On the role of intrinsic and extrinsic forces in early cardiac S‐looping

Background: Looping is a crucial phase during heart development when the initially straight heart tube is transformed into a shape that more closely resembles the mature heart. Although the genetic and biochemical pathways of cardiac looping have been well studied, the biophysical mechanisms that actually effect the looping process remain poorly understood. Using a combined experimental (chick embryo) and computational (finite element modeling) approach, we study the forces driving early s‐looping when the primitive ventricle moves to its definitive position inferior to the common atrium. Results: New results from our study indicate that the primitive heart has no intrinsic ability to form an s‐loop and that extrinsic forces are necessary to effect early s‐looping. They support previous studies that established an important role for cervical flexure in causing early cardiac s‐looping. Our results also show that forces applied by the splanchnopleure cannot be ignored during early s‐looping and shed light on the role of cardiac jelly. Using available experimental data and computer modeling, we successfully developed and tested a hypothesis for the force mechanisms driving s‐loop formation. Conclusions: Forces external to the primitive heart tube are necessary in the later stages of cardiac looping. Experimental and model results support our proposed hypothesis for forces driving early s‐looping. Developmental Dynamics 242:801–816, 2013. © 2013 Wiley Periodicals, Inc.     

A short-duration restrictive diet reduces visceral adiposity in the morbidly obese surgical patient

Background

This study aims to determine if visceral obesity can be reduced after a brief preoperative diet in obese patients.

Methods

Forty morbidly obese patients were placed on a 1,000 kCal per day diet for 14 days before bariatric surgery. Patients had weight measurements and an abdominal ultrasound performed on days 1 and 14. The ultrasound measured visceral obesity using the distance between the abdominal muscle and the aorta, the fat thickness of the perinephric space, and the distance between the abdominal muscle and splenic vein. Mesenteric fat burden was calculated and compared.

Results

Thirty-eight patients (95%) lost weight on the diet, with a mean loss of 5.2 lbs. Twenty-five patients (63%) had a reduction in mesenteric fat. The average visceral obesity lost was 7.76 cm³ or 3% of the visceral adiposity of the average obese patient (250 cm³).

Conclusions

A short preoperative calorie restricting diet is well tolerated and results in a reduction in visceral obesity.     

Analysis of risk factors for restenosis after PTCA

To identify risk factors for restenosis, we evaluated data in 473 patients with single-vessel percutaneous transluminal coronary angioplasty (PTCA) and control angiography after 6 months. Restenosis, defined as (1) loss greater than 50% of the initial gain, and (2) stenosis greater than 50% was found in 138 patients (29.2%). Univariate analysis revealed eight factors related to restenosis: (1) duration of symptoms less than 1 month (P = 0.005), (2) unstable angina (P = 0.004), (3) high-grade stenosis before PTCA (P = 0.014), (4) large residual stenosis after PTCA (P = 0.001), (5) insufficient improvement of stenosis (P = 0.042), (6) prolonged single inflation time (P = 0.017), (7) prolonged total inflation time (P = 0.055), and (8) low inflation pressure (P = 0.028). Multivariate analysis revealed four factors significantly related to restenosis: (1) large residual stenosis after PTCA (P = 0.0001), (2) prolonged single inflation time (P = 0.0047), (3) unstable angina (P = 0.0127), and (4) high-grade stenosis before PTCA (P = 0.0179). Modification of procedural factors might be helpful to reduce the risk of restenosis after successful PTCA.     

Parametric assessment of myocardial perfusion during interventional cardiac catheterization by means of X-ray densitometry-short-and long-term results

Summary X-ray densitometric evaluation of digital subtraction angiocardiograms allows an assessment of myocardial perfusion by means of the parameter MEAN RISE TIME (MRT), defined as the time from the onset of local myocardial contrast medium opacification to the point of maximum opacification. Best results are obtained when the response of that parameter is compared before and after stimulation of coronary flow by papaverine. A prolongation of this parameter, especially after papaverine, was indicative of an impairment of myocardial perfusion, when compared to the results obtained by TL-201 scintigraphy.In 50 patients with single vessel coronary artery disease the results of MRT pre and post papaverine before and after coronary angioplasty, as well as after 6 months were evaluated for 204 post-stenotic regions-of-interest. Before angioplasty papaverine induced a significant prolongation of post-stenotic MRT (2.3s ± 0.9s vs. 3.1s ± 0.8s; p<0.01), while after successful angioplasty post-stenotic MRT was measured significantly shorter after stimulation of coronary flow (2.6s ± 1.0s vs. 1.9s ± 0.9s; p<0.01). This indicated an improvement in myocardial perfusion. Nevertheless, 16/50 patients still presented pathological results of post-stenotic MRT after papaverine, although angioplasty was regarded successful. These patients presented a markedly higher rate of restenosis (14/16 patients after 6 months), a higher rate of dissections at the dilatation site and a higher rate of dilated vessels, supplying myocardial areas after a Q-wave myocardial infarction.Thus, these results demonstrate the additional information about the short-and long-term outcome of an angioplasty procedure by densitometric myocardial perfusion analysis.     

CD44 enhances tumor formation and lung metastasis in experimental osteosarcoma and is an additional predictor for poor patient outcome

Formation of metastases in the lungs is the major cause of death in patients suffering from osteosarcoma (OS). Metastases at presentation and poor response to preoperative chemotherapy are strong predictors for poor patient outcome. The elucidation of molecular markers that promote metastasis formation and/or chemoresistance is therefore of importance. CD44 is a plasma membrane glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and has been shown to be involved in metastasis formation in a variety of other tumors. Here we investigated the role of CD44 expression on OS tumor formation and metastasis. High CD44 expression, evaluated with a tissue microarray including samples from 53 OS patients and stained with a pan‐CD44 antibody (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However, nonresponders and patients with lung metastases and high CD44 expression had significantly poorer prognosis than patients with low CD44 expression. Overexpression of the standard CD44 isoform (CD44s) and its HA‐binding defective mutant R41A in osteoblastic SaOS‐2 cells resulted in HA‐independent higher migration rates and increased chemoresistance, partially dependent on HA. In an orthotopic mouse model of OS, overexpression of CD44s in SaOS‐2 cells resulted in an HA‐dependent increased primary tumor formation and increased numbers of micrometastases and macrometastases in the lungs. In conclusion, although CD44 failed to be an independent predictor for patient outcome in this limited cohort of OS patients, increased CD44 expression was associated with even worse survival in patients with chemoresistance and with lung metastases. CD44‐associated chemoresistance was also observed in vitro, and increased formation of lung metastases was found in vivo in SCID mice. © 2013 American Society for Bone and Mineral Research.     

An analysis of breast cancer risk in women with single, multiple, and atypical papilloma

Breast papillomas may be single or multiple and associated with atypical ductal or lobular hyperplasias (ADH/ALH). The risk of breast carcinoma development in patients with papillomas, particularly those with multiple or atypical lesions, is incompletely defined. Fibrocystic lesions were histopathologically classified in a benign breast disease cohort of 9155 who underwent biopsy from 1967 to 1991, with papilloma assessment in 9108. Individuals with papillomas (N=480) were classified into 4 groups: single papilloma (SP, N=372), single papilloma with ADH or ALH (SP+A, N=54), multiple (>5) papillomas (MP, N=41), and multiple papillomas with ADH or ALH (MP+A, N=13). Those without papillomas were classified as nonproliferative (NP, N=6053), proliferative without atypia (PDWA, N=2308), and ADH/ALH [atypical hyperplasia (AH), N=267]. The relative risk of cancer development within our cohort was compared to that expected in the general population using standardized incidence ratios. The relative risk of breast cancer development associated with SP [2.04, 95% confidence interval (CI) 1.43-2.81] was greater than NP (1.28, 95% CI 1.16-1.42) but similar to PDWA (1.90, 95% CI 1.66-2.16). The risk associated with SP+A (5.11, 95% CI 2.64-8.92) was highly elevated but not substantively different than atypical hyperplasia (4.17, 95% CI 3.10-5.50). Patients with MP are at increased risk compared with PDWA or SP (3.01, 95% CI 1.10-6.55), particularly those with MP+A (7.01, 95% CI 1.91-17.97). There was a marginal increase in breast cancer risk (16%) among patients with proliferative disease if a papilloma was present, but this did not reach statistical significance (P=0.29). The observed frequency of ipsilateral (vs. contralateral) breast cancer development in papilloma subsets was not significantly different than other patient groups. We conclude that SP imparts a cancer risk similar to conventional proliferative fibrocystic change. The presence of papilloma in, or associated with, atypia does not modify the risk connotation of ADH/ALH overall. MP constitutes a proliferative breast disease subset having unique clinical and biologic behavior.     

The role of pannus in the longevity of an Ionescu-Shiley pericardial bioprosthesis

As the population ages, bioprosthetic heart valves are increasingly being used to replace diseased native valves. Bioprosthetic valve durability depends on patient age and other factors, but rarely exceeds 15 years. Explanted bioprosthetic valves commonly show tissue degeneration, tears, and calcification. Host tissue overgrowth (pannus), to the extent of interfering with their function, is another finding in bioprostheses that have been in place for long periods. We present a case in which a bovine pericardial valve was explanted after more than 20 years of implantation. The longevity of this pericardial valve may have been related to excessive pannus growth, which most likely protected the valve from earlier failure.