Endoglin is required in Pax3-derived cells for embryonic blood vessel formation.

Mutations in endoglin, a TGFß/BMP coreceptor, are causal for hereditary hemorrhagic telangiectasia (HHT). Endoglin-null (Eng-/-) mouse embryos die at embryonic day (E)10.5-11.5 due to defects in angiogenesis. In part, this is due to an absence of vascular smooth muscle cell differentiation and vessel investment. Prior studies from our lab and others have shown the importance of endoglin expression in embryonic development in both endothelial cells and neural crest stem cells. These studies support the hypothesis that endoglin may play cell-autonomous roles in endothelial and vascular smooth muscle cell precursors. However, the requirement for endoglin in vascular cell precursors remains poorly defined. Our objective was to specifically delete endoglin in neural crest- and somite-derived Pax3-positive vascular precursors to understand the impact on somite progenitor cell contribution to embryonic vascular development. Pax3Cre mice were crossed with Eng+/- mice to obtain compound mutant Pax3(Cre/+);Eng+/- mice. These mice were then crossed with homozygous endoglin LoxP-mutated (Eng(LoxP/LoxP)) mice to conditionally delete the endoglin gene in specific lineages that contribute to endothelial and smooth muscle constituents of developing embryonic vessels. Pax3(Cre/+);Eng(LoxP/)(-) mice showed a variety of vascular defects at E10.5, and none of these mice survived past E12.5. Embryos analyzed at E10.5 showed malformations suggestive of misdirection of the intersomitic vessels. The dorsal aorta showed significant dilation with associated vascular smooth muscle cells exhibiting disorganization and enhanced expression of smooth muscle differentiation proteins, including smooth muscle actin. These results demonstrate a requirement for endoglin in descendants of Pax3-expressing vascular cell precursors, and thus provides new insight into the cellular basis underlying adult vascular diseases such as HHT.

Cardiac sarcoid in a heart transplant recipient: detection with cardiac magnetic resonance imaging.

We describe the case of a 54-year-old man who presented with cardiac sarcoid 1 month after tapering of corticosteroids and 3 years post-cardiac transplantation. In addition to evidence of noncaseating granulomas on endomyocardial biopsy, a cardiac magnetic resonance imaging (MRI) study showed a typical subepicardial pattern of fibrosis corroborating the pathological diagnosis of sarcoid. This is the first description of cardiac sarcoid developing so late after transplantation. This report suggests that MRI may be an effective noninvasive modality to identify sarcoid in cardiac allografts.

Use of an elastic stain to show venous invasion in colorectal carcinoma: a simple technique for detection of an important prognostic factor.

BACKGROUND: Venous invasion (VI) is an important prognostic factor in colorectal cancer; it is positively associated with visceral metastases and may affect the decision to treat with adjuvant therapy. AIMS: To evaluate whether an elastic tissue (Movat) stain facilitates identification of VI, the number of Movat-stained blocks needed to detect VI, and whether VI identified with a Movat stain is prognostically equivalent to VI identified on H&E-stained slides. METHODS: H&E-stained sections from colorectal carcinomas from the year 2000 (n = 92) were examined for VI and compared to Movat-stained slides. Clinical charts were reviewed to compare rates of metastases in VI-positive versus VI-negative patients. RESULTS: With the Movat stain, VI was identified in 44% of cases previously categorised as negative (p<0.001) on review of H&E slides alone. One Movat-stained section was often sufficient to identify VI, with a statistically significant benefit to performing multiple stains if necessary. In H&E sections, two clues helped identify VI: the "unaccompanied artery" sign, where large arteries were seen without an accompanying vein; and the "protruding tongue" sign, where smooth tongues of tumour extended into pericolic/rectal fat. Metastases were present in 61% of cases positive for VI compared to 35% in VI-negative cases (p = 0.03). 45% of cases positive for intramural VI only developed metastases (p = 0.39), while 65% of cases positive for extramural VI only developed metastases (p = 0.03). CONCLUSIONS: Pathologists should look for morphological clues of VI in H&E stained sections; when VI is not apparent, an elastic tissue stain on all tumour blocks significantly improves identification of VI. Morphological clues include the "unaccompanied artery" and "protruding tongue" signs.

Microscopic model of diffusion limited aggregation and electrodeposition in the presence of leveling molecules.

We present a cellular automata approach for microscopic modeling of the effect of unbinding in diffusion limited aggregation. The automata represent active particles, which are able to change their internal state and affect their neighbors. The geometry resembles electrochemical deposition-"ions" diffuse at random from the top of a container until encountering an aggregate in contact with the bottom, to which they stick. This model exhibits dendritic (fractal) growth in the diffusion limited case. The addition of a field eliminates the fractal nature but the density remains low. The addition of molecules that unbind atoms from the aggregate transforms the deposit to a 100% dense one (in three dimensions). The molecules are remarkably adept at avoiding being trapped. This mimics the effect of so-called leveler molecules which are used in electrochemical deposition.

Plastic bread-bag clips in the gastrointestinal tract: report of 5 cases and review of the literature.

Plastic bread-bag clips have been identified as a cause of local perforation or obstruction at many sites in the gastrointestinal tract. This study is the largest case series yet reported, consisting of 3 cases presenting as small-bowel perforation, 1 case in which the clip was found incidentally in the small bowel at laparotomy during vascular surgery and 1 case in which the clip was found incidentally in the small bowel at autopsy. In all cases there was no radiographic evidence to suggest a foreign body in the gastrointestinal tract. People older than 60 years of age who have either partial or full dentures seem to be particularly at risk for the accidental ingestion of these devices. If accidentally ingested, plastic bread-bag clips represent a significant health hazard. As the population ages, small-bowel perforation secondary to ingestion of such clips may occur with increasing frequency. The authors recommend elimination or redesign of the clips, to prevent their being swallowed and becoming impacted in the small bowel or to allow them to be identified in the gastrointestinal tract by conventional radiography.

Biologic characteristics of breast cancer detected by mammography and by palpation in a screening program: a pilot study.

OBJECTIVE: To compare the histopathologic features and expression of p53 and c-erb B2 in the tumours detected by mammography only (clinically occult tumours) and the tumours detected by a nurse examiner (clinically palpable tumours). SETTING: London branch of the Ontario Breast Screening Program, which uses both clinical breast examination and mammography as screening methods. INTERVENTIONS: Pathologic review and immunohistochemical staining of all tumours detected between 1990 and 1993. OUTCOME MEASURES: Categorization of tumours by detection method and analysis of tumour size, grade, type, lymph node status and c-erb B2 and p53 expression in each group. RESULTS: From 1990 to 1993, 131 tumours were detected in patients ranging in age from 50 to 85 years (median 63 years). Sixty-seven occult tumours and 64 palpable lesions were detected. The occult tumours were significantly smaller (1.34 cm v. 2.29 cm, p < 0.0001) than the palpable ones and included a higher proportion of special-type lesions and ductal carcinoma in situ (43.3% v. 10.9%, p < 0.0001). Occult invasive carcinomas were of lower grade than palpable carcinomas (68.4% grade 1, 21.1% grade 2, 10.5% grade 3 v. 32.8% grade 1, 36.1% grade 2, 31.1% grade 3, p < 0.0001). Fewer occult lesions showed axillary nodal metastases (19.6% v. 40.6%, p = 0.02). No statistically significant differences were found for p53 or c-erb B2 positivity between the 2 groups. CONCLUSION: Tumours detected by different screening methods in a screening program have different pathologic characteristics.

Axillary node dissection in patients with breast cancer diagnosed through the Ontario Breast Screening Program: a need for minimally invasive techniques.

OBJECTIVE: To determine the role of axillary node dissection by studying patient and tumour characteristics of invasive breast cancer through the Ontario Breast Screening Program (OBSP). DESIGN: A retrospective evaluation. SETTING: The London, Ont., branch of the OBSP. PATIENTS: Three groups of women seen were studied: 50 women with screen-detected breast cancers, which were palpable and detected by the nurse-examiner, 62 women with occult screen-detected breast cancers and 353 age matched women with invasive breast cancer from the LRCC prospective database, who served as controls. MAIN OUTCOME MEASURE: The proportion of involved axillary nodes within the 3 groups based on patient and tumour characteristics. RESULTS: Twenty-five (22.3%) of the 112 women had screen-detected tumours less than 1 cm in dimension, but only 1 had an involved axillary node. Twelve (19%) of the 62 women with occult screen-detected tumours had involved lymph nodes compared with 17 (34%) of the 50 women with palpable screen-detected cancers (NS). In the control group tumour dimension less than 1 cm versus 1 cm or larger had a marked effect on the probability of axillary node involvement (12.5% v. 40.7%, p = 0.001). In the palpable screen-detected group 3 times as many women with outer quadrant or central lesions had involved nodes as those with inner quadrant lesions (38% v. 12%) and for those with a family history of breast cancer almost twice as many had involved axillary nodes. In occult screen-detected patients there was more nodal involvement in patients aged 60 years or less than in those older than 60 years (35% v. 10%, p = 0.042); only 4 of 41 patients older than 60 years had involved nodes at surgery. A significant difference in nodal involvement was found with respect to high or intermediate grade versus low grade lesions in the occult group (44% v. 12%, p = 0.033). In the control group, tumour grade (intermediate and high [45.3%] v. low [20.0%]) and hormone replacement therapy (HRT) (current or recent use [56.5%] v. no use [34.5%]) were significant findings (p < 0.001 and p = 0.005 respectively). CONCLUSIONS: Women older than 60 years with tumours smaller than 1 cm had a low probability of nodal positivity (0% to 8.7%), but there is insufficient information in this group to give a 95% or better prediction of nodal status at the time of surgery. Studies of minimally invasive techniques such as sentinel node biopsy are needed in this group to minimize surgical morbidity in these women who, as a result of early diagnosis, have an excellent long-term outlook.