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Preoperative thallium scanning, selective coronary revascularization, and long-term survival after carotid endarterectomy.

BACKGROUND AND PURPOSE: Long-term survival in patients after carotid endarterectomy (CEA) is determined mainly by their concomitant cardiac disease. We tested to determine whether preoperative thallium scanning (PTS) and subsequent selective coronary revascularization (CR), by either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG), improve long-term survival after CEA. METHODS: Two hundred twenty-six of 255 consecutive patients (88%) undergoing CEA from 1990 to 1996 had PTS. Those with significant reversible defects on PTS were referred for coronary angiography and possible CR. Patients who had undergone PTS were divided into the following 4 groups: group 1, normal or mild defects on PTS; group 2, moderate-severe fixed and/or reversible defects in patients who did not undergo CR; group 3, patients who had CR secondary to their PTS results; and group 4, patients who had CR in the past that was not related to the PTS. Perioperative data were prospectively recorded, and data on long-term survival and cardiac and neurological complications were collected. RESULTS: Seventy-seven patients (34%) had preoperative coronary angiography, and 42 (19%) had subsequent CR: preoperative PTCA or CABG in 24, combined CEA+CABG in 10, and post-CEA CABG in 8 patients. No deaths resulted from the coronary angiography, CR, or CEA. Six patients had perioperative nonfatal myocardial infarction and 8 had stroke. During the follow-up (40+/-23 months), 47 patients (18%) died, 31 (66%) from cardiac disease and 4 (8.5%) from stroke. Independent predictors of long-term overall mortality were diabetes mellitus, preoperative T-wave inversion on ECG, lower-extremity arterial disease, and history of neurological symptoms [exp(beta)=3. 5, 3.4, 2.5, and 2.4; P=0.0003, 0.0004, 0.01, and 0.04, respectively]. In addition, preoperative moderate-severe thallium defect without CR (group 2) independently predicted long-term cardiac mortality [exp(beta)=2.8; P=0.04]. Patients with preoperative CR (group 3) had long-term survival rate similar to that of group 1 and significantly better than that of group 2 (P=0. 02). CONCLUSIONS: PTS predicts long-term survival, and selective CR based on the thallium results improves the survival rate of patients undergoing CEA.

Aged↗

Fetal intervention for mass lesions and hydrops improves outcome: a 15-year experience.

PURPOSE: The natural history of certain prenatally diagnosed masses is well known. Large thoracic mass lesions can evolve one of 2 ways, either to regress and cause minimal morbidity, or to progress and enlarge, often resulting in hydropic changes in the fetus. This nonimmune hydrops carries a dismal prognosis, with nearly all fetuses expiring before or shortly after birth. However, hydrops associated with fetal mass lesions can be halted and even reversed with fetal intervention and treatment of the underlying defect. We examined our patients with fetal mass lesions to evaluate survival after intervention. METHODS: Institutional approval was obtained by the Committee on Human Research. A retrospective review was performed of 294 fetuses evaluated over 15 years with large mass lesions. All patients were evaluated for evidence of fetal hydrops using ultrasound criteria. Patients were divided according to type of intervention. Primary outcome measure was 30-day survival after birth. RESULTS: (1) Patients without fetal hydrops did not undergo fetal intervention and survived to 30 days after birth (167/172, 97%). (2) Patients with fetal mass lesions that developed hydrops fared poorly with no intervention (1/33 survival, 3%), whereas fetuses undergoing prenatal intervention fared much better (15/30 open, 50%; 3/10 percutaneous, 30%). (3) Four patients with hydropic congenital cystic adenomatoid malformation (n = 3) or pulmonary sequestration (n = 1) received steroids in preparation for surgery but underwent no intervention, and the patients survived the neonatal period. CONCLUSION: Fetuses with prenatal diagnoses of masses not associated with hydrops have excellent prognosis with survival higher than 95%. Nonimmune hydrops associated with prenatal diagnosis of a fetal mass is a devastating complication with less than 5% survival. Open resection of a mass causing hydrops resulted in 50% survival, with reversal of hydrops in a group with near-uniform fatality. Further investigation is warranted regarding the use of minimally invasive prenatal therapies including steroid administration for hydropic fetuses.

Edema↗

The EORTC melanoma group translational research program on prognostic factors and ultrastaging in association with the adjuvant therapy trials in stage II and stage III melanoma. European Organization for Research and Treatment of Cancer.

Last year the Melanoma Group of the European Organization for Research and Treatment of Cancer (EORTC-MG) completed accrual (1418 patients) for trial EORTC 18952, a three-arm phase III trial evaluating adjuvant therapy with two different intermediate doses of interferon (IFN) alfa-2b versus observation for stage IIB-III melanoma. About 25% of the patients entered the trial with tumor-positive sentinel nodes (SNs). Prognosis was significantly better in SN-positive patients than in patients with palpable regional node involvement (P < .00001). Subsequently the EORTC-MG embarked on two large phase III trials of adjuvant therapy based on the tumor status of the SN. In trial EORTC 18961 for stage II melanoma, GM2-KLH/QS-21 vaccination is compared with observation (1300 patients); in trial EORTC 18991 for stage III melanoma, 5-year treatment with pegylated interferon alfa-2b (PEG-Intron) is compared with observation (900 patients). Translational research projects will compare SN assessment by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and reverse transcriptase-polymerase chain reaction (RT-PCR) to determine the relative accuracy of each method and its correlation to relapse and survival of patients with stage II melanoma. In stage III patients, a similar workup of the most proximal nonsentinel node in the full lymph-node dissection specimen will indicate the accuracy of each methodology to detect nodal metastasis beyond the SN and the prognostic significance thereof. These findings will be correlated to the results of sequential blood testing by RT-PCR and by tumor marker assays for S100, TA90, and angiostatin. In addition, tumor-positive and tumor-negative SNs will be assessed for activated cytotoxic T lymphocytes and downregulation of dendritic cell functions.

Antineoplastic Agents↗

Meshed reversed dermal graft in patients with surgical defects of sole and scalp: technique and long-term results.

BACKGROUND: Defects of the sole and the scalp require a reconstruction technique that combines a high survival rate in poorly vascularized areas with maximal mechanical strain. OBJECTIVE: To describe the technique of the meshed reversed dermal graft for reconstruction and to summarize the postoperative and long-term results. METHODS: Twenty-one patients have undergone reconstruction of defects following excision of acral lentiginous melanoma of the sole or squamous cell carcinoma of the sole or scalp. One patient had undergone covering of a perforating ulcer of the foot. RESULTS: In 19 of the 21 patients the meshed reversed dermal graft survived without complications. Of the patients who had undergone successful reconstruction, 14 patients were reinterviewed: 13 reported on excellent functional and satisfying cosmetic results. CONCLUSION: The meshed reversed dermal graft is an appropriate technique for reconstruction of large defects of the sole or scalp because of its high survival rate and excellent long-term functional results.

Adult↗

[Nosocomial infections due to human coronaviruses in the newborn].

Human coronaviruses, with two known serogroups named 229-E and OC-43, are enveloped positive-stranded RNA viruses. The large RNA is surrounded by a nucleoprotein (protein N). The envelop contains 2 or 3 glycoproteins: spike protein (or protein S), matrix protein (or protein M) and a hemagglutinin (or protein HE). Their pathogen role remains unclear because their isolation is difficult. Reliable and rapid methods as immunofluorescence with monoclonal antibodies and reverse transcription-polymerase chain reaction allow new researches on epidemiology. Human coronaviruses can survive for as long as 6 days in suspension and 3 hours after drying on surfaces, suggesting that they could be a source of hospital-acquired infections. Two prospective studies conducted in a neonatal and paediatric intensive care unit demonstrated a significant association of coronavirus-positive nasopharyngal samples with respiratory illness in hospitalised preterm neonates. Positive samples from staff suggested either a patient-to-staff or a staff-to-patient transmission. No cross-infection were observed from community-acquired respiratory-syncitial virus or influenza-infected children to neonates. Universal precautions with hand washing and surface desinfection could be proposed to prevent coronavirus transmission.

Adult↗

New therapeutic strategy for gastric carcinoma: a two-step evaluation of malignant potential from its molecular biologic and pathologic characteristics.

BACKGROUND AND OBJECTIVES: A previous study of ours indicated that platelet-derived growth factor-A (PDGF-A) mRNA expression in biopsy specimens can identify a subgroup of high-risk gastric carcinoma patients, while clinicopathologic studies have shown that lymph node involvement is an important risk factor for predicting overall survival. To identify gastric carcinoma patients at high risk for recurrence, we assessed a two-step evaluation consisting of mRNA expression of tumor growth-related factors and the histopathologic findings. METHODS: The reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assay the gene expression of PDGF-A and transforming growth factor-beta1 (TGF-beta1) in 69 gastric carcinoma endoscopic biopsy specimens (prospective cohort). The corresponding gastric carcinoma surgical specimens were classified histologically. Finally, the patients' survival curves were calculated. The relationships among the mRNA expression, histopathologic findings, and survival period were analyzed statistically. RESULTS: Nodal involvement correlated with PDGF-A and TGF-beta1 mRNA expression in early and advanced carcinomas, respectively. Both PDGF-A mRNA and TGF-beta1 mRNA expression were independent preoperative prognostic indicators in advanced cases. The ratio of involved nodes (n1) to total perigastric lymph nodes dissected (percentage of involved nodes) was the most independent postoperative prognostic indicator in advanced cases. Early carcinomas were divided preoperatively into two types. Advanced carcinomas were divided preoperatively into three. These were divided again postoperatively according to the percentage of involved nodes into high- and low-malignacy groups. CONCLUSIONS: A two-step evaluation of the malignant potential of gastric carcinoma by a combination of preoperative evaluation for PDGF-A and TGF-beta1 expression and postoperative pathologic examination would yield a more accurate prognosis for patients with gastric carcinoma.

Humans↗

Reverse tapered vs. straight PTFE (Gore-Tex) grafts in dogs.

Reversed Autogenous Saphenous Vein (RASV) remains the material of choice in infrainguinal arterial bypass. A characteristic of RASV not seen in other grafts is its reverse tapered (RT) configuration. The purpose of this study was to investigate this geometric configuration. Straight 6 mm PTFE (gore-tex) grafts (SG) and 4-7 mm reverse tapered PTFE (gore-tex) grafts (RTG) were both implanted in the aorto-iliac position in 16 mongrel dogs. Specimens of surviving dogs were examined by the usual methods. In terms of absolute patency, 9 of 14 RTG (64%) and 5 of 14 SG (36%) P = 0.05, anastomotic thrombus formation 6 of 14 (43%) RTG vs. 10 of 14 (71%) SG P = 0.05 and in midgraft thrombus deposition P = 0.025 the RTG performed significantly better than the SG. In light of these results and other considerations, the reverse tapered configuration merits clinical investigation with other materials and in other species.

Animals↗

Comparison of immunohistochemistry and RT-PCR for detection of CD44v-expression, a new prognostic factor in human breast cancer.

In different human tumors, splice variants of the surface glycoprotein CD44 (CD44v) are correlated with advanced stages of tumor growth and metastatic potential. In breast cancer and colon cancer, expression of epitopes encoded by exon v6 on primary tumors is an independent prognostic factor for poor patient survival. Two different screening methods for the detection of CD44 variants in tumors have been applied: immunohistochemistry (IHC) and semi-quantitative reverse transcription PCR (RT-PCR). In this study, we have compared the predictive capacity and the applicability of both approaches, using 31 human breast-tissue specimens (normal and neoplastic). IHC reveals lack of expression of CD44v on normal ductal epithelial cells but strong expression on myoepithelial cells. The majority of tumors express CD44 epitopes encoded by several variant exons. RT-PCR detects splice variants in normal epithelium, probably derived from RNA expressed in the myoepithelium. In tumors, RT-PCR reveals expression of a wide range of splice variants, including new ones that are not detected in normal breast tissue, e.g. ones that contain all variant exons. The conclusion of this comparison is that IHC is the better method for breast-tumor sample screening but that the increased sensitivity of RT-PCR can help to distinguish CD44v-positive from CD44v-negative tumors in cases where only a few tumor cells express variants or where epitopes are masked.

Antigens, Neoplasm↗

Purification of mammalian cone photoreceptors by lectin panning and the enhancement of their survival in glia-conditioned medium.

PURPOSE: In retinal diseases characterized by photoreceptor degeneration, the main cause of clinically significant vision loss is cone, rather than rod, loss. In the present study, a technique was designed to purify cones to make it possible to screen for neuroprotective molecules. METHODS: A suspension of porcine retinal cells was incubated on coverslips coated with the peanut agglutinin (PNA) lectin, which selectively binds to cones. Cones were identified and quantified by using an antibody specific for cone arrestin. Their identity and viability were also assessed by single-cell RT-PCR and patch-clamp recording. RESULTS: This panning method provided a population of cones that was 80% to 92% pure, depending on the counting strategy used. The panned cells contained both short (S)- and medium/long (M/L)-wavelength opsin cones. The panned retinal cells exhibited the physiological signature of cone photoreceptors and single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) showed that they expressed the cone arrestin mRNA. Most (69%) cone photoreceptors produced neurites and survived for up to 7 days when cultured in a glia-conditioned medium, whereas very few (4%) survived after 7 days in the control medium. CONCLUSIONS: This PNA-lectin-panning method can provide highly pure and viable mammalian cones, the survival of which can be prolonged by glia-conditioned medium. Because PNA lectin binds to cone photoreceptors from various species in both normal and pathologic conditions, this technique should enable the screening of neuroprotective molecules like those released by glial cells and enable the physiological, genomic, and proteomic characterization of cones.

Animals↗

Inhibition of intercellular adhesion molecule-1 with antisense deoxynucleotides prolongs renal isograft survival in the rat.

BACKGROUND: Delayed graft function from ischemia-reperfusion injury has a negative impact on long-term renal graft survival. We tested the utility of antisense oligodeoxynucleotide (ODN) against intercellular adhesion molecule-1 (ICAM-1) in the pretransplant treatment of renal isografts in improving long-term graft survival. METHODS: Three groups of 16 inbred Lewis rats each underwent unilateral nephrectomy and were then transplanted with a kidney from a Lewis donor rat, which had received antisense ODN, reverse sense ODN, or saline vehicle six hours prior to nephrectomy. The kidneys were subjected to one hour of warm ischemia and 30 minutes of cold ischemia, which when untreated results in delayed graft function. The remaining native kidney was removed 10 days later. Serum creatinine and urinary protein excretion were measured in surviving rats at weeks 2, 4, 6, 8, 12, 16, and 20 after native nephrectomy. RESULTS: A Kaplan-Meier analysis revealed that by week 6 one half of the animals receiving reverse sense ODN and saline vehicle treatment had died, while all but 2 rats in the antisense ODN-treatment group survived to 20 weeks. Serum creatinine concentrations and urine protein excretion of surviving reverse sense and saline vehicle-treated rats were significantly higher than antisense treated rats at every time point. Histology at week 20 revealed marked interstitial fibrosis, focal glomerular sclerosis, vascular intimal and medial thickening and tubular atrophy in reverse sense and saline vehicle-treated kidneys, while antisense ODN-treated kidneys showed only modest changes. Immunohistochemistry showed macrophage and lymphocyte infiltration, as well as substantial up-regulation of MHC class II, in reverse sense and saline vehicle-treated kidneys compared to antisense ODN-treated kidneys. CONCLUSIONS: These results suggest that by ameliorating acute nonimmunological renal isograft injury, the long-term chronic nonimmunologic processes are improved as well. Furthermore, the data suggest that an antisense ODN strategy directed against ICAM-1 may have utility in human kidney transplantation.

Animals↗

Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection.

BACKGROUND: Long-term survival of a graft requires inhibition of host immune effectors, but protective responses emanating from the graft might be equally important. Expression of the "protective" genes A20, heme-oxygenase-1 (HO-1), and Bcl-xL in rodent allo and xenografts correlates with long-term survival. Little is known of the pattern of expression of such protective genes and the implication thereof in clinical transplantation. METHODS: We analyzed, by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, expression of A20, HO-1, and Bcl-xL in 31 renal allograft biopsies from patients with suspected rejection. RESULTS: A20 is not expressed in nonrejecting (NR) grafts. Its expression is increased in grafts undergoing acute and chronic rejection (AR and CR) but is weaker in CR. HO-1 is not expressed in NR grafts; it is up-regulated in AR but not CR. Bcl-xL is detected in all biopsies with decreased levels in CR. Expression of A20, HO-1, and Bcl-xL localizes mainly to endothelial, smooth muscle, and infiltrating mononuclear cells. CONCLUSIONS: This data demonstrate that A20 and HO-1 are up-regulated in response to immune injury inferred by AR. Given the antiapoptotic and antiinflammatory functions of these genes, we hypothesize that their expression survives to limit graft injury by maintaining cell viability and controlling inflammation. Their reduced expression in CR as compared with AR represents either inadequate response to injury or a sequelae of prior injury that jeopardizes further tissue response to immune attack.

Adolescent↗

Caspase inhibitor blocks human immunodeficiency virus 1-induced T-cell death without enhancement of HIV-1 replication and dimethyl sulfoxide increases HIV-1 replication without influencing T-cell survival.

OBJECTIVES: To determine the relationship, if any, between reagents that modulate survival of T-cells and replication of human immunodeficiency virus 1 (HIV-1) and to determine the effects of the solvent dimethyl sulfoxide (DMSO) and drugs such as cyclosporin A and all-trans retinoic acid on HIV-1 replication. DESIGN: To first establish the direct effects of solvent alone (ie, DMSO) at various concentrations on HIV-1 replication, followed by the ability of various compounds such as the caspase inhibitor N-benzyloxycarbonyl-val-ala-asp-fluoromethylketone (z-VAD-fmk), cyclosporin A, and all-trans retinoic acid on HIV-1 replication. Next, to determine if HIV-1 induces T-cell apoptosis using TUNEL (TdT-mediated dUTP-biotin nick end-labeling) assays and DNA fragmentation and poly-(ADP-ribose)-polymerase (PARP) cleavage, and then to examine how the various compounds influence T-cell survival after HIV-1 exposure. METHODS: The human T-cell line, CEM cells, were exposed to HIV(IIIB) and viral replication monitored using reverse transcription assays at 3, 6, and 9 days following infection. Cells were pretreated with various compounds dissolved in DMSO over a wide range of concentrations, and DMSO itself was also examined. T-cell death and apoptosis were assessed using TUNEL staining to detect 3'-OH DNA strand breaks and agarose gel electrophoresis to detect DNA fragmentation (laddering). Furthermore, PARP cleavage implicated in the apoptotic process was also examined. RESULTS: At very low levels, such as 0.002%, DMSO itself appears to enhance HIV-1 replication at 6 and 9 days after infection. At low levels of cyclosporin A, such as 0.01 microgram/mL, HIV-1 replication was further enhanced above the solvent effect, but at 1 microgram/mL, cyclosporin A strongly inhibited HIV-1 replication. Retinoic acid between 0.01 and 1 microgram/mL did not influence HIV-1 replication. In addition, a discrepancy was noted in that HIV-1-infected T-cells were TUNEL positive, indicating DNA strand breaks; however, more complete DNA fragmentation was not detected nor was PARP cleavage identified. The induction of TUNEL positivity was blocked by the caspase inhibitor z-VAD-fmk but not by DMSO or cyclosporin A. Even though z-VAD-fmk blocked the appearance of TUNEL-positive T-cells, there was not a consistently observed increase in HIV-1 replication. CONCLUSION: Low levels of DMSO and cyclosporin A can enhance HIV-1 replication in CEM cells. At higher levels, cyclosporin A inhibits HIV-1 replication with no significant effects by all-trans retinoic acid. No evidence for classic apoptosis was detected in CEM cells after HIV-1 infection, although DNA strand breaks may be present as revealed by TUNEL positivity. There was no correlation between levels of HIV-1 replication and T-cell survival or death. The mechanism of T-cell death after HIV-1 infection requires further study, and investigators who add compounds dissolved in DMSO must include controls to carefully examine the direct effects of even trace levels of this solvent on HIV-1 replication.

Amino Acid Chloromethyl Ketones↗

The platelet response to hypotonic shock. Its value as an indicator of platelet viability after storage.

The nature of the platelet response to osmotic shock and its relationship to platelet viability were studied. Light absorbancy changes of human platelet concentrates exposed to hypotonic shock were measured in a spectrophotometer: a sudden drop of light absorbancy was followed by a reversal of light absorbancy towards normal (reversal reaction). It was confirmed that the reversal reaction is a complex phenomenon dependent on the integrity of biochemical and enzymatic functions of the platelets. It was suppressed by glycolytic inhibitors and by SH-blocking agents. Ouabain had no immediate effect, but with prolonged incubation it depressed the reaction. Suspension of the platelets in a protein-free medium caused a rapid loss of the reversal reaction. Disappearance of the marginal bundle of microtubules by exposure to colchicine did not change the reaction leading to the hypothesis that microfibrils rather than the microtubules may have been responsible for the reversal reaction. The conclusion was derived that the reversal reaction is due to cell volume contraction for which integrity of the platelet contractile protein and energy availability are essential. Platelet storage at 4 degrees C or at 22 degrees C caused a progressive depression of the reversal reaction which was more severe in platelets preserved at 4 C than in those preserved at 22 degrees C, and paralleled the loss of the platelet capacity to survive in vivo. Cryoprotective agents (DMSO, DMAC and glycerol) partially inhibited the reversal reaction. Freezing with these agents caused a more severe depression of the reaction. The least depression was observed with 5 per cent DMSO. The results demonstrated that the reversal reaction is a valid and accurate in vitro indicator of in vivo platelet viability when the results to be compared are limited to a single method of storage. Usefulness of the reversal reaction is reduced when results obtained with different methods of storage are compared.

Blood Platelets↗

Method for quantitation of low-abundance nerve growth factor mRNA expression in human nervous tissue using competitive reverse transcription polymerase chain reaction.

Nerve growth factor (NGF) is a polypeptide hormone important for the development, function, and survival of neurons. NGF is an important target for investigation because of its potential therapeutic importance in neurological diseases and injury, yet its low level of expression in nervous tissue makes it difficult to measure. We report here the development of a quantitative assay for human NGF mRNA, using competitive reverse transcription polymerase chain reaction (cRT-PCR), with mouse submandibular gland mRNA as an internal standard. Exhibiting high homology to the human transcript, mouse NGF mRNA is co-amplified with the human NGF transcript through both the reverse transcription and PCR steps using identical primers and conditions. Products are distinguished by a convenient unique restriction site in the mouse transcript. Phosphorimage detection and quantitation of radiolabeled product provides femtogram sensitivity. Generation of a standard curve from a dilution series of mouse mRNA allows the amount of co-amplified human NGF mRNA transcripts to be determined. We demonstrate the amplification and quantitation of human NGF mRNA from 175-350 nanograms of poly(A)+mRNA from human frontal and parietal cortex. This technique is ideal for rapid detection and quantitation of low-abundance NGF mRNA from limited amounts of tissue.

Animals↗

Abnormal portal venous flow at sonography predicts reduced survival after transjugular intrahepatic portosystemic shunt creation.

PURPOSE: To determine if ultrasound (US) findings of abnormal portal venous flow (APVF) before transjugular intrahepatic portosystemic shunt (TIPS) creation are predictive of increased mortality risk after TIPS creation. MATERIALS AND METHODS: Retrospective review of 141 patients with US before TIPS creation was performed. APVF was defined by (i) bidirectional flow, (ii) thrombus, and/or (iii) reversed flow. Model for End-stage Liver Disease (MELD) scores were calculated. Kaplan-Meier survival curves and log-rank tests were used to detect survival differences based on the presence of APVF. Multivariate analysis included APVF, MELD, Child-Pugh class, International Normalized Ratio, creatinine level, total bilirubin level, ascites, hepatocellular carcinoma, low serum sodium level, congestive heart failure, and myocardial infarction. RESULTS: Twenty-six percent of patients (36 of 141) exhibited APVF on US before TIPS creation. Patients with APVF had lower survival rates at 3 and 6 months after TIPS procedures in comparison with patients with normal portal flow (P = .02 at 3 months and P = .04 at 6 months). In patients with MELD scores lower than 18, there was decreased survival based on APVF at 1, 3, and 6 months (P = .04, P = .02, and P = .04, respectively). In patients with MELD scores of 18 or greater, there was a trend for lower survival rates with APVF, but it did not reach statistical significance. Multivariate analysis of patients with MELD scores lower than 18 demonstrated only APVF and low serum sodium levels as independent predictors of outcome, with APVF resulting in a greater than six-fold increased likelihood of mortality. CONCLUSION: US findings of APVF before TIPS creation are associated with increased mortality risk and may be useful in identifying patients otherwise considered safe candidates based on MELD score alone.

Adult↗

[Reconstruction of both eyebrows with scalp flaps with the anastomotic branch in occipital region of superficial temporal artery as the pedicle].

OBJECTIVE: To explore the effects of the reconstruction of both eyebrows with scalp flaps with pedicles supplied by superficial temporal arteries. METHODS: The parietal branch of the superficial temporal and its anastomotic branch of occipital artery at temporoparietal region on the same side were designed as the pedicles, with which two scalp flaps on temporoparietal and temporo-occipital regions with reverse directions were employed to restore the eyebrows on both sides. RESULTS: Four patients were treated with this method with satisfactory appearance and survival rate (100%). The reconstructed eyebrows appeared symmetrical and heavy. CONCLUSION: Scalp flaps with the anastomotic branch at occipital region of superficial temporal artery as the pedicle might be a good choice for the reconstruction of lost eyebrows.

Adolescent↗

The effect of inhibiting topoisomerase I and II on the anti-apoptotic response associated with pro-inflammatory crystals of calcium pyrophosphate dihydrate in human neutrophils.

OBJECTIVE AND DESIGN: To investigate the ability of various topoisomerase I and II inhibitors to reverse the pro-survival effects of calcium pyrophosphate dihydrate (CPPD) crystals on human neutrophils, thereby identifying potential agents that may promote the resolution of neutrophil accumulation typical of crystal associated inflammatory diseases. MATERIALS AND METHODS: Freshly isolated human neutrophils incubated in the presence of CPPD crystals, with or without the pro-apoptotic cytokine TNF-alpha, were pre-incubated in the presence or absence of the topoisomerase I inhibitors camptothecin, nogalamycin or beta-lapachone, or topoisomerase II inhibitors etoposide, doxorubicin or mitoxantrone. Neutrophil respiratory burst was assessed via chemiluminescence, and two quantitative methods were used for the determination of neutrophil apoptosis; cytoplasmic histone-associated-DNA fragmentation assessment, and endogenous caspase 3 substrate (Ac-DEVD-AMC) cleavage. RESULTS: Beta-lapachone and mitoxantrone effectively repressed CPPD crystal associated respiratory burst, whereas the other topoisomerase inhibitors had no inhibitory or stimulatory effect. Camptothecin and all of the topoisomerase II inhibitors induced neutrophil apoptosis, even in the presence of the CPPD crystals that normally repress TNF-alpha-induced and spontaneous apoptosis. CONCLUSIONS: These results suggest that although topoisomerase II antagonists are distinctively effective agents at reversing the pro-survival effects of crystals on neutrophils, camptothecin was unique as a topoisomerase I inhibitor in that it was significantly more effective as a pro-apoptosis inducer than the topoisomerase II poisons without affecting normal neutrophil activation responses.

Apoptosis↗

Prognostic value of postoperative detection of blood circulating tumor cells in patients with colorectal cancer operated on for cure.

OBJECTIVE: To assess whether postoperative detection of circulating tumor cells in peripheral blood influenced the prognosis of patients with colorectal cancer after radical surgery. SUMMARY BACKGROUND DATA: In a previous study, the authors demonstrated that baseline detection of blood circulating tumor cells does not have prognostic significance in patients with colorectal cancer. However, surgical procedures may increase tumor cell detachment and mobilization. METHODS: Sixty-six patients with histologically confirmed colorectal cancer operated on for cure were included in this study. Circulating tumor cells were detected by means of reverse transcriptase-polymerase chain reaction targeting to carcinoembryonic antigen messenger RNA in peripheral blood samples obtained 24 hours after surgery. Endpoints of the study were tumor recurrence, overall survival, and cancer-related survival. Univariate (Kaplan-Meier method) and multivariate (Cox regression model) analyses were performed. RESULTS: After a median follow-up of 36 months, 15 patients (23%) had tumor relapse and 14 had died (21%), 8 of them from a cancer-related cause. Cox regression analysis identified lymph node metastases and gender as independent predictors of tumor recurrence and cancer-related survival, whereas overall survival was dependent on the degree of differentiation of the primary tumor. More importantly, the presence of circulating tumor cells after surgery had no prognostic influence on tumor recurrence, overall survival, or cancer-related survival. CONCLUSIONS: Postoperative detection of blood circulating tumor cells had no prognostic significance in patients with colorectal cancer operated on for cure.

Aged↗