Ascending aortic aneurysm after pediatric heart transplantation: case report of an unusual complication.

A 28-month-old boy, weighing 11 kg, with severe dilated cardiomyopathy, was transplanted on December 1995. Hypertension and supraventricular tachycardia were detected in the immediate post-operative period, with favorable outcome. After 5 months of clinically asymptomatic follow-up, a dilation in the ascending aorta was observed on routine echocardiogram. Nuclear magnetic resonance imaging (NMRI) confirmed an ascending aortic aneurysm, with a diameter of 38 mm. An operation was performed, a bovine pericardium patch was sutured with reconstruction of the aortic wall, excluding the aneurysm. Good recovery was obtained and the child was discharged on Day 7 postoperatively. A post-operative echocardiogram showed absence of the aortic aneurysm and good surgical results. Another NMRI was done 5 months later, showing an intact ascending aorta. After 64 months, the patients clinical condition was confirmed as normal by echocardiogram. Surgical treatment was successful and the positive results have been maintained.     

Impact of a specialized outpatient heart failure follow-up program on hospitalization frequency and functional status of patients with advanced heart failure.

BACKGROUND: High rates of morbidity and mortality are observed in patients with advanced heart failure (AHF). AHF is now considered the most costly syndrome in cardiology owing to the substantial economic burden associated with hospitalizations for acute decompensation. A management program that involves specialized follow-up by a multidisciplinary team has been suggested as a desirable strategy for improving outcomes for these patients. ObjectivE: To evaluate the impact of a specialized outpatient heart failure (HF) follow-up program for patients with AHF on frequency and duration of hospitalization for HF and functional status. METHODS: We retrospectively studied 167 consecutive patients with AHF who were referred to the outpatient HF follow-up program in our institution between January and November 2002, of whom 147 followed for > or =30 days were included in the analysis. In addition to demographic and baseline clinical characteristics, HF medication and NYHA functional class, the number and duration of hospitalizations for HF during the previous 12 months were recorded and compared at the time of referral and after a follow-up period of 6.5+/-3 months. RESULTS: Of the 147 patients analyzed (aged 60.8+/-13 years; 79% male; left ventricular ejection fraction 27+/-11%), 67% were in NYHA functional class III, 20% in class II and 13% in class IV at the time of referral. There was a significant improvement in functional class during the mean follow-up period: 55% of the patients were in class III, 37% in class II, 5% in class I and 3% in class IV (p<0.0001). The proportion of patients on beta-blockers or spironolactone increased from 33% and 51% at the time of referral to 69% and 71% respectively after referral (p<0.0001). In the 12 months before referral, 39% of the patients had been hospitalized for acute decompensation of HF (87 hospitalizations - mean 7.2/month) versus 13% of the patients during the mean follow-up period (25 hospitalizations - 3.8/month, p<0.0001). No significant differences were found in the proportion of patients on angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, digoxin or diuretics, or in the mean duration of hospitalization before and after referral. ConclusioN: The specialized follow-up of patients with AHF by a team with expertise in HF resulted in significant therapeutic optimization. Increased use of beta-blockers and spironolactone was associated with significant improvement in functional capacity and significant reduction in hospitalizations.     

Medullar expression of type-A natriuretic peptide receptor in an animal model of hypertension induced by renal mass ablation.

INTRODUCTION: The biological activity of the natriuretic peptide (NP) system is dependent on the balance between NP tissue levels and the local expression of their receptors. In the kidney, the natriuretic peptide receptor type A (NPR-A) is the principal receptor mediating NP activity and is mainly expressed in the renal medulla. An increase in circulating NP levels is well documented in chronic renal failure (CRF); however, the renal expression of NPR-A has not been evaluated in this condition. METHODS: Wistar-Han rats were submitted to right nephrectomy plus ablation of both poles of the left kidney (3/4nx; n=27) or were sham operated (Sham; n=22) and followed for up to 26 weeks post surgery. Blood pressure measurements were performed weekly. Two, 10 and 26 weeks after surgery, renal sodium and creatinine excretion were evaluated and the kidneys removed for NPR-A mRNA quantification by real-time PCR. The results of mRNA quantification are expressed in arbitrary units (AU) set as the mean value of the Sham group (Sham=1 AU), after normalization for GAPDH (p<0.05). weeks after surgery) and in elevated fractional sodium excretion (+270%, 26 weeks after surgery). Although sodium intake was similar in 3/4nx and Sham rats, blood pressure was higher in 3/4nx rats and increased progressively throughout the study. This was accompanied by a marked decrease in NPR-A mRNA levels in the renal medulla from 3/4nx animals at 2, 10 and 26 weeks post surgery. Conclusion: In 3/4nx rats, the expression of NPR-A in the renal medulla of the remnant kidney is markedly reduced from 2 weeks up to 26 weeks post surgery. It is suggested that this may contribute to the progressive increase in blood pressure, as well as to the renal fibrosis observed in 3/4nx rats.     

Stable preference for high ethanol concentrations after ethanol deprivation in Sardinian alcohol-preferring (sP) rats.

Results of a recent study have demonstrated that exposure to multiple ethanol concentrations and repeated ethanol deprivation periods in Indiana ethanol-preferring (P) rats resulted in the development of an alcohol deprivation effect (ADE; the temporary increase in voluntary ethanol intake after a period of deprivation from ethanol) characterized by consumption of intoxicating amounts of ethanol. The current study was designed to possibly extend these results to Sardinian alcohol-preferring (sP) rats, generated with the same selective program previously used for P rats. To this aim, ethanol-naive sP rats were exposed initially to the home cage four-bottle choice [10%, 20%, and 30% (vol./vol.) ethanol solutions and water] for eight consecutive weeks. Subsequently, rats were divided into two groups: The first group had continuous access to the four-bottle regimen (nondeprived rats), and the second group was exposed to five cycles of 14-day periods of deprivation from ethanol and 14-day periods of reexposure to the four-bottle regimen. An ADE developed after each deprivation period. However, the extra intake of ethanol was limited to the first hour of each reaccess period. Magnitude of ADE did not change with repeated periods of deprivation. However, a shift in preference toward the two highest concentrations of ethanol solutions was evident from the first reexposure to ethanol and was maintained throughout the study. These results provide further evidence on the heterogeneity of ethanol-drinking behavior among rat lines selectively bred for high ethanol preference and consumption.     

A simple method for the isolation and culture of epithelial and stromal cells from benign and neoplastic prostates

Objectives. Current primary prostate cell culture techniques use an overnight digestion or extensive media preparation. In this report, we describe a method for the culture of benign and neoplastic cells from human prostatectomy specimens that is rapid and contains no undefined factors in the medium.Methods. Characterization of the human cultured prostate cells was performed using immunohistochemical methods and monoclonal antibodies AE1/AE3 and cytokeratin 8, as well as monoclonal antibodies against prostate-specific antigen (PSA). Polymerase chain reaction was used to measure the exclusive epithelial and stromal cell products, c-met and hepatocyte growth factor (HGF), respectively. Electron microscopy was performed to assess the cell junctions and morphologic features of epithelial cells. Optimum cell growth in different media was tested using a cell replication assay.Results. Microscopic evidence revealed that the cells demonstrate typical epithelial morphology, with polyhedral cells forming tight junctions in a continuous monolayer. Desmosomes were present in electron micrographs of epithelial cells. The cultured epithelial cells described in this report also demonstrate positive cytokeratin staining. The epithelial cells reacted positively with PSA antibody, indicating that the cells retain their secretory role in cell culture for a limited period. Epithelial cells expressed the HGF receptor, c-met; stromal cells secreted HGF. Insulin, transferrin, and selenium increased the growth of cells in the chemically defined media, compared with minimum essential media (MEM) and Ham's F12.Conclusions. In summary, essentially pure cultures of prostate stromal or epithelial cells have been established using simple isolation and culture methods. These cells will be useful for the investigation of related growth factors, such as insulin-like growth factor I and insulin-like growth factor II, and in understanding the basis for stromal-epithelial cell interactions.     

Interleukin 4 receptor targeted cytotoxicity: genetic construction and in vivo immunosuppressive activity of a diphtheria toxin-related murine interleukin 4 fusion protein.

The interleukin 4 (IL 4) receptor is expressed on various cells of the immune system, including T and B lymphocytes, macrophages and mast cells. We have constructed a recombinant protein, DAB389-mIL 4, that is composed of the enzymatically active and membrane translocation domains of diphtheria toxin fused to murine IL 4. We demonstrate that this fusion toxin selectively inhibits protein synsthesis in eukaryotic cells which express the murine IL 4 receptor. The cytotoxic potency of this fusion toxin is shown to be directly proportional to the reported number of IL 4 receptors on the surface of target cells. Since the action of DAB389-mIL 4 can be blocked with either excess mIL 4 or antibody to mIL 4, we conclude that its entry into target cells is mediated through the mIL 4 receptor. A mutant form of DAB389-mIL 4, DA(197)B389-mIL 4, in which the fragment A-associated ADP-ribosyltransferase is inactive, is not cytotoxic to murine IL 4 receptor-bearing cells. Finally, we demonstrate that DAB389-mIL 4 administered subcutaneously to DBA/2 mice results in suppression of delayed-type hypersensitivity (DTH); whereas, the non-toxic DA(197)B389-mIL 4 fails to dampen the DTH response.     

Kinetic immunodominance: functionally competing antibodies against exposed and cryptic epitopes of Escherichia coli beta-galactosidase are produced in time sequence.

The murine antibody response to Escherichia coli beta-galactosidase (GZ) was analyzed in vivo and in vitro by focusing on two families of antibodies that exert distinct conformational/functional activity on the antigen. Activating antibodies--defined by their capacity to increase the enzymatic activity of defective GZ produced by mutant strains of E. coli--are detected early after secondary challenge. Inhibiting antibodies, which interfere with antibody-mediated enzyme activation, appear later and cause the abrupt fall of activating titer, a scenario suggesting either idiotype/anti-idiotype interaction or opposite pulsions exerted on the antigen molecule. Supporting the latter mechanism, the confrontation of mAbs of the two families produced classical competitive inhibition curves when the readout was enzyme activation, although they recognize two different epitopes of the same molecule: the activating mAb a quaternary conformation-dependent site of wild-type GZ, the inhibiting mAb a sequential determinant exposed only in denatured or in defective enzyme. The different timing of generation of these antibodies during the response may depend on a processing step necessary for unfolding of native antigen and consequent display of certain cryptic epitopes before they can trigger specific B cells. A picture emerges where the response to the various epitopes of a complex antigen is sequentially connected and where the uptake by antigen-presenting cells of antigen complexed with antibodies specific for the exposed epitopes may favor revelation of the cryptic ones.