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Single nucleotide polymorphisms (SNPs) in diabetes related peroxisome proliferator-activated receptor gamma (PPARG) gene were investigated with a case-control approach. To examine the genetic association of this gene with Alzheimer's disease (AD) risk, we used the TaqMan technique to genotype eight SNP sites for PPARG gene, in 538 Finnish AD cases and 672 controls and conducted a single allele and genotypic distribution comparison as well as estimated haplotype frequencies between cases and controls. No significant differences in AD risk were found in single SNP and haplotype analyses for PPARG gene between the study groups. We conclude that PPARG gene does not play a major role in the genetic predisposition to AD in the Finnish population.

The aim of the study was to develop enzyme sensitive polymers for pharmaceutical applications. Thus, 2,2'-bis(2-oxazoline)-linked poly-epsilon-caprolactone (PCL-O) polymers were synthesized by using epsilon-caprolactone precursors with different molecular weights (M(n): 1500, 3900, 7500 and 12,000g/mol), and the effects of PCL block length on enzymatic degradation and erosion (weight loss) of PCL-O films were studied. Solvent cast PCL and PCL-O films were incubated (22 days) in the presence of pancreatin (1%, pH 7.5), with and without enzyme inhibitors. In the absence of enzyme inhibitors, surface erosion of the PCL-O films occurred during incubation, and the erosion of the PCL-O films increased in parallel with a decrease in the PCL block length. The presence of the lipase inhibitors, paraoxon-ethyl and tetrahydrolipstatin delayed the weight loss of the PCL-O films. These results indicate that lipase was mainly responsible for the enzymatic erosion of the PCL-O films. In comparison, practically no weight loss of the PCL or the PCL-O films was observed in phosphate buffer (pH 7.4) (28 days incubation). The results demonstrate that the studied epsilon-caprolactone based poly(ester-amide)s are enzyme sensitive polymers whose erosion rate can be controlled by the PCL block length.

Earlier studies have indicated that the degradation rate of poly(lactic acid) (PDLLA) can be modified by using 2,2'-bis(2-oxazoline) as a chain extender in polymer synthesis to form a lactic acid-based poly(ester-amide) (PEA). In the present study, the effect of an incorporated drug on the degradation rate of the PEA was evaluated. The model drugs, neutral guaifenesin, acidic sodium salicylate (pK(a) 3.0) and basic timolol (pK(a) 9.2), were incorporated into solvent cast PDLLA and PEA films. The drug content in the films was 2% (w/w). The degradation studies were carried out in PBS (pH 7.4, 37 degrees C); the resulting decrease in molecular weight of polymers was determined by size exclusion chromatography and the weight loss of films was measured. In addition, the drug release from the films in PBS (pH 7.4, 37 degrees C) was studied. The model drugs were released from the PDLLA and PEA films in a biphasic or triphasic manner. The final fast release phase of the drugs from both PDLLA and PEA films started when the molecular weight (M(n)) of the polymer had decreased close to 15,000 g/mol. The degradation rate of the PDLLA films was clearly enhanced by incorporated sodium salicylate or timolol. Whereas, the degradation rate of the PEA film was not enhanced by the incorporated drugs. The present results indicate that when compared to the PDLLA film, degradation rate of the PEA film in the presence of the drug is more predictable.

Model reduction is often required in optical diffusion tomography (ODT), typically due to limited available computation time or computer memory. In practice, this often means that we are bound to use sparse meshes in the model for the forward problem. Conversely, if we are given more and more accurate measurements, we have to employ increasingly accurate forward problem solvers in order to exploit the information in the measurements. In this paper we apply the approximation error theory to ODT. We show that if the approximation errors are estimated and employed, it is possible to use mesh densities that would be unacceptable with a conventional measurement model.

The purpose of this prospective study was to evaluate whether the shorter degradation time of the second-generation Meniscus Arrow would be adequate to allow meniscal healing and whether equally good results could be achieved compared to the first generation implant. We also wanted to assess whether some of the implant related complications could be avoided with the altered absorption time. A total of 20 patients were included in this study. The mean follow-up was 26 months. The average Lysholm score at the final follow-up was 90. There were 13 second-look arthroscopies performed during the follow-up and in them two failures of the repaired menisci to heal were seen. Seven patients were found with some degree of chondral irritation of the femoral condyle corresponding to the repair site. The second generation Meniscus Arrow seems to give results comparable to the first generation Meniscus Arrow. The potential complications caused by the implant reported in the earlier literature using the first generation arrow are possible also using this implant. In seven of the 13 second-look arthroscopies some degree of chondral irritation corresponding to the repair site was seen. The clinical relevance of these lesions remains to be seen.

In this paper, a coupled radiative transfer equation and diffusion approximation model is extended for light propagation in turbid medium with low-scattering and non-scattering regions. The light propagation is modelled with the radiative transfer equation in sub-domains in which the assumptions of the diffusion approximation are not valid. The diffusion approximation is used elsewhere in the domain. The two equations are coupled through their boundary conditions and they are solved simultaneously using the finite element method. The streamline diffusion modification is used to avoid the ray-effect problem in the finite element solution of the radiative transfer equation. The proposed method is tested with simulations. The results of the coupled model are compared with the finite element solutions of the radiative transfer equation and the diffusion approximation and with results of Monte Carlo simulation. The results show that the coupled model can be used to describe photon migration in turbid medium with low-scattering and non-scattering regions more accurately than the conventional diffusion model.

We propose a computational calibration method for optical tomography. The model of the calibration scheme is based on the rotation symmetry of source and detector positions in the measurement setup. The relative amplitude losses and phase shifts at the optic fibers are modeled by complex-valued coupling coefficients. The coupling coefficients can be estimated when optical tomography data from a homogeneous and isotropic object are given. Once these coupling coefficients have been estimated, any data measured with the same measurement setup can be corrected for the relative variation in the data due to source and detector losses. The final calibration of the data for the source and detector losses and the source calibration between the data and the forward model are obtained as part of the initial estimation for reconstruction. The calibration method was tested with simulations and measurements. The results show that the coupling coefficients of the sources and detectors can be estimated with good accuracy. Furthermore, the results show that the method can significantly improve the quality of reconstructed images.

A hybrid radiative-transfer-diffusion model for optical tomography is proposed. The light propagation is modeled with the radiative-transfer equation in the vicinity of the laser sources, and the diffusion approximation is used elsewhere in the domain. The solution of the radiative-transfer equation is used to construct a Dirichlet boundary condition for the diffusion approximation on a fictitious interface within the object. This boundary condition constitutes an approximative distributed source model for the diffusion approximation in the remaining area. The results from the proposed approach are compared with finite-element solutions of the radiative-transfer equation and the diffusion approximation and Monte Carlo simulation. The results show that the method improves the accuracy of the forward model compared with the conventional diffusion model.

The purpose of this study was to assess whether premorbid signs, such as thought disorder, could predict the subsequent manifestation of psychiatric disorders. A group of 75 adoptees at high genetic risk for schizophrenia and 96 low-risk adoptees without any psychiatric disorder at the initial assessment were assessed blindly with the Thought Disorder Index (TDI). Their psychiatric status was re-assessed according to DSM-III-R criteria in a re-interview 11 years later and based on available registers 16 years later. High scores on several TDI variables at the initial assessment predicted a psychiatric disorder of all adoptees at follow-up. Prediction was statistically unsuccessful among the high-risk adoptees because of the small number of cases, but high scores at the 0.50 severity level did predict mental disorders among the low-risk adoptees.

Study Design: A cross-sectional study was conducted., Objective: To compare maximal flexion, extension, and rotation strength as well as force-time characteristics of trunk muscles in patients who undergo lumbar disc herniation with those in healthy control subjects 2 months after surgery., Summary of Background Data: Insufficient attention has been paid to muscle strength characteristics after lumbar disc herniation surgery., Methods: For this study, 30 postoperative patients with lumbar disc herniation and 30 healthy control subjects volunteered to participate. Isometric trunk flexion, extension in the standing position, and seated rotation strength were tested bilaterally in a neutral posture and at 30 degrees axial prerotation. The area under the curve was calculated to analyze explosive force capacity. Dynamic endurance strength was measured by calculating the repetition maximum. Pain during the strength measurements was assessed by a visual analog scale., Results: The healthy control subjects showed 44% and 36% higher isometric trunk flexion (P < 0.001) and extension (P < 0.001) forces, respectively, than the patients. The respective values for the area under the curve were 41% and 37% higher for the trunk flexors (P < 0.001) and extensors (P < 0.001) in the healthy control subjects than in the patients. The differences in trunk rotation force between the groups were statistically significant when the lower body was rotated 30 degrees to the right (P = 0.023) or to the left (P = 0.043) and the upper body was rotated in the opposite direction. Furthermore, in the dynamic endurance strength test, the healthy control subjects performed 70% more repetitions both for trunk flexors and extensors than did the patients. Some of the patients reported mild pain during the strength measurements, but the level of pain did not correlate with the strength values., Conclusions: The recovery of maximal endurance and explosive type strength characteristics is incomplete in patients with lumbar disc herniation 2 months after surgery. Active strength training is recommended to restore muscle function in these patients.

The degradation and erosion of solvent cast films and injection molded bars prepared from poly(epsilon-caprolactone) (PCL) and 2,2'-bis(2-oxazoline) linked poly(epsilon-caprolactone) (PCL-O) were evaluated in simulated gastric fluid (SGF) (pH 1.2, pepsin present) and in simulated intestinal fluid (SIF) (pH 7.5, pancreatin present). After incubation of the polymer films (10 mg) and bars (70 mg) in the medium, the resulting decrease in molecular weight (degradation) was determined by size exclusion chromatography and the weight loss of the preparations was measured. In addition, the effect of pancreatin on FITC-dextran (MW 4400) release from PCL and PCL-O microparticles, prepared by w/o/w double emulsion technique, was studied. No degradation or weight loss was observed for either PCL or PCL-O films in SGF (12 h incubation, 37 degrees C). When compared to PBS pH 7.4, pancreatin hardly enhanced the weight loss of PCL films and bars. In contrast, pancreatin enhanced substantially erosion of PCL-O films and bars. Unlike PCL preparations, the PCL-O preparations showed surface erosion in SIF. Pancreatin increased considerably FITC-dextran release from both PCL and PCL-O microparticles. In conclusion, the present results demonstrate the enzyme sensitivity of the novel PCL-O polymer. In addition, the results show that pancreatin present in intestinal fluid may substantially affect drug release from PCL based preparations.

In the present study, poly (epsilon -caprolactone) (PCL) was modified by introducing oxamide groups into PCL (PCL-O). The degradation (decrease in molecular weight) and erosion (weight loss) of PCL and PCL-O films were studied in PBS (pH 7.4, USP XXIV, 37 degrees C, 26 weeks incubation). The release rates of guaifenesin (M(w) 198.2), griseofulvin (M(w) 352.8), timolol (M(w) 332.4), sodium salicylate (M(w) 160.1) and FITC-dextran (M(w) 4400) from PCL and PCL-O preparations (solvent cast films, compression-molded plates, midi injection-molded rods and microparticles) were examined in PBS (pH 7.4, 37 degrees C). The degradation rate of PCL-O film was faster than that of PCL film while no erosion was observed for either film. When compared to the corresponding drug release from PCL films, the release rates of low molecular weight drugs (M(w)< or =352.8) from PCL-O films were comparable, their releases from both films following closely square-root-of-time kinetics. These results indicate that the oxamide groups had no substantial effect on the release of the low molecular weight drugs. The exception was sodium salicylate which was released faster from PCL-O film. However, FITC-dextran release was notably faster from PCL-O microparticles than from those made of PCL. FITC-dextran release was a combination of diffusion and polymer degradation and thus, the faster degradation of PCL-O enhanced the release of FITC-dextran. In conclusion, the effects of the oxamide groups on drug release profiles were dependent on the drug release mechanisms.

The degradation rate of poly(lactic acid) (PLA) is typically modified by copolymerization of the glycolide with lactide. In the present study, the degradation rate of PDLLA was modified by a novel linking of PLA with 2,2'-bis(2-oxazoline). This modification resulted in formation of a more rapidly degrading poly(ester amide) (PEA) for controlled drug release. The hydrolytic degradation of PDLLA and PEA films was studied in PBS (pH 7.4, USP XXIV, 37 degrees C); the resulting decrease in molecular weight was determined by size exclusion chromatography and the weight loss of films was measured. Drug releases of guaifenesin (mw 198.2), timolol (mw 332.4), sodium salicylate (mw 160.1) and FITC-dextran (mw 4400) from PDLLA and PEA films and microspheres were examined in PBS (pH 7.4, 37 degrees C). The degradation rate of PEA was substantially greater than that of PDLLA. The release profiles of all small model drugs (mw <332.4) from PDLLA films were biphasic or triphasic, while the release profiles of small model drugs from PEA films varied extensively. Due to the faster weight loss of PEA, FITC-dextran (mw 4400) was released substantially more rapidly from PEA microspheres than from PDLLA microspheres. In conclusion, all model drugs, except guaifenesin, were released faster from PEA preparations than from PDLLA preparations.

Objective: The objective was to assess the associations between changes in pain and grip strength and manual tests among patients with chronic tennis elbow., Design: Measurements for 45 consecutive patients with unilateral tennis elbow were made before and after an exercise intervention., Setting: The setting was a physiatric outpatient clinic., Patients: The patients were 45 persons with chronic unilateral tennis elbow: 32 women and 13 men. The mean age was 44 (31-54) years; mean duration of symptoms was 35 (10-66) weeks., Outcome Measures: Manual tests, pressure pain thresholds at three cubital points, a pain questionnaire, a pain drawing, and grip strength measurements were assessed., Results: Grip strength became normal during the treatment. Pressure pain thresholds reached 66% of that of the healthy arm. Lowered pain thresholds and changes in pain thresholds of the lateral epicondyle were strongly associated with the findings in the manual tests. Mills test and resisted wrist extension tests were associated with perceived pain, and resisted wrist extension tests also were associated with decreased grip strength. Pain on palpation was associated with lowered pain thresholds at the lateral epicondylus and with perceived pain under physical load. After the treatment, for 13 patients all 4 manual tests were still positive; for 17 patients, 3 were still positive; and for 5 patients, all were negative. Positive clinical tests were associated with lowered pain thresholds, decreased grip strength, and high perceived pain scores., Conclusions: Pain thresholds at the lateral epicondyles are strongly associated with pain on palpation and with a positive Mills test. Resisted wrist extension test results reflect decreased grip strength. Impaired function of the hand is associated with the number of positive clinical tests. Pain threshold evaluation is a simple, easy, inexpensive method that provides useful additional quantitative data on pain and disability among patients with chronic tennis elbow.

Background and Aims: The Finnish orthopaedic tradition has preferred hemiarthroplasty to internal fixation in femoral neck fracture treatment, while in Sweden internal fixation has been the method of choice. We decided to study whether internal fixation would prove superior to hemiarthroplasty even in displaced femoral neck fractures in patients over 75 years old., Material and Methods: We randomized 32 displaced femoral neck fractures in patients over 75 years old to receive internal fixation or hemiarthroplasty., Results: Fifteen (47%) patients died within two years. Seven of 16 (44%) patients in the internal fixation group were reoperated, none in the hemiarthroplasty group (p = 0.007). Seven of the complications in the internal fixation group developed during the first year and it would have been unethical to continue the study., Conclusions: We conclude that displaced femoral neck fractures in patients over 75 years should be treated by arthroplasty.

The aim of the study was to measure the shear strength of bone/porous-glassy-carbon interface in rabbit. Glassy carbon pellets were implanted into drill holes made through the medial articular surface of the proximal tibia of 15 rabbits. Shear strengths grew statistically significantly from 1 to 6 weeks and reached a maximum of 4.6 MN/m2. Microscopical examination of the sheared surfaces revealed that at 1 and 2 weeks the shearing occurred through the tissue surrounding the implant, and at 3, 6 and 12 weeks through the porous coating of the implant. To diminish the fragility of the porous coating, its porosity should be adjusted to 40%. Results of shear strength studies on current implant materials are reviewed.

This study was designed to evaluate the growth of bone into porous glassy carbon cylinders. Porous carbon cylinders were implanted in 30 rabbits intra-articularly in the metaphysis of the femur opposite from the patella. The rabbits were sacrificed up to 24 weeks after the operation. The bone samples were examined by histologic, fluorochrome and microradiographic methods. The amount of bone ingrowth was measured histomorphometrically. Fluorochrome uptake was seen in the implant pores, which indicated new bone growth originating from surrounding bone. After 3 weeks, microradiographs revealed new bone formation in the pores and with time the bone spicules became more dense. The amount of bone tissue in the pores grew and reached a maximum at 12 weeks, when 45 per cent of the total pore volume was incorporated with bone tissue. No adverse tissue responses were observed.

Preliminary animal implantation tests with rats showed that microporous glassy carbon has good biocompatibility. Microporous glassy carbon is also stable and suitable for a hard biocompatible implant.