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Biomedical subjects

F G Cosio

Publications and source records attributed to F G Cosio.

At least 55 records · Page 3Linked to original sources
PubMed1996

Radiofrequency ablation of atrial flutter.

Activation mapping in common atrial flutter has shown circular (reentrant) activation of the right atrium around anatomic structures and areas of functional block. The direction of rotation is counterclockwise (in a frontal view), and in the low right atrium the myocardium between the inferior vena cava (IVC) and the tricuspid valve (TV) is critical to close the activation circle. The circuit can be interrupted by radiofrequency ablation of the myocardium between the TV and the IVC, and, in some cases, by ablation between the coronary sinus and TV. Flutter interruption does not mean complete isthmus ablation, as it may remain inducible, requiring further ablation. Despite attaining noninducibility, flutter may recur, and new procedures may be needed for complete ablation. Atrial fibrillation occurs in up to 30% of the cases during follow-up but is generally well controlled with antiarrhythmic drugs that were ineffective in treating flutter before ablation. Some noncommon atrial flutters show circular right atrial activation in a reversed (clockwise) direction, with the same critical areas in the low right atrium, and in these isthmus ablation is effective. Other noncommon flutters have different substrates in the right or left atrium, and mapping has to define specific critical isthmuses as ablation targets in each case. Left atrial flutter circuits remain inaccessible to ablation.

Atrial Fibrillation↗
PubMed1996

Favorable prognostic significance of raised serum C3 concentration in patients with idiopathic focal glomerulosclerosis.

This study examined the relationship between the clinical and pathologic variables and renal outcome in patients with idiopathic focal glomerulosclerosis (FGS). The study population included 106 patients with biopsy proven idiopathic FGS followed for a mean of 31 months. Forty-nine patients (46%) maintained stable renal function, 21 patients (20%) had a progressive deterioration of renal function and an additional 36 patients (34%) progressed to end-stage kidney disease. By multivariate analysis the following baseline variables (i.e. variables measured at the time of renal biopsy) were associated with the loss of renal function: 1. An elevated serum creatinine; 2. an elevated systemic blood pressure; 3. extensive interstitial fibrosis and tubular atrophy by kidney biopsy; 4. a low-normal serum C3 level. At baseline serum C3 levels were abnormally high in 31 patients (29%). Baseline C3 levels were inversely correlated with baseline serum creatinine levels (p < 0.0001), the severity of histologic changes (p < 0.0001), and better preservation of renal function during follow-up (p < 0.0001). Serum C3 levels did not correlate with proteinuria or with other clinical variables tested. The presence of C1q in the mesangium did not correlate with renal outcome. In conclusion, serum C3 levels measured at the time of biopsy correlate with renal outcome in patients with idiopathic FGS. The basis for this correlation is unknown but it cannot be fully explained by relationships between serum C3 levels and other clinical variables.

Adult↗
PubMed1996

Radiofrequency catheter ablation of atrial flutter circuits.

Common atrial flutter is due to reentrant activation of the right atrium, rotating around anatomic structures and areas of functional block, in counterclockwise direction in the frontal plane. The myocardium between the inferior vena cava and the tricuspid valve is critical to close the activation circuit, and ablation of this isthmus by catheter-delivered radiofrequency can interrupt flutter, and eventually destroy the circuit, preventing recurrence of the arrhythmia. Flutter interruption does not mean complete isthmus ablation, and the procedure endpoint is to attain flutter non-inducibility, and isthmus block. Despite non-inducibility, flutter may recur, and new procedures may be needed for complete ablation. Atrial fibrillation can occur in up to 35% of the cases during follow-up but is generally well controlled with drugs that were ineffective against flutter before ablation. Some atypical atrial flutters show circular right atrial activation, using the same circuit in a clockwise direction, and these can also be interrupted by ablation of the inferior vena cava-tricuspid valve isthmus. Other atypical flutters can have different anatomic substrates in the right or left atrium, and mapping has to define specific isthmuses as ablation targets in each case. Left atrial flutter remains inaccessible to ablation.

Atrial Flutter↗
PubMed1995

Racial differences in renal allograft survival: the role of systemic hypertension.

The rate of decline in the number of functioning renal allografts beyond the first year after transplantation has changed little in the last 25 years, and during long-term follow-up most allografts are lost due to chronic transplant rejection or patient death. The recipient race correlates with allograft survival, and African American recipients have a lower allograft survival than Caucasians. The goal of the present study was to identify clinical variables present during the first six months after transplantation that predict the loss of renal allografts beyond six months after transplantation, and in particular to determine the role of systemic hypertension on renal allograft survival in black and white recipients. This study includes 547 recipients of first cadaveric renal allografts performed at The Ohio State University. All patients were treated with a uniform immunosuppressive protocol and had a follow-up of at least three years. By multivariate analysis the following variables correlate with poor allograft survival: an elevated serum creatinine concentration measured six months after transplantation (SCr6mo) (P < 0.0001); black race (P < 0.0001); increasing numbers of acute rejection episodes (ATR) (P = 0.002); and young recipients (P = 0.026). Allograft survival is significantly worse in black (mean allograft half-life of 7.7 +/- 1.3 years) than in white recipients (24 +/- 3 years) (P < 0.0001). Black recipients also have a significantly higher six month average mean arterial blood pressure (MAP) (105 +/- 8 mm Hg) than white recipients (102 +/- 7 mm Hg) (P = 0.002). However, the prevalence of hypertension is not significantly different in black (33%) than in white recipients (26%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effects of high glucose concentrations on human mesangial cell proliferation.

High concentrations of glucose in vitro inhibit cell proliferation and stimulate matrix protein synthesis. These studies sought to characterize the relationship between the effects of glucose on cell proliferation and matrix synthesis and to assess the mechanism(s) responsible for these cellular effects of glucose. The initial experiments showed that high glucose levels stimulate fibronectin (FN) synthesis by human mesangial cells (HMC) but only in those cultures in which cell proliferation was inhibited by glucose. To assess whether this relationship was due to an effect of glucose on the capacity of HMC to respond to cytokines, the responses of HMC to serum or cytokines were measured in the presence of different glucose concentrations. High concentrations of glucose inhibited (3H)thymidine incorporation in response to serum and platelet-derived growth factor. Under the conditions of these experiments, transforming growth factor-beta (TGF-beta) also stimulated thymidine incorporation by HMC, and high glucose concentrations inhibited thymidine incorporation in response to TGF-beta. In contrast, high concentrations of glucose did not inhibit the stimulation of FN synthesis caused by platelet-derived growth factor, serum, or TGF-beta. The antiproliferative effects of high glucose levels were first observed after 48 h of incubation and were reversible after the withdrawal of high glucose from the media. The following evidence suggest that the effects of glucose may be mediated via protein kinase C (PKC): (1) incubation with high glucose concentrations caused an increase in HMC PKC levels; (2) PKC activation with phorbol esters inhibited HMC proliferation; and (3) depletion or inhibition of PKC stimulated HMC proliferation and prevented the antiproliferative effects of glucose. In contrast to these findings, inhibitors of protein glycosylation and myo-inositol supplementation of culture media did not prevent the antiproliferative effects of glucose. In conclusion, high glucose concentrations acutely and reversibly inhibit HMC proliferation, perhaps by a PKC-dependent mechanism. Because PKC can also stimulate FN synthesis, glucose-induced changes in PKC may explain the relationship between the effects of high glucose concentrations on cell proliferation and FN synthesis.

Blood Physiological Phenomena↗
PubMed1994

Angiotensin-converting enzyme inhibition partially prevents diabetic organomegaly.

The present study was conducted to evaluate whether captopril prevents the organomegaly and accumulation of matrix proteins that normally accompanies the diabetic state. The following groups of rats were studied: normal rats, normal rats treated with captopril (30 mg/kg/d orally), streptozotocin diabetic rats, and diabetic rats treated with captopril. All rats were killed at 10 weeks for histologic and morphometric evaluation of tissues. Compared with the normal rats, the diabetic rats demonstrated significant hepatomegaly, nephromegaly, and cardiomegaly, and the increase in organ size was directly related to increasing levels of protein glycosylation. The development of organomegaly was partially prevented by captopril. We determined by morphometry that the hepatomegaly seen in the diabetic rats was due to an increase in cell size and number, while the nephromegaly seen in the diabetic rats was due to an increase in tubular and glomerular cell size and is associated with glomerular hypertrophy. Captopril prevented the development of hepatic and renal cell hypertrophy and glomerular hypertrophy. These effects of captopril were not associated with detectable changes in body weight or levels of glucose, protein glycosylation, glycosuria, or renal histologic changes secondary to glycosuria. The diabetic rats demonstrated significant glomerular mesangial matrix expansion, and captopril treatment partially prevented that expansion. In conclusion, captopril prevents, in part, the development of organomegaly in diabetic rats, and this effect is due mainly to the prevention of the development of cellular hypertrophy. The present findings are most consistent with a direct effect of captopril on cell metabolism during diabetes mellitus.

Analysis of Variance↗
PubMed1994

Association of thin glomerular basement membrane with other glomerulopathies.

In the present study we assessed the prevalence of thin glomerular basement membrane (TGBM) in a large group of native kidney biopsies done for evaluation of renal disease. TGBM was present in 54 of 1078 biopsies (5%). In 12 of 54 biopsies (24%), TGBM was the only abnormality present. In the remaining biopsies TGBM was associated with other pathologic diagnoses. The overall prevalence of TGBM in this series is comparable to previous population studies. TGBM is significantly more common in patients with IgA nephropathy and mesangial proliferative glomerulonephritis. Compared to control patients, individuals with TGBM were more likely to have a history of familial hematuria (14% vs. 43%, P = 0.02). Furthermore, examination of urinary sediments in first degree relatives of patients with TGBM demonstrated microscopic hematuria in 92% of families and, in those families, hematuria was present in 47 +/- 6% of relatives. In contrast, hematuria was discovered in 38% of families of control patients, affecting 25 +/- 5% of relatives. In conclusion, the presence of TGBM in a kidney biopsy is highly predictable for the presence of familial microscopic hematuria, even in patients in whom TGBM is associated with another glomerulopathy. The present data also indicate that patients with TGBM nephropathy often have concomitant IgA nephropathy and mesangial proliferative glomerulonephritis.

Basement Membrane↗
PubMed1994

Effects of complement activation products on the synthesis of decay accelerating factor and membrane cofactor protein by human mesangial cells.

We previously demonstrated that activation of terminal complement components (C8 and/or C9) increases the synthesis and expression of decay accelerating factor (DAF) on human glomerular cells. DAF is a cell membrane-associated complement regulatory protein that inhibits complement activation on cell surfaces. In the present studies we evaluated, first, the mechanisms by which complement activation stimulates DAF synthesis, and second the effect of complement activation on the synthesis. and expression of membrane cofactor protein (MCP), another complement regulatory protein, by human mesangial cells (HMC) in culture. Complement activation by immune complexes resulted in increased DAF mRNA levels by at least two mechanisms: deposition of activated C3 on HMC and generation of soluble complement activation products, specifically C5a. The increase in DAF mRNA levels induced by activated C3 or C5a was short lived (less than 4 hr). In contrast, the up-regulation of DAF mRNA levels induced by activation of the complete complement cascade persisted for at least eight hours. The effect of complement activation on DAF mRNA levels was not affected by cycloheximide, a protein synthesis inhibitor. However, cycloheximide alone resulted in a significant up-regulation of DAF mRNA levels on HMC. In contrast to those findings complement activation did not cause an up-regulation of MCP mRNA, nor an increase in the synthesis of this protein. However, by FACS, complement produced a small but significant increase of MCP protein levels on HMC. In conclusion, both MCP and DAF are present on HMC. Several activated complement components are capable of increasing DAF mRNA levels, but DAF protein levels increase only after activation of the whole complement cascade.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1994

Effect of chronically increased erythrocyte complement receptors on immune complex nephritis.

Experimental studies in humans and other primates have shown that the erythrocyte (E) complement receptor Type 1 (CR1), which is unique to the primate, plays an important role in clearing immune complexes (IC) from the circulation by binding C3b/C4b opsonized immune complexes and carrying the IC to liver and spleen for disposal. The results of these acute experiments suggest that increasing E-CR1 levels chronically should protect against IC-mediated glomerulonephritis (IC-GN) induced by chronic formation of IC in the circulation. In the present study this hypothesis was tested in the cynomolgus monkey (CYN). IC-GN was induced by daily bolus intravenous infusion of BGG into immunized CYN for 8, 10, or 14 weeks. Prior to and during the daily bolus infusions of BGG, sustained differences in E-CR1 levels were achieved between the experimental group (increased E-CR1 levels) and the control group (maintained or decreased E-CR1 levels), by one of two methods: (1) Twice weekly exchange transfusion. The CYN donors were blood type compatible with the recipients and had either constitutive high E-CR1 expression (3,000 to 5,000 CR1/E) or constitutive low E-CR1 expression (< 100 CR/E). The recipients of the exchange transfusions (N = 2) had constitutive mid-level E-CR1 expression. (2) Weekly phlebotomy (PL) or sham PL. CYN with mid-level E-CR1 expression were randomly assigned to receive weekly either PL (causing increased E-CR1 expression by stimulating erythropoiesis) (N = 8) or sham PL (which has no effect on E-CR1 expression (N = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Erythropoietin therapy in humans increases erythrocyte expression of complement receptor type 1 (CD35).

The expression of complement receptor Type 1 (CR1, CD35) on erythrocytes (E) is unique to humans and other primates. E-CR1, a C3b/C4b receptor that also acts as cofactor for Factor I, appears to be important in clearing C3/C4-opsonized immune complexes from the circulation, in controlling complement activation in the circulation, and in regulating antibody formation. This study was undertaken to determine whether therapy with recombinant human erythropoietin (rEPO) might increase E-CR1 expression in humans. The rationale is that young erythrocytes express more E-CR1 than old erythrocytes. Thus, conditions that stimulate erythropoiesis should increase E-CR1 expression. The hypothesis that stimulating erythropoiesis by rEPO therapy can increase E-CR1 expression was tested in six anemic chronic hemodialysis (ESRD) patients and five systemic lupus erythematosus (SLE) patients without renal failure. Before the rEPO therapy, three of the SLE patients were anemic and two were not. The ESRD patients were studied before and during 9 or 10 mo of rEPO therapy. The SLE patients were studied before, during, and after 7 mo of rEPO given by sc injection two or three times weekly. It was found that rEPO therapy was associated with a progressive increase in the average number of CR1/E in each of the ESRD patients and in the anemic SLE patients: mean baseline CR1/E was 210 +/- 50 (SE) for the ESRD patients and 125 +/- 35 for the SLE patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Rate of antigen entry into the circulation in experimental versus naturally occurring immune complex glomerulonephritis.

This study tested the hypothesis that the rate of antigen entry into the circulation in systemic lupus erythematosus (SLE), a naturally occurring immune complex glomerulonephritis (IC-GN), is slow compared with that of traditional experimental models of IC-GN, in which the antigen is delivered rapidly as a daily iv bolus. This hypothesis was tested by comparing rates of decline of the third component of complement (C3) and of circulating neutrophils (PMN) in SLE patients with active disease with those of cynomolgus monkeys (CYN) undergoing induction of experimental IC-GN by means of a daily bolus infusion of antigen. It has previously been shown that, as antigen enters the circulation and forms circulating IC, C3 levels and circulating PMN decline acutely. Thus, acute changes in these parameters can be surrogates for the rate of antigen entry into the circulation. In the CYN undergoing induction of IC-GN (N = 11), infusion of the antigen (bovine gamma-globulin) over 10 min resulted in acute declines in C3 levels (25 +/- 6.6%; P = 0.0018 and PMN counts (59 +/- 9%; P < 0.0002). In addition, the CYN experienced the onset of acute respiratory distress and hypotension. By contrast, in patients with active SLE (N = 9), C3 and white blood cell counts measured at 24-h intervals did not change significantly, and episodes of acute hypotension or respiratory distress were not observed. In the CYN, the onset of visible vasculitic lesions in the omentum were also documented within minutes of the infusion of bovine gamma-globulin. The rapidity of onset of these vascular lesions suggests that the tempo at which lesions develop in experimental models of IC disease is faster than that of naturally occurring IC diseases. It was concluded that, in naturally occurring IC diseases, antigen probably enters the circulation slowly over prolonged periods of time, rather than as large boluses over short periods of time, as in traditional experimental models of IC-GN. Thus, models of IC-GN involving a daily bolus infusion of antigen may not be clinically relevant, particularly when IC clearing mechanisms are tested, because the efficiency of these mechanisms may be markedly influenced by the rate at which IC form in the circulation.

Animals↗
PubMed1993

Radiofrequency ablation of the inferior vena cava-tricuspid valve isthmus in common atrial flutter.

Endocardial mapping has suggested that common atrial flutter (AF) is based on right atrial reentry surrounding the inferior vena cava (IVC). The isthmus between the IVC and the tricuspid valve (TV) appears essential to close the circuit. To test this hypothesis, radiofrequency was applied to the IVC-TV isthmus, with catheter electrodes, in 9 patients with AF. Mapping confirmed a right atrial circuit surrounding the IVC in all. In 4 patients another type of AF was induced that followed the circuit in the opposite direction. Radiofrequency interrupted AF in all patients. Multiple endocardial recordings showed that interruption was due to activation block at the point of application. Radiofrequency produced very brief or sustained, atrial fibrillation in 2 patients, which resulted in sinus rhythm. AF recurred in 4 patients with the same activation pattern and was interrupted again with radiofrequency in the IVC-TV isthmus in 3. AF was noninducible in 7 patients after 1 to 4 sessions. AF-free periods of 2 to 18 months without drugs were observed after radiofrequency, but 2 patients had paroxysmal atrial fibrillation. These results confirm that the IVC-TV isthmus is an essential part of the AF circuit. Ablation of this area may be of therapeutic value, but technical improvements are needed. Long-term efficacy of the procedure is uncertain.

Aged↗
PubMed1993

Platelet involvement in experimental immune complex-mediated glomerulonephritis in the nonhuman primate.

Abundant glomerular platelet deposition is a hallmark of certain animal models of immune complex (IC)-mediated glomerulonephritis (GN). By contrast, conspicuous platelet deposition is uncommon in the IC-GN seen in humans. This could result from intrinsic differences between human and animal platelets, which are known to be present. To assess whether abundant glomerular platelet deposition can occur in humans with IC-GN, the present studies were undertaken in nonhuman primates (cynomolgus monkeys, CYN), with active experimental IC-GN induced by 12 weeks of daily intravenous infusion of bovine gamma globulin (BGG). CYN are appropriate for these studies because, like humans, CYN platelets do not express the C3b receptor but do express receptors for the Fc region of IgG (FcR gamma II). Furthermore, in this model of IC-GN, which is indistinguishable from IC-GN seen in humans, it is possible to time the biopsy to coincide with a period of peak activity of the GN. The present studies proceeded as follows: ten CYN were studied before and after intravenous infusion of BGG sufficient to achieve conditions near antigen/antibody equivalence for circulating precipitating antibody to BGG. The infusion of BGG, which was given over 10 minutes, resulted in an acute reduction in circulating platelets (mean 43% +/- 5 SE, P < 0.001). However, renal biopsies performed before and five minutes after the acute reduction in circulating platelets showed that relatively few of the platelets removed from the circulation lodged in glomeruli (platelets/glomerular cross section: 0.2 +/- 0.06 before BGG vs. 0.88 +/- 0.31 after BGG, P = 0.035). In five of the CYN studied under the above protocol, autologous platelets were labeled with 111In and reinfused into the CYN just prior to the BGG infusion. These studies confirmed the paucity of platelet deposition in kidney but showed major uptake of the 111In-labeled platelets by liver and spleen (mean +/- SE 111In CPM/mg of tissue: kidney cortex 18 +/- 8, liver 132 +/- 42, and spleen 808 +/- 127, P = 0.038, comparing kidney to liver or spleen by paired t-test). Thus, the platelets removed from the circulation were taken up at the sites which are also the principal sites of IC uptake (liver and spleen), and over the time interval that coincides with the period of maximum uptake of IC by liver and spleen, after BGG infusion. In vitro studies, discussed herein, showed that BGG anti-BGG IC bind to CYN platelets via FcR gamma II.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Fibronectin metabolism by human mesangial cells: effects of collagens.

In the present study we assessed whether the fibronectin (FN) metabolism of human mesangial cells (HMC) in culture is influenced by the contact of HMC with collagens type I and IV. HMC were grown on collagen gels or on collagen-coated surfaces (collagen films). FN concentrations were measured by enzyme-linked immunosorbent assay; FN synthesis was measured by metabolic labeling and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition, the structure of matrix FN was examined by immunofluorescence microscopy. Compared with cells grown on plastic, HMC on collagen gels or collagen films accumulated greater amounts of FN in the cell matrix, and in these cultures, matrix FN was organized into a complex mesh of fibers. FN fiber formation was more prominent in cells adherent to collagen IV than in cells adherent to collagen I, and these fibers were observed as early as day 1 in culture. HMC adherent to plastic deposited matrix FN as patches and only occasionally as FN fibers localized to the periphery of the cell. The accumulation of FN in the matrix of HMC on collagen was not due to an increased rate of FN synthesis. In fact, HMC on collagen gels synthesized less FN than HMC on plastic. The present results indicate that the accumulation of FN in the matrix of HMC on collagen is due to the fact that this FN is less likely to be released into the supernatant than the matrix FN produced by HMC on plastic. The decreased FN synthesis demonstrated by HMC on collagen gels was associated with an overall decrease in protein synthesis but was not associated with a decrease in FN mRNA levels. Finally, FN isolated from HMC on collagen gels contained a unique 90-kDa gelatin-binding FN fragment. In conclusion, collagens have effects on the synthesis, localization, organization, and catabolism of FN produced by HMC in culture. In particular, collagen IV, the collagen normally present in the glomerular mesangium, appears to influence uniquely the organization of mesangial matrix FN.

Cell Adhesion↗
PubMed1992

Atrial vulnerability.

The electrophysiologic substrates of atrial flutter and fibrillation (AFF) have been studied in patients with paroxysmal arrhythmias. Atrial repetitive responses to extrastimuli are a nonspecific response, even though they can precipitate AFF. AFF inducibility is rather sensitive, but not very specific, in separating patients from controls. There is no established protocol to explore vulnerability in this fashion. Atrial refractoriness is abnormal in some patients. Some authors have found a tendency toward short effective refractory periods (AERP) and others have found a poor adaptation of AERP to decreases in cycle length. Unfortunately, these abnormalities are neither sensitive nor specific enough. Atrial conduction may be abnormal basally, but subtler abnormalities are shown by premature stimulation. Early extrastimuli are conducted with increased conduction delays in patients with paroxysmal AFF in relation to controls. Again, there is not enough sensitivity and specificity in the findings to make them of diagnostic value. Electrophysiologic abnormalities are detectable in patients with AFF, but larger studies, including reproducibility and the effect of drugs on the abnormal parameters, will be necessary to develop clinical applications.

Atrial Fibrillation↗