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Biomedical subjects

V Vargas

Publications and source records attributed to V Vargas.

At least 55 records · Page 3Linked to original sources

[Hepatocarcinoma and killer cell activity].

BACKGROUND: Alterations in natural killer (NK) cell activity have been described in patients with different neoplasms including hepatocellular carcinoma (HCC). Nonetheless, the relationship between this activity and the clinical situation of the patients with HCC is not well established. METHODS: A group of 33 patients with hepatic cirrhosis and non treated HCC, a group of 22 patients with only hepatic cirrhosis, and a control group of 31 healthy blood donors were studied. In all the subjects the NK cell activity was determined against the K562 cell line marked with 51Cr by the short duration cytotoxicity test, and the number of NK cells/microliters in peripheral blood was determined by flow cytometry (FACScan) using the anti-CD3, CD16 and CD56 monoclonal antibodies. RESULTS: No statistically significant differences were observed in the NK cell activity or in the number of NK cells/microliters among the three groups studied. In the patients with HCC the NK cell activity was not related to the degree of hepatic function, however the patients with tumors greater than 5 cm in diameter or multinodular tumors showed a significant decrease in NK cell activity without a decrease in the number of NK cells/microliters. CONCLUSIONS: The natural killer cell activity in patients with hepatocellular cancer is not related to subjacent hepatic cirrhosis but is related to tumor size.

Aged↗

Stimulation of creatine kinase activity in rat skeletal tissue in vivo and in vitro by protease-resistant variants of parathyroid hormone fragments.

We have reported that mid-region fragments of human parathyroid hormone (hPTH), exemplified by hPTH-(28-48), stimulated [3H]thymidine incorporation into DNA and increased the specific activity of the brain-type isoenzyme of creatine kinase (CK) in both skeletal-derived cell cultures (ROS 17/2.8 cells) and immature rat epiphyseal cartilage and diaphyseal bone, without stimulating cyclic AMP synthesis which is a prerequisite for bone resorption. In the present study, substitution of amino acids in hPTH-(28-48), which resulted in increased resistance to proteolysis, produced variants that stimulated skeletal systems at two orders of magnitude lower concentration than the wild-type fragment. We modified hPTH-(28-48) at Leu-37 by replacement with Met, Thr or Val. Under conditions in which 20% of the native hPTH-(28-48) resisted proteolysis by cathepsin D for 6 h, approx. 40% of the L37V mutant and 70% of the L37T mutant remained intact. Substitution of Met for Phe-34 in addition to Thr for Leu-37, or the substitution of Met for Phe-34 alone, produced 100%-resistant fragments. These variants at residue 34 caused maximal stimulation of CK in ROS 17/2.8 cells at 0.24 nM compared with 24 nM for hPTH-(28-48). The double mutant stimulated CK activity significantly in immature rats, at a minimum dose of 12.5 ng/rat, and caused maximal stimulation at 125 ng/rat, a 10-fold lower dose than for hPTH-(28-48). The effect of the double mutant lasted up to 24 h which differs from the stimulation by hPTH-(28-48) in which CK specific activity returns to the control level at 24 h. This same dose also significantly stimulated CK activity in gonadectomized rats. These results show the advantage of using protease-resistant mid-region variants of hPTH-(28-48) to stimulate bone cells, in terms of lower doses and longer duration of effectiveness, both in vitro and in vivo.

Amino Acid Sequence↗

Long interval between HCV infection and development of hepatocellular carcinoma.

A high prevalence of HCV infection has been reported in patients with hepatocellular carcinoma. The progression from acute transfusion-associated hepatitis to hepatic cirrhosis and hepatocellular carcinoma has been suggested in several studies to be very long. We have investigated the prevalence of anti-HCV and the interval between HCV infection and hepatocellular carcinoma among 191 consecutive patients with cirrhosis and liver-cell carcinoma. Serum samples from 191 patients with cirrhosis and hepatocellular carcinoma, consecutively diagnosed in our hospital between 1988 and 1993, were tested for serological markers of HBV and HCV infection. One hundred and forty-eight patients (77.5%; 95% confidence interval (c.i): 76% to 80%) were anti-HCV positive by 2nd generation enzyme immunoassay (confirmed by 2nd generation recombinant immunoblot assay) and 152 patients (79.5%; 95% c.i: 76% to 80%) were anti-HCV positive by 3rd generation enzyme immunoassay, while only 14 (7.4%; 95% c.i: 5% to 10%) were HBsAg positive. Of the 29 anti-HCV positive patients with previous transfusion, the interval between the date of blood transfusion and the diagnosis of hepatic cirrhosis was 24 +/- 12.5 years and that of hepatocellular carcinoma was 26.8 +/- 12.4 years. These results confirm the high prevalence of HCV infection in patients with hepatocellular carcinoma and the slow sequential progression from HCV infection through cirrhosis and hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Two different dosages of cefotaxime in the treatment of spontaneous bacterial peritonitis in cirrhosis: results of a prospective, randomized, multicenter study.

Cefotaxime (CTX) is considered one of the first-choice antibiotics in the therapy of spontaneous bacterial peritonitis (SBP) in cirrhosis. Because CTX is largely metabolized in the liver, this drug may also be effective in SBP by administering lower doses than those habitually used. To investigate this possibility, a prospective, randomized, multicenter study was performed to compare the therapeutic efficacy of two different dosages of CTX in 143 patients with SBP: 71 (group I) were allocated to receive a high dose (2 g every 6 hours, which is one of the most frequently recommended doses in this infection), and 72 (group II) were allocated to receive a low dose (2 g every 12 hours). At inclusion, both groups were similar in relation to clinical and laboratory data, with the exception of a higher incidence of positive ascitic fluid culture in group I than in group II (59% vs. 40%; P = .029). The rate of infection resolution was similar for both groups (77% vs. 79%). Hospital survival was also similar in both groups (69% vs. 79%). No difference was observed between patients with positive or negative ascitic fluid cultures with regard to infection resolution and patient survival. The duration of antibiotic therapy was similar in both groups (9.0 +/- 3.3 days in group I vs. 8.8 +/- 3.1 days in group II). In a subset of 13 patients from group I and 11 patients from group II CTX levels were determined in serum (peak and trough) and ascitic fluid (concomitantly with trough serum). Peak serum levels were similar in patients from both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Changes in protein repletion markers in undernourished patients receiving enteral nutrition and its relation with energy and nitrogen balance].

AIM: To study the relationship between the changes in protein repletion indicators and calorie and nitrogen balance in undernourished patients receiving enteral nutrition. PATIENTS AND METHODS: Fourteen patients (11 female, age range 55-85 years old) with an initial serum albumin below 3.5 g/dl or serum transferrin below 200 mg/dl, which received enteral nutrition, were studied. On days one and ten of nutritional support, indirect calorimetry, nitrogen balance and serum levels of albumin, transferrin, pre-albumin and total lymphocyte count were measured. RESULTS: Initial resting energy expenditure was 25.1 +/- 5 Kcal/kg/day (115.4 +/- 20% of that predicted by Harris Benedict equations) and urinary urea nitrogen 5.4 +/- 3.7 g/day. Initial and final nitrogen balances were 66.9 +/- 71 and 81.4 +/- 105.9 mg N/kg/day and mean energy balance throughout the study was +9.0 +/- 7.2 Kcal/kg/day. During the ten days of nutritional support, albumin improved significantly in 0.35 +/- 0.43 g/dl (15.2 +/- 19.8%). Transferrin, pre-albumin and total lymphocyte count did not change significantly. The changes in these last parameters did not correlate with nitrogen or calorie balance. CONCLUSIONS: Probably other factors, besides nutritional balances, influence serum protein levels and these may not change despite an adequate nutritional repletion.

Aged↗

Hydrodynamics of horseradish peroxidase revealed by global analysis of multiple fluorescence probes.

Previous fluorescence studies of horseradish peroxidase conjugated with protoporphyrin IX suggested that the protein behaved hydrodynamically as a prolate ellipsoid of axial ratio 3 to 1. The present study, designed to further investigate the hydrodynamics of this protein, exploits a series of probes, noncovalently bound to the heme binding site of apo-horseradish peroxidase, having different orientations of the excitation and emission transition dipoles with respect to the protein's rotational axes. The probes utilized included protoporphyrin IX and the naphthalene probes 1-anilino-8-naphthalene sulfonate, 2-p-toluidinyl-6-naphthalene sulfonate, and 4,4'-bis(1-anilino-8-naphthalene sulfonate). Time-resolved data were obtained using multifrequency phase fluorometry. The global analysis approach to the determination of molecular shape using multiple probes was evaluated by utilizing all data sets while maintaining a constant molecular shape for the protein. The results indicated that, in such analyses, probes exhibiting a single exponential decay and limited local motion have the major weight in the evaluation of the axial ratio. Probes that show complex decay patterns and local motions, such as the naphthalene derivatives, give rise to significant uncertainties in such global treatments. By explicitly accounting for the effect of such local motion, however, the shape of the protein can be reliably recovered.

Binding Sites↗

Incidence and outcome of hepatitis C virus infection after liver transplantation.

The objective of this study was to determine the incidence and outcome of hepatitis C virus (HCV) infection after liver transplantation (OLT). Fifty-two transplanted patients were studied. Serum samples were examined for antibodies to HCV (anti-HCV) and HCV-RNA by PCR, before and after OLT. Patients were distributed into two groups: group 1 consisted of 24 patients (pretransplant anti-HCV positive) and group 2 consisted of 28 patients (pretransplant anti-HCV negative). One year after OLT, HCV-infected patients were evaluated by liver biopsy. HCV-RNA was detected in 28 of the 52 (53.9%) patients after OLT. Twenty-two patients in group 1 (96%) were reinfected. In group 2, acquired HCV infection was detected in six (21.4%) patients. At 6 and 12 months, one and five of six patients had seroconverted, respectively. Liver biopsy in 23 HCV-infected patients showed chronic hepatitis in 18 (78%) cases (2, chronic persistent hepatitis; 3, chronic lobular hepatitis and 13, chronic active hepatitis). Fourteen of the 23 (60.8%) patients were asymptomatic. Most symptomatic patients had chronic hepatitis with cholestasis. Overall, 18 of 20 cases of chronic hepatitis diagnosed in OLT recipients were HCV related. Mortality beyond 6 months after OLT was slightly higher in the HCV-infected group (P = 0.055). In conclusion, HCV reinfection is almost universal. Acquired HCV infection post-OLT is frequent. HCV-infected patients frequently develop chronic hepatitis. Most chronic hepatitis after transplantation are HCV related.

Adult↗

Dynamic behavior of hepatitis C virus quasispecies in patients undergoing orthotopic liver transplantation.

We have studied the distribution of viral sequences from the 5' noncoding region and from a fragment of the E2/NS2 region of the hepatitis C virus (HCV) genome in samples obtained before and after liver transplantation in two patients with HCV cirrhosis. The population of viral sequences in both regions were established by sequencing cloned PCR products. In both cases, the complexity of the viral quasispecies decreased after transplantation, although the consensus nucleotide and amino acid sequences remained unchanged. It is suggested that both positive and negative selection and random sampling events contribute substantially in shaping the genetic composition of HCV quasispecies and that recurrence of HCV infection may occur under equilibrium conditions.

Amino Acid Sequence↗

[Cystic hygroma. Antenatal diagnosis and clinical management].

Nine cases of cystic hygroma in pregnancy diagnostic by ultrasound are presented. Chromosomal abnormalities accompany in 7 cases occurred, with, great frequency of "Turner Syndrome". The prognostic of this congenital malformation, has relation with the chromosomopaty and the difference between septal and nonseptated cystic hygroma.

Adolescent↗

[Hepatocellular carcinoma: clinical aspects, diagnosis, and survival in 140 cases].

BACKGROUND: Hepatocellular carcinoma (HCC) constitutes a frequent clinical problem in the follow up of patients with liver cirrhosis. The clinical features and diagnoses and survival in a group of 140 cases of HCC are reviewed. METHODS: All the clinical histories of the patients diagnosed of HCC between 1987 and 1991 in the Unit of Hepatology of the General Hospital of the Vall d'Hebron were retrospectively reviewed. The clinical, analytical, diagnostic, therapeutic and evolutive data were collected. RESULTS: One hundred forty patients (121 males and 19 females) were included. In 92% of the cases the HCC was established on liver cirrhosis in which alcohol was the most frequent etiologic factor. According to the Pugh-Child classification 31% of the patients were in group A, 32.5% in group B and 36.4% in group C. Clinically, diagnosis was carried out in the course of periodic out patient follow up in 21% of the cases. HBsAg was positive in 8.5% of the cases and anti HCV was 55% and in 78% by ELISA 1 and ELISA 2, respectively. Alphafetoprotein (AFP) was greater than 500 ng/dl in 37% of the cases. The treatment received was: surgical resection in 18 cases, liver transplantation in 3, intraarterial chemotherapy in 11 and intratumoral alcoholization in 8. Symptomatic treatment was administered in 71% of the cases. Global mean survival was 4.4 +/- 0.5 months. Mean survival was greater in patients with better liver function and smaller tumor size in the patients surgically treated and in those diagnosed in the periodic controls. CONCLUSIONS: Hepatocellular cancer is normally established in patients with liver cirrhosis. The high prevalence of infection by the hepatitis C virus and the low prevalence by hepatitis B virus is of note. The patients with greater survival were those surgically treated and those diagnosed in periodic controls.

Aged↗

Comparable seropositivity for ascariasis and toxocariasis in tropical slum children.

The seropositivities for infection by Ascaris lumbricoides and Toxocara canis were determined in children (1-15 years old) of a slum area of Caracas, Venezuela, and the levels that indicate the presence of active infection were defined. In children aged from 1 to 3 years, approximately 10% were positive for either parasite, and this figure increased to about 30% in 4- to 6-year-olds. For toxocariasis, the percentage of positivity remained at this level up to the age of 15 years. Whilst the positivity in children 10-15 years of age was comparable for Ascaris and Toxocara, a peak of positivity (50%) was found for Ascaris at 7-9 years of age. These results indicate that for these urban slum children, infection by Toxocara is essentially as common as that by Ascaris and, thus, that toxocariasis represents a potential public health problem in the tropical environment that is largely overlooked.

Adolescent↗

[Changes in coagulation in patients with sepsis].

Aiming to know the coagulation disorders that occur in patients with sepsis, a retrospective study of 75 such patients hospitalized in an Intensive Care Unit was performed. The coagulation profile requested by the attending physician, that included platelet count, prothrombin time, partial thromboplastin time, thrombin time, protamine sulphate test, fibrinogen and euglobin lysis time, was analyzed. Fourteen patients that were receiving prophylactic subcutaneous heparin were excluded from further analysis. Of the 61 remaining patients, 23 had hemorrhagic manifestations and 94.4% of these had multiple alterations in coagulation parameters. Eighty one percent of patients had abnormal prothrombin time and 73% thrombocytopenia. Isolated alterations were infrequent and consisted in thrombocytopenia (3.7%) and fibrinogen elevation (1.9%). Fifty two percent of patients had shock and they had significantly lower platelet counts and higher prothrombin and thrombin times than patients without hemodynamic disturbances. Global mortality was 63.9%. No relation between coagulation disturbances and mortality was observed. Likewise, no differences in mortality between patients with or without shock was observed. It is concluded that coagulation is frequently disturbed in patients with sepsis, even without clinical hemorrhagic symptoms, that these abnormalities are more marked in patients in shock and that 53% of these are consistent with intravascular coagulation.

Adolescent↗

[Comparative study of famotidine vs ranitidine in critically ill patients in mechanical ventilation].

Stress ulcers are frequent in critically ill patients. Gastric mucosa protection with antacids, H2 blockers or sucralphate decrease the incidence of stress ulcers and upper gastrointestinal bleeding but may have adverse effects. The present study compares the efficacy of continuous infusions of famotidine on gastric pH control and bleeding prevention in critically ill patients receiving mechanical ventilation. Fifty six patients (aged 55 +/- 22 years, 26 male) were randomly assigned to receive famotidine 40 mg/day (n = 27) or ranitidine 150 mg/day (n = 29) during 5 days. Gastric pH was measured every 6 hours and when it was below 5, aluminum hydroxide (30 ml every 2 hours) was administered to obtain values over 5. Patients receiving famotidine had higher mean gastric pH (6.3 +/- 0.2 and 93% of measurements over 5 vs 5.8 +/- 0.6 and 83% of measurements over 5 (p < 0.05), and required lower amounts of aluminum hydroxide (1.880 vs 2.770 ml). No patient had evidence of gastrointestinal bleeding and one had a mild psychomotor agitation. No other adverse reactions were observed. It is concluded that famotidine was more effective than ranitidine on gastric pH control in mechanically ventilated critically ill patients.

Acute Disease↗