An Acute Ocfentanil Fatality: A Case Report with Postmortem Concentrations.

A 24-year-old man known to consume illegal drugs was found dead in his apartment. A reclosable plastic zipper bag containing several hundred milligrams of a brown powder was found close to the dead body and the first assumption of the investigators was death due to heroin intoxication. Therefore, a legal autopsy was ordered. The following toxicological analysis revealed ocfentanil in urine and in the brown powder. Four different approaches for the determination of the ocfentanil concentrations in peripheral whole blood are described. Enrichment of ocfentanil from the powder was realized. With this reference, it was possible to determine the ocfentanil concentration in the seized powder to be 0.91%. Concentrations of ocfentanil were also determined in the sampled body fluids using the standard addition procedure. In peripheral blood 9.1 µg/L, in heart blood 27.9 µg/L and in urine 480 µg/L were measured. In addition, the antidepressant citalopram, the neuroleptic quetiapine and cannabinoids were found in urine and subsequently quantified in peripheral blood.

Influence of dopexamine on hemodynamics, intramucosal pH, and regulators of the macrocirculation and microcirculation in patients undergoing abdominal aortic surgery.

OBJECTIVE: To investigate whether dopexamine hydrochloride beneficially influences splanchnic perfusion and regulators of the macrocirculation and microcirculation in patients undergoing surgery of the abdominal aorta. DESIGN: Prospective, blinded, and randomized study. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty patients undergoing elective abdominal aortic surgery. INTERVENTIONS: The patients were randomized to one of two groups. In the dopexamine group (DOP, n = 10), dopexamine, 1 microg/kg/min, was started before surgery and continued for 24 hours. In the control group (COG, n = 10), patients received saline solution as placebo. Extensive hemodynamic monitoring was carried out using a pulmonary artery catheter, and intramucosal pH was measured using a gastric tonometer. From arterial blood samples, important regulators of the circulation were measured before dopexamine was administered (T0), before aortic clamping (T1), 20 minutes after aortic clamping (T2), after declamping the first leg (T3), at the end of surgery (T4), 1 hour postoperatively (T5), and 24 hours postoperatively (T6). MEASUREMENTS AND MAIN RESULTS: Heart rate increased significantly in DOP (63+/-16 to 84+/-18 beats/min). At T5, mean pulmonary artery pressure was significantly lower in DOP (15+/-6 mmHg) than in COG (22+/-6 mmHg). During aortic clamping, pulmonary capillary wedge pressure increased significantly in both groups. Cardiac index increased significantly from baseline only in the dopexamine patients. No significant differences between the groups were seen with regard to oxygenation parameters and intramucosal pH. Renin plasma levels increased significantly only in COG (46+/-32 to 99+/-55 microU/mL). Endothelin and atrial natriuretic peptide plasma levels showed no significant differences between the two groups. Atrial natriuretic peptide increased significantly only in DOP (366+/-171 pg/mL; COG, 159+/-71 pg/mL). Antidiuretic hormone, norepinephrine, and epinephrine plasma levels increased significantly from baseline in both groups, without showing significant differences between the groups. CONCLUSIONS: In patients undergoing abdominal aortic surgery, prophylactic perioperative administration of dopexamine hydrochloride produced effects on hemodynamics but without improving oxygenation and intramucosal pH. From the measured regulators of the circulation, only renin was beneficially affected.

Inhibition of cell growth in CaCO2 cells by the polyamine analogue N1,N12-bis(ethyl)spermine is preceded by a reduction in MYC oncoprotein levels.

The polyamine analogue N1,N12bis(ethyl)spermine (BESpm) is a potent inhibitor of cell proliferation and is representative of a class of agents currently in clinical trials. Previous studies have demonstrated that BESpm treatment can produce a decrease in the mRNA levels of the protooncogene c-myc resulting from decreased transcription. Investigation into the mechanism of the antiproliferative effect of BESpm in the colon cancer cell line CaCO2 indicated that significant reduction in MYC protein, but not c-myc mRNA levels, preceded cytostasis. Specificity of the downregulation of MYC expression by BESpm treatment was demonstrated by comparison to effects on the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) and the polyamine biosynthetic enzyme ornithine decarboxylase (ODC). SSAT activity rapidly increased while levels of ODC activity decreased after BESpm treatment. Measurement of intracellular polyamines demonstrated significant uptake of the analogue after 24 hours, which was concurrent with a reduction of spermine and spermidine levels. Thus, cellular uptake of BESpm mediated a reduction of polyamine levels that was associated with a decrease of MYC protein at the post-transcriptional level.

Induction of markers of normal differentiation in human colon carcinoma cells by the v-rasH oncogene.

The molecular events that regulate differentiation of human colon mucosal cells are not known. Although a number of in vitro models to study this question exist, none have identified a gene product which could function as a mediator of cell differentiation. Although the Ki-ras gene is frequently mutated in human colon cancer, the Ha-ras protooncogene is maximally expressed in the most differentiated cells of intestinal mucosa. In order to study the effects of Ha-ras gene overexpression on the differentiation phenotype in human colon cancer cells, we have expressed the v-rasH oncogene in CaCO2 cells. This maneuver resulted in a marked induction of gene expression of multiple markers characteristic of intestinal brush border differentiation. These include a > or = 30-fold induction of sucrase, a 10-fold increase in intestinal alkaline phosphatase, a 20-fold induction of transforming growth factor alpha, and a 5-fold increase in transforming growth factor beta 1 steady-state mRNA levels. Finally, the CaCO2-ras cells undergo a > or = 95% reduction in DNA synthesis under serum-deficient conditions and cannot be restimulated after such treatment, suggesting terminal differentiation, whereas the same treatment has no effect on the proliferative capacity of the parent CaCO2 cell line. These studies with CaCO2 human colon cancer cells provide a model to study the role of v-rasH and related genes in colon epithelial differentiation.

Characterization of an endogenous RNA transcript with homology to the antisense strand of the human c-myc gene.

In addition to being regulated by a complex array of cis- and trans-acting factors, c-myc protooncogene expression may be modulated by antisense RNA transcripts. Our previous studies have determined that depletion of intracellular polyamines by alpha-difluoromethylornithine results in a marked decrease in the transcription of the human c-myc gene. Because of reports that antisense transcription occurs in the 5' and 3' regions of this gene, we used a genomic clone of the human c-myc gene to ascertain whether polyamine depletion might induce an antisense RNA transcript. These studies demonstrate that polyamine depletion of the human colon cancer cell line COLO 320 results in induction of an endogenous RNA transcript with high homology to the antisense strand of the second intervening sequence (PvuII-RsaI) of the c-myc gene. Furthermore, during such depletion, steady state levels of this transcript vary inversely to the sense direction c-myc RNA. RNase protection studies suggest that the antisense transcript may arise from a different gene locus than the c-myc gene. To further identify the origins of this RNA, a cDNA library was generated from size-selected RNA and screened with c-myc sequences. A 438-base pair cDNA was isolated with approximately 85% homology, to a 285-base region in the second intron of the c-myc gene. Computer homology analysis further reveals that a 120-base region within this cDNA also has approximately 85% homology to the antisense strands of a number of genes, including the growth-related genes, N-myc, p53, and thymidine kinase. These studies provide the initial characterization of an endogenous antisense RNA transcript which could influence cell growth by modulating the expression of c-myc and other genes.

Modulation of growth gene expression by selective alteration of polyamines in human colon carcinoma cells.

The biosynthesis of the polyamines, putrescine, spermidine and spermine, is temporally linked with expression of many growth related genes. Our previous studies have shown that generalized polyamine depletion of the human colon cancer cell line COLO 320 by 2-difluoromethylornithine is associated with decreased transcription of the c-myc, c-fos, and ornithine decarboxylase (ODC) genes. In the current study, the role of individual polyamines was further defined by the use of a specific inhibitor of spermidine synthase, S-adenosyl-1,8, diamino-3-thio-octane (AdoDATO), and a spermine analogue, N1,N12 bis(ethyl)spermine. Our data demonstrate that depletion of spermidine results in a 60-90% decrease in c-myc mRNA steady state levels. In contrast, c-fos mRNA levels are decreased only when both spermidine and spermine are diminished. Furthermore, ODC mRNA levels are increased when all polyamines are decreased by DFMO, but are unaffected by a selective reduction in intracellular spermidine levels by AdoDATO. These studies suggest that individual polyamines may have a selective role in the expression of specific growth related genes.

[Significance of computerized tomography and sonography in the staging (TNM classification) of cancers of the tongue and floor of the mouth]. / Zur Bedeutung von Computertomographie und Sonographie bei der Stadienermittlung (TNM-Klassifizierung) von Zungen- und Mundbodenkarzinomen.

Computerized tomography and sonography were used for pretherapeutic staging of 40 patients with cancer of the tongue. The size of the tumors and invasion of cervical lymph nodes were assessed, and both methods were compared in relation to the stage of the tumor. Clinical findings were amended by diagnostic imaging in 25% of the cases. There was a distinct preponderance of advanced stages. Ultrasonography proved superior to CT for T1 and T2 tumors. Full assessment of T4 tumors was feasible by CT only. We were able to develop a selective protocol for the use of CT and ultrasound scan based on the TNM classification.

[Sonography of jugular vein thrombosis]. / Sonographie bei Jugularvenenthrombose.

Based on a case report, angiographic and sonographic findings of jugular venous thrombosis are discussed. On the strength of the sonographic demarcation of anatomical and functional soft tissue structures of the neck ultrasound should rank first in the diagnostic hierarchy after clinical investigation.

[Evaluation of bone lesions in malignant lymphomas]. / Zur Beurteilung von Knochenläsionen bei malignen Lymphomen.

Skeletal involvement of non-Hodgkin's lymphoma is found in 11-16%, in Hodgkin's disease in 7.6-34%. Primary lymphoma of bone has an incidence of 1-50% among all non-Hodgkin's lymphoma. The occurrence of skeletal lesions is higher in infants and children than in adults. Skeletal lesions caused by Hodgkin's and non-Hodgkin's lymphoma are mostly seen in the axial skeleton including the skull, whereas the primary lymphoma of bone seems to prefer a more peripheral site. The aggressiveness of the tumor growth can be measured by the method of Lodwick, by judging the edge characteristic, the penetration of the cortex, the periostal and sclerotic reaction. 3 examples illustrate this method. Conventional radiographs need only be performed when there is reason to believe a lesion is located in an area of structural importance, such as the neck of the femur, and in cases of skeletal pain of unknown origin.