[Turcot syndrome associated with multiple tumors].
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Aged↗
Biomedical subjects
F Alvarez
Publications and source records attributed to F Alvarez.
Carotid blood flow in anesthetized rats: effects of carotid ligation and anastomosis.
An experimental model was developed for continuous measurement of the common carotid blood flow, in the anesthetized rat, with an electromagnetic flowmeter. The mean carotid blood flow for 41 rats averaged 3.2 +/- 0.2 ml/min at an average mean arterial pressure of 101 +/- 2.5 mm Hg and arterial pO2 of 106 +/- 3.4 mm Hg, pCO2 of 38 +/- 1.2 mm Hg, and pH of 7.36 +/- 0.02. This model allowed short- and long-term carotid hemodynamic changes to be recorded after contralateral carotid ligation or end-to-side carotid anastomosis. After ligation of the contralateral carotid, blood flow through the intact carotid increased 25% (at about 1 week) and 45% (at about 5-6 months), whereas, after anastomosis, carotid blood flow increased 76% and 89% at periods comparable to those after ligation. Arterial pressure and gases did not change throughout the experimental periods. Probable mechanisms involved in these carotid hemodynamic changes are discussed.
Anastomosis, Surgical↗
Long-term culture of adult rat hepatocyte spheroids.
Hepatocytes from adult rats were cultured on poly-HEMA-coated surface to form spheroids in hormonally defined media as previously shown with newborn rat hepatocytes. Spheroidal aggregates of adult rat hepatocytes were morphologically similar to those of newborn rat hepatocytes and could also form a monolayer of uniform liver parenchyma-like cells when transferred on collagen-coated surfaces even after 2 months of culture. Under these culture conditions, albumin and transferrin secreted in vitro by adult rat hepatocyte spheroids were detectable by immunoprecipitation method at least until 2 months of culture. The production of proteins by hepatocyte spheroids could be regulated in vitro by IL-6: the secretion of alpha 2-macroglobulin was increased and the secretion of albumin was decreased in the presence of this cytokine. In addition, cytochrome P450 IA1 was strongly induced by methylcholanthrene in adult rat hepatocyte spheroids, and the induction remained relatively constant up to 22 days of culture. These cells were also able to metabolize lidocaine to monoethylglycinexylidine when measured up to 14 days of culture, showing the presence of a relatively high level of P450 IIIA2. The UDP-glucuronyltransferase activity, specific for bilirubin conjugation, decreased to 18% of the initial value after 2 weeks of culture. This work showed that adult rat hepatocytes in long-term spheroid culture kept differentiated functions, providing a new model for the in vitro study of hepatocyte functions and complementing that of newborn rat hepatocytes using the same system.
Albumins↗
Rates and outcomes of planned pregnancy after use of Norplant capsules, Norplant II rods, or levonorgestrel-releasing or copper TCu 380Ag intrauterine contraceptive devices.
OBJECTIVES: The objectives were to measure rates of planned pregnancy and factors affecting these rates after use of very-long-acting contraceptive methods (Norplant or Norplant II implants, a levonorgestrel-releasing intrauterine contraceptive device, or the copper T (model TCu 380Ag) intrauterine contraceptive device. STUDY DESIGN: The design was a concurrent, multicenter prospective study of 372 women who stopped contraception for planned pregnancy. Analysis was by life-table, log-rank, and standard chi 2 methods. RESULTS: Pregnancy rates 12 and 24 months after cessation of contraceptive use were 82 and 89 per 100, respectively. Age at removal and family planning intentions at initiation of contraception were both significantly correlated with pregnancy rates (p less than 0.05), but former contraceptive regimen and duration of contraceptive use were not. Pregnancy outcomes did not deviate from normal limits and did not differ by contraceptive formerly used. CONCLUSION: Contraceptive implants releasing 30 micrograms/day of levonorgestrel or intrauterine contraceptive devices releasing 20 micrograms/day of levonorgestrel or having copper surface areas of 380 mm2 are associated with normal fertility after use for women seeking pregnancy at termination. Durations of use do not affect pregnancy rates.
Adult↗
Study of CYP2D6 gene in children with autoimmune hepatitis and P450 IID6 autoantibodies.
Cytochrome P450 IID6 is an autoantigen recognized by the sera of children affected with a subtype of autoimmune hepatitis. It was hypothesized that a mutation in the CYP2D6 gene could explain the autoimmune response in these patients. To examine this question, genomic DNA from peripheral lymphocytes (n = 9) and liver (n = 1) of 10 patients with anti-LKM-1 antibody was analysed by Southern blot for genetic association studies between a particular CYP2D6 haplotype and autoimmune hepatitis. In addition, a region of CYP2D6, from the same genomic DNA, was amplified by polymerase chain reaction (PCR) and digested by BstNI, in a search for the most prevalent 29B mutation, described in subjects who do not express the P450 IID6. Total RNA and proteins, prepared from the liver of an anti-LKM-1+ patient, were analysed by Northern and Western (immunoblot) blots respectively. Our results do not reveal any major structural change in the DNA of this patient at the CYP2D6 locus that could explain their autoimmune response. Corroborating this observation, no changes were noted either in P450 IID6 mRNA size or in the corresponding protein. However, these data do not exclude the possibility of subtle changes in the protein due to point mutations in critical regions that might trigger an autoimmune response.
Autoantibodies↗
Diagnosis of brain death: superiority of perfusion studies with 99Tcm-HMPAO over conventional radionuclide cerebral angiography.
The use of technetium-99m hexamethyl-propyleneamine oxime (99Tcm-HMPAO) in the diagnosis of brain death has been evaluated in 41 studies of 37 patients with severe brain injury, who were under the effect of drugs or when other diagnostic methods were equivocal. HMPAO studies were compared with conventional radionuclide angiography performed simultaneously by intravenous administration of HMPAO as a bolus. The ages of patients ranged from 4 months to 75 years. Dynamic flow images and 5-min static uptake images were acquired following bolus injection of 555 Mbq of 99Tcm-HMPAO. All patients showing no brain uptake were confirmed as brain-dead by standard clinical criteria, with no contradictory cases in the static study. In addition, all patients who were not brain-dead showed HMPAO uptake at least in the brainstem. Dynamic flow images were equivocal in five patients, four of whom had no uptake on static images and clinically confirmed brain death. In addition, two other cases showed "mismatched" dynamic and static images: in one case no perfusion was observed on flow images but uptake restricted to the posterior fossa was seen on static images; the other case showed perfusion on the dynamic study and static imaging revealed hemispheric uptake with no posterior fossa uptake. Static perfusion 99Tcm-HMPAO studies offer advantages over conventional brain scintigraphy, better results being due to adequate assessment of posterior fossa activity and avoiding equivocal studies.
Adolescent↗
A scanning electron microscope study of Toxocara genettae Warren, 1972 (Ascaridae), with data on morphometric variation.
We have carried out a morphometric study of the ascaridoid nematode Toxocara genettae, parasite of the small intestine of the genet Genetta genetta, with the aid of scanning electron microscopy (SEM). Host specimens were trapped in Galicia, NW Spain. The most characteristic features of this nematode are the absence of cervical alae, replaced by narrow lateral crests running along the length of the body and the presence of a mucron at the end of the male tail. Other features of interest include the number of labial denticles (90-98 and 96-102 on the dorsal lip, 82-96 and 90-96 on the subventral lip of male and female, respectively), the width of the transverse striations (25-28 microns) and, in many of the specimens examined, the position of the precloacal median papilla at the base of a well-defined cuticular pit.
Animals↗
[Transposition of the great arteries. A follow-up of patients operated on with atrial correction].
The late results of 146 patients with transposition of the great arteries (simple: 119, complex: 27) surviving to physiological correction (Mustard: 33, Senning: 113) are analyzed. The mean age at operation was 27 months (1-120), and the mean follow-up was 78 months (6-187). The mean P wave voltage significantly decreased (from 0.3 mV preoperatively to 0.16 mV postoperatively). Frontal mean P wave axis varied from 63.9 degrees to 71.3 degrees. Mean heart rate were significantly lower than those for age-matched normal children. Previous atrioseptectomy had been performed in 36 patients and five of them had arrhythmias before operation. 78 (55%) out of the remaining 141 showed arrhythmias in the surface ECG: sinus node disfunction in 51, tachyarrhythmias in eight, atrioventricular block in eight and several association of arrhythmias in 11. Actuarial survival free of arrhythmias is 81% at the first year, 49% at 5 years and 22% at 15 years. The incidence of arrhythmias in the group of 92 patients with Holter monitoring was higher, with 73 cases having arrhythmias (79%): sinus node disfunction in 47, tachyarrhythmias in ten, atrioventricular block in four and associated in 12. Survival free of arrhythmias by both methods (ECG and Holter) shows a 78% at the first year, 28% at 5 years and 5.6% at 15 years. No significant correlation was found between the incidence of arrhythmias and the type of TGA (simple or complex) or the surgical technique (Mustard or Senning). Permanent pacemakers were implanted in seven to a mean follow-up of 7 years. Five patients were reoperated to a mean follow-up of 46 months. There were 7 late deaths to a mean follow-up of 13 months, four of them being sudden. The actuarial survival rate for the whole group was 93.5% at 15 years. No significant correlation was found between the late mortality and the type of TGA or operation. There was also no correlation with the incidence of arrhythmias. Residual lesions were found in 46 patients, hemodynamically significant in ten. Functional status was class I (NYHA) in 123, and class II in 16. There was correlation between the functional class and the residual lesions.
Age Factors↗
[Negative ADA in pleural tuberculosis].
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Adenosine Deaminase↗
Expression of CYP2D6 in developing human liver.
The CYP2D6 protein is a polymorphic isoenzyme involved in the biotransformation of several drugs including the probe drug dextromethorphan. The rise in the protein concentration, immunochemically determined with a specific antibody, was shown to occur within the first week following birth, whatever the gestational age at birth. In fetuses, the concentration of hepatic CYP2D6 protein was very low or undetectable in 70% of samples tested. In the remaining 30%, its concentration was comparable to that of newborns aged 1-7 days. This early rise was associated with spontaneous abortion in 70% of positive samples, whereas in fetuses with an intermediate CYP2D6 protein concentration, 80% were from induced abortions. The rise in CYP2D6 protein was associated with the developmental onset of dextromethorphan O-demethylation, but not N-demethylation, even if activity was lower in fetal than in neonatal and in adult liver microsomes. Lastly, the CYP2D6 RNA is detectable earlier than the protein and exhibits a peak of hepatic accumulation in newborns, before declining in adulthood. A positive correlation between RNA accumulation and protein concentration can be demonstrated only in the adult. This suggest that regulation is primarily at the transcriptional level, but cannot rule out the participation of post-transcriptional events in the regulation process throughout ontogenesis.
Adult↗
[Blood donation in the Balearic Islands. Analysis of supply and demand of blood from 1982 to 1987].
BACKGROUND: The supply and consumption of blood products in the autonomous community of the Balearic Islands were evaluated for the years 1982 to 1987 to assess the degree of hemotherapy coverage. METHODS: The registries of blood banks from 1982 to 1987, the clinical records of patients with congenital coagulation deficiencies and the registries of the hospital pharmacies and pharmaceutic distributing agencies were reviewed. RESULTS: The rates of use per product (units) and per one thousand population were as follows: red blood cells 22-25, platelets 0.8-3.2, transfusional plasma 0.5-2.8, and cryoprecipitates less than 0,2. The consumptions of albumin and gammaglobulins were 80 and 7.7 kg per one million population, corresponding to 3.200 and 1.540 I of plasma, respectively. The consumption of factor VIII was 1.3-0.9 international units (IU) per inhabitant, in highly of very highly purified form, corresponding to 18.500-12.857 I of plasma. CONCLUSIONS: The results show that a supply of 25-27 blood donations per one thousand population and per year and with a fractionning of 80%, yield 5.000 I of plasma per one million population. This fulfils the needs of all blood products, except those of highly or very highly purified factor VIII.
Blood↗
Cytochrome P450IID subfamily in non-human primates. Catalytical and immunological characterization.
Interindividual variations of debrisoquine metabolism was recently identified in non-human primates tested in vivo. The catalytical and immunological characterization of cytochrome P450IID subfamily was undertaken in hepatic microsomes from extensive metabolizer primates. The NADPH/O2 mediated metabolism of debrisoquine, dextromethorphan and bufuralol was similar to the kinetics reported in humans. The CuOOH mediated metabolism of bufuralol suggested that at least two enzymes are responsible for bufuralol 1'-hydroxylation. Eleven compounds were tested for their capacity to modify P450IID function in vitro. Eight competitive inhibitors of P450IID6 in man were all and exclusively competitive inhibitor of P450IID subfamily in non-human primates. Quinidine, which is the strongest competitive inhibitor in man, exhibited the higher inhibitory potency in monkey (Ki = 0.75 microM). Anti-LKM antibody against P450IID subfamily cross-reacted with two proteins of 49 and 47 kDa, and sera containing anti-LKM antibody against these two proteins inhibited dextrorphan formation in vitro. These data provide evidence for catalytical and immunological similarities between human and monkey microsomes and indicate that the primate system could be a model for enzymatic studies of P450IID.
Animals↗
Molecular analysis of a human liver mitochondrial ornithine transcarbamylase deficiency.
The liver of a young girl which had been successfully transplanted was investigated at the ornithine transcarbamylase (OTC, EC 2.1.3.3) gene expression level. Northern blot hybridization using a human OTC cDNA probe showed a greater than 80% decrease in specific OTC mRNA although having the same molecular size as a normal control. OTC polypeptide was simultaneously synthesized with a normal molecular size but at a low level (20%) as shown by immunoblotting. The OTC enzyme from the deficient liver exhibited very little catalytic activity (7.2% as compared to the normal subject). These results may support several explanations of this disease such as mutation of the OTC gene promoter leading to a low transcriptional activity or mutation of the encoding sequence which results in a modified translation product but with a normal size. mRNA instability may also occur.
Blotting, Northern↗
Prolonged intrauterine contraception: a seven-year randomized study of the levonorgestrel 20 mcg/day (LNg 20) and the Copper T380 Ag IUDS.
A levonorgestrel-releasing IUD and the Copper T 380Ag IUD were in randomized comparison for seven years in five clinics. In two other clinics the randomized study was truncated at five years, but use of the Copper T continued. No pregnancies occurred to users of either device in years 6 and 7. Cumulative pregnancy rates were 1.1 per 100 at seven years for the steroid-releasing and 1.4 per 100 for the copper-releasing IUDs. Cumulative rates of PID did not differ between devices. Infection rates appeared to be lowest during the sixth and seventh years of the study. Termination attributable to amenorrhea was the principal contributor to differences in cumulative continuation rates between devices. At the five clinics that carried the comparative study to seven years, cumulative continuation rates were 24.9 per 100 for LNg20 IUD users and 29.4 per 100 for TCu 380Ag users. Women who used either method for periods of five to seven years experienced, on average, marked to mild increases in hemoglobin as compared with levels at admission. The Copper T380 family and the LNg20 IUDs represent the most effective reversible contraceptive methods yet studied in long-term randomized trials.
Adolescent↗
Two-year comparative trial of the Gyne T* 380 Slimline and Gyne T* 380 intrauterine copper devices.
In a randomized trial of the Gyne T* 380 Slimline, the-two year pregnancy rate was 0.3 per 100 and the continuation rate was 65 per 100. These rates did not differ statistically from those of the standard Gyne T* 380, nor did other performance parameters differ between devices by the log-rank test. Women under age 30 had lower continuation rates using either device than did women age 30 or older at admission because of removals for planned pregnancy. Conception rates among those who desired pregnancy were 35 per 100 at one month and 86 per 100 at one year.
Adult↗
Identification of the main epitope on human cytochrome P450 IID6 recognized by anti-liver kidney microsome antibody.
Antibodies present in the sera of a group of children with autoimmune hepatitis react with human cytochrome P450 IID6. cDNA constructions of various fragments of human P450 IID6 were made and expressed and the resulting peptides were tested in immunoblot with patients' sera. These allowed identification of at least two antigenic sites on the P450 molecule. The main one, recognized by all sera tested, is located between amino acids 239 and 271. Synthesis of three peptides covering this area of the molecule allowed identification of a sequence of three amino acids (tyrosine-tryptophane-asparagine) located at position 261-263 that constitutes the essential part of the epitope. A protein sequence data-base search revealed homologies between this region of human P450 and proteins from Salmonella typhimurium, from human T lymphotropic virus types 1 and 2 and Herpes simplex virus type 1.
Amino Acid Sequence↗
False-positive result of hepatitis C enzyme-linked immunosorbent assay in children with autoimmune hepatitis.
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Adolescent↗