Use of polypropylene mesh for incisional hernia repair

Incisional hernia is an important complication of abdominal surgery. Procedures for the repair of these hernias with sutures and with mesh have been reported, but there is no consensus about which type of procedure is best. We have performed a retrospective analysis on 1014 patients operated on in our unit between 1994 and 2003 for simple or recurrent incisional hernias. The polypropylene mesh has been used in a number of 107 patients. The mesh has been placed either intraperitoneal, extraperitoneal/subfascial or onlay. Median follow-up was 36 months. There were 1 enterocutaneous fistula and 5 wound sinus developed. The mesh had to be removed in 6 cases. All of these complication developed when the mesh has been placed either extraperitoneal/subfascial or onlay. We note 5 recurrent incisional hernias after a period of up to 24 months. The recurrence rates after open mesh repair are less then after primary closure. The intraperitoneal use of polypropylene mesh with omental coverage is a good procedure with less complications.     

An unsupervised approach to identify molecular phenotypic components influencing breast cancer features

To discover a biological basis for clinical subgroupings within breast cancers, we applied principal components (PCs) analysis to cDNA microarray data from 36 breast cancers. We correlated the resulting PCs with clinical features. The 35 PCs discovered were ranked in order of their impact on gene expression patterns. Interestingly, PC 7 identified a unique subgroup consisting of estrogen receptor (ER); (+) African-American patients. This group exhibited global molecular phenotypes significantly different from both ER (-) African-American women and ER (+) or ER (-) Caucasian women (P < 0.001). Additional significant PCs included PC 4, correlating with lymph node metastasis (P = 0.04), and PC 10, with tumor stage (stage 2 versus stage 3; P = 0.007). These results provide a molecular phenotypic basis for the existence of a biologically unique subgroup comprising ER (+) breast cancers from African-American patients. Moreover, these findings illustrate the potential of PCs analysis to detect molecular phenotypic bases for relevant clinical or biological features of human tumors in general.     

The modulator role of the hypothalamic paraventricular nucleus on immune responsiveness

Role of the paraventricular nucleus of the hypothalamus (PVH) upon immune modulation was studied by either mechanically destroying the PVH (PVHL) or by isolating the PVH (PVHI) with a knife-cut. PVHL or PVHI manipulations induced significant leukopenia characterized by a decrease in the number of neutrophils and lymphocytes two weeks post surgery. The numbers of circulating monocytes and eosinophils were not affected by PVH interventions. In addition, PVHL and PVHI were also associated with a reduction, relative to controls, in the phagocytosis by neutrophils and an increase in blastic transformation of T lymphocytes induced by phytohemagglutinin-M (PHA-M). Antibody titers rose against sheep red blood cells (SRBC) after either PVHL or PVHI were reduced. The magnitude of the SRBC antibody reduction after PVH manipulations was similar to that observed in rats that received a peripheral chemical sympathectomy two hrs prior immunization. Comparison of thyroid hormones blood levels two weeks after PVHL or PVHI revealed significant reductions in comparison with sham-operated group (SO), whereas blood corticosterone was not significantly altered. In summary, we provide evidence that lesion or isolation of the PVH selectively reduces circulating white blood cells and the primary immune response, while it enhances the cell-mediated immune function. Taken together our data showed that PVH modulates immune functions by altering both the peripheral sympathetic tone and thyroid hormone secretion.     

Diameters of topographic optical zone and programmed ablation zone for laser in situ keratomileusis for myopia

PURPOSE: To compare topographic optical zones with programmed ablation zone settings of eyes treated with laser in situ keratomileusis (LASIK) for myopia using the VISX S2 excimer laser. METHODS: Two-hundred three eyes treated with LASIK using the VISX S2 excimer laser were retrospectively evaluated to determine the size of the topographic optical zone. Three to six months after LASIK, the topographic optical zone was measured at the zone of highest curvature on topography and subtraction topography. Eyes were divided into four groups (A, B, C, D) in order of increasing myopia. RESULTS: When the topographic optical zone was compared with the programmed ablation zone, an optical zone reduction of 0.5 +/- 0.1 mm and 0.4 +/- 0.1 mm was found for the longest and shortest diameters, respectively. For eyes with spherical ablation zones, this reduction was 0.6 +/- 0.1 mm and 0.4 +/- 0.1 mm shorter than the programmed horizontal and vertical dimensions. Groups A, B, C, and D, in order of increasing myopia, all showed reductions of approximately 0.5 +/- 0.1 mm for the longest and 0.3 to 0.4 +/- 0.1 mm for the shortest diameters of the optical zone. CONCLUSIONS: The topographic optical zone was reduced from the programmed ablation zone. This reduction was statistically significant for both elliptical and spherical ablations, and seemed to be independent of the amount of myopia.     

Muscle glycogen depletion and increased oxidative phosphorylation following status epilepticus

We describe complete glycogen depletion and increased respiratory chain enzyme activity in a muscle biopsy obtained prior to the demise of a patient in multiorgan failure following status epilepticus. These findings validate the theoretical basis of muscle energy turnover during status epilepticus: the increased demand for energy leads to complete depletion of glycogen reserves. The attempt to preserve adenosine triphosphate requirements results in increased activity of respiratory chain enzymes.     

Akt inhibition up‐regulates MMP1 through a CCN2‐dependent pathway in human dermal fibroblasts

Please cite this article as: Akt inhibition up‐regulates MMP1 through a CCN2‐dependent pathway in human dermal fibroblasts. Experimental Dermatology 2010. Abstract: Akt is a key signalling molecule that was found to be down‐regulated in chronic wounds. Akt blockade has dual antifibrotic effects in human dermal fibroblasts, by up‐regulating matrix metalloproteinase 1 (MMP1) and down‐regulating collagen gene expression (J Invest Dermatol 2008: 128: 1906). The aim of this study was to gain additional insights into the mechanism of MMP1 up‐regulation following Akt blockade. As previous studies showed that CCN2 can be a positive regulator of MMP1, we examined the effects of Akt inhibition on CCN2 expression. Akt blockade using a specific pharmacological inhibitor and Akt siRNA resulted in a significant up‐regulation of CCN2, which correlated with the increase in MMP1. The MMP1 up‐regulation following Akt blockade was partially suppressed by CCN2 siRNA, suggesting that CCN2 is contributing to this effect. Additional experiments showed that CCN2 induces phosphorylation of ERK1/2, Ets1 and c‐Jun. Consistent with the stimulatory role of ERK1/2/Ets1 in the expression of MMP1, the ERK1/2 inhibitor UO126 prevented the phosphorylation of ERK1/2 and Ets1 and completely abrogated the induction of MMP1 after CCN2 overexpression, while having no effect on c‐Jun activation. Taken together these results establish CCN2 as a key regulator of MMP1 induction via activation of the ERK1/2/Ets1 pathway. Down‐regulation of Akt signalling leads to inappropriate activation of the CCN2/MMP1 pathway that may contribute to the pathogenesis of chronic wounds. Coordinate expression of CCN2, Akt and MMP1 could be important for normal wound healing to occur. Thus, targeting these specific proteins may represent a promising approach to the therapy of dysregulated wound healing.