Antiarrhythmic effect related to the plasma concentration of pentisomide in vivo and the antiarrhythmic-concentration relationship in vitro

Pentisomide, 2-(2-diisopropylaminoethyl)-4-methyl-2-(pyridyl)- pentanamide, is a novel antiarrhythmic agent structurally related to disopyramide. Using a glass bead arrhythmic model, the authors studied the antiarrhythmic effect of pentisomide in dogs by monitoring the plasma concentrations. When pentisomide was infused at 1 mg/kg/min for 20 min, the ventricular tachycardia was significantly reduced at 5 min after starting the infusion; the arrhythmias were reduced to less than 5% at the end of the 20 min infusion. The plasma-free concentration of pentisomide was about 3 micrograms/ml at 5 min; it increased to about 10 micrograms/ml at the end of 20 min infusion. With 0.3 mg/kg/min infusion, the arrhythmias were reduced to about 60% but were not significant at 20 min of infusion. The plasma-free concentration of pentisomide did not reach 3 micrograms/ml until 20 min of infusion. The 3 micrograms/ml plasma-free concentration for pentisomide seems to be a critical concentration in inducing a significant antiarrhythmic effect. Pentisomide dose-dependently inhibited ischaemia-reperfusion arrhythmia at doses of 30 microM and higher concentrations in vitro. In conclusion, pentisomide inhibits arrhythmias dependent with the plasma concentration or with the concentration of the external solution. The critical plasma-free concentration for inhibition of arrhythmias was 3 micrograms/ml (not equal to 10 microM) and the in vitro effect also had a similar concentration. Therefore, the in vivo and in vitro antiarrhythmic concentrations were well correlated.     

The use of external, noninvasive pacing for the termination of supraventricular tachycardia in the emergency department setting

STUDY OBJECTIVE: To determine the potential feasibility of external cardiac pacing for the termination of sustained supraventricular tachycardia in the emergency department setting. TYPE OF PARTICIPANTS: Three men and two women (mean age, 34 years) who presented to the ED with a narrow-complex, hemodynamically stable tachycardia that was later proven to be supraventricular in origin. INTERVENTION: Each patient underwent external overdrive pacing using a modified external pacemaker at a pulse amplitude of 120 mA and a rate between 240 and 280 pulses per minute. RESULTS: In four patients, external cardiac pacing was able to successfully terminate the tachycardia without complication. In one patient, the pacemaker was not able to terminate the tachycardia. CONCLUSION: We conclude that external, noninvasive pacing is a feasible means of terminating supraventricular tachycardia in the ED setting.     

Use of sea water in the flotation of carbonate rich sedimentary phosphate rock

There is an appreciable amount of carbonaceous sedimentary phosphate deposits in the northern Africa and the Middle East which are expected to gain importance in the near future because of the depletion of the deposits in Florida. In many of the regions where phosphate deposits are found there is a shortage of fresh water, and sea is not very far. The use of sea water instead of fresh water in flotation of carbonaceous phosphate rock is successfully demonstrated. Thus an appreciable reduction in the operating cost and an ample amount of saving in the fresh water resources of the region is expected.     

Characterization of platelet-activating factor synthesis in glomerular endothelial cell lines

Platelet-activating factor synthesis in two transformed lines of glomerular endothelial cells was characterized and contrasted with platelet-activating factor production in macrovascular-derived endothelial cells as well as with glomerular cells of mesenchymal origin. Platelet-activating factor synthesis was assessed in intact cells and in cell-free preparations. Glomerular endothelial cells constitutively synthesize bio-active alkyl-PAF, and this basal activity can be chronically augmented by various inflammatory and thrombotic agents. In contrast, thrombin-mediated platelet-activating factor formation in bovine pulmonary aortic endothelial cells as well as in glomerular mesangial cells is acute and transient. The potential role of anti-inflammatory prostanoids to function as negative feedback modulators of thrombin- or endothelin-mediated platelet-activating factor synthesis was also investigated, as the synthesis of platelet-activating factor is often associated with the formation of these prostanoids. Indomethacin augmented receptor-mediated platelet-activating factor synthesis while prostanoids of the E and I series reduced agonist-stimulated PAF synthesis. In summary, the unique capacity of glomerular endothelial cells to respond to inflammatory stimuli with sustained platelet-activating factor synthesis is a clear indication of this cell's pivotal role in augmenting the inflammatory response in the limited environment of the glomerulus.     

External surface and lamellarity of lipid vesicles: a practice-oriented set of assay methods

Three methods are presented for the determination of external surface of large lipid vesicles of different lamellarity with 2% absolute accuracy. These methods (referred to as EPR, NBD and TNBS assays) use different marker lipids which provide signals (electron paramagnetic resonance, fluorescence of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) residues, and UV absorption increase of 2,4,6-trinitrobenzenesulfonic acid after reaction with aminolipids, respectively). The signals change upon addition of different membrane-impermeant reagents due to reaction with marker lipids at the external vesicle surface. They were applied to the same vesicle samples, including unilamellar and multilamellar vesicles, both at two different lipid compositions. External surface data matched for the three assays within 2%, but only after appropriate redesign or adaptation of so far published procedures. Main improvements related to slow influx of reagents (TNBS and NBD assays) or to redistribution of marker lipids (EPR assay), obscuring determination of outer vesicle surface from fast reaction between reagent and readily accessible marker lipids. Furthermore, suitable strategies were found to obtain accurate 100% values (reaction of all marker lipids present), required to relate external vesicle surface to total surface. This included corrections for light scattering (NBD assay) and for turbidity (TNBS assay). These three methods appear to close a gap in the methodology to determine external surface of vesicles for typical practical needs. In particular, the reliability range of the NBD assay could be extended to marker lipid densities as low as 1 marker lipid per 3000 lipids.     

Fever, negative blood culture findings and absence of response to antibiotic therapy in a patient after a second aortic valve prosthesis

HISTORY AND CLINICAL FINDINGS: A 53-year-old patient had a prosthetic valve (St. Jude Medical 25) 9 years ago because of a Staphylococcus aureus endocarditis with severe aortic regurgitation. An initially mild, progressively more severe, aortic regurgitation then developed as a result of an empty paravalvular abscess cavity, requiring another valve replacement. Fever started on the 3rd postoperative day and persisted despite combined treatment with beta-lactam antibiotics and aminoglycoside. INVESTIGATIONS: At first no infectious focus could be identified radiologically or by echocardiography. But transoesophageal echocardiography revealed vegetations in the old abscess cavity. Several blood cultures were negative, while serological tests gave markedly raised antibody titers against Coxiella burnetii. DIAGNOSIS, TREATMENT AND COURSE: Assuming Coxiella burnetii endocarditis the patient was given doxycycline, 2 x 100 mg daily and cotrimoxazole, 1 x 960 mg daily. The fever subsided and the vegetations had disappeared after four weeks. Because of the high risk of recurrence the antibiotic treatment was to be continued for two years. CONCLUSION: Coxiella burnetii should be considered as a possible cause of fever of unknown origin, especially in patients with existing or operated cardiac valvar defects, when endocarditic vegetations have been demonstrated and several blood cultures have been negative.     

Requirement for transglutaminase in progesterone-induced decidualization of human endometrial stromal cells

Differentiation of endometrial stromal cells (decidualization) is essential for embryo implantation and maintenance of pregnancy. By sequential complementary DNA subtractive hybridization, one of the messenger RNAs (mRNA) induced by progesterone in human endometrial stromal cells decidualized in vitro was identified as that of a tissue transglutaminase type II (TGase). TGase mRNA was induced within 6 h after the addition of progesterone to the culture, and the effect was dose dependent. Both the TGase inhibitor monodansylcadaverine and oligodeoxynucleotide complementary to the TGase mRNA inhibited the decidualization, as assessed by PRL production and morphological transformation. Expression of TGase mRNA in human decidua and endometria exposed to high levels of progesterone in vivo was demonstrated by Northern blotting and in situ hybridization. These data suggest that TGase is necessary for the decidualization of human endometrial stromal cells and that clarification of the mechanism of action of TGase will facilitate further insight into the diagnosis and treatment of infertility.     

Spontaneous hemorrhage of an adrenal cortical adenoma causing Cushing''s syndrome

A modified surgical splint for Le Fort I osteotomies with transverse expansion is presented. The splint is made of a transpalatal stainless steel bar with acrylic abutment against the palatal surface of the molar and bicuspid tooth. It is rigid and renders excellent retention. It causes minimal patient discomfort, and oral hygiene is hardly compromised.