Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

The Safety of Atovaquone/Proguanil in Long-Term Malaria Prophylaxis of Nonimmune Adults

Background Data on the long-term safety of atovaquone/proguanil in nonimmune travelers are limited.
Methods An open-label study, involving 300 Danish soldiers stationed in Eritrea for 6 months was initiated. The subjects self-reported their symptoms on a post-travel questionnaire. The study compared the symptoms of compliers and noncompliers.
Results No serious adverse events occurred. Diarrhea, stomach pain, headache, cough, and loss of appetite were the most common symptoms reported. No case of Plasmodium falciparum malaria occurred.
Conclusions Atovaquone/proguanil was safe and well tolerated in this group of long-term nonimmune travelers.     

Lebensbedrohliche Infektionen in der Schwangerschaft

Zum Thema   Oftmals fatal verlaufende Infektionen in der Gravidit?t – vor allem postpartal – spielen immer noch trotz verbesserter Kenntnis zur Bakteriologie und Therapie, zur Infektionsprophylaxe und Hygiene eine gro?e Rolle. Als Folge der ver?nderten Immunlage in der Schwangerschaft kommt es h?ufig zu atypischen Verl?ufen, wodurch die Diagnostik erschwert wird. Auch zun?chst harmlos erscheinende Virusinfektionen k?nnen exazerbieren. Die einzelnen Krankheitsbilder (Sepsis, Amnioninfektionssyndrom, septischer Abort, Peritonitis und extragenitale Infektionen) sowie deren Diagnostik und Erreger werden besprochen. Besonders auf die antibiotische Kombinationstherapie wird eingegangen. Zusammenfassung   Schwangere mit Grundkrankheiten, Vorsch?den und Neigung zu rezidivierenden Genitalinfektionen sind in bezug auf lebensbedrohliche Infektionen vermehrt gef?hrdet. In Einzelf?llen bei hochpathogenen Erregern wie den Streptokokken der Gruppe A kann es nach Blasensprung oder operativen Eingriffen zu einer febrilen oder auch afebrilen t?dlichen Sepsis kommen. Die Beachtung der Vaginalflora, die Erkennung von Risikofaktoren und die frühzeitige und wirksame Antibiotikagabe verhindern sogenannte schicksalhafte Verl?ufe.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

The effect of systemic lidocaine on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers

Although effective in neuropathic pain, the efficacy of systemic lidocaine in non-neuropathic pain remains uncertain. We investigated the analgesic effect of systemic lidocaine on the heat/capsaicin sensitization model of experimental pain in 24 volunteers. Sensitization was produced by heating the skin to 45 degrees C for 5 min, followed by a 30-min application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin. Subjects received IV lidocaine (bolus 2 mg/kg, then infusion 3 mg. kg. h), or saline for 85 min. Areas of secondary hyperalgesia, heat pain detection thresholds, and painfulness of stimulation with 45 degrees C for 1 min (long thermal stimulation) were quantified. Systemic lidocaine reduced the area of secondary hyperalgesia to brush, but not to von Frey hair stimulation. Lidocaine did not alter heat pain detection thresholds or painfulness of long thermal stimulation in normal skin. We conclude that, at infusion rates in the low- to mid-antiarrhythmic range, lidocaine has no effect on acute nociceptive pain but does have a limited and selective effect on secondary hyperalgesia. Implications: The efficacy of systemic lidocaine in nonneuropathic pain remains uncertain. This study investigates the effect of systemic lidocaine on experimental-induced hyperalgesia in 25 volunteers. Hyperalgesia was induced by using an experimental pain model that uses heat and capsaicin in combination. Systemic lidocaine showed a selective effect on secondary hyperalgesia.