G protein beta 3 subunit 825T allele carriage and risk of coronary artery disease

C825T polymorphism in the G protein beta3 subunit gene (GNB3) is associated with increased transmembrane signal transduction via adenylyl cyclase inhibiting G (G(i)) proteins. We tested whether GNB3 C825T is associated with an increased risk of coronary artery disease (CAD). Genotypes were determined with polymerase chain reaction and allele-specific fluorogenic probes. Angiographically examined, consecutive patients (n=998) with CAD and angiographically examined, sex- and age-matched controls (n=340) with no evidence of CAD were studied. The proportion of T allele carriers was significantly higher in the group with CAD compared with the control group (55.6 vs. 48.5; P=0.02). T allele carriage was associated with a 33% increase in the unadjusted risk (OR 1.33 [95% confidence interval, 1.04-1.70]) and a 37% increase in the adjusted risk (OR from the multivariate model 1.37 [95% CI, 1.06-1.76]) for CAD. Moreover, an increase in T allele carriage was associated with an increase in disease severity (P=0.006; test for trend). The strongest association was observed between T allele carriage and three-vessel disease (unadjusted OR 1.47 [95% CI, 1.10-1.96]). Thus, carrying this allele is associated with the presence as well as the severity of CAD.     

An Acid Test: Facile SI‐ARGET‐ATRP of Methacrylic Acid

Atom transfer radical polymerization (ATRP) of methacrylic acid (MAA) is challenging. Herein is reported a study of conditions for facile surface‐initiated ATRP by activator regenerated electron transfer (SI‐ARGET‐ATRP) growth of poly‐methacrylic acid (PMAA) chains from a plasma polymer surface bearing surface‐immobilized α‐bromoisobutyryl bromide, with no deoxygenation required. Factors that affect PMAA polymer growth off the surface under ARGET‐ATRP conditions are systematically investigated, such as monomer/catalyst ratio, solvent, and, most importantly, addition of salts and change of pH. While the concentrations of the copper catalyst and acid affect grafting, the most pronounced effect arises from the concentration of chloride ions. Adding 0.1 m NaCl and acidifying the reaction solution to pH 3 offers the best trade‐off between reaction rate and reproducibility; yielding ≈60 nm thick PMAA graft polymers in 1 h under ambient conditions. Using this easily scalable recipe and surface analysis, the grafted polymers are verified to be pure PMAA and the graft coatings to be homogenous across a substrate of 100 mm diameter.     

Irreversible adsorption of human serum albumin to hydrogel contact lenses: a study using electron spin resonance spectroscopy.

Human serum albumin (HSA) was specifically spin labelled with 4-maleimido-tempo (MSL) at its cysteine 34 residue (HSA-MSL). The irreversible adsorption of HSA-MSL to hydrogel contact lenses (etafilcon A, tefilcon and vifilcon A) was investigated using electron spin resonance (ESR) spectroscopy. Changes in ESR spectral characteristics of adsorbed HSA-MSL as compared to HSA-MSL in solution displayed an additional immobilisation of the spin label due to the adsorption. This immobilisation of MSL corresponds to a large conformational alteration of the HSA-MSL near the modified Cys 34 residue. For both etafilcon A and tefilcon, the rate of irreversible adsorption was relatively slow compared with that of vifilcon A where the maximum state of immobilisation and hence conformational change occurred within the first hour of adsorption. Furthermore, tefilcon produced markedly different ESR spectra where a strong conformational change to a less mobile protein was apparent. This supported a model where the direct irreversible adsorption of HSA from solution dominated on tefilcon as opposed to conversion of the adsorbed protein from the reversible to the irreversible state on both etafilcon A and vifilcon A. HSA-MSL adsorption onto hydrophobic poly(methylmethacrylate) (PMMA) and hydrophilic poly(N-ter-butylacrylamide) (PTBAM) latex beads was also investigated. The spin label MSL was found to be less mobile when HSA was adsorbed onto PMMA compared with PTBAM beads. It was also found that the rate of irreversible adsorption of HSA is far higher onto PMMA surfaces than onto PTBAM surfaces.     

Increased I-131 uptake in local recurrence and distant metastases after second treatment with retinoic acid.

We present a case of increased I-131 uptake in a patient with papillary thyroid carcinoma with local recurrence and distant metastases after a second treatment with retinoic acid as a sign of redifferentiation of the tumor cells. When fine-needle aspiration cytology before and after a second course of retinoic acid treatment were compared, signs of tumor cell redifferentiation were found. This was accompanied by biochemical reexpression of thyroid marker proteins.     

Characterization of four crystal polymorphs and a monohydrate of s-bupivacaine hydrochloride (levobupivacaine hydrochloride)

Five crystal forms of the amide-type local anesthetic S-bupivacaine hydrochloride (levobupivacaine) were prepared and characterized by means of thermal analytical methods, FTIR- and Raman-spectroscopy, powder X-ray diffractometry, and moisture sorption analysis. Commercial lots of the substance may consist of form A degrees , the thermodynamically stable form at 20 degrees C, and/or the metastable form C. Form A degrees shows a highly reversible transformation into form B (T(trs): 85.3 degrees C) with a transition enthalpy of 4.6 kJ mol(-1). The hysteresis between the experimental transition temperatures is 3.5 K, indicating a very weak kinetic control. The hydrate shows a variable water content (0.71-1.14 mol/mol) between 10% and 90% relative humidity (RH) and dehydrates to form C under dry conditions or at elevated temperatures. All anhydrous forms transform to the hydrate at and above 90% RH (25 degrees C). Form C slowly converts to form A degrees on storage and is the polymorph with the highest hygroscopicity. At higher temperatures all forms transform into form D, which is kinetically stable at 20 degrees C. It is concluded that the forms A degrees , B, and D are enantiotropically related, whereas form C shows a monotropic relationship to these forms and is metastable in the entire temperature range.     

Intraarticular fibroma of tendon sheath

A 17-year-old male presented to us following a hyperflexion injury to his right knee sustained while playing soccer. Immediately after the traumatic event, he developed a large, tense knee effusion. Physical examination revealed limited range of motion. MRI revealed a lobulated mass in the posteromedial aspect of the knee joint. The mass was excised and sections submitted to pathology. A pathologic, microscopic, and immunohistochemical characteristics revealed the final diagnosis of fibroma of tendon sheath in the knee. At 12 months followup, the patient reported no subjective symptoms, such as pain or limitation of athletic activities and has full range of motion. Additionally, he has demonstrated no signs of recurrence. We report a case of fibroma of the tendon sheath originating from the synovial membrane of the joint capsule of the knee.     

Health-related quality of life of patients with hip fracture before and after rehabilitation therapy: discrepancies between physicians' findings and patients' ratings

BACKGROUND AND AIMS: Health-related quality of life (HrQoL) is broadly accepted as an evaluation criterion of medical therapy effects. The major objectives of this work are a) measuring of the effects of rehabilitation therapy on the HrQoL of elderly patients after hip fracture, and b) study of discrepancies between the physician's findings on one hand and subjective ratings of patients on the other, and their influence on HrQoL, depression, and independence in activities of daily living. METHODS: The study sample consisted of 95 patients surgically treated after a fall-induced hip fracture (mean age=82 years; range=61-97). Using the median as splitting criterion, ratings of patients and physicians concerning disturbance-specific functional capacity were subdivided into positive and negative. This led to separation of the sample into four subgroups: the fortunate (congruent positive ratings), satisfaction paradox (positive subjective, negative objective ratings), dissatisfaction dilemma (negative subjective, objective positive ratings), and the unfortunate (congruent negative ratings). RESULTS: The four patient subgroups diverged in their estimations. The subgroups of the fortunate and satisfaction paradox have had the highest subjective gains in HrQoL. The subgroups of dissatisfaction dilemma and the unfortunate estimated their gains as similarly low on most of the tested scales. CONCLUSIONS: Results stress the importance of subjective factors in processes concerning therapy evaluations and their influence on HrQoL. The objective success of therapy is not of primary importance for the extent of the HrQoL, but subjective evaluation of it is.     

Quantitative analysis of paracetamol polymorphs in powder mixtures by FT-Raman spectroscopy and PLS regression

A fast and simple method for the quantitative analysis of monoclinic (form I) and orthorhombic (form II) paracetamol was developed, based on FT-Raman spectroscopy and PLS regression. Three different preprocessing algorithms, namely orthogonal signal correction (OSC), standard normal variate transformation (SNV) and multiplicative scatter correction (MSC), were applied in order to eliminate effects caused by sample preparation and sample inhomogeneities. Subsequently, PLS regression models were fitted and their predictive performance was evaluated on the basis of the root mean squared error of cross-validation (RMSECV) over the complete data set. Furthermore, the data were split into two equal-sized training and test subsets by the Kennard-Stone design and the errors of calibration (RMSEC) and prediction (RMSEP) were calculated. It was found that the OSC preprocessing contributes to a significant increase in the predictive performance of the PLS regression model (RMSECV=0.500%, RMSEC=0.842% and RMSEP=0.538%) in the overall concentration range of form I, compared to the SNV (RMSECV=2.398%, RMSEC=0.911% and RMSEP=7.177%) and MSC (RMSECV=2.7648%, RMSEC=1.572% and RMSEP=4.838%). In addition, the model developed on OSC preprocessed data is more parsimonious, requiring a single latent variable, compared to three latent variables required by the models fitted to the SNV and MSC preprocessed data. The proposed multivariate calibration presents a significant improvement over existing methods for the quantitation of paracetamol polymorphs.