Safety of celecoxib in patients with adverse skin reactions to acetaminophen (paracetamol) and other non-steroidal anti-inflammatory drugs.

BACKGROUND: Acetaminophen (paracetamol-P) is a widely used analgesic-antipyretic drug with no anti inflammatory effects and its rate of adverse hypersensitivity reactions is very low. On the contrary non-steroidal anti-inflammatory drugs (NSAIDs) are commonly involved in side effects. Celecoxib (CE) is a novel drug, with high selectivity and affinity for COX-2 enzyme. OBJECTIVE: We evaluated the tolerability of CE in a group of patients with documented history of adverse cutaneous reactions to P and to classic NSAIDs. METHODS: We studied 29 patients with hypersensitivity to P and classic NSAIDs. The diagnosis of P-induced skin reactions was based on in vivo challenge. The placebo was blindly administered at the beginning of each challenge. After three days, a cumulative dosage of 200 mg of CE in refracted doses was given. After 2-3 days, a single dose of 200 mg was administered. All patients were observed for 6 hours after each challenge, and they were controlled again after 24 hours to exclude delayed reactions. The challenge was considered positive if one or more of the following appeared: erythema, rash or urticaria-angioedema. RESULTS: No reaction was observed with placebo and twenty eight patients (96.5 %) tolerated CE. Only one patient developed a moderate angioedema of the lips. CONCLUSION: Only one hypersensitivity reaction to CE was documented among 29 P-intolerant patients. Thus, we conclude that CE is a reasonably safe alternative which can be used in subjects who do not tolerate P.

Topic-vehicle interaction in metaphor comprehension.

Property comparison models of metaphor comprehension assume that the topic and vehicle terms in metaphors are both understood to be referring to their conventional literal referents. In contrast, the interactive property attribution model (Glucksberg, McGlone, & Manfredi, 1997) assumes that the vehicle is understood to be referring to a metaphoric category that includes the topic's literal referent as a member. A priming paradigm was used to test the implications of these different models. Prior to interpreting a metaphor, participants read (1) the topic or vehicle concept alone, (2) a sentence ascribing a metaphor-relevant property to one concept, or (3) a sentence ascribing a metaphor-irrelevant property to one concept. All of the prime types facilitated metaphor comprehension with the exception of sentences ascribing metaphor-irrelevant properties to vehicles. The failure of these sentences (but not their topic counterparts) to facilitate metaphor comprehension is attributable to their priming an inappropriate literal interpretation of the vehicle term. These results are consistent with the claim that irrelevant information is suppressed during language comprehension (Gernsbacher, 1990) and support the interactive property attribution model.

Anthracycline in colorectal carcinoma: an in vitro short-term assay to predict drug sensitivity. Preliminary results.

The chemosensitivity of 26 non-pretreated colorectal carcinomas (primary tumors and/or colorectal metastases) was studied by an in vitro antimetabolic assay, which evaluates the interference of drugs on the incorporation of 3H-thymidine and 3H-uridine in short-term cultures of human tumors. Our results correlate with the response rate obtained in clinical studies with monochemotherapy and justify the possibility of a future prospective study using individually tailored chemotherapy regimens. Doxorubicin-analogues, with an overall in vitro efficacy in 16.0% and 14.3% for 4-epidoxorubicin (epi-DX) and 4-deoxydoxorubicin (deo-DX), respectively, seem to deserve a modest role in the treatment of colorectal cancer, provided that a careful selection of patients is performed. Variability in anthracycline activity is indeed evident, also in our study, in relation to the different neoplastic picture of the various patients.

A proposed TNM classification for malignant primary liver tumours.

On the basis of 211 hepatic resections and reresections, a study was made to evaluate the possibility of compiling a checklist for primary liver tumours according to the TNM classification. This would aid the surgeon in planning therapy and provide a useful guide for prognosis and late results.

Gene products of the HLA-D region in normal and malignant tissues of nonlymphoid origin.

Indirect immunofluorescence staining with monoclonal antibodies has shown a differential distribution of HLA-DR, DQ, and DP antigens in normal tissues of nonlymphoid origin. The distribution of HLA-DP antigens is similar to that of HLA-DR antigens, while that of HLA-DQ antigens is more restricted. Malignant transformation of cells of nonlymphoid origin may be associated with the appearance of the gene products of the HLA-D region. HLA-DR antigens appear more frequently than the other two types of HLA class II antigens and HLA-DP antigens more frequently than HLA-DQ antigens. Differential expression of the gene products of the HLA-D region was also found in autologous metastases removed from different anatomic sites from patients with melanoma. The HLA class II phenotype of surgically removed malignant lesions did not correlate with the degree of differentiation of tumor cells and/or with the expression and/or cellular distribution of HLA class I antigens. Furthermore, in melanoma lesions, no relationship was found between the HLA class II phenotype and the expression of 3 membrane bound and 1 cytoplasmic melanoma associated antigen recognized by monoclonal antibodies. The functional significance and the practical implications of the differential expression of the gene products of the HLA-D region by tumor cells are discussed.

Our experience with resection of primary and secondary liver tumours.

The authors retrospectively analyse the results achieved in recent years by surgical treatment of 103 malignant primary or secondary liver cancers: (Three patients have been operated on twice at different times for recurrence.) 23 hepatic resections were performed for benign lesions. The operative mortality is very low, the incidence of postoperative complications is minimal, and the survival up to 8 years is rather satisfactory. In all cases we used Ton That Tung's surgical technique, that is, "finger fracture with intraparenchymal ligature of the vasculobiliary pedicles."

Distribution of human Class I (HLA-A,B,C) histocompatibility antigens in normal and malignant tissues of nonlymphoid origin.

Indirect immunofluorescence and immunoperoxidase staining of surgically removed tissues of nonlymphoid origin with monoclonal antibodies to the heavy and light chain of HLA-A,B,C antigens have shown that they have a more restricted tissue distribution than previously assumed. HLA-A,B,C antigens were not detected in brain cortex, cerebellum, sympathetic ganglia, hypophysis, parathyroid gland, thyroid, exocrine pancreas, hepatocytes, sperm, seminiferous tubules, or skeletal or smooth muscle. Malignant transformation of cells may be associated with appearance, changes in cellular distribution of HLA-A,B,C antigens, and/or dissociation in the expression of the two subunits. Analysis of primary tumors and of autologous metastases showed heterogeneity in the expression of HLA-A,B,C antigens among lesions removed from different sites. The degree of heterogeneity did not correlate with the site of origin of metastases.