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G Fornaciari

Publications and source records attributed to G Fornaciari.

At least 19 recordsLinked to original sources
PubMed2003

Efficacy of prolonged 5 million units of interferon in combination with ribavirin for relapser patients with chronic hepatitis C.

summary. Retreatment of relapser patients with chronic hepatitis C with the standard dose of interferon (IFN) of 3 million units (MU) thrice weekly (tiw) plus ribavirin for 24 weeks achieves a sustained response in 30 and 73% of patients with genotype 1 and 2 or 3, respectively. The aim of this study was to evaluate the efficacy and safety of IFN alpha-2b induction therapy, followed by prolonged treatment with a high dose of IFN alpha-2b plus ribavirin in relapser patients. A total of 119 patients were randomized to receive IFN alpha-2b 5 MU daily (Group A: 59 patients) or IFN alpha-2b 5 MU tiw (Group B: 60 patients) for 4 weeks followed by IFN (5 MU tiw) and ribavirin (1000-1200 mg/day) for 48 weeks in both groups. The primary end point was hepatitis C virus (HCV)-RNA clearance at week 24 after the end of treatment. A sustained virological response (SVR) was achieved in 68 and 60% of Group A and B patients, respectively (P = 0.37). Logistic regression analysis identified genotype 2 or 3 as the only independent factor associated with response, whereas induction regimen and baseline viraemia levels did not affect the response. The overall SVR was 53 and 72% in patients with genotype 1 or 4 and 2 or 3, respectively. In conclusion, induction IFN therapy does not enhance the SVR to a 48-week combination therapy. Our study suggests that relapsed patients with genotype 1 or 4 may achieve significant response rates of approximately 50%, if retreated with 5 MU tiw IFN plus ribavirin for 48 weeks.

Adult↗
PubMed2002

Indication of hysteroscopy in tamoxifen treated breast cancer patients.

The aim of this study was to indicate the patients treated with tamoxifen for breast cancer in which hysteroscopy with biopsy should be considered mandatory. 414 breast cancer patients who underwent hysteroscopy with bioptic evaluation were enrolled in the study. 334 subjects were treated with 20 mg of tamoxifen daily as adjuvant therapy for six up to a hundred months. Of the remaining 80 control patients, which had not received tamoxifen, 30 were in premenopause (Group IA) and 50, in postmenopause (Group IIA). The tamoxifen-treated patients were subdivided in premenopausal (Group IB = 72 patients) and in postmenopausal (Group IIB = 262 patients) groups. All patients were further classified in asymptomatic or symptomatic groups considering whether uterine bleeding was absent or present. The evaluation of the endometrial mucosa was performed by office hysteroscopy. In group IIB patients presenting uterine bleeding, malignant lesions were found in 7.8% of the cases. The incidence of premalignant and malignant lesions in IIB patients treated for longer than 3 years (11.7%) was higher than that observed in IIB patients treated for less than 3 years (1.3%). There was a significant difference in terms of endometrial pathology between Group IIB (32.8%) and Group IIA (8%) (p < 0.001); and between Group IIB (32.8%) and Group IB (13.9%) women (p = 0.003). Among IA and IIA patients there were no cases of endometrial hyperplasia or cancer; on the contrary, in IB and IIB women, 2 and 22 cases of atypical hyperplasia were observed, respectively. All cases of endometrial cancer were observed in Group IIB and had a diagnosis of poor prognosis. In conclusion the hysteroscopy with biopsy should be considered the first diagnostic procedure to perform in tamoxifen-treated postmenopausal patients presenting uterine bleeding and in postmenopausal women treated for longer than 3 years. In premenopause, hysteroscopy should be proposed to women with ultrasonographic abnormalities and/or with uterine bleeding to patients at high risk for endometrial cancer.

Antineoplastic Agents, Hormonal↗
PubMed2001

Bcl-2 expression in pancreas development and pancreatic cancer progression.

Apoptosis is important for both tissue development and differentiation; its deregulation may contribute to tumourigenesis. In order to clarify the role of Bcl-2, an apoptosis-inhibiting protein, in pancreatic morphogenesis and tumour progression, its immunohistochemical expression was evaluated in 12 samples of fetal pancreas, in 10 samples of adult pancreas with ductal hyperplastic lesions, in 120 cases of primary pancreatic ductal adenocarcinoma, and in 43 synchronous metastatic lymph nodes. To evaluate the role of apoptosis in pancreatic cancer, p53 expression was also studied in tumour samples. Bcl-2 cytoplasmic acinar and ductal immunostaining was found in all fetal and adult tissue samples; ductal hyperplastic lesions were constantly negative. Thirty out of 120 (25%) tumours and 3 out of 43 (7%) lymph nodes expressed Bcl-2, whereas 67 out of 120 (56%) expressed nuclear p53. Well-differentiated tumours (G1) were more frequently Bcl-2-positive (p=0.002); furthermore, there was an inverse correlation between Bcl-2 and p53 expression in primary tumours (p=0.02). Neither Bcl-2 nor p53 influenced patients' prognosis, which was instead affected by N (p=0.02) and M (p<0.0001) status and stage of the disease (p=0.002). It is concluded that Bcl-2 regulates pancreatic morphogenesis and tissue homeostasis from early fetal to adult life and can be considered a phenotypic marker of normal exocrine pancreas. On the other hand, the lack of expression in preneoplastic lesions and the low positivity found in primary tumours and lymph node metastases suggest that Bcl-2 does not play a centralrole in pancreatic tumourigenesis and cancer progression.

Adenocarcinoma↗
PubMed2001

Oral versus combination mesalazine therapy in active ulcerative colitis: a double-blind, double-dummy, randomized multicentre study.

BACKGROUND: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment. AIM: To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis. METHODS: Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4-12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point. RESULTS: 67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively. CONCLUSIONS: In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.

Administration, Oral↗
PubMed2001

Musculoskeletal manifestations in a population-based cohort of inflammatory bowel disease patients.

BACKGROUND: Musculoskeletal disorders are the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). Wide ranges of prevalence have been reported depending on the criteria used to define spondylarthropathy and on the selection of patients. We aimed to evaluate the prevalence and clinical spectrum of musculoskeletal manifestations in an inception cohort of European IBD patients. METHODS: From 1 October 1991 to 30 September 1993, 202 IBD patients were diagnosed in three centres of two countries (Italy and The Netherlands) by means of a population-based inception cohort study. Of this group of patients, 160 (79%) were interviewed and examined by a rheumatologist and a gastroenterologist in the period June-September 1996. A total of 139/160 patients had an antero-posterior radiograph of the pelvis, and in 140/160 HLA-B27 was determined. RESULTS: 53 (33.1%) of the 160 patients had experienced at least one musculoskeletal manifestation, 29 (18.1%) satisfied the European Spondylarthropathy Study Group (ESSG) criteria for spondylarthropathy and 5 (3.1%) satisfied the modified New York criteria for ankylosing spondylitis. However, 23 (14.4%) patients developed one or more spondylarthropathy-related manifestations without fulfilling any of the classification criteria. In patients satisfying ESSG criteria a significantly higher frequency of women (P = 0.03), of ocular and liver involvement (P = 0.01 and P = 0.03, respectively), and use of immunosuppressive drugs (P = 0.02) was observed. CONCLUSION: Our study shows a high prevalence of musculoskeletal manifestations in an inception cohort of IBD patients. The clinical spectrum is broader than that defined by spondylarthropathy criteria.

Adult↗
PubMed2001

Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype.

OBJECTIVE: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Adolescent↗
PubMed2001

Quality of health care in inflammatory bowel disease: development of a reliable questionnaire (QUOTE-IBD) and first results.

OBJECTIVES: As inflammatory bowel disease is a chronic disorder, usually with an early onset in life, quality of care plays an important role for patients. The aim of this study was to develop a questionnaire to measure quality of care through the eyes of patients with inflammatory bowel disease. METHODS: Ten generic questions were already available because the questionnaire is based on an existing instrument. Patients with inflammatory bowel disease in seven countries were involved in the development of additional disease-specific items. Validation and first field testing of the total questionnaire (QUOTE-IBD) was performed in The Netherlands. RESULTS: A total of 380 patients cooperated in the development of 13 disease-specific items, with high internal reliability (Cronbach's alpha = 0.83). Another 162 patients were involved in validating and testing of the QUOTE-IBD, which consists of 23 items in total. Pearson's correlation coefficient between QUOTE-IBD and visual analog scale scores of health care items was 0.55. Intraclass correlation coefficient of two assessments was 0.64. First testing showed that patients gave relatively poor marks to some part of health care services, such as providing information about extraintestinal complaints and the psychological as well as physical approach to complaints. CONCLUSIONS: A short, valid, reliable questionnaire was developed to measure the opinions of patients with inflammatory bowel disease on quality of health care. The QUOTE-IBD can be used for identification of areas for improvement, with the aim of optimizing health care in inflammatory bowel disease.

Europe↗
PubMed2001

Muscoloskeletal manifestations in inflammatory bowel disease.

Muscoloskeletal manifestations are the most common extraintestinal complications of inflammatory bowel disease. Wide ranges in prevalence have been reported, depending on the criteria used to define spondylarthropathy. In 1991, the European Spondylarthropathy Study Group developed classification criteria that included previously neglected cases of undifferentiated spondylarthropathies, which had been ignored in most of the oldest epidemiological studies on inflammatory bowel disease. The spectrum of muscoloskeletal manifestations in inflammatory bowel disease patients includes all of the clinical features of spondylarthropathies: peripheral arthritis, inflammatory spinal pain, dactylitis, enthesitis (Achilles tendinitis and plantar fasciitis), buttock pain and anterior chest wall pain. Radiological evidence of sacroiliitis is common but not obligatory. The articular manifestations begin either concomitantly or subsequent to the bowel disease; however, the onset of spinal disease often precedes the diagnosis of inflammatory bowel disease. The prevalence of the different muscoloskeletal manifestations is similar in ulcerative colitis and Crohn's disease. Symptoms usually disappear after proctocolectomy. The pathogenetic mechanisms that produce the muscoloskeletal manifestations in inflammatory bowel disease are unclear. Several arguments favour an important role of the intestinal mucosa in the development of spondylarthropathy. The natural history is characterized by periods of flares and remission; therefore, the efficacy of treatment is difficult to establish. Most patients respond to rest, physical therapy and nonsteroidal anti-inflammatory drugs, but these drugs may activate bowel disease. Sulphasalazine may be recommended in some patients. There is no indication for the systemic use of steroids.

Humans↗
PubMed2001

Hybridization screening of very short PCR products for paleoepidemiological studies of Chagas' disease.

Single strands of very short PCR products can be covalently immobilized to a slide and then easily detected by probe hybridization. In this work, the PCR product was a 70-nucleotide segment of ancient DNA, representing a portion of repeat mini-circle DNA from the kinetoplast of Trypanosoma cruzi, the infectious agent of Chagas' disease (American Trypanosomiasis). The target segment was initially established to be present in soft tissue samples taken from four "naturally" mummified Andean bodies using PCR followed by cloning and sequencing. Hybridization screening of the covalently immobilized PCR products positively identified products from 25 of 27 specimens of different tissues from these four mummies. The method appears to be ideal for the purpose of screening a large number of specimens when the target PCR product is very short.

Animals↗
PubMed2001

Expression and prognostic significance of urokinase and plasminogen activator inhibitor type-1 in endometrial hyperplasia and cancer.

Proteolytic enzymes, like urokinase (uPA) and plasminogen activator inhibitor type-1 (PAI-1), are involved in remodelling tissues during invasion and metastasis of tumor cells. The purpose of the study is to evaluate the expression and the prognostic significance of these enzymes in endometrial hyperplasia and cancer. We used immunohistochemical staining to localize uPA and PAI-1 antigens and evaluate their expression, and the enzyme-linked immunosorbent assay (ELISA) to measure their levels during the progression of endometrial carcinoma. The results show that the levels of uPA and PAI-1 detection are systematically weak in simplex hyperplasia and are moderate in complex hyperplasia. In the endometrial carcinoma a very strong reaction was observed in the most aggressive variant of epithelial tumors. A positive signal for uPA was found only in the cytoplasm of normal and hyperplastic cells while, in tumors, uPA was present also in the cellular areas surrounding the neoplastic glands and at the apex of the malignant cells. The PAI-1 immunoreactivity was weak to moderate in 95.4% of carcinomas, with a diffuse signal mostly distributed in the cytoplasm of neoplastic cells and tumor stroma. UPA antigen concentrations were significantly higher in endometrial carcinoma than in endometrial hyperplasia (p<0.05) and in normal endometrium (p<0.001). PAI-1 antigen concentrations in carcinoma samples were significantly higher than in normal endometrium (p=0.002), but the difference was not statistically significant with respect to that in endometrial hyperplasia. We did not find any correlation between uPA and PAI-1 concentrations and the standard prognostic parameters for evaluating endometrial carcinoma. In conclusion, this study demonstrates that in hyperplastic endometria and in endometrial carcinoma there is a progressive increase in expression of uPA and PAI-1 than in normal endometrial tissue. In carcinoma tissues, the high expression of uPA is unregulated in the surrounding stroma tissue, particularly in the most aggressive histopathologic variants. UPA and PAI-1 may be factors associated with invasive behavior in endometrial carcinoma independent of other clinicopathological parameters.

Adenocarcinoma↗
PubMed2001

Paleoandrology and prostatic hyperplasia in Italian mummies (XV-XIX century).

Prostatic hyperplasia, a very common condition today, was well known in the past as cause for bladder distension. The difficulty to identify, at autopsy of natural or artificial mummies, even a normal-sized prostate is probably the result of putrefaction processes and its usually dramatic size reduction as well. We report two ancient cases of prostatic hyperplasia recently observed in natural mummies from Italy. The first case regards Pandolfo III Malatesta (1370-1427), a leading figure of the Italian Renaissance. He was a valiant soldier and horseman with a very active life style. The tomb, containing his naturally mummified body, has recently been discovered in Fano (Marche, Central Italy). After careful X-ray and videographic examination, the autopsy showed good preservation of the skeletal muscles, cartilage, internal and external organs, included prostate gland and penis. Macroscopic examination revealed a staghorn calculus (calcium urate) of the left kidney and a severe enlargement of the prostate, with calcifications detectable by X-ray and large nodules protruding in the lumen of an ectatic urethra. Histology shows fibrous brands of connective and muscular tissue surrounding circular and oblong lacunae, with no preservation of epithelial structures. The macroscopic and histological picture allowed us to diagnose prostatic nodular hyperplasia. The second case (XIX century) concerns the natural mummy of an anonymous 50-60 years old man, found in ancient friary near L'Aquila (central Italy), which underwent computed tomography and a complete autopsy. Pelvic CT scans showed distended urinary bladder and a ring of dense tissue at the site of the prostate. At autopsy the bladder measured 7 x 6 x 5 cm and the prostate was 4 x 5 x 3 cm; prostatic urethra had a diameter of x 2 cm. Histology revealed dense fibrous tissue containing muscular fibers and roundish cavities of variable size, filled with eosinophil, PAS-positive material. Concretions were also present in some of these spaces. Strong immunohistochemical reactivy for PSA was observed in this material. The existence of glandular structures containing eosinophil, PAS-positive material, immunoreactive for PSA, confirmed the prostatic nature of the specimen, already suspected after CT scan and gross examination. The presence itself of the prostate, its histological picture, the preserved and distended urinary bladder, in addition to the age of the subject, supported the diagnosis of prostatic hyperplasia.

History, 15th Century↗
PubMed2000

Prostatic hyperplasia in the mummy of an italian renaissance prince.

BACKGROUND: Pandolfo III Malatesta (1370-1427) was a leading figure of the Italian Renaissance. He was a valiant soldier and horseman with a very active life style. Historical sources report that he died of a fever in 1427. The tomb, containing his mummified body, has recently been discovered in Fano (Marche, Central Italy). METHODS: After careful X-ray and videographic examination, autopsy was performed to diagnose possible pathologies. Samples of different tissues were collected and rehydrated by Sandison's method and submitted to routine histology processes. Sections of treated tissue were fixed on clean slides, stained with hematoxylin-eosin or Gardner's Trichromic and observed at light microscope. RESULTS AND CONCLUSIONS The autopsy showed good preservation of the skeletal muscles, cartilage, internal and external organs included prostate gland and penis. Macroscopic examination revealed stag-horn calculi (calcium urate) of the left kidney and a severe enlargement of the prostate, with calcifications detectable by X-ray and a large nodule protruding in the lumen of an ectatic urethra. Histology shows fibrous bands of connective and muscular tissue surrounding some circular and oblong lacunae, with no preservation of epithelial structures. The macroscopic and histological picture, showing clear prostatic nodular hyperplasia, makes this the first case described in paleopathology.

Autopsy↗
PubMed2000

Musculoskeletal manifestations in inflammatory bowel disease.

Musculoskeletal manifestations are the most common extra-intestinal complication of inflammatory bowel disease (IBD). They are part of the clinical spectrum of spondylarthropathies and include different articular manifestations. In addition to axial symptoms, peripheral findings such as seronegative oligoarthritis, dactylitis, and enthesopathy commonly occur, sometimes representing the only manifestation. Wide ranges of prevalence have been reported, depending on the criteria used to define spondyloarthropathy and on the selection of patients. In an inceptional cohort of newly diagnosed IBD patients, we observed musculoskeletal manifestations in 30.7% of the patients. The clinician should, therefore, carefully evaluate any rheumatological findings in order to provide an accurate and early diagnosis, and to establish an adequate therapy. In this article, epidemiological, clinical, and diagnostic aspects are discussed. Furthermore, the contribution of intestinal bacteria and immunogenetic factors to the pathogenesis of arthritis is briefly reviewed. Finally, we summarize the available therapeutic options.

Journal Article↗
PubMed1999

Isolation of Trypanosoma cruzi DNA in 4,000-year-old mummified human tissue from northern Chile.

A segment of DNA unique to the kinetoplast of Trypanosoma cruzi was isolated from spontaneously mummified human remains from the coastal area of northern Chile at sites dated from 2000 BC to about AD 1400. Following rehydration of the desiccated human tissue samples of heart, esophagus, or colon, the samples were extracted and primers employed to bind to a 330 bp kinetoplast minicircle DNA sequence present in T. cruzi. This segment was then amplified using the polymerase chain reaction (PCR), and the target segment was visualized by gel electrophoresis. This method enables the identification of Chagas' disease in an ancient body in the absence of recognizable anatomic pathological changes.

Adolescent↗
PubMed1999

Goiter in an eighteenth-century Sicilian mummy.

Goiter is still a frequent pathological condition of the thyroid gland. Goiter consists of an enlargement of the gland caused by several physiopathologic events, the most important of which is deficient intake of iodine. A series of eighteenth-century mummies housed in the church of Santa Maria della Grazia in Comiso includes one individual showing a pathological condition, with a very large swelling in the antero-inferior region of the neck. X-rays showed small scattered radiopaque foci. Routine histology showed a large number of circular follicles immersed in fibrous tissue. Finally, immunohistochemistry revealed a strong reactivity for thyroglobulin. The data confirmed the nature of the tissue as thyroid, and the macroscopic diagnosis is that of thyroid goiter.

Goiter↗
PubMed1999

Microsatellite instability and mismatch repair gene inactivation in sporadic pancreatic and colon tumours.

Genomic instability has been proposed as a new mechanism of carcinogenesis involved in hereditary non-polyposis colorectal cancer (HNPCC) and in a large number of sporadic cancers like pancreatic and colon tumours. Mutations in human mismatch repair genes have been found in HNPCC patients, but their involvement in sporadic cancer has not been clarified yet. In this study we screened 21 pancreatic and 23 colorectal sporadic cancers for microsatellite instability by ten and six different microsatellite markers respectively. Microsatellite alterations were observed at one or more loci in 66.6% (14/21) of pancreatic cancers and in 26% (6/23) colon tumours, but all the pancreatic and half of the colon samples showed a low rate of microsatellite instability. All the unstable samples were further analysed for mutations in the hMLH1 and hMSH2 genes and for hypermethylation of the hMLH1 promoter region. Alterations in the hMLH1 gene were found only in colorectal tumours with a large presence of microsatellite instability. None of the pancreatic tumours showed any alteration in the two genes analysed. Our results demonstrate that microsatellite instability is unlikely to play a role in the tumorigenesis of sporadic pancreatic cancers and confirm the presence of mismatch repair gene alterations only in sporadic colon tumours with a highly unstable phenotype.

Adaptor Proteins, Signal Transducing↗