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Intravenous Infusion (intravenous + infusion)
Kinds of Intravenous Infusion Selected AbstractsRole of nitric oxide in the reflex diuresis in rabbits during pulmonary lymphatic obstructionEXPERIMENTAL PHYSIOLOGY, Issue 4 2004K. M. McCormick The role of nitric oxide in the reflex diuresis in response to pulmonary lymphatic drainage was examined in anaesthetized, artificially ventilated New Zealand White rabbits. Pulmonary lymphatic drainage was obstructed by raising the pressure in a pouch created from the right external jugular vein. Pulmonary lymphatic obstruction resulted in a significant increase in urine flow from an initial control value of 8.9 ± 0.5 ml (10 min),1 to 12.1 ± 0.6 ml (10 min),1 during lymphatic obstruction (mean ±s.e.m.; n= 17, P < 0.001). This increase in urine flow was accompanied by a significant increase in the excretion of sodium. Additionally, renal blood flow remained unchanged during the increase in urine flow caused by lymphatic obstruction. Intravenous infusion of l -NAME, a non-selective inhibitor of nitric oxide synthase (NOS), abolished the reflex diuresis. Furthermore, intraperitoneal administration of the relatively selective neuronal NOS blocker, 7-nitroindazole also abolished the response. It was observed that infusion of a more soluble neuronal NOS blocker, 7-nitroindazole sodium salt (7-NINA), into the renal medulla also abolished the reflex diuresis. These findings suggest that the increase in urine flow in rabbits caused by pulmonary lymphatic obstruction is dependent upon the integrity of neuronal NOS activity within the renal medulla. [source] Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trialACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009A. KÄMÄRÄINEN Background: Intravenous infusion of ice-cold fluid is considered a feasible method to induce mild therapeutic hypothermia in cardiac arrest survivors. However, only one randomized controlled trial evaluating this treatment exists. Furthermore, the implementation rate of prehospital cooling is low. The aim of this study was to evaluate the efficacy and safety of this method in comparison with conventional therapy with spontaneous cooling often observed in prehospital patients. Methods: A randomized controlled trial was conducted in a physician-staffed helicopter emergency medical service. After successful initial resuscitation, patients were randomized to receive either +4 °C Ringer's solution with a target temperature of 33 °C or conventional fluid therapy. As an endpoint, nasopharyngeal temperature was recorded at the time of hospital admission. Results: Out of 44 screened patients, 19 were analysed in the treatment group and 18 in the control group. The two groups were comparable in terms of baseline characteristics. The core temperature was markedly lower in the hypothermia group at the time of hospital admission (34.1±0.9 °C vs. 35.2±0.8 °C, P<0.001) after a comparable duration of transportation. Otherwise, there were no significant differences between the groups regarding safety or secondary outcome measures such as neurological outcome and mortality. Conclusion: Spontaneous cooling alone is insufficient to induce therapeutic hypothermia before hospital admission. Infusion of ice-cold fluid after return of spontaneous circulation was found to be well tolerated and effective. This method of cooling should be considered as an important first link in the ,cold chain' of prehospital comatose cardiac arrest survivors. [source] Stimulatory Effect of N -Methyltyramine, a Congener of Beer, on Pancreatic Secretion in Conscious RatsALCOHOLISM, Issue 2010Eri Tsutsumi Background:, Alcoholic beverages stimulate gastric acid secretion and increase the appetite. Although ingested ethanol stimulates pancreatic secretion, alcoholic beverages contain several congeners. N -methyltyramine (NMT) was isolated from beer as a factor in stimulating gastric acid secretion. In this study, we examined NMT to determine whether the congener stimulated pancreatic secretion in conscious rats. Methods:, Cannulae were inserted into male Wistar rats to separately drain bile and pancreatic secretions: 2 duodenal cannulae, a gastric cannula, and an external jugular vein cannula. The rats were placed in modified Bollman-type restraint cages. After a 4-day recovery period, experiments were conducted on unanesthetized rats. Different concentrations of NMT (5, 25, and 50 ,g/kg) solutions were infused into the stomach. To examine the mechanism, the effects of the proton pump inhibitor, cholecystokinin (CCK-BR) antagonist (YM022), CCK-AR antagonist (CR1505), and atropine were administered prior to the NMT (25 ,g/kg) infusion. The effect of intravenous infusion of NMT (7.5 ,g/kg) was then determined. Moreover, dispersed acini were prepared, and the effect of different concentrations of NMT on amylase release was determined. Results:, Intragastric administration of NMT significantly increased pancreatic exocrine secretion in a dose-dependent manner. Atropine eliminated the stimulatory effect of NMT, but the infusion of the proton pump inhibitor, YM022, and CR1505 did not. Intravenous infusion of NMT did not affect pancreatic secretion, and NMT did not stimulate amylase release in vitro. Conclusions:,N -methyltyramine stimulates pancreatic secretion via the cholinergic gastro-pancreatic reflex. The NMT content in beer was 2 mg/l, so that if a person weighing 60 kg consumes a 750 ml of beer, 25 ,g/kg NMT will be ingested. Therefore, the stimulatory effect of beer on pancreatic secretion was produced not only by ethanol but also by the congener, NMT. [source] Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humansALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006J. L. MADSEN Summary Background, Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. Aim, To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. Methods, Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion of glyceryl trinitrate 1 ,g/kg × min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. Results, Glyceryl trinitrate did not change gastric mean emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. Conclusions, Intravenous infusion of glyceryl trinitrate 1 ,g/kg × min does not induce major changes in gastric or small intestinal motor function after a 1600-kJ meal in healthy volunteers. [source] Duodenogastric reflux following cholecystectomy in the dog: role of antroduodenal motor functionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2001K. Nogi Background : Duodenogastric reflux has been implicated in the pathogenesis of gastric ulcer and gastritis. Duodenogastric reflux after cholecystectomy is also a possible cause of post-cholecystectomy syndrome. Aim : To investigate the role of antroduodenal motor function in increased duodenogastric reflux following cholecystectomy and the effect of trimebutine maleate (trimebutine) on the duodenogastric reflux in conscious dogs. Methods : Antropyloric and duodenal motility and bile acids content in the gastric juice were measured for 3 h during the inter-digestive state in dogs with or without cholecystectomy. Results : Bile acids content in the gastric juice of cholecystectomized dogs was significantly higher than that of non-cholecystectomized dogs. The frequency of pyloric relaxation during phase II of the migrating motor complex was significantly increased following cholecystectomy. Intravenous infusion of trimebutine inhibited both the increased duodenogastric reflux and the frequency of pyloric relaxation in the cholecystectomized dog. Conclusion : Duodenogastric reflux and frequency of pyloric relaxations were increased in cholecystectomized dogs and trimebutine suppressed both of them. These findings suggest that the increased frequency of pyloric relaxation contributes to the duodenogastric reflux following cholecystectomy. [source] Successful uses of magnesium sulfate for torsades de pointes in children with long QT syndromePEDIATRICS INTERNATIONAL, Issue 2 2006KENJI HOSHINO Abstract Background: Administration of magnesium sulfate (MgSO4) is an effective and safe treatment for torsades de pointes (TdP) associated with acquired long QT syndrome (LQTS) in adults. As for children, there are few reports focusing on it. The authors discuss the efficacy of MgSO4 for TdP in children with congenital and acquired LQTS. The authors also discuss the optimal administration dosage and serum magnesium (SMg) concentration during MgSO4 therapy. Methods: The authors studied seven consecutive LQTS children undergoing MgSO4 therapy for TdP. Of the seven children, five were congenital LQTS and two were acquired LQTS. A bolus injection of MgSO4 was given intravenously over 1,2 min followed by continuous infusion for the next 2,7 days. Results: Of the seven patients, six responded completely to the initial bolus. The bolus dosage was 5.9 ± 3.8 mg/kg (range, 2.3,12 mg/kg) in these six, and the other remaining one (neonate with congenital LQTS) required a total of 30 mg/kg until complete abolishment. The continuous infusion was given at rates of 0.3,1.0 mg/kg per h and patients did not show recurrence of TdP. The SMg concentration was 3.9 ± 1.0 mg/dL (2.9,5.4 mg/dL) immediately after bolus injection. The mean corrected QT (QTc) interval before and after bolus injection did not show significant difference. Conclusion: Intravenous infusion of MgSO4 was effective for TdP in children with LQTS, and MgSO4 abolished TdP without shortening the QTc interval. The optimal bolus dosage, infusion rates and SMg concentration were 3,12 mg/kg, 0.5,1.0 mg/kg per h and 3,5 mg/dL, respectively. [source] A case of purpura fulminans is caused by homozygous ,8857 mutation (protein C-Nagoya) and successfully treated with activated protein C concentrateBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2000Takayuki Nakayama We report a Japanese patient who developed purpura fulminans and disseminated intravascular coagulation (DIC) shortly after birth. The patient was diagnosed to be homozygous for protein C deficiency and was treated with an activated protein C (APC) concentrate. Intravenous infusions of APC markedly improved the necrotic skin lesions and the anticoagulation by APC enabled successful DIC control. The identified mutation (,8857) results in impaired intracellular transport and protein maturation and would be the cause of the complete protein C deficiency. This is the seventh case of the mutation that has been exclusively reported in Japan, but is the first report of a homozygous case. Our findings propose new therapeutic and diagnostic tools for the management of this fatal thrombotic disease. [source] Resistin increases islet blood flow and decreases subcutaneous adipose tissue blood flow in anaesthetized ratsACTA PHYSIOLOGICA, Issue 2 2009T. Danielsson Abstract Aim:, Resistin is an adipokine which has been suggested to participate in the induction of insulin resistance associated with type 2 diabetes. The aim of the present study was to investigate whether acute administration of resistin influences tissue blood perfusion in rats. Methods:, Resistin was administered as an intravenous infusion of 7.5 ,g h,1 (1.5 mL h,1) for 30 min to rats anaesthetized with thiobutabarbital. A microsphere technique was used to estimate the blood flow to six different depots of white adipose tissue (WAT), brown adipose tissue (BAT), as well as to the pancreas, islets, duodenum, colon, kidneys, adrenal glands and liver. Results:, Resistin administration led to an increased blood flow to the pancreas and islets and a decrease in subcutaneous WAT and BAT. Intra-abdominal white adipose tissue blood flow and that to other organs were not affected. Conclusion:, Acute administration of resistin markedly affects the blood perfusion of both the pancreas and subcutaneous white adipose tissue depots. At present it is unknown whether resistin exerts a direct effect on the vasculature, or works through local or systemic activation of endothelial cells and/or macrophages. The extent to which this might contribute to the insulin resistance caused by resistin is yet unknown. [source] Noninvasive Assessment of Coronary Flow Reserve in the Left Anterior Descending Artery by Transthoracic Echocardiography before and after StentingECHOCARDIOGRAPHY, Issue 8 2007Elie Chammas M.D., F.E.S.C. Background: Noninvasive assessment of coronary flow reserve in the left anterior descending artery (LAD) by transthoracic Doppler echocardiography (TTDE) has been already validated as a new method for determining the degree of stenosis over the proximal flow. Objectives: The aim of the study is to determine, by TTDE, the feasibility and the value of the coronary flow reserve (CFR) (defined as the maximal increase in coronary blood flow above its basal pressure for a given perfusion pressure when coronary circulation is maximally dilated) in the mid-to-distal LAD before and after percutaneous angioplasty and to demonstrate the early recovery of microvascular tone immediately after stenting. Methods: The study population consisted of 36 patients with significant isolated LAD stenosis (70,90%) identified by coronary angiography. CFR was recorded in the mid-to-distal LAD at rest and during hyperemia obtained after adenosine intravenous infusion before and after stenting. Results: Adequate visualization of the LAD was obtained in 25 out of 36 patients (70%). At rest the mean CFR was 1.5132 ± 0.33 (1.1,2.58). However, after stenting the mean CFR was significantly higher: 2.18 ± 0.55 (1.3,3.8), with P <0.01. Conclusions: CFR can be easily determined by TTE in approximately 70% of patients. Noninvasive Doppler echocardiography shows impaired CFR in patients with LAD disease. After stenting CFR is restored, demonstrating early recovery of microvascular tone. These results are comparable to those published in the same conditions. Larger series with a long-term follow-up may allow identifying patients at high risk for restenosis after stenting. [source] Noninvasive Coronary Flow Velocity Reserve Measurement in the Posterior Descending Coronary Artery for Detecting Coronary Stenosis in the Right Coronary Artery Using Contrast-Enhanced Transthoracic Doppler EchocardiographyECHOCARDIOGRAPHY, Issue 3 2004Hiroyuki Watanabe M.D. Background: Coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) has been found to be useful for assessing left anterior descending coronary artery (LAD) stenosis. However, this method has been restricted only for the LAD. The purpose of this study was to detect severe right coronary artery (RCA) stenosis by CFVR measurement using contrast-enhanced TTDE. Methods: In 60 consecutive patients with angina pectoris (mean (SD) age: 60 (11), 18 women), coronary flow velocities in the RCA were recorded in the postero-descending coronary artery by contrast-enhanced TTDE at rest and during hyperemia induced by intravenous infusion of adenosine triphosphate (140 mcg/ml/kg). CFVR was calculated as the ratio of hyperemic to basal peak and mean diastolic flow velocity. CFVR measurements by TTDE were compared with the results of coronary angiography performed within 1 week. Results: Coronary flow velocity was successfully recorded in 49 (82%) of the 60 patients with contrast agent. CFVR (mean (SD)) was 1.4 (0.4) in patients with, and 2.6 (0.6) in patients without significant stenosis in the RCA (%diameter stenosis > 75%, P < 0.001). Using the cutoff value 2.0 for CFVR in the RCA, its sensitivity and specificity in detecting significant stenosis in the RCA were 88% and 91%, respectively. Conclusion: CFVR measurement in the postero-descending coronary artery by contrast enhanced TTDE is a new, noninvasive method to detect significant stenosis in the RCA. (ECHOCARDIOGRAPHY, Volume 21, April 2004) [source] Noninvasive Assessment of Significant Right Coronary Artery Stenosis Based on Coronary Flow Velocity Reserve in the Right Coronary Artery by Transthoracic Doppler EchocardiographyECHOCARDIOGRAPHY, Issue 6 2003M.D., Yoshiki Ueno Background: Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography (TTDE) has been reported to be useful for the noninvasive assessment of coronary stenosis in the left anterior descending artery. However, the measurement of CFVR in the right coronary artery by TTDE has not yet been validated in a clinical study. Objective: The aim of this study was to evaluate whether CFVR by TTDE can detect significant stenosis in the right coronary artery. Methods: We studied 50 patients who underwent coronary angiography. Coronary flow velocity in the posterior descending branch of the right coronary artery (PD) was measured by TTDE both at baseline and during hyperemia induced by the intravenous infusion of adenosine triphosphate. CFVR was calculated as the hyperemia/baseline (average diastolic peak velocity). Results: Adequate spectral Doppler recordings in the PD were obtained in 36 patients including 26 patients who were given an echocardiographic contrast agent to improve Doppler spectral signals. The study population was divided into 2 groups with (Group A;n = 11) and without (Group B;n = 25) significant stenosis in the right coronary artery. CFVR in Group A was significantly smaller than that in Group B (1.6±0.3versus2.5±0.4; P < 0.0001). The sensitivity of a CFVR of <2.0 for predicting the presence of significant stenosis in the right coronary artery was 91%, and the specificity was 88%. Conclusions: The measurement of CFVR in the PD by TTDE is useful for the noninvasive assessment of significant stenosis in the right coronary artery. (ECHOCARDIOGRAPHY, Volume 20, August 2003) [source] Anaphylaxis: Clinical concepts and research prioritiesEMERGENCY MEDICINE AUSTRALASIA, Issue 2 2006Simon GA Brown Abstract Anaphylaxis is a severe immediate-type hypersensitivity reaction characterized by life-threatening upper airway obstruction bronchospasm and hypotension. Although many episodes are easy to diagnose by the combination of characteristic skin features with other organ effects, this is not always the case and a workable clinical definition of anaphylaxis and useful biomarkers of the condition have been elusive. A recently proposed consensus definition is ready for prospective validation. The cornerstones of management are the supine position, adrenaline and volume resuscitation. An intramuscular dose of adrenaline is generally recommended to initiate treatment. If additional adrenaline is required, then a controlled intravenous infusion might be more efficacious and safer than intravenous bolus administration. Additional bronchodilator treatment with continuous salbutamol and corticosteroids are used for severe and/or refractory bronchospasm. Aggressive volume resuscitation, selective vasopressors, atropine (for bradycardia), inotropes that bypass the ,-adrenoreceptor and bedside echocardiographic assessment should be considered for hypotension that is refractory to treatment. Management guidelines continue to be opinion- and consensus-based, with retrospective studies accounting for the vast majority of clinical research papers on the topic. The clinical spectrum of anaphylaxis including major disease subgroups requires clarification, and validated scoring systems and outcome measures are needed to enable good-quality prospective observational studies and randomized controlled trials. A systematic approach with multicentre collaboration is required to improve our understanding and management of this disease. [source] Sensitization of meningeal nociceptors: inhibition by naproxenEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Dan Levy Abstract Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non-selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non-selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single-unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non-selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of A,- and C-units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX-2 inhibitor N -[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) onto the dural receptive field of A,- and C-unit nociceptors also reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache. [source] Modelflow estimates of cardiac output compared with Doppler ultrasound during acute changes in vascular resistance in womenEXPERIMENTAL PHYSIOLOGY, Issue 4 2010Kenneth S. Dyson We compared Modelflow (MF) estimates of cardiac stroke volume (SV) from the finger pressure-pulse waveform (Finometer®) with pulsed Doppler ultrasound (DU) of the ascending aorta during acute changes in total peripheral resistance (TPR) in the supine and head-up-tilt (HUT) postures. Twenty-four women were tested during intravenous infusion of 0.005 or 0.01 ,g kg,1 min,1 isoprenaline, 10 or 50 ng kg,1 min,1 noradrenaline and 0.3 mg sublingual nitroglycerine. Responses to static hand-grip exercise (SHG), graded lower body negative pressure (LBNP, from ,20 to ,45 mmHg) and 45 deg HUT were evaluated on separate days. Bland,Altman analysis indicated that SVMF yielded lower estimates than SVDU during infusion of 0.01 ,g kg,1 min,1 isoprenaline (SVMF 92.7 ± 15.5 versus SVDU 104.3 ± 22.9 ml, P= 0.03) and SHG (SVMF 78.8 ± 12.0 versus SVDU 106.1 ± 28.5 ml, P < 0.01), while larger estimates were recorded with SVMF during ,45 mmHg LBNP (SVMF 52.6 ± 10.7 versus SVDU 46.2 ± 14.5 ml, P= 0.04) and HUT (SVMF 59.3 ± 13.6 versus SVDU 45.2 ± 11.3 ml, P < 0.01). Linear regression analysis revealed a relationship (r2= 0.41, P < 0.01) between the change in TPR from baseline and the between-methods discrepancy in SV measurements. This relationship held up under all of the experimental protocols (regression for fixed effects, P= 0.46). These results revealed a discrepancy in MF estimates of SV, in comparison with those measured by DU, during acute changes in TPR. [source] The Effect of Progesterone on Coronary Blood Flow in Anaesthetized PigsEXPERIMENTAL PHYSIOLOGY, Issue 1 2001C. Molinari The present study was designed to investigate the effect of progesterone on the coronary circulation and to determine the mechanisms involved. In pigs anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary blood flow caused by intravenous infusion of progesterone at constant heart rate and arterial blood pressure were assessed using an electromagnetic flowmeter. In 14 pigs, infusion of 1 mg h,1 of progesterone caused an increase in coronary blood flow without affecting left ventricular dP/dtmax (rate of change of left ventricular systolic pressure) and filling pressures of the heart. In a further four pigs, this vasodilatory coronary effect was enhanced by graded increases in the dose of the hormone of between 1, 2 and 3 mg h,1. The mechanisms of the above response were studied in the 14 pigs by repeating the experiment after haemodynamic variables had returned to the control values observed before infusion. In six pigs, blockade of muscarinic cholinoceptors and adrenoceptors with atropine, propranolol and phentolamine did not affect the coronary vasodilatation caused by progesterone. In the remaining eight pigs, this response was abolished by intracoronary injection of N, -nitro-L-arginine methyl ester (L-NAME) even when performed after reversing the increase in arterial blood pressure and coronary vascular resistance caused by L-NAME with continuous intravenous infusion of papaverine. The present study showed that intravenous infusion of progesterone primarily caused coronary vasodilatation. The mechanism of this response was shown to involve the endothelial release of nitric oxide. [source] Pilot trial of concomitant chemotherapy with paclitaxel and split-course radiotherapy for very advanced squamous cell carcinoma of head and neck,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2002Olavo Feher MD Abstract Purpose The combination of chemotherapy and irradiation is considered the standard of care for the treatment of advanced squamous cell carcinoma of head and neck (SCCHN). Paclitaxel has shown a single-agent activity in SCCHN. Besides, this drug is a promising radiosensitizer for some human solid tumors. This is a phase II trial to evaluate the feasibility, efficacy, and toxicity of paclitaxel administered concurrently with split-course radiotherapy in advanced unresectable SCCHN. Methods and Materials Thirty-one patients with advanced SCCHN were enrolled in this trial. Radiotherapy consisted of 66 to 70 Gy delivered over 8 to 10 weeks to the primary tumor and lymphatic drainage, with a fractionation scheme of 1.8 to 2 Gy/field/d. After the initial five patients were treated, a 1-week treatment break was introduced. Paclitaxel was administered weekly in a 1-hour intravenous infusion at a projected dosage of 45 mg/m2/wk. Results The complete and partial response rates, based on a 4-week postradiation evaluation were 43.3% and 40%, respectively, with an overall response rate of 83.3%. Median survival was 49.4 weeks, and 1-year survival was 48%. Freedom from local progression was 65.6% at 1 year. Thirty-six percent and 20% of the patients are alive and disease free at 1 and 2 years, respectively. Grade 3/4 of acute toxicity consisted mostly of mucositis, cutaneous reaction, and weight loss. Conclusions Paclitaxel concurrent with radiotherapy seems to be active in squamous cell carcinoma of the head and neck. In the regimen selected for this trial, toxicity was significant and led to a prolongation of treatment time. © 2002 Wiley Periodicals, Inc. Head Neck 24: 228,235, 2002; DOI 10.1002/hed.10049 [source] Induction of cellular resistance against Kupffer cell,derived oxidant stress: A novel concept of hepatoprotection by ischemic preconditioningHEPATOLOGY, Issue 2 2003Rolf J. Schauer Ischemic preconditioning (IP) triggers protection of the liver from prolonged subsequent ischemia. However, the underlying protective mechanisms are largely unknown. We investigated whether and how IP protects the liver against reperfusion injury caused by Kupffer cell (KC)-derived oxidants. IP before 90 minutes of warm ischemia of rat livers in vivo significantly reduced serum alanine aminotransferase (AST) levels and leukocyte adherence to sinusoids and postsinusoidal venules during reperfusion. This protective effect was mimicked by postischemic intravenous infusion of glutathione (GSH), an antioxidative strategy against KC-derived H2O2. Interestingly, no additional protection was achieved by infusion of GSH to preconditioned animals. These findings and several additional experiments strongly suggest IP mediated antioxidative effects: IP prevented oxidant cell injury in isolated perfused rat livers after selective KC activation by zymosan. Moreover, IP prevented cell injury and pertubations of the intracellular GSH/GSSG redox system caused by direct infusion of H2O2 (0.5 mmol/L). IP-mediated resistance against H2O2 could neither be blocked by the adenosine A2a antagonist DMPX nor mimicked by A2a agonist CGS21680. In contrast, H2O2 resistance was abolished by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, but induced when p38 MAPK was directly activated by anisomycin. In conclusion, we propose a novel concept of hepatoprotection by IP: protection of liver cells by enhancing their resistance against KC-derived H2O2. Activation of p38 MAPK and preservation of the intracellular GSH/oxidized glutathione (GSSG) redox system, but not adenosine A2a receptor stimulation, seems to be pivotal for the development of H2O2 resistance in preconditioned livers. [source] Infliximab improves quality of life in patients with Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2002Dr. Gary R. Lichtenstein Abstract Objective The aim of this study was to assess the effect of infliximab on quality of life in patients with active Crohn's disease (CD) inadequately responsive to concomitant therapies. Methods We examined responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) from patients enrolled in a previously reported, randomized, placebo-controlled study. Patients with active CD received a single intravenous infusion of either placebo or infliximab 5, 10, or 20 mg/kg. Most patients received stable doses of mesalamine, corticosteroids, azathioprine, or 6-mercaptopurine throughout the study. Changes from baseline in overall IBDQ score and individual dimensions at 4 weeks postinfusion were compared. Results Patients treated with infliximab had a significantly larger improvement in overall IBDQ score than those treated with placebo at 4 weeks (p < 0.001). Infliximab-treated patients also had larger improvements in all IBDQ dimensions: bowel (p = 0.007), social (p = 0.002), emotional (p < 0.001), and systemic (p < 0.001). A significantly larger proportion of infliximab-treated patients reported having normal or near-normal frequency of bowel movements in the past week (p < 0.001), full or a lot of energy (p = 0.019), and no or hardly any difficulty doing leisure or sports activities (p = 0.011), and being extremely or very satisfied with their personal life (p = 0.046). They also significantly differed in responses regarding fatigue, frustration, ability to work, general well-being, depression, anxiety, and anger resulting from bowel problems. Conclusions These results indicate that infliximab significantly improved quality of life in patients with active CD, increasing their ability to work and participate in leisure activities, and decreasing feelings of fatigue, depression, and anger. [source] Suppressive effects of cyclosporine A on neutrophils and T cells may be related to therapeutic benefits in patients with steroid-resistant ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 1 2002Kenji Ina Abstract An intravenous infusion of cyclosporine A (CsA) shows clinical benefits in patients with steroid-resistant ulcerative colitis (UC). To clarify its mechanisms, we investigated the ability of CsA to inhibit the functions of neutrophils and T cells. The cytotoxic activity by mucosal T cells was analyzed by anti-CD3-triggered cytotoxicity after lamina propria mononuclear cells were cultured with recombinant interleukin (IL)-2. The chemotactic response, the generation of superoxide, and the production of chemokines, IL-8, and macrophage inflammatory protein-1, by neutrophils were examined using a multiple-well chamber assay, a chemiluminescence method, and an enzyme-linked immunosorbent assay (ELISA), respectively. Mucosal chemokine activity was determined by an ELISA using the organ culture supernatant of mucosal biopsy tissues. Pretreatment with CsA caused consistent inhibitions of cytotoxic activity by mucosal T cells and chemotactic migration, superoxide generation, and chemokine production by neutrophils mostly in a dose-dependent manner. In patients who received an intravenous infusion of CsA, mucosal chemokine activity decreased after therapy in parallel with decreases in the numbers of neutrophils and mononuclear cells in the biopsy tissues. These results suggest that suppressive effects of CsA on neutrophils and T cells may be related to therapeutic benefits in patients with steroid-resistant UC. [source] Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: A pilot studyINFLAMMATORY BOWEL DISEASES, Issue 2 2001Dr. Bruce E. Sands Abstract We report the experience of 11 patients (of 60 planned patients) enrolled in a double-blind, placebo-controlled clinical trial of infliximab in patients with severe, active steroid-refractory ulcerative colitis. The study was terminated prematurely because of slow enrollment. Patients having active disease for at least 2 weeks and receiving at least 5 days of intravenous corticosteroids were eligible to receive a single intravenous infusion of infliximab at 5, 10, or 20 mg/kg body weight. The primary endpoint used in this study was treatment failure at 2 weeks after infusion. Treatment failure was defined as 1) unachieved clinical response as defined by a modified Truelove and Witts severity score, 2) increase in corticosteroid dosage, 3) addition of immunosuppressants, 4) colectomy, or 5) death. Safety evaluations included physical examination, clinical chemistry and hematology laboratory tests, and occurrence of adverse experiences. Four of 8 patients (50%) who received infliximab were considered treatment successes at 2 weeks, compared with none of 3 patients who received placebo. Improvement in erythrocyte sedimentation rates and serum concentrations of C-reactive protein and interleukin-6 correlated with the clinical response observed in patients receiving infliximab. Infusion with infliximab produced no significant adverse events. Infliximab was well tolerated and may provide clinical benefit for some patients with steroid-refractory ulcerative colitis. [source] Radiographic lung density assessed by computed tomography is associated with extravascular lung water contentACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2010V. V. KUZKOV Background: We hypothesized that in acute lung injury (ALI), the volume of pulmonary tissue with aqueous density, as determined by spiral computed tomography (CT), is associated with extravascular lung water content. Our aim was to compare tissue volume index, as assessed by CT, before and after oleic acid-induced ALI, with extravascular lung water indexes (EVLWI), determined with single transpulmonary thermodilution (EVLWISTD), thermal-dye dilution (EVLWITDD), and postmortem gravimetry (EVLWIG). Methods: Seven instrumented sheep received an intravenous infusion of oleic acid 0.08 ml/kg (OA group) and four animals had vehicle only (Control group). The day before, and immediately after the experiment, sheep were anesthetized to undergo quantitative CT examinations during a short breath hold. Hemodynamics, oxygenation, EVLWISTD, and EVLWTDD were registered. Linear regression analysis was used to assess the relationships between EVLWISTD, EVLWTDD, EVLWIG, and lung tissue volume index (TVICT) determined with CT. Results: In the OA group, total lung volume increased compared with Controls. Poorly and non-aerated lung volumes increased a 3.6- and 4.9-fold, respectively, and TVICT almost doubled. EVLWISTD, EVLWITDD, and TVICT were associated significantly with EVLWIG (r=0.85, 0.90, and 0.88, respectively; P<0.001). TVICT deviated from the reference EVLWIG values to the greatest extent with a mean bias ± 2SD of 4.0 ± 6.0 ml/kg. Conclusions: In ovine oleic acid-induced ALI, lung tissue volume, as assessed by quantitative CT, is in close agreement with EVLWI, as determined by indicator dilution methods and postmortem gravimetry, but overestimates lung fluid content. [source] Dermatomyositis presenting as panniculitisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2000Yen-Yu Chao MD A 44-year-old obese woman was transferred to our clinic with a diagnosis of panniculitis. Examination showed multiple, indurated, erythematous, painful nodules and plaques distributed on the shoulders, back, forechest, abdomen, buttock, and bilateral thighs. These skin lesions appeared 2 months previously, measured 5,8 cm, and were tender on palpation. No obvious inducing factor was traced. The lesions seemed unresponsive to treatment with nonsteroidal anti-inflammatory drugs (ibuprofen, 400 mg three times a day) as similar lesions appeared in subsequent visits. Progressive proximal muscle weakness was found 1 month later. She was then admitted via the emergency room because of extensive painful skin plaques and abdominal pain. Diffuse erythematous to violaceous swelling of the face, neck, and shoulder was noted at about the same time ( Fig. 1). A skin biopsy specimen from the nodular lesion showed poikilomatous epidermal changes ( Fig. 2), and marked mononuclear cell infiltration in the dermis and subcutaneous fat ( Fig. 3). Dermatomyositis was considered as the diffuse violaceous facial erythema could be a form of heliotrope eruption, but Gottron's papule was not found. At admission, serum creatinine phosphokinase (CPK) was mildly elevated (436 IU/L; normal range, 20,170 IU/L), but serum asparagine transaminase (AST) and lactate dehydrogenase (LDH) levels were within normal limits (36 IU/L; normal, 11,47 IU/L; and 108 IU/L; normal, 90,280 IU/L, respectively). Antinuclear antibody was 1 : 80 positive with an atypical speckled pattern. Muscle strength was weakest during the first 2 days, about grade 3 by the Medical Research Council (MRC) of Great Britain scale. Gower's sign was positive. An electromyogram showed myopathic changes and a nerve conduction velocity study was normal. Serum enzymes were elevated further on the third day: AST, 55 IU/L; CPK, 783 IU/L with 100% MM form. The diagnosis of dermatomyositis was established. As for the work-up result, anti-dsDNA antibody, anti-ENA antibody, and anti-Jo1 antibody were negative. Tumor marker screen (,-HCG, AFP, CEA, and CA-125), was negative, and rhinolaryngopharyngoscope examination and gynecologic sonography were normal. Figure 1. Diffuse erythematous swelling with subtle violaceous hue extending from the temporal area to the cheeks, neck, and shoulders. The crusted lip ulcers of herpes simplex were also noted Figure 2. Basketweave hyperkeratosis, mild acanthosis, subtle vacuolar degeneration of the basal cells, and melanin incontinence (hematoxylin and eosin, ×400) Figure 3. Heavy mononuclear cells infiltrated in the subcutaneous fat tissue (hematoxylin and eosin, ×100) Pancreatitis was initially suspected because of epigastric pain and tenderness, elevated serum lipase (382 U/L; normal, 23,200 U/L), and amylase (145 U/L; normal, 35,118 U/L). No evidence of pancreatitis could be found in abdominal sonography and abdominal computed tomography (CT), however. The epigastric pain and tenderness subsided soon after admission and the serum pancreatic enzyme level declined on the second day (amylase 69 U/L; lipase, 276 U/L). The patient was then diagnosed with dermatomyositis and treated with prednisolone (120 mg/day). CPK dropped dramatically from 3286 IU/L the day before treatment to 1197 IU/L 3 days after. Panniculitis lessened and the muscle power improved after 1 week of treatment. The disease activity fluctuated even with treatment with prednisolone and the patient often felt listless and weak. The muscle weakness sometimes deteriorated to affect the patient's mobility. Facial erythema and panniculitis-like lesions were found during the worse times. Methotrexate and azathioprine were then added (7.5 mg and 250 mg per week, respectively), but CPK was still mildly elevated (189 IU/L), and the patient still felt ill. Human immune globulin (5%, 500 mL per day, 5 days per month) intravenous infusion was initiated thereafter. There was a dramatic response. Full muscle strength was retained and CPK was within the normal range in the following 6 months with only immune globulin therapy. [source] Prescription practices of public and private health care providers in Attock District of PakistanINTERNATIONAL JOURNAL OF HEALTH PLANNING AND MANAGEMENT, Issue 1 2002S. Siddiqi Abstract The irrational use of drugs is a major problem of present day medical practice and its consequences include the development of resistance to antibiotics, ineffective treatment, adverse effects and an economic burden on the patient and society. A study from Attock District of Pakistan assessed this problem in the formal allopathic health sector and compared prescribing practices of health care providers in the public and private sector. WHO recommended drug use indicators were used to study prescription practices. Prescriptions were collected from 60 public and 48 private health facilities. The mean (±,SE) number of drugs per prescription was 4.1,±,0.06 for private and 2.7,±,0.04 for public providers (,p,<,0.0001). General practitioners (GPs) who represent the private sector prescribed at least one antibiotic in 62% of prescriptions compared with 54% for public sector providers. Over 48% of GP prescriptions had at least one injectable drug compared with 22.0% by public providers (,p,<,0.0001). Thirteen percent of GP prescriptions had two or more injections. More than 11% of GP prescriptions had an intravenous infusion compared with 1% for public providers (,p,<,0.001). GPs prescribed three or more oral drugs in 70% of prescriptions compared with 44% for public providers (,p,<,0.0001). Prescription practices were analysed for four health problems, acute respiratory infection (ARI), childhood diarrhoea (CD), fever in children and fever in adults. For these disorders, both groups prescribed antibiotics generously, however, GPs prescribed them more frequently in ARI, CD and fever in children (,p,<,0.01). GPs prescribed steroids more frequently, however, it was significantly higher in ARI cases (,p,<,0.001). For all the four health problems studied, GPs prescribed injections more frequently than public providers (,p,<,0.001). In CD cases GPs prescribed oral rehydration salt (ORS) less frequently (33.3%) than public providers (57.7%). GPs prescribed intravenous infusion in 12.3% cases of fever in adults compared with none by public providers (,p,<,0.001). A combination of non-regulatory and regulatory interventions, directed at providers as well as consumers, would need to be implemented to improve prescription practices of health care providers. Regulation alone would be ineffective unless it is supported by a well-established institutional mechanism which ensures effective implementation. The Federal Ministry of Health and the Provincial Departments of Health have to play a critical role in this respect, while the role of the Pakistan Medical Association in self-regulation of prescription practices can not be overemphasized. Improper prescription practices will not improve without consumer targeted interventions that educate and empower communities regarding the hazards of inappropriate drug use. Copyright © 2002 John Wiley & Sons, Ltd. [source] New and innovative therapies for Behcet's diseaseINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 2 2004Fereydoun DAVATCHI Abstract Background:, Behcet's disease (BD) is a vasculitis progressing by attacks and remissions. Not all patients will respond even to the classical treatments. New treatments are emerging with the hope to overcome this failure. Biologic agents:, Interferon-, (IFN-,), anti-tumour necrosis factor-, (TNF-,), and tolerization have been used in BD. IFN-, is mainly used for ocular manifestations of BD. The result seems impressive, 92% of cases had good or excellent results. It was less impressive for mucocutaneous and joint manifestations. The dosage is 6,9 million IU/day for 4 weeks, then 4.5 million daily for 4 weeks, and then 3 million/day. The maintenance dose is 3 millions, three times/week, to continue for 8 weeks after complete remission. Etanercept (anti-TNF-,) was effective in mucocutaneous lesions of BD at the dosage of 25 mg twice weekly for 3 months (double-blind control study). Attacks relapsed after discontinuation. Etanercept was ineffective in ocular lesions (open study). Infliximab (anti-TNF-,) was very effective in many studies of ocular lesions. It dramatically suppressed the inflammatory attack. The dosage is one injection of 5 mg/kg (intravenous infusion) at weeks 0, 2, 6, and then every 8 weeks. Tolerization with oral administration of HSP peptide 336,351 seems to protect from uveitis relapse. Pentoxifylline is not particularly effective unless for oral aphthae (50% response rate). Pimecrolimus ointment may be of help in resistant genital aphthosis, reducing the healing time. [source] Metastatic urothelial cancer showing an efficacy by low-dose cisplatinINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2002Hideyasu Matsuyama Abstract A 69-year-old man who had developed multiple distant metastases on retrocaval lymph nodes after four courses of Methotraxate, Vinblastine, Adriamycin, Cisplatin (MVAC) chemotherapy was successfully treated by intravenous infusion of low-dose cisplatin (CDDP) (10 mg/time, once per week) and oral administration of 600 mg/day 5,-deoxy-5-fluorouridine (5,-DFUR), a pro-drug of 5-FU, in an outpatient setting. A partial response (62% reduction rate) was confirmed by abdominal computed tomography (CT) scan after 7 months. Although the CDDP dosage had been reduced to 5 mg/week 1 year previously, the tumor was still reducing in size in November 2000. Combination therapy of 5,-DFUR with low-dose CDDP could become an option for advanced bladder cancer that compromises the patient's quality of life, especially when used in an outpatient setting. [source] Efficacy and Safety of a Once-Yearly Intravenous Zoledronic Acid 5 mg for Fracture Prevention in Elderly Postmenopausal Women with Osteoporosis Aged 75 and OlderJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2010Steven Boonen MD OBJECTIVES: To determine the efficacy of once-yearly intravenous zoledronic acid (ZOL) 5 mg in reducing risk of clinical vertebral, nonvertebral, and any clinical fractures in elderly osteoporotic postmenopausal women. DESIGN: A post hoc subgroup analysis of pooled data from the Health Outcome and Reduced Incidence with Zoledronic Acid One Yearly (HORIZON) Pivotal Fracture Trial and the HORIZON Recurrent Fracture Trial. SETTING: Multicenter, randomized, double-blind, placebo-controlled trials. PARTICIPANTS: Postmenopausal women (aged ,75) with documented osteoporosis (T -score ,,2.5 at femoral neck or ,1 prevalent vertebral or hip fracture) or a recent hip fracture. INTERVENTION: Patients were randomized to receive an intravenous infusion of ZOL 5 mg (n=1,961) or placebo (n=1,926) at baseline and 12 and 24 months. MEASUREMENTS: Primary endpoints were incidence of clinical vertebral and nonvertebral and any clinical fracture after treatment. RESULTS: At 3 years, incidence of any clinical, clinical vertebral, and nonvertebral fracture were significantly lower in the ZOL group than in the placebo group (10.8% vs 16.6%, 1.1% vs 3.7%, and 9.9% vs 13.7%, respectively) (hazard ratio (HR)=0.65, 95% confidence interval (CI)=0.54,0.78, P<.001; HR=0.34, 95% CI=0.21,0.55, P<.001; and HR=0.73, 95% CI=0.60,0.90, P=.002, respectively). The incidence of hip fracture was lower with ZOL but did not reach statistical significance. The incidence rate of postdose adverse events were higher with ZOL, although the rate of serious adverse events and deaths was comparable between the two groups. CONCLUSION: Once-yearly intravenous ZOL 5 mg was associated with a significant reduction in the risk of new clinical fractures (vertebral and nonvertebral) in elderly postmenopausal women with osteroporosis. [source] Unilateral paravertebral block: an alternative to conventional spinal anaesthesia for inguinal hernia repairACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010P. BHATTACHARYA Background: Inguinal herniorrhaphy can be successfully performed using general, regional or local anaesthesia. Paravertebral block (PVB) has been used for unilateral procedures such as thoracotomy, breast surgery, chest wall trauma, hernia repair or renal surgery. Methods: We compared unilateral lumbar PVB with conventional spinal anaesthesia (SA) in 60 consenting ASA I and II males aged 18,65 years, scheduled for unilateral inguinal hernia repair. Patients were randomly assigned into two groups, P (n=30) or S (n=30) to receive either PVB or SA, respectively. Two patients (7%) in group P had to be converted to general anaesthesia due to block failure. During surgery, patients of both groups received intravenous infusion of propofol titrated to light sedation. Results: The time to first post-operative analgesic requirement (primary outcome measure) as 342 ± 73 min in group P and 222 ± 22 min in group S (P<0.0001). Time to ambulation was 234 ± 111 min in group P and 361 ± 32 min in group S (P<0.0001). Urinary retention requiring catheterization were found in zero (0%) patients in group P compared with five (16%) in group S (P=0.024). Conclusion: It can be concluded that unilateral PVB is more efficacious than conventional SA in terms of prolonging post-operative analgesia and reducing morbidities in patients undergoing elective unilateral inguinal hernia repair. [source] Responses of milk production to the intravenous infusion of amino acids in dairy cows given diets of grass silage and cereal-based supplementsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 9-10 2001C.-H. Kim Three experiments were carried out to examine responses of milk production to the intravenous infusion of amino acids in dairy cows given diets of grass silage and supplements based on barley, with or without added soyabean meal and ranging in crude protein content from 16 to 19% in dry matter. Particular attention was given to histidine, administered alone or in combination with methionine, lysine and tryptophan. Responses of milk protein secretion to infusion of histidine were seen only when the diet contained a supplement of barley alone. When soyabean meal was included, there were no responses of milk production to infusion of any of the infused amino acids. Calculations suggested that, although histidine remained first-limiting when soya was included in the diet, any response to infusion of histidine was blocked by the rapidly emerging deficiency of another amino acid, probably leucine. The results confirm that, for diets based on grass silage and supplements of cereal only, histidine is first-limiting such that increases of milk protein secretion can be obtained in response to infusion of histidine alone. In assessing the practical significance of this finding, it should be remembered that greater responses in the yield of milk protein can probably be obtained by substituting 1 kg of soyabean meal for 1 kg of cereal, which is likely to be an easier and cheaper option. [source] Iloprost inhalation redistributes pulmonary perfusion and decreases arterial oxygenation in healthy volunteersACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009D. RIMEIKA Background: Previous studies have shown that ventilation,perfusion matching is improved in the prone as compared with that in the supine position. Regional differences in the regulation of vascular tone may explain this. We have recently demonstrated higher production of nitric oxide in dorsal compared with ventral human lung tissue. The purpose of the present study was to investigate regional differences in actions by another vasoactive mediator, namely prostacyclin. The effects on gas exchange and regional pulmonary perfusion in different body positions were investigated at increased prostacyclin levels by inhalation of a synthetic prostacyclin analogue and decreased prostacyclin levels by unselective cyclooxygenase (COX) inhibition. Methods: In 19 volunteers, regional pulmonary perfusion in the prone and supine position was assessed by single photon emission computed tomography using 99mTc macro-aggregated albumin before and after inhalation of iloprost, a stable prostacyclin analogue, or an intravenous infusion of a non-selective COX inhibitor, diclofenac. In addition, gas distribution was assessed in seven subjects using 99mTc-labelled ultra-fine carbon particles before and after iloprost inhalation in the supine position. Results: Iloprost inhalation decreased arterial PaO2 in both prone (from 14.2±0.5 to 11.7±1.7 kPa, P<0.01) and supine (from 13.7±1.4 to 10.9±2.1 kPa, P<0.01) positions. Iloprost inhalation redistributed lung perfusion from non-dependent to dependent lung regions in both prone and supine positions, while ventilation in the supine position was distributed in the opposite direction. No significant effects of non-selective COX inhibition were found in this study. Conclusions: Iloprost inhalation decreases arterial oxygenation and results in a more gravity-dependent pulmonary perfusion in both supine and prone positions in healthy humans. [source] Restoration of Bone Mass and Strength in Glucocorticoid-Treated Mice by Systemic Transplantation of CXCR4 and Cbfa-1 Co-Expressing Mesenchymal Stem Cells,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2009Chun-Yang Lien Abstract Transplantation of gene-modified mesenchymal stem cells (MSCs) in animals for bone regeneration therapy has been evaluated extensively in recent years. However, increased endosteal bone formation by intravenous injection of MSCs ectopically expressing a foreign gene has not yet been shown. Aside from the clearance by lung and other tissues, the surface compositions of MSCs may not favor their bone marrow (BM) migration and engraftment. To overcome these hurdles, a gene encoding the chemokine receptor largely responsible for stromal-derived factor-1 (SDF-1)-mediated BM homing and engraftment of hematopoietic stem cells (HSCs), CXCR4, was transduced into mouse C3H10T1/2 cells by adenovirus infection. A dose-dependent increase of CXCR4 surface expression with a parallel enhanced chemotaxis toward SDF-1 in these cells after virus infection was clearly observed. Higher BM retention and homing of CXCR4-expressing MSCs were also found after they were transplanted by intramedullary and tail vein injections, respectively, into immunocompetent C3H/HeN mice. Interestingly, a full recovery of bone mass and a partial restoration of bone formation in glucocorticoid-induced osteoporotic mice were observed 4 wk after a single intravenous infusion of one million CXCR4-expressing C3H10T1/2 cells. In the meantime, complete recovery of bone stiffness and strength in these animals was consistently detected only after a systemic transplantation of CXCR4 and Cbfa-1 co-transduced MSCs. To our knowledge, this is the first report to show unequivocally the feasibility of ameliorating glucocorticoid-induced osteoporosis by systemic transplantation of genetically manipulated MSCs. [source] | ||||||||||||||||||||||||||||||||||||||||