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Four hours after having taken 10 ecstasy tablets a Grand Mal seizure occurred in a 19-year-old woman followed by coma, hyperthermia, tachycardia, tachypnea, and renal failure. After awakening she was oriented but presented with helplessness, disconcertion, hallucinations, panic attacks, and amnesic syndrome. Computed tomography and magnetic resonance imaging scans of the brain were normal. [99Tc]-hexamethylpropyleneamine oxime (HMPAO)-single photon emission computed tomography (SPECT), 20 days after intoxication, showed reduced, inhomogeneous, supratentorial tracer uptake bilaterally. Electroencephalography (EEG) disclosed diffuse slowing and occasionally generalized sharp waves. Valproic acid was begun. Except for slight amnesia, neuropsychological deficits had disappeared and [99Tc]-HMPAO-SPECT normalized, 29 days later. Decreased cortical blood flow was explained by vasoconstriction following ecstasy-induced depletion of serotonin.

Objective: To evaluate the claim that the tobacco industry does not market its products to youth., Design: The data for this study come from tobacco industry documents collected from the tobacco industry's document websites, presently linked at http://www.tobaccoarchives.com. The websites were searched using "request for production" (RFP) codes, specified keyword searches, and serendipitous terms identified in document citations found with RFP and keyword searches., Results: Industry documents show that the cigarette manufacturers carefully monitored the smoking habits of teenagers over the past several decades. Candid quotes from industry executives refer to youth as a source of sales and as fundamental to the survival of the tobacco industry. The documents reveal that the features of cigarette brands (that is, use of filters, low tar, bland taste, etc), packaging (that is, size, colour and design), and advertising (that is, media placements and themes and imagery) were developed specifically to appeal to new smokers (that is, teenagers). Evidence also indicates that relevant youth oriented marketing documents may have been destroyed and that the language used in some of the more recent documents may have been sanitised to cover up efforts to market to youth., Conclusions: The tobacco industry's internal documents reveal an undeniable interest in marketing cigarettes to underage smokers. The industry's marketing approaches run counter to and predicate methods for tobacco prevention: (1) keep the price of the product high; (2) keep product placements and advertising away from schools and other areas with a high volume of youth traffic; (3) make cigarette advertising (that is, themes and visual images) unappealing to youth; (4) make product packaging unappealing to youth; and (5) design the product so it is not easy to inhale.

Background: Unresectable adenocarcinomas of the biliary tree have a very poor prognosis. No good chemotherapeutic regimen is available. Irinotecan has not yet been fully tested in this disease. We evaluated its activity in unresectable bile duct cancers., Patients and Methods: Twenty-five consecutive eligible patients at our two institutions were treated with irinotecan at a starting dose of 125 mg/m2. A cycle consisted of once-a-week treatments for four consecutive weeks, followed by two weeks of rest. All patients were required to have histologically confirmed diagnosis, clinically documented metastatic or unresectable carcinoma and measurable disease. Patients were evaluated for response, toxicity, and survival., Results: A total of 83 cycles of therapy were delivered. Two patients had a partial response (8%; 95% confidence interval (CI): 0%-18%) and ten additional patients had stable disease for at least two months (40%; 95% CI: 20.8%-59.2%). The therapy was well tolerated, with moderate myelosuppression and diarrhea as the main toxicities. The overall median survival was 10 months., Conclusions: Irinotecan has minimal activity in biliary tree carcinomas, but is well tolerated with appropriate supportive care, and produces occasional objective responses.

Alveolar macrophages (Amφ) represent an immunologically distinct sub-population within the reticuloendothelial system. Phagocytosis and possibly antigen presentation by Amφ are essential components of specific and innate primary immune defence processes against inhaled material. The mφ-restricted sheep erythrocyte receptor sialoadhesin (Sn) is a member of the immunglobulin superfamily and binds specifically to sialic acid-containing structures such as selectins and was originally identified as the sheep erythrocyte receptor (SER) responsible for sialic acid-dependent binding of native sheep erythrocytes (SE) to resident murine bone marrow macrophages in rosetting assays. Sn expression has been demonstrated on murine and rat mφ in lymphatic organs and is recognised by the monoclonal antibody (mAb) ED3 in the rat. In addition, sialic acid-dependent receptor (SAR) activities that mediate rosette formation of alveolar, peritoneal, splenic and bone marrow-resident rat mφ with SE pretreated with gangliosides and SER-like activities between native SE and trypsinised Amφ, have been described. The binding activities of both SAR and Sn show similar characteristics suggesting that these molecules are closely structurally related or identical. To clarify the relationship between Sn, SAR and SER-like activities, the binding of mAb ED3 to isolated rat Amφ was investigated by flow cytometry and rosetting assays. It is demonstrated that rat Amφ express Sn and evidence is provided that SAR and SER-like activities are mediated by Sn.

Purpose: In vitro synergy between cisplatin and irinotecan (CPT-11) has been reported. We designed a combination schedule of these agents to maximize the potential for synergistic interaction., Patients and Methods: To maximize the opportunity for synergy, we divided the cisplatin into four consecutive weekly treatments, followed by a 2-week rest. Each dose of cisplatin was immediately followed by a dose of irinotecan. The dose of cisplatin was fixed at 30 mg/m2/wk. The initial irinotecan dose was 50 mg/m2/wk and this was escalated by 30% increments in successive cohorts of three to six patients to establish the maximum-tolerated dose (MTD). Pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were analyzed., Results: Of 35 patients with solid tumors enrolled onto this trial, 30 were assessable for toxicity and response. The MTD for this regimen was 30 mg/m2/wk of cisplatin plus 50 mg/m2/wk of irinotecan in previously treated patients and 30 mg/m2/wk of cisplatin plus 65 mg/m2/wk of irinotecan in chemotherapy-naive patients. Neutropenia was the dose-limiting toxicity (DLT) encountered in this trial. Diarrhea was infrequent and rarely dose-limiting. Seven of 30 assessable patients achieved a partial response. No alteration in irinotecan, SN-38, or SN-38G pharmacokinetics resulted from the administration of cisplatin with irinotecan., Conclusion: The administration of cisplatin and irinotecan on this weekly schedule provides a practical and well-tolerated regimen that has the potential to maximize any clinical synergy between the two agents. Evidence of substantial clinical activity was seen in this phase I study.

Techniques were developed for automated detection and characterization of dermatoscopic structures, including the pigment network and brown globules. These techniques incorporate algorithms for grayscale shape extraction based on differential geometry developed by Steger, a snake algorithm, and a modification of the region competition strategy of Zhu and Yuille. A novel approach was developed for global segmentation of pigmented lesions, based on stabilized inverse diffusion equations. Procedures for detection of air bubbles and hairs in dermatoscopic images are also reported.

Purpose: To determine the maximum-tolerable dose (MTD) of fluorouracil (5FU) when given with fixed doses of leucovorin and irinotecan (CPT-11), to define the dose-limiting toxicities of this combination, and to evaluate the effect of 5FU on the pharmacokinetics of CPT-11., Patients and Methods: CPT-11, leucovorin, and 5FU were administered in repeated 6-week cycles that consisted of weekly treatment with all three drugs for 4 consecutive weeks followed by a 2-week break. On day 1 of treatment, CPT-11 alone was given by 90-minute infusion, and pharmacokinetic sampling was performed over 24 hours. Leucovorin and 5FU were administered by brief intravenous injection on day 2. On days 8, 15, and 22, CPT-11 infusion was immediately followed by leucovorin and then 5FU. A second 24-hour pharmacokinetic sampling was performed on day 8, which permitted comparison of the pharmacokinetics of CPT-11 with and without 5FU. For the second 6-week cycle, leucovorin was administered first, followed by 5FU and then CPT-11, and a third pharmacokinetic sampling was performed., Results: Forty-two patients were entered onto this trial. The CPT-11 dose was initially fixed at 100 mg/m2. Leucovorin was fixed at 20 mg/m2. 5FU doses of 210, 265, 340, 425, and 500 mg/m2 were studied. When the 500-mg/m2 dose of 5FU was found to be tolerable, this was then maintained and CPT-11 was escalated to 125 and then 150 mg/m2. This final CPT-11 dose exceeded the MTD. Neutropenia was the major dose-limiting toxicity. Diarrhea was common, but was rarely dose-limiting. Coadministration of 5FU had no substantial effect on the pharmacokinetics of CPT-11 or SN-38. Among the 38 patients with colorectal cancer, six partial responses (PRs) were seen in this predominantly 5FU-refractory patient population., Conclusion: 5FU does not substantially affect the metabolism of CPT-11 to its active metabolite, SN-38. The combination of CPT-11125 mg/m2, 5FU 500 mg/m2, and leucovorin 20 mg/m2 is feasible and tolerable on this schedule.

Purpose: To determine the molecular form of type V procollagen in collagen fibrils in mammalian corneal stromas., Methods: The presence of the tyrosine-rich region in the NH2-propeptide of type V procollagen in collagen fibrils was examined in human, bovine, and mouse corneas and human corneal fibroblast cultures by immunofluorescence microscopy and immunoblot analysis using a polyclonal antibody specific for this region. The antibody was generated using a glutathione S-transferase-fusion peptide., Results: The tyrosine-rich region was detected readily in frozen sections of 5- to 6-month-old mouse corneal stromas without the need for any unmasking techniques, indicating that this domain is exposed on the surface of striated collagen fibrils. In contrast, frozen sections of adult human and bovine corneas did not label with the polyclonal sera to the tyrosine-rich region. Immunoblot analysis of bacterial collagenase digests of human and bovine corneas, however, indicated that peptide fragments containing the tyrosine-rich region of type V procollagen and of the expected molecular weight of 70 to 85 kDa were present. Further immunofluorescence microscopic studies and immunoblot analysis of mouse corneas at different ages and of collagen fibrils formed in human corneal fibroblast cultures over time indicated that, initially, the tyrosine-rich region of type V procollagen could be detected in all these collagen fibrils; however, as the age of the mouse and the culture increased, the ability to detect this region decreased., Conclusions: These results suggest that, in vivo, the tyrosine-rich region of type V procollagen is retained on type V procollagen molecules within mammalian collagen fibrils from corneal stromas and that this region becomes masked as collagen fibrils mature or the species ages.

Previous research has shown that problems in family functioning and psychological disturbances in children are closely related. To increase understanding of this complex interaction the present review sets out to make explicit certain aspects of the relationship between child psychopathology and the quality of family life. The usefulness of the concept of resources for analysing major aspects of family functioning (contextual, intra-familial and extra-familial) is discussed within a systems framework and is then applied to a wide range of empirical studies which relate important features of family functioning to disturbed behaviour in children. It is found that interpersonal conflict in the lives of parents before marriage may severely constrain their own psychological development. When the psychological effects of such early disadvantage are amplified by marital conflict other family members are also affected. The notion of resources requires such disabilities to be assessed as well as directing attention to non-family interactions which offer compensating supports.