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Biomedical subjects

M Gutierrez

Publications and source records attributed to M Gutierrez.

At least 55 records · Page 3Linked to original sources

Utility of a short-term 25% carbohydrate diet on improving glycemic control in type 2 diabetes mellitus.

OBJECTIVE: To determine if introduction of a low carbohydrate diet might be a useful option for type 2 diabetic patients who do not achieve glucose target levels despite conventional treatment. METHODS: Subjects with type 2 diabetes, either treated with diet alone (n=9) or second generation sulfonylurea agents (n= 19), which were discontinued, were placed on a diet based on ideal body weight and comprised of 25% carbohydrate. After a mean of 8 weeks, they were then switched to a caloricly equivalent diet, but composed of 55% carbohydrate. RESULTS: Compared to baseline diet, after 8 weeks of a 25% diet, subjects showed significantly improved glycemia as evidenced by fasting blood glucose values (p<0.005) and hemoglobin A1c levels (p<0.05). Those previously treated with oral hypoglycemic agents showed, in addition, a significant decrease in weight and diastolic blood pressure despite the discontinuation of the oral agent. When then placed on a 55% carbohydrate diet, the hemoglobin A1c rose significantly over the ensuing next 12 weeks (p<0.05). CONCLUSION: A low carbohydrate, caloricly-restricted diet has beneficial short-term effects in subjects with type 2 who have failed either diet or sulfonylurea therapy and may obviate the necessity for insulin. Our study also affirms the need for reassessing the role of diet whenever type 2 diabetic patients manifests hyperglycemia, despite conventional oral treatment or diet management.

Aged↗

Tobacco smoking and bipolar disorder.

BACKGROUND: We sought to determine whether tobacco smoking is associated with bipolar disorder. METHOD: This case-control study carried out in Alava, in the north of Spain, included patients with a DSM-III-R diagnosis of bipolar disorder type I (N = 51) and a representative sample of the normal population (N = 517). Smoking history of bipolar patients was assessed with the Fagerstrom Test for Nicotine Dependence and was verified by family members of the patients. RESULTS: The frequencies of ever smoking and current daily smoking were, respectively, 63% (32/51) and 51% (26/51) for the bipolar patients and 45% (235/517) and 33% (169/517) for the control group (respective odds ratios [ORs] and 95% confidence intervals [CIs] were OR = 2.0, 95% CI = 1.1 to 3.8 and OR = 2.1, 95% CI = 1.2 to 4.0). The differences were significant (p = .03 and p = .042, respectively) for bipolar versus control males. Bipolar disorder (in both genders) was also significantly associated (OR = 4.4, 95% CI = 1.7 to 11.9, p = .0015) with heavy smoking (more than 1 pack per day). CONCLUSION: Despite its small sample size, this study suggests that smoking may be more prevalent in bipolar patients than in the normal population. Since most patients started to smoke before the onset of illness, vulnerability to bipolar illness may make subjects vulnerable to become tobacco smokers.

Adolescent↗

Incidence and clinical manifestations of activated protein C resistance and factor V Leiden in young patients with venous thromboembolic disease in Spain.

In order to evaluate the actual incidence and clinical repercussion of activated protein C resistance (APCR) in our area, we performed a coagulation and thrombophillic study on 65 young patients diagnosed with deep vein thrombosis and 53 controls. Family and genetic study was carried out in APC-resistant patients. We found APCR in 26.15% of patients and the 77.7% of these and their relative were heterozygous for factor V Leiden. There's a clear relationship between phenotype APCR and thrombosis, and also between factor V Leiden and thrombosis.

Adolescent↗

Fatal myelofibrosis following fludarabine administration in a patient with indolent lymphoma.

We report a case of fulminant myelofibrosis after administration of fludarabine in a patient diagnosed as having refractory low-grade lymphoma, progressing fatally. Myelofibrosis in the setting of an indolent lymphoma is very rare; this fact, and the short period between drug administration and fibrosis suggest an etiopathogenic link, although this potential and severe adverse effect of fludarabine has not been previously reported in the literature.

Antimetabolites, Antineoplastic↗

Chromosomal mapping of two members of the human dynein gene family to chromosome regions 7p15 and 11q13 near the deafness loci DFNA 5 and DFNA 11.

We mapped expressed tagged sequences (ESTs) corresponding to two human dynein heavy chain genes: beta heavy chain of the outer dynein arm and heavy chain isotype 1B (DYH1B), by using somatic cell hybrids and radiation hybrid panels. The EST for the beta heavy chain of the outer dynein arm mapped to chromosome region 7p15, and the EST for DYH1B mapped to 11q13.5. Two loci for nonsyndromic forms of deafness, DFNA5 and DFNA11, have previously been mapped to these two chromosomal regions. Including the gene for the axonemal light chain, hp28, we have mapped three different dynein genes near loci for different forms of nonsyndromic deafness. The hypothesis that mutations in some dynein genes are associated with nonsyndromic deafness should now be tested.

Chromosome Mapping↗

Clinical and hormonal effects of the combination gonadotrophin-releasing hormone agonist plus oral contraceptive pills containing ethinyl-oestradiol (EE) and cyproterone acetate (CPA) versus the EE-CPA pill alone on polycystic ovarian disease-related hyperandrogenisms.

The aim of this study was to compare the clinical and hormonal effects of the combination of a long-acting gonadotrophin-releasing hormone analogue (GnRH-a) plus an oral contraceptive (OC) pill containing ethinyl-oestradiol (EE) and cyproterone acetate (CPA) versus the EE-CPA pill alone in patients with polycystic ovarian disease (PCOD) and related hyperandrogenisms, in order to evaluate whether the addition of GnRH-a has any advantage. A total of 12 PCOD patients were treated with the EE-CPA pill alone for 10 consecutive cycles according to an OC standard regimen. A further 12 patients were treated with GnRH-a, one i.m. injection every 28 days for a total of eight injections, combined with the EE-CPA pill for 10 consecutive cycles. The latter was thus prolonged for two cycles more than GnRH-a. Clinical evaluations (symptoms, weight, Ferriman-Gallwey score) and hormonal and biochemical analyses were assessed before, during (at 3 or 6 months) and after treatment, either when spontaneous cycles had resumed or after 3 months of amenorrhoea. There was a significant improvement in hirsutism, and a strong reduction in gonadotrophin, oestradiol, testosterone, androstenedione and 17-OH-progesterone concentrations in both treatment groups but with no significant differences between them, except in the gonadotrophin concentrations. Cortisol and triglyceride concentrations increased during treatment in both groups. The Ferriman-Gallwey score remained significantly decreased in both groups after treatment, as did androstenedione in the GnRH-a plus EE-CPA pill group, but there were no significant differences between the two groups. No changes were observed in prolactin, dehydroepiandrosterone sulphate (DHEA-S), insulin, glycaemia and cholesterol concentrations. However, when only the obese and more hirsute patients were considered, significant differences between the two groups were found during treatment in the Ferriman-Gallwey score and the gonadotrophin and DHEA-S concentrations (which increased during treatment in obese patients with the pill alone), and after treatment in the Ferriman-Gallwey score and the concentration of 17-OH-progesterone in the more hirsute patients, with the GnRH-a plus pill group having better results. In conclusion, a cyclic prolonged treatment with OC EE-CPA pills is not improved in most PCOD patients by the addition of GnRH-a, and is complicated and expensive. However, the addition of a long-acting GnRH-a may be recommended in obese and severely hirsute patients.

Adolescent↗

Complementary deoxyribonucleic acid cloning and characterization of a putative human axonemal dynein light chain gene.

Immotile Cilia Syndrome (ICS) is characterized by recurrent sinus and lung infections, bronchiectasis, and sperm immotility. Nasal cilia and sperm tails in patients with ICS exhibit a variety of ultrastructural defects, often including shortening or absence of the inner dynein arms. Immotile mutant strains of Chlamydomonas, a biflagellated algae, have ultrastructural defects similar to those seen in patients with this clinical disorder. Furthermore, splice-site mutations in the Chlamydomonas inner dynein arm gene (p28) are associated with impaired flagellar motility. We therefore hypothesized that the human homologue of the Clamydomonas dynein p28 gene would be an attractive candidate gene for patients with ICS. Accordingly, we cloned the full length complementary DNA (cDNA) and genomic clone by screening of appropriate libraries and databases, using the protein sequence of the Chlamydomonas p28 gene. The human homologue is encoded by a 921 bp transcript (accession no. AF006386) with an open reading frame of 257 amino acids. Using somatic cell and radiation hybrid panels, the hp28 gene was mapped to human chromosome 1p35.1. The hp28 cDNA probe hybridizes to sequences in all species on a zoo blot containing genomic DNA from yeast to human. Northern blot analysis reveals two hp28 gene transcripts, 0.9 and 2.5 kb, in many tissues. The 0.9 kb transcript is expressed at a 20-fold higher level than the 2.5-kb transcript in the testis. The entire gene is included in a 20-kb EcoRI genomic fragment and has 7 exons and 6 introns. Cloning of the hp28 cDNA and mapping of the intron-exon junctions should now make it possible to test whether a subset of ICS is a consequence of mutations in the human axonemal dynein light chain gene hp28.

Base Sequence↗

Histochemical distribution and accumulation of trace metals in the heart of green and normal Crassostrea angulata specimens from different southwest Spanish coasts.

Histochemical distribution and quantification of trace metals (copper-Cu-, zinc-Zn- and iron-Fe-) were studied in oyster, Crassostrea angulata heart (auricle and ventricle) from different southwest Spanish coasts. In green Crassostrea angulata specimens (green coloration in gills and visceral mass), numerous brown cells (blackish-brown) were observed in the wall of the auricles and dispersed by connective tissue, where inflammatory lesions related with granular amoebocytes were observed. However, only a few brown cells (translucent ligh-brown) were detected in auricles of normal oysters. Histochemically, Fe, Cu and Zn granules were observed in the wall of the heart (auricles), in brown cells, as well as in the granular amoebocytes, which are increased in green Crassostrea specimens. Auricle brown cells reacted weakly with PAS and Alcian Blue techniques. These cells contain proteins, as well as cysteine and cystine groups; these residues (-SH and S-S) being very abundant in the heart of green specimens, specially in brown cells and in granular amoebocytes. Lipofuscin granules were detected in these brown cells and in granular amoebocytes. On the other hand, in the heart (normal and green specimens), Zn levels were higher than Fe and Cu concentrations and heavy metals analyzed were lower in heart of normal than in green specimens. In green specimens, Cu and Zn levels were higher in auricles than in ventricles.

Animals↗

Stereoselective metabolic pathways of ketoprofen in the rat: incorporation into triacylglycerols and enantiomeric inversion.

The enantiomeric bioinversion of ketoprofen (KP) enantiomers and their incorporation into triacylglycerols were investigated in the rat (1) in vitro, using liver homogenates, subcellular fractions, and hepatocytes, and (2) in vivo, in different tissue samples after oral administration of the radiolabelled compounds. In liver homogenates or subcellular fractions, the enantiomer (S)-ketoprofen (S-KP) was recovered unchanged, whereas (R)-ketoprofen (R-KP) was partially converted into its Coenzyme A (CoA) thioester and inverted to S-KP. Both processes occurred mainly in the mitochondrial fraction. This supports the mechanism of inversion via stereoselective formation of CoA thioester of R-KP, already described for other non-steroidal anti-inflammatory drugs. Incorporation into triacylglycerols was detected after incubation with intact hepatocytes in the presence of added glycerol. The process was stereoselective for R-KP vs. S-KP (covalently bound radioactivity 26,742 +/- 4,665 dpm/10(6) cells vs. 6,644 +/- 3,179 dpm/10(6) cells, respectively). However, no incorporation was found in liver samples after oral administration of either R-KP or S-KP. On the contrary, in adipose tissue samples a significant and stereoselective formation of hybrid triacylglycerols was observed: 11,076 +/- 2,790 dpm.g-1 for R-KP vs. 660 +/- 268 dpm.g-1 for S-KP. The incorporated R/S ratio, higher in adipose tissue (R/S = 17) than in hepatocytes (R/S = 4), indicates that fat may be the main tissue store for the xenobiotic R-KP in rats.

Adipose Tissue↗

New variant Ph translocation in chronic myeloid leukemia: t(Y;22)(p11;q11).

A 4-year-old boy with chronic myeloid leukemia (CML) was shown to have a variant Ph t(Y;22)(p11;q11). To our knowledge, this is the first report of a variant Ph translocation involving Y. Molecular analysis showed that the breakpoint on chromosome 22 is in the breakpoint cluster region (bcr), typical of CML with the classic t(9;22), suggesting that it might be a complex Ph translocation with the involvement of 9q34.

Child, Preschool↗

Mechanisms involved in the spasmolytic effect of extracts from Sabal serrulata fruit on smooth muscle.

1. The effects of two extracts from Sabal serrulata fruits [total lipidic (L) and saponifiable (S)] on smooth muscle contractions have been assayed. 2. Both extracts (0.1-1 mg/ml) relaxed the tonic contraction induced by norepinefrine (30 nM) on rat aorta [EC50, 0.53 +/- 0.05 mg/ml (L) and 0.5 +/- 0.04 mg/ml (S)] and by KCl (60 mM) on rat uterus. The Sabal extracts (0.3-1 mg/ml) also antagonized the dose-response curve of contractions induced by acetylcholine (0.1-100 microM) on urinary bladder. 3. dL-Propranolol (1 microM) but not the inactive (R)-(+)-propranolol(1 microM) potentiated the Sabal extracts relaxant effect by lowering the EC50 (0.35 +/- 0.2 vs 0.20 +/- 0.01 mg/ml for L and 0.43 +/- 0.02 vs 0.19 +/- 0.02 mg/ml, P < 0.01, for S extract). 4. Cycloheximide (10 micrograms/ml) antagonized the effect of extracts from Sabal. However, actinomycin D (5 micrograms/ml) significantly (P < or = 0.01) antagonized the effect of the total lipidic extract without modifying that of the saponifiable extract. 5. The relaxant effect of both extracts was not modified by the tyrosine kinase inhibitor genistein (10 microM) or the ornithine decarboxylase inhibitor alpha-difluoromethyl-ornithine (10 mM).

Adrenergic beta-Antagonists↗

Controlled transdermal delivery of fentanyl: characterizations of pressure-sensitive adhesives for matrix patch design.

Transdermal delivery of fentanyl from various adhesive matrix formulations to achieve a steady-state skin flux was investigated. For this purpose, various pressure-sensitive adhesives selected from the three chemical classes of polymers (polyisobutylene (PIB), acrylate, and silicone adhesives) were characterized with respect to fentanyl's solubility, diffusion coefficient, and permeability coefficient. The solubility of fentanyl in various pressure-sensitive adhesives at 32 degrees C was determined by the drug absorption-desorption method. The solubilities of fentanyl in these adhesives were in the following order: acrylate > silicones > PIB. The permeability coefficient and diffusion coefficient of fentanyl in these adhesives were determined by the membrane diffusion method. The diffusion coefficient rank order was silicone-2920 > silicone-2675 > or = acrylate > PIB. The release profiles of fentanyl in the aqueous buffer from these adhesives with 2-4% drug loading was evaluated. The release rate of fentanyl from the acrylate polymer was significantly higher than those of silicone and PIB adhesives. The in vitro flux of fentanyl through cadaver skin from various adhesives with 2% drug loading was determined at 32 degrees C using modified Franz diffusion cells. The skin fluxes of fentanyl from silicone-2920 and PIB adhesives were 6.3 +/- 0.7 and 3.1 +/- 0.3 micrograms/cm2/h, respectively. On the other hand, the skin fluxes of fentanyl from acrylate and silicone-2675 adhesive matrices were about 1 microgram/cm2/h. The effect of drug loading on skin flux was investigated using PIB as a model adhesive. The drug released in the phosphate buffer (pH = 6.0) increased linearly as the drug loading in the PIB was increased from 1% to 4%; and as the drug loading exceeded 4%, an initial burst effect followed by a zero-order release was observed. The skin flux of fentanyl increased proportionally as the drug loading in the PIB adhesive was increased from 1 to 4%, and a plateau was reached beyond 4% drug loading. These results suggest that fentanyl concentration in the PIB adhesive might have reached saturation above 4% drug loading and that the optimum skin flux was accomplished from such a system because of attainment of maximum thermodynamic activity.

Acrylates↗

Prevalence of abnormal levels of serum tumour markers in elderly people.

The study was conducted to evaluate the prevalence of abnormal levels of several serum tumour markers in an institutionalized elderly population. Serum tumour markers assay of carcinoembryonic antigen (CEA), the carbohydrate antigens CA 19-9, CA 72-4 and CA 15-3 (Enzymun-test, Boehringer Mannheim GmbH Diagnostic), alpha-fetoprotein (AFP) and prostate specific antigen (PSA) (Abbot Diagnostic Division) were performed in 228 unselected, institutionalized elderly subjects, whose mean age (SD) was 82.4 (5. 79) range (66-99 years). Patients with acute or neoplastic diseases were excluded from the study. The serum markers were also measured in 52 healthy young adults (controls). Using the established threshold values, 92 subjects (40%) were found to have at least one elevated marker. PSA was elevated in 33%, CA 19-9 in 16%, CEA in 11. 5%, CA 15-3 in 11%, CA 72-4 in 8% and AFP in 3%. We found a significant difference in the serum levels between the two groups for CEA, CA 19-9. CA 15-3, and PSA (p < 0.0001). Healthy aged people appear to have an elevated prevalence of elevated levels of serum tumour markers. The results suggest that apart from PSA, elevated antigen levels in elderly subjects are related to the ageing process itself rather than to occult pathology.

Aged↗

Epidemiology of HTLV-I infection in Spain. HTLV Spanish Study Group.

BACKGROUND: The human T-lymphotropic virus type I (HTLV-I) has been implicated in the genesis of tropical spastic paraparesis (TSP), adult T-cell lymphoma (ATL), and some cases of uveitis, subacute arthropathies, chronic dermatitis and lymphocytic alveolitis. The virus is endemic in some areas of the Caribbean basin, Japan, subSaharan Africa, Central and South America, Middle East and Melanesia. Given that HTLV-I is transmitted through similar ways to HIV, screening in blood donors is recommended in some countries. MATERIALS AND METHODS: The clinical, epidemiological and virological characteristics of 27 patients with HTLV-I infection were identified in Spain up to September 1995. RESULTS: Eighteen cases were Spanish natives and 9 were immigrants from endemic areas. Fifteen were male and 12 were female. The majority (12/18; 66.7 percent) of subjects born in Spain had resided in endemic areas or had had sexual partners from these regions. Four patients had TSP, three had ATL and one developed lymphomatous granulomatosis and T-cell lymphoma. The remaining HTLV-I subjects were asymptomatic at the time of diagnosis. Four cases were identified from screening of blood donors. CONCLUSION: HTLV-I is present in Spain, affecting natives and, less frequently, immigrants from endemic areas. Both neurological and lymphoproliferative diseases have been recognized in a quarter of patients.

Adolescent↗

Variant (8;22) translocation in lymphoblastic lymphoma.

Occasional cases with the chromosomal translocations that juxtapose the c-myc oncogene to Ig genes have been reported in large cell, small lymphocytic, immunoblastic, and follicular lymphomas. In this report, we present a 20 year-old female with lymphoblastic lymphoma of B-cell type and a translocation t(8;22), in which cytogenetic, immunologic, and molecular studies were performed. To the best of our knowledge this is the first report of this association.

Adult↗

The influence of salts on the reaction between hGH and several of its monoclonal antibodies in fixed, paraffin-embedded human pituitary as a model system.

A study of the influence of three salts of monovalent cations (Nacl, KCl, and CsCl) and three salts of divalent cations (MgCl2.6H2O, anhydrous CaCl2, and SrCl2.6H2O), on the specific reaction between human hGH and three of its monoclonal antibodies has been carried out, using human pituitary glands obtained at autopsy as a model system. This study is an attempt to find out the physico-chemical laws ruling the immunohistochemical reaction in the special circumstance of fixed specimens, where the antigen (Ag) is immobilized in the tissue substrate, while the antibody (Ab) is mobile. Our interpretation of the results points to a reaction of the salts with side groups of aminoacids in the paratope (specific saline effect) and a mass salt effect on the reaction kinetic proper that is dependent on the salt concentration. The high affinity coefficient of the in situ Ag-Ab reaction is shown, at the immunohistochemical level, by the high molarity necessary to make the reaction negative. Also, it seems there is a direct relationship between the critical molarity values obtained and the affinities of the monoclonal antibodies used in this study.

Antibodies, Monoclonal↗

Functional serotonin 5-HT1D receptors and 5-HT1D beta receptor mRNA expression in human umbilical vein endothelial cells.

Pharmacological evidence has suggested the presence of 5-hydroxytryptamine (5-HT, serotonin), 5-HT(1D) receptors on endothelial cells but these receptors have never been identified unambiguously on this type of cells. We now report that human umbilical vein endothelial cells (HUVEC) express 5-HT(1D) receptors coupled to inhibition of cyclic AMP formation. 5-HT and 5-HT(1D) receptor agonists 5-carboxamidotryptamine (5-CT) and sumatriptan were approximately equipotent at inhibiting forskolin-stimulated cyclic AMP accumulation in HUVEC (mean pEC50 7.6-8.2, maximal effect 30% inhibition). The 5-HT(1A) receptor antagonist, 8-OH-DPAT was clearly less potent (pEC50 6.2) and less efficacious. The selective 5-HT(1D) receptor agonist, GR127935 (1 nM) markedly inhibited the effect of 5-HT (apparent pK(B) 10.8). Reverse transcription-polymerase chain reaction analysis showed the mRNA for 5-HT(1D beta) receptors to be expressed in HUVEC. These results demonstrate the presence of functional 5-HT(1D) receptors and the expression of 5-HT(1D beta) receptor mRNA in HUVEC. They support the involvement of 5-HT(1D beta) receptors in endothelial-mediated responses to 5-HT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗