Hepatic uptake and metabolism of benzoate: a multiple indicator dilution, perfused rat liver study. (41/450)

Multiple, noneliminated references ((51)Cr-labeled erythrocytes, (125)I-albumin, [(14)C]- or [(3)H]sucrose, and [(2)H](2)O), together with [(3)H]hippurate or [(14)C]benzoate, were injected simultaneously into the portal vein of the perfused rat liver during single-pass delivery of benzoate (5-1,000 microM) and hippurate (5 microM) to investigate hippurate formation kinetics and transport. The outflow dilution data best fit a space-distributed model comprising vascular and cellular pools for benzoate and hippurate; there was further need to segregate the cellular pool of benzoate into shallow (cytosolic) and deep (mitochondrial) pools. Fitted values of the membrane permeability-surface area products for sinusoidal entry of unbound benzoate were fast and concentration independent (0.89 +/- 0.17 ml. s(-1). g(-1)) and greatly exceeded the plasma flow rate (0.0169 +/- 0.0018 ml. s(-1). g(-1)), whereas both the influx of benzoate into the deep pool and the formation of hippurate occurring therein appeared to be saturable. Results of the fit to the dilution data suggest rapid uptake of benzoate, with glycination occurring within the deep and not the shallow pool as the rate-determining step.  (+info)

Technique for using video microscopy and indicator dilution for repeated measurements of cardiac output in small animals. (42/450)

BACKGROUND: The authors developed an indicator dilution technique for small animals to repeatedly determine cardiac output and blood volume without cardiac instrumentation or blood sampling. METHODS: Observations were made in the hamster (N = 32, 70 mg/kg pentobarbital) cremaster using in vivo fluorescence videomicroscopy. Fluorescein isothiocyanate-conjugated bovine serum albumin (10 mg/ml) was injected as a bolus dose (right jugular) while video recording the light intensity in a 20-microm arteriole (intensified charge-coupled device [CCD] camera at fixed gain). The intensity signal was analyzed over time (background subtracted) and calibrated to the dye concentration. The ex vivo calibration was performed using a constant optical path length (20 microm) and a range of dye and hematocrit concentrations. In vivo tube hematocrit was determined using standard methods with fluorescently labeled erythrocytes. Thus, quenching of the fluorescence signal by hemoglobin was corrected for the calibration, and the plasma space in the arteriole was determined. The steady state dye concentration measured by the light intensity at 2 min was not different from the dye concentration found by direct spectrophotometric analysis of the plasma. RESULTS: Cardiac index was calculated as milliliters of blood per minute per kilogram body weight. The calculated cardiac index was 359 +/- 18 ml.min(-1).kg(-1), which is not different from the reported values for hamsters. Cardiac output was increased twofold when enough intravenous nitroprusside or nitroglycerine was injected to decrease mean arterial pressure from 90 to 70 mmHg. Cardiac output was elevated during dobutamine infusion (16 microg.kg(-1).min(-1)) and decreased during esmolol infusion (50, 75.kg(-1).min(-1)). Blood volume determined from the steady state dye concentrations was 6.2 +/- 0.5 ml/100 g body weight, within the normal range for hamsters. CONCLUSIONS: Fluorescent dye dilution and video microscopy can be used to repeatedly determine cardiac output or blood volume in small animals.  (+info)

Ultrasound dilution evaluation of pediatric hemodialysis vascular access. (43/450)

BACKGROUND: Hemodialysis access thrombosis is a significant cause of morbidity for hemodialysis patients and results from decreased access flow caused by venous outflow tract stenosis. Ultrasound dilution (UD) is a practical, noninvasive, and reliable indicator of access flow and is effective in predicting venous stenosis in adult patients receiving hemodialysis. METHODS: The current study is the first to our knowledge to evaluate the accuracy of UD in predicting hemodialysis access stenosis in a pediatric hemodialysis population. Thirteen pediatric patients receiving hemodialysis via permanent access (4 AVF and 9 AVG) received 73 UD measurements over three months. RESULTS: Mean raw access flow (QA) was 720 +/- 428 mL/min, and mean corrected access flow (QAcorr) was 886 +/- 537 mL/min/1.73 m(2). QAcorr was significantly lower in accesses with stenosis (401 +/- 176 mL/min/1.73 m(2)) versus accesses without stenosis (1158 +/- 330 mL/min/1.73 m(2), P < 0.0001). Unlike flow values reported by raw QA, there was no overlap in flow values reported by QAcorr in accesses with stenosis (174 to 579 mL/min/1.73 m(2)) versus accesses without stenosis (709 to 1711 mL/min/1.73 m(2)). Two patients with an AVG who had QAcorr less than 600 mL/min/1.73 m(2) developed an access thrombosis within one week after UD measurement. No patients with QAcorr greater than 700 mL/min/1.73 m(2) developed access thrombosis in the 30 days following UD measurement. CONCLUSIONS: : The current study supports the use of monthly UD measurement to prevent access thrombosis in children receiving hemodialysis.  (+info)

Accuracy of simple techniques for estimating fractional zinc absorption in humans. (44/450)

The theoretical basis of the accuracy of a number of simple techniques for estimating fractional zinc absorption (FZA) in humans using stable isotopic tracers has not been evaluated. These techniques include fecal monitoring (FM), deconvolution analysis (DA), double isotopic tracer ratio (DITR) and indicator dilution methods. Using a compartmental model, we investigated the accuracy and logic of each of these techniques. Time-dependent estimates of FZA based on the simple techniques were simulated using the compartmental model and compared with the known FZA derived from the model. The analysis elucidated logical errors in some of the FM techniques, and even when these problems were corrected, the FM technique was still prone to errors due to incomplete fecal tracer recovery and variable gastrointestinal (GI) transit time. Although logically correct, the indicator dilution techniques were also highly sensitive to incomplete fecal tracer recovery and variable GI transit time. The DA and DITR techniques were the most robust in that they were logically correct and were insensitive to incomplete fecal tracer recovery and variable GI transit time. Although all of the DA and DITR methods provided similarly good estimates of FZA relative to the compartmental model, the DITR technique performed on a spot urine specimen obtained several days after tracer administration was the preferred choice because of its simplicity and minimal requirements for patient compliance.  (+info)

Instrumentation in antimicrobial susceptibility testing. (45/450)

Studies in the 1960s demonstrated the problems of variability in susceptibility testing methods, especially those affecting the performance of disc diffusion procedures. These studies made apparent the need for standardization and resulted in more clearly defined performance limits for growth medium, incubation conditions, inoculum concentration, disc content for diffusion methods, the setting of interpretative MIC breakpoints and the establishment of quality control parameters. More recently, there has been a growing interest in the use of instrumentation for reading disc diffusion tests and the endpoints of agar or broth dilution MIC determinations. Instrumentation ranges in complexity from the simple optical reading of zones of inhibition or growth endpoints, requiring operator interpretation, to more sophisticated devices for reading, recording and 'expert system' analysis of results with interfacing of instruments to laboratory information management systems. Some of the more developed systems are fully automated and can also identify the organisms tested. The pressure to reduce labour costs and provide results earlier favours the use of more automated systems whilst the requirement for resistance surveillance provides impetus for the use of systems that provide quantitative results and electronic data handling.  (+info)

Noninvasive transcutaneous determination of access blood flow rate. (46/450)

BACKGROUND: Current indicator dilution techniques for determining the vascular access blood flow rate (Qa) require reversal of the dialysis blood lines and are time consuming. We have recently described an indicator dilution technique for determining Qa using a novel optical transcutaneous hematocrit (Hct) sensor that does not require reversal of the dialysis lines, and have validated the accuracy of this method (TQa) in vitro. METHODS: This study compared results using the TQa method with those obtained using a similar indicator dilution technique but which required reversal of the dialysis lines (HD01 Monitor, Transonic Systems, Ithaca, NY, USA) during routine hemodialysis in 59 patients (25 native fistulas and 34 synthetic grafts). The sensor for the TQa method was placed on the skin directly over the access to measure changes in Hct approximately 25 mm downstream of the venous needle. A single 30 mL bolus of saline was infused into the dialyzer venous line over approximately six seconds without reversal of the dialysis blood lines, and the vascular access flow rate was calculated using indicator dilution methods from the time-dependent decrease in the Hct downstream of the venous needle. Two additional small-scale studies were performed to assess the effect skin pigmentation and to evaluate further the reproducibility of the TQa method. RESULTS: Qa values determined by the TQa method were highly correlated with those determined by the HD01 method (N = 72, R2 = 0.948, P < 0.001) over the range of 153 to 2,042 mL/min. There was no significant difference between vascular access flow rates determined by the TQa method and those determined by the HD01 METHOD: Results from one small-scale study showed that the relationship between Qa values determined by the TQa and the HD01 methods was similar when tested only among black patients (N = 12), suggesting that skin pigmentation is not an important determinant of the accuracy of the TQa METHOD: The second small-scale study showed that the intratreatment coefficient of variation for the TQa method was 7.8 +/- 5.6% (N = 14). CONCLUSIONS: : These results show that transcutaneous measurement of Qa is an accurate, simple, and fast technique for determining Qa without requiring the reversal of the dialysis blood lines.  (+info)

Extraction of long-chain fatty acids in isolated rat heart during acute low-flow ischemia. (47/450)

Although beta-oxidation of fatty acids is suppressed rapidly during ischemia, the behavior of fatty acid extraction at different flow rates is incompletely understood. This study assessed the relationship between flow and extraction of (123)I-iodophenylpentadecanoic acid (IPPA) in the isolated heart model, especially at low flow. METHODS: Isolated hearts from male Wistar rats (n = 15) were subjected to retrograde perfusion with constant flow (Krebs Henseleit solution containing 10 mmol/L glucose). A latex balloon in the left ventricle allowed isovolumetric contractions and ventricular pressure measurements. The extraction of (123)I-IPPA was assessed with the indicator dilution technique and (99m)Tc-albumin as the intravascular reference. The flow was either increased from the control flow (8 mL/min) until 300% or reduced until 10%. (123)I-IPPA extraction was measured three times before and 10 min after flow alteration. The tracer uptake was estimated from the product of net extraction and flow. RESULTS: The mean (123)I-IPPA extraction at the control flow (third measurement) was 51.6% +/- 2.8%. Between flow rates of approximately 25% and 300%, (123)I-IPPA extraction increased exponentially at decreasing flow rates. At flow rates < or =25% of the control flow, (123)I-IPPA extraction was exponentially higher than predicted. (123)I-IPPA uptake and flow changed largely in parallel. During low flow, the rate-pressure product showed the expected decline (perfusion-contraction matching). CONCLUSION: The extraction of (123)I-IPPA is preserved and slightly increased (relative to flow) during acute low-flow ischemia.  (+info)

Screening for subclinical stenosis in native vessel arteriovenous fistulae. (48/450)

Guidelines recommend the use of ultrasound dilution techniques (UDT), including measurement of access recirculation (AR) and access blood flow (Q(a)), to screen for subclinical vascular access dysfunction. Although these techniques are efficacious in polytetrafluoroethylene grafts, data in native vessel arteriovenous fistulae (AVF) are lacking. A prospective observational study was conducted to evaluate the utility of UDT screening in AVF. Q(a) and AR were measured bimonthly. Positive studies required fistulograms and were defined by Q(a) < 500 ml/min, DeltaQ(a) > 20% from baseline or AR > 5%. Accesses with stenosis underwent percutaneous angioplasty. After 1 yr, there were 1355 mo of follow-up in 177 patients. There were 44 positive studies in 40 patients. Q(a) was <500 ml/min in 36 (82%), DeltaQ(a) was >20% in 5 (11%), and AR was >5% in 6 (14%). Of patients with Q(a) < 500 ml/min, 29 (81%) had stenosis. Only two patients (40%) with DeltaQ(a) > 20% but Q(a) > 500 ml/min had stenosis. No patient with AR > 5% had stenosis unless Q(a) was also <500 ml/min. Immediate patency rate was 93% post-PTA. Mean Q(a) increased from 303 +/- 154 ml/min to 602 +/- 220 ml/min (P < 0.0001), and mean urea reduction ratio increased from 70.4 +/- 8.4% to 74.6 +/- 6.5% (P = 0.003) post-PTA. The results demonstrate that UDT could detect subclinical stenoses in AVF, and most lesions were amenable to angioplasty. AVF that underwent PTA delivered higher Q(a) and urea reduction ratio, and immediate patency rates were acceptable. Access failure after negative UDT was unusual. Measuring AR increases the time required to perform UDT but does not improve utility. Serial measurements of Q(a) alone may be the best strategy for screening AVF.  (+info)