Improved virological and immunological efficacy of resistance-guided switch in antiretroviral therapy: a Frankfurt HIV cohort analysis.

To evaluate the treatment outcome of antiretroviral therapy, depending on the use and utility of a concept of resistance-guided switch, patients from the Frankfurt HIV cohort have been followed for 24 weeks. If available, prior resistance data have been evaluated and patients were grouped into their expected viral response. The data of 354 patients were thus analysed, taking into account the genotypic sensitivity score of the administered medication (> or ≤2). When looking at the proportion of patients who achieved a viral load of <50/ml, the response rates differed significantly better for patients with a favourable resistance scoring as compared to an unfavourable one (71.9 % as compared to 56.0 %, p = 0.008). Interestingly, patients with a favourable resistance score also showed a better immunological response, as measured by median CD4 cell count of 391/µl [interquartal range (IQR) 250-530/µl] against 287/µl (IQR 174-449/µl) and a larger total increase of 141/µl against 38/µl. A significant virological and immunological benefit could be demonstrated for patients of a cohort with resistance-guided antiretroviral therapy adjustments.

[The development of experimental pharmacology 1790-1850]. / Die Entwicklung zur experimentellen Pharmakologie 1790-1850.

1. The use of drugs goes back to the origins of mankind. In historical times oral drug-lore became codified empiric drug theory (materia medica) and ultimately, in the 19th century, experimental pharmacology. The initiator of experimental pharmacology as an independent medical discipline is Rudolf Buchheim (1820-1879). This study traces the pathways leading to Buchheim and identifies his predecessors between 1790 and 1850. The history of empirical pharmacology and its major theories in Antiquity, the Middle Ages, and early modern times is summarized. For the 18th century an overview is given on early attempts at experimental testing of drug effects and on the new therapeutic systems and medical sects. 2. Many authors have dealt with the grievances of pharmacology and therapy between 1790 and 1850, among them chief representatives of contemporary medicine like the French Fourcroy, Bichat, Pinel, Alibert, Magendie, and the Germans Schönlein, Mitscherlich, Wunderlich, Henle, and Oesterlen. Their criticisms are a means for a better understanding of the situation. They cover the following aspects. Pharmacology is distorted by speculations on the causes of drug action and confusion with regard to terminology and indications. Drug actions are being tested with inadequate methods. An increase in the number of drugs is mistaken for an increase in knowledge. The statement is made that pharmacology is the least developed of all medical subjects. The critics point out that only a more developed chemistry, physiology, and etiology will allow a scientific pharmacology. The drug theories of the medical sects are likewise rejected. Polypharmacy, composite drugs, and absurd formulas are regarded with contempt. Aggressive drug therapy is repudiated, but this easily results in avoidance of drugs and in therapeutic nihilism. 3. In 1799 Johann Christian Reil elaborated his principles for a future pharmacology. Reil establishes the rules for clinical experiments on which a scientific pharmacology should be based. His goal is to explain the actions of drugs which are the results of biochemical alterations. Even though Reil's program is a theoretical conception, it anticipates a situation that was to take shape half a century later. Also in 1799 Adolph Friedrich Nolde published detailed rules for the critical examination of drug actions in patients, including aspects like placebo, compliance, statistics, and several ethical rules. Reil's and Nolde's programmatic messages vanished in the emerging German medicine of "Naturphilosophie". 4. In the decades after 1800 medicine was at its zenith in the Paris School. It became a hospital medicine, based on anatomy and pathology. François Magendie was one of its representatives. He started out as a physician in 1808 and became a physiologist who soon surpassed his teachers Bichat and Richerand. Magendie's sole interest were facts, which had to be unravelled by experiments, mainly on animals. He created modern physiology based on the laws of physics and chemistry. Nevertheless, he remained an outsider among the Paris School. Bichat and other predecessors of Magendie had considered an experimental pharmacology based on physiology, however, they did not provide knowledge resulting from experiments. Magendie published his first experimental study of a pharmacological problem in 1809. From then on he studied the mechanism and site of action of drugs and used them at the same time as tools for the investigation of physiological processes. After Sertürner's isolation of morphine from opium the preparation of pure alkaloids became a specialty of French pharmacists and chemists. Magendie sought their collaboration from 1817 on, convinced that pharmacology and therapy must be based on both physiology and chemistry. In 1821 he published his Formulaire pour la préparation et l'emploi de plusieurs nouveaux médicamens which marks the beginning of modern pharmacology. It grew throughout eight editions up to 1835. (ABST

A rapid method for the detection of uranium in surface water.

A method has been optimized to preconcentrate uranium from waters using the ion exchanger Hyphan. The sample (up to 10 1) is agitated thoroughly with a portion of the ion exchanger for between 40 min and 2 h. The exchanger is filtered off and treated with a small volume (< 100 ml) of either nitric acid (for ICP measurement) or hydrochloric acid (for alpha measurement). The acid is filtered off and measured directly by ICP-AES, or it is brought to pH 2 and saturated with ammonium chloride, then directly electrolyzed. Yields lie in the order of 60-90% and the overall analysis time is approximately 3 h (ICP) or approximately 4 h (alpha measurement). Precisions reached are better than 15% relative. Detection limits lie at about 2 ppb (ICP) and 0.4 ppb (alpha measurement).

Gastric acid inhibitory profile of saviprazole (HOE 731) compared to omeprazole.

Saviprazole (HOE 731), a substituted thienoimidazole, caused a dose-dependent inhibition of gastric acid secretion in dogs and rats with ID50 values which were not significantly different from that of omeprazole indicating that both compounds are equally effective. The duration of action in dogs lasted for more than 24 h and was dependent on the state of stimulation. Measurement of serum concentrations of 1 mg/kg saviprazole after intravenous or intraduodenal administration revealed a bioavailability of about 60% in dogs. The elimination half-life was about 30 min following both routes of administration. In rats basal acid secretion was inhibited by saviprazole. In addition stimulation of acid secretion by histamine, desglugastrin, carbachol and isobutylmethylxanthine-forskolin was equally inhibited. This was in agreement with the known mechanism of action, inhibition of the gastric proton pump which is the last step of acid secretion within the parietal cell. Surprisingly, at high dose levels, saviprazole differed from omeprazole. After saviprazole, 1 mg/kg i.v. to dogs, acid output dropped to zero but recovered within 30 min to a level of 90%, whereas omeprazole depressed acid output completely over the whole observation period (4.5 h). Similar results were obtained in pylorus-ligated rats.