The pain visual analog scale: is it linear or nonlinear?

The visual analog scale (VAS) is a tool widely used to measure pain, yet controversy surrounds whether the VAS score is ratio or ordinal data. We studied 52 postoperative patients and measured their pain intensity using the VAS. We then asked them to consider different amounts of pain (conceptually twice as much and then half as much) and asked them to repeat their VAS rating after each consideration (VAS2 and VAS3, respectively). Patients with unrelieved pain had their pain treated with IV fentanyl and were then asked to rate their pain intensity when they considered they had half as much pain. We compared the baseline VAS (VAS1) with VAS2 and VAS3. The mean (95% confidence interval) for VAS2:1 was 2.12 (1.81-2.43) and VAS3:1 was 0.45 (0.38-0.52). We conclude that the VAS is linear for mild-to-moderate pain, and the VAS score can be treated as ratio data. IMPLICATIONS: A change in the visual analog scale score represents a relative change in the magnitude of pain sensation. Use of the VAS in comparative analgesic trials can now meaningfully quantify differences in potency and efficacy.     

Cl- channels in basolateral TAL membranes. XIV. Kinetic properties of a basolateral MTAL Cl- channel

BACKGROUND: This article reports studies on the kinetics of chloride (Cl-) conductance in Cl- channels fused into bilayers from basolaterally enriched vesicles from rabbit outer medulla. A considerable body of evidence indicates that these channels represent rbClC-Ka, a 77 kDa kidney-specific protein of the ClC family of Cl- channels. rbClC-Ka, a candidate channel for mediating net Cl- absorption in the medullary thick ascending limb (MTAL), has been cloned from rabbit outer medulla and localized by immunofluorescence to basolateral membranes of the MTAL. Thus, this is the first account, to our knowledge, of the kinetics of ion permeation through a renal Cl- channel mediating net basolateral Cl- absorption in the thick ascending limb of Henle (TALH), and this channel may represent rbClC-Ka. METHODS: The electrophysiological properties of these channels were studied by fusing basolaterally enriched MTAL vesicles into planar bilayer membranes. RESULTS: Cl- conductance through these channels was concentration dependent and saturable. The relationship between gCl (pS) and symmetrical aqueous Cl- concentrations could be expressed in terms of the Michaelis equation with a limiting conductance (GClmax, pS) of 114 pS at infinitely high aqueous Cl- concentrations and a K1/2 of 163 mM Cl-. A log-log plot of the conductance-Cl- concentration relations, in the nonsaturating Cl- concentration range, had a slope of 0.91, that is, virtually unity. The relatively impermeant anion I- produced a voltage-dependent conductance blockade that could be overcome at high electric field strengths. CONCLUSIONS: The experimental data described earlier here fulfill the traditional criteria for a first-order process with a single Cl- ion occupying these channels at a given time. Although the channels may contain multiple ion binding sites, the latter function, in integral kinetic terms, as a single rate-limiting locus.     

Bacterial expression of the major antigenic regions of porcine rotavirus VP7 induces a neutralizing immune response in mice.

The outer capsid protein of rotavirus, VP7, is a major neutralization antigen. A chimeric protein comprising Escherichia coli (E. coli) outer membrane protein A (OmpA) and part of porcine rotavirus VP7 containing all three antigenic regions (217 amino acids) was expressed in Salmonella and E. coli as an outer-membrane associated protein. Mice immunized intraperitoneally or orally, respectively, with live E. coli or Salmonella cells expressing this chimeric protein produced antibodies against native VP7 as determined by enzyme-linked immunosorbent assays and neutralization tests. This indicates that the VP7 fragment from a porcine rotavirus which is antigenically similar to human rotavirus serotype 3, when expressed in bacteria as a chimeric protein, can form a structure resembling its native form at least in some of the major neutralization domains. These results indicate that the use of a live bacterial vector expressing rotavirus VP7 may represent a strategy for the development of vaccines against rotavirus-induced diarrhoea in infants.     

Division of the corpus callosum for uncontrollable epilepsy

Cerebral commissurotomy, the "split-brain" procedure, has been employed for the control of intractable seizures, in conjunction with moderate doses of anticonvulsant drugs. The results have been encouraging in several small series. The use of microsurgical techniques and the restriction of surgery to one commissure, the corpus callosum, has reduced morbidity without apparent change in result. The eight patients in our first series who underwent the prescribed division of several forebrain commissures are compared to the four patients in our second series who underwent division of the corpus callosum alone. The technique of callosotomy is described.     

How to use case studies: continuity cases vs. one-shot cases

Cases are a widely used instructional technique in health services administration education. This article discusses the merits of using cases in graduate education and identifies two types of cases, one-shot cases and continuity cases. The continuity case has many advantages for professional education. In particular it requires the students to recognize and cope with the interactions among decisions. Continuity cases are good vehicles both for instruction and for evaluation of students' competence. The supply of good continuity cases, however, is very limited. Consequently, despite the advantages of this type of case, instructors must consider using a blend of continuity and one-shot cases. Suggestions for the mix of cases within a curriculum are presented.     

Orthoptists reduce false-positive hospital referrals

This paper describes changes in the pattern of new referrals of children from birth to 2 years-of-age to the Hospital Eye Service in Oxford, following the implementation of a community-based orthoptic secondary vision-screening programme. The findings show that the number of false positive referrals was reduced by a half following the introduction of the service; false-positive referrals were also discharged sooner. This paper reports the findings of this survey and the results demonstrate the cost-effectiveness of the programme compared to outpatient attendance.     

Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2.

PURPOSE: Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non-small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients received paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall survival, time to progression (TTP), response rate (RR), and safety evaluation. Results A total of 1,037 patients were recruited. Baseline demographic characteristics were well balanced. There was no difference in overall survival (median, 8.7, 9.8, and 9.9 months for gefitinib 500 mg/d, 250 mg/d, and placebo, respectively; P =.64), TTP, or RR between arms. Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy. Subset analysis of patients with adenocarcinoma who received > or = 90 days' chemotherapy demonstrated statistically significant prolonged survival, suggesting a gefitinib maintenance effect. CONCLUSION: Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebo-controlled trial confirmed the favorable gefitinib safety profile observed in phase I and II monotherapy trials.     

A comparison of Rasch with Likert scoring to discriminate between patients' evaluations of total hip replacement surgery

The purpose of this study was to examine whether there are advantages in terms of outcome assessment of using Rasch methods of scoring the 12-item Oxford Hip Score (OHS) questionnaire over conventionally Likert scores. As part of a prospective cohort study of total hip replacements in five former regions of England the OHS was sent to patients pre-operatively, at 3 months and 1 year post-operatively. Post-operative data was collected on over 5000 cases. Based on the level of satisfaction with surgery, patients were divided into satisfied and dissatisfied. Analyses were performed to test the relative precision (RP) of Rasch scoring vs. conventionally Likert scores in discriminating the groups experiencing different level of satisfaction. Considerable gains in precision were achieved with Rasch scoring methods when groups were compared 3 and 12 months post-operatively. The results from the current study suggest that in some situations there may be substantial gains in measuring health related outcomes using Rasch-based scoring methods.     

Development of behavioral sensitization to the cocaine-like fungicide triadimefon is prevented by AMPA, NMDa, DA D1 but not DA D2 receptor antagonists.

Triadimefon (TDF) is a triazole fungicide that blocks the reuptake of dopamine (DA) and leads to increased locomotor activity levels in mice and rats, effects similar to those of indirect DA agonists such as cocaine. We recently found in mice that intermittent TDF administration led to robust locomotor sensitization, a phenomenon reflecting neuronal plasticity, following challenge with the same TDF dose after a 2-week withdrawal period. The current study sought to determine whether antagonists to DA D1-like receptors (SCH 23390; SCH), DA D2-like receptors (remoxipride; Rem), ionotropic glutamate n-methyl-d-aspartate (NMDA) receptors (CPP), or ionotropic glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (NBQX) could prevent the development of TDF behavioral sensitization, therefore indicating their mechanistic involvement in TDF sensitization. Mice were treated with either vehicle, SCH (0.015 mg/kg), remoxipride (Rem, 0.3 mg/kg), CPP (2.5 mg/kg) or NBQX (10.0 mg/kg), followed 30 min later by vehicle or 75 mg/kg TDF (TDF), twice a week for 7 weeks, with locomotor activity measured post-dosing once a week. After a 2-week withdrawal period, mice were challenged with 75 mg/kg TDF or vehicle, to test for the presence of behavioral sensitization. Pretreatment with SCH, CPP, or NBQX, but not Rem, blocked the development of behavioral sensitization to TDF specifically for vertical activity. Antagonists that blocked TDF vertical sensitization also attenuated the increase in extracellular DA turnover (homovanillic acid [HVA]/DA) normally associated with this behavioral response. Therefore, DA D1, NMDA and AMPA receptors appear to be necessary for the development of behavioral sensitization to TDF. As such, TDF may be considered an environmental risk factor for behavioral dysfunctions linked to glutamatergic and dopaminergic systems.