Effect of gender and race on the week 48 findings in treatment-naïve, HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE.

OBJECTIVES: A week 48 efficacy and safety analysis with respect to gender and race was conducted using pooled data from the phase III, double-blind, double-dummy efficacy comparison in treatment-naïve, HIV-infected subjects of TMC278 and efavirenz (ECHO) and TMC278 against HIV, in a once-daily regimen versus efavirenz (THRIVE) trials. METHODS: Treatment-naïve, HIV-1-infected adults were randomized to receive rilpivirine (RPV; TMC278) 25 mg once a day (qd), or efavirenz (EFV) 600 mg qd, plus tenofovir/emtricitabine (ECHO) or tenofovir/emtricitabine, zidovudine/lamivudine or abacavir/lamivudine (THRIVE). RESULTS: A total of 1368 participants (76% male and 61% White, of those with available race data) were randomized and treated. No gender-related differences in response rate (percentage of patients with HIV-1 viral load < 50 HIV-1 RNA copies/mL, using an intent-to-treat, time-to-loss-of-virological-response algorithm) were observed (RPV: men, 85%; women, 83%; EFV: men, 82%; women, 83%). Response rates were lower in Black compared with Asian and White participants (RPV: 75% vs. 95% and 85%, respectively; EFV: 74% vs. 93% and 83%, respectively); this finding was mostly a result of higher discontinuation and virological failure rates in Black patients. Safety findings were generally similar across race and gender subgroups. However, nausea occurred more commonly in women than in men in both treatment groups. In men, diarrhoea was more frequent in the EFV group, and abnormal dreams/nightmares were more frequent in men in both the EFV and RPV groups. CONCLUSIONS: Overall response rates were high for both RPV and EFV. No gender differences were observed. However, response rates were lower among Black patients, regardless of treatment group. Gender appeared to influence the incidence of gastrointestinal adverse events and abnormal dreams/nightmares for both treatments.

Biomechanical evaluation of thumb opposition transfer insertion sites.

The optimal location for insertion of the transferred tendon in opposition transfer is controversial. The purpose of this study was to examine 4 commonly used insertion sites into the thumb and determine which maximizes thumb opposition. The flexor digitorum superficialis of the ring finger was used as a donor tendon and was attached in random order to the abductor pollicis brevis (APB) tendon, the APB and extensor pollicis longus, the flexor pollicis brevis (FPB) and dorsal radial extensor hood, and the ulnar extensor hood at the base of the proximal phalanx. As normal opposition was simulated, the minimum distance between the thumb and little finger and the pinch force were measured. The FPB and radial dorsal extensor hood site resulted in the statistically highest pinch force. The FPB and radial dorsal extensor hood and the APB sites had statistically smaller minimum distances between the thumb and little finger than the ulnar extensor hood site. A subjective evaluation of the 3-dimensional thumb path of motion revealed that the FPB and radial dorsal extensor hood site and the APB insertion site allowed the closest approximation of normal thumb opposition. This biomechanical study supports the use of the FPB and radial dorsal extensor hood insertion site or APB insertion site for opposition transfers.

An anatomic study of the ligamentous structure of the triangular fibrocartilage complex.

An anatomic study of the ligamentous structures of the triangular fibrocartilage complex and their attachments on the ulnar styloid was performed using 27 embalmed cadaver wrists. The dorsal and palmar distal radioulnar ligaments of the triangular fibrocartilage complex in each specimen contained a superficial and a deep portion. The deep portion of both ligaments inserted on the fovea of the ulna. The superficial portion of both ligaments surrounded the articular disc uniting at the ulnar-most portion of the articular disc. The tissue that is between the ulnar aspect of the superficial ligament (and integrated on its periphery) and the ulnar capsule is defined as the meniscus homologue. Anatomic variations in the meniscus homologue and the prestyloid recess (the cavity adjacent to the ulnar styloid) were seen in 1 of 3 ways; the narrow opening type in 74% of specimens, the wide opening type in 11%, and the no opening type in 15%. The ulnotriquetral ligament inserted on the palmar-radial aspect of the base of the ulnar styloid and the ulnolunate ligament inserted on the palmar border of the articular disc.

Pressure distribution in the distal radioulnar joint.

Measurement of the pressure distribution within the distal radioulnar joint was performed in fresh cadaver forearms at varying positions of forearm rotation. Axial loads of 0 N, 36 N, and 89 N were applied to the wrist flexors and extensors. At neutral forearm rotation and application of 89 N axial load, an average of 12.5% of the sigmoid notch area was in contact with the ulna. Analysis of the pressure plots reveals that in pronation, the pressure was concentrated in the dorsal portion of the sigmoid notch and that in supination the pressure was distributed in the palmar portion.

Internal derangements of the knee: rates of occurrence at MR imaging in patients referred by orthopedic surgeons compared with rates in patients referred by physicians who are not orthopedic surgeons.

PURPOSE: To compare the occurrence at magnetic resonance (MR) imaging of clinically important knee abnormalities in patients referred by orthopedic surgeons with that in patients referred by other physicians. MATERIALS AND METHODS: Knee MR images in all patients referred for evaluation of internal derangement for 12 months were retrospectively reviewed. Meniscus, ligament, and articular cartilage abnormalities were tabulated. The numbers of abnormalities detected in the patients referred by orthopedic surgeons were compared with those in the patients referred by all other physicians by using chi(2) analysis. Significance was defined at P less than .05. RESULTS: Knee MR images in 439 patients were reviewed; 328 patients were referred by orthopedic surgeons, and 111 were referred by other physicians. There was no significant difference in the rates of occurrence of meniscus tear (149 [45%; orthopedic surgeon referrals] vs 50 [45%; other physician referrals], P = .96); ligament tear (82 [25%] vs 21 [19%], P = .25); isolated hyaline cartilage defect (77 [23%] vs 20 [18%], P = .29); meniscus or ligament tear (167 [51%] vs 55 [50%], P = .86); or meniscus, ligament, or articular cartilage tear (242 [74%] vs 72 [65%], P = .34). The proportion of patients who subsequently underwent surgery of the knee was also similar (39% [118 of 300] vs 28% [23 of 82], P = .14). CONCLUSION: There was no significant difference in the occurrences of clinically important knee internal derangement at MR imaging between patients referred by orthopedic surgeons and those referred by other physicians.

Changes in carpal tunnel pressures following endoscopic carpal tunnel release: a cadaveric study.

The purpose of this experiment was to determine the amount of tissue that must be sectioned to adequately decompress the median nerve during an endoscopic carpal tunnel release procedure. In 6 fresh cadaver forearms, 2 balloons were inserted into the carpal tunnel. The first balloon was filled with saline solution to cause an initial carpal intracanal pressure of 50 mmHg. Pressure measurements were recorded, using the second balloon, at various increments of the flexor retinaculum division at 3 wrist positions (neutral, 35 degrees ; flexion, 35 degrees extension). At all increments of sectioning, carpal tunnel pressures in the neutral wrist position were consistently lowest and the values in 35 degrees extension were greatest. At each wrist flexion/extension angle, the pressure statistically decreased during incremental division of the flexor retinaculum. Incomplete release of the transverse carpal ligament resulted in incomplete decompression in the canal. Sectioning the overlying aponeurosis caused a further significant decrease in intracanal pressure.

The relative contribution of selected carpal bones to global wrist motion during simulated planar and out-of-plane wrist motion.

The relative contribution of the scaphoid, lunate, triquetrum, and capitate to wrist motion was examined in 6 fresh cadaver forearms. A wrist-joint motion simulator was used to dynamically move each wrist through planar and nonplanar motions. During wrist flexion-extension, the motion of the capitate closely followed the motion of the third metacarpal, while the lunate motion was approximately 50% of the total motion; the triquetrum, 65%, and the scaphoid, 90%. Similar differences in motion for these carpal bones occurred during radioulnar deviation and circumduction and dart-throw motions. This suggests that the scaphoid, lunate, and triquetrum do not normally function as a single unit, but that each bone has an unique arc of motion during global wrist motion.

Analysis of the kinematics of the scaphoid and lunate in the intact wrist joint.

In conclusion, this study combined three different technologies to simultaneously monitor scaphoid, lunate, and global wrist motion in three dimensions and concurrently collect data on the pressure distribution in the radiocarpal and ulnocarpal joints. This information was collected dynamically in real time while the wrist was moved in reproducible, physiologic cycles of motion. The scaphoid and lunate flex and extend as well as pronate and supinate while the wrist moves in the plane of flexion and extension. There is minimal radial and ulnar deviation of these carpal bones during this motion. During wrist radial and ulnar deviation, the scaphoid and lunate both flex and extend as well as deviate radially and ulnarly. The pressures in the wrist also change as the wrist moves. Pressures in the wrist are not evenly distributed and, during some movements, are localized to specific areas. The data also support the concept that there is a hysteresis effect on both the carpal bones and the pressure distribution patterns while the wrist is moving. The results of this study can provide baseline data to compare with other studies that evaluate various pathologic abnormalities of the wrist joint.

Interactions of oxytocin and vasopressin with CRF on the rat colon.

Corticotropin-releasing factor (CRF), a primary mediator of stress responses, produces changes in the gastrointestinal tract identical to those induced by stress. CRF is tenfold more potent in females than in males, but gonadectomy reverses this difference. We postulated that positive modulators of CRF, such as oxytocin (OT) and vasopressin (AVP), may act in females to potentiate effects of CRF and thus could account for the gender-related differences in colonic sensitivity to CRF and stress. Given with CRF, neither OT, peripheral AVP, nor central AVP increased colonic transit any more than CRF alone, suggesting that OT and AVP do not potentiate CRF's actions in the colon. These data indicate that endogenous OT and AVP do not directly affect colonic transit, and that OT and AVP do not account for the gender-related differences in the effects of stress and CRF on colonic transit.

Wrist joint motion simulator.

A computer controlled wrist joint motion simulator has been developed that actively moves forearms from cadavers through cyclic planar flexion-extension motions, planar radial-ulnar deviation motions, and combined motions such as circumduction. Hybrid position-force feedback control algorithms are used to determine the wrist flexor and extensor tendon forces necessary to achieve the desired motions. The simulator was used in a series of 12 fresh cadaver forearms to produce both flexion-extension and radial-ulnar deviation motions and was found to cause repeatable, physiological movements. In these experiments, the extensor tendon forces were greater than those of the flexors, typically by a factor of two.

Arthroscopic repair of radial-sided triangular fibrocartilage complex tears.

Treatment of triangular fibrocartilage complex (TFCC) tears is receiving considerable attention. Repair of peripheral tears of the TFCC has been recommended to restore the important functions of stability and load-bearing. Techniques for the reattachment of the periphery of the TFCC are evolving. Previous reports have mainly dealt with ulnar-sided (Palmer Class I-B) repairs. This report describes an arthroscopic technique for repair of radial-sided (Palmer Class I-D) TFCC tears. The procedure utilizes arthroscopic visualization with direct reattachment of the radial edge of the horizontal disk of the TFCC into the sigmoid notch of the distal radius. Fixation is achieved using sutures driven through the distal radius using long straight meniscal repair needles. Early clinical results following arthroscopic reattachment of radial-sided TFCC tears using this technique have been favorable. The technique is presented as an alternative method for repair of these lesions.

The effect of dorsally angulated distal radius fractures on distal radioulnar joint congruency and forearm rotation.

A biomechanical cadaver study was performed to evaluate the effect of dorsally angulated distal radius fractures on the distal radioulnar joint. Frykman I distal radius fractures were simulated, and laxity measurements were taken with and without sectioning the triangular fibrocartilage complex and the interosseous membrane. The findings of this study were threefold. First, measured in terms of radial diastasis, incongruency of the distal radioulnar joint occurred with increasing dorsal tilt of the distal radius. It became most dramatic with a change of more than 20 degrees of dorsal angulation of the distal radius. This corresponds to approximately 10 degrees of dorsal tilt of the articular surface of the distal radius, as measured on an x-ray film. Second, increased dorsal angulation caused interosseous membrane tightness and limited maximum pronation and maximum supination. Third, distal radioulnar joint dislocation did not occur until both the triangular fibrocartilage complex and interosseous membrane were sectioned. These results reveal the importance of anatomic reduction of the distal radius fracture and evaluation of damaged soft tissue structures.

The stabilizing mechanism of the distal radioulnar joint during pronation and supination.

A biomechanical cadaver study was performed to determine the roles of the stabilizing structures of the distal radioulnar joint during pronation and supination. Subluxation and dislocation of the radius with respect to the ulna were evaluated in seven cadaver forearms placed in supination, pronation, and neutral forearm rotation. The amount of subluxation was measured with all structures intact, and after sectioning in various sequences the dorsal and palmar radioulnar ligaments, the distal portion of the interosseous membrane including the pronator quadratus, and the entire interosseous membrane. After sectioning two of any four structures, the distal radioulnar joint remained stable. When the interosseous membrane was disrupted first, the dorsal radioulnar ligament was found to be more important than the palmar radioulnar ligament in stabilizing the distal radioulnar joint in pronation, and conversely the palmar radioulnar ligament was more important than the dorsal radioulnar ligament in supination. Dislocation, and frequently diastasis, occurred only with sectioning of all four structures. This suggests that all four structures contribute to stability of the distal radioulnar joint.

A dynamic biomechanical study of scapholunate ligament sectioning.

A biomechanical study was performed on fresh cadaver forearms to investigate the role of the scapholunate interosseous ligament in carpal stability. Scaphoid and lunate motion and radiocarpal and ulnocarpal pressure patterns were continually monitored while the wrist was moved physiologically. Prior to ligament sectioning, it was found that the position of the scaphoid and lunate were dependent on both the wrist position and the direction of wrist motion. Sectioning the scapholunate interosseous ligament caused increased scaphoid flexion, scaphoid pronation, and lunate extension. Pressure in the radiocarpal and ulnocarpal joint was redistributed following ligament sectioning. These findings support the clinical impression that the scapholunate interosseous ligament is an important stabilizer of the scaphoid and lunate.

The change in ulnar variance with grip.

The effect of grip on ulnar variance was evaluated in 66 symptom-free wrists of 53 volunteers. Zero-rotation posteroanterior x-ray films were taken of each wrist before and after exertion of a grip force measured with a Jamar dynamometer. The volunteers were randomly divided into two groups. Group I subjects (35 wrists) were asked to exert a constant grip force of 11.3 kg. Group II subjects (31 wrists) were asked to exert a maximum grip effort, which resulted in a mean grip force of 30 kg (range, 22.8 kg to 53.6 kg). Group I demonstrated a mean increase in ulnar variance of 1.27 mm and group II showed a mean increase of 1.95 mm. The minimum increase in ulnar variance observed was 0.25 mm. The changes observed were statistically significant. The results confirm that a relative increase in ulnar variance occurs with grip. There may be an etiologic role for daily activities that involve repetitive grip and forearm rotation in development of the ulnar impaction syndrome.