Biomedical subjects

R Mancini

Publications and source records attributed to R Mancini.

At least 19 recordsLinked to original sources

PubMed2006

Carpal tunnel syndrome and ulnar neuropathy at the elbow in floor cleaners.

OBJECTIVE: To determine the occurrence of carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in a cohort of floor cleaners and to check differences between workers with and without CTS. METHODS: All female floor cleaners of three major hospitals in Tuscany (Italy) were contacted. Clinical and electrophysiological severity of CTS and UNE were evaluated with standardized scales and symptoms were assessed with the self-administered Boston Questionnaire (BQ); demographic and non-occupational factors and durations of current and previous occupations were recorded. Univariate analysis of risk factors was performed in workers with and without CTS. Logistic regression was used to evaluate the capacity of independent variables to predict CTS. RESULTS: Out of a total of 179 cleaners, 145 (81%)-mean age 39.6 years (20-64 years)-were enrolled in the study; 70 (48%) had CTS (diagnosis based on clinical and electrophysiological findings). BQ symptom and hand function scores were anomalous in 108 (74%) and 84 (58%) subjects, respectively. UNE was detected in 7/103 women. Univariate analysis showed that cleaners with CTS were older, had greater BMI and longer exposure to cleaning with previous employers than those without CTS. In the logistic regression, the only predictor of CTS was cleaning with previous employers (O.R. 12.1, 95% CI 3-49.9). CONCLUSIONS: These results indicate a high occurrence of CTS in floor cleaners; UNE is less frequent than CTS, presumably due to repetitive movements that stress wrists more than elbows. The only predictive factor of CTS was cleaning as an occupation with previous employers. Therefore, the actual risk factor for CTS could not be cleaning per se, but how this job is performed.

Adult↗

PubMed2006

Cystic pancreatic neoplasms: 12-year surgical experience.

Cystic pancreatic neoplasms have been increasingly diagnosed in the last years. Resection is recommended in most cases, but their management has not been standardized since an accurate nonoperative differentiation is often difficult. A retrospective review of 30 patients undergoing surgical resection for cystic pancreatic neoplasms between 1993 and 2005 was performed. Median age of the patients was 63 years and 63.5% were female. Twelve patients (40%) were asymptomatic. Twenty-nine had curative resections. Pathologic analysis revealed 13 serous cystadenomas, 9 mucinous cystadenomas, 3 mucinous cystadenocarcinomas, 4 intraductal papillary mucinous neoplasms and 1 solid pseudopapillary neoplasm. Overall mortality was 6.5% (2 patients). Postoperative complications occurred in 12 patients (41%). Pancreatic fistula occurred in 7 cases (24%). Reoperation was required in 2 patients (6.5%). Two patients operated for mucinous cystadenocarcinoma and invasive intraductal papillary mucinous neoplasms died of recurrence at 24 and 7 months postoperatively. Excluding another patient died from other cause, all others are currently alive with no evidence of disease. Diagnostic accuracy for cystic pancreatic neoplasms is still limited. Considering the good prognosis and acceptable morbidity and minimal mortality after surgical treatment in specialized centers, resection seems still justified in most cases.

Adult↗

PubMed2005

Effects of iron ions, protons and X rays on human lens cell differentiation.

We have investigated molecular changes in cultured differentiating human lens epithelial cells exposed to high-energy accelerated iron-ion beams as well as to protons and X rays. In this paper, we present results on the effects of radiation on gene families that include or are related to DNA damage, cell cycle regulators, cell adhesion molecules, and cell cytoskeletal function. A limited microarray survey with a panel of cell cycle-regulated genes illustrates that irradiation with protons altered the gene expression pattern of human lens epithelial cells. A focus of our work is CDKN1A (p21(CIP1/WAF1)), a protein that we demonstrate here has a role in several pathways functionally related to LET-responsive radiation damage. We quantitatively assessed RNA and protein expression in a time course before and after single 4-Gy radiation doses and demonstrated that transcription and translation of CDKN1A are both temporally regulated after exposure. Furthermore, we show qualitative differences in the distribution of CDKN1A immunofluorescence signals after exposure to X rays, protons or iron ions, suggesting that LET effects likely play a role in the misregulation of gene function in these cells. A model of molecular and cellular events is proposed to account for precataractous changes in the human lens after exposure to low- or high-LET radiations.

Cell Cycle↗

PubMed2004

Genetic and pathologic significance of 1p, 17p, and 18q aneusomy and the ERBB2 gene in colorectal cancer and related normal colonic mucosa.

Among chromosome defects in colon cancer, deletions in 1p, 17p, and 18q have been reported as frequent events. To verify this, we investigated 1p, 17p, and 18q aneusomy in 60 colorectal cancers and their surrounding mucosa by means of fluorescence in situ hybridization (FISH). We also evaluated ERBB2 gene (alias HER-2/neu) amplification in a subset of tumors. The genetic picture in tumors was correlated with chromosomal alterations in normal colonic mucosae, as well with clinicopathologic variables. A population of cells in morphologically normal epithelium possesses genetic aberrations common to those in colon cancer, although in different percentages. No significant difference emerged in terms of fraction of nuclei with 17p monosomy between primary tumors and distal mucosal samples. Of tumor samples aneusomic for the three chromosomes, 58.3% also showed aneusomy in related normal colonic mucosa. In neoplastic samples, significant correlation existed between 1p aneusomy and mucosal component (P<0.007), between 17p aneusomy and increased depth of invasion (T3-T4) (P<0.05), and between 18q aneusomy and tumor site (P<0.03). None of the evaluated samples, neoplastic or normal, showed ERBB2 gene amplification.

Adult↗

PubMed2004

Role of P53 and Bcl-2 in advanced rectal carcinomas treated with adjuvant therapy.

Rectal adenocarcinomas is usually associated to a poorer outcome than colon cancers. In this study we analyzed the impact on overall survival of p53 and Bcl-2, evaluated by immunohistochemical techniques, in 126 advanced rectal cancer patients submitted to 5 fluorouracil based adjuvant therapy. Shorter overall survival was observed in patients bearing p53 positive and Bcl-2 negative tumors, although in multivariate analysis only p53 emerged as independent predictor of a worse outcome. These results seem to indicate that, in stage III-IV rectal cancer, p53 alterations may identify high risk patients to be enrolled in more aggressive and/or innovative adjuvant/neoadjuvant treatments.

Adult↗

PubMed2003

Fate of natural estrogen conjugates in municipal sewage transport and treatment facilities.

The aim of this study was to investigate the fate of the conjugated forms of the three most common natural estrogens in the municipal aqueous environment. Levels of conjugated and free estrogens in (1) female urine; (2) a septic tank collecting domestic wastewater; (3) influents and effluents of six activated sludge sewage treatment plants (STPs) were measured. The analytical method was based on solid-phase extraction by using a Carbograph 4 cartridge and Liquid Chromatography-tandem Mass Spectrometry. On average, a group of 73 women selected to represent a typical cross section of the female inhabitants of a Roman condominium, excreted 106, 14 and 32 microg/day of conjugated estriol (E(3)), estradiol (E(2)) and estrone (E(1)), respectively. Apart from some E(3) in pregnancy urine, free estrogens were never detected in urine samples. Estrogen sulfates represented 21% of the total conjugated estrogens. This situation changed markedly in the condominium collecting tank. Here, significant amounts of free estrogens were observed and the estrogen sulfate to estrogen glucuronated ratio rose to 55/45. A laboratory biodegradation test confirmed that glucuronated estrogens are readily deconjugated in unmodified domestic wastewater, presumably due to the large amounts of the beta-glucuronidase enzyme produced by fecal bacteria (Escherichia coli). Deconjugation continued in sewer transit. At the STP entrance, free estrogens and sulfated estrogens were the dominant species. The sewage treatment completely removed residues of estrogen glucuronates and with good efficiency (84-97%) the other analytes, but not E(1) (61%) and estrone-3-sulfate (E(1)-3S) (64%). Considering that (1) E(1) has half the estrogenic potency of E(2), (2) the amount of the former species discharged from STPs into the receiving water was more than ten times larger than the latter one and (3) a certain fraction of E(1)-3S could be converted to E(1) in the aquatic environment, E(1) appears to be the most important natural endocrine disrupter.

Adolescent↗

PubMed2003

A combined approach of neoadjuvant chemotherapy and surgery for colorectal liver metastases.

Hepatic metastases represent one of major clinical problems in patients affected by solid tumours because liver is the first site of metastatic disease after lymph nodes, (1, 2). The most common origins among adults are from colon and rectum cancer followed by pancreas (adenocarcinoma or neuroendocrine), lung and breast (3-7). It is estimated that in 15-20% of patients affected by adenocarcinoma of colon-rectum liver metastases are present at the time of diagnosis (8-11), while in 40% of cases they will develop during the follow-up (10, 11). Liver metastases are the first determinant for survival (1, 3, 12-17), and both hepatic and extrahepatic involvement have a statistical significant impact on it (3, 14, 18-21). Prognosis of patients affected by untreated disease is very poor, being 5 to 14 months with rare 2-year survivors and a 5-year survival rate of 0% (10, 21-24). In half of all patients affected by colorectal cancer and undergoing to a radical surgery, disease will fail in the liver (8, 25-28); among patients dying for colorectal cancer, 60-70% have a liver involvement (9, 29), and in 20-25% liver is the only site of recurrence and death results from liver failure (3, 29-31). In Autoptic studies those rates increased up to 83% and 38% respectively (1, 10, 17, 32).

Adenocarcinoma↗

PubMed2003

Personal experience on treatment of colorectal liver metastases: a multidisciplinary approach.

UNLABELLED: Diagnosed colorectal cancer patients presents liver metastases at presentation in 25% of cases, an another 25% of patients will develop hepatic recurrence during follow-up period. Natural history of disease in untreated patients is sad without long term survivors. The only chance of curative treatment is surgical resection. Aim of this study was to evaluate recurrence and survival in the multimodal approach of colorectal liver metastases patients. MATERIALS: From 1990 to 2003, 212 colorectal cancer liver metastases patients were observed at the "Regina Elena" cancer institute of Rome, the 48.8% of cases were synchronous. Of 185 patients with minimum follow-up of 12 months, 80 were surgically resected, while 105 were not. Major resection was possible in 45.3% of cases and 66.1% of them were radicals. Tweny were treated by surgery alone, 65% were resected after i.v. chemotherapy, in the last 10% resection followed HAI chemotherapy. Of non resected patients, in the 36.2% i.v. chemotherapy was administered, 26.1% were submitted to HAI chemotherapy, in 18.9% others treatments were carried out and 18.8 were untreated. RESULTS: Operative mortality was contained to 2.5%. The hepatic recurrence was observed in 50.5% of cases while extrahepatic was in the 13.6%. In the resected cases the 5-yr. Overall survival was 38.8%, the disease-free survival decreased to 14.7% with a median time to progression of 15 months. The liver recurrence-free survival was 31.3%. Really bad prognopsis was observed in the non resected patients with none survived at 5 years and 3-yr overall survival of 18.7%. CONCLUSION: In selected patients the multimodality approach to treatment of hepatic metastases showed satisfactory results in terms of local and distal control of disease. Long term survivors were observed in the our experience.

Adenocarcinoma↗

PubMed2002

Spectroscopic determination of dynamic plasma gradients in implosion cores.

The time-dependent gradient structure of a laser-compressed, high-energy-density plasma has been determined using a method based on the simultaneous analysis of time-resolved x-ray monochromatic images and x-ray line spectra from Ar-doped D2 implosion cores. The analysis self-consistently determines the temperature and density gradients that yield the best fits to the spatial-emissivity profiles and spectral line shapes. This measurement is important for understanding the spectra formation and plasma dynamics associated with the implosion process. In addition, since the results are independent of hydrodynamic simulations, they are also important for comparison with fluid-dynamic models.

Journal Article↗

PubMed2002

Visualization of left atrial appendage and assessment of its function by transthoracic second harmonic imaging and contrast-enhanced pulsed Doppler.

BACKGROUND: Low flow velocity within the left atrial appendage, as assessed by transoesophageal echocardiography, is a predictor of thromboembolism and of a low success rate of cardioversion of atrial fibrillation. However, the semi-invasive nature does limit its serial application as a screening technique. METHODS AND RESULTS: We investigated the value of transthoracic second harmonic echocardiography and pulsed Doppler at baseline and after intravenous contrast injection to visualize the left atrial appendage and assess blood flow velocities within its cavity. We studied 51 consecutive patients undergoing transoesophageal echocardiography. After transoesophageal echocardiography, transthoracic second harmonic imaging was performed and the left atrial appendage was visualized in 46 patients. Interpretable pulsed Doppler tracings of left atrial appendage flow were obtained at baseline in 39 patients and in 45 patients during Levovist administration. The correlations between peak emptying velocity of left atrial appendage as measured by transoesophageal echocardiography and by transthoracic standard and contrast-enhanced Doppler were 0.81 and 0.91, respectively. The agreement between transoesophageal echocardiography and transthoracic contrast-enhanced pulsed Doppler echocardiography in classifying left atrial appendage flow velocity patterns was 93%. Left atrial appendage thrombus was detected by transthoracic second harmonic imaging in only one of the eight patients shown by transoesophageal echocardiography to have a thrombus. However, all but one of the patients with left atrial appendage thrombus and/or spontaneous echocardiographic contrast at transoesophageal echocardiography had <30cm/s left atrial appendage flow velocity by transthoracic Doppler. CONCLUSIONS: This study shows that left atrial appendage can be visualized by transthoracic second harmonic imaging and that the flow velocity within its cavity is reliably measured by pulsed Doppler in a substantial fraction of patients. Contrast enhancement improves the feasibility and the accuracy of transthoracic evaluation of left atrial appendage flow velocity. The practical value of these results in predicting thromboembolic risk and success of cardioversion of atrial fibrillation needs to be proved by prospective studies.

Aged↗

PubMed2001

The tumor spectrum in FHIT-deficient mice.

Mice carrying one inactivated Fhit allele (Fhit +/- mice) are highly susceptible to tumor induction by N-nitrosomethylbenzylamine, with 100% of Fhit +/- mice exhibiting tumors of the forestomach/squamocolumnar junction vs. 25% of Fhit +/+ controls. In the current study a single N-nitrosomethylbenzylamine dose was administered to Fhit +/+, +/-, and -/- mice to compare carcinogen susceptibility in +/- and -/- Fhit-deficient mice. At 29 weeks after treatment, 7.7% of wild-type mice had tumors. Of the Fhit -/- mice 89.5% exhibited tumors (average 3.3 tumors/mouse) of the forestomach and squamocolumnar junction; half of the -/- mice had medium (2 mm diameter) to large (>2 mm) tumors. Of the Fhit +/- mice 78% exhibited tumors (average 2.4 tumors/mouse) and 22% showed medium to large tumors. Untreated Fhit-deficient mice have been observed for up to 2 years for spontaneous tumors. Fhit +/- mice (average age 21 mo) exhibit an average of 0.94 tumors of different types; Fhit -/- mice (average age 16 mo) also showed an array of tumors (average 0.76 tumor/mouse). The similar spontaneous and induced tumor spectra observed in mice with one or both Fhit alleles inactivated suggests that Fhit may be a one-hit tumor suppressor gene in some tissues.

Acid Anhydride Hydrolases↗

PubMed2001

FHIT gene therapy prevents tumor development in Fhit-deficient mice.

The tumor suppressor gene FHIT spans a common fragile site and is highly susceptible to environmental carcinogens. FHIT inactivation and loss of expression is found in a large fraction of premaligant and malignant lesions. In this study, we were able to inhibit tumor development by oral gene transfer, using adenoviral or adenoassociated viral vectors expressing the human FHIT gene, in heterozygous Fhit(+/-) knockout mice, that are prone to tumor development after carcinogen exposure. We therefore suggest that FHIT gene therapy could be a novel clinical approach not only in treatment of early stages of cancer, but also in prevention of human cancer.

Acid Anhydride Hydrolases↗

PubMed2001

Cervical dysplasia, ploidy, and human papillomavirus status correlate with loss of Fhit expression.

PURPOSE: The tumor suppressor gene, FHIT, has been cloned and mapped at chromosome region 3p14.2, one of the regions most frequently deleted in cervical carcinoma. In this report, we show that the expression of the Fhit protein in relation to human papillomavirus (HPV) subtype, the type of the intraepithelial lesion, HIV-induced immunodeficiency, and the DNA content (ploidy) correlates with the biological behavior of the lesions. EXPERIMENTAL DESIGN: To investigate involvement of the FHIT gene in squamous intraepithelial lesions of low and high grade (LGSILs and HGSILs, respectively) of the uterine cervix, we examined the Fhit protein expression by immunocytochemistry in 131 cervical smears of 96 HIV-seropositive patients (42 with LGSILs and 10 with HGSILs) and 35 HIV-seronegative (5 with LGSILs) persons. RESULTS: Fhit protein was detected in normal cells, whereas dysplastic cells (independently of HPV infection and HPV subtypes) showed reduced expression of Fhit (P = 0.00001). Lesions from 52 HIV-seropositive patients, 42 LGSILs and 10 HGSILs, showed diploid DNA content in 63.5%, aneuploid in 32.7%, and polyploid in 3.8%, but 90% of the HGSILs showed an aneuploid DNA content, and all were infected by HPV 16/18 subtypes. 23.8% of LGSIL cases were associated with HPV 16. CONCLUSIONS: These data clearly suggest that loss of Fhit expression occurs in the early stages of cervical carcinogenesis. Pap test represents one of the most convenient and rapid procedures available in identification of cellular changes; hence, Fhit staining might be used as an useful tool in larger population screening to detect early alteration in cellular behaviors.

Acid Anhydride Hydrolases↗

PubMed2001

The effect of light regimen and melatonin on the development of spontaneous mammary tumors in HER-2/neu transgenic mice is related to a downregulation of HER-2/neu gene expression.

OBJECTIVES AND DESIGN: The effect and the mechanism of light regimen and melatonin on the development of mammary tumors in HER2/neu transgenic mice were investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen (LD) or constant light illumination (LL) and a part of each group was given melatonin (20 mg/l) during the night time. RESULTS: The exposure to LL failed to change the incidence of spontaneous mammary adenocarcinoma development, the size of mammary tumors, as well as the incidence and size of lung metastases. However, the number of tumors per mouse was significantly increased in the LL group as compared to the LD group. The number of mice bearing 4 and more tumors was higher in the LL group than in the LD group, whereas the number of mice bearing 1 to 3 tumors was lower in the LL group in comparison with the LD group. Melatonin decreased the incidence and size of mammary adenocarcinomas, and the incidence of lung metastases in the LD group but not in the LL group. The mean number of tumors per mouse was not changed by melatonin treatment in both light regimens. The number of mice bearing 4 and more tumors was reduced by melatonin more significantly in the LL group than in LD group. Melatonin treatment resulted in a 2.5-fold reduction in the expression of HER-2/neu mRNA in mammary tumors from HER-2 /neu transgenic mice. CONCLUSION: The data demonstrate the influence of the LD light regiment and melatonin treatment in the development of spontaneous mammary tumors in HER-2/neu mice suggesting a melatonin-dependent modulation of HER-2/neu gene expression in mammary adenocarcinoma.

Age Factors↗

PubMed2000

Muir-Torre-like syndrome in Fhit-deficient mice.

To investigate the role of the Fhit gene in carcinogen induction of neoplasia, we have inactivated one Fhit allele in mouse embryonic stem cells and produced (129/SvJ x C57BL/6J) F(1) mice with a Fhit allele inactivated (+/-). Fhit +/+ and +/- mice were treated intragastrically with nitrosomethylbenzylamine and observed for 10 wk posttreatment. A total of 25% of the +/+ mice developed adenoma or papilloma of the forestomach, whereas 100% of the +/- mice developed multiple tumors that were a mixture of adenomas, squamous papillomas, invasive carcinomas of the forestomach, as well as tumors of sebaceous glands. The visceral and sebaceous tumors, which lacked Fhit protein, were similar to those characteristic of Muir-Torre familial cancer syndrome.

Acid Anhydride Hydrolases↗

PubMed2000

Degradation of unassembled soluble Ig subunits by cytosolic proteasomes: evidence that retrotranslocation and degradation are coupled events.

Many aberrant or unassembled proteins synthesized in the endoplasmic reticulum (ER) are degraded by cytosolic proteasomes. To investigate how soluble glycoproteins destined for degradation are retrotranslocated across the ER membrane, we analyzed the fate of two IgM subunits, mu and J, retained in the ER by myeloma cells that do not synthesize light chains. Degradation of mu and J is prevented by proteasome inhibitors, suggesting that both chains are retrotranslocated to be disposed of by proteasomes. Indeed, when proteasomes are inhibited, some deglycosylated J chains that no longer contain intrachain disulfide bonds accumulate in the cytosol. However, abundant glycosylated J chains are still present in the ER at time points in which degradation would have been almost complete in the absence of proteasome inhibitors, suggesting that retrotranslocation and degradation are coupled events. This was confirmed by protease protection and cell fractionation assays, which revealed that virtually all mu chains are retained in the ER lumen in a glycosylated state when proteasomes are inhibited. Association with calnexin correlated with the failure of mu chains to dislocate to the cytosol. Taken together, these results suggest that active proteasomes are required for the extraction of Ig subunits from the ER, though the requirements for retrotranslocation may differ among individual substrates.

Animals↗

PubMed2000

8-hydroxy-2'-deoxyguanosine in cervical cells: correlation with grade of dysplasia and human papillomavirus infection.

In this study, the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level was assessed in human cervical cells by an immunoperoxidase method and was related to the presence of human papillomavirus (HPV) infection and precancerous lesions. After optimizing the immunohistochemical method of detecting oxidative DNA damage in whole cells, we have used this technique to estimate the oxidative damage in cervical cells collected during a routine PAP test. The analysis of variance (ANOVA) of the data from human samples showed significant differences in the 8-OHdG content among normal, low-grade and high-grade squamous intraepithelial lesion (SIL, HGSIL and LGSIL, respectively; P < 0.001). In the comparison of the three groups, statistically significant differences were detected between normal SIL and HGSIL (P < 0.001) and between LGSIL and HGSIL (P = 0.003), whereas no statistically significant difference was found between normal SIL and LGSIL (P = 0.1). Grouping observations by HPV status, no significant difference was detected in 8-OHdG levels between HPV(+) and HPV(-) subjects (P = 0.8). The polytomous and proportional odds models, extensions of the logistic regression analysis, showed that the effect of 8-OHdG levels in rising the risk of dysplasia was roughly constant through SIL grades. In conclusion, the immunoperoxidase method, applied to single human cervical cells, provides clear evidence that significant differences exist in 8-OHdG content between normal and dysplastic cells and that oxidative DNA damage might play an important role in cervical carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2000

Nerve-sparing surgery in rectal cancer: feasibility and functional results.

Traditional rectal cancer surgery has been burdened with a high rate of sexual and urinary dysfunctions due to intraoperative injury or the cutting of the sympathetic and/or parasympathetic nerves. The experience acquired in the last ten years with total mesorectal excisions has permitted the use of the "nerve-sparing" technique. The present study regards 239 patients from two surgical centres, most of whom underwent sphincter-saving radical surgery between 1994 and 1998 with the above mentioned technique for resectable colon cancer. Details regarding the technique were recorded in the last 58 patients, in order to examine the severity of the surgical damage. The subgroup with the longest follow-up, which included 36 patients, was diagnostically evaluated by a surgeon, psychologist, urologist and neurologist to analyze the risk of sexual and urinary dysfunctions. A complete nerve-sparing was performed in 86.3% of the cases. The parasympathetic nerve trunks were those most often damaged because of perineural tumor spreading. Partial to complete sexual impotence was observed in 44% of the patients and surprisingly, preoperative dysfunctions were detected by means of the multidisciplinary approach in one third of these patients. Therefore, only 30.5% of the patients presented with strictly postoperative sexual impotency, above all, those who had undergone high-dose preoperative chemoradiation for T3 or T4 middle to low rectal cancer. A prospective study was initiated to evaluate the genitourinary dysfunctions after rectal cancer surgery in all of the clinical phases by means of a multidisciplinary approach aimed at functional recovery and improved quality of life.

Humans↗