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Biomedical subjects

K Dahl

Publications and source records attributed to K Dahl.

At least 55 records · Page 3Linked to original sources

The pharmacokinetics of ceftazidime in patients with impaired renal function and concurrent frusemide therapy.

We have studied the pharmacokinetics of ceftazidime in 37 patients suffering from serious bacterial infections. All the patients had impairment of renal function and received moderate to high doses of frusemide concurrently. The doses of ceftazidime were given according to renal function as recommended by the manufacturer. Serum and urine samples were frequently collected, and drug concentrations measured by high performance liquid chromatography. The patients were grouped and evaluated according to renal function, mean (SD) creatinine clearances ranging from 70.1 (12.4) to 11.0 (3.2) ml.min-1. The pharmacokinetics of ceftazidime depended on renal function. A statistically significant increase in ceftazidime elimination half-life and decreases in urinary recovery, total body clearance, and renal clearance in proportion to the decrease in renal function were observed (p less than 0.05). The apparent volume of distribution also increased, but not significantly (p greater than 0.05). A linear correlation was found between the total body and renal clearances of ceftazidime and creatinine clearance. The extrarenal clearance increased from 3.9 to 14.0 ml.min-1 with decreasing renal function. Concurrent treatment with ceftazidime and moderate to high doses of frusemide did not impair renal function and no evidence of nephrotoxicity was found.

Adult↗

Definitions of differences and changes in peritoneal membrane water transport properties.

A survey is given comparing measurements of transperitoneal water transport in different clinical situations with analyses based on the so-called "pore theory." This model links the measured changes to physical alterations of the peritoneal membrane. The calculations include "equivalent pore radius," effective "membrane area" and diffusive length, the transport resistance of the unstirred dialysate layer, and the residual intraperitoneal volume after dialysate drainage. The clinical appearances include individual differences in transperitoneal transport characteristics, changes in transperitoneal transport over time on continuous ambulatory peritoneal dialysis (CAPD) and during peritonitis, the pharmacological effect on the transport properties, and the effect of peritoneal catheter dislocation on ultrafiltration capacity. The main conclusions are as follow: During CAPD treatment the measurement of intraperitoneal solute equilibration and "mass-transfer-area coefficients" for urea and creatinine is less sensitive than the measurement of ultrafiltration volume in revealing peritoneal membrane changes. Differences and changes found have mostly a combined physical explanation, but one is more or less dominant. Changes in peritoneal membrane area seem to be the most dominant cause of changes in transperitoneal transport during time on CAPD and when sodium nitroprusside was added to the peritoneal dialysate. Changes during peritonitis can be explained by changes in pore radius and depth. Individual differences can be explained by differences in "membrane" area and in resistance of the unstirred dialysate fluid. High residual dialysate volume can give rise to clinical problems and should be considered when placing the catheter in the peritoneal cavity.

Biological Transport↗

Gonadotropin-releasing hormone induces ovulation in hypophysectomized rats: studies on ovarian tissue-type plasminogen activator activity, messenger ribonucleic acid content, and cellular localization.

GnRH and its agonists are known to induce ovulation in hypophysectomized rats by acting directly at the ovary. Because tissue-type plasminogen activator (tPA) has been implicated in the gonadotropin induction of ovulation, we examined the effect of an ovulatory dose of GnRH on ovarian tPA activity, mRNA content, and cellular localization. Hypophysectomized immature rats were injected sc with 20 IU PMSG and a single dose of a GnRH agonist (GnRHa; des-Gly10,DLeu6(N alpha Me)Leu7,Pro9NHEt-GnRH) 58 h later. At different times after treatment, ovaries were prepared for morphological analysis. Using a fibrin overlay method, tPA activities were measured in ovarian homogenates and cumulus-oocyte complexes, whereas granulosa cells were cultured for 24 h to estimate tPA secretion. Total ovarian RNA was prepared for hybridization analysis of tPA message levels, and tPA localization was studied by immunohistochemistry of ovarian sections. GnRHa induced ovulation in PMSG-primed hypophysectomized rats 14-16 h after injection in a dose-dependent manner, and the GnRHa action was blocked by concomitant treatment with a GnRH antagonist. GnRHa stimulated the induction of tPA, but not urokinase-type PA, activity in ovarian homogenates and granulosa cell-conditioned medium in a time-dependent manner, reaching a maximum before ovulation. tPA activity in cumulus-oocyte complexes was also increased before ovulation, but this increase was sustained. Hybridization analysis of steady state tPA mRNA levels was performed using a rat cRNA probe. Northern blot analysis of total ovarian RNA demonstrated that GnRHa stimulated tPA mRNA levels 12 h after treatment, with a subsequent decrease 24 h after treatment. Immunohistochemistry indicated substantial increases in tPA staining in granulosa cells and oocytes of preovulatory follicles before ovulation. Thus, GnRHa acts through specific receptors to increase ovarian tPA enzyme activity, mRNA content, as well as immunostaining in granulosa cells and oocytes. Like gonadotropins, GnRH may induce ovulation by directly stimulating tPA levels in the ovary.

Animals↗

Differences among human immunodeficiency virus strains in their capacities to induce cytolysis or persistent infection of a lymphoblastoid cell line immortalized by Epstein-Barr virus.

Four strains of human immunodeficiency virus (HIV) manifest consistent differences in biologic behavior after infection of the X50-7 line of human umbilical cord lymphocytes immortalized by Epstein-Barr virus (EBV). Some dilutions of the first strain examined, human T-cell lymphotropic virus type III B, which is derived from a pool of patient isolates propagated in H9 cells, caused transient cytopathic effects (CPE) followed by recovery of a subpopulation of X50-7 cells which became virus carrier cultures. Other dilutions of the same virus stock completely lysed X50-7 cells. Two other strains, RF2 and YW, both from individual patients with acquired immune deficiency syndrome, always induced complete cytolysis of X50-7 cells at all dilutions which infected the cells. However, RF2 did establish persistent infection of H9 cells. A fourth strain, PH1-MN, from a child with acquired immune deficiency syndrome-related complex, induced only transient CPE in X50-7 and H9 cells, which thereafter always recovered to form carrier cultures. For all four strains, the dilutions of HIV stocks which caused CPE corresponded to dilutions which resulted in the detection of HIV polypeptides by immunoblot. Cytolysis in HIV-infected X50-7 cells was accompanied by a decrease in the amount of EBV nuclear antigen; however, HIV infection did not induce EBV replication. Thus CPE in X50-7 cells is due to replication of HIV per se and not to activation of EBV. The observations indicate that there are differences in the cytolytic properties of HIVs and that these differences are influenced by the target cell.

Acquired Immunodeficiency Syndrome↗

Self-poisoning with theophylline. The effect of repeated doses oral charcoal on drug elimination.

A heavy smoking male patient with moderate to severe theophylline poisoning is presented. Repeated doses of oral charcoal were given in addition to usual supportive treatment. During this treatment the elimination half-life of the drug (T1/2) was 2 hours. The toxic symptoms disappeared rapidly when the serum concentration was reduced to the therapeutic concentration range. T1/2 was approximately 24 hours in the same patient in a steady state study without oral charcoal treatment. Repeated doses of oral charcoal seem to increase theophylline elimination and should be administered in moderate to severe theophylline poisoning in addition to the usual supportive treatment and correction of metabolic disturbances.

Charcoal↗

Turns analysis (peak ratio) in EMG using the mean amplitude as a substitute of force measurement.

Several modifications of turns and mean amplitude analysis of the electrical activity of muscles have been suggested to avoid measurement of force. Previously we have shown that these modifications may overlook abnormalities if the analysis is performed at high force. A new modification is suggested: analysing the maximal value of the ratio of turns to mean amplitude (peak ratio), using the mean amplitude as an indication of force. It has been applied to a material in which the force was measured. The peak ratio was increased in 82% of 17 patients with myopathy and decreased in 36% of 14 patients with neurogenic disorders.

Adolescent↗

Pattern of electrical activity and force in normal and pathological muscle: S-index of turns and amplitude.

Cenkovich et al. (1982) found that a rotated hyperbolic curve fitted the relationship between the logarithm of cumulative amplitude (log A) and the logarithm of turns (log T). They found the intercept of the hyperbola (S-index) to be independent of force and suggested to use the S-index without measurement of the force as a diagnostic criterion. We have applied this modification of the method to our material previously published. In controls we found a slight increase in S-index with increasing force. The S-index was often increased in patients with myopathy and decreased in patients with neurogenic disorders, mostly at low to moderate force. The S-index was not better in discriminating patients from controls than the ratio of turns to mean amplitude.

Adolescent↗

Integrated electrical activity and number of zero crossings during a gradual increase in muscle force in patients with neuromuscular diseases.

In the brachial biceps muscle of 17 patients with myopathy and of 14 patients with neurogenic disorders the integrated electrical activity and number of zero crossings per unit time were analysed in 3 sites of each muscle every 100 msec during a gradual increase in force from zero to maximum within 10 sec. The analysis of integrated electrical activity could not discriminate between patients with myopathy and patients with neurogenic disorders. The slope of the linear relation between the square root of integrated electrical activity and force expressed in kilograms was increased in 44% of the patients with myopathy and in 64% of the patients with neurogenic disorders. The increase in slope may be due to increase in the ratio of electrical activity and force of individual motor units. The integrated electrical activity related to a force of 40% of maximum was decreased in about two-thirds of patients with myopathy and in about half of the patients with neurogenic disorders. This decrease in integrated electrical activity may be due to random loss of muscle fibres or to loss of whole motor units respectively. The integrated electrical activity was linearly related to mean amplitude between potential reversals per unit time (turns). The number of zero crossings was increased in 29% of the patients with myopathy and decreased in 70% of the patients with neurogenic disorders at a force of 30% of maximum. The number of zero crossings was linearly related to turns.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Processing of electrical activity in human muscle during a gradual increase in force.

The integrated electrical activity, the number of zero crossings and the number of turns, the mean amplitude and the ratio between them, of the electrical activity were compared in the brachial biceps muscle and the anterior tibial muscle of 20 controls. The electrical activity and force were analysed every 100 msec during a gradual increase in force from zero to maximum within 10 sec. The square root of integrated electrical activity increased linearly with increasing force. The slope of this relation was inversely related to maximum force when the increasing force was expressed in kilograms. The number of zero crossings per unit time increased with increasing force up to 40-60% of maximum force after which it remained constant. Comparison of 100 microV and 50 microV level detections suggested that there is a cancellation of small spike components in the electrical activity during higher force. The square root of integrated electrical activity was linearly related to mean amplitude between turns and the number of zero crossings was linearly related to the number of turns. In conclusion the information obtained by analysis of integrated activity and number of zero crossings is probably also obtained by number of turns and mean amplitude analysis.

Adolescent↗

Electrical muscle activity during a gradual increase in force in patients with neuromuscular diseases.

The electrical activity of the brachial biceps muscle from 31 patients with neuromuscular diseases were quantified during a gradual increase in force from zero to maximum within 10 sec. In patients with myopathy the ratio of potential reversals per 100 msec (turns) to mean amplitude was increased more often at 10% and 20% of maximum force than at greater force (i.e., in four-fifths of the patients). Similarly, the mean amplitude as a function of turns was more diagnostic at low than at high force, possibly due to an affection of low threshold motor units. In 14 patients with neurogenic disorders turns was decreased in nearly two-thirds of the patients at a force of 20% and 30% of maximum. In muscles where the force is easily determined it is suggested to quantitate the electrical activity during constant forces of 10% and 30% of maximum. In muscles where the force is difficult to determine the analysis of the ratio of turns to mean amplitude should be performed when motor unit potentials begin to interfere.

Adult↗

Long-term changes in transperitoneal water transport during continuous ambulatory peritoneal dialysis.

9 patients were observed prospectively during 14-40 months 003 continuous ambulatory peritoneal dialysis (CAPD) treatment. From start of CAPD, each patient recorded dwell time, drained ultrafiltration volume (delta V), initial glucose concentration in dialysate, dialy fluid intake, body weight and blood pressure on a special form. These data, together with monthly values for albumin, urea, creatinin, phosphate, glucose and beta 2-microglobulin in plasma and in instilled dialysate, were later fed into a specially designed computer program to compare changes in the monthly mean (+/- SEM) values. During 5 episodes of peritonitis, daily changes in delta V were also computed. A long-term increase in delta V was found in 4 and a decrease in 5 patients. In all 9 patients delta V changed intermittently. All changes were most pronounced for long dwell times as compared to shorter dwell exchanges. The decrease in delta V started within the first 12 months of treatment. In the daily routine were aware of decreased ultrafiltration capacity in 3 patients only. Intermittent monthly changes in delta V could partly be correlated to changes in daily fluid intake. No correlations were found between long-term changes in delta V and fluid intake. All except 1 patient gained progressively in body weight, but without correlations to fluid balance, blood pressure and plasma albumin concentration. At the start of the observation period, most patients loosing delta V during this study appeared to have a more permeable membrane with a higher absorption rate of glucose and higher equilibration ratios for creatinine and beta 2-microglobulin in 5-hours drained dialysate as compared with the other patients. However, this was not statistically different between the two groups of patients. During the observation period, most patients with decreased delta V also increased transperitoneal solute transport, while the solute transport decreased in patients with increasing delta V, but these changes were only significant for some patients. During peritonitis, delta V decreased significantly 1 day before any other signs of peritonitis. All changes in delta V were most pronounced for long dwell times as compared with short dwell times. It is suggested that changes in ultrafiltration can be related to altered permeability of the peritoneal membrane, which appear earlier and more frequent than suggested by others, and any loss of delta V can be explained by a more permeable ('open') peritoneal membrane. It is also possible that different diseases act differently on the permeability of the peritoneal membrane.

Adult↗

Biosynthesis of dimethylnitrosamine in dimethylamine-treated mice after exposure to nitrogen dioxide.

These studies demonstrate the nitrosating potential of NO2 in vivo in ICR mice. Groups of mice were gavaged with 2 mg dimethylamine (DMA) and exposed to NO2 at levels from 0.04 to 44.5 ppm for periods up to 4 hours. Mice were individually frozen and blended to a powder, aliquots of which were homogenized in ice-cold dicholoromethane and 35% aqueous methanol. Concentrates of organic extracts were analyzed or dimethylnitrosamine (DMN) by a Thermal Energy Analyzer with a gas chromatograph interface. Biosynthesis of DMN was dose- and time-dependent with relation to NO2 exposure, reaching a maximum yield of 60-70 ng/mouse (0.0035% DMA conversion) at 2 hours. DMN biosynthesis was inhibited by sodium ascorbate and, more effectively, by ammonium sulfamate.

Animals↗

Role of nitrogen dioxide in the biosynthesis of nitraosamines in mice.

Groups of three to four mice were gavaged with aqueous solutions of 2 milligrams of morpholine, after which they were exposed to nitrogen dioxide in inhalation chambers at concentrations of 0.2 to 50 parts per million for up to 4 hours. At sequential intervals during the exposure, mice were frozen and pulverized in liquid nitrogen, and the mice powder was extracted with ice-cold 35 percent aqueous methanol and dichloromethane; organic-phase concentrates were analyzed for N-nitrosomorpholine with a thermal energy analyzer interfaced to a gas chromatograph. The N-nitrosomorpholine yields, ranging up to about 2.3 micrograms per mouse, were time-dependent relative to the duration of exposure to nitrogen dioxide and dose-dependent relative to the concentrations of nitrogen dioxide; control levels (in mice that were gavaged with morpholine or distilled water and then exposed to air instead of nitrogen dioxide) were less than 5 nanograms per mouse. These preliminary studies demonstrate the in vivo nitrosating potential of nitrogen oxides.

Amines↗