bluuebunny/crossref_metadata_2025 huggingface dataset:
Religion, spirituality, health and medicine
Authors: Chattopadhyay S
Published: February 2009

Religion, spirituality, health and medicine have common roots in the conceptual framework of relationship amongst human beings, nature and God. Of late, there has been a surge in interest in understanding the interplay of religion, spirituality, health and medicine, both in popular and scientific literature. A number of published empirical studies suggest that religious involvement is associated with better outcomes in physical and mental health. Despite some methodological limitations, these studies do point towards a positive association between religious involvement and better health. When faced with disease, disability and death, many patients would like physicians to address their emotional and spiritual needs, as well. The renewed interest in the interaction of religion and spirituality with health and medicine has significant implications in the Indian context. Although religion is translated as dharma in major Indian languages, dharma and religion are etymologically different and dharma is closer to spirituality than religion as an organized institution. Religion and spirituality play important roles in the lives of millions of Indians and therefore, Indian physicians need to respectfully acknowledge religious issues and address the spiritual needs of their patients. Incorporating religion and spirituality into health and medicine may also go a long way in making the practice of medicine more holistic, ethical and compassionate. It may also offer new opportunities to learn more about Ayurveda and other traditional systems of medicine and have more enriched understanding and collaborative interaction between different systems of medicine. Indian physicians may also find religion and spirituality significant and fulfilling in their own lives.
Retrospective study of severe cases of leptospirosis admitted in the intensive care unit
Authors: Ittyachen AM , Krishnapillai TV , Nair MC , Rajan AR
Published: February 2009

Objectives:

Evaluate patient demographics, risk factors, complications, seropositivity, treatment and outcome among leptospirosis patients.

Design:

Retrospective analysis of 104 patients admitted in the intensive care unit (ICU) with a clinical suspicion of leptopirosis.

Setting:

Ten-bedded medical ICU in a medical school situated in a rural area endemic for leptospirosis.

Main Outcome Measures:

Seropositivity for leptospirosis, patient demographics, risk factors, complications, treatment and survival.

Results:

One hundred and four patients were admitted with a clinical suspicion of leptospirosis. Fifty-three (50.7%) were serologically confirmed cases. Males dominated both groups. Most of the admissions were in the monsoon season. Exposure to moist soil was the main risk factor. The mortality in the seronegative group was 26.8% while it was only 3.8% in the seropositive group. Multi-organ dysfunction syndrome, primarily acute respiratory distress syndrome with thromboctyopenia and renal failure were the causes for mortality. All the patients who died presented late into the illness.

Conclusions:

The initial diagnosis of leptospirosis depends on a high index of clinical suspicion, routinely available diagnostic tests being unreliable in the initial period. A reliable, unsophisticated test should be developed for early detection of this disease. As leptospirosis in its early stage mimics other tropical infections, both medical professionals and the general public (especially with risk of occupational exposure) should be educated about the disease and the need to seek early medical intervention.
Regional brain metabolism in schizophrenia
Authors: Seethalakshmi R , Parkar SR , Nair N , Batra SA , Pandit AG , Adarkar SA , Baghel NS , Moghe S H
Published: February 2009

Background:

Schizophrenia has been associated with a plethora of metabolic changes in the brain that vary with duration and type of psychoses. Additionally, it has been observed that antipsychotics can further alter cerebral glucose metabolism. These changes resulting from antipsychotics have been postulated to be reflective of the duration and mechanism of action of the medication.

Aims:

We aimed to examine the influence of antipsychotics on brain metabolism in individuals with schizophrenia in a naturalistic setting.

Settings and Design:

A cross-sectional study was carried out by the psychiatry department of a tertiary care hospital in collaboration with the Radiation Medicine Centre.

Materials and Methods:

Eighteen male patients with schizophrenia in different phases of treatment underwent an 18F-deoxyglucose positron emission tomography scan in a resting state 12 hours after the last dose of antipsychotic.

Statistical Analysis:

The types and duration of treatment were then compared with the regional glucose uptake in 14 predetermined regions of interest. The relative Uptake Values were further compared using SPSS 11.0.

Results:

An immediate increase followed by a decrease in cortical uptake was noted while the basal ganglia uptake remained high, albeit with a decreasing trend. Typical antipsychotics were associated with lower frontal cortical and higher basal ganglia and cerebellar uptake as compared to atypical antipsychotics.

Conclusion:

The differential influence of the type and duration of antipsychotic on glucose uptake suggests a possible trend towards long-term side effects with typical medications that were not noted on clinical examination. This however needs to be confirmed with larger, controlled studies.
Tumoral calcinosis of the foot with unusual presentation in an 11-year-old boy
Authors: Mohamed S , Jong-Hun J , Weon-Yoo K
Published: February 2009

Tumoral calcinosis is an uncommon disorder characterized by development of calcified masses within the soft tissues near the large joints such as the hip, elbow and shoulder and rarely occurs in the foot. We report the clinical, radiological and magnetic resonance imaging findings in a case of tumoral calcinosis of the foot observed in an 11-year-old boy which caused erosion of underlying bone and describe the surgical treatment and pathology results.
Immune reconstitution inflammatory syndrome in a patient with cryptococcal lymphadenitis as the first presentation of acquired immunodeficiency syndrome
Authors: Tahir M , Sharma SK , Sinha S , Das CJ
Published: February 2009

Immune reconstitution inflammatory syndrome is commonly seen in acquired immunodeficiency syndrome (AIDS) patients having concomitant opportunistic infection, following initiation of highly active anti-retroviral therapy (HAART). We describe IRIS in a young man with unknown human immunodeficiency virus (HIV) status who presented with cryptococcal lymphadenitis as the first manifestation of AIDS. At presentation the patient had features overlapping with tuberculosis (TB) lymphadenitis which was ruled out by fine needle aspiration cytology. The patient responded to antifungal treatment but following the start of HAART, symptoms recurred which were managed conservatively. Though TB is common in India, a thorough workup including histopathology of lymph node should be done before the patient is started on anti-tuberculosis treatment. HIV infected patients having opportunistic co-infection should be closely monitored following initiation of HAART.
Near‐stoichiometric O2 binding on metal centers in Co(salen) nanoparticles
Authors: Johnson Chad , Ottiger Stefan , Pini Ronny , Gorman Eric M. , Nguyen Joseph G. , Munson Eric J. , Mazzotti Marco , Borovik A. S. , Subramaniam Bala
Published: February 2009

Co(salen) [cobaltous bis(salicylaldehyde)ethylenediamine] complexes are well‐known O2 carriers in solution. In the solid phase, these complexes exhibit some O2 binding but detailed studies have been complicated because few of the known polymorphs of Co(salen) actually bind O2. The O2 binding results for nanoparticulate Co(salen) are presented in this study. Rod‐shaped Co(salen) nanoparticles, roughly 100 nm in diameter, were recrystallized by spraying a methylene chloride solution of commercially obtained Co(salen) into supercritical carbon dioxide. Temperature‐programmed desorption, thermogravimetric analysis, and a Rubotherm magnetic suspension balance measurements reveal a reversible O2 uptake of ∼1.51 mmol/(g nanoparticles) at 25°C, consistent with a binding stoichiometry involving a bridging peroxo unit between two Co centers. In contrast, no measurable O2 uptake was observed with the commercial Co(salen). These results clearly show the potential for bottom‐up design of nanoparticulate metal complexes for enhanced O2 storage and other applications. © 2009 American Institute of Chemical Engineers AIChE J, 2009
2q31.2q32.3 deletion syndrome: Report of an adult patient
Authors: Prontera Paolo , Bernardini Laura , Stangoni Gabriela , Capalbo Anna , Rogaia Daniela , Ardisia Carmela , Novelli Antonio , Dallapiccola Bruno , Donti Emilio
Published: February 2009

A 36‐year‐old patient with a disorder characterized by severe mental retardation, behavioral problems, dysmorphic face, “muscular build,” and hand/foot anomalies, is reported. Following a diagnosis of de novo pericentric inversion of chromosome 8 based on standard cytogenetic analysis, a subsequent 75 kb array‐CGH investigation disclosed a deletion spanning for about 13.7 Mb in the 2q31.2q32.3 region. Whole painting of chromosome 8 established the intrachromosomal nature of the rearrangement and FISH analysis with locus‐specific probes confirmed the deletion on the long arm of chromosome 2. The deleted region, clinical outcome, and medical history in this patient are mainly superimposable to those reported in a published 8‐year‐old boy, suggesting that this genomic segment is prone to rearrangements and its hemizygosity gives rise to a clinically recognizable syndrome. The role of some genes mapping in the deleted region and related with distinct disorders is discussed. Interestingly, deletion of MSTN gene, a negative regulator of muscle growth, was associated in our patient with a “muscular build,” a feature which could be regarded as a handle for clinical recognition of this syndrome. © 2009 Wiley‐Liss, Inc.
HDR syndrome: A novel “de novo” mutation in GATA3 gene
Authors: Ferraris Silvio , Del monaco Angelo Giovanni , Garelli Emanuela , Carando Adriana , De Vito Barbara , Pappi Patrizia , Lala Roberto , Ponzone Alberto
Published: February 2009

Human GATA3 haploinsufficiency leads to HDR (hypoparathyroidism, deafness, and renal dysplasia) syndrome. The development of a specific subset of organs in which this transcription factor is expressed appears exquisitely sensitive to gene dosage. We report on a 14‐year‐old patient with symptomatic hypoparathyroidism, sensorineural bilateral deafness, unilateral renal dysplasia, bilateral palpebral ptosis, and horizontal nystagmus. Fundoscopy displayed symmetrical pseudopapilledema, and brain CT scan revealed basal ganglia calcifications. FISH analysis did not disclose any microdeletion in the 22q11.2 or 10p14 regions. GATA3 mutation analysis identified a heterozygous deletion of GG nucleotides at codon 36 and 37 (c.108_109delGG) in exon 2 causing a frameshift with a premature stop codon after a new 15‐aminoacid sequence. Restriction endonuclease analysis performed in parents was negative. Our patient carries a novel “de novo” GATA3 mutation, providing further evidence that HDR syndrome is caused by haploinsufficiency of GATA3, which may be responsible for a complex neurologic picture besides the known triad. © 2009 Wiley‐Liss, Inc.
An Efficient Strategy to Drive Nanoparticles into Carbon Nanotubes and the Remarkable Effect of Confinement on Their Catalytic Performance
Authors: Castillejos Eva , Debouttière Pierre‐Jean , Roiban Lucian , Solhy Abderrahim , Martinez Victor , Kihn Yolande , Ersen Ovidiu , Philippot Karine , Chaudret Bruno , Serp Philippe
Published: February 2009

Drinnen oder draußen? PtRu‐Dimetallnanopartikel wurden selektiv in Kohlenstoffnanoröhren eingeschlossen oder auf ihrer äußeren Oberfläche abgeschieden (siehe Bild). Die eingeschlossenen Nanopartikel sind wesentlich selektivere und aktivere Hydrierungskatalysatoren.

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[2,6‐(Trip)2H3C6](Cp*)Si, eine stabile monomere Arylsilicium(II)‐ Verbindung
Authors: Jutzi Peter , Leszczyńska Kinga , Neumann Beate , Schoeller Wolfgang W. , Stammler Hans‐Georg
Published: February 2009

Als „Lagerform“ eines echten Silylens mit σ‐gebundener Cp*‐Gruppe lässt sich 1, die erste arylsubstituierte monomere Silicium(II)‐Verbindung, betrachten, deren Synthese und vollständige Charakterisierung ein sperriger σ‐gebundener Terphenylsubstituent und ein π‐gebundener Cp*‐Ligand ermöglichten. Die Konformation der Arylgruppe verhindert eine Aryl‐Si‐π‐Rückbindung.

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First Higher‐Order Photocycloaddition to a CN Bond: 1,3‐Diazepines from Maleimides
Authors: Cubbage Kara L. , Orr‐Ewing Andrew J. , Booker‐Milburn Kevin I.
Published: February 2009

Licht ist entscheidend für die Spaltung einer C‐N‐Bindung in einem Maleimid, die eine photochemische [5+2]‐Cycloaddition mit einer sterisch befrachteten CN‐Einheit auslöst (siehe Schema).

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Total Synthesis and Determination of the Absolute Configuration of (+)‐Omaezakianol
Authors: Morimoto Yoshiki , Okita Tatsuya , Kambara Hitomi
Published: February 2009

Synthese als Beweis: Die erste asymmetrische Totalsynthese des marinen tetracyclischen Oxasqualenoids (+)‐Omaezakianol umfasst eine konvergente Olefin‐Kreuzmetathese zwischen einem Monotetrahydrofuran‐Fragment und einem Triepoxyalken sowie eine Oxacyclisierungskaskade eines Triepoxyalkohols zum Aufbau von drei Etherringen. Die Totalsynthese bestätigte die abgebildete absolute Konfiguration von (+)‐Omaezakianol.

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Eine Familie mit komplexiertem Triphosphaallyl‐Radikal, ‐Kation und ‐Anion
Authors: Scheer Manfred , Kuntz Christian , Stubenhofer Markus , Linseis Michael , Winter Rainer F. , Sierka Marek
Published: February 2009

Radikal für Redoxstudien: Die Photolyse von [Cp*P{W(CO)5}2] mit einem Diphosphen verläuft über ein radikalisches Intermediat und liefert ein luftstabiles komplexiertes Triphosphaallylradikal, in dem das ungepaarte Elektron gleichmäßig über beide terminale P‐Atome verteilt ist. Die Oxidation des Radikals führt zu dem lediglich bei tiefen Temperaturen in Lösung stabilen Triphosphaallylkation, während bei der Reduktion das stabile Triphosphaallylanion gebildet wird. Mes*=2,4,6‐Tri‐tert‐butylphenyl.

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Nano‐ und Mikrofabrikation von Zinkoxid aus Koordinationspolymertemplaten
Authors: Liu Xiaogang
Published: February 2009

Wie eine Sechskantmutter: Ein Syntheseverfahren, das auf metall‐organischen Koordinationspolymertemplaten beruht, wurde zur Herstellung von Mikro‐ und Nanokristallen eingesetzt. Mithilfe vielfältiger molekularer Synthesebausteine lassen sich unter Verwendung konventioneller Syntheseverfahren ZnO‐Kristalle mit maßgeschneiderten Größen, Formen (z. B. als hexagonale Ringe; siehe Bild) und Oberflächeneigenschaften synthetisieren.

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An Efficient Strategy to Drive Nanoparticles into Carbon Nanotubes and the Remarkable Effect of Confinement on Their Catalytic Performance
Authors: Castillejos Eva , Debouttière Pierre‐Jean , Roiban Lucian , Solhy Abderrahim , Martinez Victor , Kihn Yolande , Ersen Ovidiu , Philippot Karine , Chaudret Bruno , Serp Philippe
Published: February 2009

Are you in? Bimetallic PtRu nanoparticles have been selectively confined inside or deposited outside carbon nanotubes (see picture). The confined nanoparticles display significantly higher selectivity and catalytic activity in hydrogenation reactions.

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First Higher‐Order Photocycloaddition to a CN Bond: 1,3‐Diazepines from Maleimides
Authors: Cubbage Kara L. , Orr‐Ewing Andrew J. , Booker‐Milburn Kevin I.
Published: February 2009

A light touch is all that is required to cleave a maleimide CN bond to effect a [5+2] photocycloaddition with a sterically encumbered CN moiety (see scheme).

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Elementary Steps of Gold Catalysis: NMR Spectroscopy Reveals the Highly Cationic Character of a “Gold Carbenoid”
Authors: Seidel Günter , Mynott Richard , Fürstner Alois
Published: February 2009

What are you? Even though the metal‐induced ring opening of 3,3‐disubstituted cyclopropenes is known to serve as a genuine carbene generator, the use of AuI in this reaction leads to a reactive intermediate with highly cationic character. This result has important implications for gold catalysis in general, which in the past has been commonly attributed to the intervention of gold carbenes.

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The effect of composition on the dynamic and mechanical properties of natural rubber–poly(methylmethacrylate) blends
Authors: Jayasuriya M. M. , Hourston D. J.
Published: February 2009

The miscibility of the components in natural rubber–poly(methylmethacrylate) blends for potential use as reinforced rubbers was evaluated using the glass transition temperatures, peak widths of the loss tangent peak at the glass transition and the complex heat capacity data obtained from dynamic mechanical thermal analysis (DMTA), and modulated differential scanning calorimetry (MDSC). In addition, the effect of the poly(methylmethacrylate) content on the dynamic mechanical and the physical properties such as tensile behavior and hysteresis loss was studied. DMTA and MDSC data clearly indicated that the blends were phase‐separated. Nevertheless, the glass transition temperature of the natural rubber component in the 30–50 wt % NR/PMMA blends has shifted to higher temperatures compared to the natural rubber treated under the same condition, indicating some limited extent of mixing of components in these blends. The physicomechanical properties including moduli at 100, 300, and 500% and tensile strength of the NR/PMMA blends were determined. Incorporation of PMMA into NR matrix improved the strength properties of the NR/PMMA blends prepared reasonably akin to interpenetrating polymer networks (IPN) polymerization method. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Maxillary Sinus Anatomy: A Cadaveric Study With Clinical Implications
Authors: Gosau M. , Rink D. , Driemel O. , Draenert F.G.
Published: February 2009

This study measured maxillary sinus volume, evaluated the location of the semilunar hiatus in correlation to the nasal floor, and the incidence, location, and height of antral septa and discusses their clinical implications. Maxillary sinus volume was quantified in 65 cadavers (130 sinuses) by water application through the semilunar hiatus and measuring the used amount. The location of the semilunar hiatus was identified as distance from the nasal floor. The septa were counted, evaluated, and the size measured from the antral floor. The medium maxillary sinus volume was 12.5 mL (range, 5–22 mL). The medium location of the semilunar hiatus was 25.6 mm above the nasal floor (range, 18–35 mm). Thirty‐five septa were counted in 130 maxillary sinuses. This equals an incidence of 27%. The medium height of the septa was 5.4 mm (2.5–11 mm). The main location of the septa was the region of the first molar (29%), the second molar (23%), and the second premolar (23%). The height, location, and number of septa as well as the height of the semilunar hiatus and volume of the maxillary sinus have to be taken into consideration to correctly plan the procedure and amount of grafting material in maxillary sinus floor elevation operations. Anat Rec, 292:352–354, 2009. © 2009 Wiley‐Liss, Inc.
New Insight on the Anatomy and Architecture of the Avian Neurocranium
Authors: Marugán‐Lobón Jesús , Buscalioni Ángela D.
Published: February 2009

This study aims to disentangle the main features of the avian neurocranium at high taxonomic scales using geometric morphometric tools. When surveying the variation across 60% of avian orders (sampled among 72 individuals), our results verify that the central nervous system has an important influence upon the architecture of the avian neurocranium, as in other very encephalized vertebrates such as mammals. When the avian brain expands relative to the cranial base it causes more “reptilian‐like” neurocranial configurations to shape into rounder ones. This rounder appearance is achieved because the cranial base becomes relatively shorter and turns its flexure from concave to convex, at the same time forcing the foramen magnum to reorient ventrally instead of caudally. However, our analyses have also revealed that an important morphological difference between birds resides between the occiput and the cranial roof. This variation was unexpected since it had not been reported thus far, and entertains two plausible interpretations. Although it could be due to a trade‐off between the relative sizes of the supraoccipital and the parietal bones, the presence of an additional bone (the intra‐ or post‐parietal) between the latter two bones could also explain the variation congruently. This descriptive insight stresses the need for further developmental studies focused in understanding the evolutionary disparity of the avian neurocranium. Anat Rec, 292:364–370, 2009. © 2009 Wiley‐Liss, Inc.
Attachment of Osteocyte Cell Processes to the Bone Matrix
Authors: McNamara L.M. , Majeska R.J. , Weinbaum S. , Friedrich V. , Schaffler M.B.
Published: February 2009

In order for osteocytes to perceive mechanical information and regulate bone remodeling accordingly they must be anchored to their extracellular matrix (ECM). To date the nature of this attachment is not understood. Osteocytes are embedded in mineralized bone matrix, but maintain a pericellular space (50–80 nm) to facilitate fluid flow and transport of metabolites. This provides a spatial limit for their attachment to bone matrix. Integrins are cell adhesion proteins that may play a role in osteocyte attachment. However, integrin attachments require proximity between the ECM, cell membrane, and cytoskeleton, which conflicts with the osteocytes requirement for a pericellular fluid space. In this study, we hypothesize that the challenge for osteocytes to attach to surrounding bone matrix, while also maintaining fluid‐filled pericellular space, requires different “engineering” solutions than in other tissues that are not similarly constrained. Using novel rapid fixation techniques, to improve cell membrane and matrix protein preservation, and transmission electron microscopy, the attachment of osteocyte processes to their canalicular boundaries are quantified. We report that the canalicular wall is wave‐like with periodic conical protrusions extending into the pericellular space. By immunohistochemistry we identify that the integrin αvβ3 may play a role in attachment at these complexes; a punctate pattern of staining of β3 along the canalicular wall was consistent with observations of periodic protrusions extending into the pericellular space. We propose that during osteocyte attachment the pericellular space is periodically interrupted by underlying collagen fibrils that attach directly to the cell process membrane via integrin‐attachments. Anat Rec, 292:355–363, 2009. © 2009 Wiley‐Liss, Inc.
Expressing pain and fatigue: A new method of analysis to explore differences in osteoarthritis experience
Authors: Gooberman‐Hill Rachael , French Melissa , Dieppe Paul , Hawker Gillian
Published: February 2009

Objective

To apply a new method of analysis to 2 large qualitative datasets in order to examine differences in osteoarthritis (OA) experience according to the affected joint (knee or hip) and sex.

Methods

A secondary analysis of qualitative data from 2 studies was conducted. Study 1 comprised 28 focus groups with 50 men and 80 women (ages 47–92 years). Study 2 comprised 14 focus groups with 32 men and 56 women (ages 56–91 years). All participants had symptomatic OA. In Study 1, secondary analysis using comparative keyword analysis (CKA) compared relative frequencies of words uttered by participants experiencing knee pain with words used by participants experiencing hip pain. In Study 2, CKA compared words used by men with words used by women. Subsequent analysis explored the contexts in which participants used key words.

Results

All participants in Study 1 described concerns with their bodies, activity limitations, and pain management, but details of their concerns differed. People with knee pain focused on stairs, weight, and stiffness, while those with hip pain were concerned with sidedness and groin pain. In Study 2, both men and women discussed activity and interaction with spouses. However, men used more factual words, especially relating to enumeration, while women offered more explanation without prompting from others.

Conclusion

CKA provides productive inroads into qualitative datasets. Understanding the different ways that affected joints are discussed, and sex differences in descriptions of OA, may lead to improvements in clinical assessment tools, better targeting of interventions, and enhanced communication between health care professionals and patients.
Perception of improvement in patients with rheumatoid arthritis varies with disease activity levels at baseline
Authors: Aletaha D. , Funovits J. , Ward M. M. , Smolen J. S. , Kvien T. K.
Published: February 2009

Objective

To analyze the minimum clinically important improvement (MCII) of disease activity measures in rheumatoid arthritis (RA) using patient‐derived anchors, and to assess whether criteria for improvement differ with baseline disease activity.

Methods

We used data from a Norwegian observational database comprising 1,050 patients (73% women, 65% rheumatoid factor‐positive, mean duration of RA 7.7 years). At 3 months after initiation of therapy, patients indicated whether their condition had improved, had considerably improved, was unchanged, had worsened, or had considerably worsened. We used receiver operating characteristic curve analysis to determine the MCII for the Disease Activity Score based on the assessment of 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI), and analyzed the effects of different levels of baseline disease activity on the MCII.

Results

On average, patients started with high disease activity and improved significantly during treatment (American College of Rheumatology 20%, 50%, and 70% improvement criteria responses were 37%, 17%, and 5%, respectively). The overall mean (95% confidence interval [95% CI]) thresholds for MCII after 3 months for the DAS28, SDAI, and CDAI were 1.20 (95% CI 1.18–1.22), 10.95 (95% CI 10.69–11.20), and 10.76 (95% CI 10.49–11.04), respectively, and the mean (95% CI) thresholds for major responses were 1.82 (95% CI 1.80–1.83), 15.82 (95% CI 15.65–16.00), and 15.00 (95% CI 14.82–15.18), respectively. With increasing disease activity, much higher changes in disease activity were needed to achieve MCII according to patient judgment.

Conclusion

The perception of improvement of disease activity of patients with RA is considerably different depending on the disease activity level at which they start.
Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: A retrospective review and case–control study of 21 patients
Authors: Komano Yukiko , Harigai Masayoshi , Koike Ryuji , Sugiyama Haruhito , Ogawa Jun , Saito Kazuyoshi , Sekiguchi Naoya , Inoo Masayuki , Onishi Ikuko , Ohashi Hiroyuki , Amamoto Fujio , Miyata Masayuki , Ohtsubo Hideo , Hiramatsu Kazuko , Iwamoto Masahiro , Minota Seiji , Matsuoka Naoki , Kageyama Goichi , Imaizumi Kazuyoshi , Tokuda Hitoshi , Okochi Yasumi , Kudo Koichiro , Tanaka Yoshiya , Takeuchi Tsutomu , Miyasaka Nobuyuki
Published: February 2009

Objective

To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan.

Methods

Data from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case–control study to compare patients with and without PCP were performed.

Results

The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground‐glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived.

Conclusion

PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.
Developmental and osteoarthritic changes in Col6a1‐knockout mice: Biomechanics of type VI collagen in the cartilage pericellular matrix
Authors: Alexopoulos Leonidas G. , Youn Inchan , Bonaldo Paolo , Guilak Farshid
Published: February 2009

Objective

Chondrocytes, the sole cell type in articular cartilage, maintain the extracellular matrix (ECM) through a homeostatic balance of anabolic and catabolic activities that are influenced by genetic factors, soluble mediators, and biophysical factors such as mechanical stress. Chondrocytes are encapsulated by a narrow tissue region termed the “pericellular matrix” (PCM), which in normal cartilage is defined by the exclusive presence of type VI collagen. Because the PCM completely surrounds each cell, it has been hypothesized that it serves as a filter or transducer for biochemical and/or biomechanical signals from the cartilage ECM. The present study was undertaken to investigate whether lack of type VI collagen may affect the development and biomechanical function of the PCM and alter the mechanical environment of chondrocytes during joint loading.

Methods

Col6a1−/− mice, which lack type VI collagen in their organs, were generated for use in these studies. At ages 1, 3, 6, and 11 months, bone mineral density (BMD) was measured, and osteoarthritic (OA) and developmental changes in the femoral head were evaluated histomorphometrically. Mechanical properties of articular cartilage from the hip joints of 1‐month‐old Col6a1−/−, Col6a1+/−, and Col6a1+/+ mice were assessed using an electromechanical test system, and mechanical properties of the PCM were measured using the micropipette aspiration technique.

Results

In Col6a1−/− and Col6a1+/− mice the PCM was structurally intact, but exhibited significantly reduced mechanical properties as compared with wild‐type controls. With age, Col6a1−/− mice showed accelerated development of OA joint degeneration, as well as other musculoskeletal abnormalities such as delayed secondary ossification and reduced BMD.

Conclusion

These findings suggest that type VI collagen has an important role in regulating the physiology of the synovial joint and provide indirect evidence that alterations in the mechanical environment of chondrocytes, due to either loss of PCM properties or Col6a1−/−‐derived joint laxity, can lead to progression of OA.
Triggering of proteinase‐activated receptor 4 leads to joint pain and inflammation in mice
Authors: McDougall Jason J. , Zhang Chunfen , Cellars Laurie , Joubert Eva , Dixon Chantelle M. , Vergnolle Nathalie
Published: February 2009

Objective

To investigate the role of proteinase‐activated receptor 4 (PAR‐4) in mediating joint inflammation and pain in mice.

Methods

Knee joint blood flow, edema, and pain sensitivity (as induced by thermal and mechanical stimuli) were assessed in C57BL/6 mice following intraarticular injection of either the selective PAR‐4 agonist AYPGKF‐NH2 or the inactive control peptide YAPGKF‐NH2. The mechanism of action of AYPGKF‐NH2 was examined by pretreatment of each mouse with either the PAR‐4 antagonist pepducin P4pal‐10 or the bradykinin antagonist HOE 140. Finally, the role of PAR‐4 in mediating joint inflammation was tested by pretreating mice with acutely inflamed knees with pepducin P4pal‐10.

Results

PAR‐4 activation caused a long‐lasting increase in joint blood flow and edema formation, which was not seen following injection of the control peptide. The PAR‐4–activating peptide was also found to be pronociceptive in the joint, where it enhanced sensitivity to a noxious thermal stimulus and caused mechanical allodynia and hyperalgesia. The proinflammatory and pronociceptive effects of AYPGKF‐NH2 could be inhibited by pepducin P4pal‐10 and HOE 140. Finally, pepducin P4pal‐10 ameliorated the clinical and physiologic signs of acute joint inflammation.

Conclusion

This study demonstrates that local activation of PAR‐4 leads to proinflammatory changes in the knee joint that are dependent on the kallikrein–kinin system. We also show for the first time that PARs are involved in the modulation of joint pain, with PAR‐4 being pronociceptive in this tissue. Thus, blockade of articular PAR‐4 may be a useful means of controlling joint inflammation and pain.
Stromal cell–derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model
Authors: Kitaori Toshiyuki , Ito Hiromu , Schwarz Edward M. , Tsutsumi Ryosuke , Yoshitomi Hiroyuki , Oishi Shinya , Nakano Masakazu , Fujii Nobutaka , Nagasawa Takashi , Nakamura Takashi
Published: February 2009

Objective

Stromal cell–derived factor 1 (SDF‐1; CXCL12/pre–B cell growth‐stimulating factor) is a dominant chemokine in bone marrow and is known to be involved in inflammatory diseases, including rheumatoid arthritis. However, its role in bone repair remains unknown. The purpose of this study was to investigate the role of SDF‐1 and its receptor, CXCR4, in bone healing.

Methods

The expression of SDF‐1 during the repair of a murine structural femoral bone graft was examined by real‐time polymerase chain reaction and immunohistochemical analysis. The bone graft model was treated with anti–SDF‐1 neutralizing antibody or TF14016, an antagonist for CXCR4, and evaluated by histomorphometry. The functional effect of SDF‐1 on primary mesenchymal stem cells was determined by in vitro and in vivo migration assays. New bone formation in an exchanging‐graft model was compared with that in the autograft models, using mice partially lacking SDF‐1 (SDF‐1+/−) or CXCR4 (CXCR4+/−).

Results

The expression of SDF1 messenger RNA was increased during the healing of live bone grafts but was not increased in dead grafts. High expression of SDF‐1 protein was observed in the periosteum of the live graft. New bone formation was inhibited by the administration of anti–SDF‐1 antibody or TF14016. SDF‐1 increased mesenchymal stem cell chemotaxis in vitro in a dose‐dependent manner. The in vivo migration study demonstrated that mesenchymal stem cells recruited by SDF‐1 participate in endochondral bone repair. Bone formation was decreased in SDF‐1+/− and CXCR4+/− mice and was restored by the graft bones from CXCR4+/− mice transplanted into the SDF‐1+/− femur, but not vice versa.

Conclusion

SDF‐1 is induced in the periosteum of injured bone and promotes endochondral bone repair by recruiting mesenchymal stem cells to the site of injury.
Scleroderma prevalence: Demographic variations in a population‐based sample
Authors: Bernatsky S. , Joseph L. , Pineau C. A. , Belisle P. , Hudson M. , Clarke A. E.
Published: February 2009

Objective

To estimate the prevalence of systemic sclerosis (SSc) using population‐based administrative data, and to assess the sensitivity of case ascertainment approaches.

Methods

We ascertained SSc cases from Quebec physician billing and hospitalization databases (covering ∼7.5 million individuals). Three case definition algorithms were compared, and statistical methods accounting for imperfect case ascertainment were used to estimate SSc prevalence and case ascertainment sensitivity. A hierarchical Bayesian latent class regression model that accounted for possible between‐test dependence conditional on disease status estimated the effect of patient characteristics on SSc prevalence and the sensitivity of the 3 ascertainment algorithms.

Results

Accounting for error inherent in both the billing and the hospitalization data, we estimated SSc prevalence in 2003 at 74.4 cases per 100,000 women (95% credible interval [95% CrI] 69.3–79.7) and 13.3 cases per 100,000 men (95% CrI 11.1–16.1). Prevalence was higher for older individuals, particularly in urban women (161.2 cases per 100,000, 95% CrI 148.6–175.0). Prevalence was lowest in young men (in rural areas, as low as 2.8 cases per 100,000, 95% CrI 1.4–4.8). In general, no single algorithm was very sensitive, with point estimates for sensitivity ranging from 20–73%.

Conclusion

We found marked differences in SSc prevalence according to age, sex, and region. In general, no single case ascertainment approach was very sensitive for SSc. Therefore, using data from multiple sources, with adjustment for the imperfect nature of each, is an important strategy in population‐based studies of SSc and similar conditions.
Work disability in systemic lupus erythematosus
Authors: Dhanhani Ali M. Al , Gignac Monique A. M. , Su Jiandong , Fortin Paul R.
Published: February 2009

Objective

To determine the prevalence, accrual over time, and risk factors of work disability in patients with systemic lupus erythematosus (SLE).

Methods

We studied 432 patients from an inception cohort. Work disability was measured from a single self‐report question. Data were prospectively collected and included sociodemographic information, clinical lupus features including activity (Systemic Lupus Erythematosus Disease Activity Index 2000 update [SLEDAI‐2K]), damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), and organ involvement, as well as health status (Short Form 36 [SF‐36]), comorbidity, and medication use. Student's t‐test and Wilcoxon's rank sum test were used to compare continuous variables and chi‐square tests were used for dichotomous variables. Descriptive survival curves of time to work disability were presented. Bivariate and multivariate logistic regressions were used to describe the relationships between clinically relevant factors and work disability.

Results

Of 432 patients, 88% were women and 73% were white. Within the first year of diagnosis, 47% of patients were employed, 7% had a disability, and 7% were on sick leave. Overall, work disability was found in 98 (23%) patients. Risk factors for work disability found in the multivariate regression analysis were younger age at diagnosis, less education, fibromyalgia, hypertension, higher first‐visit SLEDAI‐2K score, and lower first‐visit SF‐36 score.

Conclusion

Work disability is frequent in patients with SLE, with a cumulative prevalence of 23%. Work disability was associated with a complex array of health factors, including comorbidity, physical and mental health limitations, and clinical features of lupus, that warrant increased attention in future research.
Meniscal tear in knees without surgery and the development of radiographic osteoarthritis among middle‐aged and elderly persons: The multicenter osteoarthritis study
Authors: Englund Martin , Guermazi Ali , Roemer Frank W. , Aliabadi Piran , Yang Mei , Lewis Cora E. , Torner James , Nevitt Michael C. , Sack Burton , Felson David T.
Published: February 2009

Objective

Although partial meniscectomy is a risk factor for the development of knee osteoarthritis (OA), there is a lack of evidence that meniscal damage that is not treated with surgery would also lead to OA, suggesting that surgery itself may cause joint damage. Furthermore, meniscal damage is common. The aim of this study was to evaluate the association between meniscal damage in knees without surgery and the development of radiographic tibiofemoral OA.

Methods

We conducted a prospective case–control study nested within the observational Multicenter Osteoarthritis Study, which included a sample of men and women ages 50–79 years at high risk of knee OA who were recruited from the community. Patients who had no baseline radiographic knee OA but in whom tibiofemoral OA developed during the 30‐month followup period were cases (n = 121). Control subjects (n = 294) were drawn randomly from the same source population as cases but had no knee OA after 30 months of followup. Individuals whose knees had previously undergone surgery were excluded. Meniscal damage was defined as the presence of any medial or lateral meniscal tearing, maceration, or destruction.

Results

Meniscal damage at baseline was more common in case knees than in control knees (54% versus 18%; P < 0.001). The model comparing any meniscal damage with no meniscal damage (adjusted for baseline age, sex, body mass index, physical activity, and mechanical knee alignment) yielded an odds ratio of 5.7 (95% confidence interval 3.4–9.4).

Conclusion

In knees without surgery, meniscal damage is a potent risk factor for the development of radiographic OA. These results highlight the need for better understanding, prevention, and treatment of meniscal damage.
Disease control and health‐related quality of life in juvenile idiopathic arthritis
Authors: Seid Michael , Opipari Lisa , Huang Bin , Brunner Hermine I. , Lovell Daniel J.
Published: February 2009

Objective

To examine variability in health‐related quality of life (HRQOL) in children with juvenile idiopathic arthritis (JIA) experiencing no or minimal clinical symptoms, and in a subgroup with polyarticular JIA treated with biologic agents for 12 months.

Methods

We defined 3 samples using a database of patients ages 2–18 years with JIA (n = 524; patient visits [PV] = 2,354): visits (PV = 2,155) with no or minimal clinical symptoms on at least 1 of 4 measures (active joint count, pain, physician global disease rating, Childhood Health Assessment Questionnaire); visits (PV = 941) with no or minimal symptoms on all 4 measures; and children (n = 31) with polyarticular JIA treated with biologic agents for 12 months. HRQOL was measured using the Pediatric Quality of Life Inventory (PedsQL) and the percentage of patients with suboptimal HRQOL was determined.

Results

In PV with a PedsQL score, suboptimal HRQOL by self‐report occurred in 362 (20.6%) PV with at least 1 indicator of minimal symptoms, and in 64 (7.9%) PV with all 4 measures indicating minimal symptoms (519 [25.7%] and 95 [10.7%], respectively, by parent report). For children with polyarticular JIA treated for 12 months with biologic agents, 7 (25.9%) patients by self‐report and 10 (35.7%) patients by parent report were in the suboptimal range of HRQOL.

Conclusion

A substantial percentage of patients with JIA who report no or mild clinical symptoms experience suboptimal HRQOL. This is also true for patients with polyarticular JIA treated with biologic agents for 12 months. Although disease activity and clinical symptoms are related to HRQOL, considerable unexplained variation in HRQOL exists. HRQOL needs to be assessed independently regardless of clinical status.
The early disease stage in axial spondylarthritis: Results from the german spondyloarthritis inception cohort
Authors: Rudwaleit Martin , Haibel Hildrun , Baraliakos Xenofon , Listing Joachim , Märker‐Hermann Elisabeth , Zeidler Henning , Braun Jürgen , Sieper Joachim
Published: February 2009

Objective

Ankylosing spondylitis (AS) is diagnosed late, because radiographs of the sacroiliac joints often do not show definite sacroiliitis at the time of disease onset. The aim of this study was to investigate whether patients without definite radiographically defined sacroiliitis, referred to as nonradiographic axial spondylarthritis (SpA), are different from patients with AS with regard to clinical manifestations and disease activity measures. Moreover, we sought to identify determinants of the development of radiographic sacroiliitis.

Methods

In a cross‐sectional analysis of 462 patients, we compared 226 patients with nonradiographic axial SpA (symptom duration ≤5 years) and 236 patients with AS (symptom duration ≤10 years) who are participants in the German Spondyloarthritis Inception Cohort. Radiographs of the sacroiliac joints and the spine were assessed by 2 readers in a blinded manner. Logistic regression analysis was applied to identify parameters associated with structural damage.

Results

The 2 groups did not differ in the frequency of HLA–B27 positivity, inflammatory back pain, arthritis, enthesitis, and uveitis and had similar levels of disease activity, using measures such as the Bath Ankylosing Spondylitis Disease Activity Index. In both groups, HLA–B27 positivity determined the age at disease onset. Male sex (adjusted odds ratio [OR] 2.38, 95% confidence interval [95% CI] 1.19–4.73 [P = 0.014]) and an elevated C‐reactive protein (CRP) level (adjusted OR 1.85, 95% CI 0.96–3.56 [P = 0.066]) were associated with radiographic sacroiliitis. In patients with AS, male sex and an elevated CRP level were also associated with the presence of syndesmophytes.

Conclusion

Clinical manifestations and disease activity measures are highly comparable between patients with early nonradiographic axial SpA and those with early AS, suggesting that these 2 entities are part of the same disease. Male sex and an elevated CRP level are associated with structural damage on radiographs, whereas HLA–B27 positivity determines the age at disease onset.
Expression levels of human P‐glycoprotein inIn Vitrocell lines: correlation between mRNA and protein levels for P‐glycoprotein expressed in cells
Authors: Shirasaka Yoshiyuki , Konishi Reiko , Funami Nana , Kadowaki Yuko , Nagai Yuri , Sakaeda Toshiyuki , Yamashita Shinji
Published: February 2009

The purpose of this study was to investigate the correlation between mRNA and protein levels for P‐glycoprotein (P‐gp) expressed in various cell lines to validate the estimation of P‐gp activity from its mRNA levels. P‐gp expression levels in various cell monolayers, normal, P‐gp‐induced, P‐gp‐highly induced, (multidrug resistance, MDR) MDR1‐knockdown (A2‐2) and MDR1‐knockdown (B2‐2) Caco‐2 cells and MDCKII/MDR1 cells, were quantified by real‐time quantitative polymerase chain reaction (PCR) and western blot analysis. Both mRNA and protein levels of P‐gp were lowest in the MDR1‐knockdown (B2‐2) Caco‐2 cells, followed by the MDR1‐knockdown (A2‐2) Caco‐2, normal Caco‐2, P‐gp‐induced Caco‐2 and P‐gp‐highly induced Caco‐2 cells, and highest in the MDCKII/MDR1 cells. Except for the MDCKII/MDR1 cells, the protein levels of P‐gp in all Caco‐2 cell lines showed a linear correlation with its mRNA levels; however, although the MDR1 mRNA level in MDCKII/MDR1 cells was much higher than in the P‐gp‐highly induced Caco‐2 cells, the protein levels were almost the same in both cells. From these findings, it was suggested that P‐gp activity in MDCKII/MDR1 cells could not be estimated from its mRNA levels. Copyright © 2009 John Wiley & Sons, Ltd.