Rehabilitation of distal radioulnar joint instability.

Distal radioulnar joint (DRUJ) instabilities are common and often combined with other injuries of the interosseous membrane and/or the proximal radioulnar joint. Once they are diagnosed and the treatment is chosen, physiotherapists have limited choices due to the lack of validated protocols. The benefits of proprioception and neuromuscular rehabilitation have been brought to light for the shoulder, knee and ankle joints, among others. However, no program has been described for the DRUJ. The purpose of this article is to study the muscular elements responsible for active DRUJ stability, and to propose a proprioceptive rehabilitation program suited to this condition.

[Carpal tunnel syndrome revealed by digital ulcerations caused by arterial vasospasm]. / Révélation d'un syndrome du canal carpien par ulcération digitale secondaire à un vasospasme artériel.

Carpal tunnel syndrome presenting as a trophic disorder in the hand is unusual. We report the case of a 66 year old man in whom nerve conduction tests confirmed compression of the median nerve in the carpal tunnel, and vasospasm in the corresponding area was demonstrated by arteriography for, we believe, the first time. Simple decompression of the carpal tunnel brought about total recovery. The mechanism of the autonomic disorders found in carpal tunnel syndrome remains controversial. The clinical case that we report objectively demonstrates the vasospasm caused by the compression of the autonomic fibres of the median nerve.

[The effect of surgical technic of the cost of surgical treatment of carpal tunnel syndrome]. / Influence de la technique opératoire sur le coût du traitement chirurgical des syndromes du canal carpien.

INTRODUCTION: Many publications have shown the efficiency along with the harmlessness of endoscopic release, in the idiopathic carpal tunnel syndrome. Some advantages have appeared such as an increase in post-operative well-being, a quicker recovery, hence a shorter sick leave. We wanted to know wether these advantages meant a reduced cost price for the community. METHOD: Since 1997, a hundred patient belonging to the social security system have been treated according to one of the three following methods: the Agee technique endoscopic release, isolated section of annular anterior carpal ligament, section-plasty. To calculate the cost, surgery and hospitalization cost price, post-operative paramedical services and daily payments have been taken into account. RESULTS: For a working subject, the endoscopic carpal tunnel release has enabled to save about 40% of the total cost, compared with the usual technique, mainly due to a shorter sick leave. Likewise, the section-plasty has proved to save 17% of the cost. DISCUSSION: The parameters which were taken into account in the total cost together with their calculation are controversial. The main problem of the study lies in the limited number of working subjects. Therefore, studying larger series would enable to confirm the interest of one method or the other.

A single backmutation in the human kIV framework of a previously unsuccessfully humanized antibody restores the binding activity and increases the secretion in cos cells.

Humanization of rodent mAbs by CDR-grafting (also called "reshaping") is now a standard procedure for reducing immunogenicity and recruiting human effector functions. However, the design of the humanized mAb can sometimes prove circuitous. Attempts were made to humanize L-25, a mouse antibody against the human alpha-4 integrin subunit using the usual protocols. Despite reaching eight backmutations in the light chain, it was not possible to recover the binding activity to the level of the chimeric. In an effort to restore the binding activity, an analysis of the human kappa IV acceptor frameworks was undertaken. This analysis highlighted the Asp at position 9 in framework 1, which although a common amino acid in human kappa IV frameworks, was an unusual residue in mouse kappa frameworks. Backmutating this position to the mouse amino acid completely restored the binding of the humanized antibody and as a by-product also increased the secretion levels in cos cells. Mutating position 9 to the consensus residue for human kappa I also restored the binding and secretion levels although not to the same extent. The resulting humanized antibody had a light chain with only a single backmutation to the mouse sequence.

Humanization of a mouse antibody against human alpha-4 integrin: a potential therapeutic for the treatment of multiple sclerosis.

alpha 4 beta 1 integrin (VLA-4) is crucial for the adhesion of leukocytes to human vascular cell adhesion molecule-1 (VCAM-1) on inflamed endothelium. This cell adhesion event is the first step in leukocyte extravasation across the blood-brain barrier in inflammatory diseases of the central nervous system (CNS) such as experimental autoimmune encephalomyelitis (EAE). Prevention of leukocyte infiltration by antibodies against the alpha 4 integrin, which block the alpha 4 beta 1 integrin/VCAM-1 interaction, have been shown to suppress clinical and pathological features of EAE. In this study, two mouse monoclonal antibodies (MAb) directed against human alpha 4 integrin were analyzed in vitro for their ability to block the interaction of leukocytes with VCAM-1 under different assay conditions. The best blocking MAb, AN100226m, was humanized by complementarily-determining region grafting, associated with human C regions and expressed. We found that modification of two structural determinants (H27 and H29) for the heavy chain CDR1 loop in one hand, and modification of framework amino acid H38, H40 and H44 in the other hand, had no effect on antigen binding. In contrast, modification of a structural determinant (H71) for the heavy chain CDR2 loop resulted in loss of binding. The humanized antibody. AN100226, was equivalent to the murine antibody. AN100226m, in binding to alpha 4 beta 1 integrin and in blocking cell adhesion. More importantly, AN100226 was as effective as AN100226m in the reversal of active EAE in guinea pigs and thus may be useful in the treatment of autoimmune diseases such as multiple sclerosis. AN100226 is currently in phase II clinical trials in the UK for the treatment of multiple sclerosis exacerbations.

[Deep muscular lipoma of the shoulder. Apropos of 4 cases]. / Lipomes musculaires profonds de l'épaule. A propos de 4 cas.

PURPOSE OF THE STUDY: The authors report 4 cases of inter and intra-muscular lipoma of the shoulder and make a review of the diagnosis of this localization. MATERIAL AND METHODS: All 4 cases had shoulder pain and some limitation of shoulder motion, one had hypoesthesia on the lateral side of the arm. 3 had magnetic resonance imaging (MRI) and two ultrasonography examination, three of them had a surgical resection and for one surgery was considered too aggressive and had a MRI control one year later. RESULTS: There was no problem for the surgical procedure and the histology confirmed the diagnosis. The last patient had a rehabilitation program and the MRI control showed lesion stability. DISCUSSION: Lipoma are rare, X-rays, ultra-sonography and CT scans are not sufficient, MRI is the best exploration to differentiate lipoma and lipo-sarcoma, but the main problem is for low grade sarcoma. Histology is the only way to make the diagnosis with the whole tumor.

Primary structure of the variable regions encoding antibody to NG2, a tumour-specific antigen on the rat chondrosarcoma HSN. Correlation of idiotypic specificities with amino acid sequences.

Eight syngeneic rat monoclonal antibodies that recognize structurally overlapping epitopes on the chondroitin proteoglycan NG2, a tumour-specific antigen on the chemically induced rat chondrosarcoma HSN, have been analysed for the sequence of their immunoglobulin heavy (H) and light (L) chain variable (V) regions. This analysis defined five groups of antibodies which are very similar for both the H and L chains and revealed that a wide range of different V regions are capable of binding to the same antigenic determinant. However, three mAbs, 11/160, ALN/12/17 and ALN/9/94, which recognize a sequential epitope, were found to use almost identical heavy (V-D-J) and light (V-J) chains in regions demonstrating an exclusivity in specific protein-protein interaction for this particular epitope. Two other mAbs, ALN/11/53 and AL/3/12, used similar V and J segments but totally different D regions. With the exception of the pair ALN/11/53 and AL/3/12, this grouping of antibodies matches that derived from the idiotypic specificity study we have reported previously. The reactivity pattern of Ab1 11/160, ALN/12/17 and ALN/9/94 with six anti-idiotopic mAbs raised against 11/160 demonstrated that the idiotope recognized by Ab2 HIM/3/41 was defined by a single amino acid, Asn, at position 52 within the CDR2 loop of the VH region; whereas the D region of Ab1 ALN/11/53 was implicated as the structural correlate of idiotypy. The substitution of AsnH52 influenced the Id recognition but Ag binding was not affected suggesting that Ab2 HIM/3/41 did not mimic the NG2 Ag.

A study of the fasciocutaneous vascularisation of the arm. Surgical applications.

The data on the fasciocutaneous vascularisation of the medial aspect of the arm are incomplete in the literature. This study presents the methodology and results of an anatomic study on 19 upper limbs with arterial injection. The vascularisation of the upper part of this region is provided in 68% of cases by the superficial fasciocutaneous branch (SFCB) of the superior ulnar collateral artery (SUC), that of the middle and lower part by 3-4 fasciocutaneous pedicles originating from the SUC which are prolonged distally by the recurrent posterior ulnar artery. The SFCB has important relations with the ulnar nerve; it travels dorsal to the nerve in 64% of cases and then allows the raising of a distally-pedicled ulnar flap with a 3:1 ratio. In other anatomic configurations, a flap with retrograde flow supplied by the inferior pedicles of the SUC can always be raised. Its ratio is then 2:1. this flap allows coverage of all cases of posterior or anterior losses of substance at the elbow. These results supplement the data required for the raising of a distally-pedicled medial brachial flap, but also of a proximally-pedicled superior medial brachial flap and of a free superior medial brachial flap transposed by microsurgical means.

The chondroitin sulfate proteoglycan NG2 is a tumour-specific antigen on the chemically induced rat chondrosarcoma HSN.

N-terminal sequences of 19 and 11 amino acids obtained from 2 different tryptic fragments of the tumour-specific antigen on the chemically induced rat chondrosarcoma HSN show a 100% homology with the rat chondroitin sulfate proteoglycan NG2. Using a scheme of overlapping oligonucleotide primers we have cloned by PCR amplification the cDNA for the specific antigen of the HSN tumour that is immunogenic in immunocompetent CBH/Cbi rats and now report that its cDNA sequence is identical to that of NG2. The cDNA codes for a transmembrane protein of 2,325 amino acids with a large extracellular domain of 2,224 amino acids containing 2 cysteine-rich regions, a transmembrane domain (25 amino acids) and a short cytoplasmic tail (76 amino acids). The tumour-specific determinant was found to lie between amino acid residues 556 and 992 on the core glycoprotein.

[Upper femoral epiphysiolysis in French Polynesia. Hip pain with serious consequences]. / L'épiphysiolyse fémorale supérieure en Polynésie Française. Une douleur de hanche aux conséquences lourdes.

High femoral epiphysiolysis is a frequent disability in French Polynesia, occurring more in obese young people that being a morphotype quite frequent in this geographical area. It is often at the stage of acute epiphysiolysis or fixed coxa vara these patients are examined. At such stage, sequellae are major and evolving to precocious coxarthrosis. It is at a stage of progressive coxarthrosis at the beginning that treatment and recovery are possible without sequellae. Any practitioner has to think about it when confronted to any pain in a hip of teenager, so a surgical treatment, in good conditions could be performed.

Isolation and characterization of a monoclonal rheumatoid factor specific for the hinge region of rat IgG2b.

The isolation and characterization of an isotype-specific autoantibody-secreting hybridoma NET/2/3 from rats bearing the syngeneic tumour HSN is described. This rheumatoid factor of the IgM class recognizes an epitope within the hinge region of rat immunoglobulins of the IgG2b subclass which is destroyed by reduction of disulphide bonds. The specificity of NET/2/3, although not allotype-restricted, is highly isotype-restricted, as it does not bind to rat Ig other than IgG2b, nor does it react with the majority of mouse IgG, although some reactivity occurs with mouse IgG3. One remarkable feature of NET 2/3 is that it binds more strongly to F(ab')2 and Fab' fragments of rat IgG2b, obtained by digestion with pepsin, than to the whole molecule. This anti-isotype response is not peculiar to the HSN tumour model as NET/2/3-like antibodies have been found in the sera of rats immunized with various protein and cellular antigens. The possible biological role of this anti-isotype antibody is discussed.

Characterization of syngeneic rat monoclonal antibodies to the HSN tumor using syngeneic monoclonal anti-idiotopic antibodies.

Twelve syngeneic anti-idiotopic mAb (anti-idiotypic/idiotopic antibodies Ab2)) were prepared from CBH/Cbi rats immunized with one of three monoclonal anti-HSN antibodies (Ab1) (11/160, ALN/11/53, or ALN/16/53) specific for the HSN tumor. The sera of the rats used for hybridoma production and all of the monoclonal Ab2 specifically inhibited the binding to HSN of the immunizing Ab1 only. It is concluded that, in this completely syngeneic system, only the private idiotopes associated with the antibody-combining site were immunogenic. Analyses using Western blotting showed that the Ab2 bound to intact Ab1 and to isolated H chains where the intra-strand disulfide bonds remained intact. The Ab2 did not bind to L chains or to fully reduced H chains of the Ab1. It is concluded that the idiotopes expressed on the H chain were conformational. When a panel of 13 monoclonal Ab1 (including the three used for immunization) were tested for reactivity with the Ab2, three reacted specifically with their respective Ab2 and 8 gave no binding suggesting that each Ab1 had a distinct idiotypic specificity despite the fact that all the Ab1 competed with each other for binding to Ag. However, the two remaining Ab1 (ALN/9/94 and ALN/12/17) generated from different tumor-bearing rats, were found to possess the same idiotypic specificity as 11/160. A detailed analysis using seven Ab2 raised against 11/160 showed that while the idiotype of ALN/9/94 and 11/160 were very similar, that of ALN/12/17 showed some clear differences. These three Ab1 have been shown previously to bind a sequential epitope on the HSN Ag in Western blots and it is postulated that the common idiotype of these Ab1 reflects their recognition of a sequential epitope. This may also account for the relatively frequent occurrence in tumor bearer sera of antibodies with this Id.

Isolation and characterization of a serologically defined tumour membrane antigen from a chemically-induced rat sarcoma, HSN.

Polypeptides containing the tumour antigenic determinant present on the external domain of a membrane antigen of the 3-4 benzpyrene-induced rat fibrosarcoma HSN have been isolated and purified. Following cleavage from intact cells with trypsin, the peptides were purified by immunoaffinity chromatography and SDS-PAGE. Three polypeptides of molecular weight 120, 45 and 42 kDa were obtained that bound the specific rat monoclonal antibody (MAb) 11/160 in Western blots. Chemical analyses of the 45-kDa fragment yielded the following sequence: NH2-I V F P H G S L M V I L E H T Q K P All 14 of the syngeneic MAbs prepared from rats bearing the HSN tumour competed with each other to bind to the specific antigen. Western blots of the purified tryptic fragments probed with 125I-AbI revealed that, while some of the MAbs (11/160, ALN/12/17 and ALN/9/94) recognized a sequential determinant, others (ALN/11/53, ALN/16/53, and AL/3/12) bound to a conformational epitope. It is concluded that the AbI bind to distinct but overlapping epitopes.

Endogenously generated activated killer cells circulate after autologous and allogeneic marrow transplantation but not after chemotherapy.

After marrow transplantation, major histocompatibility complex (MHC)-unrestricted natural killer (NK) lymphocytes are among the first cells to appear in the circulation. After T-cell-depleted bone marrow transplantation (TD-BMT), these cells have an activated pattern of target cell killing; they also secrete lymphokines including gamma-interferon (gamma-IFN), interleukin-2 (IL-2), and tumor necrosis factor (TNF) and may have a significant role as a primary defense against viral reactivation and in the elimination of residual host malignancy. We studied 43 patients with hematologic malignancy, treated by allogeneic TD-BMT, autologous nondepleted BMT, or chemotherapy alone to investigate (a) the mechanisms underlying the generation of these activated killer cells, (b) the range of conditions under which they are produced, and (c) their surface phenotype. We showed that gamma-IFN-secreting activated killer cells with the capacity to kill MHC-nonidentical NK-resistant targets are generated 4 to 6 weeks after either allogeneic TD-BMT or autologous BMT but do not appear after treatment with chemotherapy. Production therefore is not owing to T-cell depletion per se or to host donor alloreactivity, nor is it caused by stimulation by alloantigens contained in blood product support since no significant difference exists between allograft and chemotherapy patients in the number of units of blood platelet support given in the posttreatment period. Because most patients had no evidence of stimulation from virus reactivation/infection, the phenomenon of activation therefore appears to represent posttransplant immune disregulation following repopulation of the host immune system with lymphoid subsets derived exclusively from blood and marrow. Activated killing is predominantly mediated by the CD16+ CD3- subset, but substantial activity remains in the CD16- CD3+ cell fraction. Monoclonal antibodies (MoAbs) that block interaction with class-I MHC molecules at the level of target cell (W6/32 anti-HLA class I) or effector cell (CD8) do not inhibit killing by CD16- CD3+ cells. Activated killer cells may contribute to the lower risk of relapse after marrow transplantation as compared with intensive chemotherapy.

Interleukin 2 enhances cytotoxic cell function in vitro after T-cell depleted marrow transplantation.

After T-cell depleted marrow transplantation, there is a rapid recovery of cytotoxic effector cells, with activity against targets not susceptible to killing by 'resting' natural killer cells. These targets include Epstein-Barr virus transformed B cells and leukaemic cell lines. Activated killer cell function declines by 3 months after transplantation. We find that when CD3 negative effector cells are obtained from these patients and cultured in vitro with interleukin 2 there is a further enhancement of cytotoxic activity against a range of target cells in the early post-transplant period, and a restoration of high level cytotoxic activity to effector cells obtained 3 months or more after the procedure. These results may have relevance to attempts to reduce the incidence of leukaemic relapse, and EBV + ve lymphoma outgrowth after T-cell depleted BMT.