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Biomedical subjects

M Zoppi

Publications and source records attributed to M Zoppi.

At least 19 recordsLinked to original sources

Microscopic self-dynamics in liquid hydrogen and in its mixtures with deuterium.

We have measured the dynamic structure factor of liquid parahydrogen, pure and mixed with deuterium, in various thermodynamic conditions using incoherent inelastic neutron scattering. The experiments were carried out on TOSCA-II, a new time-of-flight, inverse-geometry, crystal-analyzer spectrometer. After an accurate data reduction, the high-energy parts of the neutron spectra recorded in backward scattering were studied through the modified Young and Koppel model, from which the mean kinetic energy values for a hydrogen molecule were estimated. In addition the low-energy parts of the neutron spectra recorded in forward scattering were analyzed in the framework of the Gaussian approximation and fitted through a Levesque-Verlet model for the velocity autocorrelation function. Thus various physical quantities are determined and compared with accurate path integral Monte Carlo simulations. Despite the excellent quality of these fits, the velocity autocorrelation functions derived from the forward-scattering data appear totally unable to properly describe the backward-scattering ones. These findings prove an unquestionable breakdown of the Gaussian approximation in semiquantum liquids. The present results appear of great interest and suggest further investigation on the limits of the widely used Gaussian approximation.

Journal Article↗

Density of phonon states in solid parahydrogen from inelastic neutron scattering.

We have measured the inelastic neutron scattering spectrum of solid parahydrogen (at low pressure and T=13.3 K) using the thermal original spectrometer with cylindrical analyzers spectrometer at the ISIS pulsed neutron source (UK). From the experimental spectrum we have obtained the parahydrogen density of phonon states which has been compared with the estimates available in the literature. The present determination improves substantially the previous experimental scenario from the point of view of both statistics and accuracy. The comparison with the most recent estimate obtained from a quantum mechanical simulation of the molecular dynamics calls for an improvement of the computational methods..

Journal Article↗

Factors influencing pricking pain threshold using a CO2 laser.

The purpose of this study was the evaluation of the best experimental conditions in healthy subjects for the measurement of the minimal thermal energy density E1 which induced pricking pain on the volar surface of the left forearm by means of CO2 laser pulses. E1 was measured on a well-defined area, using laser pulses of different durations and constant power P. The dependence of E1 on the stimulus power P, the size A of the radiated area and the surface temperature T(e) were explored. In the first part of the study, these relations were obtained using a computer program, from the calculated spatio-temporal distribution of the skin temperature during, and following, a laser pulse which caused pricking pain. The second part studied a set of subsequent measurements carried out on a group of five healthy trained subjects and agreed only in part with the calculated data. We found that the measurement error on E(t) was less than 10% with P between 1.5 and 3 W, and A between 0.15 and 0.25 cm2, respectively. The influence of sensitization and adaptation phenomena on the measured data was also explored. We also show a rhythmic annual change of T(e) and E1.

Adult↗

Direct experimental access to microscopic dynamics in liquid hydrogen.

We have obtained the double-differential incoherent neutron scattering cross section of liquid and solid parahydrogen in various thermodynamic conditions using TOSCA, a time-of-flight, inverse geometry, crystal analyzer spectrometer, operating at the pulsed neutron source ISIS. The measured cross section provides direct experimental access to the self part of the center-of-mass inelastic structure factor of the parahydrogen molecules in the system. Data have been corrected for the experimental effects and then analyzed in the framework of the Young-Koppel model and the Gaussian approximation. The velocity autocorrelation functions and their energy spectra have been obtained from a fitting procedure, making use of the quantum generalized Langevin equation and of model memory functions, and finally compared to the most recent results of both molecular centroid dynamics and self-consistent quantum mode-coupling theory. Some dynamic quantities were also related to simple equilibrium properties and simulated through a standard path integral Monte Carlo code. Results are very interesting but still urge for further developments of theoretical and dynamic simulation approaches, as well as for more extensive experimental efforts.

Journal Article↗

Hypofunctionality of Gi proteins as aetiopathogenic mechanism for migraine and cluster headache.

The involvement of Gi proteins in the modulation of pain perception has been widely established, and mutations in G-proteins have already been identified as the aetiopathological cause of human diseases. The aim of the present study was to determine whether a deficiency or a hypofunctionality of the Gi proteins occurred in primary headache. The functionality and the level of expression of Gi proteins were investigated in lymphocytes from migraine without aura, migraine with aura and cluster headache sufferers. A reduced capability to inhibit forskolin-stimulated adenylyl cyclase activity in headache patients was observed. Migraine patients also showed basal adenosine cAMP levels about four times higher than controls. The reduced activity of Gi proteins seems not to be related to a reduction of protein levels since no significant reduction of the Gialpha subunits was observed. These results indicate Gi protein hypofunctionality as an aetiopathogenic mechanism in migraine and cluster headache.

Adult↗

Evidence for immune activation against oxidized lipoproteins in inactive phases of juvenile chronic arthritis.

OBJECTIVE: Oxidative stress contributes to joint inflammation and damage in rheumatoid arthritis. In a mobile inflamed joint, exercise induced multiple cycles of hypoxia-reperfusion injury may lead to the creation of a redox environment in which oxido-reductase systems, by NADPH mechanisms, produce highly reactive chemical species (i.e., oxygen free radicals). We investigated 2 endproducts of lipid peroxidation, malonildialdehyde (MDA) and diene conjugates (DC), and the formation of antibodies against oxidized low density lipoproteins (Ab oxLDL) in juvenile chronic arthritis (JCA), and assessed the role of oxidative phenomena in different phases and subsets of this disease. METHODS: To assess the role of oxidative stress in JCA, we measured the endproducts of lipid peroxidation, MDA and DC, by the increase of absorbance at 586 nm and 234 nm, respectively, and the levels of Ab oxLDL by ELISA in the sera of 58 patients with JCA and 21 healthy controls. Due to crossreactivity between Ab oxLDL and anticardiolipin antibodies (aCL), the sera were also tested by a standard ELISA for IgG-aCL. The patients were divided into 3 subsets: 29 with pauciarticular (pauci), 15 with polyarticular (poly), and 14 with systemic (sys) onset disease, and then were subdivided, according to different variables appropriate to each subset, reflecting active and inactive disease, into 30 active (14 pauci, 8 poly, 8 sys) and 28 inactive (15 pauci, 7 poly, 6 sys). RESULTS: Levels of Ab oxLDL were significantly increased in the whole group of patients (566.6 +/- 263.0 vs 206.6 +/- 136.3 mU/ml; p < 0.001) and in each of the type of onset (pauci 660.8 +/- 272.1, p < 0.001; poly 341.3 +/- 134.7, p < 0.01; sys 497.8 +/- 114.8, p < 0.001) compared to controls. Ab oxLDL were higher in the inactive than in the active group (743.5 +/- 231.9 and 404.4 +/- 169.9; p < 0.001). MDA and DC levels were not increased significantly in patients' sera. No patient was positive for IgG-aCL. CONCLUSION: These findings suggest that MDA and DC cannot be considered major markers of oxidative stress in JCA and that the Ab oxLDL may represent a delayed sign of oxidative stress previously induced by the inflammatory process in patients with JCA.

Anti-Inflammatory Agents, Non-Steroidal↗

A reduced functionality of Gi proteins as a possible cause of fibromyalgia.

OBJECTIVE: The etiopathogenesis of fibromyalgia (FM), a syndrome characterized by widespread pain and hyperalgesia, is still unknown. Since the involvement of Gi proteins in the modulation of pain perception has been widely established, the aim of the present study was to determine whether an altered functionality of the Gi proteins occurred in patients with FM. METHODS: Patients with FM and other painful diseases such as neuropathic pain, rheumatoid arthritis (RA), and osteoarthritis, used as reference painful pathologies, were included in the study. The functionality, evaluated as capability to inhibit forskolin-stimulated adenylyl cyclase activity, and the level of expression of Gi proteins were investigated in peripheral blood lymphocytes. RESULTS: Patients with FM showed a hypofunctionality of the Gi protein system. In contrast, unaltered Gi protein functionality was observed in patients with neuropathic pain, RA, and osteoarthritis. Patients with FM also showed basal cAMP levels higher than controls. The reduced activity of Gi proteins seems to be unrelated to a reduction of protein levels since only a slight reduction (about 20-30%) of the Gi3alpha subunit was observed. CONCLUSIONS: Gi protein hypofunctionality is the first biochemical alteration observed in FM that could be involved in the pathogenesis of this syndrome. In the complete absence of laboratory diagnostic tests, the determination of an increase in cAMP basal levels in lymphocytes, together with the assessment of a Gi protein hypofunctionality after adenylyl cyclase stimulation, may lead to the biochemical identification of patients with FM.

Adenylyl Cyclases↗

Incidence of lethal adverse drug reactions in the comprehensive hospital drug monitoring, a 20-year survey, 1974-1993, based on the data of Berne/St. Gallen.

OBJECTIVES: Realising the limitations of spontaneous drug monitoring systems concerning the epidemiological aspects, a comprehensive program was founded. It was based on previous publications from the US, Canada and Northern Ireland, mainly those of the BCDSP (Boston Collaborative Drug Surveillance Programme). METHODS: Drug monitoring was carried out by a group of physicians which included the medical head of each of the divisions of internal medicine, a statistician and an informatician. Only probable or definite drug event relationships were included. A probable event is defined as one in which the drug interaction was more likely to be the cause than any non-drug-related cause. The same criteria were valid for the lethal reactions. RESULTS: In the present evaluation, we found 26 probable lethal adverse drug reactions out of a total of 48,005 patients consecutively admitted to the divisions of internal medicine of three Swiss teaching hospitals during the years 1974-1993, an incidence of 0.054%. The median age of the cohort was 68 years (range 11-103 years), of which 49% were women. The median hospital stay was 14 days and the median number of drugs was eight per patient. CONCLUSION: The patients with a lethal outcome were presented under the eight pharmacologic-therapeutic classes of drugs and the classification proposed by NS Irey. This is based on long histopathologic experience and helps to identify preventable risks.

Adolescent↗

Oxidative stress in Systemic Sclerosis.

In 63 patients affected by Systemic Sclerosis (SSc) (limited subset: 40; diffuse subset: 23; early: 30; advanced: 33) the peroxidation product diene-conjugates (DC) and antibodies against oxidised low density lipoproteins (Ab oxLDL) were tested in serum by a spectrophotometer (absorbance 234 mn) and by a standard ELISA respectively. The data were compared with those obtained by 21 healthy subjects. DC was significantly higher in patients (73.3 +/- 37.2 microM/l; p < 0.0001) than in controls (48.4 +/- 16.7) as well as in the limited (80 +/- 48.8; p < 0.05) than in the diffuse subset (64.5 +/- 36.4); and in early (84.1 +/- 31.4; p < 0.05) than in advanced stage of the disease (67.9 +/- 42.5). The levels of Ab oxLDL were significantly higher in SSc patients (309.5 +/- 367.2 mU/ml; p < 0.0001) in all its subsets (limited: 351.9 +/- 351.1, p < 0.0001; diffuse: 207.7 +/- 316.1, p < 0.05; early: 428.9 +/- 417.1, p < 0.001; advanced: 302.7 +/- 89.9, p < 0.0001) than in controls (89.3 +/- 29.1). These antibodies levels were higher in limited subset than in diffuse (p < 0.05) and in early SSc than in advanced SSc (p < 0.05). The highest values of parameters of oxidative stress are found in the early stages, when the episodes of reperfusion after ischemic episodes (Raynaud's phenomenon) are very frequent. Moreover, the damage is higher in the early stages of SSc, with intact microvessels, than in late stages, when microvessels are very reduced in number, destroyed by the worsening of the disease. These data show that the respiratory burst deduced by the lipoperoxidation is higher in SSc than in controls, and may be an important pathogenetic factors involved in tissue changes in SSc.

Antibodies↗

Signal generation in a non-EU country.

One of the most important objects of post-marketing surveillance is the early detection of serious, unknown and unexpected adverse events. As spontaneous reported adverse events vary considerably in their signal-generating value the Swiss Drug Monitoring Center SANZ implemented an early signal detection system in 1991. With a set of screening criteria the individual case reports are automatically checked by the system and read into a signal file. Subsequently these potential signals are processed to quantify the signal generating value of the particular case. According to the screening criteria 2072 (53%) of the reported cases were considered as potential signals. After validating and quantifying their signal value 27% (565) were drug-related and unlabelled, 8% (173) were also rated as serious. On the basis of these cases 114 labelling changes were made. Some of the most interesting cases are discussed. This computer-assisted early signal generation model in a small country with 7 million inhabitants has a high detectability of new, rare, serious and quality of life affecting adverse drug reactions (ADRs). These newly detected ADRs must be interpreted in cognizance of the limitations and restrictions of spontaneous reporting and do not allow pharmacoepidemiologic conclusions.

Journal Article↗

Substance P in the serum of patients with rheumatoid arthritis.

Serum substance P was assayed in rheumatoid arthritis patients and healthy controls to evaluate whether neurogenic inflammation with substance P release is significant in rheumatoid arthritis. A very sensitive competitive immunoenzymetric assay was used. Mean serum substance P level was significantly higher in rheumatoid arthritis patients than in controls and was not correlated with disease duration, morning stiffness duration, Thompson's articular index, Larsen's radiographic score, or the following laboratory indices of inflammation: erythrocyte sedimentation rate, C-reactive protein, and alpha 1-acid glycoprotein. Neurogenic inflammation with substance P release may contribute significantly to the pathogenesis of rheumatoid arthritis. The absence of correlations between serum substance P and clinical or laboratory indices of inflammation may reflect complex interactions between neurogenic inflammation and other pathogenic mechanisms, which may influence clinical features and laboratory tests in rheumatoid arthritis patients.

Adult↗

[Heparin-induced thrombocytopenia. Results from the Comprehensive Hospital Drug Monitoring (CHDM) Bern/St. Gallen].

Of 23,520 consecutive hospitalizations from 1980-1988 (corresponding to 16,628 individual patients) in three departments of general internal medicine, 8261 were treated with heparin. All observations of patients displaying a probable, possible or questionable relationship of thrombocytopenia to heparin (administered i.v. or subcutaneously) were electronically collected by the CHDM program, revised on the basis of the primary case records and selected by standardized criteria. 13 of the 8261 patients exposed to heparin were considered to have a probable or possible HIT, corresponding to a frequency of 0.157%. In two of them severe thrombocytopenia was observed (corresponding to 0.024%) accompanied in one case by a white clot syndrome. Thrombocytopenia was defined as a platelet value below 100 x 10(9)/l and severe thrombocytopenia as one below 30 x 10(9)/l. In the literature we found slight, asymptomatic thrombocytopenia in < or = 1-8% of heparin treated patients. Our result of 11 out of 8261 (corresponding to 0.133%) is low, partly because the thrombocyte count was not controlled systematically, the heparin used was mainly produced from swine intestinal mucosa, and no antibody tests had been carried out. To prevent severe thrombocytopenia from heparin we propose monitoring the platelet count if the treatment is to be continued for more than 5 days. The newer low molecular weight heparins, all of swine origin, are much safer compared to the traditional preparations in regard to risk of HIT and white clot syndrome.

Aged↗

[Frequency of antibiotics-associated colitis in hospitalized patients in 1974-1991 in "Comprehensive Hospital Drug Monitoring", Bern/St. Gallen].

In 3 divisions of internal medicine of teaching hospitals of the Comprehensive Hospital Drug Monitoring (CHDM) Foundation Bern/St Gallen, 42,920 patients consecutively admitted between 1974-1991 were investigated for adverse drug reactions. Of these 16,150 patients (38%) had received at least one systemically administered antibacterial drug during the hospital stay. Antibiotic-associated colitis included the following diagnoses: pseudomembranous colitis, hemorrhagic colitis and milder forms of colitis. We collected the data of these patients by searching for all diagnoses which might represent antibiotic-associated colitis (from the list of WHO adverse drug reaction terminology). 9 individual patients with one episode of probable antibiotic-associated colitis were found. In 5 of these cases, only one drug given during the hospital stay seemed to be implicated. An additional 32 patients were admitted with antibiotic-associated colitis in relation to treatment with the same groups of drugs before hospital admission. Based on the exposure pattern of the 9 patients with antibiotic-associated colitis compared to all patients exposed during hospital stay, we estimated the following frequencies related to the drug groups with at least 1,000 patients exposed: for all antibacterial chemotherapeutics 0.6/1000 (0.25-1.06); all penicillins 0.6/1000 (0.22-1.32), for benzyl-, phenoxy-, ureido-, isoxazolyl penicillins and methicillin 2.0/1000 (0.42-5.92) and aminopenicillin or analogues, with or without clavulanic acid 0.6/1000 (0.18-1.35). For cephalosporins the frequency is 1.4/1000 (0.17-5.12). Under sulfonamides combined with trimethoprim or related substances (5077 exposed patients) and fluoroquinolones (1043 exposed patients) no case was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗