Converting hemodialysis patients from intravenous paricalcitol to intravenous doxercalciferol - a dose equivalency and titration study.

AIMS: Doxercalciferol and paricalcitol are used to treat hyperparathyroidism in chronic kidney disease. This study was conducted to define equivalent dose requirements to convert patients from intravenous paricalcitol to intravenous doxercalciferol. METHODS: Following a 4-week baseline period using a fixed dose of paricalcitol, 42 adult hemodialysis subjects were assigned to receive a fixed dose of doxercalciferol for 4 weeks using a conversion factor of either 50 or 65% of the prior paricalcitol dose. During a 12-week titration period the doxercalciferol dose was adjusted to optimize iPTH levels into the range of 150 - 300 pg/ml. Annual costs to achieve equivalent iPTH control were calculated for both vitamin D analogs. RESULTS: During the doxercalciferol fixed-dose period, the average dose of doxercalciferol was 2.1 +/- 1.3 microg and 3.1 +/- 1.8 microg in the 50 and 65% dose conversion groups, respectively. During this period mean iPTH in the 50% dose conversion group increased by 24 pg/ml (p = 0.017). During the dose titration period, doxercalciferol was increased to bring iPTH within the target range. Calcium control was maintained with both conversion factors, while slightly better phosphorus control was seen in the 65% dose conversion group. Annualized treatment cost for doxercalciferol was 28% less expensive per patient than paricalcitol. CONCLUSION: Patients can be managed safely and effectively with conversion and dose titration from paricalcitol to doxercalciferol. Both conversion strategies maintained iPTH at clinically satisfactory levels. Furthermore, doxercalciferol therapy resulted in drug acquisition cost-savings.

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.

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.

[Natural Cryptosporidium sp. infection in broiler chickens in Morocco]. / Infection naturelle à Cryptosporidium sp. chez le poulet de chair au Maroc.

The prevalence of cryptosporidium infection was assessed in 38 broiler flocks. Two-hundred-and-twenty-five broilers were subjected to clinical and post-mortem examinations. Analyses of impression smears and tissue samples from the intestine, bursa of Fabricius and trachea revealed Cryptosporidium sp. in 37% of broiler flocks investigated. The prevalence of infection within flocks varied from 14 to 100%. High incidence of Cryptosporidium infection occurred in 36 to 45-day-old broilers (52%), but Cryptosporidium was not found in chickens under 25 days of age. Cryptosporidium sp. was detected in 24% of bursa examined, intestine (15%) and trachea (2%). In the bursa of Fabricius, Cryptosporidium-induced epithelial lesions were associated in most cases (94%) with lymphoid atrophy and depletion.

Increased serum triacylglycerol and cholesterol binding reserve in acute uremic rats.

In acute uremic rats (24 h after bilateral nephrectomy, serum urea 280-300 mg/dl) the interface tension of the serum is significantly reduced. Serum levels of triacylglycerol are significantly elevated in uremia, whereas cholesterol levels do not show a significant alteration. The in vitro serum binding reserve for both, triacylglycerol and cholesterol is considerably enhanced. These results let suppose the presence of tenside-like substances in uremic serum which may be involved in disturbed triacylglycerol transport from the serum to the tissues and in development of uremic hypertriglyceridemia.

[Study of principles in pathogenesis and therapy of fat embolism. IV. In vivo studies of drug-induced mobilization of embolized lung fat]. / Grundlagenuntersuchungen zur Pathogenese und Therapie der Fettembolie. IV. In-vivo-Untersuchungen zur Frage der medikamentösen Mobilisierbarkeit des embolisierten Lungenfettes.

Pluronic F 108 added to serum in a concentration of 1 g/dl proved as the optimal means to increase the fat emulgatory capacity. Similar concentrations were achieved in living rabbits by infusing 4.5 g per kg body weight. In spite of this higher dosage we failed to mobilize 131 J labelled fat, embolized into the lungs of the animals. It is concluded that also in humans there exists no possibility to mobilize fat emboli from the lungs by the application of tensides (non-ionic detergents, lecithin-preparations, bile salts) or of organic solvents (alcohol, ether). All these agents are capable to emulsify fat in vitro, however, only under vigorous shaking.--Because of the side effects of those agents their application on patients, suffering from posttraumatic fat embolism seems not to be justified.

[Basis examinations for pathogenesis and treatment of fat embolism. III. The interface tension of blood against lipids. B. Their influence by addition of surfactants and the effect on the lipid solubility in vitro]. / Grundlagenuntersuchung zur Pathogenese und Therapie der Fettembolie III. Die Grenzflächenspannung des Blutes gegen Lipide B. Ihre Beeinflussung durch Zusatz von Tensiden und die Auswirkung auf das Fettlösungsvermögen in vitro.

Various surfactants such as Pluronic L 61, L 64, F 68 and F 108, Tween 80 und Triton WR 1339 as well as bile acids and sodium taurocholate were tested for their capacity to reduce the interface tension against neutral lipids and for their capacity to induce stable emulsions of triglycerides in rabbit sera. No positive correlation was found to exist between the interface activity against neutral lipids and the lipid emulsifying capacity of rabbit sera, added with the surfactants. When ether was added to serum, the lipid emulsifying capacity was increased most at concentrations of about 0,0075 g ether per 100 ml serum. This is about 1/10 of the ether concentration, achieved during anesthesia at the stage of tolerance. Pluronic F 108 in non toxic concentrations was the agent increasing the lipid emulsifying capacity of rabbit (and human) sera most efficiently. It proved superior also to ethanol and ether and appears to be the most suitable agent for mobilization of embolized fat in lung vessels.

[Investigations concerning the mechanism of contrast damage. The significance lipophilia (author's transl)]. / Untersuchungen über den Mechanismus von Kontrastmittelschäden, die Bedeutung der Lipophilie.

The damaging action on vascular endothelia of meglumin iothalamate and of meglumin ioxitalamate was tested on the rat aorta. Ioxitalamate was significantly better tolerated than iothalamate. The octanol-water-partition coefficient of various contrast media was evaluated by assessing the iodine content of the octanol phase after mixing. The coefficients found were about 100 fold lower than the coefficients computed by Levitan and Rapoport. The significance of the octanol-water-partition coefficient for endothelial injuries caused by contrast media is disputed.