Comparison of on-site and photographic evaluations of the suppressive effects of cetirizine, loratadine, and fexofenadine on skin response to histamine lontophoresis: A double-blind, crossover study in healthy volunteers

Background:

The standard method used to determine the potency of antihistaminesis to assess the degree of suppression of skin response to histamine challenge.

Objectives:

The aims of this study were to compare the efficacy of 3 antihistaminesusing a histamine challenge test and the usefulness of on-site evaluation with that of photographic evaluation of skin-test reactions.

Methods:

In this prospective, double-blind, crossover study, healthy volunteerswere given cetirizine 5 mg (CTZ-5) and 10 mg (CTZ-10), loratadine 10 mg (LOR), fexofenadine 60 mg BID (FEX), and placebo (PLC), in a randomly assigned order, with an interval of at least 1 week between treatments. Before and 0.5 to 24 hours after administration, the areas of flare and wheal induced by histamine iontophoresis were measured directly (on site) by 1 evaluator and by another evaluator using photographic images on a computer monitor.

Results:

Ten healthy volunteers (6 men, 4 women; mean age, 28.2 years[range, 20-39 years]; mean weight, 60.7 kg [range, 41-81 kg]) were enrolled. The data from 9 subjects were analyzed; the data from 1 subject were omitted because the subject used an over-the-counter cold medication containing diphenhydramine several times during the study. By both methods, all antihistamines were shown to suppress flare significantly from 4 to 24 hours after administration. CTZ was most potent in suppressing both flare and wheal. For flare, the areas as measured using on-site evaluation were larger overall than those measured using photographic evaluation, but the shapes of the time-course graphs were similar for both. Overall, the flare area measurements started to decrease significantly from baseline values 4 hours after drug administration, reached a nadir at 10.5 hours, and remained significantly lower compared with baseline values at 24 hours. Comparisons between antihistamines showed significant differences in mean flare areas between the 2 doses of CTZ and LOR from 8 to 12 hours after administration in both evaluation methods. The wheal areas were significantly reduced from baseline values by most of the antihistamines 4 to 12 hours after drug administration, reached their lowest values at 10.5 hours, and returned to near-baseline values at 24 hours. Comparisons with PLC values at each time point, however, showed significant differences only for CTZ-5 and CTZ-10 from 4 to 12 hours after administration. Comparison between antihistamines showed significant differences in mean flare areas between the 2 doses of CTZ and LOR from 8 to 12 hours after administration in both evaluation methods. Although the flare areas measured by both methods correlated linearly (r = 0.90; P < 0.001), the correlation for wheal areas was weaker (r = 0.76; P < 0.001).

Conclusions:

In this study in healthy volunteers, single doses of CTZ 5 mg and CTZ 10 mg were more potent compared with single-dose LOR 10 mg and FEX 60 mg BID in suppressing skin response. Although linear correlations were found between skin-response areas, as measured by on-site and photographic evaluation, it was difficult to differentiate between wheal and flare by photographic evaluation, especially when a typical wheal was suppressed to slightly edematous erythema by antihistamines.     

变应原皮肤点刺试验750例的结果分析及护理体会

目的探讨变应原皮肤试验结果对临床的指导意义,并总结试验过程中的护理配合。方法对2007年3—9月750例疑诊为变应性鼻炎患者做变应原皮肤点刺试验,统计分析变应原皮肤试验的结果,并制定严密的护理和急救措施。结果750例受检者中皮试阳性者680例（90．67％）、阴性者70例（9．33％）;室内变应原主要种类为屋尘螨614例（90．3％）、粉尘螨594例（87．4％）、热带螨300例（44．1％）,而植物性变应原为艾草38例（5．6％）、豚草34例（5．0％）。所有皮肤试验者均未发生严重全身过敏反应。结论变应原皮肤试验是诊断变应性鼻炎的重要依据,可为特异性免疫治疗提供参考;试验过程中应配合健康教育和心理护理,并加强护理观察。     

Evaluating the response of patients undergoing both allergy skin testing and in vitro allergy testing with the ImmunoCAP Technology System

PURPOSE: To evaluate the response of patients who underwent both skin and in vitro allergy testing, both of which are accepted methods. DATA SOURCES: Retrospective review of the case notes of 100 patients evaluated by both testing methods for allergic disease. CONCLUSIONS: A total of 62 patients (62%) tested positive to at least one of the tested allergens via the in vitro method. A total of 65 patients (65%) tested positive to at least one allergen via the skin-testing method. The most frequently elicited allergic response from the in vitro method was to white oak. Indoor mold and dust most frequently elicited response via skin testing. IMPLICATIONS FOR PRACTICE: Both in vitro and in vivo allergy testing have limitations. Practitioners should be aware of these when establishing a treatment plan based on the results of differing allergy testing methods. Due to differing responses to skin and in vitro testing methods, it may be prudent to perform both tests to obtain a definitive diagnosis for the allergic patient.     

Telavancin (VIBATIV) for the treatment of complicated skin and skin structure infections

Methicillin-resistant Staphylococcus aureus has emerged as a major causative pathogen in complicated skin and skin structure infections (cSSSIs). Unfortunately, treatment failure with vancomycin has been increasingly reported. Over the past decade, several alternative antimicrobial agents have been studied and approved for the treatment of cSSSIs. One such agent is the lipoglycopeptide telavancin, which was approved by the US FDA 2009. Given its dual mechanism of action, telavancin is characterized by a highly bactericidal activity and low potential for resistance selection. In addition, in clinical trials, it was efficacious and safe in the treatment of cSSSI. The purpose of this review is to give a background overview of telavancin, highlighting its microbiological, pharmacokinetic and pharmacodynamics characteristics, to summarize the available evidence for its use in the treatment of cSSSIs, and to provide an updated evaluation of its safety profile.     

Comparison of inhibition of cutaneous histamine reaction of ebastine fast-dissolving tablet (20 mg) versus desloratadine capsule (5 mg): a randomized, double-blind, double-dummy, placebo-controlled, three-period crossover study in healthy, nonatopic adults

BACKGROUND: Ebastine is a long-acting, second-generation, selective histamine H1-receptor antagonist. A fast-dissolving tablet formulation of ebastine has been developed at 10- and 20-mg doses, with the intention of facilitating administration to patients experiencing problems with swallowing, including those confined to bed and elderly people, as well as those who may need to use ebastine when they do not have easy access to water to aid swallowing a tablet. OBJECTIVES: This study was conducted to assess the pharmacodynamic effects (ie, inhibition of wheal response to cutaneous histamine challenge, and subjective assessments of itching, flare, and pain) and tolerability of the fast-dissolving 20-mg ebastine tablet formulation compared with desloratadine 5-mg capsule and placebo. Acceptability and convenience of the fast-dissolving tablet were also evaluated. METHODS: This double-blind, double-dummy, randomized, placebo-controlled, 3-period crossover study was conducted at the Drug Research Centre, Department of Clinical Pharmacology, the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Healthy, nonatopic, white adults aged 18 to 40 years were randomly assigned to 1 of 6 study sequences: ABC, ACB, BAC, BCA, CBA, or CAB, where A was the ebastine fast-dissolving 20-mg tablet, B was the desloratadine 5-mg capsule, and C was placebo. All study drugs were given orally once daily (8-9 AM) on days 1 to 5 of each study period. Study periods were separated by a washout period of 7 to 10 days. Histamine skin-prick test (SPT) challenge was performed before study drug administration on day 1 of each period (baseline), and then every 20 minutes for 2 hours after administration and again after 24 hours. The final SPT was 24 hours after the day-5 dose was administered. The primary end point was inhibition o f the histamine response, defined as the percentage reduction from baseline wheal area 24 hours after 5 days of administration. Subjective symptoms (itching, flare, and pain) were assessed by subjects using visual analog scales every 20 minutes for 2 hours after administration on day 1. At study end, acceptability (taste, convenience, and overall preference) of the fast-dissolving tablet and capsule formulations were assessed using a questionnaire completed by subjects. Tolerability was assessed using physical examination, laboratory analysis, physician questioning, and spontaneous reporting. RESULTS: Thirty-six people were randomized (22 women, 14 men; mean [SD] age, 24.7 [4.1] years; mean [SD] weight, 63.2 [9.9] kg); 35 completed the study (1 subject was lost to follow-up after the second study period). Unadjusted mean (SD) wheal areas 24 hours after dose administration on day 5 were 72.9 (29.5), 115.0 (32.1), and 146.7 (32.2) mm(2), for ebastine, desloratadine, and placebo, respectively. Mean differences in reduction from baseline in wheal area were 29.0% for ebastine versus desloratadine and 43.7% for ebastine versus placebo (both, P < 0.001). Corresponding unadjusted mean (SD) wheal areas 24 hours after administration of the first dose on day 1 were 76.5 (22.5), 128.9 (24.0), and 140.5 (33.1) mm(2). Mean itching, flare, and pain ratings were not significantly different between study drugs. Results from the preference questionnaire indicated that the majority (80%) preferred the ebastine fast-dissolving tablet to the desloratadine capsule (and hypothetically also to tablets and oral solution, which were not tested in this study). Ninety-seven percent of subjects were of the opinion that compliance in the home setting would be facilitated by the fas-tdissolving tablet formulation. Fourteen adverse events (AEs) were reported in 9 (25%) volunteers; all AEs were of mild or moderate intensity. Five occurred with ebastine 20 mg (intermittent somnolence, back pain, pharyngolaryngeal pain, pyrexia, and oral pain [1 patient each]), 5 occurred with desloratadine 5 mg (asthenia [2 patients] and dry mouth, somnolence, and back pain [1 patient each]), and 4 occurred with placebo (diarrhea [2 patients] and somnolence and headache [1 patient each]). The relationship with the study drugs was considered unlikely in 6 cases and possible in the remaining 8 cases. An additional AE (back pain) occurred during a washout period. CONCLUSIONS: In this small study in healthy, nonatopic white subjects, inhibition of the response to histamine injection was significantly greater with the ebastine 20-mg fast-dissolving tablet compared with desloratadine 5-mg capsule and placebo after 1 and 5 days of administration. Most participants expressed an overall preference for the fast-dissolving tablet formulation over capsules. All study drugs were well tolerated.     

Dalbavancin (BI-387) for the treatment of complicated skin and skin structure infection

In the era of increasing antibiotic resistance, development of new agents that could provide therapeutic options for difficult to treat pathogens is vital. Dalbavancin is a new lipoglycopeptide recently approved by the US FDA for the treatment of acute bacterial skin and skin structure infections. A derivative of the older glycopeptide class, chemical structure alterations resulted in a molecule with a similar mechanism of action, however, with a comparatively increased activity as reflected by organism MICs. These modifications also resulted in an antibiotic with distinctive properties that allow for once-weekly dosing in the treatment of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and drug resistant Streptococcus spp. As the first of these long acting compounds, understanding the pharmacokinetic and pharmacodynamic properties of agents like dalbavancin is essential for determining a place in therapy.     

Bioequivalence study of two formulations of enalapril, at a single oral dose of 20 mg (tablets): A randomized, two-way, open-label, crossover study in healthy volunteers

Background: Enalapril maleate is the monoethyl ester prodrug of enalapril- at, an angiotensin-converting enzyme inhibitor indicated in the management of essential and renovascular hypertension, and in the treatment of congestive heart failure and in asymptomatic patients with left ventricular dysfunction and an ejection fraction of ≥35%. Enalapril has little pharmacologic activity until hydrolyzed in vivo to enalaprilat.Objective: The aim of the present study was to compare the bioavailability and tolerability of 2 commercial brands (test and reference formulations) of enalapril tablets (20 mg), described as the rate and extent of absorption of the active moiety, to assess their bioequivalence.Methods: This single-dose, randomized, 2-way, open-label, crossover study in healthy volunteers aged 18 to 40 years was conducted at the Clinical Pharmacology Study Unit, Hospital Clínico San Carlos (Madrid, Spain). Subjects were randomized to receive (under fasting conditions) either the test or reference formulation of enalapril (20-mg tablet) at study period 1 and the opposite formulation at study period 2. Study periods were separated by a washout period of at least 7 days. During each study period, 15 plasma extractions were made to determine enalapril and enalaprilat plasma concentrations and to calculate the pharmacokinetic (PK) properties (maximal plasma drug concentration [C_max], time to C_max [T_max], area under the plasma concentration-time curve [AUC] to the last measurable concentration [AUC_t], AUC from time 0 to infinity [AUC_0−∞], mean residence time, and elimination half-life []) of both. Physical examination, subject interview, laboratory analyses, electrocardiogram, and blood pressure (BP) were used to assess tolerability.Results: Twenty-four subjects were included in the study (12 men, 12 women; mean [SD] age, 22.8 [2.2] years [range, 19-30 years]). Of these, 1 subject (4.2%) withdrew from the study for personal reasons; thus, PK and statistical analyses included results from 23 subjects. No statistically significant sequence or period effect was found. T_max was not statistically different between the 2 formulations, and the 90% CI calculated for T_max for the difference of the medians was within the predefined range. The 90% CIs of the logarithmically transformed concentration-derived parameters (C_max AUC_t, and AUC_0−∞) also were within the predefined range; thus, the 2 formulations are considered bioequivalent. For both formulations, systolic and diastolic BPs showed significant reductions compared with baseline values (P < 0.05). Seven adverse effects were recorded, all of them transient and none of severe intensity.Conclusions: In this study of 2 commercial brands (test and reference formulations) of enalapril in healthy subjects, designed and conducted under Good Clinical Practice guidelines, a similar rate and extent of absorption for both formulations were found to be bioequivalent. Both formulations produced a significant decrease in BP values and were generally well tolerated.     

Flunarizine (10 and 20 mg) i.v. versus placebo in the treatment of acute migraine attacks: a multi-centre double-blind study

In a multi-centre, randomized double-blind study, the effect and tolerance of 10 and 20 mg flunarizine i.v. versus placebo was tested on 102 migraineurs with acute migraine attacks with and/or without aura. Thirty-seven patients received 10 mg flunarizine, 32 received 20 mg and 33 received placebo. The groups were comparable. Response to treatment was defined as pain reduction of at least 50% within 60 min on a visual analogue scale after i.v. drug administration. This effect was noted on 59.4% with 20 mg flunarizine, on 24.3% with 10 mg flunarizine and on 30.3% with placebo. The tolerance of flunarizine i.v. was similar to placebo. Blood pressure and pulse rate were not affected by flunarizine. All in all, 20 mg flunarizine i.v. appeared to be a suitable alternative for treatment of acute migraine attacks.     

Sumatriptan nasal spray (20 mg/dose) in the acute treatment of cluster headache

Subcutaneous injection of sumatriptan is an effective treatment for attacks of cluster headache with a short onset of action. This open, randomized study evaluates whether sumatriptan nasal spray at its highest commercially available dose (20 mg/dose) is equally effective. In 26 patients, four consecutive attacks were treated alternately with nasal spray and subcutaneous injection. Treatment was given within 5 min of onset of pain, and the time interval for the start and completeness of pain relief, provided these occurred within 15 min of administration, were recorded by the patient. After completion of the study, the patients were also asked to indicate which treatment they preferred, based on efficacy, side effects, and handling of the preparation. Forty-nine of the 52 treatments with injection resulted in complete relief of pain within 15 min, with a mean of 9.6 min. The remaining three attacks were reduced by a mean of 86.7% at 15 min. Only 7 of the 52 treatments with nasal spray in the nostril ipsilateral to pain resulted in complete relief within this time period, with a mean of 13.0 min. In 18 of these treatments pain was reduced by a mean of 42.2% at 15 min, whereas no effect on pain was obtained at this time in the remaining 27 treatments. The effect was almost identical when the nasal spray was administered in the nostril on the non-painful side. As an overall judgement, only 2 of the 26 patients preferred nasal spray to injection. We conclude that sumatriptan nasal spray 20 mg/dose is less effective than subcutaneous injection in relieving pain in the great majority of cluster headache sufferers.     

A comparison of preference for and efficacy of tablet formulations of sumatriptan (50 mg and 100 mg), naratriptan (2.5 mg), rizatriptan (10 mg), and zolmitriptan (2.5 mg) in the acute treatment of migraine

Abstract This randomized, multicenter, open-label, five-way crossover study was conducted to assess patients preference for tablet formulations of sumatriptan (50 mg and 100 mg), naratriptan (2.5 mg), rizatriptan (10 mg), and zolmitriptan (2.5 mg) in the acute treatment of migraine and to identify determinants of preference. Patients treated one mild, moderate, or severe migraine with each triptan. The results show that sumatriptan 100 mg was significantly preferred over the random preference rate of 20% (p<0.001) whereas sumatriptan 50 mg, naratriptan, rizatriptan, and zolmitriptan were not. Patients primary reason for preferring a medication was best relief of migraine pain, and the treatment that patients preferred corresponded to the medication that was most likely to confer for them a pain-free response 2 hours postdose. Across all patients, efficacy 2 hours postdose was comparable among triptans with the exception of naratriptan, which was slightly less effective than the other medications (pain-free response 2 hours postdose: 40% sumatriptan 100 mg, 37% sumatriptan 50 mg, 28% naratriptan 2.5 mg, 38% rizatriptan 10 mg, 36% zolmitriptan 2.5 mg). The medications were also similarly well-tolerated. These data demonstrate that information on patients medication preference supplements and does not duplicate data from traditional efficacy measures. Patient preference data are useful in tailoring migraine therapy to the needs of the individual patient.     

Pharmacokinetic and bioequivalence evaluation of two formulations of 100 mg trimebutine maleate (Recutin and Polybutin) in healthy male volunteers using the LC-MS/MS method

BACKGROUND: Trimebutine maleate is a prokinetic agent that acts directly on the smooth muscle of the GI tract. A bioequivalence (BE) study of 2 oral formulations of 100 mg trimebutine maleate (TMB) was carried out in 24 healthy male Korean volunteers according to a crossover-randomized design. METHODS: Subjects were given a single dose of 2 100 mg tablets of each formulation. The test and reference formulations were Recutin (Hutax Co., South Korea) and Polybutin (Samil Co., South Korea), respectively. Each set of tablets was administered with 240 ml of water to subjects after 10 h overnight fasting on 2 treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 36 h. Plasma was analyzed for the main metabolite of TMB, N-monodesmethyl trimebutine (nor-TMB), by a validated LC with MS/MS detection capacity for nor-TMB in the range 5-1500 ng/ml, with a lower limit of quantification (LLOQ) of 5 ng/ml. Several pharmacokinetic (PK) parameters (including AUC(t), AUC(infinity), C(max), T(max), T(1/2), and K(e)) were determined from the plasma concentrations of nor-TMB of both formulations. AUC(t), AUC(infinity), and C(max) were tested for BE after log-transformation of the data. RESULTS: No significant difference was found based on ANOVA; 90% confidence intervals (98.98%112.03% for AUC(t); 98.60%-113.20% for AUC(infinity); 90.85%-107.87% for C(max)) for the test and reference were found within KFDA acceptance range of 80-125%. CONCLUSIONS: Based on these statistical inferences, it was concluded that Recutin is bioequivalent to Polybutin and can be used interchangeably in a clinical setting.     

Efficacy and tolerability of paracetamol/tramadol (325 mg/37.5 mg) combination treatment compared with tramadol (50 mg) monotherapy in patients with subacute low back pain: a multicenter, randomized, double-blind, parallel-group, 10-day treatment study

BACKGROUND: In various pain studies, the single-dose combination of paracetamol/tramadol (PIT) was found to be more effective than either agent alone. PIT could provide benefit in patients with subacute low back pain (LBP). OBJECTIVE: This study compared the efficacy and tolerability of PIT with tramadol alone (T) in patients with subacute LBP and assessed whether, under comparable analgesic conditions, PIT would be better tolerated. METHODS: This was a multicenter, randomized, double-blind, parallel-group study. Patients were enrolled if they suffered from nonspecific LBP lasting 10 to 42 days and experienced at least moderate pain (> or =40 mm on a 100-mm visual analog scale). Patients were randomized and treated for 10 days with PIT (325 mg/37.5 mg) or T (50 mg). The study outcomes were treatment efficacy (pain intensity, pain relief, patient satisfaction, physicians' assessment of pain control) and tolerability (adverse events [AEs], patients' tolerability judgment). RESULTS: A total of 119 patients were enrolled (PIT, n = 59; T, n = 60). Demographic characteristics of patients were comparable between the PIT and T groups in regard to age (mean, 56.5 vs 54.1 years, respectively), sex (women/men, 38121 vs 31129), race (white, 96.1% vs 94.2%), and body mass index (24.9 vs 26.1 kg/m2). Pain intensity (mean [SD] percentage of worst imaginable pain) improved from nearly identical levels at baseline (P/T, 67.5 [13.0] vs T, 65.3 [14.6]; P = NS) to similarly low levels at the final visit (P/T, 27.9 [22.7] vs T, 24.8 [21.6]; P = NS). The reduction in pain intensity was significant in both treatment groups (P < 0.001). Adequate pain relief (ie, "moderate," "important," or "complete") was observed in 81.6% (40149) of PIT patients versus 82.9% (39147) of T patients (P = NS). Comparably high rates of overall patient satisfaction (72.5% [37151] vs 72.9% [35148], respectively; P = NS) were achieved. Both treatment groups took a comparable number of daily units of study medication, which resulted in significantly (P < 0.001) lower daily doses of tramadol in the P/T group (mean [SD], 172.5 [46.6] mg) than in the T group (227.3 [59.7] mg). More P/T patients (84.3%) than T patients (68.8%) judged treatment tolerability as good or very good (P = NS). Significantly fewer AEs (P < 0.001) were observed in PIT patients, and the overall incidence of AEs (mostly opioid-typical AEs [eg, nausea, dizziness/vertigo, sleepiness/drowsiness, constipation, vomiting]) was much lower after P/T compared with T (P = 0.019). The most common AEs in the P/T and T groups were nausea (8159 vs 21160 patients, respectively; P = 0.012) and dizziness (3/59 vs 15/60 patients; P= 0.006). CONCLUSIONS: Tramadol, alone and in combination with paracetamol, provided highly effective analgesia for these patients with subacute LSP However, the combination of PIT, which resulted in 25% less tramadol than equianalgesic daily doses of T alone, considerably reduced the incidence of AEs and improved tolerability.     

Adipose-derived stem cells (ASCs) as a source of endothelial cells in the reconstruction of endothelialized skin equivalents

Tissue-engineered autologous skin is a potential alternative to autograft for burn coverage, but produces poor clinical responses such as unsatisfactory graft intake due to insufficient vascularization. Endothelialized skin equivalents comprising human umbilical vein endothelial cells (HUVECs) survive significantly longer due to inosculation with the capillaries of the host, but these cells are allogeneic by definition. The aim of this study was to reconstruct an autologous endothelialized skin equivalent by incorporating progenitor or pre-differentiated endothelial cells derived from adipose tissue, easily accessible source for autologous transplantation. Human adipose tissue-derived stem cells were isolated from lipoaspirates and amplified to obtain endothelial progenitor cells, which were subsequently differentiated into endothelial cells. These cells were then seeded along with human fibroblasts into a porous collagen-glycosaminoglycan-chitosan scaffold to obtain an endothelialized dermal equivalent. Then, human keratinocytes give rise to a endothelialized skin equivalent. Immunohistochemistry and transmission electron microscopy results demonstrate the presence of capillary-like tubular structures in skin equivalents comprising pre-differentiated endothelial cells, but not endothelial progenitor cells. The former expressed both EN4 and von Willebrand factor, and Weibel-Palade bodies were detected in their cytoplasm. This study demonstrates that adipose tissue is an excellent source of autologous endothelial cells to reconstruct endothelialized tissue equivalents, and that pre-differentiation of stem cells is necessary to obtain vasculature in such models.     

Diclofenac-K (50 and 100 mg) and placebo in the acute treatment of migraine

The aim of the present study was to assess the efficacy and tolerability of single oral doses of 50 mg and 100 mg of diclofenac-K compared to placebo in migraine sufferers during three attacks. The study was conducted in a double-blind, randomized, placebo-controlled, three-period, within-patient comparative trial; 72 migraine patients were treated with diclofenac-K (50 mg or 100 mg) or placebo at six centres (1 in Sweden and 5 in Finland). The primary efficacy end-point was the change in pain intensity assessed on a 100 mm Visual Analogue Scale (VAS) at 120 min after taking the study medication. We found that 50 mg and 100 mg of diclofenac-K reduced the pain intensity significantly better than placebo (p = 0.003 and p = 0.001, respectively), without difference between the doses; 100 mg diclofenac-K was significantly better than placebo in improving phonophobia, photophobia, working ability and need for rescue medication. Diclofenac-K 50 mg or 100 mg is an effective and well-tolerated acute treatment for migraine headache and its associated symptoms. The higher dose of diclofenac-K was only marginally more effective than the lower dose.     

Selectivity of superficial vein occlusion at the ankle and calf level: a methodological study in healthy volunteers

Judgement of deep venous function may be necessary before surgery for superficial vein incompetence is performed. Assessment of deep venous function needs selective entrapment of superficial venous compartments between the ankle and knee, which may not be guaranteed if conventional tourniquets are used. This study was, therefore, aimed at modifying the technique of selective compression of superficial vein compartments. Twenty apparently normal legs of 10 volunteers were investigated on two study days. The subjects were in a supine position with the feet resting 30 cm above heart level. Ankle cuffs (3 cm wide) were placed just above the malleoli and stepwise inflated with air. The steady-state venous volume of the forefoot as a function of the pressure within the ankle cuff was measured with a mercury-in-rubber strain gauge. The maximum venous outflow velocity from the foot was also measured at each cuff pressure step after the addition of conventional thigh vein occlusion. The same protocol was used on the second study day: calf cuffs (3 cm wide) were then used instead of the ankle cuffs. In the forefoot, venous volume increased and the maximum venous outflow velocity decreased significantly either at ankle cuff pressures >30 mmHg or at calf cuff pressures of >60 mmHg. By using small cuffs, selective superficial vein occlusion seems to occur at cuff pressures ranging between 10 and 30 mmHg (ankle) and between 30 and 60 mmHg (calf), provided the feet are 30 cm above heart level. Higher cuff pressures seem to interact with deep venous function.     

Measurement properties of the six-minute pegboard and ring test (6PBRT) in healthy adolescents

ObjectivesTo investigate the cardiorespiratory responses to the 6-min pegboard and ring test (6PBRT) and to assess its reproducibility in healthy adolescents.MethodsIt was a cross-sectional study with 52 healthy adolescents (11–18 years old of both genders). The 6PBRT was performed twice on two different days by the same examiner. Intra-rater reliability, percentage of the minimal difference chance (MDC%) and agreement of the number of moving rings were analyzed. Also, cardiopulmonary parameters were collected before and after tests.ResultsIntraclass correlation coefficient (ICC) for the number of rings moved was 0.87 (95%CI 0.69–0.93). The mean number of moved rings during the second test was higher. The MDC% with a 95 % confidence interval was greater than acceptable values. Bland-Altman analysis did not show agreement between measurements (bias = 30.1); with upper and lower limits of agreement of −67.8 to 127.9, respectively. There was a significant increase in dyspnea, fatigue and HR values at the end of the tests (p < 0.0001). In both tests, participants reached HR equivalent to 48 % of the maximum predicted.ConclusionTogether, the results suggest that the 6PBRT is not a reliable measure for a population of healthy adolescents, which indicates the necessity to perform more than one test. The 6PBRT is suggested to be a submaximal test for this population.     

Reproducibility of pulse contour analysis in children before and after maximal exercise stress test: the Physical Activity and Nutrition in Children (PANIC) study

Objective: Arterial stiffness index (SI) and reflection index (RI) from digital pulse contour analysis have been shown to be good measures of arterial stiffness and may be useful in the evaluation of endothelial function. Finger skin temperature (FST) is also considered to reflect peripheral circulatory functions. We evaluated the reproducibility of SI, RI and FST before and after the exercise stress test. Methods: The subjects were 36 children (16 boys, 20 girls) 6–8 years of age. We measured SI, RI and FST at rest both before and after the exercise stress test on a cycle ergometer and repeated these measurements within 5–14 days. The reproducibility of SI, RI and FST was evaluated by calculating intraclass correlation coefficients (ICC), coefficients of variation (CV%) and 95% limits of agreements. Results: SI had a greater reproducibility after the exercise stress test than before it (CV% 4·8 versus 6·3%, ICC 0·548 versus 0·438). RI had a better ICC (0·689 versus 0·416) but a higher CV% (28·6 versus 18·7%) after the exercise stress test than before it. Relative change in response to the exercise stress test in SI (?1·5% at first visit and 0·4% at second visit) was not as dramatic as in RI (?49·3% at first visit and ?46·5% at second visit). The reproducibility of FST was also better after the exercise test than before it (CV% 5·7 versus 10·0%, ICC 0·509 versus 0·503). Conclusion: In healthy children, the reproducibility of SI, RI and FST was relatively good, especially after the exercise stress test.