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Biomedical subjects

T L Schmidt

Publications and source records attributed to T L Schmidt.

At least 19 recordsLinked to original sources

Characterization of the rhesus cytomegalovirus US28 locus.

Human cytomegalovirus (CMV) US28 (and the related open reading frame [ORF] US27) are G-protein-coupled receptor homologs believed to play a role in viral pathogenesis. In vitro, US28 has been shown to bind and internalize ligands, as well as activate intracellular signaling in response to certain chemokines, and to initiate the migration of smooth muscle cells to chemokine gradients. To assess the role of US28 in vivo, we examined the rhesus model and sequenced and characterized the rhesus CMV US28 locus. We found that rhesus CMV carries five tandem homologs of US28, all widely divergent from US28 and from each other. By reverse transcription-PCR and Northern analysis, we demonstrated expression of these ORFs in infected cells. With stable cell lines expressing these ORFs, we analyzed the homolog's binding and signaling characteristics across a wide range of chemokines and found one (RhUS28.5) to have a ligand binding profile similar to that of US28. In addition, we localized US28 and the rhesus CMV homolog RhUS28.5 to the envelope of infectious virions, suggesting a role in viral entry or cell tropism.

Amino Acid Sequence↗

Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours.

Vitamin C (ascorbate) is toxic to tumour cells, and has been suggested as an adjuvant cancer treatment. Our goal was to determine if ascorbate, in combination with other antioxidants, could kill cells in the SW620 hollow fibre in vitro solid tumour model at clinically achievable concentrations. Ascorbate anti-cancer efficacy, alone or in combination with lipoic acid, vitamin K3, phenyl ascorbate, or doxorubicin, was assessed using annexin V staining and standard survival assays. 2-day treatments with 10 mM ascorbate increased the percentage of apoptotic cells in SW620 hollow fibre tumours. Lipoic acid synergistically enhanced ascorbate cytotoxicity, reducing the 2-day LC(50)in hollow fibre tumours from 34 mM to 4 mM. Lipoic acid, unlike ascorbate, was equally effective against proliferating and non-proliferating cells. Ascorbate levels in human blood plasma were measured during and after intravenous ascorbate infusions. Infusions of 60 g produced peak plasma concentrations exceeding 20 mM with an area under the curve (24 h) of 76 mM h. Thus, tumoricidal concentrations may be achievable in vivo. Ascorbate efficacy was enhanced in an additive fashion by phenyl ascorbate or vitamin K3. The effect of ascorbate on doxorubicin efficacy was concentration dependent; low doses were protective while high doses increased cell killing.

Antioxidants↗

Tensile properties of the physis vary with anatomic location, thickness, strain rate and age.

The variable outcome of physeal distraction has raised questions as to the mechanism by which bone lengthening is achieved. Is it by stretching of the matrix or does it stimulate growth? In order to explore the contribution of matrix stretching, we sought to answer the following questions in an animal model: (a) Are the tensile properties of the lateral side of the proximal tibial physis different from the medial? (b) Are the tensile properties strain-rate dependent? (c) Does the growth plate fracture through any preferred zone in tension? (d) Are the tensile properties of the bovine growth plate a function of age? (e) Are thicker growth plates weaker in tension? (f) Are the tensile properties of the bovine growth plate comparable to those of a child's? We compared bone-cartilage-bone specimens (0.5 x 2.5 mm2 in cross-section) from the lateral, central and medial regions of the proximal tibial growth plates of 12- to 18-month heifers. 70 specimens were tested to failure in tension at 0.0004, 0.004 and 0.04 mm/s. Tensile strength and tangent modulus were 33% and 25% greater, respectively, on the lateral side compared with the medial, and both were increased at the higher strain rates. We found no difference in the ultimate strains by region or strain rate. Thicker growth plates were weaker. Scanning electron microscopy revealed a three-dimensional fracture pattern extending from the upper columnar into the reserve zone. Bundles of intact chondrons remained intact, but only on the metaphyseal side, having been torn from an interterritorial matrix which remained mostly on the epiphyseal side of the fracture. We compared 21 specimens of 12- to 18-month and 19 specimens of 5-month calves from similar regions of the proximal tibia. These were tested to failure in tension at 0.004 mm/s. The older bovine growth plate was 25% thinner, 34% stronger and failed at 65% greater strain. For comparison, we tested eight samples from the femoral capital growth plate of two cerebral palsy patients. These were twice as thick as our bovine samples and about half as strong, but with similar ultimate strain values.

Age Factors↗

Shear strength of the physis varies with anatomic location and is a function of modulus, inclination, and thickness.

Slipped capital femoral epiphysis involves the gradual displacement of the femoral head relative to the neck. Many theories have arisen to explain this slip. Frequently cited etiological factors include increases in physeal thickness and inclination. Slipped epiphysis has been postulated to result from shear overload that causes separation through the hypertrophic cellular zone. We sought to answer the following questions: (a) Do significant regional differences in strength and stiffness exist within a given physis? (b) Are regional differences in resistance to shear related to thickness and inclination of the physis? (c) Does physeal compression cause mammillary interdigitation to begin sooner and increase the resistance to shear before, during, and after failure? (d) Does shear failure occur at displacements detectable by radiography? and (e) Does cleavage occur throughout the entire columnar zone, and do the chondrocyte columns remain intact on both sides of the cleavage plane? We prepared beam-shaped microstructural samples from different sites of the bovine proximal tibial physis. We determined thickness, inclination, ultimate stress and strain, modulus, and strain energy density at ultimate stress as a function of location. Using scanning electron microscopy, we also examined the entire failed surface of several samples. Forty-eight samples were tested by displacing the epiphysis end anteriorly, without axial (across the thickness) constraint; 41 were sheared while an average axial compressive stress of 0.3 MPa was applied to the physis. The posterior region had the greatest strength and stiffness, lowest physeal thickness, and steepest inclination. Compressing the plate did not increase the shear strength or tangent modulus. Ultimate strength varied inversely with thickness and increased when shearing up steeper inclinations; however, it was more strongly associated with the modulus, implying that additional factors control both strength and modulus. Scanning electron microscopy revealed that the plane of fracture differed widely between and within samples, involving all zones of the growth plate. On either side of the fracture, individual chondrocyte columns remained intact, although separated from neighboring columns.

Animals↗

Allograft epiphysiodesis for slipped capital femoral epiphysis.

During this retrospective investigation, use of freeze-dried irradiated allograft for achieving epiphysiodesis in patients with Grade I or Grade II slipped capital femoral epiphyses was evaluated. The study reviewed 40 grafting procedures in 33 patients: 20 patients were boys and 13 were girls, whose average age was 13 years old. The group included 31 Grade I slips and 9 Grade II slips. Six were unstable and 34 were stable. Procedure time averaged 1 hour 57 minutes and blood loss averaged 360 ml. The average time to complete physeal closure was 28 weeks. An incomplete bony physeal bridge, apparent at an average 11 weeks, may impart earlier stability. Thirty-eight cases had followup averaging 3 years 6 months. At most recent evaluation, according to the Harris hip rating system, 35 hips had excellent ratings, 1 had a good rating, and 2 had fair ratings. Six patients were identified with major postoperative complications, including 1 case each of segmental avascular necrosis, chondrolysis, femoral neck fracture, subtrochanteric hip fracture, bilateral progressive coxa vara deformities requiring corrective osteotomies, and a unilateral progressive coxa vara deformity. The senior author (TLS) currently uses a fluoroscopically guided percutaneous lateral approach, a cannulated reaming system, and freeze-dried irradiated cortical allograft. The procedure promotes premature physeal closure. Allograft epiphysiodesis is an alternative operating technique for treating patients with a slipped capital femoral epiphysis.

Adolescent↗

Intravenous sedation for the closed reduction of fractures in children.

The safety and efficacy of intravenous sedation with both a narcotic and a benzodiazepine were evaluated in 104 consecutive children who had closed reduction of a fracture. Six patients had a subsequent additional reduction with intravenous sedation, so the study involved a total of 110 procedures. The average dose of meperidine was 1.47 milligrams per kilogram of body weight, and the average dose of midazolam was 0.11 milligram per kilogram of body weight. The interval between induction of the sedation and performance of the procedure averaged ten minutes, and the total duration of the procedure averaged thirty-nine minutes. There were no episodes of apnea or cardiorespiratory complications. Ninety-six (92 percent) of the initial 104 reductions were successful. Only four patients subsequently needed general anesthesia for a repeat closed reduction. The physician's satisfaction with the method of sedation was good or excellent for 103 (94 per cent) of the 110 procedures. Eighty-one (93 per cent) of eighty-seven patients who were able to respond had no memory of the reduction. A telephone survey conducted after the procedure revealed that eighty-four (98 per cent) of eighty-six parents who responded were satisfied with the method of sedation. Intravenous sedation with a narcotic and a benzodiazepine proved to be a safe and effective method of anesthesia for the closed reduction of fractures in children in our series. Careful monitoring of the patient after sedation is imperative.

Benzodiazepines↗

Tibial cortical bone peg fixation in osteochondritis dissecans of the knee.

Ten knees in nine patients with large, symptomatic osteochondritis dissecans lesions of the knee were treated by cortical bone peg fixation. The follow-up time averaged 2.9 years (range, 0.9-6.6 years). The average age was 19.5 years (range, 15-33 years). The knees were evaluated and rated clinically and roentgenographically. Magnetic resonance (MR) imaging of nine knees was obtained at the follow-up examination to evaluate lesion and bone peg incorporation, evidence of lesion loosening, and the articular cartilage. Eight good to excellent, one fair, and one poor result were obtained clinically. MR imaging showed 33% of knees had poor lesion cartilage and 44% had partial or poor lesion incorporation possibly consistent with loosening. Complications included four partial defect healings, one tibial donor graft-site fracture, and one bone peg loosening. Four symptomatic knees had follow-up arthroscopy at an average of 1.8 years postsurgery and findings included four loose bodies, one loose peg, one meniscal tear, and one symptomatic hypertrophic synovium. MR imaging was a useful tool in evaluating lesion stability, articular cartilage quality, lesion and bone peg incorporation, the menisci, and cruciate ligaments. Bone peg fixation of large osteochondritis dissecans defects of the knee offers a physiologic approach to treatment of this lesion in nearly skeletally mature or skeletally mature patients.

Adolescent↗

Battered child syndrome simulating myositis.

The battered child syndrome is not an unusual problem to be encountered in a clinical orthopedic practice. The manifestations in abused children may be varied and many, necessitating that orthopedists be familiar with the ways in which affected children present to reduce the unfortunate consequences that occur when abuse is not initially recognized. Our purpose in reporting the case of an abused child is to attract the attention of the orthopedic surgeon, who may be the initial physician to see a battered child, to an unusual presentation of this syndrome which simulated myositis. The association of myositis with battered child syndrome has not been previously encountered in the orthopedic literature.

Battered Child Syndrome↗

The fate of the capital femoral physis and acetabular development in developmental coxa vara.

Twenty-two hips in 15 children with the diagnosis of developmental coxa vara were retrospectively reviewed regarding the fate of acetabular development and physeal growth. The relationship of acetabular development to surgical correction of neck-shaft angle and the frequency of plate closure following surgery were investigated. Acetabular depth was found to improve if neck-shaft angle correction exceeded 140 degrees and did not improve if correction was less than 140 degrees. Capital physeal closure occurred in 89% of hips following valgus osteotomy and was not related to physeal injury during surgery. Normal acetabular development is not stimulated by the proximal femoral configuration of coxa vara and will not improve postosteotomy unless adequate valgus correction is achieved. Premature capital femoral physeal closure is a frequent sequelae of valgus osteotomy leading to relative greater trochanteric overgrowth and development of leg length discrepancy.

Acetabulum↗

Congenital dislocation of the hip. Open reduction by the medial approach.

In a retrospective clinical review of patients with congenital dislocation of the hip who underwent open reduction through the Ludloff medial approach, stability of reduction, acetabular development and presence of avascular necrosis were evaluated in 11 patients with 15 dislocated hips. This approach was reserved for patients younger than 18 months of age in whom closed reduction had failed. Ten patients with 14 hips underwent preoperative traction. All 15 hips at follow-up or just prior to subsequent surgery displayed dysplastic and insufficient acetabular development, with persistent subluxation in nine hips. Subsequent surgery to obtain better concentric reduction and acetabular coverage was performed in six hips, and further surgery is being considered in four other hips. Ten hips showed signs of avascular necrosis of the ossific nucleus, with additional involvement of the growth plate in four hips. The medial approach resulted in inadequate concentric reduction, with a high incidence of avascular necrosis. In the majority of patients in this small series, a secondary procedure was needed to improve hip stability and the acetabular dysplasia.

Braces↗

Occipitoatlantal instability in a child with Kniest syndrome.

A case report of occipitoatlantal instability in a 3-year-5-month-old child with Kniest syndrome is presented. Upper cervical spine instability has not previously been reported in Kniest syndrome. Presenting symptoms are similar to those of atlantoaxial instability, which has been reported in patients with skeletal dysplasia. Our patient was effectively treated with occipito-C2 fusion and halo cast immobilization.

Atlanto-Occipital Joint↗

Calcaneal fractures in children. An evaluation of the nature of the injury in 56 children.

The traditional view of calcaneal fractures in children is that this injury and its consequences are generally less severe than its adult counterpart. The validity of this conception and other ways in which children's fractures differ were examined by a retrospective review of children's injuries. The fracture patterns encountered in children 15 years of age or older resembled those of adults. Intra-articular Type 5 fractures were predominant. Children 14 years of age or younger had predominantly extra-articular fracture patterns, a possible reflection of less frequent mechanisms of vertical compression loading in children and their ability to absorb compression loading. Extra-articular and intra-articular Type 4 fractures were characteristically nondisplaced injuries, with normal calcaneal articulations being preserved in all cases. Unrecognized calcaneal fractures were frequent, reflecting both the difficulty of detecting minimal osseous injury and the benign nature of the unrecognized fracture. Associated fractures of the extremities, twice as frequent in children as adults, and axial skeletal injuries, half as frequent as in adults, should not be overlooked. The prognosis for a normally functioning calcaneus without the presence of post-traumatic arthrosis should be expected in most cases due to the nature of the fracture in children.

Adolescent↗

Intraoperative use of nylon bands in fracture fixation.

Nylon tie bands are introduced as an intraoperative aid in the application of internal fixation. Their use for holding metal plates on reduced fractures is advantageous over metal clamps in that they do not impede access to the fracture site, are easily applied, keep intraoperative injury to soft tissue at a minimum, and reduce manipulatory efforts at the fracture site, decreasing operating time. Scuffing of metal plates is eliminated. A technique for their use is described. Our experience with the nylon tie bands indicates that they are an effective adjunct, as opposed to conventional metal clamps, in open reduction and internal fixation of fractures in our institution.

Bone Plates↗