A comparison of the effects of renin inhibition and angiotensin converting enzyme inhibition upon bradykinin potentiation.

OBJECTIVE: The goal of the present study was to show that, in contrast to an angiotensin converting enzyme (ACE) inhibitor, Ro 42-5892, a new renin inhibitor, can block the renin-angiotensin system without potentiating skin reactions induced by bradykinin. DESIGN: Potentiation of skin reaction to i.d. injections of bradykinin and histamine was evaluated in guinea pigs in the presence and absence of the drug (placebo, Ro 42-5892 or cilazapril). The elimination rate of radioactive bradykinin in blood was measured in other groups of guinea pigs treated with the same drugs. Maximal effective doses of each drug were used. METHODS: Measurements of erythema area induced by bradykinin and histamine injection were performed using a digital planimeter. Radioactive bradykinin was measured in blood by high-performance liquid chromatography and followed over 40 min. RESULTS: The ACE inhibitor cilazapril increased the area of erythema induced by bradykinin but not that induced by histamine. In contrast, Ro 42-5892 did not potentiate the effect of bradykinin. In addition, cilazapril did not change the elimination rate of i.v. radioactive bradykinin in blood. CONCLUSION: These results suggest that potentiation of bradykinin-induced skin reaction by cilazapril is due to a tissular (and not systemic) inhibition of ACE and does not occur with Ro 42-5892. Thus, side effects such as rash, angioneurotic edema or cough, which have been attributed to bradykinin accumulation by ACE inhibitors, may not occur with the use of specific renin inhibitors such as Ro 42-5892.     

Demonstration of endothelial adhesion of sickle cells in vivo: a distinct role for deformable sickle cell discocytes.

Different morphologic and density classes of sickle cells (SS) may play distinct roles in the generation of vasoocclusion, explaining the complexity of this phenomena. The densest SS red blood cells (RBCs) (SS4) can induce vasoocculsion in ex vivo microcirculatory preparations as well as in an intact animal model. Previous studies of the interaction of SS deformable discocytes with endothelial monolayers or the rat ex vivo mesocecum preparation have shown adhesion that is desmopressin (dDAVP)-stimulated, von Willebrand factor (vWF)-mediated, and limited to the small venules. However, in vivo adhesion of SS RBCs to the endothelium has neither been demonstrated nor characterized; and, in particular, the relation of adhesion to vasoocclusion is unknown. Using an intact animal model that involves injecting saline-washed, density-defined SS RBCs into the femoral artery of a rat, we find that: (1) Quantitative studies of RBCs retained in the rat thigh using 99mTc-labeled RBCs and gamma camera imaging showed that dDAVP induces a threefold increase in retention of normal (AA) cells and deformable SS discocytes (SS2). (2) electron microscopy and Microfil injection show that the retention of SS2 cells is due to adhesion to the vascular endothelium with no evidence of obstruction. (3) H-1 magnetic resonance imaging showed that retention of SS4 cells induced a dose-dependent increase in tissue edema (presumable secondary to tissue hypoxia), while retention of AA or SS2 cells produced no change. We conclude that endothelial adhesion of deformable SS discocytes can be demonstrated in an in vivo animal model, that this adhesion is enhanced by dDAVP (presumably related to, but not necessarily limited to the release of vWF), and that this phenomenon per se does not lead to vasoocclusion. Nevertheless, adhesion of deformable SS discocytes may have consequences. We hypothesize that adhesion of SS discocytes could narrow the lumen of postcapillary venules and facilitate secondary trapping of SS4 cells and lead to subsequent vasoocclusion.     

Surgical tactics in acute gastrointestinal hemorrhage]

The results of treatment of 595 patients with acute gastro-intestinal bleeding are presented. Ulcer disease is the most frequent cause of bleeding. In its diagnosis, the use of gastroduodeno-fibroscopy is effective. In ineffective conservative therapy, the operative intervention is indicated.     

Nutritional dwarfing: is it a consequence of disturbed psychosocial functioning?

Nutritional dwarfing refers to a condition in which maladaptive eating patterns play a primary role in poor linear growth and delayed pubertal development. The present controlled study assesses whether nutritionally dwarfed children and adolescents differ in their psychosocial adjustment from healthy children and adolescents of comparable height in ways that might account for their undernutrition. Children with nutritional dwarfing (n = 16) were compared by standardized questionnaires with a short-stature (ie, heights below the fifth percentile) control group composed of children and adolescents with constitutional growth delay and/or familial short stature (n = 31). Scores on a self-report screening questionnaire for eating disorders did not differentiate the groups. Moreover, the vast majority of nutritionally dwarfed patients expressed a desire to have a heavier physical appearance. Whereas the groups were generally similar in self-perceptions of domain-specific competencies and positive psychosocial adjustment, the parents of nutritionally dwarfed children reported that their children showed significantly fewer externalized behavior problems. These findings suggest the existence of an eating disturbance that compromises growth in childhood and/or adolescence which, unlike anorexia nervosa, is not associated with evidence of psychopathology.     

Release of benzalkonium chloride from a heparin-bonded umbilical catheter with resultant factitious hypernatremia and hyperkalemia

Elevated serum sodium and potassium levels were recently observed when sampled through a heparin-bonded umbilical catheter and measured with certain ion-selective electrodes. The cationic surfactant, benzalkonium chloride (BZC), is known to falsely elevate those cations in serum. Inasmuch as most heparin-bonded umbilical catheters use BZC during the bonding process, an in vitro study was performed to estimate the quantity of BZC released and the duration of sodium and potassium elevations during pooled sera infusion. Three heparin-bonded umbilical catheters and 3 silastic umbilical catheters were first flushed with 0.3 mL of normal saline and then perfused with pooled sera (sodium, 142 mEq/L; potassium, 4.6 mEq/L) at 2.5 microL/h. Effluent samples were collected from 0 to 8 hours and analyzed by ion-selective electrodes. Elevated serum sodium concentrations from 160 to greater than or equal to 250 mEq/L and potassium concentrations from 6.0 to greater than or equal to 9.6 mEq/L were observed. The BZC concentration in the catheter effluent was measured by mass spectrometry, with peak values of 10 micrograms/mL detected by this method. When varying concentrations of BZC (1 to 100 micrograms/mL) were added directly to pooled serum, a dose-dependent increase in serum sodium was observed. These data demonstrate that BZC released from heparin-bonded umbilical catheters elevates serum electrolyte values measured with some ion-selective electrodes. The observed increase in sodium and potassium concentrations may lead to clinical errors in management. Benzalkonium chloride is associated with myriad of linical symptomatology. Whether this amount of BZC is toxic in the small premature neonate is presently unknown.     

Effects of the consequences of the Chernobyl accident on the child's body]

Overall 1580 children from the regions with unsafe radiation situation were examined comprehensively at different times after the accident. The data obtained were correlated to the results of examining 610 children of the control group. The basic group children manifested a higher incidence of diverse alterations on the part of many organs and systems, which was accompanied by an increase of free radical processes signs of destabilization of cellular membranes, activation of blood cell metabolism, suppression of the T cell component of immunity in the presence of vegetovascular dysfunction. A tendency was noted toward normalization of these alterations seen over time after the accident. No clear-cut dose-effect dependence was found.