Home About us Contact
|
Home About us Contact | ||
|
|
||
Furosemide
Terms modified by Furosemide Selected AbstractsRenal Calculi Complicating Short-term Furosemide Therapy after Congenital Heart SurgeryCONGENITAL HEART DISEASE, Issue 5 2006Sulafa K.M. Ali FRCPCH ABSTRACT Background., Renal calcification is a known complication of Furosemide therapy. Methods., We describe 3 children who were diagnosed with renal calculi, not nephrocalcinosis, following the use of Furosemide for 4 weeks. All the infants (24, 18, and 8 months) had successful repair/palliation of congenital heart disease. The dose of Furosemide was 1,2 mg/kg/day and the duration between starting treatment and development of hematuria was 4 weeks. Results., In all 3 patients renal ultrasound confirmed the presence of renal calculi with no nephrocalcinosis. On follow-up, hematuria improved after 3,4 months. Conclusion., Renal calculi can complicate short-term Furosemide treatment in children after repair of congenital heart disease. Patients on Furosemide should be closely monitored by urine analysis and/or urine calcium/creatinine ratio for early detection of this complication. [source] Furosemide Terminates Limbic Status Epilepticus in Freely Moving RatsEPILEPSIA, Issue 9 2003Martin Holtkamp Summary:,Purpose: To evaluate the anticonvulsant properties of furosemide and to determine sedative side effects compared with pentobarbital and diuretic side effects compared with saline-treated controls in an experimental model of limbic status epilepticus. Methods: Self-sustaining status epilepticus was induced in rats by continuous electrical stimulation of the perforant path. Five minutes after the end of the stimulation, animals were given 100 mg/kg furosemide, 30 mg/kg pentobarbital, or an equal amount of saline, intraperitoneally. After administration of the substance, animals were monitored clinically and electrographically for 3 h regarding status epilepticus, level of sedation, and diuresis. Results: In seven of 10 animals, furosemide terminated status epilepticus after 68 ± 26 min, whereas pentobarbital was successful in all animals after 5 ± 0.8 min. In contrast to pentobarbital, sedation did not occur with furosemide. Weight loss after furosemide was 10.2 ± 1.7% compared with 6.5 ± 1.1% in animals given saline (p < 0.001). Conclusions: The results suggest that furosemide may serve as an alternative or additional agent for refractory complex partial status epilepticus in patients in whom common anesthetics are not justifiable. [source] Diversity of GABAA receptor synaptic currents on individual pyramidal cortical neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2007Timothy Ing Abstract Miniature GABAA receptor-mediated inhibitory postsynaptic currents (mIPSCs) in cortical pyramidal neurons have previously been categorized into two types: small amplitude mIPSCs with a mono-exponential deactivation (mono-mIPSCs) and relatively larger mIPSCs with bi-exponential deactivation (bi-mIPSCs). The aim of this study was to determine if the GABAA channels that underlie these mIPSCSs are molecularly distinct. We found, using non-stationary noise analysis, that the difference in their amplitude could be not accounted for by their single channel conductance (both were 40 pS). Next, using , subunit selective GABAA receptor modulators, we examined the identity of the , subunits that may be expressed in the synapses that give rise to these mIPSCs. Zolpidem (100 and 500 nm, ,1 selective) affected the deactivation of a subset of the mono-mIPSCs, indicating that ,1 subunits are not highly expressed in these synapses. However, zolpidem (100 nm) prolonged the deactivation of all bi-mIPSCs, indicating a high abundance of ,1 subunits in these synapses. SB-205384 (,3 selective) had no effect on the mono-mIPSCs but the bi-mIPSCs were prolonged. Furosemide (,4 selective) reduced the amplitude of only the mono-mIPSCs. L655,708 (,5 selective) reduced the amplitude of both populations and shortened the duration of the mono-mIPSCs. Finally, we found that the neuroactive steroid pregesterone sulphate reduced the amplitude of both mIPSC types. These results provide pharmacological evidence that synapses on cortical pyramidal neurons are molecularly distinct. The purpose of these different types of synapses may be to provide different inhibitory timing patterns on these cells. [source] Characterization of the myo -inositol transport system in Trypanosoma cruziFEBS JOURNAL, Issue 9 2000Marcelo Einicker-Lamas myo -Inositol is a growth factor for mammalian cells as well as for the pathogenic protozoa Trypanosoma cruzi. Most of the cell surface molecules in this organism rely on myo -inositol as the biosynthetic precursor for phosphoinositides and glycosylated phosphatidylinositols. The aim of this work was to investigate the process of myo -inositol translocation across the parasite cell membrane. myo -Inositol uptake was concentration-dependent in the concentration range 0.1,10 µm with maximal transport obtained at 8 µm. Using sodium-free buffers, where Na+ was replaced by choline or K+, myo -inositol uptake was inhibited by 50%. Furosemide, an inhibitor of the ouabain-insensitive Na+ -ATPase, inhibited the Na+ -dependent and Na+ -independent myo -inositol uptake by 68 and 33%, respectively. In contrast, ouabain, an (Na++/K+) ATPase inhibitor, did not affect transport. Part of the myo -inositol uptake is mediated by active transport as it was inhibited when energy metabolism inhibitors such as carbonyl cyanide p -(trifluoromethoxy)-phenylhydrazone (34%), 2,4-dinitrophenol (50%), KCN (71%) and NaN3 (69%) were added to the medium, or the temperature of the medium was lowered to 4 °C. The addition of glucose (5,50 mm) or mannose (10 mm) did not change the myo -inositol uptake, whereas the addition of 10 mm nonlabeled myo -inositol totally inhibited this transport, indicating that the transporter is specific for myo -inositol. Phloretin (0.3 mm) and phoridzin (5 mm), but not cytochalasin B, were efficient inhibitors of myo -inositol uptake. A portion of the accumulated myo -inositol is converted to inositol phosphates and phosphoinositides. These data show that myo -inositol transport in T. cruzi epimastigotes is mediated by at least two specific transporters , one Na+ -dependent and the other Na+ -independent. [source] Fluid therapy and the use of albumin in the treatment of severe traumatic brain injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009M. RODLING WAHLSTRÖM Background: Evidence-based guidelines for severe traumatic brain injury (TBI) do not include strategies for fluid administration. The protocol used in this study includes albumin administration to maintain normal colloid osmotic pressure and advocates a neutral to slightly negative fluid balance. The aim of this study was to analyze the occurrence of organ failure and the mortality in patients with severe TBI treated by a protocol that includes defined strategies for fluid therapy. Methods: Ninety-three patients with severe TBI and Glasgow Coma Score,8 were included during 1998,2001. Medical records of the first 10 days were retrieved. Organ dysfunction was evaluated with the Sequential Organ Failure Assessment (SOFA) score. Mortality was assessed after 10 and 28 days, 6 and 18 months. Results: The total fluid balance was positive on days 1,3, and negative on days 4,10. The crystalloid balance was negative from day 2. The mean serum albumin was 38±6 g/l. Colloids constituted 40,60% of the total fluids given per day. Furosemide was administered to 94% of all patients. Severe organ failure defined as SOFA,3 was evident only for respiratory failure, which was observed in 29%. None developed renal failure. After 28 days, mortality was 11% and, after 18 months, it was 14%. Conclusions: A protocol including albumin administration in combination with a neutral to a slightly negative fluid balance was associated with low mortality in patients with severe TBI in spite of a relatively high frequency (29%) of respiratory failure, assessed with the SOFA score. [source] Improvement in site-specific intestinal absorption of furosemide by Eudragit L100-55JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2001T. Terao Furosemide (frusemide) is a weakly acidic diuretic drug. Its absorption is poor and variable, in part due to its restricted sites of absorption, mainly the stomach. The narrow absorption window of this drug can be explained by pH partition theory. The purpose of this study was to investigate the feasibility of widening the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract with officially used additives. Methacrylate copolymer (Eudragit L100,55), hydroxypropylmethylcellulose phthalate (HP-55) and hydroxypropylmethylcellulose acetate succinate (AS-MF) were selected as additives. The pH of suspensions of these additives was about 4, and the pH was adjusted to about 6,7 by the addition of NaOH. The Eudragit L100,55 suspension was found to be the most resistant to NaOH titration. When Eudragit L100,55 was used in an in-situ ileal loop experiment in rats, the pH of the intestinal contents was significantly reduced, from 7.9 ± 0.1 to 5.7 ± 0.1, and the plasma concentration of furosemide 15 min after administration was about 3 times higher than that in controls, 1.81 ± 0.42 ,g mL,1 vs 0.63 ± 0.08 ,g mL,1. However, the plasma concentration of [14C] mannitol was not changed by the co-administration of Eudragit L100,55. Furthermore, the AUC of furosemide was significantly increased by a factor of about 1.6 relative to that in controls by the co-administration of Eudragit L100,55, to 21.4 ± 4.0 ,g h mL,1 from 13.3 ± 3.9 ,g h mL,1, and the gastrointestinal pH in the midgut and ileum was significantly reduced, with most of the furosemide remaining in these segments at 2 h following the oral administration of furosemide with Eudragit L100,55 to rats. These findings clearly demonstrate that the addition of Eudragit L100,55 can increase the absorption of furosemide in distal portions of the gastrointestinal tract. In conclusion, it is feasible to widen the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract by the co-administration of Eudragit L100,55. [source] Estimation of Left Ventricular Filling Pressure by Doppler Echocardiography in Dogs with Pacing-Induced Heart FailureJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2008K.E. Schober Background: Congestive heart failure (CHF) is a common clinical syndrome characterized by elevated filling pressure. Hypothesis: Doppler echocardiographic (DE) variables of left ventricular (LV) filling can predict a decline of LV end-diastolic pressure (LVEDP) induced by acute preload reduction in dogs with compensated CHF. Animals: Five male hound dogs. Methods: Dogs previously instrumented with a transvenous cardiac pacemaker and a LV pressure gauge were paced at 160,180 bpm to induce mild CHF characterized by LVEDP > 20 mmHg. LVEDP and 9 DE variables of LV filling derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler imaging were measured simultaneously at baseline and 30, 60, 120, and 240 minutes after furosemide (4 mg/kg, IV) or placebo (0.9% saline, IV). Repeated measures analysis of variance and correlation analysis were used to determine the association between the decline of LVEDP after furosemide and DE measures of LV filling pressure (LVFP). Results: Furosemide but not placebo decreased LVEDP (P < .001). The ratio of early transmitral flow velocity to LV isovolumic relaxation time (E : IVRT) predicted LVEDP best (R2= .50; P < .001). Correlations were also found between LVEDP and IVRT, E, ratio between E and late diastolic transmitral flow velocity (E : A), and early diastolic velocity of the mitral annulus (Ea). The ratio of E to Ea (E : Ea) was not useful in the prediction of LVEDP in this model. Conclusion and Clinical Importance: E : IVRT can be used to predict LVFP in dogs with mild left-sided CHF induced by rapid pacing. [source] Pre- and postsynaptic modulation of monosynaptic reflex by GABAA receptors on turtle spinal cordTHE JOURNAL OF PHYSIOLOGY, Issue 14 2010Wendy Bautista There is growing evidence that activation of high affinity extrasynaptic GABAA receptors in the brain, cerebellum and spinal cord substantia gelatinosa results in a tonic inhibition controlling postsynaptic excitability. The aim of the present study was to determine if GABAA receptors mediating tonic inhibition participate in the modulation of monosynaptic reflex (MSR) in the vertebrate spinal cord. Using an in vitro turtle lumbar spinal cord preparation, we show that conditioning stimulation of a dorsal root depressed the test monosynaptic reflex (MSR) at long condition,test intervals. This long duration inhibition is similar to the one seen in mammalian spinal cord and it is dependent on GABAA as it was completely blocked by 20 ,m picrotoxin (PTX) or bicuculline (BIC) or 1 ,m gabazine, simultaneously depressing the dorsal root potential (DRP) without MSR facilitation. Interestingly 100 ,m picrotoxin or BIC potentiated the MSR, depressed the DRP, and produced a long lasting motoneurone after-discharge. Furosemide, a selective antagonist of extrasynaptic GABAA receptors, affects receptor subtypes with ,4/6 subunits, and in a similar way to higher concentrations of PTX or BIC, also potentiated the MSR but did not affect the DRP, suggesting the presence of ,4/6 GABAA receptors at motoneurones. Our results suggest that (1) the turtle spinal cord has a GABAA mediated long duration inhibition similar to presynaptic inhibition observed in mammals, (2) GABAA receptors located at the motoneurones and primary afferents might produce tonic inhibition of monosynaptic reflex, and (3) GABAA receptors modulate motoneurone excitability reducing the probability of spurious and inappropriate activation. [source] Benefits and risks of furosemide in acute kidney injuryANAESTHESIA, Issue 3 2010K. M. Ho Summary Furosemide, a potent loop diuretic, is frequently used in different stages of acute kidney injury, but its clinical roles remain uncertain. This review summarises the pharmacology of furosemide, its potential uses and side effects, and the evidence of its efficacy. Furosemide is actively secreted by the proximal tubules into the urine before reaching its site of action at the ascending limb of loop of Henle. It is the urinary concentrations of furosemide that determine its diuretic effect. The severity of acute kidney injury has a significant effect on the diuretic response to furosemide; a good ,urinary response' may be considered as a ,proxy' for having some residual renal function. The current evidence does not suggest that furosemide can reduce mortality in patients with acute kidney injury. In patients with acute lung injury without haemodynamic instability, furosemide may be useful in achieving fluid balance to facilitate mechanical ventilation according to the lung-protective ventilation strategy. [source] Investigation of some factors contributing to negative food effectsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2009Venugopal P. Marasanapalle Abstract A drug is defined as exhibiting negative food effects, if the co-administration of food statistically decreases its area under the curve, AUC, when compared with its administration on a fasted stomach. In this study, the role of biopharmaceutical factors that contribute to negative food effects was studied using furosemide, nadolol, tacrine and atenolol (as model compounds exhibiting negative food effects), and prednisolone, hydrochlorothiazide and ibuprofen (as model compounds that do not show any food effects). The physiological pH of the upper intestinal tract is lower, at pH 5, in the postprandial state when compared with the preprandial state, pH 6.5. Drugs that exhibited negative food effects had low apical to basolateral Caco-2 permeabilities, low pKa/pKb and Log P values of less than 1. The drugs exhibiting negative food effects had low distribution coefficients at the pH conditions of the fed and fasted states. Furosemide, being a hydrophilic, poorly soluble acidic drug showed lower solubility in the fed state when compared with the fasted state. Basic drugs, atenolol, nadolol and tacrine, are ionized to a higher extent in the fed state and exhibit lower permeability and lower absorption when compared with the fasted state. Thus, drugs were found to exhibit negative food effects owing to their decrease in solubility or permeability in the upper intestinal tract of the fed state when compared with the fasted state. Copyright © 2009 John Wiley & Sons, Ltd. [source] Bodyweight change during the first 5 days of chemotherapy as an indicator of cisplatin renal toxicityCANCER SCIENCE, Issue 9 2007Ikuo Sekine To determine whether bodyweight (BW) loss, daily urine volume (UV) or furosemide use are associated with cisplatin nephrotoxicity, performance status, serum chemistries before treatment, average daily UV, maximum BW loss and use of furosemide on days 1,5 of chemotherapy were evaluated retrospectively in chemotherapy-naive patients with thoracic malignancies who had received 80 mg/m2 cisplatin. Associations between these parameters and the worst serum creatinine levels (group 1, grade 0,1; and group 2, grade 2,3) during the first cycle were evaluated. Of the 417 patients (327 men and 90 women; median age, 59 years), 390 were categorized into group 1 and 27 were categorized into group 2. More women and older patients were observed in group 2 than in group 1 (11.1 vs 5.2%, P = 0.044, and 65 vs 59 years, P = 0.041, respectively). The median average daily UV was 3902 mL in group 1 and 3600 mL in group 2 (P = 0.021). A maximum BW loss ,2.1 kg was noted in 4.4% of patients in group 1 and 18.5% of patients in group 2 (P = 0.006). Furosemide was used in 206 (49.4%) patients. The median total dose of furosemide in groups 1 and 2 were 0 mg and 26 mg, respectively (P = 0.024). A multivariate analysis showed that a maximum BW loss ,2.1 kg and the total furosemide dose were significantly associated with group category. In conclusion, BW loss and total furosemide dose were associated with cisplatin nephrotoxicity. (Cancer Sci 2007; 98: 1408,1422) [source] Pharmacokinetic Interaction of the Direct Renin Inhibitor Aliskiren with Furosemide and Extended-Release Isosorbide-5-Mononitrate in Healthy SubjectsCARDIOVASCULAR THERAPEUTICS, Issue 4 2008Sujata Vaidyanathan This study investigated the pharmacokinetics, safety, and tolerability of aliskiren administered alone or in combination with either the loop diuretic furosemide or an oral extended-release formulation of isosorbide-5-mononitrate (ISMN). In separate studies, 22 healthy subjects (ages 18,45 years) received either ISMN 40 mg or furosemide 20 mg once-daily for 3 days followed by a 3-day washout. Subjects then received aliskiren 300 mg once-daily for 7 days followed by combination therapy for 3 days. Pharmacokinetic assessments were taken at regular intervals over 24 h after dosing on the last day of each treatment period. At steady state, aliskiren AUC, was decreased by 7% (geometric mean ratio [90% CI], 0.93 [0.84, 1.04]), and Cmax by 20% (0.80 [0.65, 0.97]) with furosemide coadministration compared with aliskiren administration alone. Aliskiren coadministration reduced furosemide AUC, by 28% (0.72 [0.64, 0.81]) and Cmax by 49% (0.51 [0.39, 0.66]) compared with furosemide alone. Coadministration of aliskiren and ISMN was associated with only minor changes in the pharmacokinetic parameters of aliskiren (AUC, 1.03 [0.90, 1.18]; Cmax 0.94 [0.69, 1.29]) and ISMN (AUC, 0.88 [0.71, 1.10]; Cmax 0.94 [0.79, 1.13]). Headache and dizziness were the most common adverse events in both studies; dizziness and BP values below normal (SBP <90 and/or DBP <50 mmHg) were more frequent with aliskiren and ISMN coadministration than with either agent alone. Coadministration of aliskiren and ISMN had no clinically relevant effect on either aliskiren or ISMN pharmacokinetics. In conclusion, coadministration of aliskiren and furosemide reduced furosemide exposure and had a minor effect on aliskiren pharmacokinetics. The clinical significance of reduced systemic exposure to furosemide during coadministration of aliskiren is uncertain. [source] Furosemide in preterm infants treated with indomethacin for patent ductus arteriosusACTA PAEDIATRICA, Issue 5 2009Peter Andriessen Abstract Objective: To evaluate the effect of furosemide on renal function and water balance in preterm infants treated with indomethacin (3 × 0.2 mg/kg at 12-h intervals) for symptomatic patent ductus arteriosus. Patients and Methods: We performed a retrospective multi-centre double cohort study in preterm infants <32 weeks of gestational age. Thirty-two infants treated with furosemide (1 mg/kg i.v.) before each indomethacin dose (furosemide group) were matched with 32 infants with indomethacin treatment alone (control-group). Renal effects (urine output, weight gain, serum creatinine, sodium concentration) were registered. Results: The study groups were comparable for gestational age, birth weight and day of therapy. Pretreatment differences were observed for urine output, weight and serum sodium. However, no differences were noticed in day-to-day urine output change or weight gain between the groups. A significant increase in serum creatinine concentration (50% vs. control, 18%; p < 0.05) and a concomitant significant decrease in serum sodium (,9 vs. control, ,3 mmoL/L; p < 0.05) in the furosemide group was observed 72,96 h after starting therapy. Conclusion: Furosemide before each indomethacin dose resulted in a significant increase in serum creatinine and hyponatremia, without increasing urine output. [source] Localization and functional characterization of the human NKCC2 isoformsACTA PHYSIOLOGICA, Issue 3 2010I. Carota Abstract Aim:, Salt reabsorption across the apical membrane of cells in the thick ascending limb (TAL) of Henle is primarily mediated by the bumetanide-sensitive Na+/K+/2Cl, cotransporter NKCC2. Three full-length splice variants of NKCC2 (NKCC2B, NKCC2A and NKCC2F) have been described. The NKCC2 isoforms have specific localizations and transport characteristics, as assessed for rabbit, rat and mouse. In the present study, we aimed to address the localization and transport characteristics of the human NKCC2 isoforms. Methods:, RT-PCR, in situ hybridization and uptake studies in Xenopus oocytes were performed to characterize human NKCC2 isoforms. Results:, All three classical NKCC2 isoforms were detected in the human kidney; in addition, we found splice variants with tandem duplicates of the variable exon 4. Contrary to rodents, in which NKCC2F is the most abundant NKCC2 isoform, NKCC2A was the dominant isoform in humans; similarly, isoform-specific in situ hybridization showed high expression levels of human NKCC2A along the TAL. Compared to NKCC2B and NKCC2F, human NKCC2A had the lowest Cl, affinity as determined by 86Rb+ uptake studies in oocytes. All NKCC2 isoforms were more efficiently inhibited by bumetanide than by furosemide. A sequence analysis of the amino acids encoded by exon 4 variants revealed high similarities between human and rodent NKCC2 isoforms, suggesting that differences in ion transport characteristics between species may be related to sequence variations outside the highly conserved sequence encoded by exon 4. Conclusion:, The human NKCC2 is an example of how differential splicing forms the basis for a diversification of transporter protein function. [source] Cross-reactivity among p -amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testingCONTACT DERMATITIS, Issue 2 2004P. Tornero We studied 28 patients with fixed drug eruption (FDE) caused by sulfonamide antibiotics to investigate cross-reactivity between sulfonamide derivatives and p -amino compounds and to explore the usefulness of patch testing, as an alternative to controlled oral challenge testing (COCT), in diagnosis within this clinical area. COCT with sulfamethoxazole (SMX), sulfadiazine (SDZ), sulfamethizole (SMZ), furosemide (FU), procaine (PRO) and glipizide (GPZ) was performed. Patch testing (PT) with SMX and SDZ was carried out. In all patients, the diagnosis of FDE was confirmed by positive COCT and allergy to trimethoprim ruled out by COCT. 42.8 and 31.8% of the SMX-induced FDE patients reacted to SMZ and SDZ, respectively. All patients (n = 28) tolerated FU, PRO and GPZ. COCT performed with the 3 sulfonamide antibiotics in 12 patients was positive in 2 subjects with the 3 drugs, in 2 patients only with SMX and SMZ and in the remaining 8, SMX was the only causative drug. PT was positive in 5 of 25 patients positive on COCT. The probability of obtaining a positive PT was higher among patients who had a residual lesion than that among those who lacked this. Cross-reactivity between different sulfonamide antibiotics is thus variable, being most likely between SMX and SMZ. We have found no cross-reactivity between sulfonamide antibiotics and other sulfonamide derivatives or p -amino drugs in FDE. PT is a useful tool in the diagnosis of FDE, especially if there are residual lesions, because it avoided the need for COCT in 20% of patients. [source] Furosemide Terminates Limbic Status Epilepticus in Freely Moving RatsEPILEPSIA, Issue 9 2003Martin Holtkamp Summary:,Purpose: To evaluate the anticonvulsant properties of furosemide and to determine sedative side effects compared with pentobarbital and diuretic side effects compared with saline-treated controls in an experimental model of limbic status epilepticus. Methods: Self-sustaining status epilepticus was induced in rats by continuous electrical stimulation of the perforant path. Five minutes after the end of the stimulation, animals were given 100 mg/kg furosemide, 30 mg/kg pentobarbital, or an equal amount of saline, intraperitoneally. After administration of the substance, animals were monitored clinically and electrographically for 3 h regarding status epilepticus, level of sedation, and diuresis. Results: In seven of 10 animals, furosemide terminated status epilepticus after 68 ± 26 min, whereas pentobarbital was successful in all animals after 5 ± 0.8 min. In contrast to pentobarbital, sedation did not occur with furosemide. Weight loss after furosemide was 10.2 ± 1.7% compared with 6.5 ± 1.1% in animals given saline (p < 0.001). Conclusions: The results suggest that furosemide may serve as an alternative or additional agent for refractory complex partial status epilepticus in patients in whom common anesthetics are not justifiable. [source] Glutamate-induced elevations in intracellular chloride concentration in hippocampal cell cultures derived from EYFP-expressing miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2004Jennifer E. Slemmer Abstract The homeostasis of intracellular Cl, concentration ([Cl,]i) is critical for neuronal function, including ,-aminobutyric acid (GABA)ergic synaptic transmission. Here, we investigated activity-dependent changes in [Cl,]i using a transgenetically expressed Cl, -sensitive enhanced yellow-fluorescent protein (EYFP) in cultures of mouse hippocampal neurons. Application of glutamate (100 µm for 3 min) in a bath perfusion to cell cultures of various days in vitro (DIV) revealed a decrease in EYFP fluorescence. The EYFP signal increased in amplitude with increasing DIV, reaching a maximal response after 7 DIV. Glutamate application resulted in a slight neuronal acidification. Although EYFP fluorescence is sensitive to pH, EYFP signals were virtually abolished in Cl, -free solution, demonstrating that the EYFP signal represented an increase in [Cl,]i. Similar to glutamate, a rise in [Cl,]i was also induced by specific ionotropic glutamate receptor agonists and by increasing extracellular [K+], indicating that an increase in driving force for Cl, suffices to increase [Cl,]i. To elucidate the membrane mechanisms mediating the Cl, influx, a series of blockers of ion channels and transporters were tested. The glutamate-induced increase in [Cl,]i was resistant to furosemide, bumetanide and 4,4,-diisothiocyanato-stilbene-2,2,-disulphonic acid (DIDS), was reduced by bicuculline to about 80% of control responses, and was antagonized by niflumic acid (NFA) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). We conclude that membrane depolarization increases [Cl,]i via several pathways involving NFA- and NPPB-sensitive anion channels and GABAA receptors, but not through furosemide-, bumetanide- or DIDS-sensitive Cl, transporters. The present study highlights the vulnerability of [Cl,]i homeostasis after membrane depolarization in neurons. [source] Pulmonary involvement in Sweet's syndrome: a case report and review of the literatureINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2006Leonardo Astudillo MD Pulmonary involvement in Sweet's syndrome (SS) is rare. We report a case of SS with severe respiratory involvement responding to corticosteroid therapy. A 82-year-old man presented fever of 39 °C associated with cough and dyspnea, and crackles in the left lung. The infection work-up was negative. Chest X-ray showed cardiomegaly and left lower lobe pulmonary infiltrates. Pulmonary signs did not improve on treatment with antibiotics, and after 1 week maculopapular lesions appeared, localized on the knees, the periombilical area and the back. The antibiotics were changed without improvement. A skin biopsy revealed infiltration by neutrophilic granulocytes and marked edema in the dermis, consistent with SS. The patient's condition progressively worsened, requiring high oxygenotherapy, and he was transferred to an intensive care unit. Chest X-ray revealed an important alveolar and interstitial syndrome. Bronchoalveolar lavage found 170 leukocytes with 30% neutrophils (N < 5%), 7% lymphocytes and 63% macrophages. A search for bacteria, viruses or parasites in bronchoalveolar lavage was negative. The patient was treated with antibiotics, a high dose of furosemide and steroids for 4 days. Because the patient improved dramatically within 5 days, with a negative infection work-up and a dramatic decrease of C-reactive protein, the antibiotics were stopped. Steroids were secondarily tapered very slowly. A chest computed tomography (CT) scan showed a substantial improvement of pulmonary lesions. We also review the 22 cases of pulmonary involvement of SS reported in the literature. [source] The Appropriateness of Drug Use in an Older Nondemented and Demented PopulationJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2001Maria Stella T. Giron MD OBJECTIVE: To assess the extent of inappropriateness of drug use in an older nondemented and demented population. DESIGN: Descriptive analysis based on data from a sample of older subjects age 81 years and older. Data were collected from the second follow-up conducted in 1994,1996. SETTING: A population-based study of the Kungsholmen project in Stockholm, Sweden. PARTICIPANTS: Drug information was obtained from 681 subjects with a mean age of 86.9 years. The subjects were predominantly women (78%). Thirteen percent resided in institutions and 27.6% were diagnosed with dementia. MEASUREMENTS: Dementia diagnosis based on DSM III-R. Criteria for inappropriateness of drug use: use of drugs with potent anticholinergic properties, drug duplication, potential drug-drug and drug-disease interactions, and inappropriate drug dosage. RESULTS: The mean number of drugs used was 4.6: 4.5 drugs for nondemented and 4.8 for demented subjects. Nondemented subjects more commonly used cardiovascular-system drugs and demented subjects used nervous-system drugs. Demented subjects were more commonly exposed to drug duplication and to drugs with potent anticholinergic properties, both involving the use of psychotropic drugs. Nondemented subjects were more commonly exposed to potential drug-disease interactions, mostly with the use of cardiovascular drugs. The most common drug combination leading to a potential interaction was the use of digoxin with furosemide, occurring more frequently among nondemented subjects. The most common drug-disease interaction was the use of beta-blockers and calcium antagonists in subjects with congestive heart failure. The doses of drugs taken by both nondemented and demented subjects were mostly lower than the defined daily dose. CONCLUSION: There was substantial exposure to presumptive inappropriateness of drug use in this very old nondemented and demented population. The exposure of demented subjects to psychotropic drugs and nondemented subjects to cardiovascular drugs reflect the high frequency of prescribing these drugs in this population. [source] High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veteransJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2005I. O. Poon PharmD BCPS CGP Summary Background:, Orthostatic hypotension (OH) is defined as a reduction of systolic blood pressure of at least 20 mmHg, or diastolic blood pressure of at least 10 mmHg from a sitting to a standing position. It is a common physical finding among older adults and associated with significant morbidity and mortality. Use of medications that have the potential to induce OH, particularly concomitant use of several of such medications, is a major factor for the development of OH. Objectives:, To describe the prevalence of symptomatic and asymptomatic OH in veterans aged 75 years and older attending a geriatric clinic, and to assess the association between OH and the number of potentially causative medications used. Methods:, Charts of all patients who attended a VA geriatric clinic (Michael E. DeBakey VA Medical Center) during the period of 1 June 2002 to 1 June 2003 were reviewed retrospectively for (i) the use of potentially causative medications, i.e. medications that were reported to cause OH in at least 1% of the general population and that were available in the VA formulary, (ii) the presence or absence of OH, and (iii) the presence or absence of symptomatic OH. Patients with primary autonomic dysfunction, Parkinson's disease, and patients who were unable to stand, or who had no assessment for both sitting and standing blood pressure for other reasons were excluded. Results:, A total of 505 individual patients attended the clinic during the study period, and 342 patients fit the inclusion criteria. About 189 of these patients (55%) had OH. Among patients with OH, 61 patients (33%) were symptomatic, including 52 patients who had falls. The prevalence of OH in patients receiving zero, one, two, and three or more potentially causative medications was 35, 58, 60 and 65% respectively. Receiving hydrochlorothiazide was associated with the highest prevalence of OH (65%), followed by receiving lisinopril (60%), trazodone (58%), furosemide (56%) and terazosin (54%). Conclusion:, The prevalence of OH is very high in older veterans and significantly related to the number of concurrent causative medications used. Providers should be educated to reduce the amount of potentially causative medications in the elderly and better assess patients in which use of such medications is necessary to avoid symptomatic OH. [source] Determinants of Serum Creatinine Trajectory in Acute Contrast NephropathyJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2002NOEL V. GUTTTEREZ M.D. The aim of this study was to describe the trajectory of creatinine (Cr) rise and its determinants after exposure to radiocontrast media. Included were 98 subjects who underwent cardiac catheterization and were randomized to forced diuresis with IV crystalloid, furosemide, mannitol (if pulmonary capillary wedge pressure was<20 mmHg), and low dose dopamine versus intravenous crystalloid and matching placebos. Baseline and postcatheterization serum Cr levels were analyzed in a longitudinal fashion, allowing for differences in the time between blood draws, to determine the different critical trajectories of serum Cr. The mean age, baseline serum Cr, and Cr clearance (CrCl) were 69.3 ± 10.8 years, 2.5 ± 0.9 mg/dL, and 31.4 ± 12.1 mL/min, respectively. The clinically driven postprocedural observation time was 5.5 ± 5.1 days (range 19 hours and one Cr value to 25.7 days and 18 values). The mean maximum Cr was 3.3 ± 1.4, range 1.7,8.7 mg/dL). Longitudinal models support baseline Cr clearance predictions for the change in Cr at 24 hours, time as the determinant of Cr trajectory, and requisite monitoring. For any given individual, a rise in Cr of , 0.5 mg/dL in the first 24 hours after contrast exposure predicted a favorable outcome. Baseline renal function is the major determinant of the rate of rise, height, and duration of Cr trajectory after contrast exposure. Length of observation and frequency of laboratory measures can be anticipated from these models. [source] Evaluation of intrarenal oxygenation in mice by BOLD MRI on a 3.0T human whole-body scanner,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2007Lu-Ping Li PhD Abstract Purpose To extend observations on intra-renal oxygenation with blood oxygen level-dependent (BOLD) MRI in human and rats to mouse kidneys imaged with a human whole-body scanner. Materials and Methods Renal BOLD MRI studies were performed on a 3.0T scanner using a multiple gradient-echo (mGRE) sequence with a custom-designed 2.0-cm surface coil to acquire six T2*-weighted images in mice (N = 8) at an in-plane resolution of 156 × 156 ,m2. BOLD MRI data were obtained before and after administration of furosemide (10 mg/kg intravenously [i.v.]). Results The mean weight of eight mice was 24.6 ± 1.0 g. The baseline renal R2* (mean ± standard error [SE]) was 28.6 ± 2.1 seconds,1 in the renal cortex (CO), 35.4 ± 2.2 in the outer medulla (OM), and 21.2 ± 2.1 seconds,1 in the inner medulla (IM). The BOLD response to furosemide (,R2*) was 4.1 ± 1.4 in the CO, 10.1 ± 2.1 seconds,1 in the OM, and 3.4 ± 0.8 seconds,1 in the IM in mice. Conclusion Intrarenal BOLD MR images with sufficiently high resolution can be obtained on a human whole-body scanner when combined with a small receiver coil to allow studies in mice. Both baseline R2* and ,R2* values following administration of furosemide were consistent with previous experience in humans and rats. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc. [source] Encephalopathy after furosemide use in nephrotic syndromeJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 3 2007Ajay P Sharma Abstract: An 18-year-old girl with nephrotic syndrome presented with a life-threatening respiratory failure and a severe encephalopathy, shortly after being started on furosemide. The evaluation confirmed furosemide as the sole culprit for the clinical manifestations. This case highlights an unpredictable dose,response relationship of furosemide. The pathophysiological basis, differential diagnosis and clinical implications of the observed findings are discussed. [source] Taurocholic acid-induced secretion in normal and cystic fibrosis mouse ileumJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2001J. Hardcastle Bile acids cause secretion throughout the intestinal tract and this process contributes to maintaining the fluidity of intestinal contents. In cystic fibrosis (CF) defective intestinal secretion can lead to excessive dehydration of the luminal contents and the development of clinical symptoms. This study was designed to investigate bile acid-induced secretion in mouse ileum and to determine whether this process was defective in CF. Taurocholic acid-induced secretion was monitored as a rise in short-circuit current (SCC) in ileal sheets from normal (Swiss MF1) and transgenic CF mice. Taurocholic acid increased the SCC in both intact and stripped ileal sheets from Swiss MF1 mice. This effect was due to a stimulation of electrogenic Cl, secretion as it was inhibited by Cl, -free conditions, serosal furosemide (frusemide), mucosal diphenylamine-2-carboxylic acid (DPC) and increased serosal K+ concentration, without being affected by reduced mucosal Na+ concentration. Taurocholic acid-induced secretion was inhibited by tetrodotoxin, indicating the involvement of a neural pathway, but this did not include capsaicin-sensitive afferent neurons or muscarinic cholinoreceptors. Mucosal mast cells also contributed to the response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 animals, but ilea from CF mice exhibited a lower basal SCC with significantly reduced secretory responses to acetylcholine and taurocholic acid. We concluded that taurocholic acid induces ileal secretion by a mechanism that entails activation of enteric nerves and degranulation of mucosal mast cells. Impaired bile acid-induced secretion in CF may contribute to luminal dehydration. [source] Improvement in site-specific intestinal absorption of furosemide by Eudragit L100-55JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2001T. Terao Furosemide (frusemide) is a weakly acidic diuretic drug. Its absorption is poor and variable, in part due to its restricted sites of absorption, mainly the stomach. The narrow absorption window of this drug can be explained by pH partition theory. The purpose of this study was to investigate the feasibility of widening the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract with officially used additives. Methacrylate copolymer (Eudragit L100,55), hydroxypropylmethylcellulose phthalate (HP-55) and hydroxypropylmethylcellulose acetate succinate (AS-MF) were selected as additives. The pH of suspensions of these additives was about 4, and the pH was adjusted to about 6,7 by the addition of NaOH. The Eudragit L100,55 suspension was found to be the most resistant to NaOH titration. When Eudragit L100,55 was used in an in-situ ileal loop experiment in rats, the pH of the intestinal contents was significantly reduced, from 7.9 ± 0.1 to 5.7 ± 0.1, and the plasma concentration of furosemide 15 min after administration was about 3 times higher than that in controls, 1.81 ± 0.42 ,g mL,1 vs 0.63 ± 0.08 ,g mL,1. However, the plasma concentration of [14C] mannitol was not changed by the co-administration of Eudragit L100,55. Furthermore, the AUC of furosemide was significantly increased by a factor of about 1.6 relative to that in controls by the co-administration of Eudragit L100,55, to 21.4 ± 4.0 ,g h mL,1 from 13.3 ± 3.9 ,g h mL,1, and the gastrointestinal pH in the midgut and ileum was significantly reduced, with most of the furosemide remaining in these segments at 2 h following the oral administration of furosemide with Eudragit L100,55 to rats. These findings clearly demonstrate that the addition of Eudragit L100,55 can increase the absorption of furosemide in distal portions of the gastrointestinal tract. In conclusion, it is feasible to widen the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract by the co-administration of Eudragit L100,55. [source] The effects of midodrine on the natriuretic response to furosemide in cirrhotics with ascitesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010V. L. Misra Aliment Pharmacol Ther 2010; 32: 1044,1050 Summary Background, Resistance to loop diuretics is common in patients with ascites. Diminished glomerular filtration rate (GFR) is thought to mediate resistance to loop diuretics. Midodrine, a commonly used alpha-1 agonist, has been shown to improve GFR in non-azotemic patients with cirrhosis. Aim, To conduct a randomized, double-blind, placebo-controlled, cross-over study to test the hypothesis that midodrine significantly increases natriuretic response of IV furosemide in non-azotemic cirrhotics with ascites. Methods, All subjects participated in both phases, which were (i) furosemide IV infusion + oral midodrine 15 mg administered 30 min before furosemide (ii) furosemide IV infusion + oral placebo administered 30 min before furosemide. Primary outcomes were 6-h urine sodium excretion and 6-h total urine volume. Results, A total of 15 patients (men: 8; age: 52.7 ± 7.6 years; serum creatinine: 1.06 ± 0.2 mg/dL) were studied. Total 6-h urine sodium excretion was 109 ± 42 mmol in the furosemide + midodrine treatment phase and was not significantly different from that in the furosemide + placebo treatment phase (126 ± 69 mmol, P = 0.6). Similarly, mean 6-h total urine volume was not significantly different between two groups (1770 ± 262 mL vs. 1962 ± 170 mL, P = 0.25). Conclusions, Oral midodrine does not increase the natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. Orally administered midodrine does not increase natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. [source] Clinical trial: short-term effects of combination of satavaptan, a selective vasopressin V2 receptor antagonist, and diuretics on ascites in patients with cirrhosis without hyponatraemia , a randomized, double-blind, placebo-controlled studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010P. GINÈS Aliment Pharmacol Ther,31, 834,845 Summary Background, There is little information on the effects of vaptans in patients with cirrhosis. Aim, To investigate the short-term effects of satavaptan, a selective vasopressin V2 receptor antagonist on ascites in cirrhosis without hyponatraemia. Methods, A total of 148 patients with cirrhosis, ascites and serum sodium >130 mmol/L were included in a multicentre, double-blind, randomized, controlled study of 14 days comparing three fixed doses of satavaptan (5 mg, 12.5 mg or 25 mg once daily) vs. placebo. Average MELD scores were: 13.4, 12.3, 13.8 and 13.1 respectively. All patients received spironolactone 100 mg/day plus furosemide 20,25 mg/day. Results, Satavaptan treatment was associated with a decrease in ascites (mean change in body weight was ,0.36 kg (±3.03) for placebo vs. ,2.46 kg (±3.11), ,2.08 kg (±4.17) and ,2.28 kg (±3.24) for the 5 mg, 12.5 mg and 25 mg doses respectively; P = 0.036, P = 0.041 and P = 0.036 for satavaptan 5, 12.5 and 25 mg/day vs. placebo respectively). Thirst and slight increases in serum sodium were more common in patients treated with satavaptan compared with placebo, while other adverse events were similar. Conclusions, The administration satavaptan for a 14-day period is associated with reduction in ascites in patients with moderately severe cirrhosis without hyponatraemia under diuretic treatment. [source] Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascitesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009G. LICATA Summary Background, In patients with cirrhosis, ascites is defined as refractory when it cannot be mobilized or recurs early in standard diuretic therapy. Aim, To compare the safety and efficacy of intravenous high-dose furosemide + hypertonic saline solutions (HSS) with repeated paracentesis in patients with cirrhosis and refractory ascites. Patients and methods, Eighty-four subjects (59/25 M/F) with cirrhosis, mostly of viral aetiology, admitted for refractory ascites, were randomly assigned to receive furosemide (250,1000 mg/bid i.v.) plus HSS (150 mL H2O with NaCl 1.4,4.6% or 239,187 mEq/L) (60 patients, Group A) or to repeated paracentesis and a standard diuretic schedule (24 patients, Group B). Results, During hospitalization, Group A patients had more diuresis (1605 ± 131 mL vs. 532 ± 124 mL than Group B patients; P < 0.001) and a greater loss of weight at discharge (,8.8 ± 4.8 kg vs. ,4.5 ± 3.8 kg, P < 0.00). Control of ascites, pleural effusions and/or leg oedema was deemed significantly better in Group A. Conclusions, This randomized pilot study suggests that HHS plus high-dose furosemide is a safe and effective alternative to repeated paracentesis when treating hospitalized patients with cirrhosis and refractory ascites. Larger studies will be needed to evaluate long-term outcomes such as readmission and mortality. [source] The neurophysiology of dyspneaJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 6 2008Matthew Scott Mellema DVM Abstract Objective , To review the human and veterinary literature regarding the neurophysiology of dyspnea and to provide evidence for the beneficial effects of several novel therapies aimed at the alleviation of dyspneic sensations. Data Sources , Data sources included scientific reviews, case reports, original research publications, and recent research conference proceedings. Human Data Synthesis , The use of blood oxygenation level-dependent functional magnetic resonance imaging technology has revealed that the brain regions activated by air hunger in humans are also those activated by fear, pain, and thirst perception. In human subjects, it has been found that agents known to enhance the firing of pulmonary slowly adapting receptors (SARs) can alleviate the sensation of dyspnea without altering central respiratory drive. Several small studies have also shown that nebulized opioids can reduce the sensation of dyspnea apparently via activation of peripheral opioid receptors in the lung. Veterinary Data Synthesis , There are several animal models relevant to both small and large animal clinical patient populations. Treatment of rats with a nebulized SAR sensitizing agent (furosemide) enhances SAR firing in response to lung inflation. Behavioral escape responses to airway occlusion are reduced in lightly anesthetized cats when treated with nebulized furosemide. Opioid agonists have been shown to inhibit the release of acetylcholine and other mediators from the airways of dogs and guinea pigs. Studies using a goat model with bilateral destruction of the pre-Bötzinger Complex do not support current paradigms of air hunger origination. Conclusions , Veterinary patients may benefit from an approach to dyspnea that incorporates an understanding of the origins of the unpleasant sensations associated with the condition. Several novel therapies have shown promise in alleviating dyspneic sensations without altering respiratory drive. Further study is needed to determine the safety and efficacy of these therapies in veterinary patients. [source] Efficacy of Spironolactone on Survival in Dogs with Naturally Occurring Mitral Regurgitation Caused by Myxomatous Mitral Valve DiseaseJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2010F. Bernay Background: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. Hypothesis: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). Animals: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). Methods: Double-blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac-related death, euthanasia, or severe worsening of MR. Results: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22,0.90; log rank test, P= .017). Risk of cardiac- related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13,0.76; P= .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). Conclusion and Clinical Importance: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac-related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD. [source] | ||||||||||||||||||||||||||||||||||