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Biomedical subjects

V Fernandez

Publications and source records attributed to V Fernandez.

At least 19 recordsLinked to original sources
PubMed2005

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Adult↗
PubMed2005

Validation of IC-VIEW fluorescence videography in a rabbit model of mesenteric ischaemia and reperfusion.

BACKGROUND/AIMS: Mortality in mesenteric ischaemia can be reduced by an optimised extent of resection. Up to now, no technique supplementing a surgeon's experience has achieved clinical acceptance. Besides a qualitative interpretation, the new technique of computer-assisted laser-fluorescence videography affords quantification of staining intensities. The aim of this study was to investigate the scientific value of this technique in mesenteric ischaemia in a rabbit model of controlled mesenteric ischaemia and reperfusion. METHODS: We used an established rabbit model of mesenteric ischaemia (group I, n=6) and reperfusion (group II, n=6). In each animal, three loops (each of 10 cm) of the small intestine were clamped (group I, 40 min; group II, 60 and 20 min reperfusion). For further evaluation, all loops were divided into five segments of 2 x 2 cm (total number of investigated areas, n=180). Measurement of vascular patency was performed by laser-fluorescence videography (pixel intensity per second). As standard, we used radioactive microspheres (impulse per minute per gram). In addition, the extent of ischaemic tissue damage was identified by histological examination. Statistical data were analysed by using regression analysis to define the regression coefficient r. RESULTS/FINDINGS: Laser-fluorescence videography and the microsphere technique demonstrated a close and linear correlation: ischaemic segments, r=0.90+/-0.07; reperfusion segments, r=0.85+/-0.02; overall, r=0.92+/-0.07. There was no reproducible correlation to cellular damage in histology. INTERPRETATION/CONCLUSION: Computer-assisted laser-fluorescence videography is a feasible, reliable, and valid experimental method for the detection of mesenteric blood supply and intestinal microcirculation. Clinical application is conceivable in mesenteric ischaemia and infarction as well as the operative transposition of intestine. As limiting values to identify the irreversible necrosis are not yet defined, further studies have to analyse the clinical impact more precisely.

Animals↗
PubMed2003

[Ileocecal invagination due to a benign small intestine tumor. A case report].

We report a case of postoperative ileocecal invagination in a 63-year-old male. Forty-six days after esophageal resection and gastric tube reconstruction with cervical anastomosis for an esophageal carcinoma, the patient suffered from colicky pain in the right abdomen. The diagnostics showed an ileocecal invagination up to the right flexure of the colon. The invagination was based on a leiomyoma of the terminal ileum. Because of necrosis of the mucous membrane, an ileocecal resection with ileoascendostomy could not be avoided. We discuss this case on the basis of the existing literature.

Humans↗
PubMed2001

Role of nonimmune IgG bound to PfEMP1 in placental malaria.

Infections with Plasmodium falciparum during pregnancy lead to the accumulation of parasitized red blood cells (infected erythrocytes, IEs) in the placenta. IEs of P. falciparum isolates that infect the human placenta were found to bind immunoglobulin G (IgG). A strain of P. falciparum cloned for IgG binding adhered massively to placental syncytiotrophoblasts in a pattern similar to that of natural infections. Adherence was inhibited by IgG-binding proteins, but not by glycosaminoglycans or enzymatic digestion of chondroitin sulfate A or hyaluronic acid. Normal, nonimmune IgG that is bound to a duffy binding-like domain beta of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) might at the IE surface act as a bridge to neonatal Fc receptors of the placenta.

Animals↗
PubMed2001

[Cognitive deficits after polytrauma. Studies of quality of life].

The aim of this study was to quantify and compare the quality of life after multiple trauma for patients with and without posttraumatic cognitive achievement deficits. We examined 173 multiple trauma patients 2-6 years after their injury. The patients were asked to rate their quality of life according to the established measure scales Nottingham Health Profile, Spitzer Index, Everyday Life Questionnaire, to a visual analogue scale and to the new "revised Aachen Longterm Outcome Score" established in our hospital. To evaluate the cognitive achievement of each patient the "Kognitive Minimal Screening" (KMS) was applied. Statistical calculations result cognitive achievement deficits as a highly significant predictor for quality of life after multiple trauma. In spite of this, the craniocerebral trauma is no global predictor of posttraumatic quality of life. These results show that the quality of life after multiple trauma is not only influenced by approved predictors such as injury severity but also significantly by the presence of cognitive achievement deficits. The KMS seems to be an easy test to evaluate those cognitive deficits.

Activities of Daily Living↗
PubMed2001

Intravascular injections of a conditional replicative adenovirus (adl118) prevent metastatic disease in human breast carcinoma xenografts.

We describe a study showing that the adenovirus adl118, lacking both E1B proteins, very efficiently kills human malignant cells 'in vitro' and 'in vivo'. Since many breast cancer patients do not have metastasis at the time of diagnosis, but finally develop it, we planned to study whether intravascular injections of adl118 could prevent metastatic development. We studied the effects of this mutant adenovirus in an orthotopic model of human breast carcinoma xenografts with the breast MB435-lung 2 cell line, which is highly metastatic in the lungs. In this study, all primary tumors were excised when they reached 50-100 mm3 volume in the animals. After surgery, 10(10) p.f.u. of adl118 was intravenously injected into a random group of animals, either three times during the first week only, or once every week. At death, almost all the control animals showed numerous lung metastases of large size, which were present in only 15-40% of the treated animals, depending on the size of the primary tumor at the time of excision. Overall survival was 50-70 days in control mice, and over 120 days in mice injected with adl118. Concomitant treatment with adl118 and cisplatin did not enhance the antitumor effects of adl118. With these results, we conclude that intravenous injection of conditional replicative adenovirus, after excision of the primary tumor, induces a clear decrease in the metastatic disease, and could be a new strategy in preventing tumor metastasis of breast carcinomas.

Adenoviridae↗
PubMed2001

Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats.

In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg. kg(-1). day(-1) sc), or food restriction (HF-FR) for 12-15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulin-stimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic beta-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.

3-O-Methylglucose↗
PubMed2001

Binding of Plasmodium falciparum-infected erythrocytes to soluble platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): frequent recognition by clinical isolates.

Platelet-endothelial cell adhesion molecule-1 or CD31 (PECAM-1/CD31) is a receptor recognized by Plasmodium falciparum-parasitized erythrocytes (pRBCs). Fluorescence-labeled soluble recombinant PECAM-1/CD31 (sPECAM-1/CD31) is shown to bind to the surface of P. falciparum-infected erythrocytes on up to 70% of the cells. Binding is blocked by the addition of the unlabeled receptor in a dose-dependent fashion, but not by unrelated receptor-proteins. A significant correlation was found between the binding of sPECAM-1/CD31 to pRBCs and the binding to transfected L cells expressing the receptor as seen with six different P. falciparum lines or clones. Panning of cultures on PECAM-1/CD31 transfected L cells was paralleled by an increase in the binding of sPECAM-1/CD31. The pRBCs of 54% of fresh patient-isolates bound sPECAM-1/CD31 with a mean rate of 12.9% (range = 1.1-44%). The data suggest that PECAM-1/CD31 is a common receptor recognized by wild isolates and that the soluble PECAM-1/CD31 suspension assay is a sensitive and reliable way to study PECAM-1/CD31 binding.

Animals↗
PubMed2000

The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors.

Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36. DBL2delta was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.

ABO Blood-Group System↗
PubMed2000

The duffy-binding-like domain 1 of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a heparan sulfate ligand that requires 12 mers for binding.

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surfaces of parasitized red blood cells (pRBC), mediates rosetting, a virulent phenotype. Here, we show that pRBC specifically bind heparan sulfate (HS) and heparin onto their surfaces and that the rosetting ligand PfEMP1 specifically adheres to heparin-Sepharose when extracted from the surfaces of radioiodinated infected RBC. An analysis of the binding properties of the different regions of PfEMP1 provides evidence that the Duffy-binding-like domain-1 (DBL-1) is the predominant ligand involved in HS and heparin binding. Soluble DBL-1 requires a minimal heparin fragment size of a 12-mer ( approximately 4 kd) for binding and is critically dependent on N-sulfation. A 12-mer is also the minimal heparin fragment that disrupts naturally formed rosettes. DBL-1 binds specifically to erythrocytes and also to HS from endothelial cells and human aorta but not to chondroitin sulfate A, suggesting that different PfEMP1s mediate adhesion to distinct glycosaminoglycans in individual malaria parasites. Present data suggest that HS on endothelial cells may also be involved in the sequestration of pRBC. Elucidation of these binding mechanisms opens up new possibilities for therapeutic strategies targeting adhesive interactions of pRBC.

Animals↗
PubMed2000

[Large flank tumor after covered gallbladder perforation].

We report on a 79-year-old woman patient with a tumor with a diameter of 18 cm in the right flank. The medical history of the patient was normal except for a single asymptomatic gallstone, which had been known since 12 years. Sonography and abdominal CT showed an enormous intra-abdominal mass filled with liquid with a permanent union with the gallbladder. We than performed an explorative laparotomy with a tumor resection and a cholecystectomy. The histological examination showed perforation of the gallbladder with a great pseudocyst filled with 1800 ml infected bile and with penetration through the abdominal wall.

Aged↗
PubMed2000

[Determinants of the global quality of life after polytrauma].

This study investigated multiple trauma patients, who were injured between 1991 and 1995 and treated in our department. The aim of this study was to identify the determinants of quality of life after multiple trauma. From a total of 186 patients 173 (93%) were examined. The patients were asked to rate their quality of life according to the Nottingham Health Profile (NHP) and to a visual analogue scale (VAS). The VAS and the NHP isolated the age of the patients, the duration of artificial respiration, and the duration of rehabilitation as the predictors for a reduced overall quality of life. These results show that quality of life after multiple trauma not only depends on the severity of injury but also on demographic and psychosocial factors.

Adolescent↗
PubMed1999

Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses.

Disease severity in Plasmodium falciparum infections is a direct consequence of the parasite's efficient evasion of the defense mechanisms of the human host. To date, one parasite-derived molecule, the antigenically variant adhesin P. falciparum erythrocyte membrane protein 1 (PfEMP1), is known to be transported to the infected erythrocyte (pRBC) surface, where it mediates binding to different host receptors. Here we report that multiple additional proteins are expressed by the parasite at the pRBC surface, including a large cluster of clonally variant antigens of 30-45 kD. We have found these antigens to be identical to the rifins, predicted polypeptides encoded by the rif multigene family. These parasite products, formerly called rosettins after their identification in rosetting parasites, are prominently expressed by fresh isolates of P. falciparum. Rifins are immunogenic in natural infections and strain-specifically recognized by human immune sera in immunoprecipitation of surface-labeled pRBC extracts. Furthermore, human immune sera agglutinate pRBCs digested with trypsin at conditions such that radioiodinated PfEMP1 polypeptides are not detected but rifins are detected, suggesting the presence of epitopes in rifins targeted by agglutinating antibodies. When analyzed by two-dimensional electrophoresis, the rifins resolved into several isoforms in the pI range of 5.5-6.5, indicating molecular microheterogeneity, an additional potential novel source of antigenic diversity in P. falciparum. Prominent polypeptides of 20, 22, 76-80, 140, and 170 kD were also detected on the surfaces of pRBCs bearing in vitro-propagated or field-isolated parasites. In this report, we describe the rifins, the second family of clonally variant antigens known to be displayed by P. falciparum on the surface of the infected erythrocyte.

Amino Acid Sequence↗
PubMed1999

Effects of mild protein prenatal malnutrition and subsequent postnatal nutritional rehabilitation on noradrenaline release and neuronal density in the rat occipital cortex.

There is evidence that severe malnutrition started during gestation and continued through lactation affects adversely the morphologic development of the neocortex leading to increased neuronal cell packing density and decreased dendritic branching. Nevertheless, the effect of purely mild protein prenatal malnutrition on neocortical development remains rather unexplored. This study evaluates the effects of mild protein prenatal malnutrition (8% casein diet, calorically compensated by carbohydrates) and subsequent postnatal nutritional rehabilitation (25% casein diet) on: (i) the potassium-induced release of [(3)H]-noradrenaline (NA) in occipital cortex slices obtained from 1- and 22-day-old pups; and (ii) the packing density of neurons in lateral, dorso-lateral and dorsal regions of the occipital cortex of 22-day-old pups by using the optical dissector method. The experiments were performed in rats normally fed during gestation and lactation (G(+)L(+)), malnourished during gestation but rehabilitated during lactation (G(-)L(+)) and malnourished during gestation and lactation (G(-)L(-)). At day 1 of age, no significant differences in body and brain weights were observed between prenatally well-nourished and malnourished pups. Nevertheless, at this early age, pups born from mothers submitted to the 8% casein diet had significantly higher cortical net percent NA release than pups born from mothers receiving the 25% casein diet. At weaning (22 days of age) G(-)L(+) rats had, compared to the G(+)L(+) group, similar body weight, brain weight and [(3)H]-NA release values, but significantly higher neuron density scores in the lateral region of the occipital cortex. In contrast, at 22 days of age, G(-)L(-) rats exhibited, compared to G(+)L(+) animals, significant deficits in body and brain weights as well as significant increases in cortical net percent NA release together with enhanced packing density of neurons in the lateral, dorso-lateral and dorsal regions of the occipital cortex. Moreover, in G(-)L(-) animals was not found the laterodorsal histogenetic gradient of neuronal cell packing density observed in G(+)L(+)rats. Results suggest that mild prenatal malnutrition per se is able to induce deleterious effects on cortical neuronal density, in spite of nutritional rehabilitation during lactation, through a mechanism involving central NA hyperactivity during gestation. Prosecution of malnutrition after birth magnifies both neurochemical and morphometric disorders.

Analysis of Variance↗
PubMed1999

Acceptability of two spermicides in five countries.

Data from a large, international, multicenter, randomized trial were analyzed to compare the acceptability of two nonoxynol-9 spermicide preparations. Women who wished to use a spermicide for contraception were randomly assigned to use either a foaming tablet (n = 383) or a nonoxynol-9 film (n = 382) for 28 weeks as their only method of contraception. Participants completed questionnaires about acceptability of the assigned product 4 weeks after admission and at discontinuation. Women in both groups had very favorable opinions of the spermicide. The proportion of women who said that they liked their assigned product very much was 50% in the tablet group and 55% in the film group. Significantly more women in the film group rated the spermicide difficult to insert and stated that the product stuck to the finger during insertion. More women in the tablet group said that the product was messy and that, at least once, it did not dissolve. In both groups, liking the product was significantly associated with consistency of use, but not with subsequent pregnancy. Participants' male partners had little influence on participants' opinions about, or use of, the spermicides. Although previous analyses showed that both spermicides are associated with high pregnancy rates, they are both highly acceptable to most women.

Adolescent↗
PubMed1999

An association between viral genes and human oncogenic alterations: the adenovirus E1A induces the Ewing tumor fusion transcript EWS-FLI1.

Malignant transformation of human cells requires the accumulation of multiple genetic alterations, such as the activation of oncogenes and loss of function of tumor suppressor genes or those related to genomic instability. Among the genetic alterations most frequently found in human tumors are chromosomal translocations that may result in the expression of chimeric products with transforming capability or are able to change the expression of oncogenes. We show here that the adenovirus early region 1A (E1A) gene can induce a specific human fusion transcript (EWS-FLI1) that is characteristic of Ewing tumors. This fusion transcript was detected by RT-PCR in normal human fibroblasts and keratinocytes after expression of the adenovirus E1A gene, as well as in human cell lines immortalized by adenoviruses. Cloning and sequencing of the RT-PCR product showed fusion points between EWS and FLI1 cDNA identical to those detected in Ewing tumors. In addition, we detected a chimeric protein by western blot analysis and immunoprecipitation and a t(11,22) by fluorescent in situ hybridization. This association between a single viral gene and a specific human fusion transcript indicates a direct link between viral genes and chromosome translocations, one of the hallmarks of many human tumors.

Adenovirus E1A Proteins↗