Frank Unglaub

Effects of controlled dynamic disc distraction on degenerated intervertebral discs: An in vivo study on the rabbit lumbar spine model

Study Design. An in vivo study on the rabbit lumbar spine model. Objectives. Effects of temporary dynamic distraction on intervertebral discs were studied on the lumbar spine rabbit model to characterize the changes associated with disc distraction and to evaluate feasibility of temporary disc distraction to previously compressed discs in order to stimulate disc regeneration. Summary of Background Data. Studies have shown that accelerated degeneration of the intervertebral disc results from altered mechanical loading conditions. The development of methods for the prevention of disc degeneration and the restoration of disc tissue that has already degenerated are needed. Methods. New Zealand white rabbits (n = 32) were used for this study. The rabbits were randomly assigned to one of five groups. In 12 animals, the discs were first loaded for 28 days using a custom-made external loading device to stimulate disc degeneration. After 28 days loading time, the discs in six animals were distracted for 7 days and in six animals for 28 days using the same external device, however, modified as dynamic distraction device. In six animals, the discs were distracted for 28 days without previous loading; and in six animals, the discs were loaded for 28 days and afterwards the loading device removed for 28 days for recovery without distraction. Six animals were sham operated. The external device was situated; however, the discs remained undistracted and they also served as controls. After 28 to 56 days loading and distraction time, the animals were killed and the lumbar spine was harvested for examination. Disc height, disc morphology, cell viability, relative neutral zone, and tangent modulus were measured. Results. After 28 days of loading, the discs demonstrated a significant decrease in disc space. Histologically, disorganization of the architecture of the anulus occurred. The number of dead cells increased significantly in the anulus and cartilage endplate. These changes were re-versible after 28 days of distraction. The disc thickness increased significantly as compared with the specimens from the 28 days loading group without distraction. Histologically, the discs showed signs of tissue regeneration after 28 days of distraction. The number of dead cells decreased significantly in comparison with the loaded discs without distraction. The flexibility of compressed discs was higher than of compressed/distracted discs. Conclusions. The results of this study suggest that disc regeneration can be induced by axial dynamic distraction in the rabbit intervertebral disc. The decompressed rabbit intervertebral discs showed signs of tissue recovery on a biologic, cellular, and a biomechanical level after 28 days of distraction.

Early diagnosis and treatment.

Congratulations to the authors for choosing this important topic (1). As shown in their review, regeneration after nerve reconstruction is by no means guaranteed (1), in particular not in older patients (2). The most common nerve injury – damage to the median nerve during carpal tunnel surgery (1) – often occurs in middle-aged/ older patients where the prognosis for regeneration is not always favorable. Full recovery of motor function is the exception rather than the rule. Therefore, tendon transfers should already be considered at the time of nerve reconstruction (3). Especially proximal nerve damages with long regeneration distances have a poor prognosis, e.g. injury to the radial nerve associated with osteosynthesis of fractures of the humerus. The various tendon transfers to restore motor function are detailed in the AWMF guidelines for the treatment of peripheral nerve injuries, a publication rightfully cited by the authors of the review.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with different types of scars and keloids.

BACKGROUND Hypertrophic scars and keloids are fibroproliferative skin disorders characterised by progressive deposition of collagen. Our study is designed to investigate the expression and concentration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in different types of scars and keloids. METHODS Total RNA from 19 proliferative hypertrophic scar samples of patients with extended burns (total body surface area (TBSA): 21+/-12%), 18 mature hypertrophic scar samples from patients after elective surgery, 14 keloid samples and 18 normotrophic scar samples was, respectively, extracted, and then mRNA was isolated. Besides, biopsies were obtained from non-scarred skin of the patients and extraction of total RNA performed. Relative mRNA expression of MMP 2, MMP 9, TIMP 1 and TIMP 2 was measured with reverse transcriptase polymerase chain reaction (RT-PCR). Serum concentrations of MMP-1, -2, -9, TIMP-1, and -2 were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS Patients with extended hypertrophic scars after burn trauma presented a significantly higher TIMP-1 concentration (p<0.05) in their sera than the other patients. The relative expression of MMP 2 was significantly higher in samples of proliferative hypertrophic scars after burn injury. The relative expression of TIMP 1 and TIMP 2 was significantly higher in scar tissue of patients with proliferative and mature hypertrophic scars and keloids than in their regular skin and in scar samples of patients with normotrophic scars. The expression of TIMP 1 was significantly higher in samples of patients with keloids than in patients with hypertrophic scars. CONCLUSIONS The concentration of TIMP-1 in sera of patients varies depending on the size of the involved fibrotic scar tissue. A decrease in MMP-to-TIMP expression in scar tissue may contribute to increased synthesis and deposition of collagen, leading to a severe fibrotic reaction with pathologic scar formation. The results implicate non-operative therapy options in these patients that not only down-regulate TIMPs but also increase the activity of MMPs.

Effect of oxidised regenerated cellulose/collagen matrix on proteases in wound exudate of patients with chronic venous ulceration.

Oxidised regenerated cellulose/collagen matrix (ORC/collagen matrix) modifies wound microenvironments by binding and inactivating excess levels of proteases such as elastase, plasmin and gelatinases in wound exudates. To compare levels of the gelatinases matrix metalloproteinase 2 (MMP‐2), elastase and plasmin in wound exudates collected from chronic venous insufficiency patients with venous leg ulcers treated with either an ORC/collagen matrix or a standard control therapy. During a 12‐week treatment period, wound exudate samples were obtained from a control group of 10 patients treated with a hydrocolloid dressing and a treatment group of 17 patients treated with a combination of ORC/collagen matrix and hydrocolloid dressing. On admission and days 5, 14 and every subsequent 14th day, ulcers were photographed to determine healing rate and changes in ulcer appearance, and MMP‐2 concentration and the gelatinase, elastase and plasmin activities were analysed from wound exudates. The patients treated with ORC/collagen matrix showed a significant decrease in elastase, plasmin and gelastinase activity as compared with the control group, with no significant difference in the MMP‐2 concentrations between the two groups. The results show a significant and immediate reduction in protease activity in wound exudates from venous leg ulcers treated with ORC/collagen.

Effect of chronic wound exudates and MMP-2/-9 inhibitor on angiogenesis in vitro.

Background: New evidence suggests that matrix metalloproteinases (MMPs) may facilitate angiogenesis as well as function to generate angiogenesis inhibitors. In this study, the angiogenic effect of wound exudates from patients with venous insufficiency ulcers was examined in an in vitro angiogenesis model with and without synthetic MMP-2/-9 inhibitor. Methods: Wound exudates were obtained from 20 patients with venous insufficiency ulcers and 20 control patients with donor-site wounds after skin grafting for burns. In the angiogenesis model, suramin (20 &mgr;g/ml) was used in five wells without wound fluid as negative control, and vascular endothelial growth factor (1 &mgr;g/ml) was used in five other wells as positive control. Chronic wound fluids were analyzed without and with a synthetic MMP-2/-9 inhibitor with a concentration of 2 &mgr;M and 20 &mgr;M in the medium. The total length of tubules was calculated by map reader. Statistical analysis was performed using the Mann-Whitney test. The level of significance was considered to be p < 0.05. Results: Chronic ulcer exudates inhibited angiogenesis significantly (490 ± 130 &mgr;m) compared with acute wound fluids (1740 ± 320 &mgr;m; p < 0.05). In wells with chronic wound exudates and high concentrations of MMP-2/-9 inhibitor, angiogenesis was stimulated significantly (870 ± 220 &mgr;m, p < 0.05). Conclusions: In this model, reduced angiogenesis might be due to an antiangiogenic effect of MMP-2 and MMP-9. MMP-2/-9 inhibition results in a stimulation of angiogenesis and might be an approach for the treatment of patients with chronic wounds and reduced angiogenesis.

Die Instabilität des distalen Radioulnargelenks – Zur Wertigkeit klinischer und röntgenologischer Testverfahren – eine Literaturübersicht

The distal radioulnar joint (DRUJ) plays a tremendous role regarding the functionality of the upper extremity. Lesions of the DRUJ can limit the functionality of the upper extremity decisively. Many clinical and radiological procedures are used to diagnose instability of the DRUJ. Up to now, there has not been a general consensus concerning the standardisation of the evaluation of DRUJ instability. The TFCC (triangular fibrocartilage complex) with its ligamentum subcruentum insertions at the fovea ulnaris and at the basis of the processus styloideus ulnae is in conjunction with the membrana interossea a very important stabiliser of the DRUJ. A fall on the extended hand or a forceful wrist rotation can usually cause injuries to the stabilisers. Ulnar-sided pain, limited pronosupination and loss of grip strength are clinically apparent. Both clinical tests and radiological procedures should be judged regarding their specific efficacies. These tests have to be evaluated in comparison to the gold standard of wrist arthroscopy. Each test alone is not able to verify DRUJ instability on a regular basis. The introduction of a standardised diagnostic procedure including anamnesis and specific clinical and radiological tests should be established. The standardisation ought to be maintained strictly in order to guarantee a growing test efficacy. Finally, high diagnostic reliability is based on a thorough examination which includes complementary clinical and radiological procedures.

Arthroscopic Repair of Palmer 1B Triangular Fibrocartilage Complex Tears

PURPOSE The objective of this retrospective study was to determine functional and subjective outcomes of patients with Palmer type 1B tears repaired arthroscopically and to investigate whether clinical outcomes are related to ulna length. METHODS Forty-six patients with arthroscopic repair of Palmer type 1B tears were reviewed. There were 23 males and 23 females. The average age was 34 years (range, 10 to 58 yrs). The average follow-up was 11 months (range, 6 to 23 mos), and the delay to surgery was 9.7 months. All patients suffered ulnar-sided wrist pain and were diagnosed with Palmer type 1B tears. The tear was repaired arthroscopically with an inside-outside suture technique. The range of motion (ROM), grip strength, pain, wrist score (modified Mayo wrist score), Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) score, and ulna length (static and dynamic) were evaluated. RESULTS There was a reduction in pain and an improvement in grip strength. Postoperative ROM averaged 128 degrees +/- 23 degrees for the extension/flexion arc, 41 degrees +/- 11 degrees for the radial/ulnar deviation arc, and 171 degrees +/- 19 degrees for the pronation/supination arc of motion. However, no relation could be found between ulna length and clinical outcome. The modified Mayo wrist score was rated excellent in 22% of patients, good in 41%, fair in 27%, and poor in 10%. The average DASH score was 21.70 +/- 17.17 (range, 0 to 58.33). CONCLUSIONS Arthroscopic repair of Palmer type 1B tears yields satisfactory results. Sixty-three percent of patients achieved good to excellent results, experienced increased ROM, grip strength, and pain relief. Ulnar neutral or positive variance is not a contraindication for suture repair and does not require simultaneous ulna shortening when repairing the triangular fibrocartilage complex arthroscopically. A delay to surgery did not affect clinical outcome. LEVEL OF EVIDENCE Level IV, therapeutic case series.

Effect of oxidized regenerated cellulose/collagen matrix on proteases in wound exudate of patients with diabetic foot ulcers

PURPOSE: The aim of this study was to investigate the influence of oxidized regenerated cellulose/collagen matrix on the concentration and activity of gelatinases, elastase, and plasmin in wound exudate. SUBJECTS AND SETTING: The study included 32 patients with diabetic foot ulcers. Ten patients with a mean age of 66 ± 9 years (mean ± SD) were treated with hydrocolloid dressings; 22 patients with a mean age of 57 ± 12 years were treated with oxidized regenerated/collagen matrix and hydrocolloid dressings. METHODS: Wound exudate was collected on days 0, 5, 14, and every 14 days thereafter for 12 weeks. Total protein was determined according to Bradfords technique. The levels of elastase and plasmin were measured spectrofluorometrically. Besides, gelatinase activity and matrix metalloproteinase-2 concentration were analyzed. The surface area of all ulcers was measured by planimetry. RESULTS: Patients treated with oxidized regenerated cellulose/collagen matrix showed a significant decrease in elastase, plasmin, and gelatinase activities in wound exudates. The matrix metalloproteinase-2 concentration was significantly reduced on days 14, 28, 42, and 56 in comparison to day 0. Furthermore, wound size was significantly reduced at days 14 and 28 in oxidized regenerated cellulose/collagen matrix-treated patients (P < .05). CONCLUSION: Our results showed a significant and immediate reduction in the levels of all tested proteases in the wound exudate of diabetic foot ulcer patients treated with oxidized regenerated cellulose/collagen matrix. These patients also experienced a significantly greater reduction in wound size.

Comparison between distally based peroneus brevis and sural flaps for reconstruction of foot, ankle and distal lower leg: An analysis of donor-site morbidity and clinical outcome

BACKGROUND Skin defects of the foot, ankle and distal lower leg often require coverage by local or distant flaps. We aimed to compare functional outcome and donor-site morbidity following transfer of distally based delayed sural (DSFs) or peroneus brevis flaps (PBFs). METHODS Between 2003 and 2006, 52 patients (24 DSFs and 28 PBFs) were included. For increased reliability, all extended sural flaps were delayed for 3-15 days. At the end of the follow-up period (minimum 12 months), patients were asked to fill out a modified foot and ankle score (Foot and Ankle Outcome Score (FAOS)) questionnaire. In addition, a chart review and a physical examination were performed. RESULTS Total hospital stay and total number of operations were significantly lower in the PBF group. Minor flap necrosis (<10%) was observed in 21% of the DSF and 7% of the PBF group, and partial (>10%) or total flap loss occurred in one and three patients from the DSF group, respectively. Patient satisfaction, FAOS results and range of motion were comparable in both groups. Defect aetiology and patient age did not influence surgical outcome. CONCLUSION Donor-site morbidity and functional outcome after DSF and PBF are comparable. A higher rate of complications was observed in the DSF group. Based on our findings, the PBF is recommended as first-line procedure for reconstruction of small- to medium-sized defects at the distal tibia, fibula, ankle and heel. The sural flap might be chosen for extended skin defects especially when a larger arc of rotation is required.

Correlation of Ulnar Length and Apoptotic Cell Death in Degenerative Lesions of the Triangular Fibrocartilage

PURPOSE The purpose of this study was to investigate apoptosis in degenerative disc lesions (Palmer type IIC) and differentiate between patients with ulna-plus and ulna-neutral variance. METHODS Seventeen patients with degenerative tears (Palmer type IIC) in the articular disc of the triangular fibrocartilage were included in this study. The triangular fibrocartilage was debrided arthroscopically with a punch and the histologic sections were used to analyze necrosis and apoptosis. Apoptosis and necrosis was quantified by terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. Apoptotic cells were visualized by poly(ADP-ribose) polymerase (PARP) p85 immunohistochemistry. The number of apoptotic and necrotic cells was then correlated with ulnar length. RESULTS PARP- and TUNEL-positive cells were found in each patient. In addition, patients with an ulna plus variance showed a significantly increased number of apoptotic cells in comparison to patients with an ulna neutral variance. The distribution of the apoptosis-positive cells did not show any accumulation in the inner part of the specimen, but were evenly distributed. CONCLUSIONS This study showed that patients with ulna plus present with significantly higher numbers of apoptotic cells in degenerative lesions in comparison to patients with ulna neutral. The apoptotic cells were evenly distributed throughout the entire specimen. CLINICAL RELEVANCE The results of this study revealed that increased length of the ulna is related to increased cell death. Therefore, techniques that decrease the ulna variance would appear to be appropriate and would improve the clinical situation by preventing further cell death.