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The baseline mean T (1/2) values for controls, smokers, and asthmatics were 50.95 +/- 16.58, 20.81 +/- 5.47, 24.06 +/- 6.19 min, respectively. Post-lasix T (1/2) values were 50.83 +/- 15.84, 20.70 +/- 5.65, 41.27 +/- 15.07 min, respectively. There was a significant difference (P < 0.001) in baseline and post-lasix clearance values in asthmatics only.
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Infantile hypercalcemia becomes manifest in 15% of patients with Williams syndrome (WS) and generally is not clinically severe. However, some patients with WS can have severe hypercalcemia and do not respond well to traditional therapies. Recently, pamidronate has been used in the treatment of childhood hypercalcemia associated with many disorders, but there is little experience with the treatment of hypercalcemia with bisphosphonates in patients with WS. We present a 17-month-old female patient, who had been diagnosed as WS by genetic analysis, admitted to our clinic for the investigation of severe hypercalcemia (4.02 mmol/L). Because the patient did not respond very well to fluid administration, furosemide infusion, and dietary calcium restriction, pamidronate infusion was performed and calcium levels returned to normal within 2 days. This case report is presented to point out that pamidronate therapy seems to be a safe and efficient way of treating life-threatening hypercalcemia in WS.
We developed a new technique for measuring horizontal eye movements, corresponding to lateral head drop in total darkness, approximately 1g environment. Normal subjects (n=16, mean age: 27.3 years old) and patients (seven for pre-operative state, four for furosemide test at pre-operative state; two for post-operative state) were employed in the test. The principle of the test is to drop the head in a lateral position separately from the body with a rapid release exposing the head. Bitemporal EOG, accelometric and trigger signals for the releaser were recorded for processing at 1 KHz sampling time.
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Dispersed acini were used to investigate the effects of prostaglandins (PG) on transmembrane Cl and K transport with the aid of radioactive tracers. Neither PGE1, PG2, PGF2 alpha, arachidonic acid or phosphatidic acid (all in 1 microM final concentrations) modified the time-dependent uptake of 36Cl. Steady-state isotope content reached 6-7 nmol/mg protein with or without these substances. PG did not alter the inhibitory effect of 1 mM furosemide on 36Cl uptake, and failed to induce a net efflux of 36Cl from tracer-preloaded cells or to modify the efflux of tracer induced by 1 microM acetylcholine. PG had no significant effect on K uptake, as measured with 86Rb, and did not modify the effect of 1 mM ouabain, which inhibited K uptake or accumulation by 60 per cent. PG did not induce K (86Rb) efflux from acini preloaded with tracer, and did not prevent or enhance the K efflux induced by acetylcholine. Thus PG do not influence the major ion-transport systems that may be involved in saliva secretion by acinar cells. Any inhibitory effects of PGE1 on salivary-fluid secretion in vivo are therefore likely to be the result of extra-acinar PG actions, and not of a direct effect on ion-transport mechanisms.
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Symptoms improved after treatment with furosemide, warfarin, ramipril, and continuous positive airway pressure for obstructive sleep apnea.
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Clinical course and toxicological findings in 18 patients intoxicated with ingested chromium salts are presented. Seventeen of these patients ingested potassium and sodium dichromate while the remaining patient--chromic acid. The first stage of 6-valent chromium is characterized by its irritating effect on the gastro-intestinal mucous membrane manifested by diarrhoea, vomiting often with blood, leading to severe water-electrolyte disorders, acidosis and shock. Lesions to kidneys, liver and myocardium may develop in the next stage. Probably endothelium is also in injured with resulting increase in its permeability. Acute renal failure is not seen even with high levels of chromium in the urine provided, that the recovery from the shock is prompt, and adequate diuresis induced with mannitol and/or furosemide is maintained. All patients with blood chromium concentration exceeding 1 mg/100 g died. This level is of prognostic and diagnostic value indicating an ingestion and absorption of the high doses of this metal.
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A rapid, simple and highly sensitive first derivative synchronous spectrofluorimetric method was developed for the simultaneous analysis of a binary mixture of labetalol HCl (LBT) and furosemide (FUR) without prior separation. The method was based upon measuring the first derivative of synchronous fluorescence spectra of the two drugs at Deltalambda = 130 nm in aqueous ethanol (55% V/V). The different experimental parameters affecting the synchronous fluorescence of the studied drugs were carefully studied and optimized. The first derivative amplitude-concentration plots were rectilinear over the range of 0.10 to 1.00 microg/mL and 0.05-0.50 microg/mL with lower detection limits of 0.0149 and 7 x 10(-3) microg/mL and quantification limits of 0.045 and 0.021 microg/mL for LBT and FUR, respectively. The proposed method was successfully applied for the determination of the studied drugs in synthetic mixtures. The results obtained were in good agreement with those obtained by the reference methods.
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Routine diuretics promote an earlier diuresis but no clinical benefits are apparent in low risk patients with normal renal function. Clinicians should reconsider routine diuretic prescription in this setting.
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Pharmacologic intervention aimed at altering the natural history of acute renal failure is a routine practice without scientific support of efficacy. Oliguria has become a separate disease entity with an apparent disregard for the underlying condition that caused it. Volume expansion is clearly beneficial in preventing many volume depleted patients from progressing to acute renal failure. While mannitol and furosemide have been used to "convert" oliguric acute renal failure to the more easy to manage non-oliguric acute renal failure, published reports suggest that responders were not as ill as non-responders. The use of dopamine to increase urine flow in patients with established acute renal failure is the current fashion, but there is little evidence that this drug raises the glomerular filtration rate or shortens the course of acute renal failure. These pharmacologic therapies increase the complexity and cost of care with little tangible evidence of benefit to the patient or the physician caring for the patient.
Microvillous membrane vesicles from the term human placental syncytiotrophoblast were used to characterize further the properties of a transport mechanism for bile acids. Taurocholate (TC) uptake into an osmotically reactive intravesicular space was temperature dependent and independent of sodium. TC uptake (2 microM) was markedly inhibited by 250 microM taurine and glycine-conjugated cholate and chenodeoxycholate and unconjugated cholate but not by chenodeoxycholate, deoxycholate, etianic acid, bromosulfophthalein, pyruvate, lactate, alanine, or taurine. The initial rate of TC uptake was inhibited significantly by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) but was not inhibited significantly by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, amiloride, or furosemide. Preincubation of vesicles with DIDS in the presence of TC partially blocked the action of the inhibitor. Efflux of 5 microM TC from membrane vesicles was stimulated by the presence of 50 microM TC in the incubation media. Basal as well as transstimulated TC efflux was inhibited by DIDS. The initial rate of TC influx followed saturation kinetics with an apparent Michaelis constant of 112 +/- 23 microM and maximal velocity of 2.01 +/- 0.19 nmol.mg protein-1.min-1. When the transmembrane electrical potential difference across the brush-border membrane vesicles was altered by external anion replacement or by valinomycin-induced K+ diffusion potentials, TC uptake was not significantly affected. DIDS-sensitive TC uptake was stimulated two-to threefold by an outwardly directed hydroxyl gradient (pH 7.7in/5.5out) compared with TC influx under pH-equilibrated conditions (pH 7.7in/7.7out). These studies are consistent with an electroneutral anion-exchange mechanism that mediates transfer of conjugated bile acids across the microvillous membrane of the syncytiotrophoblast.
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Primary pulmonary hypertension with right-sided congestive heart failure and vomiting can lead to the development of uveal effusions.
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Laparoscopic pyeloplasty can be used with acceptable success rate in secondary UPJ obstruction in patients with previous open pyeloplasty.
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Tricyclic antidepressant overdose is known to cause cardiopulmonary complications, including pulmonary edema. To the best of our knowledge, this is the first reported case of pulmonary edema as a result of dibenzepin overdose. The most probable mechanism for this complication is depression of the left ventricular function.
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1. Mesenteric perfusion pressure was measured in the in situ mesentery perfused at a constant rate with blood drawn from the carotid artery of the same anaesthetized rat. Increases in perfusion pressure were produced by mesenteric periarterial electrical stimulation. These responses were measured before and 30 min after the administration of frusemide (5 mg/kg i.v.) to the rat. Loss of volume due to the frusemide-induced diuresis was prevented by a urinary bladder-venous extracorporeal circuit. 2. Responses to stimulation were reduced after frusemide and were not increased by the subsequent administration of indomethacin (2 mg/kg i.v.). This indomethacin treatment rapidly and completely prevented the fall in blood pressure produced by i.v. arachidonic acid. 3. In rats where the renal papilla had been ablated by treatment with bromoethylamine (200 mg/kg i.p.) 5 weeks previously, frusemide administration did not reduce sympathetic responses in the in situ blood-perfused mesentery. 4. A segment of rat tail artery, cannulated at both ends was mounted in an organ bath and perfused with blood withdrawn from, and returned to, an anaesthetized rat. Increases in perfusion pressure produced by periarterial electrical stimulation of this ex vivo blood perfused tail artery segment were reduced by frusemide administration to the anaesthetized rat. 5. When the endothelium was removed from the tail artery segment, frusemide administration did not lead to any reduction of vasoconstrictor responses. 6. Frusemide may lead to the release of a non-prostanoid hormone from the renal medulla which results in inhibition of peripheral sympathetic vasoconstrictor responses. The release of the hormone may involve intra-renal prostaglandins. The final antivasoconstrictor effect requires an intact vascular endothelium.
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High incidence of serious and multiple ADRs noticed. A wide clinical spectrum of ADRs and infrequently reported ADRs to newer drugs were also observed.
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This article reports the clinical investigation of a probe drug cocktail containing substrates of key drug transporters. Single oral doses of 0.25 mg digoxin (P-gp), 5 mg furosemide (OAT1 and OAT3), 500 mg metformin (OCT2, MATE1, and MATE2-K), and 10 mg rosuvastatin (OATP1B1, OATP1B3, and BCRP) were administered separately or as a cocktail in a randomized six-period crossover trial in 24 healthy male volunteers. As a cocktail, relative bioavailabilities of digoxin and metformin and furosemide AUC0-tz were similar to separate dosing. However, when administered as a cocktail the Cmax of furosemide was 19.1% lower and the Cmax and AUC0-tz of rosuvastatin were 38.6% and 43.4% higher, respectively. In addition, the effects of increased doses of metformin or furosemide on the cocktail were investigated in 11 and 12 subjects, respectively. The cocktail explored in this trial has the potential to be used for the in vivo screening of transporter-mediated drug-drug interactions. © 2016 American Society for Clinical Pharmacology and Therapeutics.
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The in vitro skin permeation of furosemide, a commonly used loop diuretic, through human epidermis, as a preliminary step towards the development of a transdermal therapeutic system, was examined. A screening study was carried out, in order to estimate the effects of the type, the concentration of enhancer and the concentration of gelling agent on the cumulative amount of furosemide permeated through human epidermis, using a 3(3) factorial design. The type and the concentration of enhancer were further evaluated as they were found to affect significantly furosemide permeation. In order to further increase the amount of the drug permeated, the combination of two enhancers, Azone and oleyl alcohol, at three concentration levels was employed, using an optimization technique. The results indicated that higher amounts of furosemide permeated were observed when Azone was used at 5.0-6.5% (v/v) and oleyl alcohol at 7.5-9% (v/v), in the gels used. These formulations seem to be suitable for possible transdermal delivery of furosemide for pediatric use.
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The management of chronic cardiac failure, a salt-sensitive state, frequently includes administration of a loop diuretic to enhance urinary Na excretion. We hypothesized that a period of timed semirecumbency (vis-à-vis upright posture) would enhance the natriuresis that accompanies oral furosemide dosing in patients with compensated cardiac failure.
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Preoperative and operative parameters were similar in both groups. Four patients from group P and none from group D reached an end-point of the study (oliguria, renal dysfunction) and received dopamine. Two patients from group P and none from group D needed an additional inotropic support. Mean arterial pressure values were similar during the first 24 hours after operation, but left atrial pressure values tended to be higher in group P (10 +/- 4 vs 7 +/- 3 mmH2O, p = 0.18). The mean pH was higher in group D at 8 hours after operation (7.38 +/- 0.2 vs 7.36 +/- 0.3, p = NS), due to higher bicarbonate levels (23 +/- 2 mmol/l vs 21 +/- 2, p = 0.49). The incidence of lung congestion in chest X-rays and CT scans was significantly higher in group P (50% vs 29%, p = 0.073 at 48 hours postoperatively). Room air blood O2 saturation and maximal expiratory volume tended to be higher in group D (at 72 hours after operation- 92 +/- 4 vs 90%+/- 5, p = 0.29 and 646 +/- 276 vs 485 ml +/- 206, p = 0.16, respectively). There was no statistical difference in urine output but the amount of furosemide given to patients in group P was significantly higher (during the first 8 hours 2.5 +/- 0.5 vs. 0.3 mg +/- 1.6, p = 0.07). Plasma creatinine levels were significantly lower in group D (at 24 hours 0.93 +/- 0.02 vs 1.05 mg/dL +/- 0.02, p = 0.02). Mobilization after surgery was faster in group D.
Ultrasonography is highly effective in diagnosing pyelocalyceal dilatation. Confirming the distension of these collecting structures, indicating probable obstruction, is more difficult since the degree of dilatation does not always correspond to the degree of distension. Renal studies were performed in 244 patients including 51 patients with dilation or renal obstruction. Doppler ultrasonography was used to measure the Pourcelot's resistive index of arcuate and interlobar arteries for each kidney. Results demonstrate: 1) for healthy patients the average vascular resistive index is 0.54 +/- 0.02 (minimum 0.48 +/- 0.02, maximum 0.60 +/- 0.02). 2) in cases of acute obstruction, this resistive index for pathologic kidney is elevated greater than 0.7. The difference in resistive indices between the pathologic and contralateral kidney was greater than 0.10. 3) in the patients with intermittent junctional syndromes when an intravenous furosemide test is used, there is an increase in the resistive index. 4) in case of chronic obstruction well tolerated, the increase in resistive index is moderate. If there is an acute deterioration, the resistive index become greater than 0.8. Concurrent abnormalities which affect only one kidney (pathology of the renal hilum, tumoral syndromes) may make it difficult to interpret certain results. Ultrasonography together with Doppler scanning may be in certain cases a reasonable alternative with IVP.