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Biomedical subjects

S Frinak

Publications and source records attributed to S Frinak.

At least 19 recordsLinked to original sources

Simplified measurement of intra-access pressure.

The measurement of intra-access pressure (P[IA]) normalized by mean arterial BP (MAP) helps detect venous outlet stenosis and correlates with access blood flow. However, general use of P(IA)/MAP is limited by time and special equipment costs. Bernoulli's equation relates differences between P(IA) (recorded by an external transducer as PT) and the venous drip chamber pressure, PDC; at zero flow, the difference in height (deltaH) between the measuring sites and fluid density determines the pressure deltaPH = P(IA) - P(DC) Therefore, P(DC) and PT measurements were correlated at six different dialysis units, each using one of three different dialysis delivery systems machines. Both dynamic (i.e., with blood flow) and static pressures were measured. Changes in mean BP, zero calibration errors, and hydrostatic height between the transducer and drip chamber accounted for 90% of the variance in P(DC), with deltaPH = -1.6 + 0.74 deltaH (r = 0.88, P < 0.001). The major determinants of static P(IA)/MAP were access type and venous outflow abnormalities. In grafts, flow averaged 555 +/- 45 ml/min for P(IA)/MAP > 0.5 and 1229 +/- 112 ml/min for P(IA)/MAP < 0.5. DeltaPH varied from 9.4 to 17.4 mmHg among the six centers and was related to deltaH between the drip chamber and the armrest of the dialysis chair. Concordance between values of P(IA)/MAP calculated from PT and from P(DC) + deltaPH was excellent. It is concluded that static P(DC) measurements corrected by an appropriate deltaPH can be used to prospectively monitor hemodialysis access grafts for stenosis.

Arteriovenous Shunt, Surgical

Measurements of potential differences in human subjects induced by motion in a superconducting magnetic field.

We have attempted to measure the electromotive forces (emfs) induced in human beings moving at a constant speed in a highly dense magnetic field. Experiments were initially conducted on a set of models, and then directly on human subjects. The models consisted of single circular loops of Tygon tubing (I.D., 0.635 cm; O.D., 0.9525 cm) filled with normal saline solution, with circumferences of 20, 40, 60, 80, and 100 cm. The models were connected to an amplifier via silver/silver-chloride electrodes. Each saline loop was mounted on a movable platform, with the plane of the loop perpendicular to the platform's axis; the platform was enabled to move at known constant speeds into and out of the bore of a 1.89-T magnet. The human subjects were then substituted for the saline loops, with the long axis parallel to the direction of motion, and with standard EKG electrodes placed at 180 degrees successively on the ankle, calf, lower thigh, upper thigh, chest, and head. In all cases, for human subjects and models, the peak induced voltage was directly proportional to the speed of movement and the square of the circumference of the bounded cross-sectional areas. Thus, for the saline loops, the correlation coefficient between induced voltage and circumference was .998, and for human subjects, .947. Under the loose assumption that for equal circumferences the bounded areas in human subjects were equal to those in the circular loops, the induced emfs in human subjects were consistently about 13% greater than those in the loops. At a mean speed of 1.18 m/s, the chest had a peak induced voltage of 260 mV, while the voltage at the ankle had a peak of 19.8 mV. The experimental data were used to estimate the corresponding induced-current density at the pericardium, 17 mA/m2. We conclude for a human subject moving at constant speed along the body's long axis into a magnetic field that Faraday's law is closely followed for various cross-sections of the body. Further, in those cases in which the magnetic field and its gradient are not well-established, one can use saline-filled loops to estimate approximate values of voltages induced in human subjects.

Electric Conductivity

Use of bioelectrical impedance for the nutritional assessment of chronic hemodialysis patients.

Although malnutrition poses a significant risk to the well-being of chronic hemodialysis patients, their nutritional assessment is usually empirical. We studied body composition by bioelectrical impedance (BEI) prospectively in 39 patients followed for 5-12 months. BEI correctly discriminated between underweight and overweight patients in terms of fat mass (21 +/- 5 vs. 34 +/- 10%; p = 0.002), lean body mass (78 +/- 4 vs. 67 +/- 10%; p = 0.004) and total body water (57 +/- 3 vs. 49 +/- 7%; p = 0.002), respectively. Serial body weights did not correlate with changes in lean body mass (LBM) as measured by BEI. While 28% of patients lost weight, 41% lost LBM. Most striking is the contrast between the patients who showed no change in LBM by BEI and those whose body weight remained neutral (3 vs. 28%). BEI is a most sensitive clinical tool for assessing changes in LBM in hemodialysis patients.

Body Composition

Filtration of dialysate using an on-line dialysate filter.

UNLABELLED: Increased concerns about pyrogenic contamination of dialysate have led to the development of an on-line dialysate filtration system. Bacteriological testing of the system was performed (n = 6) by introducing bicarbonate concentrate contaminated with E. coli 026:B 6 (3 x 10(9) cfu/ml) into a dialysis machine equipped with a two-stage polysulfone filtration system. The bacterial concentration of the dialysate entering the filtration system was maintained above 10(6) cfu/ml and endotoxin levels ranged from 30-300 ng/ml during the 3-hour test period. Bacterial and endotoxin levels on the input side of the first-stage filter reached minimum concentrations of 5.4 x 10(9) cfu/ml and 30,000 ng/ml respectively. All output samples of filtered dialysate showed no bacterial growth and endotoxin levels were below the sensitivity (0.003 ng/ml) of the LAL assay. A dialysis machine (QD = 500), equipped with a single stage filtration system, was used for 18 months of clinical testing. In order to evaluate the system's reliability with regard to membrane failures and reduced dialysate flow, filter membrane integrity was verified weekly using a pressure holding test and dialysate flow was measured under routine clinical conditions. No membrane failures occurred, and dialysate flow was maintained at 511 +/- 17 ml/min (n = 70) during the test period. IN CONCLUSION: dialysate filtration is an effective and practical method for prevention of pyrogenic reactions due to high levels of bacteria and endotoxins.

Bacterial Infections

Thermal distributions in a water bath heated mouse tumor.

In the past several years numerous investigators have employed various mouse tumor systems and a variety of heating methods to examine the effects of hyperthermia in vivo. These studies have led, in some cases, to different results in tumor response in what appear to be similar experiments. Our results indicate that these discrepancies may in part be attributable to variations in intratumor temperature and depend strongly upon the method and conditions of heating employed. In all cases, we have employed the C3H mammary carcinoma tumor system with the tumor implanted in the right hind limb of the mouse. All tumors were 7-9 mm in diameter at the time of the experiments. Water bath heating was employed with the animals under one of four possible conditions: the presence or absence of anesthesia, and the use or lack of core cooling. Thermometry was performed with an array of multiple microthermocouples, each less than 150 micron in diameter, implanted in the tumor in a grid-like pattern. Significant variations (1.0 degrees C for no anesthesia, p less than .01; 1.3 degrees C for Thorazine/Ketamine, p less than .001) in intratumor temperature were found across the tumor in the unperturbed state. These variations were essentially eliminated under all hyperthermic conditions. Control of core (rectal) temperature (with or without anesthesia) reduced the intratumor temperatures even though the water bath temperature was held constant resulting in variations between water bath and tumor temperatures of from 0.1-0.8 degrees C.

Animals

Failure of standard cardioplegic techniques to protect the conducting system.

To determine the site of persistent electrical activity during cardioplegic arrest, microelectrodes that were also capable of recording temperature were placed along the conducting system in dogs undergoing one hour of cardioplegic arrest. Electrical activity was highest in the atrioventricular (AV) junction area (AV node and proximal bundle of His), and the temperature in this area could not be lowered to the level of the temperature in the left ventricular apex by routine cardioplegic technique. Neither changing K+ concentration (16 to 20 mEq/L) nor adding procaine hydrochloride abolished the activity of the conducting system during cardioplegia, and only 2 of 15 dogs were in sinus rhythm 30 minutes after reperfusion. When the conducting system temperatures were lowered to less than 15 degrees C by right AV lavage with iced saline solution, electrical activity was abolished during arrest and all 4 of 4 animals were in sinus rhythm 30 minutes after reperfusion. This study localizes the site of persistent conducting system activity during cardioplegic arrest, confirms it can be abolished with local cooling, and establishes the relationship between conducting system activity during cardioplegia and the incidence of conduction block and junctional rhythm following reperfusion.

Animals

Direct measurement of reoxygenation in malignant mammary tumors after a single large dose of irradiation.

Measurements of the tissue O2 partial pressure distribution in C3H mouse mammary adenocarcinomas were performed just before and 72 - 74 hrs. after X- irradiation using O2 microelectrodes of the gold in glass type. The results obtained before irradiation were similar to those usually obtained previously in fast growing murine tumors during advanced growth stages. After exposure to a single dose of 60 Gy, the distribution curve significantly changed. This change was particularly evident in the very low pO2 range which is of crucial importance for the efficacy of radiotherapy. Due to this improvement of the tumor tissue oxygenation the number of radioresistant cells can be drastically reduced in the post- irradiation period at the time of maximum reoxygenation. Judiciously chosen fractionated treatment regimens, thus, should maintain tumor cells in optimum radiosensitivity states.

Animals

Heterogeneous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma.

Severe disturbances in microcirculation during advanced phases of tumor growth lead to restrictions of convective and diffusive transport. In addition, an inhomogeneous distribution of transport conditions develops, resulting in insufficient and heterogeneous substrate supply and an inadequate drainage of wastes. Polarographic measurements of the local tissue oxygen tension (PO2) using gold microelectrodes reveal that very low PO2 values are prevalent in C3H mouse mammary carcinomas. The tissue PO2 frequency distributions are shifted to low PO2 values and limited in variability. The mean PO2 value is 7 mm Hg. The median is 4 mm Hg, the modal class being 0 to 5 mm Hg. Within different microareas of the same tumor, pronounced heterogeneities exist. Due to an elevated rate of lactic acid production and its subsequent inadequate removal, a severe tissue acidosis is evidenced in malignant tumors. For C3H mouse mammary carcinomas, most of the measured pH values are in the range of 6.4 to 7.1, the modal class being 6.7 to 6.8 (mean pH, 6.73; median pH, 6.75). Within different microareas of the same tumor, clear heterogeneities in the pH distribution do occur. Very low pH values (5.8 to 6.3) have been observed in large ulcerated tumors. In extensively necrotic areas, pH values even higher than the arterial pH could be detected.

Adenocarcinoma

Effects of hyperthermia on normal and tumor microenvironment.

The effects of hyperthermia on pH, local blood flow (LBF) and tissue oxygen tension (TpO2) in several normal and tumor tissues were studied. It was found that TpO2, local blood flow and pH are inhomogeneous in tumor tissue. TpO2 is very low in certain areas which also seem deprived of blood flow and are at very low pH. Hyperthermia has a dual effect: at temperatures below 41 degrees C, it increases blood flow and TpO2 while above 41 degrees C, it causes a collapse in blood flow, lower TpO2 and a shift of the tissue pH towards acidosis from the already low pH values found in tumors.

Adenocarcinoma

Postischemic brain oxygenation with barbiturate therapy in rats.

We measured rat brain cortex PO2 (PtO2) with gold microelectrodes (tip diameter 5--10 micron) for up to 2 hours after 16 min of transient global brain ischemia with and without thiopental 90 mg/kg infused iv over 60 min beginning at 5 min postischemia. Seventeen rats were immobilized and mechanically ventilated on 1% halothane in oxygen with continuous monitoring of PtO2, ECG, end-expiratory CO2, rectal temperature, and arterial blood pressure. Global ischemia was induced by trimethaphan hypotension to an MAP of about 50 torr and a neck tourniquet inflated to 1500 torr. Postischemia, nine control rats (11 PtO2 measurements) were untreated and eight rats (8 PtO2 measurements) received thiopental 90 mg/kg. Preischemia, PtO2 values in both groups ranged from less than 5--70 torr with values of greatest frequency between 10 and 15 torr. Postischemia, PtO2 in control rats peaked at 45 +/- 8 (SEM) torr at 20 min. In thiopental treated rats, peak PtO2 was 24 +/- 6 torr at 10 min postischemia. Relative frequency histograms of PtO2 revealed that PtO2 in thiopental treated rats was lower (p less than 0.05) between 15 and 30 min postischemia. The magnitude of the decrease in PtO2 between 105 and 120 min postischemia appeared to correlate directly with the absolute preischemic value (i.e., the higher the preischemic PtO2, the greater the decrease in PtO2 postischemia). These results suggest that thiopental administered in large doses in early postischemia does not improve brain oxygenation secondary to a reduction in brain oxygen consumption. The relevance of the correlation between the magnitude of the fall in PtO2 postischemia and the magnitude of the preischemic value is discussed.

Animals

Clinical experience with heat sterilization for reprocessing dialyzers.

Use of heat sterilization for dialysis reprocessing offers significant advantages over chemical germicides. Polysulfone dialyzers (Fresenius 60M or 80M) can be sterilized by heating to 105 degrees C for 20 hr, thus permitting clinical trials of this method. One hundred eighty patients received 9,000 treatments. Pyrogenic reactions, sepsis, and subjective symptoms have not occurred. In vitro clearances (Qb 500 ml/min, Qd 800 ml/min) at baseline and after 2-8 uses did not differ (340 +/- 29 vs. 352 +/- 4 ml/min, respectively). KoA determined in vivo did not decrease (baseline 709 +/- 131 vs. 7th use 632 +/- 50 ml/min). Kt/V for urea was not different in 18 patients treated with heat sterilized dialyzers over 6 months when compared with a baseline period with formaldehyde sterilized dialyzers (1.37 +/- 0.12 vs. 1.32 +/- 0.11 at similar time and blood flows). Mean use number was 7.4 (dialyzers limited to 11 uses). Of discarded dialyzers, 44% failed a bedside integrity test (blood side pressurized at > 400 mmHg for 1 min), 36% failed automated fiber bundle or pressure holding tests, 8% had a blood leak, and 12% reached 11 uses. Clinical blood leaks occur in < 0.5% of treatments. Heat sterilization is a safe and effective method of dialysis reprocessing, but quality control of the process is essential. Based on initial clinical experience, heat sterilization of dialyzers for reuse is a promising alternative to chemical disinfection.

Blood Urea Nitrogen

Simplified measurement of intra-access pressure.

Normalized intra-access pressure (PIA), expressed as the access pressure/systemic blood pressure, detects venous outlet stenosis and correlates with access blood flow. General use of (PIA) is limited by time, special equipment needs, and cost. We therefore correlated pressure measurements from the venous drip chamber (PDC of Fresenius H-machines and from an external transducer, P tau, for blood flows (BFR) of 0 to 400-500 ml/min. Measurements were conducted 2-3 weeks apart in a cohort of 33 patients. PDC = -21 + 1.28 P tau; PDC = P tau = 75 mmHg at BFR = 146 ml/min. The major determinant of P tau at BFR = 0 was access type and venous outflow problems. The difference between P tau and PDC (delta = offset) was 17 +/- 1 mmHg (range, 2-43); delta correlated with the height difference between the two sites. Differences in systemic blood pressure, zero calibration, and hydrostatic pressure accounted for 90% of the variance between replicate measurements of PDC. Detection of outlet stenosis was compared by using PIA calculated from P tau and from PDC + 17. Only three of 66 measurements using the latter produced misclassification, and never on replicate measurements. P tau and PDC measurements in 62 additional patients showed a persistent offset of 17 mmHg. The authors conclude that PDC at BFR = 0 can be used to monitor prospectively prosthetic bridge grafts for stenosis as long as the offset for a particular dialysis machine is determined.

Blood Pressure

Increased urea kinetic modeling volume. Possible mechanisms and its significance.

The presence of access recirculation reduces delivered urea clearance and produces an increased volume/weight (V/M) ratio in three-point kinetic modeling. We measured R in 20 patients receiving conventional hemodialysis and correlated results with normalized intra-access venous pressure (PIA) and with angiographic or color-flow Doppler studies. Twenty patients were equally divided into those with and without persistently elevated modeled V/W ratios (0.64 vs 0.53), and subdivided into those with native and synthetic bridge graft accesses. Kinetic modeling parameters (Kt/V) and P1A did not differ between the two V/W groups. Modeled volume was quite accurately predicted by the equations in the normal group but deviated by 7.3 +/- 2.1 L in the high V/W ratio group. Three of 10 native and 4 of 10 graft accesses had trivial and hemodynamically insignificant abnormalities by color-flow Doppler or angiography. Recirculation was independent of V/W group and when measured by the slow flow/clamp technique was negligible (< 2.0%). Access flow always exceeded prescribed dialyzer blood flow by more than 300 ml/ min. Therefore, access recirculation was unlikely. In many of the high V/W patients, alternative explanations for falsely high modeled volume were found on follow-up modeling. Only one patient appeared to have a true high volume. The authors conclude that high urea volumes during kinetic modeling are unlikely to occur from access recirculation, but arise from other factors affecting the delivered urea clearance.

Adult

In vivo 31-P NMR of photoactivated hematoporphyrin derivative in cat brain.

In vivo 31-P nuclear magnetic resonance (NMR) spectroscopy was performed on cat brains injected with hematoporphyrin derivative (HpD). A 2-cm-diam region of the right parietal lobe was photoactivated with red light. The 31-P NMR spectra of the photoactivated hemisphere revealed increased inorganic phosphate and decreased phosphocreatine and adenosine triphosphate (ATP) levels, compared to spectra obtained from the control hemisphere. In the absence of drug, no difference in spectra was observed between the photoradiated and control lobes. Our studies suggest that in vivo 31-P NMR spectroscopy may be used to monitor the effects of phototherapy on tissue high-energy phosphate metabolism.

Animals

Brain tissue pH after global brain ischemia and barbiturate loading in rats.

Studies were done on rats to determine whether thiopental loading after complete, transient, global brain ischemia causes more rapid postischemic normalization of brain tissue pH. Fifteen halothane-anesthetized rats were subjected to 16 min of complete global brain ischemia by a combination of systemic arterial hypotension (40 torr) and a high pressure (1500 torr) neck cuff. Brain tissue pH was continuously monitored for up to 2 hour postischemia with microelectrodes (tip diameters of one to two micrometers) inserted about 500 micrometers into the parietal cortex. During ischemia, brain pH fell rapidly within the first 5 min from 7.0 to 6.2 and changed little thereafter. With restoration of arterial pressure and deflation of the neck cuff, pH did not immediately begin to rise back towards normal. Instead, after a few minutes, it transiently fell to even lower values before beginning to increase indicating increased tissue lactic acidosis when the brain is resaturated with glucose upon reperfusion. Beginning at 5 min postischemia, 7 of the 15 rats were infused with thiopental (90 mg/kg, IV over 60 min). At 30 min postischemia, brain tissue pH was similar in both groups and by 60 min, back to preischemic values. We conclude that thiopental loading postischemia does not improve normalization of brain pH. The transient decrease in brain pH with reperfusion is discussed.

Animals

Intracellular acidosis during and after cerebral ischemia: in vivo nuclear magnetic resonance study of hyperglycemia in cats.

In vivo 31P nuclear magnetic resonance spectroscopy was used to monitor the time course of intracellular pH in cat cerebral cortex subjected to global cerebral ischemia under control and hyperglycemic pretreatment conditions. Transient (16 minutes) global cerebral ischemia was induced in 14 cats using an inflatable cervical cuff combined with systemic arterial hypotension. Six cats were pretreated with infusion of 1.5 g/kg glucose prior to ischemia. Relative concentrations of high-energy phosphate metabolites and intracellular pH were continuously monitored before, during, and for 2 hours after cerebral reperfusion. During ischemia, intracellular pH fell to the same level and followed a similar time course in both groups. However, during initial reperfusion in the hyperglycemic group, there was a severe further decline (p less than 0.003) in intracellular pH. We suggest that the increased neurologic deficit and mortality found in hyperglycemic animals subjected to cerebral ischemia may be attributed to this transient severe tissue acidosis.

Acidosis

Pyridine nucleotide redox state and blood flow of the cerebral cortex following middle cerebral artery occlusion in the cat.

Acute changes in the redox state of NADH in the cerebral cortex of cats were investigated following occlusion of the middle cerebral cortex (MCA) and were correlated with alterations of regional cerebral blood flow in the ischemic cortex determined autoradiographically. Arterial occlusion was accomplished via the transorbital approach. Cortical fluorescence and reflected light signals were recorded from the central MCA territory by means of a beam-splitting fluorometer, and a fluorescence signal corrected for alterations in intravascular hemoglobin was derived. Following arterial occlusion, there was a rapid increase in cortical NADH fluorescence, peaking within 30 to 70 seconds at 20% to 40% of full scale. This was followed by a slow linear decline in fluorescence over the next several minutes. The behavior of cortical NADH fluorescence was unaffected by replacement of the ambient air over the cortical surface with nitrogen. Mean regional blood flow values in the most ischemic gyri two to 15 minutes following arterial occlusion were 21% to 23% of the corresponding values in the opposite, nonischemic hemisphere. In individual animals, peak NADH fluorescence values following arterial occlusion correlated with the extent of blood flow reduction in the affected ischemic gyri (P less than 0.05).

Animals