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Biomedical subjects

F Alvarez

Publications and source records attributed to F Alvarez.

At least 163 records · Page 9Linked to original sources
PubMed1994

The effect of hypo-, normo-, and hypercapnia induced by mechanical ventilation on intrapulmonary shunt.

The effects of hypo-, normo- and hypercapnia on the variations in arterial oxygenation and their indices in critical patients with acute respiratory failure (ARF) receiving mechanical ventilation are studied. It is a prospective and randomized study carried out in multidisciplinary ICU. Fifteen ARF patients, intubated and mechanically ventilated, were studied within the first 48 h of evolution. Three stages were delimited: I) 30 min after the beginning of anaesthesia; II) 30 min after adding 30 cm of dead space (VD); III) 30 min after replacing the previous VD with VD of 60 cm. Ventilation parameters and FiO2 were kept stable. Stage I was characterized by respiratory alkalosis and stage II by normal acid-base balance with an increase in PaO2 (p < 0.01) and a decrease in intrapulmonary shunt (Qsp/Qt) (p < 0.001); the indices alveolar to arterial oxygen tension gradient [P(A-a)O2], respiratory index (R.I.) and estimated shunt (Est Shunt) also decreased significantly, whereas arterial to alveolar oxygen tension ratio (PaO2/PAO2) and arterial oxygen tension to inspired oxygen fraction ration (PaO2/FiO2) increased significantly. In stage III there was pure hypercapnic acidosis, with decreases in PAO2 (p < 0.001), P(A-a)O2 (p < 0.01) and R.I. (p < 0.05), while PaO2, Qsp/Qt, Est Shunt, PaO2/PAO2 and PaO2/FiO2 remained stable with respect to the previous situation. The observed PaO2 differs (p < 0.05) from the expected PaO2 in stage III. It is suggested that local or regional modifications of pulmonary perfusion are responsible for the observed variations. The P(A-a)O2 and R.I. indices do not make it possible to differentiate the causes of arterial hypoxemia in the presence of hypercapnia.

Acute Disease↗
PubMed1994

[Magnitude of acid gastroesophageal reflux measured by 24-hour esophageal pH monitoring compared to the degree of endoscopic esophagitis].

Twenty four hour esophageal pH monitoring was performed in 110 patients, placing a pH electrode 5 cm above the proximal border of the lower esophageal sphincter. This test allows to measure the total lapse in which there is an acid pH in the esophagus, the ability of the esophagus to get rid of the acid reflux and documents the relationship between esophageal pH and symptoms. Upper GI endoscopy showed a normal esophagus in 38 patients, and esophagitis grade I in 25, grade II in 11, grade III in 25 and grade IV in 11. There was a high correlation between the severity of esophagitis and the total time in which the esophagus was exposed to an acid pH. It is concluded that this test can be used as a "gold standard" for gastroesophageal reflux detection.

Adolescent↗
PubMed1994

[Patients with pathologic gastroesophageal reflux without erosive esophagitis: correlation of the endoscopic and histological aspect of the esophagus].

Eighty four patients with chronic gastroesophageal reflux in whom endoscopy showed a normal or minimally altered esophageal mucosa (hyperemia, erythema or mucosal congestion) were prospectively studied. In each patient, two esophageal biopsies were obtained (1 and 3 cm above the mucosal change zone). Histological esophagitis was found in 28% of patients with endoscopically normal mucosa and in 26% of patients with minimal endoscopical mucosal alterations. It is concluded that the description of these minimal esophageal alterations during endoscopy is subjective, unreproducible and do not clearly indicate the presence of esophagitis. A classification of endoscopical findings is proposed, based on the presence of objective lesions such as erosions or Barrett esophagus.

Adult↗
PubMed1993

Intracellular retention and degradation of human mutant variant of a alpha 1-antitrypsin in stably transfected Chinese hamster ovary cell lines.

Normal (PiM) and mutant (PiZ) variants of human alpha 1-antitrypsin (alpha 1-AT) cDNA, cloned into the pTnd eucaryotic expression vector, were used to derive recombinant Chinese hamster ovary cell lines permanently expressing the corresponding proteins. Secretion, accumulation and glycosylation of PiM and PiZ alpha 1-AT proteins were studied in the presence of various transport-impairing drugs. Pulse-chase, followed by immunoprecipitation as well as immunofluorescence experiments showed that the PiZ alpha 1-AT undergoes continuous degradation that was prevented by Brefeldin A but not by incubation of cells at 16 degrees C. Moreover, monensin partially impaired the glycosylation of both PiM and PiZ alpha 1-AT but not their secretion nor the degradation of PiZ alpha 1-AT. Those results suggest that PiZ alpha 1-AT degradation occurs in the cis-Golgi network, a compartment located between the endoplasmic reticulum and the Golgi stack. The process did not apparently involve lysosomes since it was insensitive to chloroquine. In addition, inhibition of PiM and PiZ alpha 1-AT glycosylation and secretion by tunicamycin did not result in the accumulation of the protein, but instead in its rapid lag-free degradation. Treatment of cells with the A23187 ionophore, for a short (60 min) but not a long (24 h) period, improved the secretion of PiZ alpha 1-AT in a similar way as it affects retention of naturally endoplasmic-reticulum-resident proteins, suggesting that the small proportion of PiZ alpha 1-AT which is not degraded or secreted, but accumulates in the endoplasmic reticulum, is back transported as a partially glycosylated species from the post endoplasmic reticulum compartment in which degradation takes place.

Animals↗
PubMed1993

Identification and analysis of cytochrome P450IID6 antigenic sites recognized by anti-liver-kidney microsome type-1 antibodies (LKM1).

Anti-liver-kidney microsome type-1 antibodies (LKM1), present in sera from a group of patients with autoimmune hepatitis, are directed against P450IID6. Previous work, using cDNA constructions spanning most of the P450IID6 protein defined the main immunogenic site between the amino acids (aa), 254-271 and predicted the presence of other putative immunogenic sites in the molecule. Fusion proteins from new cDNA constructions, spanning so-far-untested regions between aa 1-125 and 431-522, were not recognized by LKM1-positive sera. Synthetic peptides, representing sequences from putative immunogenic regions or previously untested regions, allowed a precise definition of four antigenic sites located between peptides 257-269, 321-351, 373-389 and 410-429, which were recognized, respectively, by 14, 8, 1 and 2 out of 15 LKM1-positive sera tested. The minimal sequence of the main antigenic site (peptide 257-269) recognized by the autoantibody was established to be WDPAQPPRD (peptide 262-270). In addition, deletion and replacement experiments showed that aa 263 (Asp) was essential for the binding of the autoantibody to peptide 262-270. Analysis of the second most frequently recognized peptide between aa 321-351, was performed using peptides 321-339 and 340-351 in competitive inhibition studies. Complete elimination of antibody binding to peptide 321-351 obtained by absorption of both shorter peptides indicated that peptide 321-351 is a discontinuous antigenic site. LKM1-positive sera reacting against peptide 321-351 recognized either both the shorter peptides or just one of them preferentially. Results of the present study suggest that the production of LKM1 antibodies is an antigen-driven, poly- or oligoclonal B cell response. The identification of antigenic sites will allow: (i) the development of specific diagnostic tests and (ii) further studies on the pathogenic value of LKM1 antibodies in autoimmune hepatitis.

Amino Acid Sequence↗
PubMed1993

Pediatric liver transplantation for primary hepatocellular carcinoma associated with hepatitis virus infection.

We report two cases of early primary hepatocellular carcinoma (PHC) in children, after probable maternal transmission of hepatitis B, that were treated with orthotopic liver transplantation (OLT). Both children were 8.5 years old and had elevated levels of serum alpha-feto-protein. The diagnosis of PHC was made at 8 years and confirmed histologically. Serum hepatitis B surface antigen (HBs Ag) was detected in the mothers and suggested vertical transmission. An attempt at complete liver tumor resection failed, leading to OLT. In order to prevent recurrence of the hepatitis B virus (HBV) infection, hepatitis B immunoprophylaxis was used. Two years after OLT, one child presented with recurrent HBV infection. No tumor recurrence was observed at follow-up in either of the patients. From these two cases we conclude that (1) HBV infection may play an important causal role in PHC in children, with an even shorter incubation period than that in adults; (2) close follow-up is needed for children who are HBs Ag-positive carriers; and (3) liver transplantation should be proposed early after the diagnosis of PHC, when tumor resection is not feasible.

Carcinoma, Hepatocellular↗
PubMed1993

Four-year experience in a randomized study of the Gyne T 380 Slimline and the Standard Gyne T 380 intrauterine copper devices.

Performance of the Slimline and Standard models of the Gyne T 380 were measured through four years in a comparative study initially involving 996 women, seventy percent of whom were randomized to the Slimline device. Cumulative pregnancy rates of Slimline users were 0.3 +/- 0.2 per 100 both at three and at four years, as compared with rates of 1.5 +/- 0.9 and 3.8 +/- 1.7 at the same intervals for users of the Standard model (P > .05). The four-year explusion rate of the Slimline, 8.6 +/- 1.3 per 100, was significantly higher than the comparable rate of the Standard model, 4.4 +/- 1.6 (P < .05). The two Gyne T* models did not differ in continuation rates. First time IUD users, however, had substantially lower continuation rates than did former users (P < .001), in consequence of their relative youth and desire to have additional children. Other performance measures did not differ importantly by device.

Adolescent↗
PubMed1993

Characterization of anti-liver-kidney microsome antibody (anti-LKM1) from hepatitis C virus-positive and -negative sera.

BACKGROUND: Hepatitis C virus-related antibodies were found in sera positive for antibodies to liver/kidney microsome antibody, usually considered a marker of autoimmune hepatitis. The aim of this study was to analyze the specificity of this autoantibody in sera from patients with and without hepatitis C virus infection. METHODS: Fifteen anti-hepatitis C virus- and anti-liver kidney microsome-positive sera were compared with 11 sera from patients with autoimmune hepatitis, for reactivity against rat and human liver microsomal proteins, P450IID6 recombinant proteins, and various synthetic peptides spanning the 241-429 amino acids sequence of the P450IID6. RESULTS: Ten of 11 sera from patients with autoimmune hepatitis bound to recombinant proteins spanning the P450IID6 region between amino acids 72 and 458. These sera bound to the 254-271 peptide, and some also recognized the 321-351, 373-389 and 410-429 peptides. Four of 15 antihepatitis C virus recognized the fusion protein coded by the full-length P450IID6 complementary DNA; 3 of them also reacted with the P450IID6 region between amino acids 72-456. Only 1 sera recognized the 321-351 peptide. CONCLUSIONS: P450IID6 antigenic sites recognized by anti-hepatitis C virus-positive sera were different from those recognized by sera from patients with autoimmune hepatitis.

Adolescent↗
PubMed1993

Comparative study on the efficacy and acceptability of two contraceptive pills administered by the vaginal route: an international multicenter clinical trial.

The efficacy and acceptability of two widely used oral contraceptive tablets, one containing 250 mg levonorgestrel and 50 micrograms ethinyl estradiol and the other containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol, administered by the vaginal route were compared in 1055 women studied over 12,630 woman-months of vaginal contraceptive pill use. This multicenter clinical trial was performed in nine countries of the developing world by the "South to South Cooperation in Reproductive Health," an organization founded by scientists from the Third World working in the area of reproductive health, and the study was developed and coordinated by one of these centers. The findings of this study confirm the efficacy of both these tablets when administered by the vaginal route. Involuntary pregnancy rates at 1 year of 2.78 for subjects in the levonorgestrel group and 4.54 for subjects the desogestrel group showed no statistically significant difference between the two groups. However, total discontinuation rates of 47.01 for subjects in the levonorgestrel group and 56.33 for subjects in the desogestrel group showed a statistically significant difference between the two groups, and discontinuation rates attributable to prolonged bleeding of 0.6 for subjects in the levonorgestrel group and 3.2 for subjects in the desogestrel group were also significantly higher in the group of subjects using the desogestrel vaginal contraceptive pill. Blood pressure remained at admission values throughout treatment. A statistically significant weight increase from admission values occurred in both groups of subjects.

Administration, Intravaginal↗
PubMed1993

HBV infection in pediatric liver transplantation.

When hepatitis B virus (HBV) infection precedes orthotopic liver transplantation (OLT), an important issue is to avoid post-OLT HBV infection of the transplanted liver. When HBV infection is found after OLT, the main objective is to prevent the complication of cirrhosis. A study of HBV infection in 162 liver-transplanted children followed at Hôpital de Bicêtre is presented here. One hundred forty-one of these children were completely vaccinated against HBV; 89% of them still disposed of protective titers of serum antibodies to hepatitis B surface antigen (anti-HBs) (> 10 IU/L) 6-60 months after OLT. Four children had a HBV-associated liver disease that required OLT. In these children a passive immunoprophylaxis maintaining serum anti-HBs levels > 100 IU/L allowed three of them to remain free of serum hepatitis B surface antigen (HBsAg) and HBV-DNA during follow-up at 10, 20, and 36 months. Four other children have been found to be HBsAg+ after OLT, but it was not clear whether the source of HBV was a reactivation or a de novo infection. Low doses of cyclosporin and prednisone were administered, in order to avoid the complications of HBV infection. Liver needle biopsies in three of these patients 37, 42, and 46 months after OLT showed a moderate chronic active hepatitis and mild fibrosis. Immunostaining for HBs and hepatitis B core (HBc) antigens indicated active viral replication.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1993

Autoimmune hepatitis associated with anti-actin antibodies in children and adolescents.

The clinical, biochemical, morphological, and evolutive features of autoimmune hepatitis associated with serum smooth muscle antibodies of anti-actin specificity were retrospectively analyzed in 31 children and adolescents. Cirrhosis was present at diagnosis in all but six patients, including nine of the 12 diagnosed within 6 months from the onset. In 15 children, one or more associated diseases of an immune-mediated mechanism were present, including chronic arthritis, sclerosing cholangitis, inflammatory bowel disease, and cutaneous vasculitis. All patients were treated with prednisone and azathioprine with normalization or improvement of liver function tests: 28 children are currently alive after a mean follow-up of 4 years, 10 months. Treatment was interrupted in four patients only. Two patients died of liver failure in spite of immunosuppressive therapy before the era of liver transplantation. In spite of prolonged therapy, five other patients ultimately required liver transplantation during adolescence or early adulthood. These results (a) further define a group of autoimmune hepatitis in children characterized by the presence of serum anti-actin antibodies; (b) indicate that immunosuppressive therapy improves liver function, although in most cases it must be continued for a long period to maintain remission; and (c) suggest that progressive liver failure may occur in early adulthood and may require liver transplantation.

Actins↗
PubMed1993

Hepatitis C virus infection in pediatric liver transplantation.

To determine the prevalence of antibodies to hepatitis C virus (HCV) and the short-term evolution of HCV infection in children undergoing orthotopic liver transplantation, we retrospectively studied the sera and medical records of 149 children surviving from 9 months to 5 years after OLT. Fourteen children (9.4%) were found to be positive for anti-HCV with second-generation ELISA and RIBA tests. They were individualized in 2 distinctive groups. In 5 children, anti-HCV was present before OLT, and in 1 patient only HCV RNA was detected at that time. All 6 patients were positive for anti-HCV after OLT. In the other 8 children, anti-HCV and HCV RNA were only detected after OLT and likely reflect infection during or shortly after OLT. The antibody reactivities against the 3 antigens included in the second-generation RIBA test varied in a given patient throughout follow-up and between these 2 groups of children. In all patients, serum transaminase (ALT) activities returned to normal levels when prednisone therapy was lowered and given every other day. These results indicate that the search for HCV infection in these children is necessary in the differential diagnosis of other liver complications in order to avoid excessive immunosuppressive treatment.

Adolescent↗
PubMed1993

Cytochrome P450IID6 recognized by LKM1 antibody is not exposed on the surface of hepatocytes.

LKM1 autoantibody, directed against P450IID6, is accepted as a marker of a particular type of autoimmune hepatitis, but its role in the pathogenesis of the disease is controversial. Localization of P450IID6 on the cell surface of rat hepatocytes was previously reported, suggesting that membrane-bound P450IID6 could be the target of LKM1 antibodies, thus allowing immune lysis of hepatocytes. The objective of the present study was to determine, using various methods, the cell localization of P450IID6 in human and rat hepatocytes. Incubation of rat and human hepatocytes with LKM1-positive serum showed slight, if any, cell membrane staining using immunofluorescence, immunoperoxidase and immunoelectron microscopic studies. No staining of the plasma membrane of human hepatocytes was observed when incubations were carried out with immunoaffinity-purified antibody directed against peptide 254-271, the main epitope of P450IID6 recognized by all LKM1 sera tested. Chinese hamster ovary cells, transfected with the complete P450IID6 cDNA and incubated with the supernatant from a B cell lymphoblastoid cell line prepared with the lymphocytes of a LKM1-positive patient, did not show any staining of the cell surface by immunofluorescence. Incubation of rat microsomal fraction vesicles with LKM1-positive serum, followed by protein A-gold immunoelectron microscopy, displayed a staining of almost all vesicles, confirming that P450IID6 is present on the cytoplasmic side of the microsomal membrane, which makes it unable to be expressed on the cell surface even if it were transported from the endoplasmic reticulum (ER). Sulpho NHS Biotin labelling of rat hepatocyte cell membranes did not show the presence of a 50-kD molecule that could have reacted with LKM1 antibody. DNA sequencing of exon 1 of the CYP2D6 gene of a patient positive for LKM1 antibody did not show any difference from that of the normal published sequence of the gene. This does not favour an alteration of the NH2 terminal sequence of the P450IID6 molecule that could explain a translocation of the molecule to the luminal side of the ER, allowing its expression on the cell surface. These results indicate that, in all likelihood, P450IID6 molecule is not present on the cell surface of normal rat and human hepatocytes. Other mechanisms than antibody-mediated cell lysis directed against membrane P450IID6 antigenic determinants must be found to account for the destruction of hepatocytes observed in this disease.

Amino Acid Sequence↗
PubMed1993

A Latin American experience with levonorgestrel IUD.

The intrauterine contraceptive device is an effective, safe and convenient contraceptive method. Its use in less developed countries has been limited by the increase in menstrual blood loss, an important issue in populations with a high prevalence of anaemia. The levonorgestrel releasing IUD (LNg IUD) is the first device which is at the same time highly effective, long-lasting and reduces the blood loss during menstruation. This device was tested in 200 volunteers in Santo Domingo, Dominican Republic and in 381 in Campinas, Brazil. The cumulative pregnancy rate was 0 up to 7 years of use. The reduced bleeding was confirmed, and ferritin concentration among long-term users of the LNg IUD was significantly higher than among copper IUD users and controls using no contraception. Mean levonorgestrel plasma levels remained above 100 pg/ml until the seventh year of use. Endometrial histology showed mainly a marked reduction in epithelial growth, with variable signs of decidualization of the stroma. The most important reason for discontinuation in the two centres was amenorrhea, with cumulative rates of 10 and 15, respectively. This device should be very well accepted and will have a clear niche among reversible contraceptives, when available.

Adult↗