Correlation between the retinal nerve fiber layer thickness and the pattern electroretinogram amplitude

OBJECTIVE: To establish a correlation between the retinal nerve fiber layer (RNFL) thickness measured by a scanning laser polarimeter (GDx) and the pattern electroretinogram (p-ERG) amplitudes in a heterogeneous population sample composed of normal subjects, ocular hypertensive and glaucomatous patients. METHODS: 112 subjects were considered: 40 glaucomatous patients, 39 ocular hypertensive and 33 normal subjects. All were examined with the GDx, and the RNFL thickness was measured. A transient p-ERG was then recorded. RESULTS: A statistically significant correlation was observed between the RNFL thickness and the p-ERG amplitudes (p < 0.001) by means of linear regression analysis. CONCLUSION: We observed a strict correlation between the measurements of the RNFL thickness obtained with the GDx and the amplitude of the p-ERG signal. These techniques represent additional objective tools to detect an early glaucomatous damage.     

Biochemical and toxicological evaluation of agent-cofactor reactivity as a mechanism of action for osteolathyrism

In vitro reactivity for each of four osteolathyrogens with a model compound for the lysyl oxidase (LO) cofactor was evaluated and coupled with mixture toxicity testing to evaluate agent-cofactor reactivity as a potential mechanism of action for osteolathyrism. Reactivity of the model cofactor (mLTQ: 4-butylamino-5-methyl-o-quinone), with each of two ureides, semicarbazide (SC) and thiosemicarbazide (TSC), and each of two aminonitriles, aminoacetonitrile (AAN) and beta-aminopropionitrile (betaAPN), was assessed using UV-vis spectrophotometry; both in the absence and presence of Cu(II)-bipyridine (bipy) complex. Two sets of mixture toxicity experiments were conducted using a frog embryo assay that assessed the incidence of osteolathyrism in the notochord of tadpoles after 96-h exposure. The resulting concentration-response curves for each set were evaluated (chi(2) goodness-of-fit test) against theoretical curves for two combined effects models: dose-addition and independence, to determine the combined effect of each osteolathyrogen combination. The agents SC, TSC and AAN each showed rapid, irreversible reactivity with mLTQ, both in the absence and presence of Cu(II)-bipy complex, as indicated by bleaching of the mLTQ peak (504 nm) and formation of an adduct at 350 nm. betaAPN showed no apparent reactivity in the absence of prolonged incubation with mLTQ, whether Cu(II)-bipy complex was present or not. After prolonged incubation (24-144 h) a new peak formed at 350 nm, suggesting that betaAPN reacts weakly with the cofactor, but in a manner different from the other agents examined. The toxicity tests indicated a dose-additive combined effect for the SC:TSC, AAN:SC and AAN:SC:TSC mixtures (0.1相似文献   

A statistical method for the determination of absorption rate constant estimated using the rat single pass intestinal perfusion model and multiple linear regression

The guide "Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Dosage Forms Containing Certain Active Moieties/Active Ingredients Based on a Biopharmaceutical Classification System" (Rockville, MD: CDER, 2000) outlined non-in vivo tests of permeability that may satisfy the classification of a compound in the biopharmaceutical classification system. However, absent from that document were specific statistical methods to legitimatize the non-in vivo tests. This report describes the appropriate statistical treatment of absorption data, and recommends its adoption in the estimation of absorption and/or permeability measurements. The calculation of the absorption rate constants (k(a)) of ten compounds by a new multiple linear regression (MLR) method was completed after the separate perfusion of each compound through the rat single pass intestinal perfusion model (n = 3 rats per compound). Studentized residuals were evaluated to determine whether any statistically significant outliers were present in the data. The standard error of k(a) was estimated using variance components from the random effects model. The results were compared with the "traditional method" for k(a) calculations. Although both methods produced similar values of k(a), the MLR method's error estimate included multiple components of variability, which was largely ignored by the traditional method. The MLR method provided objective tests for outliers and achievement of steady-state. A preferred method for the statistical analysis of absorption data was demonstrated. These methods should be applied to all forms of permeability measurements, especially the non-in vivo measurements that classify a compound in the biopharmaceutical classification system.     

Evidence that stunning can be cumulative in man

Myocardial stunning and hibernation are two entities that have become increasingly recognised as clinically important causes of reversible left ventricular (LV) dysfunction. Their occurrence is important as resting myocardial dysfunction, which was once thought to be irreversible, may recover if ischaemia is lessened or abolished. Recent evidence has suggested that cumulative stunning can occur in man and may in fact be responsible for the phenomenon of hibernation. In this chapter we will review the evidence supporting the occurrence of cumulative stunning in man.     

Subjective experiences in schizophrenia and bipolar disorders

Studies comparing 'subjective experiences' in schizophrenic and affective disorders have reached inconclusive results. We investigated the pattern of 'subjective perceived cognitive disturbances' in a group of 55 schizophrenic patients and 39 bipolar patients hospitalized for an index psychotic episode. The assessment of the subjective experiences was made using the Frankfurter Beschwerde-Fragebogen (FBF). Comparing the two groups on the four FBF factors, schizophrenic patients showed significantly higher scores in the areas of 'central cognitive disturbances', 'perception and motility' other than a significantly higher FBF total score. Our results suggest that cognitive, perception and motility disturbances are the most characteristic subjective experiences of schizophrenic patients in comparison with bipolar patients. This finding need to be further explored in light of the issue of cognitive dysfunction in schizophrenia.     

Phase I trial of gemcitabine,administered as a standard and constant dose-rate infusion,in combination with paclitaxel in patients with advanced solid tumors (LOA-2)

The major purposes of this study were to determine the maximally tolerated dose (MTD), dose-limiting toxicity (DLT), toxicity profile, and antitumor activity of gemcitabine and paclitaxel combination therapy when administered to patients with advanced solid tumors, using two infusion schedules of each agent. Paclitaxel was administered on day 1, followed by gemcitabine, and gemcitabine alone was administered on day 8, of each 21-day treatment course. In the initial phase of the trial, paclitaxel was administered during 3 hours and gemcitabine during 30 minutes (schedule A). After the MTD was determined on this schedule, patients were then treated with paclitaxel during 1 hour and gemcitabine at a fixed dose-rate of 10 mg/m(2)/min (schedule B). Forty-six patients were treated with 176 courses at 7 dose levels. The MTD for schedule A was 1,300 mg/m(2) and 200 mg/m(2) and for schedule B was 1,000 mg/m(2) and 200 mg/m(2) for gemcitabine and paclitaxel, respectively. The DLT for schedule A was neutropenia and for schedule B was neutropenia and thrombocytopenia. Nonhematologic toxicity was relatively mild. Gemcitabine and paclitaxel, using both schedules of administration in the current trial, is a promising chemotherapeutic regimen.     

Association of a common polymorphism in the human GH1 gene with colorectal neoplasia

BACKGROUND: Growth hormone (GH) may be associated with the development of colorectal tumors directly and/or indirectly via an increased plasma level of insulin-like growth factor-I (IGF-I), which has been associated with colorectal cancer risk. Because a T-to-A polymorphism in the human GH1 gene at position 1663 is putatively associated with lower levels of GH and IGF-I, we investigated the relationship of this polymorphism to the risk of colorectal neoplasia. METHODS: We analyzed data from two case-control studies conducted in Hawaii: a population-based study of 535 case patients with colorectal adenocarcinoma and 650 control subjects and a sigmoidoscopy screening-based study with 139 case patients with adenoma and 202 control subjects. All subjects were tested for the GH1 polymorphism. Logistic regression was used to adjust for known risk factors. Plasma IGF-I and IGF binding protein-3 (IGFBP-3) levels were measured in a subset of 293 subjects in the adenoma study (135 case patients and 158 control subjects). All statistical tests were two-sided. RESULTS: Adjusted odds ratios (ORs) for colorectal cancer associated with T/T, T/A, and A/A genotypes were 1.00, 0.75 (95% confidence interval [CI] = 0.58 to 0.99), and 0.62 (95% CI = 0.43 to 0.90), respectively (P(trend) =.006). Adjusted ORs for adenoma were 1.00, 0.76 (95% CI = 0.46 to 1.24), and 0.62 (95% CI = 0.31 to 1.22), respectively (P(trend) =.17). Data from both studies consistently showed that the A allele was associated with a lower risk of colorectal neoplasia than the T allele, although the association with adenoma was not statistically significant. These associations were consistently suggested in Caucasians and Native Hawaiians but not in Japanese. The ratio of plasma IGF-I/IGFBP-3 was lower in individuals with the A allele than in individuals with the T allele (P =.01). CONCLUSION: The human T1663A GH1 gene polymorphism, which may confer lower levels of GH and IGF-I, appears to be associated with a decreased risk of colorectal cancer.     

Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease

CONTEXT: A large body of experimental evidence suggests that in Alzheimer disease (AD) pathogenesis an important role is played by oxidative stress, but there is still a lack of data on in vivo markers of free radical-induced damage. OBJECTIVES: To evaluate levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative damage to DNA, in peripheral lymphocytes; to measure plasma concentrations of several nonenzymatic antioxidants; and to assess the relationships between any observed changes in lymphocyte DNA 8-OHdG content and plasma antioxidant levels in patients with AD and healthy aged control subjects. SUBJECTS: Forty elderly outpatients with AD and 39 healthy age- and sex-matched controls were studied. MAIN OUTCOME MEASURES: The level of 8-OHdG was determined in DNA extracted from lymphocytes and plasma levels of vitamin C, vitamin A, vitamin E, and carotenoids (zeaxanthin, beta-cryptoxanthin, lycopene, lutein, and alpha- and beta-carotene) were measured by high-performance liquid chromatography. RESULTS: Lymphocyte DNA 8-OHdG content was significantly higher and plasma levels of antioxidants (with the exception of lutein) were significantly lower in patients with AD compared with controls. In patients with AD, a significant inverse relationship between lymphocyte DNA 8-OHdG content and plasma levels of lycopene, lutein, alpha-carotene, and beta-carotene, respectively, was observed. CONCLUSIONS: Markers of oxidative damage are increased in AD and correlate with decreased levels of plasma antioxidants. These findings suggest that lymphocyte DNA 8-OHdG content in patients with AD reflects a condition of increased oxidative stress related to a poor antioxidant status.     

Treatment of left-sided prosthetic valve thrombosis: thrombolysis or surgery?

Although, traditionally, surgery has been the treatment of choice for left-sided prosthetic valve thrombosis (PVT), there are significant risks associated with re-do surgery. Thrombolysis is an alternative to surgery and has a success rate in excess of 80%, but is associated with an -10% risk of systemic embolism and a 7% mortality rate. Guidelines for the use of thrombolytic therapy for PVT were produced using data acquired from older valves, and largely without the use of transesophageal echocardiography (TEE). Data from more recent studies suggest that thrombolysis should be regarded as first-line therapy for PVT in all NYHA classes. The use of TEE is recommended to visualize thrombus in suspected cases.