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Biomedical subjects

M Valle

Publications and source records attributed to M Valle.

At least 19 recordsLinked to original sources

Traumatic lesions of adrenal glands in paediatrics: about three cases.

Pediatric adrenal injuries, in blunt thoracoabdominal trauma, are rare and usually associated with traumatic liver and kidney lesions. This paper aims to present imaging findings and possible adrenal involvement in blunt abdominal traumas in childhood. We report three cases of thoracoabdominal trauma with adrenal involvement. Two patients were polytraumatised in car accidents. The third case was unusual because of the mild trauma. The adrenals lesions were right-sided in all cases. Post-traumatic adrenal contusion/haematoma may arise not only because of a direct trauma but also as a consequence of a sudden increase in the pressure in the inferior vena cava system-adrenal veins. This is why adrenal haemorrhage is not directly proportional to the trauma: compression of the inferior vena cava leads to increased pressure in the adrenal venous circulation, which supports the parenchymal lesion. The right adrenal gland is more frequently injured than the left gland: it can be easily compressed between the liver, spine and kidney, and its venous drainage flows directly into the inferior vena cava.

Abdominal Injuries↗

Laparoscopic intraperitoneal hyperthermic chemotherapy for palliation of debilitating malignant ascites.

AIM: To report the use of laparoscopic Intraperitoneal Hyperthermic Chemotherapy (LIPHC) in the treatment of malignant ascites. METHODS: From September 2001 to December 2003, 14 patients between the age of 56 and 78years were treated. Ascites was from gastric cancer (5 cases), colorectal cancer (3 cases), ovarian cancer (3 cases), breast cancer (2 cases) and peritoneal mesothelioma (1 case). The LIPHC was carried out at 42 degrees C for 90 min with 1.5% dextrose solution as a carrier. Chemotherapy was cisplatin and doxorubicin or mitomycin depending on the type of primary tumor. The drains were left in situ after surgery and removed when perfuse drainage ceased. RESULTS: Ascites was controlled in all the treated cases. A CT scan performed in follow-up showed a small, clinically undetectable, fluid accumulation in the pelvis of one patient. CONCLUSIONS: This method resulted in benefit for those peritoneal carcinomatosis patients with debilitating malignant ascites who were excluded from cytoreductive surgery. Proficiency in laparoscopic staging procedures and experience in the management of carcinomatosis and intraperitoneal hyperthermic chemotherapy (IPHC) are required for the success of the procedure.

Aged↗

Quantifying drug-drug interactions in pharmaco-EEG.

A drug interaction refers to an event in which the usual pharmacological effect of a drug is modified by other factors, most frequently additional drugs. When two drugs are administered simultaneously, or within a short time of each other, an interaction can occur that may increase or decrease the intended magnitude or duration of the effect of one or both drugs. Drugs may interact on a pharmaceutical, pharmacokinetic or pharmacodynamic basis. Pharmacodynamic interactions arise when the alteration of the effects occurs at the site of action. This is a wide field where not only interactions between different drugs are considered but also drug and metabolites (midazolam/alpha-hydroxy-midazolam), enantiomers (ketamine), as well as phenomena such as tolerance (nordiazepam) and sensitization (diazepam). Pharmacodynamic interactions can result in antagonism or synergism and can originate at a receptor level (antagonism, partial agonism, down-regulation, up-regulation), at an intraneuronal level (transduction, uptake), or at an interneuronal level (physiological pathways). Alternatively, psychotropic drug interactions assessed through quantitative pharmaco-EEG can be viewed according to the broad underlying objective of the study: safety-oriented (ketoprofen/theophylline, lorazepam/diphenhydramine, granisetron/haloperidol), strictly pharmacologically-oriented (benzodiazepine receptors), or broadly neuro-physiologically-oriented (diazepam/buspirone). Methodological issues are stressed, particularly drug plasma concentrations, dose-response relationships and time-course of effects (fluoxetine/buspirone), and unsolved questions are addressed (yohimbine/caffeine, hydroxizyne/alcohol).

Brain↗

Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers.

OBJECTIVE: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzheimer's disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinal fluid (CSF) pharmacokinetics of the main active metabolite of triflusal-HTB (2-hydroxy-4-trifluoro-methylbenzoic acid)-in healthy volunteers. METHODS: Data from two studies were combined. Study A: subjects received single oral doses of triflusal 900 mg. Triflusal and HTB plasma concentrations were extensively measured. Study B: triflusal 600 mg once daily was administered orally for 14 days. HTB plasma and CSF concentrations were determined in healthy volunteers. Population pharmacokinetic modeling was performed using NONMEM. RESULTS: A one-compartmental model with rapid first-order absorption for triflusal and first-order formation of HTB best described plasma concentrations. Triflusal elimination rate constant was 50 times faster than that estimated for the metabolite. CSF concentrations of HTB ranged between 0.011 microg/ml and 0.341 microg/ml. A CSF-plasma partition coefficient of 0.002 and a k(e0) value of 0.059 h(-1) were estimated by means of population modeling. CONCLUSION: In the present study in healthy volunteers, HTB penetrated into the CSF in a range of concentrations experimentally proven to have protective effects in AD. These concentrations suggest that triflusal could be used in the treatment of central nervous system diseases in doses similar to those used in cardiovascular diseases. Access to the CSF compartment was characterized by a slow equilibrium rate constant and a low CSF-plasma partition coefficient.

Adult↗

Low-grade systemic inflammation, hypoadiponectinemia and a high concentration of leptin are present in very young obese children, and correlate with metabolic syndrome.

OBJECTIVE: To determine the concentration levels of C-reactive protein (CRP), leptin and adiponectin in obese pre-pubertal children, and their possible relation with metabolic syndrome, fibrinogen and plasminogen activator inhibitor-1. METHODS: A study was carried out in 51 obese children (aged 6 to 9 years) and the same number of non-obese children (control group), matched by age and sex. (Cross-sectional study of obese children). Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined for each child. Serum CRP, leptin, adiponectin, glucose, insulin, lipid profile, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were all measured. RESULTS: The levels of CRP serum (1.67+/-0.222 vs 0.92+/-0.16 mg/l) and leptin (15.56+/-1.27 vs 4.68+/-0.62 ng/ml) were significantly higher in obese children. The adiponectin level was significantly higher in non-obese children (11.58+/-0.63 vs 9.64+/-0.49 microg/dl). In the obese group, log. CRP showed a positive correlation with BMI, insulin, homeostasis model assessment (HOMA), triglycerides, alanine aminotransferase (ALT), uric acid, PAI-1, fibrinogen and interleukin 6 (IL-6), and correlated negatively with apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-C). The leptin was positively correlated with BMI, insulin, HOMA, triglycerides and PAI-1 and negatively with Apo A-I and HDL-C. Adiponectin correlated negatively with BMI, insulin, HOMA, and triglycerides. CONCLUSIONS: Low-grade systemic inflammation, elevated leptin concentration and low adiponectin level are described in very young obese children, correlating with a range of variables of metabolic syndrome. Inflammation and adipocytokines can play an important role in the etiopathogeny of metabolic syndrome.

Adiponectin↗

[Prognostic value of syncope in the presentation of pulmonary embolism].

OBJECTIVE: Although the prognostic value of syncope has not been specifically addressed, it has generally been considered an indicator of poor prognosis in pulmonary embolism. The objective of this study was to carry out a prospective evaluation of the risk of recurrence and/or death in patients with pulmonary embolism that presents with syncope. PATIENTS AND METHODS: A total of 168 patients had a confirmed diagnosis of pulmonary embolism. Twelve were lost to follow up and did not enter statistical analysis. The mean follow-up period was 5 months. RESULTS: The prevalence of syncope in the patients studied was 22%. Of the 34 patients who presented syncope, objectively confirmed recurrence occurred in 2 (5.9%). In the patients who did not present syncope, recurrence was confirmed in 8 (6.6%; P=.8). Death occurred in 2 patients (5.9%) from the group presenting syncope and 15 (12.3%) from the remaining patients in the series (P=.4). The relative risk of recurrence and/or death associated with presentation of syncope was 0.5 (95% confidence interval, 0.2-1.8). A similar risk was obtained following adjustment for the presence or absence of cancer or deep vein thrombosis. CONCLUSIONS: Patients with pulmonary embolism that presents with syncope do not have an increased risk of recurrence and/or death.

Aged↗

A seven-year survey of susceptibility to marbofloxacin of pathogenic strains isolated from pets.

This study, Vetoquinol S.A. epidemiosurveillance, was conducted from 1994 to 2001 in order to determine the susceptibility (by MIC determination) to marbofloxacin (a third generation fluoroquinolone used only in individual administration for animals). Strains from infected pets originated from six European countries. Isolates were collected from urinary infections (Escherichia coli), respiratory infections (Pasteurella multocida), dermatological infections (Staphylococcus intermedius, Pseudomonas aeruginosa) and otitis (S. intermedius, P. aeruginosa). The MIC distribution for each species was the same both before and after the launch of marbofloxacin in 1995. In E. coli, a resistant population was present before the use of marbofloxacin; this resistance was induced by co- or cross-resistance to other antibiotics used previously. Over this period, there was no significant evolution of MIC(90) for any bacterial species studied and no development of resistance was observed. Marbofloxacin was the most active antibiotic against P. multocida isolates and had the lowest MIC. No difference in MIC distribution was seen between the S. intermedius (unimodal distribution) isolated from dermatological infections and those from otitis. This was also true for P. aeruginosa. The use of marbofloxacin was not found to have induced a significant increase or spread of resistant bacteria.

Animals↗

Childhood obesity and hormonal abnormalities associated with cancer risk.

There is growing evidence that overweight and obesity increase the risk of certain cancers. Studies in adults support the role of insulin-like growth factors (IGFs) and oestrogens in the pathogeneses of several cancers. We propose that hormone alterations described as risk factors for cancer in obese adults are present in prepubertal obese children. A group of obese children aged 6-9 years (n=40), and control group paired for age and sex, were used for the study. The obese children presented a significantly high level of IGF-I (P=0.0173) and insulin (P=0.0250), with a drop in sex hormone-binding globulin (SHBG) (P=0.0282). The 17 beta-oestradiol (E2)/SHBG ratio increase in obese subjects was marginally significant (P=0.0635). Grouping together all the children in quartiles for insulin and body mass index, the upper quartiles showed a rise in IGF-I and E2/SHBG. In a multivariant correlation analysis, only height (partial r=0.2464) and insulin (partial r=0.3002) were independent prediction variables for IGF-I concentration. The only variables statistically correlated with the E2/SHBG ratio were insulin (r=0.2879) and IGF-I (r=0.4140). The obese children in our study showed hormone changes described as risk factors for cancer in obese adults. These changes were significantly associated with the hyperinsulinaemia. We hypothesize that this potential risk should be taken into account given the long period of exposure involved in the presence of hormone alterations at such early ages.

Adult↗

The seroepidemiology of herpes simplex virus type 1 and 2 in Europe.

OBJECTIVES: To describe the seroepidemiology of herpes simplex virus (HSV) types 1 and 2 in the general populations of eight European countries to better understand recent reported changes in disease epidemiology. METHODS: Belgium, Bulgaria, Czech Republic, England and Wales, Finland, Germany, Netherlands, and Slovenia conducted national cross sectional serological surveys for HSV-1 and HSV-2 between 1989 and 2000. Survey sizes ranged from 3000 to 7166 sera. External quality control was ensured through reference panel testing. RESULTS: Large intercountry and intracountry differences in HSV-1 and HSV-2 seroprevalence were observed. Age standardised HSV-1 seroprevalence ranged from 52% in Finland, to 57% in the Netherlands, 67% in Belgium, 81% in Czech Republic, and 84% in Bulgaria. Age standardised (>12 years) HSV-2 seroprevalence ranged from 24% in Bulgaria, to 14% in Germany, 13% in Finland, 11% in Belgium, 9% in Netherlands, 6% in Czech Republic, and 4% in England and Wales. In all countries, probability of seropositivity for both infections increased with age. A large proportion of teenagers and young adults remain HSV-1 susceptible particularly in northern Europe. Women were significantly more likely to be HSV-2 seropositive in six of seven (p<0.05) countries and HSV-1 seropositive in four of seven (p<0.05) countries, particularly in northern Europe. No significant evidence of a protective role of HSV-1 for HSV-2 infection was found adjusting for age and sex (p<0.05). CONCLUSIONS: There is large variation in the seroepidemiology of HSV-1 and HSV-2 across Europe. The observation that a significant proportion of adolescents are now HSV-1 susceptible may have implications for transmission and clinical presentation of HSV-1 and HSV-2.

Adolescent↗

Bile duct injuries during laparoscopic cholecystectomy: a 1994-2001 audit on 13,718 operations in the area of Rome.

BACKGROUND: Bile duct injuries (BDIs) during laparoscopic cholecystectomy (LC) still are reported with greater frequency than during open cholecystectomy (OC). METHODS: In 1999, a retrospective study evaluating the incidence of BDIs during LC in the area of Rome from 1994 to 1998 (group A) was performed. In addition, a prospective audit was started, ending in December 2001 (group B). RESULTS: In group A, 6,419 LCs were performed (222 were converted to OC; 3.4%). In group B, 7,299 LCs were performed (225 were converted to OC; 3.1%). Seventeen BDIs (0.26%) occurred in group A and 16 (0.22%) in group B. Overall, mortality and major morbidity rates were 12.1% and 30.3%, respectively, without significant differences between the two groups. CONCLUSIONS: The incidence and clinical relevance of BDIs during LC in the area of Rome appeared to be stable over the past 8 years and were not influenced by the use of a prospective audit, as compared with a retrospective survey.

Aged↗

[Ultrasonography of peripheral nerves].

With the recent advances in broadband transducer technology and refinements in scanning technique, an increasing number of nerves and related pathologic conditions are identified with sonography. High-resolution sonography can support clinical and electrophysiological testing for detection of a variety of nerve abnormalities, including entrapment neuropathies, traumas, infectious disorders, and tumors. In addition, procedures of regional anesthesia and percutaneous treatment of painful neuromas can be effectively guided by sonography in real time. This article addresses the normal US appearance of peripheral nerves and discusses the potential role of this technique to image nerve disorders in specific clinical settings.

Animals↗

Relationship between high plasma leptin concentrations and metabolic syndrome in obese pre-pubertal children.

OBJECTIVE: To evaluate the relationship between serum leptin levels and metabolic syndrome, fasting insulin level and anthropometric index in obese pre-pubertal children. DESIGN: A cross-sectional study was carried out on obese children. SUBJECTS: A study was made of 41 obese children (aged 6-9 y) and the same number of non-obese children (control group), matched by age and sex. METHODS: Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined in each child. Serum leptin, glucose, insulin, lipid profile, sex hormone binding globulin (SHBG), plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator (t-PA) and fibrinogen were all measured. RESULTS: The serum leptin level was significantly higher in obese children (15.47 vs 4.73 ng/ml). In the obese group, leptin showed a positive correlation with BMI (P<0.001), insulin (P<0.001), triglycerides (P<0.05), PAI-1 (P<0.05) and t-PA (P<0.05), and correlated negatively with SHBG (P<0.01), apolipoprotein A-I (P<0.05) and high-density lipoproteins cholesterol (HDL-C) (P<0.05). Corrected for BMI and WHR, leptin (P partial=0.002) is only an independent predictive factor for basal insulin. Using multivariant regression analysis, only insulin (P partial=0.003) and BMI (P partial=0.018) were independent predictive factors for leptin. CONCLUSION: For this age group, high leptin resistance may be another component of metabolic syndrome, and may be involved in its etiopathogenesis. The involvement of leptin in this syndrome may be indirect, modulating the insulin's action.

Body Mass Index↗

Primary brain CD30+ ALK1+ anaplastic large cell lymphoma ('ALKoma'): the first case with a combination of 'not common' variants.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are rare tumors, mostly represented by diffuse large B cells. PCNSLs with a T phenotype are less frequently reported; even rarer are anaplastic large cell lymphomas (ALCLs). PCNSL ALCLs are commonly represented, like their systemic counterpart, by a variably prevalent amount of large pleomorphic tumor cells ('hallmark cells'), and this feature enhances their recognition. Patient and methods We report the first case of primary brain CD30+ ALK-1+ ALCL with a T-cell phenotype, showing the combination of both the 'lymphohistiocytic' and the 'small cell' variants of the disease. A few elements consistent with 'hallmark cells' were recognizable. However, these cells were never prominent, increasing diagnostic difficulties. Immunohistochemistry results were critical for the correct interpretation. Our findings also differ from the majority of PCNSL ALCLs for the absence of tumor necrosis and the lack of prominent mitotic activity. The neuroimaging picture was not specific. A comparison with literature data concerning the clinical/instrumental features shows a very frequent meningeal involvement in PCNSL ALCLs, in contrast to the majority of PCNSLs. CONCLUSION: The occurrence of such a rare form of ALCL may widen the spectrum of differential diagnoses in PCNSL and their recognition may allow a rapid diagnosis, thus encouraging adequate treatment, which should take into account the high rate of meningeal involvement observed in these cases.

Adult↗

Pharmaco-electroencephalography and pharmacokinetic/pharmacodynamic modeling in basic research: focus on human pharmacology.

Pharmacokinetic/pharmacodynamic modeling, together with electroencephalography (EEG), have been successfully applied to obtain in vivo pharmacological information of different drugs acting on the central nervous system (CNS) in humans and of the systems with which the drugs interact. Almost all types of variables used to assess the activity of drugs in the human CNS have already been applied in pharmacokinetic/pharmacodynamic research. However, compared with more traditional approaches to quantify the pharmacodynamics of neuropsychotropic drugs, the EEG method has the advantage of being objective, sensitive, continuous and reproducible. The present review focuses mostly on benzodiazepine pharmacology. A selection of some basic aspects that can be covered using pharmaco-EEG and pharmacokinetic/pharmacodynamic modeling from in vivo studies performed in humans in pharmacological research will be introduced: i) determination of the pharmacological characteristics of a compound; ii) comparison of potencies among drugs; iii) comparison of efficacy among drugs; iv) tolerance development; v) metabolite role; vi) enantiomers; vii) drug-drug interactions; viii) circadian rhythms; ix) factors affecting the observed effect; and x) the gain of physiopathological information about the systems with which drugs interact. Looking at the quantity and quality of the results obtained for the benzodiazepines, pharmacokinetic/pharmacodynamic modeling using EEG measures appears to be an ideal tool, and is potentially useful for other drugs acting on the CNS.

Benzodiazepines↗

Uses of pharmaco-EEG and pharmacokinetic-pharmacodynamic modeling in the clinical scenario.

In order to place pharmaco-EEG within the clinical context, the distinction between biomarkers, surrogate endpoints, clinical endpoints and clinical outcomes is introduced. State-of-the-art applications of pharmaco-EEG, together with pharmacokinetic-pharmacodynamic modeling in everyday clinical practice in anesthesiology (semilinear canonical correlation), psychiatry (discrimination between responders and nonresponders to pharmacological treatment using the test dose), neurology (antiepileptic field) and neurophysiology (first-order Markov model of sleep stage transitions) are discussed. The combination of both procedures, although successfully used during some drug development programs (opioids or benzodiazepines), is not widely applied in the clinical scenario where the central nervous system (CNS) is concerned. Much work is still need to develop fully the potentials that pharmaco-EEG together with pharmacokinetic-pharmacodynamic modeling could bring to therapeutics in neuroscience.

Biomarkers↗

Diagnosis of human parvovirus B19 infections by detection of epitope-type-specific VP2 IgG.

In the B19 VP2 molecule an immunodominant heptapeptide epitope has been detected, recently for which IgG antibodies are synthesized exclusively in the acute phase of B19 infection. Using this acute-phase-specific epitope (KYVTGIN) a 2(nd)-generation epitope-type EIA was developed, which compares serum IgG activity for native VP2 capsids exhibiting conformational VP2 epitopes with IgG activity for the KYVTGIN epitope. In this study the diagnostic performance (clinical sensitivity and specificity) of the 1st and 2nd-generation epitope-type EIAs and of a peptide-based EIA utilising as antigen the KYVTGIN epitope alone was assessed in comparison with various high-quality IgM- and IgG- based B19 assays. Serum samples from 489 patients with B19-related symptoms and asymptomatic controls from three countries were studied. Among 323 patients with B19-IgG, 20% were diagnosed as acute infection, 73% had past immunity and 7% were not classified due to contradictory results among the different assays. The unclassified samples were explored for viral strain diversity by PCR and DNA sequencing but all sequences obtained were B19-like with variance of only a few per cent. The 2nd-generation epitope-type EIA had a diagnostic sensitivity of 98% and a diagnostic specificity of 94%. In combination with conventional approaches, the epitope-type assays increase greatly the accuracy of B19 serodiagnosis.

Acute Disease↗

Paediatric hip--ultrasound screening for developmental dysplasia of the hip: a review.

This paper will try to deal with the following questions: Which is the correct screening model for the developmental dysplasia of the hip (DDH)? What is the clinical significance of "sonographic" DDH? Can overtreatment produced by ultrasound (US) screening cause a waste of resources and eventually morbidity? We reviewed the literature since January, 1996 through December, 2000. To compare our experience with the literature, we analysed the results of the US examinations of the hip performed in our Institute. Over 4 years of US screening 11326 infants (22652 hips), aged 3 days to 4 months, were examined consecutively. Sonographic hip findings were abnormal in 531 infants (4.7%). The screening showed 381 subjects (3.36% of the population) with a type IIa hip (bilateral or unilateral); 65% of these infants were normal at follow up and only 35% worsened. On the whole we treated 282 infants (2.5%). No open reduction was performed. Avascular necrosis appeared in 2/282 treated cases (1.06%). We support the routine generalised US screening of neonatal hips. The excess of doubtful cases and, consequently, of the extra referrals may be limited, and the overtreatment decreased to the lowest rates reported by optimisation of everyone's approach.

Cost-Benefit Analysis↗