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Biomedical subjects

M Pope

Publications and source records attributed to M Pope.

At least 55 records · Page 3Linked to original sources

A dynamic material parameter estimation procedure for soft tissue using a poroelastic finite element model.

A three-dimensional finite element model for a poroelastic medium has been coupled with a least squares parameter estimation method for the purpose of assessing material properties based on intradiscal displacement and reactive forces. Parameter optimization may be based on either load or displacement control experiments. In this paper we present the basis of the finite element model and the parameter estimation process. The method is then applied to a test problem and the computational behavior is discussed. Sequential optimization on different parameter groups was found to have superior convergence properties. Some guidelines for choosing the starting parameter values for optimization were deduced by considering the form of the objective function. For load control experiments, in which displacement data is used for the optimization, the starting values for the elastic modulus should be lower in magnitude than an "anticipated" modulus. The permeability starting values should be higher than an anticipated permeability. For displacement control experiments, the reverse is true. The optimization scheme was also tested on data with random variations.

Anisotropy

Induction of Lyt-2+ cytotoxic T lymphocytes following primary and secondary Salmonella infection.

Investigations of the cytotoxic activity of T cells induced following one or two intraperitoneal doses of live Salmonella revealed that cytotoxicity was restricted to the Lyt-2+ T-cell subset and was enhanced following secondary infection with Salmonella. Initial studies using the lectin-dependent cellular cytotoxicity (LDCC) assay detected Lyt-2+ cytotoxic T cells in peritoneal cell suspensions of S. enteritidis 11RX (11RX)-infected mice, with the peak of activity occurring 5 days after infection. This did not correlate with the proliferative activity of these cells, which peaked 10-12 days after infection. Secondary challenge with 11RX or S. typhimurium C5 (C5) induced a rapid increase in the cytotoxic activity of Lyt-2+ peritoneal T cells and was detected even 21 days later. The antigen specificity of some of these cells was confirmed in cytotoxicity assays using P815 tumour cells infected with 11RX organisms as targets. No cytotoxic activity was detected in the spleen cell suspensions of infected (and normal) mice unless the cells were first activated by in vitro culture with concanavalin A (Con A). Both types of activated spleen cells showed LDCC but Salmonella-specific cytotoxic Lyt-2+ T cells were detected only in spleen cell (SC) cultures prepared from mice challenged with a second dose of Salmonella.

Animals

Detection of Salmonella-specific L3T4+ and Lyt-2+ T cells which can proliferate in vitro and mediate delayed-type hypersensitivity reactivity.

This study was based on an initial observation that, although culture of T cells from Salmonella-infected mice with concanavalin A induced both L3T4+ T cells and Lyt-2+ T cells to proliferate, there was a relative increase in the responsiveness of the Lyt-2+ T cells in suspensions harvested from mice with secondary infection. Accordingly, primed T cells, obtained from the peritoneal cavities and spleens of mice that had received one or two intraperitoneal doses of Salmonella were examined for the presence of antigen-specific, class I major histocompatibility complex (MHC)-restricted Lyt-2+ T cells. After primary infection with avirulent Salmonella enteritidis 11RX (11RX) only L3T4+ T cells could be induced to proliferate in response to formalin-killed 11RX organisms, and a second dose of live 11RX did not change the phenotype of the responding T-cell population. In contrast, secondary challenge with S. typhimurium C5 (C5) generated cell populations where both L3T4+ and Lyt-2+ T cells proliferated when cultured with formalin-killed 11RX. Transfer of delayed-type hypersensitivity (DTH) using mixtures of primed T cells and either killed or live Salmonella organisms demonstrated that DTH was mediated by L3T4+ T cells, and secondary infection with either the 11RX or C5 strain did not change this result. However, antigen-specific Lyt-2+ T cells which mediated DTH reactivity were detected using a Salmonella-infected cell line which expressed MHC-coded class I but not class II products. These Lyt-2+ T cells were present in the spleen and peritoneal cavity after secondary infection and in the peritoneal cavity late after a primary infection with 11RX.

Animals

Dendritic cells freshly isolated from human blood express CD4 and mature into typical immunostimulatory dendritic cells after culture in monocyte-conditioned medium.

A procedure has been developed to isolate dendritic cells to a high degree of purity from fresh blood. Prior enrichment methods have relied upon an initial 1-2-d culture period. Purified fresh isolates lack the characteristic morphology, phenotype, and immunostimulatory function of dendritic cells. The purified cells have the appearance of medium sized lymphocytes and express substantial levels of CD4, but lack the T cell molecules CD3, CD8, and T cell receptor. When placed in culture, the cells mature in a manner resembling the previously described, cytokine-dependent maturation of epidermal dendritic cells (Langerhans cells). The cells enlarge and exhibit many cell processes, express much higher levels of major histocompatibility complex class II and a panel of accessory molecules for T cell activation, and become potent stimulators of the mixed leukocyte reaction. Among the many changes during this maturation process are a fall in CD4 and the appearance of high levels of B7/BB1, the costimulator for enhanced interleukin 2 production in T cells. These changes are not associated with cell proliferation, but are dependent upon the addition of monocyte-conditioned medium. We suggest that the freshly isolated CD4-positive blood dendritic cells are recent migrants from the bone marrow, and that subsequent maturation of the lineage occurs in tissues in situ upon appropriate exposure to cytokines.

Antigen-Presenting Cells

Sociogrid analysis of a child and adolescent psychiatric clinic.

The diverse roles of medical health professionals working in a child psychiatry clinic were examined using sociogrid analysis allowing for idiographic and nomothetic analyses, the latter enabling assessment of larger numbers of individuals. Role repertory grid analysis was further used to explore the cognitive structure of the doctor and the nurse. As a result, insight was offered regarding the configuration of the clinic organisation, with detailed evaluation of occupational boundaries and interaction between roles. Central figures in the social network were those of the physician and the parents of the patient. The social worker and the psychologist appeared isolated from the rest of the treatment group and seemed to work independently with the parents, in contrast to the physician who did not relate to either the parent or the patient. Administrators occupied a unique pivotal position between these two core occupational clusters (parents, social worker, patient and psychologist; physician, nursing and care, occupational therapist and physiotherapist).

Adolescent

Malignant benign neonatal sacrococcygeal teratoma.

Thirty-six patients with benign neonatal sacrococcygeal teratoma (SCT) were treated in our medical center from 1972 to 1990. Mean gestational age was 38.6 +/- 3.3 weeks with a mean birth weight of 3,484.0 +/- 938.5 g. Twenty-nine patients (89%) were females. The majority of the tumors (75%) contained cystic components and 96% were Altman classification I and II. The initial surgical removal of the SCT (including the coccyx) was carried out during the first 7 days of life. Six patients (22%) developed recurrence of the tumor. Three were benign and reappeared locally after 12 +/- 3 months and were reexcised. The mean serum alpha-fetoprotein level in this group was 13 +/- 1 g/L. The malignant recurrence (all originally reported as being mature benign SCT) appeared at 20.3 +/- 1.5 months and had markedly elevated serum alpha-fetoprotein levels (7,320 +/- 4,630 micrograms/L). All the patients in this group had multimodal therapy including complete excision of the recurrent tumor. We conclude that SCT, although histologically benign, has an alarming potential to recur either as a benign or malignant tumor during the first 2 years of life. Close follow-up for at least 3 years (frequent examination, serum alpha-fetoprotein, and diagnostic imaging) is recommended for all patients who had undergone excision of SCT in the newborn period.

Combined Modality Therapy

Sonographic estimation of fetal weight based on a model of fetal volume.

OBJECTIVES: To derive a formula for sonographic estimated fetal weight (EFW) based on a two-compartment model of fetal volume and to test it against two widely used formulas, especially at the extremes of fetal weight for which existing formulas are generally inaccurate. METHODS: We analyzed 865 consecutive sonograms that met the following inclusion criteria: singleton pregnancy, normal anatomy, delivery within 3 days of sonography, and measurements of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The weight of the fetal head was modeled to be proportional to HC3, and the weight of the trunk proportional to AC2 x FL. The proportionality constants were found by multiple linear regression on 380 sonograms performed in 1990 (the "derivation set"). The new formula was tested for accuracy of prediction of actual birth weight against the formulas of Hadlock et al and Shepard et al using 485 sonograms from 1991-1992 (the "validation set"). RESULTS: In the derivation set, the formula EFW = (0.23718 x AC2 x FL) + (0.03312 x HC3) was fit; the correlation with actual birth weight had an r value of 0.996. In the validation set, the new formula produced smaller systematic errors and smaller absolute errors than either the Hadlock or Shepard formula both overall and in fetal weight strata from less than 1000 g to over 4000 g. CONCLUSION: The new formula makes geometric sense and provides accurate estimates of fetal weight across a broad range of weights.

Birth Weight

Effect of tension and placement of a prosthetic anterior cruciate ligament on the anteroposterior laxity of the knee.

We wished to determine the optimal tension required to restore normal joint laxity to anterior cruciate ligament (ACL)-deficient knees using a braided polyethylene ACL prosthesis (PACL). In 10 cadaveric specimens, we measured the anteroposterior (AP) laxity of the intact knee at 10 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion. The ACL was then removed and replaced with the PACL using tunnel-tunnel (T-T) and "over-the-top" (OTT) placement techniques. In both positions, the PACL was initially tensioned to 0, 9, 18, and 27 N with the knee flexed to 30 degrees. AP joint laxity was then measured at each flexion angle. With an increase in initial tension, there was a corresponding decrease in AP laxity. At 30 degrees and 90 degrees of flexion, AP laxity was not significantly different from normal using T-T placement and an initial tension of 0 N. At 90 degrees of flexion, AP laxity was not significantly different from normal using OTT placement at 0 or 9 N of initial tension. For both positions, all other tension levels and flexion angles constrained AP laxity. No laxity differences were detected between the OTT and T-T positions at any flexion angle. The variability in AP laxity of the T-T position was significantly greater than OTT. With a 150-N anterior shear force applied to the proximal tibia, the maximum tensions developed in the PACL were not significantly different between the two positions except at 90 degrees. The results suggest that implantation of the PACL is best performed using OTT positioning with an initial tension of 0 N applied at 30 degrees of knee flexion.

Adult

Effect of one-legged exercise on the strength, power and endurance of the contralateral leg. A randomized, controlled study using isometric and concentric isokinetic training.

The purpose of this investigation was to study the effect of one-legged exercise on the strength, power and endurance of the contralateral leg. The performance of the knee extensor and flexor muscle of 20 healthy young adults (10 men and 10 women) was first tested by Cybex II+ and 340 dynamometers. Then 10 subjects were chosen at random to train using one leg three times a week for 7 weeks whilst the other 10 served as controls. During the 8th week, the tests were repeated. Both quadriceps and hamstring muscles of the trained subjects showed a cross-transfer effect from the trained limb to the untrained side. This concerned the strength and power, as well as endurance characteristics of these muscles. The average change in peak torque of the quadriceps muscle was +19% (P less than 0.001) in the trained limb, +11% (P less than 0.01) in the untrained limb and 0% in the control limbs. In hamstring muscles the changes were +14% (P less than 0.01), +5% and -1%, respectively. Concerning muscle endurance (work performed during the last 5 contractions in the 25-repetition test) the corresponding changes were +15% (P less than 0.01), +7% (P less than 0.01), and -1% in quadriceps muscle, and +17% (P less than 0.05), +7%, and -3% in hamstring muscles. The average strength benefit in the untrained limb was +36% (hamstring muscles) and +58% (quadriceps muscle) of that achieved in the trained limb. Untrained hamstring muscle showed better benefits in the endurance parameters than in strength or power parameters, while in the quadriceps muscle this effect was reversed. A positive relationship was observed between the changes (greater improvement in the trained limb resulted in greater improvement in the untrained limb) (hamstring muscles: r = 0.83, P less than 0.001, quadriceps muscle: r = 0.53, P less than 0.001). In endurance parameters, this relationship was almost linear while in the strength and power parameters the results were more in favour of a curvilinear relationship with limited benefit.

Adult

Measurement of height loss during whole body vibrations.

An experimental, in vivo study was performed to measure height changes in subjects exposed to whole body vibrations while seated. Twelve women, with an average age of 22 years, were exposed to sinusoidal vibrations for 5 mins. The vibration frequency was 5 Hz, and the acceleration was 0.1 g Rms. The height loss stemming from vibration exposure was compared with that experienced while sitting without being subjected to vibrations. The height losses that always occurred from the two exposures were corrected for the effect of posture change. The height loss from vibration was significantly greater than when no vibration was present. Height loss due to posture change was responsible for approximately 50% of the total height loss. From this study it was concluded that whole body vibrations cause increased height loss.

Adult

Antigen-presenting characteristics of peritoneal cells of Salmonella enteritidis 11RX-infected mice.

Investigation of the possibility that infection with intracellular bacterial parasites such as Salmonellae may modulate the function of antigen-presenting cells (APC) revealed no major change in APC function of peritoneal cells (PC) harvested from the peritoneal cavity of mice 1-3 days after intraperitoneal immunization with S. enteritidis 11RX. Analysis of the phenotype of the Salmonella-primed T cells which responded when cultured with PC from either normal or infected mice and Salmonella-antigen showed that only L3T4+ T cells proliferated. This was also true when PC from normal and infected mice were compared for their ability to induce allogeneic responses; both L3T4+ and Lyt-2.2+ T cells were induced to proliferate, with the majority belonging to the class I restricted, Lyt-2.2+ phenotype. Significant levels of alloantigen-specific Lyt-2.2+ cytotoxic T-cell activity were also induced in both types of cultures. However, a minor population of adherent cells which inhibited Salmonella antigen-specific T-cell proliferation in vitro was detected in peritoneal cell suspensions harvested 3 days after intraperitoneal immunization with S. enteritidis 11RX. Further characterization of these peritoneal cells revealed that they also inhibited the induction of in vitro T-cell responses to alloantigens. It is likely that the cells mediating these inhibitory effects belonged to a macrophage-like subset.

Animals

A technique for needle localization in paraspinal muscles with cadaveric confirmation.

Invasive electromyography (EMG) of the paraspinal muscles is useful in clinical and research settings. No technique for localization of the needle in specific fascicles has been validated. Recent descriptions of the segmented innervation of the multifidus imply that such a technique would add greatly to the EMG determination of root level of a radiculopathy. We have developed a technique for localization which relies on palpation of bony structures and needle insertion at certain angles and depths. The technique was evaluated by injecting latex dye in 199 locations in 13 cadavers. Dissection demonstrated that the technique was accurate in 91 of 112 injections into specific fascicles of the multifidus (originating from different spinous processes), 39 of 43 injections into the longissimus, and 35 of 44 injections into the iliocostalis. Certain types of errors would not have occurred with the aid of EMG in vivo. When these are added to the correct injections, accuracy improves 97%, 93%, and 82%, respectively. The technique described here should be useful for kinesiological studies, biopsies and injections, as well as for the EMG confirmation of a radiculopathy.

Back

Injuries to the posterior cruciate ligament of the knee.

The posterior cruciate ligament (PCL) is the strongest ligament about the knee and is approximately twice as strong as the anterior cruciate ligament. Its main function is to prevent the posterior dislocation of the tibia in relation to the femur, providing 95% of the strength to resist the tibial posterior displacement. Along with the anterior cruciate ligament (ACL) the PCL controls the passive 'screw home' mechanism of the knee in terminal knee extension. It also provides mechanical support for the collateral ligaments during valgus or varus stress of the knee. PCL ruptures are uncommon apparently due to its strong fibre structure. The most frequent injury mechanism in isolated PCL tears is a direct blow on the anterior tibia with the knee flexed thus driving the tibia posteriorly. Automobile accidents (in which the knee hits the dashboard) and soccer injuries (in which an athlete receives a blow to the anterior surface of the tibia during knee flexion) characteristically produce this type of injury. In other PCL injury mechanisms (hyperextension, hyperflexion or rotational injuries with associated valgum/varum stress), other knee structures are also often damaged. The most characteristic diagnostic finding in a knee with a PCL rupture is the 'posterior sag sign' meaning the apparent disappearance of the tibial tubercle in lateral inspection when the knee is flexed 90 degrees. This is due to gravity-assisted posterior displacement of the tibia in relation to the femur. A positive posterior drawer test performed at 90 degrees of flexion and a knee hyperextension sign are sensitive but nonspecific tests. False negative findings are frequent, especially in acute cases. If necessary, the clinical diagnosis of the PCL tear can be verified by magnetic resonance imaging, examination under anaesthesia, arthroscopy, or a combination of these modalities. If a PCL avulsion fragment has been dislocated, surgical treatment is recommended. In isolated, complete midsubstance tears of the PCL the majority of the recent studies recommend conservative treatment, since abnormal residual posterior laxity1 in most of these knees is consistent with functional stability and minimal symptoms. This has been the case even in athletes. In isolated PCL tears, the outcome seems to depend more on the muscular (quadriceps) status of the knee than on the amount of residual posterior laxity. Therefore, the conservative treatment protocol emphasises intensive quadriceps exercises, and only a short (under 2 weeks) immobilisation period followed by early controlled activities and early weightbearing.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Longitudinal crack propagation in bone around femoral prosthesis.

Intraoperative femoral fracture is a well-recognized technical complication of cementless total hip arthroplasty. This study was designed to establish an in vitro model for initiation and propagation of fractures of the proximal femur in cementless THA and to assess the effect of fracture fixation in the form of cerclage wiring and drilling a hole in the distal extent of the fracture line. Fourteen human anatomic femur specimens were studied. Longitudinal cracks were made and propagation was performed on a materials testing system machine. A drill hole at the tip of a longitudinal crack does not prevent crack propagation. However, cerclage wiring has a statistically significant effect (p less than 0.025) on the ability of the fractured femur to withstand increased load.

Aged

Presentation of Salmonella antigens by peritoneal cells of normal and Salmonella-infected mice.

A comparison of the ability of normal peritoneal cells (PC) and those harvested from mice 1-3 days after intraperitoneal immunization with live Salmonella enteritidis 11RX (11RX) to present antigen to 11RX-primed T cells was made using formalin-killed 11RX and a soluble 11RX antigen extract as antigens. Unfractionated PC and the adherent and non-adherent PC populations were analysed separately and the effects of the lysosomal function-impairing drug chloroquine and the fixative paraformaldehyde, used before or after antigen-pulsing, were also determined. The results presented indicate that immunization with live 11RX did not induce any detectable modulation of APC function which could account for the ability of live 11RX to induce cell-mediated immune responses involving Lyt 2+ T cells.

Animals

Mechanical evaluation of external fixators used in limb lengthening.

Four external fixator systems (five configurations) used for limb lengthening were tested to determine the fixator stiffness and the fracture gap rigidity. There was a statistical difference between fixators in all modes of loading with respect to stiffness, shear, and axial motion. The fixators were graded to determine their relative stiffness, shear rigidity, and axial rigidity. The EBI Orthofix proved to be the most rigid fixator relative to the configurations tested with minimal shear or axial motion at the fracture site. The Ilizarov tibial configuration was the least rigid, demonstrating more shear and axial motion at the fracture gap. The Ilizarov femoral system combined excellent stability and shear resistance with preservation of axial dynamization. Fixators with a high stiffness provide less motion at the fracture site, which may cause stress shielding of the osteotomy. Fixators that provide more motion at the fracture gap are less stable. These data may be useful in determining which fixator may be ideal for a particular clinical situation.

Biomechanical Phenomena