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Biomedical subjects

H Carton

Publications and source records attributed to H Carton.

At least 19 recordsLinked to original sources
PubMed1998

Bladder cancer in patients with multiple sclerosis treated with cyclophosphamide.

PURPOSE: We define the risk of bladder cancer in multiple sclerosis related to the use of indwelling catheters and cyclophosphamide administered as an immunomodulating agent. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,351 patients with multiple sclerosis referred to the National Center for Multiple Sclerosis. RESULTS: Of the 2,351 patients 2 women and 5 men (0.29%) had bladder cancer. Of the 850 chronically catheterized patients the incidence was 0.7%. One patient with cancer performed intermittent catheterization for a rate of 0.23% in this group. In a subgroup of 70 patients treated with cyclophosphamide 5 chronically catheterized patients (5.7%) had bladder cancer. Hematuria was the most common presenting symptom. These data were compared with those in the literature on bladder cancer in spinal cord injury. CONCLUSIONS: These data suggest a possible synergistic role of cyclophosphamide and chronic catheterization in the induction of secondary bladder cancer. Regular cystoscopy is warranted in these patients to allow early detection of bladder tumors. Nitric oxide metabolism may be an important factor in the carcinogenesis of this type of bladder cancer.

Adjuvants, Immunologic↗
PubMed1998

Utilisation and cost of professional care and assistance according to disability of patients with multiple sclerosis in Flanders (Belgium)

OBJECTIVES: To assess the utilisation of medical services and social (community) assistance in patients with multiple sclerosis of different disability and to calculate the direct healthcare costs to society. METHODS: (1) One hundred and eighty four patients with multiple sclerosis were classified into four grades of disability according to a simplified Kurzke disability status scale. (2) Patients were interviewed with a structured questionnaire containing questions on their sociodemographic status, the use of inpatient and outpatient medical services and pharmaceutical products during the previous year, the use of social assistance, and the purchase of prosthetics and charges for house adaptations during the previous five years. (3) Data were also prospectively collected by means of four week diary annotations of all medical and social acts and their duration. RESULTS: After correction for the disability distribution the yearly costs for the 5500 patients with multiple sclerosis in Flanders was estimated to be ECU 13106000 for ambulatory care including rehabilitation and district nursing and ECU 3234000 for pharmaceutical products. To these direct medical costs ECU 3491000 for social assistance and ECU 4938000 for prosthetics and adaptations should be added. The yearly costs for admissions to hospital including permanent residence in an institution and pharmacy was ECU 26581000 . Home nursing and long term or permanent residence in an institution of the most severely disabled, 17% of the multiple sclerosis population, are responsible for 50% of the total direct healthcare costs and care for the 6.5% institutionalised patients accounts for 23%. Direct costs for medical care and social assistance for patients with multiple sclerosis, who account for about 0.1 % of the total population, amounts to 1% of the total healthcare budget in Flanders. CONCLUSION: This information on utilisation of medical services and social assistance can be used for good healthcare planning and cost effectiveness studies.

Activities of Daily Living↗
PubMed1998

Toxicity in a double-blind, placebo-controlled pilot trial with D-penicillamine and metacycline in secondary progressive multiple sclerosis.

The serine proteinase tissue-type plasminogen activator (t-PA) and the metalloproteinase gelatinase B (MMP-9) have recently been demonstrated in MS lesions. Both enzymes are interconnected in an enzyme cascade which contributes to destruction of the blood brain barrier and demyelination and both enzymes are inhibited by D-penicillamine. Metacycline was shown in in vitro experiments to inhibit gelatinase B. The combination of peroral D-penicillamine plus metacycline was evaluated in a double-blind placebo-controlled way in two groups of 10 patients suffering from secondary progressive multiple sclerosis. The major objectives of this pilot trial were to examine the safety of this combination and the possibility of blinding, while the effect on disease progression was considered as a secondary endpoint. Over a follow-up period of 1 year and in this selected patient group, there was no significant improvement in the Expanded Disability Status Scale score (EDSS) as compared with that of the placebo-control group. Toxicity was too high to consider additional trials with this combination of metalloproteinase inhibitors. Although peroral treatment is by most MS patients acknowledged as a major improvement in treatment compliance, one has to await the development of more selective and efficacious protease inhibitors than those used in the combination therapy described here.

Adult↗
PubMed1997

Risks of multiple sclerosis in relatives of patients in Flanders, Belgium.

OBJECTIVES: To calculate age adjusted risks for multiple sclerosis in relatives of Flemish patients with multiple sclerosis. METHODS: Lifetime risks were calculated using the maximum likelihood approach. RESULTS: Vital information was obtained on 674 probands with multiple sclerosis in Flanders and a total of their 26225 first, second, and third degree relatives. Full medical information to allow documentation of multiple sclerosis status was available for 21351 (81.4%) relatives. The age adjusted risk for parents was 1.61 (SEM 0.35)%, for siblings 2.10 (SE 0.36)%, and for children 1.71 (SEM 0.70)%. For aunts and uncles, the risk was 0.66 (SEM 0.13)%. CONCLUSIONS: The risk for first degree relatives of patients with multiple sclerosis in Flanders is increased 10-fold to 12-fold; for second degree relatives, it is increased threefold. This information can be used for risk counselling in families and provides additional support for the role of more than one locus contributing to the susceptibility of multiple sclerosis.

Adult↗
PubMed1997

Positron emission tomography, magnetic resonance imaging and proton NMR spectroscopy of white matter in multiple sclerosis.

OBJECTIVE: To assess characteristics of MS lesions and normal appearing white matter (NAWM) with various imaging modalities. Glucose metabolism was investigated with FDG-PET, metabolite concentration with proton NMR spectroscopy, and lesion detection with routine brain MRI. METHODS: Thirteen patients were studied in a stable phase of their disease, and two during an acute episode. Nine healthy volunteers served as controls. RESULTS: Three patients had a normal brain MRI, 12 had typical lesions. MR images were registered to the PET planes. Lesions and contra-lateral control areas were analyzed, 10/15 lesions showed relative hyper-metabolism and 2 hypo-metabolism. NAA concentration was significantly decreased in both lesions and NAWM. CONCLUSION: In stable MS, most large lesions have a relatively increased glucose utilization and decreased NAA concentration. NAWM showed a significantly decreased NAA concentration compared to healthy subjects, but no difference in glucose metabolism. Active lesions in acute MS are also hyper-metabolic. This finding opens a new window on the classification of white matter lesions based on glucose utilization.

Acute Disease↗
PubMed1996

[Prevalence of human T-lymphotropic virus, Type 1 and 2 in blood donors and patients with sexually transmissible diseases in Surinam].

OBJECTIVE: To determine the prevalence of HTLV-1 and HTLV-2 infection in the population of Surinam in order to enhance the safety of blood transfusion in Surinam. DESIGN: Descriptive. SETTING: Academic Hospital, Paramaribo, Surinam. METHOD: Blood was examined of the 777 regular donors (constituting 97% of the total pool) who donated blood between February 1 and June 1 1995 at the Blood Transfusion Centre of the Surinam Red Cross in Paramaribo, and also of the 140 patients with a sexually transmitted disease (STD) seen during the same period at the Dermatology centre of the Ministry of Health. All sera were screened with a particle agglutination test. Sera which were not negative were subsequently tested with a western blot method which distinguishes between HTLV-1 and HTLV-2. RESULTS: Three sera (0.4%) of the blood donors and 2 (1.4%) of the STD patients were positive for HTLV-1 (difference not significant). Nobody was found to be HTLV-2 positive. CONCLUSION: The HTLV-1 prevalence in the Surinam blood donors is similar to that of blood donors and the general population of many regions in Brazil but substantially lower than in several other regions in the Caribbean. Since examination of all donated blood is not a realistic option in Surinam it is recommended that all new regular blood donors should be tested for HTLV antibodies.

Blood Donors↗
PubMed1995

Prevention of acute autoimmune encephalomyelitis and abrogation of relapses in murine models of multiple sclerosis by the protease inhibitor D-penicillamine.

The in vitro activity of gelatinase B, an enzyme whose appearance in the cerebrospinal fluid is associated with inflammatory diseases of the central nervous system, was dose-dependently inhibited by the antirheumatic D-penicillamine. Inhibition of gelatinase B in electrophoretically pure preparations and in cell culture supernatants and human body fluids was obtained at dosages reached in the circulation of patients treated with a peroral dosis of 750 mg D-penicillamine per day. In mice, developing acute demyelination, D-penicillamine significantly reduced the mortality and morbidity rates of experimental allergic encephalomyelitis (EAE). In chronic relapsing EAE in Biozzi AB/H mice, an animal model for relapses in multiple sclerosis (MS), it attenuated the exacerbations, even when the treatment was started after the primary full-blown disease had developed. We infer protease inhibition as the mechanism of action of D-penicillamine and suggest that its use may be effective as peroral treatment for MS.

Acute Disease↗
PubMed1995

Importance of HLA-DRB1 and DQA1 genes and of the amino acid polymorphisms in the functional domain of DR beta 1 chain in multiple sclerosis.

The association of some HLA class II alleles with multiple sclerosis (MS) has been amply documented. In the present study the role of HLA class II haplotypes and genotypes and of polymorphic amino acids at the DR beta 1 locus, located in the antigen binding groove and the CD4 binding domain of the DR beta 1 chain, were studied in 78 unrelated Caucasian chronic progressive MS (CP MS) patients and 204 controls. The results confirmed the positive association of the DRB1*1501 allele and through linkage also of the DRB1*1501-DQA1*0102 haplotype with MS. In addition, the results showed that the DRB1*1501/DRB1*0400 or DR beta 1Ala71+ His13+ genotype conferred the highest relative risk for MS (RR = 9.14). Alleles encoding for DR beta 1Phe47+, DR beta 1Asp70+ and DR beta 1Thr140+, DQ alpha 1Phe25+, DQ alpha 1Leu69+ residues were protective and the highest protection (RR = 0.24) was provided by the DR beta 1(Phe47+)-DQ alpha 1Phe25+ and DR beta 1(Ser13+)-DQ alpha 1Phe25+ haplotypes. Our results suggest that both DQ and DR alpha beta heterodimers might contribute to the increased or decreased risk to develop MS by the shape of their antigen-binding groove.

Adult↗
PubMed1995

HTLV-negative and HTLV type I-positive tropical spastic paraparesis in northeastern Brazil.

A type-specific serological survey among 1042 random nonneurological outpatients in two cities in the state of Ceara (northeastern Brazil) shows a low prevalence of HTLV-I (0.34% in Fortaleza; 0.44% in Crato) and of HTLV-II (0.34% in Fortaleza; 0% in Crato). Among 62 chronic myelopathic patients seen in Fortaleza 27 patients were found with clinical features of tropical spastic paraparesis (TSP); 10 of 27 were found HTLV-I seropositive (37%; 95% confidence limits, 19-58%). Proviral genome detection by polymerase chain reaction in 5 seropositive and 12 seronegative patients confirmed the serological findings. This excludes HTLV-I or -II infection as a cause in the seronegative TSP patients. The HTLV-positive and -negative patients did not differ clinically and by history, except that seropositives had a longer mean disease duration, a female predominance, and a higher proportion of white Caucasians. In this population with low HTLV-I and HTLV-II prevalences, HTLV-negative TSP is at least as frequent as the HTLV-I-associated TSP.

Brazil↗
PubMed1994

HLA and T-cell receptor polymorphisms in Belgian multiple sclerosis patients: no evidence for disease association with the T-cell receptor.

There are compelling data to indicate that the susceptibility to multiple sclerosis (MS) is inherited, at least in part. Particular HLA genotypes may be associated with MS and recently also polymorphisms in the T-cell receptor (TCR) genes have been reported to correlate with the disease; however, these data have been difficult to confirm. We investigated the TCRA and TCRB chain genes of HLA-typed Belgian CP MS patients employing four DNA restriction fragment length polymorphisms (RFLPs) detected with TCR constant (TCRAC1, TCRBC2) and variable (TCRBV8, TCRBV11) gene segments. Similar frequencies in patients and controls were observed for all RFLPs studied. Although the HLA DR2 genotype was significantly associated with MS, no interactive effects were seen with MS, DR2, TCRAC1, TCRBC2 and TCRBV alleles. We conclude that, while a clear association with HLA DR2 is observed, little convincing evidence exists for an association of CP MS with RFLPs of the TCRA or TCRB chain genes.

Alleles↗
PubMed1994

Pregnancy and multiple sclerosis: the influence on long term disability.

We studied 200 female patients with multiple sclerosis (MS) to investigate whether pregnancy after the onset of disease influences long term disability. As an index of progression, we used the time between disease onset and wheelchair dependence. Patients who had at least one pregnancy after onset were wheelchair dependent after 18.6 years, versus 12.5 years for the other women (P < 0.0001). This difference remains statistically significant after correction for age at onset of disease.

Activities of Daily Living↗
PubMed1994

Familial transmission and minimal sequence variability of human T-lymphotropic virus type I (HTLV-I) in Zaire.

Our group previously reported a strong familial clustering of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Zaire, suggesting a familial transmission of the virus together with the presence of cofactors. In the present study among 84 relatives of 16 HTLV-I-positive or HAM/TSP index cases, we found that all 15 seropositive children had a seropositive mother and that all 15 children with a seropositive father but a seronegative mother were seronegative. Lymphocytes of 17 relatives from 2 families with a familial HTLV-I-associated neuropathy were tested in 2 polymerase chain reaction (PCR) assays amplifying pol and tax/rex gene fragments. The 10 seropositive individuals were PCR positive for HTLV-I and the 7 seronegatives were negative in both PCR assays. The PCR results showed no evidence for a long lag period between infection with HTLV-I and seroconversion. The HTLV-I long terminal repeat (LTR) of these 10 individuals, related in the first to the fourth degree, was amplified and sequenced. Identical sequences were found within the families except for one woman infected with two variants, one being the familial strain and the other a mutated one with a single nucleotide substitution in the 755 sequenced nucleotides of the LTR region. The family strain and the mutant were both present in two samples taken 1 year apart. Together, the HTLV-I serology, PCR, and sequencing results point toward mother-to-child transmission as the main mode of HTLV-I infection in this population. Comparison of the LTR sequences of the two families with other HTLV-I strains from different geographical regions shows that the Zairean HTLV-I strains form a separate cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Prevalence of multiple sclerosis in Flanders, Belgium.

Two hundred twenty patients fulfilling the Poser diagnostic criteria for definite and probable multiple sclerosis (MS) were ascertained in an area of Flanders (Belgium) including the city of Leuven through the general practitioners and the neurologists practicing in the area, through the medical records of the National Center for MS and through the membership list of the MS patient society. Leuven is located at a latitude of 50 degrees 53 N. A prevalence rate of 73.8 per 100,000 [95% confidence limits (95% CI) 58.7-89.0] for men and 101.3 (95% CI 80.4-114.5) for women, and of 87.9 for both sexes (95% CI 76.2-99.4) was found on October 1, 1991. This prevalence rate is not significantly different from rates recently reported for other areas in Europe at the same latitude. The female to male ratio however was only 1.41, which is significantly lower than that in neighboring regions.

Adolescent↗
PubMed1994

[Tropical spastic paraparesis in the tropics and Brazil. A historical analysis].

The tropical spastic paraparesis (TSP) is a chronic myelopathy, predominant in the tropics, recently known to be of retroviral origin (HTLV-I). This paper aims at delineating the clinico-etiological evolution of this entity. The historical analysis of it showed that the TSP has had, along decades, many different denominations and the discovery of the retroviral origin for some of them has stimulated new paths of research and epidemiological interest in the tropics and Brazil.

Brazil↗
PubMed1994

Brazilian studies on tropical spastic paraparesis. A meta-analysis.

Tropical spastic paraparesis (TSP) is a chronic progressive myelopathy and in most of the cases has a retroviral (HTLV-1) etiology, when it is denominated HTLV-1 associated-mielopathy (HAM/TSP). Around 433 cases of TSP have been described in Northeast and Southeast Brazil. Among these cases, 157 (36.2%) are HTLV-1 positive and 276 (63.7%) are negative. Their mean age is 43.8 years with a slight predominance of females and mulattoes, although white patients are also numerous. Clinically all patients exhibit a spastic paraparesis with variable sphincter and sensory disturbance. Pain and autonomic symptoms seem to be expressive in the HTLV-1 positive HAM/TSP Brazilian patients.

Adult↗
PubMed1994

Carotid artery surgery in the presence of an occlusion of the contralateral carotid artery: perioperative risk analysis and follow-up.

A retrospective study of 129 carotid artery reconstructions with an occlusion of the contralateral internal carotid artery (group CO) is presented. A control group comprised 489 patients with a stenosis of < 50% at the contralateral side (group CN). Both groups had the same mean age. There were fewer women in group CO (14% versus 31%, P < 0.0001), and more patients had a history of coronary heart disease (57% versus 44%, P < 0.05). In addition more patients of group CO had suffered a stroke (36% versus 27%, P < 0.05). A temporary shunt was used selectively and more frequently in group CO (87% versus 31%, P < 0.001). Major postoperative complications occurred with equal frequency in both groups: all strokes plus non-cerebral mortality (total combined morbidity and mortality): 4.65% versus 5.5%. The late incidence of stroke was the same in both groups: 8% in CO and 7% in CN at 5 years. The authors conclude that, under the described circumstances and with the appropriate surgical technique, the presence of an occlusion of the contralateral internal carotid artery does not imply an increase in major postoperative complications nor a higher stroke rate during follow-up.

Aged↗
PubMed1993

Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein.

Gelatinases in inflammatory demyelinating diseases of the central nervous system (CNS) were studied using actively induced experimental autoimmune encephalomyelitis (EAE) in mice as a model system. Clinical disease scores correlated in time and in intensity with pathology parameters such as cytosis in the cerebrospinal fluid (CSF), inflammatory infiltrates, and demyelination in the CNS. Zymographic analysis was employed to measure gelatinases A and B in the CSF from individual animals. According to their apparent molecular weight (MW), gelatinases A and B appeared with a MW of 65 and 95 kDa, respectively. The 65 kDa form was present in all samples, even in those derived from non-induced animals, whereas the 95 kDa form was present only in samples from animals developing EAE. The levels of 95 and 65 kDa gelatinase correlated with the CSF cytosis. In vitro digestion of myelin basic protein (MBP) with gelatinase B and analysis of the cleavage products by protein sequence analysis pinpointed two cleavage sites in conserved regions of MBP. Gelatinase production within the CNS may constitute an important pathogenic mechanism for both the disruption of the blood-brain barrier and the destruction of myelin, as observed in several neuroinflammatory disorders.

Amino Acid Sequence↗