Risk factors for the progression of carotid intima-media thickness over a 16-year follow-up period: the Malmö Diet and Cancer Study.

OBJECTIVE: To evaluate the progression of carotid intima-media thickness (IMT) in the common carotid artery (CCA) and the bifurcation over a mean follow-up of 16 years in relation to cardiovascular risk factors. METHODS: The study population included 3426 middle-aged Swedish men and women participating in the 1991-1994 (baseline) and the 2007-2012 (re-examination) investigation of the cardiovascular cohort of the Malmö Diet and Cancer Study (MDCS). RESULTS: There were differences in risk factor patterns in arterial segments in that diabetes and male sex were associated with the progression of IMT in the bifurcation, but not in the CCA, and high-density lipoprotein cholesterol (HDL) was associated with the progression of IMT in the CCA, but not in the bifurcation. Favourable changes in systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL) and HDL during follow-up decreased the IMT progression rate in the CCA. There was a cumulative relationship between traditional cardiovascular risk factors (i.e., regular smoking, LDL/HDL-ratio ≥ 3, hypertension) and IMT progression rates. The odds ratio (OR) of high IMT CCA progression rate (>75th percentile) was 1.0 (reference), 1.4 (95% CI: 1.1, 1.7), 1.7 (95% CI: 1.3, 2.2) and 2.1 (95% CI: 1.4, 3.1), respectively, for individuals with none, one, two, and three risk factors. CONCLUSION: There were differences in the associations between risk factors and progression rate in different arterial segments. Favourable changes in SBP and lipids during the follow-up period were associated with reduced IMT progression rates in the CCA.

Measures of atherosclerotic burden are associated with clinically manifest cardiovascular disease in type 2 diabetes: a European cross-sectional study.

BACKGROUND: There is a need to develop and validate surrogate markers of cardiovascular disease (CVD) in subjects with diabetes. The macrovascular changes associated with diabetes include aggravated atherosclerosis, increased arterial stiffness and endothelial dysfunction. The aim of this study was to determine which of these factors is most strongly associated with clinically manifest cardiovascular events. METHODS: Vascular changes were measured in a cohort of 458 subjects with type 2 diabetes (T2D) and CVD (myocardial infarction, stroke or lower extremity arterial disease), 527 subjects with T2D but without clinically manifest CVD and 515 subjects without T2D and with or without CVD. RESULTS: Carotid intima-media thickness (IMT) and ankle-brachial pressure index were independently associated with the presence of CVD in subjects with T2D, whereas pulse wave velocity and endothelial function provided limited independent additive information. Measurement of IMT in the carotid bulb provided better discrimination of the presence of CVD in subjects with T2D than measurement of IMT in the common carotid artery. The factors most significantly associated with increased carotid IMT in T2D were age, disease duration, systolic blood pressure, impaired renal function and increased arterial stiffness, whereas there were no or weak independent associations with metabolic factors and endothelial dysfunction. CONCLUSIONS: Measures of atherosclerotic burden are associated with clinically manifest CVD in subjects with T2D. In addition, vascular changes that are not directly related to known metabolic risk factors are important in the development of both atherosclerosis and CVD in T2D. A better understanding of the mechanisms involved is crucial for enabling better identification of CVD risk in T2D.

Determination of moisture in hard gelatin capsules using near-infrared spectroscopy: applications to at-line process control of pharmaceutics.

A method is proposed in which diffuse reflectance near-infrared spectroscopy (NIR) is applied in an at-line process analytical interface to determine moisture content in bulk hard gelatin capsules. Capsule samples were equilibrated at various relative humidities and the moisture contents were determined using loss on drying (LOD). Different multivariate calibration methods using multiple linear regression (MLR) and partial least squares regression (PLSR) and various spectral pretreatments were compared. No sample pretreatment was required and the analysis time was 1-2 min. The investigated range for the moisture determination was 5.6-18.0% w/w and the root mean square error of prediction (RMSEP) value was 0.1% w/w.

Accelerated dissolution rate analysis (ACDRA) for controlled release drugs. Application to Roxiam.

Accelerated dissolution rate analysis by elevated temperature has been applied to the release of remoxipride from a controlled release drug. Roxiam, and compared to the standard USP method. A PLS model has been used in evaluating the factors of importance of the release as well as for the comparison to the standard USP method. Accelerated Dissolution Rate Analysis (ACDRA) offers the possibility of substantial reduction of analysis time. The time needed for one analysis with ACDRA is less than 5% of the USP-method. The automated analytical procedure is well suited for use in process control as well as in the early stages of the formulation development.

Serum albumin reserve for bilirubin binding during pregnancy in healthy women.

The concentrations of serum albumin and albumin reserve for bilirubin binding were studied in 24 healthy women during and after pregnancy, using monoacetyl-4,4'-diamino-diphenylsulphone as a deputy ligand for bilirubin. In the first trimester, the serum albumin concentration was already diminished. Likewise, the serum reserve albumin for bilirubin binding was reduced gradually during pregnancy. These reductions were evident as early as the 20th week of gestation, and at delivery the level averaged 53% of the nonpregnant level. The reduction in bilirubin binding capacity was partly dependent on the decreasing serum albumin concentration, but a reduction in the albumin molecule's binding capability was also shown. This binding defect, which is also present in neonates, is not fully explained. The reduction in bilirubin binding capability probably reflects a reduced degree of protein binding for many protein-bound drugs during pregnancy, which may contribute to pharmacokinetic alterations in pregnancy.

Rapid spectrophotometric pH measurements based on the dual-wavelength technique.

A spectrophotometric method for the measurement of pH in solutions of lidocaine hydrochloride (Xylocaine) for injection is presented. 4-Nitrophenol is used as an indicator for determinations of pH in the range 6.5-7.0. The method was found to be faster than the conventional potentiometric method, mainly due to the utilization of a computer-controlled photodiode array spectrophotometer for the measurements. A further advantage with the spectrophotometric method is that errors arising from varying liquid junction potentials are avoided.

Anaphylactoid reactions in connection with infusion of invert sugar solutions are due to macromolecular contaminants.

13 untoward mold anaphylactoid reactions were observed in patients infused with invert sugar solutions in Sweden during a 7-month period in 1973: an incidence of 1/31,000 infusions. Immunological and physicochemical analysis of invert sugar solutions and of the raw material, sucrose, revealed traces of native alpha-1,6-glucan with molecular weight of 10-100 millions as contaminant. This indicates, that the sucrose had been exposed to microbial contamination during its manufacture from sugar-beet or sugar-cane. Reversed single radial immunodiffusion was used for alpha-1,6-glucan detection and screening of all sucrose batches. Rejection of contaminated sucrose as raw material reduced the incidence of anaphylactoid invert sugar reactions to about 1/575,000 infusions. Examination of all sucrose raw material for traces of crude alpha-1,6-glucan is recommended as a test for detection of microbial contamination.