Enhanced extracorporeal elimination of valproic acid in overdose.

The treatment of the poisoned patient has been based on three main approaches: use of supportive nonspecific therapy, if available administration of antidotes and removal of the offending drug from the body. Gastric lavage and binding of nonabsorbed drug by activated charcoal are often used in an attempt to eliminate the intoxicating agent from the body. In addition, elimination of already absorbed drug can sometimes be enhanced by the induction of brisk diuresis coupled to manipulation of urine pH (e.g. alkalinise for salicylates) or applying extracorporeal techniques such as haemodialysis, haemofiltration or haemoperfusion. In this issue of the journal Meek et al. describe the application of haemodialysis in a patient with severe valproic acid (VPA) overdose and demonstrate an increased elimination after the start of haemodialysis.

Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 microM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations.

Induction of Ca2+ oscillations by selective, U73122-mediated, depletion of inositol-trisphosphate-sensitive Ca2+ stores in rabbit pancreatic acinar cells.

The effect of the putative inhibitor of phospholipase C activity, U73122, on the Ca2+ sequestering and releasing properties of internal Ca2+ stores was studied in both permeabilized and intact rabbit pancreatic acinar cells. U73122 dose dependently inhibited ATP-dependent Ca2+ uptake in the inositol (1,4,5)-trisphosphate-[Ins(1,4,5)P3]-sensitive, but not the Ins(1,4,5)P3-insensitive, Ca2+ store in acinar cells permeabilized by saponin treatment. In a suspension of intact acinar cells, loaded with the fluorescent Ca2+ indicator, Fura-2, U73122 alone evoked a transient increase in average free cytosolic Ca2+ concentration ([Ca2+]i,av), which was largely independent of external Ca2+. Addition of U73122 to cell suspensions prestimulated with either cholecystokinin octapeptide or JMV-180 revealed an inverse relationship in size between the U73122- and the agonist-evoked [Ca2+]i,av transient. Moreover, thapsigargin-induced inhibition of intracellular Ca(2+)-ATPase activity resulted in a [Ca2+]i,av transient, the size of which was not different following maximal prestimulation with either U73122 or agonist. These observations suggest that U73122 selectively affects the Ins(1,4,5)P3- casu quo agonist-sensitive internal Ca2+ store, whereas thapsigargin affects both the Ins(1,4,5)P3-sensitive and -insensitive Ca2+ store. Digital-imaging microscopy of Fura-2-loaded acinar cells demonstrated that U73122, in contrast to thapsigargin, evoked sustained oscillatory changes in [Ca2+]i. The U73122-evoked oscillations were abolished in the absence of external Ca2+. The ability of U73122 to generate external Ca(2+)-dependent Ca2+ oscillations suggests that depletion of the agonist-sensitive store leads to an increase in Ca2+ permeability of the plasma membrane and that the Ins(1,4,5)P3-insensitive Ca2+ pool is necessary for the Ca2+ oscillations.

[A single blood pressure reading during check-up for hypertension leads to a change in management more often than multiple readings]. / Enkelvoudige bloeddrukmeting bij een controlebezoek wegens hypertensie leidt vaker tot beleidsaanpassing dan multipele metingen.

OBJECTIVE: To define the number of blood pressure readings necessary during a patient's visit to serve as a correct reference for patient management. DESIGN: Observational study. SETTING: Outpatient clinic in the Netherlands. METHOD: In a period of 30 months blood pressure was measured in 250-300 patients with hypertension during 1008 patients' visits. All readings were done by the same physician in the same room with the same system, after the patients had been submitted to at least 10 minutes of supine rest. Three readings were taken simultaneously with a mercury sphygmomanometer and (via a Y-connector) with a semiautomatic oscillometric method. RESULTS: Blood pressure readings of 932 visits were available for further analysis. Both methods gave similar results for the mean of each reading and for the combination of 2 or 3 readings. Based on the first diastolic reading alone instead of the mean of 3 readings, 25% of the patients would have been subjected to different patient management. On the basis of the first two readings II% would have been treated differently. CONCLUSION: No definite recommendation can be made for the ideal number of blood pressure readings per visit, but with only 1 or 2 readings, 11-25% of the subjects would have been submitted to different management.