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Biomedical subjects

R C Manfro

Publications and source records attributed to R C Manfro.

At least 19 recordsLinked to original sources
PubMed2005

The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis.

End-stage renal disease (ESRD) patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH). The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH) levels and left ventricular mass (LVM) in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years), 61% males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (< 100 pg/ml; group I = 10 patients), intermediate levels (100 to 280 pg/ml; group II = 10 patients) and high levels (> 280 pg/ml; group III = 21 patients). A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient) in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003). LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03). In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

Adolescent↗
PubMed2005

Effect of hepatitis C serology on C-reactive protein in a cohort of Brazilian hemodialysis patients.

Hepatitis C (HCV) is not an uncommon feature in hemodialysis (HD) patients and may be a cause of systemic inflammation. Plasma cytokine interleukin-6 (IL-6) is mainly produced by circulating and peripheral cells and induces the hepatic synthesis of C-reactive protein (CRP), which is the main acute phase reactant. The aim of this study was to investigate the influence of HCV on two markers of systemic inflammation, serum CRP and IL-6, in HD patients. The study included 118 HD patients (47% males, age 47 +/- 13 years, 9% diabetics) who had been treated by standard HD for at least 6 months. The patients were divided into two groups depending on the presence (HCV+) or absence (HCV-) of serum antibodies against HCV. Serum albumin (S-Alb), plasma high sensitivity CRP (hsCRP), IL-6, and alanine aminotransferase (ALT) were measured and the values were compared with those for 22 healthy controls. Median hsCRP and IL-6 values and hsCRP/IL-6 ratio were: 3.5 vs 2.1 mg/l, P < 0.05; 4.3 vs 0.9 pg/ml, P < 0.0001, and 0.8 vs 2.7, P < 0.0001, for patients and controls, respectively. Age, gender, S-Alb, IL-6 and hsCRP did not differ between the HCV+ and HCV- patients. However, HCV+ patients had higher ALT (29 +/- 21 vs 21 +/- 25 IU/l) and had been on HD for a longer time (6.1 +/- 3.0 vs 4.0 +/- 2.0 years, P < 0.0001). Moreover, HCV+ patients had a significantly lower median hsCRP/IL-6 ratio (0.7 vs 0.9, P < 0.05) compared to the HCV- group. The lower hsCRP/IL-6 ratio in HCV+ patients than in HCV- patients suggests that hsCRP may be a less useful marker of inflammation in HCV+ patients and that a different cut-off value for hsCRP for this population of patients on HD may be required to define inflammation.

Adolescent↗
PubMed2005

Dialysis water treated by reverse osmosis decreases the levels of C-reactive protein in uremic patients.

Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age +/- SD: 51.3 +/- 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients.

Adult↗
PubMed2005

Occult hepatitis B in renal transplant patients.

BACKGROUND: Occult hepatitis B (HB) is characterized by the presence of HBV-DNA in patients who do not have HB surface antigen (HBsAg) detectable in sera, and is frequently described in patients with hepatitis C virus (HCV) infection. These viral liver diseases are common and may have a negative impact on the survival of renal transplant patients, especially if they are both present. In this study we aimed to evaluate the prevalence of occult HB in renal transplant patients either with or without HCV infection. PATIENTS AND METHODS: In a cross-sectional survey 101 HbsAg-negative renal transplant patients were evaluated; 51 were anti-HCV positive. Sera were analyzed for the presence of the S and core genes of the HBV-DNA by a nested polymerase chain reaction technique. Markers of HBV infection and liver function tests were also analyzed. RESULTS: The core gene was identified in 1 HCV-infected patient and 1 anti-HCV-negative patient who also presented the S gene (prevalence: 2% and 1% for each gene, respectively). HCV-infected patients had longer pre-transplant dialysis time (50.8 +/- 34.6 vs. 32.0 +/- 20.9; P < 0.001). Liver function tests were also increased in the HCV-infected group: alanine aminotransferase (P < 0.001), aspartate aminotransferase (P < 0.05), gamma-glutamyl transpeptidase (P<0.02), and alkaline phosphatase (P < 0.04). Multivariate analysis revealed that HCV infection was the only determinant of the altered results of the liver function tests. CONCLUSION: We found that occult HB is a condition present in our population of renal transplant patients and that HCV infection does not seem to be associated with occult HB infection in this setting.

Adult↗
PubMed2004

Cyclosporine increases endothelin-1 plasma levels in renal transplant recipients.

Endothelin-1 (ET-1) has been associated with the development of hypertension in cyclosporine-treated renal transplant recipients. To clarify this association, this observational study compared ET-1 levels in 33 patients taking cyclosporine therapy versus 10 controls. Three hours after cyclosporine administration, ET-1 levels were higher than in the controls, namely 1.81 + 0.99 versus 1.17 + 0.46 pg/mL (P <.04). These results suggest a role of ET-1 in the pathogenesis of post-renal transplantation hypertension in cyclosporine-treated recipients.

Adult↗
PubMed2004

Posttransplant diabetes mellitus in cyclosporine-treated renal allograft patients: a case-control study.

The incidence and risk factors for the development of posttransplant diabetes mellitus (PTDM) was retrospectively evaluated in cyclosporine-treated renal transplant patients. An incidence of 9.4% was observed over a 10-year period. Weight and body mass index were risk factors identified in a case-controlled study. Age, race, family history of DM, and cyclosporine and prednisone doses were not associated with the development of PTDM. We concluded that the development of PTDM is mainly related to weight. All efforts must be taken to avoid this complication.

Adult↗
PubMed1997

Ex vivo adenovirus-mediated gene delivery leads to long-term expression in pancreatic islet transplants.

BACKGROUND: Replication-deficient adenovirus, one of the most efficient vectors in gene therapy, has been limited by transient transgene expression due to its episomal location and loss during cell division, as well as a host immune response against viral proteins. METHODS: Murine pancreatic islets were infected ex vivo with ad5-cytomegalovirus (CMV)-beta-galactosidase and transplanted into diabetic recipients with normalization of glucose metabolism. RESULTS: High levels of beta-galactosidase activity were detectable histologically for at least 20 weeks after transplant, and beta-galactosidase and viral mRNA were also present that long. Sera from transplanted animals did not significantly inhibit ad5-CMV-interleukin-2-Ig infection of HeLa cells in vitro, whereas sera from intravenously delivered ad5-CMV-beta-galactosidase drastically diminished HeLa cell infection, suggesting the presence of reduced levels of antibodies in transplanted animals as compared with intravenously infected animals. Immunofluorescent staining of islet isografts infected with ad5-CMV-beta-galactosidase revealed the presence of CD8+ and CD4+ T lymphocytes at all time points, however, no islet destruction was seen. CONCLUSIONS: Treatment of islet isografts ex vivo with ad5-CMV-beta-galactosidase results in prolonged transgene expression, possibly due to an attenuated immune response against adenovirus.

Adenoviridae↗
PubMed1997

CTLA4Ig attenuates accelerated rejection (presensitization) in the mouse islet allograft model.

BACKGROUND: Sensitization to donor antigens is a problem of growing magnitude in clinical transplantation. At a molecular level, this is due to the interaction between antigen bearing antigen-presenting cells and recipient T cells and involves both antigen presentation and co-stimulation. METHODS: Allogeneic islet transplantation was performed using DBA/2J donors and B6AF1 recipients. Four weeks before transplantation, recipient animals were given donor-specific transfusion (DST) alone, DST + CTLA4Ig, DST + control IgG, or no treatment. Graft loss was defined as a blood glucose >300 mg/100 ml. RESULTS: Administration of DST + control IgG 4 weeks before transplantation resulted in accelerated rejection due to presensitization (median survival time of 8 days, compared with 14.5 days for the no-treatment group). Animals treated with CTLA4Ig in combination with DST had a median survival time of 12 days, compared with 8 days for DST + IgG. CONCLUSIONS: CTLA4Ig attenuates the tempo of accelerated rejection in this islet allograft model of presensitization, but does not prolong allograft survival as compared with no treatment.

Abatacept↗
PubMed1997

Adenovirus-mediated expression of Fas ligand induces hepatic apoptosis after Systemic administration and apoptosis of ex vivo-infected pancreatic islet allografts and isografts.

Fas ligand (FasL) mediates apoptosis of Fas-bearing cells and is expressed on a limited number of tissues, predominantly activated T lymphocytes. We describe the construction and biological activity of a replication-deficient type-5 adenovirus encoding murine FasL under the control of the cytomegalovirus (CMV) promoter (adCMV-FasL). In vitro, Jurkat cells undergo apoptosis when co-incubated with adCMV-FasL-infected COS cells. Systemic administration of adCMV-FasL to Wistar rats or DBA/2J mice results in widespread hepatic apoptosis and death in a dose-dependent manner within 72 hr, an effect not seen in lpr mice, or animals administered equivalent doses of adCMV-beta gal. Murine pancreatic islets also undergo apoptosis when infected ex vivo with adCMV-FasL, resulting in uniform primary nonfunction when transplanted into syngeneic or allogeneic diabetic recipients. These results indicate that adCMV-FasL is a potentially useful tool to study Fas/FasL biology.

Adenoviridae↗
PubMed1996

Analysis of ICAM-1 and HLA-DR expression on renal allograft aspirates.

ICAM-1 and HLA-DR expressions were studied on parenchymal cells obtained by aspirative biopsies of renal allografts. Patients were evaluated during 3 months after transplantation. Conventional cytology and immunoperoxidase stainings using anti-ICAM-1 and anti-HLA-DR antibodies were employed. The value of the total corrected increment was significantly higher (p < 0.05) during acute rejection episodes than during acute tubular necrosis or stable renal function. The percentage of HLA-DR positive cells were higher in rejection than in stable function periods (p < 0.05). The percentage of ICAM-1 positive cells was higher in rejection than in acute tubular necrosis periods (p < 0.05). The sensitivities to the diagnosis of rejection were 71.8% (TCI), 68.4% (ICAM-1) and 55.0% (HLA-DR). The specificities were 87.3%, 81.3% and 68.4% respectively. Combinations of the tests resulted in increased sensitivity. We concluded that the use of these monoclonal antibodies improves the sensitivity of conventional aspiration cytology to the diagnosis of acute renal rejection.

Biopsy, Needle↗
PubMed1995

Reproducibility of fine-needle aspiration biopsy in the diagnosis of acute rejection of renal allografts.

BACKGROUND: Although it has been used as a diagnostic tool in many renal transplant centres the reproducibility of fine-needle aspiration biopsy (FNAB) has not been critically evaluated. METHODS: In the present study material sequentially obtained from 15 patients (177 aspirations) over a 3-month period following renal transplantation was evaluated by two independent observers. Intraobserver reproducibility was studied through the analysis of two evaluations by observer 1 performed 8 months apart. Interobserver reproducibility was calculated comparing the second evaluation of observer 1 with the evaluation of observer 2. All evaluations were performed blindly. Slides and protocols of individual patients were chronologically arranged and thus interpreted. Representation, total corrected increment (TCI), accuracy, and the percent agreement for the diagnosis of acute rejection were evaluated. RESULTS: No intraobserver statistically significant differences were observed. Differences observed in interobserver evaluation of TCI either during, or out of acute rejection episodes, well as the representative quality of the sample and accuracy, were not statistically significant. The percent of agreement for the presence or absence of acute rejection was 77.5% for the intraobserver comparison and 76.7% for the interobserver evaluation. Both values showing either a non-significant value for the difference or a statistical significance for the concordance. CONCLUSION: We concluded that FNAB is an accurate method with fairly good intra- and interobserver reproducibility for the diagnosis of acute rejection of renal allografts.

Acute Disease↗