Effect of Emulphor, an Emulsifier, on the Pharmacokinetics and Hepatotoxicity of Oral Carbon Tetrachloride in the Rat

Emulphor, a polyethoxylated vegetable oil, is now being usedwidely to incorporate volatile organic compounds (VOCs) andother lipophilic compounds into aqueous solutions for biochemical,pharmacokinetic, and toxicological studies. Previous work inthis laboratory demonstrated that 0.25% Emulphor did not alterthe kinetics or hepatotoxicity of low doses of CCl₄ comparedto when the halocarbon was given to rats orally in water. Thepresent study was undertaken as there was concern that higherconcentrations of Emulphor (necessary to maintain lipophilicVOCs in stable aqueous emulsions for extended periods) mightalter the VOCs' absorption, disposition, and/or toxicity. Dosagesof 10 and 180 mg CCl₄/kg bw were given, as an aqueous emulsionusing 1, 2.5, 5, or 10% Emulphor, by gavage to fasted male Sprague–Dawleyrats. Serial microsamples of blood were collected from an indwellingcannula in unanesthetized, freely moving rats at intervals of2-60 min for up to 12 hr. The samples' CCl₄ content was measuredby headspace gas chromatography. Thereby, it was possible toobtain blood CCl₄, concentration-versus-time profiles. Animalswere euthanized 24 hr postdosing and blood was collected formeasurement of serum enzymes as indices of hepatotoxicity. Notoxicologically significant differences in pharmacokinetic parametersas a function of Emulphor concentration were found. Similarlythe hepatotoxic potency of 10 and 180 mg/kg CCl₄, as reflectedby elevation in serum enzyme activities, did not vary significantlywith the concentration of Emulphor utilized. Hence, it can beconcluded that Emulphor, in concentrations as high as 10% (equivalentto 260 mg Emulphor/kg bw) in aqueous emulsions, does not significantlyaffect the absorption, disposition, or acute hepatotoxicityof CCl₄ in male Sprague–Dawley rats.     

Length of hospital stay and associated costs for olanzapine vs. haloperidol in the treatment of schizophrenia relapse in Germany

We examined the number of days spent in hospital due to a relapse of schizophrenia and the associated costs for patients treated with olanzapine or haloperidol. Twenty-one German psychiatric hospitals participated in this retrospective study. Data on the last hospitalisation following a relapse of schizophrenia were documented for equal numbers of patients on olanzapine and haloperidol. Matching for time since diagnosis and severity of symptoms was performed. Data were collected on 136 matched pairs. Total length of time spent in hospital was the same on average for patients in both groups (median about 5 weeks), but olanzapine patients spent nearly 1 week less in the in-patient setting than haloperidol patients, resulting in a saving of Euro 411 per patient. Our findings are consistent with those of randomised clinical trials in concluding that olanzapine is preferable to haloperidol in terms of the direct cost of treating schizophrenia. Andrea Spannheimer Kendle GmbH & Co. GMI KG, Stefan-George-Ring 6, 81929 Munich, Germany, e-mail: spannheimer.andrea@kendle.com     

Intrahepatic hematoma: a rare complication of exchange transfusion

A four-day-old male neonate who underwent three exchange transfusions for jaundice owing to ABO incompatibility on three consecutive days is presented. A large intrahepatic hematoma developed as a complication of the third exchange transfusion. The baby fully recovered.     

Nasal mucosa in tropical climate]

Morphological and functional results of the factors influencing the nasal mucous membranes of 150 persons living in a tropical zone are presented. In particular, an increased rate of hyperplastic mucosa was found in comparison with a group of 850 subjects from central Germany. The macroscopic results correlated with exfoliative cytological examination. On the other hand, the rates of moderate and severe hyposmia (9.3%) as well as moderate and extreme nasal obstruction (34%) were lower.     

Incidence of fetal chromosome abnormalities in insulin dependent diabetic women.

In order to screen for fetal neural tube defects and chromosome abnormalities, amniocentesis was carried out in 334 women with insulin-dependent diabetes mellitus (IDDM) between 1979 and 1987. Two cases (0.6%; 95% confidence limits 0.1-2.2%) of fetal chromosome abnormality were found: one case of Klinefelter's syndrome and one case of de novo translocation. This is comparable to the overall incidence of chromosome abnormality found at birth and is also comparable to the incidence of fetal chromosome abnormality (1.0%) found by amniocentesis at our Department in a group of 2,264 young non-diabetic women with little risk of contracting genetic disorders. The results suggest that maternal IDDM does not increase the risk of fetal chromosome abnormality and consequently screening by amniocentesis for chromosome abnormalities among diabetic women does not seem to be indicated.     

Rejuvenation in the early 20th century

Summary. The first theoretical reflections concerning the relation of hormone production with the ageing process stemmed from Charles Edouard Brown-Sequard (1817–1894). At the age of 72 years he experimented on himself with an injection of animal testicular extract.
The Viennese physiologist Eugen Steinach (1861–1944) gained world-wide acknowledgement for his theory of 'autoplastic' treatment of ageing. He deduced that after vasoligation, an increased incretory hormonal production would ensue following the cessation of the secretory output of the gonads. The first operation was performed in 1918 and resulted in a vasectomy boom over the next two decades.
The Russian Serge Voronoff (1866–1951), working in Paris, was one of the first to transplant testicular tissue from a monkey into a human reproductive gland in 1920. Five years later he had already performed this procedure on 300 patients and attracted patients from all over the world.
In America early efforts of human testicular transplantation were performed by Frank Lydston and V.D. Lespinasse. Steinach's vasoligation was taken over by many American doctors, e.g., Harry Benjamin and Charles H. Chetwood. Among the patients who underwent a rejuvenation operation according to Steinach's method were Sigmund Freud (1856–1939) and the Irish poet and Nobel Prize winner William Butler Yeats (1865–1939). Two caricatures from the German magazine Simplicissimus published in 1927, confirm that the rejuvenation operations were constantly in the limelight of the printed media. From 1935 onwards rejuvenation operations gradually lost their appeal due to the introduction of artificial androgens.     

Structure-activity studies of potassium channel opening in pinacidil-type cyanoguanidines, nitroethenediamines, thioureas, and ureas.

Potassium channel opening activity for pinacidil-type cyanoguanidines, nitroethenediamines, thioureas, and ureas, has been assessed through simultaneous measurement of spontaneous contractile activity and stimulation of 86Rb+ efflux from rat portal veins loaded with 86Rb+. The good correlation between these two effects suggests that the vasodilator activity of the compounds is directly attributable to an increased opening of potassium channels. The resulting quantitative in vitro data has been used to analyze the structure-activity relationships for potassium channel opening, allowing the biological activity to be rationalized in terms of a pharmacophore involving a hydrogen-bond-acceptor element, a hydrogen-bond-donor element, and a lipophilic binding group. A model for the binding of pinacidil-related compounds to their potassium channel receptor has been developed, and compounds designed to test this model have been synthesized and tested. Prototropic equilibria are implicated as playing a fundamental role in determining the hydrogen-bonding ability of the compounds, and conformational changes in the receptor are invoked to explain disparities in the chiral recognition of lipophilic groups in different compounds.     

Postoperative pulmonary complication rate and long-term changes in respiratory function following esophagectomy with esophagogastrostomy

Upper abdominal surgery has a high incidence of postoperative respiratory complications. Although operations involving a thoracic as well as an upper abdominal incision as encountered in esophageal surgery are likely to be associated with an even higher complication rate and perhaps permanent alterations of respiratory function, only a few studies have addressed this problem. We evaluated the postoperative course of patients undergoing thoracoabdominal esophagectomy with esophagogastrostomy. Twenty patients were evaluated, of whom 10 (50%) developed respiratory complications as defined by our criteria, which were the simultaneous occurrence of rectal temperature over 38 degrees C on the first postoperative day and radiographic evidence of pulmonary infiltration. Although there is no general consensus regarding the diagnostic criteria of a postoperative pulmonary complication, we were able to validate the clinical relevance of our definition by showing that these patients suffered from a more severe and more prolonged impairment of global oxygen exchange than those who did not fulfill the criteria. They also required a longer period of respiratory support (median duration of intubation 12 vs. 3 days, P less than 0.005). A comparison of the preoperative pulmonary function with that determined at least 6 months after the operation showed that only vital capacity (VC) and total lung capacity (TLC) were significantly (P less than 0.05) reduced following the operation, but not to a clinically relevant degree (VC-6%, TLC-7%).