Does Open Reduction and Internal Fixation versus Primary Arthrodesis Improve Patient Outcomes for Lisfranc Trauma? A Systematic Review and Meta-analysis.

BACKGROUND: Although Lisfranc injuries are uncommon, representing approximately 0.2% of all fractures, they are complex and can result in persistent pain, degenerative arthritis, and loss of function. Both open reduction and internal fixation (ORIF) and primary fusion have been proposed as treatment options for these injuries, but debate remains as to which approach is better. QUESTIONS/PURPOSES: We asked whether ORIF or primary fusion led to (1) fewer reoperations for hardware removal; (2) less frequent revision surgery; (3) higher patient outcome scores; and (4) more frequent anatomic reduction. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Three trials met the criteria for inclusion within the meta-analysis. Qualifying articles for the meta-analysis had data extracted independently by two authors (NS, AF). The quality of each study was assessed using the Center for Evidence Based Medicine's evaluation strategy; data were extracted from articles rated as good and fair: two and one article, respectively. RESULTS: The risk ratio for hardware removal was 0.23 (95% confidence interval [CI], 0.11-0.45; p < 0.001) indicating more hardware removal for ORIF than fusion. For other revision surgery, the risk ratio for ORIF was 0.36 (95% CI, 0.08-1.59; p = 0.18) favoring neither. Similarly, neither was favored using patient-reported outcomes; the standard mean difference was calculated to be 0.50 (95% CI, -2.13 to 3.12; p = 0.71). When considering the risk of nonanatomic alignment, neither was favored (risk ratio, 1.48; 95% CI, 0.34-6.38; p = 0.60). CONCLUSIONS: The surgeon should consider the increased risk of hardware removal along with its associated morbidity and discuss this with the patient preoperatively when considering ORIF of Lisfranc injuries. Because no new trials have been performed since 2012, further randomized controlled trials will be needed improve our understanding of these interventions. LEVEL OF EVIDENCE: Level I, therapeutic study.

Plain film measurement error in acute displaced midshaft clavicle fractures.

BACKGROUND: Clavicle fractures are common and optimal treatment remains controversial. Recent literature suggests operative fixation of acute displaced mid-shaft clavicle fractures (DMCFs) shortened more than 2 cm improves outcomes. We aimed to identify correlation between plain film and computed tomography (CT) measurement of displacement and the inter- and intraobserver reliability of repeated radiographic measurements. METHODS: We obtained radiographs and CT scans of patients with acute DMCFs. Three orthopedic staff and 3 residents measured radiographic displacement at time zero and 2 weeks later. The CT measurements identified absolute shortening in 3 dimensions (by subtracting the length of the fractured from the intact clavicle). We then compared shortening measured on radiographs and shortening measured in 3 dimensions on CT. Interobserver and intraobserver reliability were calculated. RESULTS: We reviewed the fractures of 22 patients. Bland-Altman repeatability coefficient calculations indicated that radiograph and CT measurements of shortening could not be correlated owing to an unacceptable amount of measurement error (6 cm). Interobserver reliability for plain radiograph measurements was excellent (Cronbach α = 0.90). Likewise, intraobserver reliabilities for plain radiograph measurements as calculated with paired t tests indicated excellent correlation (p > 0.05 in all but 1 observer [p = 0.04]). CONCLUSION: To establish shortening as an indication for DMCF fixation, reliable measurement tools are required. The low correlation between plain film and CT measurements we observed suggests further research is necessary to establish what imaging modality reliably predicts shortening. Our results indicate weak correlation between radiograph and CT measurement of acute DMCF shortening.

CONTEXTE: Les fractures de la clavicule sont fréquentes, et le choix du traitement optimal ne fait pas l'unanimité. Selon la littérature récente, la fixation chirurgicale des fractures du tiers médial déplacées (FTMD) aiguës raccourcies de plus de 2 cm donnerait de meilleurs résultats. Nous avons voulu établir une corrélation entre la mesure du déplacement obtenue par radiographie simple et par tomodensitométrie (TDM) et la fiabilité inter- et intra-observateur des mesures radiographiques répétées. MÉTHODES: Nous avons obtenu les radiographies et les TDM de patients ayant subi une FTMD aiguë. Trois orthopédistes et 3 résidents ont mesuré le déplacement radiographique au temps zéro et 2 semaines plus tard. Les mesures par TDM ont permis d'identifier un raccourcissement absolu en 3 dimensions (en soustrayant de la longueur de la clavicule intacte celle de la clavicule brisée). Nous avons ensuite comparé le raccourcissement mesuré par radiographie au raccourcissement en 3 dimensions mesuré par TDM. La fiabilité inter- et intra-observateur a ensuite été calculée. RÉSULTATS: Nous avons ainsi analysé les fractures de 22 patients. Les calculs du coefficient de répétabilité de Bland et Altman ont indiqué qu'il était impossible d'établir des corrélations entre les mesures obtenues par radiographie et par TDM compte tenu de l'ampleur inacceptable de l'erreur de mesure (6 cm). La fiabilité inter-observateur a été excellente pour les mesures radiographiques (coefficient α de Cronbach = 0,90). De même, la fiabilité intra-observateur pour les mesures radiographiques calculée par test t pour échantillons appariés a indiqué une excellente corrélation (p > 0,05 chez tous les observateurs, sauf 1 [p = 0,04]). CONCLUSION: Pour que le raccourcissement devienne une indication de la FTMD, il faut disposer d'outils de mesure fiables. La faible corrélation que nous avons observée entre les mesures obtenues par radiographie et par TDM montre qu'il faut approfondir la recherche afin de déterminer quelle modalité permet de prédire de manière fiable le raccourcissement. Nos résultats démontrent une faible corrélation entre les mesures du raccourcissement obtenues par radiographie et par TDM dans la FTMD aiguë.

Radiographic evaluation of the ankle syndesmosis.

BACKGROUND: Radiographic measurements to document ankle anatomy have been suggested in recent literature to be inadequate. Focus has been put on stress views and computed tomography; however, there are also issues with these modalities. An orthogonal view that could be used both statically and dynamically could help determine syndesmotic stability. The purpose of this study was to determine a parameter on a normal lateral ankle radiograph that will increase the reliability of standard radiography in diagnosing syndesmotic integrity. METHODS: Three orthopedic surgeons reviewed 80 lateral ankle radiographs. Thirty of those radiographs were reviewed on a second occasion. Rotation of the radiographs was determined by evaluating the overlap of the talar dome. Four radiographic parameters were measured 1 cm above the tibial plafond: fibular width, tibial width, and anterior and posterior tibiofibular intervals. RESULTS: Seventy-two radiographs were determined by consensus to be adequate. Means and ratios were documented to determine the relationship of the fibula to the tibia. Interrater reliability ranged from moderate to near-perfect, and the intrarater reliability was documented for each ratio. The anterior tibiofibular ratio was shown to be strong to near-perfect. It demonstrates that 40% of the tibia should be seen anterior to the fibula at 1cm above the tibial plafond. CONCLUSION: The anterior tibiofibular ratio provides an orthogonal measure for the syndesmosis that, in conjunction with those parameters previously documented, could clinically and economically improve the diagnosis of syndesmotic disruptions.

CONTEXTE: Selon la littérature récente, les mesures radiographiques utilisées pour documenter l'anatomie de la cheville seraient inadéquates. L'accent a été placé sur les clichés de cheville en position de stress et sur la tomodensitométrie, mais ces modalités présentent également des inconvénients. Une vue orthogonale utilisée en position statique et en position dynamique pourrait aider à évaluer la stabilité syndesmotique. Le but de cette étude était de déterminer quel paramètre de la radiographie latérale normale de la cheville accroîtrait la fiabilité de la radiographie standard pour le diagnostic de l'intégrité syndesmotique. MÉTHODES: Trois chirurgiens orthopédistes ont passé en revue 80 radiographies latérales de la cheville. Trente de ces radiographies ont été interprétées une deuxième fois. La rotation des radiographies a été déterminée par l'évaluation du chevauchement du dôme talien. Quatre paramètres radiographiques ont été mesurés à 1 cm audessus du plafond tibial : la largeur du péroné, la largeur du tibia et les intervalles tibiofibulaires antérieur et postérieur. RÉSULTATS: Soixante-douze radiographies ont consensuellement été jugées adéquates. Les moyennes et les ratios ont été notés pour établir le rapport péroné-tibia. La fiabilité inter-examinateur a varié de modérée à quasi-parfaite et la fiabilité intra-examinateur a été documentée pour chaque ratio. Le ratio tibiofibulaire antérieur s'est révélé être un paramètre solide à quasi-parfait. Il démontre que 40 % du tibia devrait être visible à l'avant du péroné à 1 cm au-dessus du plafond tibial. CONCLUSION: Le ratio tibiofibulaire antérieur constitue une mesure orthogonale pour la syndesmose qui, en conjonction avec les paramètres précédemment documentés, permettrait d'améliorer le diagnostic des troubles syndesmotiques aux plans clinique et économique.

Functional outcome of supracondylar elbow fractures in children: a 3- to 5-year follow-up.

BACKGROUND: Long-term functional outcomes of supracondylar elbow fractures (SCEF) have not been well documented in the literature. We retrospectively evaluated functional outcomes of pediatric SCEF using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. METHODS: We retrospectively reviewed the outcomes of patients who presented to our tertiary care pediatric emergency department with SCEF between January 2005 and December 2009. We reviewed their charts to assess several clinical parameters, including age, sex, Gartland classification of SCEF, weight, comorbidities, treatment intervention, physiotherapy and the extremity involved. The DASH questionnaire was administered in 2012. We performed a multiple linear regression analysis to determine the significance of these clinical parameters as they related to the DASH score for functional outcome. RESULTS: We included 94 patients with SCEF in our review. Pediatric SCEF had good functional outcomes based on the DASH questionnaire (mean score 0.77 ± 2.10). We obtained the following DASH scores: 0.45 ± 2.20 for type I, 1.09 ± 1.70 for type II and 1.43 ± 2.40 for type III fractures. There was no statistical difference in functional outcome, regardless of sex (p = 0.07), age at injury (p = 0.96), fracture type (p = 0.14), weight (p = 0.59), right/left extremity (p = 0.26) or surgery (p = 0.52). CONCLUSION: Our results demonstrate that good functional outcomes can be expected with pediatric SCEF based on the DASH questionnaire, regardless of age at injury, sex, weight, right/left extremity or surgical/nonsurgical intervention, provided satisfactory reduction is achieved and maintained.

CONTEXTE: Les répercussions fonctionnelles à long terme des fractures du coude supracondyliennes (FCSC) n'ont pas été bien documentées dans la littérature. Nous avons évalué de manière rétrospective les résultats fonctionnels des FCSC pédiatriques à l'aide du questionnaire DASH (Disabilities of the Arm, Shoulder and Hand). MÉTHODES: Nous avons passé en revue rétrospectivement les résultats chez les patients amenés pour une FCSC au service d'urgence pédiatrique de notre établissement de soins tertiaires entre janvier 2005 et décembre 2009. Nous avons examiné leurs dossiers pour évaluer plusieurs paramètres cliniques, dont l'âge, le sexe, la classification de Gartland pour les FCSC, le poids, les comorbidités, l'intervention thérapeutique, la physiothérapie et la latéralité du membre affecté. Le questionnaire DASH a été administré en 2012. Nous avons procédé à une analyse de régression linéaire multiple pour déterminer la signification de ces paramètres cliniques en regard du score DASH d'évaluation fonctionnelle. RÉSULTATS: Nous avons inclus 94 patients ayant subi une FCSC dans notre analyse. La FCSC pédiatrique évolue bien au plan fonctionnel selon le questionnaire DASH (score moyen 0,77 ± 2,10). Nous avons obtenu les scores DASH suivants : 0,45 ± 2,20 pour les fractures de type I, 1,09 ± 1,70 pour les fractures de type II et 1,43 ± 2,40 pour les fractures de type III. On n'a noté aucune différence statistique quant aux résultats fonctionnels, indépendamment du sexe (p = 0,07), de l'âge au moment de la fracture (p = 0,96), du type de fracture (p = 0,14), du poids (p = 0,59), de la latéralité (p = 0,26) ou de la chirurgie (p = 0,52). CONCLUSION: Nos observations démontrent qu'on peut s'attendre à de bons résultats fonctionnels dans les cas de FCSC en se fondant sur le questionnaire DASH, indépendamment de l'âge au moment de la fracture, du sexe, du poids, de la latéralité ou de l'intervention chirurgicale ou non chirurgicale, à la condition d'obtenir et de maintenir une réduction satisfaisante.

The Nkx5/HMX homeodomain protein MLS-2 is required for proper tube cell shape in the C. elegans excretory system.

Cells perform wide varieties of functions that are facilitated, in part, by adopting unique shapes. Many of the genes and pathways that promote cell fate specification have been elucidated. However, relatively few transcription factors have been identified that promote shape acquisition after fate specification. Here we show that the Nkx5/HMX homeodomain protein MLS-2 is required for cellular elongation and shape maintenance of two tubular epithelial cells in the C. elegans excretory system, the duct and pore cells. The Nkx5/HMX family is highly conserved from sea urchins to humans, with known roles in neuronal and glial development. MLS-2 is expressed in the duct and pore, and defects in mls-2 mutants first arise when the duct and pore normally adopt unique shapes. MLS-2 cooperates with the EGF-Ras-ERK pathway to turn on the LIN-48/Ovo transcription factor in the duct cell during morphogenesis. These results reveal a novel interaction between the Nkx5/HMX family and the EGF-Ras pathway and implicate a transcription factor, MLS-2, as a regulator of cell shape.

Timing of femoral prosthesis insertion during cemented arthroplasty: cement curing and static mechanical strength in an in vivo model.

BACKGROUND: Modern cementing techniques aim to fix the implanted femoral prosthesis in the medullary cavity to minimize long-term complications such as aseptic loosening. The cure stage of bone cement into which the femoral component is being inserted is an important variable that is decided at the time of surgery. Late-cure cement is more viscous than early-cure cement and requires greater force on the part of the surgeon to insert the femoral prosthesis. We compared 2 cementing techniques, femoral component insertion into early-cure cement and insertion into late-cure cement, using an in vivo model to identify if cement cure stage affects the strength of the bone-cement interface. METHODS: We performed bilateral hemiarthroplasties using only the femoral component in vivo on paired porcine femora. The femora were harvested and cross-sectioned in preparation for strength testing. We measured bond strength by peak load required to push the femoral prosthesis and surrounding cement mantle free of the cancellous bone. RESULTS: All radiographs showed good cement interdigitation with no evidence of radiolucent lines at the bone-cement interface. We could not differentiate the early-cure and late-cure groups on postoperative radiographs. The mean failure load for the late-cure arthroplasties was 908 N (standard deviation [SD] 420 N), whereas the mean failure load for the conjugate early-cure arthroplasties was 503 N (SD 342 N). CONCLUSION: Femoral component insertion into late-cure cement required significantly higher loads for push-out than femoral component insertion into early-cure cement.

Resection arthroplasty, external fixation, and negative pressure dressing for first metatarsophalangeal joint ulcers.

BACKGROUND: A frequent complication for the diabetic patient is neuropathic ulceration on the plantar surface of the first metatarsophalangeal (MTP) joint which can be difficult to manage. Debridement and resection arthroplasty with temporary external fixation and VAC dressing (Kinetic Concepts Inc, San Antonio, TX) is an alternative operative treatment to amputation. This study examined the outcomes of one center's experience with patients who have undergone this procedure. MATERIALS AND METHODS: This retrospective cohort study examined patients who underwent the procedure between March 2002 and March 2010. Information was obtained on relevant outcomes including: the initial procedure, secondary procedures on either foot, total time in external fixation, time until amputation, cause of ulceration and co-morbid conditions. During the study period, 16 patients underwent resection arthroplasty with external fixation for first MTP ulceration. Fourteen of these patients had underlying diabetes mellitus, one had Charcot-Marie-Tooth disease and one had neuropathy of unknown cause. All were available for followup at the end of the study period. Median followup was 38 (range, 3 to 96) months. RESULTS: At latest followup, six patients required amputation, either transmetatarsal or transtibial, to treat their recurring ulceration. CONCLUSION: Resection arthroplasty with temporary external fixation appears to be a safe, effective and possible alternative to amputation for the treatment of neuropathic ulceration of the first MTP.

Lipocalin signaling controls unicellular tube development in the Caenorhabditis elegans excretory system.

Unicellular tubes or capillaries composed of individual cells with a hollow lumen perform important physiological functions including fluid or gas transport and exchange. These tubes are thought to build intracellular lumina by polarized trafficking of apical membrane components, but the molecular signals that promote luminal growth and luminal connectivity between cells are poorly understood. Here we show that the lipocalin LPR-1 is required for luminal connectivity between two unicellular tubes in the Caenorhabditis elegans excretory (renal) system, the excretory duct cell and pore cell. Lipocalins are a large family of secreted proteins that transport lipophilic cargos and participate in intercellular signaling. lpr-1 is required at a time of rapid luminal growth, it is expressed by the duct, pore and surrounding cells, and it can function cell non-autonomously. These results reveal a novel signaling mechanism that controls unicellular tube formation, and provide a genetic model system for dissecting lipocalin signaling pathways.

Evaluation of the Characteristics of a Workplace Assessment Form to Assess Entrustable Professional Activities (EPAs) in an Undergraduate Surgery Core Clerkship.

OBJECTIVE: Entrustable Professional Activities (EPAs) are explicit, directly observable tasks requiring the demonstration of specific knowledge, skills, and behaviors that learners are expected to perform without direct supervision once they have gained sufficient competence. Undergraduate level implementation of EPAs is relatively new. We examined the characteristics of a workplace assessment form (clinic card) as part of a formative programmatic assessment process of EPAs for a core undergraduate surgery rotation. DESIGN: A clinic card was introduced to assess progression towards EPA achievement in the clerkship curriculum phase. Students completing their core eight (8) week clerkship surgery rotation submitted at least 1 clinic card per week. We compiled assessment scores for the 2015 to 2016 academic year, in which EPAs were introduced, and analyzed relationships between scores and time, EPA, training site, and assessor role. We surveyed preceptors and students, and conducted a focus group with clinical discipline coordinators of all core rotations. SETTING: This study took place at the Faculty of Medicine, Memorial University in St. John's, Newfoundland, Canada. PARTICIPANTS: Third year medical students (n = 79) who completed their core eight (8) week surgery clerkship rotation during the 2015 to 2016 academic year, preceptors, and clinical discipline coordinators participated in this study. RESULTS: EPAs reflecting tasks commonly performed by students were more likely to be assessed. EPAs frequently observed during preceptor-student encounters had higher entrustment ratings. Most EPAs showed increased entrustment scores over time and no significant differences in ratings between teaching sites nor preceptors and residents. Survey and focus group feedback suggest clinic cards fostered direct observation by preceptors and promoted constructive feedback on clinical tasks. A binary rating scale (entrustable/pre-entrustable) was not educationally beneficial. CONCLUSIONS: The findings support the feasibility, utility, catalytic and educational benefits of clinic cards in assessing EPAs in a core surgery rotation in undergraduate medical education.

Airway Management for Trauma Patients.

Trauma airway management is a critical skill for medical providers supporting combat casualties since it is an integral component of damage control resuscitation and surgery. This clinical practice guideline presents methods for optimizing the airway management of patients with traumatic injury in the operational medical treatment facility environment. The guidelines represent the knowledge and experience of 10 co-authors from 3 allied countries representing Emergency Medicine, Surgery and Anesthesia.

The Lipocalin LPR-1 Cooperates with LIN-3/EGF Signaling To Maintain Narrow Tube Integrity in Caenorhabditis elegans.

Lipocalins are secreted cup-shaped glycoproteins that bind sterols, fatty acids, and other lipophilic molecules. Lipocalins have been implicated in a wide array of processes related to lipophilic cargo transport, sequestration, and signaling, and several are used as biomarkers for human disease, but the functions of most lipocalins remain poorly understood. Here we show that the Caenorhabditis elegans lipocalin LPR-1 is required to maintain apical membrane integrity and a continuous lumen in two narrow unicellular tubes, the excretory duct and pore, during a period of rapid lumen elongation. LPR-1 fusion protein is expressed by the duct and pore and accumulates both intracellularly and in apical extracellular compartments, but it can also function cell nonautonomously when provided from outside of the excretory system. lpr-1 mutant defects can be rescued by increased signaling through the epidermal growth factor (EGF)-Ras-extracellular signal regulated kinase (ERK) pathway, which promotes the more elongated duct vs. less elongated pore tube fate. Spatial and temporal rescue experiments indicate that Ras signaling acts within the duct and pore tubes during or prior to cell fate determination to bypass the requirement for LPR-1 lpr-1 mutations did not disrupt LIN-3/EGF-dependent duct-fate specification, prevent functioning of any specific LIN-3/EGF isoform, or alter LET-23/EGFR localization, and reduced signaling did not phenocopy or enhance lpr-1 mutant defects. These data suggest that LPR-1 protects lumen integrity through a LIN-3/EGF-independent mechanism, but that increased signaling upregulates some target(s) that can compensate for lpr-1 absence.

How pilot-hole size affects bone-screw pullout strength in human cadaveric cancellous bone.

OBJECTIVE: Screw failure of cancellous bone screws is not uncommon. To compare the effect of varying pilot-hole size on pullout strength of cancellous bone screws in human cadaveric bone, we designed and performed a biomechanical study to allow quantitative analysis. METHODS: Three pairs of distal femurs and 4 pairs of proximal tibias from embalmed human cadavers were stabilized in a mould, and the bone cortex was overdrilled. Four sites in a linear transverse plane were randomly assigned, anatomically matched with the paired bone and drilled with either pilot-hole size 3.2 mm or 2.5 mm. The cancellous screw (Synthes noncannulated 4.5-mm shaft, 6.5-mm external diameter) was guided into the pilot hole and pulled on by a test frame (Instron 8874 biaxial servo-hydraulic test frame) with increasing force to the point of failure, and the forces at which failure resulted were compared. RESULTS: A comparison of 25 anatomically paired sites with a 2-tailed paired t test and Wilcoxon matched-pairs signed rank test indicated significantly stronger pullout strength (p = 0.047 and p = 0.047) of the 2.5-mm compared with the 3.2-mm pilot hole. Subanalysis of the 4 studied locations indicated that 3 supported the above findings and 1 supported a reverse trend. CONCLUSIONS: Generally, cancellous screws demonstrated a significantly (p < 0.05) stronger hold using a smaller size pilot hole than the recommended standard diameter. All locations except the inner lateral site supported this finding.

Os calcis fractures: analysis of interobserver variability in using Sanders classification.

The os calcis is the most frequently fractured tarsal bone. In 1992 Sanders developed a classification system based on coronal and axial computed tomography (CT) scans of the calcaneus. This classification is the one used most frequently today in treatment decision making and reporting of results. The objective of this study was to assess the degree of interobserver variability in using this classification system. Thirty CTs of calcaneal fractures were chosen randomly from the past 5 years in 2 tertiary care centers. The CTs were reviewed by 3 orthopedic surgeons and one senior orthopedic resident who classified the fractures according to Sanders' classification. The results were first tabulated and analyzed by using a weighted kappa test including the subcategories. The weighted kappa value achieved was.56, with a 95% confidence interval of.45-.67. The subcategories of the classification were then further combined and a second weighted kappa test was performed to assess agreement between general classes. The weighted kappa value achieved was.48, with a 95% confidence interval of 0.37-0.59. We concluded that Sanders' classification system did prove to achieve moderate agreement among users, thus representing a useful classification system.

Determinants of Rab5 interaction with the N terminus of early endosome antigen 1.

The Rab5 effector early endosome antigen 1 (EEA1) is a parallel coiled coil homodimer with an N-terminal C(2)H(2) Zn(2+) finger and a C-terminal FYVE domain. Rab5 binds to independent sites at the N and C terminus of EEA1. To gain further insight into the structural determinants for endosome tethering and fusion, we have characterized the interaction of Rab5C with truncation and site-specific mutants of EEA1 using quantitative binding measurements. The results demonstrate that the C(2)H(2) Zn(2+) finger is both essential and sufficient for the N-terminal interaction with Rab5. Although the heptad repeat C-terminal to the C(2)H(2) Zn(2+) finger provides the driving force for stable homodimerization, it does not influence either the affinity or stoichiometry of Rab5 binding. Hydrophobic residues predicted to cluster on a common face of the C(2)H(2) Zn(2+) finger play a critical role in the interaction with Rab5. Although the homologous C(2)H(2) Zn(2+) finger of the Rab5 effector Rabenosyn binds to Rab5 with comparable affinity, the analogous C(2)H(2) Zn(2+) finger of the yeast homologue Vac1 shows no detectable interaction with Rab5, reflecting non-conservative substitutions of critical residues. Large changes in the intrinsic tryptophan fluorescence of Rab5 accompany binding to the C(2)H(2) Zn(2+) finger of EEA1. These observations can be explained by a mode of interaction in which a partially exposed tryptophan residue located at the interface between the switch I and II regions of Rab5 lies within a hydrophobic interface with a cluster of non-polar residues in the C(2)H(2) Zn(2+) finger of EEA1.