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Biomedical subjects

P Puddu

Publications and source records attributed to P Puddu.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2001

What proportion of dermatological patients receive evidence-based treatment?

OBJECTIVE: To determine the proportion of dermatological patients who are offered evidence-based therapy in the routine dermatological practice. METHODS: For every patient seen for the first time at one of our tertiary hospital setting clinics between April and May 1999, the primary diagnosis and the primary intervention were recorded. For each primary diagnosis-primary intervention combination, evidence was searched for in electronic databases from January 1966 to December 1999. The proportion of patients who were offered evidence-based interventions was calculated as the main outcome measure. RESULTS: With a study sample of 136 patients, 61 different diagnosis-treatment couples were generated and 94 queries on electronic databases were performed (to account for "primary interventions" including more than 1 drug or treatment modality). Eighty-seven (64%) of 136 patients received evidence-based interventions. Evidence from randomized controlled trials was found for 69 patients (50.7% of the sample). Controlled studies lacking randomization or double blinding or including fewer than 20 patients per treatment group dealt with treatments offered to 14 patients (10.3%). The treatments offered to 4 patients (2.9%) were judged to have self-evident validity (ie, trials unanimously judged unnecessary). Symptomatic and supportive measures accounted for most interventions lacking substantial evidence (36% of the patients), but we had to include in this class other important treatment regimens, mainly for rare conditions. CONCLUSIONS: Most of the study patients received evidence-based care. However, published trials should be carefully appraised, and relevance of clinical end points should be evaluated together with methodological issues. More accessible, clinically oriented, evidence-based information sources are needed.

Controlled Clinical Trials as Topic↗
PubMed2001

[A Pediatric case of lupoid leishmaniasis diagnosed by PCR].

The purpose of this paper is to describe the clinical features of lupoid leishmaniasis in a child and to underline the use of PRC as a necessary and reliable tool in controversial diagnosis. Lupoid leishmaniasis, also known as chronic or relapsing leishmaniasis, is mainly widespread in the Middle East, where it represents up to 5% of all cutaneous Leishmaniasis. It strongly resembles Lupus Vulgaris, both clinically and histologically, and is therefore not usually diagnosed immediately but after a certain period of time. The amastigotic forms are rare or absent. The cutaneous nodules or plaques can slowly enlarge over the years. The case of an eleven-year-old albanian child living in Durazzo (Albania), suffering since three years with a plaque formed by apple-jelly nodules and scars on his right cheek, is presented. Using PCR, the presence of Leishmania infantum DNA led to a diagnosis of lupoid leishmaniasis. The therapeutic strategy of a combination of oral itraconazole and infiltration of metilglucamina antimoniate has been carried out, with good result, as checked through "telemedicine".

Administration, Oral↗
PubMed2001

Becker's nevus syndrome.

Becker's nevus (BN) is a unilateral hyperpigmented, often hairy, cutaneous hamartoma, with geographic borders. It is usually localized on the shoulder, anterior chest, scapula, or upper arm, but there have been reports of BN in other areas (eg, lower extremities, face). In most cases, the lesion appears in late childhood or adolescence, and both congenital and familial cases have been described.

Adolescent↗
PubMed2000

Inhibition of the constitutive and induced IFN-beta production by IL-4 and IL-10 in murine peritoneal macrophages.

We had previously reported that freshly harvested peritoneal macrophages (PM) are in a type I IFN-mediated antiviral state, which is lost during in vitro culture of PM, concomitantly with a progressive decline in the expression of IFN-beta. We report herein that in vitro culture of PM in the presence of IL-4 or IL-10 results in an enhanced decay of the IFN-beta-mediated antiviral state to vesicular stomatitis virus (VSV). Moreover, IL-4 and IL-10 inhibited the production of type I IFN induced by LPS or NDV infection, as assessed by IFN production and induction of IFN-mediated antiviral state. The accumulation and physiological turnover of IFN-beta mRNA was not affected by IL-4 or IL-10. Finally, neither IL-10 nor IL-4 exerted any inhibitory effect on the antiviral activity induced by exogenous type-I IFN. These results suggest that Th2 cytokines, such as IL-4 and IL-10, act as negative regulators of the type I IFN-mediated antiviral response in PM and may represent stop signals for the constitutive or induced type I IFN expression in PM.

Animals↗
PubMed2000

Disparate cytotoxic activity of nickel-specific CD8+ and CD4+ T cell subsets against keratinocytes.

Allergic contact dermatitis (ACD) is the result of an exaggerated immune reaction to haptens mediated by skin-homing T cells, but the effector mechanisms responsible for the tissue damage are poorly understood. Here we studied the capacity of distinct subsets of hapten-specific T cells to induce apoptosis in autologous keratinocytes. Skin- and blood-derived nickel-specific CD8+ T cytotoxic 1 (Tc1) and Tc2 clones as well as CD4+ Th1 and Th2 expressed the cutaneous lymphocyte-associated Ag and exhibited strong MHC-restricted cytotoxicity against nickel-coupled B lymphoblasts, as detected by the [3H]TdR release assay. Both Tc1 and Tc2 clones, but not CD4+ T cells, displayed a significant cytotoxic activity against resting nickel-modified keratinocytes. Following IFN-gamma treatment, keratinocytes expressed MHC class II and ICAM-1 and became susceptible to Th1-mediated, but not Th2-mediated, cytotoxicity. The molecules of the two major cytotoxic pathways, Fas ligand (FasL) and perforin, were expressed by Tc1, Tc2, and Th1 cells, whereas Th2 cells expressed only FasL. Experiments performed in the presence of specific inhibitors of the perforin (concanamycin A) and FasL (brefeldin A) pathway indicated that perforin-mediated killing dominated in Tc1 and Tc2, and FasL-mediated cytotoxicity prevailed in Th2 clones, with a more heterogeneous behavior in the case of Th1 cells. Finally, perforin mRNA was expressed in ACD lesional skin, as assessed by RT-PCR analysis. In aggregate, our results indicate that keratinocytes can be target of multiple hapten-specific CTL responses, that may have distinct roles in the epidermal injury during ACD.

B-Lymphocytes↗
PubMed2000

IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines.

IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha-chemoattractant (I-TAC) belong to the non-glutamate-leucine-arginine motif CXC chemokine family and act solely through the CXCR3 receptor for potent attraction of T lymphocytes. In this study, we evaluated the capacity of the T cell-derived cytokines IL-4, IL-10, and IL-17 to modulate IP-10, Mig, and I-TAC in cultured human keratinocytes and CXCR3 expression in T cells from allergic contact dermatitis (ACD). IL-4, but not IL-10 or IL-17, significantly up-regulated IFN-gamma- or TNF-alpha-induced IP-10, Mig, and I-TAC mRNA accumulation in keratinocytes and increased the levels of IP-10 and Mig in keratinocyte supernatants. Immunohistochemistry of skin affected by ACD revealed that >70% of infiltrating cells were reactive for CXCR3 and that CXCR3 staining colocalized in CD4+ and CD8+ T cells. Nickel-specific CD4+ and CD8+ T cell lines established from ACD skin produced IFN-gamma and IL-4 and expressed moderate to high levels of CXCR3. Finally, CXCR3 agonistic chemokines released by stimulated keratinocytes triggered calcium mobilization in skin-derived nickel-specific CD4+ T cells and promoted their migration, with supernatant from keratinocyte cultures stimulated with IFN-gamma and IL-4 attracting more efficaciously than supernatant from keratinocytes activated with IFN-gamma alone. In conclusion, IL-4 exerts a proinflammatory function on keratinocytes by potentiating IFN-gamma and TNF-alpha induction of IP-10, Mig, and I-TAC, which in turn may determine a prominent recruitment of CXCR3+ T lymphocytes at inflammatory reaction sites.

Adjuvants, Immunologic↗