Recovery of shoulder joint function after humeral shaft fracture: a comparative study between antegrade intramedullary nailing and plate fixation.

Introduction Antegrade intramedullary (IM) nailing of humeral shaft fractures is reported to cause shoulder joint impairment. This retrospective study compared shoulder joint symptoms, range of motion (ROM), and isometric strength after antegrade IM nailing and dynamic compression (DC) plating of humeral shaft fractures.Materials and methods We compared 29 patients with DC plating and 44 with antegrade IM nailing of their humeral shaft fractures. Shoulder pain, LInsalata and Constant scores, shoulder joint ROM and isometric shoulder strengths were measured after mean follow-up of 6.2 (1–15) years (DC plating) and 5.5 (2–10) years (IM nailing).Results Patients had nonsignificantly more shoulder pain after IM nailing than after DC plating. Shoulder scores and isometric strength measurements showed no difference between the groups. Flexion was significantly better after DC plating, but none of the other ROM parameters differed between the groups. The shoulder scores and all ROM and strength parameters of the injured side were significantly lower than on the uninjured side in both groups.Conclusions Shoulder joint ROM and strength does not recover to normal after humeral shaft fracture. Antegrade IM nailing if performed properly is not responsible for shoulder joint impairment.     

Blood biochemistry and the risk of cancer

A longitudinal study based on a serum sample bank was carried out in Finland to find out the association between biochemical substances and the subsequent risk of cancer. The objective was to evaluate the consistency between means of individually estimated levels of these compounds and levels based on pooling. Levels of alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and ceruloplasmin were estimated by primary site and sex and partly by age and morphology. The concentrations in pooled samples were consistently lower than the averages of the individual samples. On the basis of individual samples, all the five biochemical compounds had a rather consistent protective effect on the risk of cancers at most primary sites. This protective effect disappeared in the pool analyses, and more than half of exposure contrasts showed an opposite sign. For ceruloplasmin, the effect of pooling was smaller but not negligible. The results of this study emphasize the demand to standardize the collecting, handling, and analysing of samples in serum banks. They are, furthermore, consistent with the hypothesis that pooling of biochemical samples affects the levels of the substances and may affect the conclusions of epidemiological studies on causes of diseases.     

Regional cerebral glucose metabolism in monozygotic twins discordant for Alzheimer's disease

We investigated regional cerebral glucose metabolic rates (rCMRgluc) with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in 7 monozygotic twin pairs discordant for Alzheimer's disease (AD). Ten healthy volunteers with comparable mean age and educational level served as controls. In the hippocampus, the mean +/- SD rCMRgluc were 0.20 +/- 0.03 micromol/ml/min for the demented twins, 0.21 +/- 0.03 micromol/ml/min for their non-demented co-twins, and 0.23 +/- 0.02 micromol/ml/min for the controls. The mean hippocampal rCMRgluc was reduced in the demented twins (p = 0.006), compared with the controls. In the lateral temporal cortex, the mean +/- SD rCMRgluc were 0.27 +/- 0.05, 0.28 +/- 0.04, and 0.32 +/- 0.02 micromol/ml/min, respectively. These mean rates were reduced both in the demented (p = 0.02) and the non-demented (p = 0.01) twins, compared with the controls. In conclusion, in the demented twins, the reduction of rCMRgluc was detected in the hippocampus and lateral temporal cortex, i.e. the 2 brain areas which show early changes in pathological and imaging studies in AD. Their non-demented co-twins showed milder reductions, which may be an indication of genetic susceptibility for dementia, and an early sign of a dementing illness in them.     

Disc height and signal intensity of the nucleus pulposus on magnetic resonance imaging as indicators of lumbar disc degeneration

STUDY DESIGN: A cross-sectional magnetic resonance imaging (MRI) study of degeneration of the lumbar spine. OBJECTIVES: To compare the usefulness of disc height and that of T2-weighted signal intensity as indicators of disc degeneration. SUMMARY OF BACKGROUND DATA: Disc height and signal intensity have been used as indicators for disc degeneration. Their relation to each other and to early degeneration has not been well documented. There is evidence that physical load can affect disc height. METHODS: Forty-one machine operators, 41 construction carpenters, and 46 office workers, aged 40-45 years, and 22 students aged 18-20 years were examined with sagittal magnetic resonance imaging. All study participants were men. The mean value of the anterior and posterior disc height and the relative T2-weighted signal intensity of the nucleus pulposus of discs L2-L3 to L5-S1 were measured. RESULTS: Young men showed the lowest disc height but the highest relative signal intensity. Disc height showed an increasing trend from the office workers (sedentary) to blue-collar workers (more physical work) at all disc levels but L5-S1. Relative signal intensity showed a decreasing trend for these same worker types at all levels. In generalized linear modeling, signal intensity and the occupations, in reference to the young students, showed a significant effect on disc height. CONCLUSIONS: Relative signal intensity was lower in the middle-aged men than in the young men, indicating age-related disc degeneration. Despite the general positive association between disc narrowing and decreased relative signal intensity, disc narrowing may behave unexpectedly in relation to signal intensity and age. Signal intensity may be a more sensitive measure of disc degeneration. The validity of disc height as an indicator of early degeneration seems questionable.     

MR findings in humeral epicondylitis. A systematic review

Purpose: To highlight the importance of meta-analysis in diagnostic imaging by presenting a systematic search of the literature on the accuracy of MR imaging in epicondylitis.Material and Methods: The literature was comprehensively reviewed to identify studies on MR findings in epicondylitis. Reviewers blind to the clinical diagnoses screened the data according to predetermined inclusion criteria. Data were collected and validity and relevance were assessed on structured forms.Results: Seven studies including 148 patients with epicondylitis were accepted for the analysis. Eleven asymptomatic contralateral elbows and 29 elbows of healthy volunteers served as controls. The volunteers were distinctly younger than the patients. The MR technique was divergent, and the observed pathological changes also varied. The most frequent alteration was a change in the common extensor tendon signal (90%, 95% confidence interval 84-94%); 14% of the healthy volunteers and 50% of the contralateral elbows displayed the similar alteration.Conclusion: Small sample size and methodological shortcomings in the original studies make the assessment of MR findings in epicondylitis questionable. There is a need for well-designed studies in which clinical features and occupational backgrounds as well as imaging parameters are carefully documented.     

Automated production of [18F]FTHA according to GMP

14‐(R,S)‐[¹⁸F]fluoro‐6‐thia‐heptadecanoic acid is a tracer for fatty acid imaging by positron emission tomography. High demand for this tracer required us to replace semiautomatic synthesis with a fully automated procedure. An automated synthesis device was constructed in‐house for multistep nucleophilic ¹⁸F‐fluorination and a control system was developed. The synthesis device was combined with a sterile filtration unit and both were qualified. 14‐(R,S)‐[¹⁸F]fluoro‐6‐thia‐heptadecanoic acid was produced according to good manufacturing practice guidelines set by the European Union. The synthesis includes an initial nucleophilic labelling reaction, deprotection, preparative HPLC separation, purification of the final product, and formulation for injection. The duration and temperature of the reaction and hydrolysis were optimized, and the radiochemical stability of the formulated product was determined. The rotary evaporator used to evaporate the solvent after HPLC purification was replaced with solid phase extraction purification. We also replaced the human serum albumin used in the earlier procedure with a phosphate buffer‐ascorbic acid mixture in the final formulation solution. From 2011 to 2016, we performed 219 synthesis procedures, 94% of which were successful. The radiochemical yield of 14‐(R,S)‐[¹⁸F]fluoro‐6‐thia‐heptadecanoic acid, decay‐corrected to the end of bombardment, was 13% ± 6.3%. The total amount of formulated end product was 1.7 ± 0.8 GBq at end of synthesis.     

Effects of the wood extractives dehydroabietic acid and betulinol on reproductive physiology of zebrafish (Danio rerio)-a two-generation study

Two wood extractives, dehydroabietic acid (DHAA) and betulinol (BET), present in wood industry effluents were evaluated for their potential effects on the reproductive physiology of zebrafish. Adult zebrafish (F0) were exposed in a continuous flow-through system to 50 microg/l DHAA, 5 microg/l BET and 0.27 microg/l (1 nM) 17beta-estradiol (E2) for 3 months. Eggs were collected from F0 fish and the following F1 generation was exposed for 6 months. Biomarkers analyzed in both F0 and F1 fish were plasma vitellogenin (Vtg), testosterone (T), E2 (only females) and gonadal histology. DHAA and BET affected growth in terms of increased condition factor, and spawning was stimulated in BET-exposed fish of the F0 generation. F0 males exposed to DHAA and F0 females exposed to BET showed lower plasma Vtg concentration, but F1 males exposed to BET showed an increase in Vtg. In fish exposed to E2, the positive control for estrogenic effects, a pronounced increase in Vtg concentration was observed. Plasma sex steroids were not significantly affected by the wood extractives. However, although not statistically significant, the T concentration tended to be lower in fish of all BET treatments. The histological study revealed alterations in spermatogenic stages of F0 males exposed to DHAA and BET, which were different from those caused by E2. In F1 females, the percentage of vitellogenic oocytes was decreased in DHAA, BET and E2 exposures. This study shows that DHAA and BET may contribute to growth alterations and reproductive disturbances reported in fish exposed to pulp and paper mill effluents. Further, these wood extractives may have different effects in F0 and F1 generation fish, which highlights the value of two-generation studies in investigations regarding endocrine disrupting compounds.     

A methylester of the glucuronide prodrug DOX-GA3 for improvement of tumor-selective chemotherapy

The glucuronide prodrug of doxorubicin, DOX-GA3, can be selectively activated in tumors by extracellular human beta-glucuronidase, resulting in a better therapeutic index than doxorubicin. DOX-GA3, however, is rapidly excreted by the kidney. We hypothesized that slow release of DOX-GA3 from its methylester, DOX-mGA3, by esterase activity in blood would result in improved circulation half-life (t(1/2)) of DOX-GA3. DOX-mGA3 was synthesized more efficiently with an overall yield of 60% as compared to 37% in the case of DOX-GA3. We showed that DOX-mGA3 was enzymatically converted to DOX-GA3 with a t(1/2) of approximately 0.5 min in mouse plasma to 2.5 h in human plasma, which was in agreement with differences in esterase activity between species. DOX-mGA3, similar to DOX-GA3, was at least 37-fold less potent than the parent drug doxorubicin in growth inhibition of four different human malignant cell lines in vitro. Incubation of OVCAR-3 cells with DOX-mGA3 in combination with an excess of human beta-glucuronidase (0.05 U mL(-1)) resulted in a similar growth inhibition to that of doxorubicin. Intravenous administration of DOX-mGA3 in FMa-bearing mice resulted in an area under the concentration versus time curve (AUC) of DOX-GA3 in tumor and most normal tissues that was 2.5- to 3-fold higher than after the same dose of DOX-GA3 itself. In tumor tissue, this was accompanied by a 2.7-fold increase in the AUC of doxorubicin from DOX-mGA3 than from DOX-GA3. In conclusion, an advantage of DOX-mGA3 over DOX-GA3 is that this prodrug can be produced with a higher yield. Another important advantage is the improved pharmacokinetics of the lipophilic DOX-mGA3 as compared to that of the hydrophilic DOX-GA3. This effect may even be more pronounced in man, because of the lower plasma esterase activity than measured in mice.