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Biomedical subjects

T D Brown

Publications and source records attributed to T D Brown.

At least 163 records · Page 9Linked to original sources
PubMed1991

Stress wave effects in a finite element analysis of an impulsively loaded articular joint.

A dynamic contact finite element formulation was used to study transient stresses in the impulsively loaded rabbit knee, an established experimental model of mechanically induced osteoarthrosis. The computations were used to test the hypothesis that stress wave propagation and reflection, from juxtarticular interfaces of material property discontinuity, could be responsible for markedly increased levels of transient local cartilage stress. The finite element results demonstrated intuitively credible stress wave propagation and interfacial reflection phenomena. However, the magnitude of these waves was not nearly large enough to appreciably alter the quasi-static stress distributions otherwise prevailing. Thus, local stress wave reflection from interfaces of modulus discontinuity (for example the cartilage/subchondral plate) probably does not contribute appreciably to the heightened tissue sensitivity to impulsive loading experimentally observed in this animal model.

Animals↗
PubMed1990

Phase I and clinical pharmacology trial of 502U83 using a monthly single dose schedule.

502U83 is an arylmethylaminopropanediol derivative exhibiting significant antineoplastic activity in a number of murine and human tumor models. In this Phase I trial, a 1-h or 4-h infusion of the agent was administered i.v. in 250 ml of 5% dextrose in water every 28 days. Fifty-three courses at doses of 25 to 2000 mg/m2 were administered to 36 patients with refractory solid tumors. Prolongation of the PR, QRS, and QT intervals on electrocardiograms was dose limiting at 2000 mg/m2. This prolongation appeared dose related and was reversible upon discontinuation of the infusion. No hematological toxicity was observed. Other toxicities included only sporadic and mild to moderate nausea and vomiting. No tumor responses were noted. 502U83 plasma concentrations were determined by high-pressure liquid chromatography. Complete pharmacokinetic profiles were obtained for 21 of the 36 patients. After infusion, plasma concentrations declined in a biexponential or in a triexponential manner with a harmonic mean terminal t 1/2 of 8.83 h. Using a three-compartment model, the mean apparent volume of distribution at steady state and total-body clearance were 195 liters/m2 and 42.5 liters/h/m2, respectively, indicative of extensive tissue distribution. No correlation could be found between the pharmacokinetic parameters and prolongation of the cardiac conduction intervals. Because of the cardiac effects with the drug, the schedule of administration of 502U83 used in this study cannot be recommended.

Adult↗
PubMed1990

The effects of contact pressure elevations and aseptic necrosis on the long-term outcome of congenital hip dislocation.

The relationship between excessive articular contact pressure, aseptic necrosis, and the long-term outcome with unilateral congenital dislocation of the hip (CDH) was studied in a series of 84 patients treated by closed reduction and followed for an average of 29.2 years. Contact stress was estimated from archived radiographs taken at the time of maturity and at several follow-up visits. At a recent review, each patient was rated both clinically for pain and function and radiographically for deformity, degeneration, and aseptic necrosis. For each of 431 archived films, articular contact stress (force/area) was estimated mathematically, based upon a frontal plane equilibrium (force) analysis and a landmark-based inference of three-dimensional head surface (area). Good correlation with final deformity (Spearman rho = 0.78) was obtained when the hips were ranked in terms of a new cumulative overpressure index Pc, defined as a time-pressure product involving years of pressure exposure beyond a 2 MPa pressure damage level. An unsatisfactory outcome occurred in 90.4% of the hips experiencing Pc greater than 10 MPa-years (most of which had aseptic necrosis involvement), whereas the outcome was satisfactory in 80.9% of hips with Pc less than 10 MPa-years.

Adolescent↗
PubMed1990

Flow field mapping in the anesthetized rat.

This study measured the hemodynamics of peripheral arterial sites in the rat, using 20 MHz pulsed ultrasonic Doppler velocimeter (PUDVM) methods. The lower extremities of 14 male Sprague-Dawley rats were studied. The targeted sites included the abdominal aorta, external iliac, proximal femoral, mid-femoral, and saphenous arteries. The hemodynamic variables of pulse period, maximum centerline velocity, lumen diameter, and mean volumetric flow were calculated interactively from temporal-spatial plots of local velocity distributions. An analysis of variance revealed significant differences between right and left sides for lumen diameter (P = 0.028) and mean volumetric flow (P less than 0.0001). The analysis showed no statistical difference for pulse period (P = 0.0836) among sites. However, three distinct groupings of sites: 1) abdominal aorta, 2) external iliac, proximal femoral, and mid-femoral arteries, and 3) saphenous artery were noted for the remaining hemodynamic variables (P less than 0.05). These results indicate that three hemodynamically distinct regions are available for microvascular research in the rat lower extremity arterial tree.

Anesthesia, General↗
PubMed1990

Hypersensitivity reactions to trimetrexate.

Trimetrexate is a nonclassical antifol currently being tested for efficacy in cancer patients and as an antiparasitic agent against Pneumocystis carinii pneumonia in AIDS patients. We have now received the first reports of hypersensitivity reactions in Phase II cancer trials. Two types of reactions were noted. The most severe reaction, immediate hypotension with loss of consciousness, occurred in only one patient. Four other patients exhibited an immediate systemic effect with one or more of the following symptoms: facial flushing, fever, shaking, pruritus, bronchospasm, periorbital edema, and difficulty in swallowing. Immediate hypersensitivity should now be considered a known side effect of trimetrexate therapy, occurring in less than 2% of patients.

Adult↗
PubMed1990

Some effects of global joint morphology on local stress aberrations near imprecisely reduced intra-articular fractures.

Cadaver models of contact pressure aberration near displaced intra-articular fractures complement clinical experience, but inter-specimen variability often complicates interpretation of in vitro data. A contact finite element formulation is here used to study juxta-articular stress distributions in a plane strain model of tibial plateau step-off incongruity. Attention is focused on the influence of global morphologic parameters: intact joint surface curvatures, cartilage thickness, and cartilage stiffness. The computed stress distributions agreed well with experimental recordings for a typical 3 mm incongruity in an otherwise normal joint. Both decreased cartilage thickness and increased cartilage modulus led to elevations in the peak local contact stress, and to concentration of contact stress near the edge of the step-off incongruity. Similar effects were seen when reduction of global joint congruency was modelled by decreasing the concavity of the tibial plateau. While the observed degree of coupling between global morphology and local stress aberration was by no means negligible, the sensitivity of the stresses to variations in individual parameters was relatively mild. This suggests that the finite element results will be useful for experimental data interpretation.

Biomechanical Phenomena↗
PubMed1990

Contribution of passive tissues to the intersegmental moments at the hip.

Many anatomic structures around the hip contribute either actively (i.e., muscle contractile elements) or passively (i.e., capsule, ligaments, non-contractile portions of muscles) to the intersegmental resultant forces and moments. Investigators have often assumed that the passive elements contribute negligibly to those moments, but without substantial supporting data. We explored this assumption by measuring the 'passive moments' in 15 normal subjects from near full extension to 60 degrees of hip flexion at speeds used in slow and normal walking. The data suggest that throughout most of the gait cycle and normal stair climbing, the passive structures contribute a small portion of the total moment, usually well less than 10%. Thus, for this limited range of activities, the assumption of negligible contribution of passive structures is reasonable.

Activities of Daily Living↗
PubMed1990

Toward an identification of mechanical parameters initiating periosteal remodeling: a combined experimental and analytic approach.

The ability of bone to adapt to its mechanical environment is well recognized, although the specific mechanical parameters initiating or maintaining the adaptive responses have yet to be identified. Recently introduced mathematical models offer the potential to aid in the identification of such parameters, although these models have not been well validated experimentally or clinically. We formulated a complementary experimental/analytic approach, using an animal model with a well-controlled mechanical environment combined with finite element modeling (FEM). We selected the functionally isolated turkey ulna, since the loading could be completely characterized and the periosteal adaptive responses subsequently monitored and quantified after four and eight weeks of loading. Known loads input into a three-dimensional, linearly elastic FEM of the ulna then permitted full-field mechanical characterization of the ulna. The FEM was validated against a normal strain-gaged turkey ulna, loaded in vivo in an identical fashion to the experimental ulnae. Twenty-four candidate mechanical parameters were then compared to the quantified adaptive responses, using statistical techniques. The data supported strain energy density, longitudinal shear stress, and tensile principal stress/strain as the mechanical parameters most likely related to the initiation of the remodeling response. Model predictions can now suggest new experiments, against which the predictions can be supported or falsified.

Adaptation, Physiological↗
PubMed1990

Identification of a new membrane-associated polypeptide specified by the coronavirus infectious bronchitis virus.

Nucleotide sequences from the third open reading frame of mRNA D (D3) of infectious bronchitis virus (IBV) were expressed in bacteria as part of a fusion protein with beta-galactosidase. Antiserum raised in rabbits against this fusion protein immunoprecipitated from IBV-infected chick kidney or Vero cells a polypeptide of 12.4K, the size expected for a D3-encoded product. The D3 polypeptide is apparently non-glycosylated, and appears to be associated with the membrane fraction of infected cells, as judged by cell fractionation and immunofluorescence.

Amino Acid Sequence↗
PubMed1990

A dynamic finite element analysis of impulsive loading of the extension-splinted rabbit knee.

A dynamic nonlinear finite element model was developed to study juxtarticular stresses in the splinted rabbit knee, an established laboratory model for creating osteoarthrosis due to impulsive loading. Plane strain finite element results were validated by comparison with corresponding experimental data. Parametric effects studied included the input tibial displacement speed, the local bone density distribution, and the modulus of cartilage and subchondral bone. While the computed resultant contact force magnitude was sensitive to a number of model parameters, the stress patterns, when normalized to a given resultant force magnitude, were not. Despite comparable force peaks, the finite element results showed approximately six-fold higher effective strain rate levels for a severely impulsive loading protocol known to induce rapid osteoarthrosis, versus those for a mildly impulsive loading protocol not usually associated with cartilage damage. A propensity for elevated shear in the deep cartilage layer near the contact periphery, observed in nearly all computed stress distributions, is consistent with previous experimental findings of fissuring at that level in the impulsively loaded rabbit knee.

Animals↗
PubMed1990

Phase II evaluation of recombinant gamma-interferon in patients with advanced pancreatic carcinoma: a Southwest Oncology Group study.

Thirty evaluable patients with advanced carcinoma of the pancreas received treatment with either daily x 5 bolus or continuous infusion x 5 days recombinant gamma-interferon. No responses were noted. Major toxicities included fever, hypotension, and flu-like symptoms. gamma-Interferon does not appear to be an active single agent for patients with advanced pancreatic cancer.

Aged↗