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Biomedical subjects

C Clausen

Publications and source records attributed to C Clausen.

At least 55 records · Page 3Linked to original sources

Piperacillin pharmacokinetics in pediatric patients.

The pharmacokinetics of piperacillin were studied in 15 pediatric patients (age range, 3.3 to 14.3 years). Piperacillin was administered in a dosage of 1.5 +/- 0.4 g/m2 (mean +/- standard deviation) every 4 to 6 h. Peak serum concentrations ranged from 69 to 354 micrograms/ml. The mean elimination half-life was 37.0 +/- 13.3 min, which is shorter than that observed in most adults with normal renal function. The mean elimination half-life in three patients with renal impairment was 60.1 +/- 12.4 min, and the mean ratio of renal clearance to total clearance was 0.57. These results suggest a significant nonrenal elimination of piperacillin. Based on these data, a dosage of 1.5 g/m2 given as a 30-min infusion every 4 h is suggested for children with normal renal function. For patients with renal impairment, the daily dosage could be calculated as follows: corrected dose = normal dose x (0.35 + [0.65 x (ClCr/0.06)]), where ClCr is the creatinine clearance expressed as liters per minute per square meter.

Adolescent↗

A low-cost method for rapid transfer function measurements with direct application to biological impedance analysis.

The measurement of the linear transfer function of a biological system has found wide use in the characterization of the system's input/output properties, and in the separation and measurement of the properties of the different subelements that make up the system. Unfortunately sophisticated and expensive instrumentation has traditionally been required to make these measurements. In this paper, we present detailed design specifications of a low-cost instrument that is capable of yielding transfer function measurements with a high degree of accuracy and speed. The instrument is comprised of a pseudo-random binary sequence signal generator with precise date acquisition synchronization circuits, interfaced to a general-purpose mini-or microcomputer system common to many laboratory environments. The instrument is capable of measuring the transfer function of an arbitrary biological system up to a bandwidth of 8.3 KHz, with a frequency resolution of 425 points. In cases where the biological measurements are not contaminated with experimental noise, the transfer function can be determined in as little as 47 ms of data collection. In the case where experimental noise is present in the biological measurements, a simple averaging method is described which results in an effective increase in the signal-to-noise ratio, thereby yielding accurate transfer function estimates. The instrument is especially well suited to the measurement of transfer functions of biological systems, where experimental noise is a problem and where only limited time is available to acquire stable measurements.

Costs and Cost Analysis↗

Lithium pharmacokinetics: single-dose experiments and analysis using a physiological model.

The kinetics of lithium (Li+) distribution after a single dose was studied in healthy human subjects. Experiments were performed by simultaneously following changes of Li+ concentration in plasma, erythrocytes (RBC), and urine. The data were fitted by a simple but physiologically realistic model, so that extracted rate constants could be assigned to real body compartments and compared with independent measurements of cellular transport characteristics. The extracted rate constants were used to calculate steady-state cell-to-plasma Li+ ratios for RBC and for inaccessible cells (mainly muscle). In both cell types, the intracellular Li+ concentration is far below electrochemical equilibrium. This finding suggests that the Li+ countertransport efflux mechanism of RBC may be shared with muscle. We also present evidence for a circadian rhythm in Li+ excretion that parallels the daily cycle of Na+ and K+ excretion.

Adult↗

Dihydroergotamine--stimulation of intestinal peristalsis. An experimental and clinical study.

In an experimental study in 15 beagle hounds using strain gauges a significantly increased motility in the small and large intestine after dihydroergotamine was observed. Since this assessment did not provide any information about mucus transport, gastro-intestinal passage time in patient and control groups was determined using radioopaque catheter material. While transit time in the patient group was significantly reduced by 2 x 0.5 mg DHE s.c./day, this effect was not observed in controls. We related the significantly reduced passage time after DHE in the patient group to a normalisation of a functional disturbance of regulation. The action of the drug is seen in the blocking of the stress induced increased sympathetic tone, without the side effects often seen after pure alpha-antagonists of the phentolamine type or the adrenergic guanethidine type neuronal blocking agents. The specific efficacy of DHE as a partial alpha-antagonist is pointed out. For the clinician, postoperative gastro-intestinal atony might be an indication for its use.

Animals↗

Impedance analysis of a tight epithelium using a distributed resistance model.

This paper develops techniques for equivalent circuit analysis of tight epithelia by alternating-current impedance measurements, and tests these techniques on rabbit urinary bladder. Our approach consists of measuring transepithelial impedance, also measuring the DC voltage-divider ratio with a microelectrode, and extracting values of circuit parameters by computer fit of the data to an equivalent circuit model. We show that the commonly used equivalent circuit models of epithelia give significant misfits to the impedance data, because these models (so-called "lumped models") improperly represent the distributed resistors associated with long and narrow spaces such as lateral intercellular spaces (LIS). We develop a new "distributed model" of an epithelium to take account of these structures and thereby obtain much better fits to the data. The extracted parameters include the resistance and capacitance of the apical and basolateral cell membranes, the series resistance, and the ratio of the cross-sectional area to the length of the LIS. The capacitance values yield estimates of real area of the apical and basolateral membranes. Thus, impedance analysis can yield morphological information (configuration of the LIS, and real membrane areas) about a living tissue, independently of electron microscopy. The effects of transport-modifying agents such as amiloride and nystatin can be related to their effects on particular circuit elements by extracting parameter values from impedance runs before and during application of the agent. Calculated parameter values have been validated by independent electrophysiological and morphological measurements.

Animals↗

Nystatin as a probe for investigating the electrical properties of a tight epithelium.

We show how the antibiotic nystatin may be used in conjunction with microelectrodes to resolve transepithelial conductance Gt into its components: Ga, apical membrane conductance; Gbl, basolateral membrane conductance; and Gj, junctional conductance. Mucosal addition of nystatin to rabbit urinary bladder in Na+-containing solutions caused Gt to increase severalfold to ca. 460 micrometerho/muF, and caused the transepithelial voltage Vt to approach +50 mV regardless of its initial value. From measurements of Gt and the voltage-divider ratio as a function of time after addition or removal of nystatin, values for Ga, Gbl, and Gj of untreated bladder could be obtained. Nystatin proved to have no direct effect on Gbl or Gj but to increase Ga by about two orders of magnitude, so that the basolateral membrane then provided almost all of the electrical resistance in the transcellular pathway. The nystatin channel in the apical membrane was more permeable to cations than to anions. The dose-response curve for nystatin had a slope of 4.6. Use of nystatin permitted assessment of whether microelectrode impalement introduced a significant shunt conductance into the untreated apical membrane, with the conclusion that such a shunt was negligible in the present experiments. Nystatin caused a hyperpolarization of the basolateral membrane potential in Na+-containing solutions. This may indicate that the Na+ pump in this membrane is electrogenic.

Animals↗

Measurement of the impedance of frog skeletal muscle fibers.

Impedance measurements are necessary to determine the passive electrical properties of cells including the equivalent circuits of the several pathways for current flow. Such measurements are usually made with microelectrodes of high impedance (some 15 MOmega) over a wide frequency range (1-10,000 Hz) and so are subject to many errors. An input amplifier has been developed which has negligible phase shift in this frequency range because it uses negative feedback to keep tiny the voltage on top of the microelectrode. An important source of artifact is the extracellular potential produced by capacitive current flow through the wall of the microelectrodes and the effective resistance of the bathing solution. This artifact is reduced some 10 times by shielding the current microelectrode with a conductive paint. The residual artifact is analyzed, measured, and subtracted from our results. The interelectrode coupling capacitance is reduced below 2 x 10(-17) F and can be neglected. Phase and amplitude measurements are made with phase-sensitive detectors insensitive to noise. The entire apparatus is calibrated at different signal to noise ratios and the nature of the extracellular potential is investigated. The phase shift in the last 5-20 mum of the microelectrode tip is shown to be small and quite independent of frequency under several conditions. Experimental measurements of the phase characteristic of muscle fibers in normal Ringer are presented. The improvements in apparatus and the physiological significance of impedance measurements are discussed. It is suggested that the interpretation of impedance measurements is sensitive to small errors and so it is necessary to present objective evidence of the reliability of one's apparatus and measurements.

Animals↗

Circuit models of the passive electrical properties of frog skeletal muscle fibers.

The relation between the fine structure, electric field equations, and electric circuit models of skeletal muscle fibers is discussed. Experimental evidence illustrates the profound variation of potential with circumferential position, even at low frequencies (100 Hz). Since one-dimensional cable theory cannot account for such variation, three-dimensional cable theory must be used. Several circuit models of a sarcomere are presented and plots are made of the predicted phase angle between sinusoidal applied current and potential. The circuit models are described by equations involving normalized variables, since they affect the phase plot in a relatively simple way. A method is presented for estimating the values of the circuit elements and the standard deviation of the estimates. The reliability of the estimates is discussed. An objective measure of fit, Hamilton's R test, is used to test the significance of different fits to data. Finally, it is concluded that none of the proposed circuit models provides an adequate description of the observed variation of phase angle with circumferential location. It is not clear whether the source of disagreement is inadequate measurements or inadequate theory.

Animals↗

Impedance of frog skeletal muscle fibers in various solutions.

The linear circuit parameters of 140 muscle fibers in nine solutions are determined from phase measurements fitted with three circuit models: the disk model, in which the resistance to radial current flow is in the lumen of the tubules; the lumped model, in which the resistance is at the mouth of the tubules; and the hybrid model, in which it is in both places. The lumped model fails to fit the data. The disk and hybrid model fit the data, but the optimal circuit values of the hybrid model seem more reasonable. The circuit values depend on sarcomere length. The conductivity of the lumen of the tubules is less than, and varies in a nonlinear manner with, the conductivity of the bathing solution, suggesting that the tubules are partially occluded by some material like basement membrane which restricts the mobility of ions and has fixed charge. The x2.5 hypertonic sucrose solution used in many voltage clamp experiments produces a large increase in the radial resistance, suggesting that control of the potential across the tubular membranes would be difficult to achieve. Glycerol-treated fibers have 90% of their tubular system insulated from the extracellular solution and 10% connected to the extracellular solution through a high resistance. We discuss the implications of our results for calculations of the nonlinear properties of muscle fibers, including the action potential and the radial spread of contraction.

Action Potentials↗

Lymphocytosis and histamine sensitization of mice by fractions from Bordetella pertussis.

Administration of Bordetella pertussis cell extracts induced in mice hypersensitivity to histamine, as well as pronounced leukocytosis and hypoglycemia. The leukocytosis was mainly caused by an increase in the small lymphocytes in the circulating blood, and it was most pronounced 3 to 4 days after injection of B. pertussis extracts. Rabbit antimouse lymphocyte serum produced a decrease in the lymphocyte count in normal mice, as well as in mice treated with B. pertussis extracts. This depression in lymphocytes was observed whether the antilymphocyte serum was given 1 day or 2 days after the administration of B. pertussis extracts. The increased histamine sensitivity and hypoglycemia of mice treated with B. pertussis extract were not affected by treatment with antilymphocyte serum, although a marked lymphopenia was present. These observations indicate that the three phenomena observed in pertussis-treated mice are independent of each other.

Animals↗

Bone and joint infections caused by Kingella kingae: six cases and review of the literature.

Six cases of Kingella kingae arthritis, osteomyelitis, and diskitis were studied, and data were reviewed from an additional 23 cases in the English-language literature. K. kingae is a slow-growing, fastidious, gram-negative microorganism that colonizes mucous membranes of the upper respiratory tract. Infections were predominantly seen in infants and young children (86% of cases) and were preceded by an upper respiratory tract infection in 31% of patients. Low-grade fever (38 degrees C-39 degrees C) and pain or swelling involving the affected limb developed insidiously. However, 76% of the infections were diagnosed within 1 week after the onset of symptoms. The knee was involved in 47% and the hip in 33% of cases of arthritis. Osteomyelitis mainly involved the femur (36%); four cases of osteomyelitis (29%) were diagnosed as diskitis. The erythrocyte sedimentation rate was greater than 20 mm/h in all patients. Gram stains of aspiration fluid were positive in 19% of cases, whereas blood cultures yielded growth in only 5%. Radiographic signs indicating the presence of osteomyelitis were observed in 93% of patients. All patients recovered completely. K. kingae is an important causative agent in indolent bone, joint, and intervertebral disk infections.

Arthritis, Infectious↗