Characteristics of hand injuries caused by powered wood splitters.

Accidents with powered wood splitters cause a distinct group of hand injuries in which the injury spectrum ranges from a minor lesion to mutilating defects. We studied these injuries in order to assess the consequences and estimate the associated costs. A 2-year cohort of patients was retrospectively identified from medical records. The details of the injuries and the treatment were collected, and estimates of the resources used were based on hospital billing and the average costs of sick leave and disability. A total of 67 patients were identified and seven of those were children. Most patients sustained a major hand injury and an emergency microsurgical operation was indicated in 40% of patients. The total cost associated with the injuries was estimated at €3.33 million (£2.56 million, US$3.62 million). The treatment of this relatively small number of injuries demands substantial medical resources, and most of the costs are due to sick leave and disability. Level of evidence IV.

Suture configurations and biomechanical properties of flexor tendon repairs by 16 hand surgeons in Finland.

The aim of this study was to find out how common it is to modify standard core suture configurations in flexor tendon repair and whether the use of standard core suture configurations gives a stronger repair. A total of 16 hand surgeons or residents participated in a workshop, in which they were asked to draw the suture configurations they used and to repair a porcine tendon. The properties of the repaired tendons were measured. Seven participants used a standard core suture configuration, and nine used a modified core suture. The biomechanical properties of the repairs were not affected by modifications to the core suture. However, they were affected by the number and lengths of peripheral suture bites, type of peripheral suture and the location of the core suture knot.

The suture loop holding capacity of flexor digitorum profundus tendon within and outside the digital tendon sheath.

In a previous study we found that the strength of a Kessler core suture in the flexor tendon was greater in flexor zone 2 than in zone 3. To further investigate the material properties of the flexor tendon without the influence of a locking suture configuration, we measured the ultimate strength of a simple loop suture in the flexor digitorum profundus tendon in zones 1, 2, and 3. Eight cadaver flexor digitorum profundus tendons were tested in 10 mm increments with a 3-0 polyester suture loop pull-out test in the mid-substance of the tendon. The mean strength in zones 1 and 2 (26.7 N, SD 5.6) was significantly higher than the mean strength in zone 3 (17.7 N, SD 5.4). We conclude that the difference is owing to variations of the structure of the flexor tendon in different sections of the tendon, as the suture configuration was a simple loop without a locking or grasping component.

Comparison of modified Kessler tendon suture at different levels in the human flexor digitorum profundus tendon and porcine flexors and porcine extensors: an experimental biomechanical study.

This study compared the biomechanical behaviour of repairs in the human flexor digitorum profundus tendon in zones I, II and III with repairs of different segments of the porcine flexor tendon of the second digit and the extensor digiti quarti proprius tendon, in order to assess the validity of porcine tendons as models for human flexor tendon repairs. These porcine tendons were selected after comparing their size with the human flexor digitorum profundus tendon. The tendon repairs were done in three segments of each porcine tendon and repairs in the human tendons were done in zones I,II and III. Ten tendons in each group yielded a total of 90 specimens. A modified Kessler repair was done with 3-0 coated braided polyester suture and subjected to uniaxial tensile testing. In human flexor tendons, the ultimate force was higher in zones I and II than in zone III. The porcine flexor digitorum profundus tendon from the second digit and the proximal segment of the extensor digiti quarti proprius tendon behaved similarly to the human flexor tendon in zone III and can be considered as surrogates for the human flexor tendon.

3D visualization and quantification of rat cortical bone porosity using a desktop micro-CT system: a case study in the tibia.

Although micro-computed tomography (micro-CT) has become the gold standard for assessing the 3D structure of trabecular bone, its extension to cortical bone microstructure has been relatively limited. Desktop micro-CT has been employed to assess cortical bone porosity of humans, whereas that of smaller animals, such as mice and rats, has thus far only been imaged using synchrotron-based micro-CT. The goal of this study was to determine if it is possible to visualize and quantify rat cortical porosity using desktop micro-CT. Tibiae (n = 10) from 30-week-old female Sprague-Dawley rats were imaged with micro-CT (3 µm nominal resolution) and sequential ground sections were then prepared. Bland-Altman plots were constructed to compare per cent porosity and mean canal diameter from micro-CT (3D) versus histology (2D). The mean difference or bias (histology-micro-CT; ±95% confidence interval) for per cent porosity was found to be -0.15% (±2.57%), which was not significantly different from zero (P= 0.720). Canal diameter had a bias (±95% confidence interval) of -5.73 µm (±4.02 µm) which was found to be significantly different from zero (P < 0.001). The results indicated that cortical porosity in rat bone can indeed be visualized by desktop micro-CT. Quantitative assessment of per cent porosity provided unbiased results, whereas direct analysis of mean canal diameter was overestimated by micro-CT. Thus, although higher resolution, such as that available from synchrotron micro-CT, may ultimately be required for precise geometric measurements, desktop micro-CT--which is far more accessible--is capable of yielding comparable measures of porosity and holds great promise for assessment of the 3D arrangement of cortical porosity in the rat.

PDGF-C and -D and their receptors PDGFR-alpha and PDGFR-beta in atherosclerotic human arteries.

BACKGROUND: Platelet derived growth factors (PDGFs) are mitogens for fibroblasts and smooth muscle cells. This growth factor family contains four members PDGF-A, PDGF-B, PDGF-C and PDGF-D. Biology of recently discovered PDGF-C and PDGF-D is not well-established. Here we studied the expression of PDGF-C and PDGF-D and their receptors PDGFR-alpha and PDGFR-beta in normal and atherosclerotic human arteries. MATERIALS AND METHODS: Human arterial samples from amputations and autopsies were classified according to the atherosclerotic stage and the expression of PDGF-C and PDGF-D proteins and their receptors was studied by immunohistochemistry. In situ hybridization and reverse transcriptase-PCR were used to study mRNA expression. RESULTS: Both growth factors were expressed in medial smooth muscle cells (SMCs) in normal arteries and atherosclerotic lesions. However, clear differences were found in the expression profiles in endothelium: PDGF-C was strongly expressed in endothelial cells in both normal arteries and lesions whereas PDGF-D was only weakly expressed in endothelium. PDGF-C expression was very prominent in lesion macrophages. PDGF-D was expressed throughout the artery wall in lesions. PDGFR-alpha expression was strong in endothelium and in lesion macrophage-rich areas, whereas PDGFR-beta was mostly expressed in SMCs. CONCLUSIONS: Our results suggest that PDGF-C may play an important role in endothelium in normal and atherosclerotic arteries and in macrophages in lesions. PDGF-D was expressed in all types of lesions with the same intensity and thus differs from the expression of PDGF-C.

Targeting of biotinylated compounds to its target tissue using a low-density lipoprotein receptor-avidin fusion protein.

The very high binding affinity of avidin to biotin is one of the highest to occur in nature. We constructed a fusion protein composed of avidin and the endocytotic LDL receptor in order to target biotinylated molecules to cells of the desired tissues. In addition to the native avidin, charge-mutated and nonglycosylated avidins were utilized as part of the fusion proteins, in order to modify its properties. All of the fusion protein versions retained the biotin-binding capacity. Although the specificity was not increased, however, fusion proteins composed of natural avidin and nonglycosylated avidin bound most efficiently to the biotinylated ligands. Fluorescence microscopy and atomic force microscopy studies revealed the expression of the fusion protein on cell membranes, and demonstrated specific and high-affinity binding of biotin to the low-density lipoprotein receptor (LDLR)-avidin fusion protein in vitro. Additionally, systemically administered biotinylated ligand targeted with high specificity the intracerebral tumors of rats that were expressing fusion protein after the virus-mediated gene transfer. These results suggest that local gene transfer of the fusion protein to target tissues may offer a novel tool for the delivery of biotinylated molecules in vitro and in vivo for therapeutic and imaging purposes.

Mapping of ATP, glucose, glycogen, and lactate concentrations within the arterial wall.

OBJECTIVE: In large- and medium-sized arteries, the diffusion distances for oxygen and nutrients are long. This has been suggested to make these vessels prone to develop local energy metabolic deficiencies that could contribute to atherogenesis. To validate this hypothesis, we introduced a new method to measure energy metabolites within the arterial wall at high spatial resolution. METHODS AND RESULTS: Bioluminescence imaging was used to quantify local metabolite concentrations in cryosections of snap frozen (in vivo) and incubated pig carotid artery rings. Incubation at hypoxia resulted in increased lactate concentrations, whereas ATP, glucose, and glycogen concentrations were decreased, especially in the mid media, where concentrations of these metabolites were close to zero. In snap frozen arteries, glycogen concentrations were markedly higher in deep layers of the media than toward the lumen. ATP, glucose, and lactate were more homogenously distributed. CONCLUSIONS: Bioluminescence imaging is a new and powerful tool to assess arterial wall energy metabolism at high spatial resolution. Our experiments demonstrate heterogeneous distributions of energy metabolites under hypoxic in vitro conditions. Furthermore, we show that glycogen concentrations are higher in deep medial layers in vivo. This might represent a local adaptation to a low-oxygen microenvironment.

Monitoring of intrathecal oxygen tension during experimental aortic occlusion predicts ultrastructural changes in the spinal cord.

OBJECTIVE: To study the correlation between intrathecal PO2 and ultrastructural changes in the spinal cord during thoracic aortic occlusion in pigs. MATERIAL AND METHODS: In 18 pigs, online intrathecal oxygenation was monitored by a multiparameter Paratrend catheter (Biomedical Sensors, High Wycombe, United Kingdom) during 60 minutes' clamping of the proximal and distal descending thoracic aorta. The animals were randomly divided into 2 groups (A and B) depending on the level of distal aortic clamping. Distal aortic perfusion was restored through an aorto-iliac shunt, which also maintained low thoracic segmental perfusion of the spinal cord in group B. Perfusion-fixation technique was used before harvesting the spinal cord specimens, which later were evaluated with light and electron microscopy by an independent observer. Intrathecal parameters were interpreted as normal if PO2 was more than 0.8 kPa and PCO2 was less than 12 kPa, as intermediate ischemia if PO2 was 0.8 or less or PCO (2) was more than 12 kPa, and as absolute ischemia if PO2 was 0.8 or less and PCO2 was more than 12 kPa. RESULTS: Among 6 animals with ultrastructural changes of absolute spinal cord ischemia-reperfusion injury, 5 also had absolute ischemia according to variables derived by the Paratrend catheter. The 2 methods were in agreement in 3 of 5 animals with intermediate ischemia-reperfusion changes and in 5 of 6 animals with normal findings. The accuracy of cerebrospinal fluid PO2 and PCO2 to predict electron microscopy-verified intermediate or absolute ischemia-reperfusion injury was 94%. CONCLUSIONS: Monitoring of intrathecal PO2 after clamping of the descending aorta correlated with ultrastructural changes in the spinal cord in this pig model.

Intimal hyperplasia recurs after removal of PDGF-AB and -BB inhibition in the rat carotid artery injury model.

Several antagonists specific for platelet-derived growth factor (PDGF) or its receptors have recently been developed and shown to inhibit intimal hyperplasia formation in various animal models, but data investigating the durability of this intervention is limited. The present study was designed to investigate the potency of PDGF B-chain aptamer, a novel type of PDGF-AB and -BB antagonist, in the rat carotid model and to characterize intermediate-term effects on lesion formation. One hundred thirty-four animals were randomized to aptamer treatment or placebo. Daily treatment with the antagonist resulted in a 50% reduction in lesion size at 2 weeks (P<0.001). The beneficial effect involved increased apoptosis and possibly an interference with smooth muscle cell migration. Discontinuing administration 1 week earlier did not give any significant benefit compared with phosphate-buffered saline-treated controls. When the antagonist was administered for 2 weeks and the vessels analyzed 6 weeks later, the beneficial effect was lost and the treated lesions had a higher intima-media and area-cell ratio compared with the treated lesions in the 2-week-endpoint study. Our findings confirm a role of PDGF B-chain in intimal hyperplasia, but the successful use of PDGF antagonists may require either prolonged treatment or combination therapy with other agents.

Predimerization of recombinant platelet-derived growth factor receptor extracellular domains increases antagonistic potency.

Platelet-derived growth factor (PDGF) is a dimeric growth factor acting through tyrosine kinase alpha- and beta-receptors. In both receptors, the extracellular parts are composed of five Ig-like domains. Functional mapping of the extracellular part of the receptors have shown that ligand-binding occurs to Ig-like domains 2 and 3 and that Ig-like domain 4 is involved in receptor-receptor interactions. Recombinant GST-fusion proteins of PDGF alpha-receptor Ig-like domains 1-4 and beta-receptor Ig-like domains 1-3 (alphaRD1-4-GST and betaRD1-3-GST) were generated and compared with their cleaved counterparts (alphaRD1-4 and betaRD1-3) with regard to their ability to block PDGF binding to cell surface receptors. In the case of both the alpha- and the beta-receptors, 100-1000-fold lower concentrations of the GST-fusion proteins were required, as compared to the cleaved forms, for inhibition of PDGF binding to cell surface receptors. alphaRD1-4-GST and betaRD1-3-GST, in contrast to alphaRD1-4 and betaRD1-3, were shown to occur as ligand independent dimers. Covalently cross-linked alphaRD1-4 dimers displayed a 50-fold increased potency as compared to alphaRD1-4. We thus conclude that the dimeric nature of alphaRD1-4-GST and betaRD1-3-GST is responsible for the high antagonistic potency of the fusion proteins.

Role of immunoglobulin-like domains 2-4 of the platelet-derived growth factor alpha-receptor in ligand-receptor complex assembly.

Platelet-derived growth factor (PDGF) is a dimeric protein that exerts its effects through tyrosine kinase alpha- and beta-receptors. The extracellular part of each receptor is composed of five Ig-like domains. Recombinant forms of alpha-receptor domains 1-4 (alphaRD1-4), 1-3 (alphaRD1-3), and 1 and 2 (alphaRD1-2) were prepared after expression in Chinese hamster ovary cells and were used to study the assembly of soluble ligand-receptor complexes. When incubated with micromolar concentrations of PDGF, both alphaRD1-3 and alphaRD1-4 formed complexes of 1:2 molar composition, i.e. one dimeric PDGF molecule bound two soluble receptors. alphaRD1-3, in contrast to alphaRD1-4, formed detectable 1:1 complexes under conditions of ligand excess. alphaRD1-4 displayed an increased ability to form 1:2 complexes as compared with alphaRD1-3 under conditions of limiting concentrations of ligand. We thus conclude that Ig-like domain 4-mediated receptor-receptor interactions contribute to 1:2 PDGF.alphaRD1-4 complex formation. Since alphaRD1-4 and alphaRD1-3 were equipotent in blocking binding of subnanomolar concentrations of PDGF to cell-surface receptors, we also conclude that this effect is predominantly achieved through formation of Ig-like domain 4-independent 1:1 ligand-receptor complexes. Finally, since alphaRD1-2 bound PDGF-BB with high affinity, whereas PDGF-AA was bound only with low affinity, we conclude that Ig-like domain 3 of the PDGF alpha-receptor contains epitopes of particular importance for PDGF-AA binding and that most of the PDGF-BB-binding epitopes reside in Ig-like domains 1 and 2.

Spectrophotofluorometric method for quantitative determination of sulpiride in human plasma and urine.

A new spectorophotofluorometric method for the determination of sulpiride (S) in the human plasma and urine is described. The plasma concentrations (0--24 hours) and renal excretions (0--48 hours) of sulpiride were measured after Dogmatil forte (Schürholtz), or Sulpiril (Leiras) tablets both containing 200 mg of sulpiride, after two Sulpiril capsules (Leiras) containing 50 mg of sulpiride in each capsule, and after 20 ml Dogmatil saft (Schürholtz) and 20 ml Sulpiril mixt. (Leiras) both containing 5 mg/ml of sulpiride. There were no significant differences in the sulpiride concentrations in plasma or cumulative urinary excretion of sulpiride after Dogmatil forte (200 mg S) or Sulpiril tablet (200 mg S). Two Sulpiril capsules (100 mg S) produced significantly lower plasma concentrations of sulpiride at 3 hours than a Sulpiril tablet (200 mg S) and these were also lower at 4 and 6 hours than with either a Dogmatil forte (200 mg S) or a Sulpiril tablet (200 mg S). Two Sulpiril capsules (100 mg S) gave significantly higher plasma sulpiride concentrations from 1 to 6 hours than 20 ml Sulpiril mixt. (100 mg S) and from 2 to 6 hours higher than 20 ml Dogmatil saft (100 mg S). The plasma half-life of sulpiride measured after two Sulpiril capsules, 20 ml Dogmatil saft and 20 ml Sulpiril mixt., was 9.4 hours, 9.5 hours, and 10.2 hours, respectively. The renal excretion of sulpiride after two Sulpiril capsules (100 mg S) was significantly lower than after a Sulpiril tablet (200 mg S) from 8 to 48 hours, and also significantly lower than after a Dogmatil forte tablet (200 mg S) from 24 to 48 hours. Two Sulpiril capsules (100 mg S) gave significantly higher sulpiride urine concentrations from 8 to 24 hours than 20 ml Sulpiril mixt. (100 mg S) and from 24 to 48 hours than 20 ml Dogmatil saft (100 mg S). There was no significantly differences in this respect between either a Dogmatil forte tablet (200 mg S) and a Sulpiril tablet (200 mg S) or between Dogmatil saft (100 mg S) and Sulpiril mixt. (100 mg S). Comparied with a Dogmatil forte tablet, the bioavailability, calculated by the AUC24 for a Sulpiril tablet was 159%, for a Sulpiril capsule 118%, for Dogmatil saft 77%, and for Sulpiril mixt. 89%. The same values calculated from the sulpiride urine concentrations were 118%, 114%, 71%, and 67%, respectively. There were no significant differences in the blood pressure or heart rate of the volunteers during the experiment. 2 volunteers reported a sedative effect after a Dogmatil forte tablet.