Fluvoxamine does not interact with alcohol or potentiate alcohol-related impairment of cognitive function.

OBJECTIVE: To assess whether fluvoxamine alters the pharmacokinetics of alcohol or potentiates alcohol-related impairment of cognitive function. METHODS: The study design required partially "blinded" balanced crossover studies, each involving 12 healthy male volunteers who each received a 40 gm dose of intravenous or oral alcohol after single and multiple doses of 50 mg fluvoxamine. Main outcome measures for pharmacokinetics were venous blood alcohol and plasma fluvoxamine. Main outcome measures for pharmacodynamics were word recall, simple and choice reaction time, number vigilance, memory scanning, and word recognition. RESULTS: The pharmacokinetics of intravenous alcohol were not affected by concomitant administration of fluvoxamine. Compared with placebo-alcohol, alcohol slightly increased the rate of fluvoxamine absorption, but the area under the plasma concentration-time curve from 0 to 12 hours at steady state was unchanged. As expected, alcohol significantly impaired cognitive function in volunteers. However, fluvoxamine did not potentiate the effects of alcohol and in some instances appeared to reverse the effects or reduce their duration. Fluvoxamine was well tolerated: only mild adverse effects were reported, and none of those required intervention. CONCLUSION: Fluvoxamine does not interact significantly with alcohol or potentiate alcohol-related impairment of cognitive function.     

Calcitonin gene-related peptide receptor antagonism does not affect the severity of myocardial ischemia during atrial pacing in dogs with coronary artery stenosis

Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide that also has potent vasodilator activity. There are conflicting preclinical reports regarding the effect of CGRP receptor antagonism in the setting of myocardial ischemia. The present study was conducted in a canine model in which regional myocardial ischemia was reproducibly evoked by serial periods of atrial pacing (80 beats per min above baseline rate) in the presence of a 40% stenosis of the left anterior descending (LAD) coronary artery. Ischemia severity was quantitated by changes in unipolar epicardial electrograms (EG) recorded in the area of ischemia. In validation studies, the calcium entry blocker diltiazem reduced ischemia severity (before versus after treatment: DeltaEG, 1.92 +/- 0.23 versus 0.54 +/- 0.24 mV; p < 0.05) and tended to increase LAD flow (7.7 +/- 0.7 versus 9.4 +/- 1.4 ml/min; p = 0.10), whereas the coronary constrictor serotonin increased ischemia severity (before versus after treatment: DeltaEG, 2.11 +/- 0.44 versus 4.90 +/- 1.46 mV; p < 0.05) concomitant with a reduction in LAD flow (9.1 +/- 1.1 versus 5.4 +/- 1.5 ml/min; p < 0.05). A 30 microg/kg/min i.v. infusion test dose of the CGRP receptor antagonist CGRP((8-37)) was validated by demonstrating complete block of the depressor effects of exogenous i.v. 0.03 to 0.3 microg/kg CGRP. This dose of CGRP((8-37)), administered either intravenously or intra-atrially, had no effect on ischemia severity or paced LAD flow, indicating no intrinsic effect of CGRP receptor antagonism on the severity of acute myocardial ischemia. Likewise, the administration of a hemodynamically active dosing regimen of CGRP (0.03 microg/kg/min i.v.) had no effect on paced coronary flow or ischemia severity, suggesting no major role of CGRP in regulating ischemic blood flow.     

Flavocoxid,an anti-inflammatory agent of botanical origin,does not affect coagulation or interact with anticoagulation therapies

Introduction  

Flavocoxid, a botanical, anti-inflammatory agent, nonspecifically inhibits the peroxidase activity of cyclooxygenase (COX-1 and COX-2) enzymes and 5-lipooxygenase (5-LOX). Due to the concomitant use of aspirin or warfarin in many osteoarthritis (OA) patients with increased cardiovascular risk, we felt it necessary to assess the anticoagulation properties of flavocoxid.     

Efficacy of enrofloxacin or doxycycline for treatment of Bartonella henselae or Bartonella clarridgeiae infection in cats.

Enrofloxacin and doxycycline are antimicrobial agents used to treat bacterial diseases of cats. In vitro susceptibility data indicate that either drug should be effective against Bartonella species. In vivo efficacies of these drugs for eradication of chronic Bartonella henselae or Bartonella clarridgeiae infections were examined in 18 experimentally infected cats and 25 naturally exposed cats treated with enrofloxacin (22.7 mg given orally [PO] every 12 h [q12h] [14 days, n = 10; 28 days, n = 13]) or with doxycycline (25 mg PO q12h [14 days, n = 9; 28 days, n = 8]) or not treated (n = 3). Plasma drug concentrations were determined in experimental cats by high-performance liquid chromatography. Only 23 of 43 cats enrolled ultimately met inclusion criteria. Bacteremia was eliminated for 12 to 25 weeks posttreatment in four of seven cats receiving 14 days of enrofloxacin, five of seven cats receiving 28 days of enrofloxacin, one of six cats receiving 14 days of doxycycline, and one of two cats receiving 28 days of doxycycline. Defining a negative result by blood culture as treatment success may be erroneous; these results may reflect the insensitivity of blood culture or the relapsing nature of Bartonella bacteremia. Our results suggest that MICs obtained with axenic media do not predict antimicrobial activity against intracellular Bartonella, that a long treatment course is required to eliminate infection, and that duration of therapy correlates with pretreatment bacterial load. Given current concern about the development of antimicrobial resistance, we would reserve recommendation for treatment to cats owned by an immunocompromised individual or as an alternative to euthanasia of a pet.     

A multi-arterial clamping method with arterial hypotension does not bring about complete brain ischemia in dogs.

The completeness of brain ischemia with a multi-arterial clamping method in dogs was examined using EEG, evoked potentials (EPs) and vessel staining with Evans blue. EEG was monitored by bipolar parietal lead. EPs stimulating electrodes were inserted into the first thoracic (T1) epidural space and recording electrodes into the C2 epidural space, brain stem and cerebral cortex. EPs were measured at 30 s intervals with 50 measurements each time using 3.0 mA current of 100 microseconds duration. In dogs in which brain ischemia was brought about by ventricular fibrillation (VF group, n = 5) EEG disappeared within 40 s in all dogs and the amplitudes of EPs at the C2 spinal cord, brain stem and cerebral cortex after 10 min ischemia were 57%, 0% and 0%, respectively. In the dogs in which a multi-arterial clamping method (clamping internal thoracic arteries, brachiocephalic trunk and left subclavian artery while lowering systolic arterial pressure (AP) below 50 Torr) was used (AC group, n = 5) EEG was still recognizable at 5 min in 2 dogs and the amplitudes of EPs at the C2, brain stem and cerebral cortex at 10 min ischemia were 103%, 53% and 0%, respectively. Stainings with Evans blue were observed in all soft tissue at and below thoracic level, entire intervertebral venous plexus, venous sinuses of cranial dura mater and spinal cord below the lower part of cervical region. Bright red fluorescence by Evans blue was observed microscopically in the vessels of the spinal cord, brain stem and cerebrum (1 dog only). In conclusion a multi-arterial clamping method with arterial hypotension brings about only incomplete brain ischemia.     

Use of impedance threshold device in conjunction with our novel adhesive glove device for ACD-CPR does not result in additional chest decompression

Objective

To evaluate the hemodynamic effects of using an adhesive glove device (AGD) to perform active compression–decompression CPR (AGD-CPR) in conjunction with an impedance threshold device (ITD) in a pediatric cardiac arrest model.

Design

Controlled, randomized animal study.

Methods

In this study, 18 piglets were anesthetized, ventilated, and continuously monitored. After 3 min of untreated ventricular fibrillation, animals were randomized (6/group) to receive either standard CPR (S-CPR), active compression–decompression CPR via adhesive glove device (AGD-CPR) or AGD-CPR along with an ITD (AGD-CPR + ITD) for 2 min at 100–120 compressions/min. AGD is delivered using a fingerless leather glove with a Velcro patch on the palmer aspect and the counter Velcro patch adhered to the pig's chest. Data (mean ± SD) were analyzed using one-way ANOVA with pair wise multiple comparisons to assess differences between groups. p-Value ≤ 0.05 was considered significant.

Results

Both AGD-CPR and AGD-CPR + ITD groups produced lower intrathoracic pressure (IttP, mmHg) during decompression phase (−13.4 ± 6.7, p = 0.01 and −11.9 ± 6.5, p = 0.01, respectively) in comparison to S-CPR (−0.3 ± 4.2). Carotid blood flow (CBF, % of baseline mL/min) was higher in AGD-CPR and AGD-CPR + ITD (respectively 64.3 ± 47.3%, p = 0.03 and 67.5 ± 33.1%, p = 0.04) as compared with S-CPR (29.1 ± 12.5%). Coronary perfusion pressure (CPP, mmHg) was higher in AGD-CPR and AGD-CPR + ITD (respectively 19.7 ± 4.6, p = 0.04 and 25.6 ± 12.1, p = 0.02) when compared to S-CPR (9.6 ± 9.1). There was no statistically significant difference between AGD-CPR and AGD-CPR + ITD groups with reference to intra-thoracic pressure, carotid blood flow and coronary perfusion pressure.

Conclusion

Active compression decompression delivered by this simple and inexpensive adhesive glove device resulted in improved cerebral blood flow and coronary perfusion pressure. There was no statistically significant added effect of ITD use along with AGD-CPR on the decompression of the chest.     

Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis.

Five patients with laboratory evidence of latent or neurosyphilis were treated orally with doxycycline (200 mg) twice a day for 21 days. After the seventh dose, the mean level of doxycycline in serum was 5.8 micrograms/ml, with a mean drug level in cerebrospinal fluid of 1.3 micrograms/ml. The mean penetration into cerebrospinal fluid was 26%. These preliminary findings suggest that doxycycline, administered orally at a dose of 200 mg twice a day, reaches a sufficient concentration in cerebrospinal fluid to be worthy of further evaluation as an alternative regimen to penicillin therapy for latent or neurosyphilis.     

Mechanical ventilation with lower tidal volumes does not influence the prescription of opioids or sedatives

Introduction  

We compared the effects of mechanical ventilation with a lower tidal volume (V_T) strategy versus those of greater V_T in patients with or without acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) on the use of opioids and sedatives.     

Total denervation of the pancreas does not alter the pancreatic polypeptide-induced inhibition of pancreatic exocrine secretion in dogs

Pancreatic polypeptide (PP) is a potent inhibitor of pancreatic exocrine secretion in vivo. The mechanism of pancreatic inhibition by PP is unknown, but the absence of PP receptors on pancreatic exocrine cells makes a direct effect of this hormone on the gland unlikely. In this study, we investigated the hypothesis that PP exerts its inhibitory effect via extrinsic neural pathways. Ten dogs with gastric and pancreatic fistulas were given an intravenous infusion of 250 ng/kg⁻¹ h⁻¹ secretion and 50 ng/kg⁻¹ h⁻¹ caerulein over 3 h. One hour after starting the infusion, 400 pmol kg⁻¹ h⁻¹ porcine PP were administered over 1 h. Pancreatic bicarbonte and protein secretions were measured. Later, the pancreas was extrinsically denervated. PP infusion decreased bicarbonate secretion in the intact gland by 47% and in the denervated pancreas by 57%. Protein secretion was diminished by exogenous PP by 31% in the intact and by 44% in the denervated pancreas. Despite pancreatic denervation, PP still exerted a significant inhibitory effect. Atropine infusion completely blocked the inhibitory effect of PP on caerulein-stimulated pancreatic protein secretion both in the intact and denervated pancreas and of secretion-evoked bicarbonate output in the denervated gland. We conclude that the inhibitory action of the hormone is not mediated via extrinsic neural pathways of the pancreas, but PP may exert its effect via intrinsic atropine-sensitive mechanisms.     

Protein does not interfere with the ion-selective electrode determination of calcium, sodium or potassium ions

The protein interference with the determination of ionised Ca2+, Na+ and K+ reported in several studies could be due to effects on liquid/liquid junction potentials or on the ion-selective electrodes, but could also be due to Donnan effects during sample preparation, e.g. ultrafiltration or dialysis. The possible interference of protein was studied by subjecting a bovine serum albumin solution, 100 g/l, to gel-filtration in Sephadex G-25 columns equilibrated with 150 mmol/l NaCl, 5 mmol/l KCl, 20 mmol/l MOPS, pH 7.4 and varying concentrations of Ca2+; 0.75 and 1.25 mmol/l. The albumin was dissolved in the basic electrolyte solution and pH adjusted before the gel-filtration. Samples were taken for measurements before, during and after the elution of the protein peak. In this way it was ensured that the activities were not changed by the presence of albumin. Also the temperature, the ionic strength of the electrolyte and the bridge solution were varied. Ca2+, Na+ and K+ activities were measured with the aid of a Kone Microlyte instrument and Ca2+ in addition with the Radiometer ICA-1 instrument or a measuring system consisting of a Philips IS 561-Ca electrode, a Beckman KCl reference electrode connected to the sample chamber via a 2% agarose bridge containing either 0.15 or 2 mol/l KCl, a pH/voltmeter and a voltage-bucking device. No interference by protein was found.     

Patient satisfaction with pain management does not correlate with initial or discharge VAS pain score, verbal pain rating at discharge, or change in VAS score in the Emergency Department

The aim of this study was to correlate patient satisfaction with pain management in the Emergency Department (ED) with initial and discharge visual analog scale (VAS) pain score, verbal pain rating at discharge, and change in VAS pain score between presentation and discharge. It was conducted as a prospective observational study of patients who presented to an urban, adult ED experiencing pain and who were later discharged. Fifty-four patients completed the study of whom 70% rated the management of their pain as 'good' or 'very good.' There was no correlation between patient satisfaction with pain management initial VAS pain score, discharge VAS pain score, verbal rating of pain at discharge, or change in VAS pain score between presentation and discharge. The study suggests that patient satisfaction with pain management does not correlate with initial or discharge VAS pain score, verbal rating of pain at discharge or change in pain score in the ED. Therefore, information about the quality of analgesia provided in an ED cannot be inferred from patient satisfaction surveys.     

Acute lung injury with endotoxin or NO2 does not enhance development of airway epithelium from bone marrow.

Adult marrow-derived stem cells can localize to lung and acquire immunophenotypic characteristics of lung epithelial cells. Lung injury increases recruitment of the marrow-derived cells. We speculated that comparing patterns of lung engraftment following different lung injuries would provide insight into potential mechanisms by which marrow-derived cells were recruited to lung. To evaluate this, adult female C57Bl/6 mice irradiated and engrafted with marrow from adult male transgenic GFP mice were exposed to either intranasal inhalation of endotoxin (25 microg/mouse) or 3 days of 25 ppm NO(2) and then compared 1 or 3 months later to transplanted but otherwise uninjured mice. In all cases, the majority of marrow-derived cells recruited to lung were CD45(+) leukocytes. In lungs of transplanted but otherwise uninjured mice, small numbers of CD45(-) donor-derived cells in alveolar septae stained positively for pro-surfactant protein C. Rare donor-derived cells located in the airway epithelium stained positively with cytokeratin. Subsequent exposure of engrafted mice to NO(2) or endotoxin did not significantly increase the number or pattern of donor-derived CD45(-) cells found in recipient lungs. These results suggest that NO(2) or endotoxin lung injury does not result in significant engraftment of marrow-derived cells in lung.     

Inhaled nitric oxide does not improve cardiac or pulmonary function in patients with an exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To determine whether inhaled nitric oxide (NO) improves right ventricular function in mechanically ventilated patients with severe chronic obstructive pulmonary disease (COPD). DESIGN: Open, prospective, controlled trial. SETTING: General intensive care unit of a community hospital. PATIENTS: Twelve patients with acute respiratory failure caused by acute exacerbation of COPD requiring mechanical ventilation. INTERVENTIONS: Insertion of a pulmonary artery catheter modified with a rapid response thermistor and a radial arterial catheter. Nitric oxide was then administered to the patient via a T piece placed between the Y piece of the ventilator and the endotracheal tube. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and gasometric variables were recorded before NO inhalation, during administration of inhaled NO (20 ppm, 20 mins), and 20 mins after NO discontinuation. Inhaled NO reduced pulmonary artery pressure from 26 +/- 6 to 22 +/- 5 mm Hg (p = .0004), but arterial oxygenation, cardiac output, and right ventricular ejection fraction remained unmodified (41% +/- 9% vs. 41% +/- 8%; not significant). Calculated pulmonary vascular resistance decreased from 453 +/- 233 to 348 +/- 108 dyne x sec/cm5 x m2 (p = .02), and right ventricular volumes did not change. Subsequently, right ventricular end-systolic pressure/volume ratio decreased from 0.52 +/- 0.22 to 0.44 +/- 0.19 mm Hg/mL/m2 (p = .01). No significant correlation was observed between the changes of pulmonary artery pressure (or pulmonary vascular resistance) and changes of right ventricular ejection fraction. CONCLUSION: Inhalation of NO does not seem to improve either right ventricular function or arterial oxygenation in patients with acute respiratory failure caused by acute exacerbation of COPD.     

Long-distance mountain biking does not disturb the measurement of total, free or complexed prostate-specific antigen in healthy men.

PURPOSE: Mechanical manipulation of the prostate is a generally accepted interfering factor for the measurement of prostate-specific antigen (PSA). However, only few studies have focused on common daily mechanical manipulations, such as bicycle riding. Furthermore, physical exercise is also supposed to modulate PSA serum concentration. Long-distance mountain biking is an excellent model to study the combined effect of mechanical prostate manipulation by bicycle riding and strenuous endurance exercise on total, free and complexed PSA (tPSA, fPSA, cPSA). MATERIALS AND METHODS: We investigated tPSA, fPSA and cPSA in 42 healthy male cyclists (mean age 35+/-6 years) before and after a 120 km off-road mountain bike race. Blood sampling was done before, 15 min and 3 h after the race. RESULTS: Mean race time was 342+/-65 min. All athletes had normal serum levels of tPSA, fPSA or cPSA. None of these parameters was modified by the race. CONCLUSIONS: In healthy men the measurement of tPSA, fPSA and cPSA is not disturbed by preceding long distance mountain biking or endurance exercise. Based on the present data, there is no evidence for a recommendation to limit bicycle riding or physical activity before the measurement of tPSA, fPSA or cPSA.     

Acute administration of tumour necrosis factor-alpha or interleukin-1-alpha does not mimic the hypoketonaemia associated with sepsis and inflammatory stress in the rat.

1. Administration of tumour necrosis factor (cachectin) and of interleukin-1-alpha increased the plasma level of nonesterified fatty acids in fed rats, and in the case of interleukin-1-alpha the blood glycerol level was also increased, suggesting stimulation of adipose tissue lipolysis. There were parallel increases in the plasma level of triacylglycerols. Neither cytokine had significant effects on blood or liver total ketone body (acetoacetate plus 3-hydroxybutyrate) concentrations. 2. In starved rats, the higher plasma non-esterified fatty acid concentration was not increased further by the cytokines. The plasma triacylglycerol level was increased, although the absolute change was less than in fed rats. The ketonaemia associated with starvation tended to be increased by the cytokines, but this was only significant in the case of interleukin-1-alpha. Parallel changes occurred in hepatic ketone bodies. 3. It is concluded that tumour necrosis factor-alpha and interleukin-1-alpha are not responsible for the hypoketonaemia associated with sepsis or other inflammatory states.