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Biomedical subjects

M Concha

Publications and source records attributed to M Concha.

At least 19 recordsLinked to original sources
PubMed2003

Evidence for modulation of human epidermal differentiation and remodelling by CD40.

BACKGROUND: It is widely accepted that CD40 plays a critical role in the regulation of immune response. However, the significance of CD40 expression on normal human keratinocytes is only partially known. OBJECTIVES: To perform a morphological re-examination of the role of CD40 on the differentiation of human keratinocytes and remodelling of the epidermis. METHODS: Keratinocytes were grown on fibroblasts transfected with the CD40 ligand (CD40L) to investigate the formation of epidermal sheets in culture under the influence of the CD40L. Control experiments were carried out using the same cells but transfected with CD32. Further, three specific anti-CD40 monoclonal antibodies were used as soluble agonists to analyse the effect of CD40 ligation on keratinocyte differentiation. RESULTS: Epidermal sheets developing from keratinocytes cocultured with fibroblasts transfected with CD40L but not with CD32 showed an up to 50% reduction in thickness compared with control sheets. This change depended mostly on cellular flattening and a decrease in the number of cell layers, and was coincident with a transient decrease in cell surface CD40 immunoreactivity. On the other hand, normal epidermis, and freshly isolated and cultured keratinocytes revealed a predominant CD40+/Ki-67- phenotype that was demonstrated by double immunocytochemistry. Consistent with these observations, keratinocytes primed with interferon-gamma responded to the three soluble agonists, but not to control IgG1, producing immunoreactive (pro)filaggrin and displaying morphological changes in shape and size equivalent to those seen in differentiated cells. CONCLUSIONS: As a whole, our findings provide evidence that CD40+ keratinocytes represent a poorly differentiated population, not actively engaged in the cell cycle, which under specific stimulation is committed towards terminal differentiation.

Antibodies, Monoclonal↗
PubMed2003

Topotecan in the treatment of acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) affects about 1 in 20 individuals with the acquired immunodeficiency syndrome (AIDS) and has been associated with poor survival. This report describes the results of a phase II clinical trial using the drug topotecan, a semisynthetic analogue of camptothecan, administered to a cohort of subjects with AIDS-related PML. Data were evaluated on 11 of 12 subjects enrolled in the study. Three responded to therapy. Additionally, one patient was treated off-protocol and showed a response to treatment. Progression occurred after the first course; however, a partial response was noted after five courses. One study patient died from accidental overdose of topotecan. Overall, responders had higher pretreatment Karnofsky and lower Kurtzke expanded disability status scale scores than nonresponders. The most frequent toxicities were hematologic (anemia, neutropenia, and thrombocytopenia). Five patients had dose delays; all delays were due to hematologic adverse events. This study demonstrates that topotecan treatment may be associated with decreased lesion size and prolonged survival from the infection. Because of the small number of subjects in the study, further studies are required to evaluate the efficacy of topotecan in treating this disease.

Acquired Immunodeficiency Syndrome↗
PubMed2001

[Clinical Characteristics and Evolution of Recurrent Infectious Endocarditis in non Drug Addicts].

INTRODUCTION AND OBJECTIVES: Recurrence of infection is observed in a high proportion of patients who have had infective endocarditis in the past. The aim of our study was to evaluate the possible differences between the first and the recurrent episodes of endocarditis, as well as to assess the outcome and prognosis of patients with recurrent endocarditis. PATIENTS AND METHOD: We reviewed a series of 13 episodes of recurrent endocarditis from among 196 cases of infective endocarditis involving non-drug-addict patients in two hospitals from 1987 to 2000. RESULTS: There were no differences between recurrent and first episodes of endocarditis according to age, sex, heart valve involved or causal microorganisms. Prosthetic valve endocarditis was more common in patients with recurrent endocarditis (86% versus 27%; p < 0.001). Although there were no differences in the rate of complications or early surgery, overall mortality was significantly higher in patients with recurrent endocarditis (53% versus 27%: p < 0.05). When early and late mortality were analysed separately, the differences did not achieve significance. CONCLUSIONS: Recurrent endocarditis was frequent in our series (7% of all cases). The features were similar to those of the first episode except for a higher rate of prosthetic valve endocarditis and a higher overall mortality.

Endocarditis, Bacterial↗
PubMed2001

Aging and neuro-AIDS conditions and the changing spectrum of HIV-1-associated morbidity and mortality.

Older individuals (>50 years of age) now comprise over 11% of patients with AIDS in the United States. This percentage is expected to continue to grow, due both to the improved longevity of patients prescribed highly active antiretroviral therapy (HAART) and to new infections among older individuals. This review focuses on the neuropsychiatric and neurological conditions that are most likely to be affected by advancing age-HIV-1-associated cognitive-motor disorder, peripheral neuropathy, progressive multifocal leukoencephalopathy, primary CNS lymphoma, and risk for cerebrovascular accident. Age associations with incidence of these disorders and with treatment foci are specified. Implications for future changes in management are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Anticoagulation and microembolus detection in a case of internal carotid artery dissection.

BACKGROUND: Microembolic signals (MES) have been demonstrated by transcranial Doppler (TCD) in cases of internal carotid artery dissection. The influence of treatment on MES in arterial dissection is uncertain. The authors here present a case of internal carotid artery dissection in which we detected a reduction of MES after the initiation of intravenous heparin. METHODS: A 37-year-old woman developed a right temporal headache 10 days prior to admission. This was followed by episodes of left arm numbness and weakness. Magnetic resonance imaging (MRI) showed a right frontal and deep subcortical ischemic infarct. Catheter angiography confirmed a right internal carotid artery dissection with intracranial extension. She was then monitored with TCD for MES before and after intravenous heparin was started. RESULTS: The first TCD, performed 12 days after symptom onset, showed 39 MES during 60 minutes of insonation of the right middle cerebral artery. Treatment with intravenous heparin resulted in a decline in MES by 50% after 96 hours. This decline continued and no further MES were detected after 11 days of anticoagulation. CONCLUSION: The authors were able to demonstrate a decline of MES with heparin anticoagulation in a case of internal carotid artery dissection.

Adult↗
PubMed2001

Left ventricular remodeling after pulmonary autograft replacement of the aortic valve (Ross operation).

BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement (AVR) with a pulmonary autograft is an alternative treatment for young patients with aortic valve disease. Superior hemodynamic performance of the pulmonary autograft, and impact on parameters of left ventricular function were analyzed. METHODS: Thirty patients (21 males, nine females; mean age 29.97+/-12.29 years; range: 6-54 years) underwent a Ross procedure between November 1997 and November 1999. Seven patients (23%) were children (aged <15 years). In total, 22 patients were analyzed; each had at least three months follow up. Eleven patients had predominant aortic stenosis (AS), and 11 had aortic insufficiency (AI). RESULTS: There were no operative deaths. Two patients developed severe insufficiency, and the autograft was replaced with a mechanical valve. Pre- and postoperative echocardiograms were reviewed. The mean neoaortic maximal gradient was 7.85+/-5.59 mmHg (range: 3-29 mmHg). AS patients showed reduced interventricular septal (IVS) thickness at one month (from 13.27+/-3.69 to 11.60+/-2.44 mm; p = 0.0165) and 18 months after surgery (p = 0.0104). Left ventricular posterior wall (LVPW) thickness was reduced from 12.04+/-3.75 to 9.48+/-2.47 mm (p = 0.0338) at one month and 18 months (p= 0.0128) after surgery. The left ventricular end-diastolic internal dimension (LVIDd) decreased from 50.71+/-10.20 to 44.98+/-7.29 mm (p = 0.0491) at one month after surgery. In AI patients, LVPW and IVS thicknesses showed no significant variation, and LVIDd was decreased at one month (from 68.50+/-8.39 to 59.04+/-9.21 mm; p = 0.0017) and 18 months (p = 0.0229) after surgery. Left ventricular end-systolic internal dimension (LVIDs) decreased from 44.06+/-6.39 to 39.03+/-7.99 mm (p = 0.0081) at three months after surgery. Left ventricular mass index (LVMI) in the AS group decreased from 179.01+/-62.26 to 115.74+/-37.62 g/m2 (p = 0.0021) at one month after surgery, and at 18 months was normal, with a decrease from 208.77+/-32.89 to 95.89+/-28.82 g/m2 (p= 0.0003) (n = 5). In the AI group, LVMI decreased from 186.25+/-85.21 to 140.58+/-62.02 g/m2 (p = 0.0011) at one month after surgery, and at 18 months from 217.70+/-98.02 to 146.73+/-84.55 g/m2 (p= 0.0131) (n = 5). CONCLUSION: The pulmonary autograft procedure can be used safely to replace the aortic valve, and allows optimal hemodynamic performance, with no significant aortic regurgitation. The Ross procedure results in normalization of left ventricular dimensions and improvement of left ventricular function early in the postoperative period.

Adolescent↗
PubMed2001

Behavior of the pulmonary autograft in systemic circulation after the Ross procedure.

OBJECTIVE: The purpose of this study was to evaluate performance in systemic circulation following pulmonary autograft aortic root replacement by means of serial postoperative echocardiographic studies. METHODS: From November 1997 to November 1999, 30 patients (21 males, 9 females) with a mean age of 29.97 +/- 12.97 years (age range 6-54 years) underwent pulmonary autograft aortic root replacement. Seven of these patients (23.33%) were less than 15 years old. Postoperative echocardiographic measurements of the neo-aortic root were performed within three months of operation, at six months, one year, and annually thereafter. Analysis of this study includes 22 patients with at least three months of follow-up. RESULTS: Operative mortality was 0%. Compared with preoperative values, the mean autograft annulus diameter exhibited an increase of 8.44% in the first month (1.44 +/- 0.22 cm/m2 vs. 1.55 +/- 0.21 cm/m2, p = 0.0101). An additional aortic annular dilation of 11.33% from baseline preoperative values was observed within the first year (1.41 +/- 0.15 cm/m2 preoperatively vs. 1.57 +/- 0.22 cm/m2, p = 0.0449). After the immediate postoperative period, the pulmonary autograft seemed to adapt to systemic circulation, and there were no differences in aortic annular size between 1-3 months after surgery and the 18-21 month follow-up period (1.60 +/- 0.18 cm/m2 vs. 1.60 +/- 0.27 cm/m2, n = 10). Diameter increase was not associated with the presence of aortic regurgitation. Mean neo-aortic maximal gradient was 7.85 +/- 5.59 mm Hg (3-29 mm Hg). There was a significant decrease in left ventricular size three months after surgery (50.71 +/- 10.20 mm preoperatively vs. 44.98 +/- 7.29 mm, p = 0.0491 in aortic stenosis patients and 68.50 +/- 8.39 mm vs. 59.04 +/- 9.21 mm, p = 0.0017 in aortic insufficiency patients). CONCLUSIONS: Pulmonary autograft annulus increases up to the first year after the Ross procedure but does not appear to progress beyond that time. The pulmonary autograft allows optimal hemodynamic performance without causing substantial aortic regurgitation, thereby permitting normalization of left ventricular dimensions and improvement of left ventricular function early in the postoperative period.

Adolescent↗
PubMed2000

Horseradish peroxidase binding to intestinal brush-border membranes of Cyprinus carpio. Identification of a putative receptor.

Morphologic studies have shown that the classic endocytosis tracer horseradish peroxidase (HRP) is actively internalized by vesicular transport in the carp intestine, suggesting the existence of specific binding sites in the apical membrane of enterocytes. The aim of the present study was to develop an in vitro binding assay using isolated carp intestinal brush-border membranes (BBM) to demonstrate and characterize these specific HRP binding sites. The results obtained show that HRP binding to BBM exhibits a saturable mode and high affinity (K(d) = 22 nM). In addition, HRP binding sites are highly enriched in BBM compared to basolateral membranes. On the other hand, HRP interaction with these sites is apparently of an ionic character because binding increased concomitantly with decreasing NaCl concentrations in the assay, reaching a maximum in the absence of NaCl. Other proteins that are also internalized in carp intestine did not significantly inhibit HRP binding to BBM. A lectin-type of interaction was discarded because neither manan nor ovoalbumin inhibited HRP binding. Proteinase K treatment of BBM reduced HRP binding by 70%, suggesting a proteic nature for this binding site. Finally, ligand blotting assays showed that HRP binds specifically to a 15.3-kDa protein. Taken together, these results are consistent with the existence of a functional receptor for HRP in carp intestinal mucosa that could mediate its internalization.

Animals↗
PubMed2000

Intramucosal gastric pH during liver transplantation.

Intramucosal gastric pH (pHi) was measured during liver transplantation in a 3-year-old girl. The basal value was below that reported as normal for paediatric patients under stable normal ventilatory and haemodynamic conditions. Additional reductions of the pHi were observed during the hepatectomy and anhepatic phase, in the absence of haemodynamic or ventilatory alterations. The reperfusion phase was characterized by a progressive return toward normal values. Because we did not measure oxygen delivery and consumption, we cannot determine whether the reduction of the pHi was due to insufficient oxygen delivery or a result of the vascular anatomical alterations due to the surgical procedure.

Child, Preschool↗
PubMed2000

CD40 ligation alters the cell cycle of differentiating keratinocytes.

CD40 is expressed in normal human keratinocytes, especially in the basal cell layer. We have recently reported that CD40 ligation strongly inhibits keratinocyte proliferation and induces their differentiation. In this study, the CD40 pathway that prevents keratinocyte growth was investigated. We first reported that interferon-gamma treatment potentiated the CD40-mediated inhibition of keratinocyte proliferation. CD40-CD40 ligand interactions, in the presence or absence of interferon-gamma, neither enhanced spontaneous keratinocyte apoptosis, nor did it enhance apoptosis induced by various agents. More importantly, we showed that CD40 signaling altered the keratinocyte cell cycle, as demonstrated by a decreasing number of cells in the G1 and S phases and an accumulation in G2/M phase of the cell cycle. Furthermore, western blot analysis of cell cycle regulatory proteins, showed a decrease in cyclin A and E expression in CD40-activated keratinocytes. Collectively, these results indicate that CD40 ligation inhibits keratinocyte renewal by a mechanism independent of cell apoptosis and that modulation of the keratinocyte cell cycle is an additional outcome of CD40 signaling.

Apoptosis↗
PubMed2000

Long term outcome of infective endocarditis in patients who were not drug addicts: a 10 year study.

OBJECTIVE: To determine the clinical features and long term prognosis of infective endocarditis in patients who were not drug addicts. DESIGN: Prospective case series. SETTING: A university hospital that is both a referral and a primary care centre. PATIENTS: 138 consecutive cases of infective endocarditis diagnosed and treated from January 1987 to March 1997. RESULTS: Mean patient age was 44 (20) years old. 95 patients (69%) had native valve endocarditis and 43 (31%) had prosthetic valve endocarditis. Staphylococci were the causal microorganisms in 34% of cases and streptococci in 33%. Severe complications occurred in 83% of patients and 51% of patients underwent surgery during the active phase (22% was emergency surgery). Inpatient mortality was 21%. During a follow up of 56 (44) months, 10 patients (9%) needed late cardiac surgery and seven (5% of the whole series) died. Overall 10 year survival was 71%. There were no significant differences in survival depending on the type of treatment received during the hospital stay (medical or combined medical-surgical). CONCLUSIONS: A high early surgery rate is related to good long term results and does not increase in-hospital mortality. Medical treatment, however, also offers favourable long term results in cases of responsive infective endocarditis where poor prognostic factors are absent.

Adult↗
PubMed2000

[Aortic valve replacement with pulmonary autograft (the Ross procedure) in adult and pediatric patients].

Aortic valve replacement with pulmonary autograft was first performed by Donald Ross in 1967. Initially, the procedure was not widely accepted, by Cardiologists and Cardiac surgeons fundamentally due to its complexity and demanding surgical technique, and because innumerous series two cardiac valves were at risk. The results published in the last 10-15 years established the pulmonary autograft as one of the best methods of aortic valve replacement, especially in pediatric patients and young adults. In the present article, we reviewed present indications and contraindications, and our clinical experience with 26 patients (pediatrics and adults). Analysis of the first 22 the patients with a minimum of 6 months of follow-up (180-620 days) was performed. Follow-up is complete (100%). Mean age was 31.4 +/- 12.6 years. Five patients were pediatrics (<= 14 years). Three patients (11%) with previous percutaneous procedures and 4 patients (14%) with previous surgical procedures. There was no early or late mortality. In the last follow-up, 19 of 22 (86.36%) had no autograft insufficiency (>= grade 1), and in one patient it was moderate (grade 2). The 2 remaining patients developed severe autograft insufficiency (grade 4) and were reoperated on, with satisfactory postoperative outcome. Mean maximal gradient was 7.85 +/- 5 mmHg at 18 months (3-29). Patients with preoperative aortic stenosis showed a significant reduction in myocardial mass index (208.7 +/- 32 a 95.8 +/- 28.8 g/m2) at 18 months. In these patients, septal and posterior wall thickness decreased significantly, in the first month. Two pediatric patients have developed transpulmonar gradient > 50 mmHg. One of them underwent successful stent implantation. We have not observed significant homograft insufficiency in any of our patients. All our patients remain asymptomatic (functional class I) without medical treatment. We have not observed either thromboembolic or haemorrhagic episodes, nor endocarditis. No patient is receiving anticoagulants. Clinical and echocardiographic mid term results in pulmonary autograft and homograft in our series, are excellent after the Ross procedure.

Adult↗
PubMed1999

[Aortic valve replacement with a pulmonary autograft (the Ross operation) in adult and pediatric patients. A preliminary study].

INTRODUCTION AND OBJECTIVES: Aortic valve replacement with the patients own pulmonary autograft (the Ross procedure) is by now, the best surgical method for the replacement of the diseased aortic valve in certain groups of patients, this is particularly true for young adults and children or neonates with complex left ventricular outflow tract obstructions. The procedure was described by Donald Ross in 1967, and many years have passed. So in view of the accumulated experience the indications have extended to a wide group of patients which include children, neonates and young adults with formal contraindications for anticoagulation. In this publication we present our experience and our preliminary results in a group of fifteen patients which include adult and pediatric. MATERIAL AND METHODS: In six patients the etiology of lesion was congenital and in the remainder nine the valve had an acquired lesion. Two patients had an open heart procedure before this operation both of them to relieve an obstruction to the left ventricular outflow tract. In this group of patients the Ross procedure was carried out inserting the pulmonary autograft in the aortic position as a total root which was always reconstructed with cryopreserved pulmonary homograft, the mean homograft diameter was 26.1 +/- 4 mm (19-35). RESULTS: In all patients a transesophageal echocardiogram was performed in the operating room and postoperative, 1 or 2 months later. Only in one patient a mild aortic regurgitation was detected, no significant transaortic or transpulmonary gradients were detected postoperative. One patient was reoperated for bleeding in the postoperative course, there was no hospital mortality in our group and all the patients had an uneventful postoperative period. In the short term follow-up (41-155 days). All the patients are free of anticoagulant therapy, all them are in New York Heart Association Functional Class I. CONCLUSIONS: The patients presented in this publication which include adult and pediatric, are the first group of patients operated in our country with some excellent preliminary results. We hope that this procedure will become popular and that other surgical groups will adopt it as another surgical tool to replace a diseased aortic valve.

Adolescent↗
PubMed1998

[Influence of genetic variation at apoprotein A-1 gene promoter region on plasma lipid levels in heart transplantation patients].

BACKGROUND: To study if the presence of the G/A polymorphism at the apo A-I gene promoter region could determine the lipid profile in patients with hyperlipidemia after heart transplantation, or if it is related with the type of heart disease that determined the transplantation. PATIENTS AND METHODS: This study included 31 patients with hyperlipidemia after heart transplantation. Anthropometric parameters, basic analytic and lipid study were measured in these subjects. Identification of the G/A mutation in the promoter region of the apo A-I gene was performed. RESULTS: 22 patients had the G/G genotype and 9 the G/A. 14 were transplanted by coronary heart disease and 17 by non ischemic heart disease. Patients with the A allele had higher cHDL (63 [SD 15] vs 53 [10]; p = 0.034) and apo A-I plasma levels (156 [34] vs 132 [24]; p = 0.040) than G/G subjects. The A allele was present in the 18% of the patients transplanted by ischemic heart disease and in the 43% of the transplanted by another etiology (p = 0.073). CONCLUSIONS: The presence of the G/A genotype in the promoter region of the apo A-I gene determines higher plasma levels of cHDL in patients with hyperlipidemia after heart transplantation.

Adult↗
PubMed1998

Effects of CD40 ligation on human keratinocyte accessory function.

CD40/CD40 ligand interactions are known to play a key role in the development of immune reactions, especially by enhancing the costimulatory function of professional antigen-presenting cells (APC). Little is known, however, about the role this receptor plays on occasional APC, i.e. cells that are induced to express MHC class II molecules following an inflammatory process. In this study, we used CD40 ligand-transfected cells to analyze the effect of CD40 ligation on the phenotype, as well as accessory function, of human keratinocytes. We found that CD40 ligation enhanced ICAM-1 expression and did not upregulate HLA-DR, CD80 or CD86 expression on IFN-gamma-treated keratinocytes. CD40 triggering was not sufficient to generate primary allogeneic T-cell responses even in the presence of anti-CD28 monoclonal antibody (mAb). Moreover, CD40 ligation, in the presence or not of IFN-gamma, did not alter the accessory function of keratinocytes in PHA- or superantigen-induced T-cell activation. The lack of effect on the T-cell response was confirmed in blocking experiments using anti-CD40 mAbs. Collectively, these results suggest that CD40-CD40 ligand interactions on nonprofessional APC may amplify the inflammatory reaction without providing a mitogenic signal to the T cells.

3T3 Cells↗