bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Continuous Glucose Monitoring to Measure the Frequency of Low Glucose Values When Using Biphasic Insulin Aspart 30 Compared With Biphasic Human Insulin 30
Authors: McNally Paul G. , Dean John D. , Morris Andrew D. , Wilkinson Peter D. , Compion Gerhard , Heller Simon R.
Published: April 2007

OBJECTIVE—Rapid-acting insulin analogs in basal-bolus regimens can reduce nocturnal hypoglycemia, so it is conceivable that twice-daily biphasic insulin analogs might reduce hypoglycemia in patients with insulin-treated type 2 diabetes. We used a continuous glucose monitoring system (CGMS) and self-reported episodes to investigate differences in the frequency of low glucose values in patients with type 2 diabetes, using either biphasic insulin aspart 30 (BIAsp 30) or biphasic human insulin 30 (BHI 30).

RESEARCH DESIGN AND METHODS—This was a double-blind, two-period, crossover trial involving 160 subjects. After 8 weeks’ run-in, subjects were randomized to the first of two 16-week treatment periods.

RESULTS—No differences in overall incidence of low interstitial glucose (IG) were found. Twenty-four–hour plots of CGMS showed low IG was more frequent at night than during the day and was unrecognized by patients. At night, subjects spent significantly less time (percentage of total CGMS recorded) with IG <3.5 and <2.5 mmol/l during BIAsp 30 than during BHI 30 treatment, respectively (<3.5 mmol/l: 6.36 vs. 7.93% [mean], 0.67 vs. 2.43% [median], P = 0.018; <2.5 mmol/l: 2.35 vs. 2.86% [mean], 0 vs. 0% [median], P = 0.0467). No treatment difference in A1C was observed.

CONCLUSIONS—Overall rates of low glucose over 24 h were not different but were twice as frequent at night than during the day in individuals with type 2 diabetes. Compared with BHI 30, BIAsp 30 was associated with similar low IG readings over 24 h but with fewer nocturnal episodes and less self-reported nocturnal hypoglycemia.
Microvascular Complications in Cystic Fibrosis–Related Diabetes
Authors: Schwarzenberg Sarah Jane , Thomas William , Olsen Timothy W. , Grover Trish , Walk David , Milla Carlos , Moran Antoinette
Published: April 2007

OBJECTIVE—The incidence of cystic fibrosis–related diabetes (CFRD) and the prevalence of diabetic microvascular complications were determined at the University of Minnesota.

RESEARCH DESIGN AND METHODS—Cystic fibrosis patients have undergone annual oral glucose tolerance testing since 1990. Database review was performed to determine diabetes duration and the results of annual urine albumin-to-creatinine ratio (Ualb:Cr) screening and dilated retinal exams. In addition, 59 individuals underwent detailed retinopathy, nephropathy, neuropathy, and gastroenterpathy screening.

RESULTS—During 1990–2005, 775 patients aged ≥6 years were followed. CFRD was diagnosed by an oral glucose tolerance test or fasting hyperglycemia in 285 subjects (52% female), 64% of whom had fasting hyperglycemia. Most patients with CFRD without fasting hyperglycemia progressed to CFRD with fasting hyperglycemia over time. No subject with CFRD without fasting hyperglycemia had retinopathy or abnormal Ualb:Cr. In CFRD subjects with fasting hyperglycemia and diabetes for ≥10 years, 14% had microalbuminuria and 16% had retinopathy. Autonomic neuropathy and gastrointestinal symptoms each were seen in 52% and somatic abnormalities in 22% of patients with or without fasting hyperglycemia.

CONCLUSIONS—Diabetic microvascular complications occur in CFRD, although the prevalence of retinopathy and nephropathy appears to be less than that found in other forms of diabetes. Annual complication screening should occur after known diabetes duration of 5 years in patients with CFRD with fasting hyperglycemia.
Rising Incidence of Type 2 Diabetes in Children in the U.K.
Authors: Haines Linda , Wan Kay Chong , Lynn Richard , Barrett Timothy G. , Shield Julian P.H.
Published: April 2007

OBJECTIVE—To estimate the incidence of type 2 diabetes in children <17 years of age and to investigate the relationship of diabetes with increasing childhood obesity in the U.K. and the Republic of Ireland (ROI).

RESEARCH DESIGN AND METHODS—Active monthly reporting of cases by consultant pediatricians occurred through the framework of the British Pediatric Surveillance Unit, with additional reports from specialist diabetes nurses. All children <17 years of age and diagnosed by their clinician as having non–type 1 diabetes from 1 October 2004 to 31 October 2005 were included.

RESULTS—A total of 168 confirmed cases of non–type 1 diabetes were reported, resulting in a national incidence (excluding the ROI) of 1.3 · 100,000−1 · year−1. Of these, 40% were diagnosed with type 2 diabetes giving a minimum incidence of 0.53 · 100,000−1 · year−1. Children of ethnic minorities were greatly overrepresented, with those of black and South-Asian origin (England data only) having an incidence of 3.9 and 1.25 · 100,000−1 · year−1, respectively, compared with 0.35 · 100,000−1 · year−1 in those defined as white. Of those diagnosed with type 2 diabetes, 95% were overweight and 83% obese according to International Obesity Task Force guidelines. Eighty-four percent had a family history of type 2 diabetes.

CONCLUSIONS—Type 2 diabetes is still less common than type 1 diabetes in U.K. children. However, compared with previous prevalence data, the frequency of type 2 diabetes appears to be increasing. Incidence among ethnic minorities is far higher than in whites, as previously described in the U.S. Increased adiposity and family history of type 2 diabetes were strongly associated with the diagnosis of type 2 diabetes in U.K. children.
The Prediction of Major Outcomes of Type 1 Diabetes: a 12-Year Prospective Evaluation of Three Separate Definitions of the Metabolic Syndrome and Their Components and Estimated Glucose Disposal Rate
Authors: Pambianco Georgia , Costacou Tina , Orchard Trevor J.
Published: April 2007

OBJECTIVE—The metabolic syndrome has been shown to confer an increased risk of cardiovascular disease in both the general and type 2 diabetic populations, but few studies have assessed the metabolic syndrome in type 1 diabetic patients. In a type 1 diabetic cohort, we assessed the prevalence and value of the metabolic syndrome in improving the prediction of major complication outcomes compared with its components and a surrogate measure of insulin resistance, estimated glucose disposal rate (eGDR).

RESEARCH DESIGN AND METHODS—A total of 514 (78%) subjects participating in the Pittsburgh Epidemiology of Diabetes Complications Study with complete 12-year follow-up clinical data were classified by baseline metabolic syndrome status according to three definitions: those of the National Cholesterol Education Program Adult Treatment Panel III (modified by the American Heart Association), the International Diabetes Federation (IDF), and the World Health Organization (WHO). The complication outcomes included coronary artery disease, renal failure, diabetes-related death, and the aggregate of these three major outcomes of diabetes (MOD).

RESULTS—Metabolic syndrome prevalence ranged from 8% (IDF) to 21% (WHO). All definitions showed reasonable specificity (≥83%) for each outcome, while the WHO definition had the highest sensitivity for all outcomes except renal failure, for which eGDR was most sensitive. However, the components of each definition predicted better than the overall syndrome. Microalbuminuria was clearly the strongest predictor of all individual measures, yielding hazard ratios of 9 and 6 for mortality and MOD, respectively.

CONCLUSIONS—Though the three metabolic syndrome classifications predict major complication outcomes in type 1 diabetes, their individual components predict better. Of the variables studied, including HbA1, microalbuminuria appears to be the best single predictor of MOD.
Noninvasive Assessment of Plaque Characteristics With Multislice Computed Tomography Coronary Angiography in Symptomatic Diabetic Patients
Authors: Pundziute Gabija , Schuijf Joanne D. , Jukema J. Wouter , Boersma Eric , Scholte Arthur J.H.A. , Kroft Lucia J.M. , van der Wall Ernst E. , Bax Jeroen J.
Published: April 2007

OBJECTIVE—Cardiovascular events are high in patients with type 2 diabetes, whereas their risk stratification is more difficult. The higher risk may be related to differences in coronary plaque burden and composition. The purpose of this study was to evaluate whether differences in the extent and composition of coronary plaques in patients with and without diabetes can be observed using multislice computed tomography (MSCT).

RESEARCH DESIGN AND METHODS—MSCT was performed in 215 patients (86 [40%] with type 2 diabetes). The number of diseased coronary segments was determined per patient; each diseased segment was classified as showing obstructive (≥50% luminal narrowing) disease or not. In addition, plaque type (noncalcified, mixed, and calcified) was determined. Plaque characteristics were compared in patients with and without diabetes. Regression analysis was performed to assess the correlation between plaque characteristics and diabetes.

RESULTS—Patients with diabetes showed significantly more diseased coronary segments than nondiabetic patients (4.9 ± 3.5 vs. 3.9 ± 3.2, P = 0.03) with more nonobstructive (3.7 ± 3.0 vs. 2.7 ± 2.4, P = 0.008) plaques. Relatively more noncalcified (28 vs. 19%) and calcified (49 vs. 43%) and less mixed (23 vs. 38%) plaques were observed in patients with diabetes (P < 0.0001). Diabetes correlated with the number of diseased segments and nonobstructive, noncalcified, and calcified plaques.

CONCLUSIONS—Differences in coronary plaque characteristics on MSCT were observed between patients with and without diabetes. Diabetes was associated with higher coronary plaque burden. More noncalcified and calcified plaques and less mixed plaques were observed in diabetic patients. Thus, MSCT may be used to identify differences in coronary plaque burden, which may be useful for risk stratification.
Prandial Insulin Dosing Using Run-to-Run Control
Authors: Palerm Cesar C. , Zisser Howard , Bevier Wendy C. , Jovanovič Lois , Doyle Francis J.
Published: April 2007

OBJECTIVE—We propose a novel algorithm to adjust prandial insulin dose using sparse blood glucose measurements. The dose is adjusted on the basis of a performance measure for the same meal on the previous day. We determine the best performance measure and tune the algorithm to match the recommendations of experienced physicians.

RESEARCH DESIGN AND METHODS—Eleven subjects with type 1 diabetes, using continuous subcutaneous insulin infusion, were recruited (seven women and four men, aged 21–65 years with A1C of 7.1 ± 1.3%). Basal insulin infusion rates were optimized. Target carbohydrate content for the lunch meal was calculated on the basis of a weight-maintenance diet. Over a period of 2–4 days, subjects were asked to measure their blood glucose according to the algorithm's protocol. Starting with their usual insulin-to-carbohydrate ratio, the insulin bolus dose was titrated downward until postprandial glucose levels were high (180–250 mg/dl [10–14 mmol/l]). Subsequently, physicians made insulin bolus recommendations to normalize postprandial glucose concentrations. Graphical methods were then used to determine the most appropriate performance measure for the algorithm to match the physician's decisions. For the best performance measure, the gain of the controller was determined to be the best match to the dose recommendations of the physicians.

RESULTS—The correlation between the clinically determined dose adjustments and those of the algorithm is R2 = 0.95, P < 1e − 18.

CONCLUSIONS—We have shown how engineering methods can be melded with medical expertise to develop and refine a dosing algorithm. This algorithm has the potential of drastically simplifying the determination of correct insulin-to-carbohydrate ratios.
Masked Hypertension, Urinary Albumin Excretion Rate, and Echocardiographic Parameters in Putatively Normotensive Type 2 Diabetic Patients
Authors: Leitão Cristiane B. , Canani Luís H. , Kramer Caroline K. , Boza Juliana C. , Pinotti Antônio F. , Gross Jorge L.
Published: April 2007

OBJECTIVE—To evaluate the impact of masked hypertension in normotensive type 2 diabetic patients on microvascular complications and echocardiographic parameters.

RESEARCH DESIGN AND METHODS—A cross-sectional study was conducted in 135 normotensive patients with type 2 diabetes. Patients underwent urinary albumin excretion rate (UAER) measurement, echocardiography, and 24-h ambulatory blood pressure monitoring (ABPM). Patients with increased daytime blood pressure levels (≥135/85 mmHg) were classified as having masked hypertension.

RESULTS—The prevalence of masked hypertension was 30% (n = 41). Normotensive and masked hypertensive subjects, based on ambulatory blood pressure, were not different in terms of age, diabetes duration, smoking status, BMI, waist circumference, serum creatinine, glycemic, or lipid profiles. The office systolic blood pressure was higher in those with masked hypertension (127.8 ± 7.5 vs. 122.9 ± 10.2 mmHg, P = 0.003) than in the normotensive group. UAER also was increased in the group with masked hypertension (21.3 μg/min [range 2.5–1,223.5] vs. 8.1 μg/min [1.0–1,143.0], P = 0.001), as was the interventricular septum (1.01 ± 0.15 vs. 0.94 ± 0.13 cm, P = 0.015) and posterior wall (0.96 ± 0.12 vs. 0.90 ± 0.10 cm, P = 0.006) thickness. After adjustments for diabetes duration, sex, smoking, LDL cholesterol, and A1C values, all associations were sustained for daytime systolic blood pressure but not for office systolic blood pressure.

CONCLUSIONS—Type 2 diabetic patients with masked hypertension have higher UAER as well as enlargement of ventricular walls compared with the normotensive patients, according to ABPM. Therefore, ABPM is important to identify this high-risk group so as to be able to take interventionist measures.
High-Viscosity Hydroxypropylmethylcellulose Blunts Postprandial Glucose and Insulin Responses
Authors: Maki Kevin C. , Carson Michael L. , Miller Marvin P. , Turowski Maciej , Bell Marjorie , Wilder Donna M. , Reeves Matthew S.
Published: April 2007

OBJECTIVE—High-viscosity hydroxypropylmethylcellulose (HV-HPMC) is a modified cellulose fiber that produces a viscous gel in the gastrointestinal tract. Clinical trials demonstrate that consumption of HV-HPMC significantly lowers cholesterol, but limited information has been available on the influence of HV-HPMC on postprandial insulin and glucose responses. The objective of this investigation was to assess the influence of HV-HPMC on postprandial glucose and insulin responses in overweight and obese men and women.

RESEARCH DESIGN AND METHODS—Participants were 31 overweight or obese men and women without diabetes who underwent three breakfast meal tests in random order, separated by ≥72 h. Test meals containing 75 g carbohydrate plus 4 or 8 g HV-HPMC or control meals containing 8 g cellulose were delivered in a double-blind fashion.

RESULTS—Peak glucose was significantly lower (P < 0.001) after both HV-HPMC–containing meals (7.4 mmol/l [4 g] and 7.4 mmol/l [8 g]) compared with the control meal (8.6 mmol/l). Peak insulin concentrations and the incremental areas for glucose and insulin from 0 to 120 min were also significantly reduced after both HV-HPMC doses versus control (all P < 0.01).

CONCLUSIONS—These findings indicate that HV-HPMC consumption reduces postprandial glucose and insulin excursions, which may favorably alter risks for diabetes and cardiovascular disease.
Adipokines and Risk of Type 2 Diabetes in Older Men
Authors: Wannamethee S. Goya , Lowe Gordon D.O. , Rumley Ann , Cherry Lynne , Whincup Peter H. , Sattar Naveed
Published: April 2007

OBJECTIVE—The aim was to assess the relationship between adipokines, including interleukin (IL)-6, leptin, and adiponectin, with development of type 2 diabetes and assess the role of obesity and insulin resistance in these relationships.

RESEARCH DESIGN AND METHODS—We conducted a prospective study of 3,599 nondiabetic men aged 60–79 years and followed up for a mean period of 5 years, during which time there were 108 incident cases of type 2 diabetes.

RESULTS—Elevated IL-6, leptin, and low adiponectin were associated with increased risk of type 2 diabetes even after adjustment for BMI, lifestyle factors, preexisting cardiovascular disease, and systolic blood pressure. The relative risks (RRs) (top vs. bottom third) were 2.02 (95% CI 1.14–3.58) for IL-6, 1.91 (0.97–3.76) for leptin, and 0.40 (0.23–0.70) for adiponectin. Further adjustment for insulin resistance made minor differences to the IL-6 diabetes relationship (adjusted RR 2.12 [1.18–3.81]), weakened the associations with adiponectin (0.59 [0.33–1.04]), and abolished the association between leptin and diabetes (1.12 [0.55–2.26]). The inverse relation between low adiponectin and diabetes was significantly stronger in men who were obese (waist circumference >102 cm or BMI ≥30 kg/m2) (0.30 [0.11–0.79]) relative to leaner men (0.93 [0.44–1.96]) (test for interaction P = 0.04).

CONCLUSIONS—The association between leptin and incident diabetes is mediated by insulin resistance. By contrast, the positive association between IL-6 and diabetes appeared to be independent of obesity and insulin resistance. Finally, the association between low adiponectin and increased risk of diabetes appears to be significantly stronger in obese men than in leaner counterparts.
Impact of Insulin Resistance on Risk of Type 2 Diabetes and Cardiovascular Disease in People With Metabolic Syndrome
Authors: Meigs James B. , Rutter Martin K. , Sullivan Lisa M. , Fox Caroline S. , D'Agostino Ralph B. , Wilson Peter W.F.
Published: April 2007

OBJECTIVE—Metabolic syndrome increases the risk for type 2 diabetes and cardiovascular disease (CVD) and may be associated with insulin resistance.

RESEARCH DESIGN AND METHODS—We tested the hypothesis that the metabolic syndrome confers risk with or without concomitant insulin resistance among 2,803 Framingham Offspring Study subjects followed up to 11 years for new diabetes (135 cases) or CVD (240 cases). We classified subjects by presence of metabolic syndrome (using the National Cholesterol Education Program's [NCEPs] Third Adult Treatment Panel [ATP III], International Diabetes Federation [IDF], or European Group for the Study of Insulin Resistance [EGIR] criteria) and insulin resistance (homeostasis model assessment of insulin resistance ≥75th percentile) and used separate risk factor–adjusted proportional hazards models to estimate relative risks (RRs) for diabetes or CVD using as referents those without insulin resistance, metabolic syndrome, or without both.

RESULTS—Fifty-six percent of individuals with ATP III, 52% with IDF, and 100% with EGIR definitions of metabolic syndrome had insulin resistance. Insulin resistance increased risk for diabetes (RR 2.6 [95% CI 1.7–4.0]) and CVD (1.8 [1.4–2.3]) as did metabolic syndrome for diabetes (ATP III, 3.5 [2.2–5.6]; IDF, 4.6 [2.7–7.7]; and EGIR, 3.3 [2.1–5.1]) and CVD (ATP III, 1.8 [1.4–2.3]; IDF, 1.7 [1.3–2.3]; and EGIR, 2.1 [1.6–2.7]). Relative to those without either metabolic syndrome or insulin resistance, metabolic syndrome and insulin resistance increased risk for diabetes (ATP III, 6.0 [3.3–10.8] and IDF, 6.9 [3.7–13.0]) and CVD (ATP III, 2.3 [1.7–3.1] and IDF, 2.2 [1.6–3.0]). Any instance of metabolic syndrome without insulin resistance increased risk for diabetes approximately threefold (P < 0.001); IDF metabolic syndrome without insulin resistance (RR 1.6, P = 0.01), but not ATP III metabolic syndrome without insulin resistance (RR 1.3, P = 0.2), increased risk for CVD.

CONCLUSIONS—Metabolic syndrome increased risk for diabetes regardless of insulin resistance. Metabolic syndrome by ATP III criteria may require insulin resistance to increase risk for CVD. The simultaneous presence of metabolic syndrome and insulin resistance identifies an especially high-risk individual.
Recurrence of Gestational Diabetes Mellitus
Authors: Kim Catherine , Berger Diana K. , Chamany Shadi
Published: April 2007

OBJECTIVE—The purpose of this study was to examine rates and factors associated with recurrence of gestational diabetes mellitus (GDM) among women with a history of GDM.

RESEARCH DESIGN AND METHODS—We conducted a systematic literature review of articles published between January 1965 and November 2006, in which recurrence rates of GDM among women with a history of GDM were reported. Factors abstracted included recurrence rates, time elapsed between pregnancies, race/ethnicity, diagnostic criteria, and, when available, maternal age, parity, weight or BMI at the initial and subsequent pregnancy, weight gain at the initial or subsequent pregnancy and between pregnancies, insulin use, gestational age at diagnosis, glucose tolerance test levels, baby birth weight and presence of macrosomia, and breast-feeding.

RESULTS—Of 45 articles identified, 13 studies were eligible for inclusion. After the index pregnancy, recurrence rates varied between 30 and 84%. Lower rates were found in non-Hispanic white (NHW) populations (30–37%), and higher rates were found in minority populations (52–69%). Exceptions to observed racial/ethnic variations in recurrence were found in cohorts that were composed of a significant proportion of both NHW and minority women or that included women who had subsequent pregnancies within 1 year. No other risk factors were consistently associated with recurrence of GDM across studies. The rates of future preexisting diabetes in pregnancy, socioeconomic status, postpartum diabetes screening rates after the index pregnancy, and the average length of time between pregnancies were generally not reported.

CONCLUSIONS—Recurrence of GDM was common and may vary most significantly by NHW versus minority race/ethnicity.
Incidence of Coronary Heart Disease in Type 2 Diabetic Men and Women
Authors: Avogaro Angelo , Giorda Carlo , Maggini Marina , Mannucci Edoardo , Raschetti Roberto , Lombardo Flavia , Spila-Alegiani Stefania , Turco Salvatore , Velussi Mario , Ferrannini Ele ,   for the Diabetes and Informatics Study Group, Association of Clinical Diabetologists, Istituto Superiore di Sanità
Published: April 2007

OBJECTIVE—Cardiovascular disease (CVD) is the main cause of morbidity/mortality in diabetes. We set forth to determine incidence and identify predictors (including microvascular complications and treatment) of first coronary heart disease (CHD) event in CVD-free type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—A cohort of 6,032 women and 5,612 men, sampled from a nationwide network of hospital-based diabetes clinics, was followed up for 4 years. Baseline assessment included retinopathy, nephropathy, and foot ulcers. First CHD events (myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, and electrocardiogram-proven angina) were analyzed for 29,069 person-years.

RESULTS—The age-standardized incidence rate (per 1,000 person-years) of first CHD event (n = 881) was 28.8 (95% CI 5.4–32.2) in men and 23.3 (20.2–26.4) in women. Major CHD (myocardial infarction, coronary artery bypass grafting, and percutaneous transluminal coronary angioplasty) was less frequent in women (5.8 [4.3–7.2]) than in men (13.1 [10.9–15.4]; a sex ratio of 0.5 [0.4–0.6]). Incidence rates of all outcomes were higher in patients with microvascular complications (for major CHD, age-adjusted rate ratios were 1.6 [1.2–2.21] in men and 1.5 [1.0–2.2] in women). By multivariate Cox analysis, age and diabetes duration were risk predictors common in both sexes. In men, glycemic control and treated hypertension were additional independent risk factors, but residing in the south was associated with a significant 29% risk reduction. In women, higher triglycerides/lower HDL cholesterol and microvascular complications were independent risk factors.

CONCLUSIONS—In CVD-free patients with type 2 diabetes, risk of first CHD event depends on sex, geographic location, and presence of microvascular disease. Hyperglycemia and hypertension, particularly in men, and diabetic dyslipidemia, especially in women, are risk factors amenable to more aggressive treatment.
Ultrastructural and cytochemical studies on vitellogenesis in the trypanorhynch cestode Parachristianella trygonis Dollfus, 1946 (Eutetrarhynchidae)
Authors: Świderski Zdzisław , Miquel Jordi , Neifar Lassad , Mackiewicz John
Published: April 2007

During vitellogenesis in Parachristianella trygonis Trypanorhyncha, Eutetrarhynchidae) we distinguished four stages: (1) gonial or stem cell stage; (2) early differentiation stage concentrated on protein synthetic activity and shell-globule formation; (3) advanced differentiation stage with main cell activity concentrated on carbohydrate synthesis (glycogenesis) and massive glycogen storage in the form of α-glycogen rosettes and β-glycogen particles; and finally (4) mature vitellocyte stage. Early vitellocyte maturation is characterised by: (1) an increase in cell volume; (2) extensive development of large, parallel cisternae of GER that produce proteinaceous granules; (3) development of Golgi complexes engaged in packaging this material; (4) continuous enlargement of proteinaceous granules within vacuoles and their transformation into shell-globule clusters composed of heterogeneous material. Cytochemical staining with periodic acid-thiosemicarbazide-silver proteinate for polysaccharides indicated a strongly positive reaction for the presence of α-glycogen rosettes and β-glycogen particles in the advanced stage of vitellocyte maturation. Both protein synthesis for shell-globule formation and carbohydrate synthesis or glycogenesis, important storage of nutritive reserves for the developing embryos, observed during cytodifferentiation of P. trygonis vitellocytes overlap in time to some extent. Mature vitelline cells are very rich in three types of cell inclusions accumulated in large amounts in their cytoplasm: (1) shell-globule clusters, playing an important role in egg-shell formation; (2) numerous large lipid droplets, as well as a high accumulation of lipid and α-glycogen rosettes and β-glycogen particles that undoubtedly represent important nutritive reserves for the developing embryos. Despite the fact that the type of vitellogenesis and ultrastructure of the mature vitellocyte in P. trygonis appears to differ to some extent from those of three other trypanorhynch species, its general pattern and ultrastructure greatly resembles those observed in other lower cestodes. Factors that may have contributed to the qualitative and quantitative variation in lipids during vitellogenesis among the four species of Trypanorhyncha, are identified and discussed.
Probing canonical geometrical objects by digital spiral imaging
Authors: Molina-Terriza Gabriel , Rebane Liis , Torres Juan P. , Torner Lluis , Carrasco Silvia
Published: April 2007

We recently proposed a novel concept to remotely acquire information of objects, based on the discrete orbital angular momentum of light. Here we use two different schemes for implementing the technique. In order to test the two acquisition methods and to compare their results, we use as target the simplest canonical phase jump.
Surface‐Engineered Nanocontainers for Entrapment of Corrosion Inhibitors
Authors: Shchukin D. G. , Möhwald H.
Published: April 2007

The release properties and reloading ability of polyelectrolyte‐modified halloysite nanotubes, polyelectrolyte‐modified SiO2nanoparticles, and polyelectrolyte capsules are studied. Three containers are distinguished by keeping the low‐molecular‐weight corrosion inhibitor benzotriazole in a hollow lumen inside or within the polyelectrolyte matrix and allowing release in either one direction or into all space dimensions. Polyelectrolyte shells, which modify the outer surface of the nanocontainers, are fabricated by using layer‐by‐layer assembly of poly(diallyldimethylammonium chloride)/poly(styrene sulfonate), poly(allylamine hydrochloride)/poly(styrene sulfonate), and poly(allylamine hydrochloride)/poly(methacrylic acid) polyelectrolyte bilayers. All nanocontainers reveal an increase of the benzotriazole release in aqueous solution at alkaline or acidic pH. The highest reloading efficiency (up to 80 %) is observed for halloysite‐based nanocontainers; however, after five reloading cycles the efficiency decreases to 20 %. The application of appropriate nanocontainers depends on the demands required from feedback‐active anticorrosion coatings. For coatings where the immediate release of the inhibitor is necessary, SiO2‐based or halloysite‐based nanocontainers with a shell consisting of weak polyelectrolytes are preferable. When continuous, gradual release is required, halloysite‐based nanocontainers with a shell consisting of one weak and one or two strong polyelectrolytes are preferable.
Dynamic history of low‐grade gliomas before and after temozolomide treatment
Authors: Ricard Damien , Kaloshi Gentian , Amiel‐Benouaich Alexandra , Lejeune Julie , Marie Yannick , Mandonnet Emmanuel , Kujas Michèle , Mokhtari Karima , Taillibert Sophie , Laigle‐Donadey Florence , Carpentier Antoine F. , Omuro Antonio , Capelle Laurent , Duffau Hugues , Cornu Philippe , Guillevin Rémy , Sanson Marc , Hoang‐Xuan Khê , Delattre Jean‐Yves
Published: April 2007

Objective

To evaluate the natural progression and the impact of temozolomide in low‐grade gliomas and to correlate these changes with the profile of genetic alterations.

Methods

The mean tumor diameter (MTD) of low‐grade gliomas was evaluated on serial magnetic resonance images before (n = 39), during, and after (n = 107) treatment with neoadjuvant temozolomide. MTD growth curves were correlated with chromosomes 1p‐19q loss and p53 overexpression in the tumors.

Results

Before temozolomide onset, MTD increased linearly over time, indicating a continuous growth that was significantly slower in 1p‐19q deleted tumors (3.4 vs 5.9mm/year; p = 0.0016) and in tumors that did not overexpress p53 (4.2 vs 6.3mm/year; p = 0.05). During temozolomide treatment, almost all patients (92%) experienced initial decrease of MTD. Subsequently, some tumors started to resume growth despite continuous administration of temozolomide, with a lower rate of relapse in 1p‐19q deleted tumors (16.6 vs 58%; p = 0.0004) and in tumors that did not overexpress p53 (26 vs 68%; p = 0.003). When temozolomide was discontinued in the absence of tumor progression, a majority of tumors resumed their progressive growth within a year.

Interpretation

Untreated low‐grade gliomas grow continuously at a rate that is influenced by the genetic alterations of the tumors. Temozolomide reverses this pattern at the onset, but this effect is often brief in patients whose tumors overexpress p53 and do not harbor the 1p‐19q codeletion, suggesting acquired chemoresistance. A majority of tumors will resume their growth when treatment is discontinued, raising the issue of the optimal duration of treatment in continuously responding patients. Ann Neurol 2007;61:484–490
Polio and nobel prizes: Looking back 50 years
Authors: Norrby Erling , Prusiner Stanley B.
Published: April 2007

In 1954, John Enders, Thomas Weller, and Frederick Robbins were awarded the Nobel Prize in Physiology or Medicine “for their discovery of the ability of poliomyelitis viruses to grow in cultures of various types of tissue.”53, 70 This discovery provided for the first time opportunities to produce both inactivated and live polio vaccines. By searching previously sealed Nobel Committee archives, we were able to review the deliberations that led to the award. It appears that Sven Gard, who was Professor of Virus Research at the Karolinska Institute and an adjunct member of the Nobel Committee at the time, played a major role in the events leading to the awarding of the Prize. It appears that Gard persuaded the College of Teachers at the Institute to decide not to follow the recommendation by their Nobel Committee to give the Prize to Vincent du Vigneaud. Another peculiar feature of the 1954 Prize is that Weller and Robbins were included based on only two nominations submitted for the first time that year. In his speech at the Nobel Prize ceremony, Gard mentioned the importance of the discovery for the future production of vaccines, but emphasized the implications of this work for growing many different, medically important viruses. We can only speculate on why later nominations highlighting the contributions of scientists such as Jonas Salk, Hilary Koprowski, and Albert Sabin in the development of poliovirus vaccines have not been recognized by a Nobel Prize. Ann Neurol 2007;61:385–395
TDP‐43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
Authors: Amador‐Ortiz Catalina , Lin Wen‐Lang , Ahmed Zeshan , Personett David , Davies Peter , Duara Ranjan , Graff‐Radford Neill R. , Hutton Michael L. , Dickson Dennis W.
Published: April 2007

Objective

This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD‐U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP‐43), a putative marker for FTLD‐U.

Methods

Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD‐U with TDP‐43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP‐43 antibodies was assessed using double‐immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry.

Results

TDP‐43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP‐43 and phospho‐tau showed that the TDP‐43–immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP‐43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP‐43 that was not present in AD cases without TDP‐43 immunoreactivity.

Interpretation

These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD‐U. Whether this represents concomitant FTLD‐U or is analogous to colocalization of α‐synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined. Ann Neurol 2007;61:435–445
Biomimetic synthesis of gold nanoparticles and their aggregates using a polypeptide sequence
Authors: Wang Zheng , Chen Jinchun , Yang Peng , Yang Wantai
Published: April 2007

The polypeptide sequence MS14 (MHGKTQATSGTIQS) was used to explore a new method for biomimetic preparation of gold nanoparticles and their aggregates. Self‐congregation of gold nanoparticles into aggregates in MS14 aqueous solution and self‐assembly of gold crystallites onto the designed complex of MS14‐PET film [protonated poly(ethylene terephthalate)] proved the specific gold‐binding characteristic of the single‐copy peptide MS14 in vitro. In aqueous solution MS14 could recover Au(III) to Au(0), tested by means of TEM, EDX and XPS. Further research suggested that the pH of the solution and the concentration of Au(III) influenced the morphology and size of the gold nanoparticles formed. In addition, extra reducing agent, sodium citrate, was introduced into the HAuCl4–MS14 system and uniformly dispersed nanoparticles under neutral condition were obtained. Finally, we discuss the possible mechanism of this biomimetic synthesis. Copyright © 2007 John Wiley & Sons, Ltd.
Mono‐ and heterodi‐nuclear complexes of aluminium: synthesis, characterization and antifungal activity
Authors: Vajpayee Vaishali , Singh Y. P. , Nandani Durgesh , Batra Amla
Published: April 2007

Some new types of mononuclear derivatives, AlL(1–4)L(1–4)H (1a–1d) of aluminium were synthesized by the reaction of Al(OPri)3 and LH2 [XC(NYOH)CHC(R)OH], X = CH3, Y = (CH2)2, R = CH3(L1H2); X = C6H5, Y = (CH2)2, R = CH3(L2H2); X = CH3, Y = (CH2)3, R = CH3(L3H2); X = C6H5, Y = (CH2)3, R = CH3(L4H2) in 1:2 molar ratio in refluxing benzene. Reactions of AlL(1–4)L(1–4)H with hexamethyldisilazane in 2:1 molar ratio yielded some new ligand bridged heterodinuclear derivatives AlL(1–4)L(1–4)SiMe3 (2a–2d). All these newly synthesized derivatives were characterized by elemental analysis and molecular weight measurements. Tentative structures were proposed on the basis of IR and NMR spectra (1H, 13C,27Al and 29Si) and FAB‐mass studies. Schiff base ligands and their mono‐ and heterodi‐nuclear derivatives with aluminium have been screened for fungicidal activities. These compounds showed significant antifungal activity against Aspergillus niger and A. flavus. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis and characterization of carboxyl‐functionalized magnetic nanogel via “green” photochemical method
Authors: Hong Jun , Gong Peijun , Xu Dongmei , Sun Hanwen , Yao Side
Published: April 2007

Carboxyl‐functionalized magnetic nanogel was synthesized by facile “green” photochemical method. A possible mechanism of photochemical synthesis was proposed. Effects of irradiation time and volume of monomer dropped on the hydrodynamic diameter of the magnetic nanogel were investigated by photo correlation spectroscopy. The image of atomic force microscopy presented that the magnetic nanogel was with loosed structure. X‐ray diffraction analysis showed that UV irradiation did not induce phase change of Fe3O4. Superparamagnetic behaviors were retained for Fe3O4 while slightly reducing the value of saturation magnetization for surface coating. High magnetic content of (as high as 85%) and strong magnetization of Fe3O4 guaranteed that the magnetic nanogel was susceptive to external applied magnetic field. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Characterization of poly(isobornyl acrylate) as a construction material for microfluidic applications
Authors: López‐García M. d. C. , Beebe D. J. , Crone W. C.
Published: April 2007

Isobornyl acrylate (IBA) is a photopolymerizable monomer that is employed in microfluidic devices because of desirable properties, such as inertness, transparency, and resolution. However, some of the mechanical properties of poly(isobornyl acrylate) are greatly affected by subtle changes in the manufacturing techniques. In this study, the parameters of exposure time, UV intensity, and aging are varied to study their effect on the material properties of thin samples of isobornyl acrylate construction material (<0.25 mm). Mechanical testing was used to obtain properties, such as elasticity, maximum strength, and maximum strain. It was observed that when using high levels of both exposure time and intensity, the polymers strength was increased. Lowering one of these two parameters immediately reduced the construction materials strength. It was also noted that aging weakens the material in as little as 1 day. In addition, an anisotropic response that produces curling in samples has been studied. It showed to have a negligible effect on the mechanical properties of the material; however it may have a major effect on device quality and shelf‐life. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Effects of drying process for amorphous waxy maize starch on theophylline release from starch‐based tablets
Authors: Yoon Hyun‐Sung , Kweon Dong‐Keon , Lim Seung‐Taik
Published: April 2007

Physical properties and theophylline‐release profiles of compressed tablets prepared with amorphous waxy maize starches dried using different methods were examined. A gelatinized waxy maize starch paste (10% solids in water) was either freeze‐dried or oven‐dried (40 or 105°C) until the moisture content reached to <5%. To form the tablets, the dried amorphous starch powders, either with or without theophylline (3 : 10, w/w), were remoistened to a water content of (17 ± 0.2)%, and compressed into tablets. The drying process applied to the amorphous starch powders affected both the compactness and swelling behavior of the tablets. Although no crystallinity was detected in all the starches tested, X‐ray diffraction patterns indicated that starch chains dried at the lower temperature (40°C) are allowed more time to re‐associate during the drying process than those dried at the higher temperature (105°C). The freeze‐dried starch powders formed tablets characterized by greater compactness and rigidity than was observed in the oven‐dried starch samples. The drug release of the tablets prepared with the starch dried at the higher temperature (105°C) occurred at a much slower rate than that of the tablets made with the starch dried at the lower temperature (40°C). The drug release characteristics of the freeze‐dried starch tablets were nearly identical to those of the tablets prepared with the starch dried at 105°C. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Morphological study of LLDPE‐NR reactive blending with maleic anhydride
Authors: Magaraphan Rathanawan , Skularriya Rewadee , Kohjiya Shinzo
Published: April 2007

A binary blend and ternary reactive blends of 90/10 LLDPE/NR using maleic anhydride (MA) as a reactive agent with and without dicumyl peroxide (DCP) were made at 150°C in an internal mixer. The fracture surfaces of the blends were conventionally observed by TEM and atomic force microscope, revealing that the rubber domains became smaller with the addition of MA and DCP. This suggested that the in situ graft copolymer (LLDPE‐g‐NR) was formed and acted as an in situ compatibilizer to enhance interfacial adhesion. This was further supported by FTIR results. Importantly, after removal of NR phase from the blends, the remaining LLDPE part was dissolved in hot xylene, purified by precipitation in methanol, and carefully prepared by solvent casting for TEM observation. The microstructures of the solvent‐extracted LLDPE from all blends are unlike that of solvent cast‐ pure LLDPE, which shows only crystalline structure. This leads to an unambiguous way to disclose the existence of an in situ graft copolymer. The solvent‐extracted LLDPE from the blends shows mixed morphology of LLDPE crystalline structure and its in situ graft copolymer as nanofibrillar networks of the NR phase protruded from the amorphous region of the LLDPE matrix due to spinodal decomposition by the solvent removal. Adding MA makes more branches and fibril connections of the NR phase, whereas a thinner fibril network and more links of the NR and the LLDPE amorphous region are found in the reactive blend with MA and DCP, where the most compatibilized blend is obtained. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Contribution of shape on ignition of polymeric materials
Authors: Endoh Kotaroh , Mizuno Kohshiroh , Ueno Tomonaga , Ishikawa Tomoyuki , Yukumoto Masao , Takeda Kunihiko
Published: April 2007

The contribution of the shape and size of polymers towards ignition for four kinds of polymers, PP (polypropylene), HIPS (rubber reinforced polystyrene), ABS (acrilonitril‐butadiene‐styrene copolymer) and PC (bisphenor‐A type polycarbonate) was studied. The critical heat flux (CHF), which means that the specimen ignites after infinite time, depended on the shape and kind of polymer at the plane position heating. But it was not affected by these conditions at the side position heating. The CHF and other phenomena of ignition were analyzed and the two regions in one of which the shape and the kind of polymer affects them and in another region they was not affected. It will be useful to design electrical parts that reduce fire risks. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Country as the primary risk factor for renal amyloidosis in familial mediterranean fever
Authors: Touitou Isabelle , Sarkisian Tamara , Medlej‐Hashim Myrna , Tunca Mehmet , Livneh Avi , Cattan Daniel , Yalçinkaya Fatos , Özen Seza , Majeed Hassan , Ozdogan Huri , Kastner Daniel , Booth David , Ben‐Chetrit Eldad , Pugnère Denis , Michelon Cécile , Séguret Fabienne , Gershoni‐Baruch Ruth ,   International Study Group for Phenotype‐Genotype Correlation in Familial Mediterranean Fever
Published: April 2007

Objective

Familial Mediterranean fever (FMF), the prototype of autoinflammatory disorders, is caused by recessive mutations in the MEFV gene. Some FMF patients develop renal amyloidosis, a potentially fatal condition. This complication has mainly been associated with the M694V mutation, although the different study designs, small numbers of patients, and/or evaluation of few or no covariables calls this association into question. The aim of this study was to examine the controversial issue of amyloidosis susceptibility in FMF by determining the relative contributions of MEFV and numerous epidemiologic factors to the risk of renal amyloidosis.

Methods

Online questionnaires were completed at the MetaFMF database by patients at 35 centers in 14 countries. Using a standardized mode of data collection, we retrieved crude initial data from over half of the genetically confirmed FMF patients referred worldwide until May 2003 (2,482 cases, including 260 patients who developed renal amyloidosis).

Results

Amyloid nephropathy was present in 11.4% of the cases. In the total study population, country of recruitment was the leading risk factor for this manifestation (odds ratio 3.2 [95% confidence interval 1.8–5.9]), followed by M694V homozygosity, proband status, and disease duration. Differing results were found when countries were stratified.

Conclusion

Country of recruitment, rather than MEFV genotype, is the key risk factor for renal amyloidosis in FMF. This risk, which parallels infant mortality rates, indicates a possible environmental origin of amyloidosis susceptibility. The patient's country should be considered in addition to MEFV genotype as an indication for prophylactic colchicine, a treatment suggested for asymptomatic individuals who are incidentally discovered to be M694V homozygous.
B cell depletion may be more effective than switching to an alternative anti–tumor necrosis factor agent in rheumatoid arthritis patients with inadequate response to anti–tumor necrosis factor agents
Authors: Finckh Axel , Ciurea Adrian , Brulhart Laure , Kyburz Diego , Möller Burkhard , Dehler Silvia , Revaz Sylvie , Dudler Jean , Gabay Cem ,   Physicians of the Swiss Clinical Quality Management Program for Rheumatoid Arthritis
Published: April 2007

Objective

Patients with rheumatoid arthritis (RA) in whom the response to anti–tumor necrosis factor (anti‐TNF) therapy is inadequate have several therapeutic options, such as switching to an alternative anti‐TNF agent or initiating B cell–depleting therapy with rituximab (RTX). Although both therapeutic options have been proven effective in trials, no head‐to‐head comparisons are available. The aim of this study was to compare the effectiveness of RTX with that of an alternative anti‐TNF agent in the management of patients with RA who had an inadequate response to anti‐TNF therapy.

Methods

This prospective cohort study was nested within the Swiss Clinical Quality Management RA cohort and included all patients who had an inadequate response to at least 1 anti‐TNF agent and subsequently received either 1 cycle of RTX or an alternative anti‐TNF agent. The primary outcome was the evolution of RA disease activity (as measured on the Disease Activity Score in 28 joints [DAS28]), which was analyzed using multivariate regression models for longitudinal data.

Results

One hundred sixteen patients with RA were included; 50 patients received 1 cycle of RTX, and 66 patients were treated with a second or a third alternative anti‐TNF agent. At baseline, there were no significant differences between the 2 groups in age, sex, disease duration, and disease activity. Evolution of the DAS28 was more favorable in the group that received RTX compared with the group that received an alternative anti‐TNF agent (P = 0.01). At 6 months, the mean decrease in the DAS28 was −1.61 (95% confidence interval [95% CI] −1.97, −1.25) among patients receiving RTX and −0.98 (95% CI −1.33, −0.62) among those receiving subsequent anti‐TNF therapy.

Conclusion

The results of this observational study suggest that treatment with RTX may be more effective than switching to an alternative anti‐TNF agent in patients with RA in whom active disease persists despite anti‐TNF therapy.