Concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during pregnancy.

WHAT IS KNOWN AND OBJECTIVE: Depression during pregnancy is common and includes risks for mother and child. Pharmacokinetics of venlafaxine may be changed during pregnancy. This study aimed to describe changes in metabolic ratios and concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during and after pregnancy. METHODS: To study this, we used data from our study of compliance to Antidepressants During Pregnancy (the ADAP study) to investigate the course of venlafaxine and O-desmethylvenlafaxine concentrations during pregnancy and in the period post-partum. RESULTS AND DISCUSSION: We found that the venlafaxine concentration significantly changed during pregnancy when compared to the post-partum period (P = 0·028). The median concentration of venlafaxine in the first trimester was 98·9% (54·2-292·0%), the second 100·0% (46·5-264·0%) and the third trimester 87·0% (61·5-217·2%). We did not found differences in O-desmethylvenlafaxine concentrations in the different trimesters of pregnancy compared with the post-partum period, P = 0·565. Also the ratio of O-desmethylvenlafaxine/venlafaxine concentrations increased significantly from 76·9% (range 32·8-142·0%) in the first trimester to 196·7% (range 83·3-427·6%) in the third trimester compared with the post-partum period, P = 0·004. Further, three of seven patients had concentrations below the therapeutic reference range (100-400 µg/L) in any period of pregnancy, whereas no one had subtherapeutic concentrations in the post-partum period. WHAT IS NEW AND CONCLUSION: Venlafaxine concentrations decreases during pregnancy, and the ratio of the concentrations of O-desmethylvenlafaxine/venlafaxine increases during pregnancy. Pregnant women using venlafaxine are at risk for subtherapeutic concentrations, therefore routine monitoring of concentrations venlafaxine and O-desmethylvenlafaxine is recommendable during pregnancy.

Radiation-induced inhibition of tumor growth as monitored by PET using L-[1-11C]tyrosine and fluorine-18-fluorodeoxyglucose.

The potential use of PET to monitor radiotherapeutic effects on tumors has been evaluated with L-[1-11C]tyrosine and 18FDG. Single x-ray doses of 10, 30, or 50 Gy have been applied to rhabdomyosarcoma tumors growing in the flank of rats. Dose-dependent reductions of tracer uptake were registered by PET 4 and 12 days after treatment. These later effects on tracer uptake appeared to correlate with changes in tumor volume. Therefore, PET using L-[1-11C]tyrosine and 18FDG is suitable to monitor kinetics of tumor growth and tumor regression after radiotherapy. Direct effect on tracer uptake was not observed within 8 hr after irradiation. This indicates that, using PET, early predictions on the outcome of radiotherapy are not possible. When combining a radiation treatment with hyperthermia, radiation-induced inhibition of tumor growth was clearly enhanced. Tracer uptake remained at the pretreatment value, possibly due to invasion of host cells. From these experiments, it can be concluded that it is difficult to monitor a combined treatment of radiation and hyperthermia by PET.

PET measurements of hyperthermia-induced suppression of protein synthesis in tumors in relation to effects on tumor growth.

Hyperthermia-induced metabolic changes in tumor tissue have been monitored by PET. Uptake of L-[1-11C]tyrosine in rhabdomyosarcoma tissue of Wag/Rij rats was dose-dependently reduced after local hyperthermia treatment at 42, 45, or 47 degrees C. Tumor blood flow, as measured by PET with 13NH3, appeared to be unchanged. The L-[1-11C]tyrosine uptake data were compared to uptake data of L-[1-14C]tyrosine and with data on the incorporation of L-[1-14C]tyrosine into tumor proteins. After intravenous injection, the 14C data were obtained from dissected tumor tissue. Heat-induced inhibition of the incorporation of L-[1-14C]tyrosine into tumor proteins tallied with the L-[1-11C]tyrosine uptake data. Heat-induced inhibition of amino acid uptake in the tumor correlated well with regression of tumor growth. It is concluded that PET using L-[1-11C]tyrosine is eligible for monitoring the effect of hyperthermia on tumor growth.

Ectopic hematopoiesis in the human iris.

Hematopoietic islands of erythroblastic precursor cells with mitotic activity were found pathologically in the distorted iris of a 35-year-old diabetic male. The eye had been enucleated for absolute hemorrhagic glaucoma occurring secondary to central vein occlusion and complicating previous vitrectomy, repair of retinal detachment and extracapsular cataract extraction.

[Lidocaine prophylaxis in the pre-hospital phase of acute myocardial infarction (author's transl)]. / Lidocain-Prophylaxe in der Prähospitalphase des akuten Myokardinfarkts.

In a double blind study performed in cooperation with 69 emergency doctors and general practitioners in the catchment areas of the university and of the city hospital in Lübeck the action of intramuscular lidocaine on mortality and on the incidence of arrhythmias was investigated in patients with acute myocardial infarction aged less than 70 years. The mortality in the lidocaine group was significantly lower than in the placebo group. The incidence of ventricular arrhythmias up to 120 minutes after the lidocaine injection was also lower than in the placebo group. However, the only case of primary ventricular fibrillation was in the lidocaine group. As the difference in mortality between the two groups appeared at a time when an antifibrillatory action of lidocaine can no longer be assumed one must question whether the positively beneficial effect was real or whether the lower mortality was in fact due to primarily milder disease in the lidocaine group.