Oligodendroglioma in a patient with AIDS: case report and review of the literature

In the last years, new techniques of neuroimages and histopathological methods have been added to the management of cerebral mass lesions in patients with AIDS. Stereotactic biopsy is necessary when after 14 days of empirical treatment for Toxoplasma gondii encephalitis there is no clinical or neuroradiologic improvement. We report a woman with AIDS who developed a single focal brain lesion on the right frontal lobe. She presented a long history of headache and seizures. After two weeks of empirical treatment for toxoplasma encephalitis without response, a magnetic resonance image with spectroscopy was performed and showed a tumoral pattern with a choline peak, diminished of N-acetyl-aspartate and presence of lactate. A stereotactic biopsy was performed. Histopathological diagnosis was a diffuse oligodendroglioma type A. A microsurgical resection of the tumor was carried out and antiretroviral treatment was started. To date she is in good clinical condition, with undetectable plasma viral load and CD4 T cell count > 200 cell/uL.     

Divergent effects of low versus high dose anti-TGF-beta antibody in puromycin aminonucleoside nephropathy in rats

BACKGROUND: Transforming growth factor-beta (TGF-beta) modulates immune/inflammatory cells, promotes extracellular matrix (ECM) accumulation, and is increased in fibrotic organs. Here we report the effects of administering a puromycin aminonucleoside nephropathy (PAN)-specific TGF-beta neutralizing antibody on glomerulosclerosis in vivo. METHODS: Adult male Sprague-Dawley rats underwent uninephrectomy (Nx) followed by intraperitoneal PAN at weeks 2, 6, 7 and 8. Rats were treated with either high (5 mg/kg body weight) (N= 9) or low (0.5 mg/kg body weight) (N= 7) dose TGF-beta antibody intraperitoneally three times weekly until sacrifice at week 10. A PAN untreated control group (N= 7) was dosed with an isotype specific, null antibody. The nephrectomy samples were studied as normal kidney control (NL) (N= 5). Rats undergoing left kidney Nx (N= 5) only were also included as age-matched control. Renal function and morphology were assessed, and molecular studies performed. RESULTS: Systolic blood pressure was increased in parallel over time in all groups (at 10 weeks, control 137 +/- 10 mm Hg; high 129 +/- 4 mm Hg; low 137 +/- 3 mm Hg) (P= NS). Both TGF-beta antibody treatments decreased renal cortex mRNA expressions similarly for TGF-beta1, TGF-beta2, and collagen III (TGF-beta1, control 0.36 +/- 0.02 mm Hg; high 0.19 +/- 0.01 mm Hg; low 0.19 +/- 0.02 mm Hg; P < 0.01 low and high vs. control; TGF-beta2, control 0.38 +/- 0.03 mm Hg; high 0.19 +/- 0.02 mm Hg; low 0.20 +/- 0.03 mm Hg; P < 0.01 low and high vs. control; and collagen III, control 0.33 +/- 0.01 mm Hg; high 0.14 +/- 0.01 mm Hg; low 0.19 +/- 0.01 mm Hg; P < 0.01 low and high vs. control; P < 0.05 low vs. high, data expressed as mRNA normalized density units vs. 18S RNA). However, only low dose TGF-beta antibody improved renal function and sclerosis measured by serum creatinine and creatinine clearance (serum creatinine, control 2.3 +/- 0.5 mg/dL; high 2.5 +/- 0.5 mg/dL; low 0.8 +/- 0.1 mg/dL; P < 0.05 low vs. control and high; creatinine clearance, control 0.44 +/- 0.11 mL/min; high 0.70 +/- 0.26 mL/min; low 1.34 +/- 0.30 mL/min; P < 0.05 low vs. control, P= NS vs. high). In parallel, sclerosis index (0 to 4+ scale) was improved in low dose (control 2.67 +/- 0.27; high 2.37 +/- 0.30; low 1.78 +/- 0.24; P < 0.05 low vs. control). This improved function and structure was linked to decreased glomerular infiltrating macrophages (0 to 4+ score, control 2.3 +/- 0.2; high 1.8 +/- 0.4; low 0.8 +/- 0.1; P < 0.01 low vs. control; P < 0.05 low vs. high; P= NS high vs. control). Further, plasminogen activator inhibitor-1 (PAI-1) mRNA expression in renal cortex was attenuated after low dose TGF-beta antibody treatment compared to control and high dose group (PAI-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratio, NL 0.18 +/- 0.003; control 0.45 +/- 0.03; high 0.40 +/- 0.04; low 0.23 +/- 0.01; P < 0.05 low vs. control and high). Matrix metalloproteinase-9 (MMP-9) activity was maintained at higher levels in kidneys of the low dose TGF-beta antibody-treated group. CONCLUSION: These results show an in vivo dose-response with an agent that blocks the biologic activity of TGF-beta. Higher dose of TGF-beta antibody was without beneficial effect, suggesting that TGF-beta-mediated effects on PAI-1 and macrophage influx are bimodal and closely regulated. Given that both antibody doses reduced the expression of TGF-beta isoforms and collagen III production, but only low dose ameliorated histologic sclerosis, it appears that pharmacologic effects of anti-TGF-beta antibody on matrix synthesis and degradation are not equivalent.     

Thorough intraoperative analysis of breast sentinel lymph node biopsies: histologic and immunohistochemical findings

BACKGROUND: We report the use of a thorough intraoperative sentinel lymph node (SLN) biopsy screening procedure for patients with small N0 breast tumors. METHODS: Sixty-eight consecutive female patients with monofocal stage I or "small" stage II (ie, 2.1-3.0 cm) N0 tumors received intraoperative SLN screening according to a procedure on the basis of comprehensive histologic analysis and cytokeratin immunohistochemical determination (CkID) of adjacent frozen sections of the SLN taken at 50-microm cutting levels. RESULTS: The maximum duration of intraoperative analysis including CkID was 40 minutes. Positive SLN were found in 15/68 (22%) patients (always in a single node); they included 5 instances of micrometastasis and 3 of carcinomatous lymphangitis. In the 14 patients who underwent axillary lymph node dissection, no further metastasis was found at histologic analysis or CkID. SLN positivity correlated with histologic type (P=.044), intratumoral or peritumoral vascular invasion (P<.001) and Mib1 score (P=.042). CONCLUSIONS: It is possible for an experienced team to perform intraoperative SLN screening for T1 or small T2 N0 breast tumors with frozen sections taken at 50-microm cutting levels. This procedure facilitates identification of micrometastasis, as well as of carcinomatous lymphangitis to help understand the biologic implications of these small lesions in the long term. SLN positivity appears to correlate with histologic type, intratumoral/peritumoral vascular invasion and Mib1 score.     

The role of linezolid in the therapy of infections caused by multiresistant gram-positive cocci

Gram-positive cocci are becoming more and more common agents of nasocomial infections, primarily enterococci and staphylococci in the field of surgical site and bloodstream infection. At the same time, the frequency of multiresistant enterococci and methicillin-resistant staphylococci has increased, whereas glycopeptide-resistant enterococcal strains and, recently, staphylococci with reduced susceptibility to glycopeptides have appeared, so making the use of glycopeptides as the "last-chance drugs" ineffective. Under those circumstances, the synthesis of new potent antibiotics, such as oxazolidinones, is both desirable and welcome. Linezolid possesses a high activity against all multiresistant gram-positive cocci, favourable pharmacokinetics, a good safety profile, a complete bioavailability after and administration permitting switch therapy, a low capacity of inducing resistance, and both clinical and microbiologic efficacy as demonstrated by a number of clinical trials conducted on thousands of patients. So, linezolid is an important therapeutic option in the treatment of infections caused by multiresistant enterococcal and staphylococcal strains.     

Follicular fluid antibodies to Chlamydia trachomatis and human heat shock protein-60 kDa and infertility in women

BACKGROUND: The objective of this study was to establish the relationship between presence of anti-Chlamydia trachomatis and anti-HSP60 antibodies in serum and follicular fluid of infertile women. METHODS: Serum IgG and follicular fluid IgA to Chlamydia trachomatis and human heat shock protein 60 (HSP60) were determined in 41 women undergoing in vitro fertilization (IVF). RESULTS: A significant association was found between presence of bacterial antibodies in serum and IgA anti-HSP60 in follicular fluid. CONCLUSIONS: Chlamydia trachomatis infection might be triggering an autoimmune process that could negatively affect the success of IVF.     

Investigation into the effect of household triatomine infestation on awareness among inhabitants of settlements and re-settlements in areas infested with Triatoma sordida in São Paulo State, Brazil

This study aims to analyze the effect of domiciliary infestation by triatomine bugs on the degree to which inhabitants are aware of potential vector transmission of Chagas disease. Such recently constructed dwellings comprise housing groups classified as settlements and re-settlements, selected respectively in the municipalities of Euclides da Cunha Paulista and Paulicéia, S?o Paulo State, Brazil. Both municipalities are under the jurisdiction of the Presidente Prudente Health Administrative Region. Of the 319 residents, some 100 (76.0% of whom were re-settlement residents) knew about triatomine bugs. Housing units infested with triatomines were inhabited by 93 people. In 79.2% of the infested houses, 26.8% of the residents knew about Chagas disease and its vectors, but in 50.0% of the households, some people did not know what to do in case of triatomine infestation. Population samples from settlements and re-settlements, regardless of sex, age, and the State of origin, showed no difference in attitudes towards the prevention of Chagas disease or knowledge of the disease vector.     

Developmental and tissue-specific regulation of a novel dysferlin isoform

Dysferlin plays an essential role in the muscle repair machinery, and its deficiency is associated with limb-girdle muscular dystrophy type 2B and with two different distal myopathies (Miyoshi myopathy and distal anterior compartment myopathy). Our aims were to characterize the pattern of dysferlin expression during myogenic cell differentiation and to assess possible differentially spliced isoforms of the DYSF gene. Human primary myogenic cells express a splice variant of dysferlin mRNA lacking exon 17 (Delta17), together with full-length dysferlin mRNA. Real-time polymerase chain reaction analysis of human myoblasts, myotubes, and normal skeletal muscle showed that Delta17 expression inversely correlates with muscle differentiation. Indeed, Delta17 is progressively replaced by the wild type as myoblast fusion proceeds, and it disappears in adult skeletal muscle. Conversely, Delta17 is the predominant dysferlin variant in mature peripheral nerve. Our findings suggest that the two proteins play different roles in myogenic cell differentiation and that dysferlin function in peripheral nerve might be accomplished by this novel isoform.     

Vasopeptidase inhibitors: will they have a role in clinical practice?

The human cardiovascular system is regulated by haemodynamic, neurohumoral and structural mechanisms. The endothelium and the neurohumoral system play a key role in modulating both vascular tone and structure by producing vasoactive substances, and in the modulation of blood cell adhesion. Although the neurohormonal systems are essential in vascular homeostasis, they become maladaptive in conditions such as hypertension, coronary disease and heart failure. The clinical success of blocking the renin-angiotensin system by angiotensin converting enzyme (ACE)-inhibitors and the sympathetic nerve system by beta-blockers demonstrates the importance of neurohumoral blockade. The inadequate effect of angiotensin converting enzyme (ACE) or neutral endopeptidase (NEP) inhibitor monotherapy seen in some patients treated for hypertension or congestive heart failure, and the promising effect seen after their combination, led to the development of drugs that simultaneously inhibit both enzyme systems. Neutral endopeptidase, like ACE, is an endothelial cell surface zinc metallopeptidase with similar structure and catalytic site to ACE. NEP is the major enzymatic pathway for degradation of natriuretic peptides. The natriuretic peptide system can be viewed as the endogenous inhibitor of the renin angiotensin system. The dual metalloprotease inhibitors of ACE and NEP, called vasopeptidase inhibitors therefore represent a new and attractive therapeutic strategy for the treatment of cardiovascular disease. The ability to add incremental benefit over already proven therapy, with an acceptable side-effect profile however, is questionable in this new class of agents.     

Predictive value of biological markers for hepatocellular carcinoma patients treated with orthotopic liver transplantation.

PURPOSE: To help stratify candidates with hepatocellular carcinoma (HCC) for orthotopic liver transplantation (OLT), biomarkers are needed that are capable of predicting recurrence of disease (ROD). We investigated the prognostic role in this setting of immunohistochemical markers reported previously to predict poor prognosis in HCC patients treated with resection. EXPERIMENTAL DESIGN: Eighty-three patients with HCC who underwent OLT between 1987 and 2001 with a minimum clinical follow up of 12 months were included in this retrospective study. We analyzed immunohistochemical expression of the adhesion molecules E-cadherin and beta-catenin (membrane/nuclear localization), MIB-1 proliferative index and the cyclin-dependent kinase inhibitor p27, alongside the main clinical-pathological variables. RESULTS: At univariate analysis, vascular thrombosis, high MIB-1 index, lower membrane expression of E-cadherin and beta-catenin, and nuclear beta-catenin localization were associated with ROD. At multivariate analysis, only MIB-1 index, low equal E-cadherin (with respect to non-neoplastic surrounding tissue), and nuclear beta-catenin appeared as independent predictors of ROD. The logistic regression analysis model indicated that detection of any one parameter was associated with at least 88% estimated risk of ROD (up to 99% for all three). CONCLUSIONS: We propose these three molecular parameters as an additional tool for rational selection of OLT candidates among HCC patients (stratification according to the risk of ROD might help provide a similar life expectancy for cirrhotic candidates with and without HCC).