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Biomedical subjects

D Johnston

Publications and source records attributed to D Johnston.

At least 109 records · Page 6Linked to original sources

Fatigue in patients with cancer: results with National Cancer Institute of Canada Clinical Trials Group studies employing the EORTC QLQ-C30.

The purpose of this study was to examine the factors which affect the level of fatigue among patients participating in clinical trials in which this symptom had been assessed with the EORTC QLQ-C30. Data were assembled from 2390 patients in ten clinical trials in which the QLQ-C30 had been used to assess baseline and on-study quality of life. The relationship between the level of fatigue reported by the patients on the fatigue scale of this questionnaire and patient and disease characteristics was assessed in univariate and multivariate cross-sectional analyses. In addition, changes in fatigue scores were compared in a longitudinal analysis among patients on two arms of an anti-emetic trial whose emesis control was markedly different. Baseline fatigue levels differed substantially among patients taking part in the different trials. Factors associated with greater fatigue severity on univariate analysis included: female gender, presence of metastatic disease, and poorer performance status. In addition, on multivariate analyses the oldest patients were found to have less fatigue, as were patients with breast cancer, while patients with ovarian and lung cancer experienced greater fatigue. Patients on the arm of the anti-emetic trial in which emesis was better controlled showed significantly less increase in fatigue after receiving chemotherapy. The fatigue scale of the QLQ-C30 appears to provide a useful approach to assessing this important symptom. The relationships found between fatigue and patient and disease characteristics need further exploration as does the degree to which the QLQ-C30 fully captures this dimension of quality of life.

Adult↗

Decreased total antioxidant capacity but normal lipid hydroperoxide concentrations in sera of critically ill patients.

Oxidative stress (when free radical generation exceeds antioxidant defense) occurs in many human diseases and makes significant contributions to their pathogenesis. We automated assays estimating the antioxidant status of serum, and lipid hydroperoxide concentrations using the Monarch analyzer. In this assay, the antioxidant status of serum is measured by its ability to inhibit generation of free radicals from 2,2'-amino-di-[3-ethylbenzthiazole sulphonate] by metmyoglobin and hydrogen peroxide. The assay for measuring lipid peroxidation products in serum utilizes the ability of lipid hydroperoxides to generate methylene blue from 10N-methylcarbamyl 3,7-dimethylamino 10H-phenothiazine. We detected no lipid hydroperoxide in sera obtained from 24 controls. The mean antioxidant status was 1.69 mmol/l (SD; 0.20 mmol/l) in controls. The antioxidant capacity of serum was significantly reduced in sera of critically ill patients in the medical intensive care unit (mean = 1.05, SD = 0.26 mmol/l) with p value less than 0.05 by independent t-test, two tailed. Lipid peroxidation products were not significantly elevated in critically ill patients, however lipid peroxidation products were significantly elevated in hemodialysis patients (mean = 1.40, SD = 0.47 mumol/l) and in some kidney transplant recipients. We conclude that antioxidant capacity of sera in critically ill patients is significantly reduced.

Antioxidants↗

Prognostic significance of microsatellite instability in patients with gastric carcinoma.

A proportion of gastric adenocarcinomas exhibit replication errors manifested as microsatellite instability. The clinicopathological and prognostic significance of this abnormality remains uncertain. This study aimed to determine the importance of microsatellite instability by analysing a large series of gastric carcinomas from an English population. Using a novel fluorescent polymerase chain reaction technique, we amplified 11 microsatellite sequences from paired normal and carcinoma DNA from 101 patients who underwent a potentially curative resection for gastric carcinoma. Overall, 21% of cases demonstrated microsatellite instability in at least one locus. At least four loci were examined in each case. A replication error positive phenotype (minimum of 29% of loci affected) was detected in 9% of cases. There was no statistically significant association between the presence of microsatellite instability or replication error positive phenotype and the patient's age, sex, tumour site, stage, node status, histological subtype or grade. Carcinomas confined to the mucosa or submucosa (T1) showed a significantly higher frequency of instability and replication error positive phenotypes than T3 lesions (P = 0.03 and P = 0.05, respectively). A larger proportion of patients who were microsatellite instability or replication error positive were alive at 5 years compared with those who were negative but this did not reach statistical significance (P = 0.15 and P = 0.16, respectively). We identified a subset of gastric carcinomas from a relatively low-risk population which showed evidence of microsatellite instability. There were no statistically significant 5-year survival advantages in cases demonstrating microsatellite instability or replication error positive phenotypes. The detection of microsatellite instability is of limited prognostic value in gastric carcinoma.

Adult↗

Induction of mammary cancer and lymphoma by multiple, low oral doses of 7,12-dimethylbenz[a]anthracene in SENCAR mice.

Existing models of mouse mammary carcinogenesis induced by the model polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA) typically use a small number of bolus doses applied intragastrically. In contrast to this, typical human exposures to carcinogens are thought to be at lower doses and to occur with chronic or sporadic timing. When the classical dosage (1 mg DMBA given once a week for 6 weeks) was split into five daily doses of 200 microg given intragastrically to female SENCAR mice each week for 6 weeks, toxicity was high and the major tumor type seen was lymphoma. Lowering the dose to 60 microg/day gave less toxicity, a 75% incidence of lymphoma and a 30% incidence of mammary carcinoma. However, 20 microg DMBA given five times per week for 6 weeks resulted in a 65-70% incidence of mammary carcinoma within approximately 50 weeks. This represents a 50-fold lower daily dosage of DMBA than that used in the classical model. DNA was prepared from 10 mammary adenocarcinomas and 10 lymphomas and exons 1 and 2 of the H-ras1, K-ras and N-ras genes were sequenced using PCR techniques. Mutations altering codons 12 or 61 of one of the ras family genes were found in 4/10 mammary carcinomas and 5/10 lymphomas. Three mammary tumors exhibited codon 61 mutations, one in each of the genes studied, and a fourth tumor contained a codon 12 mutation in the K-ras gene. Among the lymphomas, two mutations in codon 12 of K-ras, one mutation in codon 61 of K-ras and two mutations in codon 61 of N-ras were also found. Each of the mutations could be interpreted as a G-->T or A-->T transversion. It is suggested that the high incidence of lymphoma at the higher, repetitive doses may be related to immunotoxicity. These low dose models of lymphomagenesis and mammary carcinogenesis should prove useful for tests of chemopreventive agents that target the initiation phase of carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Effect of naturally occurring coumarins on the formation of epidermal DNA adducts and skin tumors induced by benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in SENCAR mice.

Several naturally occurring coumarins previously found to be potent inhibitors of mouse hepatic ethoxyresorufin-O-deethylase (EROD) and/or pentoxyresorufin-O-dealkylase (PROD) were examined for their effects on formation of benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) DNA adducts in mouse epidermis, as well as, their effects on skin tumor initiation by these polycyclic aromatic hydrocarbons (PAH). Bergamottin, a potent inhibitor of hepatic EROD, given topically 5 min prior to an initiating dose of B[a]P, significantly decreased total covalent binding of B[a]P to DNA in a dose-dependent manner 24 h after treatment. A dose of 400 nmol bergamottin reduced covalent binding of B[a]P by 72%. Coriandrin, at a dose of 400 nmol also significantly reduced total covalent binding of B[a]P by 59%. In addition, formation of the major (+)anti-B[a]P-diol epoxide-N2-dGuo adduct was selectively reduced by both of these coumarins. In contrast, bergamottin and coriandrin did not significantly decrease covalent binding of DMBA to epidermal DNA at doses of either 400 nmol or 800 nmol. Imperatorin and isopimpinellin, which are more potent inhibitors of hepatic PROD activity, significantly reduced overall binding of DMBA to epidermal DNA by 67% and 52%, respectively, when applied at doses of 400 nmol. These two coumarins also inhibited B[a]P-DNA adduct formation at similar doses but to a lesser extent. Imperatorin at a dose of 400 nmol dramatically decreased formation of covalent DNA adducts derived from both the anti and syn diol epoxides of DMBA. Bergamottin was a potent inhibitor of tumor initiation by B[a]P while coriandrin was less effective in this regard. Imperatorin was an effective inhibitor of skin tumor initiation by DMBA and also inhibited complete carcinogenesis by this PAH. At dose levels higher than those effective against DMBA, imperatorin also inhibited tumor initiation by B[a]P. The results demonstrate that several naturally occurring coumarins possess the ability to block DNA adduct formation and tumor initiation by PAHs such as B[a]P and DMBA. The mechanism for reduced DNA adduct formation and tumor initiation appears to involve inhibition of the P450s involved in the metabolic activation of these hydrocarbons. Finally, the differential effects of certain coumarins on B[a]P vs DMBA DNA adduct formation and tumor initiation may be useful for dissecting the role of specific cytochromes P450 in their metabolic activation.

9,10-Dimethyl-1,2-benzanthracene↗

Spiral computed tomography and operative staging of gastric carcinoma: a comparison with histopathological staging.

BACKGROUND: Much controversy exists as to the value of computed tomography (CT) in the preoperative staging of gastric cancer, because of its limited ability to identify correctly lymph node (LN) metastases, invasion of adjacent organs, or hepatic and peritoneal metastases. Spiral CT scanners have a number of potential advantages over conventional scanners, including the absence of respiratory misregistration, image reconstruction smaller than scan collimation permitting overlapping slices and optimisation of intravenous contrast enhancement. AIM: To compare the performance of spiral CT and operative assessment against formal (TNM) pathological staging. PATIENTS AND METHODS: A study of 105 consecutive patients who underwent both spiral CT and operative staging was performed. All CT scans were reviewed by a radiologist who commented on tumour location and size, evidence of adjacent organ invasion, lymph node metastases to both N1 and N2 nodes, and evidence of hepatic and peritoneal metastases. All patients underwent careful operative assessment at the time of surgery, along the lines suggested by Rohde and colleagues. RESULTS: Spiral CT remained poor at identifying LN metastases to both N1 and N2 lymph nodes, with sensitivity ranging from 24 to 43%; specificity, however, was 100%. Operative staging was superior, with sensitivities between 84 and 94%, but specificity was much lower (63-74%). Spiral CT correctly detected 13 of 17 cases of invasion of either the colon or the mesocolon (sensitivity 76%) compared with 16 of 17 cases at operative staging (sensitivity 94%). Spiral CT correctly identified three of six cases with invasion of the pancreas (sensitivity 50%) compared with six of six cases on operative staging (sensitivity 100%). Spiral CT correctly identified 12 of 17 cases of peritoneal metastases (sensitivity 71%) and four of seven cases of hepatic metastases (sensitivity 57%). CONCLUSION: Whilst spiral CT remains poor at identifying lymph node metastases, it correctly identified most cases with invasion of either the colon or the mesocolon and half the cases of pancreatic invasion. It was of value in detecting peritoneal metastases and some cases with hepatic metastases. At present, at Leeds General Infirmary spiral CT is performed routinely on all patients with gastric cancer and a selective staging laparoscopy policy is adopted in those patients in whom the status of the peritoneal cavity and liver is in doubt.

Adult↗

Ca2+ channel antagonist U-92032 inhibits both T-type Ca2+ channels and Na+ channels in hippocampal CA1 pyramidal neurons.

The effects of 7-[[4-[bis(4-fluorophenyl)-methyl]-1-piperazinyl]methyl] -2-[(2-hydroxyethyl)amino] 4-(1-methylethyl)-2,4,6-cycloheptatrien-1-one (U-92032), a newly described Ca2+ channel blocker, on voltage-gated ionic currents were measured. Whole cell voltage-clamp records were obtained from acutely isolated CA1 hippocampal pyramidal neurons from 7- to 14-day-old rats. Dimethyl sulfoxide, at either 0.01% or 0.1%, partially inhibited T-type Ca2+ currents (approximately 20% inhibition) but not high-voltage-activated (HVA) Ca2+ currents. Ethanol (0.2%) did not affect Ca2+ currents. U-92032 selectively inhibited T-type Ca2+ currents (median inhibiting concentration approximately 500 nM). HVA Ca2+ currents were less sensitive, with approximately 75% of the current resistant at 10 microM. Inhibition of Ca2+ currents was reversible. U-92032 inhibited Na+ currents at concentrations similar to those required for T-type currents (> 33% block at 1 microM). Block of Na+ currents took several minutes to develop and was irreversible. Voltage-gated K+ currents were insensitive to U-92032 (1 or 10 microM). These results indicate that U-92032 inhibits both T-type Ca2+ channels and Na+ channels, constraining its utility in certain studies. Among Ca2+ channels, however, U-92032 should prove a useful tool for distinguishing physiological contributions of T-type channels.

Animals↗

Contribution of voltage-gated Ca2+ channels to homosynaptic long-term depression in the CA1 region in vitro.

Homosynaptic long-term depression (LTD) of synaptic efficacy was induced in field excitatory postsynaptic potentials by administration of 900 pulses at either 1 or 3 Hz in 2- to 3-wk-old Sprague-Dawley rats. The stimulation was administered via a bipolar stimulating electrode placed immediately adjacent to the recording electrode in the stratum radiatum region of the hippocampal CA1 subfield. Equivalent LTD induction occurred whether the slices were maintained at room temperature or at 32 degrees C. Lowering bath Ca2+ to 0 mM, or increasing it to 4 mM, prevented the induction of the depression. The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (50 microM) reversibly blocked the induction of homosynaptic LTD. In addition, the L-type voltage-gated calcium channel (VGCC) antagonist nimodipine (10 microM) and the R- and T-type VGCC antagonist NiCl2 (25 microM) also prevented homosynaptic LTD induction. These results indicate that in addition to N-methyl-D-aspartate receptor activity, Ca2+ influx via VGCCs can play an important role in the induction and expression of LTD induced by low-frequency stimulation in the hippocampal formation.

Animals↗

Active dendrites reduce location-dependent variability of synaptic input trains.

We examined the hypothesis that dendritic voltage-gated channels can reduce the effect synaptic location has on somatic depolarization in response to patterns of short synaptic trains (referred to as location-dependent variability). Three computer models of a reconstructed hippocampal CA1 cell, each of increasing realism and complexity, were used. For each model, the goal was to identify the dendritic composition that best reduced the location-dependent variability. The first model was linear and a single parameter, dendritic membrane conductance (GDm, where Rm = 1/GDm), was varied. Surprisingly, a negative GDm minimized the location-dependent variability. Superposition of the synaptic inputs showed that, compared with passive dendrites, active dendrites increase the mean of the individual responses while decreasing the variance between synapses at different locations. Active dendrites compensate the three components of passive cable signal interference that increase with distance from the soma: the accumulation of charge on dendritic membrane capacitance, the escape of charge across synaptic and nonsynaptic dendritic membrane conductances, and the reduction in synaptic charge entry due to increased depolarization of dendrites located farther from the soma. We also found that the entire active dendritic tree contributes charge to any one active synapse. The second model contained an artificial voltage-dependent current (Iboost) added to passive apical dendrites. The optimal amount of Iboost that minimized location-dependent variability was found to be independent of the strength of individual synaptic inputs but inversely related to the synaptic duration. In the third model, realistic T-type Ca2+ and persistent Na+ channel models were added to passive dendrites and numerically fit to reproduce the effects of Iboost. Both realistic currents minimized synaptic variability. The densities for the realistic dendritic currents were not uniform but showed subtle variations and a slight reduction with distance from the soma. A heteroassociative memory network also was modeled to demonstrate the important relationship between location-dependent variability and memory recall performance. Compared with passive dendrites, active dendrites increased memory storage by reducing recall errors. These simulations demonstrate that active dendrites can minimize the cable properties of passive dendrites and enhance the soma's ability to determine the strength of the synaptic input. These models predict dendrites that minimize location-dependent variability will have an overall negative slope conductance I-V relationship that is tuned precisely.

Animals↗

Labor positions on worksite tobacco control policies: a review of arbitration cases.

Although worksite smoking restrictions have become increasingly common in recent years, organized labor has generally not been involved in the adoption of these policies; some evidence suggests that unions often oppose the adoption of worksite smoking policies. To contribute to an understanding of labor's role in tobacco control policies, this paper reports the results of a review of 85 arbitration cases and 5 cases of unfair labor practices charges published between 1986 and 1994. In most of the cases reviewed, management unilaterally imposed a new smoking policy, which the union then grieved. Union opposition to the policy generally focused on the process by which the policy was adopted, rather than the content of the policy; the concern was that management had breached its duty to bargain with the union regarding the adoption of the policy. These results underline the importance of joint labor-management actions on worksite tobacco control policies.

Employee Grievances↗

Establishment of two human prostate cancer cell lines derived from a single bone metastasis.

Human prostate cancer cell lines are particularly difficult to establish, and most existing cell lines do not exhibit features commonly seen in human prostate cancer. Most available models either grow only in vivo as xenografts or are androgen insensitive and fail to express prostate-specific antigen (PSA). The lack of functionally relevant model systems of advanced prostate cancer has limited prostate cancer research and therapy development. Of 30 processed samples derived from patients with prostate cancer, we established two cell lines (MDA PCa 2a and MDA PCa 2b) that express PSA and androgen receptor, grow in vitro, and are androgen sensitive. Cells from these lines produced tumors in nude mice when injected either s. c. or orthotopically (intraprostatic). Both cell lines were established from a bone metastasis of a patient whose cancer was exhibiting androgen-independent growth. Although both were derived from two samples of the same specimen, they have different genetic features (as assessed by karyotype analysis) and different phenotypes (e.g., morphology and growth rate). It is likely that they are distinct clones isolated by the use of different culture procedures and reflect the genetic heterogeneity of the tumor. These new cell lines are the first available derived from a bone metastasis of an androgen-independent prostatic adenocarcinoma that grow both in vivo and in vitro and have retained PSA expression and androgen sensitivity. They therefore constitute important model systems to address critical questions related to the androgen-independent growth of human prostate cancer and to the complex process of bone metastasis.

Androgens↗

Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons.

A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH-IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH-IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH-IS (30-60 microm from the soma) raised the apparent somatic threshold by approximately 8 mV. We estimated the Na+ current density in the AH-IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3-4 pA/microm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH-IS and that the minimum threshold for spike initiation of the neuron is not determined by a high density of Na+ channels in the AH-IS region.

Action Potentials↗

Multiple channel types contribute to the low-voltage-activated calcium current in hippocampal CA3 pyramidal neurons.

Hippocampal neurons exhibit low-voltage-activated (LVA) and high-voltage-activated (HVA) calcium currents. We characterized the LVA current by recording whole-cell Ca2+ currents from acutely isolated rat hippocampal CA3 pyramidal neurons in 2 mM Ca2+. Long depolarizing steps to -50 mV revealed two components to the LVA current: transient and sustained. The transient phase had a fast decay time constant of 59 msec. The sustained phase persisted throughout the depolarization, even for steps lasting several seconds. The transient current was inhibited by the classic T-type channel antagonists Ni2+ and amiloride. The anticonvulsant phenytoin preferentially blocked the sustained phase, but ethosuximide had no effect. Steady-state inactivation of the transient component was half-maximal at -80 mV. Nimodipine, an L-type channel antagonist, partly inhibited the sustained current. BayK-8644, an L-type channel agonist, potentiated the sustained current. Calciseptine, another L-type channel antagonist, inhibited the sustained component. omega-Conotoxin-MVIIC, a nonselective toxin for HVA channels, had no effect on either of the LVA current components. omega-Grammotoxin-SIA, another nonselective toxin, partially inhibited the sustained component. The voltage dependence of activation of the nimodipine-sensitive current could be fit with a single Boltzmann, consistent with a homogenous population of L-type channels in CA3 neurons. Half-maximal activation of the nimodipine-sensitive current occurred at -30 mV, considerably more negative than the remaining HVA current. These results suggest that in physiologic Ca2+ more than one type of Ca2+ channel contributes to the LVA current in CA3 neurons. The transient current is carried by T-type channels. The sustained current is carried, at least in part, by dihydropyridine-sensitive channels. Thus, the designation "low-voltage-activated" should not be limited to T-type channels. These findings challenge the traditional designation of L-type channels as exclusively HVA and reveal a possible role in subthreshold Ca2+ signaling.

Animals↗

Actions of endogenous opioids on NMDA receptor-independent long-term potentiation in area CA3 of the hippocampus.

The opioid peptides represent a major class of neurotransmitter in the vertebrate nervous system and are prevalent in the hippocampus. There is considerable interest in the physiological function of the opioids contained in the mossy fiber pathway. The release of opioids from mossy fibers shows a strong frequency dependence. Long-term potentiation (LTP) at this synapse, an NMDA receptor-independent form of LTP, also depends on high-frequency synaptic activity, and this has led to speculation that endogenous opioids may be a critical factor in LTP induction. Previous reports using extracellular recordings have provided evidence for and against a role for opioids in mossy fiber LTP. Using single-cell recording techniques, we have tested the hypothesis that endogenous opioids are required for mossy fiber LTP induction. We recorded from a defined population of synapses that had EPSCs with fast rise times, short latencies, and monophasic decays, consistent with a proximally terminating synapse. The opioid antagonist naloxone prevented mossy fiber LTP in the rat, but had no effect on the commissural/associational system, a nonopioid-containing pathway. The action of naloxone was not mediated through disinhibition because GABAA receptors were pharmacologically blocked in these experiments. We also tested the hypothesis that variations in postsynaptic receptor subtype distribution between species might explain previous controversies regarding the role of endogenous opioids. In contrast to the rat, LTP of the mossy fiber field potential in guinea pig was not blocked by naloxone. Our data suggest that opioids may be the presynaptically released, frequency-dependent, associative factor for mossy fiber LTP induction.

Animals↗

Dendritic calcium channels and hippocampal long-term depression.

The authors examine the potential role of the different sources of dendritic Ca2+ influx in long-term depression (LTD) of synaptic efficacy. Recent data on the location and functional distribution of voltage-gated Ca2+ channels obtained from fluorescence imaging and patch clamp experiments are presented. This is followed by a discussion of the existing evidence for different sources of Ca2+ playing a role in the induction of LTD. The authors conclude that a number of key issues need to be resolved before any conclusions are drawn as to the involvement of any specific route of Ca2+ entry in LTD.

Animals↗

Does eversion of the anorectum during restorative proctocolectomy influence functional outcome?

PURPOSE: The aim of this study was to determine the effect of eversion of the anorectum during restorative proctocolectomy (RP) for ulcerative colitis on functional outcome. METHODS: One hundred seventeen patients underwent RP with stapled end-to-end ileal pouch-anal anastomosis (EEA), without resection of the anal mucosa. Sixty-four underwent EEA with eversion of the anorectum, and 53 underwent EEA without eversion. Each patient underwent paired studies of anorectal function before and a median of 12 months after RP. RESULTS: One year after RP, median (interquartile range) maximum resting pressure was 69 (range, 51-88) cmH2O in those patients who underwent eversion vs. 80 (range, 64-90) cmH2O in patients without eversion (P < 0.04). Threshold sensation in the upper, middle, and lower thirds of the anal canal were 9.1, 7.4, and 6.8 mA after eversion vs. 6.9, 4.9, and 3.8 mA without eversion (P = 0.003, P < 0.001, P < 0.001, respectively). Before operation, all patients had a rectoanal inhibitory reflex; however, after RP, 54 of 64 patients in the eversion group and 50 of 53 patients with a stapled EEA without eversion had an inhibitory reflex (P = not significant). Leakage of mucus was experienced by 11 patients who underwent eversion, compared with 9 patients without eversion. Fifty-six of 64 patients with eversion could defer defecation for more than 30 min compared with 43 of 53 patients without eversion. Twenty-two of 64 patients in the eversion group retained perfect discrimination between flatus and feces compared with 38 of 54 without eversion (P < 0.001). Level of the anastomosis was 1 (range, 0.5-3) cm above dentate line after eversion compared with 1.5 (range, 0-6) cm without eversion. CONCLUSION: Clinical outcome after RP with eversion was not as good as outcome after stapled EEA without eversion. Such a conclusion requires confirmation in a prospective control trial.

Adult↗

The calcium code.

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Action Potentials↗