patients reporting greater treatment satisfaction than those receiving one‐to‐one teaching. Copyright © 2003 John Wiley & Sons, Ltd.
Hypertension in diabetes: what's new, what's true, what's next?
Authors: Perry CG , Kernohan AFB , Petrie JR
Published: November 2003

Until recently, people with type 2 diabetes were excluded from hypertension trials and diabetes care ignored the importance of managing hypertension, instead focusing exclusively on glycaemia. However, recent large clinical trials have confirmed that tight blood pressure control is central to the management of type 2 diabetes and compares favourably with good glycaemic control. Here we review the evidence base that has emerged from these trials and consider the implications for improving the care of people with diabetes. Copyright © 2003 John Wiley & Sons, Ltd.
Running a nurse‐led hypertension clinic to empower patients and achieve blood pressure targets
Authors: Trowbridge S , Cavan D , Kerr D
Published: November 2003

At Bournemouth, we have developed a blood pressure service for patients with diabetes and established complications, which aims to empower patients to take responsibility for their heath. High‐risk patients with diabetes and hypertension are able to monitor their blood pressure and adjust their medicaton competently when given clear instructions and education. Patients are likely to require up to three antihypertensive drugs to manage their blood pressure. Copyright © 2003 John Wiley & Sons, Ltd.
Use of fluoride oxalate tubes to monitor the accuracy of home capillary glucose measurements during pregnancy
Authors: Stanaway SERS , Schofield CE , Nicholson A , Smethurst P , Ewins DL , Worth RC
Published: November 2003

Tight control of glycaemia during gestation is the mainstay of antenatal care in women with diabetes. This relies heavily on blood glucose monitoring. A simple technique for assessing the accuracy of the patients' own blood glucose monitoring is described. The method involves patients collecting a few drops of blood in fluoride oxalate‐coated plastic capillary tubes, which they store in their own refrigerator before delivery for laboratory analysis on the day of the antenatal clinic assessment. The readings can be compared with blood glucose monitor readings recorded by the patient and subsequently used by clinicians and nurses to guide therapy. Copyright © 2003 John Wiley & Sons, Ltd.
Maternal hyperglycaemia – food for thought
Authors: Dornhorst A
Published: November 2003

Improvements in obstetric and diabetic care over the last fifty years have ensured that the majority of diabetic women today give birth to a live and healthy infant. However, there is increasing evidence that these children undergo metabolic adaptation in utero, due to maternal hyperglycaemia, which predisposes them to future obesity and type 2 diabetes. With the rise in the prevalence of type 2 diabetes among women of child‐bearing age, the number of pregnancies affected by maternal hyperglycaemia will continue to increase. In the Native American population, maternal hyperglycaemia has been shown to be a major contributor to adolescent obesity and type 2 diabetes. To what extent maternal hyperglycaemia is fuelling the global rise in obesity and type 2 diabetes is unknown, but on available evidence its contribution is likely to be highly significant. Copyright © 2003 John Wiley & Sons, Ltd.
Chronic malaise in uncontrolled type 2 diabetes due to obstructive sleep apnoea
Authors: Large DM , Routledge A , Cowley ML , Mustchin CP , Gibson GJ
Published: November 2003

A 57‐year‐old morbidly obese man with type 2 diabetes for five years, poorly controlled on gliclazide therapy, was referred with hyperglycaemic symptoms including severe daytime malaise and weariness. Features of obstructive sleep apnoea syndrome (OSA) were identified, and confirmed by limited polysomnography. Treatment with nocturnal nasal continuous positive airways pressure (CPAP) was instituted with dramatic relief of daytime symptoms, including morning headaches and also nocturia, which might otherwise have been attributed to changes in blood glucose. Copyright © 2003 John Wiley & Sons, Ltd.
An educational class on diabetes self‐management during Ramadan
Authors: Chowdhury TA , Hussain HA , Hayes M
Published: November 2003

All healthy Muslims are required to fast during the month of Ramadan. Diabetes is common among UK Muslims, and poses a considerable challenge for such patients, who feel the spiritual need to fast. Many patients, particularly those on insulin therapy, require considerable advice and support to manage their fast during the month of Ramadan. In our unit, around 50% of our patients with type 2 diabetes are of Bangladeshi origin. In this article, we describe a Patient Group Education Class for management of diabetes over Ramadan. Copyright © 2003 John Wiley & Sons, Ltd.
Improving polyethylene–octene elastomer/chitosan by graftation of acrylic acid onto polyethylene–octene elastomer—mechanical properties and biodegradability examination and composites characterization
Authors: Wu Chin‐San
Published: November 2003

In this study, the properties of polyethylene–octene elastomer/chitosan (POE/chitosan) and acrylic acid (AA)‐grafted‐polyethylene–octene elastomer/chitosan (POE‐g‐AA/chitosan) were examined using various characterizing instruments. Mechanical and thermal properties of POE deteriorated noticeably when it was blended with chitosan, due to the unsatisfactory compatibility between the two phases. The greater compatibility of POE‐g‐AA with chitosan, due to the formation of ester carbonyl and imide groups, led to a much better dispersion and homogeneity of chitosan in the POE‐g‐AA matrix and consequently to noticeably better mechanical properties. Furthermore, with a lower melting point temperature, the POE‐g‐AA/chitosan blend was more easily processed than POE/chitosan. POE‐g‐AA/chitosan had a higher water resistance than POE/chitosan. Both blends suffered weight loss when buried in soil, especially at high levels of chitosan substitution, indicating that both were biodegradable. The mechanical properties of both blends, such as tensile strength and elongation at break, also deteriorated after being buried in soil. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3882–3891, 2003
Mechanism and kinetics of the crosslinking reaction between biopolymers containing primary amine groups and genipin
Authors: Butler Michael F. , Ng Yiu‐Fai , Pudney Paul D. A.
Published: November 2003

The reaction mechanism of chitosan, bovine serum albumin (BSA), and gelatin with genipin (a natural crosslinking reagent) was examined with infrared, ultraviolet–visible, and 13C NMR spectroscopies; protein‐transfer reaction mass spectrometry; photon correlation spectroscopy; and dynamic oscillatory rheometry. Two reactions that proceeded at different rates led to the formation of crosslinks between primary amine groups. The fastest reaction to occur was a nucleophilic attack on genipin by a primary amine group that led to the formation of a heterocyclic compound of genipin linked to the glucosamine residue in chitosan and the basic residues in BSA and gelatin. The second, slower, reaction was the nucleophilic substitution of the ester group possessed by genipin to form a secondary amide link with chitosan, BSA, or gelatin. A decreased crosslinking rate in the presence of deuterium oxide rather than water suggested that acid catalysis was necessary for one or both of the reactions to proceed. The behavior of the gel time with polymer concentration was consistent with second‐order gelation kinetics resulting from an irreversible crosslinking process, but was complicated by the oxygen radical‐induced polymerization of genipin that caused the gels to assume a blue color in the presence of air. The lower elastic modulus attained after a given time during crosslinking of the globular protein BSA as compared to the coiled protein gelatin, despite possessing more crosslinkable basic residues, demonstrated the importance of protein secondary and tertiary structures in determining the availability of sites for crosslinking with genipin in protein systems. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3941–3953, 2003