Crossover Clinical Study Research Articles

Actigraphic Monitoring During Sleep of Children With ADHD on Methylphenidate and Placebo

Sleep disturbances appear as a comorbid condition in children with attention-deficit/hyperactivity disorder. The aim of this study was to investigate the relationship of activity levels during sleep and therapeutic response to methylphenidate (MPH). Nightly sleep actigraphic recordings during a double-blind, placebo-controlled, crossover clinical study (1-week of 0.5 mg/kg MPH; 1-week of placebo) were obtained on 44 children, 6 to 12 years old, diagnosed with attention-deficit/hyperactivity disorder (DSM-IV). Significant (p <.005) differences between the conditions were found in several software-computed parameters: sleep onset latency (MPH, 39.3 minutes; placebo, 28.2 minutes), sleep efficiency (MPH, 78.0%; placebo, 80.4%), total sleep time (MPH, 7 hours; 57 minutes; placebo, 8 hours, 16 minutes). No significant differences on any of these measures were found among the 26 subjects who showed a moderate or large global improvement on MPH over placebo compared with 18 subjects who showed mild or no clinical improvement. MPH, given twice daily, induces a slight but significant sleep disturbance. Motor activity levels during sleep did not differentiate children who responded to MPH from those who did not respond. This suggests that responders to MPH treatment do not experience greater sleep disturbances than nonresponders, at least at the dose studied.

The effects of a chlorhexidine mouthrinse on culturable microorganisms of the tongue and saliva

A randomized and cross-over design clinical study with normal adult volunteers examined the effects of a 0.12% chlorhexidine (CHX) mouthrinse and a control rinse on a range of microflora including those implicated in halitosis on the tongue and saliva. Saliva and tongue scrapings were collected from 13 subjects prior to treatments with additional samples collected at 3 h post-treatment cultured on media to enumerate anaerobic, Gram-positive and Gram-negative bacteria, odorigenic bacteria producing hydrogen sulphide (H2S) and oral bacteria with proteolytic activity. In comparison to the control, rinsing with CHX demonstrated statistically significant reductions that ranged from 81-90% for tongue microflora with a 89-95% decrease noted on salivary flora (p<0.05). The effects of CHX on anaerobic, Gram-positive and Gram-negative bacteria are in accord with those noted on odorigenic bacteria producing H2S or proteolytic activity. These results help to explain previous clinical results on the malodor efficacy of CHX and highlight microbiological approaches for bacteria implicated in malodor.

Clinical Significance of Preserving Spontaneous QRS Wave in the Therapy of DDD Pacing for Sick Sinus Syndrome

The aim of this clinical crossover study was to elucidate the effects of atrioventricular (AV) synchronous pacing on cardiac function in patients with sick sinus syndrome (SSS). Thirty SSS patients, each with dual chamber pacemaker (DDD), were enrolled and divided into two groups based on echocardiographic findings. Group A (n = 16) had hypertensive heart disease (wall thickness 11 approximately 12 mm) or mitral or aortic regurgitation (Grade I or II). Group B (n = 14) had no organic heart disease. Three successive 3-month pacing periods were tested. For the first 3 months, long AV delay that achieved > 80% ventricular sensing was chosen. For the next 3 months, AV delay was abbreviated to achieve > 80% ventricular pacing at an optimal AV interval. For the final 3 months, the first setting was resumed. At the end of each period, M mode echocardiography, pulsed-Doppler study, and measurement of plasma brain natriuretic peptide (BNP) level were conducted. In both groups, echocardiographic parameters were not significantly changed during the evaluation. In group A, plasma BNP level was significantly higher at the end of the short AV delay period than at the long AV delay period (P = 0.009), while in group B it did not differ during each period. AV synchronous pacing (> 80% ventricular pacing) in the SSS patients with a DDD pacemaker implanted could increase the ventricular load, and it is better to preserve the spontaneous QRS with the DDD mode with prolonged AV delay in patients with mild hypertensive or valvular disease.

Effect of β-blockers on peripheral skin microcirculation in hypertension and peripheral vascular disease

This study was undertaken to investigate the possible negative effect of beta-blockers on skin microcirculation in patients with intermittent claudication and hypertension. Methods and materials In this clinical crossover study, 20 patients with mild to moderate hypertension, treated with long-term beta-blockade, and intermittent claudication or ischemic rest pain, underwent assessment of peripheral circulation before and after 2-week withdrawal of beta-blocking therapy and again 2 weeks after restarting therapy. Replacement therapy (calcium antagonist) was given if considered necessary to control hypertension. Skin microcirculation was assessed with three noninvasive techniques: capillary microscopy of the hallux nailfold, transcutaneous oximetry of the forefoot, and laser Doppler fluxmetry of the great toe. Mean initial blood pressure was 163/81 mm Hg. Mean heart rate significantly increased with withdrawal of beta-blocker, from 65 bpm to 85 bpm. No significant differences in skin microcirculation and blood pressure were found between measurements obtained before, during, and after withdrawal of beta-blocking therapy. Patients experienced no change in symptoms during the study. beta-Blockers do not appear to have a negative effect on peripheral skin microcirculation and are therefore not contraindicated to treat hypertension when intermittent claudication or ischemic rest pain is also present.

A Comparison of the Pharmacokinetics, Clinical Efficacy, and Tolerability of Once-Daily Tramadol Tablets with Normal Release Tramadol Capsules

This report describes a pharmacokinetic study and a clinical study of three different formulations of oral tramadol: once-daily tramadol tablets 150 and 200 mg, and normal release tramadol capsules 50 mg 8-hourly. The randomized, open-label, crossover pharmacokinetic study included 22 subjects. The three treatments showed equivalent mean systemic availability of tramadol. The mean relative systemic availabilities (90% confidence intervals) for the once-daily tablets 150 mg and the once-daily tablets 200 mg versus the normal release capsules were 89.6 (83.3–95.8)% and 90.5 (84.6–96.8)%, respectively. The values for the once-daily tablet 150 mg versus the once-daily tablet 200 mg were 99.0 (92.6–105.9)%. The randomized, double-blind, double-dummy, crossover clinical study included 134 patients with moderate osteoarthritic pain. The three treatments showed similar efficacy; they all reduced patients' pain scores from baseline and there were no significant treatment differences in pain scores during treatment. The three treatments were also well tolerated.

Effects of Introducing Linseed in Livestock Diet on Blood Fatty Acid Composition of Consumers of Animal Products

Reducing the ratio between essential fatty acids: C18:2 n–6/C18:3 n–3 down to 5 is recommended by Nutritional Guidelines. We studied the fatty acid (FA) changes in consumers’ plasma following changes in livestock diet. First, a zootechnical study introduced 5% of extruded linseed into the diet of livestock to replace other oleaginous ingredients, and on an iso-nutritional values basis. The products from linseed-fed animals contained more n–3 fatty acids (precursor α-linolenic and derivatives obtained by elongations and desaturations) than control animal products (issued from animals fed without linseed), and more conjugated linoleic acids (CLA). The n–6/n–3 ratio was reduced by 54% in butter, 60% in meat and 86% in eggs. Following this, a double-blind, randomised, cross-over clinical study involving 75 healthy volunteers compared plasma and erythrocyte FA profiles in consumers of animal products (from livestock fed the linseed diet or from livestock fed standard diet). It showed modifications in the FA composition of the experimental human regimen with more C18:3 n–3 (1.65 vs. 0.75 g/day), and more n–3 derivatives. The C18:2 n–6/C18:3 n–3 ratio decreased (7 vs. 15). In volunteers’ plasma, C18:3 n–3 increased in the essay group (0.93 vs. 0.44% of the FA), so did n–3 derivatives and CLA. The n–6/n–3 ratio decreased from 14.3 to 10.2. In erythrocytes, C20:5 n–3 increased in the essay group (0.59 vs. 0.45%) and so did C22:6 n–3. The n–6/n–3 ratio decreased in parallel from 4.2 to 3.8. Without any changes in consumers’ eating habits, foodstuffs from animals fed linseed diets induced significant modifications of human plasma and erythrocyte fatty acid composition (comparable to that noted under the ‘Cretan’ diet) and a sharp increase in CLA.

Pressure controlled versus volume controlled ventilation with laryngeal mask airway

Study Objective: To quantify the impact on peak airway pressure of pressure-controlled and volume-controlled ventilation during Laryngeal Mask Airway™ (LMA) use. Design: Prospective, crossover clinical study. Setting: University-affiliated hospital. Patients: 32 ASA physical status I and II patients undergoing general anesthesia with the LMA. Interventions: Patients were ventilated for three minutes both with pressure-controlled and volume-controlled ventilation, provided that tidal volume (V T ) and inspiratory time (It) were constant. Measurements and Main Results: The monitored parameters were electrocardiography, arterial blood pressure, pulse oximetry, capnography, neuromuscular transmission, airway pressure and flow, and concentration of ventilated vapors and gases. The actually delivered V T was similar with both types of ventilation (volume-controlled = 0.67 ± 0.13 lt, pressure-controlled = 0.67 ± 0.14 lt; p = 0.688). Peak airway pressure was lower during pressure-controlled ventilation (14.6 ± 3.5 cmH 2O) than during volume-controlled ventilation (16 ± 4 cmH 2O) ( p < 0.001). Furthermore, we noted that the higher the airway pressure with volume-controlled ventilation, the greater was the reduction in airway pressure during pressure-controlled ventilation. Conclusions: Pressure-controlled rather than volume-controlled ventilation can improve the effectiveness of mechanical ventilation in patients with high airway pressure.

Comparison of two filter combinations for membrane differential filtration (MDF): a prospective, cross-over controlled clinical study

Membrane differential filtration (MDF) is an accepted procedure for the extracorporeal removal of low-density lipoprotein (LDL) in hyperlipidemia. The selectivity and quality of LDL elimination by MDF largely depends on the properties of the membrane plasma fractionator. However, clinical data allowing a direct comparison between existing systems are not sufficient.

A crossover study of triptorelin and leuprorelin acetate

Objective: To compare the potency, side effects, and duration of action of triptorelin and leuprorelin acetate after i.m. injections. Design: Prospective, double-blind crossover clinical study. Setting: A teaching hospital. Patient(s): Fifty-four patients with pelvic endometriosis. Intervention(s): Twenty-seven patients had three doses of i.m. triptorelin (3.75 mg) followed by three doses of i.m. leuprorelin acetate at 4-week intervals. Twenty-one patients had three doses of i.m. leuprorelin acetate (3.75 mg) followed by three doses of i.m. triptorelin, also at 4-week intervals. Main Outcome Measure(s): Menopausal symptoms, time taken for menstruation to return, serum E 2, FSH, LH levels, lipid profiles, and liver function tests. Result(s): The potencies of triptorelin and leuprorelin acetate in lowering the serum E 2, FSH, and LH levels were comparable. The severity of menopausal symptoms, changes in the lipid profile and liver function parameters were similar after triptorelin and leuprorelin acetate. The resurgence of ovarian activities and the spontaneous return of menstruation occurred significantly earlier after leuprorelin acetate than triptorelin. Conclusion(s): Both drugs are equally potent in down-regulating the pituitary-ovarian function, and their side effects are similar. Triptorelin has a longer duration of drug action and can be administered over a longer interval period.

Effects of Nitric Oxide Inhalation After Pulmonary Thromboendarterectomy for Chronic Pulmonary Thromboembolism

To examine the hypothesis that nitric oxide (NO) inhalation improves hemodynamics and gas exchange in patients with chronic pulmonary thromboembolism after pulmonary thromboendarterectomy. Prospective crossover clinical study. : Surgical ICU in a national education and research hospital. : Seven patients (mean age +/- SD, 54 +/- 11 years) who underwent elective pulmonary thromboendarterectomy for chronic pulmonary thromboembolism. Patients breathed 20 parts per million of NO gas for 30 min at 12-h intervals until extubation of the trachea. Hemodynamics and arterial blood gas levels were analyzed before, during, and after NO inhalation. Waveform of pulmonary artery pressure (PAP) was evaluated using fractional pulse pressure (PPf): (systolic PAP - diastolic PAP)/mean PAP. After surgery, pulmonary vascular resistance decreased, PPf decreased, and cardiac index increased significantly. At the first trial, NO inhalation resulted in a slight improvement in arterial oxygen tension (from 173 +/- 33 to 196 +/- 44 mm Hg; p < 0.05), while hemodynamics did not change significantly. Twelve hours later, NO inhalation decreased pulmonary vascular resistance index (from 312 +/- 98 to 277 +/- 93 dyne.s. cm(-5)/m(2); p < 0.01), while the change in oxygenation was not significant. Immediately after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism, NO inhalation improved oxygenation; at 12 h after surgery, NO inhalation resulted in decreased pulmonary vascular resistance, although both changes were small.

Reduction of Neutrophil Activation by Vitamin E Modified Dialyzer Membranes

Background/Aim: Transient leukopenia during hemodialysis due to neutrophil activation is attributed to bioincompatibility of the dailysis membrane, but the mechanism remains unclear. We studied the mechanism of neutrophilic activation by comparing a vitamin E modified membrane (CLEE) and a regular cellulose membrane (CLSS). Methods: (1) CLSS and CLEE membranes were used in a crossover clinical study in 7 chronic hemodialysis patients. Neutropenia, CD11b expression, and plasma C3a and myeloperoxidase concentrations were compared between the two dialyzer membranes. (2) Normal blood was circulated through CLEE and CLSS minimodels, and the same parameters were compared. (3) Blood samples with modified complement activities (EDTA: both classical and alternative pathways inactivated; EGTA+Mg: classical pathway inactivated; heating: alternative pathway inactivated; control: no modification) were incubated in the CLSS minimodel, and the neutrophilic activation was compared. Results: In clinical hemodialysis, neutropenia, CD11b expression, and C3a and myeloperoxidase levels were significantly lower when CLEE membranes were used. The same tendency was observed in minimodels. However, the degrees of inhibition in clinical dialysis, especially at the venous line, were significantly higher than in minimodels. As compared with controls, CD11b expression and myeloperoxidase level were significantly lower when both classical and alternative pathways were inactivated or when the classical pathway alone was inactivated, but were not significantly different when the alternative pathway alone was inactivated. Conclusions: Vitamin E modification of the dialyzer reduces some reactions of neutrophilic activation, such as CD11b expression and myeloperoxidase release, more effectively in the clinical situation than in ex vivo models, suggesting a possible effect of vitamin E in inhibiting bioreactions due to pyrogen in the dialysate. The classical complement pathway is required in membrane-induced neutrophilic activation, at least during the initial stage.

Effect of transdermal iontophoresis codelivery of hydrocortisone on metoclopramide pharmacokinetics and skin‐induced reactions in human subjects

The effects of transdermal iontophoresis (IP) codelivery of hydrocortisone (HC) on metoclopramide hydrochloride (MCP) pharmacokinetics and on skin‐induced reactions were evaluated in a randomized, crossover clinical study. MCP, an antiemetic, low molecular weight, cationic drug intended for systemic delivery, was delivered from the anode of IP systems at a constant current of 100 μA/cm2. HC, a neutral endogenous antiinflammatory agent, was codelivered from the same electrode, primarily by electroosmotic processes. Each subject (n = 7) wore two identical IP systems (MCP alone or MCP plus HC), each supplying 500 μA, one on each upper arm for 4 h. One week later, each subject repeated the procedure with the alternate type of MCP system. HC did not change the pharmacokinetics of MCP: There were no statistically significant differences in MCP plasma concentrations, half‐life, area under the curve (AUC), or rate of absorption between the two treatment groups. However, HC significantly decreased erythema and edema scores produced by the IP of MCP. In both groups, a steady‐state MCP flux of about 100 μg/(cm2 × h) was achieved after only 1 h of transport, and input rate dropped dramatically immediately after removal of the system. In vitro, HC flux through human epidermis from an MCP plus HC formulation was 2.8 ± 1.1 μg/(cm2 × h) after 4 h transport at 100 μ A/cm2, suggesting negligible systemic exposure to hydrocortisone. These data indicate that MCP input rate and its clearance from the skin are unaltered by HC and that the codelivery of HC by IP is an effective strategy for inhibition of local reactions resulting from the transdermal delivery of drugs.

Surface Antigen Expression and Platelet Neutrophil Interactions in Haemodialysis

Background: There is increasing evidence to show the clinical implications of membrane biocompatibility in haemodialysis therapy. Methods: We conducted a cross-over clinical study examining the clinical biocompatibility profile of three derivatised cellulosic membranes obtained by means of different modifications to the cellulose polymer (haemophan, cellulose diacetate, benzyl cellulose) in comparison to the parent polymer (cuprophan) and a reference synthetic membrane (polysulfone). Results: In terms of leukopenia production, derivatised cellulosic membranes were generally intermediate between cuprophan and polysulfone, haemophan being more marked than the other two membranes. Upregulation of CD11b/CD18 molecule on neutrophils was found with all membranes, to a greater extent with the dialyser containing cuprophan. The expression of CD11b/CD18 on monocytes was slightly affected with cuprophan only. The neutrophil and monocyte counts throughout the entire dialysis session showed a much better correlation with the cellular expression of sialyl-Lewis x (CD15s) molecule than with CD11b/CD18 expression. An increased formation of platelet-neutrophil coaggregates occurred at 15 and 30 min during dialysis with all membranes but benzyl cellulose, the increase with cuprophan being higher than with the other membranes. In concomitance with the increase in platelet-neutrophil coaggregation, an increased hydrogen peroxide production by neutrophils occurred, which proved to be significantly higher compared to the unchanged neutrophil hydrogen peroxide production during HD with benzyl cellulose. Conclusions: Our results demonstrate that derivatised cellulose is associated with a considerable improvement in the clinical biocompatibility profile. Derivatised cellulosic membranes show many similarities but also several significant differences which very likely stem from the different type of structural modification to the cellulose polymer rather than from the degree of hydroxyl group replacement.

Application of models of defibrillation to human defibrillation data: implications for optimizing implantable defibrillator capacitance.

Theoretical models predict that optimal capacitance for implantable cardioverter-defibrillators (ICDs) is proportional to the time-dependent parameter of the strength-duration relationship. The hyperbolic model gives this relationship for average current in terms of the chronaxie (t(c)). The exponential model gives the relationship for leading-edge current in terms of the membrane time constant (tau(m)). We hypothesized that these models predict results of clinical studies of ICD capacitance if human time constants are used. We studied 12 patients with epicardial ICDs and 15 patients with transvenous ICDs. Defibrillation threshold (DFT) was determined for 120-microF monophasic capacitive-discharge pulses at pulse widths of 1.5, 3.0, 7.5, and 15 ms. To compare the predictions of the average-current versus leading-edge-current methods, we derived a new exponential average-current model. We then calculated individual patient time parameters for each model. Model predictions were validated by retrospective comparison with clinical crossover studies of small-capacitor and standard-capacitor waveforms. All three models provided a good fit to the data (r2=.88 to .97, P<.001). Time constants were lower for transvenous pathways (53+/-7 omega) than epicardial pathways (36+/-6 omega) (t(c), P<.001; average-current tau(m), P=.002; leading-edge-current tau(m), P<.06). For epicardial pathways, optimal capacitance was greater for either average-current model than for the leading-edge-current model (P<.001). For transvenous pathways, optimal capacitance differed for all three models (P<.001). All models provided a good correlation with the effect of capacitance on DFT in previous clinical studies: r2=.75 to .84, P<.003. For 90-microF, 120-microF, and 150-microF capacitors, predicted stored-energy DFTs were 3% to 8%, 8% to 16%, and 14% to 26% above that for the optimal capacitance. Model predictions based on measured human cardiac-muscle time parameter have a good correlation with clinical studies of ICD capacitance. Most of the predicted reduction in DFT can be achieved with approximately 90-microF capacitors.

Evidence of interplay between plasma endothelin-1 and 17β-estradiol in regulation of uterine blood flow and endometrial growth in infertile women

Objective: To determine the effects of gonadotropin-induced ovarian stimulation on the plasma levels of endothelin-1 as well as on uterine blood flow and endometrial thickness. Design: Controlled cross-over clinical study. Setting: Academic research environment. Patient(s): Eighteen volunteer infertile women (31.4 ± 2.5 years, mean ± SE) participating in an IVF-ET program. Intervention(s): Transvaginal Doppler ultrasound was performed and blood samples were collected 4 days after the LH surge in a spontaneous cycle and 4 days after hCG administration in a subsequent gonadotropin-stimulated cycle. Main Outcome Measure(s): Plasma levels of E 2, P, and endothelin-1; uterine artery pulsatility index; and endometrial thickness. Result(s): Stimulated cycles were associated with significantly higher E 2 levels (101.0 ± 10.2 versus 723.5 ± 57.3 pg/mL [conversion Factor to SI unit, 3.671]; spontaneous versus stimulated), thicker endometrium (9.2 ± 2.5 versus 11.4 ± 2.9 mm), and lower endothelin-1 levels (2.5 ± 0.1 versus 2.1 ± 0.1 pg/mL [conversion factor to SI unit, 0.4]) and pulsatility index (3.22 ± 0.12 versus 2.63 ± 0.08) than spontaneous cycles. Endothelin-1 correlated negatively with E 2 (r = −0.38), but not with P or pulsatility index. Differences in endothelin-1 and endometrial thickness between spontaneous and stimulated cycles correlated negatively (r = −0.56) with each other. Conclusion: Our results suggest an inhibitory role for E 2 in the release of endothelin-1, which could be a factor in the regulation of uterine and endometrial blood flow.

Luteal support with both estradiol and progesterone after clomiphene citrate stimulation for in vitro fertilization

To determine if pregnancy rates (PRs) for clomiphene citrate (CC)-stimulated IVF-ET can be increased by luteal support with E2 and P. Prospective randomized crossover clinical study. Infertile women volunteers in an academic research environment. Ninety-three infertile women underwent a total of 143 IVF-ET cycle using CC for ovulation induction. Each woman received either no luteal support (control group) or luteal support with both oral E2 (2 mg three times daily) starting on the day of retrieval and vaginal P suppositories (100 mg twice daily) starting on the day of ET. Clinical PR. In 79 of 143 (55%) of the cycles, at least one embryo was transferred. Compared with the control group (n = 35 cycles), the luteal support group (n = 44 cycles) had a significantly higher PR per retrieval (control: 2% versus luteal support: 16%) and were older (control: 33 +/- 4 versus luteal support: 35 +/- 4 years; mean +/- SEM). They did not differ in terms of E2 or P levels, endometrial thickness on the day of hCG, number of follicles > 16 mm in diameter, mature oocytes retrieved, or embryos transferred. Luteal support with both E2 and P significantly increase the clinical PRs for CC-stimulated IVF-ET.

A randomized, double-blind, placebo-controlled, crossover trial of systemic flunisolide in the treatment of children with severe atopic dermatitis

A multicenter, randomized, double-blind, placebo-controlled, cross-over clinical study was performed to determine the effects of systemic flunisolide on the symptoms of 20 children with chronic severe atopic dermatitis. The study lasted 5 weeks. Ten of the 20 patients received flunisolide for 2 weeks followed by placebo for 2 weeks; the other 10 patients received placebo for 2 weeks and then flunisolide for 2 weeks. A 1-week washout period separated the administration of each treatment. Clinical symptoms were assessed at baseline (week 0) and weeks 2, 3, and 5. Total clinical severity scores indicated a significant improvement of symptoms in patients after 2 weeks of flunisolide treatment, compared with the placebo group. After treatment with flunisolide, no worsening of symptoms or relapse occurred. In the placebo group, no significant reduction in clinical scores was observed and, moreover, three patients demonstrated worsening of symptoms during the washout period that followed the placebo treatment. However, this group had a prompt reduction in clinical scores after administration of flunisolide. No side effects were observed during the study. The data suggest that, in children with severe atopic dermatitis, short courses of flunisolide can provide relief while awaiting response to other agents or during severe exacerbations of symptoms. Thus flunisolide is an alternative to traditional oral steroids and has no noticeable side effects.

Erratum to: Clinical Interest of once-Daily Felodipine Extended-Release in Patients with Mixed and Exertional Angina

24 patients with mixed or exertional angina pectoris were enrolled in a double-blind crossover clinical study to compare the efficacy and safety of felodipine extended-release (ER) 10mg once daily versus amlodipine 10mg once daily. Admission criteria did not restrict patient selection according to exercise endurance. The crossover treatment with two 4-week phases started after washout of all antianginal drugs except sublingual nitrates. Maximal multistage exercise tests were performed before initial administration at baseline and 23 hours after the last dose of each of the 2 study drugs. Two patients dropped out, so that efficacy could be evaluated on an intention-to-treat basis in 22 patients (15 with mixed and 7 with exertional angina). At baseline the ischaemic threshold (time to onset of ST depression 21mm) was high, with a mean of 485.3 ± 174.8 seconds (n = 22, range 180 to 840 seconds). After 4 weeks of treatment, time to test termination showed an increase with both drugs, which attained statistical significance only with felodipine ER (n = 22, + 9.03%; p<0.05). The duration of ischaemia showed a decrease that was more evident with felodipine ER (n = 17, −31.19%) than with amlodipine (n = 18, −16.70%), without attaining statistical significance in either case. The significant decrease in maximal ST depression was more evident with felodipine ER (n = 17, −27.72%; p<0.001) than with amlodipine (n = 18, −19.12%; p<0.01). Furthermore, the increase in the time to onset of angina attained statistical significance with felodipine ER (n = 7, + 34.25%; p<0.05) and not with amlodipine (n = 10, + 20.72%). The decrease in the duration of angina also attained statistical significance with felodipine ER (n = 7, −24.34%; p<0.05) and not with amlodipine (n = 10, −24.58%). Adverse reactions occurred with felodipine ER in 2 of 24 (8.3%) cases and with amlodipine in 6 of 24 (25%) cases. The most frequent adverse reaction was mild to moderate peripheral oedema that occurred only during treatment with amlodipine (16.7% cases). The possible pharmacological rationale for the better therapeutic results obtained with felodipine ER is discussed by considering both its efficacy and safety.

Possible clinical effects of the interaction of hemodialysis membranes with adhesion proteins

In this study data obtained in an in vitro hemodialysis model are related to various parameters measured in patients' plasma during hemodialysis in a clinical crossover study. In vitro, blood from healthy volunteers was dialyzed under standardized conditions using the capillaries Fresenius MTS C (Cuprophane) and Hospal AN 69 (Polyacrylonitrile). Following dialysis, surface bound proteins were eluted with saline, 1 M Tris and 2% SDS, and analyzed by immunoblotting. Depending on the capillary, different protein patterns could be identified in the eluates. Intact forms of adhesion proteins were predominantly (fibrinogen) or exclusively (vitronectin) found in PA eluates. In contrast, low molecular weight products of fibrinogen as well as high molecular weight components containing antithrombin III (AT III) were present in CP eluates. Their presence may reflect fibrinolytic and procoagulatory activity during dialysis with CP capillaries. A microscopic investigation of CP membranes demonstrated fibrin lined platelet conglomerates. In the plasmas of patients dialyzed with CP capillaries high D-Dimer concentrations were found. We also noticed that during dialysis with PA membranes less heparin was consumed than during dialysis with CP membranes. Our study showed a good correlation of the observations in the vitro system and the measurements in patient samples.

Experiments With Triclosan-Containing Mouthrinses: Dose Response—and an Attempt to Locate the Receptor Site(S) of Triclosan in the Mouth

A double-blind cross-over clinical study was performed on eight volunteers to determine the plaque-inhibiting effect of different triclosan- and sodium lauryl sulfate (SLS)-containing mouthrinses. An attempt was also made to locate the binding site(s) of triclosan in the oral cavity. After the volunteers rinsed for four days with solutions of various concentrations of triclosan and/or SLS, plaque deposits were scored according to the Silness and Löe Plaque Index. The study showed that 0.15% and 0.3% concentrations of triclosan yielded a comparable plaque-inhibiting effect in vivo. Furthermore, the 0.1% triclosan with 1.5% SLS exhibited a higher (though not significant) effect than 0.1% triclosan with 0.75% SLS. The mouthrinse containing 0.05% triclosan and 0.25% SLS was as effective as the two mentioned mouthrinses containing 0.1% triclosan. Collectively, the results indicate that triclosan alone has an antiplaque effect, independent of the effect of SLS. Furthermore, the results suggest that the SLS monomers may play a role as carriers of triclosan and that the teeth are not the only binding site of triclosan, since topical application of 0.3% triclosan failed to produce a clinically discernible effect.