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PubMed2002

Effects of managed care on teaching, research, and clinical practice in academic plastic surgery.

The aim of this study was to determine: 1) if there have been changes in teaching, research, and clinical practice in academic plastic surgery in recent years; and 2) if there have been, are they associated with changes in the managed care environment? Gaining a clearer perspective on how managed care affects academic plastic surgery will enable academicians to define better the problems and opportunities they face mutually and to respond effectively to these issues. This study used a cross-sectional study design. Reference time periods were the premanaged care era (1990-1991) versus the current time (1997-1998). Data were collected by questionnaires sent to 94 academic program directors in plastic surgery. The main independent variable of managed care was measured as the difference in the percent of income from health maintenance organizations generated by each program in 1990 to 1991 versus 1997 to 1998. The dependent variables of teaching, research, and clinical practice were measured by the percentage of time spent in each category, the number of work hours per week, the number of staff personnel, the location of teaching, the number of grants and publications, and the percentage of reconstructive and cosmetic cases in 1990 to 1991 versus 1997 to 1998. Univariate analysis, paired Student's t-test, Fisher's exact test, Pearson's correlation, Spearman's correlation, and linear regression were used to establish significance (alpha = 0.05) of the effects of managed care on dependent variables. Sixty-six questionnaires were completed and returned (70% response rate). There were significant changes in the managed care environment, clinical practice (operating room and clinics), and research in academic plastic surgery from 1990 to 1997. The percentage of income generated from managed care increased from 9.8% (of total revenue) in 1990 to 23.6% in 1997 (an increase of 13.8%; p < 0.0001). Academic plastic surgeons were found to spend significantly more time in clinical practice (3% more of total time spent; 5.3 hours more per week in 1997; p < 0.016). This change correlated significantly with the increase in managed care (p < 0.015). In addition, the percentage of cosmetic cases increased from 18.0% in 1990 to 28.3% in 1997 (p < 0.001), and that of reconstructive surgery was reduced proportionately (p < 0.001). Also, a significant decrease in the time spent for research was observed (mean reduction, 2.8 hours less per week; p < 0.001). Although the trend was to a lower number, there were no significant changes in the amount of time spent in teaching (p > 0.08) and in administrative duty (p > 0.06), or in the number of personnel employed in the teaching programs (p > 0.05). In summary, these findings suggest that: 1) a greater percentage of revenue was generated from managed care in 1997 than in 1990, indicating a growing fiscal influence by managed care on academic plastic surgery; 2) furthermore, this change is associated with academic plastic surgeons devoting more time to clinical practice and less time to research endeavors; and 3) although managed care policies do affect teaching adversely, this effect has not yet reached significance for the period examined during this study.

Academic Medical Centers↗
PubMed1999

Analysis of workforce, distribution of care, and practice preference in pediatric plastic surgery.

To determine the future needs in manpower for pediatric care as it relates to pediatric specialists, a study was conducted by the American Academy of Pediatrics to see the needs of manpower that will provide access of pediatric care to all. A pediatric plastic surgery survey was set in the form of a list of questions that was mailed to the respective societies with pediatric plastic surgeons as members. The survey was reviewed, and the results were studied. The outcome is presented in the form of findings related to the overall practice of plastic surgery. Based on the percentage of pediatric care that is provided, there were two types of pediatric plastic surgeons. Those with the high percentage of pediatric care tend to stay near health science centers; however, both groups tend to spend time (each to a different extent) tending to other plastic surgery problems. Today we have adequate access to care in the health system for pediatric plastic surgery problems despite the shift in the health care environment. Managed care continues to use the pediatrician as a "gatekeeper" in determining the overall access for patients with problems related to pediatric plastic surgery.

Canada↗
PubMed1999

Psychological complications in 281 plastic surgery practices.

Surgery is a high-stakes stressor with possible consequences that include death, pain, disfigurement, economic losses, and alterations in social roles. Often, the most disturbing complications to surgeons and patients are psychological rather than physical. Ineffective management of psychological complications of surgery can have profound consequences, resulting in delayed recuperative times, delayed return to work, poor patient compliance, dissatisfaction with the surgical outcome, hostility toward surgeons, and anxiety. The purpose of this study was to investigate in a large randomized group of plastic surgery practices the relative incidence of negative psychological outcomes and to compare these with the incidence of adverse physical outcomes to gain a greater appreciation of the relative magnitude of each type of perioperative complication. The study design was a descriptive, correlational survey that assessed psychological complications reported by plastic surgeons. The Plastic Surgery Questionnaire was sent to 702 randomly selected board-certified plastic surgeons. The sample consisted of 281 board-certified plastic surgeons (40 percent response rate). The study instrument was found to be highly reliable, with inter-item Cronbach's alpha r = 0.85. The demographics were representative of the specialty as a whole. It was found in general that psychological complications were much more prevalent than physical problems such as hematoma or infection. Anxiety reactions were commonly encountered by 95.4 percent of surgeons; disappointment (96.8 percent), depression (95.0 percent), nonspecific physical complaints (92.2 percent), and sleep disorders (88.5 percent) were the next most commonly reported complications. Most surgeons (75.8 percent) reported that screening for depression was important, but only 18.8 percent identified screening for post-traumatic stress disorder as important, even though 86 percent had diagnosed post-traumatic stress disorder in their postoperative patients. Psychological complications occur at rates equal to or greater than those of physical complications in the plastic surgery practice. Patients who experience physical complications are much more likely to simultaneously experience psychological complications. Patients with preexisting psychological conditions are more at risk for postoperative psychological complications. Disappointment, anxiety, and depression were the most frequently seen psychological complications. Nursing personnel are perceived by plastic surgeons to have the primary role in screening patients for pertinent psychological history. Directed research should be undertaken to determine which treatment regimens are most effective in reducing preoperative psychological complications. Controlled clinical trials of pharmaceuticals and alternative therapies must be designed and carried out in a prospective manner to establish the optimum treatment for alleviation of adverse emotional consequences of surgery. The next frontier for the specialty is to actively and consciously investigate and improve our patients' emotional and psychological results from surgery.

Anxiety↗
PubMed2003

Residency training in plastic surgery: a survey of educational goals.

With the advent of integrative plastic surgical training programs, requirements for earlier specialization decisions, and an increasing subspecialization within the practice of plastic surgery, the educational goals of residency training may have changed. The duration and extent of training required are also currently being questioned. This study was performed to better understand the necessary roles of plastic surgery residencies and to determine how these demands might optimally be met. Of 151 practicing plastic surgeons in the Ontario, Canada, region, 81 (53.6 percent) responded to a survey. General agreement was that 2 years was an optimal length of time for core surgical training, which should then be followed by at least 3 years of plastic surgical training. Opinions on the ideal length of time training in specific medical and surgical disciplines are discussed. Overall, respondents thought that two thirds of training should occur in tertiary care centers, with the remaining time spent at smaller community centers and private clinics. Nearly half of respondents thought that research training should be a mandatory part of the residency, although the amount of protected time for this activity varied substantially. Most thought that unrestricted elective time should also be available. Academic plastic surgeons rated the importance of research training (p < 0.01), critical appraisal skills (p < 0.05), and teaching skills (p < 0.05) as significantly more important than did their nonacademic colleagues. The authors present results from the Ontario region and a template for determining optimal characteristics for training programs. Further investigation may be of timely importance during a foreseeable future transition from traditional to integrative plastic surgery residency training.

Curriculum↗
PubMed2005

Corticofugal feedback for auditory midbrain plasticity elicited by tones and electrical stimulation of basal forebrain in mice.

The auditory cortex (AC) is the major origin of descending auditory projections and is one of the targets of the cholinergic basal forebrain, nucleus basalis (NB). In the big brown bat, cortical activation evokes frequency-specific plasticity in the inferior colliculus and the NB augments this collicular plasticity. To examine whether cortical descending function and NB contributions to collicular plasticity are different between the bat and mouse and to extend the findings in the bat, we induced plasticity in the central nucleus of the mouse inferior colliculus by a tone paired with electrical stimulation of the NB (hereafter referred to as tone-ES(NB)). We show here that tone-ES(NB) shifted collicular best frequencies (BFs) towards the frequency of the tone paired with ES(NB) when collicular BFs were different from tone frequency. The shift in collicular BF was linearly correlated to the difference between collicular BFs and tone frequencies. The changes in collicular BFs after tone-ES(NB) were similar to those found in the big brown bat. Compared with cortical plasticity evoked by tone-ES(NB), the pattern of collicular BF shifts was identical but the shifting range of collicular BFs was narrower. A GABA(A) agonist (muscimol) or a muscarinic acetylcholine receptor antagonist (atropine) applied to the AC completely abolished the collicular plasticity evoked by tone-ES(NB). Therefore, our findings strongly suggest that the AC plays a critical role in experience-dependent auditory plasticity through descending projections.

Acoustic Stimulation↗
PubMed2006

Different forms of homeostatic plasticity are engaged with distinct temporal profiles.

Global changes in network activity have been reported to induce homeostatic plasticity at multiple synaptic and cellular loci. Though individual types of plasticity are normally examined in isolation, it is their interactions and net effect that will ultimately determine their functional consequences. Here we examine homeostatic plasticity of both inhibition and intrinsic excitability in parallel in rat organotypic hippocampal slices. As previous studies have not examined inhibitory plasticity using a functional measure, inhibition was measured by the ability of evoked inhibitory postsynaptic potentials (IPSPs) to suppress action potentials, as well as IPSP amplitude. We show that manipulations of network activity can both up- and downregulate functional inhibition, as well as intrinsic excitability. However, these forms of plasticity are dissociable. Specifically, robust changes in intrinsic excitability were observed in the absence of inhibitory plasticity, and shifts in inhibition, but not excitability, appear to be sensitive to developmental stage. Our data establish that while the two forms of homeostatic plasticity can be engaged in parallel, there is a specific order in which they are expressed, with changes in excitability preceding those in inhibition. We propose that changes in intrinsic excitability occur first in order to stabilize network activity while optimizing the preservation of information stored in synaptic strengths by restricting changes that will disrupt the balance of synaptic excitation and inhibition.

2-Amino-5-phosphonovalerate↗
PubMed2006

Partial inhibition of PP1 alters bidirectional synaptic plasticity in the hippocampus.

Synaptic plasticity is an important cellular mechanism that underlies memory formation. In brain areas involved in memory such as the hippocampus, long-term synaptic plasticity is bidirectional. Major forms of bidirectional plasticity encompass long-term potentiation (LTP), LTP reversal (depotentiation) and long-term depression (LTD). Protein kinases and protein phosphatases are important players in the induction of both LTP and LTD, and the serine/threonine protein phosphatase-1 (PP1), in particular, has emerged as a key phosphatase in these processes. The goal of the present study was to assess the contribution of PP1 to bidirectional plasticity and examine the impact of a partial inhibition of PP1 on LTP, LTD and depotentiation in the mouse hippocampus. For this, we used transgenic mice expressing an active PP1 inhibitor (I-1*) inducibly in forebrain neurons. We show that partial inhibition of PP1 by I-1* expression alters the properties of bidirectional plasticity by inducing a shift of synaptic responses towards potentiation. At low-frequency stimulation, PP1 inhibition decreases LTD in a frequency-dependent fashion. It favours potentiation over depression at intermediate frequencies and increases LTP at high frequency. Consistently, it also impairs depotentiation. These results indicate that the requirement of bidirectional plasticity for PP1 is frequency-dependent and that a broad range of plasticity is negatively constrained by PP1, a feature that may correlate with the property of PP1 to constrain learning efficacy and promote forgetting.

Action Potentials↗
PubMed1998

Functional plasticity after left anterior temporal lobectomy: reconstitution and compensation of verbal memory functions.

PURPOSE: This study investigated the functional plasticity of the brain to reconstitute and compensate for verbal memory functions after epilepsy surgery of left temporocortical and temporomesial structures. We hypothesized that memory outcome would be best when surgery is performed within the period of cerebral plasticity, and that the outcome should be worst when fluid intelligence starts to decrease with physiologic aging. We also raised the question of different plasticity and compensation mechanisms for temporomesial and temporocortical memory functions. METHODS: We evaluated preoperative and 1-year-postoperative memory data and other verbal functions in 104 patients with epilepsy, who underwent a standard left anterior temporal lobe resection. We used memory measures that had been previously shown to be most selective for mesial and lateral functions, respectively. Determinants of postoperative memory outcome were evaluated by multiple regression analysis. Group statistics were calculated on the basis of the periods that are usually assumed to be significant for plasticity and behavioral compensation. Individual postoperative changes in memory functions were evaluated on the basis of test-retest data obtained in a group of 100 nonsurgical patients with localization-related epilepsies (mean retest interval >12 months). RESULTS: Only changes in cortically represented learning and data acquisition were related to age, plasticity, and capacities for behavioral compensation. No patient in the youngest group (younger than 15 years), 33% of patients who had surgery between the ages of 15 and 30 years, and 61% of the patients undergoing surgery older than age 30 years had significant deterioration in verbal learning. In contrast, postoperative changes in temporomesial consolidation/retrieval processes were independent of age at the time of surgery, plasticity, and capacities for behavioral compensation. CONCLUSIONS: Our data indicate different time windows for the reconstitution and compensation of mesial and cortical aspects of memory. Whereas the reconstitution of and compensation for cortical functions appear restricted by decreasing plasticity and physiological aging, mesial functions seem to be reconstituted by contralateral mesial structures over a much longer period. Concerning drug-resistant localization-related epilepsies, our results justify early consideration of surgery, especially when cortical structures are affected.

Adolescent↗
PubMed2004

Evaluation of a new generation of plastic culture bottles with an automated microbial detection system for nine common contaminating organisms found in PLT components.

BACKGROUND: A microbial detection system (BacT/ALERT 3D, bioMérieux [formerly Organon Teknika]) has previously been validated with a variety of bacterial contaminants in PLTs. The recovery of nine organisms seeded into PLTs with new plastic culture bottles was studied in comparison to the current glass bottles. The use of plastic instead of glass would be expected to reduce the risk of injury. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated into Day 2 (>24 hr <48 hr) apheresis PLT units to 10 and 100 CFUs per mL. Replicate samples (4 mL) were inoculated into both current- and new-generation standard aerobic and anaerobic bottles. RESULTS: All organisms (with the exception of P. acnes) were detected in a mean time of 9.3 to 18.9 hours (10 CFUs/mL) or 8.7 to 18.2 hours (100 CFUs/mL). In aggregate (with the exception of P. acnes), the plastic and glass aerobic bottles had a mean difference in detection of 1.2 hours (p < 0.0001), and the plastic and glass anaerobic bottles had a mean difference of 3.3 hours (p < 0.0001). In all cases, the mean detection time was superior or clinically comparable (within 0.1 hr) with the new plastic bottles. P. acnes (an anaerobic organism) was detected with the new and current anaerobic bottles in a mean of 72.8 and 90.4 hours (10 CFUs/mL) or 64.0 and 80.8 hours (100 CFUs/mL), respectively. The narrower bottle neck and smaller inoculation septum present with the new-generation plastic bottles were inoculated with comparable ease to that of the glass bottles. CONCLUSIONS: These data demonstrate that the new plastic bottles are clinically comparable or superior to the current glass standard aerobic and anaerobic culture bottles.

Bacillus cereus↗
PubMed2006

Stability and plasticity of intrinsic membrane properties in hippocampal CA1 pyramidal neurons: effects of internal anions.

CA1 pyramidal neurons from animals that have acquired hippocampal tasks show increased neuronal excitability, as evidenced by a reduction in the postburst afterhyperpolarization (AHP). Studies of AHP plasticity require stable long-term recordings, which are affected by the intracellular solutions potassium methylsulphate (KMeth) or potassium gluconate (KGluc). Here we show immediate and gradual effects of these intracellular solutions on measurement of the AHP and basic membrane properties, and on the induction of AHP plasticity in CA1 pyramidal neurons from rat hippocampal slices. The AHP measured immediately after establishing whole-cell recordings was larger with KMeth than with KGluc. In general, the AHP in KMeth was comparable to the AHP measured in the perforated-patch configuration. However, KMeth induced time-dependent changes in the intrinsic membrane properties of CA1 pyramidal neurons. Specifically, input resistance progressively increased by 70% after 50 min; correspondingly, the current required to trigger an action potential and the fast afterdepolarization following action potentials gradually decreased by about 50%. Conversely, these measures were stable in KGluc. We also demonstrate that activity-dependent plasticity of the AHP occurs with physiologically relevant stimuli in KGluc. AHPs triggered with theta-burst firing every 30 s were progressively reduced, whereas AHPs elicited every 150 s were stable. Blockade of the apamin-sensitive AHP current (I(AHP)) was insufficient to block AHP plasticity, suggesting that plasticity is manifested through changes in the apamin-insensitive slow AHP current (sI(AHP)). These changes were observed in the presence of synaptic blockers, and therefore reflect changes in the intrinsic properties of the neurons. However, no AHP plasticity was observed using KMeth. In summary, these data show that KMeth produces time-dependent changes in basic membrane properties and prevents or obscures activity-dependent reduction of the AHP. In whole-cell recordings using KGluc, repetitive theta-burst firing induced AHP plasticity that mimics learning-related reduction in the AHP.

Animals↗
PubMed1997

Ingredient selection for plastic composite supports for L-(+)-lactic acid biofilm fermentation by Lactobacillus casei subsp. rhamnosus.

Plastic composite supports containing 50% agricultural products (oat hulls, soybean hulls, yeast extract, soybean flour, dried bovine erythrocytes, bovine albumin, and/or mineral salts) and 50% (wt/wt) polypropylene were produced by high-temperature twin-screw extrusion. The research employed two half sets of a five-factorial fractional design (2(5 - 1)) to evaluate the effects of different agricultural components on the properties of the plastic composite supports and to select the best plastic composite support formulation for lactic acid fermentation. The biofilm population was affected by the contact angle and relative hydrophobicity of the supports (r = 0.79 to 0.82). Lactic acid was produced by the suspended cells (r = 0.96) and the biofilm on the plastic composite support discs (r = 0.85). Incorporation of yeast extract into plastic composite supports enhanced growth of free and attached cells in minimal medium (P < 0.0001). The presence of soybean hulls, yeast extract, or mineral salts in plastic composite supports produced less hydrophobic supports (P < 0.0001) and enhanced cell attachment (P < 0.03). Under all conditions, suspended-cell and polypropylene disc controls gave negligible lactic acid production and cell density. Plastic composite supports containing soybean hulls, yeast extract, soybean flour, bovine albumin, and mineral salts gave the highest biofilm population (2.3 x 10(9) CFU/g of support), cell density (absorbance of 1.8 at 620 nm), and lactic acid concentration (7.6 g/liter) in minimal medium.

Animals↗
PubMed1988

Adherence of Candida albicans germ tubes to plastic: ultrastructural and molecular studies of fibrillar adhesins.

Germ tubes of Candida albicans produced an additional fibrillar surface layer responsible for enhanced adherence to plastic. The correlation between germination of C. albicans and adherence of germ tubes to a plastic matrix led us to consider the existence of germ tube-specific adhesive components involved in the attachment process. Using concanavalin A-sensitized latex microspheres, we first detected extracellular molecules on the plastic surface after removal of the adherent germ tubes. Electron microscopy confirmed that fibrils of the germ tube involved in cell-substratum interconnections were retained on the plastic surface. Cytochemistry with concanavalin A-gold labeling demonstrated that these fibrillar structures contained mannoproteins. Dithiothreitol and iodoacetamide treatment of washed plastic allowed us to further characterize these fibrillar adhesins. Through analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, two components with molecular weights (MWs) of 68,000 and 60,000 were detected on the plastic surface. The 68,000-MW component appeared to be one of the major constituents of the germ tube surface layers. Biosynthetic labeling experiments performed with L-[35S]methionine revealed two additional proteins: a high-MW component (greater than 200,000), and a 200,000-MW component. These four proteins, strongly labeled on the plastic surface and on the germ tube cell wall layers, were in contrast slightly labeled or even nonidentified in the culture supernatant, suggesting their involvement in germ tube adherence.

Adhesiveness↗
PubMed1995

Immunohistochemical staining of plastic embedded bone marrow trephine biopsy specimens after microwave heating.

AIMS: To investigate (1) whether adequate immunohistochemical staining can be achieved on sections cut from plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer; and (2) whether this immunohistochemical staining is comparable with that achieved on routine sections cut from paraffin wax embedded trephine biopsy specimens after decalcification procedures. METHODS: Sixty five consecutive bone marrow trephine biopsy specimens of more than 1 cm in length were divided transversely into two equal parts. One part was processed in paraffin wax followed by decalcification. The other part was embedded in the epoxyresin Polarbed 812 followed by the cutting of 1 micron sections. Both parts underwent immunohistochemical staining by an identical panel of antibodies. With Polarbed 812 plastic embedded sections, microwave heating in citrate buffer was undertaken before the application of antisera. RESULTS: On sections cut from plastic embedded material, immunohistochemical staining was generally satisfactory, easy to interpret and comparable with that achieved with paraffin wax embedded material. Exceptions were antibodies to neutrophil elastase and CD61 where immunostaining was consistently negative on plastic embedded sections. Immunohistochemical staining for CD20 was consistently more reliable on plastic embedded sections. CONCLUSIONS: The results provide evidence that, with few exceptions, satisfactory immunohistochemical staining is possible on plastic embedded bone marrow trephine biopsy specimens after microwave heating in citrate buffer. This, combined with the advantage of superior cellular morphology with semi-thin (1 micron) sections of plastic embedded material, make such embedding procedures the preferred method for the processing of bone marrow trephine biopsy specimens.

Antibodies, Monoclonal↗
PubMed1994

Air embolus risk with glass versus plastic syringes: in vitro study and implications for neuroangiography.

PURPOSE: To assess syringe use among neuroangiographers and evaluate air emboli produced with glass and plastic syringes. MATERIALS AND METHODS: Questionnaires on syringes use were sent to 100 members of the American Society of Neuroradiology (ASNR). An in vitro system counted emboli during injections of contrast material and saline solution with either glass or plastic syringes. At Doppler sonography, an embolic signal was defined as the power of the reflected amplitude with auditory and visual confirmation. RESULTS: Of 62 respondents, 11.3% used glass syringes exclusively and 80.6% used plastic exclusively. Glass breakage was experienced by 72.5%, and 40% of them recalled an injury associated with such a breakage. No statistically significant difference was found between glass and plastic syringes for introduction of air emboli, though two outlying values represented larger numbers of emboli in the group with plastic syringes and contrast material. CONCLUSION: No reason for the continued use of glass syringes was found. No statistically greater risk of air emboli was shown with plastic syringes, and risk of breakage and injury is prevented. Caution is advised when injecting contrast material with plastic syringes because more air emboli may be introduced.

Cerebral Angiography↗
PubMed2006

Presynaptic plasticity in an immature neocortical network requires NMDA receptor activation and BDNF release.

Activity-dependent developmental maturation of the neocortical network is thought to involve the stabilization and potentiation of immature synapses. In particular, N-methyl-d-aspartate (NMDA) receptor-dependent long-term plasticity that is expressed presynaptically appears to be crucial for the selection of functionally adequate synapses. However, presynaptic expression of long-term plasticity in neocortical neurons has mainly been studied indirectly by electrophysiological techniques. Here we analyzed presynaptic plasticity directly by repeated imaging of actively cycling presynaptic vesicles with the styryl dye FM4-64 in cultured neocortical neurons at 34 degrees C. To monitor long-term changes, stimulation-induced saturating FM4-64 staining and subsequent destaining was performed twice with an interval of 1.5 h between stainings and with the first staining serving as a plasticity stimulus. In the vast majority of presynaptic release sites, we found an increase in the mean fluorescence intensity after the second staining indicating an enhanced number of cycling synaptic vesicles. Most intriguingly, we additionally observed the appearance of new active release sites. As demonstrated by the addition of the NMDA receptor antagonist d-2-amino-5-phosphonopentanoic acid (d-AP5), both plasticity phenomena were strictly dependent on NMDA receptor activation. This suggests that a subpopulation of release sites was functionally silent during the first round of staining. Moreover, we studied a potential role of brain-derived neurotrophic factor (BDNF) in this type of presynaptic plasticity by imaging BDNF-deficient neocortical neurons. The increase in fluorescence intensity was strongly inhibited in BDNF-knockout neurons and was absent in wild-type neurons in the presence of BDNF scavenging trkB receptor bodies. These results indicate that BDNF might play an important role as a plasticity-related messenger molecule in neocortical neurons.

2-Amino-5-phosphonovalerate↗
PubMed1999

Enhanced NR2A subunit expression and decreased NMDA receptor decay time at the onset of ocular dominance plasticity in the ferret.

Enhanced NR2A subunit expression and decreased NMDA receptor decay time at the onset of ocular dominance plasticity in the ferret. The NMDA subtype of glutamate receptor is known to exhibit marked changes in subunit composition and functional properties during neural development. The prevailing idea is that NMDA receptor-mediated synaptic responses decrease in duration after the peak of cortical plasticity in rodents. Accordingly, it is believed that shortening of the NMDA receptor-mediated current underlies the developmental reduction of ocular dominance plasticity. However, some previous evidence actually suggests that the duration of NMDA receptor currents decreases before the peak of plasticity. In the present study, we have examined the time course of NMDA receptor changes and how they correlate with the critical period of ocular dominance plasticity in the visual cortex of a highly binocular animal, the ferret. The expression of NMDA receptor subunits NR1, NR2A, and NR2B was examined in animals ranging in age from postnatal day 16 to adult using Western blotting. Functional properties of NMDA receptors in layer IV cortical neurons were studied using whole cell patch-clamp techniques in an in vitro slice preparation of ferret primary visual cortex. We observed a remarkable increase in NR1 and NR2A, but not NR2B, expression after eye opening. The NMDA receptor-mediated synaptic currents showed an abrupt decrease in decay time concurrent with the increase in NR2A subunit expression. Importantly, these changes occurred in parallel with increased ocular dominance plasticity reported in the ferret. In conclusion, molecular changes leading to decreased duration of the NMDA receptor excitatory postsynaptic current may be a requirement for the onset, rather than the end, of the critical period of ocular dominance plasticity.

Aging↗
PubMed2000

A new lactate-based, plasticizer-free, neutral peritoneal dialysis fluid provided in a two-compartment system: effect on peripheral leukocyte function.

BACKGROUND: A new neutral peritoneal dialysis fluid (PDF; Balance) provided in a two-compartment bag (pH 7.4, no plasticizers, minimal glucose degradation products - GDP) was investigated in comparison with a neutral control (Hanks' balanced salt solution with gelatin 0.1%) and other PDFs with standard properties and plasticizers (Andy plus, pH 5.2, GDP), plasticizer free (stay safe, pH 5.2, GDP), and in addition plasticizer free after sterile filtration instead of heat sterilization (pH 5.2) regarding the function of peripheral blood leukocytes. METHODS: Blood was drawn from 12 volunteers, and blood monocytes (MN) and polymorphonuclear leukocytes (PMNL) were collected. The cells were incubated for 30 min in control medium and the PDFs: glucose 1.5% (83 mmol/l) and 4.25% (238 mmol/l). Respiratory burst of cells was evaluated by chemiluminescence and superoxide (SO) generation after stimulation with phorbol myristate acetate. RESULTS: In comparison with the control medium, incubation of MN in the two-compartment PDF showed preservation of respiratory burst. In contrast, the incubation of MN in standard PDF and plasticizer-free PDF showed impaired functions. The same was found for PMNL. SO anion measurement in MN and PMNL after incubation in the new two-compartment PDF also showed preservation of cell function in comparison with the control medium. The incubation of PMNL in standard PDF and plasticizer-free PDF with a high glucose content showed depressed SO anion generation. CONCLUSIONS: These in vitro data demonstrate a better preservation of in vitro phagocyte function with adaptation of pH and reduction of glucose, GDP, and plasticizers in PDFs. The best results are achieved with the two-compartment, lactate-based neutral PDF.

Adult↗
PubMed2005

The NMDA antagonist memantine affects training induced motor cortex plasticity--a study using transcranial magnetic stimulation.

BACKGROUND: Training of a repetitive synchronised movement of two limb muscles leads to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS) mapping. We used this paradigm to study the effect of memantine, a NDMA antagonist, on short-term motor cortex plasticity in 20 healthy human subjects, and we were especially interested in possible differential effects of different treatment regimens. In a randomised double-blinded cross over study design we therefore administered placebo or memantine either as a single dosage or as an ascending dosage over 8 days. Before and after one hour of motor training, which consisted of a repetitive co-contraction of the abductor pollicis brevis (APB) and the deltoid muscle, we assessed the motor output map of the APB muscle by TMS under the different conditions. RESULTS: We found a significant medial shift of the APB motor output map after training in the placebo condition, indicating training-induced short-term plastic changes in the motor cortex. A single dosage of memantine had no significant effect on this training-induced plasticity, whereas memantine administered in an ascending dosage over 8 days was able to block the cortical effect of the motor training. The memantine serum levels after 8 days were markedly higher than the serum levels after a single dosage of memantine, but there was no individual correlation between the shift of the motor output map and the memantine serum level. Besides, repeated administration of a low memantine dosage also led to an effective blockade of training-induced cortical plasticity in spite of serum levels comparable to those reached after single dose administration, suggesting that the repeated administration was more important for the blocking effect than the memantine serum levels. CONCLUSION: We conclude that the NMDA-antagonist memantine is able to block training-induced motor cortex plasticity when administered over 8 days, but not after administration of a single dose. This differential effect might be mainly due to the prolonged action of memantine at the NMDA receptor. These findings must be considered if clinical studies are designed, which aim at evaluating the potency of memantine to prevent "maladaptive" plasticity, e.g. after limb amputation.

Adult↗