Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.     

Nuclear deoxyribonucleic acid content (ploidy) of endodermal sinus (yolk sac) tumor

Paraffin sections from 30 endodermal sinus (yolk sac) tumors were Feulgen-stained, and nuclear DNA content (ploidy) was assessed through DNA cytophotometry using the microTICAS image analysis system. The series consisted of 20 ovarian, 8 testicular, 1 sacrococcygeal, and 1 mediastinal tumors. Of the 30 endodermal sinus (yolk sac) tumors 29 were shown to be aneuploid, whereas the remaining tumor which exhibited the recently described primitive intestinal or enteric pattern was diploid and may thus be considered a neoplasm showing a somewhat higher degree of differentiation as compared to tumors showing the other histologic patterns of endodermal sinus (yolk sac) tumors.     

The role of pRb2/p130 protein in diagnosing lung carcinoma on fine needle aspiration biopsies

The retinoblastoma gene family is composed of three members: the retinoblastoma gene, one of the most studied tumor suppressor genes, and two related genes: p107 and pRb2/p130. These proteins are also known as the pocket proteins due to a unique structural and functional domain composed of subdomains A and B separated by a spacer region that is highly conserved among each of the proteins. These proteins exhibit unique growth suppressive properties that are cell type specific, suggesting that although the pocket proteins may complement each other, they are not fully functionally redundant. With the development of antibodies recognizing these three proteins it is now possible to detect expression in formalin-embedded specimens. Recent studies on 235 lung cancers, using immunohistochemical techniques, suggested an independent role for Rb2/p130 in the development and/or progression of human lung carcinoma. We found a statistically significant inverse relationship between the histological grading (degree of malignant potential) and the expression of pRb/p105, p107 and pRb2/p130 in squamous cell carcinomas, meaning that an increase in grading resulted in a significant decrease in protein expression. This phenomenon was particularly evident for pRb2/p130 (p < .0001) which had the highest percentage of undetectable levels in all the specimens examined and the tightest inverse correlation (p value) with both the histological grading and PCNA expression in the most aggressive tumor types, suggesting an important role for pRb2/p130 in the pathogenesis and progression of certain lung cancers. We further explored the expression of pRb2/p130 protein in routine archival FNAB cytological material from 30 Patients with lung cancer using immunocytochemical techniques, comparing protein expression with tumor type. Two pathologists evaluated the staining pattern and scored the percentage of positive cells. Of the 30 neoplasms, 27 displayed a positive staining for pRb2/p130. In particular, we detected pRb2/p130 in 9 (100%) squamous carcinomas, 11 (84%) adenocarcinomas, 5 (100%) BAC, and 2 (66%) SCC. The percentage of positive nuclei varied in different tumors with the highest expression level in adenocarcinomas. Immunocytochemistry represents a sensitive method for detection of pRb2/p130 expression in cytological or archival specimens, and the level of detection seems to be comparable to paraffin sections. Therefore, this methodology could be used in the preoperative evaluation of routine cytological specimens in order to improve the diagnostic and prognostic evaluation of lung cancer patients.     

First human case of retrograde transcatheter implantation of an aortic valve prosthesis

The transcatheter route is an emerging approach to treating valvular disease in high-risk patients. The 1st clinical antegrade transcatheter placement of an aortic valve prosthesis was reported in 2002. We describe the first retrograde transcatheter implantation of a new aortic valve prosthesis, in a 62-year-old man with inoperable calcific aortic stenosis and multiple severe comorbidities. Via the right femoral artery, a Cook introducer was advanced into the abdominal aorta. The aortic valve was crossed with a straight wire, and a pigtail catheter was advanced into the left ventricle to obtain pressure-gradient and anatomic measurements. An 18-mm valvuloplasty balloon was then used to predilate the aortic valve. Initial attempts to position the prosthetic valve caused a transient cardiac arrest. Implantation was achieved by superimposing the right coronary angiogram onto fluoroscopic landmarks in the same radiographic plane. A balloon-expandable frame was used to deliver the valve. After device implantation, the transvalvular gradient was <5 mmHg. The cardiac output increased from 1 to 5 L/min, and urine production increased to 200 mL/h. The patient was extubated on the 2nd postimplant day. Twelve hours later, he had to be reintubated because of respiratory distress and high pulmonary pressures. His condition deteriorated, and he died of biventricular failure and refractory hypotension on day 5. Despite the severe hypotension, valve function was satisfactory on echo-Doppler evaluation. In our patient, retrograde transcatheter implantation of a prosthetic aortic valve yielded excellent hemodynamic results and paved the way for further use of this technique in selected high-risk patients.     

VERSAJETtm Hydrosurgery Technique for the Preparation of Full Thickness Skin Grafts and the Creation of Retrograde Split Thickness Skin Grafts

Full- and split-thickness skin grafts continue to serve a vital role in lower extremity wound coverage, and meticulous preparation of the recipient site is vital to incorporation of the transplanted skin. A technique for the rapid, controlled preparation of full-thickness skin grafts and creation of thick-split thickness skin grafts from full-thickness donor tissue, using a high-pressure stream of saline solution, is described.