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Biomedical subjects

R Marti

Publications and source records attributed to R Marti.

At least 19 recordsLinked to original sources

Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study.

BACKGROUND: Environmental exposures in early life have been implicated in the aetiology of inflammatory bowel disease. OBJECTIVE: To examine environmental risk factors prior to the development of inflammatory bowel disease in a paediatric population based case control study. METHODS: A total of 222 incident cases of Crohn's disease and 60 incident cases of ulcerative colitis occurring before 17 years of age between January 1988 and December 1997 were matched with one control subject by sex, age, and geographical location. We recorded 140 study variables in a questionnaire that covered familial history of inflammatory bowel disease, events during the perinatal period, infant and child diet, vaccinations and childhood diseases, household amenities, and the family's socioeconomic status. RESULTS: In a multivariate model, familial history of inflammatory bowel disease (odds ratio (OR) 4.3 (95% confidence interval 2.3-8)), breast feeding (OR 2.1 (1.3-3.4)), bacille Calmette-Guerin vaccination (OR 3.6 (1.1-11.9)), and history of eczema (OR 2.1 (1-4.5)) were significant risk factors for Crohn's disease whereas regular drinking of tap water was a protective factor (OR 0.56 (0.3-1)). Familial history of inflammatory bowel disease (OR 12.5 (2.2-71.4)), disease during pregnancy (OR 8.9 (1.5-52)), and bedroom sharing (OR 7.1 (1.9-27.4)) were risk factors for ulcerative colitis whereas appendicectomy was a protective factor (OR 0.06 (0.01-0.36)). CONCLUSIONS: While family history and appendicectomy are known risk factors, changes in risk based on domestic promiscuity, certain vaccinations, and dietary factors may provide new aetiological clues.

Adolescent↗

Opposite evolution in incidence of Crohn's disease and ulcerative colitis in Northern France (1988-1999).

BACKGROUND: Northern France was characterised by a high incidence of Crohn's disease (CD) and a low incidence of ulcerative colitis (UC) according to the first inquiry undertaken in the late 1980s. AIMS: To assess the trends in the incidence of inflammatory bowel disease (IBD) over a 12 year period (1988-1999) in the same area of Northern France. PATIENTS: Patients living in Northern France (Nord, Pas-de-Calais, Somme, and Seine Maritime--total of 5,790,526 inhabitants) between 1988 and 1999 were included in the study. Case ascertainment was established according to methodology previously described. METHODS: Trends in incidence were studied using a Poisson regression model in four three year periods (1988-90, 1991-93, 1994-96, and 1997-99) adjusted for age at diagnosis and sex. Incidence rates were standardised for age with the European standard population. RESULTS: During 1988-99, 7066 cases of IBD were recorded (56.8% CD, 37.7% UC, and 5.5% indeterminate colitis). Mean annual incidence rate of CD increased from 5.2/100,000 inhabitants in 1988-90 to 6.4 in 1997-99 (adjusted p for trend <0.001). In contrast, the incidence of UC decreased from 4.2 to 3.5 (adjusted p for trend <0.001). The ileocolonic subtype of CD increased by 25% even though median age at diagnosis and frequency of digestive investigations were not different. CONCLUSIONS: Contrary to what has been reported in other countries in Northern Europe, the incidence of CD increased by 23% in 12 years in Northern France while that of UC decreased by 17% during the same period. This indicates that some factors which influence IBD frequency (in both directions) are still at work in this area of Europe, and that further studies aimed at identifying these should be performed. The rising incidence of CD could enhance the burden of this disease on the public health system in France.

Adult↗

Pleural-fluid myeloperoxidase in complicated and noncomplicated parapneumonic pleural effusions.

The diagnostic accuracy of myeloperoxidase (MPO) in pleural fluid, for differentiating between complicated and noncomplicated parapneumonic pleural effusions (PPE) evaluated prospectively. Seventy patients aged >18 yrs with PPE (36 complicated and 34 noncomplicated) were studied after admission to a tertiary referral teaching hospital. MPO concentration was measured in plasma and pleural fluid using a double-antibody competitive radioimmunoassay. The concentrations of MPO in complicated and noncomplicated PPE were compared using a Mann-Whitney U-test and multiple logistic regression models were used to predict the odds that an effusion was complicated. MPO pleural-fluid concentrations were significantly higher in complicated than in noncomplicated PPE. After excluding purulent effusions, pleural-fluid MPO was the marker that best differentiated between the two types of PPE: the area under the receiver operating characteristic curve was 0.912, the sensitivity was 87.5% and the specificity was 85.1% at a cut-point limit of 3.000 microg x L(-1). The authors concluded that the concentration of pleural-fluid myeloperoxidase helps to differentiate between nonpurulent complicated and noncomplicated parapneumonic pleural effusions.

Biomarkers↗

Probing the effects of membrane cholesterol in the Torpedo californica acetylcholine receptor and the novel lipid-exposed mutation alpha C418W in Xenopus oocytes.

The effects of cholesterol on the ion-channel function of the Torpedo acetylcholine receptor (nAChR) and the novel lipid-exposed gain in function alpha C418W mutation have been investigated in Xenopus laevis oocytes. We found conditions to increase the cholesterol/phospholipid (C/P) molar ratio on the plasma membrane of Xenopus oocytes from 0.5 to 0.87, without significant physical damage or change in morphology to the oocytes. In addition, we developed conditions to deplete endogenous cholesterol from oocytes using a methyl-beta-cyclodextrin incubation procedure without causing membrane instability of the cells. Methyl-beta-cyclodextrin was also used to examine the reversibility of the inhibitory effect of cholesterol on AChR function. Depletion of 43% of endogenous cholesterol from oocytes (C/P = 0.3) did not show any significant change in macroscopic response of the wild type, whereas in the alpha C418W mutant the same cholesterol depletion caused a dramatic gain-in-function response of this lipid-exposed mutation in addition to the increased response caused by the mutation itself. Increasing the C/P ratio to 0.87 caused an inhibition of the macroscopic response of the Torpedo wild type of about 52%, whereas the alpha C418W mutation showed an 81% inhibition compared with the responses of control oocytes. The wild type receptor did not recover from this inhibition when the excess cholesterol was depleted to near normal C/P ratios; however, the alpha C418W mutant displayed 63% of the original current, which indicates that the inhibition of this lipid-exposed mutant was significantly reversed. The ability of the alpha C418W mutation to recover from the inhibition caused by cholesterol enrichment suggests that the interaction of cholesterol with this lipid-exposed mutation is significantly different from that of the wild type. The present data demonstrate that a single lipid-exposed position in the AChR could alter the modulatory effect of cholesterol on AChR function.

Animals↗

Defects of intergenomic communication: autosomal disorders that cause multiple deletions and depletion of mitochondrial DNA.

Depletion and multiple deletions of mitochondrial DNA (mtDNA) have been associated with a growing number of autosomal diseases that have been classified as defects of intergenomic communication. MNGIE, an autosomal recessive disorder associated with mtDNA alterations is due to mutations in thymidine phosphorylase that may cause imbalance of the mitochondrial nucleotide pool. Subsequently, mutations in the mitochondrial proteins adenine nucleotide translocator 1, Twinkle, and polymerase gamma have been found to cause autosomal dominant progressive external ophthalmoplegia with multiple deletions of mtDNA. Uncovering the molecular bases of intergenomic communication defects will enhance our understanding of the mechanisms responsible for maintaining mtDNA integrity.

Chromosome Disorders↗

Pleural fluid myeloperoxidase as a marker of infectious pleural effusions.

Background: The aim of this study was to establish the diagnostic accuracy of neutrophil markers (elastase, lysozyme, myeloperoxidase) found in pleural fluid in differentiating between infectious and non-infectious pleural effusions (PE). Methods: We studied 184 patients over 18 years of age with PE, classified as either infectious (34 complicated parapneumonic, 32 non-complicated parapneumonic, 45 tuberculous) or non-infectious (31 neoplasms and 42 undiagnosed exudates). Polymorphonuclear elastase (PMN-E) was determined using an immunoactivation method and lysozyme using a turbidimetric method. Myeloperoxidase (MPO) was measured by double antibody competitive radioimmunoassay. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. Results: Pleural fluid MPO was the biochemical marker that best differentiated between infectious and non-infectious PE. The ROC area under the curve (AUC) for myeloperoxidase was 0.86. MPO values over 550 &mgr;g/l diagnosed infectious PE with a specificity of 90.4% and a sensitivity of 77.4%. After excluding purulent parapneumonic PE, the sensitivity of a pleural MPO value >/=550 &mgr;g/l was 72.6%. Conclusions: Pleural fluid MPO was the marker that best differentiated between infectious and non-infectious PE.

Journal Article↗

Nitric oxide may contribute to nocturnal hemodynamic changes in cirrhotic patients.

OBJECTIVE: Patients with liver cirrhosis have a nocturnal worsening of hemodynamic parameters that has been associated with an increased risk of variceal bleeding at nighttime. The aim of this study was to investigate whether nitric oxide and cytokines are implicated in these hemodynamic changes. METHODS: Ten cirrhotic patients and eight controls were studied. Mean blood pressure, heart rate, plasma norepinephrine, tumor necrosis factor alpha and interleukin-6 levels, and serum nitrite + nitrate levels were determined at 0800, 1600, and 2400 h. All determinations were performed in supine rest and at least 4 h after meals. In a second study, nitrite + nitrate levels were assessed in 10 cirrhotic patients before and after eating a standard meal. RESULTS: Mean arterial pressure levels that were always lower in the patient group showed a nocturnal decrease in both groups of subjects. Heart rate values that were always higher in cirrhotic patients showed a nocturnal fall in controls, whereas cirrhotics maintained elevated values at nighttime. Norepinephrine levels were higher in cirrhotics and maintained similar values during the study, whereas controls had a significant nocturnal decrease. Nitrite + nitrate levels that were higher in cirrhotic patients showed a significant mean increase of 40% from morning (0800 h) to night (2400 h) in the patient group, whereas in controls no change was observed (p < 0.05). Tumor necrosis factor alpha and interleukin-6 levels did not change either in patients or controls during the entire period. Cirrhotic patients with or without ascites maintained a pattern of hemodynamic and biochemical changes similar to the pattern observed in the entire group of patients. Finally, no changes in serum nitrite + nitrate levels were observed in patients before and after eating the standard meal. CONCLUSION: An increased nocturnal nitric oxide production might contribute to the hemodynamic changes observed in cirrhotic patients during nighttime.

Aged↗

Diagnostic accuracy of pleural fluid polymorphonuclear elastase in the differentiation between pyogenic bacterial infectious and non-infectious pleural effusions.

BACKGROUND AND OBJECTIVES: To establish the diagnostic accuracy of the markers of neutrophil activity (elastase and lysozyme) determined in pleural fluid, for differentiating between pyogenic bacterial infectious and non-infectious pleural effusions. PATIENTS AND METHODS: At our tertiary referral teaching hospital, 160 patients over 14 years with pleural effusion (PE), classified as pyogenic bacterial infectious (41 parapneumonic complicated, 32 parapneumonic non-complicated) and non-infectious (32 neoplasm and 55 undiagnosed pleural exudates) were examined in a prospective study. Polymorphonuclear elastase (PMN-E) was determined by an immunoactivation method and lysozyme by a turbidimetric method. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. RESULTS: Pleural fluid PMN-E was the biochemical marker that best differentiated between pyogenic bacterial infectious and non-infectious PE. The ROC area under the curve (AUC) for PMN-E was 0.8276. A PMN-E value over 230 microg/l diagnosed infectious PE with a specificity of 0.81 and a sensitivity of 0.74. The ROC AUC for proteins plus lactate dehydrogenase was 0. 7430. Differences between the two ROC curves were significant (p = 0. 032). After excluding purulent parapneumonic complicated PE, the sensitivity of a pleural fluid PMN-E value equal to or greater than 230 microg/l was 0.64 and the specificity 0.81. CONCLUSIONS: Pleural fluid PMN-E was the marker that best differentiated infectious from non-infectious PE, and PMN-E values lower than 230 microg/l suggest non-infectious PE.

Adolescent↗

Hemostasis using high intensity focused ultrasound.

High intensity focused ultrasound (HIFU) has been shown to be an effective method of hemostasis, in animal studies, for both solid organs and blood vessels. Two distinct effects of HIFU, thermal and mechanical, appear to contribute to hemostasis. Acoustic hemostasis may provide an effective method in surgery and prehospital settings for treating trauma and elective surgery patients. A review of the methodology is given.

Animals↗

Interleukin-6, nitric oxide, and the clinical and hemodynamic alterations of patients with liver cirrhosis.

OBJECTIVE: Nitric oxide has been proposed as a mediator of hyperdynamic circulation in cirrhosis. Endotoxin and cytokines induce the synthesis of nitric oxide. The aim of this study was to investigate the relationship between endotoxemia, cytokines, and nitric oxide in patients with cirrhosis, and to correlate these findings with clinical, biochemical, and hemodynamic parameters. METHODS: Clinical, biochemical, and hemodynamic parameters were assessed in 66 patients with cirrhosis and 15 controls. Levels of antidiuretic hormone, plasma renin activity, aldosterone, interferon gamma, interleukin-1, interleukin-6, tumor necrosis factor alpha, endotoxin, and nitrates-nitrites were determined. RESULTS: Mean arterial pressure was lower and interleukin-6, tumor necrosis factor alpha, nitrites-nitrates levels, and endotoxin positivity rates were higher in cirrhotics than in controls (p < 0.005). Mean arterial pressure decreased and interleukin-6 levels increased with worsening of Child score (p < 0.005). Patients with ascites had higher levels of interleukin-6, tumor necrosis factor alpha, and nitrates-nitrites than patients without ascites (p < 0.01). Elevated levels of interleukin-6 were found in patients with encephalopathy grade I, compared with patients without (p < 0.001); this association was independent of the severity of liver disease. In patients with low mean arterial pressure, interleukin-6 levels were higher than in patients with high mean arterial pressure (p = 0.001), whereas tumor necrosis factor alpha and nitrates-nitrites levels were not different. By multivariate analysis, high interleukin-6 levels showed independent associations with the presence of ascites, encephalopathy, and low mean arterial pressure. Only interleukin-6 levels had significant correlations with Child score, plasma renin activity, serum and urinary sodium, and mean arterial pressure (r > or = 0.4, p < 0.005). CONCLUSIONS: Although the activity of the nitric oxide pathway is increased in patients with cirrhosis and might contribute to the hemodynamic alteration, other factors are involved. Interleukin-6, possibly through nitric oxide-independent mechanisms, also might play a role in the vasodilatation of cirrhosis and the pathogenesis of hepatic encephalopathy.

Aged↗

[Diagnostic and therapeutic management of patients with chronic inflammatory bowel disease].

BACKGROUND: The period of time required for the diagnosis of a chronic illness depends on initial clinical symptoms and their perception by the patient and the physicians. The aim of this study was to describe the procedures of diagnosis of incident cases of Inflammatory Bowel Disease (IBD). METHODS: Patients reported by the Registry of inflammatory bowel disease of northern France (EPIMAD) in 1994 were included. Standardized questionnaires describing clinical history, patient behavior, medical consultations and examinations were collected by an interviewer practitioner from three sources: patients, general practitioners (GP) and gastroenterologists (GE). Patients were divided in 2 groups according to the time between symptom onset and diagnosis: more than 9 months or less than 9 months (D > 9 and D < or = 9). RESULTS: 258 patients were included: 144 Crohn's disease (CD) (56%), 106 ulcerative colitis (UC) (41%) and 8 chronic unclassifiable colitis (CUC). Median time between symptom onset and diagnosis was 3 months, 196 (76%) patients belonged to the group D < or = 9 and 62 (24%) to the group D > 9. There was no difference between the 2 groups for initial clinical symptoms. The delay between symptom onset and the consultation to the GP and the GE was longer in the group D > 9: respectively 1 month vs 0 and 7.6 vs 2. Thirty-five percent of patients in the group D > 9 had consulted more than one GP vs 14% (p < 0.05). Diagnosis management by the GE was the same in both groups. Patients of group D < or = 9 had more often perceived their symptoms as serious (p < 0.05). CONCLUSIONS: Delay to diagnosis in a quarter of patients with IBD was more than 9 months. This later diagnosis was not due to patient management by the GE but rather to a longer delay to consulting the GP and between GP and GE referral. Patient interpretation of the symptoms could also explain the variability of this delay.

Abdomen↗

[Cost of early management of chronic inflammatory intestinal disease].

OBJECTIVES: The aim of this study was to assess the cost of the first management of inflammatory bowel disease (IBD) from the onset of first symptoms until 6 weeks after the diagnosis. This cost was calculated in French francs (FF) for all IBD and namely for Crohn's disease (CD), ulcerative colitis (UC), and ulcerative proctitis (UP). MATERIAL AND METHODS: Data concerning 258 patients were collected by the mean of a standardized questionnaire from 3 different sources: the patient, his general practitioner, and his gastroenterologist. RESULTS: Two hundred and fifty eight patients were included: 144 CD (55.8%), 76 UC (29.5%), 30 UP (11.6%), and 8 chronic unclassifiable colitis (CUC) (3.1%). The mean direct costs of the diagnosis (m +/- SD) were 23,116 +/- 40,820 FF for CD, 10,628 +/- 17,316 FF for UC and 3,451 +/- 2,743 FF for UP. Although unplanned hospitalizations occurred in only 38% of the patients (98/258), they represented the 3/4 of the mean costs: 78.2% for CD and 64% for UC. Indirect costs generated by days off work were 4,719 +/- 6,610 FF for CD, 2,996 +/- 6,897 FF for UC and 1,230 +/- 3,622 FF for UP. CONCLUSION: The first management of a patient with CD was twice more expensive than the one with UC and 6.5 times than the one with UP.

Adolescent↗

Interleukin-8 and markers of neutrophil degranulation in pleural effusions.

In order to know the degree of interleukin-8 (IL-8) production in the pleural space and its relationship to neutrophil activation, IL-8, neutrophil elastase (NE), and myeloperoxidase (MPO) were assessed in blood and pleural fluid (PF) of 219 patients with pleural effusions. Correlations between blood and PF IL-8, NE, and MPO were either absent or weak, except for IL-8 in transudates (r = 0.6745, p < 0.001). PF IL-8, NE, and MPO concentrations in cases of empyema were higher than in cases of effusion of other causes (p < 0.001). No significant differences in inflammatory markers were observed between parapneumonic and tuberculous fluids. IL-8, NE, and MPO levels in malignant, nonspecific, and transudative effusions were lower than in those due to infection, the lowest levels corresponding to transudates. No significant correlation was observed between PF IL-8 and neutrophil count in any group; in contrast, IL-8 was associated with NE and MPO in empyema (r = 0.7545, and r = 0.7283; p < 0.001), tuberculosis (r = 0.4016, p = 0.008 and r = 0.6545, p < 0.001), and nonspecific effusions (r = 0.3748, p = 0.007 and r = 0.3085, p = 0.028). Our results indicate that local production of markers of the nonspecific inflammatory response is high in both chronic and acute pleural infection, and suggest a role for IL-8 in the release of NE and MPO.

Adolescent↗

[Pseudarthrosis of the proximal femur].

Mechanical and biological factors are responsible for non-unions of the proximal femur. We analyse the causal treatment-possibilities of the different localisations. Fifty-five patients with non-unions of the femoral neck (average age 53 years) with or without preexistent femoral head necrosis (44%) were treated by abduction osteotomy and followed up at regular intervals. In 15% of cases a second operation was necessary after an average of 9.3 years, including the early complications. At the latest control 90% of the patients were satisfied, with an average Harris hip score (HHS) of 91. The survivorship analysis with end point total hip replacement is favourable. In the same period 22 patients were treated with a total hip replacement. The 11 survivors had a clearly worse HHS of 65. The low-risk, technically demanding valgization osteotomy should be the first step in the treatment of femoral neck non-unions, even in the presence of femoral head necrosis; secondary operations are not compromised. Pertrochanteric non-unions are rare. The pertrochanteric fragment very often heals, leaving a lateral femoral neck non-union which can be treated with valgization osteotomy. Depending on the type of non-union and the age of the patient, anatomical reduction, medial displacement and valgization osteotomy can be employed. With the angulated plates of the ASIF (95 degrees, 120 degrees, 130 degrees) 23 of the 24 non-unions could be healed in one operation. Fourteen patients underwent total hip replacement. In the subtrochanteric area mechanical and vascular instability leads to implant failure or fatigue fracture. Rigid compression-re-osteosynthesis is the therapy of choice, the 95 degrees condylar plate the implant. Twenty-three of our documented 24 subtrochanteric non-unions healed, 4 in the presence of an infection. Multiple operations have been necessary in 2 of the 4 non-unions following a pathological fracture.

Adult↗

Effect of HMG-CoA reductase inhibitors on red blood cell membrane lipids and haemorheological parameters, in patients affected by familial hypercholesterolemia.

Eighteen patients with familial hypercholesterolemia treated with lovastatin (40 mg/day) for three months were studied to find out whether the drug induces modifications in the lipid composition of the erythrocyte membrane and whether these induce changes in the rheological behaviour of the red blood cell. Our results show that the changes observed in plasma lipids correlate with a significant decrease in the cholesterol/phospholipid ratio of the red blood cell membrane. These changes in the lipid composition of the cell are statistically related to a decrease in the erythrocyte aggregability and an improvement in blood filterability probably due to an increase in the red blood cell deformability.

Adult↗