A mutation in the voltage-gated sodium channel gene associated with pyrethroid resistance in Latin American Aedes aegypti.

Pyrethroids are commonly used as mosquito adulticides and evolution of resistance to these compounds is a major threat to public health. 'Knockdown resistance' to pyrethroids (kdr) is frequently caused by nonsynonymous mutations in the voltage-gated sodium channel transmembrane protein (para) that reduce pyrethroid binding. Early detection of kdr is critical to the development of resistance management strategies in mosquitoes including Aedes aegypti, the most prevalent vector of dengue and yellow fever viruses. Brengues et al. described seven novel mutations in hydrophobic segment 6 of domain II of para in Ae. aegypti. Assays on larvae from strains bearing these mutations indicated reduced nerve sensitivity to permethrin inhibition. Two of these occurred in codons Iso1011 and Val1016 in exons 20 and 21 respectively. A transition in the third position of Iso1011 encoded a Met1011 replacement and a transversion in the second position of Val1016 encoded a Gly1016 replacement. We have screened this same region in 1318 mosquitoes in 32 additional strains; 30 from throughout Latin America. While the Gly1016 allele was never detected in Latin America, we found two new mutations in these same codons. A transition in the first position of codon 1011 encodes a Val replacement while a transition in the first position of codon 1016 encodes an Iso replacement. We developed PCR assays for these four mutations that can be read either on an agarose gel or as a melting curve. Selection experiments, one with deltamethrin on a field strain from Santiago de Cuba and another with permethrin on a strain from Isla Mujeres, Mexico rapidly increased the frequency of the Iso1016 allele. Bioassays of F(3) offspring arising from permethrin susceptible Val1016 homozygous parents and permethrin resistant Iso1016 homozygous parents show that Iso1016 segregates as a recessive allele in conferring kdr. Analysis of segregation between alleles at the 1011 and 1016 codons in the F(3) showed a high rate of recombination even though the two codons are only separated by a ~250 bp intron. The tools and information presented provide a means for early detection and characterization of kdr that is critical to the development of strategies for resistance management.

Influence of metacarpophalangeal joint position on basal joint-loading in the thumb.

BACKGROUND: Conventional wisdom holds that hyperextension of the metacarpophalangeal joint of the thumb is secondary to degenerative subluxation of the trapeziometacarpal joint as occurs in osteoarthritis. We propose that a hypermobile metacarpophalangeal joint may have a causative role in the development of primary osteoarthritis at the base of the thumb by concentrating forces on the palmar aspect of the trapeziometacarpal joint. METHODS: Twenty fresh-frozen cadaveric forearm specimens were obtained post mortem from donors with no history of connective-tissue disease. Each specimen was categorized by its passive range of metacarpophalangeal joint motion. Testing was conducted with Fuji ultra-low-pressure-sensitive film while the hand was in the lateral-pinch mode with the metacarpophalangeal joint in each of the following positions: unrestrained, pinned in neutral, pinned in 30 degrees of flexion, and pinned in maximal hyperextension. Quantitative analysis of the trapezial contact surface at each of the metacarpophalangeal joint positions was performed, and the center of pressure was determined. Each specimen was then classified according to the extent of arthritic disease (nonarthritic, moderately arthritic, or affected by end-stage arthritis). RESULTS: In specimens affected by end-stage osteoarthritis, the center of pressure on the trapeziometacarpal joint moved dorsally by 56.8% of the length of the trapezial surface with metacarpophalangeal joint flexions of 30 degrees (p < 0.01), whereas the corresponding values were 28.2% and 40.9% in the hyperextended and neutral metacarpophalangeal joint positions, respectively. In specimens with moderate osteoarthritis, 30 degrees of metacarpophalangeal joint flexion also produced the most dorsal trapeziometacarpal center of pressure (44.8%); however, this center of pressure was not significantly different from the centers of pressure at the other metacarpophalangeal joint positions. In nonarthritic specimens, the center of pressure was again significantly more dorsal with metacarpophalangeal joint flexion of 30 degrees than it was at the other positions (p < 0.01). CONCLUSION: Metacarpophalangeal joint flexion effectively unloaded the most palmar surfaces of the trapeziometacarpal joint regardless of the presence or severity of arthritic disease in this joint.

Mechanism underlying mechanical dysfunction in the border zone of left ventricular aneurysm: a finite element model study.

BACKGROUND: The global left ventricular dysfunction characteristic of left ventricular aneurysm is associated with muscle fiber stretching in the adjacent noninfarcted (border zone) region during isovolumic systole. The mechanism of this regional dysfunction is poorly understood. METHODS: An anteroapical transmural myocardial infarct was created by coronary arterial ligation in an adult Dorset sheep and was allowed to mature into left ventricular aneurysm for 10 weeks. The animal was imaged subsequently using magnetic resonance imaging with simultaneous recording of intraventricular pressures. A realistic mathematical model of the three-dimensional ovine left ventricle with an anteroapical aneurysm was constructed from multiple short-axis and long-axis magnetic resonance imaging slices at the beginning of diastolic filling. RESULTS: Three model simulations are presented: (1) normal border zone contractility and normal aneurysmal material properties; (2) greatly reduced border zone contractility (by 50%) and normal aneurysmal material properties; and (3) greatly reduced border zone contractility (by 50%) and stiffened aneurysmal material properties (by 1000%). Only the latter two simulations were able to reproduce experimentally observed stretching of border zone fibers during isovolumic systole. CONCLUSIONS: The mechanism underlying mechanical dysfunction in the border zone region of left ventricular aneurysm is primarily the result of myocardial contractile dysfunction rather than increased wall stress in this region.

Safe placement of proximal tibial transfixation wires with respect to intracapsular penetration.

OBJECTIVES: To determine the safe zone for transfixation wires in the proximal tibia to avoid intracapsular penetration. METHODS: The material consisted of five fresh cadaver knees (two paired) and seven knees of volunteer subjects (three paired). High-resolution magnetic resonance imaging (MRI) was performed on each knee after distension with a gadolinium solution. The distance d from the subchondral bone to the insertion of the reflected joint capsule was measured. Selected cadaver knees were then anatomically sectioned to correlate the MRI findings with anatomic measurements. RESULTS: On the anteromedial side of the knee, the distance from the reflected joint capsule to the subchondral bone was less than eleven millimeters in all specimens except one. Posteromedially, d was smaller and ranged from two to four millimeters. On the lateral side of the knee anterior to the proximal tibiofibular joint, this distance ranged from six to nine millimeters. In all knees but two, d was greatest at the posterior aspect of the proximal tibiofibular joint, ranging from eight to thirteen millimeters. In one volunteer knee, the septum that separates the knee joint from the proximal tibiofibular joint was either torn or attenuated, resulting in complete communication between these two synovial cavities. CONCLUSIONS: Proximal tibial transfixation wires away from the tibiofibular joint are likely to be extraarticular if kept greater than fourteen millimeters from the subchondral bone. In the region of the proximal tibiofibular joint, a safe distance is unclear because it is difficult to know preoperatively which knee has a torn septum.

Effects of interference fit screw length on tibial tunnel fixation for anterior cruciate ligament reconstruction.

Graft-tunnel mismatch during arthroscopically assisted anterior cruciate ligament reconstruction using the central-third patellar tendon results in less than 20 mm of bone plug remaining in the tibial tunnel. We decided to evaluate the strength of bone plug fixation using interference fit screws that were less than 20 mm in length. Biomechanical testing was performed on 48 porcine hindquarters using 9-mm diameter interference fit screws that measured 12.5, 15, and 20 mm in length. No significant difference was noted between the different-length screws for insertion torque, divergence, stiffness, displacement, or load to failure. We believe, therefore, that comparable graft fixation can be achieved in the tibial tunnel using 9-mm diameter interference fit screws that are less than 20 mm long, and that these shorter screws may be useful in cases of graft-tunnel mismatch.

Epicardial suction: a new approach to mechanical testing of the passive ventricular wall.

The lack of an appropriate three-dimensional constitutive relation for stress in passive ventricular myocardium currently limits the utility of existing mathematical models for experimental and clinical applications. Previous experiments used to estimate parameters in three-dimensional constitutive relations, such as biaxial testing of excised myocardial sheets or passive inflation of the isolated arrested heart, have not included significant transverse shear deformation or in-plane compression. Therefore, a new approach has been developed in which suction is applied locally to the ventricular epicardium to introduce a complex deformation in the region of interest, with transmural variations in the magnitude and sign of nearly all six strain components. The resulting deformation is measured throughout the region of interest using magnetic resonance tagging. A nonlinear, three-dimensional, finite element model is used to predict these measurements at several suction pressures. Parameters defining the material properties of this model are optimized by comparing the measured and predicted myocardial deformations. We used this technique to estimate material parameters of the intact passive canine left ventricular free wall using an exponential, transversely isotropic constitutive relation. We tested two possible models of the heart wall: first, that it was homogeneous myocardium, and second, that the myocardium was covered with a thin epicardium with different material properties. For both models, in agreement with previous studies, we found that myocardium was nonlinear and anisotropic with greater stiffness in the fiber direction. We obtained closer agreement to previously published strain data from passive filling when the ventricular wall was modeled as having a separate, isotropic epicardium. These results suggest that epicardium may play a significant role in passive ventricular mechanics.

Chondronecrosis of the hip. The protective role of the ossific nucleus in an animal model.

The presence of the ossific nucleus and its role in reducing the risk of ischemic necrosis in developmental dysplasia of the hip remains a matter of controversy. Ischemic necrosis of the pre-osseous capital femoral epiphysis, defined as chondronecrosis, was evaluated in a rabbit model. Histologic evidence of chondronecrosis after casting in maximum abduction was greater in 1-day-old New Zealand White rabbits before the radiographic appearance of the ossific nucleus, compared with 16-day-old New Zealand White rabbits with an ossific nucleus already present. This preliminary study supports the hypothesis that the ossific nucleus may decrease the risk of intracapsular compressive ischemic injury to the developing capital femoral epiphysis in a rabbit model.

Self-esteem differences as a function of race and weight preoccupation: findings and implications.

The relationship of weight and diet preoccupation and self-esteem among black and white college females is examined.

MRI-radiofrequency tissue tagging in patients with aortic insufficiency before and after operation.

BACKGROUND: Magnetic resonance imaging tissue tagging is a relatively recent methodology that describes ventricular systolic function in terms of intramyocardial ventricular deformation. Because the analysis involves the use of many intramyocardial points to describe systolic deformation, it is theoretically more sensitive at describing subtle differences in regional myocardial fiber shortening when compared with conventional measures of ventricular function such as wall thickening. The objectives of this study were (1) to define sensitive indices of ventricular systolic deformation to assist the clinician in the surgical evaluation of patients with aortic insufficiency, and (2) to quantify differences in regional systolic deformation before and after surgery for aortic insufficiency. METHODS: Magnetic resonance imaging with tissue tagging was performed on 10 normal volunteers and 8 patients with chronic severe aortic insufficiency. Follow-up postoperative studies (5.4+/-1.1 months) were obtained in 6 patients who underwent Ross procedure (1 patient), David procedure (1), and St. Jude aortic valve replacement (4). RESULTS: There was no significant difference in fractional area change, overall circumferential shortening, or overall radial thickening among the normal group, the preoperative aortic insufficiency group, or the postoperative aortic insufficiency group. However, on a regional basis, there was a decrease in posterior wall circumferential strains in the postoperative aortic insufficiency group (29%+/-13% preoperative aortic insufficiency (n=6) versus 24%+/-12% postoperative aortic insufficiency (n=6), p=0.02). CONCLUSIONS: On regional analysis, there was a small but significant decrease in posterior wall circumferential shortening after operation. Magnetic resonance imaging tissue tagging is a sensitive and clinically applicable method of quantifying regional ventricular wall function before and after intervention for aortic insufficiency.

The Frank Stinchfield Award. Inhibition of heterotopic ossification with radiation therapy in an animal model.

An animal model for the study of heterotopic ossification was developed and the effects of perioperative radiation were analyzed. In Phase I, New Zealand White rabbits (n = 18) underwent surgery either with or without muscle injury on each hip to establish the most reliable model in which to study heterotopic ossification. In Phase II, rabbits (n = 36) underwent either 400, 800, or 1200 cGy radiation to one hip 24 hours after bilateral hip surgery to establish a dose response relationship for postoperative radiation therapy. In Phase III, rabbits (n = 24) underwent preoperative radiation therapy (800 cGy) at 4, 16, or 24 hours preoperatively to investigate the mechanism of action and efficacy of preoperative radiation therapy. Monthly radiographs were graded by blinded observers for severity of heterotopic ossification. Mean grade, intraobserver and interobserver variability, and statistical significance were evaluated. In Phase II, 17 of 18 rabbits generated heterotopic ossification in both hips, and the mean grade of heterotopic ossification was always greater on the operative side with intentional muscle injury. Variability in the grading was considered excellent. Phase II revealed that 800 cGy was the minimal effective dose. Contrary to hypothesis, Phase III revealed an increasing grade of heterotopic ossification coinciding with a decreasing preoperative time interval, with the difference in heterotopic ossification grade with 24-hour versus 4-hour preoperative radiation being significant. The rabbit model is reliable and reproducible and closely resembles the human clinical situation after hip surgery. Preoperative and postoperative radiation effectively prevented heterotopic ossification formation. The results support the use of preoperative radiation and establish a need for additional investigation regarding the mechanism of action and timing of preoperative radiation therapy.

Percutaneous pinning of proximal humerus fractures: a biomechanical study.

Mechanical testing of two-part surgical neck fractures fixed with four different pin configurations was performed. Ten fresh, frozen, unembalmed humeri stripped of all soft tissues were used; the surgical neck was osteotomized perpendicular to the humerus long axis. Terminally threaded 2.5-mm AO pins were used to fix the fracture. Humeri then were tested in both torsion and bending on a custom-made jig using Instron 1331 to assess the rigidity of pinning constructs. In torsion, two lateral pin construct was significantly less rigid than all other pin configurations. The addition of an anterior pin to two lateral pins did not increase bending rigidity, but significantly increased torsional stiffness. The addition of two bicortical tuberosity pins or two bicortical tuberosity pins and one anterior pin to two lateral pins significantly increased rotational and bending rigidity. Results confirm clinical data, and the authors conclude that multiplanar pins are needed to augment torsional stiffness, and that the addition of two bicortical tuberosity pins enhances bending rigidity.

Orderly oriented wire mesh: a novel porous coating.

As an alternative to commercially available porous beads and fiber metal mesh, a new porous coating, orderly oriented wire mesh (OOWM), was developed. Rectangular plugs, 10 x 5 x 5 mm with porous-coated beads, and four different OOWM configurations were inserted into bilateral femoral condyles of adult beagles. Dogs were sacrificed immediately after implantation, and at 4 weeks, 8 weeks, and 12 weeks postimplantation. Mechanical pullout strength of plugs revealed that porous beads are equivalent to the simplest OOWM at 12 weeks postimplantation. Of the four OOWMs tested, the 25 x 25 single layer was significantly more stable than others at 4 weeks postimplantation. These results indicate that in an in vivo unloaded model, OOWM is just as effective as the porous beads in achieving early bone ingrowth and stability.

The role of athletic trainers in counseling collegiate athletes.

OBJECTIVE: To assess athletic trainers' perceptions with regard to (a) their role in counseling athletes, (b) how qualified they felt to address counseling issues, and (c) current training room procedures for providing psychological services to athletes. DESIGN AND SETTING: A 47-item, open-ended survey was administered to Division I certified athletic trainers who volunteered to participate. SUBJECTS: Fourteen Division I certified athletic trainers (mean age, 33 yr; range, 24 to 47 yr) volunteered to participate in the survey. They included five head athletic trainers, five assistant athletic trainers, three graduate assistants, and one associate director of athletics and sports medicine. MEASUREMENTS: Survey results were tabulated and reported in percentages. RESULTS: Athletic trainers felt that their roles went beyond the care and prevention of athletic injuries, yet they did not necessarily feel qualified to counsel athletes. Most athletic trainers were familiar with on-campus student support services to which student athletes with personal issues could be referred for assistance, but none had access to a sport psychologist. CONCLUSIONS: It is recommended that the NATA include counseling preparation in curriculums and that continuing education be offered to provide certified athletic trainers with current information and skills for delivering psychological services to athletes.

Percutaneous pinning of distal radius fractures: a biomechanical study.

Mechanical testing of extra-articular distal radius fractures stabilized with percutaneous pins was performed. Twelve fresh-frozen unembalmed radii stripped of all soft tissues were used. An osteotomy with dorsal comminution was made 2.5 cm proximal to the radial styloid. Three pin sizes and four pin configurations were used to fix the fracture, and the constructs were mechanically tested. Results show that at least a .062-inch pin was required for any significant changes in rigidity of the four pin configurations tested to be discerned. Cross-pinning with two radial styloid pins and placement of a pin from the ulnar corner of the radius as the most rigid construct in both torsion and cantilever bending.

Insulin-like growth factor I preserves renal function postoperatively.

Deterioration of renal function, which can lead to postoperative renal failure, is a complication of surgery involving the suprarenal aorta and surgery involving the renal arteries. Fifty-four patients who were at risk for developing this complication were enrolled in a double-blind, randomized, placebo-controlled trial of insulin-like growth factor (IGF-I) as a therapeutic agent to prevent the decline in renal function. The primary end point was the incidence of renal dysfunction, defined as a reduction of the glomerular filtration rate (creatinine clearance) at each of three measurements over 72 h. IGF-I (100 microg/kg subcutaneously every 12 h for 6 doses) or placebo was administered on admission to the intensive care unit immediately postoperatively. IGF-I- and placebo-treated groups were well matched for sex, age, type of surgery, renal ischemic time during surgery (ischemic index), baseline creatinine clearance, and baseline serum creatinine. No patient in the study developed acute renal failure postoperatively. IGF-I was well tolerated. A smaller proportion of patients in the IGF-I group had a postoperative decline in renal function (22%) than in the placebo-treated group (33%). There were no significant differences in levels of serum creatinine at time of discharge, length of hospital stay, length of intensive care unit stay, length of intubation, or incidence of dialysis or death. Our findings establish the feasibility and potential utility for the use of IGF-I to reduce the incidence of postoperative renal dysfunction in high-risk patients.

Radiation-induced physical changes in UHMWPE implant components.

Post-irradiation aging of ultra-high molecular weight polyethylene (UHMWPE) is not well understood. Retrieval studies and in vitro aged specimens have shown oxidative changes along with increases in crystallinity. Critical analysis and review of the polymer science and polymer physics literature shows that while oxidation may be important during the first year post-irradiation, subsequent aging occurs because of initial gamma radiation-induced chain scission leading to eventual isothermal crystallization of polymer chains in the amorphous regions of the UHMWPE bulk. Mechanical properties of aged UHMWPE are not as yet clear and, until such data become available, gamma irradiation sterilization must be used with caution.

Obesity is not a risk factor for significant adverse outcomes after cardiac surgery.

BACKGROUND: Obese patients undergoing cardiac surgery are often thought to have prohibitive perioperative risk despite the lack of sufficient data to support this assumption. METHODS AND RESULTS: To assess the significance of obesity as a risk factor in patients undergoing cardiac surgery, we analyzed data from 2299 patients undergoing procedures requiring cardiopulmonary bypass from January 1, 1991, to December 31, 1993. Obesity was defined by use of the body mass index, defined as weight in kilograms divided by height in meters squared. Potential adverse outcomes analyzed included operative mortality, deep sternal wound infection, superficial sternal wound infection, infection at the saphenous vein harvest site, stroke, renal failure, adult respiratory distress syndrome, prolonged mechanical ventilation, pneumonia, sepsis, atrial arrhythmias, pulmonary embolism, need for early reexploration for bleeding, and ventricular arrhythmias. To control for the confounding effects of other risk factors, we performed a multivariate logistic regression analysis. Potential covariates considered in the logistic model included age, sex, race, history of reoperation, congestive heart failure, prior myocardial infarction, renal failure, diabetes, hypertension, chronic obstructive pulmonary disease or stroke, and cardiopulmonary bypass and aortic cross-clamp time. Twenty-five percent of patients (567/2299) were classified as obese. The results of the multivariate regression demonstrated that obesity was a risk factor only for superficial sternal wound infection (P < .001; odds ratio, 2.3), leg infections (P = .005; odds ratio, 1.8), and atrial dysrhythmias (P = .04; odds ratio, 1.2). Notably, obesity did not predispose toward increased pulmonary complications or deep sternal wound infection (P = .65). CONCLUSIONS: With the exception of superficial wound complications and atrial dysrhythmias, obesity is not a significant multivariate risk factor for adverse outcomes. The results indicate that obese patients may safely undergo cardiac surgery with due attention to technical considerations designed to minimize wound complications.

Magnetic resonance imaging provides evidence for remodeling of the right ventricle after single-lung transplantation for pulmonary hypertension.

BACKGROUND: In end-stage pulmonary hypertension (PH), the degree of right ventricular (RV) dysfunction has been considered so severe as to require combined heart-lung transplantation. Nevertheless, left ventricular (LV) and RV hemodynamics return to relatively normal levels after single-lung transplantation (SLT) alone. Accordingly, to test the hypothesis that LV and RV systolic function improves after SLT and that the dilated, thick-walled RV reverts to more normal geometry, we used cine MRI and finite-element (FE) analysis to study patients with end-stage PH. METHODS AND RESULTS: Seven patients with end-stage PH underwent cine MRI before and after SLT, and eight normal volunteers were also imaged with cine MRI. Short-axis images at the midventricular level were analyzed with customized image-processing software. The LV and RV ejection fractions, velocity of fiber shortening, RV end-diastolic (ED) and end-systolic (ES) chamber areas, and RV ES and ED wall thicknesses were calculated directly from the MRI images. Two-dimensional FE models of the heart were constructed from the MRI images at early diastole. LV and RV pressures were measured in the patients with a cardiac catheterization before and after SLT. Models were solved to yield diastolic LV, RV, and septal wall stresses. By use of a nonlinear optimization algorithm, LV and RV diastolic maternal properties were determined by minimization of the leastsquares difference between FE model-predicted and MRI-measured LV, RV, and epicardial chamber areas and circumferences. The results demonstrated a substantial reduction in RV wall stress after SLT (1.8 x 10(5) dynes/cm2 pre-SLT to 2 x 10(4) dynes/cm2 post-SLT; P < .001). The average RV diastolic elastic modulus was reduced significantly after SLT (1.5 x 10(6) dynes/cm2 pre-SLT to 1 x 10(5) dynes/cm2 post-SLT; P = .01), but there was no change in the LV elastic modulus. RV velocity of fractional shortening increased significantly after SLT (0.23 pre-SLT to 0.58 post-SLT, P = .02), and RV ED and ES wall thicknesses were reduced significantly (ED, 0.86 cm pre-SLT to 0.65 cm post-SLT, P = .03 and ES, 1.06 cm pre-SLT to 0.72 cm post-SLT, P = .005). CONCLUSIONS: These results provide evidence supporting the contention that LV and RV systolic function improved after SLT for end-stage PH and that the RV underwent significant remodeling within 3 to 6 months after lung transplantation.

Myocardial material property determination in the in vivo heart using magnetic resonance imaging.

OBJECTIVES: To determine nonlinear material properties of passive, diastolic myocardium using magnetic resonance imaging (MRI) tissue-tagging, finite element analysis (FEA) and nonlinear optimization. BACKGROUND: Alterations in the diastolic material properties of myocardium may pre-date the onset of or exist exclusive of systolic ventricular dysfunction in disease states such as hypertrophy and heart failure. Accordingly, significant effort has been expended recently to characterize the material properties of myocardium in diastole. The present study defines a new technique for determining material properties of passive myocardium using finite element (FE) models of the heart, MRI tissue-tagging and nonlinear optimization. This material parameter estimation algorithm is employed to estimate nonlinear material parameter sin the in vivo canine heart and provides the necessary framework to study the full complexities of myocardial material behavior in health and disease. METHODS AND RESULTS: Material parameters for a proposed exponential strain energy function were determined by minimizing the least squares difference between FE model-predicted and MRI-measured diastolic strains. Six mongrel dogs underwent MRI imaging with radiofrequency (RF) tissue-tagging. Two-dimensional diastolic strains were measured from the deformations of the MRI tag lines. Finite element models were constructed from early diastolic images and were loaded with the mean early to late left ventricular and right ventricular diastolic change in pressure measured at the time of imaging. A nonlinear optimization algorithm was employed to solve the least squares objective function for hte material parameters. Average material parameters for the six dogs were E = 28,722 +/- 15984 dynes/cm2 and c = 0.00182 +/- 0.00232 cm2/dyne. CONCLUSION: This parameter estimation algorithm provides the necessary framework for estimating the nonlinear, anisotropic and non-homogeneous material properties of passive myocardium in health and disease in the in vivo beating heart.