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Biomedical subjects

G Castellano

Publications and source records attributed to G Castellano.

At least 19 recordsLinked to original sources

Association of pretreatment serum interferon gamma inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C.

BACKGROUND: Increased serum and intrahepatic interferon gamma inducible protein 10 (IP-10) levels in patients with chronic hepatitis C (CHC) have been described. AIM: To analyse the possible association of serum IP-10 levels with different outcomes to antiviral therapy. PATIENTS: A total of 137 CHC patients treated with peginterferon plus ribavirin. METHODS: Serum IP-10 levels were determined by enzyme linked immunosorbent assay before therapy, after 12 weeks of treatment, and 24 weeks after cessation of therapy. Variables significantly associated with a sustained virological response (SVR) on univariate analysis were included in a multivariate logistic regression model. RESULTS: Pretreatment serum IP-10 levels in patients with SVR were significantly lower than in non-responders (NR) (332.4 (222.1) v 476.8 (305.3) pg/ml, respectively; p=0.004). Serum IP-10 concentrations significantly decreased in patients with SVR (pretreatment: 332.4 (222.1) pg/ml; post-treatment: 170.2 (140.1) pg/ml; p<0.001) but not in NR (pretreatment: 476.8 (305.3) pg/ml; post treatment: 387.3 (268.1) pg/ml; p=0.06). By multivariate analysis, non-1 genotype (odds ratio (OR) 3.5 (95% confidence interval (CI) 1.1-10.4); p=0.003) and low viral load at baseline (OR 0.34 (95% CI 0.14-0.79); p=0.01) were independent predictors of SVR in all patients. When multivariate analysis was restricted to patients with genotype 1, only baseline viral load (OR 0.38 (95% CI 0.155-0.96); p=0.04) and pretreatment serum IP-10 levels (OR 0.99 (95% CI 0.996-0.999); p=0.03) were identified as predictive factors of SVR. CONCLUSION: Pretreatment serum IP-10 behaves as a predictive factor of SVR to peginterferon plus ribavirin therapy in genotype 1 infected patients.

Adult↗

Texture analysis of medical images.

The analysis of texture parameters is a useful way of increasing the information obtainable from medical images. It is an ongoing field of research, with applications ranging from the segmentation of specific anatomical structures and the detection of lesions, to differentiation between pathological and healthy tissue in different organs. Texture analysis uses radiological images obtained in routine diagnostic practice, but involves an ensemble of mathematical computations performed with the data contained within the images. In this article we clarify the principles of texture analysis and give examples of its applications, reviewing studies of the technique.

Algorithms↗

Higher proliferative capacity of T lymphocytes from patients with Crohn disease than from ulcerative colitis is disclosed by use of Herpesvirus saimiri-transformed T-cell lines.

BACKGROUND: T lymphocytes play a crucial role in the pathogenesis of inflammatory bowel disease. Achieving stable T-cell lines, rather than continuous bleeding of patients, is desirable in order to dissect their implication in the disease. METHODS: Long-lasting T-cell lines from patients with Crohn disease and ulcerative colitis and from healthy volunteers have been obtained by transformation of T lymphocytes using the lymphotropic Herpesvirus saimiri. Lines were subjected to phenotypic and functional analyses, and the results compared with freshly isolated peripheral blood mononuclear cells. RESULTS: Fresh cells revealed only minor differences between patients and controls, with regard to phenotype and proliferative capacity. In contrast, the use of T-cell lines showed that cells from Crohn disease patients, but not ulcerative colitis patients, over-responded to several membrane or cytoplasmic stimuli when compared to control T-cell lines. Thus, higher responses were found when stimulated with alphaCD3 and IL2, alphaCD3 and alphaCD28, IL2 alone, phorbol esters (PMA) and alphaCD3 and, finally, PMA and alphaCD2 (P < 0.05 in all instances). Further, lines from patients with Crohn disease responded more vigorously to alphaCD3 and alphaCD28 or alphaCD3 and PMA when compared to ulcerative colitis (P < 0.05 in both instances). CONCLUSIONS: The data obtained with these lines suggest that T cells from patients with Crohn disease differ in vivo in their proliferative capacity, as compared with those from ulcerative colitis patients, a finding that may reflect the clear Th-1 phenotype found in the former and absent in the latter.

Adult↗

Porphyria cutanea tarda as a predictor of poor response to interferon alfa therapy in chronic hepatitis C.

BACKGROUND: Porphyria cutanea tarda (PCT) is sometimes associated with hepatitis C virus chronic infection. The aim of this study was to describe the effect of interferon alfa (IFN-alpha) in the treatment of patients with chronic hepatitis C and PCT. METHODS: We treated a total of 66 patients with chronic hepatitis C with IFN-alpha 2b (5 MU t.i.w.) for 12 months. Twenty-two of these patients suffered from PCT as well. These patients differed from patients without PCT in that they were men, past history of alcohol abuse and HFE gene mutations were more common and the source of infection was almost always unknown. RESULTS: Sustained virologic response was obtained in 19.7% of the 66 treated patients, 27.3% in the non-PCT group and 4.5% in the PCT group (P < 0.05). This difference could not be ascribed to the difference in sex of patients, history of alcohol abuse, HCV genotype or iron status. CONCLUSION: Multivariate logistic regression analysis revealed that PCT is independently and significantly associated with non-sustained response to IFNalpha therapy. In conclusion, patients with chronic hepatitis C and PCT rarely responded to IFNalpha treatment.

Adult↗

[Celiac disease and Bud-Chiari syndrome: an uncommon association].

Celiac disease can present great clinical heterogeneity. Its association with a series of intestinal and non-intestinal diseases, whether immunologically mediated or otherwise, presents a higher than normal frequency. We present a patient with celiac disease and Budd-Chiari syndrome of unknown cause. This association has previously been described only in isolated cases in northern Africa. The appearance of this case in Spain reveals that the coexistence of both processes in a single patient is unlikely to be due to environmental or geographical factors.

Adolescent↗

Influence of remote substituents on the equatorial/axial selectivity in the monooxygenation of methylene C--H bonds of substituted cyclohexanes.

The reactivity of individual C--H bonds in the methyl(trifluoromethyl)dioxirane TFDO oxygenation of stereogenic methylene groups in conformationally homogeneous monosubstituted cyclohexanes (2) has been determined. The unexpectedly high occurrence of O-atom insertion into C--H(ax) bonds suggests an in plane trajectory attack in the oxygenation while the diastereoselectivity of the reaction is qualitatively interpreted on the basis of the distinct hyperconjugative stabilization by the substituent of diastereomeric transition states due to long-range through bond interactions.

Journal Article↗

pH-dependent modulation of relaxivity and luminescence in macrocyclic gadolinium and europium complexes based on reversible intramolecular sulfonamide ligation.

A series of macrocyclic Eu, Gd, and Tb complexes has been prepared in which the intramolecular ligation of a beta-arylsulfonamide nitrogen is rendered pH-dependent, giving rise to changes in the hydration state, q, at the lanthanide center. In complexes based on DO3A, variation of the p-substituent in the arylsulfonamide moiety determines the apparent protonation constant log K(MLH) with values of 5.7, 6.4, and 6.7 for the -CF(3), -Me, and -OMe substituents, respectively. Introduction of three beta-carboxyalkyl substituents, alpha to three ring nitrogens, inhibits displacement of the bound water by added protein and also suppresses intermolecular binding by endogenous anions (lactate, HCO(3)(-)). Measurements of the pH dependence of the form and intensity of the Eu complexes revealed that intramolecular carboxylate coordination occurred competitively. This was reduced either by enhancing the electron density at the sulfonamide nitrogen or by enlarging the chelate ring from 7--8. Amplification of the relaxivity changes in the pH range 8--5 occurred on protein binding, and over the pH range 7.4--6.8 a 48% change in relaxivity was defined for [Gd.3a] (298 K, 65.6 MHz) in 50% human serum solution.

Journal Article↗

Choosing new adsorbents for endogenous ultrapure infusion fluid: performances, safety and flow distribution.

Adsorption may notably contribute to the removal of uremic toxins and to the efficiency of hemodialysis. We examined different uncoated stationary matrixes, charcoals and synthetic resins to establish their adsorptive capacities in relation to low (urea, creatinine) and high molecular weight (beta2-microglobulin, myoglobin) compounds in in vitro conditions (steady state and flow-through) using isotonic solutions or uremic ultrafiltrate. Trace metal, particle release analyses and scanning electron microscopy of different adsorbents were performed. Dynamic flow-distribution studies were made using 99Technetium and analysing the different regions of interest by single head gamma-camera. We show that adsorbents may differ greatly as to their adsorptive capacity depending on flow rate, nature, and total mass of the compounds to be removed from the ultrafiltrate. These studies suggest a methodological approach for screening stationary matrixes for possible application in hemodialysis.

Adsorption↗

Hyperconjugative Control by Remote Substituents of Diastereoselectivity in the Oxygenation of Hydrocarbons.

The oxidation of 2-substituted adamantanes (2) with TFDO (1) is reported. The data show a stereodifferentiation of the chemical environments induced by remote electron-withdrawing substituents which produces remarkable Z/E diastereoselectivity in the oxidation of the tertiary C(5)-H and C(7)-H bonds. The results show a bell-shaped correlation between the Z/E stereoselectivity and the substituent constant sigma(I), which is interpreted in terms of hyperconjugative stabilization of the diastereomeric transition states.

Journal Article↗

Simultaneous determination of hydrocortisone, dexamethasone, indomethacin, phenylbutazone and oxyphenbutazone in equine serum by high-performance liquid chromatography.

Ethyl acetate extracts of equine serum, containing 0-5 microg/ml of hydrocortisone (HYD), dexamethasone (DEX), oxyphenbutazone (OPB), indomethacin (IND), phenylbutazone (PB) and probenecid as internal standard, were evaporated with nitrogen, resuspended in methanol and analyzed by HPLC, using a C-18 column equilibrated with 51:49 acetonitrile-water, 0.1% trifluoroacetic acid, at 1 ml/min. The eluate was monitored at 254 nm. The selectivity (inter-assay C.V.<4%), sensitivity (limits of quantitation of 0.25 microg/ml for HYD, DEX and IND, 0.5 microg/ml for PB and 1 microg/ml for OPB, despite the occurrence of significant degradation of OPB and PB during the analysis) and precision (intra-assay and inter-assay C.V.'s of about 3-6 and 9-15%, respectively) of the method appeared appropriate for anti-doping control of racehorses.

Animals↗

Decreased bone mineral density after therapy with alpha interferon in combination with ribavirin for chronic hepatitis C.

BACKGROUND/AIMS: Several thousand patients with chronic hepatitis C have been treated with interferon plus ribavirin. After observing a male patient who developed severe bone loss during this treatment, we studied skeletal status and bone mineral metabolism in patients on therapy with interferon plus ribavirin. METHODS: Bone mineral density and biochemical bone markers were studied in 32 male patients (31-58 years old) treated for 12 months with either interferon alone (group 1; n=13) or interferon plus ribavirin (group 2; n= 19). RESULTS: Bone mineral density was significantly lower in group 2 (0.877-0.07 g/cm2) than in group 1 (1.108+/-0.08 g/cm2, p<0.001). Likewise, T- and Z-score values were also decreased in group 2 (T: -1.95+/-0.6. Z: -1.76+/-0.51) compared with group 1 (T: 0.19+/-0.6; p<0.001. Z: 0.26+/-0.6; p<0.001). Serum and urine biochemical bone markers were normal in both groups. However, urinary calcium excretion was decreased in patients on combined therapy. CONCLUSION: Treatment of chronic hepatitis C with interferon plus ribavirin may induce bone loss. This secondary effect should be investigated during the follow-up of these patients, since they may require therapies aimed at prevention or amelioration of these defects.

Bone Density↗

Painful supernumerary phantom arm following motor cortex stimulation for central poststroke pain. Case report.

In this report, the authors describe a case in which the patient began to experience a supernumerary phantom arm after she received motor cortex stimulation for central pain. The patient had a history of right thalamocapsular stroke. It is speculated that the motor cortex activation triggered a response in the patient's parietal lobe, precipitating perception of the phantom limb. To the authors' knowledge this is the first reported case of its kind.

Cerebrovascular Disorders↗

G proteins are involved in the suppression of collagen alpha 1 (I) gene expression in cultured rat hepatic stellate cells.

We analyse the role of the G proteins in regulating collagen gene expression by measuring collagen alpha 1(I) mRNA levels in cultured hepatic stellate cells in basal conditions and after stimulating or inhibiting the major intracellular signalling pathways. Stimulation of Gs protein and adenylyl cyclase or the addition of 8Br-cAMP to the cells led to a decrease in collagen alpha 1(I) mRNA levels, while blocking protein kinase A abolished this effect. Blocking Gi protein, phospholipase A2 and C, calcium channels and calmodulin resulted in a significant increase in collagen mRNA levels. PKC stimulation led to a marked decrease in these levels. These results suggest that collagen gene expression is inhibited by a number of intracellular pathways. A Gs and a pertussis toxin-sensitive G protein seem to initiate cellular response. Transcription factors, acting in these pathways, must be identified. However, it seems that they do not need to be synthesised.

Adenylyl Cyclases↗

Lipoprotein changes in patients with chronic hepatitis C treated with interferon-alpha.

OBJECTIVE: The aim of this study was to evaluate the effects of interferon-alpha therapy on the lipid profile of patients with chronic hepatitis C. METHODS: In 36 consecutive patients with chronic hepatitis C, fasting lipoproteins were evaluated prospectively at baseline, 1, 3 and 6 months during interferon-alpha therapy and 3 months after the end of treatment. RESULTS: During interferon-alpha therapy, there was a progressive increase in total and very low density lipoprotein (VLDL)-triglycerides, VLDL-cholesterol and a sustained raise in apolipoprotein (apo) B. In parallel, there was a reduction in high density lipoprotein (HDL)-cholesterol and apo A1 levels. In contrast, total and low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels remained essentially unchanged during interferon-alpha therapy. Three patients developed chylomicronemia, two of them with severe hypertriglyceridemia, although none of them presented with pancreatitis. Chylomicronemia and severe hypertriglyceridemia were more common in patients with basal triglycerides above 200 mg/dl. Nineteen patients responded to interferon-alpha therapy, but their lipid profile did nor differ from that of nonresponders. Three months after the end of interferon-alpha therapy lipid changes subsided, although VLDL and HDL-cholesterol and apo B did not reach basal levels. CONCLUSION: In patients with chronic hepatitis C, interferon-alpha therapy is associated with an increase of total and VLDL-triglycerides, VLDL-cholesterol and apo B, and a decline of HDL-cholesterol and apo A1. The development of chylomicronemia and severe hypertriglyceridemia in some cases makes mandatory a close monitoring of triglycerides during interferon-alpha therapy, particularly among patients with increased triglycerides at baseline.

Adult↗