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Biomedical subjects

S Martin

Publications and source records attributed to S Martin.

At least 73 records · Page 4Linked to original sources
PubMed2003

Variability of the coat protein gene of Citrus psorosis virus in Campania, southern Italy.

Variability of the Coat protein (CP) gene of Citrus psorosis virus (CPsV) was assessed serologically, and by sequence analyses of two genomic regions located in the 3' (region C) and 5' (region V) halves of the gene. Analysis of 53 psorosis field sources from Campania, Italy, with 23 monoclonal antibodies revealed nine serogroups and at least ten different epitopes. Sequence analysis of 19 of these sources showed limited nucleotide diversity of the CP gene in the population. Diversity was slightly higher in region V than in region C. Phylogenetic analysis of the V and C regions of the CP showed that the Campania sources of CPsV were clearly separated from the CPsV-4 isolate from Florida. For C region, most of the CPsV sources clustered together, whereas two clusters were observed for region V. The ratio between nonsynonymous and synonymous substitutions for regions C (0.083) and V (0.345) indicated negative selective pressure for amino acid changes, more intense in the C region. No correlation was found between serogroups and specific aminoacid sequences, field location or citrus cultivar.

Base Sequence↗
PubMed2003

Financial costs of alcoholism treatment programs: a longitudinal and comparative evaluation among four specialized centers.

BACKGROUND: Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow-up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification. METHODS: We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service. RESULTS: The mean cost of hospitalization ranged from 1326 euros to 1917 euros(p = 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow-up per patient ranged from 419 euros to 1704 euros (p = 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately 500 euros/month in three centers and 658 euros in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p = 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost. CONCLUSIONS: This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost-efficient, and beneficial for patients and the public health office economy.

Adult↗
PubMed2003

Cell-associated variants of disease-specific prion protein immunolabelling are found in different sources of sheep transmissible spongiform encephalopathy.

Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSEs) or prion diseases affecting domestic and exotic ruminants. In previous immunohistochemical studies, we have shown that different sheep TSE sources may be distinguished by both the proportion of disease-specific prion protein (PrP(d)) accumulation relative to different cell types in the brain (the 'PrP(d) profile') and by different labelling patterns for PrP peptide sequences within phagocytic cells. In the present study, we have further characterized the intracellular accumulation patterns of PrP(d) in the lymphoreticular system (LRS) and in the brain of sheep clinically affected with scrapie or BSE. BSE-infected PrP(ARQ/ARQ) sheep of different breeds were compared with scrapie-infected sheep of different PrP genotypes. Cases of BSE infection could be distinguished from scrapie cases by a marked reduction in labelling of PrP(d) containing the 84-105 amino acid residues in phagocytic cells of the LRS and in neurones and glia of the brain. These results therefore indicate that TSE agent-dependent processing of PrP in specific cell types within the brain and LRS can be used to distinguish between BSE in PrP(ARQ/ARQ) sheep and scrapie in sheep of several PrP genotypes. Three different N-terminal peptide antibody labelling patterns were recognized for different cell types in different tissues of BSE-infected sheep, suggesting that different truncated forms of PrP(d) are formed following infections with this agent strain. These variations in the cleavage sites of BSE PrP(d) may be due to cell-specific variation in endosomal-lysosomal digestion or to cell- and tissue-specific differences in BSE PrP(d) conformation.

Animals↗
PubMed2003

Transient cholestasis in newborn infants with perinatal asphyxia.

UNLABELLED: In asphyxiated newborn infants, cholestasis often leads to extensive investigations and a cause can rarely be found. OBJECTIVE: To assess the frequency of transient neonatal cholestasis in an unselected group of asphyxiated newborn infants in a mother-child centre. METHOD: Charts of 181 asphyxiated newborn infants born with appropriate birth weight for gestational age (AGA) or small weight for gestational age (SGA) at Sainte-Justine Hospital, Montreal, Quebec between 1989 and 1993 were reviewed. RESULTS: Transient neonatal cholestasis was found in 8.5% of asphyxiated AGA and 33% of SGA newborn infants, compared with 3.94% cholestasis of any etiology in nonasphyxiated SGA infants. Asphyxiated neonates born before the age of 35 weeks had an increased risk for transient neonatal cholestasis (odds ratio 2.84, CI 1.0-8.1) CONCLUSION: Transient neonatal cholestasis is associated with several contributing factors related to the severity of the neonatal distress. Asphyxia is frequently accompanied by cholestasis in this group of newborns and without symptoms other than uncomplicated cholestasis. Investigations should be focussed on conditions requiring immediate therapy.

Apgar Score↗
PubMed2003

[Unusual molecular changes in two families with Friedreich's ataxia].

Friedreich's ataxia is an autosomal recessive disease generally characterized by the presence of microsatellite expansion in a GAA triplet. The patients inherit a pathologic allele from each one of their parents, that may sometimes show GAA triplet expansions or contractions. Two familial studies of typical Friedreich's ataxia are described. Their molecular study demonstrated marked intergenerational instability and an abnormally long expansion of the GAA triplet in the father in the other one. In the first case, there were expansions of 680/815 repetitions, being characterized by an expansion of 290 repetitions GAA in the father-patient transmission. The second case presented GAA of 1,260/1,095 expansions, while the expanded allele of the father was 1,350 repetitions. These cases illustrate that there can be both expansion as well as contraction of the GAA triplet from alleles of paternal origin in the disease, without any apparent phenotypic changes.

Alleles↗
PubMed2002

Very fast hollow-atom decay processes in Xe30+-C60 collisions.

In Xe30+-C60 collisions at low velocity (0.2 a.u.<v<0.4 a.u.), very fast electron ejection is observed not only for frontal collisions but also for near C60 cage collisions. In frontal collisions, the exit-charge distributions obtained with three projectile velocities are reproduced using a multistep exponential decay model. A mean Auger rate of about 0.4 a.u. is estimated for the decay of hollow atoms during the very short interaction time (<3 fs).

Journal Article↗
PubMed2002

A structural approach to understanding the iron-binding properties of phylogenetically different frataxins.

Friedreich's ataxia (FRDA), an autosomal recessive cardio- and neurodegenerative disease, is caused by low expression of frataxin, a small mitochondrial protein, encoded in the nucleus. At the biochemical level, the lack of frataxin leads to dysregulation of mitochondrial iron homeostasis and oxidative damage, which eventually causes neuronal death. It is, however, still unclear whether frataxin is directly involved in iron binding, since the yeast orthologue, but not the human protein, has been shown to form large aggregates in the presence of large iron excess. We have compared the properties of three proteins from the frataxin family--the bacterial CyaY from Escherichia coli, the yeast Yfh1 and human frataxin--as representative of organisms of increasing complexity. We show that the three proteins have the same fold but different thermal stabilities and iron-binding properties. While human frataxin has no tendency to bind iron, CyaY forms iron-promoted aggregates with a behaviour similar to that of yeast frataxin. However, aggregation can be competed by chelator agents or by ionic strength. At physiological salt conditions, almost no aggregation is observed. The design of mutants produced to identify the protein surface involved in iron-promoted aggregation allows us to demonstrate that the process is mediated by a negatively charged surface ridge. Mutation of three of these residues is sufficient to convert CyaY in a protein with properties similar to those of human frataxin. On the other hand, mutation of the exposed surface of the beta sheet, which contains most of the conserved residues, does not affect aggregation, suggesting that iron binding is a non-conserved part of a more complex cellular function of frataxins.

Amino Acid Sequence↗
PubMed2002

2nd to 4th digit ratio and offspring sex ratio.

There is evidence that the ratio of the length of the 2nd and 4th digit (2D:4D) is negatively related to prenatal and adult concentrations of testosterone. It has also been reported that high levels of testosterone at conception in both fathers and mothers are associated with an increased sex ratio (proportion of males at birth). It follows from these observations that low values of 2D:4D may be related to high sex ratio. We present evidence from three populations (English, Spanish and Jamaican) that 2D:4D is negatively related to sex ratio, independent of the sex and ethnicity of the parents.

Adult↗
PubMed2002

Successful antiviral treatment for fulminant reactivated hepatitis B after autologous stem cell transplantation and prophylaxis during subsequent allogeneic stem cell transplantation.

The risk of severe hepatic damage due to reactivation of hepatitis B virus (HBV) infection after intensive myelosuppressive chemotherapy is well known. Two of the most evolved nucleotide analogues showing good activity against the hepatitis B virus are lamivudine and famciclovir. We report the successful therapeutic use of lamivudine and famciclovir for fulminant reactivated hepatitis B after autologous peripheral blood stem cell transplantation (PBSCT) and the subsequent prophylactic use of lamivudine during allogeneic blood stem cell transplantation (alloSCT) for chronic lymphocytic leukemia (CLL) in a 40-year-old patient. Antiviral therapy was well tolerated and no hematotoxicity occurred. Our observation warrants further investigation of antiviral therapy with famciclovir and lamivudine in HBV carriers receiving intensive myelosuppressive chemotherapy.

2-Aminopurine↗
PubMed2002

Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors.

AIMS/HYPOTHESIS: A population-based sample was studied to define immune abnormalities in individuals at risk of Type II (non-insulin-dependent) diabetes mellitus because of impaired glucose tolerance. METHODS: A total of 1653 individuals aged 55 to 74 years participated in a population based survey in Southern Germany (KORA Survey 2000). Those without a history of diabetes were subjected to an OGTT. Randomly selected subjects with IGT ( n=80) were compared with non-diabetic control subjects ( n=77) and patients with Type II diabetes ( n=152) of the same population-based sample after matching for age and sex. Immune parameters were analysed in serum with rigidly evaluated ELISA. RESULTS: Serum pro-inflammatory cytokine interleukin 6 (IL-6) concentrations were higher in subjects with IGT and Type II diabetes than in the control subjects (median 1.8 and 2.5 vs 0.8 pg/ml, p<0.0001). Soluble IL-6 receptors potentiate IL-6 bioactivity and their concentrations were mildly increased in Type II diabetes ( p<0.05). These immune changes seem relevant because IL-6 dependent acute-phase proteins C-reactive protein, serum amyloid A protein and fibrinogen were also increased in IGT and Type II diabetes. Circulating concentrations of TNF-alpha and its two receptors sTNF-R60 and sTNF-R80 were not increased in IGT subjects compared with the control subjects. CONCLUSION/INTERPRETATION: Our study shows systemic up-regulation of selected inflammatory mediators in patients with Type II diabetes and IGT. The pattern observed is non-random and fits with an IL-6 associated rather than TNF-alpha associated response.

Acute-Phase Proteins↗
PubMed2002

Modulation of autoimmunity to beta-cell antigens by proteases.

AIMS/HYPOTHESIS: Proteases are used in therapy for autoimmune diseases yet the mechanism of their action remains to be determined. We studied the immunological basis of protease therapy in the context of Type I (insulin-dependent) diabetes mellitus. METHODS: We studied the effects of proteases (trypsin, papain, chymotrypsin, bromelain) on immune reactivity of a series of autoreactive T-cell clones from prediabetic subjects and patients with a recent onset of Type I diabetes and specific to the autoantigens GAD65, IA-2 and insulin-secretory granule protein. RESULTS: Cell surface expression of adhesion, co-stimulatory and homing molecules on both antigen-presenting cells and T cells was changed after protease treatment. Cytokine analyses showed a selective inhibition of proinflammatory (Th-1) but not Th-2 cytokine production. Autoreactive T-cell proliferation was inhibited at pharmacological serum concentrations, whereas non-specific proliferation to phytohaemagglutinin was not affected at these concentrations. Preincubation experiments on T cells and antigen-presenting cells separately showed that this effect was mediated by APCs, but not T-cells. CONCLUSION/INTERPRETATION: Proteases have pleiotropic immunological effects supporting an immunomodulatory potential for the intervention of chronic inflammatory diseases and Th-1 mediated oedema formation.

Amino Acid Sequence↗
PubMed2002

Pulmonary rehabilitation for chronic obstructive pulmonary disease.

BACKGROUND: The widespread application pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function attributable to the programs. This review updates that reported by Lacasse et al Lancet 1996; 748:1115-1119. OBJECTIVES: To determine the impact of rehabilitation on health-related quality of life (QoL) and exercise capacity in patients with COPD. SEARCH STRATEGY: The 14 randomized controlled trials (RCTs) included in the original meta-analysis were included. Additional RCTs were identified from the Cochrane Airways Group's registry of COPD RCTs using the strategy: [exp, lung diseases, obstructive] and [exp, rehabilitation or exp, exercise therapy] and [research design or longitudinal studies or evaluation study or randomized controlled trial]. Abstracts presented at American Thoracic Society 1980-2000, American College of Chest Physicians 1980-2000 and European Respiratory Society 1987-2000 were also searched. SELECTION CRITERIA: RCTs of rehabilitation in patients with COPD in which quality of life (QoL) and/or functional (FEC) or maximal (MEC) exercise capacity were measured. Rehabilitation was defined as exercise training for at least 4 weeks with or without education and/or psychological support. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: Weighted mean differences (WMD) were calculated using a random-effects model. Missing data from the primary study reports were requested from the authors. MAIN RESULTS: 23 RCTs met the inclusion criteria. Statistically significant improvements were found for all the outcomes. In three important domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue and Mastery), the effect was larger than the minimal clinically important difference of 0.5 units using this instrument. For example Dyspnoea score: WMD 0.98 units, 95% Confidence Interval (95% CI) 0.74 - 1.22 units; n=9 trials. For FEC and MEC, the effect was small and a little below the threshold of clinical significance for the 6- minute walking distance: WMD 49 m, 95% CI: 26 - 72 m; n=10 trials. REVIEWER'S CONCLUSIONS: Rehabilitation relieves dyspnea and fatigue and enhances patients' sense of control over their condition. These improvements are moderately large and clinically significant. The average improvement in exercise capacity was modest. Rehabilitation forms an important component of the management of COPD.

Dyspnea↗
PubMed2002

Image-guided surgery for anal fistula in a 0.5T interventional MRI unit.

PURPOSE: To determine whether MR-guided anorectal surgery is feasible, and to develop techniques for MR-guided anal fistula surgery. MATERIALS AND METHODS: Six patients with pilonidal sinus (PNS), and 21 with suspected anal fistulae were operated on in the GE Signa SPIO 0.5T interventional MRI unit. Procedures were performed with magnet-safe Lockhart-Mummery fistula probes. Preprocedural and intra-operative MRI (IOMRI) techniques were used to identify the extent of the fistula tracts and septic foci, and to ensure the adequacy of the surgical procedure. RESULTS: IOMRI demonstrated the PNS lesions and the adequacy of excision. Imaging failed to demonstrate a fistula in two patients, as confirmed by surgical examination. No images were obtained in one patient due to his size (weight in excess of 100 kg). In 18 patients a fistula tract or abscess was demonstrated and IOMRI was used to assess the adequacy of the surgical procedure. In three patients this demonstrated incomplete drainage of septic foci, which was not obvious on inspection of the surgical field. We believe that in these patients IOMRI prevented an incomplete procedure and the potential requirement for a second operation. Further surgery was performed to rectify this situation. The fistula tract was laid open in 13 patients, and a Seton drain was inserted in five. CONCLUSION: MRI-guided surgery for anal fistula is feasible. IOMRI demonstrates the exact anatomy of the tracts and abscesses, and confirms that all have been adequately treated. We believe it may become particularly useful in surgery for recurrent and complex anal fistulae, and may lead to fewer recurrences.

Adult↗
PubMed2002

[Cellular mechanism of vasculo-protection induced by polyphenols on the endothelium].

Epidemiological studies have suggested that dietary factors, including moderate red wine consumption, might reduce the risk of cardiovascular diseases. The beneficial effect of fruits, vegetables, or red wine may be in part explained by the presence of polyphenols with a multitude of biological activities, including antioxidant and free radical-scavenging properties, anti-aggregatory platelet property and inhibition of vascular smooth muscle cell proliferation. Another therapeutically relevant effect of polyphenols may be their ability to interact with the generation of nitric oxide from vascular endothelium that leads not only to vasodilatation but also to the expression of genes protective of the cardiovascular system. Finally, polyphenols contribute to the preservation of endothelial integrity by acting on the processes implicated in endothelial proliferation, migration and apoptosis. All these effects of polyphenols might interfere with atherosclerotic plaque development and stability, vascular thrombosis and occlusion and therefore might explain their cardio- and vascular protective properties.

Animals↗
PubMed2002

Interaction between smoking and the stromelysin-1 (MMP3) gene 5A/6A promoter polymorphism and risk of coronary heart disease in healthy men.

Smoking is a major risk factor for coronary heart disease (CHD), but this risk may be modified by an individual's genotype. A common functional 5A/6A polymorphism in the promoter of the stromelysin-1 (matrix metalloproteinase 3, MMP3) gene has been identified. The 6A allele has been consistently associated with faster progression of angiographically determined CHD, while the 5A allele has recently been associated with risk of acute myocardial infarction (MI) in patients with unstable angina. To date there has been no prospective study of the relationship of this genotype to CHD risk in smokers and non-smokers. DNA was available from 2,743 middle-aged men, free of CHD at baseline, recruited through nine general practices in the UK for prospective surveillance. To date there have been almost 24,000 person-years of follow-up with 125 CHD events (fatal and non-fatal MI, sudden coronary death, need for coronary artery surgery or new major ECG Q-wave abnormality). Men with events were each matched for age, practice and cholesterol level with three healthy men. Smoking habit was determined by questionnaire. 5A/6A genotype was determined using a heteroduplex generator method. Associations between genotype and disease outcome, according to smoking status, were assessed using conditional logistic regression. Overall, current smoking was associated with a relative risk (RR) of 1.99 (95% CI 1.30-3.06) as compared with never-smokers and ex-smokers combined (p&0.002). In non-smoking men, and after adjustment for conventional risk factors, compared with the 5A5A group, the RR was 1.37 (0.64-2.94) in those with the genotype 5A6A and 3.02 (1.38-6.61) in those with the genotype 6A6A. Smoking increased risk 1.4 fold in the 5A6A group to 1.91 (1.84-4.36), by 1.3 fold in the 6A6A group to 4.01 (1.57-10.24), but by 3.81 fold (1.54-9.40) in the 5A5A group (smoking-genotype interaction p = 0.01). The data indicate a key role for stromelysin in the atherosclerotic process. Men with the stromelysin genotype 5A5A represent 29% of the general population, and their high risk, if smokers, provides a further strong argument for smoking avoidance.

Alleles↗
PubMed2002

Hepatic insufficiency and liver transplantation in a patient with COACH syndrome.

An 8-yr-old-patient was diagnosed with COACH syndrome at the moment of her first bleeding episode from esophageal varices. Investigations revealed biliary cirrhosis as the cause of portal hypertension, no visible kidney cyst or impairment of renal function, cerebellar dysplasia with non-disabling ataxia, and minimal mental retardation. By the age of 12 yr she had developed liver insufficiency and, after a challenging discussion, underwent a liver transplantation. She subsequently developed an abdominal aspergillosis, which required several abdominal explorations and splenectomy as well as 6 months of therapy with liposomal amphotericin B, but survived and in long-term follow-up is in good health, with completed puberty, and has finished school.

Abnormalities, Multiple↗