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Biomedical subjects

F G Cosio

Publications and source records attributed to F G Cosio.

At least 109 records · Page 6Linked to original sources

Atheroembolic renal disease causes hypocomplementaemia.

7 patients with atheroembolic renal disease were found to have hypocomplementaemia. Evidence obtained in an experimental model of atheroembolic disease shows that the hypocomplementaemia is the result of complement activation by the atheromatous material in vivo. In addition to hypocomplementaemia, 6 patients had thrombocytopenia and 5 had eosinophilia. These observations indicate that atheroembolic disease should now be included in the differential diagnosis of hypocomplementaemia. In addition, atheroembolic disease should be considered in patients presenting with a combination of multisystem disease, hypocomplementaemia, thrombocytopenia, and eosinophilia--a syndrome which previously would have been regarded as diagnostic of immune-complex-mediated vasculitis.

Aged↗

Decreased plasma fibronectin levels in children with hemolytic-uremic syndrome.

Fibronectin is a normal plasma glycoprotein thought to have an important role in platelet aggregation and clot formation. Because of the participation of the coagulation system in hemolytic-uremic syndrome, the present study sought to determine if fibronectin plays a role in the pathogenesis of this disease. With this purpose in mind, plasma fibronectin levels were measured in 17 children with the clinical diagnosis of hemolytic-uremic syndrome and in 22 age-matched control subjects. Fibronectin levels were significantly depressed in 13 of 17 (76 percent) patients with hemolytic-uremic syndrome during the acute phase of their illness. The levels did not correlate with age, sex, serum creatinine level, platelet count, or hemoglobin concentration. Serial plasma samples were available in eight of these patients: fibronectin remained depressed from two to 10 days and then returned toward the normal range concomitant with increasing platelet counts and improvement in renal function. During remission, fibronectin levels were normal in all nine patients tested. To try to determine if fibronectin is deposited in the kidney during hemolytic-uremic syndrome, kidney biopsy specimens from six patients with hemolytic-uremic syndrome were examined by immunofluorescence for the presence of fibronectin, fibrinogen, and platelet antigens. Extensive deposition of all three antigens was demonstrated along the glomerular capillary wall in all biopsy specimens. In conclusion, plasma fibronectin levels are decreased during the acute phases of hemolytic-uremic syndrome in the majority of patients. Kidney biopsy findings suggest that fibronectin is intimately involved in the activation of the coagulation system in this disease and that decreased plasma fibronectin levels in hemolytic-uremic syndrome may be due, at least in part, to accelerated consumption of the protein at the sites of injury.

Adolescent↗

Plasma concentrations of the natural anticoagulants protein C and protein S in patients with proteinuria.

We measured the plasma concentrations of the natural anticoagulant protein C and its cofactor protein S in 17 patients with severe proteinuria. In addition, prothrombin and antithrombin III levels were measured in the same group of patients. These results were compared with results obtained in 26 healthy controls and a group of 14 patients with chronic renal insufficiency (CRI) but minimal proteinuria. Protein C, protein S, and prothrombin levels were not significantly different between healthy controls and patients with CRI. However, protein C, protein S, and prothrombin levels were significantly elevated in 71%, 82%, and 76%, respectively, of patients with proteinuria. Antithrombin III levels were decreased in three of these 17 patients with proteinuria. Plasma concentrations of protein C, protein S, and prothrombin correlated significantly with each other and were inversely correlated with serum albumin concentrations. In three patients, high protein C, protein S, and prothrombin levels returned to normal during remission of the proteinuric state. Proteins C and S were not detectable in the urine of two patients with high-grade proteinuria. Thus, the plasma levels of the vitamin K-dependent, natural anticoagulant protein C and its cofactor protein S are increased in patients with proteinuria. The elevated plasma levels of other vitamin K-dependent proteins, such as prothrombin, suggest a generalized elevation in vitamin K-dependent protein synthesis in patients with proteinuria.

Adolescent↗

Influence of basic atrial rhythm on intraatrial conduction of extrastimuli.

Atrial arrhythmias appear to be related to the genesis of intraatrial conduction delays by extrastimuli. To clarify the effects of the basic atrial cycle on intraatrial conduction of extrastimuli, atrial conduction delays and conduction delay zones were measured in 22 patients with and without atrial arrhythmias. Basic cycles were (A) sinus rhythm; (B) paced at the right atrial (RA) appendage with maximum cycle length possible; (C) paced at the RA appendage with cycle length of 600 ms; and (D) paced at the proximal coronary sinus at the same cycle length as B. Extrastimuli were always delivered at the RA appendage. Conduction delays and conduction delay zones were 5- to 7-fold longer when driving stimuli and extrastimuli were delivered through the same electrodes than when the basic cycle was sinus or driven at a distance from the extrastimuli (p less than 0.001). This effect must be considered when groups of patients or the results of interventions are compared.

Atrial Fibrillation↗

Abnormal plasma fibronectin levels in patients with proteinuria.

We measured plasma fibronectin levels in 21 patients with severe proteinuria secondary to primary renal disorders and compared those results with values obtained in 77 healthy volunteers and 15 patients with chronic renal disease but minimal proteinuria. Seventeen of the 21 patients with proteinuria (81%) demonstrated plasma fibronectin concentrations greater than 2 SDs above control values. Fibronectin levels in the group with chronic renal disease did not differ from normal values. In the group with proteinuria, plasma fibronectin levels were inversely correlated with total serum protein and serum albumin concentrations but were not correlated with the degree of proteinuria, serum creatinine level, or histologic diagnosis of kidney disease. The possible relevance of these findings to the hypercoagulable state of the nephrotic syndrome is discussed.

Adolescent↗

Human fibronectin is an opsonin for IgG antibody-coated sheep erythrocytes.

We studied the effect of human fibronectin on the binding and phagocytosis of IgG antibody-coated sheep erythrocytes (EA) by human monocytes. EA were preincubated with or without fibronectin (100 micrograms/ml) at 37 degrees C for 3 hours and both EA and EA-fibronectin were subsequently exposed to monocyte monolayers. A significantly higher percent of monocytes formed rosettes and phagocytosed EA-fibronectin than EA. To determine if the enhancing effect of fibronectin was on the EA or on the monocytes, several experiments were performed. EA were preincubated with or without fibronectin for 3 hours, washed, and added to monocyte monolayers. Percent rosettes and phagocytosis was significantly higher in monocytes incubated with EA-fibronectin than with EA. By contrast, preincubation of monocytes with soluble fibronectin at 37 degrees C for 15 minutes had no significant effect on their ability to bind or phagocytose EA. Thus fibronectin affects EA and enhances its binding to the monocytes. Both monocyte-EA and EA-fibronectin rosettes were completely inhibited by preincubation of monocytes with large concentrations of heat-aggregated IgG. However, below this maximal inhibitory concentration, heat-aggregated IgG produced significantly less inhibition of EA-fibronectin than EA rosettes. Our results suggest that EA-fibronectin binds exclusively to the monocyte Fc receptor and that fibronectin enhances the affinity of EA for the receptor. We did not demonstrate any effect of fibronectin on the interaction of monocytes with IgM antibody-coated or heat-damaged sheep erythrocytes. In conclusion under our test conditions, fibronectin acts as a opsonin for EA.

Animals↗

Electrophysiologic studies in atrial fibrillation. Slow conduction of premature impulses: a possible manifestation of the background for reentry.

Extrastimulus-induced intraatrial conduction delays were measured in 12 patients with documented episodes of atrial fibrillation (AF) by recording atrial electrograms at the high right atrium, His bundle region, and coronary sinus. Seventeen patients with and without heart disease, but without atrial arrhythmias served as the control group. During baseline-paced atrial rhythms, a conduction delay zone could be delineated, near the atrial effective refractory period, during which all extrastimuli produced conduction delays. When compared at the same paced cycle lengths (500 to 650 ms), the patients with AF had shorter atrial effective refractory periods (mean +/- standard deviation 206 +/- 24.1 versus 233 +/- 28.2 in control patients, p less than 0.02), wider conduction delay zones (79 +/- 21.7 ms versus 52 +/- 21 in control patients, p less than 0.01), and longer conduction delays both to the His bundle region (64 +/- 18.3 ms versus 35 +/- 21.7 in control patients, p less than 0.005) and the coronary sinus (76 +/- 18.9 ms versus 35 +/- 16.1 in control patients, p less than 0.001). Repetitive atrial responses were recorded in 6 patients with AF and in 9 control subjects. Sinus nodal function abnormalities were detected in 6 of the patients with fibrillation. Patients with AF had a higher tendency than control subjects to develop slow intraatrial conduction, as well as shorter effective refractory periods. Since both features would favor reentry, they may be the electrophysiologic manifestations of the abnormalities making these patients prone to atrial reentrant arrhythmias. Repetitive atrial responses were of no predictive value. Sinus nodal dysfunction was frequently found, but was not essential for the occurrence of AF.

Adult↗

Onset of atrial fibrillation during antidromic tachycardia: association with sudden cardiac arrest and ventricular fibrillation in a patient with Wolff-Parkinson-White syndrome.

Electrophysiologic evaluation in an 18 year old youth with the Wolff-Parkinson-White syndrome who had a sudden cardiac arrest while playing racquetball revealed two types of paroxysmal reciprocating tachycardia: (1) A normal QRS tachycardia with a short ventriculoatrial (V-A) interval fulfilled the criteria for reentry within the atrioventricular (A-V) node; and (2) a wide QRS tachycardia with a QRS configuration of maximal preexcitation was demonstrated to be the result of an antidromic mechanism. During laboratory study, the wide QRS tachycardia spontaneously degenerated into atrial fibrillation. In the basal state, the shortest R-R interval between preexcited QRS complexes was 270 ms, but after infusion of isoproterenol (1.6 microgram/min intravenously), the shortest R-R interval became 180 ms. Consequently, this electrophysiologic study suggested that evolution of antidromic reciprocating tachycardia into atrial fibrillation with a rapid ventricular response during exercise-induced catecholamine release may have been the mechanism for ventricular fibrillation in this patient.

Adolescent↗

The human FcR. III. Effects of pronase on soluble immune complex binding by polymorphonuclear leucocytes, monocytes and pulmonary macrophages.

The effect of Pronase incubation on the Fc receptors of human polymorphonuclear leucocytes (PMN), monocytes and pulmonary alveolar macrophages was evaluated by Scatchard analysis of the binding of soluble immune complexes at equilibrium. All three cell types, when preincubated with Pronase, demonstrated a significant increase in Fc receptor affinity. Maximum binding (which measures the number of Fc receptors) on polymorphonuclear leucocytes was reduced 45%-50% but was unchanged on monocytes and pulmonary macrophages. The changes in Fc receptor affinity and maximum binding of the PMN were reversible in short-term culture, an effect which was prevented by cycloheximide. These studies indicate that the affinity of the Fc receptor of human phagocytic cells may change significantly independent of changes in receptor number and that this effect can be caused by extracellular proteases. In addition, the human polymorphonuclear leucocyte demonstrates a subpopulation of Fc receptors which is decreased by Pronase and which recovers, in vitro, by a process requiring protein synthesis.

Antigen-Antibody Complex↗

Binding of soluble immune complexes by human monocytes and pulmonary macrophages: effects of cigarette smoking.

The Fc receptor of human monocytes and pulmonary macrophages has been evaluated quantitatively by binding of radiolabeled soluble IC. On both cell types, binding was mediated by saturable surface receptors specifically inhibited by aggregated human IgG1 and IgG3. The affinity of the Fc receptor was similar on monocytes and pulmonary macrophages from nonsmokers, but macrophages demonstrated four to 13 times more surface receptors than circulating monocytes. No difference in Fc receptor binding of monocytes was observed between cigarette smokers and nonsmokers. However, pulmonary macrophages from smokers demonstrated a significantly lower Fc receptor affinity than did those of nonsmokers, although the number of Fc receptors was the same.

Antigen-Antibody Complex↗

Pneumococcal vaccination in patients with chronic renal disease and renal allograft recipients.

Polyvalent pneumococcal vaccine was administered to 7 patients with chronic renal failure, 14 patients on chronic hemodialysis, 14 splenectomized and 11 nonsplenectomized renal allograft recipients, and 14 normal adults. Ninety-three percent of normal subjects had at least a twofold rise in serum antibody concentration after vaccination, with a geometric mean antibody concentration after vaccination greater than 200 ng N/ml. The response to vaccination in hemodialysis patients was similar to that in normal persons. Renal failure patients showed impaired antibody synthesis in response to the vaccine, with 43% achieving at least a twofold rise in antibody concentration. Allograft recipients had a lower antibody concentration before as well as after vaccination, and among splenectomized recipients the prevaccination antibody concentration was directly related to the interval between transplantation and antibody determination. But, 80% of allograft recipients achieved a twofold rise in antibody concentration after vaccination. The response to pneumococcal vaccine was quantitatively similar for splenectomized and nonsplenectomized allograft recipients.

Adolescent↗

Severe renal failure in multiple myeloma.

Twenty-four patients with multiple myeloma and renal failure severe enough to require dialysis were retrospectively analyzed. Most patients initially presented with renal failure and multiple myeloma was subsequently diagnosed. Intravenous pyelography precipitated irreversible renal failure in 2 patients. Absence of light chain disease and treatment with peritoneal dialysis were associated with increased recovery of renal fraction. The one year survival rate of myeloma patients on chronic dialysis was similar to the general myeloma population but was much worse than a group of age matched non-myeloma chronic dialysis patients. Survival rate was diminished in patients with elevated serum calcium levels.

Acute Kidney Injury↗

Soluble immune complexes binding to human monocytes and polymorphonuclear leucocytes.

Soluble human serum albumin anti-albumin immune complexes (IC) have been shown to bind to freshly isolated human peripheral blood monocytes and polymorphonuclear leucocytes (PMN) in vitro. Binding sites on both cell types were saturable and specifically inhibited by heat aggregated IgG1 and IgG3 subclasses. PMN contained a greater number of binding sites than monocytes although the affinity was similar for both cell types. The enhanced binding of IC by both cell types observed after incubation at low pH (pH 6.0) was a consequence of increased affinity of the PMN binding site and an increase in the number of sites in monocytes. Binding of IC by both cell types was inhibited by normal human serum. Enhanced IC binding associated with enhanced affinity and number of sites was observed in PMN and monocytes preincubated in suspension with trypsin. However, monocytes exposed to trypsin while adherent to microexudate coated flasks demonstrated a marked increase in affinity without any change in the number of sites.

Animals↗