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Biomedical subjects

Paolo Rossi

Publications and source records attributed to Paolo Rossi.

At least 55 records · Page 3Linked to original sources

Effect of painful heterotopic stimulation on the cutaneous silent period in the upper limbs.

OBJECTIVE: To evaluate the effect of heterotopic painful stimulation (HPS) on the cutaneous silent period (CSP) and the withdrawal flexor reflex (WFR) in the upper limbs, in an attempt to better identify the nociceptive component of the CSP and its functional relationship with the flexor reflex. METHODS: The CSP at different stimulus intensities, the WFR and the H/M ratio were studied in 12 healthy adults. Neurophysiological measurements were recorded in the following 4 conditions: (1) control session; (2) non-painful session (dipping hand in water at 25 degrees C); (3) painful (cold pressor test, CPT); and (4) after-effect (3-8 min after taking hand out of water at 5-6 degrees C). RESULTS: During the CPT, the duration of the high-threshold CSP was approximately 23% shorter than the baseline value, the high-threshold CSP latency was approximately 10% longer than the baseline value, and the mean RIII reflex area was approximately 40% smaller than the baseline reflex area (all P<0.05). A significant correlation was found between the percentage decrease in the CSP duration and the WFR area (r=0.61, P<0.05). CONCLUSIONS: Our findings indicate that the HPS specifically inhibits both the high-threshold CSP and the WFR, thereby providing further evidence that these cutaneous reflexes are functionally and anatomically related, and that they represent different aspects of a complex nocifensive response.

Adult↗

Trigemino-cervical-spinal reflexes in humans.

INTRODUCTION: Electrical stimulation of the supraorbital nerve (SON) induces late reflex responses in the neck muscles; these responses are hypothesised to be polysynaptic reflexes participating in a defensive withdrawal retraction of the head from facial nociceptive stimuli. Such responses may extend to the proximal muscle of the arms. OBJECTIVE: (1) to investigate reflexes in the upper limb muscles (trigemino-spinal responses, TSR) and their relationship with trigemino-cervical responses (TCR); and (2) to identify the nociceptive component of such reflexes and their functional significance. METHODS: Reflex responses were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the SON in 12 healthy subjects. The sensory (ST), painful (PT) and reflex thresholds, the latency and area of the responses, the effect of heterotopic painful stimulation (HTP), the recovery cycle as well as the effect of the expected and unexpected stimuli were measured. RESULTS: Stable reproducible TCR and TSR responses were identified at 2.5+/-0.4 x ST, which corresponded exactly to the PT in all the subjects. The TCR and TSR areas were markedly reduced after HTP. The recovery cycle of the TSR area was faster than that of the TCR. Repeated rhythmic stimulation failed to induce progressive reflex suppression. CONCLUSIONS: These results confirm the nociceptive nature of the TCR and indicate that the biceps brachii response (TSR) has the same nocifensive significance as the posterior neck muscle responses. TCR and TSR are mediated different polysynaptic pathways The presence of trigemino-cervical-spinal responses in our study clearly indicates that there is a reflex interaction between nociceptive trigeminal afferents and both upper and lower cervical spinal cord motoneurons.

Adult↗

Congenital coronary artery anomalies angiographic classification revisited.

Many fragmental classification of coronary artery anomalies (CAAs) exist, but a simple practical angiographic classification for angiographers has been never proposed. This study is aimed to suggest a simplified angiographic classification of congenital CAAs based on just a few univocal common angiographic patterns. The authors reviewed 5100 coronary angiographies in order to select CAAs patients and identify simple common angiographic features. Sixty-two patients (1.21%, female/male 20/42, mean age 65.3 +/- 10.6 years) had CAA on coronary angiography. The authors identified seven classes for seven angiographic patterns: I--hypoplasia/atresia, II--hyperdominance, III--fistula, IV--originating from wrong sinus, V--originating from other arteries, VI--splitting, and VII--tunnelling. A, P, B, R, L, PA, AO refer to anterior, posterior or passage between the aorta and pulmonary artery and to right, left, pulmonary artery and aorta. Three blind observers were be able to categorize all the CAAs according to this classification with no inter-observer differences: 3.2% were classified as class I, 8.1% as class II, 3.2% as class III, 24.2% as class IV, 22.5% as class V, 29% as class VI, and finally 9.7% as class VII. Eleven patients (17.7%) had 'A' passage, 10 (16.1%) 'P' passage and 9 (14.5%) 'B' passage. Twelve patients (19.5%) had anomalous origin from the right sinus of Valsalva, 2 (3.2%) from the left. This simplified classification was applicable to all most significant CAAs and in the authors' view it may make for a more rapid and univocal CAA angiographic description.

Aged↗

Hepatitis C virus-related cryoglobulinemic glomerulonephritis: long-term remission after antiviral therapy.

BACKGROUND: Renal involvement in patients with hepatitis C virus (HCV) infection commonly manifests as cryoglobulinemic glomerulonephritis (CGN). The combination of interferon-alpha (IFN-alpha) and ribavirin, which is currently considered the standard antiviral therapy in chronic hepatitis C, could be difficult to carry out in cryoglobulinemic patients who are frequently anemic, even in the absence of renal failure. Clinical and histologic long-term results of this therapeutic regimen have not been so far reported in patients with CGN. METHODS: Three patients with HCV-related CGN and slightly impaired kidney function were treated with IFN-alpha and ribavirin for 12 months, and subsequently were followed up for 24 to 36 months. Two of these patients who were anemic were pretreated with erythropoietin (EPO). In each patient renal biopsy was performed before starting therapy and repeated 14 to 26 months after the end of treatment. RESULTS: In all three patients, antiviral therapy induced sustained virologic response, which was followed by clear improvement in clinical, biochemical, immunologic, and histologic features. Clinical and biochemical improvement steadily progressed in all three patients, achieving normal or nearly normal results at the end of follow-up. In contrast, some immunologic features, such as serum levels of C4 and rheumatoid factor activity, did not normalize in two and three patients, respectively. Posttreatment renal biopsies showed mildly active histologic lesions. CONCLUSION: Antiviral therapy with IFN-alpha and ribavirin may be considerably beneficial in patients with HCV-related CGN who obtain sustained virologic response.

Adult↗

CD4 and major histocompatibility complex class I downregulation by the human immunodeficiency virus type 1 nef protein in pediatric AIDS progression.

The human immunodeficiency virus type 1 (HIV-1) nef gene is a crucial determinant in AIDS disease progression. Although several in vitro activities have been attributed to the Nef protein, identifying the one critical for in vivo pathogenicity remains elusive. In this study, we examined a large number of nef alleles derived at various time points from 13 perinatally infected children showing different progression rates: six nonprogressors (NPs), three slow progressors (SPs), and four rapid progressors (RPs). The patient-derived nef alleles were analyzed for their steady-state expression of a Nef protein, for their relative ability to downregulate cell surface expression of CD4 and major histocompatibility complex class I (MHC-I) and for their capacity to bind the clathrin adaptor AP-1 complex. We found that NP-derived nef alleles, compared to nef alleles isolated from SPs and RPs, had reduced CD4 and MHC-I downregulation activities. In contrast, SP- and RP-derived nef alleles did not differ and efficiently downregulated both CD4 and MHC-I. AP-1 binding was a conserved function of primary nef alleles not correlated with clinical progression. Defective Nef proteins from NPs, rather than sharing common specific changes in their sequences, accumulated various amino acid substitutions, mainly located outside the conserved domains previously associated with Nef biological properties. Our data indicate that Nef-mediated downregulation of cell surface CD4 and MHC-I significantly contributes to the expression of the pathogenic potential of HIV-1.

Alleles↗

A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency.

X-linked anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the gene encoding NEMO/IKKgamma, the regulatory subunit of the IkappaB kinase (IKK) complex. IKK normally phosphorylates the IkappaB-inhibitors of NF-kappaB at specific serine residues, thereby promoting their ubiquitination and degradation by the proteasome. This allows NF-kappaB complexes to translocate into the nucleus where they activate their target genes. Here, we describe an autosomal-dominant (AD) form of EDA-ID associated with a heterozygous missense mutation at serine 32 of IkappaBalpha. This mutation is gain-of-function, as it enhances the inhibitory capacity of IkappaBalpha by preventing its phosphorylation and degradation, and results in impaired NF-kappaB activation. The developmental, immunologic, and infectious phenotypes associated with hypomorphic NEMO and hypermorphic IKBA mutations largely overlap and include EDA, impaired cellular responses to ligands of TIR (TLR-ligands, IL-1beta, and IL-18), and TNFR (TNF-alpha, LTalpha1/beta2, and CD154) superfamily members and severe bacterial diseases. However, AD-EDA-ID but not XL-EDA-ID is associated with a severe and unique T cell immunodeficiency. Despite a marked blood lymphocytosis, there are no detectable memory T cells in vivo, and naive T cells do not respond to CD3-TCR activation in vitro. Our report highlights both the diversity of genotypes associated with EDA-ID and the diversity of immunologic phenotypes associated with mutations in different components of the NF-kappaB signaling pathway.

Child↗

25th-order high-temperature expansion results for three-dimensional Ising-like systems on the simple-cubic lattice.

25th-order high-temperature series are computed for a general nearest-neighbor three-dimensional Ising model with arbitrary potential on the simple cubic lattice. In particular, we consider three improved potentials characterized by suppressed leading scaling corrections. Critical exponents are extracted from high-temperature series specialized to improved potentials, obtaining gamma=1.2373(2), nu=0.63012(16), alpha=0.1096(5), eta=0.036 39(15), beta=0.326 53(10), and delta=4.78 93(8). Moreover, biased analyses of the 25th-order series of the standard Ising model provide the estimate Delta=0.52(3) for the exponent associated with the leading scaling corrections. By the same technique, we study the small-magnetization expansion of the Helmholtz free energy. The results are then applied to the construction of parametric representations of the critical equation of state, using a systematic approach based on a global stationarity condition. Accurate estimates of several universal amplitude ratios are also presented.

Journal Article↗

Pre-perceptual pain sensory responses (N1 component) in type 1 diabetes mellitus.

We investigated the integrity of the ascending pathways for pain sensitivity in the early stage of type 1 diabetes mellitus, by measuring the N1 component and the conventional N2/P2 vertex potentials of laser evoked potentials (LEPs). Brain responses to laser stimuli were obtained in 21 healthy volunteers and 21 type 1 diabetic patients, without either clinical neuropathy or electrophysiological evidence of large-fiber damage. In diabetic patients N1 and P2 latencies were prolonged and the N1 and N2/P2 amplitudes were decreased after foot stimulation. A significant reduction of the conduction velocity of Adelta fibers in the lower limbs was also observed. LEPs reveal an early, subclinical and selective damage of pain sensation in diabetic patients. N1 and P2 potentials are delayed and decreased in parallel giving evidence that LEP abnormalities are not secondary to a cognitive dysfunction and mostly reflect a small-fiber dysfunction.

Afferent Pathways↗

Prognostic value of the stromal cell-derived factor 1 3'A mutation in pediatric human immunodeficiency virus type 1 infection.

A mutation of the stromal cell-derived factor 1 gene (SDF-1 3'A) was shown to protect adults exposed to human immunodeficiency virus type 1 (HIV-1) from infection and to affect HIV disease progression in adults. The presence of this mutation in HIV-1-infected Kenyan children did not predict mother-to-child virus transmission. The SDF-1 3'A polymorphism was studied in 256 HIV-1-infected, 118 HIV-1-exposed but uninfected, and 170 unexposed and uninfected children of Italian origin, and the frequency of SDF-1 3'A heterozygosity and homozygosity in each of the 3 groups was similar. Of the 256 HIV-1-infected children, 194 were regularly followed up and were assigned to groups according to disease progression. The frequency of the SDF-1 3'A allele was substantially lower among children with long-term nonprogression than among children with rapid (P =.0329) or delayed (P =.0375) progression. We show that the presence of the SDF-1 3'A gene correlates with accelerated disease progression in HIV-1-infected children born to seropositive mothers but does not protect against mother-to-child HIV-1 transmission.

Adolescent↗

Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study.

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG.

Adolescent↗

A preliminary study of magnetization transfer and diffusion tensor MRI of multiple sclerosis patients with fatigue.

To investigate whether multiple sclerosis (MS) tissue damage is associated with the presence and severity of fatigue, we obtained magnetization transfer (MT) and diffusion tensor (DT) magnetic resonance imaging from 28 patients with MS (14 with and 14 without fatigue). MT ratio and mean diffusivity did not differ between fatigued and non-fatigued MS patients. No correlation was found between Fatigue Severity Scale scores and any of the MT and DT MRI-derived quantities. This preliminary study suggests that the severity of overall MS pathology in the brain seems not to be a critical factor contributing to the development of fatigue in MS.

Adult↗

Neuropeptide enzyme hydrolysis in allergic human saliva.

The activity of neuropeptide-degrading enzymes, and possible variations in this activity under allergic conditions, was examined in human saliva obtained from allergic volunteers and from an age- and sex-matching group of healthy controls, using leucine enkephalin as model substrate. The results obtained indicate that, under experimental conditions, the substrate was partially hydrolyzed by all three classes of enzymes known to degrade it in human saliva: aminopeptidases, dipeptidylaminopeptidases and dipeptidylcarboxypeptidases. In the presence of saliva obtained from allergic donors, a large increase in the activity of aminopeptidases, and a more limited increase in the activity of dipeptidylaminopeptidases, induced an increase of substrate hydrolysis with respect to that measured in the controls. The activity of all substrate-active enzymes, the allergy-associated variations in this activity, and the amount of substrate hydrolyzed, were found to be different in male and female saliva. Specifically, in the controls the gender-related differences in substrate hydrolysis were mainly caused by the higher activity of aminopeptidases observed in male as compared to female saliva. In contrast, in allergic saliva, a greater increase in the activity of aminopeptidases in female saliva reduced the gender-related differences in the pattern of hydrolysis, which was also different from that observed in the controls.

Adult↗

Different effects of steroidal therapy on neuropeptide-active enzymes in male and female human saliva.

The hydrolysis of a model neuropeptide (leucine enkephalin) was studied in the presence of saliva obtained from normal and allergic male and female volunteers in the absence and in the presence of steroidal treatment. Possible variations in the formation of substrate hydrolysis by-products were studied in whole samples and after steric exclusion chromatography fractionation. The results obtained confirm already-described variations in substrate hydrolysis in allergic as compared to control saliva, as well as the effect of steroidal treatment on the activity of the substrate-active enzymes. In addition, whereas in male saliva, therapy was associated with a net decrease of substrate hydrolysis, in female saliva hydrolysis remained near the levels measured in the absence of treatment. Finally, therapy induced modifications of enzyme apparent molecular weight distribution that appear to be similar for all substrate-active enzyme classes, but different in male and female saliva. In male saliva, therapy decreased the activity of the enzymes eluted at high apparent molecular weight, while it increased the activity of the enzymes of low apparent molecular weight. Because the increase was considerably less than the decrease, the net effect was to decrease the activity of the substrate-active enzymes, nearly to the low levels measured in the controls. In female saliva the therapy-associated decrease in the activity of the enzymes eluted at high apparent molecular weight was offset by the increase in the activity of those eluted at low apparent molecular weight, consequently, substrate hydrolysis remained near the level measured in the absence of treatment, a level that was higher than that measured in the controls.

Adrenal Cortex Hormones↗

Evaluation of the relevance of humoral immunodeficiencies in a pediatric population affected by recurrent infections.

Recurrent infections are a common cause of morbidity in childhood. Several reports have associated this condition to low levels of IgA and IgG subclasses and/or lack of specific antipolysaccharide antibody response, although the relevance of these defects in terms of prognosis and therapeutic approach is still unclear. The aim of our study was to determine the frequency and the clinical relevance of humoral immunodeficiency (HID) other than hypogammaglobulinemia in children affected by recurrent infections. We recruited 67 pediatric patients affected by recurrent infections. Serum IgG, IgA, IgM, IgG2, IgG3, and specific anti-Haemophilus influenzae (anti-Hib) antibodies were determined. Thirty-seven out of 67 patients showed antibody defects (55%). IgA deficiency was observed in 21 out of 67 patients (31%), followed by IgG2 (18%), IgG3 (15%) and IgM (6%) defects. Anti-Hib deficiency was present in three out of 44 patients (7%). A tendency for a higher occurrence of pneumonia and otitis, although not statistically significant (p > 0.05), was observed in HID patients compared to children with normal humoral function. No statistical difference as to the frequency of mild infections (URI) was found between HID and non-HID patients. We therefore suggest that the therapeutic program is based on the clinical status of the patients. Long-term follow-up with repeated determinations of antibody levels is crucial, however, to detect those defects that might evolve into more complex immunodeficiencies.

Adolescent↗

24-hour blood pressure profile in centenarians.

OBJECTIVE: Ambulatory blood pressure in the elderly has been studied in the past, the age range most frequently examined being 65 to 80 years. The present study was aimed at determining 24-h blood pressure means and profile in centennial human beings. PATIENTS AND METHODS: Sphygmomanometric blood pressure (average of three values) and 24-h ambulatory blood pressure measurements were performed in 16 centennial subjects (age 101.7 0.4 years, mean SEM) and in 20 healthy normotensives aged 80.7 1.1 years. All subjects were in good clinical and mental conditions for their age. They had no history, signs or symptoms of cardiovascular or non-cardiovascular diseases and were under no drug treatment. RESULTS: In the centennial group sphygmomanometric blood pressure amounted to 131.2 3.0/70.7 2.2 mmHg (systolic/diastolic) and 24-h blood pressure and heart rate average values to 125.6 +/- 3.4/64.8 2.0 mmHg and 77.5 4.3 bpm, respectively. Blood pressure and heart rate showed no difference between daytime and night-time values, i.e. night-time was accompanied by no blood pressure and heart rate fall. In contrast, in all subjects, a significant reduction in blood pressure was observed during the post-prandial period, with no significant heart rate changes. In the octogenarian group, sphygmomanometric and 24-h blood pressure averages were 146.6 4.4/82.8 2.2 and 131.8 2.5/75.3 1.6 mmHg, respectively, with a clearcut reduction in night-time as well as in post-prandial values. CONCLUSIONS: In centenarians 24-h blood pressure values are: (1) lower than sphygmomanometric blood pressures and (2) slightly less than in subjects aged 80 years. At variance with these subjects, however, in centenarians nocturnal hypotension and bradycardia are abolished, presumably because of a derangement in the central sleep influences on the cardiovascular system.

Aged↗