Combined anti-bradycardia/anti-tachycardia pacemaker-cardioverter-defibrillator systems in patients with recurrent ventricular tachyarrhythmias]

In 41 patients with recurrent sustained ventricular tachycardia and/or ventricular fibrillation an integrated pacemaker-defibrillator-system (PCD, Medtronic, model 7216 A or 7217 B) was implanted. In 21 out of 24 (88%) patients a new transvenous implantation technique in combination with a subcutaneous patch electrode was used. The implanted devices comprise antibradycardiac pacemaker functions, two different forms of antitachycardiac pacemaker functions (ramp and burst pacing), and internal cardioversion or defibrillation capabilities. During a mean follow-up of 8 months 147 episodes of ventricular tachycardia were detected, 131 of them were terminated successfully by antitachycardiac pacing; in 13 episodes internal cardioversion was applied to revert ventricular tachycardia. Twenty-seven episodes of ventricular fibrillation or rapid ventricular tachycardia (greater than 200/min) were detected and successfully terminated by internal defibrillation. In six patients with intermittent rapid atrial fibrillation, change of antiarrhythmic therapy was required to avoid activation of the device. The new integrated pacemaker-defibrillator systems improve therapy in patients with life-threatening tachyarrhythmias by reducing the number of internal cardioversions/defibrillations; the non-thoracotomy approach reduces the post operative risk.     

A chimeric EGFR/neu receptor in functional analysis of the neu oncoprotein.

As the factor binding to the neu protein has been unknown, it has not been possible to confirm experimentally the proposed growth-factor receptor like functions of the neu protein. To approach this problem we constructed a recombinant receptor which enabled ligand regulation of the neu tyrosine kinase. The hybrid receptor consisted of the extracellular ligand binding, transmembrane and protein kinase C-substrate domains joined to the intracellular tyrosine kinase and carboxyl-terminal domains of the neu protein. Several properties of NIH3T3 cells carrying this construct were tested. We obtained the first experimental evidence that the neu proto-oncogene has mitogenic and transforming activities only in the presence of a ligand stimulating its tyrosine kinase activity. Various cellular and molecular biological parameters indicated that the chimeric receptor behaved very similarly to the EGFR. Also, this chimeric receptor has allowed us to compare the constitutive oncogenic and the ligand-activated non-oncogenic activities of the neu tyrosine kinase. In the future we plan to focus on characterization of possible differences between EGFR and neu signalling in more differentiated cellular backgrounds.     

The relation of the accumulation of cadmium in human placenta to the intake of high-fibre grains and maternal iron status.

Exposure to cadmium via the diet is known to depend to a large extent on the intake of cereal grains, particularly the high-fibre fractions of wheat. Subjects with low iron status absorb more cadmium than those with better iron status. The purpose of the present study was to determine to what extent cadmium accumulation in human placenta is affected by the intake of grain fibre and maternal iron status during pregnancy. Thirty-nine pregnant women participated in the study. In each trimester the women were requested to complete a dietary history and to allow blood samples to be taken for haemoglobin, serum ferritin and serum thiocyanate determinations, the latter as a marker for smoking. At delivery the whole placenta was taken for the determination of the cadmium concentration. The 32 women who had serum thiocyanate levels less than 70 mumol/l, who had completed at least one dietary history and from whom a blood sample was obtained in the third trimester, were included in the final statistical analyses. In the group of women who consumed less than the median intake of grain fibre and had more than 15 micrograms ferritin/l serum in the third trimester, the placenta cadmium concentration was nearly half that in the placentae of women who had consumed more grain fibre or had lower iron status in late pregnancy.     

Formation of mitochondrial phospholipid adducts by nephrotoxic cysteine conjugate metabolites.

Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur-containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S-treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine.     

How to assess fetal metabolic acidosis from cord samples.

The degree of metabolic acidosis at birth has been calculated in cord artery and vein samples from 21 term fetuses with cord artery pH less than 7.20. The aim of the study was to compare base deficit values calculated from either Siggaard-Andersen alignment nomogram (BD blood) or the Acid-Base chart (BD extra cellular fluid, BDecf). BDblood was found to be consistently higher in the cord artery as compared with BDecf, 13.2 +/- 3.5 and 9.9 +/- 2.9 mmol/l (Mean +/- SD), respectively. A significant correlation was found between cord artery PCO2 and BDblood whereas BDecf appeared unaffected by PCO2. In cases with cord entanglement BDecf a-v differences were increased to 3.4 +/- 2.3 mmol/l as compared with the small a-v difference noted in acidotic cases without cord entanglement, 1.1 +/- 1.25 mmol/l. It is speculated that with acutely emerging, intermittent asphyxia due to cord compression, a cord artery and vein difference in metabolic acidosis may exist and where the vein captures the basal level and the artery the acute changes. It is concluded that BDecf in both cord artery and vein add valuable information on the mechanisms behind metabolic acidosis.     

Microtuboplasty as an outpatient procedure

Fifteen cases of microtuboplasty were done as outpatient procedures at low cost and with increased patient convenience. Advances in outpatient surgery at free-standing surgery centers have allowed many new patient care innovations, and microsurgery should now be considered an outpatient procedure for gynecologic patients. Outpatient microtuboplastic surgery is not only feasible but perhaps preferable to that done as an inpatient procedure.