Intoxication with Taxus Baccata: Cardiac Arrhythmias Following Yew Leaves Ingestion

WILLAERT, W., et al. : Intoxication with Taxus Baccata: Cardiac Arrhythmias Following Yew Leaves In-gestion. The use of yew leaves (Taxus Baccata) as a means of deliberate self-harm is infrequent. The potent effect of the toxin is primarily cardiac and results in rhythm alterations and ultimately ventricular fibrillation. As there is no known antidote, and classic antiarrhythmic therapy proves to be ineffective, a prompt diagnosis is of great importance as immediate supportive action is the only valuable alternative. This case describes a 43-year-old women who attempted suicide by ingesting the leaves of Taxus Baccata. We discuss the effects and the difficulty of treatment associated with yew leaf poisoning.     

A treatment system for combined psychiatric and addictive illness

Patients with combined general psychiatric and addictive disorders are a major public health problem in the US, and are being increasingly recognized as such world-wide. The authors describe a model treatment system for such patients in one municipal hospital in New York. It is composed of three complementary units: a locked ward, a halfway house and a day program. Treatment is based on a peer leadership approach coupled with professional treatment, and provides multiple levels of care to address the needs of respective patients. Of 464 admissions evaluated and treated, most were from disadvantaged minorities, homeless and abusers of cocaine. All were admitted with acute psychiatric or perinatal presentations, and carried Axis I diagnoses in addition to their substance abuse. Clinical experience over 6 years is reviewed, suggesting the feasibility of reorganizing general hospital psychiatric services to address the needs of the dually diagnosed.     

Testosterone in Chronic Alcoholic Men

Reduced testosterone levels in chronic alcoholic men may be associated with the age, alcohol consumption history, severity of liver injury, and nutritional status of these patients. In this study, total testosterone levels were measured in 163 alcoholic men upon admission to an alcohol treatment program (ATP) and at 3 months follow-up. Values of testosterone below the clinical normal range were found in over 17% of the subjects, a finding significantly predicted by age, alcohol consumption and liver injury tests. Follow-up at 3 months further demonstrated that abnormally low testosterone values significantly increased in men who remained abstinent as compared to those who continued to drink.     

Persistence of residual tumour cells after cytokine-mediated ex vivo expansion of mobilized CD34+ blood cells in multiple myeloma

Mobilized CD34⁺ blood cells were immunomagnetically enriched from leukapheresis products in five multiple myeloma (MM) patients. Thawed samples of selected CD34⁺ cells were cultured for up to 21 d in a liquid and stroma-free culture system with different combinations of recombinant cytokines. The most successful cell expansion was obtained when a combination of rh-IL-1β, rh-IL-3, rh-IL-6, rh-SCF, rh-G-CSF and rh-GM-CSF was used. After 14 d this mixture gave a 120–187-fold overall increase of total nuclear cells and a 4–8-fold overall increase of early CFU-GM numbers. In four patients a very sensitive patient-specific PCR analysis showed the presence of monoclonal cells in the initial leukapheresis products. After immunomagnetic separation a tumour cell depletion of 2–4 logs was observed, although all samples still contained malignant cells. Cell suspensions that were cultured with the most potent cytokine combination showed tumour contamination in two-thirds of evaluable cases at the moment of maximal CFU-GM output. Serial cDNA dilution experiments indicated that the positive PCR results at day 14 reflected the persistence of pre-culture tumour cells rather than in vitro expansion of tumour cells in two cases. This study demonstrates that ex vivo expansion of myeloid precursor cells from mobilized CD34⁺ cells in MM patients does not always result in an effective purging of residual tumour cells. On the other hand, our culture conditions do not seem to favour in vitro expansion of malignant cells, despite the use of a cytokine cocktail that includes potential myeloma growth factors.     

Chemical synthesis of phosphorylated peptides of the carboxy-terminal domain of human p53 by a segment condensation method

A segment condensation method was developed for the chemical synthesis of large (>90 amino acid) phosphopeptides and was used to produce phosphorylated and non-phosphorylated derivatives of the C-terminal tetramerization and regulatory domains of human p53 (residues 303-393). Efficient condensation synthesis of the 91 residue p53 domain was achieved in two steps. The non-phosphorylated N-terminal segment p53(303-334) (1) and its derivative phosphorylated at serine 315 (1P315), and the non-phosphorylated middle segment p53(335-360) (2), were synthesized as partially protected peptide thioesters in the solid phase using Boc chemistry. The C-terminal segment p53(361-393) (3) and its derivative phosphorylated at serine 392 (3P392) were synthesized as partially protected peptides in the solid phase using Fmoc chemistry. Phosphoamino acid was incorporated into the N-terminal segment (1P315) at the residue corresponding to p53 serine 315 as Boc-Ser(PO₃(Bzl)₂)-OH during synthesis. Serine 392 in the C-terminal segment was selectively phosphorylated after synthesis by phosphitylation followed by oxidation. A derivative phosphorylated at serine 378 was synthesized in a one-step condensation of the unphosphorylated N-terminal segment (1) and the phosphorylated long C-terminal segment p53(335-393) (2-3P378). Yields of the ligated peptides after removal of the protecting groups and HPLC purification averaged 60% for the first condensation and 35% for the second condensation. All five p53 peptides exhibited monomer-tetramer association as determined by analytical ultracentrifu-gation. Circular dichroism spectroscopy revealed that phosphorylation at Ser315 increased the α-helical content, which was abolished when Ser392 also was phosphorylated, suggesting an interaction between N-terminal and C-terminal residues of the C-terminal domain of p53. © Munksgaard 1996.     

Alternate Ventriculo-Atrial Wenckebach Conduction during Ventricular Tachycardia

Although pacing-induced ventriculo-atrial (VA) Wenckebach conduction has been previously described, the occurrence of this phenomenon during ventricular tachycardia has received little attention. The latter is defined as 2:1 VA block in which the conducted beats show progressive lengthening of VA conduction until the sequence is terminated by two or three blocked ventricular beats. This phenomenon was observed in a 16-year-old boy who underwent electrophysiologic study for ventricular tachycardia as a late complication of surgical correction of tetralogy of Fallot. During pacing-induced ventricular tachycardia with a morphology similar to that of the spontaneous tachycardia, 8:4 alternating VA block was observed. This sequence suggested that the AV node was the site of block, the 2:1 block being located at the upper level, and the VA Wenckebach block at the lower level. Alternate VA Wenckebach conduction appears as a possible cause of variation in atrial depolarization intervals during ventricular tachycardias with short cycle lengths.     

Synthesis and biological activity of 2-phenylethyl ester analogues of C-terminal heptapeptide of cholecystokinin modified in Trp 30 region

We have tried to evaluate the significance of the tryptophan side chain residue and of the surrounding peptide bonds in the antagonist activity of cholecystokinin analogues lacking the C-terminal amide function and having a d -tryptophan. In order to perform this study, analogues of the C-terminal heptapeptide of cholecystokinin were synthesized by replacing the C-terminal phenylalanine residue with 2-phenylethyl alcohol and by either replacing the tryptophan residue with an alanine, a norleucine and a phenylalanine residue, or introducing a “reduced peptide bond” in the tryptophan 30 region. Most of these compounds were able to reproduce only part of the response of cholecystokinin in stimulating amylase release from rat pancreatic acini, as was already observed for 2-phenylethyl ester analogues of CCK. These results point out the key role of tryptophan 30 in the biological response of cholecystokinin.