Comparison of CD44 expression in early colorectal carcinomas of the de novo and ex adenoma types

Small colorectal carcinomas without morphological evidence of origin from an adenoma have been called ”de novo” carcinomas. As changes in the expression of the adhesion molecule CD44 and its variants have been described along the adenoma-carcinoma sequence in colorectal carcinoma, we compared patterns of CD44 expression in early de novo and ex-adenoma colorectal carcinomas by staining specimens from a group of early (pT1) colorectal carcinomas by immunohistochemistry for CD44 (standard and variant forms v3, v5, v6, v7, v7/8, v10). We evaluated carcinoma, adenoma (ex-adenoma cases), transitional mucosal areas and apparently nonneoplastic mucosa peripheral to the lesions (when present). A marked increase was seen in numbers and intensity of standard and variant forms of CD44 in carcinomatous areas compared with nonneoplastic mucosa in both groups, with no significant difference between the groups. However, adenoma areas of the ex-adenoma cases and the transitional mucosa of the de novo carcinomas had nearly identical staining patterns. Together with data from other molecular studies, this may be interpreted as evidence for an adenoma-type precursor lesion in so-called de novo colorectal carcinomas.     

Health effects associated with sulfuryl fluoride and methyl bromide exposure among structural fumigation workers.

OBJECTIVES: This study assessed the health effects associated with occupational exposure to methyl bromide and sulfuryl fluoride among structural fumigation workers. METHODS: A cross-sectional study of 123 structural fumigation workers and 120 referents in south Florida was conducted. Nerve conduction, vibration, neurobehavioral, visual, olfactory, and renal function testing was included. RESULTS: The median lifetime duration of methyl bromide and sulfuryl fluoride exposure among workers was 1.20 years and 2.85 years, respectively. Sulfuryl fluoride exposure over the year preceding examination was associated with significantly reduced performance on the Pattern Memory Test and on olfactory testing. In addition, fumigation workers had significantly reduced performance on the Santa Ana Dexterity Test of the dominant hand and a nonsignificantly higher prevalence of carpal tunnel syndrome than did the referents. CONCLUSIONS: Occupational sulfuryl fluoride exposures may be associated with subclinical effects on the central nervous system, including effects on olfactory and some cognitive functions. However, no widespread pattern of cognitive deficits was observed. The peripheral nerve effects were likely caused by ergonomic stresses experienced by the fumigation workers.     

Electrochemical characterization of cobalt-based alloys using the mini-cell system.

OBJECTIVES: The aim of this work was to investigate the electrochemical behavior of cobalt-based alloys of different compositions using the mini-cell system (MCS) and to test the sensitivity of this technique in the detection of variations in the electrochemical behavior caused by the different compositions of cobalt-based alloys. METHODS: The electrochemical measurements were performed on two cobalt-based alloys, having a small content of gold (B?rlight and Gold Core); one cobalt-platinum-ruthenium alloy (Porta Smart) and one classical Co-based alloy (Wironit), in two different electrolytes, 1% NaCl and phosphate buffered solution (PBS). RESULTS: Based on I versus E curves, enhanced pitting corrosion capability was observed for the cobalt-based alloys, especially for those with lower chromium content and with the addition of a small amount of gold. The alloying of Co with Pt and Ru (Porta Smart), and the standard Co-based alloy do not show any critical instability; in contrast, a small addition of Au enhanced the pitting corrosion activity and reduced the corrosion stability. For higher alloy stability, a minimum 30% atomic ratio of chromium in the alloy composition is necessary. Furthermore, it was shown that MCS has sensitivity for the qualitative comparison of the alloys as well as in the electrochemical characterization of each alloy. SIGNIFICANCE: Electrochemical measurements are essential to assess the quality of an alloy. MCS might help in understanding the role the elements play in the electrochemical behavior of the alloys and at the same time contribute to the selection of the alloys in terms of their quality, even before more complex tests in vitro or in vivo are applied, and might reduce the costs for materials research.     

Adenomatous polyposis coli truncation alters cytoskeletal structure and microtubule stability in early intestinal tumorigenesis

Partial loss of function of adenomatous polyposis coli (APC) protein by truncation of its carboxy (C)-terminus is an early factor in the development of many sporadic colorectal cancers. In the C57BL/6J Min/+ (Min/+) mouse, an animal with a germline mutation of Apc, we found that APC truncation was associated with reduced enterocyte migration and loss of association and membrane expression of adherens junction proteins. We hypothesized that these defects were related to changes in cytoskeletal function resulting from truncation of the APC C-terminus, which contains microtubule binding regions, as well as putative sites for indirect actin binding. We investigated this further by determining whether APC truncation produced in vivo changes in actin cytoskeletal structure and microtubule stability. The actin cytoskeleton of histologically normal enterocytes from Min/+mice was compared to that of Apc+/+(wild-type) mice by confocal indirect immunofluorescence microscopy. We found a significant loss of actin localization at the apical plasma membrane in Min/ + enterocytes. In addition, immunoblotting revealed increased levels of both unstable Tyr-tubulin and+ -tubulin turnover in Min/+enterocytes, indicating an alteration in microtubule dynamics. These studies suggest that loss of actin localization and changes in microtubule dynamics may be dominant negative effects of truncated APC. These changes are consistent with the defects in enterocyte migration and junctional complex formation observed in the Min/+ model of early APC-associated colorectal tumorigenesis. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation). Supported by grants from the National Cancer Institute (NCI-IR29CA74162) (M.M.B.), the Irving Weinstein Foundation (A.M.C.), and National Institutes of Health Surgical Oncology Research Training grants T32-CA-68971 (D.H.H.) and T32-CA-09535 (S.A.H.).     

Experimental evaluation of the Medtronic Maxima Forté hollow fiber membrane oxygenator.

A new hollow fiber membrane oxygenator, the Medtronic Maxima Forté, was tested for gas transfer, blood path resistance and blood handling characteristics in a standardized setting with surviving animals. Three calves (mean body weight: 71 +/- 9.6 kg) were placed on cardiopulmonary bypass at a mean flow rate of 50 ml/kg/min for six hours. The circuit included the Maxima Forté oxygenator. The animals were weaned from cardiopulmonary bypass and then from the ventilator. After seven days, the animals were sacrificed electively. Physiologic blood gas values could be maintained throughout perfusion in all animals. Mean pressure drop through the oxygenator varied between 49 mmHg and 66 mmHg. The respective baseline values for red blood cell count, white blood cell count and platelets were 8.90 +/- 1.26 10(6)/mm3, 7.46 +/- 3.17 10(3)/mm3. and 680 +/- 216 10(3)/mm3. Red blood cell and platelet counts dropped slightly to 7.26 +/- 1.61 10(6)/mm3 and 400 +/- 126 10(3)/mm3 at the end of the bypass, whereas the white blood cell count increased up to 9.13 +/- 5.25 10(3)/mm3. All three cell lines returned to near their baseline values after seven days. Blood trauma evaluated as a function of plasma hemoglobin (plasma Hb) and lactate dehydrogenase (LDH) showed stable values during all the perfusion time. Both peaked at 24 hours before returning to their baseline values at seven days. LDH showed a statistically significant variation: 3255 +/- 693 IU at 24 hours versus 2029 +/- 287 IU at baseline (p = 0.04). The variation of plasma Hb was not statistically significant (93.5 +/- 7.7 mumol/l at 24 hours versus 77.3 +/- 52.3 mumol/l at baseline) indicating a weak effect of the perfusion on blood trauma. The Medtronic Maxima Forté hollow fiber membrane oxygenator offered good gas exchange capabilities, a low pressure drop, and low blood trauma over a prolonged perfusion time of six hours in this evaluation.     

Legislative and Policy Strategies for Supporting Rural Health Network Development: Lessons from the 103rd Congress

There was considerable support in most major health reform bills considered by the 103rd Congress for the development of rural integrated service networks. The demise of comprehensive health reform, together with the pace of current market-driven changes in the health care system, suggests the need to assess the impact of specific policy strategies considered in the last Congress on rural integrated service network development. Toward this end, this article evaluates the rural health policy strategies of the major bills in relation to three essential preconditions for the development of rural integrated service networks: (1) the need for a more stable financial base for rural providers; (2) the need for administrative, service and clinical capacity to mount a successful network; and finally, (3) the need for appropriate market areas to ensure fair competition among networks and plans. Key policy strategies for supporting rural network development include reform of insurance and payment policies, expansion of targeted support and technical assistance to the underserved, limited-capacity rural areas, and policies governing purchasing groups or alliances that will ensure appropriate treatment of rural providers and networks.