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Biomedical subjects

I Silver

Publications and source records attributed to I Silver.

15 recordsLinked to original sources
PubMed2002

Cerebrospinal fluid outflow resistance in sheep: impact of blocking cerebrospinal fluid transport through the cribriform plate.

Recent studies in sheep suggest that a significant proportion of global cerebrospinal fluid (CSF) drainage (50% or greater) occurs through the cribriform plate into nasal mucosal lymphatics. If this is true, obstructing CSF clearance through the cribriform plate should have an impact on the ability of the intracranial pressure regulating systems to compensate for volume infusions. To test this concept, bolus infusions of artificial CSF were administered into one lateral ventricle in sheep and the intracranial pressure monitored from the contralateral side. Peak intracranial pressures (ICP) were measured and CSF outflow resistances were calculated from the pressure patterns observed in response to bolus infusions administered before and after the cribriform plate was sealed in the same animal. To obstruct the cribriform plate, a portion of nasal bone was removed to expose the nasal mucosa. The olfactory mucosa, a portion of the nasal mucosa and all soft tissue on the extracranial surface of the cribriform plate were scraped away with a curette and the bone surface sealed with bone wax. Obstruction of CSF transport through the cribriform plate increased the peak ICP after infusion (P = 0.016) and augmented the time required for ICP to return to baseline. CSF outflow resistance was elevated approximately 2.7 times (P = 0.006). When the cribriform plate was left intact (sham surgery), no significant changes in peak ICP or CSF outflow resistance were observed. We conclude that the cribriform plate represents an important site for CSF clearance. Obstruction of this pathway reduces volumetric CSF transport significantly.

Animals↗
PubMed2001

Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics.

Tracer studies indicate that cerebrospinal fluid (CSF) transport can occur through the cribriform plate into the nasal submucosa, where it is absorbed by cervical lymphatics. We tested the hypothesis that sealing the cribriform plate extracranially would impair the ability of the CSF pressure-regulating systems to compensate for volume infusions. Sheep were challenged with constant flow or constant pressure infusions of artificial CSF into the CSF compartment before and after the nasal mucosal side of the cribriform plate was sealed. With both infusion protocols, the intracranial pressure (ICP) vs. flow rate relationships were shifted significantly to the left when the cribriform plate was blocked. This indicated that obstruction of the cribriform plate reduced CSF clearance. Sham surgical procedures had no significant effects. Estimates of the proportional flow through cribriform and noncribriform routes suggested that cranial CSF absorption occurred primarily through the cribriform plate at low ICPs. Additional drainage sites (arachnoid villi or other lymphatic pathways) appeared to be recruited only when intracranial pressures were elevated. These data challenge the conventional view that CSF is absorbed principally via arachnoid villi and provide further support for the existence of several anatomically distinct cranial CSF transport pathways.

Animals↗
PubMed2001

Improving the psychiatric knowledge, skills, and attitudes of primary care physicians, 1950-2000: a review.

OBJECTIVE: The authors reviewed the literature on mental health education for primary care physicians and made recommendations for the design of educational programs and research. METHOD: They searched the MEDLINE and PsycLIT databases from 1950 to 2000 by using a variety of key words and subjects. RESULTS: More than 400 articles were identified, ranging from empirical studies to philosophical articles. Many identified a perceptual gap between primary care and psychiatry as the basis for problems of contextual relevance in psychiatric education for primary care practitioners. There were few empirical studies; most reported only results of satisfaction surveys or simple tests of knowledge. Long-term outcomes were less positive; there were important negative findings. CONCLUSIONS: An extensive literature published over five decades identified a strong need for ongoing mental health training for primary care physicians. Helpful recommendations exist related to objectives, methods, and evaluation. However, there are organizational and attitudinal issues that may be equally or more important for educators to consider than the selection of educational methods.

Clinical Competence↗
PubMed1999

Relationship between intracranial pressure and cervical lymphatic pressure and flow rates in sheep.

Previous reports from our group demonstrated that about one-half of the total volume of cerebrospinal fluid (CSF) removed from the cranial vault in sheep is transported into extracranial lymphatics, especially cervical lymphatic vessels in the neck. In this study, we tested the hypothesis that an elevation of intracranial pressure (ICP) would increase cervical lymphatic pressure and lymph flow rates in anesthetized sheep. Catheters were inserted into both lateral ventricles, the cisterna magna, cervical lymphatics, and the jugular vein. A ventriculo-cisternal perfusion system was employed to regulate ICP. Mean (P = 0.008), peak (P = 0.007), and baseline (P = 0.013) cervical lymphatic pressures increased as ICP was elevated from 10 to 70 cmH2O in 20-cmH2O increments. Similarly, cervical lymph flow rates increased (P < 0.001), with flows at 70 cmH2O ICP observed to be approximately fourfold higher than those at 10 cmH2O ICP. No changes were observed in mesenteric lymph flow rates (vessels not expected to drain CSF). We conclude that cervical lymphatic vessels play an important role in the transport of CSF from the cranial vault when ICP is elevated.

Animals↗
PubMed1998

Pressure-volume relationships in sheep mesenteric lymphatic vessels in situ: response to hypovolemia.

We applied the principles of cardiac mechanics to study the contraction cycles of postnodal sheep mesenteric lymphatic vessels in an in situ preparation. A segment of intestinal lymphatic was isolated from lymph input and provided with Krebs solution from a reservoir. Pressure-volume relationships were assessed under various transmural pressure conditions using videomicroscopic techniques to measure diameter changes and a miniature catheter pressure transducer to monitor intralymphangion pressure. The contraction cycles were quite variable but, on average, exhibited three phases of systole and three phases of diastole with periods of isovolumetric contraction and relaxation. Elevations of transmural pressure up to 4 cm H2O resulted in significant increases in stroke volume, ejection fraction, pulse pressure, and output/minute but not contraction frequency. Regression analysis of the end systolic (ESPVR) and end diastolic pressure-volume relations (EDPVR) revealed a linear ESPVR (r2 = 0.83 +/- 0.03) and exponential EDPVR (r2 = 0.83 +/- 0.02), a result that is similar to that observed in cardiac contraction cycles. Following a 25% whole blood volume bleed (a stimulus known to enhance lymphatic pumping), significant increases in stroke volume, ejection fraction, and output/minute were observed up to transmural pressures of 4 cm H2O. While an index used to assess cardiac contractility (end systolic elastance-Ees) was not observed to change after the bleed, a shift to the left of the end-systolic pressure-volume relations compared with the sham-bled group (significant shift of regression lines for ESPVR) suggested that hemorrhage exerted a positive inotropic effect on mesenteric lymphatics.

Animals↗
PubMed1998

Oxygen and ion concentrations in normoxic and hypoxic brain cells.

The goal of the present contribution is to discuss the relationships among brain oxygen tension, energy (ATP) level, and ion gradients and movements. The function of the CNS, the generation and transmission of impulses, is determined to a large extent by the movements of ions. Hence elucidation of these relationships is necessary to the understanding of how brain works. Moreover, such knowledge is indispensable for the design of rational therapies for treatment of a large group of pathological states caused by lack of oxygen. This paper is partly a review and partly an original contribution although the former involves to a considerable extent, results obtained in our laboratories. It is divided into 3 parts: a) a very brief general introduction which reminds the reader some well-known facts; b) presentation and discussion of data; and c) conclusions and/or predictions.

Adenosine Triphosphate↗
PubMed1998

Bicycle helmet promotion among low income preschool children.

OBJECTIVE: To evaluate the effectiveness of a multifaceted bicycle helmet promotion program for low income children attending preschool enrichment programs throughout Washington State. STUDY SAMPLE: Preschool Head Start programs that conducted routine home visits among their enrolled families at least five times during the school year were eligible. Eighteen sites and 880 children met this criterion and were able and willing to carry out evaluation activities. Two hundred children were from control sites where no helmet promotion activities were carried out. INTERVENTION: Classroom activities with children, education of parents during school meetings and home visits, fitting and distribution of helmets, a bicycle skills and safety "rodeo" event, and requiring children to wear helmets while riding on school grounds. EVALUATION METHODS: Regularly scheduled home visits were used to observe helmet use of enrolled preschool children before and after the promotion program. Home visitors requested parental permission for enrolled children to ride, and then noted whether the child wore a helmet. RESULTS: Helmet use in the intervention group more than doubled, from 43% to 89%, while use in the control group increased from 42% to 60% (p < 0.05 for intervention group changes v control group changes). CONCLUSIONS: This multifaceted helmet promotion program successfully increased helmet use. Similar home visit protocols may be useful to evaluate the impact of other injury intervention programs.

Bicycling↗
PubMed1997

Breast cancer cells have a high capacity to acidify extracellular milieu by a dual mechanism.

The extracellular pH in malignant tumors is known to be lower than in normal tissues and may therefore facilitate extracellular activation of secreted lysosomal cathepsins. We have tested the capability of human mammary cells (continuous cell lines and primary culture) to acidify their extracellular environment, using two techniques. By measuring pH changes through alterations of phenolsulfone phthaleine absorbance, we found that the more aggressive MDA-MB-231 human breast cancer cells were more active in acidifying a non-buffered balanced salt solution than the estrogen receptor positive MCF7 and ZR75 cell lines and than normal mammary epithelial cells in primary culture. Metastatic breast cancer cells from pleural effusions were up to 200-fold more active in acidifying their extracellular milieu than non-malignant mammary cells cultured in the same conditions, strongly suggesting that this difference also occurs in vivo. The use of inhibitors in the presence or absence of glucose showed that both lactate and an ATP-driven proton pump sharing some characteristics of the vacuolar H+ pump were involved. Bafilomycin A1, a specific inhibitor of the vacuolar (V-type) ATP-H+ pump inhibited part of the acidification by MCF7 cells, but not by MDA-MB-231 cells. We also used microelectrodes to measure extracellular pH, in close contact to the MCF7 breast cancer cells. The pH at the free surface of MCF7 cells was lower by 0.33 +/- 0.14 unit than that of the surrounding medium, while insertion of the microelectrode tip beneath the attached surface of the cells showed a greater lowering of pH from 0.3 to 1.7 pH unit as long as cell attachment on the substrate prevented H+ diffusion. We conclude that breast carcinoma cells have a higher capacity for acidifying their extracellular milieu than normal mammary cells, and that both a plasma membrane H(+)-ATPase, and lactic acid production are involved in this acidification. It is therefore possible that the aspartyl and cysteinyl pro-cathepsins secreted in excess by tumor cells may be activated extracellularly in vivo close to the basement membrane.

Acids↗
PubMed1996

Dizocilpine prevents the development of tolerance to ethanol-induced error on a circular maze test.

Dizocilpine [(+)MK-801] and ketamine, in doses that disrupt learning and memory, also prevent the development of tolerance to the motor impairing effects of ethanol (EtOH). However, dizocilpine itself affects motor behavior. In order to separate the possible influence of these two effects on the development of tolerance to EtOH, food-reinforced performance on a circular maze test was used in two different experiments. EtOH alone (1.2 g/kg) tended to increase the error score and reduce number of runs per trial, running speed, and total distance run, but on chronic administration of EtOH, tolerance developed progressively to all these effects. Dizocilpine also increased the error score, but had a biphasic effect on measures of running: low and intermediate doses (0.009 and 0.075 mg/kg, IP) increased running distance, whereas a high dose (0.15 mg/kg) decreased running speed and distance. When combined with EtOH, dizocilpine tended to overcome the effect of EtOH on running activity, but not on error score. Chronically, dizocilpine (0.075 and 0.15 mg/kg) prevented the development of tolerance to the effect of EtOH on error score, even though the lower dose of dizocilpine permitted tolerance to the effects of EtOH on running. These results suggest that NMDA receptor antagonists selectively inhibit tolerance to cognitive effects of ethanol even when the antagonists do not affect motor performance.

Animals↗
PubMed1990

Teaching physicians about teaching: an experiential workshop.

Teaching improvement workshops are most effective when they engage teachers actively in practice teaching, particularly when the teaching situation is similar to the actual one to which the teachers will return. Teachers, however, often find such involvement threatening. In this paper we describe a 3 h workshop which succeeds in overcoming teachers' reluctance to participate in situations that are relevant to their real teaching problems, students, and subject matter. The most exciting outcome, in our view, was teachers' increased sensitivity to the limitations of their teaching approach and their increased awareness of the role of their concept of teaching in shaping their teaching strategies. Weaknesses of the workshop include its dependence on the skills of a group director, the tendency of the group to seek a single right answer instead of exploring alternatives and the usual danger of role rigidity which troubles all role enactment procedures.

Ontario↗
PubMed1987

The 14 & 6-associated clinical complex: a rejected hypothesis revisited.

The 14 & 6 Hz positive spike phenomenon is generally considered a normal variant finding. Our experience prompted this re-evaluation, which consisted of three parts: In children referred for sleep electroencephalograms (EEGs), 100 children with normal EEG and 100 with 14 & 6--the 14 & 6 correlated with behavior disorder and aggression; In 75 children referred for neurological evaluation and EEG because of behavior problems, 52% had 14 & 6 (excluding those with paroxysmal EEGs); and In 57 symptomatic children having prominent 14 & 6, tabulation of symptoms yielded a complex but coherent clinical picture, including disturbances of temper, mood, attention, learning, and sleep. We conclude that 14 & 6 has clinical associations and deserves study.

Adolescent↗