[Cytochrome P450 isoenzymes and liver-kidney microsome antibodies. An antigen-antibody relationship].
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Biomedical subjects
Publications and source records attributed to F Alvarez.
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Neonatal tracheomalacia is a disease in which there is a softening of the tracheal wall with lost of this consistency. This cause expiratory collapse cough and respiratory difficulty it is generally associated with Esophageal atresia and Vascular Rings. Exceptionally is a primary disease. In this paper we present three cases of neonatal tracheomalacia treated by aortopexy who is at the moment the best treatment that we have in severe cases. Soft cases will remit with conservative treatment.
Two patients with epidural cavernous hemangiomas located at the lumbar and cervical spine are reported. The first case presented clinically as progressive paraparesis, and the second began with sudden tetraparesis after a strong physical exercise. Myelography and MRI were the diagnostic tools. Surgical decompression improved the signs and symptoms in both cases. Spinal epidural cavernous hemangiomas are rare lesions that are usually regarded as vascular hamartomas. Symptom onset may be insidious or acute and the prognosis after timely surgery is better when compared with that of intrathecal cavernous hemangiomas. The histology and treatment of these processes are discussed.
Hypokalemia has been associated with the taking of gossypol, a potential oral antifertility drug for men. Because the frequency of this response differed in different parts of the world, this study was done to learn if "normal" serum [K+] also differed. [K+] was measured by flame photometry in serum from apparently normal men from Austria (n = 30), China (53), Brazil (100), the Dominican Republic (38), and the US (103), and in plasma from Nigerian men (82). The mean (SD) for [K+] in Chinese men, 3.82 (0.27) mmol/L, was lower than that in Brazilians [4.06 (0.29) mmol/L], Austrians [4.14 (0.44) mmol/L], Dominicans [4.37 (0.33) mmol/L], or Americans [4.38 (0.37) mmol/L]. Apparently there are regional differences in average serum [K+], with men in China having lower serum [K+] than men elsewhere. This may predispose them to hypokalemia.
From may 1986 to december 1991, we have performed 90 heart transplantation in the Hospital "Reina Sofía" from Córdoba. In the present study we analyze the early morbidity and mortality in a retrospective study on complications and factors determining its incidence. Seventy patients were male (86%) and 13 female (14%). Age ranged from 12 and 65 years. The 31% of patients needed in pharmacological support before transplantation, 15 of them were operated in a emergency situation because of cardiogenic shock. The pulmonary resistances oscillated between 0.5 and 8.7 units/m2 (Wood) (mean 2.5 +/- 1.4 units/m2). The mean time of ischaemia was 136 +/- 38 minutes (range 5-255 min). Hospital mortality (< or = 30 days) was 8.8% (8/90). No predictive factors from donor and recipient were found. Three main influences on complications were analyzed: a) influence of myocardial temperature, b) role of hematic cardioplegia, and c) usefulness of Aprotinin. Eighteen patients (20%) developed severe bradyarrhythmia needing a pacemaker in the post-operative period. We found a significant relationship with myocardial temperature (4.3 +/- 2.1 vs 6.2 +/- 2.6; p < 0.05) and transport solution temperature (5.8 +/- 2.3 vs 7.3 +/- 1.9; p < 0.05). No significant influence was found on the time of ischaemia, previous heart disease, previous treatment with Amiodarona, clinical condition, etc.(ABSTRACT TRUNCATED AT 250 WORDS)
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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.
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.
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.
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.
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.
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.
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.
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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.
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