Carcinogenesis in ureterosigmoidostomy

Both clinical and experimental observations establish that an adenocarcinoma of the colon is likely to occur at the suture line of ureterosigmoidostomy. The carcinogenesis depends on the initial presence of urine, feces, urothelium, and colonic epithelium in close apposition at a healing suture line. It does not occur in isolated colon loops used for urinary diversion. In our rat model, tumors were completely prevented by interposing ileum between the urothelium and colon. Clinical prevention requires that accurate hospital registries of patients at risk be established and that repeated annual colonoscopy be carried out on all of them.     

Use of pulse oximetry for blood pressure measurement after cardiac surgery

Blood pressure measurement using pulse oximeter waveform change was compared with an oscillometric measurement and the gold standard, intra-arterial measurement, in children after cardiac surgery. Forty six patients were enrolled and divided into groups according to weight. Simultaneous blood pressure measurements were obtained from the arterial catheter, the oscillometric device, and the pulse oximeter. Pulse oximeter measurements were obtained with a blood pressure cuff proximal to the oximeter probe. The blood pressure measurements from the pulse oximeter method correlated better with intra-arterial measurements than those from the oscillometric device (0.77-0.96 v 0.42-0.83). The absolute differences between the pulse oximeter and intra-arterial measurements were significantly smaller than between the oscillometric and intra-arterial measurements in children less than 15.0 kg. The pulse oximeter waveform change is an accurate and reliable way to measure blood pressure in children non-invasively, and is superior to the oscillometric method for small patients.     

Fibroblast response to hypoxia: the relationship between angiogenesis and matrix regulation.

A number of studies have demonstrated the critical role of angiogenesis for successful wound repair in the surgical patient. Vascular disruption from tissue injury due to trauma or surgery leads to a hypoxic zone in the healing wound. In this dynamic process, angiogenesis is vital for the delivery of oxygen, nutrients, and growth factors necessary to initiate the synthetic processes of wound healing. Fibroblasts, invading the wound early in the healing process, are involved in extracellular matrix (ECM) deposition as well as wound contraction. However, the exact mechanisms by which important genes are regulated remain unknown. In order to examine these processes, we studied the effects of hypoxia on fibroblasts for the expression of VEGF, type IalphaI collagen, and matrix-metalloproteinase-3, three genes essential for the regulation of angiogenesis, ECM deposition, and ECM degradation in wound healing. Primary cell cultures of normal human dermal fibroblasts (NHDFs) were placed in hypoxia for varying periods of time. Northern blot hybridization was performed with [alpha32P]dCTP-labeled cDNA probes for VEGF, type IalphaI collagen, and MMP-3. The results demonstrated a time-dependent VEGF mRNA upregulation (470% of baseline) under hypoxia. Type IalphaI collagen increased (170% of baseline) at 24 h, but was then abruptly downregulated to 3.8% of baseline at 48 h. MMP-3 was incrementally downregulated to 2.2% of baseline at 48 h. These experiments focused on the effect of hypoxia on genes thought to play a role in wound repair. VEGF upregulation in the hypoxic microenvironment of the early wound may serve to stimulate angiogenesis. Type IalphaI collagen, though upregulated early on, was abruptly downregulated at 48 h. This downregulation may reflect the in vivo requirement for angiogenesis to deliver oxygen for successful hydroxylation and collagen synthesis in the wound. MMP-3, also downregulated at 48 h, may also implicate the need for angiogenesis. These data support the theory that hypoxia-driven angiogenesis is critical for ECM formation and remodeling in successful soft tissue repair. Furthermore, they may represent the role of hypoxia as an important regulator to efficiently balance these complex processes in the healing wound.     

Combined use of Amplified Fragment Length Polymorphism and IS<Emphasis Type="Italic">6110</Emphasis> -RFLP in fingerprinting clinical isolates of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> from Kerala,South India

Background  

DNA fingerprinting by IS6110-RFLP has shown a high incidence of Mycobacterium tuberculosis isolates having no and low copies of the insertion sequence in Kerala, South India. Amplified Fragment Length Polymorphism (AFLP) would scan the entire genome rather than a few repetitive elements, we thought that this technique would help us in differentiating the large reservoir of isolates from an endemic region. Here we evaluate the ability of Amplified Fragment Length Polymorphism (AFLP) to type clinical isolates.     

Increased PDX-1 expression is associated with outcome in patients with pancreatic cancer

BACKGROUND: During pancreatic development, pancreatic duodenal homeobox gene-1 (PDX-1) is expressed in pancreatic duct cells that have the potential to differentiate into islets. Therefore, PDX-1 is thought to be a marker of de-differentiated cells with the capacity to redifferentiate into several pancreatic cell types. We analyzed PDX-1 expression in human pancreatic cancer specimens, pancreatic cancer cell lines, and the effects of forced expression of PDX-1 in pancreatic cancer cells. METHODS: Thirty-five pancreatic adenocarcinomas were immunohistochemically stained with a polyclonal rabbit antibody against mouse PDX-1. Correlations with tumor characteristics were made with chi-squared analysis. The influence of clinicopathologic factors on survival was assessed. The expression of PDX-1 in pancreatic cancer cells was examined. Replication-deficient recombinant adenoviruses were constructed by the cosmid-adenoviral DNA terminal protein complex method. PANC-1 cells were infected with Ad-pdx-1 or Ad-LacZ. PANC-1 cells that were infected with adenovirus were used in a cell growth assay and a migration assay and for morphologic analysis. RESULTS: Interestingly, 43% of pancreatic cancers were positive for PDX-1 expression, and 57% of pancreatic cancers were negative (normal pancreatic exocrine tissue shows little or no staining for PDX-1). Lymph node metastasis (P =.02) and histologic grade (P =.04) were correlated significantly with PDX-1 expression. Patients with positive PDX-1 had a significantly worse prognosis than those patients with negative PDX-1 (P =.02). Importantly, PDX-1 was an independent variable that effected overall survival (P =.03). Pancreatic cancer cell lines showed no PDX-1 expression. There were no significant differences in cell proliferation or morphologic condition between Ad-pdx-1- and Ad-lacZ-infected PANC-1 cells. However, Ad-pdx-1-infected PANC-1 cells did show a significantly higher migration rate than Ad-lacZ-infected PANC-1 cells. CONCLUSIONS: Re-expression of PDX-1 may represent a return to a more de-differentiated state by more aggressive pancreatic cancers and may also represent an important new tumor marker for these aggressive cancers.     

Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro

The effects of transforming growth factor beta 1 or beta 2 (TGF-beta 1 or -beta 2) on the in vitro proliferation and differentiation of normal and malignant human hematopoietic cells were studied. Both forms of TGF- beta suppressed both the normal cellular proliferation and colony formation induced by recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the presence of GM-CSF or IL-3, optimal concentrations of TGF-beta (400 pmol/L) inhibited colony formation by erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor cells by 90% to 100%, whereas granulocyte or monocyte cluster formation was not inhibited. In contrast, neither form of TGF-beta had any effect on G- CSF-induced hematopoiesis. The suppressive action appeared to be mediated directly by TGF-beta since antiproliferative responses were also observed in accessory cell-depleted bone marrow cells. In contrast to normal bone marrow cells, both GM- and G-CSF-induced proliferation of cells from patients with chronic myelogenous leukemia were suppressed in a dose-dependent manner by TGF-beta. Differential effects of TGF-beta on the proliferation of established leukemic lines were also observed since most cell lines of myelomonocytic nature studied were strongly inhibited where erythroid cell lines were either insensitive or poorly inhibited by TGF-beta. These results suggest that TGF-beta is an important modulator of human hematopoiesis that selectively regulates the growth of less mature hematopoietic cell populations with a high proliferative capacity as opposed to more differentiated cells, which are not affected by TGF-beta.     

Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke

Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evaluated through the reporting of infarct volume and/or neurological score as outcomes. Overall efficacy was evaluated using weighted mean difference random effects meta-analysis. We also evaluated for study quality and publication bias. We identified eight publications that met our inclusion criteria describing a total of 29 comparisons and 454 animals. Overall methodological quality of studies was moderate (median = 4/9). Carnosine reduced infarct volume by 29.4% (95% confidence interval (CI), 24.0% to 34.9%; 29 comparisons). A clear dose-response effect was observed, and efficacy was reduced when carnosine was administered more than 6 h after ischemia. Our findings suggest that carnosine administered before or after the onset of ischemia exhibits robust efficacy in experimental ischemic stroke. However, the methodological quality of some of the studies was low and testing occurred only in healthy young male animals.