bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased blood pressure can reduce fatigue of thenar muscles paralyzed after spinal cord injury
Authors: Butler Jane E. , Ribot‐Ciscar Edith , Zijdewind Inge , Thomas Christine K.
Published: March 2004

The aim of this study was to evaluate whether increases in blood pressure, and presumably muscle perfusion pressure, improve the endurance of thenar muscles paralyzed chronically by cervical spinal cord injury (SCI). Resting mean arterial pressure (MAP) was low in all eight subjects (64 ± 2 mmHg). Muscle fatigue (force decline) was produced on 2 days by intermittent supramaximal electrical stimulation of the median nerve at 20 Hz for 2 min. During one of the fatigue tests, a concurrent sustained voluntary contraction of the contralateral elbow flexors was used to increase resting MAP (by 22%, on average). Although this change in blood pressure resulted in no significant change in mean fatigue for the group, changes in MAP with exercise (median nerve stimulation with and without voluntary contraction) correlated with changes in thenar muscle fatigue in seven subjects. For every 10% increase in MAP, fatigue was reduced by ∼3%. The data suggest that low blood pressure after chronic cervical SCI and poor blood pressure control during exercise exacerbate the fatigability of paralyzed muscles. Muscle Nerve 29: 575–584, 2004
Carpal tunnel syndrome with normal nerve conduction studies
Authors: Witt John C. , Hentz Joseph G. , Stevens J. Clarke
Published: March 2004

The utility of electrodiagnostic testing in the evaluation of carpal tunnel syndrome (CTS) has been questioned. We studied patients who met the clinical criteria for CTS and compared patients who had normal nerve conduction studies (NCS) with patients who had abnormal NCS. We found that 25% of the CTS patients without confounding neurologic disorders had normal NCS with median palmar nerve stimulation. Patients with abnormal NCS were older and heavier and had more clinical features of CTS. NCS results could not be predicted accurately from clinical features by use of logistic regression models. This was especially true in clinically borderline cases. NCS did not predict the outcome of conservative management. We concluded that NCS provide independent information in the evaluation of suspected CTS, especially when fewer clinical criteria are present, but that NCS are not helpful in predicting the outcome of nonsurgical management. Muscle Nerve 29: 515–522, 2004
Attenuation of free radical production and paracrystalline inclusions by creatine supplementation in a patient with a novel cytochrome b mutation
Authors: Tarnopolsky Mark A. , Simon David K. , Roy Brian D. , Chorneyko Kathy , Lowther Stuart A. , Johns Donald R. , Sandhu Jagdeep K. , Li Yan , Sikorska Marianna
Published: March 2004

Mitochondrial cytopathies are associated with increased free radical generation and paracrystalline inclusions. Paracrystalline inclusions were serendipitously found in a young male athlete with a very high respiratory exchange ratio during steady‐state exercise; he also had an unusually low aerobic capacity. Direct sequencing of the mitochondrial DNA (mtDNA) coding regions revealed a novel missense mutation (G15497A) resulting in a glycine→serine conversion at a highly conserved site in the cytochrome b gene in the subject, his mother, and sister. Cybrids, prepared by fusion of the subject's platelets with either U87MG ρ° or SH‐SY5Y ρ° cells, generated higher basal levels of reactive oxygen species (ROS), had a lower adenosine triphosphate (ATP) content, and were more sensitive to oxygen and glucose deprivation and peroxynitrite generation compared to control cybrids with wild‐type mtDNA. Cell survival was significantly enhanced with 50 mmol/L creatine monohydrate (CM) administration. The subject was also treated with CM (10 g/d) for a period of 5 weeks and a repeat muscle biopsy showed no paracrystalline inclusions. The results suggest that the development of exercise‐induced paracrystalline inclusions may be influenced by the G15497A mtDNA mutation, and that CM mitigates against the pathological consequences of this mutation. Muscle Nerve 29: 537–547, 2004
Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy
Authors: Van Den Bergh Peter Y. K. , Piéret Françoise
Published: March 2004

Electrodiagnosis plays an important role in the early detection and characterization of inflammatory demyelinating polyradiculoneuropathies, because timely treatment reduces morbidity and disability. The challenge consists of defining electrodiagnostic criteria that are highly specific for primary demyelination but sufficiently sensitive to be useful in clinical practice. We compared 10 published sets of criteria in 53 patients with demyelinating Guillain–Barré syndrome (GBS) and 28 with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Specificity of criteria sets was tested in 40 patients with amyotrophic lateral sclerosis (ALS) and 32 with diabetic polyneuropathy (DPN). Sensitivity ranged from 24 to 83% (mean, 54.3%) in GBS and 39 to 89% (mean, 64.9%) in CIDP. With regard to ALS, specificity was 100% for nine sets but was 97% in one. In contrast, 3–66% of DPN patients fulfilled criteria in eight of ten sets. We propose a set of criteria with 72% and 75% sensitivity in our GBS and CIDP patient series, respectively, and 100% specificity with regard to ALS and DPN. Our data illustrate that most, but not all, patients can be electrodiagnostically ascertained. Muscle Nerve 29: 565–574, 2004
Numerical simulation of flow over delta wing with trailing‐edge jet at high angle of attack
Authors: Zhang Z. K. , Tang H. S.
Published: March 2004

The incompressible Reynolds‐averaged Navier–Stokes equations, together with a modified mixing length algebraic turbulence model, are solved to simulate the flow over a delta wing with trailing‐edge jets at high angles of attack. An artificial compressibility method and a Beam–Warming implicit approximate factorization scheme are employed to discretize the equations. The computed results indicate that trailing‐edge jets tend to not only decrease the pressure but also increase the velocity at the cores of the streamwise primary vortices. This moves the vortex breakdown locations aft and stabilizes the vortical flow. As a result, the jets lead to a decreased pressure on the upper wing surface and an increased pressure on the lower wing surface, thereby increasing the overall lift. Computations further show that as the exit area of the trailing‐edge jets is enlarged, or, as the jets are deflected downward, the above‐mentioned effects become more pronounced. Copyright © 2004 John Wiley & Sons, Ltd.
Role of radiotherapy in Ewing tumors
Authors: Dunst Juergen , Schuck Andreas
Published: March 2004

Background

The objective of this review article is to outline the role of radiotherapy in a curative multimodal treatment concept.

Procedure

We have analyzed the data from major multi‐institutional prospective trials in Ewing tumors for to evaluate the impact of radiotherapy on local control and survival.

Results

Surgery yields in general better local control and survival figures as compared to radiotherapy. The efficacy of radiotherapy as compared to surgery varies among the studies and seems to be dependent on patient selection and sequencing with chemotherapy. Combined local therapy (surgery plus post‐ or pre‐operative radiotherapy) has yielded excellent local control rates in patients with high‐risk lesions (e.g., pelvic tumors); although not proven by randomized studies, an impact on survival is likely. Indications for post‐operative radiotherapy are unradical or marginal resections and poor histological response. In patients with chest wall primaries, adjuvant hemithorax irradiation has reduced the relapse rate significantly. Pre‐operative irradiation offers theoretical advantages. Bilateral lung irradiation (as consolidation after chemotherapy) seems to improve prognosis in patients with metastases at diagnosis.

Conclusions

Patients with high‐risk lesions probably benefit from combined local treatment (surgery plus radiotherapy). Improving local control after radiotherapy is a major issue for future studies, and sequencing with chemotherapy seems to be critical factor. The possible curative potential of radiotherapy in metastatic disease requires further investigation. © 2004 Wiley‐Liss, Inc.
Technical Aspects in Cerebrospinal Irradiation
Authors: Bernier Valérie
Published: March 2004

Background

Craniospinal irradiation (CSI) is commonly used for medulloblastoma patients and some others; for example, those with ependymoma. It is a complex technique where accuracy of field placement and choice of irradiation source and energy can play a major role in determining success or failure.

Procedure

A literature review of the techniques used and reported by treatment centers was undertaken.

Results

Great variability was found in methods and practices. This is striking because many hospitals treat fewer than five patients per year.

Conclusion

Standardized techniques with strict central review for quality control before therapy is initiated should become the norm. Standardization is especially important when clinical trials are planned. Valid outcome data depend on CSI uniformity. © 2004 Wiley‐Liss, Inc.
Measuring the neuro‐cognitive side‐effects of irradiation in children with brain tumors
Authors: Grill Jacques , Kieffer Virginie , Kalifa Chantal
Published: March 2004

Background

Reduction of the treatment‐related side effects has become one of the main goals of the recent study protocols for brain tumor therapies. When the treatment burden is decreased in patients with good prognostic features, the potential increased risk of relapse has to be counterbalanced by a significantly improved cognitive outcome. This objective is always clearly stated but comprehensive data on the neuropsychological outcomes are seldom reported.

Procedures and Results

The appropriate means to measure the long‐term morbidity need to be clarified. Health Status and Quality of Life (QOL) questionnaires can be easily administered but these questionnaires represent usually a composite evaluation where cognition is analyzed along with other items such as mood or pain. However, none of these questionnaires has ever been used to measure a difference in cognitive outcome when comparing two different therapeutic strategies in children. Complete neuropsychological evaluations are time consuming, need specialized psychologists and most of the tests have not been rigourously validated. In this respect, Wechsler scales are, however, robust and objective methods to evaluate intelligence. Several studies have been able to show meaningful differences in IQ scores between treatments in children with posterior fossa tumors, even with small numbers of patients.

Conclusions

In order to evaluate any refinement in the treatment of these patients, widely accepted evaluation tools are needed. Ideally, these methods will have to be sensitive, reproducible, and widely applicable. None of the available tools fullfil all of these criteria but their development should be a major endeavour in modern neuro‐oncology. © 2003 Wiley‐Liss, Inc.
Review of radiotherapy dose and volume for intracranial ependymoma
Authors: Taylor Roger E.
Published: March 2004

Background

Radiotherapy (RT) is well established in the management of intracranial ependymoma (EP) and post‐operative RT is employed for the majority of patients. There are no randomised trials of RT in EP and evidence for dose and volume relies on retrospective single institution series, usually comprising a heterogeneous mix of relatively small numbers of patients recruited over several decades.

Procedure

The literature including RT dose and response data reported since the early 1990s was reviewed.

Results

Five‐year overall survival (OS) ranges from 40 to 79%. There is some evidence of a dose response relationship from <45 Gy to >50 Gy. In the majority of series outcome is related to WHO grade and extent of resection. There is no evidence of benefit for ‘prophylactic’ craniospinal RT (CSRT). In all series there is a significant risk of local recurrence, usually within the target volume. Early results of conformal RT have suggested that a margin for CTV of 1 cm around the post‐operative tumour bed and any residual GTV is feasible.

Conclusions

The main aims of future studies will be to maximise the number of patients achieving complete resection, and RT dose escalation. Hyperfractionated radiotherapy (HFRT) has been employed in some studies and results are awaited. The role of CSRT needs to be evaluated further for patients presenting with leptomeningeal metastases. Multi‐institutional and international studies are necessary to improve understanding of the clinical behaviour, biology and management of EP. © 2004 Wiley‐Liss, Inc.
Ewing sarcoma: Radiation dose and target volume
Authors: Donaldson Sarah S.
Published: March 2004

Background

The outcome of children and adolescents with Ewing sarcoma is impacted by many prognostic factors and often measured by estimates of: event‐free, relapse‐free, disease‐free, or overall survival. However, the preferred assessment following radiation therapy is local control.

Procedure

A review of large group experiences over the past several decades was undertaken to assess the optimal radiation dose and volume for patients with localized, osseous Ewing sarcoma. New approaches and techniques to improve local control were also investigated.

Results

With multidisciplinary therapy, 5‐year overall local control rates range from 58 to 93%. Following definitive irradiation, they are 53–86%. Recommended radiation therapy doses are 55.8–60.0 Gy. In the postoperative setting, gross disease requires 55.8 Gy; microscopic disease requires 45 Gy. Altered fractionation schemes have not improved local control. The appropriate irradiated volume is an involved field to the pretreatment tumor volume plus 2.0–2.5 cm margin, followed by a boost to the post‐induction chemotherapy tumor volume with margin. Good radiation quality control with central review improves local control. Use of an involved radiation field requires accuracy in defining tumor volume. Techniques to improve local control include risk‐adapted multidisciplinary therapy, intraoperative boost radiation, and high radiation doses as delivered by 3‐dimensional conformal radiation. Intensity modulated and proton beam radiotherapy may offer an advantage at special sites.

Conclusions

Innovative uses of radiation in the multidisciplinary setting will continue to provide excellent local control, improved function, and quality of life for young patients with localized Ewing sarcoma of bone. © 2004 Wiley‐Liss, Inc.
Ewing sarcoma: The pediatrician's point of view
Authors: Marec‐Bérard Perrine , Philip Thierry
Published: March 2004

Background

Integrated multimodal care is needed for patients with Ewing sarcoma, which is the second most common primary bone malignancy in children and adolescence. Chemotherapy increases survival from less than 5% to 65–70% for patients with localized tumors and to 25–30% for those with metastases at diagnosis. Surgery is a major tool, whereas advances in imaging techniques have improved the indications for and the optimization of treatment. Radiotherapy remains useful, either alone or in addition to surgery, and new techniques (conformational RT and IMRT) will reduce short‐term toxic effects. Pediatric oncologists do not outweigh surgeons or radiation therapists, but they are the ones who coordinate the medical team, which also includes pathologists and imaging specialists.

Methods

The point of view of the pediatric oncologist was assessed as follows: the place of chemotherapy in Ewing tumor treatment, the place of radiotherapy in Ewing tumor treatment (including why avoid radiotherapy when technically possible in children), and how to proceed into the future? The place of surgery as local treatment for Ewing tumors was also evaluated.

Results

These reviews show a dynamic and kaleidoscopic panorama of intense activity at the laboratory and clinical levels.

Conclusions

Though good survival rates have been achieved, improvements using entirely new approaches are needed. © 2003 Wiley‐Liss, Inc.
Influence of Age Upon Ifosfamide‐Induced Nephrotoxicity
Authors: McCune Jeannine S. , Friedman Debra L. , Schuetze Scott , Blough David , Magbulos Madonna , Hawkins Douglas S.
Published: March 2004

Background

Ifosfamide‐induced nephrotoxicity is well recognized in children, although it has also been reported in adults. Whether ifosfamide nephrotoxicity is more common in children than in adults is not known.

Procedure

Medical records of adults and children diagnosed with sarcoma whom received ifosfamide with a cumulative dose >20 g/m2 were evaluated. Twenty‐five children (≤18‐years of age) and 28 adults were identified.

Results

National Cancer Institute Common Toxicity Criteria grade 3–4 ifosfamide‐induced nephrotoxicity was present in 24 and 17% of children and adults, respectively (P = 0.58). Cumulative ifosfamide doses were similar between the two populations, with the median (range) of 70.2 g/m2 (22.4–72) for children and 59 g/m2 (20.8–146) for adults (P = 0.25). Logistic regression analysis indicated that neither age or cumulative ifosfamide dose were associated with grade 3–4 ifosfamide‐induced nephrotoxicity (P = 0.36).

Conclusions

Children and adults receiving >20 g/m2 of ifosfamide have similar susceptibility to ifosfamide‐induced nephrotoxicity. Factors other than age and cumulative dose should be considered for understanding the inter‐individual variation in nephrotoxicity. © 2004 Wiley‐Liss, Inc.
Significance of serum immunoglobulin G for leukocytosis and prognosis in childhood B‐lineage acute lymphoblastic leukemia
Authors: Potapnev Michael P. , Belevtsev Michael V. , Bortkevich Ludmila G. , Grinev Vasily V. , Martsev Sergey P. , Kravchuk Zinaida I. , Migal Natalia V. , Aleinikova Olga V.
Published: March 2004

Background

This study was conducted to evaluate the significance of serum level of immunoglobulins (Igs) and particularly IgG for leukemic cell persistence in peripheral blood (PB) and prognosis for childhood acute lymphoblastic leukemia (ALL).

Procedure

Human sera were obtained from 68 children with primary B‐lineage ALL at diagnosis and 46 healthy children (control). Serum level of IgM, IgG, IgA, IgG1, IgG2, IgG3, IgG4, antitumor antibody, homogeneous IgG were quantified by turbidimetric or enzyme‐linked immunosorbent assays.

Results

The mean values of serum IgM, IgG, IgA at diagnosis were not differed significantly in ALL patients and control children. The level of IgM and IgG1 inversely correlated with white blood cell (WBC) count in PB of patients. Normal range of serum IgG, separated by 25th and 75th percentiles of IgG variables, was associated in patients with decreased WBC count in PB but not in bone marrow (BM) versus patients with low concentration of IgG. Normal range of IgG also favors low frequency of homogeneous IgG and antitumor antibodies. Patients with high level of IgG, besides increased frequency of homogeneous IgG and antitumor antibodies, had worse 3‐year overall survival (OS) rate as compared to patients with normal level of IgG (58.8 vs. 91.2%, P = 0.014).

Conclusions

The normal level of serum IgG at diagnosis is a beneficial prognostic factor associated with lower rate of leukemic cell persistence in PB and better outcome of childhood B‐lineage ALL. © 2004 Wiley‐Liss, Inc.
Permanent consequences in Langerhans cell histiocytosis patients: A pilot study from the Histiocyte Society—Late Effects Study Group
Authors: Haupt Riccardo , Nanduri Vasanta , Calevo Maria Grazia , Bernstrand Cecilia , Braier Jorge L. , Broadbent Valerie , Rey Guadalupe , McClain Kenneth L. , Janka‐Schaub Gritta , Egeler R. Maarten
Published: March 2004

Background

Permanent consequences (PC) are often described among subjects with Langerhans cell histiocytosis (LCH) but data on the real incidence are scarce. Within the Histiocyte Society (HS), and in order to design a definitive late effects study, a retrospective survey was organized to describe the prevalence of PC among long‐term survivors of LCH.

Methods

Nine institutions contributed with their LCH patients having a minimum follow‐up of 3 years. Information was collected on their disease‐history, and on type and date of onset of any PC. Because of the retrospective type of this study, it was accepted that each institution might have used different criteria to assess PC.

Results

One hundred eighty‐two subjects were registered and in 95 (52%) at least 1 PC was reported. For some specific PC (e.g., anterior pituitary dysfunction) information was too scarce to provide reliable data. PC were more frequent among subjects with multisystem (MS) disease (71%), compared to those with single system (SS) disease (24%); P < 0.0001. The most frequently reported PC were diabetes insipidus (DI) (24%) orthopedic abnormalities (20%), hearing loss (13%), and neurological consequences (11.0%). Analysis of cumulative risk showed that some types of PC may become manifest more than 10 years from diagnosis.

Conclusions

This survey on selected cases of LCH survivors has confirmed that late sequels are frequent, and that they are even more common among those with MS LCH. Our findings highlight the need for long‐term and patient‐oriented follow‐up in children with LCH. © 2004 Wiley‐Liss, Inc.
Tumor cells are present in stem cell harvests of Ewings sarcoma patients and their persistence following transplantation is associated with relapse
Authors: Yaniv I. , Cohen I.J. , Stein J. , Zilberstein J. , Liberzon E. , Atlas O. , Grunshpan A. , Sverdlov Y. , Ash S. , Zaizov R. , Avigad S.
Published: March 2004

Background

Tumor cells frequently contaminate autologous stem cell products in a variety of malignancies, but their clinical significance remains controversial. We retrospectively monitored tumor contamination in stem cell harvests from patients with Ewing family of tumors (EFT) all harboring the specific translocation EWS‐FLI‐1 that characterize these tumors.

Procedure

Twenty‐ seven harvests from 11 patients were included in the study. In addition, 6 and 19 bone marrow (BM) or peripheral blood (PBL) samples were available before and after transplantation, respectively, for RT‐PCR and nested PCR analyzes.

Results

All 11 patients had contaminating tumor cells in their harvests. All samples prior to transplantation were RT‐PCR positive. Two out of the 11 patients who underwent transplantation died of complications. Out of the remaining nine patients, two are alive and well 68 and 84 months from diagnosis, and are the only patients with no detectable tumor cells in their samples after transplantation. One of these patients harbored contaminating tumor cells in only one of the two harvests collected. Seven patients relapsed after transplant, and in four patients BM/PBL samples were available prior to the clinical relapse. All these samples harbored contaminating tumor cells.

Conclusions

We suggest a possible correlation between the amount of contaminating cells in the harvest and relapse after transplantation. Quantitative RT‐PCR studies of the chimeric transcripts are underway to explore this issue. © 2004 Wiley‐Liss, Inc.
Tensile properties of cellulose fiber reinforced hydroxypropylcellulose films
Authors: Borges J. P. , Godinho M. H. , Martins A. F. , Stamatialis D. F. , de Pinho M. N. , Belgacem M. N.
Published: March 2004

The tensile properties of cross‐linked and uncross‐linked composite films (thickness ∼20–35 μm) prepared from Hydroxypropylcellulose (HPC) with incorporation of microcrystalline cellulose fibers (Avicel) were studied. The concentration of fibers in the composites ranged from 0 to 30 w/w% and cross‐linked composites were obtained by the reaction of HPC‐Avicel mixtures with 1,4‐butyldiisocyanate. It was demonstrated that the inclusion of fibers in a HPC matrix produces composites with enhanced mechanical properties that are improved by cross‐linking. Mechanical results seem to indicate that the elastic deformation of the cross‐linked composites is predominantly dominated by the fiber content while the cross‐linking affects mainly the plastic deformation. Maximum values of the Young's Modulus, yield stress and tensile stress were observed at 10 w/w% for the cross‐linked and 20 w/w% for the uncross‐linked composites. Furthermore cross‐linked films with 10 w/w% of fibers present values of yield stress and tensile stress that are in average 15 to 20% higher than those obtained for uncross‐linked composites with 20 w/w% of fibers. Studies in Polarizing Optical Microscopy and Atomic Force Microscopy (AFM) seem to indicate that tensile properties of these composites are correlated to the packing of fibers. For the concentration of the utilized cross‐linking agent, and for a fiber content of 10 w/w%, an optimal packing of fibers throughout the matrix has been correlated to the minimal difference between the roughness parameters obtained by AFM analysis of the top and bottom surfaces of the films.
Primary diabetes care: yesterday, today and tomorrow
Authors: Kenny C
Published: March 2004

Starting in the early 1970s general practitioners (GPs) in the United Kingdom developed diabetes clinics in their practice. Momentum was initially slow, but following the 1990 GP contract and the St Vincent Declaration, GPs were encouraged to take more responsibility for diabetes care. The 1997 contract provided further impetus for this, and primary care organisations were developed. Throughout this time there was a realisation that it was important to apply best evidence to primary diabetes care. The United Kingdom Prospective Diabetes Study was an impetus for GPs to improve care and changed the emphasis of care from solely blood sugar management to a wider cardiovascular risk assessment in people with diabetes.

At the beginning of this decade the Scottish Intercollegiate Guideline Network, National Institute for Clinical Excellence and American Diabetes Association guidelines for diabetes management were published setting out best practice. Each of the four nations in the United Kingdom then published national service framework (NSF) documents outlining best practice. In 2003, GPs voted for a new General Medical Services contract. This will introduce formalised payments for quality work in practice and will encourage GPs and their practice nurses to follow protocols adapted from these guidelines and NSFs and apply best evidence to their patients.

In the future, the numbers of patients with diabetes will increase as will the workload. Further innovative measures will have to be adopted to cope with this epidemic. Primary care will remain vital for information gathering, follow up, management and probable screening for diabetes, with patients encouraged to be empowered to understand and manage their condition. Copyright © 2004 John Wiley & Sons, Ltd.
Diabetes care in Slovenia: now and in the future
Authors: Urbancic V , Koselj M
Published: March 2004

Slovenia has about two million inhabitants: the estimated total number of diabetic patients is approximately 100‐000 (prevalence circa 5%). The first specialised hospital diabetes department was established in 1945. Today, diabetes health care is delivered at primary, secondary and tertiary health care levels. Patients on diet and exercise or oral hypoglycemic agents are treated by general practitioners and those on insulin by specialist diabetologists. Specialist out‐patient diabetes clinics are held at all general hospitals. A structured foot care prevention and treatment programme is running at the majority of out‐patient diabetes clinics, as well as screening for retinopathy. Renal dialysis is available throughout the country for those patients with end‐stage renal failure. A specialised clinic for diabetic pregnancy has been set up at the University Hospital in Ljubljana. Diabetic health care in Slovenia is provided free of charge.

The Slovenian Endocrinology Association (which brings together physicians engaged in diabetology), the Slovenian Nurse Endocrinology and Diabetology Association, and the Slovenian Diabetic Foot Working Group were established in 1970, 1988 and 1995, respectively. Postgraduate diabetology courses for doctors have been run since 1982, and for nurses since 1996; diabetic foot training courses have been held since 1995. In addition, countrywide there are 39 diabetic patients' societies which are united under the umbrella of the Slovenian Diabetic Association. Copyright © 2004 John Wiley & Sons, Ltd.
Compression behavior of pulp fiber networks
Authors: Lundquist L. , Willi F. , Leterrier Y. , Månson J.‐A. E.
Published: March 2004

The forced compression behavior of random 3D and 2D pulp fiber networks is investigated. Existing theories are found to describe well the evolution of packing stress with fiber volume fraction for the pulp networks. It was moreover found that the packing behavior of an initially random 3D network of pulp fibers does not go through a transition to a 2D network packing behavior as it is compressed. Rather, the fibers exhibit localized collapse at contact points, a result of the hollow nature of the pulp fibers. The implications of this phenomena on the overall packing response was further examined by means of compression tests performed on a series of representative tubes of varying wall thickness. This analysis allowed determining the pressure range within which localized fiber buckling takes place.
Investigation of fundamental data for nitrile butadiene rubber in monochlorobenzene and o‐dichlorobenzene
Authors: Pan Qinmin , Rempel Garry L.
Published: March 2004

Fundamental data, including density and rheological behavior, of nitrile butadiene rubber in solutions of monochlorobenzene and o‐dichlorobenzene were investigated, under a wide range of experimental conditions, including operation temperatures and polymer concentrations up to 165°C and 20% (wt), respectively. Shear rates of up to 1300/s were used for the measurement of rheological behavior. Within the range of the operational conditions employed, the solutions of nitrile butadiene rubber show Newtonian fluid behavior. A characteristic viscosity is proposed as a model parameter to correlate the viscosity of the NBR solutions. As a result, empirical correlation equations for density and viscosity are formed. The purpose of this work is to provide fundamental data for process development of the solution hydrogenation of nitrile butadiene rubber.
Crystallization kinetics of poly(L‐lactide) in contact with pressurized CO2
Authors: Takada Mitsuko , Hasegawa Shigeki , Ohshima Masahiro
Published: March 2004

The effect of CO2 on the isothermal crystallization kinetics of poly(L‐lactide), PLLA, was investigated using a high‐pressure differential scanning calorimeter (DSC), which can perform calorimetric measurements while keeping the sample polymer in contact with pressurized CO2. It was found that the crystallization rate followed the Avrami equation. However, the crystallization kinetic constant was changed depending upon the crystallization temperature and concentration of CO2 dissolved in the PLLA. The crystallization rate was accelerated by CO2 at the temperature in the crystal‐growth rate controlled region (self‐diffusion controlled region), and depressed in the nucleation‐controlled region. CO2 has also decreased the glass transition temperature, Tg, and the melting temperature, Tm. As a result, the CO2‐induced change in the crystallization rate can be predicted from the magnitudes of depression of both Tg and the equilibrium melting temperature. The crystalline structure and crystallinity of polymers crystallized in contact with pressurized CO2 were also investigated using a wide angle X‐ray diffractometer (WAXD). The resulting crystallinity of the sample was increased with the pressure level of CO2, although the presence of CO2 did not change the crystalline structure.
UV‐ignited frontal polymerization of an epoxy resin
Authors: Mariani Alberto , Bidali Simone , Fiori Stefano , Sangermano Marco , Malucelli Giulio , Bongiovanni Roberta , Priola Aldo
Published: March 2004

By combining frontal polymerization and radical‐induced cationic polymerization, it was possible to cure thick samples of an epoxy monomer bleached by UV light. The effect of the relative amounts of cationic photoinitiator and radical initiator was thoroughly investigated and was related to the front's velocity and its maximum temperature. The materials obtained were characterized by quantitative conversion also in the deeper layers, not reached by UV light. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2066–2072, 2004
Autonomic healing of a pinhole in polyethylene and photografted polyethylene‐g‐poly(hexyl methacrylate) films
Authors: Shimada Shigetaka , Takahasi Yasunori , Sugino Yusuke , Hara Shigeo , Yamamoto Katsuhiro
Published: March 2004

The structural changes of polyethylene (PE) and photografted polyethylene‐g‐poly(hexyl methacrylate) (PE‐g‐PHMA) with the mechanical formation of pinholes were evaluated with differential scanning calorimetry, wide‐angle X‐ray scanning, and small‐angle X‐ray scanning. The crystallinity and the long period of the lamella increased with pricking under extremely high compression stress. The partial transformation of an orthorhombic crystal into a monoclinic one was also detected. The autonomic healing of pinholes in PE and PE‐g‐PHMA was studied in detail. The degree of healing increased with an increase in the grafting ratio of poly(hexyl methacrylate) (PHMA). Three mechanisms for the healing were investigated and related to the molecular motions of PE and PHMA grafted chains, which were evaluated with dynamic mechanical analyses. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1705–1714, 2004
Crystalline morphologies in segmented copolymers with hard segments of uniform length
Authors: Sauer Bryan B. , McLean R. Scott , Gaymans Reinoud J. , Niesten Meike C. J. E.
Published: March 2004

The crystal morphological properties of segmented poly(ether ester aramide) elastomers with aromatic hard‐segment amide units of uniform length were studied. Four samples with hard‐segment fractions ranging from 3.4 to 9 wt % were studied by tapping atomic force microscopy (AFM). For one sample, both solution and melt‐processed surfaces were examined, and similar crystal morphologies were found. The semicrystalline morphologies of these polymers had some similarities to other low‐hard‐segment segmented elastomers. The very thin needlelike or ribbonlike crystallites at the surface had a high aspect ratio for all the samples. The main difference observed for the different compositions was a decrease in the surface area density of ribbons with a decrease in the hard‐segment fraction. One sample was chosen for in situ AFM studies during film extension. The details of the crystallite orientation and breakup were studied in increments up to 700% elongation (8× stretch ratio) and after relaxation. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1783–1792, 2004
Psychometric refinement of an outpatient, visit‐specific satisfaction with doctor questionnaire
Authors: Loblaw D. Andrew , Bezjak Andrea , Singh P. Mony , Gotowiec Andrew , Joubert David , Mah Kenneth , Devins Gerald M.
Published: March 2004

Measuring patient's satisfaction with their physician is gaining interest but requires a questionnaire that is valid, reliable and acceptable to patients. We previously published a self‐administered visit‐specific satisfaction with physician questionnaire for cancer patients. Eighty outpatients at a Canadian Cancer Center completed the Princess Margaret Hospital Patient Satisfaction with Doctor Questionnaire and the FACT‐G questionnaires along with demographic information just after clinic visit and again 3–5 days later. Exploratory factor analysis extracted two factors, labeled ‘physician disengagement’ and ‘perceived support,’ with average coefficient alpha values of 0.93 and 0.90. Test–retest reliability was 0.83 and 0.73, respectively, for the two factors. Confirmatory factor analysis applied to the data from 174 patients in the original study indicated excellent goodness of fit. PMH/PSQ‐MD correlated moderately with FACT‐G (average r=0.37, p<0.005). The PMH/PSQ‐MD questionnaire is a brief, valid and reliable questionnaire that taps two complementary facets of patient satisfaction. Copyright © 2003 John Wiley & Sons, Ltd.
Coping responses following breast cancer diagnosis predict psychological adjustment three years later
Authors: Hack Thomas F. , Degner Lesley F.
Published: March 2004

The relationship between coping responses and psychological adjustment to a breast cancer diagnosis is well documented for time periods close to diagnosis. The purpose of the present study was to assess the long term association between these two variables. Fifty‐five women completed measures of coping response, decisional control, frustration expression, and psychological adjustment within six months of receiving their breast cancer diagnosis. These women were contacted three years later and their psychological adjustment—as measured by the profile of mood states (POMS)—was reassessed. Univariate and multivariate analyses were performed. The results showed that women who were depressed at time of treatment planning, and who responded to their cancer diagnosis with cognitive avoidance, i.e. acceptance/resignation, had significantly worse psychological adjustment three years later. Poor adjustment was significantly associated with cognitive avoidance and minimal use of approach‐based coping responses. The findings suggest that women who respond to their breast cancer diagnosis with passive acceptance and resignation are at significant risk for poor long term psychological adjustment. Psychological interventions for these women should address cognitive avoidance, with the aim of fostering approach‐based coping and positive well‐being. Copyright © 2003 John Wiley & Sons, Ltd.
Progressive combinatorial algorithm for multiple structural alignments: Application to distantly related proteins
Authors: Ochagavía María Elena , Wodak Shoshana
Published: March 2004

MALECON is a progressive combinatorial procedure for multiple alignments of protein structures. It searches a library of pairwise alignments for all three‐protein alignments in which a specified number of residues is consistently aligned. These alignments are progressively expanded to include additional proteins and more spatially equivalent residues, subject to certain criteria. This action involves superimposing the aligned proteins by their hitherto equivalent residues and searching for additional Cα atoms that lie close in space. The performance of MALECON is illustrated and compared with several extant multiple structure alignment methods by using as test the globin homologous superfamily, the OB and the Jellyrolls folds. MALECON gives better definitions of the common structural features in the structurally more diverse proteins of the OB and Jellyrolls folds, but it yields comparable results for the more similar globins. When no consistent multiple alignments can be derived for all members of a protein group, our procedure is still capable of automatically generating consistent alignments and common core definitions for subgroups of the members. This finding is illustrated for proteins of the OB fold and SH3 domains, believed to share common structural features, and should be very instrumental in homology modeling and investigations of protein evolution. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Two histidines of the coat protein of turnip yellow mosaic virus at the capsid interior are crucial for viability
Authors: Bink Hugo H. J. , Roepan Shalendra K. , Pleij Cornelis W. A.
Published: March 2004

RNA–coat protein interactions in turnip yellow mosaic virus (TYMV) have been shown to involve low pK proton‐donating groups. Two different types of interaction have been proposed. In the so‐called type I interaction, protonated C‐residues interact with acidic amino acids at low pH, thereby providing a rationale for the high C‐content (38%) of the genomic RNA. The type II interaction involves charged histidines interacting with phosphates of the RNA backbone. Site‐directed mutagenesis of the TYMV coat protein and subsequent in vivo analysis were performed to distinguish between these two types of RNA–protein interaction. The results reveal a prominent role for the histidines H68 and H180, since mutation to an alanine residue inhibits symptom development on secondary leaves, indicating that spreading of the virus in the plant is blocked. Viral RNA and coat protein synthesis are not altered, showing that these two histidines may play a role in the process of RNA encapsidation. Overexpression of the TYMV coat protein in Escherichia coli leads to the formation of bona fide capsids, showing that the two histidines are not critical in capsid assembly. Mutagenesis of the acidic amino acids D11, E135, and D143 to alanine apparently did not interfere with virus viability. The functional role of the histidines during the infection cycle is discussed in terms of the structure of the coat protein, both at the level of amino acid sequence conservation among the members of the Tymoviridae family and as the three‐dimensional structure of the coat protein. Proteins 2004;9999:000–000. © 2004 Wiley‐Liss, Inc.
A hierarchical approach to all‐atom protein loop prediction
Authors: Jacobson Matthew P. , Pincus David L. , Rapp Chaya S. , Day Tyler J.F. , Honig Barry , Shaw David E. , Friesner Richard A.
Published: March 2004

The application of all‐atom force fields (and explicit or implicit solvent models) to protein homology‐modeling tasks such as side‐chain and loop prediction remains challenging both because of the expense of the individual energy calculations and because of the difficulty of sampling the rugged all‐atom energy surface. Here we address this challenge for the problem of loop prediction through the development of numerous new algorithms, with an emphasis on multiscale and hierarchical techniques. As a first step in evaluating the performance of our loop prediction algorithm, we have applied it to the problem of reconstructing loops in native structures; we also explicitly include crystal packing to provide a fair comparison with crystal structures. In brief, large numbers of loops are generated by using a dihedral angle‐based buildup procedure followed by iterative cycles of clustering, side‐chain optimization, and complete energy minimization of selected loop structures. We evaluate this method by using the largest test set yet used for validation of a loop prediction method, with a total of 833 loops ranging from 4 to 12 residues in length. Average/median backbone root‐mean‐square deviations (RMSDs) to the native structures (superimposing the body of the protein, not the loop itself) are 0.42/0.24 Å for 5 residue loops, 1.00/0.44 Å for 8 residue loops, and 2.47/1.83 Å for 11 residue loops. Median RMSDs are substantially lower than the averages because of a small number of outliers; the causes of these failures are examined in some detail, and many can be attributed to errors in assignment of protonation states of titratable residues, omission of ligands from the simulation, and, in a few cases, probable errors in the experimentally determined structures. When these obvious problems in the data sets are filtered out, average RMSDs to the native structures improve to 0.43 Å for 5 residue loops, 0.84 Å for 8 residue loops, and 1.63 Å for 11 residue loops. In the vast majority of cases, the method locates energy minima that are lower than or equal to that of the minimized native loop, thus indicating that sampling rarely limits prediction accuracy. The overall results are, to our knowledge, the best reported to date, and we attribute this success to the combination of an accurate all‐atom energy function, efficient methods for loop buildup and side‐chain optimization, and, especially for the longer loops, the hierarchical refinement protocol. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Improving the tolerance of a protein a analogue to repeated alkaline exposures using a bypass mutagenesis approach
Authors: Linhult Martin , Gülich Susanne , Gräslund Torbjörn , Simon Annelie , Karlsson Martin , Sjöberg Anna , Nord Karin , Hober Sophia
Published: March 2004

Staphylococcal protein A (SPA) is a cell surface protein expressed by Staphylococcus aureus. It consists of five repetitive domains. The five SPA‐domains show individual interaction to the Fc‐fragment as well as certain Fab‐fragments of immunoglobulin G (IgG) from most mammalian species. Due to the high affinity and selectivity of SPA, it has a widespread use as an affinity ligand for capture and purification of antibodies. One of the problems with proteinaceous affinity ligands in large‐scale purification is their sensitivity to alkaline conditions. SPA however, is considered relatively stable to alkaline treatment. Nevertheless, it is desirable to further improve the stability in order to enable an SPA‐based affinity medium to withstand even longer exposure to the harsh conditions associated with cleaning‐in‐place (CIP) procedures. For this purpose, a protein engineering strategy, which was used earlier for stabilization and consists of replacing the asparagine residues, is employed. Since Z in its “nonengineered” form already has a significant tolerance to alkaline treatment, small changes in stability due to the mutations are difficult to assess. Hence, in order to enable detection of improvements regarding the alkaline resistance of the Z domain, we chose to use a bypass mutagenesis strategy using a mutated variant Z(F30A) as a surrogate framework. Z(F30A) has earlier been shown to possess an affinity to IgG that is similar to the wild‐type but also demonstrates decreased structural stability. Since the contribution of the different asparagine residues to the deactivation rate of a ligand is dependent on the environment and also the structural flexibility of the particular region, it is important to consider all sensitive amino acids one by one. The parental Z‐domain contains eight asparagine residues, each with a different impact on the alkaline stability of the domain. By exchanging asparagine 23 for a threonine, we were able to increase the stability of the Z(F30A) domain in alkaline conditions. Also, when grafting the N23T mutation to the Z scaffold, we were able to detect an increased tolerance to alkaline treatment compared to the native Z molecule. Proteins 2004. © 2004 Wiley‐Liss, Inc.
A method using active‐site sequence conservation to find functional shifts in protein families: Application to the enzymes of central metabolism, leading to the identification of an anomalous isocitrate dehydrogenase in pathogens
Authors: Das Rajdeep , Gerstein Mark
Published: March 2004

We have introduced a method to identify functional shifts in protein families. Our method is based on the calculation of an active‐site conservation ratio, which we call the “ASC ratio.” For a structurally based alignment of a protein family, this ratio is the average sequence similarity of the active‐site region compared to the full‐length protein. The active‐site region is defined as all the residues within a certain radius of the known functionally important groups. Using our method, we have analyzed enzymes of central metabolism from a large number of genomes (35). We found that for most of the enzymes, the active‐site region is more highly conserved than the full‐length sequence. However, for three tricarboxylic acid (TCA)‐cycle enzymes, active‐site sequences are considerably more diverged (than full‐length ones). In particular, we were able to identify in six pathogens a novel isocitrate dehydrogenase that has very low sequence similarity around the active site. Detailed sequence–structure analysis indicates that while the active‐site structure of isocitrate dehydrogenase is most likely similar between pathogens and nonpathogens, the unusual sequence divergence could result from an extra domain added at the N‐terminus. This domain has a leucine‐rich motif similar one in the Yersinia pestis cytotoxin and may therefore confer additional pathogenic functions. Proteins 2004. © 2004 Wiley‐Liss, Inc.