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Biomedical subjects

E Eisenberg

Publications and source records attributed to E Eisenberg.

At least 19 recordsLinked to original sources
PubMed2006

Opioids for neuropathic pain.

BACKGROUND: The use of opioids for neuropathic pain remains controversial. Studies have been small, have yielded equivocal results, and have not established the long-term risk-benefit ratio of this treatment. OBJECTIVES: To assess the efficacy and safety of opioid agonists for the treatment of neuropathic pain. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (2nd Quarter 2005), MEDLINE (1966 to June 2005), and EMBASE (1980 to 2005 Week 27) for articles in any language, and reference lists of reviews and retrieved articles. SELECTION CRITERIA: Trials were included in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology, pain was assessed using validated instruments, and adverse events were reported. Studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse effects. MAIN RESULTS: Twenty-three trials met the inclusion criteria and were classified as short-term (less than 24 hours; n = 14) or intermediate-term (median = 28 days; range = eight to 70 days; n = 9). The short-term trials had contradictory results. In contrast all nine intermediate-term trials demonstrated opioid efficacy for spontaneous neuropathic pain. Meta-analysis of seven intermediate-term studies showed mean post-treatment visual analog scale scores of pain intensity after opioids to be 13 points lower on a scale from zero to 100 than after placebo (95% confidence interval -16 to -9; P < 0.00001). The most common adverse events were nausea (33% opioid versus 9% control: number needed to treat to harm (NNH) 4.2) and constipation (33% opioid versus 10% control: NNH 4.2), followed by drowsiness (29% opioid versus 12% control: NNH 6.2), dizziness (21% opioid versus 6% control: NNH 7.1), and vomiting (15% opioid versus 3% control: NNH 8.3). Where reported, 23 (11%) of 212 participants withdrew because of adverse events during opioid therapy versus nine (4%) of 202 receiving placebo. AUTHORS' CONCLUSIONS: Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain, whereas intermediate-term studies demonstrate significant efficacy of opioids over placebo, which is likely to be clinically important. Reported adverse events of opioids are common but not life threatening. Further randomized controlled trials are needed to establish long-term efficacy, safety (including addiction potential), and effects on quality of life.

Analgesics, Opioid↗
PubMed2006

Analysis of the ordering transition of hard disks through the Mayer cluster expansion.

The available virial coefficients for the two-dimensional hard-disks model are transformed into a matrix representation of the thermodynamic potentials, which allows for an accurate description of the whole fluid phase, up to the phase transition. We find that the fluid phase terminates at the transition point, implying a second-order phase transition in accordance with the Kosterlitz-Thouless-Halperin-Nelson-Young scenario of a transition into a hexatic phase. The density and pressure at the transition are calculated from the available first ten virial coefficients, and are found to be in excellent agreement with recent Monte-Carlo calculations. Finally, we calculate the equation of state in the critical region.

Journal Article↗
PubMed2003

Random matrix theory for closed quantum dots with weak spin-orbit coupling.

To lowest order in the coupling strength, the spin-orbit coupling in quantum dots results in a spin-dependent Aharonov-Bohm flux. This flux decouples the spin-up and spin-down random matrix theory ensembles of the quantum dot. We employ this ensemble and find significant changes in the distribution of the Coulomb blockade peak height, in particular, a decrease of the width of the distribution. The puzzling disagreement between standard random matrix theory and the experimental distributions by Patel et al. [Phys. Rev. Lett. 81, 5900 (1998)]] might possibly be attributed to these spin-orbit effects.

Journal Article↗
PubMed2003

Prevalence and characteristics of pain induced by percutaneous liver biopsy.

UNLABELLED: Percutaneous needle liver biopsy is an important procedure for the diagnosis and evaluation of liver disease and is frequently associated with pain. In this prospective study, we investigated the prevalence and characteristics of this pain syndrome. Fifty-four subjects, who underwent liver biopsy under ultrasound guidance, received 5 mg of diazepam orally 1 h before the procedure and local infiltration with 10 mL of 2% lidocaine just before needle insertion. Outcome measures included the visual analog scale for measuring pain intensity over 24 h, pain localization on a body scheme, and the Spielberger questionnaire for measuring anxiety levels. Forty-seven (84%) of the 54 respondents reported pain 30 min after the biopsy (visual analog scale, 4.2 +/- 0.5; mean +/- SEM), and 21 (39%) reported pain at the 24-h time point. Biopsy site pain was reported by 9 subjects, right shoulder pain by 14, and pain at both sites by 24. Higher pain intensities were reported by women and by subjects with higher anxiety levels. This study indicates that liver biopsy is a painful condition in most patients. Mild anxiolytic treatment plus local anesthetic infiltration seem to produce insufficient analgesia, thus indicating that a more profound analgesic treatment is required for better control of this pain. IMPLICATIONS: Percutaneous liver biopsy is a painful procedure in most patients. Mild anxiolytic treatment plus local anesthetic infiltration seem to produce insufficient analgesia. A more profound analgesic treatment is required for better control of this pain.

Adult↗
PubMed2002

Coherent electron transport in a Si quantum dot dimer.

We show that the coherence of charge transfer through a weakly coupled double-dot dimer can be determined by analyzing the statistics of the conductance pattern, and does not require a large phase coherence length in the host material. We present an experimental study of the charge transport through a small Si nanostructure, which contains two quantum dots. The transport through the dimer is shown to be coherent. At the same time, one of the dots is strongly coupled to the leads, and the overall transport is dominated by inelastic cotunneling processes.

Journal Article↗
PubMed2001

Clathrin exchange during clathrin-mediated endocytosis.

During clathrin-mediated endocytosis, clathrin-coated pits invaginate to form clathrin-coated vesicles (CVs). Since clathrin-coated pits are planar structures, whereas CVs are spherical, there must be a structural rearrangement of clathrin as invagination occurs. This could occur through simple addition of clathrin triskelions to the edges of growing clathrin-coated pits with very little exchange occurring between clathrin in the pits and free clathrin in the cytosol, or it could occur through large scale exchange of free and bound clathrin. In the present study, we investigated this question by studying clathrin exchange both in vitro and in vivo. We found that in vitro clathrin in CVs and clathrin baskets do not exchange with free clathrin even in the presence of Hsc70 and ATP where partial uncoating occurs. However, surprisingly FRAP studies on clathrin-coated pits labeled with green fluorescent protein-clathrin light chains in HeLa cells show that even when endocytosis is blocked by expression of a dynamin mutant or depletion of cholesterol from the membrane, replacement of photobleached clathrin in coated pits on the membrane occurs at almost the same rate and magnitude as when endocytosis is occurring. Furthermore, very little of this replacement is due to dissolution of old pits and reformation of new ones; rather, it is caused by a rapid ATP-dependent exchange of clathrin in the pits with free clathrin in the cytosol. On the other hand, consistent with the in vitro data both potassium depletion and hypertonic sucrose, which have been reported to transform clathrin-coated pits into clathrin cages just below the surface of the plasma membrane, not only block endocytosis but also block exchange of clathrin. Taken together, these data show that ATP-dependent exchange of free and bound clathrin is a fundamental property of clathrin-coated pits, but not clathrin baskets, and may be involved in a structural rearrangement of clathrin as clathrin-coated pits invaginate.

Adenosine Triphosphate↗
PubMed2001

Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study.

OBJECTIVE: To study the efficacy of lamotrigine in relieving the pain associated with diabetic neuropathy. METHODS: The authors randomly assigned 59 patients to receive either lamotrigine (titrated from 25 to 400 mg/day) or placebo over a 6-week period. Primary outcome measure was self-recording of pain intensity twice daily with a 0 to 10 numerical pain scale (NPS). Secondary efficacy measures included daily consumption of rescue analgesics, the McGill Pain Questionnaire (MPQ), the Beck Depression Inventory (BDI), the Pain Disability Index (PDI), and global assessment of efficacy and tolerability. RESULTS: Twenty-four of 29 patients (83%) receiving lamotrigine and 22 of 30 (73%) patients receiving placebo completed the study. Daily NPS in the lamotrigine-treated group was reduced from 6.4 +/- 0.1 to 4.2 +/- 0.1 and in the control group from 6.5 +/- 0.1 to 5.3 +/- 0.1 (p < 0.001 for lamotrigine doses of 200, 300, and 400 mg). The results of the MPQ, PDI, and BDI remained unchanged in both groups. The global assessment of efficacy favored lamotrigine treatment over placebo, and the adverse events profile was similar in both groups. CONCLUSIONS: Lamotrigine is effective and safe in relieving the pain associated with diabetic neuropathy.

Diabetic Neuropathies↗
PubMed2001

Prevalence and characteristics of post coronary artery bypass graft surgery pain (PCP).

Coronary artery bypass grafting (CABG) is one of the most common surgical procedures performed worldwide. However, its frequent complication, the post-CABG pain (PCP) syndrome, remains poorly documented. This retrospective cohort study was aimed to investigate the prevalence and characteristics of this syndrome. Five hundred and four of 540 subjects, who underwent CABG surgery at our institution between January 1995 and December 1996 and who could be identified, were mailed questionnaires regarding the presence and characteristics of chest wall pain. Eighty of 217 patients, who were defined as having PCP based on these questionnaires, were evaluated in detail. Main outcome measures included a preliminary pain questionnaire, pain localization on a body scheme, a five-point verbal scale and the Visual Analogue Scale (VAS) for measuring pain intensity. Pain qualities, disability and depression were measured by the McGill Pain Questionnaire (MPQ), the Pain Disability Index (PDI), and the Beck Depression Inventory (BDI), respectively. Medical and neurological examinations were also conducted, as well as quantitative thermal testing (QTT) of the chest wall. The preliminary pain questionnaires indicated that 219 of the 387 respondents (56%) reported chest wall pain, which was categorized as PCP. One hundred and forty-two (65%) of the patients with PCP reported pain of at least moderate severity, and 151 (72%) reported that the pain interfered with their daily activities. Eighty PCP patients were available for a detailed evaluation. Left-sided chest wall pain was noted by 53 subjects, midline scar pain by 47, and right-sided pain by nine subjects. Pain intensity (VAS) was 35 +/- 22 (mean +/- SD), MPQ score was 4.9 +/- 3.7, PDI score was 2.0 +/- 0.7, and BDI score was 9.3 +/- 7.3. The neurological examination and the QTT indicated three subcategories of PCP: (1) left-sided chest wall pain often associated with hypoesthesia, mechanical allodynia, and elevated thermal thresholds; (2) midline scar pain accompanied primarily by mechanical allodynia; (3) right-sided, relatively infrequent pain. While the first two subcategories seem to have a neurogenic etiology, this later subcategory of pain is of a mal-defined etiology. This study indicates that PCP is a group of pain syndromes with a high prevalence, and with a negative effect on mood and performance of daily activities. The risk of developing PCP and its potential consequences should therefore be discussed with every patient prior to CABG surgery. These results will need to be confirmed in larger, multi-center studies.

Aged↗
PubMed2001

Caenorhabditis elegans auxilin: a J-domain protein essential for clathrin-mediated endocytosis in vivo.

The budding of clathrin-coated vesicles is essential for protein transport. After budding, clathrin must be uncoated before the vesicles can fuse with other membranous structures. In vitro, the molecular chaperone Hsc70 uncoats clathrin-coated vesicles in an ATP-dependent process that requires a specific J-domain protein such as auxilin. However, there is little evidence that either Hsc70 or auxilin is essential in vivo. Here we show that C. elegans has a single auxilin homologue that is identical to mammalian auxilin in its in vitro activity. When RNA-mediated interference (RNAi) is used to inhibit auxilin expression in C. elegans, oocytes show markedly reduced receptor-mediated endocytosis of yolk protein tagged with green fluorescent protein (GFP). In addition, most of these worms arrest during larval development, exhibit defective distribution of GFP-clathrin in many cell types, and show a marked change in clathrin dynamics, as determined by fluorescence recovery after photobleaching (FRAP). We conclude that auxilin is required for in vivo clathrin-mediated endocytosis and development in C. elegans.

Adaptor Proteins, Vesicular Transport↗
PubMed2001

Effect of salicis cortex extract on human platelet aggregation.

The bark of Salix species contains several prodrugs of salicylate, mainly salicin. The aim of this study was to investigate if during pain treatment with Salicis cortex extract platelet aggregation was affected. A total of 51 patients were enrolled in the study. Thirty-five patients suffering from acute exacerbations of chronic low back pain received randomly and double-blind either Salicis cortex extract with 240 mg salicin/day (n = 19) or placebo (n = 16). Further sixteen patients with stable chronic ischemic heart disease were given 100 mg acetylsalicylate per day. Platelet aggregation was studied using an aggregometer. As aggregating agents, arachidonic acid (500 micrograms/ml), adenosine di-phosphate (2 x 10(-5) M) and collagen (0.18 microgram/ml) were used. The mean maximal arachidonic acid induced platelet aggregation was 61%, 78% and 13% in the Salicis cortex extract, placebo and acetylsalicylate groups. Acetylsalicylate had a significant inhibitory effect on platelet aggregation compared to Salicis cortex extract (p = 0.001) and placebo (p = 0.001). There was also a significant difference between the placebo and the willow bark-treated groups in the maximal platelet aggregation induced by arachidonic acid (p = 0.04) and ADP (p = 0.01). No statistical difference was found between the groups when collagen was applied to the human platelets. Daily consumption of Salicis cortex extract with 240 mg salicin per day affects platelet aggregation to a far lesser extent than acetylsalicylate. Further investigation needs to clarify if this finding is of clinical relevance in patients with impaired thrombocyte function.

Adenosine Diphosphate↗
PubMed2001

Contribution of heat shock proteins to cell protection from complement-mediated lysis.

The possible participation of hsc70 and hsp70 in cellular protection from complement damage was studied. Human erythroleukemia K562 cells were pretreated with reagents affecting hsc70 or hsp70, and cell sensitivity to lysis by antibody and human complement was examined. Treatment with deoxyspergualin, an hsc70 inhibitor, sensitized K562 cells to complement lysis, whereas treatment with ethanol, butanol or hemin, inducers of hsc70 synthesis, protected the cells from complement-mediated lysis. Incubation of K562 at either 42 degrees C or with the amino acid analogue L-azetidine-2-carboxylic acid induced synthesis of hsp70, but not of hsc70. The latter treatment also conferred elevated resistance to complement lysis on K562 cells. Pretreatment of K562 cells with sub-lethal doses of complement desensitizes them to lethal complement doses. No effect of sublytic complement on synthesis of hsc70 and hsp70 was found. However, the results demonstrated that complement stress causes translocation of hsc70 from the cytoplasm to the K562 cell surface. Two monoclonal and two polyclonal antibodies identified hsc70 on the surface of intact, viable complement-stressed cells, while antibodies directed to hsp70 did not bind to these cells. Altogether, the results suggest that the heat shock proteins hsc70 and hsp70 play a role in cell defense against complement.

Alcohols↗
PubMed2001

Expression of auxilin or AP180 inhibits endocytosis by mislocalizing clathrin: evidence for formation of nascent pits containing AP1 or AP2 but not clathrin.

Although uncoating of clathrin-coated vesicles is a key event in clathrin-mediated endocytosis it is unclear what prevents uncoating of clathrin-coated pits before they pinch off to become clathrin-coated vesicles. We have shown that the J-domain proteins auxilin and GAK are required for uncoating by Hsc70 in vitro. In the present study, we expressed auxilin in cultured cells to determine if this would block endocytosis by causing premature uncoating of clathrin-coated pits. We found that expression of auxilin indeed inhibited endocytosis. However, expression of auxilin with its J-domain mutated so that it no longer interacted with Hsc70 also inhibited endocytosis as did expression of the clathrin-assembly protein, AP180, or its clathrin-binding domain. Accompanying this inhibition, we observed a marked decrease in clathrin associated with the plasma membrane and the trans-Golgi network, which provided us with an opportunity to determine whether the absence of clathrin from clathrin-coated pits affected the distribution of the clathrin assembly proteins AP1 and AP2. Surprisingly we found almost no change in the association of AP2 and AP1 with the plasma membrane and the trans-Golgi network, respectively. This was particularly obvious when auxilin or GAK was expressed with functional J-domains since, in these cases, almost all of the clathrin was sequestered in granules that also contained Hsc70 and auxilin or GAK. We conclude that expression of clathrin-binding proteins inhibits clathrin-mediated endocytosis by sequestering clathrin so that it is no longer available to bind to nascent pits but that assembly proteins bind to these pits independently of clathrin.

Adaptor Protein Complex 1↗
PubMed2000

The molecular chaperones Hsp90 and Hsc70 are both necessary and sufficient to activate hormone binding by glucocorticoid receptor.

Glucocorticoid receptors must be complexed with Hsp90 in order to bind steroids, and it has been reported that at least three other proteins, Hop, Hsc70, and a J-domain protein (either Hsp40 or Ydj1), are required for formation of active Hsp90-steroid receptor complex. In the present study, we reinvestigated activation of stripped steroid receptors isolated from either L cells or WCL2 cells. Surprisingly, we found, using highly purified proteins, that only Hsp90 and Hsc70 are required for the activation of glucocorticoid receptors in the presence of steroids; in the absence of steroids, either p23 or molybdate are also required as reported previously. Addition of Hop or Ydj1 had no affect on the rate or magnitude of the activation of the stripped receptors, and quantitative Western blots confirmed that neither Hop or Hsp40 were present in our protein preparations or in the stripped receptors. Furthermore, a truncated recombinant Hsp70 that does not bind Hop or Hsp40 was as effective as wild-type Hsp70 in activating stripped receptor. Since Hsc70 does not bind directly to Hsp90 but both proteins bind to Hop, it has been suggested that Hop acts as a bridge between Hsp90 and Hsp70. However, we found that after Hsc70 or Hsp90 bind directly to the stripped receptors, they are fully reactivated by Hsp90 or Hsc70, respectively. We, therefore, conclude that Hsp90 and Hsc70 bind independently to stripped glucocorticoid receptors and alone are sufficient to activate them to bind steroids.

Animals↗
PubMed2000

Hsc70 chaperones clathrin and primes it to interact with vesicle membranes.

When Hsc70 uncoats clathrin-coated vesicles in an auxilin- and ATP-dependent reaction, a single round of rapid uncoating occurs followed by very slow steady-state uncoating. We now show that this biphasic time course occurs because Hsc70 sequentially forms two types of complex with the dissociated clathrin triskelions. The first round of clathrin uncoating is driven by formation of a pre-steady-state assembly protein (AP)-clathrin-Hsc70-ADP complex. Then, following exchange of ADP with ATP, a steady-state AP-clathrin-Hsc70-ATP complex forms that ties up Hsc70, preventing further uncoating. This steady-state complex forms only during uncoating in the presence of APs; in the absence of APs, Hsc70 rapidly dissociates from the uncoated clathrin and continues to carry out uncoating. Whether it is complexed with ATP or ADP, the steady-state complex has very different properties from the pre-steady-state complex in that it cannot be immunoprecipitated by anti-clathrin antibodies and is readily dissociated by fast protein liquid chromatography. Remarkably, when the steady-state complex is incubated with uncoated vesicle membranes in ATP, the pre-steady-state complex reforms, suggesting that the clathrin triskelions in the steady-state complex rebind to the membranes and are again uncoated by Hsc70. We propose that Hsc70 not only uncoats clathrin but also chaperones it to prevent it from inappropriately polymerizing in the cell cytosol and primes it to reform clathrin-coated pits.

Adaptor Proteins, Vesicular Transport↗
PubMed2000

Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells.

Auxilin is a brain-specific DnaJ homolog that is required for Hsc70 to dissociate clathrin from bovine brain clathrin-coated vesicles. However, Hsc70 is also involved in uncoating clathrin-coated vesicles formed at the plasma membrane of non-neuronal cells suggesting that an auxilin homolog may be required for uncoating in these cells. One candidate is cyclin G-associated kinase (GAK), a 150-kDa protein expressed ubiquitously in various tissues. GAK has a C-terminal domain with high sequence similarity to auxilin; like auxilin this C-terminal domain consists of three subdomains, an N-terminal tensin-like domain, a clathrin-binding domain, and a C-terminal J-domain. Western blot analysis shows that GAK is present in rat liver, bovine testes, and bovine brain clathrin-coated vesicles. More importantly, liver clathrin-coated vesicles, which contain GAK but not auxilin, are uncoated by Hsc70, suggesting that GAK acts as an auxilin homolog in non-neuronal cells. In support of this view, the clathrin-binding domain of GAK alone induces clathrin polymerization into baskets and the combined clathrin-binding domain and J-domain of GAK supports uncoating of AP180-clathrin baskets by Hsc70 at pH 7 and induces Hsc70 binding to clathrin baskets at pH 6. Immunolocalization studies suggest that GAK is a cytosolic protein that is concentrated in the perinuclear region; it appears to be highly associated with the trans-Golgi where the budding of clathrin-coated vesicles occurs. We propose that GAK is a required cofactor for the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells.

Adaptor Proteins, Vesicular Transport↗
PubMed2000

Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study.

PURPOSE: Herbal medicines are widely used for the treatment of pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) bark extract, which is widely used in Europe, for the treatment of low back pain. SUBJECTS AND METHODS: We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oral willow bark extract with either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain-free without tramadol for at least 5 days during the final week of the study. RESULTS: The treatment and placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain-free patients in the last week of treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. Significantly more patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severe allergic reaction, perhaps to the extract. CONCLUSION: Willow bark extract may be a useful and safe treatment for low back pain.

Administration, Oral↗