Maurice Hinsenkamp

Adverse reactions and events related to musculoskeletal allografts: reviewed by the World Health Organisation Project NOTIFY

PurposeThe use of bone and connective tissue allografts has grown rapidly and surpassed the use of autografts in many countries. Being of human origin, bone and tendon allografts carry the risk of disease transmission and complications have been reported. As part of the Project NOTIFY led by the World Health Organisation, an effort to improve recognition, reporting, tracking and investigation of adverse outcomes of allografts was initiated, achieving a comprehensive review of associated disease transmission and failures. Those involving the use of musculoskeletal allografts are reported here. A major objective is to involve orthopaedic surgeons in the improvement of the safe use of the musculoskeletal allografts.MethodsWe reviewed the medical literature, requested reports from surgeons in selected professional organisations and informally surveyed tissue bank organisations and selected tissue bank professionals to discover reported and unreported cases of adverse outcomes. We analysed each case to decide the likelihood that the complication was truly allograft related.ResultsThe efficiency of the procedures involved in bone banking and bone and tendon allograft has improved significantly during the last three decades. The evolution of the incidence of reported adverse reactions and events reflects positively on the safety of transplanted tissues. Cases of bacterial and viral transmission by bone and tendon allografts occurred mainly with those that contained viable cells, were not processed to remove cells, or were not disinfected or sterilised. We documented cases of transmission of human immunodeficiency virus (HIV), hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), unspecified hepatitis, tuberculosis and other bacteria. Reporting of these adverse outcomes has led to corrective actions and has significantly improved the safety of allograft use. However, it is probable that not all cases have been reported and investigated.ConclusionsConsidering the high quality standards achieved in many countries, the best approach for further improvement in the safety of allografts is through a systematic reporting of all serious adverse reactions and events in the context of a global biovigilance programme.

Clinical manifestations of Kashin-Beck disease in Nyemo Valley, Tibet.

Summary. Clinical manifestations of Kashin-Beck disease have been studied in Central Tibet. Statistical analysis of physical signs allowed a definition of the clinical diagnosis and a scale for the functional severity for the disease to be drawn up. This classification is used for the assessment of patients who received palliative physical treatment. A group of 136 patients have been examined and their disabled joints classified according to pain, bony enlargement and restriction of movement. 57% were between 20 and 35 years of age. The patients mainly complained about their distal weightbearing joints. The clinical evolution of the disease is described from childhood to adult life.Résumé. Les signes cliniques de la maladie de Kashin-Beck (KBD) sont étudiés dans le Tibet central. L’analyse statistique des symptômes a permis aux auteurs de mieux définir le diagnostic clinique évoqué dans la littérature et de proposer une classification fonctionnelle de l’évolution de la maladie. Cette classification sera utilisée ultérieurement pour l’évaluation des patients KBD qui recevront un traitement de kinésithérapie. La distribution des cas est étudiée en fonction de l’âge, du sexe et de la gravité. Les articulations atteintes sont classées en fonction des principales manifestations cliniques: la douleur, l’élargissement des articulations et la limitation de l’amplitude articulaire. Cinquante-sept pour cent des cas étudiés sont de jeunes adultes (20 à 35 ans). Les symptômes principaux sont très constants. Les plaintes dominantes des patients ont pour origines les articulations distales des membres inférieurs. L’évolution clinique est décrite depuis l’enfance jusqu’à l’âge adulte.

Effects of low frequency pulsed electrical current on keratinocytes in vitro

The effects of low frequency pulsed electrical current on epidermal repair in vitro were examined. Charge-balance current stimuli proposed for chronic wound treatment were tested on skin keratinocytes cultured at an air-liquid interface on dead human dermis. Results imply that the balance between proliferation and differentiation in electrically treated samples is significantly modified in favor of differentiation. More advanced differentiation, shown through epidermal histology, was obtained in cultures exposed to electrical current, whereas the culture growth, the result of keratinocyte migration and proliferation, was greater in control samples.

Effects of physical environment on the evolution of Kashin-Beck disease in Tibet

In previous studies we observed a proximo-distal gradient of lesion frequencies along the limb, with the distal joints being the most often affected. This suggests an associated effect of environmental factors on the most exposed joints. On a population of 820 children (mean age 13 years) of endemic areas distributed in groups of healthy and severity stages I to III of KBD (Kashin-Beck disease), the effects of different working activities were studied. Heavy work like that of a ploughman were compared to light physical work, e.g. school children, and exposure to cold and history of frostbite were also considered. The most severe stages, II and III, were present in 72% of the ploughman vs. 29% of the schoolchildren, 70% of the shepherds vs. 30% (p < 0.001) of the schoolchildren, and in 65% of the shepherds working in winter vs. 40% of those working in the other seasons (p < 0.001). In the group with history of frostbite, 58% present the severest stages vs. 40% without (p < 0.001). The results confirm a highly significant relation between microtrauma and cold and the severity of the KBD alterations.RésuméDans nos précédentes études, nous avions observé un gradient de fréquence proximo-distale des lésions le long des membres, les articulations distales étant les plus souvent atteintes. Ceci suggère un effet associé des facteurs environnementaux sur les articulations les plus exposées. Sur une population de 820 enfants (âge moyen 13ans) provenant de régions endémiques et distribués en groupes sains et de stades de gravité de la maladie de KASHIN-BECK s´échelonnant de I à III, nous avons étudié les effets de différents types d´activités. Les travaux lourds, comme celui de laboureur, ont été comparés à une activité plus légère telle que celle d´écolier. Les stades les plus sévères (II et III) sont présents chez 72% des laboureurs contre 29% chez les écoliers, chez 70% des bergers contre 30% des écoliers (p<0.001) et chez 65% des bergers travaillant en hiver contre 40% chez ceux travaillant pendant les autres saisons (p<0.001). Dans le groupe présentant des antécédents de gelure, 58% présentent les stades les plus sévères contre 40% dans le groupe sans antécédents (p<0.001). Ces résultats confirment une relation très hautement significative entre les microtraumas et l´exposition au froid et la sévérité des lésions de la maladie de Kashin-Beck..

Treatment of chronic osteomyelitis using the Papineau technique.

Summary. From 1984 to 1994, 41 cases of chronic osteomyelitis were treated in Kinshasa by the Papineau technique; 75.5% were men and 24.5% women. The mean age was 28 years (range: 7 – 77), and the average duration of the infection was 3 years (range: 1 month to 28 years). The aetiology was “trauma”“ in 53.5%, haematogenous in 44% and drepanocytosis in 2.5%. Infections of the femur and tibia each constituted 41.5% of the cases. Immobilisation was by external fixation in 44%, and by a cast in 39%. Wound healing was complete after an average of 3 months with spontaneous healing, and in 4.5 months after skin grafting. Control of the infection and bone healing were obtained in 89% after a period of 3 – 7 months. We discuss the Papineau technique and the modifications which were required in Kinshasa.Résumé. De 1984 à 1994, 41 cas d’ostéomyélites chroniques (OMC) ont été traitées par la technique de Papineau dans les Hôpitaux de Kinshasa. La population étudiée est composée de 75,5% d’hommes et de 24,5% de femmes. La moyenne d’âge est de 28 ans (7 – 77 ans). La durée d’évolution de l’OMC est en moyenne de 3 ans (1 mois – 28 ans). L’origine de la lésion est traumatique dans 53,5% des cas, hématogène dans 44% et dépranocytaire dans 2,5%. Le fémur et le tibia représentent chacun 41,5% des cas. Une contention associée a été réalisée dans 44% des cas par fixateur externe et par plâtre dans 39%. La cicatrisation cutanée est obtenue en moyenne en 3 mois après épidermisation et en 4,5 mois après greffe cutanée. L’assèchement de l’infection et la consolidation osseuse sont obtenus dans 89% des cas après un délai de 3 à 7 mois en fonction de la localisation et de la gravité de la lésion. La discussion reprend les remarques et les attitudes spécifiques de traitement qui ont été imposées par l’environnement et les conditions de soins propres à la ville de Kinshasa.

In vitro study of the effects of ELF electric fields on gene expression in human epidermal cells

An acceleration of differentiation, at the expense of proliferation, is observed after exposure of various biological models to low frequency and low amplitude electric and electromagnetic fields. Following these results showing significant modifications, we try to identify the biological mechanism involved at the cell level through microarray screening. For this study, we use epidermis cultures harvested from human abdominoplasty. Two platinum electrodes are used to apply the electric signal. The gene expressions of 38,500 well-characterized human genes are analyzed using Affymetrix(®) microarray U133 Plus 2.0 chips. The protocol is repeated on three different patients. After three periods of exposure, a total of 24 chips have been processed. After the application of ELF electric fields, the microarray analysis confirms a modification of the gene expression of epidermis cells. Particularly, four up-regulated genes (DKK1, TXNRD1, ATF3, and MME) and one down-regulated gene (MACF1) are involved in the regulation of proliferation and differentiation. Expression of these five genes was also confirmed by real-time rtPCR in all samples used for microarray analysis. These results corroborate an acceleration of cell differentiation at the expense of cell proliferation.

Morphological effect of electromagnetic stimulation on the skeleton of fetal or newborn mice

In vitro cultures of limbs from fetuses or newborn mice allow for a strict control of the experimental parameters. Moreover the use of controlateral limbs as a control series avoids inter-individual variations and staining artefacts. The results show that the electromagnetic signal used produces modifications in the morphology and the metabolism of the different components of the bone. The modifications observed in the stimulated limbs are: a thicker proliferative layer of chondrocytes, a better lining up of the trabecula and a better configuration of the cartilage. These modifications are probably due to a change on the components of the cartilaginous matrix. The histochemical demonstration of mucopolysaccharides would probably clarify this matter.

Osteotomy at the knee for advanced cases of Kashin-Beck disease

Summary. The results of 247 osteotomies at the knee were analysed in 195 patients with Kashin-Beck disease. Since 1983, 37 varus and 210 valgus deformities have been operated on. Supracondylar osteotomy was carried out so that there is a cortical spike in the distal metaphysis which is impacted into the femoral condyle. A U-shaped tibial osteotomy is made 0.5 cm below the growth plate and around the insertion of the patellar ligament. The mechanical axis is corrected and stability obtained by impacting the fragments; internal fixation is not used. Correction of the initial angular deformities was achieved after the osteotomies, and function was improved.Résumé. Les résultats de 247 ostéotomies du genou sont analysés sur 195 patients atteints de la maladie de Kashin-Beck. La technique d’ostéotomie utilisée se caractérise, au niveau de la métaphyse distale du fémur, par la réalisation d’une section supracondylienne présentant un ergot cortical et au niveau de la métaphyse proximale du tibia par une section respectant l’insertion du ligament rotulien en la contournant distalement. Vu l’absence de matériel de fixation interne ou externe, l’impaction des fragments permet de stabiliser efficacement la correction de l’axe mécanique. Depuis 1983, 37 genu vara et 210 genu valga ont été ostéotomisés. Les résultats présentent la distribution des déformations angulaires initiales et les corrections obtenues après ostéotomie. L’amélioration fonctionelle confirme l’intérêt de cette technique en l’absence de matériel d’ostéosynthèse.

Treatment of non-unions by electromagnetic stimulation.

Since 1974, we have studied on electromagnetic stimulation of bone growth and repair in the Interdisciplinary Center of Bone Biomechanics. It was necessary to realize a rigorous scientific approach of the fundamental mechanisms and of the clinical data of treatments which were prematurely sold throughout the European countries under different forms, devices and distributors. Moreover, the conception and the biological effects of some stimulators distributed in our country had no scientific base at all.

External fixation of the fracture of the humerus: a review of 164 cases.

During our experience with external fixation for the fractures of the shaft of the humerus since 1967, the indications have been extended to include complex metaphyseal and epiphyseal fractures of both the proximal and the distal part of the bone. We propose elastic fixation of the fragments using half frame Hoffmann external fixation. Because of anatomical considerations, the two proximal pins must be inserted laterally in the upper third of the humerus, and the two distal pins in the posterior aspect of the lower third above the olecranon fossa. If the mechanical properties of the bone are poor (due to osteoporosis) more than two pins must be used in each fragment. The advantages of the technique include fast and easy application requiring simple materials; versatility of use for fractures at different levels; possible closed reduction, as in conservative treatments; early rehabilitation of joint function; fast periosteal callus formation; and retrieval of the fixator on an outpatient basis.The reduction and the immobilization of the fracture by osteotaxis are done in emergency. Closed reduction is performed as in conservative treatments. In cases of important muscular interposition, open reduction is possible. Associated internal fixation was required in 18.4% (unstable or articular fractures). A secondary transient radial palsy is observed in 5% of the patients. Intolerance to the external fixation appears in 5.6% of cases, usually consisting of drain age and redness around the pin tracts. A general evaluation of the results gives 73.8% very good results and 93.6% satisfactory results after rehabilitation.