Effect of volume loading with 1 liter intravenous infusions of 0.9% saline, 4% succinylated gelatine (Gelofusine) and 6% hydroxyethyl starch (Voluven) on blood volume and endocrine responses: a randomized, three-way crossover study in healthy volunteers

To study the changes in blood volume and hormones controlling sodium and water homeostasis after infusions of 0.9% saline, Gelofusine (4% succinylated gelatin in 0.7% saline, weight-average molecular weight 30 kD), and Voluven (6% hydroxyethyl starch in 0.9% saline, weight-average molecular weight 130 kD) in healthy volunteers.

The butterbur extract petasin has no effect on skin test reactivity induced by different stimuli: a randomized, double-blind crossover study using histamine, codeine, methacholine, and aeroallergen solutions

BACKGROUND: Petasin (Ze 339) was recently introduced on the market as a potent herbal antiallergic drug for treatment of respiratory allergies such as hay fever. Few clinical studies have been performed so far addressing the clinical effectiveness of Ze 339. OBJECTIVE: To evaluate the antiallergic properties of Ze 339 using skin prick tests with different stimuli, such as codeine, histamine, methacholine, and a relevant inhalant allergen. METHODS: A randomized, double-blind, placebo-controlled study was performed in which Ze 339 was compared to acrivastine, a short-acting antihistamine, in 8 patients with respiratory allergy and in 10 nonatopic, healthy volunteers. Antiallergic activity of Ze 339 was determined by analyzing inhibitory potency in skin prick tests with codeine, histamine, methacholine, and an inhalant allergen. Wheal-and-flare reactions were assessed 90 minutes after a double dose of Ze 339, acrivastine, or placebo. An interval of at least 3 days was left between the skin tests. RESULTS: Acrivastine was identified as the only substance that significantly inhibited skin test reactivity to all solutions analyzed in all study subjects. In contrast, no significant inhibition could be demonstrated for Ze 339 with any test solution. Moreover, the results of Ze 339 did not differ significantly from placebo. CONCLUSIONS: In this study we found no antiallergic, particularly antihistaminic, effect of Ze 339 in skin tests using a variety of stimuli often used to evaluate immediate skin test reactivity. The mechanism by which Ze 339 is effective in the treatment of seasonal allergic rhinitis still needs to be elucidated.

Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study

Postprandial metabolism is impaired in patients with type 2 diabetes (T2Dm). Two thiazolidinediones pioglitazone (PGZ) and rosiglitazone (RGZ) have similar effects on glycaemic control but differ in their effects on fasting lipids. This study investigated the effects of RGZ and PGZ on postprandial metabolism in a prospective, randomized crossover trial.

The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.

Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients

The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2mg, and tropisetron 5mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.

Compression hosiery for occupational leg symptoms and leg volume: a randomized crossover trial in a cohort of hairdressers

OBJECTIVE: Occupational leg symptoms are highly prevalent in the general population and impair the psychic state of health. We investigated hairdressers, a cohort exposed to prolonged standing during work, in a randomized crossover trial. We hypothesized that hairdressers wearing low-strength compression hosiery would benefit from less leg volume increase and discomfort. METHODS: One hundred and eight hairdressers were randomized to wear medical compression stockings (MCS; 15-20 mmHg) in a crossover study. The effect of MCS on symptoms and on lower leg volume was compared with no compression treatment. Symptoms were assessed with a comprehensive questionnaire, categorized using factor analysis with varimax rotation and correlated with leg volume changes. RESULTS: Wearing MCS reduced the symptom score for pain and feelings of swelling (range 0-4) by an average of 0.22 (12%, P < 0.001). Sleep disturbance, feeling of unattractive legs and depressiveness improved with MCS compared with no MCS. Subjects initially obliged to refrain from wearing stockings showed a significant decrease of pain and feelings of swelling as well (by 0.10 [6%], P = 0.015). Wearing MCS was associated with a decrease of lower leg volume by an average of 19 mL (P < 0.001), with preference in older hairdressers (P < 0.001). The effects of wearing MCS on symptoms and on leg volume were not correlated with each other. CONCLUSIONS: Individuals working in a standing profession experience leg pain, feelings of swelling, heaviness and various other disturbing feelings. These symptoms can be alleviated by wearing low-strength MCS.

A randomized crossover study to compare efavirenz and etravirine treatment

Efavirenz (EFV) causes neuropsychiatric side-effects and an unfavourable blood lipid profile. We investigated the effect of replacing EFV with etravirine (ETR) on patient preference, sleep, anxiety and lipid levels.

The effect of increased lipid intake on hormonal responses during aerobic exercise in endurance-trained men

In view of the growing health problem associated with obesity, clarification of the regulation of energy homeostasis is important. Peripheral signals, such as ghrelin and leptin, have been shown to influence energy homeostasis. Nutrients and physical exercise, in turn, influence hormone levels. Data on the hormonal response to physical exercise (standardized negative energy balance) after high-fat (HF) or low-fat (LF) diet with identical carbohydrate intake are currently not available. The aim of the study was to investigate whether a short-term dietary intervention with HF and LF affects ghrelin and leptin levels and their modulators, GH, insulin and cortisol, before and during aerobic exercise. Eleven healthy, endurance-trained male athletes (W(max) 365 +/- 29 W) were investigated twice in a randomized crossover design following two types of diet: 1. LF - 0.5 g fat/kg body weight (BW) per day for 2.5 days; 2. HF - 0.5 g fat/kg BW per day for 1 day followed by 3.5 g fat/kg BW per day for 1.5 days. After a standardized carbohydrate snack in the morning, metabolites and hormones (GH, ghrelin, leptin, insulin and cortisol) were measured before and at regular intervals throughout a 3-h aerobic exercise test on a cycloergometer at 50% of W(max). Diet did not significantly affect GH and cortisol concentrations during exercise but resulted in a significant increase in ghrelin and decrease in leptin concentrations after LF compared with HF diet (area under the curve (AUC) ghrelin LF vs HF: P < 0.03; AUC leptin LF vs HF: P < 0.02, Wilcoxon rank test). These data suggest that acute negative energy balance induced by exercise elicits a hormonal response with opposite changes of ghrelin and leptin. In addition, the hormonal response is modulated by the preceding intake of fat.

Prospective, paired crossover comparison of multiple, single-needle plateletpheresis procedures with the Amicus and Trima Accel cell separators

BACKGROUND: The Baxter Amicus Version 2.51 (A) and the Gambro BCT Trima Accel Version 5.0 (T) cell separators may produce multiple platelet (PLT) concentrates within a single donation. STUDY DESIGN AND METHODS: The single-needle multiple plateletpheresis procedures of the two devices were compared in a prospective, randomized, paired crossover study in 60 donors. The 120 donations were compared for donor comfort, collection efficiency, residual white blood cell (WBC) count, and (in selected patients) corrected count increment (CCI). RESULTS: The mean PLT yield and the resultant mean number of units per donation were significantly lower for A (6.06 x 10(11) vs. 7.48 x 10(11) and 2.57 vs. 3.19, respectively, both p < 0.001), in spite of a longer apheresis duration (89 min vs. 79 min; p < 0.001). This resulted in a higher collection rate of T (5.68 x 10(11) PLTs/hr vs. 4.10 x 10(11) PLTs/hr, p < 0.001). Residual WBC count of every unit was fewer than 5 x 10(6), but significantly fewer A-PLT donations contained more than 10(5) WBCs per unit (1 vs. 9, p = 0.008). Although the ACD-A consumption was slightly higher for A (489 mL vs. 469 mL, p = 0.04), a trend to a higher frequency of side effects was found for T (42.4% vs. 23.7%, p = 0.06). The 1-hour CCIs of 33 transfused A-PLT units were comparable with those of 43 T-PLT units (11.8 vs. 13.9, p = 0.480). CONCLUSIONS: Both cell separators showed safe collections of up to 4 PLT units per donation with adequate CCI. T produced a higher PLT yield despite shorter apheresis duration, but with slightly higher residual WBC counts and a trend to a higher side-effect frequency.

Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers

Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3x15 g daily) and placebo (sucrose, 3x15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid.

Effect of transcutaneous electrical muscle stimulation and passive cycling movements on blood pressure and removal of urea and phosphate during hemodialysis

BACKGROUND: Intradialytic exercise has been described to improve blood pressure stability and dialysis efficacy. However, comorbid conditions in the dialysis population often preclude the widespread use of active intradialytic exercise. Therefore, we investigated the effect of intradialytic transcutaneous muscle stimulation (TEMS) and passive cycling movements (PCMs) on blood pressure and dialysis efficacy in patients. STUDY DESIGN: Prospective, controlled, randomized, crossover investigation. SETTING ; PARTICIPANTS: Ten patients were randomly allocated to TEMS, PCMs, or no intervention (NI) for 9 consecutive dialysis sessions. INTERVENTION: Participants were studied with NI, PCMs using a motor-driven ergometer, and bilateral TEMS of the leg musculature. Individual dialysis prescriptions were unchanged during the investigation. OUTCOMES ; MEASUREMENTS: The effect of TEMS and PCMs on blood pressure and dialysis efficacy in patients was assessed. RESULTS: Mean blood pressure increased from 121/64 +/- 21/15 mm Hg with NI to 132/69 +/- 21/15 mm Hg (P < 0.001) during sessions with PCMs and 125/66 +/- 22/16 mm Hg (P < 0.05) during sessions with TEMS. Urea and phosphate removal during dialysis were significantly (P < 0.001) greater with TEMS (19.4 +/- 3.7 g/dialysis and 1,197 +/- 265 mg/dialysis) or PCMs (20.1 +/- 3.4 g/dialysis and 1,172 +/- 315 mg/dialysis) than with NI (15.1 +/- 3.9 g/dialysis and 895 +/- 202 mg/dialysis). Body weight, ultrafiltration, Kt/V, and increases in hemoglobin and albumin levels during dialysis did not differ among the NI, PCMs, and TEMS groups. LIMITATIONS: The study design does not allow extension of the findings to prolonged treatment. CONCLUSION: Future studies during longer observation periods will have to prove the persistence of these acute findings. Both TEMS and PCMs deserve future investigations in dialysis patients because they increase intradialytic blood pressure and facilitate urea and phosphate removal when applied short term.

Dilution and redistribution effects of rapid 2-litre infusions of 0.9% (w/v) saline and 5% (w/v) dextrose on haematological parameters and serum biochemistry in normal subjects: a double-blind crossover study

Although hypoalbuminaemia after injury may result from increased vascular permeability, dilution secondary to crystalloid infusions may contribute significantly. In this double-blind crossover study, the effects of bolus infusions of crystalloids on serum albumin, haematocrit, serum and urinary biochemistry and bioelectrical impedance analysis were measured in healthy subjects. Ten male volunteers received 2-litre infusions of 0.9% (w/v) saline or 5% (w/v) dextrose over 1 h; infusions were carried out on separate occasions, in random order. Weight, haemoglobin, serum albumin, serum and urinary biochemistry and bioelectrical impedance were measured pre-infusion and hourly for 6 h. The serum albumin concentration fell in all subjects (20% after saline; 16% after dextrose) by more than could be explained by dilution alone. This fall lasted more than 6 h after saline infusion, but values had returned to baseline 1 h after the end of the dextrose infusion. Changes in haematocrit and haemoglobin were less pronounced (7.5% after saline; 6.5% after dextrose). Whereas all the water from dextrose was excreted by 2 h after completion of the infusion, only one-third of the sodium and water from the saline had been excreted by 6 h, explaining its persistent diluting effect. Impedances rose after dextrose and fell after saline (P<0.001). Subjects voided more urine (means 1663 and 563 ml respectively) of lower osmolality (means 129 and 630 mOsm/kg respectively) and sodium content (means 26 and 95 mmol respectively) after dextrose than after saline (P<0.001). While an excess water load is excreted rapidly, an excess sodium load is excreted very slowly, even in normal subjects, and causes persistent dilution of haematocrit and serum albumin. The greater than expected change in serum albumin concentration when compared with that of haemoglobin suggests that, while dilution is responsible for the latter, redistribution also has a role in the former. Changes in bioelectrical impedance may reflect the electrolyte content rather than the volume of the infusate, and may be unreliable for clinical purposes.

Effect of a chitosan additive to a Sn(2+)-containing toothpaste on its anti-erosive/anti-abrasive efficacy-a controlled randomised in situ trial

OBJECTIVES It is well known that Sn(2+) is a notable anti-erosive agent. There are indications that biopolymers such as chitosan can enhance the effect of Sn(2+), at least in vitro. However, little information exists about their anti-erosive/anti-abrasive in situ effects. In the present in situ study, the efficacy of Sn(2+)-containing toothpastes in the presence or absence of chitosan was tested. METHODS Ten subjects participated in the randomised crossover study, wearing mandibular appliances with human enamel specimens. Specimens were extraorally demineralised (7 days, 0.5 % citric acid, pH 2.6; 6 × 2 min/day) and intraorally exposed to toothpaste suspensions (2 × 2 min/day). Within the suspension immersion time, one half of the specimens were additionally brushed intraorally with a powered toothbrush (5 s, 2.5 N). Tested preparations were a placebo toothpaste (negative control), two experimental toothpastes (F/Sn = 1,400 ppm F(-), 3,500 ppm Sn(2+); F/Sn/chitosan = 1,400 ppm F(-), 3,500 ppm Sn(2+), 0.5 % chitosan) and an SnF2-containing gel (positive control, GelKam = 3,000 ppm Sn(2+), 1,000 ppm F(-)). Substance loss was quantified profilometrically (μm). RESULTS In the placebo group, tissue loss was 11.2 ± 4.6 (immersion in suspension) and 17.7 ± 4.7 (immersion in suspension + brushing). Immersion in each Sn(2+)-containing suspension significantly reduced tissue loss (p ≤ 0.01); after immersion in suspension + brushing, only the treatments with GelKam (5.4 ± 5.5) and with F/Sn/chitosan (9.6 ± 5.6) significantly reduced loss [both p ≤ 0.05 compared to placebo; F/Sn 12.8 ± 6.4 (not significant)] CONCLUSION Chitosan enhanced the efficacy of the Sn(2+)-containing toothpaste as an anti-erosive/anti-abrasive agent. CLINICAL RELEVANCE The use of Sn(2+)- and chitosan-containing toothpaste is a good option for symptomatic therapy in patients with regular acid impacts.

Effect of phrenic nerve palsy on early postoperative lung function after pneumonectomy: a prospective study

BACKGROUND The issue of phrenic nerve preservation during pneumonectomy is still an unanswered question. So far, its direct effect on immediate postoperative pulmonary lung function has never been evaluated in a prospective trial. METHODS We conducted a prospective crossover study including 10 patients undergoing pneumonectomy for lung cancer between July 2011 and July 2012. After written informed consent, all consecutive patients who agreed to take part in the study and in whom preservation of the phrenic nerve during operation was possible, were included in the study. Upon completion of lung resection, a catheter was placed in the proximal paraphrenic tissue on the pericardial surface. After an initial phase of recovery of 5 days all patients underwent ultrasonographic assessment of diaphragmatic motion followed by lung function testing with and without induced phrenic nerve palsy. The controlled, temporary paralysis of the ipsilateral hemidiaphragm was achieved by local administration of lidocaine 1% at a rate of 3 mL/h (30 mg/h) via the above-mentioned catheter. RESULTS Temporary phrenic nerve palsy was accomplished in all but 1 patient with suspected catheter dislocation. Spirometry showed a significant decrease in dynamic lung volumes (forced expiratory volume in 1 second and forced vital capacity; p < 0.05) with the paralyzed hemidiaphragm. Blood oxygen saturation levels did not change significantly. CONCLUSIONS Our results show that phrenic nerve palsy causes a significant impairment of dynamic lung volumes during the early postoperative period after pneumonectomy. Therefore, in these already compromised patients, intraoperative phrenic nerve injury should be avoided whenever possible.

The effect of inner speech on arterial CO2 and cerebral hemodynamics and oxygenation: a functional NIRS study

The aim of the present study was (i) to investigate the effect of inner speech on cerebral hemodynamics and oxygenation, and (ii) to analyze if these changes could be the result of alternations of the arterial carbon dioxide pressure (PaCO2). To this end, in seven adult volunteers, we measured changes of cerebral absolute [O2Hb], [HHb], [tHb] concentrations and tissue oxygen saturation (StO2) (over the left and right anterior prefrontal cortex (PFC)), as well as changes in end-tidal CO2 (PETCO2), a reliable and accurate estimate of PaCO2. Each subject performed three different tasks (inner recitation of hexameter (IRH) or prose (IRP) verses) and a control task (mental arithmetic (MA)) on different days according to a randomized crossover design. Statistical analysis was applied to the differences between pre-baseline, two tasks, and four post-baseline periods. The two brain hemispheres and three tasks were tested separately. During the tasks, we found (i) PETCO2 decreased significantly (p < 0.05) during the IRH ( ~ 3 mmHg) and MA ( ~ 0.5 mmHg) task. (ii) [O2Hb] and StO2 decreased significantly during IRH ( ~ 1.5 μM; ~ 2 %), IRP ( ~ 1 μM; ~ 1.5 %), and MA ( ~ 1 μM; ~ 1.5 %) tasks. During the post-baseline period, [O2Hb] and [tHb] of the left PFC decreased significantly after the IRP and MA task ( ~ 1 μM and ~ 2 μM, respectively). In conclusion, the study showed that inner speech affects PaCO2, probably due to changes in respiration. Although a decrease in PaCO2 is causing cerebral vasoconstriction and could potentially explain the decreases of [O2Hb] and StO2 during inner speech, the changes in PaCO2 were significantly different between the three tasks (no change in PaCO2 for MA) but led to very similar changes in [O2Hb] and StO2. Thus, the cerebral changes cannot solely be explained by PaCO2.