Late consolidation of the scaphoid. Case report and literature review.

Scaphoid fractures are a common wrist injury accounting for 2-7% of all adult fractures. Nonunion is described in 5-12% of cases leading to osteoarthritis. Several classifications have been developed focused on this pathology and its complication. We present a case of a 28 years old male patient with a scaphoid fracture and nonunion who spontaneously consolidates without treatment. We performed a literature review to recognize this pathology, its common evolution and possible treatment options.

Las fracturas de escafoides son una lesión frecuente de la muñeca y representan de 2-7% de todas las fracturas en adultos. La no unión se describe en 5-12% de los casos y conduce a la osteoartritis. Se han desarrollado varias clasificaciones centradas en esta patología y su complicación. Presentamos el caso de un paciente varón de 28 años con fractura y no unión de escafoides que consolida espontáneamente sin tratamiento. Realizamos una revisión bibliográfica para reconocer esta patología, su evolución habitual y las posibles opciones de tratamiento.

The use of an anatomical implant compared to a straight LCP decreases extraction in posterior humeral MIPO. / La utilización de un implante anatómico comparado a una LCP recta disminuye su extracción en la osteosíntesis percutánea posterior del húmero.

PURPOSE: Posterior MIPO approach in the humerus has been described by using a 4.5mm LCP plate. Although straight plates have shown good results, they have not been designed to adapt to the distal humeral metaphysis. The goal of the study was to test the null hypothesis that there is no difference in hardware removal after posterior MIPO with either a straight or a pre-contoured plate. METHODS: Patients older than 18 years, who had suffered mid-distal humeral shaft fracture, were treated by a posterior MIPO technique with a locking plate and had a minimum of 12-month follow-up were retrospectively included. Patients were separated into: group 1 (LCP 4.5mm straight plate); and group 2 (3.5mm anatomically shaped plate). Clinical and radiological evaluation were performed in the postoperative period. Patient-reported outcomes and the need of hardware removal because of pain were assessed. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. Twenty-seven patients in group 1 and 40 in group 2. No patient was lost to follow-up. There were no statistical differences between in patient reported outcomes measures. All the fractures healed. Within group 1, 18% (95%CI: 6-38%) of the patients required implant removal while in group 2 this incidence was 0% (95%CI: 0-9%) (P 0.009). CONCLUSION: These results suggest that the use of a 4.5mm LCP compared to an anatomical 3.5mm LCP in posterior MIPO of the humerus generates greater discomfort and therefore leads to a 18% increase in the risk of implant removal.

[Digital artery pseudoaneurysm. Case report and systematic review of the literature]. / Pseudoaneurisma de arteria digital. Reporte de un caso y revisión sistemática de la bibliografía.

INTRODUCTION: aneurysms are focal and permanent dilations of an artery; in pseudoaneurysms, the normal layers of the blood vessel are replaced by fibrous tissue. Due to their low incidence, as well as the diagnostic and therapeutic challenge they represent; our objective is to present the clinical case of a pseudoaneurysm of a digital artery of the hand and to carry out a systematic review of this pathology. MATERIAL AND METHODS: literature search in Medline, using the terms "digital artery" and "aneurysm." Studies of vascular dilation pathology affecting the hand and fingers were incorporated. Studies with pathology of proximal involvement of the hand were excluded. CASE PRESENTATION: a 79-year-old female patient who, after a sharp force trauma to the fifth finger of the left hand, develops a rapidly growing necrotic tumor. She had ultrasound and angiography that suggested hematoma. Surgical management was decided, during which it was observed that the tumor involved ulnar collateral digital artery of the fifth finger. The lesion and the arterial segment involved were resected. Post-surgical course without complications. The histopathological diagnosis of pseudoaneurysm of the lesion was confirmed. DISCUSSION: traumatic etiology is the most frequent cause of digital aneurysms. Risk factors for pseudoaneurysms include sharp force trauma and alterations of the coagulation pathways, as in the case presented. CONCLUSION: the pseudoaneurysm of a digital artery is a rare pathology with great variability of therapeutic management. Surgical resection of the lesion with vascular flow reconstruction is the recommended treatment.

INTRODUCCIÓN: los aneurismas son dilataciones vasculares localizadas y permanentes de una arteria; en los pseudoaneurismas, las capas normales del vaso sanguíneo son reemplazadas por tejido fibroso. Debido a su baja incidencia, así como el desafío diagnóstico y terapéutico que representan; nuestro objetivo es presentar el caso clínico de un pseudoaneurisma de una arteria digital de la mano y realizar una revisión sistemática sobre dicha patología. MATERIAL Y MÉTODOS: búsqueda bibliográfica en Medline, utilizando los términos "arteria digital" y "aneurisma". Se incorporaron estudios de patología de dilatación vascular que afecte la mano y los dedos. Se excluyeron trabajos con patología de afección proximal de la mano. PRESENTACIÓN DE CASO: paciente femenino de 79 años de edad, que posterior a herida cortante de quinto dedo de mano izquierda, desarrolla tumoración necrótica de rápido crecimiento. Contaba con ecografía y angiografía que sugerían hematoma. Se decidió manejo quirúrgico, durante el cual se observó que la tumoración involucraba arteria digital colateral cubital del quinto dedo. Se resecó lesión y segmento arterial involucrado. Cursó postquirúrgico sin complicaciones. Se confirmó el diagnóstico histopatológico de pseudoaneurisma de la lesión. DISCUSIÓN: la etiología traumática es la causa más frecuente de los aneurismas digitales. Los factores de riesgo para los pseudoaneurismas incluyen lesiones penetrantes y alteraciones de la cascada de coagulación, como en el caso presentado. CONCLUSIÓN: el pseudoaneurisma de una arteria digital es una patología rara y con gran variabilidad de manejo terapéutico. La resección quirúrgica de la lesión con la reconstrucción del flujo vascular, es el tratamiento recomendado.

[Translated article] The use of an anatomical implant compared to a straight LCP decreases extraction in posterior humeral MIPO.

PURPOSE: Posterior MIPO approach in the humerus has been described by using a 4.5mm LCP plate. Although straight plates have shown good results, they have not been designed to adapt to the distal humeral metaphysis. The goal of the study was to test the null hypothesis that there is no difference in hardware removal after posterior MIPO with either a straight or a pre-contoured plate. METHODS: Patients older than 18 years, who had suffered mid-distal humeral shaft fracture, were treated by a posterior MIPO technique with a locking plate and had a minimum of 12-month follow-up were retrospectively included. Patients were separated into: group 1 (LCP 4.5mm straight plate); and group 2 (3.5mm anatomically shaped plate). Clinical and radiological evaluations were performed in the postoperative period. Patient-reported outcomes and the need of hardware removal because of pain were assessed. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. Twenty-seven patients in group 1 and 40 in group 2. No patient was lost to follow-up. There were no statistical differences between in patient reported outcomes measures. All the fractures healed. Within group 1, 18% (95%CI: 6-38%) of the patients required implant removal while in group 2 this incidence was 0% (95%CI: 0-9%) (P 0.009). CONCLUSION: These results suggest that the use of a 4.5mm LCP compared to an anatomical 3.5mm LCP in posterior MIPO of the humerus generates greater discomfort and therefore leads to a 18% increase in the risk of implant removal.

Galeazzi fracture-dislocations: Long-term prognosis of the distal radioulnar joint.

The aim of the present study was to evaluate long-term functional and radiographic outcome in the distal radioulnar joint (DRUJ) for Galeazzi fracture-dislocation after anatomic reduction and rigid fixation of the radius. Fourteen patients, with an average age of 38 years, presenting with Galeazzi fracture-dislocation treated by open reduction and internal fixation (ORIF) of the radius and closed reduction of the DRUJ were retrospectively evaluated, with a minimum follow-up of 6 years. At final evaluation (mean: 8 years), the DRUJ was objectively and subjectively evaluated for range of motion (RoM), grip strength, ballottement test, pain on axial loading, function on visual analog scale (VAS) and DASH score. Radiographs and dynamic CT scans were performed to screen for DRUJ instability and/or osteoarthritis. Six of the patients had a positive comparative ballottement test, but none reported pain during the maneuver. No significant differences in RoM were found between the injured and uninjured wrist. Mean grip strength in the injured wrist was 77% of the contralateral value. Mean pain on VAS was 0.6. Mean global function on VAS was 9. Mean DASH score was 3. Dynamic CT showed no clear subluxation in any of the patients, and none showed severe articular changes. Our findings suggest that long-term clinical and radiological prognosis for the DRUJ in Galeazzi lesions is favorable when adequate closed reduction of the ulna is achieved after anatomical ORIF of the radius. LEVEL OF EVIDENCE: IV. Therapeutic case series.

Asynchronic steroid activity of Leydig and Sertoli cells related to spermatogenic and testosterone cycle in Phymaturus antofagastensis.

The severe environments where Phymaturus lizards inhabit in the Andes highlands and in Patagonia, Argentina, impose restrictions on their reproduction, offering a framework for the development of life history strategies to overcome hard weather conditions. Among them, prolonged female cycles, asynchrony between sexes in receptivity, and sperm storage in males, were described. Asynchrony in the reproductive timing between males and females is a consequence of different energy requirements for gametogenesis, and often imply the existence of cellular mechanisms to enhance fertilization, such as the asynchronic steroid synthesis between testicular compartments, allowing gametogenesis independently of mating. In the present study ultrastructural and hormone assays were combined for the first time in liolaemids. Specifically, morphological features of steroid activity in Leydig and Sertoli cells, and serum testosterone concentrations have been studied in the lizard Phymaturus antofagastensis. Leydig and Sertoli cells presented morphological features characteristic of steroid synthesis during the spermatogenesis, and evident asynchronic steroid production between testicular compartments. Active Sertoli cells and inactive Leydig cells were observed in spring and autumn, while in mid-summer their steroid activity was synchronic in coincidence with maximal abundance of spermatozoa in epididymis. Serum testosterone concentration was at its maximum in mid-summer (126-230 ng ml(-1)), and minimum in late spring (4-24 ng ml(-1)) and early autumn (2-17 ng ml(-1)). In view of these results, P. antofagastensis males show an original approach to adjust their reproductive activity to physiological and environmental constraints at high latitudes and altitudes in the Andean highlands of Argentina.

[Dorsally displaced intra-articular distal radius fractures treated by locked palmar plate. Technique and results]. / Les fractures intraarticulaires du radius distal à déplacement postérieur traitées par plaque palmaire à stabilité angulaire. Technique et résultats.

OBJECTIVES: The purpose of this study was to evaluate the results and complications of locked palmar plating in patients with articular fracture of the distal radius. METHODS: Twenty-two patients were reviewed retrospectively. The average age was 68 years. All fractures were classified as Type C according to the AO classification. Clinical and functional examination including range of motion, grip strength, pain and return to previous activities were assessed. Loss of radial height, radial inclination, palmar tilt and ulnar variance were evaluated with preoperative and postoperative radiographs. RESULTS: At an average follow-up of 10 months, the range of motion was 124 degrees in flexion and extension and 178 degrees in pronation and supination. Grip strength was 80% of the opposite side. Fifteen patients were free of pain. Three patients suffered tenosynovitis of the extensor tendons. Radiographic measurements averaged 11 mm radial height, 21 degrees radial inclination, 4 degrees palmar tilt and 1 mm ulnar variance. CONCLUSIONS: The result of this study showed that locked palmar plating of articular distal radius fractures is effective even in cases of metaphyseal comminution with a low rate of complications.

Atraumatic Bilateral Instability of Ulnar Nerve and Extensor Carpi Ulnaris in a Patient with Marfan's Syndrome.

INTRODUCTION: Marfan's syndrome is a hereditary, autosomal dominant multisystemic disorder involving connective tissue. Bilateral extensor carpi ulnaris and ulnar nerve (UN) instability is rare, usually caused by the alteration of structures mainly formed by connective tissue. The association between Marfan's syndrome and bilateral instability of UN and extensor carpi ulnaris has never been reported. CASE REPORT: We present the case of a 38-year-old female with no history of trauma, diagnosed with Marfan's syndrome, who developed bilateralinstability of the UN and extensor carpi ulnaris. Bilateral UN transposition and extensor carpi ulnaris tenoplasty were performed. CONCLUSION: Atraumatic bilateral instability of UN and extensor carpi ulnaris is a new rare clinical profile caused by Marfan's syndrome whether standard treatment is successful in a long-term basis in these particular cases of collagen intrinsic pathology remains unclear.

Calcified glomus tumor of the shoulder. A case report.

The authors report a case of calcified glomus tumor of the shoulder in a 54-year-old woman. The nonspecific clinical findings and the noncharacteristic imaging results made diagnosis of this tumor impossible before surgery. The diagnosis was confirmed by a biopsy. The outcome after surgical resection was excellent.

Extensor Tendons Rupture after Volar Plating of Distal Radius Fracture Related to a Dorsal Radial Metaphyseal Bone Spur.

Extensor tendon ruptures due to volar plating in distal radius fractures have mostly been described in relation with technique failures such as screw prominence and drill penetration. We report the case of a 71-year-old female with a C2 distal radius fracture with severe dorsal metaphyseal comminution. The patient underwent surgical treatment with reduction of the large fragments and fixation with a volar locking plate; the small dorsal metaphyseal nonarticular fragments were not reduced. Six months later, the patient developed extensor digitorum communis (EDC) rupture and extensor indicis proprius (EIP) laceration in coincidence with the dorsal comminution turned into a bony spur. The possible association between the extensor tendon injury and the dorsal residual metaphyseal bony spur in the distal radius fractures is unusual but should be taken into account in fracture patterns presenting dorsal comminution.

Late consolidation of the scaphoid. Case report and literature review / Consolidación tardía del escafoides. Reporte de un caso y revisión de la literatura

Abstract: Scaphoid fractures are a common wrist injury accounting for 2-7% of all adult fractures. Nonunion is described in 5-12% of cases leading to osteoarthritis. Several classifications have been developed focused on this pathology and its complication. We present a case of a 28 years old male patient with a scaphoid fracture and nonunion who spontaneously consolidates without treatment. We performed a literature review to recognize this pathology, its common evolution and possible treatment options.

Resumen: Las fracturas de escafoides son una lesión frecuente de la muñeca y representan de 2-7% de todas las fracturas en adultos. La no unión se describe en 5-12% de los casos y conduce a la osteoartritis. Se han desarrollado varias clasificaciones centradas en esta patología y su complicación. Presentamos el caso de un paciente varón de 28 años con fractura y no unión de escafoides que consolida espontáneamente sin tratamiento. Realizamos una revisión bibliográfica para reconocer esta patología, su evolución habitual y las posibles opciones de tratamiento.

La utilización de un implante anatómico comparado a una LCP recta disminuye su extracción en la osteosíntesis percutánea posterior del húmero / The use of an anatomical implant compared to a straight LCP decreases extraction in posterior humeral MIPO

Antecedentes y objetivo: El abordaje posterior percutáneo del húmero se ha descrito utilizando una placa LCP de 4,5mm. A pesar de que las placas rectas han demostrado buenos resultados, estas no han sido diseñadas para adaptarse a la metáfisis del húmero distal. El objetivo de este estudio es probar la hipótesis nula de que no existen diferencias en la extracción de la osteosíntesis después de una MIPO posterior utilizando una placa recta comparado a una placa anatómica. Materiales y métodos: Se incluyeron retrospectivamente en 2 instituciones pacientes mayores de 18 años que habían sufrido una fractura diafisaria de húmero distal tratados mediante técnica percutánea posterior con una placa bloqueada y con un seguimiento mínimo de 12 meses. Los pacientes se dividieron en: grupo 1 (placa recta LCP de 4,5mm) y grupo 2 (placa de forma anatómica de 3,5mm). Durante el postoperatorio se reportó la evaluación clínica y radiológica, así como la necesidad de retirar el implante debido al dolor. Resultados: Sesenta y siete pacientes cumplieron los criterios de inclusión. Veintisiete pacientes en el grupo 1 y 40 en el grupo 2. No se perdió ningún paciente durante el seguimiento. Dentro del grupo 1, el 18% (IC 95%: 6-38%) de los pacientes requirieron extracción del implante, mientras que en el grupo 2 esta incidencia fue del 0% (IC 95%: 0-9%) (p 0,009). No hubo diferencias estadísticas entre las medidas de resultado informadas por los pacientes; todas las fracturas consolidaron. Conclusión: Los resultados de nuestro estudio demostrarían que el uso de placas LCP rectas de 4,5mm comparado a las placas anatómicas LCP de 3,5mm en MIPO posterior de húmero genera mayores molestias y, por lo tanto, conllevan un incremento en el riesgo de extracción del implante de un 18%.(AU)

Purpose: Posterior MIPO approach in the humerus has been described by using a 4.5mm LCP plate. Although straight plates have shown good results, they have not been designed to adapt to the distal humeral metaphysis. The goal of the study was to test the null hypothesis that there is no difference in hardware removal after posterior MIPO with either a straight or a pre-contoured plate. Methods: Patients older than 18 years, who had suffered mid-distal humeral shaft fracture, were treated by a posterior MIPO technique with a locking plate and had a minimum of 12-month follow-up were retrospectively included. Patients were separated into: group 1 (LCP 4.5mm straight plate); and group 2 (3.5mm anatomically shaped plate). Clinical and radiological evaluation were performed in the postoperative period. Patient-reported outcomes and the need of hardware removal because of pain were assessed. Results: Sixty-seven patients fulfilled the inclusion criteria. Twenty-seven patients in group 1 and 40 in group 2. No patient was lost to follow-up. There were no statistical differences between in patient reported outcomes measures. All the fractures healed. Within group 1, 18% (95%CI: 6-38%) of the patients required implant removal while in group 2 this incidence was 0% (95%CI: 0-9%) (P 0.009). Conclusion: These results suggest that the use of a 4.5mm LCP compared to an anatomical 3.5mm LCP in posterior MIPO of the humerus generates greater discomfort and therefore leads to a 18% increase in the risk of implant removal.(AU)

[Translated article] The use of an anatomical implant compared to a straight LCP decreases extraction in posterior humeral MIPO / La utilización de un implante anatómico comparado a una LCP recta disminuye su extracción en la osteosíntesis percutánea posterior del húmero

Purpose: Posterior MIPO approach in the humerus has been described by using a 4.5mm LCP plate. Although straight plates have shown good results, they have not been designed to adapt to the distal humeral metaphysis. The goal of the study was to test the null hypothesis that there is no difference in hardware removal after posterior MIPO with either a straight or a pre-contoured plate. Methods: Patients older than 18 years, who had suffered mid-distal humeral shaft fracture, were treated by a posterior MIPO technique with a locking plate and had a minimum of 12-month follow-up were retrospectively included. Patients were separated into: group 1 (LCP 4.5mm straight plate); and group 2 (3.5mm anatomically shaped plate). Clinical and radiological evaluations were performed in the postoperative period. Patient-reported outcomes and the need of hardware removal because of pain were assessed. Results: Sixty-seven patients fulfilled the inclusion criteria. Twenty-seven patients in group 1 and 40 in group 2. No patient was lost to follow-up. There were no statistical differences between in patient reported outcomes measures. All the fractures healed. Within group 1, 18% (95%CI: 6–38%) of the patients required implant removal while in group 2 this incidence was 0% (95%CI: 0–9%) (P 0.009). Conclusion: These results suggest that the use of a 4.5mm LCP compared to an anatomical 3.5mm LCP in posterior MIPO of the humerus generates greater discomfort and therefore leads to a 18% increase in the risk of implant removal.(AU)

Antecedentes y objetivo: El abordaje posterior percutáneo del húmero se ha descrito utilizando una placa LCP de 4,5mm. A pesar de que las placas rectas han demostrado buenos resultados, estas no han sido diseñadas para adaptarse a la metáfisis del húmero distal. El objetivo de este estudio es probar la hipótesis nula de que no existen diferencias en la extracción de la osteosíntesis después de una MIPO posterior utilizando una placa recta comparado a una placa anatómica. Materiales y métodos: Se incluyó retrospectivamente en 2 instituciones a pacientes mayores de 18 años que habían sufrido una fractura diafisaria de húmero distal tratados mediante técnica percutánea posterior con una placa bloqueada y con un seguimiento mínimo de 12 meses. Los pacientes se dividieron en: grupo 1 (placa recta LCP de 4,5mm) y grupo 2 (placa de forma anatómica de 3,5mm). Durante el postoperatorio se reportó la evaluación clínica y radiológica, así como la necesidad de retirar el implante debido al dolor. Resultados: Sesenta y siete pacientes cumplieron los criterios de inclusión. Veintisiete pacientes en el grupo 1 y 40 en el grupo 2. No se perdió ningún paciente durante el seguimiento. Dentro del grupo 1, el 18% (IC del 95%: 6-38%) de los pacientes requirieron extracción del implante, mientras que en el grupo 2 esta incidencia fue del 0% (IC del 95%: 0-9%) (p = 0,009). No hubo diferencias estadísticas entre las medidas de resultado informadas por los pacientes; todas las fracturas consolidaron. Conclusión: Los resultados de nuestro estudio demostrarían que el uso de placas LCP rectas de 4,5mm comparado a las placas anatómicas LCP de 3,5mm en MIPO posterior de húmero genera mayores molestias y, por lo tanto, conllevan un incremento en el riesgo de extracción del implante de un 18%.(AU)

Infected nonunion of the humerus treated with an antibiotic cement rod. Case report.

The authors present a case of an infected nonunion of the humerus treated initially with reaming of the medullar canal followed by the introduction of an antibiotic-impregnated intramedullary rod. Reconstruction of the humerus with bone fixation and bone graft was performed in a second stage. The final result was healing of the fracture and a good functional result with no evidence of recurrence of infection at a 25 months follow up.

Total elbow arthroplasty for the treatment of distal humeral fractures. / Artroplastia total de codo para el tratamiento de fracturas del húmero distal.

OBJECTIVE: To report the clinical-functional outcomes of the treatment of humeral distal fractures with a total elbow prosthesis. MATERIAL AND METHODS: This retrospective study was performed in two surgical centres. A total of 23patients were included, with a mean age of 79years, and of which 21 were women. The inclusion criteria were: patients with humeral distal fractures, operated on using a Coonrad-Morrey prosthesis, and with a follow-up of more than one year. According to AO classification, 15fractures were type C3, 7 C2 and 1 A2. All patients were operated on without de-insertion of the extensor mechanism. The mean follow-up was 40 months. RESULTS: Flexor-extension was 123-17°, with a total mobility arc of 106° (80% of the contralateral side). Pain, according to a visual analogue scale was 1. The Mayo Elbow Performance Index (MEPI) was 83 points. Excellent results were obtained in 8 patients, good in 13, medium in 1, and poor in 1. The mean DASH (disability) score was 24 points. CONCLUSION: Treatment of humeral distal fractures with total elbow arthroplasty could be a good treatment option, but indications must be limited to patients with complex fractures, poor bone quality, with osteoporosis and low functional demands. In younger patients, the use is limited to serious cases where there is no other treatment option. LEVEL OF EVIDENCE: Level of Evidence IV.

Posterior minimally invasive plate osteosynthesis (MIPO) of distal third humeral shaft fractures with segmental isolation of the radial nerve.

UNLABELLED: The aim of this study was to evaluate the clinical, radiographic, and functional outcomes of a cohort of patients with distal third humeral shaft fractures treated using a posterior minimally invasive plate osteosynthesis (MIPO) technique. Twenty-one patients were retrospectively evaluated, 13 men and 8 women with an average age of 37 years. The surgery was performed through two posterior incisions away from the fracture site. The radial nerve was identified and protected. The fracture was fixed with a narrow 4.5/5.0mm locking compression plate. After an average follow-up of 22 months, flexion-extension of the elbow was 138°±7°, with a range of motion of 131°. Shoulder motion was 160° in forward flexion, 59° in external rotation, and internal rotation was to the spinous process of 9th thoracic vertebra. Pain severity was 0.5 on the VAS. The DASH score was 9. Average Constant score was 84. MEPI was 97. Fracture union was obtained in all patients. One patient developed transient postoperative radial nerve palsy. These results demonstrate that the posterior MIPO technique is a reliable option for treating distal third humeral shaft fractures. LEVEL OF EVIDENCE: 4.

Structural determinants and molecular mechanisms for the resistance of HIV-1 RT to nucleoside analogues.

The reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) is an RNA- and DNA-dependent DNA polymerase capable of copying the viral genome before it gets integrated into the human host DNA. Hence, HIV-1 RT plays a major role in viral replication and represents a key target for anti-AIDS treatments. Amongst the eleven licensed drugs that inhibit RT, eight are chain-terminating nucleoside analogues (NRTIs) that compete with their natural counterparts during the DNA polymerization process. Unfortunately, under therapeutic pressure, the HIV-1 inevitably develops resistance to these inhibitors by accumulating mutations in the viral pol gene encoding RT. Mechanisms for this resistance can be sorted in two categories, depending on the nature of the drug and the selected mutations. The first category includes mutations involving a specific alteration of the discrimination between natural nucleotides and NRTIs. The second category includes mutations able to promote the removal of the incorporated NRTI and thus repair the nascent DNA chain. This review summarizes the modes of inhibition of HIV-1 RT with NRTIs, and describes the mechanisms of resistance to these drugs, based on enzymatic data correlated to crystal structures and molecular models involving HIV-1 RT. We also give insights into different aspects of resistance such as antagonistic mutations, replication capacity, and the implications for a rational, structure-based drug design.

Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity.

RhoA/B/C and CDC42/Rac, which form two subgroups of the rho guanosine triphosphatase (GTPase) family, regulate various aspects of actin cytoskeleton organisation. In cytosol, guanosine diphosphate (GDP) dissociation inhibitor (GDI) interacts with and maintains rho GTPases in their inactive GDP-bound form. RhoGDI is a ubiquitously expressed GDI, whereas D4/LyGDI is hematopoietic cell-specific and 10-fold less potent than RhoGDI in binding to and regulating rho GTPases. We have combined microanalytical liquid chromatography with the use of specific antibodies in order to separate D4/LyGDI and RhoDGI-complexes from the cytosol of U937 cells and to demonstrate that the two GDIs associate with different rho protein partners. RhoGDI can form a complex with CDC42Hs, RhoA, Rac1 and Rac2, while none of these GTPases was found to interact with D4/LyGDI. In addition, we found that stimulation of U937 cells with phorbol ester leads to phosphorylation of D4/LyGDI. Our results suggest that LyGDI forms complexes with specific rho GTPases expressed in hematopoietic cells where it may regulate specific pathways.

Activation of anti-reverse transcriptase nucleotide analogs by nucleoside diphosphate kinase: improvement by alpha-boranophosphate substitution.

Nucleoside activation by nucleoside diphosphate kinase and inhibition of HIV-1 reverse transcriptase were studied comparatively for a new class of nucleoside analogs with a borano (BH3-) or a thio (SH) group on the alpha-phosphate. Both the alpha-Rp-borano derivatives of AZT and d4T improved phosphorylation by NDP kinase, inhibition of reverse transcription as well as stability of alpha-borano nonophosphate derivatives in terminated viral DNA chain.

Comparative clinical study of locking screws versus smooth locking pegs in volar plating of distal radius fractures.

The present study was performed to test the null hypothesis on no difference in stability of fixation after volar plating of intra-articular distal radius fractures (AO C2-C3) with either locking smooth pegs or locking screws in a clinical setting. A retrospective evaluation included adult patients with C2-C3 AO fractures treated with a volar plate with locking smooth pegs or locking screws. Radiographic assessment was performed to evaluate extra- and intra-articular parameters in the early postoperative period and after bone union. Twenty-seven consecutive patients were included. Thirteen cases had fixation with locking screws and 14 had fixation with locking smooth pegs. Both groups had bone fragment displacement after fixation. However, there were no significant differences between the groups either in extra- or intra-articular parameters defined by Kreder et al. (1996). Our study shows that, in a clinical setting, there is no difference in stability fixation between locking screws or smooth locking pegs in C2-C3 distal radius fractures.