Diamicron MR once daily is effective and well tolerated in type 2 diabetes: a double-blind, randomized, multinational study

In a double-blind, multicenter, multinational study, the long-term efficacy and safety of Diamicron(R)MR, a new gliclazide formulation taken once daily at lower dose (30-120 mg/day) was compared with Diamicron(R) (80-320 mg/day) taken twice daily in type 2 diabetic outpatients. After a 2-week run-in period, 800 patients with poor blood glucose control were randomized to Diamicron(R)MR (n=401) or Diamicron(R) (n=399). After a 4-month titration period, the efficacy and safety of Diamicron(R)MR was compared with Diamicron(R) over a 6-month fixed-dose treatment period. The ability to switch from Diamicron(R) to Diamicron(R)MR was then assessed during an additional 2-month follow-up period. Equivalence between treatment with Diamicron(R)MR and Diamicron(R) was compared by a non-inferiority test; the limit of equivalence was set at 0.5% for HbA(1c) and 1 mmol/l for fasting plasma glucose (FPG). The treatment groups were comparable at baseline.After 10 months of treatment, Diamicron(R)MR was as efficient as Diamicron(R) in controlling blood glucose, with a mean end point difference in HbA(1c) of -0.08 (0. 08)%, significantly lower than the equivalence limit (p<0.001). Similar results were obtained for FPG.The safety of Diamicron(R)MR and Diamicron(R) was equally high. The incidence of hypoglycemia was particularly low (0.2 hypoglycemia/100 patient months) in the elderly population, which represented almost 40% of the included patients.This study demonstrates that 30 to 120 mg of Diamicron(R)MR taken once daily is at least as efficient as 80 to 320 mg of Diamicron(R) taken in divided doses with respect to HbA(1c) and FPG levels, with a similar safety profile.     

Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis

The metabolism of apolipoprotein (apo) A-IV in diabetes mellitus (DM) is poorly understood. Several factors, such as dietary fat intake, fat malabsorption, acute inflammation, and hormonal dysregulation can disturb the plasma apo A-IV concentration. We have compared the plasma apo A-IV concentrations in patients with type 1 DM and DM secondary to chronic pancreatitis to determine the effects of combinations of these factors. We examined 4 groups of male patients with chronic pancreatitis without diabetes (ND-CP) (n = 12), diabetes secondary to chronic pancreatitis and insulin-treated (CP-DM) (n = 32), type 1 diabetes (n = 25), and controls (n = 20). Plasma apo A-IV was significantly lower in the chronic pancreatitis patients (ND-CP and CP-DM) than in the other patients. Inflammatory proteins (fibrinogen, ceruloplasmin, and haptoglobin) were significantly elevated in the 2 chronic pancreatitis groups. The apo A-IV concentration was positively correlated with hemoglobin A(1c) (HbA(1c)) percentage in each group of diabetic patients (CP-DM, r =.35; P =.046; type 1 DM, r =.53; P =.010), in both groups of diabetic patients (r =.472; P <.0001) and negatively correlated with ceruloplasmin concentration in each group of diabetic patients (CP-DM, r = -.48; P =.0052; type 1 DM, r = -.66; P =.003), in both groups of diabetic patients (r = -.561; P <.0001), and in the whole population (r = -.463; P <.0001). Apo A-IV was also negatively correlated with haptoglobin in type 1 DM patients (r = -.434; P =.0435), in the both groups of diabetic patients (r = -.349; P =.0154), and in the whole population (r = -.351; P =.0019). Multiple linear regression analysis revealed that only HbA(1c) and ceruloplasmin were independent explanatory variables. Plasma apo A-IV is positively correlated with HbA(1c) suggesting that hyperglycemia per se selectively affects apo A-IV metabolism. The correlation between the concentrations of inflammatory protein and apo A-IV suggest a link between chronic inflammation and apo A-IV synthesis or catabolism. As apo A-IV is involved in reverse cholesterol transport, its low level in CP-DM may contribute to the accelerated development of atherosclerosis in these patients.     

Leisure activities and service knowledge and use among the rural elderly

This exploratory study uses Andersen's service utilization model to examine the relationship between the leisure activity patterns of older people and their knowledge and use of health and social services. Hierarchical stepwise multiple regression analyses of data from 418 people ages 65 and older in rural Qu/ebec revealed that leisure activity patterns may explain a greater amount of variation in service knowledge and use than conventional need characteristics such as physical and psychological health. Various activity patterns were significantly related to knowledge and use of services even after controlling for variables such as age and health status. Although some types of leisure activities appeared to augment knowledge and use of services, others seemed to deter it. Future explanatory models of service utilization among the elderly should be expanded to include leisure activity patterns.     

An autosomal dominant, qualitative platelet disorder associated with multimerin deficiency, abnormalities in platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen and an epinephrine aggregation defect

Multimerin is a massive soluble, multimeric protein found in platelets and endothelial cells. Recent studies identified multimerin as a specific coagulation factor V binding protein, complexed with platelet, but not plasma, factor V. These findings led us to investigate individuals with inherited factor V deficiencies for possible multimerin abnormalities. Platelet proteins were evaluated using immunoassays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, immunoprecipitation, and direct binding studies. Patients with factor V Quebec, a disorder with abnormal platelet factor V, had a quantitative deficiency in multimerin (n = 11 tested; mean, 12.5%; range, 5% to 27% of the normal pool; normal range, 45% to 214%) with a normal multimer pattern. Quantitative and qualitative abnormalities were detected in their platelet factor V. An unrelated patient who was deficient in platelet and plasma factor V had normal platelet multimerin. The levels of platelet beta- thromboglobulin, von Willebrand factor, thrombospondin, and fibrinogen antigen were normal in the factor V Quebec patients. However, proteins with abnormal mobility were detected in their platelet lysate and releasate, and their platelet thrombospondin, von Willebrand factor, and fibrinogen showed evidence of proteolytic degradation. Platelet counts of the factor V Quebec patients ranged from mildly thrombocytopenic to low normal (mean, 159 x 10(9)/L; range, 104 to 198 x 10(9)/L). In addition, their platelets failed to aggregate in response to 6 to 10 micromol/L epinephrine despite normal numbers of platelet alpha 2-adrenergic receptors. These data indicate that patients with factor V Quebec have an inherited bleeding disorder distinct from other platelet disorders and associated with multiple abnormalities, including multimerin deficiency, abnormal platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen, and an epinephrine aggregation defect.     

Transition zone and anterior stromal prostate cancers: Evaluation of discriminant location criteria using multiparametric fusion-guided biopsy

Purpose

The purpose of this study was to evaluate precise location criteria on magnetic resonance imaging (MRI) to improve detection of transition zone (TZ) and anterior stroma (AS) prostate cancers using targeted MRI/transrectal ultrasound fusion biopsies as a reference standard.

User-friendly freehand ultrasound calibration using Lego bricks and automatic registration

Purpose

As an inexpensive, noninvasive, and portable clinical imaging modality, ultrasound (US) has been widely employed in many interventional procedures for monitoring potential tissue deformation, surgical tool placement, and locating surgical targets. The application requires the spatial mapping between 2D US images and 3D coordinates of the patient. Although positions of the devices (i.e., ultrasound transducer) and the patient can be easily recorded by a motion tracking system, the spatial relationship between the US image and the tracker attached to the US transducer needs to be estimated through an US calibration procedure. Previously, various calibration techniques have been proposed, where a spatial transformation is computed to match the coordinates of corresponding features in a physical phantom and those seen in the US scans. However, most of these methods are difficult to use for novel users.

Methods

We proposed an ultrasound calibration method by constructing a phantom from simple Lego bricks and applying an automated multi-slice 2D–3D registration scheme without volumetric reconstruction. The method was validated for its calibration accuracy and reproducibility.

Results

Our method yields a calibration accuracy of \(1.23\pm 0.26\) mm and a calibration reproducibility of 1.29 mm.

Conclusion

We have proposed a robust, inexpensive, and easy-to-use ultrasound calibration method.

     

Validity of the Foot and Ankle Ability Measure in athletes with chronic ankle instability

CONTEXT: The Foot and Ankle Ability Measure (FAAM) is a region-specific, non-disease-specific outcome instrument that possesses many of the clinimetric qualities recommended for an outcome instrument. Evidence of validity to support the use of the FAAM is available in individuals with a wide array of ankle and foot disorders. However, additional evidence to support the use of the FAAM for those with chronic ankle instability (CAI) is needed. OBJECTIVE: To provide evidence of construct validity for the FAAM based on hypothesis testing in athletes with CAI. DESIGN: Between-groups comparison. SETTING: Athletic training room. PATIENTS OR OTHER PARTICIPANTS: Thirty National Collegiate Athletic Association Division II athletes (16 men, 14 women) from one university. MAIN OUTCOME MEASURE(S): The FAAM including activities of daily living (ADL) and sports subscales and the global and categorical ratings of function. RESULTS: For both the ADL and sports subscales, FAAM scores were greater in healthy participants (100 +/- 0.0 and 99 +/- 3.5, respectively) than in subjects with CAI (88 +/- 7.7 and 76 +/- 12.7, respectively; P < .001). Similarly, for both ADL and sports subscales, FAAM scores were greater in athletes who indicated that their ankles were normal (98 +/- 6.3 and 96 +/- 6.9, respectively) than in those who classified their ankles as either nearly normal or abnormal (87 +/- 6.6 and 71 +/- 11.1, respectively; P < .001). We found relationships between FAAM scores and self-reported global ratings of function for both ADL and sports subscales. Relationships were stronger when all athletes, rather than just those with CAI, were included in the analyses. CONCLUSIONS: The FAAM may be used to detect self-reported functional deficits related to CAI.     

Binding of outer surface protein A and human lymphocyte function–associated antigen 1 peptides to HLA–DR molecules associated with antibiotic treatment–resistant Lyme arthritis

Objective

To assess the binding of outer surface protein A (OspA) and human lymphocyte function–associated antigen 1 (hLFA‐1) peptides to 5 major histocompatibility complex (MHC) molecules.

Methods

Peptide binding to the MHC molecules was determined by in vitro binding assays, and binding was correlated with the frequencies of the 5 MHC molecules in patients with treatment‐resistant Lyme arthritis.

Results

The HLA–DRB1*0401 molecule bound both OspA_163–175 and hLFA‐1α_L330–342 well. Although the magnitude of the binding was less, the DRB1*0404 molecule also showed binding of both peptides. The DRB1*0101 molecule bound OspA_163–175 well, but hLFA‐1α_L330–342 only weakly; the DRB1*0801 or *1101 molecule bound both peptides weakly, if at all. The magnitude of OspA_163–175 binding correlated well with the frequencies of the DRB1 alleles in patients with treatment‐resistant arthritis, but the binding of hLFA‐1α_L330–342 showed only an association with the DRB*04 alleles.

Conclusion

These correlations support the hypothesis that OspA_163–175 is the critical epitope in triggering antibiotic treatment–resistant Lyme arthritis. However, the inability of the DRB*0101 molecule to bind hLFA‐1α_L330–342 suggests that this peptide may not be a relevant autoantigen, at least in DRB1*0101‐positive patients.