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Biomedical subjects

A Panizo

Publications and source records attributed to A Panizo.

At least 19 recordsLinked to original sources
PubMed2003

PTEN protein expression correlates with PTEN gene molecular changes but not with VEGF expression in astrocytomas.

PTEN gene (10q23) is a relevant tumor suppressor gene whose protein is a phosphatase involved in the control of angiogenesis of some tumors including astrocytomas. There are no studies correlating molecular changes of PTEN and the immunohistochemical expression of its protein (pPTEN) with the expression of vascular endothelial growth factor (VEGF) in astrocytomas. Fifty-six surgically resected brain gliomas, 10 grade 2, 16 grade 3, and 30 grade 4, were studied by a combined approach, consisting of (1) PCR analysis using four microsatellite markers against the PTEN gene region (10q23), (2) the FISH technique to test chromosome 10 using a pericentromeric probe, and (3) immunohistochemical evaluation of pPTEN and VEGF. Loss of heterozygosity (LOH) of PTEN was observed in 10% of fibrillary grade 2 astrocytomas and all gemistocytic ones. In high-grade tumors, LOH was more frequent in grade 4 than in grade 3 (> or =2 loci deleted, 83% and 56%, respectively). Monosomy for chromosome 10 was observed especially in high-grade tumors (6% of grade 3 and 50% of grade 4) and in 20% of grade 2 tumors, corresponding to gemistocytic astrocytomas. Results with both antibodies against PTEN were concordant: loss of cytoplasmic immunoreactivity was frequently observed according to homogeneous or heterogeneous patterns in 70% and 50% of grades 4 and 3, respectively, but not in grade 2. Immunonegativity of pPTEN was associated with PTEN gene deletion (> or =2 loci deleted) (P = 0.04) but not with monosomy. Cytoplasmic immunoreactivity against VEGF was observed in high-grade and in gemistocytic astrocytomas, but not in conventional grade 2 tumors. Tumor expression of pPTEN was not associated with immunoreactivity against VEGF when the same areas were considered. In conclusion, loss of PTEN expression is frequent in high-grade astrocytomas, but not in grade 2 tumors, and correlates with PTEN deletion and loss of chromosome 10. PTEN immunoreactivity does not correlate with VEGF expression in astrocytomas when similar areas are considered.

Astrocytoma↗
PubMed2001

Immunocytochemistry in the differential diagnosis of serous effusions: a comparative evaluation of eight monoclonal antibodies in Papanicolaou stained smears.

BACKGROUND: The distinction between pleural mesothelioma (MS), reactive mesothelium (RM), and adenocarcinoma (AC) in serous effusions continues as a diagnostic problem in pathology. Immunohistochemistry can help, especially in surgical samples, but the optimum panel of antibodies has yet to be reported. The application of these antibodies to serous effusions has displayed variable results. The aim of this study was to evaluate the usefulness of eight monoclonal antibodies in the differential diagnosis of MS, RM, and AC in serous effusions. METHODS: A total of 44 cytologic specimens of serous effusions (26 pleural, 15 peritoneal, and 3 pericardial) from 30 ACs, 3 MSs, and 11 RMs, previously stained with Papanicolaou stain, were selected retrospectively from our files and stained with HBME-1, thrombomodulin, calretinin, MOC-31, Ber-EP4, E-cadherin, CEA, and CD-15. The immunoreactions were evaluated independently by two pathologists. A stepwise logistic regression analysis was applied to the data to select an appropriate panel of antibodies. RESULTS: Statistical significance was found with HBME-1, thrombomodulin, MOC-31, Ber-EP4, and CD-15, when comparing both AC versus MS, and AC versus any type of mesothelial proliferation (MS or RM). Using HBME-1, 80% of ACs were negative whereas all three MSs reacted strongly with P = 0.003. A P = 0.02 was reached with thrombomodulin with 76.5% of ACs showing no immunoreactivity. Ber-EP4 and MOC-31 displayed good results with a P < 0.001 and 0.01, respectively. CD-15 reached a P = 0.034. No differences were found using the other antibodies. Ten ACs, all 3 MSs, and 10 RMs were double immunostained with HBME-1 and/or MOC-31 and Ber-EP4 successfully. CONCLUSIONS: Immunohistochemical studies performed on Papanicolaou stained cytologic smears proved to be useful in the differentiation between metastatic AC and mesothelial proliferation. HBME-1, thrombomodulin, MOC-31, Ber-EP4, and CD-15 were the most useful. In selected cases, it appeared that double immunostaining aided the differential diagnosis. Cancer (Cancer Cytopathol)

Adenocarcinoma↗
PubMed2000

Prognostic impact of P53 status in Ewing sarcoma.

BACKGROUND: Disease stage at the time of diagnosis and response to therapy are the main prognostic factors for patients with Ewing sarcoma or peripheral neuroectodermal tumor (ES/PNET). The primary genetic alteration in ES/PNET, the fusion of the EWS gene with FLI1 or ERG, is diagnostically highly specific for these tumors, and molecular variation in the structure of the EWS-FLI1 fusion gene also is of prognostic significance. In contrast, secondary genetic alterations, such as P53 alterations, are relatively uncommon in ES/PNET, and their prognostic impact has not been extensively studied. METHODS: Prechemotherapy, paraffin embedded, nondecalcified, primary tumor material in a well-characterized series of 55 patients with ES/PNET with defined EWS-FLI1 fusion transcripts (32 patients with type 1 and 23 patients with other types) was studied retrospectively by immunohistochemical techniques for cell cycle regulators and proliferative markers, such as P53, P21(WAF1), and Ki-67, as well as by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique for apoptosis. Nuclear P53 expression in > 20% of tumor cells was scored as aberrant overexpression. Histologic response to neoadjuvant chemotherapy was assessed. RESULTS: Aberrant P53 expression (in > 20% of tumor cells) was present in 6 patients (11%) but showed no statistically significant correlation with disease stage, tumor size, proliferation rate (Ki-67), apoptotic rate (TUNEL), or EWS-FLI1 fusion type. By univariate analysis, the P53 > 20% group showed a significantly poorer overall survival among patients with localized disease (n = 43 patients) (P = 0.001) and in the entire study group (P = 0.01). In multivariate Cox analyses of overall survival, P53 > 20% was the strongest negative factor among prognostic factors available at the time of diagnosis (P = 0.001; relative risk [RR] = 9) and when chemotherapy response was included in the analysis (P53 > 20%: P = 0.01; RR = 10). CONCLUSIONS: P53 alteration appears to define a small clinical subset of patients with ES/PNET with a markedly poor outcome. The current observations warrant a systematic prospective study with comprehensive P53 mutation analysis. [See related article on pages 793-9, this issue.]

Adolescent↗
PubMed2000

Mast cells in chronic rejection of human renal allografts.

An increased number of mast cells (MCs) is found in renal specimens of patients with diseases associated with persistent chronic inflammation. MCs proliferation is partly dependent on the presence of T lymphocytes. Both chronic inflammation and T-lymphocytes are essential in the development of chronic rejection (CR), and probably for the infiltration of MCs. MC-derived products such as heparin, histamine, and serine proteases may be responsible for endothelial proliferation and excess collagen production by fibroblasts. In this study, a quantitative evaluation of the MCs infiltration in kidney allografts with CR is performed. The extent of renal fibrosis was analysed in samples stained with Masson's trichrome. To evaluate the potential relationship between MCs and fibrosis in CR we analysed 30 kidneys with CR (25 from nephrectomies and 5 from autopsies). Ten transplanted kidneys obtained from patients died by causes not related with rejection were used as controls. CR was graded according to the Banff schema, which assesses the degree of vasculopathy, tubular atrophy, interstitial fibrosis and transplantation glomerulopathy. Giemsa-stained sections and immunohistochemistry using anti-MC tryptase and c-kit monoclonal antibodies were used to detect MCs. The mean number of MCs per 20 high-power fields (HPF) in the transplanted kidney with CR was 101.8+/-15.3 in the renal cortex and 46.60+/-6.52 in the medulla. MCs were significantly more numerous in CR with respect to normal kidneys, both in the cortex (P<0.01; Mann-Whitney U test) and in the medulla (P<0.01; Mann-Whitney U test). There was a positive correlation between the number of MCs and extent of fibrosis (P<0.01; Kruskal-Wallis one-way anova test) and tubular atrophy (P<0.01). These results suggest that MCs may play a role in the process of development of interstitial fibrosis in CR.

Adolescent↗
PubMed2000

Association of EWS-FLI1 type 1 fusion with lower proliferative rate in Ewing's sarcoma.

The Ewing's sarcoma (ES) family of tumors, including peripheral neuroectodermal tumor (PNET), is defined genetically by specific chromosomal translocations resulting in fusion of the EWS gene with a member of the ETS family of transcription factors, either FLI1 (90-95%) or ERG (5-10%). A second level of molecular genetic heterogeneity stems from the variation in the location of the translocation breakpoints, resulting in the inclusion of different combinations of exons from EWS and FLI1 (or ERG) in the fusion products. The most common type of EWS-FLI1 fusion transcript, type 1, is associated with a favorable prognosis and appears to encode a functionally weaker transactivator, compared to other fusion types. We sought to determine whether the observed covariation of structure, function, and clinical course correlates with tumor cell kinetic parameters such as proliferative rate and apoptosis, and with expression of the receptor for insulin-like growth factor I (IGF-1R). In a group of 86 ES/PNET with defined EWS-ETS fusions (45 EWS-FLI1 type 1, 27 EWS-FLI1 non-type 1, 14 EWS-ERG), we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n = 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with EWS-FLI1 type 1 than those with non-type 1 EWS-FLI1, whether analyzed as a continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression analysis suggests that this association was secondary to the association of type 1 EWS-FLI1 and lower IGF-1R expression (P = 0.04). Comparing EWS-FLI1 to EWS-ERG cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney test; P = 0.02, Fisher's exact test), but there was no significant difference in IGF-1R. TUNEL results showed no significant differences between groups. Our results suggest that clinical and functional differences between alternative forms of EWS-FLI1 are paralleled by differences in proliferative rate, possibly mediated by differential regulation of the IGF-1R pathway.

Adolescent↗
PubMed2000

Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology.

BACKGROUND: The histopathological spectrum and role of hepatitis viruses in cases of hypertransaminasaemia of unknown aetiology have not been correctly analysed in a sufficiently large number of patients. METHODS: We studied 1075 consecutive patients referred for liver biopsy because of elevation of alanine aminotransferase (ALT) levels for more than six months. From this population we selected those cases in whom the aetiology could not be defined from clinical, biochemical, and serological data obtained before biopsy. In these patients liver biopsies were reviewed, and hepatitis B virus (HBV)-DNA and hepatitis C virus (HCV)-RNA were assayed in serum by polymerase chain reaction (PCR). Serum hepatitis G virus (HGV)-RNA was determined by PCR in 74 patients. RESULTS: Of 1075 patients studied, the cause of the increased serum ALT levels remained elusive after appropriate testing in 109 patients (10.1%). Liver biopsies from these patients showed non-specific changes in 32.7% of cases, non-alcoholic steatohepatitis (NASH) in 15.8%, and chronic hepatitis or cirrhosis in 51.5%. HBV-DNA and/or HCV-RNA was detected more frequently in cryptogenic liver disease than in healthy blood donors (26.7% v 3.4%; p<0.001). HGV-RNA was found in only one patient. The proportion of cases with detectable HBV-DNA or HCV-RNA was 14.3% in patients with non-specific changes or NASH, 30.7% in patients with chronic hepatitis, and 61.5% in patients with cirrhosis. Cirrhosis was found more frequently in patients with positive HBV-DNA and/or HCV-RNA in serum than in those who tested negatively (p=0.005). CONCLUSIONS: In our series, patients in whom biochemical and serological data did not determine the aetiology of the disease represented 10% of all cases referred for liver biopsy for persistent elevation of serum transaminases. Approximately 50% of patients had chronic hepatitis or cirrhosis and the remainder had NASH or non-specific changes. Occult viral infections were found in a high proportion of cases in the first group and in a low percentage of patients in the second.

Alanine Transaminase↗
PubMed1999

Susceptibility to apoptosis measured by MYC, BCL-2, and BAX expression in arterioles and capillaries of adult spontaneously hypertensive rats.

Hypertension results in microvascular rarefaction or disappearance of microvessels. In the present study, we investigated the pathogenic role of apoptosis in hypertension-induced rarefaction of heart arterioles and capillaries of spontaneously hypertensive rats (SHR). Experiments were performed on hearts from 6-week-old, 16-week-old, and 30-week-old SHR (n = 30 rats) (SHR6, SHR16, SHR30). We used as controls 6-week-old, 16-week-old, and 30-week-old normotensive rats (WKY) (n = 30 rats) (WKY6, WKY16, WKY30). We analyzed the expression of c-myc, bcl-2, and bax and in situ end-labeling DNA fragmentation in vascular smooth muscle cells of arterioles and endothelial cells of arterioles and capillaries. Endothelial cells of capillaries and endothelial and smooth muscle cells of arterioles of hypertensive animals (SHR) express more Bax protein and Myc protein than their respective normotensive controls by margins that were statistically significant. The SHR30 group expressed the lowest levels of Bcl-2 protein by a margin that was statistically significantly different from WKY30. We did not find evidence of apoptosis in arterioles or capillaries on the basis of in situ end-labeling. However, our results indicated that alterations in the expression of members of the Bcl-2 family of proteins and Myc protein occurred in smooth muscle cells and endothelial cells of arterioles and capillaries of SHR. In conclusion, although evidence of apoptosis in arterioles and capillaries was not found by in situ end-labeling, our findings suggest that in hypertension they may have a higher susceptibility to apoptosis, and therefore rarefaction may be a consequence of apoptosis.

Animals↗
PubMed1999

Decrease of apoptosis rate in patients with renal transplantation treated with mycophenolate mofetil.

BACKGROUND/AIMS: Mycophenolate mofetil (MMF) is a powerful immunosuppressant that inhibits the proliferation of lymphocytes by blocking the enzyme inosine monophosphate dehydrogenase. MMF prevents acute graft rejection in organ transplants. The aim of this investigation is to study whether MMF has any influence on apoptosis and proliferation rates of cells other than lymphocytes. METHODS: We conducted a retrospective study of renal allograft biopsies taken during the 1st week after transplantation in 25 patients receiving triple therapy with prednisone, ciclosporin and azathioprine 75 mg/day and in 25 patients treated with MMF at a dose of 2 g/day instead of azathioprine, in order to investigate the differences in the proliferation and apoptosis rates of the glomerular, tubular, interstitial and endothelial cells of the kidney. Twelve normal kidneys were used as controls. Conventional histopathological techniques were applied as usual for pathological diagnosis. Proliferative activity was assessed by use of MIB-1 antibody. Sections of formalin-fixed, paraffin-embedded tissue blocks were stained for the presence of apoptotic cells by TUNEL assay. Evaluation of proliferative or apoptotic rates was made by counting the number of positive cells in 10 glomeruli and in 10 transversely cut tubuli in each biopsy. The positive cells in the interstitium were counted in ten high-power fields. Positive cells in the endothelium were scored semiquantitatively from 0 to 3: 0 = none, 1 = isolated cells, 2 = small groups of cells, 3 = most endothelial cells. Mann-Whitney U and chi-square tests were used for intergroup comparisons. RESULTS: All biopsies were normal or had borderline (Banff classification) acute rejection. MIB-1 rates were similar in both groups, without statistical differences (p > 0.05) between them. Significantly lower apoptotic rates were found in the group treated with MMF in tubular epithelium (23.41 +/- 8.86 vs. 57.4 +/- 13.42; p = 0.021), in glomerular (1.25 +/- 0.78 vs. 5.3 +/- 1.66; p = 0.027), and interstitial cells (1.58 +/- 0.6 vs. 5.8 +/- 1.54; p = 0.043). Apoptosis in endothelial cells (p > 0.05) was similar in both groups. CONCLUSION: We conclude that treatment with MMF of kidney transplant patients does not affect the proliferative rate of cells of the allograft, but decreases the number of apoptotic cells in tubular epithelium.

Adult↗
PubMed1998

Molecular features in a biphenotypic small cell sarcoma with neuroectodermal and muscle differentiation.

We report a case of a 13-year-old girl with soft tissue sarcoma of the hand, which showed muscle and neuroectodermal immunophenotypes. Molecular studies were performed on RNA collected from fine-needle aspiration (FNA) cytology and peripheral blood samples by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. This biphenotypic tumor showed simultaneous expression of EWS-FLI1 and PAX3-FKHR transcripts, specific of Ewing family tumors and alveolar rhabdomyosarcoma, respectively. Although childhood sarcomas with simultaneous muscle and neural differentiation have been described to have EWS-FLI1 transcripts, there are no reports of tumors with both transcripts. Cytological specimens are a good source of RNA for molecular studies.

Adolescent↗
PubMed1998

CD44v6 expression is related to progression in renal epithelial tumours.

AIMS: Expression of CD44 variant isoform including exon 6 has been associated to tumour progression in several carcinomas. However, no studies have been performed to assess the prognostic value of the expression of this marker in renal cell tumours. METHODS AND RESULTS: We studied 58 renal cell tumours. All patients were followed up for at least 3 years after nephrectomy. Tumours were analysed for expression of CD44v6 assessed by two isoform-specific monoclonal antibodies. RT-PCR was performed to detect CD44 variant transcripts in 10 cases in which immunohistochemistry was negative. Twenty-two tumours showed reactivity in at least 1% cells for both antibodies with a strong membrane pattern. RT-PCR did not show CD44v6 transcripts in any of 10 studied tumours. Immunohistochemical staining was more frequent in perivascular areas or in areas of vascular invasion. In fact, CD44v6 expression correlated well with nuclear grade (P = 0.009), stage at diagnosis (P = 0.04) and appearance of metastasis after nephrectomy (P = 0.007). Although univariate survival analysis showed stage (P < 0.001), grade (P = 0.009) and CD44v6 expression (P = 0.04) to be significant predictive factors, only stage remained significant (P = 0.0013) in the multivariate analysis. CONCLUSIONS: CD44v6 expression, assessed immunohistochemically, is related to tumour progression. However, its prognostic value in renal cell tumours is dependent on tumour stage at diagnosis.

Carcinoma↗
PubMed1997

Quinapril inhibits c-Myc expression and normalizes smooth muscle cell proliferation in spontaneously hypertensive rats.

A number of data suggest that angiotensin II-dependent activation of the protooncogene c-myc participates in the proliferative response of smooth muscle cells (SMC) of rats with spontaneous hypertension (SHR). We therefore investigated the effects of chronic treatment with the angiotensin converting enzyme (ACE) inhibitor quinapril on the oncoprotein c-Myc and the proliferating cell nuclear antigen cyclin A in SMC of small intramyocardial arteries from the left ventricle of SHR. The expression of c-Myc and cyclin A was assessed by immunocytochemical analysis. The number of smooth muscle cells was assessed by morphometrical analysis. As compared to normotensive Wistar-Kyoto (WKY) rats, untreated SHR exhibited an increased percentages of cells expressing c-Myc (33% +/- 4% v 19% +/- 2%, mean +/- SEM, P < .005) and cyclin A (25 +/- 2 v 11% +/- 1%, P < .001). In quinapril-treated SHR compared with untreated SHR, we found decreased expression of c-Myc (22% +/- 2%, P < .005) and cyclin A (13% +/- 1%, P < .001). No significant differences were found between WKY rats and quinapril-treated SHR in the above parameters. Cyclin A was directly correlated with the number of SMCs in each group of rats. These results suggest that an enhanced expression of c-Myc may be involved in the increased proliferation seen in SMCs from small arteries of SHR. Quinapril administration normalizes proliferation in the SMCs of SHR, possibly by inhibiting the expression of the oncoprotein c-Myc and its effects on the cell cycle.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Is the regulation of apoptosis altered in smooth muscle cells of adult spontaneously hypertensive rats?

Whereas the protein product of the Bcl-2 gene inhibits apoptosis, the protein product of the Bax gene acts as a promoter of apoptosis. To gain insight into the regulation of apoptosis in vascular smooth muscle cells in arterial hypertension, we investigated the expression of the proteins Bcl-2 and Bax in small intramyocardial arteries of 36-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In addition, 16-week-old SHR were treated for 20 weeks with the angiotensin-converting enzyme inhibitor quinapril and killed at 36 weeks of age. We measured the percentages of smooth muscle cells expressing these proteins using monoclonal antibodies and the avidin-biotin immunoperoxidase method. Compared with WKY, untreated SHR exhibited increased (P<.001) Bcl-2 expression and similar Bax expression. Values of Bcl-2 measured in quinapril-treated SHR were significantly lower than values measured in untreated SHR and similar to values measured in WKY. Quinapril-treated SHR showed higher (P<.001) Bax expression than WKY and untreated SHR. Bcl-2 expression was directly correlated with systolic pressure. Inverse correlations were found between the expression of Bax and the activities of both cardiac and circulating angiotensin-converting enzyme. These findings suggest that smooth muscle cell apoptosis might be inhibited in small arteries of adult SHR as a consequence of an excess of the protein Bcl-2. In addition, our results suggest that chronic angiotensin-converting enzyme inhibition might restore the susceptibility to apoptosis in these cells through stimulation of the protein Bax.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats.

Increased apoptosis has been reported in the heart of rats with spontaneous hypertension and cardiac hypertrophy. This study was designed to investigate the relationship between apoptosis and hypertrophy in cardiomyocytes from the left ventricle of spontaneously hypertensive rats (SHR). In addition, we evaluated whether the development of cardiomyocyte apoptosis is related to blood pressure or to the activity of the local angiotensin-converting enzyme (ACE) in SHR. The study was performed in 16-week-old SHR, 30-week-old untreated SHR, and 30-week-old SHR treated with quinapril (10 mg x kg[-1] x d[-1]) during 14 weeks before they were killed. Cardiomyocyte apoptosis was assessed by direct immunoperoxidase detection of digoxigenin-labeled 3'-hydroxyl ends of DNA. Nuclear polyploidization measured by DNA flow cytometry was used to assess cardiomyocyte hypertrophy. Compared with 16-week-old normotensive Wistar-Kyoto rats, 16-week-old SHR exhibited increased blood pressure (P<.001), increased rate of tetraploidy (P<.05), and similar levels of ACE activity and apoptosis. Compared with 30-week-old Wistar-Kyoto rats, 30-week-old SHR showed increased blood pressure (P<.001), increased ACE activity (P<.05), increased rate of tetraploidy (P<.01), and increased apoptosis (P<.01). Untreated 30-week-old SHR exhibited similar values of blood pressure and tetraploidy and higher ACE activity (P<.05) and apoptosis (P<.001) than 16-week-old SHR. A direct correlation (P<.01) was found between ACE activity and the apoptotic index in untreated 30-week-old SHR. The long-term administration of quinapril was associated with the normalization of ACE activity and apoptosis in treated SHR. These results suggest that the timing and mechanisms responsible for apoptosis and hypertrophy of cardiomyocytes are different in SHR. Whereas hypertrophy seems to be an earlier alteration that develops in parallel with hypertension, apoptosis develops later in association with overactivity of the local ACE. Our data suggest that cell death dysregulation may be a novel target for antihypertensive agents that interfere with the renin-angiotensin system in hypertension.

Animals↗
PubMed1997

Heart transplantation for Finnish type familial systemic amyloidosis.

A patient with Finnish type familial systemic amyloidosis associated with lattice corneal dystrophy (Meretoja's syndrome) underwent heart transplantation with uneventful postoperative course. Five years later the patient has mild chronic renal failure, normal cardiac allograft function and almost total bilateral blindness.

Amyloidosis↗
PubMed1997

Role of endomyocardial biopsy in the diagnosis of chronic rejection in human heart transplantation.

To assess the pathologic findings observed in the setting of post-transplant graft atherosclerosis, we have studied 18 endomyocardial biopsies (EMB) from 18 heart-transplanted patients collected at the same time that a coronary angiography (CA) showed changes consistent with graft atherosclerosis. Twenty-two EMB from patients with heart transplant with normal CA were used as controls. In spite of the small size of the sample, the number of acute rejection (AR) episodes correlated with the appearance of graft atherosclerosis (p < 0.001). Heart biopsies in graft atherosclerosis showed myointimal proliferation, thickening and folding of the wall of precapillary arteries, myocyte hypertrophy, and interstitial and perivascular fibrosis. Type III and type IV collagen, laminin, and fibronectin were increased in areas of interstitial and perivascular fibrosis, as well as in the vessel's wall. Fibronectin accumulation was more evident in the subendothelium and inner media of affected vessels. These changes were never found all together in control biopsies. Even though the inespecificity of some of those findings, we conclude that chronic graft atherosclerosis in a heart transplant may be suspected by endomyocardial biopsy when most of these alterations are seen together, especially if small precapillary arteries are present in the specimen.

Acute Disease↗