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Biomedical subjects

A Gentile

Publications and source records attributed to A Gentile.

At least 73 records · Page 4Linked to original sources

Preliminary results of a dose-finding study of paclitaxel and carboplatin in patients with advanced non-small cell lung cancer.

This ongoing phase I study sought to establish the maximum tolerated dose of the combination of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. Paclitaxel was administered as a 3-hour intravenous infusion. The carboplatin infusion was administered over 30 minutes immediately afterward. Patients were assigned sequentially to one of eight treatment groups in which paclitaxel and carboplatin were administered in doses ranging from 130 to 185 mg/m2 and from 230 to 350 mg/m2, respectively. Twenty-four patients have been treated to date, and the maximum tolerated dose has been reached at paclitaxel 185 mg/m2 and carboplatin 350 mg/m2. The combination has an excellent safety profile, with only a few, short-lasting episodes of neutropenia observed and no evidence of infection. At the doses tested, thrombocytopenia has not occurred.

Adolescent↗

Drug interaction between cyclosporine and two antimicrobial agents, josamycin and rifampicin, in organ-transplanted patients.

In the post-transplant period, antimicrobial agents are often coadministered with cyclosporine (CsA) to treat the infections occurring in the immunosuppressed patients. These agents produce drug interactions with cyclosporine and can increase or reduce the blood concentration of the immunosuppressant. We report two cases of drug interaction between cyclosporine and two antimicrobial agents, josamycin and rifampicin, coadministered in a kidney-transplanted and a liver-transplanted patient, respectively. Josamycin increased the CsA blood levels by inhibiting the CsA metabolism through the hepatic cytochrome P450 enzymes. Conversely, rifampicin decreased the CsA blood levels by stimulating the same enzymatic system. When using these agents it is necessary to adjust the CsA doses to avoid risks of CsA toxicity or allograft rejection.

Acne Vulgaris↗

[Invasive papillary and pseudopapillary (micropapillary) carcinoma of breast].

Classical invasive papillary carcinoma of the breast, is rare. In their pure form, they constitute 1.5% of all invasive breast carcinomas. Only one study clearly distinguishes them from intra-ductal papillary carcinomas; in this study they display a low metastatic potential and a relatively good prognosis. Lately, a new type of papillary carcinoma has been described which is characterized by inversion of the tumor cell polarity and papillations devoid of fibrovascular cores. Described by several authors by the term "micropapillary" carcinoma, the originally suggested term "pseudo-papillary" seems to be more appropriate; moreover, this designation would more clearly distinguish them from papillary carcinomas from which they clearly differ by their behavior. Furthermore, the pseudo-papillary carcinomas present an important lymphotropism, the effect of which on their clinical course is not yet clear. Further studies are necessary to determine whether these tumors, more frequent than classical papillary carcinomas, should be considered as a distinct clinical entity.

Breast Neoplasms↗

Effect of amiodarone therapy on mortality in patients with left ventricular dysfunction and asymptomatic complex ventricular arrhythmias: Argentine Pilot Study of Sudden Death and Amiodarone (EPAMSA).

The efficiency of prophylactic antiarrhythmic treatment with amiodarone in reducing 1-year mortality in patients with reduced left ventricular ejection fraction ( < 35%) and asymptomatic ventricular arrhythmias (Lown classes 2 and 4) was investigated in a prospective, multicenter, randomized, controlled study. Among 127 patients who entered the study, 61 were assigned to no antiarrhythmic therapy (control group [CG] and 66 to amiodarone treatment (amiodarone group [AG]). Amiodarone was administered at a dosage of 800 mg/day for 2 weeks followed by 400 mg/day thereafter. A 12-month follow-up was completed for 106 patients (57 in the AG and 49 in the CG). Amiodarone reduced the overall mortality rate, which was 10.5% in the AG versus 28.6% in the CG (odds ratio [OR] 0.29; 95% confidence interval [CI] 0.10 to 0.84; log-rank test 0.02) and sudden death rate, which was 7.0% in the AG versus 20.4% in the CG (OR 0.29; 95% CI 0.08 to 1.00; log-rank test 0.04). Side effects were rare, and in only three patients did amiodarone treatment have to be discontinued.

Aged↗

Laryngeal schwannomas.

As laryngeal schwannomas are a threat to breathing, they must be removed. CT and MR provide an accurate pre-operative work-up of these lesions. The clear delineation of the tumoral attachment to the larynx proved to be very useful in the difficult management of our second patient. Our two laryngeal schwannomas exhibited a similar appearance which differed from those of the few other laryngeal nerve sheath tumors reported in the literature The low attenuating outer part correlated with Antoni B areas. The denser enhancing inner part correlated with Antoni A areas containing large vessels. This unusual tumoral appearance, which has been observed in some other peripheral schwannomas, must bring this diagnostic possibility to mind. However, this clearly contrasting distribution of the two components of schwannomas is not the most commonly observed in other locations. More reports are needed to establish whether this special appearance is characteristic of laryngeal location.

Adult↗

[Selective use of intra-operative cholangiography in gallstone surgery].

The authors report their experience of the use of intraoperative cholangiography in 350 operations for biliary stones. The cholangiography was performed on all 52 patients with preoperative diagnosis of stones in CBD. In the 298 patients with gallbladder stones intraoperative colangiography was performed in 32 times, on the basis of previous jaundice, pancreatitis, microlithiasis, enlarged cystic duct or choledochus, and suspected palpatory reports of hepatic duodenal ligament. Intraoperative colangiography showed stones in all the patients of the first group and in 8 (25%) of the second. No patients reported disturbances attributable to residual stone with an average follow-up of 6 months.

Adult↗

[Acidity of the rumen liquid of calves after intra-ruminal administration of solutions for oral rehydration].

UNLABELLED: Investigations on the acidity of the rumen liquid after intraruminal administration of oral rehydration solutions (ORS) were carried out in 7 young calves. After voluntary intake of about one liter of milk replacer, three times a day, 1 liter of rehydration solution (A, B, C or D) was administered intraruminally by a stomach tube. Prior to every meal rumen fluid samples were aspirated for the determination of the pH, the concentrations of lactic acid and volatile fatty acids. Number of experiments: solution A: n = 2; B: n = 4; C: n = 2; D: n = 5. In 3 experiments, the pH of the rumen fluid was measured continuously for 4 hours using a special pH probe introduced intraruminally. After intraruminal administration of the oral rehydration solutions the pH values of the rumen fluid samples decreased from initial values of about 6.5 to values of about 5.0 or even lower in all calves. Simultaneously, the concentrations of the acids, mainly lactic acid, increased markedly, with some differences depending on the respective solution. The course of the pH measured continuously by means of the pH probe corresponded to the results obtained from the intermittent rumen fluid samples. CONCLUSIONS: The results confirm, that force-feeding of young calves with ORS as used in these experiments can induce ruminal acidosis and, therefore, should be avoided as far as possible.

Animals↗

Gallbladder motor function in gallstone patients: sonographic and in vitro studies on the role of gallstones, smooth muscle function and gallbladder wall inflammation.

Gallbladder motility was studied by ultrasound in 100 healthy adult volunteers and 150 gallstone patients, in a subgroup of whom gallstone burden, type and number, gallbladder histology and tensiometric responses of gallbladder strips to cholecystokinin octapeptide were evaluated. Patients were divided into contractors (n = 108) and hypocontractors (n = 42), according to their gallbladder motility pattern in vivo. Contractors showed slower gallbladder emptying and increased fasting and postprandial residual volumes, although the ejected amount of bile was greater than that of controls (20.2 +/- SEM 1.1 vs 16.0 +/- 0.7 ml; p < 0.001). In contrast, hypocontractors exhibited slower and less complete gallbladder emptying than controls with a reduction in the absolute amount of ejected bile. Although gallbladder wall inflammation was mild and comparable in specimens from both groups of patients, the thickness of the muscular layer was greater in hypocontractors than in contractors (1073 +/- 76 vs 745 +/- 75 microns, p < 0.01) and related inversely to postprandial ejected volume (r = -0.42; p < 0.03; n = 32) but positively to gallstone volume (r = 0.40; p < 0.03; n = 32). Compared to contractors, gall-bladder muscle strips of hypocontractors exhibited a decrease in frequency and amplitude of spontaneous contraction and in maximal stress and receptor sensitivity to cholecystokinin octapeptide (0.1 nM-1 microM). Postprandial gallbladder evaculation was unaffected by stone number, and by the presence or absence of stone calcification. Gallstone volume was larger in hypocontractors (19.4 +/- 3.0 ml vs 9.6 +/- 0.9 ml, p < 0.001) than contractors. The comparison of in vitro contractility patterns between cholesterol, mixed and pigment stone patients showed a more severe defect in patients with cholesterol and mixed stones than in those with pigment calculi. In conclusion, in gallstone patients: (i) gallbladder motor dysfunction manifests mainly with increased fasting and postprandial residual volumes in contractors and with markedly increased postprandial residual volumes and decreased gallbladder emptying in hypocontractors; (ii) gallbladder kinetics seem to be influenced by stone volume and cholesterol content of calculi but not stone number, calcification or mild chronic cholecystitis; (iii) a form of hypertrophic leiomyopathy is observed in gallstone patients with the most impaired gallbladder motor function.

Adult↗

Prognostic value of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in breast carcinomas.

It is now clearly established that proteolytic enzymes, including plasminogen activator (uPA), play an important role in breaking down the extracellular matrix, which is considered to be a step in metastasis formation. Plasminogen activators are controlled at various levels. Two inhibitors, PAI-1 and PAI-2, have been identified, the latter being more specific for uPA. In attempts to determine their prognostic value, it is essential to investigate the relative importance of these parameters and their interactions. We used an immunoenzymatic method to assay uPA, PAI-1 and PAI-2 antigens in cytosols prepared from 314 primary breast tumours. The patients were followed up for a minimum of 6 years and all relevant clinical and laboratory findings were recorded. Univariate analysis confirmed the poor outcome of patients whose tumours contained large amounts of uPA and PAI-1. In addition, low levels of PAI-2 correlated with shorter disease-free survival in the overall population (P = 0.02), post-menopausal women (P = 0.02) and women without lymph node involvement (P = 0.02). Multivariate analysis in the 'main effects' Cox model identified node involvement, macroscopic tumour size and PAI-2 as significant variables. The 'interactive' model, taking into account interactions between uPA and its two inhibitors, identified a first subgroup with a very poor prognosis associating either high levels of PAI-1 with low levels of PAI-2 in the overall population and the women with no node involvement or high levels of uPA with low levels of PAI-2 in the group of menopausal women. We conclude that PAI-1 provides the same prognostic information as uPA, and does not appear to play a role as an inhibitor. In contrast, PAI-2 increases the prognostic value of uPA, particularly in post-menopausal women, and PAI-1 in patients with no node involvement.

Adult↗

[Prognostic value of urokinase-type plasminogen activator and 2 inhibitors PAI-1 and PAI-2 in breast cancer].

It is now clearly established that proteolytic enzymes, and in particular plasminogen activator (uPA), play an important role in breaking down the extracellular matrix, which is considered to be a step in metastasis formation. Plasminogen activators are controlled at various levels. Two inhibitors, PAI-1 and PAI-2, have been identified, the latter being more specific for uPA. In attempts to determine their prognostic value, it is essential to investigate the relative importance of these parameters and their interactions. We used an immunoenzymatic method to assay uPA, PAI-1 and PAI-2 antigens in cytosols prepared from 314 primary breast tumors. The patients were followed up for a minimum of six years and all relevant clinical and laboratory findings had been recorded. Univariate analysis confirmed the poor outcome of patients whose tumors contained large amounts of uPA and PAI-1. In addition, low levels of PAI-2 correlated with shorter disease-free survival in the overall population (P = 0.02), post-menopausal women (P = 0.02) and women without lymph node involvement (P = 0.02). Multivariate analysis using the "Main Effects" Cox model identified node involvement, macroscopic tumor size and PAI-2 as significant variables. The "interactive" Cox model, taking into account interactions between uPA and its two inhibitors, identified a first subgroup with a very poor prognosis associating either high levels of PAI-1 with low levels of PAI-2 in the overall population as well as following stratification for axillary node negative disease, or high levels of uPA with low levels of PAI-2 in the group of menopausal women. We conclude that PAI-1 provides the same prognostic informations as uPA, and does not appear to play its role as an inhibitor. In contrast, PAI-2 increased the prognostic value of both uPA, particularly in post-menopausal women, as well as PAI-1 in a subgroup of axillary node negative patients.

Adult↗

[Local recurrence after conservative therapy of breast cancer: risk factors, site of recurrence, evolution].

The identification of factors associated with breast recurrence as first event (62 cases, 10%) following conservative surgery and radiation therapy are drawn out from a series++ of 618 mammary carcinomas of clinical size less than 40 mm, stage I and II (UICC), with a median follow up of 8 years. The most powerful predictive characteristic associated with the likelihood of breast recurrence is multiple foci of invasion (42.9% vs 8.9, P = 0.0001, relative risk [RR]: 6). After this rarely cited feature, young age, less than 40 years (20% vs 7.3%, P = 0.0001, RR: 2.8), extensive in situ carcinoma more than 25% (19.2% vs 8.7%, P = 0.003, RR: 2.5) were found also persistent in the Cox model, but not histologic size more than 25 mm (18.9% vs 9.1%, P = 0.01, RR: 2.3). The site of recurrence was studied on the 54 salvage mastectomy done. A high rate of recurrence at distance of the initial site was found: 37% whose more than half, 22%, were multicentric. No significant difference in the mean delay of appearance was noted between recurrence near or at distance of the initial cancer (mean delay 52 months vs 64 months). From the recurrence the evolution is not very favourable: excluding simultaneous metastases found at the preoperative investigation, ten cases, mammary recurrence is followed by a metastatic syndrome in 36% of cases against 17% without it (P = 0.01, RR: 1.9). Metastatic evolution is not significantly linked with the time, early or late, of the mammary recurrence (54.5% before 5 years vs 39% after) but with the association of a controlateral cancer (P = 0.03). Locally ten of the 54 mastectomy presented a thoracic recurrence, often in case of multicentric breast recurrence (P = 0.05) and not significantly when skin or areola were invaded by carcinoma.

Adenocarcinoma↗

Use of texture parameters in the classification of soft tissue tumors.

Soft tissue tumors are a challenging group of tumors that presents wide morphologic variety. For pathologists, the degree of cellular differentiation, the cellular and nuclear polymorphism and the mitotic rate are major criteria for diagnosis. In image analysis, the architectural organization of such tumors shows local variations that can be understood as texture variations. This study introduced a method of measuring the architectural organization of soft tissue tumors from texture analysis of tissue sections at low magnification. We studied 40 cases of soft tissue tumors classified by pathologists into three groups according to their histologic patterns. Twelve texture parameters were calculated on subimages of 128 x 128 pixels. Our results show that tissue architecture evaluated by texture analysis provides good discrimination of myxoid, spindle cell and round cell tumors.

Cell Differentiation↗

Grading of cystosarcoma phyllodes by texture analysis of tissue architecture.

Conventional histologic grading of cystosarcoma phyllodes of the breast has not been entirely successful in the prognosis of recurrence or metastasis. Our study first developed a tumor grade classification based on computerized texture features and then compared the classification to conventional grading of these tumors. Evaluation of the tissue architecture of histologic sections was obtained by measuring nine texture features on an image analysis system. Forty cases of cystosarcoma phyllodes were studied. Each parameter was calculated on subimages of 128 x 128 pixels. This size resulted from a preliminary study that confirmed that the difference between texture primitives depends on the area of subimages. We also compared our series to a panel of 20 extramammary sarcomas. The results show that tissue architecture evaluated by texture analysis allows good discrimination between benign, borderline and malignant cystosarcoma phyllodes. Furthermore, extramammary sarcomas and malignant cystosarcoma phyllodes were discriminated well in most cases.

Breast Neoplasms↗

Decaffeinated coffee and acute myocardial infarction. A case-control study in Italian women.

The relationship between consumption of decaffeinated coffee and acute myocardial infarction was analyzed in a case-control study conducted in Italy between 1983 and 1992. Case patients were 433 women with acute myocardial infarction, aged 24 to 69 years (median age, 52 years), and control subjects included 869 women in hospital for a wide spectrum of acute conditions, other than cardiovascular, neoplastic, digestive, and hormone-related diseases or conditions associated with long-term modification of diet. Regular use of decaffeinated coffee was reported by 11% of the case patients and 7% of the control subjects. Compared with women who did not drink decaffeinated coffee, the relative risk (RR) was 1.3 (95% confidence interval (CI), 0.8 to 2.2) for one cup/d and 2.1 (95% CI, 1.1 to 3.9) for 2 or more cups (chi 2(1) for trend = 5.62, P = 0.02). The estimates were somewhat higher after allowance for education, marital status, body mass index, and smoking status (RR for > or = 2 cups of decaffeinated coffee per day, 2.5; 95% CI, 1.2 to 4.9), and somewhat lower after further allowance for diabetes, hypertension, and hyperlipidemia (RR, 1.7; 95% CI, 0.8 to 3.6). There was no association between duration of use of decaffeinated coffee and infarction risk. The relationship between decaffeinated coffee and infarction was consistent across strata of age, education, smoking, and history of hyperlipidemia. Thus, a relationship of marginal significance was observed in this study between decaffeinated coffee and myocardial infarction, of similar magnitude to that described for caffeinated coffee. This indicates that (i) caffeine is unlikely to be a relevant factor in any potential coffee-myocardial infarction relationship, and (ii) shifting from caffeinated to decaffeinated coffee is unjustified in order to reduce any possible coffee-related infarction risk.

Adult↗

Keratins 6, 13 and 19. Differential expression in squamous cell carcinoma of the head and neck.

One hundred forty-one head and neck squamous cell carcinomas were analyzed for keratin (K) 6, 13 and 19. Staining was evaluated by light microscopy (with or without grading) and image analyzer and expressed as a percentage of positive versus all tumor surface (PSA). Both techniques rendered strongly correlated results. Strong expression was noted in 108 carcinomas (76.1%) for K6, in 18 (12.7%) for K19 and in 21 (14.8%) for K13 (P = .001). One hundred thirty-six (96%) tumors were positive for K6, and their PSA ranged from 0.6% to 48.8%; K19, 48 cases (0.2-44%); K13, 59 (0.2-38.1%). Expression of K6 was related to differentiation. K19 was expressed mainly in moderately and poorly differentiated tumors, and K13 was manifest more in well-differentiated carcinomas or in keratinized areas of less-differentiated ones. Nineteen (13.38%) tumors were positive for both K13 and K19. K19 thus was related to tumor progression and K13 to differentiation. There was no correlation with tumor site or TNM category.

Adult↗

Medullary carcinoma of the breast. A multicenter study of its diagnostic consistency.

Nine pathologists from different institutions reviewed in a double-blind study 16 breast tumors previously indexed as typical medullary carcinoma, atypical medullary carcinoma, or infiltrative ductal carcinoma. A set of 16 slides was circulated two times among the nine pathologists. The diagnoses of typical and atypical medullary carcinomas were based on a definition given by Ridolfi et al. The interobserver and intraobserver agreement was low, with a kappa value of less than .50. The only histological criterion that had more than 50% agreement was the presence or absence of an in situ component in the tumor, assuming that the disagreement of one pathologist is accepted. This study is a snapshot of the problems encountered in the diagnosis of typical medullary carcinoma in a routine context and it shows high levels of variations in diagnostic consistency.

Breast Neoplasms↗

Family history and the risk of stomach and colorectal cancer.

BACKGROUND: The role of a family history of selected neoplasms in first-degree relatives in the risk of gastrointestinal cancers has been investigated, but requires further quantification. METHODS: A case-control study was conducted in northern Italy on 628 histologically confirmed incident cases of stomach cancer, 766 cases of colon cancer, 456 cases of rectal cancer, and 1766 controls admitted to hospital for acute, nonneoplastic, non-digestive tract disorders. RESULTS: Significant associations were observed between a family history of gastric cancer and stomach cancer risk (relative risk [RR], 2.6), and between a family history of intestinal cancer and colon (RR, 2.4) and rectal cancer (RR, 1.7). There was a tendency for the risks to be above unity for a family history of stomach cancer and for a number of other cancer sites (including esophagus, intestines, liver, pancreas, gallbladder, and lung), and the RR were of borderline statistical significance for cancer of the liver and intestines. The RR for a family history of lung cancer was 1.5 for stomach, 1.2 for colon, and 1.3 for rectal cancer, with none of the estimates being significant. There was no consistent pattern of risk with reference to the type of first-degree relationship; the RR was similar for stomach cancer with reference to parents and siblings, and for colon and rectal cancer, it was only moderately higher with reference to siblings. Significant trends in risk with the number of first-degree relatives were observed for all three cancer sites investigated. CONCLUSIONS: In terms of population attributable risk, approximately 8% of stomach cancers and 3% of colorectal cancers would be related to this familial component.

Aged↗

Alcohol and epithelial ovarian cancer.

The relationship between alcohol consumption and the risk of epithelial ovarian cancer was analysed using data from a case-control study of 801 histologically confirmed epithelial ovarian cancers and 2114 controls in hospital for acute, non-neoplastic, gynecological, or hormone-related conditions, admitted to a network of teaching and general hospitals in the greater Milan area, northern Italy, i.e. a region with comparatively frequent alcohol consumption by women. Compared to alcohol abstainers, the multivariate relative risks (RRs) were 1.0 [95% confidence interval (CI), 0.7 to 1.4] for less than one, 1.1. (95% CI 0.9 to 1.6) for one to two, 1.2 (95% CI 1.0 to 1.5) for two to three and 1.3 (95% CI 0.9 to 1.8) for three or more drinks per day. A significant direct trend in risk with dose emerged. This finding chiefly derived from an association between ovarian cancer risk and consumption of wine (which accounts for over 90% of alcohol intake in this female population). Although no significant interaction between the effect of alcohol consumption and various women's characteristics emerged, there was a hint that the adverse influence of alcohol consumption is more marked in middle-age and less educated women. Thus, the results of this study suggest that relatively elevated alcohol intake (of the order of 40 g per day or more) may cause a modest increase of epithelial ovarian cancer risk.

Adult↗