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Temporal dynamics in bistable perception.

Bistable perception is fundamentally a dynamic process: Our perceptual experience continuously alternates when an ambiguous or rivalrous stimulus is observed. Here we present a method to analyze instantaneous measures of dominance and transition between percepts. The analysis extracts three time-varying probabilities. First, the transient preference represents the probability of perceiving one interpretation at one instant. Second, the reversal probability is the probability that the current percept will change at the next evaluation. Finally, the survival probabilities are the probability that at one instant the current percept will not switch to the alternative interpretation. We derive the relationships between these probabilities and offer a test of independence between consecutive percepts. We also introduce a simple technique to sample the observer's perception at regular intervals. The analyzing method is illustrated with the example of binocular rivalry. We demonstrate Levelt's second proposition with the survival probability measure and show that the consecutive rivalrous percepts are not independent.

Dominance, Ocular↗

[The experiences in correction of cicatricial foot drop in 28 patients].

OBJECTIVE: To summarize the experiences in correction of cicatricial foot drop. METHODS: 37 cicatricial drop feet in 28 postburn patients were treated in recent 4 years. The cicatricial flap survival rate was documented to compare the effects of two surgical designs, the different intervals from burn to the operation and three surgical methods used in early burn stage. RESULTS: All of the 37 wounded feet got satisfactory correction. There was no significant statistic difference in flap survival between the two surgical designs. More necrosis of the flap was observed in patients who received early escharectomy (including full thickness skin and fat) or had been burned for less than 1.5 years. CONCLUSIONS: The reverse design of the Achilles tendon flap for correction of drop foot was as safe and effective as a routine design. The operation method used in early burn stage and the interval from burn to the corrective operation should be considered in cicatricial flap design.

Achilles Tendon↗

Prognostic value of tyrosinase reverse-transcriptase polymerase chain reaction in metastatic melanoma.

BACKGROUND: Circulating tumor cells can now be identified in subjects with metastatic melanoma by using the reverse-transcriptase polymerase chain reaction (RT-PCR) to detect the messenger RNA of tyrosinase, a key enzyme of melanogenesis. AIM AND METHODS: The aim of this study was to determine whether the detection of positive tyrosinase cells in patients at metastatic stage was associated with a worse evolution. 32 patients were included with metastatic melanoma (AJCC IV). RESULTS: 66% had a positive tyrosinase RT-PCR and a shorter survival compared with patients with a negative RT-PCR, but this difference is not statistically significant. However, a positive test could appear indicative of rapid progression and poor prognosis. CONCLUSION: The prognostic value of this method could be improved by combining it with PCR of other melanoma markers (Melan A, Mage 3) or assays of serum markers (S 100 protein or lactate dehydrogenase).

Humans↗

Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies.

PURPOSE: This was a pilot study to assess the biologic effects of lapatinib on various tumor growth/survival pathways in patients with advanced ErbB1 and/or ErbB2-overexpressing solid malignancies. PATIENTS AND METHODS: Heavily pretreated patients with metastatic cancers overexpressing ErbB2 and/or expressing ErbB1 were randomly assigned to one of five dose cohorts of lapatinib (GW572016) administered orally once daily continuously. The biologic effects of lapatinib on tumor growth and survival pathways were assessed in tumor biopsies obtained before and after 21 days of therapy. Clinical response was determined at 8 weeks. RESULTS: Sequential tumor biopsies from 33 patients were examined. Partial responses occurred in four patients with breast cancer, and disease stabilization occurred in 11 others with various malignancies. Responders exhibited variable levels of inhibition of p-ErbB1, p-ErbB2, p-Erk1/2, p-Akt, cyclin D1, and transforming growth factor alpha. Even some nonresponders demonstrated varying degrees of biomarker inhibition. Increased tumor cell apoptosis (TUNEL) occurred in patients with evidence of tumor regression but not in nonresponders (progressive disease). Clinical response was associated with a pretreatment TUNEL score > 0 and increased pretreatment expression of ErbB2, p-ErbB2, Erk1/2, p-Erk1/2, insulin-like growth factor receptor-1, p70 S6 kinase, and transforming growth factor alpha compared with nonresponders. CONCLUSION: Lapatinib exhibited preliminary evidence of biologic and clinical activity in ErbB1 and/or ErbB2-overexpressing tumors. However, the limited sample size of this study and the variability of the biologic endpoints suggest that further work is needed to prioritize biomarkers for disease-directed studies, and underscores the need for improved trial design strategies in early clinical studies of targeted agents.

Adult↗

Clinical implications of microsomal prostaglandin e synthase-1 overexpression in human non-small-cell lung cancer.

BACKGROUND: Microsomal prostaglandin E synthase-1 (mPGES-1) has recently been found to overexpress in human cancers, including non-small-cell lung cancer (NSCLC). However, the clinical value is largely unknown. The aim of this study was to investigate the associations between mPGES-1 expression in NSCLC and the clinical characteristics and survival outcome. METHODS: Between 2001 and 2003, paired fresh tumorous and nontumorous samples were prospectively procured from patients undergoing surgery for NSCLC. The expression of mPGES-1 was assessed by using Western blot in 93 subjects and reverse transcriptase-polymerase chain reaction in 35. Overexpression of mPGES-1 was defined as a more than 2-fold expression in the tumorous sample compared with the corresponding nontumorous one. Immunohistochemistry was used to confirm its localization to the tumor cells. In a subset of 30 cases, cyclooxygenase-2 (COX-2) was also analyzed to assess its association with mPGES-1. RESULTS: The protein and messenger RNA of mPGES-1 were both expressed at higher levels in the tumor samples (P < .001 and P = .006, respectively). The expressions of mPGES-1 and COX-2 were unrelated (P = .715). Overexpression of mPGES-1 protein was observed in 61 (65.6%) of 93 patients, but it was not significantly associated with the clinicopathologic characteristics or overall and disease-free survivals. However, mPGES-1 overexpression seemed to be associated with the likelihood of subsequent pulmonary metastases and a lower tendency for developing bony metastases (P = .001 and P = .006, respectively). CONCLUSIONS: Our results demonstrated that mPGES-1 was overexpressed in NSCLC, unassociated with COX-2. Overexpression of mPGES-1 per se was not a prognostic indicator, but it might be implicated in the organ preference of metastasis.

Adenocarcinoma↗

Local graft irradiation after failure of modern immunosuppression in acute cellular and vascular graft rejection.

PURPOSE: With improved chemical immunosuppressive agents, approximately 90% of rejection episodes can be reversed. However, in situations of failed immunosuppression, graft loss becomes inevitable. Our objective is to assess the efficacy of local graft irradiation (LGI) as an effort of last resort in a contemporary group of patients in whom graft failure to irreversible cellular and vascular rejection is imminent. METHODS AND MATERIALS: A total of 308 renal transplantations were performed at our institution from 1992 to 1995, and an overall 1-year graft survival rate of 90% has been seen as a result of improvement in chemical immunosuppression. However, 6 patients were referred for LGI when all other measures failed to reverse the rejection crisis. Parameters that were studied in these patients included graft function and postirradiation graft histology. RESULTS: Irradiation was associated with reversal of the rejection crisis and resulted in documented histological long-term graft survival in 1 of the 6 patients (17%). Two of the six patients (33%) had reversal of the rejection episode based on postirradiation biopsy of the renal allograft. Three of the six patients showed some level of clinical improvement of graft function for varying periods of time. One patient maintained stable allograft function without deterioration and with continued independence from hemodialysis. One recipient died from sepsis despite histologic improvement after irradiation. CONCLUSIONS: Our impression is that LGI is indicated when all other measures have failed to reverse an acute rejection episode in the transplanted renal allograft. The role of radiation in this setting should be studied further.

Graft Rejection↗

[Repair of the facial tissue defects with reversed narrow pedicle lateral maxillocervical fasciocutaneous flap].

OBJECTIVE: To introduce a method of repairing facial tissue defects caused by various factors. METHODS: The reverse narrow pedicle lateral maxillocervical fasciocutaneous flap was designed with its pedicle located in front of auricle. The size of the flaps ranged from 5 cm x 6 cm to 10 cm x 11 cm. The length and width of the pedicle ranged 2 cm-5 cm and 1 cm-1.5 cm. RESULTS: This fasciocutaneous flap was used in 21 cases. All flaps survived except 1 flap showing distal skin necrosis. CONCLUSION: This fasciocutaneous flap didn't include any major blood vessel. The ratio of the pedicle width to flap length broke that of traditional flap and was reverse transfer. The transposition of the narrow pedicle flap was easy. The postoperative appearance (color, texture, cosmetic aspect) was satisfactory. This method was a new design and was ideal for large facial tissue defect repair.

Adolescent↗

Prospective evaluation of circulating hepatocytes by alpha-fetoprotein messenger RNA in patients with hepatocellular carcinoma.

BACKGROUND: The significance of alpha-fetoprotein (AFP) messenger RNA as a surrogate marker for isolated tumor cells in the blood of patients with hepatocellular carcinoma (HCC) is controversial. Our goals were to correlate AFP mRNA with tumor recurrence and overall survival after patients with HCC received curative operations and to analyze AFP mRNA findings in control patients. METHODS: In this prospective controlled study, RNA was purified from the blood of 85 patients with HCC before, during, and after therapy and from 116 control patients. Complementary DNA synthesis by reverse transcriptase and polymerase chain reaction amplification was performed with primers specifically for the AFP gene. Patients with HCC were divided into 4 subgroups depending on the therapy performed: (1) orthotopic liver transplantation (OLT), (2) resection, (3) transarterial chemoembolization, and (4) no therapy. RESULTS: AFP mRNA was detected in 28% of the patients with HCC and 3% of the control patients (P <.01) before therapy. Of patients with HCC and OLT, 2 of the 6 patients who were AFP mRNA positive had a recurrence; none of the 4 patients who were negative had a recurrence. In the HCC patients who underwent tumor resection or received no therapy, the survival rates did not differ between patients who were AFP mRNA positive and negative (P =.21 and P =.94, respectively). After the tumor resection, no difference in survival at 2 years was evident in patients who were AFP mRNA positive versus those who were AFP mRNA negative. In the HCC patients who had curative operations (OLT and resection) the sensitivity and specificity of this test for tumor recurrence were 73% and 53%, respectively, excluding surgical mortality. The International Union Against Cancer tumor stages in the subgroups of OLT and resection showed no differences between patients with positive and negative findings (P =.76 and P =.15, respectively). AFP mRNA results and serum AFP levels revealed no correlation (P =.45). CONCLUSIONS: The qualitative measurement of AFP mRNA in the blood of patients with HCC is not a clinically relevant method for determining therapy and prognosis, especially if AFP mRNA is detected during the surgical procedure or any other liver manipulation.

Carcinoma, Hepatocellular↗

Developing a long-term surviving piglet model of neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: This study was designed to develop a piglet model of neonatal hypoxic-ischemic encephalopathy, which would allow for serial assessments of long-term neurodevelopmental impairment. METHODS: In 12 newborn piglets, we produced hypoxia by 8% oxygen breathing for 5-91 minutes. We combined ischemia by reversible bilateral common carotid artery occlusion for varying times. Outcome measures were clinical neurological evaluation, magnetic resonance spectroscopy studies and brain histology. RESULTS: Those animals which received intravenous sedation and no mechanical ventilation showed poor tolerance to hypoxia-ischemia and died early in the course of the experiments. The use of inhalation anesthesia during surgical procedures and mechanical ventilation during hypoxia-ischemia was associated with long-term survival. Seven of eight animals that survived > or = 48 hr showed clinical neurological abnormalities, that later resolved. Magnetic resonance spectroscopy measurements did not change significantly following hypoxia-ischemia. None of the animals had histopathological brain lesions. CONCLUSION: When subjected to acute hypoxia-ischemia, piglets were likely to survive only if they were given such supportive measures as anesthesia and mechanical ventilation. Even with hypoxic-ischemic injury sufficient to produce acute signs of neurological dysfunctions, longterm, stable survival with no evident brain histopathological abnormalities was possible.

Animals↗

Examination of regional lymph nodes by sentinel node biopsy and molecular analysis provides new staging facilities in primary cutaneous melanoma.

Histopathologic parameters of the primary tumor, such as Breslow's tumor thickness and Clark's level of invasion are the current basis for prognostic classifications of primary cutaneous melanoma. Once patients develop regional node metastasis, histopathologic features of the primary melanoma no longer contribute significantly to survival prediction. In this tumor stage, the extent of lymph node involvement is the main prognostic factor. This study addresses the question whether application of a highly sensitive molecular biology assay for detection of submicroscopic melanoma cells in sentinel lymph nodes may be suitable to improve melanoma staging. One hundred and sixteen patients with primary cutaneous melanoma with a total of 214 sentinel lymph nodes were enrolled. Sentinel lymph nodes were analyzed by histopathology including immunohistochemistry and by reverse transcription-polymerase chain reaction for tyrosinase. Patients were examined for tumor recurrences during a follow-up period of 19 mo (median). Disease-free survival probabilities were calculated and independent prognostic factors were determined by multivariate analysis. Using histopathology, micrometastatic nodal involvement was detected in 15 patients (13%). Of the 101 patients with histopathologically negative sentinel lymph nodes, 36 were reclassified by positive tyrosinase reverse transcription-polymerase chain reaction and 65 patients were still negative by reverse transcription-polymerase chain reaction. Recurrences were observed in 23 (20%) of 116 patients. These tumor recurrences were demonstrated in 10 patients (67%) with histopathologically positive sentinel lymph nodes, in nine patients (25%) with submicroscopic tumor cells detected by reverse transcription-polymerase chain reaction, and in four patients (6%) negative by both methods. The differences in recurrence rates were statistically significant (p = 0.01). In a multivariate analysis, histopathologic and reverse transcription-polymerase chain reaction status of the sentinel lymph node were demonstrated to be the only significant prognostic factors for predicting disease-free survival. Tyrosinase reverse transcription-polymerase chain reaction for the detection of minimal residual melanoma in sentinel lymph nodes is a powerful tool to determine patients who are at increased risk for subsequent metastasis. Moreover, a group of patients with high tumor thickness was identified by negative reverse transcription-polymerase chain reaction to be at low risk for recurrent disease. These data may have an impact on future tumor classifications of primary cutaneous melanoma.

Adult↗

Application of the model for end-stage liver disease score for transjugular intrahepatic portosystemic shunt in cirrhotic patients with refractory ascites and renal impairment.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) can manage severe complications of portal hypertension. The Mayo Clinic group proposed a so-called model for end-stage liver disease (MELD) to predict survival in cirrhotic patients. High creatinine levels determine a decrease in calculated survival chances with MELD but functional renal disease can be reversed by TIPS. The aim of this study was to evaluate the efficacy of MELD in predicting survival after TIPS, particularly in patients with refractory ascites associated with functional renal failure. METHODS: This retrospective analysis examines 68 cirrhotic patients who underwent elective TIPS: 48 patients had refractory ascites and 20 patients had recurrent variceal bleeding. Multivariate analysis was used to establish predictive parameters of survival after TIPS. Kaplan-Meier and log-rank tests were used to compare survival rates observed in our patients with those evaluated with the MELD score. RESULTS: The age of patients was the only variable shown to have an independent value in predicting survival after TIPS. In patients undergoing shunting for refractory ascites, the survival rates at 6, 12 and 24 months after the procedure were significantly higher than expected with the MELD score. CONCLUSIONS: The MELD scale may underestimate the efficacy of TIPS in end-stage cirrhotic patients with refractory ascites and functional kidney dysfunction. Further studies are needed to confirm this finding and ultimately to assess a correction factor to better predict survival after TIPS in patients with functional renal impairment.

Adult↗

Investigation of sequential mitomycin C and photodynamic therapy in a mitomycin-resistant bladder cancer cell-line model.

OBJECTIVES: To investigate the hypothesis that sequential mitomycin C and 5-aminolaevulinic acid (ALA)-mediated photodynamic therapy (PDT) interact additively in both the J82 bladder cancer cell line and its mitomycin-C-resistant derivative, J82/MMC, and to assess the theoretical basis of this interaction by measuring the relative mitochondrial density of the respective cell lines, on the basis that the mitochondria are the intracellular site where ALA is metabolized to the active photosensitizer, protoporphyrin IX. MATERIALS AND METHODS: Cell survival was assayed in J82 cell line and the J82/MMC derivative after treating them with sequential ALA-mediated PDT and mitomycin C, and with the sequence of treatments reversed. Cell survival was estimated using the tetrazolium assay. The relative mitochondrial density of the two cell lines was estimated using flow cytometry to measure 123rhodamine fluorescence. RESULTS: The effect of sequential mitomycin C followed by ALA-mediated PDT enhanced the effect of PDT in both cell lines. In J82/MMC this effect was marginally supra-additive. When ALA-mediated PDT was administered before mitomycin C, the combined effect was 'sub-additive'. 123Rhodamine fluorescence was > 10 times greater in J82/MMC than J82, suggesting a significantly higher mitochondrial density in the former than the latter. CONCLUSION: Mitomycin C appears to enhance ALA-mediated PDT when administered first. This appears to be particularly so in J82/MMC. This phenomenon may have clinical significance in recurrent superficial bladder cancer.

Aminolevulinic Acid↗

Spironolactone prevents early renal injury in streptozotocin-induced diabetic rats.

BACKGROUND: Glomerular and tubulointerstitial injury leads to chronic impairment of renal function, and thus, reversal of the injury may improve renal function and survival. The present study investigated whether and how mineralocorticoid receptor antagonist spironolactone ameliorates early renal injury in streptozotocin-induced diabetic rats. METHODS: Streptozotocin (65 mg/kg, single intraperitoneal injection)- or vehicle-administered rats were used as diabetic or control rats, respectively. The streptozotocin-administered rats were treated with spironolactone (50 mg/kg/day sc) for 3 weeks. Among the 3 groups of rats, we compared renal fibrosis and renal hypertrophy, using picro-sirius red staining and immunohistochemistry of ED-1 macrophage marker, plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor (TGF)-beta1. RESULTS: Three weeks after administration of streptozotocin, rats exhibited increased collagen deposition in glomerular, tubulointerstitial, and perivascular areas in the kidney, which was completely attenuated by spironolactone treatment. In rats given streptozotocin alone, there were increases in ED-1-positive cell, PAI-1 expression, and TGF-beta1 expression in glomeruli and tubulointerstitiums, which were also suppressed by spironolactone treatment. Maximal glomerular and proximal tubular areas were not significantly different among the 3 groups. Rats given streptozotocin alone revealed an increase in proximal tubule wall-to-lumen ratio that was not influenced by treatment with spironolactone. CONCLUSION: Streptozotocin-induced renal fibrosis, PAI-1 expression, TGF-beta1 expression, and macrophage infiltration occur via mineralocorticoid receptor, and spironolactone ameliorates renal fibrosis presumably via the inhibition of macrophage infiltration, PAI-1 expression, and TGF-beta1 expression in streptozotocin-induced early diabetic injury.

Animals↗

[Repair of multiple fingers degloving injury with abdominal "s"-type skin flap].

OBJECTIVE: To explore a new surgical management of multiple fingers degloving injury. METHODS: In 1994 to 1997, 47 cases with multiple fingers degloving injury were sutured by two reverse "s"-type skin flaps on abdominal flank. RESULTS: The skin flaps in 46 cases survived and the wounds obtained primary heal. CONCLUSION: The application of abdominal flank "s"-type skin flap is reliable and convenient in the treatment of multiple fingers degloving injury.

Adolescent↗

[Effect of benzo[a]pyrene on DNA damage and expression of genes involved in nucleotide excision repair in lung cancer cells].

OBJECTIVE: To investigate the effect of benzo[a] pyrene(BaP) on DNA damage and expression of genes involved in nucleotide excision repair[xeroderma pigmentosum group B, C, G(XPB, XPC, XPG) and excision repair cross-complementing 1 (ERCC1)] in lung cancer A549 cells. METHODS: Cell survival was measured using MIT metabolic viability assay. Single cell gel assay was applied to determine the DNA damage and repair. The level of gene expression was measured by reverse transcription-polymerase chain reaction. RESULTS: The cell survival decreased from 95.0% to 70.0% after 24 h treatment with BaP of varying concentration ranging 0.625-20.000 mumol/L. The cell survival decreased to 87.0% and 73.0% respectively after 12 h and 24 h treatment with 10 mumol/L BaP, with DNA damage gradually elevated. At 12 h after 24 h treatment, the cell survival further decreased to 59.0% and DNA damage became most serious. At 24 h after 24 h treatment, cell survival recovered to 71.0%, and damaged DNA was repaired gradually. XPB and XPC gene expression increased to 4.5-fold and 11.2-fold respectively compared with basal level at 24 h treatment or 12 h after 24 h treatment with 10 mumol/L BaP respectively. However, ERCC1 and XPG gene expression was inhibited in 24 h treatment period, then recovered gradually after treatment. CONCLUSION: Benzo[a]pyrene could lead to DNA damage and expression level change of genes involved in nucleotide excision repair in lung cancer A549 cells.

Benzo(a)pyrene↗

[Identification of the related gene of mouse tolerant to exposure to perfluoroisobutylene by DDRT-PCR].

OBJECTIVE: The mice surviving acute exposure to low dose of perfluoroisobutylene (PFIB) could tolerant to lethal dose of PFIB. Discovering the gene related with the tolerance would be significant to find preventive agents for PFIB. METHODS: By static exposure to PFIB for 3 times, the survival animals could tolerate to lethal dose of PFIB. Three anchoring primers and 4 arbitrary primers were applied in differential display reverse transcription PCR (DDRT-PCR) of lung tissues and the products were analyzed by sequencing PAGE and silver staining. The differential DNA fragments were cloned and sequenced. RESULTS: There were obvious differences of gene expression between control and tolerant animals. Three expressed sequence tags (EST) have been cloned and sequenced,which were homologous to some mouse gene in Genbank. CONCLUSION: Specific gene up-regulation might be the cause of tolerance to PFIB, and they are very important to clarity the tolerant mechanisms to PFIB.

Animals↗

An 18-year retrospective survival study of full crowns with or without posts.

PURPOSE: This study of full crowns investigated long-term survival in relationship to biologic and technical variables. MATERIALS AND METHODS: A total of 1,037 full crowns in 456 patients, made in an undergraduate university clinic, were evaluated over an 18-year period. All patients were offered a supportive maintenance program. Failures of full crowns were classified as irreversible (loss of full crown and/or tooth) or reversible (full crown intact after conservative treatment) complications and as biologic or technical/patient-related failures. RESULTS: The Kaplan-Meier survival rate after 18 years was 78%. No statistically significant differences were found between restorations in the maxilla and mandible (P= .150); between restorations on molars, premolars, and anterior teeth (P = .671); and between restorations on posts and cores compared to restorations without posts and cores (P = .602). For the surviving restorations, the improved plaque score over time was statistically significant (P = .001). Biologic failures (66.4%) resulting in removal were more common than technical and patient-related failures (33.6%). Caries was the most frequent reason for failure (irreversible complication). CONCLUSION: The survival of full crowns made in an undergraduate university clinic during an 18-year period is comparable to the results published by university departments or private practitioners. Plaque scores and bleeding on probing were not directly related to failures. Occurrence of a previously reversible complication is a predicting factor for an irreversible complication. A reversible complication within the first 2 years will probably lead to an early irreversible complication.

Adolescent↗