Experimental comparison of albumin-sealed and gelatin-sealed knitted Dacron conduits. Porosity control, handling, sealant resorption, and healing.

Two high-porosity knitted Dacron vascular grafts sealed with aldehyde cross-linked gelatin or albumin were compared with respect to the following characteristics. Porosity control by the absorbable sealant was assessed with a water porosity meter at 120 mm Hg pressure. Ease of suturing was determined by an objective needle penetration test. Sealant resorption was assessed histologically in a subcutaneous immature rat model as well as in circulatory implants. Gross and microscopic healing characteristics were compared in circulatory implants in the thoracic aorta of sheep with use of a composite conduit in every animal, which allowed direct comparison of the two graft materials and minimized differences in healing between individual animals. Both grafts demonstrated excellent porosity control and better handling characteristics than woven Dacron. Sealant resorption was generally rapid, although residual albumin sealant was often seen adjacent to anastomoses. Residual sealant appeared to result in focally poor healing with focal loss of adhesion of surrounding tissue to graft. We conclude that details of sealant preparation and application can importantly influence the performance of presealed knitted Dacron grafts and should be carefully evaluated in the laboratory before clinical implantation is begun.     

Imidazoline antagonists of alpha 2-adrenoceptors increase insulin release in vitro by inhibiting ATP-sensitive K+ channels in pancreatic beta-cells.

1. Islets from normal mice were used to study the mechanisms by which imidazoline antagonists of alpha 2-adrenoceptors increase insulin release in vitro. 2. Alinidine, antazoline, phentolamine and tolazoline inhibited 86Rb efflux from islets perifused with a medium containing 3 mM glucose, i.e. under conditions where many adenosine 5'-triphosphate (ATP)-sensitive K+ channels are open in the beta-cell membrane. They also reduced the acceleration of 86Rb efflux caused by diazoxide, an opener of ATP-sensitive K+ channels. 3. ATP-sensitive and voltage-sensitive K+ currents were measured in single beta-cells by the whole-cell mode of the patch-clamp technique. Antazoline more markedly inhibited the ATP-sensitive than the voltage-sensitive current, an effect previously observed with phentolamine. Alinidine and tolazoline partially decreased the ATP-sensitive K+ current. 4. The four imidazolines reversed the inhibition of insulin release caused by diazoxide (through opening of ATP-sensitive K+ channels) or by clonidine (through activation of alpha 2-adrenoceptors) in a concentration-dependent manner. Only the former effect correlated with the ability of each drug to increase control insulin release stimulated by 15 mM glucose alone. 5. It is concluded that the ability of imidazoline antagonists of alpha 2-adrenoceptors to increase insulin release in vitro can be ascribed to their blockade of ATP-sensitive K+ channels in beta-cells rather than to their interaction with the adrenoceptor.     

ESWL in hemophilia B]

One of the most dramatic dangers in treating nephrolithiasis by ESWL is the development of intra- and perirenal bleeding, which requires therapeutic intervention. Even in patients whose blood parameters suggest they are healthy, hematomas are found in up to 80%. Therefore, ESWL must be regarded as contraindicated in patients with blood disorders. A case of a patient suffering from hemophilia B and from a large renal pelvic stone is reported, whom we treated by ESWL twice after sufficient substitution. X-ray revealed that the patient was stone-free on the 25th day after the first ESWL session. ESWL. A review of the literature is presented.     

Conservative therapy of phosphate calculi

Phosphate stones are divided in two groups: I. Infection stones = triple phosphate stones (struvite and carbonate apatite). II. Calcium phosphate stones = Hydroxy apatite. Ad I. For the formation of this stone, infection with urease-producing bacteria is essential. It is important to look for factors that cause infection and for metabolic abnormalities. Three possibilities for treatment are discussed: Acidifying the urine: orally with NH4NO3 or NH4Cl; dosage is possible up to 12 g a day (metabolic acidosis!). Irrigation for instance with Renacidin ; when using a nephrostomy-tube, one can start 5 days after the operation. It is important to look for fever and flank pain. Especially useful in cases with small residual stones. Reduction of phosphate excretion in urine ( Shorr -regimen). Some aluminium combinations reduce the intestinal phosphate absorption as a result of the formation of a nonabsorbable aluminium-phosphate combination. This can be combined with a low calcium- and phosphate diet. In several publications good results are shown. Also when using a less rigid regimen, satisfactory results are seen: decrease of the phosphate excretion from 30 to 17 mmol/24 h (own investigation). Urease-inhibitors result in a lower urine-pH and a decrease of the ammonium-concentration. there are only a few publications with results, but AHA seems able to reduce the stone size in 24% of the patients. Ad II. This stone is concerning formation and treatment much like the calcium oxalate stone. In case of an alkaline urine one must look for primary hyperparathyroidism and renal tubular acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variations in sheep serum conglutinating complement activity and pathway involved in reactivity with sheep erythrocytes sensitized by rabbit antibody

Based on conglutination tests with the sheep E-rabbit A indicator system, three types of sheep sera were encountered. Type 1 sera failed to directly conglutinate or sensitize sheep E-rabbit A for conglutination by bovine conglutinin. Type 2 sera also failed to directly conglutinate sheep E-rabbit A but sensitized the indicator for conglutination by bovine conglutinin. Type 3 sera both directly conglutinated and sensitized sheep E-rabbit A for conglutination. Changes in serum type were induced in sheep by venepuncture (type 1 to type 2) or venepuncture and an intraperitoneal injection of yeast cells (type 2 to type 3). Direct conglutinating activity of type 3 sera was inhibited by heating serum at 50 degrees C for 30 min and was not restored by alternative activation pathway factor B. Chelation of Ca2+ in type 2 and 3 sera blocked sensitization of sheep E-rabbit A for conglutination by bovine conglutinin, indicating that the classical activation pathway was involved.     

Decreased ferritin levels, despite iron supplementation, during erythropoietin therapy in anaemia of prematurity

Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions. There is, however, only scanty data on the effect of rHuEPO therapy on iron metabolism. We studied 29 preterm infants (age 34 ± 14 days) who were randomly assigned to receive either rHuEPO 900 U kg^-1 week^-1 with 6 mg kg^-1 day^-1 of iron for 4 weeks ( n= 15) or no therapy. The following parameters were evaluated and compared between and within groups at the beginning, during and at the end of the study: Haematocrit (SI), reticulocytes (10⁹μgl^-1), serum ferritin (μg1^-1) and iron (μmol 1^-1). The results were as follows. At the baseline, erythropoietin levels were similar in both groups: 7.2 ± 5.6 versus 6.2 ± 3.2 mU ml^-1 (NS). In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study: 0.34 ± 0.03 versus 0.28 ± 0.05 ( p = O.001). rHuEPO therapy increased the reticulocyte count from 130 ± 70 to 430 ± 200 ( p = 0.0002). However, rHuEPO therapy depleted both serum ferritin and it-on levels from 321 ± 191 to 76 ± 58 $uMgl^-1 ( p = 0.04) and from 18 ± 5 to 13 ± 4 μmoll^-1 ( p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and its sequelae; however, serum ferritin and iron levels were depleted. We suggest that the effect of rHuEPO may be further increased by higher iron supplementation.     

Ketamine and midazolam decrease cerebral blood flow and consequently their own rate of transport to the brain: An application of mass balance pharmacokinetics with a changing regional blood flow

Mass balance pharmacokinetics, with simultaneous blood sampling from an artery and the internal jugular vein, was used to characterize the cerebral uptake of ketamine, norketamine, and midazolam in normoventilated pigs. Intravenous injections of ketamine or midazolam decreased the cerebral blood flow (CBF)by one third, as measured by intermittent ¹³³Xewashout. By means of pharmacodynamic models, the effects on the CBFcould be predicted from the arterial drug concentrations. The high-resolution CBFvs. time curves thus generated allowed the calculation of cerebral drug levels from arteriovenous concentration gradients in spite of a continuously changing regional blood flow. By their effects on the CBF,ketamine and midazolam decreasetheir own rateof transport to the brain, the immediate 30-35% drops in CBFgiving similar reductions in initial net influx of drug. Physiological pharmacokinetic models assuming a constant regional blood flow are therefore not appropriate. Under clinical conditions, the CBFis determined mainly by the effects of the anesthetics and by the arterial CO ₂ tension. CBFchanges in either direction influence the transport of drugs to the brain and may consequently result in impaired or exaggerated drug effects.The study was supported by grants from the Swedish Medical Research Council (B91-14X-00084-27A), the Medical Faculty at Lund University, Malmö General Hospital, The Tore Nilsson Foundation for Medical Research, Warner-Lambert Scandinavia AB, Roche-Produkter AB, and the Laerdal Foundation for Acute Medicine.