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Biomedical subjects

A Casali

Publications and source records attributed to A Casali.

At least 19 recordsLinked to original sources

Impact of highly active antiretroviral therapy on outcome of cholecystectomy in patients with human immunodeficiency virus infection.

BACKGROUND: Highly active antiretroviral therapy (HAART) reduces virus proliferation and significantly decreases the rate of septic and opportunistic complications in patients infected with human immunodeficiency virus (HIV). Although surgery is performed routinely on patients receiving HAART, the effect of this treatment on surgical outcome has not been examined in detail. METHODS: This retrospective study reviewed 54 consecutive patients with HIV infection who underwent surgical cholecystectomy: 31 patients were on HAART, 13 on nucleoside analogue reverse transcriptase inhibitors (NRTIs) and ten were receiving no specific therapy. Characteristics of HIV-1 infection, laboratory investigations, characteristics of the gallbladder disease, type of operation, postoperative course, morbidity and mortality were recorded. Univariable analysis and unconditional logistic regression were performed to determine factors related to postoperative complications and death. RESULTS: The three groups were similar in terms of HIV-1 infection characteristics. In univariable analysis HAART and laparoscopic cholecystectomy were associated with a significantly lower complication rate, whereas only HAART was shown to be protective by logistic regression analysis. A low HIV RNA load and a high CD4(+) cell count were significant predictors of uncomplicated surgical outcomes. CONCLUSION: HAART significantly reduces the risk of complications after cholecystectomy in patients with HIV infection or acquired immune deficiency syndrome.

Adult↗

Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): is a clinical benefit still achievable?

BACKGROUND: There are few clinical data on the sequential use of aromatase inhibitors (AI). This paper focuses on the relevance of clinical benefit CB (CR + PR + SD > or = 6 months) in postmenopausal metastatic breast cancer (MBC) patients treated with the steroidal aromatase inhibitor (SAI) formestane (FOR). who had already received non-steroidal aromatase inhibitor (nSAI): letrozole (LTZ) or anastrozole (ANZ). PATIENTS AND METHODS: Twenty postmenopausal women with MBC were analysed in this retrospective two-centre study with the sequence nSAI-FOR. When receiving ANZ, 1 of 11 achieved a complete response and 9 of 11 a stable disease > or = 6 months, and receiving LTZ 1 of 9 achieved a partial response and 4 of 9 a stable disease > or = 6 months. The analysis of the entire population treated with FOR showed an overall CB of 55% (11 of 20) with a median duration of 15 months and median time to progression (TTP) of 6 months. CONCLUSIONS: Formestane 250 mg once bi-weekly seems to be an attractive alternative third-line hormonal therapy for the treatment of patients with MBC, previously treated with nSAI.

Adult↗

Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis (LC) in more than 90% of cases. Early diagnosis and treatment of HCC are expected to improve survival of patients. AIMS: To assess the cost effectiveness of a surveillance programme of patients with LC for the early diagnosis and treatment of HCC. PATIENTS: A cohort of 313 Italian patients with LC were enrolled in the surveillance programme between March 1989 and November 1991. In the same period, 104 consecutive patients with incidentally detected HCC were referred to our centre and served as a control group. METHODS: Surveillance was based on ultrasonography (US) and alpha fetoprotein (AFP) determinations repeated at six month intervals. Risk factors for HCC were assessed by multivariate analysis (Cox model). Outcome measures analysed were: (1) number and size of tumours; (2) eligibility for treatment; and (3) survival of patients. Economic issues were: (1) overall cost of surveillance programme; (2) cost per treatable HCC; and (3) cost per year of life saved (if any). Costs were assessed according to charges for procedures at our university hospital. RESULTS: Surveillance lasted a mean of 56 (31) months (range 6-100). During the follow up, 61 patients (19.5%) developed HCC (unifocal at US in 49 cases), with an incidence of 4.1% per year of follow up. AFP, Child-Pugh classes B and C, and male sex were detected as independent risk factors for developing HCC. Only 42 (68.9%) of 61 liver tumours were treated by surgical resection, orthotopic liver transplantation, or local therapy. The cumulative survival rate of the 61 patients with liver tumours detected in the surveillance programme was significantly longer than that of controls (p=0.02) and multivariate analysis showed an association between surveillance and survival. The overall cost of the surveillance programme was US$753 226, the cost per treatable HCC was US$17 934, and the cost for year of life saved was US$112 993. CONCLUSION: Our surveillance policy of patients with LC requires a large number of resources and offers little benefit in terms of patient survival. The decision whether to adopt a surveillance policy towards HCC should rely on the prevalence of the disease in the population and on the resources of a particular country.

Adult↗

The spatial control of Torso RTK activation: a C-terminal fragment of the Trunk protein acts as a signal for Torso receptor in the Drosophila embryo.

Regulated activation of receptor tyrosine kinases depends on both the presence of the receptors at the cell surface and on the availability of their ligands. In Drosophila, the torso tyrosine kinase receptor is distributed along the surface of the embryo but it is only activated at the poles by a diffusible extracellular ligand generated at each pole that is trapped by the receptor, thereby impeding further diffusion. Although it is known that this signal depends on the activity of several genes, such as torso-like and trunk, it is still unclear how is generated. The identification of the signal responsible for the torso receptor activation is an essential step towards understanding the mechanism that regulates the local restriction of torso signalling. Here we report that a fragment containing the carboxy-terminal 108 amino acids of the trunk protein retains trunk activity and is sufficient to activate torso signalling. We also show that this fragment bypasses the requirements for the other genes involved in the activation of the torso receptor. These results suggest that a cleaved form of the trunk protein acts as a signal for the torso receptor. We therefore propose that the restricted activation of the torso receptor is defined by the spatial control of the proteolytic processing of the trunk protein.

Animals↗

Gemcitabine in pre-treated advanced renal carcinoma: a feasibility study.

Eigtheen patients affected by metastatic renal cell carcinoma, 16 which were assesable, were treated with 1 g/m2 of Gemcitabine (GCB) on days 1, 8 and 15 of a 28-day treatment cycle up to a maximun of ten cycles. All patients in neoplastic progression were treated with chemo- and immunotherapy (5 FU, IL-2, IFN alpha d 13-cis-retinoic acid.) Out of the 16 assessable patients, 5/16 (31%) showed overall response (ICR, 4 PR), 5 (31%) stable disease (SD) and 6 (38%) progression of disease (PD). Toxicity was limited to WHO grades I only, primarily hematological.

Adult↗

Assessment of vascular patterns of small liver mass lesions: value and limitation of the different Doppler ultrasound modalities.

OBJECTIVES: This study aimed to investigate the value and limitation of the different Doppler ultrasound modalities (spectral analysis, color, and power Doppler imaging) in the differential diagnosis of small liver tumors to identify the optimal diagnostic approach with the presently available Doppler technology. METHODS: Presence and distribution of color and power Doppler signals, Doppler peak frequency, resistive index, and systolic acceleration time were examined in 133 liver nodules (< or = 4 cm). RESULTS: Color and power Doppler did not identify specific diagnostic vascular patterns. By discriminant analysis, peak frequency (cut-off 1320 Hz) differentiates small hematocellular carcinoma (< or = 2 cm) from macroregenerative nodules and hemangiomas (accuracy 92.6%); resistive index (cut-off 0.65) differentiates malignancies from benign lesions (accuracy 83.8%); and systolic acceleration time (cut-off 105 ms) differentiates hepatocellular carcinoma from metastases (accuracy 80.9%). CONCLUSIONS: Power Doppler imaging is able to assess vascularity in the majority of small liver nodules, but the pattern distribution of tumoral vascular signals does not provide reliable differential diagnostic criteria. Using conventional Doppler technology, power Doppler should be used to detect vascular signals and spectral analysis, and subsequently to measure quantitative parameters such as high peak frequency and resistive index (which identify malignancy) and prolonged systolic acceleration time (which identifies primary from metastatic liver tumors).

Carcinoma, Hepatocellular↗

Letrozole for the treatment of pretreated advanced breast cancer patients: preliminary report.

Twenty patients (pts) with metastatic breast cancer with disease progression, previously treated with chemotherapy and tamoxifen, were administered oral letrozole (2.5 mg/day) therapy. Fifteen of the patients were postmenopausal and 5 were premenopausal. Ten were estrogen receptor (ER)-positive, 7 were unknown and 3 were ER-negative. All the patients were assessed after 6 months (mo) of chemotherapy. Nine pts (45%) presented a partial response (PR), five (25%) had a stable disease (SD) and six (30%) had a progressive disease (PD). In the pts with PD, six out of 15 (33%) obtained a PR while undergoing tamoxifen therapy. The treatment caused no significant toxicity.

Administration, Oral↗

Imbalance of IL-1 beta and IL-1 receptor antagonist mRNA in liver tissue from hepatitis C virus (HCV)-related chronic hepatitis.

Increased levels of IL-1 beta and IL-1 receptor antagonist (IL-1Ra) have been found in serum of patients with chronic liver diseases, although their expression in liver tissue has not been extensively investigated. The aim of this study was therefore to examine the relationship between IL-1 beta and IL-1Ra at tissue level in patients with HCV-related chronic active hepatitis (CAH) of varying degrees of severity. IL-1 beta and IL-1Ra mRNA expression was investigated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 31 patients with CAH of varying severity (classified as minimal/mild in 13 cases and moderate/severe activity in 18 cases) and in 12 control subjects. Quantitative evaluation of IL-1 beta and IL-1Ra corresponding bands was performed by densitometric image analysis, and expressed in arbitrary units. The 12 controls expressed a similar pattern with a mean IL-1 beta/IL-1Ra ratio of 1.03 (1.03 +/- 0.15 (mean +/- s.e.m.), median 0.92, range 0.71-1.45). Minimal/mild activity CAH showed a prevalence of IL-1Ra mRNA expression (1.14 +/- 0.64, median 0.43, range 0-8.75) when compared with controls (0.27 +/- 0.04, median 0.23, range 0.11-0.45) and with moderate/severe activity CAH (0.20 +/- 0.04, median 0.12, range 0-0.67; P = 0.01). Since IL-1 beta expression was similar in the three groups, a significantly different IL-1 beta/IL-1Ra ratio emerged between controls, patients with moderate/severe CAH (2.22 +/- 0.48, median 2.76, range 0-6.12) and those with minimal/mild activity CAH (0.62 +/- 0.15, median 0.5, range 0-1.58, P = 0.005). Patients with higher grades of fibrosis showed a higher IL-1 beta/IL-1Ra ratio (2.49 +/- 0.56, median 2.15, range 0.35-6.12) in comparison with lower grade fibrosis (1.06 +/- 0.30, median 0.59, range 0.03-4.50) and control patients (P = 0.01). These results suggest that an imbalance between IL-1 beta and IL-1Ra, at the tissue level, may contribute to the pathogenesis and the activity of chronic active hepatitis C.

Adult↗

Dissecting the mechanism of torso receptor activation.

Regulated activation of receptor tyrosine kinases depends both on the presence of the receptors at the cell surface and on the availability of their ligands. In Drosophila the torso (tor) tyrosine kinase receptor is distributed along the surface of the embryo but it is only activated at the poles by a diffusible extracellular ligand generated at each pole which is trapped by the receptor, thereby impeding further diffusion. However, it is not well understood how this signal is generated, although it is known to depend on the activity of many genes such as torso-like (tsl) and trunk (trk). To further investigate the mechanism involved in the local activation of the tor receptor we have altered the normal expression of the tsl protein by generating females in which the tsl gene is expressed in the oocyte under the control of the tor promoter rather than in the ovarian follicle cells. Analysis of the phenotypes generated by this hybrid gene and its interactions with mutations in other genes in the pathway has enabled us to further dissect the mechanism of tor receptor activation and to define more precisely the role of the different genes acting in this process.

Animals↗

Characterization of platyhelminth POU domain genes: ubiquitous and specific anterior nerve cell expression of different epitopes of GtPOU-1.

POU domain proteins are a large family of transcription factors that have been identified in a variety of metazoans, from freshwater sponges, planarians and nematodes to arthropods, echinoderms and vertebrates. Many of these proteins are implicated in the development and establishment of the nervous system. In this paper we describe the identification of the planarian genes GtPOU-1, GtPOU-3 and GtPOU-4, which belong to the subclasses III and IV of POU-domain genes. Their similarity with other members of the POU family is restricted to the POU and homeo domains, plus some peptide sequences scattered in the linker and flanking regions. As with other subclass III POU genes, GtPOU-1 is devoid of introns. Axial transcript distribution by RT-PCR and immunohistochemical assays, performed with a polyclonal antibody raised against the GtPOU-1 fusion protein, indicate that both the GtPOU-1 transcript and protein are continuously expressed along the antero-posterior axis. A monoclonal antibody raised against the same fusion protein indicates that a GtPOU-1-specific epitope, probably obtained by post-translational modification, is present in neural cells from both the central and peripheral nerve systems of the adult planarian's anterior third. Moreover, the GtPOU-1-specific epitope shows a dynamic expression pattern during regeneration, always marking the most anterior region of the planarian nervous system. Both the rapid and general GtPOU-1-specific epitope modification, during posterior regeneration, indicate that regeneration is a global process involving all planarian regions, including those that are far from the wound, by a combination of morphallactic and epimorphic mechanisms.

Amino Acid Sequence↗

13-cis retinoic acid and interferon alfa-2a in the treatment of metastatic renal cell carcinoma.

Eleven patients, pre-treated with chemotherapy and immunotherapy, with renal cell carcinoma were given 13-cis-retinoic acid (CRA) in association with interferon alfa-2a (IFN 2a). 13-ci retinoic acid was administered at the dose of 1 mg/Kg/die while interferon alfa-2a at the dose of 3X10 U.I./die s.c. All patients had been previously treated with chemotherapy in association with immunotherapy. Therapy was not discontinued until neoplastic progression occurred. Clinical results were as follows: partial responses (PR) were observed in two patients, disease stabilization (SD) in 5 and progression (PD), with 8-month median treatment duration, in 4. Side effects were mild.

Adult↗

A case of extracranial vertebral artery dissection with spontaneous recovery Diagnosis and follow-up by duplex and color Doppler.

A 47-year-old women developed an acute vestibular syndrome with a peripheral facial palsy not associated with any trauma. Magnetic resonance imaging showed an ischemic lesion in the territory of the posterior inferior cerebellar artery. Color Doppler ultrasonography detected an occlusion of the right vertebral artery and dissection of the artery was confirmed by a subsequent angiography. During follow-up Duplex-Doppler allowed a non-invasive monitoring of recanalization of the occluded artery. Copyright 1997 Elsevier Science Ireland Ltd.

Journal Article↗

Intra- and extrahepatic arterial resistances in chronic hepatitis and liver cirrhosis.

Thirty patients with chronic hepatitis (CH), 84 with liver cirrhosis (LC) and 42 controls, underwent noninvasive measurement of hepatic artery resistance index (RI) by means of Doppler ultrasound (US), at the porta hepatis and in the intrahepatic branches, in order to investigate possible changes related to: (a) the liver disease; (b) the site of measurement; and (c) ageing. The intrahepatic RI differed among LC, CH and controls (0.731, 0.690 and 0.643, p < 0.05), whereas the RI at the porta hepatis did not (0.754, 0.748 and 0.729, respectively). Intrahepatic RI correlated with age in LC (r = 0.51, p < 0.0001) and in controls (r = 0.49, p < 0.001). In LC, it correlated also with the presence and size of esophageal varices (r = 0.32, p < 0.05). In conclusion, an increase of hepatic artery RI in chronic liver diseases can be demonstrated when assessed in the intraparenchymal branches. The increase of hepatic artery RI with ageing should be considered in future studies.

Adult↗

Triple combination antimicrobial regimen in the treatment of infections of neutropenic cancer patients.

Twenty-six cancer patients (pts) with chemotherapy-related neutropenic fever were treated with vancomycin 30 mg/m2/day i.v. every 12 hrs, imipenem 1500 mg/day i.v. every 8 hrs, and pefloxacin 800 mg/day i.v. every 12 hrs. Twelve fevers of unknown origin (FUO), 10 gram-positive, 3 gram-negative and 1 mycoplasma were also treated. Globally, cure was observed in 22 pts (84%) and failure in 4 pts (16%); in gram-positive infections alone, cure was observed in 10 pts (80%) and failure in 4 pts (20%). Defervescence was obtained within 3 days in 77% pts. No relevant side effects were observed.

Anti-Bacterial Agents↗

Alteration of DNA ploidy and cell nuclearity in human hepatocellular carcinoma associated with HBV infection.

BACKGROUND/AIMS: Hepatocellular carcinoma usually arises in cirrhotic livers as a complication of chronic liver disease, and may show a variable trend towards increasing ploidy. The aim of this study was to investigate possible associations between different etiological factors, particularly hepatitis B virus and hepatitis C virus infection, and alteration of DNA-ploidy and nuclearity of neoplastic hepatocytes. METHODS: DNA-ploidy, the percentage of binucleated cells in the total cell population and the fraction of mononucleated hepatocytes in the polyploid compartment were assessed by image cytometry on cellular suspensions obtained by fine-needle biopsy from 60 hepatocellular carcinomas in patients whose viral status had previously been assessed. RESULTS: Significantly higher DNA-ploidy values (p = 0.005), with a reduction in the percentage of binucleated hepatocytes (p = 0.003) and an increase in the fraction of mononucleated hepatocytes in the polyploid compartment (p < 0.0001), were found in hepatocellular carcinoma with actual or previous hepatitis B virus infection (including also HCV+ve patients) in comparison to those not associated with hepatitis B virus infection, but not when HCV+ve hepatocellular carcinomas were compared to HCV-ve ones. Statistically significant differences for ploidy values (p < 0.05), percentage of binucleated hepatocytes (p < 0.05) and fraction of mononucleated hepatocytes in the polyploid compartment (p = 0.003) were also found between hepatocellular carcinoma associated only to hepatitis B virus infection ("pure" hepatitis B virus cases) and those associated only to hepatitis C virus infection ("pure" hepatitis C virus cases). CONCLUSIONS: Hepatocellular carcinoma associated with a previous or actual hepatitis B virus infection shows a peculiar phenotypical appearance, characterized by a trend towards increasing ploidy and reduction of binuclearity.

Adult↗

High copy number of highly similar mariner-like transposons in planarian (Platyhelminthe): evidence for a trans-phyla horizontal transfer.

Several DNA sequences similar to the mariner element were isolated and characterized in the platyhelminthe Dugesia (Girardia) tigrina. They were 1,288 bp long, flanked by two 32 bp-inverted repeats, and contained a single 339 amino acid open-reading frame (ORF) encoding the transposase. The number of copies of this element is approximately 8,000 per haploid genome, constituting a member of the middle-repetitive DNA of Dugesia tigrina. Sequence analysis of several elements showed a high percentage of conservation between the different copies. Most of them presented an intact ORF and the standard signals of actively expressed genes, which suggests that some of them are or have recently been functional transposons. The high degree of similarity shared with other mariner elements from some arthropods, together with the fact that this element is undetectable in other planarian species, strongly suggests a case of horizontal transfer between these two distant phyla.

Amino Acid Sequence↗

Sonographic assessment of the distal end of the thoracic duct in healthy volunteers and in patients with portal hypertension.

OBJECTIVE: Our study assessed the feasibility of detecting and measuring by sonography the diameter of the thoracic duct in healthy subjects and in patients with cirrhosis and portal hypertension. We also evaluated the relationship of thoracic duct size with age and with clinical, endoscopic, and sonographic signs of portal hypertension. SUBJECTS AND METHODS: The left supraclavicular area of 24 patients with cirrhosis and 23 healthy subjects was examined with high-frequency probes using transverse and oblique scans to visualize the distal end of the thoracic duct. All patients with cirrhosis, diagnosed by liver biopsy or clinical and biochemical data, had endoscopic or sonographic signs of portal hypertension. The severity of the liver disease was determined by Child-Pugh's criteria; the diameter of portal vessels and the size of esophageal varices were also considered. RESULTS: The thoracic duct was visualized in 19 of 24 patients with cirrhosis and in 18 of 23 control subjects (percent of visualization was 79% and 78%, respectively). The diameter of the duct was larger in patients with cirrhosis than in healthy subjects (3.1 +/- 1.2 mm versus 1.9 +/- 0.5 mm; p < .0001), but no relationship was found among clinical, endoscopic, and sonographic signs of portal hypertension. A direct relationship between age and the size of the thoracic duct was found only among healthy subjects. CONCLUSION: This is the first report of the sonographic visualization of the distal end of the thoracic duct. Its diameter is small in healthy young subjects, whereas in patients with cirrhosis its increased diameter seems to be associated only with the presence of portal hypertension and not with its severity.

Humans↗