bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-Effectiveness of the Interventions in the Primary Prevention of Diabetes Among Asian Indians
Authors: Ramachandran Ambady , Snehalatha Chamukuttan , Yamuna Annasami , Mary Simon , Ping Zhang
Published: September 2007

OBJECTIVE—In the Indian Diabetes Prevention Programme (IDPP), a 3-year randomized, controlled trial, lifestyle modification (LSM) and metformin helped to prevent type 2 diabetes in subjects with impaired glucose tolerance (IGT). The direct medical costs and cost-effectiveness of the interventions relative to the control group are reported here.

RESEARCH DESIGN AND METHODS—Relative effectiveness and costs of interventions (LSM, metformin, and LSM and metformin) in the IDPP were estimated from the health care system perspective. Costs of intervention considered were only the direct medical costs. Direct nonmedical, indirect, and research costs were excluded. The cost-effectiveness of interventions was measured as the amount spent to prevent one case of diabetes within the 3-year trial period.

RESULTS—The direct medical cost to identify one subject with IGT was Indian rupees (INR) 5,278 ($117). Direct medical costs of interventions over the 3-year trial period were INR 2,739 ($61) per subject in the control group, INR 10,136 ($225) with LSM, INR 9,881 ($220) with metformin, and INR 12,144 ($270) with LSM and metformin. The number of individuals needed to treat to prevent a case of diabetes was 6.4 with LSM, 6.9 with metformin, and 6.5 with LSM and metformin. Cost-effectiveness to prevent one case of diabetes with LSM was INR 47,341 ($1,052), with metformin INR 49,280 ($1,095), and with LSM and metformin INR 61,133 ($1,359).

CONCLUSIONS—Both LSM and metformin were cost-effective interventions for preventing diabetes among high risk-individuals in India and perhaps may be useful in other developing countries as well. The long-term cost-effectiveness of the interventions needs to be assessed.
Type 2 Diabetes Prevention in the “Real World”
Authors: Absetz Pilvikki , Valve Raisa , Oldenburg Brian , Heinonen Heikki , Nissinen Aulikki , Fogelholm Mikael , Ilvesmäki Vesa , Talja Martti , Uutela Antti
Published: September 2007

OBJECTIVE—“Real-world” implementation of lifestyle interventions is a challenge. The Good Ageing in Lahti Region (GOAL) Lifestyle Implementation Trial was designed for the primary health care setting, with lifestyle and risk reduction objectives derived from the major diabetes prevention efficacy trials. We report on the program's effectiveness as well as findings related to the program's reach, adoption, and implementation.

RESEARCH DESIGN AND METHODS—A total of 352 middle-aged participants with elevated type 2 diabetes risk were recruited from the health care centers in Päijät-Häme Province in Finland. The intervention included six group counseling sessions, delivered by trained public health nurses. Measurement was conducted at baseline and 12 months. Clinical risk factors were measured by study nurses, and lifestyle outcomes were analyzed from self-reports. Lifestyle outcomes were compared with the outcomes achieved in relevant efficacy trials, and within-subject changes were tested for risk reduction.

RESULTS—At baseline, mean BMI was >32 kg/m2, and 25% of the participants had impaired glucose tolerance. At 12 months, 20% of participants achieved at least four of five key lifestyle outcomes, with these results being comparable with the reference trials. However, physical activity and weight loss goals were achieved significantly less frequently (65 vs. 86% and 12 vs. 43%, respectively). Several clinical risk factors decreased, more so among men than women.

CONCLUSIONS—This trial demonstrates that lifestyle counseling can be effective and is feasible in real-world settings for individuals with elevated risk of type 2 diabetes. To increase program impact, program exposure and treatment intensity need to be increased.
Pelvic Floor Disorders, Diabetes, and Obesity in Women
Authors: Lawrence Jean M. , Lukacz Emily S. , Liu In-Lu Amy , Nager Charles W. , Luber Karl M.
Published: September 2007

OBJECTIVE—We examined associations between obesity and diabetes and female pelvic floor disorders (PFDs), stress urinary incontinence (SUI), overactive bladder (OAB), and anal incontinence (AI) in community-dwelling women.

RESEARCH DESIGN AND METHODS—Women were screened for PFD using a validated mailed survey. Diabetes status, glycemic control, and diabetes treatment were extracted from clinical databases, while other risk factors for PFDs were obtained through self-report. Women were categorized hierarchically as nonobese/nondiabetic (reference), nonobese/diabetic, obese/nondiabetic, and obese/diabetic.

RESULTS—Of 3,962 women, 393 (10%) had diabetes. In unadjusted analyses, women with diabetes and women who were obese had greater odds of having PFDs. Among women with diabetes, being obese was associated with SUI and OAB. After adjusting for confounders, we found that obese/diabetic women were at the highest likelihood of having SUI (odds ratio 3.67 [95% CI 2.48–5.43]) and AI (2.09 [1.48–2.97]). The odds of having OAB among obese women was the same for obese/diabetic women (2.97 [2.08–4.36]) and obese/nondiabetic women (2.93 [2.33–3.68]). Nonobese/diabetic women had higher odds of SUI (1.90 [1.15–3.11]) but did not differ significantly in their OAB (1.45 [0.88–2.38]) and AI (1.33 [0.89–2.00]) prevalence from nonobese/nondiabetic women.

CONCLUSIONS—Given the impaired quality of life experienced by women with PFDs, health care providers should counsel women that obesity and diabetes may be independent modifiable risk factors for PFDs.
Serum Levels of Adipokine Retinol-Binding Protein-4 in Relation to Renal Function
Authors: Ziegelmeier Michaela , Bachmann Anette , Seeger Jeannette , Lossner Ulrike , Kratzsch Jürgen , Blüher Matthias , Stumvoll Michael , Fasshauer Mathias
Published: September 2007

OBJECTIVE—Retinol-binding protein (RBP)-4 was recently identified as an adipokine that induces insulin resistance. In the current study, we investigated RBP-4 serum levels in diabetic and nondiabetic patients on chronic hemodialysis (CD) compared with control subjects with a glomerular filtration rate >50 ml/min. The majority of the diabetic subjects used oral hypoglycemic agents or insulin.

RESEARCH DESIGN AND METHODS—RBP-4 was determined by enzyme-linked immunosorbent assay in control subjects (n = 59) and CD patients (n = 58) and correlated with clinical and biochemical measures of renal function, glucose and lipid metabolism, and inflammation in both groups.

RESULTS—Mean serum RBP-4 levels were almost fourfold higher in CD patients (102 ± 30 mg/l) compared with control subjects (28 ± 8 mg/l). Furthermore, serum creatinine independently predicted RBP-4 concentrations in multiple regression analyses in both control subjects and CD patients. In addition, C-reactive protein and systolic blood pressure independently and negatively correlated with RBP-4 serum concentrations in CD patients but not control subjects. In contrast, markers of glucose and lipid metabolism were not independently related to serum RBP-4 in control subjects or CD patients.

CONCLUSIONS—We show that markers of renal function are independently related to serum RBP-4 levels.
Risk of Type 2 Diabetes Attributable to C-Reactive Protein and Other Risk Factors
Authors: Dehghan Abbas , van Hoek Mandy , Sijbrands Eric J.G. , Stijnen Theo , Hofman Albert , Witteman Jacqueline C.M.
Published: September 2007

OBJECTIVE— To calculate the population-attributable risk (PAR) of C-reactive protein (CRP) and other risk factors for type 2 diabetes.

RESEARCH DESIGN AND METHODS— The Rotterdam Study is a population-based, prospective follow-up study among 7,983 participants aged ≥55 years. Risk factors including serum CRP were determined at baseline. Participants with diabetes at baseline were excluded, and the cohort was followed for a mean of 10.8 years. The hazard ratio (HR) and PAR for diabetes were computed for all studied risk factors.

RESULTS— Serum CRP >1 mg/l (HR 1.67, PAR 0.33), BMI >25 kg/m2 (HR 2.51, PAR 0.51), waist circumference >102 for men and >88 cm for women (HR 1.36, PAR 0.14), current smoking (HR 1.16, PAR 0.03), age >65 years (HR 1.35, PAR 0.15), and family history of diabetes (HR 1.87, PAR 0.16) were related to diabetes and contributed to the risk of the disease. Serum CRP was a greater contributor to the risk of diabetes in women than in men (PAR values of 0.37 vs. 0.28, respectively). Age and current smoking PARs were not statistically significantly contributing to the risk of diabetes in women. Combined PAR was 0.80 (95% CI 0.74–0.85) for all six studied risk factors and 0.71 (0.64–0.78) for modifiable risk factors (serum CRP, BMI, waist circumference, and current smoking).

CONCLUSIONS— High CRP is one of the major contributors to the risk of type 2 diabetes. The contribution of modifiable risk factors to the risk of diabetes is considerable.
Serum Adipocyte Fatty Acid–Binding Protein as a New Biomarker Predicting the Development of Type 2 Diabetes
Authors: Tso Annette W.K. , Xu Aimin , Sham Pak C. , Wat Nelson M.S. , Wang Yu , Fong Carol H.Y. , Cheung Bernard M.Y. , Janus Edward D. , Lam Karen S.L.
Published: September 2007

OBJECTIVE— Adipocyte fatty acid–binding protein (A-FABP) is abundantly expressed in adipocytes and plays a role in glucose homeostasis in experimental animals. We have previously shown that circulating A-FABP levels are associated with the metabolic syndrome, which confers an increased risk of type 2 diabetes. Here we investigated whether serum A-FABP levels could predict the development of diabetes in a 10-year prospective study.

RESEARCH DESIGN AND METHODS— Baseline serum A-FABP levels were measured with an enzyme-linked immunosorbent assay in 544 nondiabetic subjects, recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort, who were followed prospectively to assess the development of type 2 diabetes. The role of A-FABP in predicting the development of type 2 diabetes over 10 years was investigated using Cox regression analysis.

RESULTS— At baseline, serum sex-adjusted A-FABP levels were higher in subjects with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) (P < 0.00001 versus normal glucose tolerance) and correlated positively with adverse cardiometabolic risk factors. Over 10 years, 96 subjects had developed type 2 diabetes. High baseline A-FABP was predictive of type 2 diabetes, independent of obesity, insulin resistance, or glycemic indexes (relative risk [RR] 2.25 [95% CI 1.40–3.65]; P = 0.001; above versus below sex-specific median). High A-FABP levels remained an independent predictor of type 2 diabetes in the high-risk IGT/IFG subgroup (adjusted RR 1.87 [1.12–3.15]; P = 0.018).

CONCLUSIONS— Serum A-FABP was associated with glucose dysregulation and predicted the development of type 2 diabetes in a Chinese cohort.
Family History and Prevalence of Diabetes in the U.S. Population
Authors: Valdez Rodolfo , Yoon Paula W. , Liu Tiebin , Khoury Muin J.
Published: September 2007

OBJECTIVE—We sought to test the association between stratified levels of familial risk of diabetes and the prevalence of the disease in the U.S. population.

RESEARCH DESIGN AND METHODS—This study includes 16,388 adults interviewed for the National Health and Nutrition Examination Survey between 1999 and 2004. Fasting glucose was available for a subsample of 6,004 participants. Familial risk of diabetes was classified as average, moderate, or high. The prevalence and the odds of having diabetes were estimated for each risk class after accounting for other risk factors.

RESULTS—Overall, 69.8% of the U.S. adults were in the average, 22.7% in the moderate, and 7.5% in the high familial risk for diabetes. The crude prevalence of diabetes for each risk class was 5.9, 14.8, and 30%, respectively. The graded association between familial risk and prevalence of diabetes remained even after accounting for sex, race/ethnicity, age, BMI, hypertension, income, and education. Versus people in the average risk class, independently of other risk factors considered, the odds of having diabetes for people in the moderate and high familial risk categories were, respectively, 2.3 and 5.5 times higher.

CONCLUSIONS—In the U.S. population, family history of diabetes has a significant, independent, and graded association with the prevalence of diabetes. This association not only highlights the importance of shared genes and environment in diabetes but also opens the possibility of formally adding family history to public health strategies aimed at detecting and preventing the disease.
Association of Oxidative Stress, Insulin Resistance, and Diabetes Risk Phenotypes
Authors: Meigs James B. , Larson Martin G. , Fox Caroline S. , Keaney John F. , Vasan Ramachandran S. , Benjamin Emelia J.
Published: September 2007

OBJECTIVE—Systemic oxidative stress causes insulin resistance in rodents. We tested the hypothesis that oxidative stress and insulin resistance are associated in humans.

RESEARCH DESIGN AND METHODS—We used cross-sectional data from 2,002 nondiabetic subjects of the community-based Framingham Offspring Study. We measured insulin resistance with the homeostasis model and defined categorical insulin resistance as homeostasis model assessment of insulin resistance (HOMA-IR) >75th percentile. We measured oxidative stress using the ratio of urine 8-epi-prostaglandin F2α (8-epi-PGF2α) to creatinine and used age- and sex-adjusted regression models to test the association of oxidative stress with insulin resistance in individuals without diabetes and among subgroups at elevated risk of diabetes.

RESULTS—Across 8-epi-PGF2α/creatinine tertiles, the prevalence of insulin resistance increased (18.0, 27.5, and 29.4% for the first, second, and third tertiles, respectively; P < 0.0001), as did mean levels of HOMA-IR (3.28, 3.83, and 4.06 units; P < 0.0001). The insulin resistance–oxidative stress association was attenuated by additional adjustment for BMI (P = 0.06 across tertiles for insulin resistance prevalence; P = 0.004 for mean HOMA-IR). Twenty-six percent of participants were obese (BMI ≥30 kg/m2), 39% had metabolic syndrome (according to the Adult Treatment Panel III definition), and 37% had impaired fasting glucose (IFG) (fasting glucose 5.6–6.9 mmol/l). Among 528 obese participants, respectively, insulin resistance prevalence was 41.3, 60.6, and 54.2% across 8-epi-PGF2α/creatinine tertiles (P = 0.005); among 781 subjects with metabolic syndrome, insulin resistance prevalence was 41.3, 56.7, and 51.7% (P = 0.0025); and among 749 subjects with IFG, insulin resistance prevalence was 39.6, 47.2, and 51.6% (P = 0.04).

CONCLUSIONS—Systemic oxidative stress is associated with insulin resistance in individuals at average or elevated risk of diabetes even after accounting for BMI.
Carotid Intima-Media Thickness in Pediatric Type 1 Diabetic Patients
Authors: Rodriguez Rocio Rabago , Gómez-Díaz Rita A. , Haj Janet Tanus , Garnica Francisco Jose Avelar , Soriano Eleazar Ramirez , Meguro Elisa Nishimura , Aguilar-Salinas Carlos A. , Wacher Niels H.
Published: September 2007

OBJECTIVE—To compare the carotid artery intima-media thickness in Hispanic pediatric type 1 diabetic patients against that in healthy control subjects matched for age, sex, height, and BMI.

RESEARCH DESIGN AND METHODS—The evaluation consisted of anthropometric measurements, biochemical parameters, and a carotid Doppler and real-time ultrasound, in which carotid artery intima-media thickness (cIMT), peak systolic velocity, and end diastolic velocity were measured using standardized procedures.

RESULTS—A total of 52 diabetic patients and 47 control subjects were included. No significant differences existed in the characteristics between case and control subjects (mean age 11.8 ± 3.1 vs. 11.8 ± 2.8 years, weight 42.2 ± 15.3 vs. 44.2 ± 14.4 kg, height 1.45 ± 0.15 vs. 1.47 ± 0.15 m, BMI 19.3 ± 3.2 vs. 19.9 ± 4.4 kg/m2, systolic blood pressure 99.1 ± 9.9 vs. 99.6 ± 9 mmHg, and diastolic blood pressure 63 ± 6.4 vs. 62.0 ± 5.7 mmHg, respectively). The mean duration of diabetes was 4.8 ± 3.2 years (range 6–144 months), and the mean A1C was 8.6 ± 1.6%. A significantly higher cIMT was found in the patients with type 1 diabetes (0.463 ± 0.04 vs. 0.441 ± 0.04 mm; P = 0.001). In contrast, both peak systolic velocity (107.1 ± 22.8 vs. 119.3 ± 19.2, P < 0.005) and end diastolic velocity (28.4 ± 6.0 vs. 33.0 ± 7.0, P < 0.001) were higher in the control subjects.

CONCLUSIONS—Type 1 diabetes is associated with higher cIMT and decreased flow velocities in a Hispanic pediatric population.
Screening for Coronary Artery Disease in Patients With Diabetes
Authors: Bax Jeroen J. , Young Lawrence H. , Frye Robert L. , Bonow Robert O. , Steinberg Helmut O. , Barrett Eugene J.
Published: September 2007

Coronary artery disease (CAD) accounts for a large fraction of the morbidity, mortality, and cost of diabetes. Recognizing this, nearly 10 years ago the American Diabetes Association published a consensus recommendation that clinicians consider a risk factor–guided screening approach to early diagnosis of CAD in both symptomatic and asymptomatic patients. Subsequent clinical trial results have not supported those recommendations. Since the prior consensus statement, newer imaging methods, such as coronary artery calcium scoring and noninvasive angiography with computed tomography (CT) techniques, have come into use. These technologies, which allow quantitation of atherosclerotic burden and can predict risk of cardiac events, might provide an approach to more widespread coronary atherosclerosis screening. However, over this same time interval, there has been recognition of diabetes as a cardiovascular disease (CVD) equivalent, clear demonstration that medical interventions should provide primary and secondary CVD risk reduction in diabetic populations, and suggestive evidence that percutaneous coronary revascularization may not provide additive survival benefit to intensive medical management in patients with stable CAD. This additional evidence raises the question of whether documenting asymptomatic atherosclerosis or ischemia in people with diabetes is warranted. More data addressing this issue will be forthcoming from the BARI 2-D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Until then, for patients with type 2 diabetes who are asymptomatic for CAD, we recommend that testing for atherosclerosis or ischemia, perhaps with cardiac CT as the initial test, be reserved for those in whom medical treatment goals cannot be met and for selected individuals in whom there is strong clinical suspicion of very-high-risk CAD. Better approaches to identify such individuals based on readily obtained clinical variables are sorely needed.
Identification of Intranasal Cerebrospinal Fluid Leaks by Topical Application with Fluorescein Dye
Authors: Jones Michael E. , Reino Tony , Gnoy Alex , Guillory Samuel , Wackym Phillip , Lawson William
Published: September 2007

The purpose of this paper is to describe a safe new technique for intraoperative identification of the site of cerebrospinal fluid rhinorrhea. Cerebrospinal fluid (CSF) rhinorrhea after intracranial or intranasal surgery is a known potential complication with significant morbidity and mortality. It is currently accepted that endoscopic intranasal management of CSF rhinorrhea is the preferred method of surgical repair, with higher success rates and less morbidity than intracranial surgical repair in selected cases. Accurate identification of the site of CSF leakage is necessary for a successful endoscopic surgical repair. Computer tomography (CT) with or without intrathecal contrast and preoperative nasal endoscopy are frequently used to preoperatively localize the site of the leak. Intrathecal fluorescein administered immediately before surgery has aided in the intraoperative identification of the site of CSF leak in 25–64% of patients undergoing endoscopic repair of CSF rhinorrhea in whom preoperative CT scanning and nasal endoscopy had not identified the site of CSF leak. Intrathecal fluorescein, however, has been associated with severe complications, such as lower extremity weakness, numbness, generalized seizures, opisthotonus, and cranial nerve deficits. We present three cases of CSF rhinorrhea in which fluorescein was applied intranasally during the endoscopic surgical repair. Ten percent fluorescein was applied to the nose with a cotton swab. Under endoscopic visualization the fluorescein changed its fluorescent color from amber/yellow to a dark green and was found streaming from high in the nasal cavity, which led to accurate identification of the site of the CSF leak.
Mucosal Pathology of the Nose and Sinuses: A Study in Experimental Maxillary Sinusitis in Rabbits Induced by Streptococcus Pneumoniae, Bacteroides Fragilis, and Staphylococcus Aureus
Authors: Fukami Masaya , Norlander Tomas , Stierna Pontus , Westrin Karl Magnus , Carlsöö Bengt , Nord Carl Erik
Published: September 2007

Unilateral maxillary sinusitis was experimentally induced in New Zealand White rabbits with Streptococcus pneumoniae serotype 3, Bacteroides fragilis NCTC 9343, and Staphylococcus aureus V8 in order to study possible differences in the inflammatory response of the sinus and nasal mucosa at different time-intervals during a 12-week period of infection. The initial sinus mucosal response, most pronounced in pneumococcal sinusitis, was characterized by leukocytosis, epithelial desquamation, and squamous cell metaplasia. Tissue reactions at later intervals included fibrosis of lamina propria, gland involution, polyp formation, and bone remodelling, and were most pronounced in S. aureus and B. fragilis sinusitis. The nasal mucosa was altered with a redistribution of goblet cells, development of polyps in the ethmoidal region, involution of Bowman's glands and locally, areas of degenerated olfactory sensory epithelium. These findings endorse that the degree of local pathology depends on the infecting microorganism's specific pathogenetic factors. However, local tissue factors guiding the cellular inflammatory proliferative and regenerative processes are also of fundamental importance for the type of pathological changes occurring in an infected nasal or sinus mucosa.
Sinonasal Hemangiopericytoma: DNA Content and Pathological Features
Authors: Wilson Charles J. , Garcia Fernando U. , Hoover Larry A.
Published: September 2007

Hemangiopericytomas are rare vasoformative tumors representing varied clinical courses and histology. Sinonasal hemangiopericytomas (SNHP) are thought to be low grade malignancies with possible late local recurrences and rare metastases even after therapy. We present four cases of SNHP and evaluate the pathological features of diagnostic and prognostic significance. Our cases are compared with all previously reported SNHP series. Cases were retrieved from medical records from our teaching institutions for the last 20 years. Clinical presentation, course, and pathology were reviewed in all cases. DNA content by image analysis, proliferation antigen (MIB-1), estrogen and progesterone receptor status, and other immunohistochemical markers were performed. All patients were females with mean age at presentation of 48.5 (18–77) years. Initial therapy was surgery alone or in combination with radiation therapy. Three patients had local recurrences at 5, 9, and 10 years, one of whom died of metastatic disease 11 years after diagnosis. DNA analysis revealed that three patients had diploid tumors. The patient who died of metastatic disease had a large aneuploid population. The proliferative fraction of the tumors studied with MIB-1 was less than 5% in all tumors. Estrogen receptors were negative in all tumors, and two tumors showed 10% positivity for progesterone receptors. All tumors stained positively with antibodies to vimentin and variably positive with smooth muscle actin. SNHP patients require life-long follow-up because of possible late recurrences and the potential for metastasis. DNA content may be useful for identifying malignant potential.
Characterisation and Simple Synthesis of S-[3-Hydroxy-1-propylpropyl]-L-cysteine
Authors: Luisier Jean-Luc , Veyrand Julien , Piantini Umberto
Published: September 2007

A convenient new synthetic approach has been established to prepare S-[3-hydroxy-1-propylpropyl]-L-cysteine 4 by Michael-addition of enantiomerically pure L-cysteine to (2E)-2-hexenoic acid ethyl ester followed by selective reduction of the ester function with sodium trimethoxyborohydride.
All compounds were obtained as a diastereomeric mixture in good yields and their structures were determined by NMR and MS analyses.
Toughening of unsaturated polyester resins with core–shell rubbers
Authors: Huang Yan‐Jyi , Wu Jia‐Horng , Liang Jiing‐Guan , Hsu Mann‐Wen , Ma Jiun‐Kwei
Published: September 2007

The effects of core–shell rubbers (CSRs) as tougheners on the fracture properties of unsaturated polyester (UP) resins during curing at 110°C are investigated. CSRs were synthesized by two‐stage soapless emulsion polymerizations; the soft core was made from rubbery poly(n‐butyl acrylate), whereas the hard shell was made from methyl methacrylate, ethylene glycol dimethacrylate, and various concentrations of glycidyl methacrylate. Depending on the content of glycidyl methacrylate in the CSR shell and the amount of CSR added to the UP, the fracture properties of the CSR‐toughened UP resins varied. The experimental results are explained by an integrated approach of measurements of the static phase characteristics of a styrene/UP/CSR system, the reaction kinetics, the cured sample morphology, the glass‐transition temperatures, and the fracture toughness with differential scanning calorimetry, scanning electron microscopy, transmission electron microscopy, and dynamic mechanical analysis. Finally, the toughening mechanism for the CSR‐toughened UP resins is also explored. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Engineering properties of poly(vinyl chloride)–poly(butyl methacrylate) semi‐1 and semi‐2 interpenetrating polymer networks
Authors: Chakrabarti Rupa , Chakraborty Debabrata
Published: September 2007

Semi‐1 and semi‐2 interpenetrating polymer networks (IPNs) of poly(vinyl chloride) (PVC) and in situ formed poly(butyl methacrylate) (PBMA) have been synthesized using diallyl phthalate and ethylene glycol dimethacrylate as the crosslinkers of PVC and PBMA, respectively. These were then characterized with reference to their mechanical, thermal, and morphological properties. The mechanical and thermal characteristics revealed modification over the unmodified polymeric systems in relation to their phase morphologies. The semi‐1 IPNs displayed a decrease in their mechanical parameters of modulus and UTS while semi‐2 IPNs exhibited a marginal increase in these two values. The semi‐1 IPNs, however, also revealed a decrease in the elongation and toughness values away from the normal behavior. The thermomechanical behavior of both the systems is in conformity with their mechanicals in displaying the softening characteristics of the system and stabilization over unmodified PVC. The DSC thermograms are also correlated to these observations along with the heterogeneous phase morphology which is displayed by both the systems especially at higher concentration of PBMA incorporation. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
The preparation and characterization of chitosan wound dressings with different degrees of acetylation
Authors: Qin Yimin
Published: September 2007

Chitosan fibers have in recent years found applications in various fields such as antimicrobial textiles and wound dressings. In this study, chitosan fibers with different degrees of acetylation were prepared by controlling the ratio between the amount of acetic anhydride and the weight of the fibers during the acetylation process. The absorption and antimicrobial properties, as well as the dry and wet strength of nonwoven chitosan wound dressings with different degrees of acetylation were studied. Results showed that the partially acetylated chitosan wound dressing had a much higher absorption capacity than the original untreated chitosan samples, while there was a reduction in the wet strength and antimicrobial property for the partially acetylated chitosan nonwoven dressing. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Role of raloxifene as a potent inhibitor of experimental postmenopausal polyarthritis and osteoporosis
Authors: Jochems Caroline , Islander Ulrika , Kallkopf Anna , Lagerquist Marie , Ohlsson Claes , Carlsten Hans
Published: September 2007

Objective

In postmenopausal rheumatoid arthritis (RA), both estrogen deficiency and the inflammatory disease contribute to the development of generalized osteoporosis. Hormone replacement therapy (HRT) with estradiol preserves bone mineral density (BMD) and ameliorates arthritis, but long‐term therapy is no longer an option due to significant side effects. We therefore used a mouse model of human RA to test the hypothesis that a selective estrogen receptor modulator (SERM), the raloxifene analog LY117018, could be beneficial in the treatment of both arthritis and osteoporosis.

Methods

Female DBA/1 mice were ovariectomized and arthritis was induced with collagen immunization. Mice received an injection of raloxifene, estradiol, or vehicle control, administered prophylactically or therapeutically, and thereafter the clinical arthritis score was evaluated continuously. At termination, BMD was analyzed with peripheral quantitative computed tomography. Paws were collected for histology, and sera were analyzed for cytokines and markers of bone and cartilage turnover. Levels of cytokine messenger RNA (mRNA) were investigated with real‐time polymerase chain reaction.

Results

Treatment with raloxifene dramatically decreased the frequency and severity of arthritis. Effective preservation of bone and cartilage was seen in raloxifene‐exposed mice, as demonstrated by increased BMD and decreased serum levels of cartilage oligomeric matrix protein in the raloxifene‐treated mice compared with controls. Decreased levels of mRNA for both tumor necrosis factor α and RANKL in spleen cells from raloxifene‐treated arthritic mice indicated an immunosuppressive action of this SERM.

Conclusion

In a well‐established model of postmenopausal RA, the raloxifene analog LY117018 potently inhibits the progression of arthritis and the associated development of osteoporosis, both in a prophylactic and in a therapeutic regimen. Since long‐term HRT has been associated with significant side effects, raloxifene may be a useful adjuvant treatment for postmenopausal RA.
BAFF synthesis by rheumatoid synoviocytes is positively controlled by α5β1 integrin stimulation and is negatively regulated by tumor necrosis factor α and toll‐like receptor ligands
Authors: Alsaleh Ghada , Messer Laurent , Semaan Noha , Boulanger Nathalie , Gottenberg Jacques‐Eric , Sibilia Jean , Wachsmann Dominique
Published: September 2007

Objective

It was recently demonstrated that synoviocytes (FLS) from rheumatoid arthritis (RA) patients express BAFF transcripts that are up‐regulated by tumor necrosis factor α (TNFα) and interferon‐γ (IFNγ). Thus, BAFF increases in RA target cells might be related to activation of the receptors of innate immunity. The purpose of this study was to determine whether ligands of Toll‐like receptor 2 (TLR‐2), TLR‐4, TLR‐9, and α5β1 integrin are able to induce BAFF synthesis by RA FLS.

Methods

Quantitative reverse transcription–polymerase chain reaction analyses and enzyme‐linked immunosorbent assays were performed to evaluate BAFF messenger RNA induction and BAFF release from FLS after stimulation by ligands for TLR‐2, TLR‐4, TLR‐9, α5β1 integrin (bacterial lipopeptide [BLP] palmitoyl‐3‐cysteine‐serine‐lysine‐4, lipopolysaccharide [LPS], CpG, and protein I/II, respectively), TNFα, and IFNγ.

Results

In contrast to IFNγ, neither TNFα, LPS, BLP, nor CpG induced the de novo synthesis and release of BAFF by FLS. Priming of cells with IFNγ did not have a synergistic effect on BAFF synthesis by FLS stimulated with bacterial products known as pathogen‐associated molecular patterns. Moreover, we found that IFNγ‐induced BAFF synthesis is inhibited by simultaneous stimulation with either TLR ligands or TNFα. We also showed that interplay between TLRs, TNF receptors, and IFNγ signaling induces the expression of suppressor of cytokine signaling 1 (SOCS‐1) and SOCS‐3 and reduces IFNγ‐dependent STAT‐1 phosphorylation, which might explain this inhibition. In contrast, we demonstrated that stimulation of α5β1 integrin can induce BAFF synthesis and release per se and that stimulation of this pathway has no inhibitory effect on IFNγ‐induced BAFF synthesis.

Conclusion

Our findings indicate that BAFF secretion by resident cells in target organs of autoimmunity is tightly regulated by innate immunity, with positive and negative controls, depending on the receptors and the pathways triggered.
Laser Doppler flowmetry for assessing localized scleroderma in children
Authors: Weibel Lisa , Howell Kevin J. , Visentin Maria Teresa , Rudiger Alain , Denton Christopher P. , Zulian Francesco , Woo Patricia , Harper John I.
Published: September 2007

Objective

Assessment of disease activity is a major challenge in the management of children with localized scleroderma. The aim of this study was to evaluate the role of laser Doppler flowmetry (LDF) in comparison with infrared thermography in the detection of scleroderma disease activity.

Methods

In 41 children with localized scleroderma, 111 lesions were assessed on 2 separate occasions, by clinical examination, LDF, and thermography. Measurements from contralateral areas of unaffected skin served as intrapatient controls, and differences in blood flow and temperature were calculated between the corresponding sites. The sensitivity and specificity to detect clinically active lesions were compared between LDF and thermography.

Results

Seventy‐five active lesions (34%) and 147 inactive lesions (66%) were identified clinically. The median relative increase in blood flow measured by LDF was +89% (range −69% to +449%) for clinically active lesions and +11% (range −46% to +302%) for clinically inactive lesions (P < 0.001). Thermography showed a median difference in temperature of +0.5°C (range −0.1°C to +4.1°C) and +0.3°C (range −1.9°C to +2.7°C) for clinically active lesions and clinically inactive lesions, respectively (P = 0.024). Using a cutoff level of 39% to indicate increase in blood flow, a sensitivity of 80% and specificity of 77% to detect clinically active lesions were observed; for thermography, no useful cutoff level was identified. The correlation between differences in blood flow and differences in temperature was small, but significant (r2 = 0.120, P < 0.001).

Conclusion

LDF is a helpful, noninvasive diagnostic technique that can be used to discriminate disease activity in children with localized scleroderma, and is more accurate than thermography for this purpose.
Blocking of experimental arthritis by cleavage of IgG antibodies in vivo
Authors: Nandakumar Kutty Selva , Johansson Björn P. , Björck Lars , Holmdahl Rikard
Published: September 2007

Objective

To investigate whether IgG‐degrading enzyme of Streptococcus pyogenes (IdeS), a bacterial cysteine endopeptidase that cleaves human IgG in the hinge region, can be used for blocking the development of arthritis.

Methods

Recombinant IdeS was purified and tested for specificity against mouse IgG. IdeS was injected intravenously into mice with collagen antibody–induced arthritis (CAIA), collagen‐induced arthritis (CIA), or relapsing CIA, and its effects on arthritis development and severity were assessed.

Results

IdeS efficiently cleaved mouse IgG2a/c and IgG3 in vitro. Even at low dosage (10 μg), IdeS specifically cleaved IgG2a in vivo without any apparent side effects. IdeS treatment efficiently blocked CAIA induced by IgG2a antibodies. No effect was observed when arthritis was induced with IgG2b anti–type II collagen antibodies; since IdeS does not cleave IgG2b, this indicated that IgG cleavage was the mechanism of action. IdeS treatment reduced the severity of arthritis if administered within 24 hours after the onset of clinical arthritis, but did not block ongoing severe arthritis. IdeS treatment also significantly prevented an antibody‐induced relapse in mice that had chronic arthritis, and delayed the onset and reduced the severity of arthritis in classic CIA.

Conclusion

IdeS has therapeutic potential in IgG antibody–mediated autoimmune arthritis, representing a new and unique means of blocking pathogenic antibodies.
Development of a preliminary scleroderma gastrointestinal tract 1.0 quality of life instrument
Authors: Khanna Dinesh , Hays Ron D. , Park Grace S. , Braun‐Moscovici Yolanda , Mayes Maureen D. , McNearney Terry A. , Hsu Vivien , Clements Philip J. , Furst Daniel E.
Published: September 2007

Objective

Gastrointestinal tract (GIT) involvement occurs in ∼90% of patients with systemic sclerosis (SSc) and has a major impact on health‐related quality of life (HRQOL). We developed an HRQOL instrument for persons with SSc.

Methods

The Scleroderma Gastrointestinal Tract 1.0 (SSC‐GIT 1.0) survey was developed after an extensive literature search, solicitation and consideration of experts' opinions, and 2 focus groups of 16 subjects with SSc and GIT involvement. A 75‐item, self‐reported measure assessing bowel involvement, emotional well‐being, and social functioning was administered to subjects with SSc and GIT involvement. Also, subjects completed the Short Form 36 and rated the severity of their GIT symptoms (very mild to very severe), and items were transformed linearly to a scale with a possible range of 0 (worse health) to 100 (better health). Evaluation of psychometric properties included internal consistency reliability, test–retest reliability (1.3‐week median time interval), multitrait scaling analysis, and exploratory factor analysis.

Results

Study participants (n = 88) were primarily female (95.5%), white (79.3%), and had a mean age of 52.4 years. Self‐rated severity of GIT involvement ranged from very mild or mild (36.0%) to moderate (44.0%) to severe or very severe (20.0%). Of 75 items, 23 had low item‐total correlations (≤0.39) and were excluded, leaving a 52‐item instrument. Analyses supported 6 multi‐item HRQOL scales: reflux/indigestion, diarrhea, constipation, pain, emotional well‐being, and social functioning. Test–retest reliability estimates ranged 0.69–0.90 and Cronbach's alpha ranged 0.69–0.93. Participants who rated their GIT disease as mild had the highest scores (better health) on all 6 scales; participants who rated their GIT as severe had the lowest scores (poor health).

Conclusion

The results support the reliability and validity of the SSC‐GIT 1.0 as a measure of SSc GIT involvement. Further research is needed to examine the ability to detect change over time and define minimally important differences.
Mapping hand functioning in hand osteoarthritis: Comparing self‐report instruments with a comprehensive hand function test
Authors: Stamm Tanja , Mathis Mona , Aletaha Daniel , Kloppenburg Margreet , Machold Klaus , Smolen Josef
Published: September 2007

Objective

To determine which self‐report instruments best explain hand functioning measured by a generic comprehensive hand function test.

Methods

Six questionnaires currently used in hand osteoarthritis (OA), namely, the Arthritis Impact Measurement Scales 2 Short Form (AIMS2‐SF), the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Cochin scale, the Functional Index of Hand OA (FIHOA), the Health Assessment Questionnaire (HAQ), and the Score for Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (SACRAH), were administered once in 100 patients with hand OA together with the Jebsen‐Taylor Hand Function Test (JTHFT). In addition, 3 other hand function tests with short administration time were used: the Moberg Picking‐Up Test (MPUT), the Button Test (BT), and grip strength. The Short Form 36 was used to describe health status. The relationship between the instruments and the JTHFT was determined by correlation analyses.

Results

AIMS2‐SF total scores had the highest raw correlation coefficient to the JTHFT, followed by AIMS2‐SF upper body limitation subscale, SACRAH stiffness subscale, and SACRAH total score. If controlled for age, the HAQ had the highest correlation coefficient. Of the 3 short hand function tests, the MPUT showed the highest raw correlation coefficient to the JTHFT; if controlled for age, the BT had the highest correlation coefficient.

Conclusion

To comprehensively assess hand functioning in patients with hand OA, we recommend using both a self‐report instrument used more generally in various arthritides and a self‐report instrument specifically developed for hand OA. If a short test is preferred, we recommend using the MPUT or BT.
Problems faced at work due to inflammatory arthritis: New insights gained from understanding patients' perspective
Authors: Lacaille Diane , White Margaret A. , Backman Catherine L. , Gignac Monique A. M.
Published: September 2007

Objective

A qualitative study was conducted to better understand patients' perspective on their experience at work in relation to their inflammatory arthritis (IA). Objectives were to identify the problems and barriers to employment that persons with IA face at work because of arthritis, understand why these issues are problematic, and identify strategies helpful for maintaining employment.

Methods

Five focus groups were conducted with 36 employed adults with IA (75% rheumatoid arthritis) recruited from rheumatology practices and outpatient arthritis treatment programs. Script design used brainstorming techniques to identify problems and helpful strategies, and root cause analysis to capture in‐depth information about underlying causes of problems. Descriptive qualitative analysis of transcripts was performed by 2 researchers independently to identify problems and organize them into topics and broad categories.

Results

Problems clustered around 4 categories: arthritis symptoms, working conditions, interpersonal difficulties at work, and emotional challenges. New insights gained included identifying fatigue as the aspect of IA most limiting employment; challenges posed by invisibility, fluctuation, and unpredictability of arthritis; complexity of interpersonal relationships at work; reluctance to disclose or draw attention to arthritis; numerous barriers to using available supports and requesting job accommodations, including fear of disclosure and concern it could be perceived by coworkers as favoritism; loss of self‐efficacy at work; and many emotional challenges.

Conclusion

This research identified new issues that are meaningful to individuals working with arthritis and that deserve greater attention by professionals counseling people on employment, in intervention efforts to help maintain employment, and in arthritis employment studies.
Long‐Term effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: A systematic review
Authors: Pisters Martijn F. , Veenhof Cindy , van Meeteren Nico L. U. , Ostelo Raymond W. , de Bakker Dinny H. , Schellevis François G. , Dekker Joost
Published: September 2007

Objective

To determine the long‐term effectiveness (≥6 months after treatment) of exercise therapy on pain, physical function, and patient global assessment of effectiveness in patients with osteoarthritis (OA) of the hip and/or knee.

Methods

We conducted an extensive literature search in PubMed, EMBase, CINAHL, SciSearch, PEDro, and the Cochrane Central Register of Controlled Trials. Both randomized clinical trials and controlled clinical trials on the long‐term effectiveness of exercise therapy were included. The followup assessments were at least 6 months after treatment ended. Methodologic quality was independently assessed by 2 reviewers. Effect estimates were calculated and a best evidence synthesis was performed based on design, methodologic quality, and statistical significance of findings.

Results

Five high‐quality and 6 low‐quality randomized clinical trials were included. Strong evidence was found for no long‐term effectiveness on pain and self‐reported physical function, moderate evidence for long‐term effectiveness on patient global assessment of effectiveness, and conflicting evidence for observed physical function. For exercise programs with additional booster sessions, moderate evidence was found for long‐term effectiveness on pain, self‐reported physical function, and observed physical function.

Conclusion

The positive posttreatment effects of exercise therapy on pain and physical function in patients with OA of the hip and/or knee are not sustained in the long term. Long‐term effectiveness was only found for patient global assessment of effectiveness. However, additional booster sessions after the treatment period positively influenced maintenance of beneficial posttreatment effects on pain and physical function in the long term.
Effect of Mindfulness‐Based stress reduction in rheumatoid arthritis patients
Authors: Pradhan Elizabeth K. , Baumgarten Mona , Langenberg Patricia , Handwerger Barry , Gilpin Adele Kaplan , Magyari Trish , Hochberg Marc C. , Berman Brian M.
Published: September 2007

Objective

To assess the effect of a meditation training program, Mindfulness‐Based Stress Reduction (MBSR), on depressive symptoms, psychological status, and disease activity in patients with rheumatoid arthritis (RA) through a randomized, waitlist‐controlled pilot study.

Methods

Participants were randomized to either an MBSR group, where they attended an 8‐week course and 4‐month maintenance program, or to a waitlist control group, where they attended all assessment visits and received MBSR free of charge after study end. Participants received usual care from their rheumatologists throughout the trial. Self‐report questionnaires were used to evaluate depressive symptoms, psychological distress, well‐being, and mindfulness. Evaluation of RA disease activity (by Disease Activity Score in 28 joints) included examination by a physician masked to treatment status. Adjusted means and mean changes in outcomes were estimated in mixed model repeated measures analyses.

Results

Sixty‐three participants were randomized: 31 to MBSR and 32 to control. At 2 months, there were no statistically significant differences between groups in any outcomes. At 6 months, there was significant improvement in psychological distress and well‐being (P = 0.04 and P = 0.03, respectively), and marginally significant improvement in depressive symptoms and mindfulness (P = 0.08 and P = 0.09, respectively). There was a 35% reduction in psychological distress among those treated. The intervention had no impact on RA disease activity.

Conclusion

An 8‐week MBSR class was not associated with change in depressive symptoms or other outcomes at 2‐month followup. Significant improvements in psychological distress and well‐being were observed following MBSR plus a 4‐month program of continued reinforcement. Mindfulness meditation may complement medical disease management by improving psychological distress and strengthening well‐being in patients with RA.