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Biomedical subjects

F Martínez

Publications and source records attributed to F Martínez.

At least 19 recordsLinked to original sources
PubMed2001

Current understanding and management of chronic hepatosplenic suppurative brucellosis.

To outline the characteristics and define appropriate management of chronic hepatosplenic suppurative brucellosis (CHSB), 905 patients with brucellosis were analyzed. Sixteen episodes of CHSB (14 in the liver and 2 in the spleen) were found in 15 patients. Six patients had had previous remote brucellosis. Twelve patients presented with systemic symptoms, and 12 with local symptoms. Cultures of blood samples yielded negative results in all cases except 1, and the results of cultures of pus specimens were positive for Brucella melitensis in only 2 cases. All patients showed calcium deposits surrounded by a hypodense area on computed tomography. Patients often had low titers of agglutinating antibody. In patients who were receiving conservative management, early response was successful in 50% and late response was successful in 33.3%. In the patients who underwent surgery and concomitant antibiotic therapy, early and late response was successful in 100%. Thus, CHSB mainly represents a local reactivation of previous brucellosis. Its diagnosis may be difficult to establish and surgery may be required to cure many patients.

Adult↗
PubMed2001

Fatal upper and lower gastrointestinal cytomegalovirus disease following autologous peripheral blood stem cell transplantation.

Although the life-threatening cytomegalovirus (CMV) disease is a well known complication following allogeneic hematopoietic stem cell transplantation (HSCT), it has been considered infrequent after autologous peripheral blood stem cell transplantation (PBSCT). On the other hand, the massive involvement of the gastrointestinal (GI) tract as the primary site of fatal CMV disease is particularly rare after autologous PBSCT. We present the case of a woman who suffered from CMV disease after high-dose busulphan/melphalan/thiotepa (BuMelTT) and autologous PBSCT. The primary site of infection was the GI tract, which was extensively affected. During the fifth week post-transplant the patient started with epigastralgia, diarrhea, fever, GI bleeding, and thrombocytopenia, and she died on day +52. Another case of fatal CMV disease among the few patients treated with BuMelTT has been recently reported, which suggests that the immunodeficiency associated with that regimen can be as intense as that occurring after allogeneic BMT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Ultrasound-guided embryo transfer: immediate withdrawal of the catheter versus a 30 second wait.

It is essential to deposit embryos as gently as possible during IVF, avoiding manoeuvres that might trigger uterine contractions which could adversely affect the results of this treatment. The time during which the embryo transfer catheter remains in the cervical canal might be related to stimulation of contractions. This study investigates the influence that the time interval before withdrawal of the catheter after ultrasound (US)-guided embryo deposit might have on the pregnancy rate in patients under IVF cycles. A total of 100 women about to undergo transfer of at least two optimal embryos was studied. The women were prospectively randomized into two groups: (i) slow withdrawal of the catheter immediately after embryo deposit (n = 51); and (ii) a 30 s delay before catheter withdrawal (n = 49). The pregnancy rates for transfer in the two groups were 60.8 and 69.4% respectively, with no significant differences. There were no statistically significant differences in pregnancy rates between the two patient groups. The results indicate either that the waiting interval was insufficient to detect differences, or that the retention time before withdrawing the catheter is not a factor that influences pregnancy rate.

Adult↗
PubMed2001

Assessment of hematologic progenitor engraftment by complete reticulocyte maturation parameters after autologous and allogeneic hematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Hematopoietic restoration after marrow ablation is initiated by the erythroid compartment. However, the absolute microscope counts or corrected percentage of reticulocytes have proven to be poor markers of hematopoietic engraftment. Some reports have highlighted the usefulness of automatic flow cytometry methods to determine highly fluorescent reticulocytes, or mean fluorescence index. In this series of 60 hematopoietic stem cell transplants, we sought the normal kinetics throughout the post-transplant period of the following reticulocyte maturing parameters: highly fluorescent reticulocytes (RETH), immature reticulocyte fraction (IRF), mean fluorescence index (MFI) and also mean reticulocyte volume (MRV). DESIGN AND METHODS: Sixty consecutive patients undergoing allogeneic bone marrow (30 cases) and autologous mobilized stem cell transplantation (30 cases) were studied. Parameters of reticulocyte maturation were measured every other day from the beginning of the conditioning regimen until myeloid engraftment. RESULTS: Nadir values for the analyzed reticulocyte parameters were found between days +4 and +7 and thereafter, increases in these reticulocyte parameters appeared earlier than the rise in neutrophils. We considered erythroid engraftment to have occurred on the day when RETH reached 3%, IRF 10%, MFI 10 and MRV 110 fL. These cut-offs were assigned considering the 25% quartile for each parameter on the day that the myeloid engraftment occurred. The median engraftment days for RETH were +9 and +16, for IRF +9 and +13, for MFI +9 and +13 and for MRV +11 and +13 in autologous and allogeneic procedures, respectively. When compared to standard neutrophil engraftment, IRF and MFI engraftment occurred significantly earlier in all patients. Remarkably, we found a statistical correlation between the day a reticulocyte parameter reached its cut-off and the subsequent day of absolute neutrophil count (ANC) recovery for MFI after allogeneic transplants and for MRV after autologous procedures (p < 0.001 and p= 0.02, respectively). Of all the clinical parameters tested, only the number of infused CD34 cells showed a statistical influence on erythroid engraftment in autologous transplant. INTERPRETATION AND CONCLUSIONS: Early reticulocytes appear sooner than neutrophils after both autologous and allogeneic transplants, and any determined reticulocyte parameter can reliably measure this fraction. Nevertheless, our results show that MRV and MFI cut-offs are useful for determining subsequent myeloid engraftment. These findings could be relevant to decision-making in those patients with primary graft failure heralded by an absence of increasing values of MFI and MRV, indicating very low production of reticulocytes from the graft, who could, therefore, benefit from earlier rescue therapy.

Adolescent↗
PubMed2001

New mutations in exon 28 of the von Willebrand factor gene detected in patients with different types of von Willebrand's disease.

BACKGROUND AND OBJECTIVES: von Willebrand's disease (vWD), the most common hereditary bleeding disorder in humans, is caused by qualitative and/or quantitative deficiencies of von Willebrand factor, and can manifest itself under several different phenotypes. Most of the molecular defects have been detected in qualitative variants involving exon 28 of the vWF gene. Patients from four unrelated families with different types of vWD were included in the mutation screening of this region. DESIGN AND METHODS: The whole exon 28 was analyzed in three gene specific fragments, two of them comprising the region involved in the platelet glycoprotein Ib vWF interaction. The search for mutations was carried out by single-stranded conformation polymorphism analysis. The mutations were then identified by automatic sequencing of the anomalous electrophoretic pattern samples. RESULTS: The following candidate mutations were detected. The 3941T-->A transversion, which predicts the amino acid change V1314D, was detected in a sporadic patient with type 2B vWD and severe thrombocytopenia. The 4309G-->A transition, resulting in the amino acid substitution A1437T, was identified in four patients classified as having type 2M vWD. Six unclassified patients from another family carry the 4135C-->T mutation, which gives rise to a cysteine instead of the normal arginine (R1379C) that segregates with the phenotype. The amino acid change C1227R, predicted by the mutation 4135C-->T, was identified as a compound heterozygote in a patient with moderately severe type 1 vWD. None of these mutations had been described previously. INTERPRETATION AND CONCLUSIONS: These findings confirm the importance already given to this region for the correct function of von Willebrand factor since the mutations detected, which affect the D3 and A1 domains, could give rise to different variants of the disease.

Child↗
PubMed2000

Protein Adsorption and Deposition onto Microfiltration Membranes: The Role of Solute-Solid Interactions.

The mass of gamma-globulin fouling an Anodisc alumina membrane with a nominal pore diameter of 0.1 µm has been measured at several concentrations and pHs. This fouling resulted from filtering through the membrane in a continuous recirculation device. The low-concentration fouling can be attributed mainly to adsorption. The complete concentration dependence of fouling mass has been obtained and fitted to a Freundlich heterogeneous isotherm, from which the pH dependence of active fouling sites and energies has been also obtained. Adsorption is studied as a function of the electrostatic forces between the solute and the membrane. A sharp maximum in the adsorbed mass for zero electrostatic force is observed. At high concentrations, accumulation plays a relevant role at alkaline pH, as confirmed by flux decay experiments, retention measurements, and AFM (atomic force microscopy) pictures. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Q1311X: a novel nonsense mutation of putative ancient origin in the von Willebrand factor gene.

Type 3 von Willebrand disease, a recessive autosomally inherited bleeding disorder, refers to complete deficiency of von Willebrand factor (VWF). The novel Q1311X mutation was detected in the homozygous state in four Spanish patients from two apparently unrelated families of gypsy origin. The lack of specific amplification of platelet VWF cDNA from two of the patients indicates reduced levels of mutated gene expression. The similar haplotype linked to mutated alleles suggests a common origin. On the basis of the two instabilities observed and the estimated mutation rate of the microsatellites of intron 40 of the VWF gene, we can estimate that this mutation could have arisen about 2300 years ago.

Codon, Nonsense↗
PubMed2000

A trypsin-sensitive protein is required for utilization of exogenous cholesterol for pregnenolone synthesis by placental mitochondria.

The utilization of cholesterol for steroid hormone synthesis by human placental mitochondria is poorly understood. The human placenta does not express the steroidogenic acute regulator protein, which is critical for cholesterol delivery to the cholesterol side chain cleavage system in adrenal and gonadal mitochondria. We explored the mechanism underlying cholesterol transport in human placental mitochondria by measuring its transformation into pregnenolone. Mitochondria of syncytiotrophoblast from human term placenta were isolated by centrifugation through a sucrose gradient. The synthesis of pregnenolone in the presence of exogenous cholesterol was increased two-fold in syncytiotrophoblast mitochondria. Treatment of mitochondria with trypsin prevented the increase in the synthesis of pregnenolone in the presence of exogenous cholesterol. However, when 22-OH cholesterol, a substrate that readily crosses membranes, was added, the trypsin-treated mitochondria synthesized increased amounts of pregnenolone. The trypsin-treated mitochondria were intact, since oxygen consumption, succinate dehydrogenase and the adenine nucleotide translocase activities were not significantly different from in untreated mitochondria. However, activity of NADH cytochrome c oxidoreductase, an outer mitochondrial membrane enzyme, was reduced in the trypsin-treated mitochondria, reflecting the selective degradation of proteins. In addition, SDS-PAGE analysis revealed the loss of a prominent 34 kDa band which proved to be a novel porin-like protein that binds to cholesterol. These results support our previous assumption that human placental mitochondria employ a novel protein(s)-mediated the mechanism to take up cholesterol for steroidogenesis.

Amino Acid Sequence↗
PubMed2000

Haemophilia B in a female caused by skewed inactivation of the normal X-chromosome.

Hemophilia B (factor IX deficiency) is an X-linked recessive disorder with a prevalence of 1:30,000 male births, which rarely affects females. A missense mutation T38R (6488C>G) of the factor IX (FIX) gene was characterized in a young female with moderate-to-severe hemophilia B. She is heterozygous for this mutation, which she inherited from her carrier mother. Analysis of the methyl-sensitive HpaII sites in the first exon of the human androgen-receptor locus indicated a de novo skewed X-chromosomal inactivation. This indicates that the paternal X-chromosome carrying her normal FIX gene is the inactive one, which has led to the phenotypic expression of hemophilia B in this patient.

Dosage Compensation, Genetic↗
PubMed1999

[Multiple endocrine neoplasia type 1: genetic study of a large family].

Multiple endocrine neoplasia syndrome type 1 (MEN-1) is an inherited disorder characterised by the predisposition of the cells from parathyroid glands, endocrine pancreas and adenohypophysis to develop neoplasms. We report the genetic study of an extended family with at least 8 affected patients and 10 putative carriers of a mutation in MEN-1 gene. One intragenic (Asp418 GAC-->GAT), and five flanking markers were characterised in the family by PCR amplification and polyachrylamide gel electrophoresis. Association of the disease to MEN-1 gene was confirmed for this family: all the affected members show a haplotype in common. Three patients at risk were diagnosed as non-carriers, since they have not inherited that haplotype. The remaining seven members, presymptomatic carriers, are included in a follow-up protocol. The genetic study of families segregating MEN-1 syndrome are useful in avoiding indiscriminate follow-up determinations to those members who have not received the genetic predisposition to develop any of the manifestations of the syndrome. Segregation analysis with linked markers is useful, under certain circumstances, to perform such type of studies.

Biomarkers, Tumor↗
PubMed1999

Enhancement of resistance in mice treated with Lactobacillus casei: effect on Trichinella spiralis infection.

The ability of viable Lactobacillus casei, administered by an intraperitoneal route, to induce resistance in mice against Trichinella spiralis infection was tested. The percent reduction of adult worms in the intestine 5 days after T. spiralis infection observed in L. casei-treated animals, compared with those of the control group, fluctuated between 70.9 and 88.5%; reductions of larvae per gram of muscle tissue, evaluated at 30 days after infection, varied from 46.6 to 84.4% in L. casei-treated mice compared with controls. At 5 days after infection, intestinal villus height was shorter in T. spiralis-infected animals than in L. casei-treated or uninfected mice. There were fewer mast cells/crypt unit in L. casei-treated and uninfected mice than in T. spiralis-infected animals. Lactobacilli-treated mice showed twice as many mononuclear cells/crypt unit as T. spiralis-infected animals. The IFN-gamma serum level was higher in L. casei-treated animals at the time of worm challenge as compared with T. spiralis-infected or uninfected mice. The results indicate that: (1) L. casei increased resistance that acted against T. spiralis infection in mice, (2) this resistance apparently was directed against adult worms in the intestine.

Animals↗
PubMed1999

Identification of a new candidate mutation, G1629R, in a family with type 2A von Willebrand disease.

Type 2A is a qualitative variant of von Willebrand disease (vWD) characterized by a reduced platelet-dependent function, associated with an absence of large multimers. A G5135A transition, resulting in a glycine to arginine substitution at the codon 1629 of the von Willebrand factor, was identified by automated sequencing in one type 2A vWD Spanish patient. To detect this new candidate mutation a modified primer that creates a Ddel restriction site when the mutation is present was designed. This approach allowed detection of the mutation in the other three patients from the same family. On the other hand, the fact that this new mutation was not found in the 110 normal alleles screened further supports their causal relationship with the disease.

Arginine↗
PubMed1999

An alternative model for the transmembrane segments of the yeast H+-ATPase.

An alternative topological model for the yeast plasma membrane H(+)-ATPase from K. lactis was deduced by joint prediction, using 11 algorithms for the prediction of transmembrane segments complemented with hydrophobic moment analysis. Similarly to the model currently used in the literature, this alternative model contains 10 transmembrane segments, four in the N-half and six in the C-half of the protein. However, the distribution of the membrane-associated segments on the C-half of the enzyme differs in both models. Nine of the 10 transmembrane segments are highly hydrophobic with low hydrophobic moments, and are probably involved in structural roles. The fifth transmembrane segment is, on the other hand, less hydrophobic, with the highest hydrophobic moment, suggesting that this segment might have a dynamic role in the coupling of the hydrolysis of ATP with the translocation of protons across the membrane. The alignment of the Ca(2+)-ATPase, the Na(+)/K(+)-ATPase and the H(+)-ATPase sequences showed that these proteins have the same topology in the N-half, but important differences were found at the C-half of the enzymes. In contrast with the mammalian ATPases, the fifth transmembrane segment in the H(+)-ATPase appears early in the sequence, giving rise to a shorter cytoplasmic central loop. This alternative model will be useful in the designing of site-directed mutagenesis experiments and contains information for the fitting of the amino acid sequence into the transmembrane region of the three-dimensional model of the ATPase.

Algorithms↗
PubMed1999

High lovastatin doses combined with hypercholesterolemic diet induce hepatic damage and are lethal to the CD-1 mouse.

The addition of 1% lovastatin (LVT) to hypercholesterolemic diets [1% cholesterol or 1% cholesterol plus 0.1% sodium deoxycholate (HD)] induced hepatic damage and was lethal to CD-1 mice in the first days of treatment; the females were more resistant than males. LVT or HD administered alone was harmless to male or female mice. After a 3-day treatment all groups that received LVT (1%, 0.1% or 0.05%) plus HD showed a higher percentage of liver weight, with respect to whole body weight. Cholesterol serum levels increased in males with HD, but remained low in female mice. In the liver, total lipids and cholesterol levels increased in male mice with HD, but cholesterol remained unchanged in females. The addition of LVT to HD prevented the increase of serum and liver cholesterol levels in male mice. These results allow us to propose the CD-1 male-mouse as a model to evaluate the toxicity of LVT or other vastatins.

Animals↗
PubMed1999

Comparative toxicity of high doses of vastatins currently used by clinicians, in CD-1 male mice fed with a hypercholesterolemic diet.

The CD-1 male-mouse model was employed to evaluate comparatively the toxicity of four vastatins (VTS) currently used in clinical medicine: lovastatin (LVT), simvastatin (SVT), pravastatin (PVT) and fluvastatin (FVT). Each vastatin was used orally in doses of 500 mg/Kg body weight/day, in animals with a hypercholesterolemic diet (HD) 5 days, or with a control diet (CD) 30 days. The association of high doses of VTS + HD produced a significant increase in liver weight and liver weight to body weight ratio in animals with SVT and FVT. Cholesterol (Chol) and triacylglycerols (TAG) in the liver increased significantly with FVT but not with the other VTS; Chol increased and TAG decreased in serum very significantly with FVT and SVT. The serum aminotransferases increased quite significantly with FVT but not with other VTS. In the experiment with high doses of VTS + CD, the animals receiving SVT or FVT showed a moderate loss of body weight. Liver weight and liver weight to body weight ratios were similar among all groups. Liver Chol showed a significant decrease with all VTS. Serum Chol decreased moderately with LVT and FVT. TAG in serum and liver showed a moderate decrease with all VTS. The serum aminotransferases were not modified by any vastatin. Our results indicate that high doses of VTS in male mice with a hypercholesterolemic diet result in a decreasing toxicity as follows: FVT>SVT>LVT>PVT.

Animals↗