Uncommon syndromes and treatment manifestations of malignancy: Case 1. Unusual association of lupus and sarcoma.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
A Martini
Publications and source records attributed to A Martini.
High circulating levels of biologically inactive IL-6/SIL-6 receptor complexes in systemic juvenile idiopathic arthritis: evidence for serum factors interfering with the binding to gp130.
We previously demonstrated that high levels of IL-6/sIL-6R complexes are present in sera of patients with systemic juvenile idiopathic arthritis (s-JIA) and that the amount of IL-6 estimated in the IL-6/sIL-6R complexes is markedly higher than that measured by the B9 assay. Here, we show that two additional bioassays, employing human myeloma XG-1 cells and human hepatoma Hep3B cells, detected serum IL-6 levels similar to those measured by the B9 assay and approximately 10-fold lower than the IL-6 levels estimated to be present in the IL-6/sIL-6R complex. Using an assay for the measurement of the amount of circulating IL-6 complexed with the sIL-6R and available for binding to gp130 (gp130 binding activity), we show that the IL-6/gp130 binding activity is similar to that detected by the bioassays and again significantly lower than that estimated to be present in the IL-6/sIL-6R complex. Addition of recombinant human IL-6 (rhIL-6) to sera of patients or controls results in a markedly lower increase in the gp130 binding activity in patients than in controls. Moreover, sera from s-JIA patients inhibited in a dose dependent manner the gp130 binding activity assay. These results show that sera from patients with s-JIA contain a factor, or factors, that inhibit(s) the binding of the IL-6/sIL-6R complex to gp130. This inhibitory activity does not appear to be due to soluble gp130, C-reactive protein or autoantibodies to IL-6.
Adolescent↗
Mapping of a new autosomal dominant non-syndromic hearing loss locus (DFNA43) to chromosome 2p12.
Hearing impairment (HI) is the most frequent sensory defect with wide genetic heterogeneity. Approximately 80% of genetic hearing loss is non-syndromic and 15-25% of exhibit autosomal dominant inheritance. We analysed an Italian three generation family in which non-syndromic hearing impairment is transmitted as an autosomal dominant trait. Onset of HI in all affected subjects occurred in the second decade of life, with subsequent gradual progression from moderate to profound loss. HI was bilateral and symmetrical, involving all frequencies. After exclusion of the known DFNA loci with markers from the Hereditary Hearing Loss Homepage (URL: http://dnalab-www.uia.ac.be/dnalab/hhh), a genome wide scan was carried out using 358 highly informative microsatellite markers. Significant linkage (Zmax=4.21, theta=0) was obtained with chromosome 2p12 markers. The results were confirmed by multipoint analysis (Zmax=4.51), using the location score method. Haplotype analysis defined a 9.6 cM disease gene interval on chromosome 2 without overlap with the other identified loci. Fine mapping and identification of candidate genes are in progress.
Chromosome Mapping↗
Outcome of primary antiphospholipid syndrome in childhood.
The objective of this paper is to investigate the long-term outcome of primary antiphospholipid syndrome (APS) in the paediatric age. The features of unselected patients with primary APS who had disease onset before the age of 16 years were retrospectively analysed in three Italian referralcentres. Clinical and laboratory manifestations were assessed to establish whether, at the end of follow-up, the final diagnosis was still primary APS or whether they had developed definite SLE or lupus-like syndrome. Fourteen patients, nine boys and five girls, who had the presenting clinical manifestation of APS between three and 13 years of age (median nine years) and were followed for two to 16 years (median six years). Six patients presented with deep vein thrombosis, five with cerebral stroke, two with peripheral artery occlusion and onewith myocardial infarction. During follow-up, four patients had one or more recurrences of vascular thrombosis. At last observation, 10 patients could still be classified as having primary APS, two had developed SLE, one lupus-like syndrome and one Hodgkin's lymphoma. In conclusion; our analysis suggests that some children who present with the features of primary APS may progress to develop SLE or lupus-like syndrome.
Adolescent↗
Exploring the clinical and epidemiological complexity of GJB2-linked deafness.
GJB2 mutation analysis was performed in 179 unrelated subjects with sporadic or familial hearing loss (HL). Among 57 families, 18 showed a vertical transmission of HL, the disease being present in two or three generations. Besides 155 nonsyndromic cases, 24 patients presenting with extra-auditory clinical signs were included in the molecular study. GJB2 mutation analysis was also performed in 19 subjects with an anamnestic history of perinatal risks factors for acquired HL. The 35delG mutation accounted for 22.1% of analyzed chromosomes in sporadic cases and 39.4% in familial cases; 35delG prevalence reached 41% in autosomal recessive and 44.4% in pseudodominant pedigrees. Two novel GJB2 mutations were identified in compound heterozygosity with 35delG allele (D159V, 284ins/dup[CACGT]). Two 35delG homozygous subjects were identified among HL cases classified as environmental in origin. Four patients 35delG heterozygous (35delG/V95M, 35delG/L90P, 35delG/167delT, and 35delG/?) and two homozygous presented with extra-auditory clinical signs involving different organs (skin, vascular system, hemopoietic lineages, and thyroid). In a high proportion of 35delG heterozygous HL patients (52%), no second GJB2 mutation was detected. The reported data highlight the complexity of the genetic epidemiology of GJB2-linked deafness, further enlarging the spectrum of situations in which GJB2 mutation analysis should be performed. The presence of extra-auditory signs in a significant portion of GJB2-mutated patients suggests the possibility that GJB2 loss of function could contribute to clinical phenotypes presenting in association with deafness. This hypothesis deserves further investigation. The failure to identify a presumed partnering GJB2 mutation in a high proportion of deaf patients remains a challenging problem to be clarified.
Amino Acid Sequence↗
L-Dopa decreases cutaneous nociceptive inhibition of motor activity in Parkinson's disease.
OBJECTIVES: To estimate changes in motor inhibitory mechanisms at the spinal level in Parkinson's disease (PD) patients by measuring cutaneous silent responses to nociceptive stimuli in the course of L-Dopa therapy. MATERIALS AND METHODS: Fourteen patients with idiopathic PD (Group 1) and 13 patients with other forms of parkinsonism (Group 2) participated in the study. The cutaneous silent period (CSP) from the hand and clinical scores (UPDRS, part III) were measured "off" therapy (T0), after a single dose of L-Dopa (T1) and 3 months after the beginning of L-Dopa daily therapy (T2). RESULTS: At T0 the duration of the CSP was significantly prolonged in Group 1 and Group 2. At T1 and T2 the mean duration of the CSP significantly decreased in Group 1 (P < 0.05) and a significant correlation was found between the shortening of the CSP and the improvement of rigidity and bradikynesia in the upper limb. CONCLUSIONS: Our findings show that L-Dopa decreases the cutaneous nociceptive inhibition of motor activity in PD patients. CSP may be useful to assess L-Dopa responsiveness during the clinical course of PD.
Administration, Oral↗
Extracellular enzymatic activity profiles in yeast and yeast-like strains isolated from tropical environments.
AIMS: The objective of this study was to investigate the extracellular enzymatic activity (EEA) profile of yeasts isolated from tropical environments of the Brazilian rain forest. This screening survey could constitute the first approach in selecting yeast strains of environmental origin potentially exploitable as enzyme producers. METHODS AND RESULTS: In this study, 348 yeast (193 ascomycetes and 155 basidiomycetes) and 46 yeast-like strains (Aureobasidium pullulans) were screened for their EEA profile. The spread occurrence of extracellular amylases, esterases, lipases, proteases, pectinases and chitinases appeared to be a strain-related character. CONCLUSIONS: Yeasts isolated from tropical environments could represent a promising source of EEA. Selected strains showed maximum levels of EEA under acidic or neutral conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the potential for yeasts isolated from extreme environments as sources of industrially relevant enzymes for biotechnological purposes.
Ascomycota↗
Hearing loss evaluation of Sjögren's syndrome using distortion product otoacoustic emissions.
Sjögren's syndrome (SS) is a cell-mediated immune disorder primarily affecting the exocrine glands and hearing loss may be the first otological manifestation of this autoimmune disease. In order to assess the degree of sensorineural hearing loss in SS, 22 female patients were examined by means of standard audiometric tests (pure-tone audiometry, acoustic reflexes and impedance testing) and using distortion product otoacoustic emissions (DPOAEs). The results indicated that only 36.3% of the patients had mild sensorineural hearing loss. Hearing level and distortion product threshold estimates were found to be significantly correlated. No relationship was found between the duration of the disease and the DPOAE and hearing threshold variables. The data suggest that SS may not directly cause sensorineural hearing loss.
Adult↗
Visceral leishmaniasis as a cause of unexplained fever and cytopenia in systemic lupus erythematosus.
Explore the source record for details and available documents.
Adolescent↗
Role of interleukin-6 in growth failure: an animal model.
Indirect evidence suggests a link between factors produced during the inflammatory response and stunted growth. The demonstration of this link was provided by the observation that mice transgenic for the inflammatory cytokine interleukin-6 (IL-6), expressing high circulating levels of IL-6 since birth, show a marked decrease in growth rate leading to adult mice 50-70% the size of wild-type littermates. The growth defect is completely abolished by neutralization of IL-6. In these mice the production of GH is normal, while circulating levels of IGF-I are markedly decreased. Administration of IL-6 to wild-type mice results in a marked decrease in IGF-I levels. These observations show that in vivo high levels of IL-6 are associated with low levels of IGF-I. However, IL-6 does not directly affect IGF-I production both in vitro and in vivo. In contrast, markedly decreased levels of IGFBP-3 are present in the IL-6 transgenic mice and administration of IL-6 to wild-type mice results in a marked decrease in IGFBP-3 levels. In these mice the decrease in IGFBP-3 levels is associated with impaired formation of the 150 kD ternary complex, even in the presence of normally functional ALS. As a consequence, IL-6 transgenic mice show increased clearance of circulating IGF-I, suggesting that IL-6 decreases IGF-I levels by increased clearance. Proteolytic degradation of IGFBP-3 occurs in the IL-6 transgenic mice, suggesting that the decrease in IGFBP-3 could be at least in part due to proteolysis. The abnormalities of the IGF-I system observed in the IL-6 transgenic mice are similar to those found in patients with systemic juvenile idiopathic arthritis, one of the chronic inflammatory diseases characterized by stunted growth and prominent production of IL-6. The IL-6 transgenic mice represent a faithful animal model of the growth impairment associated with chronic inflammation and may therefore provide information relevant to the understanding and treatment of this complication of inflammatory diseases.
Animals↗
In vivo neutralization of human IL-6 (hIL-6) achieved by immunization of hIL-6-transgenic mice with a hIL-6 receptor antagonist.
Neutralization of IL-6 represents an attractive therapeutic option in several diseases, including B cell neoplasia, osteoporosis, and autoimmunity. Therapeutic attempts in humans have shown that administration of injectable doses of a mAb to IL-6 does not provide efficient neutralization of the cytokine in vivo. Therefore, alternative approaches are needed. In this study, we evaluated whether the Ab response to human IL-6 (hIL-6) elicited by vaccination with Sant1 (a hIL-6 variant with seven amino acid substitutions) was able to fully correct in vivo the clinical and biological effects of a chronic endogenous overproduction of hIL-6 in the hIL-6-transgenic NSE/hIL-6 mice. Because of the overexpression of hIL-6, occurring since birth, with circulating levels in the nanogram per milliliter range, NSE/hIL-6 mice have a marked decrease in growth rate, associated with decrease in insulin-like growth factor I levels, and represent an animal model of the growth impairment associated with human chronic inflammatory diseases. Following immunization with Sant1, but not with hIL-6, NSE/hIL-6 mice developed high titers of polyclonal Abs to hIL-6. The Abs, acquired by transplacental transfer, effectively neutralized IL-6 activities in vivo as shown by the complete correction of the growth defect and normalization of insulin-like growth factor levels in the hIL-6-transgenic offspring. Immunization with Sant1 could therefore represent a novel and simple therapeutic approach for the specific neutralization of IL-6 in humans.
Amino Acid Substitution↗
Asymptomatic persistent pulmonary infiltrates in an immunocompetent boy with cat-scratch disease.
We describe here an immunocompetent boy with fever, regional adenopathy, multifocal hepatosplenic granulomas, and high and increasing serum antibody titers for Bartonella henselae in whom diffuse bilateral reticulonodular pulmonary infiltrates developed in the absence of respiratory symptoms.
Bartonella henselae↗
Juvenile systemic scleroderma.
Systemic scleroderma in children is very rare and is considered similar to adult-onset disease. In adults, new etiopathogenetic and therapeutic approaches have emerged in recent years. For instance, it has been shown that microchimerism could play a role in disease pathogenesis and that immunoablation followed by stem cell rescue could be of potential therapeutic benefit. There is also evidence that these new approaches can be of value for childhood-onset disease.
Adolescent↗
Mapping of a new autosomal dominant nonsyndromic hearing loss locus (DFNA30) to chromosome 15q25-26.
Hearing impairment is the most common inherited human sensory defect. Nonsyndromic Hearing Impairment (NSHI) is the most genetically heterogeneous trait known. Over 70 loci have been mapped and a total of 19 genes have been identified. We report here a novel locus (DFNA 30) for autosomal dominant NSHI that we mapped to chromosome 15q25-26 in an Italian four-generation family. The haplotype analysis has identified a critical interval of 18 cM between markers D15S151 and D15S130. This region does not overlap with DFNB16 locus but partially coincides with the otosclerosis (OTS) locus. Localisation of the locus DFNA30 is a first step towards the identification of the gene.
Chromosome Mapping↗
Efficient otoacoustic emission protocols employed in a hospital-based neonatal screening program.
Within the context of a hospital-based newborn hearing screening program, we have studied the application of two OAE protocols (TEOAE and DPOAE) on a group of 250 well babies. The main goal of this study was to evaluate the performance of DPOAE protocol in a relatively large population sample. using a preset number of five tested frequencies, in comparison with a default TEOAE screening protocol. The data were collected on the second day of life and during spontaneous sleep. The TEOAE recordings were acquired with linear protocols using click stimuli of 70-75 dB SPL and were used as indicators of normal cochlear function. The cubic distortion product DPOAE responses were evoked by an asymmetrical 75-65 dB SPL protocol, with a frequency ratio of 1.22. Five frequencies (referring to F2) were tested at 1.5, 2.0, 3.0, 4.0 and 5.0 kHz. The data from the DPOAE responses show a similar pass rate (similarity = 0.98) to the linear TEOAE protocol. The data presented suggest that a DPOAE cochlear evaluation, at 5 pre-selected frequencies, has clinical potential.
Deafness↗
Large-scale screening of selected Candida maltosa, Debaryomyces hansenii and Pichia anomala killer toxin activity against pathogenic yeasts.
The killer activity of selected crude toxins produced by nine Candida maltosa, Debaryomyces hansenii and Pichia anomala strains was tested at 37 degrees C against 383 strains belonging to 19 pathogenic species of 10 genera (Candida, Clavispora, Cryptococcus, Filobasidiella, Issatchenkia, Kluyveromyces, Pichia, Saccharomyces, Stephanoascus and Trichosporon). The broad killer spectra exhibited by all crude toxins may lead to the development of new antimycotic agents against medically important yeasts.
Antifungal Agents↗
Environmental and biological monitoring of traffic wardens from the city of Rome.
A molecular epidemiological study on Roman policemen is ongoing. The results of a first assessment of the occupational exposure to aromatic compounds of 66 subjects engaged in traffic control and of 33 office workers are presented in this paper. Passive personal samplers and urinary biomarkers were used to assess exposure to benzene and polycyclic hydrocarbons during work shifts. The results obtained indicate that benzene exposure in outdoor workers is about twice as high as in office workers (geometric mean 7.5 and 3.4 micrograms/m3, respectively). The distribution of individual exposure values was asymmetrical and skewed toward higher values, especially among traffic wardens. Environmental benzene levels recorded by municipal monitoring stations during work shifts (geometric mean 11.2 micrograms/m3) were in the first instance comparable to or greater than individual exposure values. However, several outlier values were observed among personal data that greatly exceeded average environmental benzene concentrations. Among the exposure biomarkers investigated, only blood benzene correlated to some extent with previous exposure to benzene, while a seasonal variation in the excretion of 1-hydroxypyrene and trans-muconic acid was observed in both study groups. In conclusion, these results suggest that outdoor work gives a greater contribution than indoor activities to benzene exposure of Roman citizens. Moreover, relatively high-level exposures can be experienced by outdoor workers, even in the absence of large-scale pollution episodes.
Adult↗
Discordance between proxy-reported and observed assessment of functional ability of children with juvenile idiopathic arthritis.
OBJECTIVE: To determine the level of agreement between parents and clinicians in rating dysfunction in children with juvenile idiopathic arthritis (JIA). METHODS: A parent of each patient completed the Italian version of the Childhood Health Assessment Questionnaire (CHAQ). Subsequently, an examiner assessed, in a specially equipped room, the child's performance of tasks as described by the CHAQ. Demographic and clinical variables were recorded for all patients. RESULTS: Seventy consecutive JIA patients and their parents were included. The mean proxy-reported and observed CHAQ score was 0.64+/-0.53 and 0.47+/-0.62 respectively, the difference ranging from -1.75 to 1.5. There were 30 cases (43%) of agreement (difference < or =0.25 CHAQ units) between the parent's and clinician's ratings, whereas in 40 cases (57%) there was discordance (difference >0.25 CHAQ units). In 30 cases the parent rated the child's functional ability as worse than that observed by the clinician (i.e. the parent underestimated the child's function), whereas in 10 cases the parent rated the child's functional ability as better than that observed by the clinician (i.e. overestimated the child's function). Multivariate regression analysis showed that children's functional ability was overestimated by parents with increasing erythrocyte sedimentation rate and global articular severity score and underestimated with increasing level of pain. Among the functional areas of the CHAQ, the level of agreement was poorest in the areas of eating and hygiene and was best for activities. CONCLUSIONS: Discordance between proxy-reported and observed functional ability was frequent in our patients with JIA. The children's functional ability was overestimated by parents as the severity of arthritis increased and underestimated as the level of pain increased.
Adolescent↗