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Biomedical subjects

M Sanders

Publications and source records attributed to M Sanders.

At least 55 records · Page 3Linked to original sources

After the strike: using facilitation in a residency training program.

Methods of alternative dispute resolution, including facilitation, can be used to identify and resolve areas of conflict. Facilitation was used by the University of Saskatchewan's Department of Family Medicine (Saskatoon division) after the strike by residents in July and August 1995 so as to allow optimal use of the remaining educational time. Through facilitation, experiences of the strike and areas of potential conflict were explored. Participants had a broad range of responses to the strike. Specific coping strategies were developed to deal with identified concerns. Although outcomes were not measured formally, levels of trust improved and collegial relationships were restored. Because so many changes occur in health care and medical education, conflict inevitably arises. Facilitation offers one way of dealing with change constructively, thereby making possible the optimal use of educational time.

Faculty, Medical↗

Algorithm for nutritional support: experience of the Metabolic and Infusion Support Service of St. Jude Children's Research Hospital.

The Metabolic and Infusion Support Service (MISS) at St. Jude Children's Research Hospital was established in 1988 to improve the quality of nutritional support given to children undergoing therapy for cancer. This multidisciplinary group, representing each of the clinical services within the hospital, provides a range of services to all patients requiring full enteral or parenteral nutritional support. In 1991, the MISS developed an algorithm for nutritional support which emphasized a demand for a compelling rationale for choosing parenteral over enteral support in patients with functional gastrointestinal tracts. Compliance with the algorithm was monitored annually for 3 years, with full compliance defined as meeting all criteria for initiating support and selection of an appropriate type of support. Compliance rates were 93% in 1992, 95% in 1993 and 100% in 1994. The algorithm was revised in 1994 to include criteria for offering oral supplementation to patients whose body weight was at least 90% of their ideal weight and whose protein stores were considered adequate. Full support was begun if no weight gain occurred. Patients likely to tolerate and absorb food from the gastrointestinal tract were classified into groups defined by the absence of intractable vomiting, severe diarrhea, graft-vs.-host disease affecting the gut, radiation enteritis, strictures, ileus, mucositis and treatment with allogeneic bone marrow transplant. Overall, the adoption of the algorithm has increased the frequency of enteral nutritional support, particularly via gastrostomies, by at least 3-fold. Our current emphasis is to define the time points in therapy at which nutritional intervention is most warranted.

Algorithms↗

Three-dimensional visualization and measurement of conformal dose distributions using magnetic resonance imaging of BANG polymer gel dosimeters.

PURPOSE/OBJECTIVE: The measurement of complex dose distributions (those created by irradiation through multiple beams, multiple sources, or multiple source dwell positions) requires a dosimeter that can integrate the dose during a complete treatment. Integrating dosimeter devices generally are capable of measuring only dose at a point (ion chamber, diode, TLD) or in a plane (film). With increasing use of conformal dose distributions requiring shaped, noncoplanar beams, there will be an increased requirement for a dosimeter that can record and display a 3D dose distribution. The use of a 3D dosimeter will be required to confirm the accuracy of treatment plans produced by the current generation of 3D treatment-planning computers. METHODS AND MATERIALS: The use of a Fricke-infused gel and magnetic resonance imaging (MRI) to demonstrate the localization of stereotactic beams has been demonstrated (11). The recently developed BANG polymer gel dosimetry system (MGS Research, Inc., Guilford, CT), based on radiation-induced chain polymerization of acrylic monomers dispersed in a tissue-equivalent gel, surpasses the Fricke-gel method by providing accurate, quantitative dose distribution data that do not deteriorate with time (6, 9). The improved BANG2 formulation contains 3% N,N'-methylene-bisacrylamide, 3% acrylic acid, 1% sodium hydroxide, 5% gelatin, and 88% water, where all percentages are by weight. The gel was poured into volumetric flasks, of dimensions comparable to a human head. The gels were irradiated with complex beam arrangements, similar to those used for conformal radiation therapy. Images of the gels were acquired using a Siemens 1.5T imager and a Hahn spin-echo pulse sequence (90 degrees-tau-180 degrees-tau-acquire, for different values of tau). The images were transferred via network to a Macintosh computer for which a data analysis and display program was written. The program calculates R2 maps on the basis of multiple TE images, using a monoexponential nonlinear least-squares fit based on the Levenberg-Marquardt algorithm. The program also creates a dose-to-R2 calibration function by fitting a polynomial to a set of dose and R2 data points, obtained from gels irradiated in test tubes to known doses. This function can then be applied to any other R2 map, so that a dose map can be computed and displayed. RESULTS: Through exposure to known doses of radiation, the gel has been shown to respond linearly with dose in the range of 0 to 10 Gy, and its response is independent of the beam energy or modality. Dose distributions have been imaged in orthogonal planes, and can be displayed in a convenient form for comparison with isodose plans. The response of the gel is stable; the gel can be irradiated at any time after its manufacture, and imaging can be conducted any time following a brief interval after irradiation. CONCLUSION: The polymer gel dosimeter has been shown to be a valuable device for displaying three-dimensional dose distributions. The imaged dose distribution can be compared easily with calculated dose distributions, to validate a treatment planning system. In the future, gels may be prepared in anthropomorphic phantoms, to confirm unique patient dose distributions.

Gels↗

High rates of actin filament turnover in budding yeast and roles for actin in establishment and maintenance of cell polarity revealed using the actin inhibitor latrunculin-A.

We report that the actin assembly inhibitor latrunculin-A (LAT-A) causes complete disruption of the yeast actin cytoskeleton within 2-5 min, suggesting that although yeast are nonmotile, their actin filaments undergo rapid cycles of assembly and disassembly in vivo. Differences in the LAT-A sensitivities of strains carrying mutations in components of the actin cytoskeleton suggest that tropomyosin, fimbrin, capping protein, Sla2p, and Srv2p act to increase actin cytoskeleton stability, while End3p and Sla1p act to decrease stability. Identification of three LAT-A resistant actin mutants demonstrated that in vivo effects of LAT-A are due specifically to impairment of actin function and implicated a region on the three-dimensional actin structure as the LAT-A binding site. LAT-A was used to determine which of 19 different proteins implicated in cell polarity development require actin to achieve polarized localization. Results show that at least two molecular pathways, one actin-dependent and the other actin-independent, underlie polarity development. The actin-dependent pathway localizes secretory vesicles and a putative vesicle docking complex to sites of cell surface growth, providing an explanation for the dependence of polarized cell surface growth on actin function. Unexpectedly, several proteins that function with actin during cell polarity development, including an unconventional myosin (Myo2p), calmodulin, and an actin-interacting protein (Bud6/Aip3p), achieved polarized localization by an actin-independent pathway, revealing interdependence among cell polarity pathways. Finally, transient actin depolymerization caused many cells to abandon one bud site or mating projection and to initiate growth at a second site. Thus, actin filaments are also required for maintenance of an axis of cell polarity.

Actin Cytoskeleton↗

Two cholinesterase activities and genes are present in amphioxus.

To obtain information about the evolution of the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the vertebrates, we investigated the cholinesterase (ChE) activity of the cephalochordate amphioxus (Branchiostoma floridae and Branchiostoma lanceolatum). On the basis of evidence from enzymology, pharmacology, and molecular biology, we conclude that amphioxus possesses two ChE activities and two ChE genes. Two covalent inhibitors of cholinesterases were able to pharmacologically isolate the two activities as drug-sensitive ChE and drug-resistant ChE. Kinetically, in terms of substrate specificity, the drug-sensitive ChE resembles vertebrate AChE, and the drug-resistant ChE resembles the BuChE of cartilaginous and bony fish or the intermediate ChE of protostome invertebrates. We also used the polymerase chain reaction with degenerate oligonucleotide primers and genomic DNA to obtain clones of 1,574 and 1,011 bp corresponding to two cholinesterase genes from amphioxus, which we designated as ChE1 and ChE2. ChE2 codes for an enzyme with an acyl-binding pocket sequence, a portion of the protein that plays an important role in determining substrate specificity, typical of invertebrate ChE. ChE1, which contains a 503-bp intron, encodes a protein with a novel acyl binding site. Phylogenetic analysis of the sequences suggests that the two genes are a result of a duplication event in the lineage leading to amphioxus. We discuss the relevance of our results to the evolution of the cholinesterases in the chordates. Previously, we reported that amphioxus contained a single cholinesterase activity with properties intermediate to AChE and BuChE (Pezzementi et al. [1991] In: Cholinesterases: Structure, Function, Mechanism, Genetics and Cell Biology. J. Massoulié et al., eds. ACS: Washington, D.C., pp. 24-31).

Acetylcholinesterase↗

Nicotine discrimination and self-administration in humans as a function of smoking status.

Nicotine's discriminative stimulus effects may be critical to understanding reinforcement of tobacco smoking. It is not known whether regular nicotine exposure produces tolerance or sensitivity to these effects. In this study, male and female smokers (n = 11) and never-smokers (n = 10) were trained to discriminate 20 micrograms/kg nicotine by nasal spray from placebo (0) on day 1. On day 2, both groups were tested on generalization of this discrimination across intermittent presentations of 0, 3, 6, 12, and 20 micrograms/kg nicotine in random order. Quantitative and quantal behavioral discrimination tasks, used in previous research, were employed. On day 3, subjects were instructed to self-administer sprays from the 20 micrograms/kg nicotine versus 0 bottles in a concurrent-choice procedure. All but one subject (female smoker) learned reliably to discriminate 20 micrograms/kg nicotine from placebo (> or = 80% correct) on day 1. Nicotine-appropriate responding on day 2 was attenuated in smokers versus never-smokers at 20 micrograms/kg on the quantitative task and at 12 micrograms/kg on the quantal task, suggesting tolerance. There was no difference in responding at other doses. Smokers also showed attenuated responses on the subjective measure of "head rush", which was associated with discrimination responding in both groups. Nicotine self-administration was significantly greater in smokers versus never-smokers, who self-administered nicotine below chance levels, and was inversely related to discrimination behavior in never-smokers but unrelated in smokers. Women smokers showed less change in nicotine-appropriate responding across generalization doses, reported less confidence in discriminating training doses during acquisition on day 1, and tended to self-administer less nicotine on day 3. These results indicate that smokers may become tolerant to the discriminative stimulus effects of nicotine, perhaps promoting increased use.

Adult↗

Hypopnea, a floating metric: implications for prevalence, morbidity estimates, and case finding.

The respiratory disturbance index (RDI) is the most frequently used metric to characterize sleep-disordered breathing. Clinically, the RDI is used to classify disease status and guide treatment decisions. For research purposes, the RDI is used to describe population distributions of sleep-disordered breathing. Its popularity as a cardinal disease-defining measure, however, may not be justified given that standardized criteria do not exist for defining hypopnea, a key component of the RDI. This paper reviews sources of variability in identifying hypopneas, including: the magnitude of changes in breathing amplitude necessary to describe breathing as "reduced" (from "discernible" to >50%), variations in the utilization of sensors with different sensitivities to detect airflow/ventilation (i.e. thermocouples, thermistors, and pressure transducers), and differential use of data on oxygen saturation and arousals to discriminate normal breathing from hypopneas. The extent to which disparate approaches influence the overall RDI and population estimates of disease also is discussed.

Adult↗

Special Olympics, special smiles: assessing the feasibility of epidemiologic data collection.

No comprehensive national study has ever been completed on the oral health status of people with disabilities, their patterns of use of oral health services and access-to-care barriers. The authors describe the Special Olympics, Special Smiles program, conducted as part of the New Jersey Summer Special Olympics Games, and assess a pilot-tested model for collecting epidemiologic data. The results of this initial data collection are also compared with the goals of the U.S. Public Health Service, as outlined in the Healthy People 2000 publication.

Adult↗

Efficacy of sphenopalatine ganglion blockade in 66 patients suffering from cluster headache: a 12- to 70-month follow-up evaluation.

This study was conducted to evaluate the efficacy, based on 12- to 70-month follow-up data, of radiofrequency (RF) lesions of the sphenopalatine ganglion made in patients suffering from cluster headache. Sixty-six patients suffering from either episodic (Group A, 56 patients) or chronic (Group B, 10 patients) cluster headache who were not responsive to pharmacological management were treated by RF lesioning in the sphenopalatine ganglion. Complete relief of pain was achieved in 34 (60.7%) of 56 patients in Group A and in three (30%) of 10 patients in Group B. No relief was found in eight patients (14.3%) in Group A and in four (40%) in Group B. The mean time of follow up was 29.1 +/- 10.6 months in Group A and 24 +/- 9.7 months in Group B, ranging from 12 to 70 months. With regard to side effects and complications, temporary postoperative epistaxis was observed in eight patients and a cheek hematoma in 11 patients; a partial RF lesion of the maxillary nerve was inadvertently made in four patients. Nine patients complained of hypesthesia of the palate, which disappeared in all cases within 3 months. The authors conclude that RF lesioning in the sphenopalatine ganglion via the infrazygomatic approach may be performed in patients suffering from cluster headache that does not respond to pharmacological therapy.

Acute Disease↗

[Aggression and violence in children in different contexts].

Starting with the hypothesis that children's aggressive and potentially violent behavior is the climax of escalating conflicts that cannot be expressed or showed in any other way, we analyse, in the following article, the conditions from which these behavior pattern arise. We have focused on the following areas; the individual, the family, the school and society, and we have tried to show how the development of children's aggressive behavior is determined by the problem constellations in these different contexts. Insecure and disorganised early bonding experiences and/or dysfunctional family relationship patterns combined with parental upbringing methods that support or condone aggressive behavior, can lead to children having fewer resources or social skills available than their peers in kindergarten and school. This may result in conflict and lack of social integration in these institutions.

Adolescent↗

[FAUSTLOS--a curriculum for promoting social competence and preventing aggressive and violent behavior in children].

FAUSTLOS is a curriculum that has been developed for the prevention of aggression and potentially violent behavior in children in nursery and primary school. A lack of social skills is regarded as one of the fundamental causes that deteriorates problem and conflict solving. FAUSTLOS is the German version of an American program called Second Step that has been developed by the Committee for Children in Seattle and has been successfully put into practice in several American states over the last eight years. The project "Kinder und Gewalt" has adapted it for the German speaking countries. FAUSTLOS is at present in its pilot phase. The following is a general survey of the inception, contents and methods of the curriculum and the planning and execution of the pilot phase.

Aggression↗

Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience.

Between 1989 and 1993, 255 tumor biopsies representing 4 tumor histologies (melanoma, breast cancer, colon cancer and renal cell cancer) were received by the Surgery Branch of the National Cancer Institute. Tumor-infiltrating lymphocytes (TIL) were grown from single-cell suspensions of tumor biopsies over the course of 30-45 days. The TIL were grown in medium containing IL-2. To obtain numbers suitable for therapy (>10(11)), TIL were expanded using a large-scale system of cell culture and harvesting. While the largest number of biopsies was obtained from melanoma patients, TIL were successfully grown from 160 of 255 tumor biopsies representing all 4 histologies. Under the culture conditions employed, several characteristics of TIL expansion were observed. The cell surface phenotype of TIL which grew out from the tumor biopsies was generally a mix of CD3+/CD4+ or CD3+/CD8+ lymphocytes. Only TIL from melanoma biopsies were found to be consistently cytolytic and, in many cases, lysed autologous tumor cells preferentially. Interestingly, TIL derived from extra-nodal sites of metastatic melanoma biopsies (subcutaneous, lung, bowel; 36 of 67, 54%) were more likely to have these cytolytic characteristics than TIL derived from tumor-involved lymph node biopsies (7 of 39, 18%). The present study summarizes 5 years of laboratory effort and validates the technologies developed for the large-scale growth and harvesting of TIL. In addition, it summarizes the laboratory effort supporting previously published clinical reports on TIL from our group.

Breast Neoplasms↗

Influence of training dose on nicotine discrimination in humans.

Non-human research indicates that drug discrimination results may depend largely on the specific training conditions, including initial training dose. It has recently been shown that humans can discriminate among different doses of nicotine delivered by nasal spray. In this study, we examined the influence of training dose on subsequent behavioral discrimination of a range of nicotine doses. Male (n = 17) and female smokers (n = 16) were randomly assigned to "low" (10 micrograms/kg) versus "high" (30 micrograms/kg) nicotine training dose groups and trained reliably to discriminate this dose from placebo (0) on day 1 (> or = 80% correct identification). All but six subjects (four in low, two in high) learned this discrimination and continued on to day 2, in which both groups received 0, 5, 10, 20, and 30 micrograms/kg in ascending order (30 min between dosings) and were tested for generalization with their training dose using quantal and quantitative behavioral discrimination tasks. Subjective responses via traditional self-report measures were also assessed. Nicotine-appropriate responding on day 2 was significantly greater in low- versus high-dose groups, especially at 5 micrograms/kg. However, this difference due to training dose was seen more in women than in men. Discrimination behavior was associated with subjective effects of head rush in males, and with head rush and decline in urge to smoke in females. These results show that discriminative stimulus effects of nicotine are not fixed properties of the drug, but can be influenced by training conditions, and that effects associated with this discrimination may differ between men and women.

Adult↗

MRI of the optic nerve in benign intracranial hypertension.

We investigated the MRI appearance of the optic nerve and its cerebrospinal-fluid-containing sheath in 17 patients with benign intracranial hypertension (BIH) and 15 normal controls. Using phased-array local coils, 3-mm coronal T2-weighted fat-suppressed fast spin-echo images were obtained with an in-plane resolution of < 0.39 mm. The optic nerve and its sheath were clearly differentiated. An enlarged, elongated subarachnoid space around the optic nerve was demonstrated in patients with BIH. High-resolution MRI of the optic nerve offers additional information which may be of value for diagnosis and in planning and monitoring treatment.

Adolescent↗

Placental basal plate myometrial fibers: clinical correlations of abnormally deep trophoblast invasion.

OBJECTIVE: To assess the incidence of placental basal plate myometrial fibers in preterm and term gestations and correlate this finding with clinical observations and placental histopathology. METHODS: Placentas from 457 singleton births before 32 weeks' gestation and 108 uncomplicated singleton births after 37 weeks' gestation were examined histopathologically. Pregnancies complicated by maternal chronic hypertension, diabetes mellitus, coagulopathy, placenta previa, stillbirth, multiple fetuses, and fetal congenital anomalies were excluded from both groups. In the preterm group, 158 patients had preterm labor with intact membranes, 192 had preterm premature rupture of membranes (PROM), 31 had placental abruption without hypertension, and 76 had preeclampsia. Histopathology detected the presence of placental basal plate myometrial fibers, placental vascular lesions, and villous damage related to vascular insufficiency. RESULTS: Forty-four of 457 (9.6%) of preterm placentas had basal plate myometrial fibers, compared with one of 108 (0.9%) term controls (P < .001). Uteroplacental vessels with abnormal physiologic changes were more frequent and placental weights were lower in cases with basal plate myometrial fibers (P < .003 and P < .03, respectively). No other uteroplacental vascular lesions were related to basal plate myometrial fibers. The frequency of placental basal plate myometrial fibers was nine of 76 (12%) in cases complicated by preeclampsia, 21 of 192 (11%) cases of PROM, nine of 158 (5.7%) cases of preterm labor, and four of 31 (13%) cases of placental abruption without hypertension; these frequencies were not significantly different, and there was no significant relationship to gravidity, parity, mode of delivery, or birth weight. CONCLUSION: Placental basal plate myometrial fibers occur in ten times as many preterm births as term births. This finding is associated with both abnormal uteroplacental physiologic changes and decreased placental weight, and may explain the increased incidence of abnormalities of the third stage of labor associated with preterm delivery.

Female↗

Biochemical and molecular characterization of acetylcholinesterase from the hagfish Myxine glutinosa.

To obtain information about the evolution of the cholinesterases, we investigated the cholinesterase activity of an agnathan vertebrate, the hagfish Myxine glutinosa. On the basis of evidence from enzymology, pharmacology, and molecular biology, we conclude that the cholinesterase activity is due to acetylcholinesterase (AChE). The enzyme hydrolyzes acetylthiocholine preferentially and exhibits substrate inhibition. The hydrolysis of both acetylthiocholine and butyrylthiocholine are inhibited in parallel by cholinesterase inhibitors, with the AChE-specific drug BW284c51 being the most potent; however, this drug and propidium, a peripheral anionic site ligand, are much weaker inhibitors of the hagfish enzyme than of Torpedo AChE. We used sequential extraction, collagenase digestion, and velocity sedimentation on sucrose gradients to determine that the AChE from the skeletal muscle of the hagfish is present in both globular and asymmetric forms. We also used the polymerase chain reaction with degenerate oligonucleotide probes and genomic DNA to obtain a 1 kb gene fragment for hagfish AChE. The enzyme has an acyl binding site typical of other vertebrate AChE, but lacks two aromatic residues implicated in the function of the peripheral anionic subsite. We discuss the relevance of our findings to the evolution of the cholinesterases in the vertebrates.

Acetylcholinesterase↗

A randomised prospective study of outpatient haemodilution for central retinal vein obstruction.

PURPOSE: Central retinal vein obstruction (CRVO) has significant visual morbidity. We prospectively evaluated an outpatient haemodilution (HD) regimen for CRVO. METHODS: We recruited 59 patients with CRVO of less than three months' duration and visual acuity (VA) worse than or equal to 6/9.5. Thirty patients underwent HD (packed cell volume of <0.35, 12 weeks); there were 29 controls and follow-up was for six months. RESULTS: Incidence rates for VA improvement (P = 0.708) and rubeosis iridis (P = 0.619) between the two groups were not different. The incidence rate of VA deterioration was 5.315 times higher with HD (P = 0.035, Cox Proportional analysis). CONCLUSION: This data does not support the previous studies on haemodilution.

Adult↗