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Biomedical subjects

A Solari

Publications and source records attributed to A Solari.

At least 37 records · Page 2Linked to original sources

Aminopyridines for symptomatic treatment in multiple sclerosis.

BACKGROUND: Because of their ability to increase nerve conduction in demyelinated nerve fibers, potassium channel blockers 4-aminopyridine (AP) and 3,4-diaminopyridine (DAP) have been proposed as a symptomatic therapy for people with multiple sclerosis (MS). OBJECTIVES: To determine the efficacy and safety of aminopyridines in improving neurological deficits in people with MS. SEARCH STRATEGY: Computerised general (MEDLINE, EMBASE) and specialised databases (Cochrane MS Group's trials register, CCTR). Hand search of bibliographic references from retrieved studies and recent MS symposia reports. Contact with principal investigators of known studies. SELECTION CRITERIA: Trials were included if they fulfilled all following criteria: randomised controlled trials (RCTs); adults with MS, out of exacerbation; AP or DAP treatment versus placebo; clinical endpoints. DATA COLLECTION AND ANALYSIS: We identified 26 potentially pertinent studies. Three reviewers independently extracted data and assessed trial quality from the 16 studies available as full papers. MAIN RESULTS: Five studies (six publications) and 144 participants were considered in this review. Two more abstracts are awaiting assessment. All five studies were single-centre, double-blind, crossover trials. Four studies assessed the efficacy of AP versus placebo, one compared DAP with active placebo. The duration of treatment ranged from hours to three months. The median quality score of the studies was 3 (range 2-5). The heterogeneity of outcome assessment and the absence of information on individual study periods, allowed quantitative pooling of results for few categorical variables. Of the 144 treated patients, there were six major side effects: one acute encephalopathy, three episodes of confusion, and two seizures. Manual muscle testing was assessed in three studies (54 patients), with 29 patients (54%) improving in at least one muscular district during study treatment versus four patients (7%) during placebo (odds ratio [OR] 14.5, 95% confidence interval [CI] 4.7-43.7). Ambulation was assessed in three studies (54 patients): 9 patients (17%) improved during study treatment versus none during placebo (p<0.001). An improvement in EDSS score was found in 13 of the 144 participants during study treatment (9%) versus none during placebo (p<0.001). No improvement in neuropsychological tests was found in the two trials that evaluated cognitive function. Finally, 47 of 136 people with MS (35%) felt improved when receiving the study drug, against 7(5%) on placebo (OR 9.7, 95% CI 4.3-22.0). REVIEWER'S CONCLUSIONS: Based on currently available information, no unbiased statement can be made about the safety or efficacy of aminopyridines for treating MS symptoms. Furthermore, we could not obtain any data on three unpublished RCTs involving more than 300 participants. We conclude that publication bias remains a pervasive problem in this area, and that until the results of these unpublished studies are available to the scientific community, no confident estimate of effectiveness of aminopyridines in the management of MS symptoms is possible.

4-Aminopyridine↗

Identification of Trypanosoma cruzi genotypes circulating in Chilean chagasic patients.

Parasite DNA amplified by PCR from blood of 73 chagasic children and adults of two endemic areas of Chile were studied by Southern blot and/or dot blot hybridization analysis with a panel of three minicircle probes corresponding to the parasite genotypes (clonets 19, 33 and 39). The hybridization pattern of the PCR positive samples identified clonets 39, 19/20, and 32/33 with frequencies of 0.84, 0.32 and 0.26, respectively. A total of 31 samples corresponded to mixed infections. The most frequently found mixtures were: clonets 39 and 19/20 (14 cases), followed by clonets 39 and 32/33 (8 cases), clonets 39, 32/33 and 19/20 (8 cases), and clonets 32/33 and 19/20 (1 case). Amplified DNA from 9 cases showed no hybridization signal with none of the three studied probes indicating that other genotypes different to the ones mentioned are circulating in humans, but that the clonets used as probes are the most prevalent ones in terms of transmission in the endemic areas studied. A biological characterization of 34 T. cruzi populations isolated from the xenodiagnosis of the patients was performed on an experimental murine model. The biochemical characterization of the parasite populations by molecular karyotype determined that the most frequent parasite isolated from patients belongs to clonet 39.

Adult↗

Health status of people with multiple sclerosis: a community mail survey.

We assessed the self-perceived health status of people with multiple sclerosis (MS) living in the Province of Milan, and the consequences of the disease on family, social and occupational status, using a cross-sectional mail survey. We identified 1350 adults with MS living in the Province of Milan. To a random sample of 400 of these, we sent out the multiple sclerosis quality-of-life-54 questionnaire (MSQOL-54), the proxy version of the short form-36 (SF-36), and a sociodemographic and clinical questionnaire. We received 261 replies (65%). Demographic and clinical data of responders and non-responders were similar except for frequency of hospitalisation over the last year, which was higher in responders. Compared to Italian norms, the MS patients had lower scores in all SF-36 domains; the differences were greatest for physical function, physical role limitations, vitality, and general health perceptions. Unemployment was 103 (41%) overall, 45% in women, and 54% in the less educated. A proxy informant was available for 245 (96%) responders. Concordance between patient and proxy reports on the SF-36 was moderate to excellent. MS had a pervasive impact on patients' lives, with substantial negative consequences for family and working life, that generally make themselves felt in the most active and productive period of people's live.

Adolescent↗

Treatment of Trypanosoma cruzi-infected children with nifurtimox: a 3 year follow-up by PCR.

Patients suffering from Chagas' disease, as determined by positive serological results, were tested for further evidence of Trypanosoma cruzi infection by xenodiagnosis and PCR. The patients included 67 children aged from 0 to 10 years and 75 adults. All children were positive by PCR on their pre-therapy sample, while only 69% of the seropositive adults and none of the 78 seronegative control adults were PCR positive. Xenodiagnosis was positive in 79% of the children, but only in 21% of the adults. A group of 66 children was treated with nifurtimox, and followed up every 3 months during the first year and every 6 months during the second and third year post-therapy, by PCR, xenodiagnosis and serology. We concluded that PCR was the most effective test to monitor children for 3 years post-chemotherapy, when all the cases converted from positive to negative. Conventional serology, however, remained positive after that period in most cases. In contrast, conversion to negative xenodiagnosis occurred very early after treatment.

Adult↗

Studies on parasitemia courses and mortality in mice infected with genetically distant Trypanosoma cruzi clonets.

The biological characterization of bloodstream forms of eleven Trypanosoma cruzi cloned stocks, corresponding to two genetically similar clonets (19 and 20) and one distant clonet (39), according to multilocus enzyme electrophoresis analysis, showed dissimilar parasitemia in an experimental isogenic mouse model. While clonet 39 stocks gave low parasitemias, clonets 19 or 20 stocks gave high parasitemias, independently of the inocula (10(2) and 10(4) bloodstream forms) used. High parasitemia did not always associate with greater mortality. Statistical studies on mortality using a low inocula showed significantly higher mortality with clonet 39 stocks when compared to clonets 19 or 20 stocks. Finally, in order to confirm the identity of each stock studied, typing by molecular karyotype was performed before inoculating mice.

Animals↗

Chronic inflammatory demyelinating polyradiculoneuropathy: long-term course and treatment of 60 patients.

The objective of this study was to assess the long-term course and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We evaluated, according to a predefined protocol, a series of 60 CIDP patients who received a long-term course of steroids and immunosuppressants. Eighteen of them also had monoclonal gammopathy of undetermined significance (MGUS). Mean follow-up was 4.4 years and was similar for CIDP and CIDP-MGUS patients. At the end of the follow-up, improvement was ascertained in 60% of patients (69% CIDP, 39% CIDP-MGUS). Complete remission was achieved in 13%. Out of 26 patients receiving steroids as a monotherapy, 19 improved (73%). The following variables were predictive of a better outcome: female gender, younger age at onset, relapsing-remitting course, and absence of axonal damage at neurophysiologic study. In the multivariate analysis, younger age at onset and demyelination without axonal damage still retained an independent positive value.

Adolescent↗

Isolation and partial characterization of three DNA polymerases from Trypanosoma cruzi.

Three distinct DNA polymerase fractions (A, B and C), were isolated from Trypanosoma cruzi epimastigote forms. Fraction A is a low molecular mass enzyme corresponding to beta-like DNA polymerase of T. cruzi. Fraction B co-purified along several purification steps with fraction A, but in the last step it was clearly separated by a phosphocellulose chromatography. Fraction C was separated from fractions A and B by binding to DEAE-cellulose column, since the other two fractions were eluted in the flowthrough. This enzyme has an apparent native molecular mass of 100 kDa and showed a high preference for poly(dC)-oligo(dG) among different template-primers tested as substrate. Western-blot and biochemical analysis strongly suggest that the three DNA polymerase fractions correspond to different molecular entities. These results are in agreement with the idea that fraction C is a new DNA polymerase of T. cruzi, not described before.

Animals↗

[Diagnosis by electron microscopy of recessive dystrophic epidermolysis bullosa].

Inherited epidermolysis bullosa (EB) includes a number of distinctive diseases that are characterized by the presence of fragile skin and the tendency to develop blisters and erosions. The current classification separates the types of EB on the basis of the ultrastructural level of the blisters. The electron microscopy is very important for the diagnosis and in the recessive dystrophic EB shows that the lamina densa forms the roof of the blister and that the number of anchoring fibrils are absent or reduced. We present the case of a 30 year old woman with a diagnosis of recessive dystrophic EB diagnosed by electron microscopy.

Adult↗

Physical rehabilitation has a positive effect on disability in multiple sclerosis patients.

BACKGROUND: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established. OBJECTIVE: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial. METHODS: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician. RESULTS: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001). CONCLUSIONS: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.

Activities of Daily Living↗

Effects of luteectomy on the maintenance of pregnancy, circulating progesterone concentrations and lambing performance in sheep.

In sheep, there have been few and conflicting data regarding the necessity of the corpus luteum (CL) for the maintenance of pregnancy. The aims of the present study were to examine the effect of luteectomy on and after Day 50 of pregnancy on maternal plasma progesterone concentrations and the progression of pregnancy, to determine the minimum placental progesterone support required for the maintenance of pregnancy, and to evaluate the effect of luteectomy on lambing performance. In Experiment 1, four ewes luteectomized on Day 50 of pregnancy aborted 2-7 days after surgery, whereas pregnancy progressed and parturition occurred between Days 143 and 149, with live lambs, in three of four ewes and in four ewes luteectomized on Days 60 and 70 of pregnancy respectively. The mean (+/- SEM) progesterone concentrations on the day before and one day after luteectomy decreased from 4.87+/-0.85 to 0.42+/-0.06 ng mL(-1) (P<0.01), from 4.57+/-0.51 to 0.80+/-0.12 ng mL(-1) (P<0.02) and from 6.05+/-0.52 to 1.67+/-0.11 ng mL(-1) (P<0.01), respectively, for the ewes luteectomized on Days 50, 60 and 70 of pregnancy. The fall in progesterone concentrations was 90%, 80% and 71%, respectively, for the ewes luteectomized on Days 50, 60 and 70 of pregnancy. In Experiment 2, pregnancy progressed in four ewes luteectomized on Day 70 and parturition occurred between Days 146 and 149, with live lambs. The mean progesterone concentrations declined (P<0.01) from 6.9+/-0.7 ng mL(-1) on the day before luteectomy to 2.1 = 0.3 ng mL(-1) the day after surgery. The concentrations of progesterone in blood collected every 3 h during a 24-h period were stable on Days 60 and 80 of pregnancy, but they were lower (P<0.03) on Day 80 than on Day 60 of pregnancy, for each time period examined. In Experiment 3, the gestation length and birthweights of single, twin and triplet lambs were not different between the control intact ewes (n = 111) and the ewes luteectomized on Days 70-80 of pregnancy (n = 71). Lamb mortality was not different between the two groups (7.2% v. 8.4%, control v. luteectomized). In conclusion, these results showed that (1) the sheep CL is necessary to maintain pregnancy until at least Day 60, (2) progesterone withdrawal induced by luteectomy on and after Day 50 of pregnancy must be of a critical magnitude to provoke abortion, (3) after Day 60 of pregnancy, the CL and the placenta together secrete more progesterone than required for pregnancy maintenance, (4) there is no apparent 24-hour rhythm in maternal plasma progesterone concentrations before and after luteectomy, and (5) luteectomy at mid pregnancy has no apparent effect on gestation length, lamb birthweight or lamb mortality.

Animals↗

Validation of Italian multiple sclerosis quality of life 54 questionnaire.

OBJECTIVES: Health related quality of life (HRQOL) inventories are multi-dimensional measures of patient-centred health status developed for clinical research. The MS quality of life 54 (MSQOL-54) is an MS-specific HRQOL inventory originally devised for English speaking patients. It consists of a core measure, the 36-item short form health survey (SF-36) previously adapted into Italian, and 18 additional items exploring domains relevant to patients with MS (MS-18 module). The authors translated and culturally adapted into Italian the MS-18 module of the MSQOL-54 questionnaire, and clinically validated the whole questionnaire. METHODS: The MS-18 module was translated following the methodology of the International Quality of Life Assessment (IQOLA) project. The MSQOL-54 was validated in 204 consecutive patients with MS seen between April and September 1997 at three participating centres. The questionnaire was explained by the physician who also administered the expanded disability status scale (EDSS) and mini mental status scale examination, and the patient filled in the MSQOL-54 and Beck depression inventory questionnaires (BDI), with assistance if required. The contribution of impairments and disabilities to MSQOL-54 scores were assessed, and mean scores were compared with normative data for the general Italian population, and with the original sample of United States MS patients. RESULTS: The mean age of the 204 patients was 42 years; mean EDSS score was 4.5 (range 0-8. 5). Patients' participation in the assessment was satisfactory, and all scales satisfied the usual psychometric standards. The characteristics of the United States sample matched those of our patients in all but gender (72% United States patients v 52% Italian patients were women), and education (90% United States patients and 44% Italian patients completed high school); MSQOL-54 profiles were also similar. The EDSS was significantly associated with the physical health composite but not with the mental health composite score. Multiple linear regression modelling showed that age and BDI independently predicted physical health composite (p < 0.001), and mental health composite (p < 0.001). Clinical worsening in the previous year had an independent effect on the physical health composite (p < 0.001). CONCLUSIONS: The Italian version of MSQOL-54 is easy to administer and is well accepted by patients. Neurological impairment has a limited influence on perceived quality of life, while age and depressive symptoms has a major influence.

Adult↗

Genetic structure and phylogenetic relationships of Colombian Trypanosoma cruzi populations as determined by schizodeme and isoenzyme markers.

Twenty-four Trypanosoma cruzi stocks isolated from vectors and from human and Didelphis marsupialis hosts from highly separated sylvatic localities in Colombia were characterized by isoenzyme and schizodeme analyses. The stocks were collected primarily from sylvatic ecotopes representing areas of low, moderate, and high endemicity for Chagas' diseases in Colombia. Parasites were characterized mainly by schizodeme analysis with the restriction enzyme Eco RI and the isoenzyme analysis was performed at 10 genetic loci. These analyses demonstrated an agreement between the classifications based on the isoenzyme analysis and on the restriction fragment length polymorphism patterns obtained with the Colombian stocks. There is clear evidence of demic subdivision between the eastern (E) and western (W) stocks separated by the Andean Mountains and Magdalena River, which is likely due to the geographic isolation generated by these topographic features. Heterozygosity estimates indicate that the E group could be more ancient than the W group. As was postulated in a previous study, these results are also compatible with the existence of a clonal population structure in Colombian sylvatic T. cruzi. Evidence presented here failed to demonstrate a correlation between the degree of endemy and genetic clustering. Finally, schizodeme and isoenzymatic analyses comparing Colombian T. cruzi stocks with others from Chile confirm that Colombian isolates are genetically related to zymodeme 1 and distant from zymodeme 2.

Animals↗

Detection of hereditary neuropathy with liability to pressure palsies among patients with acute painless mononeuropathy or plexopathy.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies or brachial plexopathies, commonly associated with a chromosome 17p11.2-12 deletion encompassing the peripheral myelin protein-22 (PMP22) gene. We tried to identify criteria distinguishing HNPP among patients with acute painless mononeuropathy/plexopathy. We investigated by pulsed-field gel electrophoresis the presence of the deletion in 27 patients with isolated or recurrent acute painless mononeuropathy or brachial plexopathy, and no obvious cause of neuropathy. Eight patients carried the deletion, whereas 19 had neither the deletion nor mutations in the PMP22 gene. Age at onset, presenting modality, precipitating events, and rate of recovery did not significantly differ in the two groups. Family history was informative for HNPP diagnosis in 3 cases only. HNPP patients more often showed recurrent episodes, brachial plexopathy, and clinical or electrophysiologic involvement of other nerves. Non-HNPP patients more frequently had peroneal palsy, recent weight loss, and normal electrophysiologic examination in other nerves. Signs of generalized neuropathy and evidence of disease in other family member are often subtle in HNPP and must be thoroughly investigated in patients with acute painless mononeuropathy/plexopathy.

Action Potentials↗

Biological characterization of Trypanosoma cruzi stocks from Chilean insect vectors.

Fifty-seven Trypanosoma cruzi stocks isolated from Triatoma infestans and Triatoma spinolai of the five different geographic endemic areas of Chile were studied by schizodeme and molecular karyotype analysis. Four different genotypes are found in the sylvatic T. spinolai vector and five in the T. infestans domiciliary vector. Of these genotypes, two common genotypes overlap on both transmission cycles exclusively in the extreme northern endemic areas of Chile. Metacyclic trypomastigotes obtained in vitro or cell-derived trypomastigotes proved to be infective in gamma-irradiated Balb/c mice for the study of the immune response and biological behavior. Of a total of 57 T. cruzi stocks obtained, 19 of them, representing all the different genotypes found in Chile, were tested on a murine experimental model and then fully studied. Female compared with male animals demonstrated greater resistance to Chagas disease with all the T. cruzi stocks tested. The immune response was assessed by lytic antibodies that were studied by the in vitro antibody-dependent complement-mediated lytic assay with the use of bloodstream trypomastigotes as target cells. In one unique parasite genotype the elicited lytic antibodies reacted in a genotype-specific manner, in contrast with lytic antibodies generated by other T. cruzi genotypes. Parasitemias were high, moderate, and low, with mortality ranges of 6-50%, 0-45%, and 0-10%, respectively. No association was found between specific infective genotypes and virulence or mortality. Independently of the T. cruzi strain studied, each population displayed a characteristic parasitemia curve and prepatent period. A considerable number of the parasite stocks proved to be mixed populations, according to molecular karyotype patterns obtained before and after differentiation and amplification of the parasites. This fact created difficulty in assessing the identity of the genotype really infective to mice.

Animals↗

Affective disorders and multiple sclerosis: a controlled study on 65 Italian patients.

A high prevalence of major mood disorders in multiple sclerosis (MS) patients has been reported. In this study, we investigated the frequency of previous or present major mood disorders in 65 patients with clinically definite multiple sclerosis (Poser criteria) and in 31 polyneuropathy (PNP) patients. All patients underwent a questionnaire designed after DSM-IV definitions for major mood disorders. A higher lifetime risk for development of a major mood disorder was evident in MS patients (log rank test, p<0.001). Of all MS patients with a major mood disorder, at least 34% had one first-degree relative affected by a mood disorder, while the corresponding figure was 14% among PNP cases. Our data confirm the high lifetime risk for depression in MS patients and suggest that, at least in a subset of MS patients with depression, the genetic basis for depression operates with similar mechanisms as those at work in families with primary depression. However, this is not necessarily true for other subsets of depressed MS patients' families.

Adolescent↗

Immunization of sheep against GnRH early in life: effects on gonadotropins, follicular growth and responsiveness of granulosa cells to FSH and IGF-I in two breeds of sheep with different prolificacy (Romanov and Ile-de-France).

The profile Romanov (R, ovulation rate = 3) and non-prolific Ile-de-France (IF, ovulation rate = 1) breeds were compared for their ovarian sensitivity to gonadotropins and IGF-I before puberty. For this purpose, the effects of in vivo immunization against GnRH on populations of ovarian follicles and in vitro sensitivity of granulosa cells to FSH and IGF-I were studied in prepuberal lambs from both breeds. Seventeen prepuberal lambs of each breed were actively immunized against GnRH between 3 wk and 6 mo of age. Relative to untreated lambs, FSH levels at 4, 5, and 6 mo of age were (respectively) 41%, 25% and 29% for IF, and 43%, 24%, and 36% for R lambs. In a first experiment, histological analysis of ovaries was performed. Immunization treatment decreased the number of small (100-390 microns in diameter) and large size follicles (< 1500 microns) in both breeds at 6 mo of age. In both breeds, gonadotropin (FSH-LH-hCG) treatment increased the number of large size follicles (< 1500 microns in diameter) and induced the formation of preovulatory follicles in immunized as well as untreated lambs. The ovulation rate was less in immunized animals, but it was not different between breeds. In a second experiment, the effects of FSH and IGF-I were studied on granulosa cells from follicles between 1000 and 2000 microns in diameter. In both breeds, IGF-I increased granulosa cell proliferation, but enhanced progesterone secretion was observed only in R lambs after FSH and IGF-I stimulation. Granulosa cell response to FSH treatment was lost by immunization, whereas response to IGF-I remained unchanged in both breeds. These results indicate that long-term immunization of prepuberal lambs against GnRH reduced systemic concentrations of FSH, follicular development, and response to gonadotropins in vivo, similarly in the prolific R and the non-prolific IF breed. However, granulosa cells from R lambs had higher steroidogenic capacities and were more responsive to FSH. In addition, these results suggest that IGF-I could play an important role in regulating growth of small follicles both in immunized and non-immunized lambs.

Animals↗

Incidence and survival of childhood CNS tumours in the Region of Lombardy, Italy.

Incidence rates for CNS tumours in children of age 0-14 years in the Region of Lombardy, Italy, during the period 1988-93 were analysed; survival probability updated to December 1995 was also estimated. CNS tumours defined according to the International Classification of Diseases for Oncology codes were actively searched for. CNS tumours were diagnosed in 296 children. The age-standardized rates were 40.0 per million child years for both sexes together, and 45.3 for boys and 34.4 for girls. In all age groups, boys had a higher incidence than girls. The annual incidences were 13.7, 7.0, 5.8 for astrocytoma, medulloblastoma and ependymoma, respectively. The overall survival percentages at 5 and 8 years after diagnosis were 68 and 66, respectively. Prognosis was good for astrocytoma (5-year survival, 81%), and declined in the order: other gliomas (5-year survival, 76%); ependymoma (5-year survival, 62%), and medulloblastoma (5-year survival, 43%). The histological type of the tumour was the most powerful independent predictor of survival in children with a CNS tumour. Medulloblastoma/primitive neuroectodermal tumours appeared to have the highest risk of a poor prognosis compared with astrocytoma (relative risk, 3.27; 95% confidence interval, 1.81-5.91). Age at diagnosis and sex had no significant effect on survival. The incidence of childhood CNS tumours found in this study is higher than previously reported in Italy, and is one of the highest in the world from population-based data. Survival of children with brain tumours has improved greatly in recent years. These results suggest that children in Lombardy with CNS tumours had a good survival experience compatible with high quality of care.

Adolescent↗