On-site screening and GC-MS analysis of cocaine and heroin metabolites in body-packers urine.

The illicit transportation of cocaine and heroin either swallowed or inserted into the rectum and/or vagina of individuals, defined as "body-packers", is becoming increasingly common. Assessment of smuggling by urinalysis from body-packers has been sparsely reported and on-site rapid screening methods are essentially lacking. We screened the presence of cocaine and heroin metabolites in urine from suspected body-packers by an on-site immunochromatographic test and confirmed the obtained results by gas chromatography-mass spectrometry and X-ray examination. Samples were collected from 64 individuals (45 men, 19 women) stopped at Fiumicino and Ciampino airports of Rome (Italy) for suspicion of internal concealment of cocaine and heroin between October 2006 and July 2007. Urine was immediately screened on-site by Cozart rapid urine test. Irrespective of test results, individuals underwent X-ray examination and urine samples were analyzed by gas chromatography-mass spectrometry (GC-MS). In 48 out of 64 cases (24 positives and 24 negatives) screening results were confirmed by GC-MS assay and X-ray examination. In 5 cases, positive to the on-site test and GC-MS analysis, abdominal radiography was negative and individuals resulted to be drug users. In 11 cases, negative to the on-site test and radiological investigation, GC-MS analysis found benzoylecgonine in 10 cases and morphine in one case. Concentration of both substances was in all cases lower than 50ng/ml and compatible with personal drug use. From obtained results, on-site detection of cocaine and heroin metabolites in the urine of suspected body-packers appears to be a reliable screening test to disclose internally concealed drugs and justify subsequent radiological investigations.

Epirubicin and etoposide combination chemotherapy to treat hepatocellular carcinoma patients: a phase II study.

Approximately half the patients affected with hepatocellular carcinoma (HCC) present with unresectable disease, so that efficacious systemic chemotherapy protocols are badly needed. We report the results of a phase-II study aimed at testing the efficacy and toxicity of a combination of epirubicin and VP-16. Thirty six patients (80 men and 6 women) received epirubicin (40 mg/m2, on day 1) and VP-16 (120 mg/m2, on days 1, 3 and 5) every 28th day. Chemotherapy was stopped in case of disease progression, while the patients who achieved an objective response or who had stable disease continued treatment for a maximum of 10 cycles. One patient (3%) achieved a complete response, while 13 patients (36%) achieved partial response, i.e. 14 objective responses in all (39%, 95% CI: 23-55%). 11 patients (31%) exhibited stable disease, while in the other 11 patients (31%) the disease progressed. Median overall survival time was 10 months and 13.5 months in the subgroup of patients responding to treatment. Significant, especially haematological, toxicity was documented, but in no case was it so severe as to require discontinuation of treatment or reduction of the dosage. In conclusion, this combination appears to be an active and tolerable therapeutic option for HCC patients who are not candidates for surgical or locoregional procedures, and in our opinion it deserves further exploration within a randomised controlled trial versus best supportive therapy.

Scrotal angiokeratoma (Fordyce): histopathological and ultrastructural findings.

Bioptic findings related to four cases of scrotal angiokeratoma-Fordyce, were studied under light and electron microscopy. A particular heterogeneity of the structural and ultrastructural patterns typical of this lesion was thus observed. Light microscopy study pointed out, in particular, different degrees of dilation of papillary vessels, whereas ultrastructural study highlighted marked alterations of endothelial cells with structural and quantitative modifications of cytoplasmic organelles.

A search for double minute chromosomes in cultured lymphocytes from different types of tumors.

Double minutes are considered the products of DNA amplification and are rare in normal human cells. They have been observed in cultured lymphocytes in selected samples of human populations as one of the characteristics of the so-called rogue cells. We scored 9500 metaphases of cultured lymphocytes from 65 subjects with a variety of heredity and sporadic tumors and from 30 healthy subjects. The 15 cells with double minutes were found in subjects with multiple endocrine neoplasia type 1 (14 cases) and with familial adenomatous polyposis (1 case). Only one rogue cell was found among the 15 cells with double minutes.

5-methyltetrahydrofolate or 5-formyltetrahydrofolic acid to modulate 5-fluorouracil's cytotoxic activity in vivo. A phase II study in patients with advanced colon cancer.

The purpose of this study was to test the hypothesis that 5-methyltetrahydrofolate (Me-THF), a source of reduced folates alternative to leucovorin, could effectively modulate 5-fluorouracil's (5-FU) cytotoxic activity in patients with advanced colon cancer. A total of 23 patients were enrolled in a phase 11 trial; they received 5-FU as a 30-min infusion at a dose of 370 mg/m2 following a rapid i.v. push of 200 mg/m2 Me-THF, both drugs being given for 5 consecutive days. Cycles were repeated every 4 weeks until disease progression. No patient achieved a complete response. In all, 4 patients showed a partial response (17.4%), 7 developed stable disease (30.4%), and the remaining 12 (52.2%) progressed. Toxicity was acceptable and never exceeded WHO grade III intensity. According to our experience, the MeTHF/5-FU combination does not appear to be an effective treatment for advanced colon cancer. Despite its low toxic profile, in our opinion its wider use should be discouraged.

Pharmacological effect of hyaluronic acid (HA) on phagocytes: hypothesis for an HA-induced monocyte chemotactic factor for neutrophils.

The connection between hyaluronic acid and phagocyte function is not well documented in the literature. Its action may either inhibit or enhance polymorphonuclear neutrophil (PMN) function, depending on its concentration. Studies were conducted to verify the effect of hyaluronic acid on phagocytes, both directly using hyaluronic acid and indirectly via a mediated route using the medium from a hyaluronic acid monocyte incubation. Determinations were made of phagocytosis, reduction of nitroblue tetrazolium, superoxide production, and chemotaxis before and after incubation with hyaluronic acid. Chemotaxis of PMNs was used to evaluate the chemotactic action of a medium in which monocytes had been incubated with hyaluronic acid. This method resulted in progressive improvement in the chemotactic index. The authors conclude that the monocytes incubated with hyaluronic acid produce a chemotactic factor for neutrophils.

5-Fluorouracil combined with the pure L-stereoisomer of leukovorin calcium to treat advanced colon-cancer patients - a phase-ii study.

A theoretical superiority of 5-fluorouracil (FUra) activity when combined with l-leucovorin (LV) might be postulated on the basis of a possible interference of the inactive d-stereoisomer of LV with the active l-form. We treated 47 patients by means of FUra (370 mg/m2/day) and l-LV (100 mg/m2/day), for 5 consecutive days, every 4 weeks. An objective response was observed in 12 patients (25.5%, 95% confidence interval: 12.5-38.5%), with 2 complete responses. As regards toxicity, 53.1% of the patients experienced mucositis, 51% diarrhea, 31.9% nausea and vomiting, 12.7% leukocytopenia, 8.5% cutaneous toxicity, 4.25% neurotoxicity, conjunctivitis and phlebitis. This regimen appears to be substantially superimposible to the classic FUra/d,l-LV combination. Therefore, the use of l-LV, in those countries where this compound is commercially available, should not be discouraged.

Intrahepatic fluorodeoxyuridine to treat unresectable hepatocellular carcinoma patients.

Of 16 HCC patients who received intrahepatic FdUrd at a dose of 0.3 mg/kg/day for 14 consecutive days by continuous infusion, every 28 days, no one achieved a complete response, while 3 patients achieved partial response (18.75%), lasting 6, 9 and 18 months, respectively. Seven patients (43.75%) exhibited stable disease and their mean time to progression was 4.28 months; in the extant 6 patients (37.5%) the disease progressed. Major biliary toxicity was observed. On the basis of these data, intra-arterial chemotherapy should not yet be considered the standard treatment of unresectable HCCs.

Inadequacy of combined 5-Fluorouracil, very-high-dose leucovorin, mitomycin-C and Cisplatin as 2nd-line therapy for advanced colon-cancer.

Fourteen patients with metastatic colon cancer which had progressed under fluoro-folates chemotherapy were treated with MM-C (10 mg/m(2) on day 1), 5-FU (370 mg/m(2) for 5 consecutive days), l-LV (500 mg/m(2) for 5 consecutive days) and CDDP (70 mg/m(2) on day 4), every 29th day till further disease progression. Neither CR nor PR were observed; 3 patients only had stable disease, while the extant 11 patients progressed. Resulting toxicity was severe. Since no antitumor effects were evidenced in the first 14 patients, the study was discontinued according to commonly accepted criteria.

Endodermal sinus tumor of the ovary in pregnancy.

The ultrasonographic evidence of an irregular mixed mass, cystic and solid, in retrouterine area and the high levels of alpha(1)-FP values in a young pregnant woman, indicated the possibility of an ovarian germ cell neoplasia. Respecting the patient's will, pregnancy was protracted until the 36th week. A cesarian section allowed the releasing of a vital fetus and the removal of a neoplastic mass which proved to be an endodermal sinus tumor (EST) at stage Ia. Then the patient, the 12th case of EST in pregnancy reported in the literature, underwent 5 PVB chemotherapy cycles and, 3 years after the intervention, appears disease-free.

Allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis.

This study was aimed at assessing the efficacy of allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis. A randomized double-blind, placebo-controlled trial was thus designed to test its efficacy to treat oral mucositis in advanced cancer patients receiving 5-fluorouracil-containing chemotherapy. There were 44 patients randomized to receive allopurinol mouthwashes, or placebo, as soon as mucosal lesions were observed during any treatment cycle. Stomatitis was evaluated at the end of each 5-day treatment cycle. Allopurinol mouthwashes resolved stomatitis in 9 of 22 treated patients (40.9%), and diminished its intensity in 10 more patients (45.4%); stomatitis resolved completely in none of the 22 patients, and partially in 3 patients in the placebo group (p < .001 by chi 2 test). Duration of symptoms was also significantly different between the two groups (median: 4 days for the allopurinol group, 7.5 days for the control group; p < .0005 by Student's t-test). In conclusion, our results suggest that allopurinol mouthwashes can be effective to treat 5-fluorouracil-induced stomatitis.

Endothelin-1 and 5-fluorouracil-induced cardiotoxicity.

Cardiotoxicity is an uncommon side-effect of 5-FU-based chemotherapy. Coronary artery vasospasms have been postulated to be involved in the pathogenesis of this rare but serious problem. We found high plasma levels of ET-1, a potent natural vasoconstrictor, in two patients who experienced two of the commonest clinical manifestations of 5-FU-induced cardiac toxicity--i.e., angina pectoris and chronic heart failure. We, therefore, propose ET-1 as the ultimate mediator of this toxicity, even though the mechanism of ET-1 increase in peripheral venous blood is still unknown. Finally, another important question still remains unresolved: is the release of ET-1 from normal coronary endothelial cells the prime cause or simply the consequence of 5-FU-related cardiotoxicity?

Folinic acid does improve 5-fluorouracil activity in vivo. Results of a phase III study comparing 5-fluorouracil to 5-fluorouracil and folinic acid in advanced colon cancer patients.

We report the results of a phase III trial in which we compared 5-fluorouracil (5-FU) to 5-FU and folinic acid (FA) in 150 previously untreated metastatic colon cancer patients. Patients were randomized in the ratio of 1:2 to receive 5-FU (370 mg/m2, i.v., for 5 days) in arm A or equidose 5-FU plus FA (200 mg/m2, i.v., for 5 days) for arm B, each cycle being repeated every 4 weeks. Five of 49 evaluable arm A patients (10.2%) and 31 of 97 arm B (31.9%) achieved a complete or partial response (p < or = 0.01). Median survival time of arm A patients was 6 months (mean: 6.18), while it was 8 months (mean: 9.01) for arm B cases (p < or = 0.05). In conclusion, our data indicate that FA can enhance 5-FU activity and that this combination is an effective palliative treatment for metastatic colon cancer patients.

Catheter seeding of hepatocellular carcinoma following placement of a total implantable access port system.

A 61-year-old cirrhotic patient underwent hepatic resection for hepatocellular carcinoma and placement of a total implantable access port system in the hepatic artery for chemotherapy infusion. A year later, he developed a parietal metastasis at the port site as a consequence of tumor seeding along the arterial catheter. The metastasis was excised but the patient died because of disseminated disease two years after the first operation. Tumor seeding along the catheter should be included in the group of potential complications after placement of total implantable access port systems for intrahepatic chemotherapy The possible causes of this rare but life-threatening complication are discussed.

Myeloprotective effect of early primary granulocyte-colony stimulating factor during six courses of intensified 5-fluorouracil, epirubicin and cyclophosphamide (120FEC) chemotherapy for advanced breast cancer. Cooperative Group of Study and Treatment of Breast Cancer.

AIMS AND BACKGROUND: The neutropenia induced by six courses of an intensified FEC regimen is expected to be checked by early primary administration of G-CSF which is stopped eight days before the next chemotherapy course. Less information is available about megakaryocytic and erythroid toxicity over six courses. METHODS AND STUDY DESIGN: Sixty-six consecutive patients with metastatic breast cancer completed six courses of a randomized treatment with two FEC regimens administered every 21 days, in which 600 mg/m2 of cyclophosphamide and 5-FUwas associated with 60 or 120 mg/m2 of epirubicin (60FEC, 35 patients, vs 120FEC, 31 patients). 120FEC was supported by early primary G-CSF (days 4 to 13). Blood counts were obtained seven times during each course. RESULTS: The non-hematologic toxicity over 364 courses was similar in 60FEC and 120FEC. No cumulative hematologic toxicity was observed for white blood cells (WBC) and platelets (PLT), while for hemoglobin (Hb) a somewhat higher cumulative toxicity was observed with 120FEC than with 60FEC. WBC, PLT and Hb grade III-IV toxicity occurred in 40.1% and 45.6% (P=ns), in 23.1% and 0.8% (P <.0001) and in 15.6% and 3.0% (P <.005) of the two regimens, respectively. There were no febrile or hemorrhagic episodes. The epirubicin relative dose intensity delivered was 1.95 in 120FEC with respect to 60FEC. CONCLUSIONS: Our G-CSF schedule permitted to deliver six courses of 120FEC without any clinically relevant side effects. Grade III-IV leukopenia was similar with 120FEC and 60FEC, while grade III-IV thrombocytopenia and anemia occurred more often with 120FEC than with 60FEC.

Atrial septal aneurysm in a patient with pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a rare heritable disorder of the connective tissue characterized by marked clinical heterogeneity. Common cardiovascular complications of PXE include renovascular hypertension, premature coronary artery disease and calcification of peripheral arteries frequently leading to claudicatio intermittens; fibrous thickening of the endocardium and atrioventricular valves, leading to restrictive cardiomyopathy and/or mitral valve prolapse have been also described. We herein report on a PXE patient who developed an atrial septal aneurysm as a previously undescribed cardiologic manifestation of her disease.

[The infusion of high-dose immunoglobulins in a case of idiopathic thrombocytopenic purpura]. / Infusione di immunoglobuline ad alte dosi in un caso di porpora trombocitopenica idiopatica.

Idiopathic thrombocytopenic purpura (ITP) is a disease characterized by the presence of circulating antiplatelet antibodies, which can cause platelet destruction, through the mediation of the reticuloendothelial system (RES). We report on a patient affected with ITP insensible to first line steroid therapy, who achieved a complete response following the administration of high-dose immunoglobulins (HDIgG, 400 mg/kg/die for 5 days), in association with decreasing doses of steroids. At the end of the treatment with immunoglobulins, the patient presented a normal platelet count and, up to date, 5 moths from the end of therapy, he is in good shape and presents normal platelets values.

[Hypokalemic rhabdomyolysis and thiazide diuretics. 3 clinical cases]. / Rabdomiolisi ipopotassiemica e diuretici tiazidici. Tre casi clinici.

Rhabdomyolysis is an acute skeletal muscle disorder characterized by altered integrity of the cell membranes of muscle fiber cells and can be caused by a variety of factors whose nature is not necessarily traumatic. Hypokalemia is one of the most common metabolic causes, accounting for about 14-28% of rhabdomyolytic syndromes. We report and discuss three cases of hypokalemia caused by diuretic treatment with hydrochlorothiazide: the main clinical features were muscle symptoms following massive rhabdomyolysis.

Anti-HCV antibodies and hepatocellular carcinoma. Relationship in a medium-risk population.

By means of an accurate immunoenzymatic assay, the prevalence was studied of antibodies to hepatitis C virus (HCV) in three different populations: 74 patients affected with hepatocellular carcinoma (HCC) on preexisting cirrhosis, 82 patients with liver cirrhosis but with no apparent neoplasm, and 70 control subjects, hospitalized for various conditions, of internal medicine or geriatric interest. 70.2% of HCC patients exhibited anti-HBC antibodies, versus 47.5% of cirrhotic subjects with no tumor and 7.1% of controls. Such results suggest the possible role of HCV in the etiopathogenesis of HCC, and its possible synergy with other agents-e.g., hepatitis B virus, alcohol--in causing chronically injured hepatocytes to become neoplastic.

4-mer hyaluronan oligosaccharides stimulate inflammation response in synovial fibroblasts in part via TAK-1 and in part via p38-MAPK.

4-mer hyaluronan (HA) oligosaccharides stimulate pro-inflammatory effects in different cell types by interacting with both the toll-like receptor-4 (TLR-4) and -2 (TLR-2). This interaction induces the activation of the transforming growth factor activated kinase-1 (TAK-1) that activates the nuclear factor kappaB (NF-kB) either directly and/or through the activation of p38-mitogen-activated protein kinase (p38-MAPK). This in turn induces the transcription of proinflammatory mediators that prime inflammation. Our aim was to investigate the involvement of TAK-1 and p38-MAPK in 4-mer HA oligosaccharide-induced inflammatory response in mouse synovial fibroblasts obtained from normal DBA/J1 mice (NSF) and from mice subjected to collagen-induced arthritis (CIA). Treatment of NSF and rheumatoid arthritis synovial fibroblasts (RASF) with 4-mer HA showed a marked up-regulation of TLR-4, TLR-2, TAK-1 and p38-MAPK mRNA expression and of the related proteins, as well as NF-kB activation. High levels were also detected of TNF-α, IL- 1ß, MMP-13 and iNOS. Treatment of NSF and RASF, previously stimulated with 4-mer HA oligosaccharides, with TAK- 1 and/or p38-MAPK specific inhibitors significantly reduced all the parameters, although the inhibitory effect of p38- MAPK was less effective than that of TAK-1. The addition of CD44 antibody to both NSF and RASF showed that CD44 was not involved in 4-mer HA-induced inflammation.