Diabetic muscle infarction-an orthopedic disease pattern?

Diabetic muscle infarction (DMI) is a largely unfamiliar disease. It affects mainly patients around 40 years of age with long-standing diabetes and concomitant end-organ complications. The symptoms represent a classic pattern of a musculoskeletal disease with muscle pain without trauma, swelling, and functional impairment. Although its short-term prognosis is good, with improvement of the symptoms over weeks or months under analgesia and rest, a high recurrence rate of up to 60% can be observed. Additionaly, the long-term survival of patients after DMI is reduced mostly due to major vascular complications.Since many diabetic patients are in orthopedic care for musculoskeletal disorders, the orthopedic surgeon should be aware of this disease to avoid unnecessary invasive diagnostic procedures and initiate suitable therapy. Furthermore, a better knowledge of the disease could lead to definite conclusions regarding its real incidence and aid in establishing new therapeutic measures for prophylaxis and better long-term survival.     

The impact of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) on osseointegration,degradation and biomechanical properties of a synthetic bone substitute

INTRODUCTION: It was the purpose of this investigation to test the osteointegrative capacity and the degradation rate of a neutralized glass ceramic within an animal model after loading with different growth factors. MATERIALS AND METHODS: The glass ceramic GB9N was implanted in the medial tibial head of mature merino sheep (n = 48) after being loaded with either Bone Morphogenetic Protein-2 (BMP-2, 100 micro g/100 micro l), Vascular Endothelial Growth Factor (VEGF, 100 micro g/100 micro l), basic Fibroblast Growth Factor (b-FGF, 60 micro g/100 micro l) or unloaded. At 4 weeks (n = 24) and 9 months (n = 24) after operation histomorphological, histomorphometrical and biomechanical investigations were performed. RESULTS: The amount of newly formed bone was different within the study groups after 4 weeks. BMP-2 induced a significant increase in bone formation and a significant decrease of residual substitute. b-FGF and VEGF induced no such effects in comparison to the controls. Biomechanical investigations could only demonstrate slight increases of the maximal fracture load in the BMP-2 group after 4 weeks in comparison to the others. At 9 months after operation no differences concerning newly formed bone could be found in the study groups comparing to the controls. Only the amount of residual substitute was still significantly lower in the BMP-2 group. Biomechanical data could demonstrate maximal fracture loads of all study samples achieving the level of the controls. CONCLUSION: This investigation has demonstrated that by combining synthetic bone substitutes with growth factors certain parameters of the bone remodelling process can intitially be influenced in a positive way.     

Morphologische Untersuchung über die Polymerisation von Knochenzement

Zusammenfassung Die Beeinflußbarkeit der Polymerisation des Methylmethacrylates durch Kühlung, unterschiedliches Mischungsverhältnis Monomeres zu Polymerem und Luftsauerstoffeinwirkung wurde mit dem Rasterelektronenmikroskop untersucht. Es konnte gezeigt werden, daß Abweichungen vom vorgeschriebenen Mischungsverhältnis ebenso eine Störung der Polymerisation bedingen wie Kühlung während der Polymerisation und die Einwirkung von Luftsauerstoff.Die damit verbundene klinisch bedeutsame Gefahr eines erhöhten Restmonomerengehaltes im Polymerisatblock wird im Hinblick auf die Toxicität der monomeren Form des Methylmethacrylates betont. Auf die verstärkte Schrumpfung des Knochenzementes bei vermehrter Zugabe von Monomeren wird hingewiesen. Die sich aus den Untersuchungen ergebenden Möglichkeiten, den Gehalt an Restmonomeren gering zu halten, werden aufgezeigt.

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Summary The influence of cooling, different proportions of monomers to polymers, and the admittance of air-oxygen upon the polymerization of methyl-methacrylate were studied with the scanning electron microscope. It was shown, that all three factors interfere with the process of polymerization.This results in an increased amount of free monomers within the polymerized block an the inherent clinical danger is stressed in view of the toxicity of the monomeric form of methyl-methacrylate. It is pointed out, that an increased amount of monomers results in an increased shrinkage of the bone cement. The possibilities to reduce the amount of free monomers, deduced from this observations, are shown.

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Résumé Nous avons étudié l'effet de réfrigération, de mélanges différents monomèrespolymériques et de l'oxygénisation sur la polymérisation de methylmethacrylate (PMMA). On a mis en évidence la disturbation de la polymérisation à cause de changement dans les rélations de la mélange, de la réfrigération et par l'oxygénisation. On a discuté le danger de l'augmentation de la partie monomérique dans un bloc de la PMMA causant en plus un retrécissement du ciment.

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Für die freundliche Beratung auf dem Gebiet der Monomeren-Chemie danken wir den Herren Dr. Quis und Götz der Firma Röhm & Haas, Darmstadt.     

Oberflächenbetrachtungen des Gelenkknorpels

Zusammenfassung Es wurden Oberflächenbetrachtungen am menschlichen Gelenkknorpel mit dem Rasterelektronenmikroskop durchgeführt. Das Untersuchungsmaterial wurde einerseits bei orthopädisch-chirurgischen Eingriffen, andererseits anläßlich von Obduktionen entnommen. Es stammt von Individuen im Alter von 4 Tagen bis 71 Jahren. Ziel der Arbeit war die Erfassung der Oberflächenfeinstruktur des menschlichen Gelenkknorpels in Abhängigkeit vom Alter, um so eine Basis für weitere Untersuchungen pathologisch veränderter Oberflächenstrukturen zu schaffen.Die Ergebnisse zeigen, daß die Feinstruktur der Oberfläche des menschlichen Gelenkknorpels charakteristischen Veränderungen in Abhängigkeit vom Alter und der funktionellen Belastung unterliegt. Die makroskopisch unauffällig erscheinende Knorpeloberfläche kann unter der Betrachtung mit dem Rasterelektronenmikroskop deutliche Veränderungen, die auf lichtmikroskopischen Schnitten nicht oder nur undeutlich nachweisbar sind, aufweisen. Es ergeben sich dabei fließend alle Übergänge bis zu schweren arthrotischen Veränderungen.Mit der geschilderten Methode der Oberflächenbetrachtung ist es erstmalig möglich, einen den tatsächlichen Verhältnissen entsprechenden plastischen Eindruck der Gelenkoberfläche zu erhalten. Dies war mit den bisher zur Verfügung stehenden Verfahren nicht gegeben.

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Summary A report is given upon surface structures of the human joint cartilage as seen with the scanning electron microscope. Part of material was recovered during orthopedic — surgical operations, part during obductions.The age distribution was between 4 days and 71 years. The intention of the study was to find out the characteristics of the surface structure of human joint cartilage in their relation to different age groups.The results should serve as a basis for future studies on pathologically altered structures. Characteristic changes of fine surface structure of human joint cartilage could be shown according to age and mode of function.Distinct changes can be seen with the scanning electron microscope in a cartilage surface, which macroscopically may appear normal and microscopically normal or only slightly altered. There are all possible states of transition between these slight and severe arthrotic changes.The described method of surface scanning allows for the first time to gain a three dimensional picture of the joint surface representing the actual conditiones. This has not been possible with technics hitherto in use.

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Résumé Nous avons axaminé la surface du cartilage humain à l'aide du microscope électronique Raster. Le matérial étudié provenait tantôt d'interventions chirurgicales, tantôt de pièces nécropsiques et a permis l'étude de cartilage d'individus agés de 4 jours à 71 ans. Nous avions comme but de décrire la structure superficielle du cartilage en fonction de l'âge, de façon à pouvoir mener des études ultérieures sur des cartilages pathologiques.Les résultats montrent que le cartilage subit des modifications en fonctions de l'âge et de la charge qu'il subit, et ce, dans les couches les plus superficielles. Des surfaces cartilagineuses qui macroscopiquement et même en coupes ordinaires apparaissent normales ou peu altérées montrent avec le microscope électronique Raster des altérations importantes. On reconnait tous les stades progressifs jusqu'à l'arthrose terminale.La technique décrite permet pour la première fois d'obtenir des images en relief de la surface du cartilage, ce qui n'était pas permis avec les autres méthodes d'examen.

     

BMP-4 of Xenopus laevis stimulates differentiation of human primary osteoblast-like cells

Since bone morphogenetic proteins (BMPs) are highly homologous, we investigated the hypothesis that recombinant BMP-4 of the genome of Xenopus laevis (rxBMP-4) may influence the proliferation or differentiation of human primary osteoblast-like cells (HPOC), as occurs with recombinant human BMP (rhBMP-2). HPOC were incubated in the presence of either rxBMP-4, rhBMP-2 or basic fibroblast growth factor (rh-bFGF). The last two were used as positive controls and are known to induce differentiation or proliferation of HPOC, respectively. rxBMP-4 (50 ng/ml and 100 ng/ml) induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied in the same concentration, failed to have any influence on cell differentiation. rh-bFGF however, provoked an increase in cell proliferation of up to 150% when compared with non-stimulated HPOC, while rhBMP-2 and rxBMP-4 had no such effect. Our results indicate an equipotent effect of rhBMP-2 and rxBMP-4 obtained from Xenopus laevis on the differentiation and proliferation of human primary osteoblast-like cells.     

Growth hormone administration and exercise effects on muscle fiber type and diameter in moderately frail older people

OBJECTIVE: Reduced muscle mass and strength are characteristic findings of growth hormone deficiency (GHD) and aging. We evaluated measures of muscle strength, muscle fiber type, and cross sectional area in response to treatment with recombinant human growth hormone (rhGH) with or without a structured resistance exercise program in frail older subjects. DESIGN: Placebo-controlled, randomized, double blind trial. SETTING: Outpatient clinical research center at an urban university-affiliated teaching hospital. PARTICIPANTS: Thirty-one consenting older subjects (mean age 71.3 +/- 4.5 years) recruited as a subset of a larger project evaluating rhGH and exercise in older people, who underwent 62 quadricep-muscle biopsies. INTERVENTION: Random assignment to a 6-month course of one of four protocols: rhGH administered subcutaneously daily at bedtime, rhGH and a structured resistance exercise program, structured resistance exercise with placebo injections, or placebo injections only. MEASUREMENTS: Muscle biopsy specimens were obtained from the vastus lateralis muscle. Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program. Serum insulin-like growth factor-I (IGF-I) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer. RESULTS: The administration of rhGH resulted in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment. Muscle strength increased significantly in both the rhGH/exercise (+55.6%, P =.0004) as well as the exercise alone (+47.8%, P =.0005) groups. There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH (P =.027). CONCLUSIONS: Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit. IGF-I was increased by administrating rhGH and muscle strength was increased by exercise. The administration of rhGH to frail older individuals in this study resulted in significant changes in the proportions of fiber types. Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study.     

Childhood obesity: a societal problem to solve

In contrast to other threats to American children's health, the treatment and prevention of childhood obesity are considered the responsibility of individual children and their parents. This pressure exists in the context of the societal stigmatization of overweight children and the powerful environmental inducements aimed directly at children to eat nutritionally poor foods. Parents of overweight children are left in the difficult position of fearing the social and health consequences of their child's obesity, and fighting a losing battle against the omnipotent presence of the media and constant exposure to unhealthy foods. This paper brings together several literatures to provide a comprehensive examination of the major challenges facing obese children and their families. In particular, this paper documents the extent of stigmatization towards overweight children and reviews evidence of the conflicting advice given to parents about how to help children develop healthful eating in the face of biological and learned food preferences. We conclude with a call for a shift in thinking about the role of our society in the aetiology, treatment and prevention of childhood obesity.     

Technical feasibility of liver transplantation without cold storage

Purpose

The success of liver transplantation (LT) is accompanied by an increased need for organs. The wider use of older donors and marginal organs with risk factors such as steatosis has lead to a new interest to improve the outcome with marginal organs. We herewith report a novel technique for LT with in situ preparation and immediate warm-ischemia liver transplantation (WI-LT). The aim of our study was to demonstrate the technical feasibility and report the transplant course.

Methods

Six patients underwent WI-LT at our institution. Hepatectomies during procurement and LT were both performed in parallel by different surgical teams. Technical factors and postoperative allograft function were analyzed.

Results

All six WI-LTs were performed without intraoperative complications with a mean warm-ischemia time (WIT) of 29.0 min. No patient developed primary non-function or required retransplantation. Mean alanine aminotransferase (194.0?±?170.4 U/l) and aspartate aminotransferase (316.3?±?222.1 U/l) values on the first postoperative day were low, indicating a low ischemia/reperfusion injury and an excellent liver function.

Conclusions

These results demonstrate that WI-LT is a safe and technically feasible approach for LT with possibly reduced IRI and an excellent postoperative allograft quality. WI-LT may therefore be considered in individual patients especially with extended criteria donors to eventually improve postoperative allograft quality.