Tilt Table Testing of Young Adult Patients: Improved Speed and Sensitivity Using an Isoproterenol Bolus and a Continuous 60° Tilt

The tilt table is a diagnostic device used to induce vagal syncope and determine etiology. Sensitivity enhancing techniques, such as the administration of isoproterenol, can be applied to children and young adults to compensate for the otherwise low sensitivity (20%-30%) observed in that population. This study describes an improved test that offers a simplified approach while decreasing the amount of time involved by up to 50%, without compromising sensitivity. This 45-minute procedure relies on sensitization with isoproterenol administered as a 2- to 8-μg bolus instead of a continuous infusion. The isoproterenol is injected at the 30th minute of a 45-minute 60° tilt test without returning the patient to the supine position. In this study, the isoproterenol bolus tilt test was found to be "positive" in 24 of 30 patients reporting unexplained syncope: 10 cases before the 30th minute (11.2 ± 8.4 min) and 14 cases after administration of 5.1 ± 1,9 μg of isoproterenol.     

Solution-structure of a Peptide Designed to Mimic the C-terminal Hexapeptide of Endothelin

The peptide: Ac-cyclo(Cys-His-Leu-Asp-Cys)-Ile-Trp-OH, has been designed by computer-aided molecular-modelling techniques to mimic the proposed α-helical conformation of the C-terminal hexapeptide of endothelin. Two-dimensional proton nuclear magnetic resonance spectra were acquired for the peptide dissolved in d₆-DMSO or D₂O-H₂O and the distance and angle constraints incorporated into simulated annealing experiments. Conformers generated from the D₂O-H₂O data superposed on the corresponding main-chain atoms in the crystal structure of endothelin 1 and the solution structure of BQ-123 with root mean square co-ordinate differences of 0·9 Å and 0·77 Å, respectively. The peptide did not elicit antagonism of endothelin-induced in-vitro contractions of rabbit aorta (endothelin A receptor) or rabbit bronchus (endothelin B receptor) preparations. Because the peptide can adopt a conformer which closely matches the equivalent residues in the endothelin 1 crystal structure and in BQ-123, we suggest BQ-123 does not necessarily mimic the endothelin C-terminal region to achieve its antagonism, and that a helical conformation of the endothelin C-terminal hexapeptide does not favour its interaction at the endothelin B receptor.     

Stimulatory as well as inhibitory effects of ethinyloestradiol on the metabolic clearances of propranolol in young women

1   The metabolism of a single 80  mg oral dose of propranolol was determined in nine young women before and after administration of ethinyloestradiol alone (EE₂) or in combination with norethindrone (OC).
2   Whereas the total clearance of propranolol (2713±404  ml min⁻¹ (mean±s.e.mean)) was not significantly altered by either EE₂ (3365±347  ml min⁻¹) or the combined OC (2905±345  ml min⁻¹), significant changes in all three primary metabolic pathways were observed.
3   The clearance through side-chain oxidation decreased from 345±55  ml min⁻¹ to 262±33  ml min⁻¹ after EE₂ ( P <0.05). A similar reduction of cytochrome P450 metabolism by EE₂ has been observed for other drugs.
4   The clearance through glucuronidation increased from 364±61  ml min⁻¹ to 625±117  ml min⁻¹ after EE₂ ( P <0.01). Similar stimulation of glucuronic acid conjugation by EE₂ has also been observed for other drugs.
5   The clearance through ring oxidation increased from 697±109  ml min⁻¹ to 1280±162  ml min⁻¹ after EE₂ ( P <0.01). This observation appears to be a novel finding with EE₂ and cytochrome P450 metabolism.
6   The treatment with OC produced changes in propranolol's metabolic clearances which were qualitatively similar to those generated by EE₂.     

Cellular Fibronectin in Rheumatoid Synovium and Synovial Fluid: a Possible Factor Contributing to Lymphocytic Infiltration

Mouse monoclonal antibodies against ED sequence-containing cellular fibronectin (cFn) were used to show that Fn in the inflamed synovium is distinct from the major form of plasma Fn (pFn). An accumulation of cFn was seen at sites of hyperplasia of the rheumatoid synovial membrane and in the walls of small vessels in the synovium by immunofluorescence microscopy. cFn was also found in rheumatoid synovial fluid by immunoblotting. Approximately one-fifth of the T lymphocytes from rheumatoid synovial fluid bound to Fn. The binding of synovial fluid T cells was always higher than that from peripheral blood. These results have two implications. On the one hand, the cellular type of Fn may be an indicator of synovial inflammation. On the other hand, the deposition of Fn may be a factor contributing to the infiltration of mononuclear cells into the synovium.     

COSMETIC TATTOOING AS A TREATMENT OF PORT-WINE STAINS

Background. Medical treatment for port-wine stains frequently is cosmetically unsatisfactory. An alternative possibility is cosmetic medical tattooing. Methods. By means of a traditional Japanese tattooing technique, five patients were treated in multiple sessions until the color of the lesion matched that of the surrounding skin. Results. The results were excellent, the skin texture remained normal, and the patients could discontinue cosmetic camouflage. Discussions. Cosmetic medical tattooing when carefully done is a valuable addition to the medical armamentarium and may replace more aggressive techniques.     

Increased Expression of VLA-5 Adhesion Molecules on Synovial Fluid T Lymphocytes in Chronic Polyarthritis: a Consequence of T-Cell Activation

This study focuses on the consequences of T-lymphocyte activation in chronic polyarthritis in terms of expression of cell surface receptors interacting with extracellular matrix (ECM). The expression of the VLA group of integrins was studied on in vitro -stimulated peripheral-blood T cells, and on peripheral-blood and synovial-fluid mononuclear cells (MNC) of patients with polyarthritis. The VLA expression was measured by flow cytometry using monoclonal antibodies (MoAbs) against α-subunits of the VLA family. VLA-α4 and VLA-α5, but not VLA-α1, were expressed on a major fraction of unstimulated peripheral-blood T cells both in the patients with polyarthritis and in healthy individuals. Two distinct populations, VLA-α5-high and VLA-α5-low, were found in resting peuplieral-blood T lymphocytes. Two days after stimulation by phorbol 12-myristate 13-acetatc (PMA) and concanavalin A, most T cells became VLA-α5-high. In patients with chronic polyarthritis, the expression of VLA-α1 and VLA-α5 was always higher on synovial-fluid T cells than on peripheral-blood T cells. These results give further support to the hypothesis that upon activation the induction of the VLA adhesion-molecule expression may be a factor contributing to the accumulation of T cells in the inflamed synovium.     

CHANGES IN INTRAOCULAR PRESSURE ASSOCIATED WITH THE ADMINISTRATION OF PROPOFOL

The effect of propofol on intraocular pressure (IOP) was measuredin 25 patients presenting for elective non-ophthalmologicalsurgery when propofol was used for the induction and maintenanceof anaesthesia (together with 67% nitrous oxide in oxygen, andvecuronium). Normocapnia was maintained. After induction ofanaesthesia, intraocular pressure was significantly lower thanthe baseline value; during maintenance IOP never exceeded thepreinduction value. There was a temporary decrease in arterialpressure after induction. In nine patients a cutaneous flushwas observed and in seven patients there was discomfort on injection.Spontaneous movement in 20% and hiccup in 12% of the patientswere observed at the time of tracheal intubation.