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Biomedical subjects

D A Turner

Publications and source records attributed to D A Turner.

At least 73 records · Page 4Linked to original sources

Relative risks of ventriculostomy infection and morbidity.

Ventricular catheter placement is a common procedure for the management of increased intracranial pressure. Hypotheses regarding the etiology of infection of catheters center on two alternative assumptions: 1) contamination leading to infection occurs at the time of catheter insertion, implying that catheter duration has minimal effect on infection risk; and 2) infection of catheters derives from catheter contamination after insertion, suggesting that duration of catheter use may significantly affect infection risk. We have studied the relative complication rate of ventricular catheter insertions using a retrospective approach (n = 161 patients and 253 catheter insertion procedures). The overall infection rate was 4.1%, but the daily infection hazard increased exponentially with time, to a maximum daily rate of 10.3% by day 6 of catheter insertion. This increasing risk appears most consistent with the second hypothesis. The risk of non-infectious complications was 5.6%, including hemorrhagic occurrences and misplacement severe enough to require a new catheter insertion. The daily hazard of infection approximately equalled the non-infectious risk of routine catheter replacement by day 5. Additional prospective data on the daily risk of CSF infection and the appropriateness of antibiotic prophylaxis either at the time of ventricular catheter insertion or continued through the catheter's presence may be required to both definitively identify which hypothesis of infection risk is correct and whether antibiotics can significantly ameliorate this risk.

Catheters, Indwelling↗

Semiautomatic evaluation of left ventricular diastolic function with cine magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Cine magnetic resonance (MR) imaging is a relatively new technique that can be used to study cardiac function with high spatial and temporal resolution. However, detailed functional analysis of the entire cardiac cycle with cine MR imaging is time consuming and labor intensive. We analyzed diastolic function using a semiautomatic routine that reduces the time necessary for analysis. METHODS: Twenty subjects (10 normal control subjects and 10 patients with isolated diastolic dysfunction) were examined. Short-axis cine MR images were obtained at 32 phases of the cardiac cycle. A semiautomatic boundary-finding routine was used to determine left ventricular (LV) volumes at each phase. Volume-versus-time and first-derivative curves were created from these data. Several parameters derived from the MR imaging curves were used to characterize diastole. RESULTS: Two parameters--the ratio of early peak filling rate to late peak filling rate and the percentage of filling during early diastole--perfectly distinguished subjects with LV diastolic dysfunction from the normal control subjects. The semiautomatic analysis method substantially reduced the time necessary for analyzing the MR imaging data, compared with manual analysis. CONCLUSION: Cine MR imaging, especially with time-saving techniques such as our service automatic analysis method, has promise as a research and clinical tool in evaluating LV diastolic function.

Adult↗

Severity of articular cartilage abnormality in patients with osteoarthritis: evaluation with fast spin-echo MR vs arthroscopy.

OBJECTIVE: The purpose of this study was to assess the accuracy of fast spin-echo MR imaging for depicting the severity of articular cartilage abnormalities in patients with osteoarthritis. SUBJECTS AND METHODS: Twenty-three subjects (10 volunteers less than 35 years old and 13 patients with proved, symptomatic, idiopathic osteoarthritis of the knee of 6 months' to 10 years' clinical duration) underwent fast spin-echo MR imaging of the knee. Two observers graded each articular surface using a five-category scale that took into account abnormalities in the signal intensity of cartilage as well as thickness and contour. The 13 patients also underwent arthroscopic evaluation (as part of a separate protocol) in which cartilage abnormalities were graded by using a similar five-category grading scale, without the graders knowing the results of MR imaging. Articular cartilage was assumed to be normal in the volunteers. RESULTS: One hundred thirty-seven joint surfaces were graded; one surface was obscured by artifact and was excluded. The Spearman rank linear correlation between arthroscopic and MR grading was highly significant (p < .002) for each of the six articular regions evaluated. The MR and arthroscopic grades were the same in 93 (68%) of 137 joint surfaces, they were the same or differed by one grade in 123 surfaces (90%), and they were the same or differed by one or two grades in 129 surfaces (94%). CONCLUSION: Our results suggest that fat-presaturated fast spin-echo MR imaging depicts the severity of articular cartilage abnormalities in osteoarthritis with reasonable accuracy, as compared with arthroscopic evaluation as the standard of reference.

Adult↗

MR spectroscopy and imaging of breast cancer. A brief history.

The application of nuclear magnetic resonance (NMR) techniques to the diagnosis of breast cancer has come a long way in a relatively brief period of time. Early investigators focused on diagnosis by in vitro NMR spectroscopy. More recently, in vivo NMR spectroscopy, contrast-enhanced MR imaging, and MR imaging-controlled biopsy have been investigated. The author predicts that MR imaging of breast cancer quickly will make the transition from experimental method to useful clinical technique.

Biopsy, Needle↗

3-dimensional optimization of multiple arcs for stereotactic radiosurgery.

PURPOSE: During linear accelerator-based radiosurgery, the physicians and physicists need to determine which combination of treatment arcs are "best" with regard to target coverage and incidental dose to adjacent structures. This is a complex problem, especially when targets are geometrically close to critical structures. The purpose of this article is to present a method to mathematically determine a set of arcs to produce desired target and normal structure dose distributions in linear accelerator radiosurgery. METHODS AND MATERIALS: Nonlinear least squares regression was used to determine the table angles and gantry angle arc ranges and their associated beam weights appropriate to linear accelerator radiosurgery. RESULTS: Three cases are presented: (a) critical structure close to target volume; (b) target volume too large for the largest collimator to cover the volume with one isocenter and a standard plan; (c) target volume located within one critical structure and close to another critical structure. The optimized treatment plans are all shown to be superior to a defined standard plan. CONCLUSION: The method successfully enables one to determine nonstandard arcs which achieve the desired results. In particular, the method enables one to find clinical treatment solutions, even when the desired results cannot be a priori defined.

Humans↗

Induction of neuronal morphology in adrenal chromaffin cells cocultured with denervated Schwann cells.

We have studied the interactions of adrenal chromaffin and Schwann cells in a coculture system to observe whether denervated Schwann cells induce and support chromaffin cell differentiation in a manner analogous to nerve growth factor (NGF). Schwann cells induce both the accumulation of intense clumps of cocultured chromaffin cells on their surfaces and intense neurite outgrowth. This interaction is not blocked by antibodies to NGF or laminin. Conditioned medium from Schwann cell cultures fosters neurite outgrowth in chromaffin cells in a fashion qualitatively similar to NGF. Our data indicate that denervated Schwann cells exert a profound aggregating and differentiating effect upon chromaffin cells, inducing the expression of a neuronal phenotype via a predominantly NGF-independent mechanism.

Adrenal Glands↗

Bayesian analysis of mixtures applied to post-synaptic potential fluctuations.

Bayesian inference techniques have been applied to the analysis of fluctuation of post-synaptic potentials in the hippocampus. The underlying statistical model assumes that the varying synaptic signals are characterized by mixtures of (unknown) numbers of individual gaussian, or normal, component distributions. Each solution consists of a group of individual components with unique mean values and relative probabilities of occurrence and a predictive probability density. The advantages of bayesian inference techniques over the alternative method of maximum likelihood estimation (MLE) of the parameters of an unknown mixture distribution include the following: (1) prior information may be incorporated in the estimation of model parameters; (2) conditional probability estimates of the number of individual components in the mixture are calculated; (3) flexibility exists in the extent to which the estimated noise standard deviation indicates the width of each component; (4) posterior distributions for component means are calculated, including measures of uncertainty about the means; and (5) probability density functions of the component distributions and the overall mixture distribution are estimated in relation to the raw grouped data, together with measures of uncertainty about these estimates. This expository report describes this novel approach to the unconstrained identification of components within a mixture, and provides demonstration of the usefulness of the technique in the context of both simulations and the analysis of distributions of synaptic potential signals.

Action Potentials↗

Scientific and ethical concerns in neural fetal tissue transplantation.

This report presents a brief overview of the medical and ethical issues involved with the procurement, preparation, safety, efficacy, and subject protection of human fetal central nervous system tissue in the context of neural transplantation. The ethical perspectives from which to view the clinical use of fetal tissue include the following: 1) that fetal tissue from elective abortions is a surgical specimen; 2) that the use of such tissue involves fetal experimentation in which the fetus is a subject; and 3) that fetal tissue is considered as a cadaveric organ specimen, similar to other organs, but with special considerations compared with adult cadaveric tissue. The latter approach appears to be the most applicable and is parallel to the use of cadaveric organs and tissues after a declaration of brain death. Additional issues include the following: 1) the safety and quality of fetal tissue for implantation; 2) the hypothesis that "legitimization" and "redemption" (potentially positive effects of tissue donation in general) may lead to an increase in elective abortion rates; 3) the ethical issues of the validity and value of human experimentation involving neural grafting; and 4) the type of consent to be obtained and the appropriate timing. Elective abortions, however, probably will continue to be the primary source of fetal tissue for grafting for some time, until other tissue sources become available.

Aborted Fetus↗

Collagen production by human smooth muscle cells isolated during intestinal organogenesis.

The extracellular matrix influences organogenesis by modulating cell behavior. In humans, collagen is the major matrix constituent of the adult intestinal wall and is synthesized by smooth muscle cells. The objective of the current study was to examine collagen production by fetal human intestinal smooth muscle cells isolated during intestinal morphogenesis. Techniques were developed for the isolation and culture of human fetal intestinal smooth muscle cells. The cultured cells were confirmed as muscle by immunohistochemical stains for cytoskeletal filaments and documentation of contractile behavior. In culture, these cells stained for mesenchymal and muscle cytoskeletal proteins: vimentin, actin, and desmin, and did not stain for neural or epithelial markers. The muscle cells contracted in response to acetylcholine, in contrast to human fetal dermal fibroblasts which did not contract appreciably. Collagen production was assayed by the uptake of [3H]-proline into collagenase-digestible protein. Collagen production was greatest at 11 weeks gestation, the youngest age studied. By 20 weeks gestation, collagen production had decreased to adult levels. However, when compared to another matrix-producing fetal mesenchymal cell, the dermal fibroblast, intestinal smooth muscle cells produced twice as much collagen. Collagen types were determined by polyacrylamide slab gel electrophoresis. Smooth muscle cells predominantly produced types I and III collagen alpha chains. Therefore, collagen production is a significant function of human fetal intestinal smooth muscle cells, and probably plays a major role in the development of intestinal structure. The in vitro model presented here provides a means of studying the regulation of this collagen production throughout intestinal organogenesis.

Collagen↗

Anatomical and physiological localization of prelabeled grafts in rat hippocampus.

Dissociated rat fetal hippocampal cells were grafted into normal adult rats. The fetal cells were incubated with one of a number of fluorescent compounds at the time of the dissociation to facilitate identification of the individual grafted cells. The fluorescent labels which were analyzed for this purpose included rhodamine latex microspheres, Cascade blue latex beads, rhodamine-dextran-amine, DiI, and carboxyfluorescein ester. The labeled cells were stereotaxically placed as a suspension into normal rat host hippocampi. The rats were sacrificed 2 to 6 weeks after the grafting for in vitro physiological recordings, and the prelabeled grafts were located using fluorescence optics. During intracellular recordings neurons within the prelabeled grafts were injected with Lucifer yellow to visualize the morphology and integration of neuronal processes within the host. Following the recordings the host slices with the grafts were fixed in 4% paraformaldehyde for anatomical analysis. The ability to prelabel cellular grafts allows subsequent anatomical and physiological analysis of the integration of grafted neurons at the resolution of a single neuron. Such an analysis will improve our understanding of the survival, differentiation, migration, and integration of the grafted neurons and their potential to replace lost function in the lesioned hippocampus.

Animals↗

Fluorescent labeling of dissociated fetal cells for tissue culture.

The ability to pre-label cells used in transplantation experiments would have the potential benefits of identification of cell type and associated processes and the analysis of graft migration in the host. We have used an in vitro tissue culture system as a model to test several fluorescent dyes for this application. Fetal rat hippocampal tissue (E17-E18) was dissociated and incubated in the presence of carboxyfluorescein ester (CFSE), rhodamine-B dextran amine (RBD), DiI, or rhodamine-labeled latex microspheres. Cells were cultured in defined medium for up to 1 month. Cells labeled with CFSE were initially bright but faded over several days. RBD labeled the soma of cells, but fluorescence intensity was lost over a period of a few weeks. Cells labeled with DiI possessed brilliant staining of neuronal processes for weeks. Latex microspheres brightly labeled the soma but not the processes of neurons; fluorescent debris and sterility were problems with this label. We conclude that CFSE and DiI have significant potential usefulness in vitro as markers of cell viability and process formation with mammalian fetal CNS cells, whereas RBD is much less permanent. Latex microspheres may be suitable for pre-labeling of cells for transplantation if purification and sterility can be enhanced over present preparations.

Animals↗

Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-induced hemiparkinsonism on the kinematics of a two-dimensional,multijoint arm movement in the rhesus monkey.

The effects of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) on the kinematics of two-dimensional arm movements in the primate were studied. Two rhesus monkeys were trained to move a manipulandum at various distances and directions in horizontal space from a centrally located target box. Several kinematic parameters including reaction time, and time and amplitude of peak tangential velocity were analysed. Following an extensive control evaluation period, the animals were unilaterally injected with MPTP into the internal carotid artery. The animals were restudied for up to 289 days following induction of hemiparkinsonism. Larger-amplitude movements (greater than 3.5 cm) were more severely affected than smaller amplitude movements. Both animals exhibited marked changes in the arm movements including increased time-to-peak velocity and decreased peak velocity. The degree of the kinematic changes was spatially dependent, with the decrease in velocity as well as the time-to-peak velocity being more pronounced for the larger, outward movements. Reaction time increased but showed no spatial dependency. Kinematic deficits persisted over the entire time-period studied. Also, the kinematic changes were reduced by levo-3,4 dihydroxyphenylalanine in a dose-dependent manner. Tyrosine hydroxylase immunohistochemistry documented extensive cell loss in the substantia nigra. These results show that both the timing as well as the amplitude of the velocity profiles are disrupted by MPTP consistent with the known akinesia and bradykinesia of parkinsonism. Although abnormalities were present for all directions and distances, a spatial dependency to the deficits was detected. The observation of more pronounced changes for larger, outward movements suggests a role for the basal ganglia in production of larger-amplitude movements directed away from the body.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes.

Forty-three patients were treated with extended field irradiation for periaortic metastasis from carcinoma of the uterine cervix (FIGO stages IB-IV). Twelve patients (28%) remained continuously free of disease to the time of analysis or death from intercurrent disease, 20 (46%) had persistent cancer within the pelvis, 11 (26%) had persistent periaortic disease, and 23 (53%) developed distant metastasis. The actuarial 5-year survival rate was 32%. The results correlated well with the periaortic tumor burden at the time of irradiation. None of 19 patients (0%) with microscopic or small (less than 2 cm) periaortic disease had periaortic failures, compared to 29% (4/14) of those with moderate-sized (2-5 cm) disease and 70% (7/10) of those with massive (greater than 5 cm) periaortic metastasis. Similarly, the 5-year survival rates were 50% (6/12) with microscopic disease, 33% (2/6) with small gross disease, 23% (3/13) with moderate-sized disease, and 0% (0/10) with massive periaortic metastases. Only 10% (1/10) of patients whose tumor extended to the L1-2 level survived 5 years, compared with 31% (9/29) of those whose disease extended no higher than the L3-4 level. The periaortic failure rates correlated to some extent with the dose delivered through extended fields, although the difference was not statistically significant. Only 8% (1/13) of those who had undergone extraperitoneal lymphadenectomies developed small bowel complications, compared with 25% (7/29) of those who had had transperitoneal lymphadenectomies. The incidence of small bowel obstruction was 8% (1/13) following periaortic doses of 4000-4500 cGy, 10% (1/10) after 5000 cGy, and 32% (6/19) after approximately 5500 cGy. From this, we concluded that the subset of patients who would benefit most from extended field irradiation are those in whom the residual disease in the periaortic area measures less than 2 cm in size at the time of treatment, whose disease extends no higher than L3, and whose cancer within the pelvis has a reasonable chance of control with standard radiation therapy techniques.

Adult↗

Sustained release of nerve growth factor from biodegradable polymer microspheres.

Although grafted adrenal medullary tissue to the striatum has been used both experimentally and clinically in parkinsonism, there is a definite need to augment long-term survival. Infusion of nerve growth factor (NGF) or implantation of NGF-rich tissue into the area of the graft prolongs survival and induces differentiation into neural-like cells. To provide for prolonged, site-specific delivery of this growth factor to the grafted tissue in a convenient manner, we fabricated biodegradable polymer microspheres of poly(L-lactide)co-glycolide (70:30) containing NGF. Biologically active NGF was released from the microspheres, as assayed by neurite outgrowth in a dorsal root ganglion tissue culture system. Anti-NGF could block this outgrowth. An enzyme-linked immunosorbent assay detected NGF still being released in vitro for longer than 5 weeks. In vivo immunohistochemical studies showed release over a 4.5-week period. This technique should prove useful for incorporating NGF and other growth factors into polymers and delivering proteins and other macromolecules intracerebrally over a prolonged time period. These growth factor-containing polymer microspheres can be used in work aimed at prolonging graft survival, treating experimental Alzheimer's disease, and augmenting peripheral nerve regeneration.

Adrenal Medulla↗

Spatial performance correlates with in vitro potentiation in young and aged Fischer 344 rats.

Young adult (2-4 months old) and aged (24-26 months old) Fischer 344 (F344) rats were trained for spatial behavior (locating a hidden escape platform) in a circular water maze. The aged rats showed deficits in both the acquisition and retention of the learned response. Following the behavioral training, hippocampal slices from the rats were prepared. Potentiation of CA1 extracellular, somatic field potentials was studied in vitro following either a short stimulus train (4 pulses) or a longer train (50 pulses). Slices from the aged rats showed less short-term potentiation (124.8 +/- 4.9% baseline, mean +/- S.E.M.) at 1 min following the short train in comparison to slices from the young rats (151.8 +/- 7.5%, P less than 0.05). However, following the longer train, no differences were found between the groups in the degree of either short-term (measured at 1 min after stimulation) or long-term potentiation (measured at 60 min). The amount of potentiation seen at various time points after either train correlated with the behavioral measure of retention. These results indicate that F344 rats exhibit age-related behavioral deficits, and age-related synaptic potentiation deficits in response to short stimulation trains. The correlation between the degree of potentiation (both short-term and long-term) and retention of a behavioral task adds strength to the hypothesis that potentiation mechanisms may underlie memory processes.

Aging↗

Blood conservation.

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Blood Loss, Surgical↗