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Biomedical subjects

P Morales

Publications and source records attributed to P Morales.

At least 19 recordsLinked to original sources
PubMed2006

Plasticity of the central nervous system (CNS) following perinatal asphyxia: does nicotinamide provide neuroprotection?

We have investigated the idea that nicotinamide, a non-selective inhibitor of the sentinel enzyme Poly(ADP-ribose) polymerase-I (PARP-1), provides neuroprotection against the long-term neurological changes induced by perinatal asphyxia. Perinatal asphyxia was induced in vivo by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Sibling caesarean-delivered pups were used as controls. The effect of perinatal asphyxia on neurocircuitry development was studied in vitro with organotypic cultures from substantia nigra, neostriatum and neocortex, platted on a coverslip 3 days after birth. After approximately one month in vitro (DIV 25), the cultures were treated for immunocytochemistry to characterise neuronal phenotype with markers against the N-methyl-D-aspartate receptor subunit 1 (NR1), the dopamine pacemaker enzyme tyrosine hydroxylase (TH), and nitric oxide synthase (NOS), the enzyme regulating the bioavailability of NO. Nicotinamide (0.8 mmol/kg, i.p.) or saline was administered to asphyctic and caesarean-delivered pups 24, 48 and 72 h after birth. It was found that nicotinamide treatment prevented the effect of perinatal asphyxia on several neuronal parameters, including TH- and NOS-positive neurite atrophy and NOS-positive neuronal loss; supporting the idea that nicotinamide constitutes a therapeutic alternative for the effects produced by sustained energy-failure conditions, as occurring during perinatal asphyxia.

Animals↗
PubMed2006

Perioperative complications of lung transplantation in patients with emphysema and fibrosis: experience from 1992-2002.

UNLABELLED: Our objective was to describe the incidence of perioperative complications of lung transplantation among patients with emphysema and fibrosis and the morbidity and mortality risk factors. MATERIALS AND METHODS: We performed a retrospective study of 111 lung transplant patients engrafted from 1992 to 2002 for emphysema (n = 65) or lung fibrosis (n = 46). This descriptive study included the most frequent complications during the perioperative period in the intensive care unit. RESULTS: The most frequent intraoperative complications were reperfusion syndrome, hemodynamic instability, and cardiac arrhythmias. Among patients with emphysema, the follow-up of postoperative complications proved statistically significant on univariate analysis for an association of patient mortality with prolonged intubation (P = .005), rejection (P = .0001), hemorrhage (P = .0001), sepsis (P = .0001), renal failure (P = .001), and implantation response (P = .014). Mortality among these patients was 16.9%. Mechanical ventilation for over 48 hours and postoperative hemorrhage were the variables with the greatest predictive value for mortality in the postoperative period. Among patients with fibrosis, the complication-related mortality were reperfusion syndrome (P = .039), implantation response (P = .039), renal failure (P = .013), rejection (P = .016), and sepsis (P < .001). The mortality rate was 23.9% with sepsis (P = .000) being the most frequent cause of death in the immediate postoperative period. CONCLUSIONS: The most frequent intraoperative complications were reperfusion syndrome and hemodynamic instability. The most frequent postoperative complications were implantation response, sepsis, prolonged intubation, hemorrhage, and renal failure.

Emphysema↗
PubMed2006

Interpreting post-transplant proteinuria in patients with proteinuria pre-transplant.

Increasing numbers of patients receive kidney transplants before initiation of dialysis or shortly thereafter. Some of these patients have significant proteinuria pre-transplant making the interpretation of post-transplant proteinuria problematic. In this study, we evaluated post-transplant proteinuria in 115 patients who had urine protein measured within 3 months of transplant and assessed the association of proteinuria with allograft pathology. Proteinuria declined rapidly from 3650 +/- 3702 mg/day pre-transplant to 550 + 918 at 3 weeks (p < 0.0001) and continued to decline until 1 year post-transplant (472 +/- 1116, p < 0.0001 vs. 3 weeks). Proteinuria greater than 3000 mg/day was present in 48 patients (42%) pre-transplant, in 1 patient (1%) at 3 weeks and in 4 patients (4%) at 1 year. Surveillance graft biopsies were done at 1 year in 93% of patients. Proteinuria > or = 1500 mg/day and/or an absolute increase in proteinuria > 500 mg/day after 3 weeks post-transplant was associated with allograft glomerular pathology. In conclusion, pre-transplant proteinuria, even when high grade, declines rapidly after transplantation. Failure to decline or persistence of proteinuria greater than 1500 mg/day is indicative of allograft pathology.

Adolescent↗
PubMed2005

Effects of perinatal asphyxia on cell survival, neuronal phenotype and neurite growth evaluated with organotypic triple cultures.

The effect of perinatal asphyxia on brain development was studied with organotypic cultures from substantia nigra, neostriatum and neocortex. Asphyxia was induced by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Following asphyxia, the pups were nursed by a surrogate dam and sacrificed after three days for preparing organotypic cultures. Non-asphyxiated caesarean-delivered pups were used as controls. Morphological features and cell viability were recorded during in vitro development. At day in vitro (DIV) 24, the cultures were treated for immunocytochemistry using antibodies against the N-methyl-D-aspartate receptor subunit 1 (NR1) and tyrosine hydroxylase (TH). While in vitro survival was similar in cultures from both asphyxiated and control animals, differences were observed when the neuronal phenotype was assessed. Compared to controls, the total number of NR1-positive neurons in substantia nigra, as well as the number of secondary to higher level branching of TH-positive neurites from asphyxiated pups were decreased, illustrating the vulnerability of the dopaminergic systems to perinatal asphyxia.

Animals↗
PubMed2005

Effects of perinatal asphyxia on cell proliferation and neuronal phenotype evaluated with organotypic hippocampal cultures.

The present report summarizes studies combining an in vivo and in vitro approach, where asphyxia is induced in vivo at delivery time of Wistar rats, and the long term effects on hippocampus neurocircuitry are investigated in vitro with organotypic cultures plated at postnatal day seven. The cultures preserved hippocampus layering and regional subdivisions shown in vivo, and only few dying cells were observed when assayed with a viability test at day in vitro 27. When properly fixed, cultures from asphyxia-exposed animals showed a decreased amount of microtubule-associated protein-2 immunocytochemically positive cells (approximately 30%), as compared with that from controls. The decrease in microtubule-associated protein-2 immunocytochemistry was particularly prominent in Ammon's horn 1 and dentate gyrus regions (approximately 40%). 5-Bromo-2'deoxyuridine labeling revealed a two-fold increase in cellular proliferation in cultures from asphyxia-exposed, compared with that from control animals. Furthermore, confocal microscopy and quantification using the optical disector technique demonstrated that in cultures from asphyxia-exposed animals approximately 30% of 5-bromo-2'deoxyuridine-positive cells were also positive to microtubule-associated protein-2, a marker for neuronal phenotype. That proportion was approximately 20% in cultures from control animals. Glial fibrillary acidic protein-immunocytochemistry and Fast Red nuclear staining revealed that the core of the hippocampus culture was surrounded by a well-developed network of glial fibrillary acidic protein-positive cells and glial fibrillary acidic protein-processes providing an apparent protective shield around the hippocampus. That shield was less developed in cultures from asphyxia-exposed animals. The increased mitotic activity observed in this study suggests a compensatory mechanism for the long-term impairment induced by perinatal asphyxia, although it is not clear yet if that mechanism leads to neurogenesis, astrogliogenesis, or to further apoptosis.

Animals↗
PubMed2005

Lymphoproliferative disease after lung and heart-lung transplantation: first description in Spain.

Lymphoproliferative syndromes are the most common tumors in transplant recipients. More than 90% of posttransplantation lymphoproliferative syndromes (PTLS) are considered to be associated with Epstein-Barr virus, and 86% are of the B-cell line. Histopathology ranges from polymorphic-reactive to monomorphic forms. Clonality should be studied using molecular biology techniques. Clinically, a differentiation is usually made between early PTLS (occurring within 1 year after transplantation) and late PTLS, which occur as localized or disseminated nodal lymphomas. In localized forms, immunosuppression should be discontinued or decreased, and the involved area should be subsequently resected or irradiated. In disseminated cases, immunosuppression should be decreased and administration of acyclovir/ganciclovir should be considered. If this is not effective, treatment should be started with anti-CD20 monoclonal antibodies (rituximab). If no response occurs, use of chemotherapy, possibly with interferon, should be considered. Our aim was to report the incidence, clinical signs, and treatment in a series of patients undergoing lung transplantation (LTx).

Adolescent↗
PubMed2005

Pulmonary tuberculosis in lung and heart-lung transplantation: fifteen years of experience in a single center in Spain.

The increase in the number of solid organ transplants has resulted in an increased incidence of opportunistic infections, including infection by typical and atypical mycobacteria, with risk of developing tuberculosis. Pretransplant chemoprophylaxis with isoniazid has become increasingly common in an attempt to prevent the disease. The source of infection in tuberculosis (TB) may be difficult to identify. Infection may be caused by reactivation of a primary infection in the recipient, reactivation of a lesion from the donor lung, or primary infection. There are few reports on TB in lung transplantation. Incidence in the reported series ranges from 6.5% to 10%. Our series of 7 patients out of a total 271 patients (2.58%) represents a rate higher than reported for the general Spanish population, 26.7/10(5) inhabitants and for lung transplant candidates (0.18%). Our aim was to evaluate the incidence, clinical signs, and outcome of TB in our series of patients undergoing lung transplantation in the 15 years since inception of the program (February 1990 to December 2004). Morbidity and mortality was high (42.8%), but limited to patients in whom treatment was not administered or could not be successfully completed. However, early detection and treatment are essential.

Adult↗
PubMed2005

MHC-F DNA sequences in bonobo, gorilla and orangutan.

The major histocompatibility complex (MHC)-F class Ib locus shows a limited polymorphism, and the function of its mainly intracellular protein is not clear. We have identified human leucocyte antigen (HLA)-F orthologous DNA sequences in Pongidae in order to study the MHC-F gene evolution and its products' function. HLA-F orthologous cDNA transcripts are found in chimpanzee and in the new primate species studied (bonobo, gorilla and orangutan). Analyses of the predicted amino acid sequences and their comparison with other primate MHC-F proteins show that MHC-F may be a protein with a typical class I structure and that the key residues of the peptide-binding region (PBR) are highly conserved in MHC-F in all studied primates species. Thus, MHC-F conservation along the primate evolution suggests an important role in cellular physiology. It is possible that the MHC-F protein could be involved, together with MHC-G and MHC-E, in the natural killer (NK) cell activity regulation, although rhesus macaque does not express MHC-G and MHC-E orthologues. The evolutionary pathway of the six-base-pair deletion at exon 2 existing in some primates is put forward.

Amino Acid Sequence↗
PubMed2005

Aspergillus infections in lung transplant recipients: risk factors and outcome.

This retrospective study of 251 lung transplant patients aimed to determine the prevalence, clinical presentation and mortality of Aspergillus infection in order to define specific risk factors and to compare survival in patients with and without infection. Aspergillus was isolated from 86 (33%) cases, which involved colonisation (n = 50), tracheobronchial lesions (n = 17) or invasive aspergillosis (n = 19). Overall, aspergillosis had an impact on survival (p < 0.05); in fact the 5-year mortality rate was substantially higher in single lung transplant recipients with bronchial anastomotic infection, and in those with late-onset infections and chronic rejection. A significant association (p < 0.05) was found between acute rejection and the time at which fungal infection was diagnosed. Aspergillus infection was not related to cytomegalovirus infection or treatment with corticosteroids. The mortality rate for invasive infections was 78% and was related to survival (p < 0.0001); invasive aspergillosis was also associated with chronic rejection (p < 0.05), but not with high corticosteroid doses (p 0.49) or use of tacrolimus (p 0.73). In conclusion, Aspergillus infection was associated with a reduction in the 5-year survival rate of lung transplant recipients, and this was particularly true for patients infected with the invasive forms and for patients with single lung transplants, bronchial anastomotic infection and chronic rejection. Isolation of Aspergillus spp. from respiratory samples preceded acute rejection, and may be a marker of graft dysfunction and/or airway inflammation. Close monitoring, or even pre-emptive antifungal therapy, is recommended for patients with chronic rejection or bronchial airway mechanical abnormalities and persistent Aspergillus colonisation.

Aspergillosis↗
PubMed2005

[Microscopic polyangiitis in a patient with rheumatoid arthritis].

Rheumatoid arthritis (RA) is a systemic disorder that primary involves joints, although renal disease has also been associated it is not common that rapidly progressive glomerulonephritis (RPGN) appears. We report the case of a patient with nodular and aggressive RA who had an acut renal failure secondary to ANCA positive RPGN due to a Microscopic polyangiitis who was not responsive to steroids and cyclophosphamide therapy.

Acute Kidney Injury↗
PubMed2004

Safety of the concomitant use of caspofungin and cyclosporin A in patients with invasive fungal infections.

Caspofungin, an echinocandin antifungal agent, is active against invasive Aspergillus and Candida infections. In a phase I study in healthy volunteers, mild transient increases in serum aminotransferases were observed with the concomitant administration of caspofungin and cyclosporin A (CsA). As a result, it is recommended that the concomitant use of the two drugs be limited to those settings with appropriate risk-benefit balance. We retrospectively assessed safety data in 14 patients with refractory invasive mycoses who were treated concomitantly with CsA and caspofungin before the drug was licensed in Spain. In all, 13 patients were adults (median age, 31.5 years; range, 14-67 years). The average duration of concomitant therapy was 15 days (range, 2-43 days). No clinically significant elevations of serum aminotransferases were observed, and no patient had concomitant therapy discontinued or interrupted due to a drug-related adverse event. In this study of a limited number of patients, the coadministration of caspofungin and CsA was generally well tolerated.

Adolescent↗
PubMed2004

Comparison of two techniques to evaluate the acrosomal status of zona pellucida bound sperm in humans.

In this work, we have compared two procedures that evaluate the acrosomal status of human sperm bound to the human zona pellucida. Motile sperm, selected by a Percoll gradient, were capacitated by incubation at 37 degrees C, 5% CO2, for 4.5 h, at 20 x 10(6) cells ml(-1). Then, the sperm were incubated with nonviable human oocytes for 10 min at 37 degrees C, 5% CO2. The oocytes with bound sperm were transferred to 500 microl phosphate-buffered saline (PBS) and washed to remove loosely bound sperm. The oocytes were then processed according to the procedures of Cross et al. (1986) or Liu & Baker (1996). In the Cross's procedure, the sperm were labelled while they were bound to the zona. In the Liu's procedure, the sperm were first dislodged from the zona into a droplet of PBS and labelled in there. Both procedures gave equivalent percentages of acrosome-reacted sperm. However, the total number of zona-bound sperm available for assessment with the procedure of Liu & Baker was greater than that of Cross et al. We suggest to use the former procedure to evaluate the acrosomal status of zona-bound sperm in humans. Moreover, this procedure also provided information about sperm ability to bind to the zona pellucida.

Acrosome Reaction↗
PubMed2003

Perinatal asphyxia impairs connectivity and dopamine neurite branching in organotypic triple culture from rat substantia nigra, neostriatum and neocortex.

The effect of perinatal asphyxia on brain development was studied with organotypic cultures from substantia nigra, neostriatum and neocortex. Asphyxia was induced by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Following asphyxia, the pups were nursed by a surrogate dam and sacrificed after 3 days to prepare organotypic cultures. Non-asphyxiated caesarean-delivered pups were used as controls. Morphological features were recorded during in vitro development. At day in vitro (DIV) 24, the cultures were treated for histochemistry using fast red for cell nucleus labelling and antibodies against tyrosine hydroxylase for dopaminergic neurons. Compared to controls, cultures from asphyxiated pups revealed a diminished integration quantified during 21 DIV. After immunocytochemistry and camera lucida reconstruction, tyrosine hydroxylase-positive neurons showed a decreased number of neurites from secondary and higher level branching, demonstrating a vulnerability of the dopaminergic systems after perinatal asphyxia.

Animals↗
PubMed2003

Visceral leishmaniasis in lung transplantation.

Infection by intracellular microorganisms with a special geographic distribution, such as Leishmania spp, has been reported in a limited number of patients undergoing solid-organ transplant (SOT). No cases of Leishmania spp infection in lung transplant patients were found in a review of the literature. In our series of 222 lung or heart and lung transplantations performed from February 1990 to October 2002, two cases of visceral leishmaniasis (VL) were diagnosed and treated with liposomal amphotericin B. All cases reported to date in transplant patients, including the ones discussed here, occurred in people living in or traveling to countries in the Mediterranean area. We therefore consider it advisable to include serological testing for latent infection due to Leishmania spp in pretransplantation screening for our geographical setting, despite the limited return of this strategy.

Adult↗
PubMed2003

Cardiopulmonary transplantation: experience of a lung transplant group.

Cardiopulmonary transplantation (CPT) is indicated for patients eligible for heart transplantation (HT) or lung transplantation (LT) who have severe concomitant lung or heart disease. Only 2 groups perform CPT in Spain. We report our experience with 18 CPTs representing 8.2% and 5% compared with LT (220) and HT (362), respectively, from February 13, 1990 to October 15, 2002. The mean time on a waiting list was 138 days. The current number of surviving patients is 7 (39%), with a mean follow-up of 602 days (range, 3 to 4627 days). They all remain asymptomatic with normal respiratory function in 4 patients. No cardiac graft rejection has been detected. Two patients experienced sustained gastroparesis during the first year with spontaneous resolution. Death occurred within the first 3 months in 9 patients. These outcomes contrast with the early mortality associated with LT and HT in our series, namely 10.6% and 11%, respectively. The different causes of death were as follows: sepsis and multiorgan failure in 5 patients, hemorrhagic shock in 3 patients, and suture dehiscence and fungal aortic perforation in 1 patient. Late mortalities were recorded in 2 cases. Overall patient survival in our series is lower than that reported by the International Registry (IR), with an early mortality rate of 50% (30% IR). Nevertheless, our survival rate at 10 years after transplantation is 30% (26% IR). We conclude that CPT should be considered despite the greater early morbidity and mortality.

Adolescent↗
PubMed2003

Lung transplantation in patients with x-linked agammaglobulinemia.

Lung transplantation is an established procedure to treat patients with end-stage lung disease. The criteria for recipient selection are broadening to include patients with congenital defects of the immune system, such as X-linked hypogammaglobulinemia (XLA). We report 2 cases of successful double lung transplantation in patients with XLA. The 2 men had developed bronchiectasis and end-stage lung disease despite early institution of intravenous immunoglobulin (IVIG) replacement therapy. Before transplantation, hypogammaglobulinemia was well controlled with IVIG in both patients. After transplantation, IVIG was administered every 48 hours during the first 10 days and then tapered slowly in the following weeks until returning to an every 3 weeks schedule. One patient has been followed up for 12 months and the other for 6 months. Lung function normalized in the first case and showed a restrictive pattern in the second one. Lung transplantation may be considered as a therapeutic option for patients with XLA and end-stage lung disease. Regular administration of IVIG overcomes the high risk of infections due to the severe immunodeficiency and the intensive immunosuppressive therapy.

Adult↗