Examination of the roles of glycoprotein Ib and glycoprotein IIb/IIIa in platelet deposition on an artificial surface using clinical antiplatelet agents and monoclonal antibody blockade

The mechanism of platelet thrombus growth on an artificial surface is incompletely understood. While glycoprotein (GP)Ib and GPIIb/IIIa are required for normal attachment and thrombus formation on subendothelium, their roles in platelet deposition to artificial surfaces remain unclear. Using selected platelet inhibitors (aspirin [ASA], low molecular weight dextran, monoclonal antibodies 10E5 [v GPIIb/IIIa], and 6D1 [GPIb]) we examined the mechanism of platelet deposition to polyethylene (PE) surfaces under steady laminar and oscillatory flow conditions. Polyethylene-100 (PE-100) tubes (0.86 mm internal diameter) were perfused under steady laminar flow with citrated human whole blood reconstituted with 111indium-labeled platelets at 312 seconds-1 shear rate in the presence and absence of platelet inhibitors. The effect of oscillatory flow on platelet deposition was examined in a microwell system using 3/16-inch diameter discs of National Heart, Lung, and Blood Institute primary reference PE as the test surface. ASA and dextran did not significantly (P greater than .05) inhibit platelet deposition in laminar flow (not tested in oscillatory). Antibody 10E5 was a potent inhibitor (laminar less than 1%, P less than .0001, oscillatory less than 1.6%, P less than .01) of platelet deposition in both systems, and in this case, true adhesion (first attached layer) was blocked. Antibody 6D1 unexpectedly inhibited 70% of platelet deposition (P less than .01) in steady laminar flow and 56.5% in oscillatory flow (P less than .01). Scanning electron microscopy demonstrated platelets atop platelets in the controls, rare platelets in the 10E5 group, and a patchy monolayer of platelets in the 6D1 group. Transmission electron microscopy of cross-sections confirmed these observations. We conclude that the adhesion of the first platelet layer to an artificial surface requires GPIIb/IIIa. The data also suggest that GPIb is required for the development of the second layer in vertical platelet thrombus growth.     

Opioid inhibition of cholinergic transmission in the guinea-pig ileum is independent of intracellular cyclic AMP

This study examined whether the inhibitory actions of opioids in the guinea-pig ileum were influenced by agents which mimic or elevate intracellular cyclic adenosine 3′,5′-monophospate (cyclic AMP) levels. In longitudinal muscle-myenteric plexus preparations, the mu agonist, [D-Ala², NMePhe⁴,Gly-ol⁵]enkephalin (DAGO) and the kappa agonist, dynorphin A-(1–13) depressed contractions of the longitudinal muscle evoked by electrical stimulation of myenteric neurons. Mean IC₅₀ values were 19 and 2.8 nM for DAGO and dynorphin, respectively. Neither forskolin, cholera toxin nor dibutyryl cyclic AMP affected significantlythe IC₅₀s for the opioid agonists. The experiments suggest that μ and agonists inhibit excitatory cholinergic transmission to the longitudinal muscle by intracellular effector mechanisms that do not involve cyclic AMP.     

The role of arthroscopy in the problem total knee replacement

Fourteen patients were retrospectively reviewed to examine the role of arthroscopy in the diagnosis and treatment of the problem total knee arthroplasty (TKA), and to define parameters for indications, techniques, and results. All patients had undergone a previous TKA, and postoperatively had problems with pain and/or range of motion. Routine evaluation failed to reveal sepsis or aseptic loosening. Arthroscopy was used to evaluate and treat certain specific conditions. The arthroscope was successful in removing loose bodies, correcting patella subluxation with an arthroscopic lateral release, excising a symptomatic pseudomeniscus, and releasing intraarticular adhesions to improve motion and relieve pain. The postoperative knee score improved 73%. Arthroscopy is a valuable tool to evaluate a painful TKA, and can be used to treat certain conditions that would otherwise require an arthrotomy. The rehabilitation time is easier on the patient and much quicker. Arthroscopy of a TKA does not compromise any future procedures. However, it remains a technically demanding procedure whose indications and expectations are still being defined.     

Effects of prostaglandins and the autonomic nervous system on the vasodilatory properties of nitroglycerin in conscious dogs.

This study was designed to assess the respective roles of prostaglandins and the autonomic nervous system in the responses to nitroglycerin (NTG) in conscious dogs. In vivo, NTG (1, 10, and 100 micrograms/kg i.v.) induced dose-dependent decreases in blood pressure and increases in heart rate and cardiac output. Coronary and carotid blood flows increased simultaneously, whereas responses in renal blood flow were biphasic, i.e., an initial decrease was followed by an increase above control at 10 and 100 micrograms/kg. NTG responses were not changed by indomethacin but were affected by chlorisondamine alone or in combination with indomethacin; tachycardia was abolished, and increases in cardiac output after 10 and 100 micrograms/kg were reduced by 26 and 32%, respectively, after ganglionic blockade and by 19 and 32%, respectively, after chlorisondamine plus indomethacin. In addition, increases in carotid blood flow in doses of 100 micrograms/kg were reduced by 88% after chlorisondamine and 83% after chlorisondamine plus indomethacin. Finally, in the presence of chlorisondamine plus indomethacin, NTG induced a more pronounced hypotension associated with a more pronounced renal vasodilation at the highest dose. Independent of indomethacin pretreatment, NTG in vitro induced a dose-dependent relaxation of the carotid, coronary, and renal arteries. Depending on the vascular bed, the reflex and local controls of circulation are affected differently by NTG.     

Prevalence of Legionella in pharyngeal secretions of patients with pharyngitis

A serological investigation has suggested that Legionella pneumophila may be associated with sore throat in adults. In a study of 177 adults and children with acute pharyngitis, Legionella species were not isolated from pharyngeal cultures, which utilized selective and nonselective buffered charcoal-yeast extract media. Group A beta-hemolytic streptococci were isolated from 14 percent of the 177 symptomatic patients. Throat cultures from 88 asymptomatic control subjects were negative for Legionella and beta-hemolytic streptococci. Further studies are needed to determine if Legionella species are associated with acute pharyngitis.     

Do viscous polysaccharides slow absorption by inhibiting diffusion or convection?

Viscous polysaccharides such as guar gum delay absorption probably by impairing the access of luminal contents to the absorptive epithelium. Measurements of the electrical resistivity of saline solutions were carried out to determine if guar gum (0.5, 0.75 and 1 per cent w/v), in concentrations which impaired absorption in vitro, delayed diffusion of solutes or inhibited convection of luminal contents. Our results indicated that guar had no effect on the mobility of ions in a completely unstirred solution but delayed the time taken for saline solutions of different resistivity to achieve complete mixing, when they were brought into contact inside a vessel, which was rotated at a constant speed. The time taken to achieve complete mixing was directly related to the viscosity of the guar solutions. The effect of intestinal contraction on the absorption of glucose was simulated in an in vitro model, consisting of a length of dialysis tubing, alternately contracted at each end. Movement of glucose out of the dialysis tubing was increased by increasing the rate of contraction. The incorporation of guar gum into the solution prevented the rise in glucose uptake produced by increasing the rate of contraction. These effects suggest that guar probably reduces absorption by resisting the convective effects of intestinal contractions.