Meta-analysis of randomized controlled trials and individual patient data comparing minimally invasive with open oesophagectomy for cancer.

BACKGROUND: Minimally invasive oesophagectomy (MIO) for oesophageal cancer may reduce surgical complications compared with open oesophagectomy. MIO is, however, technically challenging and may impair optimal oncological resection. The aim of the present study was to assess if MIO for cancer is beneficial. METHODS: A systematic literature search in MEDLINE, Web of Science and CENTRAL was performed and randomized controlled trials (RCTs) comparing MIO with open oesophagectomy were included in a meta-analysis. Survival was analysed using individual patient data. Random-effects model was used for pooled estimates of perioperative effects. RESULTS: Among 3219 articles, six RCTs were identified including 822 patients. Three-year overall survival (56 (95 per cent c.i. 49 to 62) per cent for MIO versus 52 (95 per cent c.i. 44 to 60) per cent for open; P = 0.54) and disease-free survival (54 (95 per cent c.i. 47 to 61) per cent versus 50 (95 per cent c.i. 42 to 58) per cent; P = 0.38) were comparable. Overall complication rate was lower for MIO (odds ratio 0.33 (95 per cent c.i. 0.20 to 0.53); P < 0.010) mainly due to fewer pulmonary complications (OR 0.44 (95 per cent c.i. 0.27 to 0.72); P < 0.010), including pneumonia (OR 0.41 (95 per cent c.i. 0.22 to 0.77); P < 0.010). CONCLUSION: MIO for cancer is associated with a lower risk of postoperative complications compared with open resection. Overall and disease-free survival are comparable for the two techniques. LAY SUMMARY: Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

Interleukin-6 secreted by oral cancer- associated fibroblast accelerated VEGF expression in tumor and stroma cells.

Oral cancer represents the sixth most common cancer type worldwide. Patients with oral cancer express high levels of IL-6 which is associated with very poor prognosis. Previous studies illustrated that IL-6 cytokine induces angiogenesis. It has also been reported that the presence of Cancer- Associated Fibroblasts (CAFs) is essential for angiogenesis. In this study, we examined the correlation between IL-6 and CAF and the role of this correlation on VEGF production. In this study, quantitative expression level of IL-6 and VEGF in CAF and Oral Cancer Cells (OCCs) examined through Real Time PCR and ELISA and western blot analysis. In addition, maintenance and retention of IL-6 and VEGF checked out in co-culture experiment of CAF and OCC cells. These experiments demonstrated that in oral cancer, CAF cell line secretes significantly more IL-6 than OCC. Also IL-6 is a factor that causes VEGF secretion in CAF cell line. CAF is the basic and the most essential source for producing IL-6 in patients with oral cancer. Secreted IL-6 is able to induce VEGF production in both CAF and OCCs. Correlation between CAF, IL-6 and VEGF could be considered as an approach for cancer therapy.

Bacteremic pneumococcal pneumonia: clinical outcomes and preliminary results of inflammatory response.

PURPOSE: Further examination of clinical outcomes and inflammatory response of bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest to enhance the care of patients with pneumococcal CAP. METHODS: This is a secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to compare the time to clinical stability (TCS), length of hospital stay (LOS), and in-hospital mortality of hospitalized pneumococcal CAP patients with and without bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on outcomes, we modeled all-cause in-hospital mortality using a Poisson regression model, and TCS and LOS using Cox proportional hazards models. Adjusted multivariate regression models were also used to predict the probability of occurrence of each of the study outcomes. To investigate the inflammatory response, we measured the plasma levels of pro- and anti-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1rα, IL-6, IL-8, IL-10], inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B-type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10 patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and every other day during the first 6 days of hospitalization. Functional data were presented as median and standard error of the median (SEM); due to small number of samples no statistical comparisons were performed between groups. RESULTS: From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic. Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard ratio (AHR) of 0.82 (95 % CI 0.69-0.97; p = 0.02) and had higher in-hospital mortality with an AHR of 1.63 (95 % CI 1.06-2.50, p = 0.026). Bacteremic pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP (p < 0.003). Higher plasma levels of CRP, PCT, and BNP were found in bacteremic than in non-bacteremic patients. The bacteremic group had consistently higher plasma levels of both pro- and anti-inflammatory cytokines. The blood neutrophil functional responses were similar in both groups of patients. CONCLUSIONS: Bacteremic pneumococcal CAP patients were significantly associated with higher in-hospital mortality, lower TCS, and longer LOS. HIV-infected patients showed a greater mortality which was not statistically significant. Bacteremic pneumococcal CAP patients had higher levels of biomarkers and systemic cytokines.

Fungal Planet description sheets: 281-319.

Novel species of fungi described in the present study include the following from South Africa: Alanphillipsia aloeicola from Aloe sp., Arxiella dolichandrae from Dolichandra unguiscati, Ganoderma austroafricanum from Jacaranda mimosifolia, Phacidiella podocarpi and Phaeosphaeria podocarpi from Podocarpus latifolius, Phyllosticta mimusopisicola from Mimusops zeyheri and Sphaerulina pelargonii from Pelargonium sp. Furthermore, Barssia maroccana is described from Cedrus atlantica (Morocco), Codinaea pini from Pinus patula (Uganda), Crucellisporiopsis marquesiae from Marquesia acuminata (Zambia), Dinemasporium ipomoeae from Ipomoea pes-caprae (Vietnam), Diaporthe phragmitis from Phragmites australis (China), Marasmius vladimirii from leaf litter (India), Melanconium hedericola from Hedera helix (Spain), Pluteus albotomentosus and Pluteus extremiorientalis from a mixed forest (Russia), Rachicladosporium eucalypti from Eucalyptus globulus (Ethiopia), Sistotrema epiphyllum from dead leaves of Fagus sylvatica in a forest (The Netherlands), Stagonospora chrysopyla from Scirpus microcarpus (USA) and Trichomerium dioscoreae from Dioscorea sp. (Japan). Novel species from Australia include: Corynespora endiandrae from Endiandra introrsa, Gonatophragmium triuniae from Triunia youngiana, Penicillium coccotrypicola from Archontophoenix cunninghamiana and Phytophthora moyootj from soil. Novelties from Iran include Neocamarosporium chichastianum from soil and Seimatosporium pistaciae from Pistacia vera. Xenosonderhenia eucalypti and Zasmidium eucalyptigenum are newly described from Eucalyptus urophylla in Indonesia. Diaporthe acaciarum and Roussoella acacia are newly described from Acacia tortilis in Tanzania. New species from Italy include Comoclathris spartii from Spartium junceum and Phoma tamaricicola from Tamarix gallica. Novel genera include (Ascomycetes): Acremoniopsis from forest soil and Collarina from water sediments (Spain), Phellinocrescentia from a Phellinus sp. (French Guiana), Neobambusicola from Strelitzia nicolai (South Africa), Neocladophialophora from Quercus robur (Germany), Neophysalospora from Corymbia henryi (Mozambique) and Xenophaeosphaeria from Grewia sp. (Tanzania). Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.

Inversion Recovery Ultrashort TE MR Imaging of Myelin is Significantly Correlated with Disability in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: MR imaging has been widely used for the noninvasive evaluation of MS. Although clinical MR imaging sequences are highly effective in showing focal macroscopic tissue abnormalities in the brains of patients with MS, they are not specific to myelin and correlate poorly with disability. We investigated direct imaging of myelin using a 2D adiabatic inversion recovery ultrashort TE sequence to determine its value in assessing disability in MS. MATERIALS AND METHODS: The 2D inversion recovery ultrashort TE sequence was evaluated in 14 healthy volunteers and 31 patients with MS. MPRAGE and T2-FLAIR images were acquired for comparison. Advanced Normalization Tools were used to correlate inversion recovery ultrashort TE, MPRAGE, and T2-FLAIR images with disability assessed by the Expanded Disability Status Scale. RESULTS: Weak correlations were observed between normal-appearing white matter volume (R = -0.03, P = .88), lesion load (R = 0.22, P = .24), and age (R = 0.14, P = .44), and disability. The MPRAGE signal in normal-appearing white matter showed a weak correlation with age (R = -0.10, P = .49) and disability (R = -0.19, P = .31). The T2-FLAIR signal in normal-appearing white matter showed a weak correlation with age (R = 0.01, P = .93) and disability (R = 0.13, P = .49). The inversion recovery ultrashort TE signal was significantly negatively correlated with age (R = -0.38, P = .009) and disability (R = -0.44; P = .01). CONCLUSIONS: Direct imaging of myelin correlates with disability in patients with MS better than indirect imaging of long-T2 water in WM using conventional clinical sequences.

Altered secondary myogenesis in transgenic animals expressing the neural cell adhesion molecule under the control of a skeletal muscle alpha-actin promoter.

The majority of skeletal muscle fibers are generated through the process of secondary myogenesis. Cell adhesion molecules such as NCAM are thought to be intricately involved in the cell-cell interactions between developing secondary and primary myotubes. During secondary myogenesis, the expression of NCAM in skeletal muscle is under strict spatial and temporal control. To investigate the role of NCAM in the regulation of primary-secondary myotube interactions and muscle fusion in vivo, we have examined muscle development in transgenic mice expressing the 125-kD muscle-specific, glycosylphosphatidylinositol-anchored isoform of human NCAM, under the control of a human skeletal muscle alpha-actin promoter that is active from about embryonic day 15 onward. Analysis of developing muscle from transgenic animals revealed a significantly lower number of myofibers encased by basal lamina at postnatal day 1 compared with nontransgenic littermates, although the total number of developing myofibers was similar. An increase in muscle fiber size and decreased numbers of VCAM-1-positive secondary myoblasts at postnatal day 1 was also found, indicating enhanced secondary myoblast fusion in the transgenic animals. There was also a significant decrease in myofiber number but no increase in overall muscle size in adult transgenic animals; other measurements such as the number of nuclei per fiber and the size of individual muscle fibers were significantly increased, again suggesting increased secondary myoblast fusion. Thus the level of NCAM in the sarcolemma is a key regulator of cell-cell interactions occurring during secondary myogenesis in vivo and fulfills the prediction derived from transfection studies in vitro that the 125-kD NCAM isoform can enhance myoblast fusion.

Apoptosis induction by different local anaesthetics in a neuroblastoma cell line.

BACKGROUND: Local anaesthetics are known to induce apoptosis in clinically relevant concentrations. Hitherto, it is unknown what determines the apoptotic potency of local anaesthetics. Therefore, we compared apoptosis induction by local anaesthetics related to their physicochemical properties in human neuronal cells. METHODS: Neuroblastoma cells (SHEP) were incubated with eight local anaesthetics, two of the ester and six of the amide types. At least, five concentrations of each local anaesthetic were evaluated. After incubation for 24 h, rates of cells in early apoptotic stages and overall cell death were evaluated by annexin V and 7-amino-actinomycin D double staining by flow cytometry. The concentrations that led to half-maximal neurotoxic effects (LD50) were calculated and compared for all local anaesthetics. RESULTS: All local anaesthetics were neurotoxic in a concentration-dependent manner. All drugs induced similar rates of early apoptotic cell formation at low concentrations, whereas at high concentrations, late apoptotic or necrotic cell death predominated. Comparison of LD50 values of the different local anaesthetics resulted in the following order of apoptotic potency from high to low toxicity: tetracaine>bupivacaine>prilocaine=mepivacaine=ropivacaine>lidocaine>procaine=articaine. The toxicity correlated with octanol/buffer coefficients and also with experimental potency of the local anaesthetic, but was unrelated to the structure (ester or amide type). CONCLUSIONS: All commonly used local anaesthetics induce neuronal apoptosis in clinically used concentrations. The neurotoxicity correlates with lipid solubility and thus with the conduction blocking potency of the local anaesthetic, but is independent of the chemical class (ester/amide).

Conformal invariance of isoheight lines in a two-dimensional Kardar-Parisi-Zhang surface.

The statistics of isoheight lines in the (2+1) -dimensional Kardar-Parisi-Zhang (KPZ) model is shown to be conformally invariant and equivalent to those of self-avoiding random walks. This leads to a rich variety of exact analytical results for the KPZ dynamics. We present direct evidence that the isoheight lines can be described by the family of conformally invariant curves called Schramm-Loewner evolution (or SLE_{kappa} ) with diffusivity kappa=8/3 . It is shown that the absence of the nonlinear term in the KPZ equation will change the diffusivity kappa from 8/3 to 4, indicating that the isoheight lines of the Edwards-Wilkinson surface are also conformally invariant and belong to the universality class of domain walls in the O(2) spin model.

The granule cell density of the dentate gyrus following administration of Urtica dioica extract to young diabetic rats.

Urtica dioica L. Stinging nettle has long been known worldwide as a medicinal plant. To study the benefits of the nettle in diabetic encephalopathy, the granule cell density of the dentate gyrus of diabetic rats was studied following administration of Urtica dioica extract. A total of 24 male albino Wistar rats were allocated equally to normal, diabetic, preventive and treatment groups. Hyperglycaemia was induced by streptozotocin (80 mg/kg) in the animals of the diabetic and treatment groups. One week after injection of the streptozotocin the animals in the treatment group received a hydroalcoholic extract of Urtica dioica (100 mg/kg/day) for 4 weeks intraperitoneally. The rats of the preventive group received hydroalcoholic extract of U. dioica (100 mg/kg/day) IP for the first 5 days and an injection of streptozotocin (80 mg/kg) on the 6th day. After 5 weeks of study all the rats were sacrificed and coronal sections were taken from the dorsal hippocampal formation of the right cerebral hemispheres and stained with cresyl violet. The area densities of the granule cells were measured and compared in the four groups. The density was lower in the diabetic rats compared with the controls (p > 0.05). The preventive group showed lower cell density than the controls (p > 0.05). The densities in the treated rats were higher than in the diabetic rats (p > 0.05). Furthermore, the control and treated rats showed similar densities (p > 0.05). It seems that U. dioica extract can help compensate for granule cell loss in the diabetic rat dentate gyrus, which can ameliorate cognitive impairment in diabetes. However, preventive use of the extract showed no significant benefit.

Morphometric alterations of the rat spleen following formaldehyde exposure.

Formaldehyde is commonly used in the production of various industrial and medical products. At room temperature formaldehyde easily evaporates. Exposure to formaldehyde can be hazardous to human health. Studies show that the vapour can be the cause of clinical symptoms such as throat, eye, skin and nasal irritation. It can also decrease the production of IgM in the spleen cells. This study was designed to determine the morphometric changes to the spleen in rats when samples were exposed to formaldehyde for 18 weeks. A total of 28 albino Wistar rats aged 6-7 postnatal weeks were divided into the following three case groups according to their exposure to formaldehyde: E1 (2 h/day, 2 days/week), E2 (2 h/day, 4 days/week), E3 (4 h/day, 4 days/week) and one control group. When the exposure period had expired the animals were anaesthetised with chloroform. After cervical dislocation, the abdomen was dissected and spleen specimens were taken. These were sectioned and stained with the haematoxylin and eosin technique for morphometric study. Data was obtained from an Olympus light microscope and then analysed with SPSS (version 11.5) and one-way ANOVA test. The white pulp area and diameter and the marginal zone diameter were greater in group E3 than those in the other groups. The germinal centre area and diameter and the diameter of the periarterial lymphoid sheaths (PALS) were greater in group E2 than in other groups, although there was no significant difference between groups in the area of white pulp and the PALS diameter (p<0.05). This study showed that formaldehyde vapour can cause morphometric changes in the white pulp of the spleen in rats.

Formaldehyde exposure induces histopathological and morphometric changes in the rat testis.

Formaldehyde is a chemical which is traditionally used for fixing cadavers and routine histopathology techniques. It is vaporised during the dissection and practical study of a cadaver. Previous studies have shown that this vapour may cause clinical symptoms such as throat, eye, skin and nasal irritation. This study was designed to determine the histopathology and morphometrics of the rat testis when all the experimental animals were exposed to formaldehyde for 18 weeks. The study was performed in 2004 on 28 albino Wistar rats of 6-7 postnatal weeks. The rats were divided into three case groups (E1: 4 h/d, 4 d/w; E2: 2 h/d, 4 d/w; E3: 2 h/d, 2 d/w) and one control group. The testes specimens were sectioned at 5 microm and stained with the haematoxylin and eosin staining technique for histological and morphometrical studies. We found a severe decrease in germ cells associated with spermatogenesis arrest in the E1 group. A decrease in germ cells and a thickening of the basal membrane of the seminiferous tubules were seen in E2. Displacement of Sertoli and germinal cells were also found in the E3 group. The mean seminiferous tubular diameter and seminiferous epithelial height in the experimental groups were decreased in comparison with the control group and the differences were statistically significant (p < 0.05). The findings of this study revealed that chronic formaldehyde exposure can cause histopathological and morphometric changes to the seminiferous epithelium in rats and that these changes depend on the duration of the formaldehyde exposure.

Analytic height correlation function of rough surfaces derived from light scattering.

We derive an analytic expression for the height correlation function of a homogeneous, isotropic rough surface based on the inverse wave scattering method of Kirchhoff theory. The expression directly relates the height correlation function to diffuse scattered intensity along a linear path at fixed polar angle. We test the solution by measuring the angular distribution of light scattered from rough silicon surfaces and comparing extracted height correlation functions to those derived from atomic force microscopy (AFM). The results agree closely with AFM over a wider range of roughness parameters than previous formulations of the inverse scattering problem, while relying less on large-angle scatter data. Our expression thus provides an accurate analytical equation for the height correlation function of a wide range of surfaces based on measurements using a simple, fast experimental procedure.

Ectopic expression of NCAM in skeletal muscle of transgenic mice results in terminal sprouting at the neuromuscular junction and altered structure but not function.

The neuromuscular system provides an excellent model for the analysis of molecular interactions involved in the development and plasticity of synaptic contacts. The neural cell adhesion molecule (NCAM) is believed to be involved in the development and plasticity of the neuromuscular junction, in particular the axonal sprouting response observed in paralyzed and denervated muscle. In order to explore the role of myofiber NCAM in modulating the differentiation of motor neurons, we generated transgenic mice expressing a GPI-anchored NCAM isoform that is normally found in developing and denervated muscle, under the control of a skeletal muscle-specific promoter. This results in the constitutive expression of NCAM at postnatal ages, a time when the endogenous mouse NCAM is absent from the myofiber. We found that a significant number of neuromuscular junctions in adult transgenic animals displayed terminal sprouting (>20%) reminiscent of that elicited in response to cessation of neuromuscular activity. Additionally, a significant increase in the size and complexity of neuromuscular synapses as a result of extensive intraterminal sprouting was detected. Electrophysiological studies, however, revealed no significant alterations of neuromuscular transmission at this highly efficient synapse. Sprouting in response to paralysis or following nerve crush was also significantly enhanced in transgenic animals. These results suggest that in this ectopic expression model NCAM can directly modulate synaptic structure and motor neuron-muscle interactions. The results contrast with knockout experiments of the NCAM gene, where very limited changes in the neuromuscular system were observed.

Stochastic analysis and regeneration of rough surfaces.

We investigate the Markov property of rough surfaces. Using stochastic analysis, we characterize the complexity of the surface roughness by means of a Fokker-Planck or Langevin equation. The obtained Langevin equation enables us to regenerate surfaces with similar statistical properties compared with the observed morphology by atomic force microscopy.