Effect of estradiol on accelerated atherosclerosis in rabbit heterotopic aortic allografts.

Migration and proliferation of vascular smooth muscle cells are early and major events in the formation of atherosclerotic lesions. We report on an aorta transplant model in rabbits wherein myointimal proliferation is inhibited by 17-beta-estradiol. The abdominal aortas of outbred white New Zealand rabbits were harvested and allografted to the carotid artery of the recipient. The animals, which were fed either a normal or a high-cholesterol (0.5%) diet, were killed 3 weeks later. The degree of myointimal proliferation was measured with a digitized system attached to a light microscope. The myointimal hyperplasia was expressed as the cross section area of the intima/the area of the intima + the area of the media x 100. Transmission electron micrographs were obtained for all vessels. Intimal thickening was shown mainly to consist of proliferating smooth muscle cells. The cholesterol diet resulted in significantly higher serum total cholesterol levels compared to animals on a normal diet (p < 0.0001) but did not affect serum high-density lipoprotein-cholesterol or serum triglyceride levels. The cholesterol diet was also associated with a greater but not significant amount of intimal thickening. Treatment with 17-beta-estradiol significantly decreased both serum triglyceride concentration (p < 0.05) and myointimal thickening (p < 0.01) in cholesterol-fed animals. Transmission electron microscopy showed that the endothelial cells appeared structurally normal in the estradiol-treated animals. Further, estradiol prevented the appearance of vacuolized macrophages. Thus estradiol may decrease myointimal thickening by preserving the endothelium and preventing macrophage appearance in the intima.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chemical constituents of Isodon albopilosus (C.Y. Wu et H.W. Li) Hara]

Five compounds have been isolated from the stems and leaves of Isodon albopilosus. On the basis of spectroscopic and chemical data, they were identified as macrocalyxin C, stearic acid, beta-sitosterol, ursolic acid and beta-sitosterol-beta-D-glucoside, respectively.     

Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors.

The over-representation of chromosome 12p sequences is crucial for the development of invasive testicular germ cell tumors. Testicular cancer patients may have metastatic tumors of diverse histologic types, including adenocarcinoma, undifferentiated carcinoma, sarcoma, or other malignancies that lack features of germ cell tumors. We sought to investigate the possible germ cell origin of such tumors using interphase fluorescence in situ hybridization. In all, 10 metastatic malignant somatic-type tumors from patients with histories of testicular cancer, as well as one malignant somatic-type tumor from a patient with primary mediastinal germ cell tumor were studied and included: adenocarcinoma (five cases), poorly differentiated carcinoma (one), sarcoma (four), and neuroendocrine carcinoma (one). The tumors were analyzed using fluorescence in situ hybridization using 12p spectrum green and 12 centromeric spectrum orange probes in paraffin sections. The patients ranged in age from 27 to 55 years (mean, 43). Colon and lung cancers from patients without germ cell tumors were used as controls. Adequate signals were observed in all tumors. Gain of chromosome 12p was seen in six tumors. None of the control tumors showed 12p amplification. Fluorescence in situ hybridization for 12p amplification in routinely processed surgical specimens is a useful adjuvant diagnostic tool in confirming the germ cell origin of metastatic tumors having the histologic appearance of somatic-type neoplasms.     

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.     

Monitoring the protective effects of minocycline treatment with radiolabeled annexin V in an experimental model of focal cerebral ischemia.

Minocycline is an antibiotic now recognized to have antiapoptotic and antiinflammatory properties. Because of these properties, minocycline may be of benefit in reducing neuronal apoptosis from ischemia and subsequent postischemic inflammation if administered soon after a stroke. We now explore the feasibility of using (99m)Tc-annexin V, an in vivo marker of apoptosis, with SPECT to monitor the antiapoptotic effects of minocycline therapy. METHODS: CB6/F1 adult male mice underwent unilateral distal middle cerebral artery occlusion (dMCA) occlusion and were imaged and sacrificed at 1, 3, 7, or 30 d after injury. Animals were given minocycline (or vehicle) 30 min and 12 h after dMCA occlusion and then given 22.5 mg/kg twice daily for up to 7 d. Before imaging, behavioral tests were performed to evaluate the neurologic function. After imaging, brains were collected for histology and assessed for the degree of apoptosis and microglial activation. RESULTS: (99m)Tc-Annexin V uptake in injured hemispheres was significantly decreased 2- to 3-fold by minocycline at all time points. Minocyline reduced infarct size as seen histologically and improved behavioral indices as late as 30 d. Infarct volume as seen histologically correlated with radiolabeled annexin V uptake seen by SPECT. In situ fluorescent microscopy demonstrated that annexin V bound primarily to neurons at 1 and 3 d, with a shift toward microglia by 7 and 30 d. CONCLUSION: We found that minocycline significantly reduces neuronal apoptosis and infarct size and improves neurologic outcome in mice after acute focal cortical ischemia.     

Hepatic pseudotumor in long-standing biliary atresia patients undergoing liver transplantation.

A pseudotumor, giant regenerative nodule, or macroregenerative nodule is an unusual benign hepatic lesion in biliary atresia (BA) patients. This tumor may mimic malignant transformation and may preclude liver transplantation (LT). The clinical and imaging surveillance of patients after the Kasai procedure is therefore an important aspect of management of BA patients. Our objective is to report our experience and describe the incidence, imaging, and pathologic features of pseudotumors in BA patients awaiting LT. From August 1990 to December 2006, 133 LTs for BA were performed. Five (3.8%; 4 female, 1 male) patients were diagnosed with pseudotumor. The patients' records were reviewed. The diagnostic imaging modalities used were abdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI). Histologic confirmation of the lesions was obtained in all cases. All underwent the Kasai operation in early infancy. Six of 7 lesions in 4 of 5 patients were demonstrated by pretransplant imaging. Two of 7 tumors were detected by US. Five of 7 lesions were detected by CT, and 5 of 7 lesions were demonstrated by MRI. In 1 patient, the lesion was not seen in the US, CT, or MRI but was found during surgery and confirmed by histology. An additional tumor was found incidentally during histologic examination in a patient previously diagnosed to have 2 tumors by CT and MRI. In another patient diagnosed to have 2 tumors on imaging, pathology revealed only a single tumor. In conclusion, although unusual, pseudotumor should be included in the differential diagnosis of liver masses in BA children.     

Septal-lateral annnular cinching perturbs basal left ventricular transmural strains.

OBJECTIVE: Septal-lateral annular cinching ('SLAC') corrects both acute and chronic ischemic mitral regurgitation in animal experiments, which has led to the development of therapeutic surgical and interventional strategies incorporating this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3). Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after SLAC, however, remain unknown. METHODS: Eight normal sheep hearts had two triads of transmural radiopaque bead columns inserted adjacent to (anterobasal) and remote from (midlateral equatorial) the mitral annulus. Under acute, open chest conditions, 4D bead coordinates were obtained using videofluoroscopy before and after SLAC. Transmural systolic strains were calculated from bead displacements relative to local circumferential, longitudinal, and radial cardiac axes. Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f), X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes using fiber (alpha) and sheet (beta) angle measurements. Results: SLAC markedly reduced (approximately 60%) septal-lateral annular diameter at both end-diastole (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to 1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural systolic strains did not change. In the anterobasal region adjacent to the mitral annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/-0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural systolic and remodeling strains in the lateral midwall (remote from the annulus) were unaffected. CONCLUSIONS: Although SLAC is an alluring concept to correct ischemic mitral regurgitation, these data suggest that extreme SLAC adversely effects systolic wall thickening adjacent to the mitral annulus by inhibiting systolic sheet thickening, sheet shear, and sheet extension. Such alterations in LV strains could result in unanticipated deleterious remodeling and warrant further investigation.     

Improved documentation of wound care with a structured encounter form in the pediatric emergency department.

OBJECTIVE: Accurate and complete documentation may enhance reimbursement and compliance with financial intermediary regulations, protect against litigation, and improve patient care. We measured the effect of introduction of a structured encounter form on the completeness of documentation of pediatric wound management in a teaching hospital. METHODS: The Children's Hospital Emergency Department introduced a structured encounter form for use in the documentation of wound care in place of the existing free-text dictation method. Attending physicians and trainees, all unaware of the study, had the option of using the form in place of free-text dictation for patients with lacerations requiring closure. We abstracted 100 consecutive free-text dictations from patients treated before the form's introduction. Following a 3-month run-in period, we abstracted 100 consecutive structured wound records. We compared the 2 chart types for completeness of documentation based on 20 predetermined criteria relevant to pediatric wound care. RESULTS: Overall completeness of documentation improved with structured forms (80% vs 68% for free text, P < .001), with significant improvements in 6 of 20 individual criteria. Trainees demonstrated improvement in documentation with the structured form, with the greatest improvements among senior-level residents. Documentation of the general physical examination worsened with structured charting. DISCUSSION: In an academic pediatric emergency department, the use of a structured complaint-specific form improved overall completeness of wound-care documentation. Structured encounter forms may provide for more standardized documentation for a variety of pediatric chief complaints, thereby facilitating communication and ultimately transition to template-driven systems in anticipation of an electronic medical record.