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Biomedical subjects

A Martini

Publications and source records attributed to A Martini.

At least 127 records · Page 7Linked to original sources

Antiphospholipid antibody syndrome in pediatric patients.

The antiphospholipid antibody syndrome is characterized by the association between recurrent arterial or venous thrombosis and the presence of circulating antiphospholipid antibodies. Antiphospholipid antibody-related thrombosis seems to constitute a significant proportion of childhood thromboses. About one third of children suffering a thrombotic event have circulating antiphospholipid antibodies, and more than two thirds of children with idiopathic cerebral ischemia meet the criteria for the diagnosis of antiphospholipid antibody syndrome. Because the other risk factors for thrombosis commonly found in adults have no impact on the pediatric patient, the risk for thrombosis and thrombotic recurrences and the optimal anticoagulation therapy may differ from adults.

Adolescent↗

Soluble tumour necrosis factor receptor levels reflect coagulation abnormalities in systemic juvenile chronic arthritis.

The objective was to evaluate tumour necrosis factor (TNF) status in patients with systemic juvenile chronic arthritis (s-JCA). Plasma levels of TNF-alpha, and serum levels of soluble TNF receptor 1 and 2 (sTNFR1 and sTNFR2) were measured using specific immunoassays in 20 patients with s-JCA, 10 with polyarticular JCA and 15 with pauciarticular JCA, and in 20 controls comparable for age. In patients with active s-JCA, circulating levels of TNF-alpha, sTNFR1 and sTNFR2 were significantly (P < 0.001) higher than those of controls. The levels of sTNFR1 and sTNFR2, but not those of TNF-alpha, were associated with the persistence and severity of systemic symptoms and were significantly correlated with prolongation of partial thromboplastin time and decrease in prothrombin activity. In two patients evaluated during a s-JCA-associated macrophage activation syndrome, a marked increase in sTNFR1 and sTNFR2 was found. Our results suggest that in s-JCA, TNF is involved in systemic manifestations, in the subclinical coagulation abnormalities, and in the development of the macrophage activation syndrome.

Adolescent↗

Cytokines in juvenile rheumatoid arthritis.

Most data concerning the role of cytokines in chronic arthritides have been obtained in adult rheumatoid arthritis. In this paper we review the available evidence regarding the role of the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor in juvenile rheumatoid arthritis, focusing in particular on the differences among the various onset types. Results from the analysis of cytokine expression may provide the basis for the use of specific anticytokine treatment. Recent clinical trials in adult rheumatoid arthritis have demonstrated the feasibility and clinical usefulness of these treatments.

Arthritis, Juvenile↗

Correlation between conventional disease activity measures in juvenile chronic arthritis.

OBJECTIVE: To estimate in a cross sectional analysis the degree of colinearity among the disease activity measures more commonly used in juvenile chronic arthritis (JCA). METHODS: This study assessed in a single clinical evaluation three subjective variables, three measures of functional capacity, eight articular indices, and two laboratory indicators of systemic inflammation in 55 consecutive children with JCA. The relation between the clinical measures of JCA activity was determined by Pearson correlation coefficients. An r value of 0.7 or greater was considered evidence of colinearity. RESULTS: Among the subjective variables, parent global assessment of overall well being and parent assessment of pain were correlated with each other; the physician assessment of disease activity did not show evidence of colinearity with any other variable. The functional status measures were correlated with each other, but not with the indices of articular inflammation. There was a high degree of colinearity among the articular variables, with the number of active joints and the overall severity score being correlated with each other as well as with all the single articular indices. The laboratory variables were correlated with each other, but not with any of the articular, functional or subjective variables. CONCLUSION: Our results show a high degree of colinearity among the disease activity measures belonging to the same category, whereas this is uncommon for variables that investigate different domains of disease activity. These data underline the need to include the evaluation of each domain in the assessment of JCA activity.

Adolescent↗

Chimeric calsequestrin and its targeting to the junctional sarcoplasmic reticulum of skeletal muscle.

Calsequestrin (CS) is the junctional sarcoplasmic reticulum (jSR) Ca2+ binding protein responsible for intraluminal Ca2+ storage. The targeting mechanisms of CS to the jSR are yet to be unraveled. The nine-amino acid epitope of the influenza virus hemoagglutinin (referred to as HA1) was added at the COOH-terminal of CS by polymerase chain reaction cloning. The HA1-tagged CS cDNA was transiently transfected in either HeLa cells, myogenic cell lines, such as C2 and L8 cells, myoblasts of rat skeletal muscle primary cultures, or regenerating soleus muscle fibers of adult rats. The expression and intracellular localization of chimeric CS-HA1 were monitored by epifluorescence and confocal microscopy using either anti-CS antibodies or anti-HA1 antibodies. About 30% of transfected HeLa cells and 20-40% of myogenic cells expressed CS-HA1 into intracellular compartments, such as the perinuclear cisternae of endoplasmic reticulum (ER). Myoblasts of newborn rat skeletal muscles were first transfected and subsequently stimulated to differentiate into myotubes. CS-HA1 was detected in approximately 20% of transfected myotubes and did not affect CS distribution in myotubes. In the soleus muscle of adult rat, intramuscular injection of bupivacaine induced necrosis followed by regeneration. In vivo transfection of HA1-tagged CS cDNA in regenerating skeletal muscles determined expression in a few skeletal muscle fibers; CS-HA1 was localized only in jSR, as judged by confocal microscopy of longitudinal sections. The present results show that chimeric CS-HA1 is correctly sorted to ER/SR compartments and that the free COOH-terminal is not requested for sorting, retention, and segregation of CS to the SR.

Animals↗

The clinical significance of antiphospholipid antibodies.

The antiphospholipid syndrome is defined as the association between the presence of antiphospholipid antibodies, detected as anticardiolipin antibodies and/or lupus anticoagulant, and a history of either arterial or venous thrombosis and/or recurrent pregnancy loss. Because thrombosis may occur in virtually any organ system, diagnosing the antiphospholipid syndrome and taking appropriate anticoagulation measures are important considerations in all medical specialties. Antiphospholipid antibody-associated thrombosis tends to recur. Antithrombotic prophylaxis to prevent recurrences is therefore needed. Prophylaxis in individuals with circulating antiphospholipid antibodies who have no history of thrombosis is still controversial. Although direct evidence for a pathogenetic role of antiphospholipid antibodies in the development of thrombosis is still lacking, recent studies suggest that it is causative rather than coincidental. New insights on the possible mechanisms leading to thrombosis were provided by the discovery of the serum cofactor (beta2-GPI), a coagulation inhibitor which is required for binding of anticardiolipin antibodies to cardiolipin. More recently, patients with antiphospholipid antibodies were found to possess autoantibodies directed against other coagulation factors, including prothrombin, protein C and protein S. Future studies should clarify whether these different antigenic specificities are associated with particular clinical events and assess the risk of thrombosis associated with the presence of antiphospholipid antibodies in asymptomatic individuals.

Antibodies, Antiphospholipid↗

Damage to the nasopharyngeal mucosa induced by current levels of urban air pollution: a field study in lambs.

This study concerns the effects of urban air pollution on the nasopharyngeal epithelium, with the aim of evaluating the possible harmful activity of levels of atmospheric pollution which are not currently considered to be dangerous. Over a 3 month period, 10 lambs kept in a zone characterized by numerous vehicles were sacrificed at regular intervals, and their nasopharyngeal mucosa was examined by scanning electron microscopy and image analysis. Two lambs kept in a rural area were used as controls. The local levels of some airborne contaminants (NO(x), NO2, NO, SO2, CO and particulate matter with aerodynamic diameter < or =10 microm (PM10)) were monitored throughout the experiment. The urban air had an irritating effect, inducing hypersecretion of mucus and morphological damage to the ciliated epithelium. These alterations increased with the duration of exposure to urban air and with increasing pollution levels, although the levels remained below current legal levels. We conclude that the harmful effects of airborne contaminants are probably underestimated. Moreover, physicochemical evaluation of pollution parameters should be complemented by morphological study of upper respiratory epithelium in exposed animals, since this mucosa is a sensitive target for irritating agents.

Air Pollutants↗

Long-term health outcomes and quality of life in American and Italian inception cohorts of patients with juvenile rheumatoid arthritis. I. Outcome status.

OBJECTIVE: To assess the long-term health outcomes and quality of life of patients with juvenile rheumatoid arthritis (JRA) using health and functional assessment questionnaires in 2 populations, one from the USA and one from Italy. METHODS: Patient eligibility criteria: (1) first examined in our units between 1958 and 1990 during the first 6 months after onset of symptoms, (2) diagnosis of JRA by the American College of Rheumatology criteria, (3) disease duration of at least 5 years at the time of assessment of outcome. Instruments used: (1) the Health Assessment Questionnaire (HAQ, short form, or childhood HAQ (CHAQ), and (2) Quality of Life Scales (QOLS, adults only). Eligible patients were identified by computer search and chart review and were then mailed a packet containing a consent/assent form and the assessment instruments. RESULTS: Of 346 patients who met the eligibility criteria were able to locate 301, and 290 verbally agreed to participate and were mailed packets. Signed consent and complete information were received from 227 of the 290 (78%), 178 from the USA and 49 from Italy. Mean duration of disease at the time of outcome assessment was 15 yrs. 127 had pauciarticular, 55 polyarticular, and 45 systemic onset disease. Mean and (median) scores of the outcomes are shown in the table. [table: see text] CONCLUSION: Long-term outcome, as assessed by the instruments used, is very favorable in most patients with JRA 5 years or more after onset of symptoms.

Adolescent↗

Long-term health outcomes and quality of life in American and Italian inception cohorts of patients with juvenile rheumatoid arthritis. II. Early predictors of outcome.

OBJECTIVE: To determine whether demographic, clinical, and immunogenetic variables measurable during the first 6 months of illness long-term health outcomes and quality of life in patients with juvenile rheumatoid arthritis (JRA). METHODS: Patient eligibility criteria: (1) first examined in our units between 1958 and 1990 within 6 months of onset of symptoms; (2) diagnosis of JRA by American College of Rheumatology criteria; (3) disease duration of at least 5 years at the time of assessment of outcome. Instruments used: (1) the Health Assessment Questionnaire (HAQ, short form), or Childhood HAQ (CHAQ) to measure disability (0-3 scale), (2) pain, and (3) parental assessment of overall well being, each scored on a 15 cm visual analog scale; (4) the Quality of Life Scales (QOLS) (adults only). Independent variables that showed significant results using univariate tests underwent multiple logistic regression analysis. RESULTS: 227 patients were available for analysis. Mean duration of disease at time of assessment of outcome was 15 years (range 5.3-36.1). Univariate tests allowed 11 variables for disability, 9 for pain, 7 for overall well being, and 4 for QOL into the multivariate analysis. The best predictor of higher disability was the articular severity score (odds ratio, OR, 5.69) while antinuclear antibody positivity foretold less disability (OR 0.29). HLA-DR5 positivity conferred the greatest risk for pain (OR 3.34), while HLA-B5, DR3, and C3 were protective (OR 0.25, 0.28, 0.33, respectively). Early hand involvement was the strongest predictor of poorer overall well being (OR 8.75). Only the erythrocyte sedimentation rate was predictive of future QOL, but the model yielded a low C statistic (< 70%) and the OR 95% confidence limits were extreme (OR 9.77; 95% confidence interval, 1.22-77.8). CONCLUSION: Clinical and immunogenetic variables measurable within 6 months of onset of JRA can be used to predict future disability, pain, and well being. QOL appears more difficult to forecast, perhaps due to the multiple domains that make up this outcome. Further study is needed to identify other genetic and laboratory factors that predict outcome in JRA with greater precision.

Adolescent↗

Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis.

OBJECTIVE: To evaluate quantitative or qualitative differences in synovial fluid (SF) cytokine levels among patients with systemic juvenile rheumatoid arthritis (JRA), antinuclear antibody positive pauciarticular JRA, or adult RA. METHODS: SF levels of interleukin 1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist (IL-1Ra) IL-11, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1), leukemia inhibitory factor (LIF), all measured by immunoassays, and of IL-6, measured with a bioassay using B9 cells, were evaluated in 11 patients with systemic JRA, 24 with pauciarticular JRA, and 22 adult patients with RA. RESULTS: SF IL-6 levels were significantly higher in patients with systemic JRA than patients with pauciarticular JRA (p = 0.003) or RA (p = 0.002). IL-1alpha was detectable in 12/24 SF samples from pauciarticular JRA, in 2/22 SF from RA, and in no sample from systemic JRA (p = 0.004 vs RA; p = 0.005 vs systemic JRA). SF IL-11 levels were significantly higher in patients with RA than patients with systemic JRA (p = 0.012) or pauciarticular JRA (p = 0.005). We found no significant differences in SF levels of IL-1beta, IL-1Ra, TNF-alpha, sTNFR1, or LIF. CONCLUSION: In systemic JRA, SF levels of IL-6 are significantly higher than in pauciarticular JRA or in RA; IL-1alpha is present in a significant proportion of patients with pauciarticular JRA, but not in those with RA or systemic JRA.

Adolescent↗

Argon laser photocoagulation in the treatment of the palpebral lobe cysts of the lacrimal gland (dacryops).

Dacryops is a closed cyst that develops on the palpebral lobe of the lacrimal gland, manifesting in the region of the external canthus. Its slow and insidious growth causes mechanical and aesthetic problems that do not regress spontaneously. Treatment involves excision of the cyst while sparing the adjacent glandular tissues. In cases associated with hypolacrimation, marsupialization of the cyst is indicated. To obtain a reduction of the cyst to an aesthetically acceptable level in cases of simple dacryops, the authors suggest argon laser therapy, which avoids the risks related to surgery and general anesthesia and eliminates the need for hospitalization. Two patients with simple dacryops were treated with blue-green argon laser under local anesthesia. At the end of follow-up, the cysts had been clinically reduced in volume and were not visible by external examination. In cases of simple dacryops, laser therapy is suitable for the reduction of the cyst. Photocoagulation treatment is not advisable in cases that are complicated by fistulas or where the clinical presentation is atypical.

Aged↗

[Pattern of normal fetal heart rate in the third trimester of pregnancy].

BACKGROUND: It has been shown by previous studies that the mean fetal heart rate (FHR) decreases from the 11th to the 30th week, afterwards the values remain more stable. In the present study we evaluated the FHR pattern throughout the last stages of pregnancy and particularly we estimated the interindividual variability to achieve the maturation of the parasympathetic nervous system in the control of the FHR rythm. METHODS: Serial FHR determinations were made from the 28th week until term in 126 physiological pregnancies, submitted to umbilical Doppler velocimetry. The mean FHR was measured on the length of 6 cardiac beats. The FHR patterns of 48 healthy pregnancies, were also analyzed longitudinally. RESULTS: The transversal data, related to the 126 physiological pregnancies, show a further decrease of the FHR during the last stages of pregnancy: from the 28th to 40th week it drops from the average value of 141 bpm to 133 bpm (r = -0.1469). The longitudinal data show that this decrease occurs in 27% of patients between the 30th and the 33rd week and in 73% of patients between the 34th and the 40th week. CONCLUSIONS: The conclusion is drawn that the physiological decrease of the mean FHR value occurs for each fetus at different gestational ages due to a different balance between the sympathetic and parasympathetic tone; moreover, we find that the interindividual variability in achieving the full maturation of the parasympathetic nervous system is quite wide.

Adult↗

Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis.

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released.

Administration, Oral↗

The effect of clofilium, a K-channel blocker, on the electrogenic K secretion and the sensory discharge at the frog semicircular canal.

Potassium transport by dark cells produces marked K-concentration differences between endo- and perilymphatic fluids in labyrinthine organs and generates the transepithelial potential. The ensuing electrochemical potential for K sustains the transduction current which regulates activity at the cytoneural junction. Clofilium, a compound which is known to block cardiac K channels and to decrease the endocochlear potential, was applied to the endolymphatic side of the isolated frog semicircular canal. The drug abolished the transepithelial potential and increased K outflux from the lumen to the dark cells (or the basolateral perilymph) with no apparent interference with active K secretion. When applied to the perilymphatic side in the intact labyrinth, clofilium reduced the rate of occurrence of miniature excitatory postsynaptic potentials (mEPSPs), both at rest and in response to mechanical stimulation (sinusoidal rotation at 0.1 Hz, 12.5 deg/s2 peak acceleration). This effect may be related to a reduced K-electrochemical unbalance and a decreased transduction current. The drug consistently reduced mEPSP size, although amplitude distributions remained log-normal and time intervals between successive mEPSPs remained exponentially distributed; this suggests a direct effect of clofilium on the postsynaptic membrane, in addition to any possible presynaptic effects. Spike discharge by the afferent fibre was almost completely abolished at rest and responses to mechanical stimulation were reduced by 85-90%. These effects cannot be accounted for by the mild reduction of mEPSP rates and confirm a direct action of clofilium on the afferent postsynaptic terminal.

Animals↗

Compensatory hypertrophy and progressive renal damage in children nephrectomized for Wilms' Tumor.

Clinical, biochemical, and sonographic evaluation of the remaining kidney function and size was performed in 34 patients, 12 males and 22 females, ages 2.1-19.6 years, nephrectomized (NP) for Wilms' tumor (WT) at least 2 years before (mean 8.6). All patients had normal blood pressure and serum bicarbonates. Two of them had microhematuria, four proteinuria 4 mg/m2/hr, and 11 microalbuminuria (MA) > 20 mg/24 hr. Only one patient had reduced creatinine clearance and maximum bipolar length (MBL) as well as kidney volume (KV) < 100% of expected. In the other patients, average MBL was 128 +/- 11% (P = 0.0001). MBL, but not KV, was inversely correlated (P = 0.04) to age at NP. KV, but not MBL, was directly correlated (P = 0.009) to MA. Average MA was 48 +/- 94 mg/24 hr and was correlated to the time from NP (P = 0.026). The remaining kidney increases in volume much more than in length. The increase in KV is related to the degree of MA, whereas the increase in MBL is higher in subjects younger at NP. The high prevalence of significant MA, which is in turn related to the time from NP and to the KV, raises some concerns about the long-term renal prognosis of children NP for WT.

Adolescent↗

Otoneurological study in workers exposed to styrene in the fiberglass industry.

Twenty workers exposed to styrene and acetone in small fiberglass factories were monitored for 8 h using passive dosimeters. Urine samples were collected at the end of the workshift and before the start of work on the next morning. The 8-h time-weighted average exposure values for styrene and acetone ranged from 14 to 416 mg/m3 and from 70 to 277 mg/m3, respectively. The sum of styrene metabolites, mandelic acid and phenylglyoxylic acid (MA + PGA), in the next-morning urine samples ranged from 81 to 943 mg/g creatinine. Different test sensitivity was identified in the otoneurological battery: it was low for audiometric tests and ABR, and relatively high for vestibular tests. The vestibular system seems partially sensitive to the toxic effects of styrene in the absence of clinical signs and symptoms. The actual exposure levels for styrene cannot be considered devoid of functional subclinical consequences.

Acetone↗

Differential killer sensitivity as a tool for fingerprinting wine-yeast strains of Saccharomyces cerevisiae.

The extreme variability of the killer phenomenon in nature, expressed differently in different strains of the same yeast species, embodies an exceptional potential for the discrimination of yeasts at the strain level. Killer-sensitive relationships between a killer reference panel of 24 yeasts belonging to 13 species of six genera, and different industrial wine-starters of Saccharomyces cerevisiae can be used profitably for a rapid and simple fingerprinting procedure.

Antibiosis↗