The induction of yeast diploid meiotic products by treatment with bleomycin and mitomycin C is reduced when sporulating cells are treated in combination with propranolol, and increased when they are treated in combination with caffeine. We show that bleomycin and mitomycin C act by blocking the second meiotic division. The frequency of this event appears to be directly related to the intracellular cAMP concentration which is known to be influenced in opposite ways by caffeine and propranolol.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Immunological identification of Tacaribe virus proteins.

Tacaribe virus (TV), an arenavirus, is an enveloped virus with genetic information encoded in two segments of single-stranded RNA. The completed sequence of TV led to the identification of four open reading frames (ORF). In order to establish a direct link between ORFs in the sequence of TV and proteins present in virus particles and virus-infected cells, segments of the molecularly cloned TV genome were engineered so as to be expressed in Escherichia coli to produce fusion proteins that were used to raise antisera. The antisera were in turn employed to identify the TV gene products. Serum to the putative nucleocapsid (N) protein reacted with a 68-kDa protein, both in TV particles and in the infected cells. Sera raised to the glycoprotein precursor (GPC) immunoprecipitated two proteins of 68 and 70 kDa from infected cell lysates. Analysis of GPC synthesis in the presence of tunicamycin revealed that the unglycosylated GPC appeared as two polypeptides of 43 and 46 kDa. The putative RNA polymerase gene product (L) was detected as a approximately 240-kDa protein. Serum to the small zinc-binding domain protein (p11-Z) recognized a protein of approximately 11kDa. Immunological evidence is presented that in addition to N and L, two glycoproteins (GP1 and GP2) and p11-Z are structural components of Tacaribe virions.

Animals↗

PubMedDate not supplied

Portal vein arterialization: a new surgical option against acute liver failure?

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself, avoiding transplantation, is a major goal in the treatment of ALF. We report our clinical experience of portal vein arterialization in one case of massive liver necrosis after liver transplantation and in two patients with ALF caused by idiosyncratic drug reaction and mushroom intoxication. Portal vein arterialization, at least in two cases, was a turning point in the course of the disease since a close temporal association between surgery and clinical improvement was clearly evident. We believe that this novel approach, which should promote liver regeneration by providing an additional oxygen supply to the liver, may disclose a new possibility in the treatment of ALF and prompt new clinical and experimental research.

Adult↗

PubMedDate not supplied

Mini-invasive treatment of arterial and biliary complications after orthotopic liver transplantation.

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Catheterization↗

PubMedDate not supplied

Driving p53 response to Bax activation greatly enhances sensitivity to taxol by inducing massive apoptosis.

The proapoptotic gene bax is one of the downstream effectors of p53. The p53 binding site in the bax promoter is less responsive to p53 than the one in the growth arrest mediating gene p21. We introduced the bax gene under the control of 13 copies of a strong p53 responsive element into two ovarian cancer cell lines. The clones expressing bax under the control of p53 obtained from the wild-type (wt) p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold) to the anticancer agent taxol than the parent cell line, with a higher percentage of cells undergoing apoptosis after drug treatment that was clearly p53-dependent and bax-mediated. Xenografts established in nude mice from one selected clone (A2780/C3) were more responsive to taxol than the parental line and the apoptotic response of A2780/C3 tumors was also increased after treatment. Introduction of the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity to taxol or the induction of apoptosis. In conclusion, driving the p53 response (after taxol treatment) by activating the bax gene rather than the p21 gene results in induction of massive apoptosis, in vitro and in vivo, and greatly enhances sensitivity to the drug.

Animals↗

PubMedDate not supplied

How do Italian pharmacoeconomists evaluate indirect costs?

OBJECTIVES: To investigate how indirect costs are evaluated in pharmacoeconomic studies in Italy and the attitude of Italian pharmacoeconomists toward indirect costs. METHODS: A literature review was conducted, specifically focused on pharmacoeconomic studies including indirect costs carried out in Italy, and a suevey among Italian pharmacoeconomics experts. RESULTS: Nineteen studies were available for review. Although the methods used to calculate the value of production loss due to morbidity were all based on the Human Capital Approach (HCA), there was a wide variability among studies in practical methods. The parameters used to value production losses varied widely too. Of the 25 survey responders, 20 considered it important to include indirect costs in pharmacoeconomic studies; 56% of those interviewed stated that health authorities should require indirect cost evaluations. Most of these experts would include indirect cost estimates in drug-pricing calculation. CONCLUSIONS: In Italy studies evaluating indirect costs are still only few, although there is evidence of an increase. Italian pharmacoeconomists are far from reaching any consensus on methods for evaluating these costs. Methods need to be standardized particularly with respect to the parameters used to quantify productive time lost in monetary terms.

Journal Article↗

PubMedDate not supplied

Distant metastases in ovarian carcinoma.

Distant metastases are unusual at presentation and during the course of ovarian carcinoma. The aim of the present study was to determine the incidence and prognostic factors of distant metastases consistent with stage IV disease in ovarian cancer patients. A retrospective chart review was conducted on 162 patients with epithelial ovarian carcinoma treated at our Unit between 1991 and 2000. Pertinent clinical information, pathologic data, treatment, and prognostic factors for survival following documentation of distant metastatic disease were collected. The significance of the association between metastatic status and various clinical variables was assessed using the standard chi-square test. Survival time was calculated from the time of diagnosis of ovarian cancer and from the time of diagnosis of the distant metastases. A logistic regression procedure was used to estimate the odds of metastatic status given the presence of certain clinical variables. A total of 67 metastatic sites were diagnosed in 50 patients. Thirteen patients (8%) had distant metastatic disease at the time of diagnosis, 37 patients (22%) had distant metastases at the time of recurrent of progressive disease. Site of metastases were: liver, 21; pleura, 11; lung, 8; central nervous system and skin, 7 each; extra-abdominal lymph nodes and spleen, 5 each; bone, 2; and breast, 1. Significant risk factors for the development of distant metastases were stage, grade, and lymph node involvement. Median interval time between diagnosis of ovarian cancer and documentation of metastatic disease was 44 months (range 3-105), and at the time of diagnosis of distant disease, 36 of 50 patients (72%) had other sites of disease (intra-abdominal or extra-abdominal). Median survival from diagnosis of distant disease was 12 months (range 1-58). In univariate analysis performance status (P = 0.03), the presence of other sites of disease (P = 0.04) and interval time between diagnosis of ovarian cancer and documentation of distant metases (P = 0.03) were the only factors significantly associated with survival. Long interval time remained significant for prognosis in multivariate analysis also (P = 0.04). Distant metastasis consistent with stage IV disease is a late complication that occurs in about one third of ovarian cancer patients. Prognosis after documentation of distant metastases is poor. We conclude the most important prognostic factor associated with survival is the interval time between diagnosis of ovarian cancer and documentation of distant metastases.

Carcinoma↗

PubMedDate not supplied

Randomized control trials on chemoembolization for hepatocellular carcinoma: is there room for new studies?

Hepatocellular carcinoma (HCC) generally occurs in patients with cirrhosis. Curative options, such as liver transplantation, hepatic resection, and percutaneous alcohol injection, are applicable to a minority of cases. Because systemic chemotherapy and radiation therapy provide dismal results, transarterial chemoembolization (TACE) remains the sole approach to antagonizing the cancer growth in most patients. Although most tumors show an extensive necrosis after TACE, the beneficial effect on survival has not been properly substantiated, so that its application still remains a matter of debate. This review analyzes the results of randomized clinical trials on TACE. In most studies, TACE did not increase the survival of patients as compared with the palliative treatment. However, several methodologic and technical pitfalls may have adversely affected the results of these trials, such as inadequate patient selection and statistical power of the study design, a nonoptimal procedure, and treatment repetition not tailored to the cancer response and patient tolerance. Nonetheless, the literature will hardly be enriched by new trials including untreated patients because, wrong or right, TACE is currently considered the standard treatment of unresectable HCC. It seems more realistic to expect randomized studies comparing different techniques and time schedules of treatment, as well as TACE alone versus combined procedures.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Clinical features of hepatic metastasis in patients with ovarian cancer.

The purpose of this study was to investigate the clinical features of hepatic metastasis in patients with epithelial ovarian cancer. From 1998 to 2002, all women with hepatic metastasis from ovarian cancer were identified at the University of Bari. Twenty-nine patients identified included one having stage IIC, one stage IIIA, two stage IIIB, 17 stage IIIC, and eight stage IVB. Eight women had hepatic metastasis at the time of the diagnosis of ovarian cancer (group I), 10 patients had hepatic metastasis as first recurrence (group II), and 11 (group III) as a second relapse. The median survival from the time of liver metastasis diagnosis was 19 months in group I patients, 24 months in group II patients, and 10 months in group III patients. No statistical differences in survival were seen among the three groups (P = 0.7). Cell type, performance status at the time of the primary tumor diagnosis, number of hepatic lesions, the presence of other sites of disease at the time of hepatic metastasis, and platinum-based chemotherapy were significantly related to survival. Better performance status, serous cell-type tumor, single hepatic lesion, the absence of other sites of disease, and platinum-based chemotherapy are good prognostic factors.

Adenocarcinoma↗

PubMedDate not supplied

Body image disturbance, parental bonding and alexithymia in patients with eating disorders.

BACKGROUND: To evaluate if body image disturbance and alexithymia, two major clinical features of eating disorders (ED), are predicted by an altered parental bonding. SAMPLING AND METHODS: 64 female ED outpatients and 68 female healthy controls were assessed by means of the Parental Bonding Instrument (PBI), the Body Uneasiness Test (BUT), and the Toronto Alexithymia Scale (TAS-20). Pearson's correlations and multiple stepwise regression analysis were applied to explore the contribution of PBI factors on BUT and TAS scores. RESULTS: BUT weight phobia, body image concerns, avoidance, depersonalization, Global Severity Index and positive symptom total were predicted by low parental care, while compulsive self-monitoring was predicted by parental overprotection. TAS total score and difficulty in describing feelings were predicted by low maternal care. CONCLUSIONS: Body image disturbance in ED may be conceptualized as a deficit in self-development, resulting from failures in parent-child interactions which impaired the ability to distinguish bodily needs from emotional experiences.

Adult↗

PubMedDate not supplied

[Determination of benzo(a)pyrene in mineral tars for pharmaceutical use (author's transl)].

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Benzopyrenes↗

PubMedDate not supplied

Gastric cancer with bone marrow invasion at presentation: case-report and review of the literature.

A case of extensive bone marrow infiltration due to gastric cancer is reported. A 65-year old man with an acute episode of anemia (Hb 4.1 mg/dl) and dyspnea was admitted to the Medical Department of a general hospital. Bone marrow biopsy showed extensive paratrabecular infiltration of a poorly differentiated adenocarcinoma of gastric origin. The primary tumor in the stomach was confirmed, and the patient was referred to our Institute and treated with combination chemotherapy (FAMTX) for 6 cycles. Due to the disappearance of bone marrow infiltration, the patient was considered for curative resection of the primary gastric cancer. After 27 months the patient is alive and in clinical complete remission.

Adenocarcinoma↗