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Biomedical subjects

M Carducci

Publications and source records attributed to M Carducci.

At least 19 recordsLinked to original sources
PubMed2006

Vascular endothelial growth factor gene polymorphisms increase the risk to develop psoriasis.

We investigated the relationship between eight polymorphisms in the gene encoding for vascular endothelial growth factor (VEGF) (-1540C > A, -1512Ins18, -1451C > T, -460T > C, -160C > T, -152G > A, -116G > A and +405G > C) and plaque-type psoriasis stratified for age at onset, gender and family history of dermatosis. For this purpose, 117 patients with chronic plaque-type psoriasis and 215 healthy subjects were enrolled. We found that being homozygous -1540AA, -1512InsIns, -1451TT, -460CC and -152AA conferred a significant risk in developing psoriasis compared with heterozygous (-1540CA, -1512 + Ins, -1451CT, -460CT and -152AG) and homozygous genotypes (-1540CC, -1512 + +-1451CC, -460TT and -152GG) grouped together [odds ratio (ORs) = 1.73, 1.73, 1.73, 1.77 and 1.87, respectively]. Conversely, having the -116AA or +405GG genotype did not significantly increase the risk of disease expression compared with other genotypes of the same loci. Interestingly, we found that -1540AA, -1512InsIns, -1451TT, -460CC and -152AA homozygous genotypes have a significant two-fold increased risk in developing psoriasis after the age of 40 years (late-onset psoriasis) (ORs = 2.19, 2.19, 2.19, 2.05 and 2.26; P = 0.02, 0.02, 0.02, 0.04 and 0.02, respectively) as compared with controls. On the contrary, we found no phenotype-genotype association of the same magnitude among the patients in whom psoriasis developed at or before the age of 40 years (early-onset psoriasis) compared with controls. Genotype distributions were not significantly different when cases and controls were stratified either by gender or family history of psoriasis. Finally, VEGF plasma concentration was not significantly different between patients and controls and was not correlated with the severity of the disease.

5' Untranslated Regions↗
PubMed2006

Simultaneous occurrence of linear scleroderma and homolateral segmental vitiligo.

Localized scleroderma and vitiligo only rarely have been reported to occur simultaneously. Here we report a case of a 21 year old man affected with both linear scleroderma of the left upper limb and homolateral segmental vitiligo of the trunk. Since the two diseases appeared during the same period, involved the same side of the body and their progression paralleled, a possible non-coincidental association between these two diseases is discussed.

Abdomen↗
PubMed2006

Malignant glucagonoma. New options of treatment.

Few cases of malignant glucagonomas have been described in the literature. In this paper we present a case of a 77-year-old woman with necrolytic migratory erythema and high plasma glucagon and chromogranin A levels caused by a neuroendocrine tumour. An abdominal CT scan suggested a pancreatic lesion and two liver metastases. The patient underwent pancreatic debulking and liver metastasectomy. Histological and immunohistochemical investigations revealed a well differentiated neuroendocrine tumour with vascular invasion and scattered immunopositivity for somatostatin receptors. The patient was treated with octreotide (20 mg i.m. every 28 days) for three years without side effects. Three months after surgery symptoms of disease recurred accompanied by hyperglucagonaemia and newly diagnosed liver lesions. The patient was treated with octreotide (30 mg i.m. every 28 days) and interferon-alpha (6 MU s.cc 3 times per week) plus three cycles of hepatic chemoembolisation. Symptoms resolved after the first month of therapy, hormone levels decreased compared to untreated levels and metastatic growth slowed as observed by radiographic evidence. The patient is now asymptomatic with persistent hepatic disease and normal serum glucagon levels forty months after primary treatment. So far, only few immunohistochemical studies are reported on malignant glucagonoma and combined treatment schedules. We demonstrated, for the first time, a scattered immunopositivity for somatostatin receptors in a malignant glucagonoma. For this reason, the somatostatin analogs therapy was instituted. A combined antiproliferative medical treatment and the hepatic chemoembolization have been able to control tumor growth and disease symptoms for a long time after surgery.

Aged↗
PubMed2005

Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis.

The pathogenic mechanism underlying the hyperproliferation of keratinocytes in psoriasis is still not completely clarified. The production of cytokines released by activated T lymphocytes infiltrating the upper dermis probably has a crucial role. Even dermal fibroblasts can participate in the process through the secretion of growth factors, and some studies have reported an increased expression of the insulin-like growth factor 1. Few studies, however, have focused on the possible involvement of the keratinocyte growth factor (KGF/FGF-7) and the fibroblast growth factor 10 (FGF-10/KGF-2), which are secreted by fibroblasts and stimulate keratinocyte proliferation acting through a receptor specifically expressed by epithelial cells. The aim of this study was to investigate the expression of KGF and FGF-10 on the skin of patients with psoriasis by immunohistochemical analysis and to evaluate the correlation with the lymphocyte infiltrate and the epidermal proliferation. Immunostaining for KGF and FGF-10 showed that both the growth factors are upregulated in the upper dermis of psoriatic skin, and that the expression is correlated with the presence of T-cell infiltrate and with keratinocyte proliferation. Our data suggest that in psoriatic lesions activated lymphocytes can stimulate fibroblasts to produce KGF and FGF-10, which in turn contribute to sustain the hyperproliferative status of the keratinocytes.

Adult↗
PubMed2005

Early but not lasting improvement of recalcitrant subcorneal pustular dermatosis (Sneddon-Wilkinson disease) after infliximab therapy: relationships with variations in cytokine levels in suction blister fluids.

Subcorneal pustular dermatosis (SCPD) is an uncommon disorder, characterized by a chronic relapsing vesiculopustular eruption, mainly involving the trunk and intertriginous areas, and usually seen in women > 40 years old. Various therapies have been reported to be effective in treating SCPD, such as dapsone, systemic glucocorticoids, acitretin, etretinate, infliximab and phototherapy. We report a case of a 54-year-old woman affected by SCPD who after failure of different therapies showed a dramatic but only temporary improvement of her disease during a cycle of therapy with infliximab. In addition, an array of cytokines was simultaneously measured in suction blister fluids obtained from involved or uninvolved skin at various time intervals during the first 12 weeks of observation.

Antibodies, Monoclonal↗
PubMed2004

Erythema multiforme during cytomegalovirus infection and oral therapy with terbinafine: a virus-drug interaction.

The authors report a case of erythema multiforme in a 32-year-old woman who was also taking oral terbinafine for an onychomycosis. The patient data analysis showed serological positivity for cytomegalovirus (IgM and IgG) and hepatitis C virus and serological titre of antinuclear antibody was elevated. After a brief review of the literature the authors propose the possibility of virus-drug interaction as a model of adverse drug reactions.

Adult↗
PubMed2004

Evaluation of recombinant antigen-based assays for diagnosis of bullous autoimmune diseases.

The diagnosis of autoimmune bullous diseases is based on clinical observation and on the presence of autoantibodies directed to molecules involved in the adhesion systems of the skin. Immunofluorescence assays are the currently accepted method for detection of autoantibodies; such assays depend greatly on the skill of operators and are difficult to standardize. Recombinant desmoglein-1 (Dsg1), Dsg3, and BP180 peptides, the main autoantigens in pemphigus or bullous pemphigoid, have been used to develop new quantitative enzyme immunoassays (EIA) for the detection of specific antibodies. The present study was undertaken to evaluate the sensitivity and specificity of these immunoassays and to determine the correlation between the results and the clinical aspects of diseases. Serum samples from patients with pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, or mucous membrane pemphigoid, from healthy individuals, and from patients with unrelated autoimmune conditions were tested. Anti-desmoglein reactivity was detected in all the patients with pemphigus and in none of the controls. Patients with the more benign form of cutaneous disease had anti-Dsg1 antibodies, while patients with deeper cutaneous lesions or with mucosal involvement had anti-Dsg3 reactivity also, or exclusively. The BP180-based assay was positive for 66.6% of patients with bullous pemphigoid and for none of the patients with mucous membrane pemphigoid, and no reactivity was detected in the control sera. In conclusion, the anti-Dsg1 and anti-Dsg3 assays are useful in the diagnosis of pemphigus and provide information on the clinical phenotype of the disease. However, the sensitivity of EIA for detection of autoantibodies in bullous pemphigoid should be improved by the use of additional antigens or epitopes.

Antibody Specificity↗
PubMed2001

Prostate cancer prevention strategies using antiproliferative or differentiating agents.

Differentiation or antiproliferative therapies have been most effective in the treatment of promyelocytic leukemia and are being investigated for the treatment of solid tumors including prostate cancer (PCa). Research suggests that these agents may induce terminal differentiation (arrest in G(0)), induce differentiation to a mature cell with cellular functions and a growth pattern similar to nonmalignant cells, or trigger apoptosis. This review focuses on classes of agents under laboratory and clinical evaluation as antiproliferative or differentiating agents: polyamine inhibitors, vitamin D and its analogs, metabolites of vitamin A, the short-chain fatty acid, phenylbutyrate, and nonsteroidal anti-inflammatory agents. Because differentiation therapies offer a reduced toxicity profile and have potential for preventing or slowing cancer progression, they may offer an alternative to chemotherapy for men with advanced PCa, or may be useful as low-toxicity agents given chronically for chemoprevention in men at high risk for PCa. Clinical trials are needed to define the role of these agents in primary and secondary prevention.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Contemporary identification of patients at high risk of early prostate cancer recurrence after radical retropubic prostatectomy.

OBJECTIVES: To develop a model that will identify a contemporary cohort of patients at high risk of early prostate cancer recurrence (greater than 50% at 36 months) after radical retropubic prostatectomy for clinically localized disease. Data from this model will provide important information for patient selection and the design of prospective randomized trials of adjuvant therapies. METHODS: Proportional hazards regression analysis was applied to two patient cohorts to develop and cross-validate a multifactorial predictive model to identify men with the highest risk of early prostate cancer recurrence. The model and validation cohorts contained 904 and 901 men, respectively, who underwent radical retropubic prostatectomy at Johns Hopkins Hospital. This model was then externally validated using a cohort of patients from the Mayo Clinic. RESULTS: A model for weighted risk of recurrence was developed: R(W)'=lymph node involvement (0/1)x1.43+surgical margin status (0/1)x1.15+modified Gleason score (0 to 4)x0.71+seminal vesicle involvement (0/1)x0.51. Men with an R(W)' greater than 2.84 (9%) demonstrated a 50% biochemical recurrence rate (prostrate-specific antigen level greater than 0.2 ng/mL) at 3 years and thus were placed in the high-risk group. Kaplan-Meier analyses of biochemical recurrence-free survival demonstrated rapid deviation of the curves based on the R(W)'. This model was cross-validated in the second group of patients and performed with similar results. Furthermore, similar trends were apparent when the model was externally validated on patients treated at the Mayo Clinic. CONCLUSIONS: We have developed a multivariate Cox proportional hazards model that successfully stratifies patients on the basis of their risk of early prostate cancer recurrence.

Adult↗
PubMed2001

A novel method for the determination of basal gene expression of tissue-specific promoters: an analysis of prostate-specific promoters.

Because the toxicity of suicide gene therapeutics is directly related to basal promoter activity, we developed an assay to test for promoter "leakiness" using a diphtheria toxin mutant. Sequences of 15 prostate-specific gene promoter constructs were cloned in an expression plasmid (pBK; Stratagene, La Jolla, CA) backbone driving expression of an attenuated mutant of diphtheria toxin A (tox176). Low expression levels of the DT-tox176 result in significant protein synthesis inhibition reflected by a decreased expression of the luciferase activity of a simultaneously transfected CMV luciferase construct. ID50 (dose of plasmid with 50% luciferase inhibition) was calculated for each promoter construct in different cell lines. Highest transactivational activity (ID50 <75 ng) was found for the CMV promoter in all cell lines, which is in agreement with the dual luciferase assay findings. Unlike the dual luciferase findings, however, the DT-tox176 assay showed protein inhibition of CN65 (PSA promoter/enhancer) and PSE-hK2 (PSA enhancer and basal human kallikrein 2 promoter) in HEK293 and DLD cells indicating "leakiness" of these promoter constructs. Low basal promoter activity in nonprostate cell lines was found for the minimal PSA promoter, hK2, DD3, and OC promoters. The DT-tox176 assay can better predict basal promoter activity compared to less sensitive dual luciferase assay.

Biological Assay↗
PubMed2000

Phase II trial of gemcitabine plus cisplatin in patients with metastatic urothelial cancer.

PURPOSE: To assess the activity and toxicity of the combination of gemcitabine and cisplatin in the treatment of chemotherapy-naive patients with metastatic urothelial cancer. PATIENTS AND METHODS: Forty-six patients with measurable stage IV carcinoma of the urothelium were enrolled onto this trial. Gemcitabine 1,000 mg/m(2) was administered intravenously for 30 to 60 minutes on days 1, 8, and 15 of each 28-day cycle. Cisplatin was administered after gemcitabine on day 1 of each cycle. The first 11 patients received an initial cisplatin dose of 100 mg/m(2). Due to the hematologic toxicity observed in several of these patients, the dose was reduced to 75 mg/m(2) in the remaining 35 patients. Patients were treated with six cycles, unless disease progression or severe toxicity necessitated earlier discontinuation. RESULTS: Ten of the 46 patients achieved a complete response and nine showed a partial response. The overall response rate was 41%. The median time to treatment failure was 5.5 months. The median survival was 14.3 months, and the 1-year survival probability was 54%. Most of the toxicities were hematologic and, in general, easily manageable. CONCLUSION: Gemcitabine plus cisplatin is active in the treatment of metastatic urothelial cancer in chemotherapy-naive patients and has an acceptable clinical safety profile. Studies are under way to further define the place of gemcitabine in combination with other chemotherapeutic agents in the treatment of metastatic urothelial cancer.

Adult↗
PubMed1999

Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group.

PURPOSE: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. RESULT: We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point. CONCLUSION: Through this consensus conference, we believe we have developed practical guidelines for using PSA as a measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point.

Androgens↗
PubMed1999

Preliminary evaluation of a short course of estramustine phosphate and docetaxel (Taxotere) in the treatment of hormone-refractory prostate cancer.

Preclinical data suggest that small quantities of estramustine phosphate are synergistic with taxanes and may be useful in the treatment of hormone-refractory prostate cancer. The current trial was designed to reduce the duration of exposure to estramustine phosphate, which carries with it the risk of anorexia and gastrointestinal, cardiovascular, and thromboembolic toxicity during long-term treatment. Patients with histologically confirmed adenocarcinoma of the prostate showing evidence of progressing disease 4 to 6 weeks after antiandrogen withdrawal were enrolled into the study. Patients may have received up to two prior chemotherapy regimens. Patients received estramustine phosphate 280 mg orally every 6 hours for a total of five doses (24-hour exposure), docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) 70 mg/m2 intravenously over 1 hour, coumadin 2 mg orally every day, and dexamethasone as premedication for docetaxel. Cycles were repeated every 21 days, up to a maximum of 6. Of the 18 evaluable patients, seven showed more than 50% declines in prostate-specific antigen for a duration > or =4 weeks; two of eight patients had soft tissue partial responses. Nine of 11 had improvement in pain and/or urinary symptoms. In a total of 98 cycles, grade 3 toxicities observed included leukopenia (N = 7), neutropenia (N = 6), fatigue (N = 13), headache (N = 1), local skin reactions after extravasation (N = 2), nail changes (N = 1), diarrhea (N = 2), and hyperglycemia (N = 3); grade 4 toxicities included neutropenia/fever requiring admission (N = 2), leukopenia (N = 2), and neutropenia (N = 6). No thromboembolic complications were seen. All toxicities were reversible within 1 week after occurrence. Thus, preliminary evidence suggests that in this heavily pretreated patient population 1-day treatment with an estramustine/docetaxel combination is active and has acceptable toxicity.

Adenocarcinoma↗
PubMed1998

Endothelin-1 levels are increased in sera and lesional skin extracts of psoriatic patients and correlate with disease severity.

Endothelins (ETs), in addition to their systematical activities, exert important functions at the skin level, such as increase of keratinocyte proliferation, neo-angiogenesis and leukocyte chemotaxis, which are among the main characteristics of psoriasis. To assess a possible ET-1 involvement in plaque-type psoriasis, ET-1 determinations were carried out in 15 sera and 8 lesional and non-lesional biopsy skin extracts from psoriatic patients and in 15 sera and 5 biopsy skin extracts from healthy volunteers, sex- and age-matched, using commercially available ELISA kits. A statistical analysis of the results showed that ET-1 levels were increased in sera of psoriatic patients, as compared to normal subjects (p = 0.04). In addition, there was a significant correlation between both serum (r = 0.60, p = 0.02) and lesional skin (r = 0.80, p = 0.03) ET-1 values versus the Psoriasis Area and Severity Index scores. Significant increases of the lesional versus the non-lesional (p = 0.01) and versus the normal (p = 0.04) ET-1 skin extract values were observed, together with a significant correlation between lesional and non-lesional ET-1 skin levels (r = 0.79, p = 0.03). These findings were also confirmed at the mRNA level, using RT-PCR analysis, where increased ET-1 mRNA levels, densitometrically measured, were found in the lesional samples versus non-lesional and normal skin. Since interleukin-8 is involved in psoriasis and shares some biological properties with ET-1, we further evaluated the levels of this cytokine in skin extracts. The behaviour of interleukin-8 paralleled that of ET-1, and a significant correlation between these two molecules was observed in the lesional skin (r = 0.76, p = 0.05). Taken together, these data stress that, as previously described for interleukin-8, ET-1 may be involved in inflammatory processes associated with psoriasis.

Adult↗
PubMed1998

Recognition and treatment of psoriasis. Special considerations in elderly patients.

Psoriasis is a chronic dermatological disorder that affects 1 to 2% of the general population. Although its aetiology is still unknown, the importance of genetic factors has been confirmed by many studies, mainly in young individuals. With respect to clinical features, plaque-type psoriasis (localised or generalised) is the most common form. At present, there is no cure for psoriasis and the available treatments can only temporarily clear the skin manifestations. The choice of treatment regimen for psoriasis is based on the severity of the disease, the patient's gender, age, treatment history and level of compliance, and the physician's personal experience. All therapies for psoriasis have different and potentially toxic effects. Therefore, a good knowledge of their relative and absolute contraindications, adverse effects and interactions with other drugs is mandatory. The elderly represent a significant proportion of patients with psoriasis because its prevalence increases with age. Physicians, particularly general practitioners, dermatologists and gerontologists, must be aware of the problems that the treatment of psoriasis in the elderly can present. This is especially important because of the increased risk of adverse drug reactions in the elderly.

Aged↗
PubMed1997

Increased interleukin-7 concentrations in lesional skin and in the sera of patients with plaque-type psoriasis.

Several cytokines have been shown to be increased in psoriasis, mainly at the local and sometimes at the systemic level. At present, no data concerning the relationships between psoriasis and interleukin-7 (IL-7) are available. This biological modifier regulates immune response by means of its pleomorphic activities, including the ability to stimulate different monocyte functions, such as killing of intracellular pathogens, induction of cytokines, and enhancement of some membrane molecule expression. Study groups consisted of nine psoriatic and nine normal subjects. Using a commercially available immune-enzyme method, IL-7 concentrations were determined in various samples: biopsy and scale extracts, peripheral blood mononuclear cells (PBMCs) supernatants, and sera. The results show that IL-7 levels are significantly increased both in biopsy and in scale extracts obtained from lesional skin compared to those obtained from nonlesional and normal skin (P at least < 0.01). In addition, the serum values were higher in psoriatic patients than in the controls (P = 0.003). In contrast, no significant differences were observed in the supernatants of unstimulated PBMCs maintained in culture for 48 hr. These data suggest that IL-7 is involved in some way in the pathomechanisms of psoriasis and that the keratinocyte may be a candidate for psoriatic IL-7 overproduction.

Adult↗