[Trigger digits]. / Les doigts à ressort.

Trigger finger is an entity seen commonly by hand surgeons. It is produced by a size mismatch between the flexor tendon and the A1 pulley, which causes pain, clicking, catching, and loss of motion of the affected finger. The diagnosis is usually easy but other pathological processes (extensor apparatus instability, locked metacarpo-phalangeal joint) must be excluded. Treatment modalities in trigger finger include splinting, corticosteroid injection and/or surgery. Indication depends on the clinical form of trigger finger.

[Prevention and management of the conflict patient-doctor]. / Prévention et gestion du conflit médecin-patient.

A surgeon's daily practice evolves according to techniques, but also according to a legal and associative environment. The patient is becoming a health consumer, demanding and informed, legitimately exacting security and transparency, but also compensation in the event of accidental injury. The constraints that weigh upon this profession are growing heavier: knowledge and respect of laws, ordinances and regulations are becoming essential and law suits more and more frequent. Ever present in surgery, risk evaluation and assessing the risk-benefit ratio for the patient must be clearly stated by the practitioner and his team, despite the inherent difficulties in sharing information. A classification of surgical risk facilitates an approach to the definitions of a fault, medical accident, iatrogenic condition or undesirable event. This is a fundamental concept, since precise criteria apply to a fault in the legal sense, whereas no normative definition exists for a medical fault. Prevention of conflict requires the implementation of collective steps aimed at ensuring security in a complex system, confidence between the surgeon and his patient based on appropriate information and strict adherence to current regulations. In the event of complications, difficult after-effects, objectively unsatisfactory results or those perceived as such by the patient, post-operative follow-up must face these difficulties squarely with transparency and responsibility. Following a legal summons involving the responsibility of the practitioner, management of the conflict between the physician and the patient requires solid preparation of the medical file and his active participation in the judicial expertise so as to best inform the judge.

Quantitative optical coherence tomography of arterial wall components.

Optical coherence tomography (OCT) can be used to visualize the arterial wall and atherosclerotic plaques with high resolution. In this study, we verified the application of OCT to the quantitative analysis of plaque structural dimensions and optical attenuation coefficients of the components. We assessed the effect of balloon dilation on the OCT signal from the medial layer of porcine carotid artery ex vivo. Imaging of human autopsy samples was performed from the luminal side with a high (3.5 microm axial and 7 microm lateral) resolution OCT system (approximately 800 nm) or a regular (15-20 microm axial and 20 microm lateral resolution) OCT system (approximately 1,300 nm). For each sample, dimensions were measured by histomorphometry and OCT, and the optical attenuation was measured. In a tissue culture set-up, porcine carotid arteries were dilated and the attenuation coefficients of the dilated segments were compared to a control segment for 4 h. Quantitative analysis showed a strong and significant correlation between OCT and histology cap thickness measurements for both OCT systems. For both systems, the measured attenuation coefficients for diffuse intimal thickening and lipid-rich regions differed significantly from that of calcified tissue. Balloon dilation induced a time-dependent increase in the attenuation coefficient, which may be attributed to the induction of apoptosis. In conclusion both the high and regular resolution OCT systems can image the atherosclerotic plaques precisely. Quantitative analysis of the OCT signals allowed in situ determination of the intrinsic optical attenuation coefficient for atherosclerotic tissue components within regions of interest, which can help to discriminate between plaque and arterial wall components.

[Eight days of hand emergencies. Report of the audit carried out at the FESUM centers from June 3 to June 9, 2002]. / Huit jours d'urgences mains. Rapport de l'audit réalisé dans les centres FESUM du 3 au 9 juin 2002.

All the FESUM centers in France, Belgium and Switzerland were invited to participate in this prospective audit, during 1 week in June 2002. In these FESUM centers, the patients are operated by senior hand surgeons or trainees graduated with a microsurgical and a hand surgery University degrees. All acute hand disorders, requiring surgery or not, were to be included. For every case, a standardized form was to be filled. This form included 22 fields concerning the specificities of the patient, the circumstances of the accident, the lesions and initial treatment up to exit of the patient out of the Hand Center. Out of the 43 French centers, 38 (90%) participated in this study, but only 30% in the other French speaking countries. A total of 2360 forms were completed and analyzed, representing a mean of 8 forms per day center (6-147). The population was predominantly active men with a mean age of 31. Manual workers represented 41%, scholars 33%. Most of them came to the Hand Center with a non-specilized vehicle (86%). Emergency medical transportation was required in 130 cases (5.8%). A majority of the patients were treated on an outdoor basis. A 1-day admission concerned 29% of the patients, and 4.6% have been admitted on an indoor basis during several days. Work accident represented 28% of all the cases, while the majority was daily living (62%) or sport (15%) accidents. Closed trauma represented 50% of the cases. Amongst open trauma (974 cases), 862 were simple skin lacerations, 156 skin loss, 140 extensor tendon lacerations, 70 flexor tendon lacerations. A preliminary wound exploration had been performed in a non-specialized center in 124 cases (12%). Complete amputation of some part was observed in 33 cases. In 32%, the initial severity of the lesion led to expect some degree of definitive consequences. Some kind of anesthesia was required in 43% of the cases (local in 41%, troncular in 19%, plexical in 28% and general in 9%). A surgical procedure was performed in 45% of the patients. Microsurgery was necessary in 15%, six of which were replantations. The period between presentation to the Hand Center and treatment was less than 1 day in 95% of the cases. Time of treatment was considered to be delayed in 113 cases (5%). Following this audit, it is considered that the FESUM centers make provision for the care of 120,000 cases per year, 54,000 of which needing a surgical procedure. This may be a small part of the total load of emergency hand surgery throughout the country (generally estimated over 1.4 million), but compares quite favorably with other European studies. We believe that improvement relies essentially on a better orientation of the patients whether they need a simple skill or specialist skill treatment. An information leaflet about orientation of hand trauma has been distributed to non-specialized emergency centers. Hand surgery training must be reevaluated inside the universitary system to avoid a dramatic lack of hand surgeons within a few years. A new audit will be presented next year.

[Musculoskeletal disorders of the upper extremity associated with work: from presentation to work maintenance]. / Les troubles musculosquelettiques du membre supérieur liés au travail: de la présentation au maintien à l'emploi.

The so called Musculo-Squeletal-Disorders in the upper extremity are frequent and are responsible for a significant cost. The increase in registered work-related affections has been quite impressive in the past few years. The type of social undertaking is determinant on the evolution and final outcome of the pathology. Our proposal for a "Passport to work continuation" follows two goals: facilitate and enhance the relations between medical and social workers concerned by the patient's course reduce the time off-work, improve prevention of work related pathologies, avoid dismissal for inaptitude, start earlier a vocational training, a rehabilitation or an adaptation of the work station.

Identification of a novel stretch-responsive skeletal muscle gene (Smpx).

Skeletal muscle is able to respond to a range of stimuli, including stretch and increased load, by increasing in diameter and length in the absence of myofiber division. This type of cellular growth (hypertrophy) is a highly complex process involving division of muscle precursor cells (myoblasts) and their fusion to existing muscle fibers as well as increased protein synthesis and decreased protein degradation. Underlying the alterations in protein levels are increases in a range of specific mRNAs including those coding for structural proteins and proteins that regulate the hypertrophic process. Seven days of passive stretch in vivo of tibialis anterior (TA) muscle has been shown to elicit muscle hypertrophy. We have identified a cDNA corresponding to an mRNA that exhibits increased expression in response to 7 days of passive stretch imposed on TA muscles in vivo. This 944-bp novel murine transcript is expressed primarily in cardiac and skeletal muscle and to a lesser extent in brain. Translation of the transcript revealed an open reading frame of 85 amino acids encoding a nuclear localization signal and two overlapping casein kinase II phosphorylation sites. This gene has been called "small muscle protein (X chromosome)" (Smpx; HGMW-approved human gene symbol SMPX) and we hypothesize that it plays a role in skeletal muscle hypertrophy.

Visualization and functional characterization of the developing murine cardiac conduction system.

The cardiac conduction system is a complex network of cells that together orchestrate the rhythmic and coordinated depolarization of the heart. The molecular mechanisms regulating the specification and patterning of cells that form this conductive network are largely unknown. Studies in avian models have suggested that components of the cardiac conduction system arise from progressive recruitment of cardiomyogenic progenitors, potentially influenced by inductive effects from the neighboring coronary vasculature. However, relatively little is known about the process of conduction system development in mammalian species, especially in the mouse, where even the histological identification of the conductive network remains problematic. We have identified a line of transgenic mice where lacZ reporter gene expression delineates the developing and mature murine cardiac conduction system, extending proximally from the sinoatrial node to the distal Purkinje fibers. Optical mapping of cardiac electrical activity using a voltage-sensitive dye confirms that cells identified by the lacZ reporter gene are indeed components of the specialized conduction system. Analysis of lacZ expression during sequential stages of cardiogenesis provides a detailed view of the maturation of the conductive network and demonstrates that patterning occurs surprisingly early in embryogenesis. Moreover, optical mapping studies of embryonic hearts demonstrate that a murine His-Purkinje system is functioning well before septation has completed. Thus, these studies describe a novel marker of the murine cardiac conduction system that identifies this specialized network of cells throughout cardiac development. Analysis of lacZ expression and optical mapping data highlight important differences between murine and avian conduction system development. Finally, this line of transgenic mice provides a novel tool for exploring the molecular circuitry controlling mammalian conduction system development and should be invaluable in studies of developmental mutants with potential structural or functional conduction system defects.

A role for Engrailed-2 in determination of skeletal muscle physiologic properties.

The molecular basis underlying the establishment of the myogenic lineage, subsequent differentiation, and the establishment of specific fiber types (i.e., fast versus slow) is becoming well understood. In contrast, the regulation of the general properties of a specific anatomical muscle group (e.g., leg versus jaw muscles) and the regulation of muscle-fiber properties within a particular group are less well characterized. We have investigated the potential role of the homeobox-containing gene, Engrailed-2 (En-2), in the mouse, which is specifically expressed in myoblasts in the first arch and maintained in the muscles of mastication in the adult. We have generated mice that ectopically express En-2 in all muscles during early development and primarily in fast muscles in the adult. Ectopic En-2 in nonjaw muscles leads to a decrease in fiber size, whereas overexpression in the jaw muscles leads to a shift in fiber metabolic properties as well as a decrease in fiber size. In contrast, loss of En-2 in the jaw leads to a shift in fiber metabolic properties in the jaw of female mice only. Jaw muscles are sexually dimorphic, and we propose that the function of En-2 and mechanisms guiding sexual dimorphism of the jaw muscles are integrated. We conclude that the specific expression of En-2 in the jaw therefore plays a role in specifying muscle-fiber characteristics that contribute to the physiologic properties of specific muscle groups.

The emergence of molecular gynecology: homeobox and Wnt genes in the female reproductive tract.

Reproductive tissues respond to steroid hormones and thus are particularly vulnerable to the effects of exogenous steroid 'mimic' compounds (endocrine disrupters). One such endocrine disrupter, diethylstilbestrol (DES), is linked to gynecological cancers and changes in uterine structure that reduce or completely abrogate reproductive competence. Until recently, little was known about the identity of target genes and signaling pathways involved in pathologies linked to endocrine disrupters such as DES. We outline genetic, cellular and molecular roles for patterning genes, with emphasis on homeobox and Wnt genes. There is evidence that changes in the expression of Wnt and homeogenes underlie many of the defects induced by DES. Data obtained from murine systems will likely apply to a broad spectrum of gynecological pathologies involving abnormal cell behaviors ranging from fibroids to malignant tumors. Knowledge garnered from modern molecular genetics should lead to progress in the emerging field of molecular gynecology.

Developmental expression pattern of the cdo gene.

CDO is a cell-surface protein of the immunoglobulin/fibronectin type III repeat family that positively regulates myogenic differentiation in vitro. To gain a better understanding of the role of cdo during vertebrate development, we carried out an extensive in situ hybridization study to characterize its expression pattern from postimplantation to late stages of mouse embryogenesis and in rat brain from E13 to adult. Our results show a broad pattern of cdo expression that is spatially and temporally restricted during embryogenesis. In the central nervous system (CNS), cdo expression is detected as early as E7.5 and maintained in the dorsal ventricular zones of the brain and spinal cord, becoming increasingly restricted in the adult. High levels of cdo are detected in developing sensory organs, such as the eye and ear. Outside the CNS, cdo is expressed mainly in neural crest and mesodermal derivatives, including skeletal muscle precursors. Overall, the highest levels of cdo expression are seen from E9.0 to E15.5. The temporal onset and restricted expression of cdo suggest that cdo plays a role in the determination and/or differentiation of a number of cell types during embryogenesis.

Identification of Ankrd2, a novel skeletal muscle gene coding for a stretch-responsive ankyrin-repeat protein.

Mechanically induced hypertrophy of skeletal muscles involves shifts in gene expression leading to increases in the synthesis of specific proteins. Full characterization of the regulation of muscle hypertrophy is a prerequisite for the development of novel therapies aimed at treating muscle wasting (atrophy) in human aging and disease. Using suppression subtractive hybridization, cDNAs corresponding to mRNAs that increase in relative abundance in response to mechanical stretch of mouse skeletal muscles in vivo were identified. A novel 1100-bp transcript was detected exclusively in skeletal muscle. This exhibited a fourfold increase in expression after 7 days of stretch. The transcript had an open reading frame of 328 amino acids encoding an ATP/GTP binding domain, a nuclear localization signal, two PEST protein-destabilization motifs, and a 132-amino-acid ankyrin-repeat region. We have named this gene ankyrin-repeat domain 2 (stretch-responsive muscle) (Ankrd2). We hypothesize that Ankrd2 plays an important role in skeletal muscle hypertrophy.

Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis.

Induction of wild-type p53 in mouse fibroblasts causes cell cycle arrest at the G(1) phase, whereas coexpression of p53 and the protooncogene c-myc induces apoptosis. Although p53 transcriptional activity generally is required for both pathways, the molecular components mediating p53-dependent apoptosis are not well understood. To identify factors that could mediate p53-induced cell death, we used a comparative RNA differential display procedure. We have identified Pw1/Peg3 as a gene product induced during p53/c-myc-mediated apoptosis. Pw1/Peg3 is not induced during p53-mediated G(1) growth arrest nor by c-myc alone. Although it is not clear whether the induction of Pw1/Peg3 depends on p53 activity, we show that Pw1/Peg3 interacts with a p53-inducible gene product Siah1a. We demonstrate that coexpression of Pw1/Peg3 with Siah1a induces apoptosis independently of p53 whereas expression of Pw1/Peg3 or Siah1a separately has no effect on cell death. These data suggest that Siah1a and Pw1/Peg3 cooperate in the p53-mediated cell death pathway. Furthermore, we show that inhibiting Pw1/Peg3 activity blocks p53-induced apoptosis. The observation that Pw1/Peg3 is necessary for the p53 apoptotic response suggests a pivotal role for this gene in determining cell death versus survival.

Wnt genes and endocrine disruption of the female reproductive tract: a genetic approach.

Reproductive tract development and function is regulated by circulating steroid hormones. In the mammalian female reproductive tract, estrogenic compounds direct many aspects of cytodifferentiation including uterine gland formation, smooth muscle morphology, and epithelial differentiation. While it is clear that these hormones act through their cognate nuclear receptors, it is less clear what signaling events follow hormonal stimulation that govern cytodifferentiation. Recent advances in molecular embryology and cancer cell biology have identified the Wnt family of secreted signaling molecules. Discussed here are recent advances that point to a definitive role during uterine development and adult function for one member of the Wnt gene family, Wnt-7a. In addition, recent data is reviewed that implicates Wnt-7a deregulation in response to pre-natal exposure to the synthetic estrogenic compound, DES. These advances point to an important role for the Wnt gene family in various reproductive tract pathologies including cancer.

CDO, a robo-related cell surface protein that mediates myogenic differentiation.

CDO, a member of the Ig/fibronectin type III repeat subfamily of transmembrane proteins that includes the axon guidance receptor Robo, was identified by virtue of its down-regulation by the ras oncogene. We report here that one prominent site of cdo mRNA expression during murine embryogenesis is the early myogenic compartment (newly formed somites, dermomyotome and myotome). CDO is expressed in proliferating and differentiating C2C12 myoblasts and in myoblast lines derived by treating 10T1/2 fibroblasts with 5-azacytidine, but not in parental 10T1/2 cells. Overexpression of CDO in C2C12 cells accelerates differentiation, while expression of secreted soluble extracellular regions of CDO inhibits this process. Oncogenic Ras is known to block differentiation of C2C12 cells via downregulation of MyoD. Reexpression of CDO in C2C12/Ras cells induces MyoD; conversely, MyoD induces CDO. Reexpression of either CDO or MyoD rescues differentiation of C2C12/Ras cells without altering anchorage-independent growth or morphological transformation. CDO and MyoD are therefore involved in a positive feedback loop that is central to the inverse relationship between cell differentiation and transformation. It is proposed that CDO mediates, at least in part, the effects of cell-cell interactions between muscle precursors that are critical in myogenesis.

Differential expression patterns of Wnt genes in the murine female reproductive tract during development and the estrous cycle.

The murine female reproductive tract differentiates during postnatal development. This process of cytodifferentiation and morphogenesis is dependent upon specific mesenchymal-epithelial interactions as well as circulating steroid hormones (Cunha, G.R., 1976. Int. Rev. Cytol. 47, 137-194; Pavlova, A. et al., 1994. Development 120, 335-346). Members of the Wnt family of signaling molecules have been recently identified in this system (Pavlova, A. et al., 1994. Development 120, 335-346; Bui, T.D. et al., 1997. Br. J. Cancer 75, 1131-1136; Miller, C., Sassoon, D.A., 1998. Development, in press). We describe the expression patterns of Wnt genes in the developing and adult female reproductive tract. Additionally, we note that changes in the levels of expression occur during the estrous cycle. Wnt gene expression patterns are regulated by the presence of epithelium in tissue graft experiments, suggesting that Wnt genes may indeed play roles in the mesenchymal-epithelial interactions critical for female reproductive tract development and function.

Antepartum cervical ripening: applying prostaglandin E2 gel in conjunction with scheduled nonstress tests in postdate pregnancies.

OBJECTIVE: Our purpose was to evaluate whether inserting prostaglandin E2 gel at the time of scheduled nonstress tests in patients with postdate pregnancies can decrease rates of intervention. STUDY DESIGN: A multicenter pilot study enrolled women with postdate pregnancies with Bishop score < or = 6 who were undergoing antepartum fetal heart rate testing. Patients were randomized in a double-blind fashion to receive either a prostaglandin E2 intracervical gel (Prepidil) or a placebo gel after each of their scheduled nonstress tests. RESULTS: There were no significant differences in the number of antepartum tests, labor inductions, or cesarean sections, the maximum oxytocin dosage, or the interval from admission to delivery in the prostaglandin E2 gel and placebo gel groups (n = 90). In the subset of patients with a Bishop score between 3 and 6 (63 patients), there were fewer inductions in the prostaglandin E2 group (30% vs 55%, P < .05). CONCLUSION: Application of prostaglandin E2 gel at the time of scheduled antepartum testing in patients with postdate pregnancies with unfavorable cervices decreased the induction rate only among patients with intermediate Bishop scores.

Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract.

The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350-353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.