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Biomedical subjects

P Puddu

Publications and source records attributed to P Puddu.

At least 19 recordsLinked to original sources
PubMed2003

Distinct delayed T-cell response to beta-methasone and penicillin-G in the same patient.

BACKGROUND: Multiple drug allergy syndrome is a clinical condition characterized by reactions against more than one different class of, both pharmacologically and structurally, unrelated drugs. Scanty data are available to date about a multiple drug delayed hypersensitivity syndrome. Our aim was to report the case of a delayed reaction to both beta-methasone (beta-MT) and penicillin-G (pen-G) occurring in the same patient, and analyse beta-MT- and pen-G-specific T-cell Lines (TCLs) with regard to their specificity, phenotype and cytokine profile. METHODS: We generated two drug-specific TCLs from biopsies at the site of positive intradermal reactions, and analysed their immunophenotype, T-cell receptor Vbeta (TCR-Vbeta) domains expression and cytokine profile. RESULTS: We demonstrated the specificity of the T cells isolated from positive intradermal test reactions to pen-G and beta-MT through the strict dose-dependent proliferation in response to drug-pulsed autologous antigen presenting cells. Fluorescence activated cell sorter (FACS) analysis revealed a predominance of CD4+ cells in the inflammatory cell infiltrate of intradermal test with beta-MT, while a predominance of CD8+ T cells in the site of delayed reaction to pen-G was found. The drug specific CD4+ and CD8+ T cells were heterogeneous, with regard to TCR-Vbeta usage. CD8+ pen-G-TCL displayed a preferential T helper 2 (Th2) profile, while a substantially heterogeneous pattern of cytokine production characterized specific beta-MT TCL. CONCLUSION: The study describes the coexistence in the same patient of a delayed hypersensitivity to both penicillin G and beta-MT, driven, respectively, by pen-G-specificTh2-skewed CD8+ and beta-MT specificTh0 CD4+ T cells. This case further support the existence of a multiple drug allergy syndrome also for delayed hypersensitivity.

Adult↗
PubMed2003

A comparison of acute phase proteins and traditional risk factors as markers of combined plaque and intima-media thickness and plaque density in carotid and femoral arteries.

OBJECTIVES: To test the hypothesis that some acute phase proteins may be better independent predictors of objective measures of arterial wall impairment than traditional risk factors. DESIGN: Cross-sectional study. MATERIALS AND METHODS: C-reactive protein (CRP), fibrinogen, C3 complement and traditional risk factors were measured in 288 men aged 55-64 years, randomly chosen from the local registry lists. By ultrasound assessment of the bifurcations of carotid and femoral arteries, maximum combined plaque/intima-media thickness (CPIMTmax) and mean plaque density (MPD, in a grey scale from 0 to 255) were also measured. RESULTS: In multivariate analysis only traditional risk factors remained associated with the overall CPIMTmax: smoking (r = 0.35, p < 0.0001), cholesterol (r = 0.23, p = 0.0001), age (r = 0.22, p = 0.0002), glucose (r = 0.18, p = 0.002) and systolic blood pressure (r = 0.13, p = 0.02). However, with regard to carotid disease only, fibrinogen was the strongest covariate of CPIMT (r = 0.18, p = 0.002). The overall MPD was independently associated with CRP (r = 0.25, p = 0.0008), physical activity (r = 0.19, p = 0.009), triglycerides (r = -0.18, p = 0.02) and body mass index (r = 0.15, p = 0.04). CRP was mainly associated with femoral MPD, while triglycerides were the major (inverse) covariate of carotid MPD. CONCLUSIONS: Traditional risk factors are the main determinants of CPIMTmax, although fibrinogen seems to play a role in carotids. CRP was associated with high density femoral plaques. Finally, no acute phase protein was independently associated with low density, potentially vulnerable, plaques.

Acute-Phase Proteins↗
PubMed2002

Different associations of C-reactive protein, fibrinogen and C3 with traditional risk factors in middle-aged men.

BACKGROUND: Some acute phase proteins are associated with both ischemic events and traditional risk factors. Since they are strongly interrelated, each of them partly reflects the characteristics of other proteins. This study was carried out to ascertain the specific preferential associations of some acute phase proteins with traditional risk factors for atherosclerotic disease. METHODS: High-sensitivity C-reactive protein, fibrinogen and C3-complement were assessed in 288 unselected men aged 55-64 years. Three multiple linear regression analyses were performed, in which each of the three acute phase proteins was considered the dependent variable of both traditional risk factors and the other two proteins. RESULTS: The three acute phase proteins strongly correlated with each other. Moreover, C-reactive protein was independently associated with triglycerides (P<0.0001), age (P=0.0130), body mass index (P=0.0179), and acute (P=0.0280) and chronic (P=0.0582) inflammations (R2=0.17). Fibrinogen was associated with alcohol consumption (inversely, P=0.0001) and smoking (P=0.0598) (R2=0.06). Finally, C3 was associated with insulin (P<0.0001), cholesterol (P=0.0001), sedentarity (P=0.0028), glucose (P=0.0077), and systolic blood pressure (P=0.0124) (R2=0.28). CONCLUSIONS: When simultaneously studied in multivariate analysis, acute phase proteins have different preferential associations with traditional risk factors, a probable consequence of their involvement in different cellular activations and metabolic processes.

Age Factors↗
PubMed2002

[Sentinel node biopsy for malignant melanoma. Technical details and clinical results on 390 patients].

BACKGROUND: The purpose of this paper is to present personal experience with sentinel node biopsy for the treatment of malignant melanoma. Technical details influencing the efficacy of the procedure are presented and the clinical, therapeutic and prognostic advantages of this technique discussed. METHODS: A total of 390 consecutive patients with primary skin melanoma (T2-3,N0,M0) underwent sentinel node biopsy between March 1996 and May 2001. All patients underwent previous excisional biopsy of the primary lesion and clinical and radiographic examination to exclude lymphatic or systemic macroscopic spreading of the disease. Preoperative lymphoscintigraphy (99mTc nanocoll) was routinely performed in the last 315 patients. Intraoperative detection of the sentinel nodes was performed by perilesional, intradermical, injection of blue dye associated with a g probe (Neoprobe(R) 2000) in the last 315 patients. Sentinel nodes, serially sectioned, were all Haematoxylin-Eosin and immunohistochemically stained. All patients positive for micro-metastasis underwent radical lymphadenectomy. Comparative analysis between the incidence of metastasis in sentinel and non-sentinel nodes, according to the clinical stage of the disease, was done. RESULTS: The overall detection rate of sentinel nodes was 97.4%. Relevant differences were found according to the site of dissection and the use of a g probe. The g-probe makes the procedure more effective, less invasive and less expensive. Timing and accuracy of the preoperative lymphoscintigraphy is a basic step of the procedure. The overall incidence of positive sentinel nodes was 14.7% with differences correlated with thickness of primary lesion (0.75-1.5 mm: 5,8%; 1.5-3 mm:18%; 3-4 mm: 24.6%). Metastasis in other non-sentinel nodes was found only with primary tumour thickness exceeding 2 mm. CONCLUSIONS: Sentinel node biopsy is a procedure requiring a multidisciplinary approach (surgery, nuclear medicine and pathology). A specific learning phase (>30 patients) is recommended to obtain reliable results.

Biopsy↗
PubMed2002

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Adolescent↗
PubMed2001

Risk factors for basal cell carcinoma in a Mediterranean population: role of recreational sun exposure early in life.

OBJECTIVE: To investigate the role of pigmentary traits, different patterns of sun exposure, artificial sources of UV radiation, and lifestyle-related factors on the risk of basal cell carcinoma (BCC) in a Mediterranean population from central-southern Italy. DESIGN: Hospital-based case-control study. SETTING: A referral dermatological hospital in Rome, Italy. PATIENTS: A convenience sample of 166 case patients with histologically confirmed BCC and 158 cancer-free control subjects with minor dermatological conditions observed between March 1995 and June 1997. RESULTS: In the multivariate analysis, the mean number of weeks per year spent at the beach before the age of 20 years was significantly associated with BCC. A dose-response trend was found for subjects who had spent 3 to 4 (odds ratio, 1.8; 95% confidence interval, 0.8-4.4), 5 to 8 (odds ratio, 3.7; 95% confidence interval, 1.5-9.0), or more than 8 (odds ratio, 4.5; 95% confidence interval, 1.9-10.5) weeks per year at the beach (P =.01 for trend). There was a significant association with the presence of actinic keratoses or solar lentigines, whereas no effect was found for skin type, history of sunburns, exposure to nonsolar UV radiation, and lifestyle-related habits such as cigarette smoking, alcohol consumption, and coffee drinking. Subjects reporting a family history of skin cancer had an extremely increased risk of BCC. CONCLUSION: The definite association with recreational sun exposure during childhood and adolescence and the strong relation with family history of skin cancer suggest that genetic predisposition and peculiar exposure patterns to UV radiation are key independent risk factors for the development of BCC in a southern European population.

Adolescent↗
PubMed2001

Identification of a LFA-1 region involved in the HIV-1-induced syncytia formation through phage-display technology.

We have identified a peptide region on CD18 molecule (the beta subunit of the LFA-1 molecule) involved in syncytia formation of HIV-1-infected lymphocytes. Several phage clones mimicking an epitope of the CD18 cell-surface determinant were isolated from two 9-mer random peptide phage-displayed libraries via their binding to the CD18-specific monoclonal antibody (mAb) MHM23, which in in vitro assay inhibits syncytia formation in HIV-1-infected cells. The peptide sequences displayed on phages that blocked immunolabeling of this mAb on LFA-1-expressing cells were used to identify the epitope recognized by mAb MHM23 by sequence comparison. On the basis of this analysis, two peptides which inhibited syncytia formation in HIV-1-infected cells in vitro were synthesized, thus confirming that they mimic a CD18 domain that is involved in this phenomenon. The results here presented highlight the potential of phage-display technology for the study of biological processes at the basis of virus infection, but also suggest new approaches for the therapy of AIDS.

Animals↗
PubMed2001

Short term effect of atorvastatin and vitamin E on serum levels of C3, a sensitive marker of the risk of myocardial infarction in men.

C3 complement is produced in response to macrophage activation and is a reliable marker of the risk of myocardial infarction in men. This study was designed to ascertain whether the treatment with atorvastatin, a powerful cholesterol lowering drug, and/or vitamin E, a natural antioxidant, may induce a short term decrease in serum C3 in subjects with persistently elevated levels. From an initial random sample of 1100 men aged 55-64 years, 140 subjects with 3 consecutive C3 measurements in the high tertile (>1.19 g/l) were selected. Those with total cholesterol <5.56 mmol/l were double blindly randomized in groups 1 (placebo, N = 28, G1) and 2 (vitamin E 600 IU/day, N= 30, G2). The subjects with total cholesterol values >5.56 mmol/l were randomized in groups 3 (placebo, N= 30, G3), 4 (atorvastatin 10 mg/day, N = 27, G4) and 5 (atorvastatin 10 mg/day + vitamin E 600 IU/day, N = 25, G5). After 3 months C3 levels were substantially unchanged in the first 4 groups, while in G5 a very significant decrement occurred: -0.070 g/l (5.2%); 95% CI 0.043-0.098; p <0.0001. "Normal" levels of C3 (< 1.19 g/l) were reached by 28% of G5 subjects. In G2 and G5 vitamin E levels increased by 60 and 36%, while in G4 they decreased by 23% (p < 0.0001), paralleling cholesterol and triglyceride fall. In all groups a progressive decrease in HDL cholesterol occurred (-17%, p < 0.0001). In conclusion, treatment with atorvastatin plus vitamin E for three months can lower persistently elevated C3 levels.

Anticholesteremic Agents↗
PubMed2001

Novel mutations in the LAMC2 gene in non-Herlitz junctional epidermolysis bullosa: effects on laminin-5 assembly, secretion, and deposition.

Laminin-5 is the major adhesion ligand of epithelial cells. Mutations in the three genes (LAMA3, LAMB3, LAMC2) encoding the laminin-5 chains cause junctional epidermolysis bullosa, a clinically and genetically heterogeneous blistering skin disease. Here, we describe a non-Herlitz junctional epidermolysis bullosa patient, compound heterozygote for two novel mutations affecting the LAMC2 gene. The mutation in the paternal allele is a de novo splice site mutation (522-1G-->A) that results in in-frame skipping of exon 4 and synthesis of a mutated gamma2 polypeptide (gamma2Delta4) carrying a 33 amino acid deletion within the N-terminal domain V. The maternal mutation is a one base pair insertion (3511insA) in the 3' terminal exon of LAMC2 resulting in a frameshift and a premature termination codon. Mutation 3511insA is predicted to lead to the synthesis of a gamma2 polypeptide (gamma2t) disrupted in its alpha-helical C-terminal structure and truncated of the last 25 amino acids. Keratinocytes isolated from the patient's skin showed a markedly decreased level of gamma2 chain mRNA and secreted scant amounts of laminin-5, which undergoes physiologic proteolytic processing. To investigate the biologic function of the laminin-5 molecules synthesized by the patient, mutant gamma2 cDNAs were transiently expressed in gamma2-null keratinocytes. Transfection of the gamma2Delta4 cDNA resulted in restoration of laminin-5 deposition onto the culture substrate, which demonstrates that the gamma2 polypeptides carrying a deletion in domain V, upstream of the gamma2 proteolytic cleavage site, are assembled into native laminin-5 that is secreted and extracellularly processed. In contrast, transfection of a mutant cDNA expressing the gamma2t chain failed to restore laminin-5 immunoreactivity, which indicates that integrity of the gamma2 C-terminal amino acid sequences is required for laminin-5 assembly. These results correlate for the first time a functional alteration in a laminin-5 domain with a mild junctional epidermolysis bullosa phenotype.

Amino Acid Sequence↗
PubMed2001

Factors associated with patient satisfaction with care among dermatological outpatients.

BACKGROUND: It has been shown that poor patient satisfaction can lead to poor adherence to treatment with consequently poor health outcomes. In order to improve the quality of care perceived by the patient and thus the health outcome, it is important to understand which are the main factors influencing patient satisfaction. OBJECTIVES: To examine factors associated with patient satisfaction with care among dermatological out-patients. METHODS: This longitudinal study is based on a sample of dermatology out-patients. The independent effects on patient's satisfaction of patient characteristics (sociodemographic characteristics, disease severity, quality of life) and of specific aspects of provided health care (the time the physician spent with patients, physician's interpersonal skills, etc.) were examined by multiple logistic regression. RESULTS: A total of 1389 out-patients were selected at random and invited to participate. Of the 722 patients who agreed to participate, 424 fulfilled the inclusion criteria and 396 of these patients (93.4%) completed the study. Overall satisfaction was reported by 60.0% of patients. The likelihood of overall satisfaction was found to be significantly and independently increased by the physician's ability to give explanations and to show empathy for the patient's condition, and by the older age of patients. The likelihood of satisfaction also increased with increasing disease severity, but decreased with symptom-related poor quality of life. The lowest level of satisfaction was found among patients whose symptom-related quality of life was worse than the clinical severity rated by the dermatologist. CONCLUSIONS: Improving the physician's interpersonal skills can increase patient satisfaction, which is likely to have a positive effect on treatment adherence and health outcomes. Dermatologists succeeded better in establishing a good relationship with clinically more severely affected patients than with patients who were clinically mildly affected despite their quality of life being impaired. Thus, the inclusion of a patient-rated quality of life can be a useful measure in dermatology, as it enables clinicians to perceive the patients' perception of their health status.

Adolescent↗
PubMed2001

Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi.

BACKGROUND: The validity of clinical and histologic criteria in identifying dysplastic nevi is controversial. Recognition of the dysplastic nevus as a distinct clinicopathologic entity requires demonstration of significant agreement between clinical atypia and histologic dysplasia. OBJECTIVE: We attempted to determine the correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi and to evaluate the sensitivity and specificity of clinical criteria for dysplastic nevi when compared with histopathologic features. METHODS: A total of 940 acquired melanocytic nevi 3 mm in diameter or larger were selected by initially choosing clinically unequivocal dysplastic and nondysplastic nevi and then, from these, histologically unequivocal dysplastic and nondysplastic lesions. The level of concordance between clinical atypia and histologic dysplasia was estimated by kappa statistics. RESULTS: Nevi were classified as clinically dysplastic (n = 499) or nondysplastic (n = 441). On the basis of histologic features, 739 were classified as dysplastic and 201 as nondysplastic. Agreement between clinical atypia and histologic dysplasia was found in 432 nevi, that is, a sensitivity of 58.4% (3-5 mm = 27.2%, >5 mm = 69.8%). Agreement between clinical and histologic criteria on the absence of dysplasia was found in 134 nevi, a specificity of 66.6% (3-5 mm = 92.4%, >5 mm = 47.9%). The kappa value was 0.17 (3-5 mm = 0.14, >5 mm = 0.10). CONCLUSION: The limited sensitivity and specificity together with the negligible kappa value indicate a poor agreement between clinical and histologic diagnoses of dysplastic nevus. The dysplastic nevus cannot be considered a distinct clinicopathologic entity because histologic dysplasia is found in a range of nevi that may or may not show clinical atypia.

Adult↗
PubMed2001

Suture materials and other factors associated with tissue reactivity, infection, and wound dehiscence among plastic surgery outpatients.

The most common complications in plastic surgery are tissue reactivity, infections, and wound dehiscence. In the literature, there are only a few studies with sample sizes large enough and methods of statistical analysis appropriate for evaluating the role of suture materials in inducing such complications. In the 1000 plastic surgery outpatients in this study, the association of different suture materials, individual patient characteristics, surgeon skill, and wound site and length with postoperative wound complications (i.e., tissue reactivity, infection rate, and wound dehiscence) were investigated. No substantial differences were found between the different suture materials and suturing techniques. A moderate increase in the risk of tissue reactivity for silk and polyglactin 910 and a protective effect of thinner internal sutures were observed. In multivariate analysis, such differences were not statistically significant. Male sex [odds ratio (OR), 1.7; 95 percent confidence interval (CI), 1.06 to 2.72] and older age (OR, 2.34; 95 percent CI, 1.36 to 4.05) were found to be the most important risk factors for tissue reactivity and infection rate (male sex: OR, 5.1; 95 percent CI, 1.7 to 15.9; older age: OR, 5.6; 95 percent CI, 1.9 to 16), whereas younger age was associated with an increased risk of dehiscence (OR, 3.06; 95 percent CI, 1.41 to 6.65). Wounds on the lower limbs showed a lower risk of tissue reactivity and wounds on the back a higher risk of dehiscence. Wound length was associated with the risk of tissue reactivity in one-layer sutures (OR, 2.92; 95 percent CI, 1.51 to 5.65). An increased risk of both tissue reactivity (OR, 1.53; 95 percent CI, 1.03 to 2.27) and dehiscence (OR, 2.44; 95 percent CI, 1.1 to 5.43) was observed for operations performed by less-experienced surgeons. Rather than factors related to suture materials and different surgical techniques, and with the exception of surgeon experience, general characteristics of the patients (i.e., sex and age) and of the wounds (i.e., length and site) seemed to be primarily responsible for local wound complications.

Absorbable Implants↗
PubMed2001

HMG-CoA reductase inhibitors: Is the endothelium the main target?

Endothelial dysfunction is an early event in atherosclerosis and could be considered a response to the injury induced by major risk factors. There is evidence that endothelial dysfunction is intimately involved in the onset and the progression of cardiovascular disease through abnormalities in the production, release or degradation of endothelium-derived factors, mainly nitric oxide and endothelin 1. Several reports have shown that drugs of the statin class could have multiple beneficial effects related to endothelium-mediated vasoactive, antithrombotic, antiproliferative and anti-inflammatory actions. Thus, the question arises of whether endothelial cells are the main target of statin therapy, in the setting of both hypercholesterolemia and normocholesterolemia. Experimental and clinical studies are reported that could support this hypothesis.

Animals↗
PubMed2001

Current thinking in statin therapy.

The HMG-CoA reductase inhibitors (statins) are now considered the most potent lipid-lowering drugs. Treatment with statins reduces both morbidity and mortality rates due to coronary artery disease. There is now increasing evidence that the clinical benefits obtained with statins cannot be solely attributed to a decrease in low-density lipoprotein (LDL) level. These drugs may also have beneficial effects on endothelial dysfunction, LDL oxidation, rheological and thrombogenic factors, cellular inflammation and plaque formation and stability. Further, there are differences among the various statins on these non-lipid variables. The biochemical effects of statins, as well as their clinical benefits, should be taken into consideration.

Cholesterol, LDL↗
PubMed2001

Conditional risk factors in men with previous myocardial infarction: relevance of C3 and homocysteine.

OBJECTIVE: To establish which traditional and conditional risk factors were effectively treated, and which remained active, in patients with previous myocardial infarction (PMI). METHODS AND RESULTS: In 47 PMI patients recently submitted to cardiological assessment and in 42 controls (50-70 years old men), traditional risk factors (total cholesterol, high-density lipoprotein cholesterol, blood glucose, blood pressure, cigarette smoking and body mass index) and the following variables were measured: fibrinogen, plasminogen activator inhibitor-1 (PAI-1), lipoprotein(a) [Lp(a)], total homocysteine, plasma folates, vitamin B12, high sensitivity C-reactive protein and C3 complement. Most patients were taking beta-blockers, ACE inhibitors and statins. Accordingly, patients had lower blood pressure and cholesterol values than controls. Moreover, they consumed less alcohol and coffee and did not differ from controls in cigarette smoking and body mass index. Conversely, patients had higher levels of homocysteine, fibrinogen, C3 complement and Lp(a), although of these factors only C3 and homocysteine remained significantly associated with PMI in multivariate analysis. C-reactive protein, PAI-1 and especially C3 often correlated with traditional risk factors in controls, but these correlations tended to disappear or reverse in PMI patients. Fibrinogen inversely correlated with alcohol consumption. Homocysteine correlated (inversely) with plasma folates only. Lp(a) did not correlate with any variable. CONCLUSIONS: Forty-seven patients with previous myocardial infarction displayed an excellent control of traditional risk factors, but they had higher mean C3 and homocysteine levels than the control group.

Aged↗