Cross section for inelastic neutron scattering from 193Ir at 6 MeV.

Two samples, one of natural iridium and the other of enriched 193Ir, were irradiated with a monoenergetic neutron beam of energy 6.0 MeV at the Triangle Universities Nuclear Laboratory. The product of the 193Ir [Formula: see text] Ir reaction was determined by means of measuring X-rays following electron conversion of the isomeric state at 80.2 keV in 193Ir. The cross section for inelastic neutron scattering is reported disagreeing with the literature data.

Nuclear deformation and neutron excess as competing effects for dipole strength in the pygmy region.

The electromagnetic dipole strength below the neutron-separation energy has been studied for the xenon isotopes with mass numbers A=124, 128, 132, and 134 in nuclear resonance fluorescence experiments using the γELBE bremsstrahlung facility at Helmholtz-Zentrum Dresden-Rossendorf and the HIγS facility at Triangle Universities Nuclear Laboratory Durham. The systematic study gained new information about the influence of the neutron excess as well as of nuclear deformation on the strength in the region of the pygmy dipole resonance. The results are compared with those obtained for the chain of molybdenum isotopes and with predictions of a random-phase approximation in a deformed basis. It turned out that the effect of nuclear deformation plays a minor role compared with the one caused by neutron excess. A global parametrization of the strength in terms of neutron and proton numbers allowed us to derive a formula capable of predicting the summed E1 strengths in the pygmy region for a wide mass range of nuclides.

Elevated serum CXCL16 is an independent predictor of poor survival in ovarian cancer and may reflect pro-metastatic ADAM protease activity.

BACKGROUND: In certain cancers, expression of CXCL16 and its receptor CXCR6 associate with lymphocyte infiltration, possibly aiding anti-tumour immune response. In other cancers, CXCL16 and CXCR6 associate with pro-metastatic activity. In the current study, we aimed to characterise the role of CXCL16, sCXCL16, and CXCR6 in ovarian cancer (OC). METHODS: CXCL16/CXCR6 expression was analysed on tissue microarray containing 306 OC patient samples. Pre-treatment serum sCXCL16 was determined in 118 patients using ELISA. In vitro, (primary) OC cells were treated with an ADAM-10/ADAM-17 inhibitor (TAPI-2) and an ADAM-10-specific inhibitor (GI254023x), whereupon CXCL16 levels were evaluated on the cell membrane (immunofluorescent analysis, western blots) and in culture supernatants (ELISA). In addition, cell migration was assessed using scratch assays. RESULTS: sCXCL16 independently predicted for poor survival (hazard ratio=2.28, 95% confidence interval=1.29-4.02, P=0.005), whereas neither CXCL16 nor CXCR6 expression correlated with survival. Further, CXCL16/CXCR6 expression and serum sCXCL16 levels did not associate with lymphocyte infiltration. In vitro inhibition of both ADAM-17 and ADAM-10, but especially the latter, decreased CXCL16 membrane shedding and strongly reduced cell migration of A2780 and cultured primary OC-derived malignant cells. CONCLUSIONS: High serum sCXCL16 is a prognostic marker for poor survival of OC patients, possibly reflecting ADAM-10 and ADAM-17 pro-metastatic activity. Therefore, serum sCXCL16 levels may be a pseudomarker that identifies patients with highly metastatic tumours.

What is the best predictor of mortality in a very low birth weight infant population with a high mortality rate in a medical setting with limited resources?

OBJECTIVE: To determine the best predictor of mortality risk in very low birth weight (VLBW) infants in resource limited settings. METHODS: The Clinical Risk Index for Babies (CRIB) II score and the simplified age-weight-sex (SAWS) score for all VLBW infants born during the period January 2005 to June 2006 at the University Hospital of the West Indies were retrospectively calculated. The respective ability of each score, birth weight, and calculated or assessed gestational age to predict mortality was quantified using the area under receiver operating curves. RESULTS: Fifty two (48%) males and 57 (52%) females were entered into the study, out of which 58 (53%) infants died. The CRIB II score was found to be a better predictor of mortality (p = 0.02) when compared with calculated gestational age but had similar predictive power when compared with assessed gestational age. The SAWS score was found to have equal predictive value of mortality (p = 0.1) as the CRIB II score, however it was a better predictor of mortality than calculated gestational age (p = 0.002) but had no predictive advantage over assessed gestational age. Birth weight however, proved to be the best predictor of mortality (p < 0.01) with an area under the curve of 0.91 (standard error 0.03; 95% confidence interval 0.85-0.96). CONCLUSION: In resource poor settings where mortality of VLBW infants is high there may be no benefit in the addition of other variables to birth weight in predicting outcome.

The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are often found in tumours, presumably reflecting an immune response against the tumour. We carried out a systematic review and meta-analysis, aiming to establish pooled estimates for survival outcomes based on the presence of TILs in cancer. METHODS: A Pubmed and Embase literature search was designed. Studies were included, in which the prognostic significance of intratumoural CD3+, CD4+, CD8+, and FoxP3+ lymphocytes, as well as ratios between these subsets, were determined in solid tumours. RESULTS: In pooled analysis, CD3+ TILs had a positive effect on survival with a hazard ratio (HR) of 0.58 (95% confidence interval (CI) 0.43-0.78) for death, as did CD8+ TILs with a HR of 0.71 (95% CI 0.62-0.82). FoxP3+ regulatory TILs were not linked to overall survival, with a HR of 1.19 (95% CI 0.84-1.67). The CD8/FoxP3 ratio produced a more impressive HR (risk of death: HR 0.48, 95% CI 0.34-0.68), but was used in relatively few studies. Sample size and follow-up time seemed to influence study outcomes. CONCLUSION: Any future studies should be carefully designed, to prevent overestimating the effect of TILs on prognosis. In this context, ratios between TIL subsets may be more informative.

Childhood chorea-encephalopathy associated with recent parvovirus B19 infection in two Jamaican children.

This case report highlights the course of two healthy unrelated children with an encephalopathy characterised by dyskinesia, seizures, hemiparesis and behavioural change associated with recent human parvovirus B19 infection. The cases are compared with a previously described case of childhood chorea encephalopathy associated with human parvovirus B19 infection.

Identification of genes and pathways associated with cytotoxic T lymphocyte infiltration of serous ovarian cancer.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are predictors of disease-specific survival (DSS) in ovarian cancer. It is largely unknown what factors contribute to lymphocyte recruitment. Our aim was to evaluate genes and pathways contributing to infiltration of cytotoxic T lymphocytes (CTLs) in advanced-stage serous ovarian cancer. METHODS: For this study global gene expression was compared between low TIL (n=25) and high TIL tumours (n=24). The differences in gene expression were evaluated using parametric T-testing. Selectively enriched biological pathways were identified with gene set enrichment analysis. Prognostic influence was validated in 157 late-stage serous ovarian cancer patients. Using immunohistochemistry, association of selected genes from identified pathways with CTL was validated. RESULTS: The presence of CTL was associated with 320 genes and 23 pathways (P<0.05). In addition, 54 genes and 8 pathways were also associated with DSS in our validation cohort. Immunohistochemical evaluation showed strong correlations between MHC class I and II membrane expression, parts of the antigen processing and presentation pathway, and CTL recruitment. CONCLUSION: Gene expression profiling and pathway analyses are valuable tools to obtain more understanding of tumour characteristics influencing lymphocyte recruitment in advanced-stage serous ovarian cancer. Identified genes and pathways need to be further investigated for suitability as therapeutic targets.

Clinicopathological features of atypical nephrotic syndrome in jamaican children / Características clínico-patológicas del síndrome nefrótico atípico en los niños jamaicanos

OBJECTIVES: To document the histopathological spectrum of atypical nephrotic syndrome in Jamaican children and to make clinicopathological correlations which will assist physicians in identifying patients needing nephrology consultation. METHODS: This was a retrospective review of renal biopsy data of Jamaican children who were referred to the University Hospital of the West Indies and the Bustamante Hospital for Children between January 1985 and December 2008. The study population consisted of children < 12 years old with atypical nephrotic syndrome. RESULTS: Biopsies were done in 157 children - 85 males and 72 females (mean age 8.91 ± 3.44 years). Indications for biopsy were steroid resistance (35%), frequent relapses (8.9%) and other atypical presentations (56.1%). Overall, mesangial proliferative glomerulonephritis (MesGN) was the commonest histology (49/157, 31.2%), followed by minimal change disease (MCD) (36/157, 22.9%) and diffuse proliferative glomerulonephritis (DPGN) (26/157, 16.6%). Infection was present in 38/157 (24%) cases. Diffuse proli ferative glomerulonephritis was the predominant type associated with streptococcal infection (52.9%) while Hepatitis B was seen in 83% ofcases ofmembranous nephropathy. CONCLUSION: Mesangial proliferative glomerulonephritis is the commonest histology seen in Jamaican children with atypical nephrotic syndrome. Most membranous nephropathy is Hepatitis B related. Hypertension with hypocomplementaemia, renal failure and anaemia are features ofmore serious renal disease (eg membranoproliferative glomerulonephritis and crescentic nephritis) rather than MCNS and should warrant urgent nephrology consultation for renal biopsy.

OBJETIVOS: Documentar el espectro histopatológico del síndrome nefrótico atípico en los niños jamaicanos y hacer correlaciones clínico-patológicas que ayuden a los médicos a identificar pacientes que necesitan la consulta de nefrología.. MÉTODOS: Se trata de un estudio retrospectivo de datos de biopsias renales de niños jamaicanos remitidos al Hospital Universitario de West Indies y al Hospital Pediátrico Bustamante, entre enero de 1985 y diciembre de 2008. La población del estudio consistió en niños < 12 años de edad que padecían el síndrome nefrótico atípico. RESULTADOS: Se realizaron biopsias a 157 niños - 85 varones y 72 hembras (edad promedio 8.91 + 3.44 años). Las indicaciones para la biopsia se debieron a resistencia a los esteroides (35%), recaídas frecuentes (8.9%) y otras manifestaciones atípicas (56.1%). En general, la glomerulonefritis proliferativa mesangial (GNMes) fue la histología más común con 49/157 (31.2%), seguida por la enfermedad de cambio mínimo (ECM) con 36/157(22.9%) y la glomerulonefritis proliferativa difusa (GNPD) con 26/157 (16.6%). La infección estuvo presente en 38/157 (24%) de los casos. La glomerulonefritis proliferativa difusa fue el tipo predominante asociado con la infección estreptocóccica (52.9%), mientras que Hepatitis B fue observada en el 83% de los casos de nefropatía membranosa. CONCLUSIÓN: La glomerulonefritis proliferativa mesangial es la histología que con mayor frecuencia se observa en los niños jamaicanos que padecen el síndrome nefrótico atípico. La mayoría de los casos de nefropatía membranosa guardan relación con la hepatitis B. La hipertensión con hipocomplementemia, la insuficiencia renal y la anemia son rasgos más bien de enfermedades renales más serias (p.ej, glomerulonefritis membranoproliferativa, nefritis crescéntica) que del síndrome nefrótico de cambios mínimos (SNCM) y debe asegurarse la consulta urgente con el nefrólogo para se realice una biopsia renal.

Renal biopsy findings in Jamaican children / Hallazgos en las biopsias renales en niños jamaicanos

OBJECTIVE: To document the histological findings in Jamaican children undergoing renal biopsy in order to determine the relative prevalence of varying types of glomerular disease in the island. METHODS: This study analyses retrospectively the renal histology in all Jamaican children less than age 12 years undergoing their first adequate renal biopsy between January 1985 and December 2008. Clinicopathological data were obtained solely from the histology reports from the University Hospital of the West Indies where all paediatric renal biopsies are processed. RESULTS: Of the 270 children, aged 1 month to 11 years (mean 7.58 years), 147 [58.1%] were males. The commonest indications for renal biopsy were nephrotic syndrome (57.4%) and glomerulonephritis (30%). Most biopsied children (260/270) had glomerular disease. The predominant glomerulonephritides were diffuse proliferative glomerulonephritis (DPGN) (27.7%) and mesangialproliferative glomerulonephritis (MesGN) (25.5%). Glomerular disease was idiopathic in 136/260 (53%) but was infection-associated in 32.3% (84 cases) of which Poststreptococcal glomerulonephritis (PSGN) was the commonest (75%) -predominantly DPGN (74.6%). Hepatitis B followed at 15.5% (13/84) manifested as membranous nephropathy in 83.3% (10/12). In patients with SS disease, DPGN was the commonest histology (47.4%). Systemic lupus erythematosus accounted for 5% ofall renal biopsies. Over time, PSGNoccurred less frequently, with a parallel reduction in DPGN and MesGN. CONCLUSION: In Jamaican children, DPGN is the commonest nephritis. Membranous nephropathy is primarily due to Hepatitis B. The commonest histology in SS disease is DPGN. The role ofinfection in the pathogenesis ofrenal disease in Jamaican children is probably underestimated.

OBJETIVO: Documentar los hallazgos histológicos en niños jamaicanos a los que se les ha realizado biopsias renales para determinar la prevalencia relativa de los diversos tipos de enfermedad glomerular en la isla. MÉTODOS: Este estudio analiza retrospectivamente la histología renal en todos los niños jamaicanos menores de 12 años sometidos a su primera biopsia renal adecuada entre enero de 1985 y diciembre de 2008. Los datos clinicopatológicos fueron obtenidos exclusivamente de los reportes de histología del Hospital Universitario de West Indies, dónde se procesan todas las biopsias renales. RESULTADOS: De 270 niños, cuyas edades fluctuaban de 1 mes a 11 años (media 7.58 años), 147 [58.1%] eran varones. Las indicaciones más comunes para la biopsia renal fueron el síndrome nefrótico (57.4%) y la glomerulonefritis (30%). La mayoría de los niños sometidos a biopsia (260/270) tenían la enfermedad del glomerular. Las glomerulonefritis predominantes fueron la glomerulonefritis proliferativa difusa (GNPD) (27.7%) y glomerulonefritis proliferativa mesangial (GNMes) (25.5%). La enfermedad glomerular fue idiomática en 136/260 (53%) pero estuvo asociada con infecciones en 32.3% (84 casos) en los cuales la glomerulonefritis poststreptocóccica (GNPS) fue la más común (75%) - predominantemente GNDP (74.6%). La hepatitis B siguió con 15.5% (13/84), manifestada como nefropatía membranosa en 83.3% (10/12). En los pacientes con la enfermedad de la hemoglobina SS, la GNDP fue la histología más común (47.4%). El lupus eritematoso sistémico representó el 5% de todas las biopsias renales. Al pasar el tiempo, la GNPS ocurrió menos frecuentemente, con una reducción paralela en GNPD y GNMes. CONCLUSIÓN: En los niños jamaicanos, la GNPD es la nefritis más común. La nefropatía membranosa se debe principalmente a la Hepatitis B. La histología más común en el caso de la enfermedad de hemoglobina SS es la GNPD. Probablemente se subestima el papel que las infecciones desempeñan en la patogénesis de la enfermedad renal en los niños jamaicanos.

Clinicopathological features of atypical nephrotic syndrome in Jamaican children.

OBJECTIVES: To document the histopathological spectrum of atypical nephrotic syndrome in Jamaican children and to make clinicopathological correlations which will assist physicians in identifying patients needing nephrology consultation. METHODS: This was a retrospective review of renal biopsy data of Jamaican children who were referred to the University Hospital of the West Indies and the Bustamante Hospital for Children between January 1985 and December 2008. The study population consisted of children < 12 years old with atypical nephrotic syndrome. RESULTS: Biopsies were done in 157 children--85 males and 72 females (mean age 8.91 +/- 3.44 years). Indications for biopsy were steroid resistance (35%), frequent relapses (8.9%) and other atypical presentations (56.1%). Overall, mesangial proliferative glomerulonephritis (MesGN) was the commonest histology (49/157, 31.2%), followed by minimal change disease (MCD) (36/157, 22.9%) and diffuse proliferative glomerulonephritis (DPGN) (26/157, 16.6%). Infection was present in 38/157 (24%) cases. Diffuse proliferative glomerulonephritis was the predominant type associated with streptococcal infection (52.9%) while Hepatitis B was seen in 83% of cases of membranous nephropathy. CONCLUSION: Mesangial proliferative glomerulonephritis is the commonest histology seen in Jamaican children with atypical nephrotic syndrome. Most membranous nephropathy is Hepatitis B related. Hypertension with hypocomplementaemia, renal failure and anaemia are features of more serious renal disease (eg membranoproliferative glomerulonephritis and crescentic nephritis) rather than MCNS and should warrant urgent nephrology consultation for renal biopsy.

Renal biopsy findings in Jamaican children.

OBJECTIVE: To document the histological findings in Jamaican children undergoing renal biopsy in order to determine the relative prevalence of varying types of glomerular disease in the island. METHODS: This study analyses retrospectively the renal histology in all Jamaican children less than age 12 years undergoing their first adequate renal biopsy between January 1985 and December 2008. Clinicopathological data were obtained solely from the histology reports from the University Hospital of the West Indies where all paediatric renal biopsies are processed. RESULTS: Of the 270 children, aged 1 month to 11 years (mean 7.58 years), 147 [58.1%] were males. The commonest indications for renal biopsy were nephrotic syndrome (57.4%) and glomerulonephritis (30%). Most biopsied children (260/270) had glomerular disease. The predominant glomerulonephritides were diffuse proliferative glomerulonephritis (DPGN) (27.7%) and mesangial proliferative glomerulonephritis (MesGN) (25.5%). Glomerular disease was idiopathic in 136/260 (53%) but was infection-associated in 32.3% (84 cases) of which Poststreptococcal glomerulonephritis (PSGN) was the commonest (75%)--predominantly DPGN (74.6%). Hepatitis B followed at 15.5% (13/84) manifested as membranous nephropathy in 83.3% (10/12). In patients with SS disease, DPGN was the commonest histology (47.4%). Systemic lupus erythematosus accounted for 5% of all renal biopsies. Over time, PSGN occurred less frequently, with a parallel reduction in DPGN and MesGN. CONCLUSION: In Jamaican children, DPGN is the commonest nephritis. Membranous nephropathy is primarily due to Hepatitis B. The commonest histology in SS disease is DPGN. The role of infection in the pathogenesis of renal disease in Jamaican children is probably underestimated.

Failure to screen for sickle cell disease at the University Hospital of the West Indies

OBJECTIVE: Universal neonatal screening for sickle cell disease using cord blood has taken place in the University Hospital of the West Indies (UHWI) since 1997. Comprehensive quality control of the screening programme has not been implemented. Our aim was to determine how many deliveries were left unscreened, and to ascertain factors contributing to failure to screen for sickle cell disease. METHODS: All live births in 1999 entered in the delivery book of the Labour Ward, UHWI, were scrutinized against the sample book of the Neonatal Screening Laboratory, Sickle Cell Unit. Identified unscreened infants were matched with a randomly chosen control, born on the same day. Time and mode of delivery, persons assisting the delivery, birth weight, level of urgency, location of delivery and Apgar scores at 1 and 5 minutes were collected for unscreened infants and screened controls. Secular variation within the year was assessed by comparing the frequency of unscreened births in each month to the previous month. Frequencies of potential determinants of failure to screen were tabulated. The independent predictive power of these potential determinants was assessed using conditional logistic regression, to account for correlations between predictors, and for the case-control design of the study. RESULTS: Of 2,763 live births in 1999, 139 (5 percent) infants were not screened for sickle cell disease. There was no statistically significant secular variation within the year (relative risk 1.02, 95 percent confidence interval 0.97, 1.07, x2 = 0.77, p = 0.38). Independently significant predictors of failure to screen were: emergency delivery (odds ratio 4.8, 95 percent confidence interval 2.3, 10.0), nigttime delivery (OR2.5, 0.9) CONCLUSIONS: This study identified that 5 percent of infants born in UHWI in 1999 were discharged from hospital without having been screened for sickle cell disease. Statistically significant associations with failure to screen were found to be emergency delivery, night-time delivery, and low 5 minute Apgar score. The risk of being left unscreened increased 5-fold for emergency deliveries. Increased awareness of these risk factors may reduce failure to screen. Of course, such effort does not obviate the need for regular quality control, including timely identification and tracing of unscreened infants. (AU)

Intimal growth and neovascularization in human stenotic vein grafts.

BACKGROUND: Myointimal thickening and microvessel ingrowth are commonly observed in vein graft stenosis, which complicates a third of infrainguinal bypass procedures. But a direct correlation between these two features has not been established. Our purpose was to analyze the relationship between neovascularity and intimal thickness in human vein grafts. STUDY DESIGN: Twenty-two explant stenotic vein grafts (STVG), 8 nonstenotic arterialized vein grafts (AVG), and 20 age-matched control greater saphenous veins (CGSV) were analyzed histologically and compared morphologically by light microscopy. Digitized computer image analysis was used to measure intimal thickness and quantitate microvessel ingrowth. Immunolocalization of endothelial cells around the lumen and in microvessels was determined using antibodies to factor VIII and to endothelial nitric oxide synthase (eNOS), respectively. RESULTS: Focal areas of endothelial disruption and thrombus deposition were present in 23% (5 of 22) of stenotic vein grafts. The neointima of STVG grafts was two- and fourfold thicker than that of AVG and CGSV, respectively (p < 0.0001). Microvessels were most frequently observed in the adventitia and media of STVG and increased in number with increasing intimal thickness (p < 0.001 by ANOVA). CONCLUSIONS: A fourfold increased neointimal thickness in critically stenotic vein grafts is associated with increased medial and adventitial neovascularization. Remodeling alone with doubling of the intimal thickness in nonstenotic arterialized vein grafts does not appear to be associated with enhancement of the graft microvasculature. More specific observations using an experimental model may allow us to further define the role of angiogenesis in vein graft stenosis and to determine the therapeutic implications of such observations.

Characterization of cellular density and determination of neointimal extracellular matrix constituents in human lower extremity vein graft stenoses.

UNLABELLED: Arterial restenosis has been attributed to a hyperproliferative smooth muscle cell response. Paradoxically, studies of human coronary atherectomy and vein graft stenotic lesions have demonstrated a relatively low nuclear proliferative rate with the majority of the neointimal mass consisting of extracellular matrix. The purpose of the present study was to characterize the cellular density and determine the relative composition of the extracellular matrix protein constituents in stenotic, human lower extremity vein-bypass graft lesions. METHODS: Duplex surveillance of 148 consecutive infrainguinal bypass grafts identified 17 patients with 22 preocclusive autogenous vein graft stenoses (mean graft age 7 months). Morphological analyses of these stenotic lesions were compared with excised samples of 20 greater saphenous vein segments taken at the time of graft implantation from matched control patients. Intimal and medial areas were compared and cell density was determined with fluorescent nuclear (Bisbenzimide) staining. Differential light microscopy with pentachrome staining was performed to determine the relative percent composition of intimal matrix constituents by stereological morphometric (point-count) techniques. RESULTS: The intimal areas for control and stenotic vein segments were 1.64 x 10(6) microm2 and 3.85 x 10(6) microm2, P < 0.0001, whereas the intimal nuclear densities (cells/unit volume) were 1.42 x 10(3) and 1.70 x 10(3) cells/microm2, P = 0.03. respectively. The corresponding medial area and medial nuclear densities were 5.01 x 10(6) microm2, 3.31 x 10(6) microm2; P = 0.08, and 2.27 x 10(3), 3.29 x 10(3); P = 0.001, for control and stenotic specimens, respectively. The intima:media area ratios were much greater, whereas the intimal and medial cell densities were only slightly greater in the stenotic compared with control veins. The relative composition of intimal extracellular matrix proteins of stenotic vein graft segments consisted of 21% cellular (fibrous) material, 33% collagen, and 46% glycosaminoglycan ground substance. CONCLUSION: The intimal lesions responsible for lower extremity vein graft stenosis are more hypertrophic than hyperplastic. Therapies aimed at preventing arterial and vein graft restenosis may thus need to inhibit matrix biosynthetic processes in addition to cellular proliferation.

Cell cycle-dependent nuclear location of the matricellular protein SPARC: association with the nuclear matrix.

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that inhibits cellular adhesion and proliferation. In this study, we report the detection of SPARC in the interphase nuclei of embryonic chicken cells in vivo. Differential partitioning of SPARC was also noted in the cytoplasm of these cells during discrete stages of M-phase: cells in metaphase and anaphase exhibited strong cytoplasmic immunoreactivity, whereas cells in telophase were devoid of labeling. Immunocytochemical analysis of embryonic chicken cells in vitro likewise showed the presence of SPARC in the nucleus. Furthermore, elution of soluble proteins and DNA from these cells indicated that SPARC might be a component of the nuclear matrix. We subsequently examined cultured bovine aortic endothelial cells, which initially appeared to express SPARC only in the cytoplasm. However, after elution of soluble proteins and chromatin, we also detected SPARC in the nuclear matrix of these cells. Embryonic chicken cells incubated with recombinant SPARC were seen to take up the protein and to translocate it to the nucleus progressively over a period of 17 h. These observations provide new information about SPARC, generally recognized as a secreted glycoprotein that mediates interactions between cells and components of the extracellular matrix. The evidence presented in this study indicates that SPARC might subserve analogous functions in the nuclear matrix.

Vein patching reduces neointimal thickening associated with prosthetic graft implantation.

PURPOSE: Modified anastomotic techniques utilizing autogenous vein-cuffs or patches have been devised with the hope of improving prosthetic graft patency. The mechanisms of the presumed improvement in patched anastomoses have never been elucidated and remain speculative. We characterized the healing response of the Taylor vein patch in prosthetic arteriovenous fistulae in a canine model of intimal hyperplasia. METHODS: Six adult dogs underwent placement of bilateral (6 patched, 6 control) 4-mm diameter expanded polytetrafluoroethylene loop femoral artery-vein fistulae. Serial duplex ultrasound examinations confirmed graft patency until explant at 6 weeks. Differential light microscopy with computerized image analysis was performed on serial 5-microm sections. Intimal thickness through the venous anastomosis and outflow veins of Taylor patch and control (nonpatched) grafts were compared. Cell type-specific immunocytochemical antibody stains for smooth muscle cells (alpha SMC actin) and endothelial cells (von Willebrand factor) were performed. RESULTS: Eleven of 12 grafts remained patent for 6 weeks, 1 control graft thrombosed. Mean duplex-derived peak systolic velocities of patched (96 cm/sec) and control (108 cm/sec) grafts were similar. Microscopy revealed more intimal pannus anastomotic suture line ingrowth in controls (mean thickness = 178 microm) than Taylor patched grafts (mean 147 microm, p = 0.0002). Significantly less intimal thickening was present in the outflow vein of patched (mean thickness = 90 microm) versus control grafts (mean 195 microm, P <0.0001). The intima maintained a single cell layer of vWF + endothelial cells, while the majority of the cells comprising the lesion expressed alpha SMC actin. CONCLUSION: Perianastomotic pannus is primarily composed of intimal smooth muscle cells. Neointimal thickening is significantly reduced in prosthetic arteriovenous fistulae created with the Taylor vein patch in a canine model. Reduction in perianastomotic intimal thickening may explain the reported clinical improvement in prosthetic bypass graft patency when modified with vein patch techniques.

Free tissue transfer to extend the limits of limb salvage for lower extremity tissue loss.

BACKGROUND: The extent of tissue loss amenable to primary healing after revascularization is unknown. Salvage of limbs with large soft-tissue defects with exposed tendon, joint, or bone lies beyond the limits of conventional techniques. We report our results using free tissue transfer as an adjunct to lower extremity vascular reconstruction in patients with complex ischemic or infected wounds. METHODS: Retrospective chart review of patient and wound characteristics. RESULTS: From January 1992 to June 1996, 585 procedures were performed in 544 patients, including 27 free flaps in 26 patients: 17 free flaps combined with distal bypass (7 staged, 10 simultaneous) and 10 isolated free flaps. Flap donor sites included radial forearm (8), latissimus dorsi (7), rectus abdominus (9), and scapula (3). Surgical indications included extensive ischemic/neurotrophic ulcers, and nonhealing vein graft harvest incision or transmetatarsal amputation site. Mean area of tissue loss was 70 cm2, mean ulcer duration was 5 months, and 92% of patients had exposed tendon, joint, or bone. During a mean follow-up of 14 months, 2 patients died of cardiopulmonary disease and 3 flaps failed, resulting in below-knee amputation. Six flaps were revised for graft stenosis (1), venous thrombosis (1), or flap edge necrosis (4). Limb salvage rate was 70% at 24 months by life-table analysis. Functional ambulation was achieved in 21 of 24 (88%) patients, including 7 of 8 with diabetes, end-stage renal disease, and heel ulcers. CONCLUSION: In select ambulatory patients with large soft-tissue defects and exposed deep structures, functional limb salvage is obtainable in more than 80% of patients. For lesions not amenable to vascular reconstruction with conventional methods of wound coverage, free tissue transfer extends the limits of limb salvage and is a viable alternative to amputation.

Salvage of femoropedal bypass graft complicated by interval gangrene and vein graft blowout using a flow-through radial forearm fasciocutaneous free flap.

We report the case of a 71-year-old man who had interval gangrene of his calf with subsequent vein graft blowout 3 months after undergoing a femoral-to-dorsalis pedis saphenous vein bypass grafting procedure. To provide wound coverage, restore vascular continuity, and preserve functional ambulation, a flow-through radial forearm fasciocutaneous free flap was interposed between cut ends of the bypass graft. Venous drainage of the flap was from the cephalic vein to the popliteal vein. At 1 month after the operation, the patient had complete wound healing and began to ambulate. At 11 months an asymptomatic high-grade stenosis in the distal radial artery segment of the reconstruction was successfully treated with percutaneous angioplasty. After 22 months of follow-up there have been no further complications, and the patient continues to have full, functional ambulation. The radial forearm flow-through free flap allows single-stage restoration of bypass graft continuity and coverage of extensive, complex tissue defects. This technique represents a novel approach to this difficult problem and provides a viable alternative to major limb amputation.