Heterogeneity of chemosensitivity of esophageal and gastric carcinoma

Esophageal and gastric cancer have a poor prognosis, and chemotherapy is rarely of long-term benefit. This may be related in part to heterogeneity of chemosensitivity and to constitutive resistance to individual cytotoxic drugs. This study aimed to demonstrate the degree of heterogeneity of chemosensitivity between tumors. We have examined the heterogeneity of chemosensitivity in esophageal and gastric cancer specimens (n=85) using an ex vivo ATP-based chemosensitivity assay (ATP-TCA). A variety of chemotherapeutic agents were tested. Sixty-four specimens were endoscopic biopsy samples; the remainder were from resection specimens. Cells were obtained from 62 specimens (73%). Eight assays were infected due to contamination/infection of the biopsy material, giving an evaluability rate of 87%. Analysis of the data showed considerable heterogeneity of chemosensitivity. The most active single agents identified by the assay were mitomycin C (56% sensitivity) and 5-fluorouracil (5-FU; 42% sensitivity). Exposure of tumor cells to combinations of drugs showed ECF (epirubicin, cisplatin, 5-FU) and mitomycin C+5-FU to be moderately active regimens. Other experimental drug combinations showed greater activity. There is a marked heterogeneity of chemosensitivity in esophageal and gastric cancers. The degree of heterogeneity observed suggests that the ATP-TCA could be used to individualize chemotherapy by selecting agents for particular patients. This approach provides the rationale for a trial of ATP-TCA-directed therapy to determine whether individualization of chemotherapy might improve patient response and survival.     

Psychiatric comorbidity and physicians with substance use disorders: a comparison between the 1980s and 1990s

The assessment and treatment of physicians with substance use disorders has been of considerable interest over the past twenty years. This study compares two cohorts of addicted physicians treated at a single program. Data from 101 physicians treated during 1985 to 1987 were compared with 73 physicians treated from 1995 to 1997. Although the cohorts were similar on demographic, physician specialty, and drug of choice variables, psychiatric comorbidity was significantly more prevalent in the later sample.     

In vitro release: comparative evaluation of vertical diffusion cell system and automated procedure

In vitro release for topical drug products is carried out using a vertical diffusion cell system and a synthetic support membrane. The improvements in vertical diffusion cell design and automated procedures have been carefully studied and evaluated to establish their reproducibility and ruggedness of the experimental procedure. The data were analyzed using 90% confidence interval procedure developed and published by the US Food and Drug Administration in SUPAC-SS (Start Up and Post Approval Changes-Semi Solid) guidance.     

Evaluation of tricyclic antidepressant false positivity in a pediatric case of cyproheptadine (periactin) overdose

CASE REPORT: The authors report a case of pediatric cyproheptadine toxicity, initially misdiagnosed as tricyclic toxicity based on the results of a preliminary rapid toxicological serum screen. Although such cross-reactivity has been reported, the chemical basis of this observation has not yet been evaluated. By GC/MS methods and HPLC assays adapted for the detection of tricyclic compounds, the authors confirmed that cyproheptadine was indeed responsible for this patient's toxicity. In addition, the authors identified the presence of a cyproheptadine metabolite in the patient's serum. Further testing in an immunoassay-based toxicologic screen demonstrated some cross-reactivity exhibited by the patient's serum, but not the parent compound. These findings showed that the cross-reactivity correlated with the presence of the cyproheptadine metabolite, highlighting the value of confirmatory toxicologic testing of routine rapid toxicologic screens.     

Empirical science meets moral panic: an analysis of the politics of needle exchange

The paper presents an analysis of the policy advocacy strategies used by both proponents and opponents of needle exchange programs in the US, drawing on the analytic framework developed by Stone. Based on a case study of the politics of needle exchange in Massachusetts, we argue that proponents of needle exchange have relied almost exclusively on empirical scientific arguments to build their case, while opponents have generally resorted to normative ethical arguments. Since the frames of argument are unrelated, the two sides talk past one another, bypassing progress towards resolution or consensus. By failing to address the ethical concerns raised by opponents, public health advocates of needle exchange are losing the larger public debate. The paper concludes with specific recommendations for how public health advocates should respond to the normative dimensions of this public policy issue.     

Wild and synanthropic hosts of Leishmania (Viannia) braziliensis in the endemic cutaneous leishmaniasis locality of Amaraji, Pernambuco State, Brazil

Evidence of Leishmania infection was found in small mammals captured between 1996 and 2000 in the Amaraji region, Pernambuco State, Brazil. The kDNA polymerase chain reaction (PCR), using primers specific for subgenus L. (Viannia), was positive for 43/153 water rats (Nectomys squamipes), 13/81 black rats (Rattus rattus), 15/103 grass mice (Bolomys lasiurus), 1/14 marsh mice (Holochilus scieurus), 2/50 field mice (Akodon arviculoides), 2/12 woolly opossums (Marmosa sp.), and 5/37 common opossums (Didelphis albiventris). This same kDNA PCR was positive for 12/61 dog and 8/58 horse skin samples. In paired PCR tests of 203 small mammals, 18.7% were positive with the kDNA primers and 18.2% with rDNA primers. Amastigotes were seen in 26/460 and L. (V.) braziliensis was isolated from 5 grass mice and 1 black rat. We concluded that small mammals, particularly rodents, are infected with parasites of the subgenus L. (Viannia). The isolation of L. (V.) braziliensis zymodeme IOC/Z74 from 6 rodents and the fact that all the other described L. (Viannia) species that commonly infect humans have never been found in rodents or marsupials leads us to suggest that the positive PCRs indicate infections of L. (V.) braziliensis. The isolation of zymodeme IOC/Z74 from humans reinforces our hypothesis that small, ground-loving mammals, such as rodents are the primary reservoirs of L. (V.) braziliensis.