Isolation and determination of quaternary ammonium compounds by means of amberlite XAD-columns and thin layer chromatography

The potentials of XAD-columns for the isolation of quaternary ammonium compounds from aqueous media have been investigated. When adequate amounts of counter ions (perchlorate, chloride, phosphate, nitrate) were added to the aqueous sample, to the column pretreatment fluid and to the aqueous washing fluid, most quaternary compounds investigated were retained on the column and could be recovered by elution with methanol. This approach proved also suitable for urine. Quantitation of quaternaries isolated in this way from urine samples could be performed on silicagel thin layer plates through visualization with iodine, followed by densitometric evaluation. For decamethonium detection limits were 0.1 g/ml. Recoveries at the 1 g/ml level were between 80–90% with variation coefficients of less than 10%.Presented at the European Meeting of The International Association of Forensic Toxicologists, July 4–7, 1978, Utrecht, The Netherlands     

Disposition and clinical pharmacokinetics of microcrystalline theophylline

Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1^–1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.     

Pathophysiologische Beiträge zur Kenntnis körperlicher Vorgänge bei endogenen Psychosen,besonders bei der Schizophrenie

Ohne ZusammenfassungDie Untersuchungen wurden durch Unterstützung der Rockefeller-Foundation ermöglicht.Meiner Mitarbeiterin, FräuleinEmilie Schnalke, möchte ich an dieser Stelle für die mühevolle Arbeit, die die chemischen und Gasstoffwechselbestimmungen erforderten, besonders danken.     

Does comorbidity explain trends in prescribing of newer antihypertensive agents?

OBJECTIVE: Concerns exist about heavily prescribing of new drugs when the evidence on hard outcomes is still limited. This has been the case for the newer classes of antihypertensives, especially in hypertensive patients without additional comorbidity. The association between comorbidity and trends in prescribing of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) was examined for the period 1996-2000. DESIGN AND METHODS: Data were obtained from the Integrated Primary Care Information database, which contains medical records from more than 100 general practitioners in the Netherlands. Prevalent drug use in hypertensive patients was determined per calendar year. As initial treatment, the first antihypertensive drug prescribed within 1 year after diagnosis of hypertension was considered. Logistic regression was used to estimate the likelihood of receiving either ACE-I or ARBs. RESULTS: The overall prevalent ACE-I use remained stable (31%), but it increased from 33 to 41% in hypertensive patients with diabetes, heart failure, proteinuria and/or renal insufficiency. ARB use increased significantly from 2 to 12%; this trend did not differ between patients with or without specific comorbidities. Initial ACE-I use slightly decreased (from 29% to 24%), whereas initial ARB use significantly increased (from 4% to 12%). ACE-I were more likely to be the first treatment in patients with diabetes [odds ratio (OR)=3.9; 95% confidence interval (CI) 3.2-4.9] or hypercholesterolemia (OR=1.4; 95% CI 1.1-1.8). ARBs were more likely to be the initial treatment in patients with asthma/chronic obstructive pulmonary disease (OR=1.6; 1.2-2.3), diabetes (OR=2.1; 1.5-2.9) or hypercholesterolemia (OR=1.7; 1.2-2.4). CONCLUSIONS: The increased use of ACE-I is mostly restricted to hypertensive patients with comorbidities for which their use has been recommended. Trends in prescribing of ARBs are not related to relevant comorbidities.     

Verhandlungen Ärztlicher Gesellschaften

Ohne Zusammenfassung     

Interferon-alpha-2b + ribavirin for the treatment of chronic hepatitis C in non-responders to interferon-alpha-monotherapy

The efficacy of a therapy with interferon-alpha-2b and ribavirin in patients with hepatitis C not responding to the initial treatment remains controversial. Objective of the present study was to determine the efficacy of a combination therapy with 3 MU interferon-alpha thrice weekly and 1,000-1,200 mg ribavirin daily for six months in an open label trial. METHODS: 44 consecutive patients (genotype 1: 79.5%) who had been previously treated with a minimum dose of 3 MU interferon-alpha thrice weekly for at least three months were monitored. Sustained response was defined as virological response with clearance of HCV-RNA after a follow-up period of six months after the end of therapy. RESULTS: A significant decrease of the mean levels of AST (34.3 +/- 27.6 vs. 16.4 +/- 13.5 U/L) and ALT (59.6 +/- 48.8 vs. 23.2 +/- 20.7 U/L) was observed. In 15/44 patients (34.1%) a virological end-of-treatment response was evident. 8/44 patients (18.2%) achieved a sustained response. In 33.3% of the previous non-responders biochemical response with normal aminotransferases, but no virological response was evident. A significant decrease of the mean hemoglobin level was observed during therapy (12.0 +/- 1.7 vs. 14.6 +/- 1.0 g/dl; p < 0.005), which returned to the pretreatment values after the end of treatment (14.4 +/- 1.6 g/dl; n.s.). In ten patients (22.7%) decrease of hemoglobin levels < 10 g/dl led to a dose reduction of ribavirin. CONCLUSION: This study--in agreement to recently published data--provides evidence for the efficacy of the combination therapy with interferon-alpha-2b and ribavirin in a relevant subset of non-responders to interferon-alpha. Therapeutic nihilism should be reevaluated in non-responders to interferon-alpha.     

Effects of intraduodenal application of peppermint oil (WS(R) 1340) and caraway oil (WS(R) 1520) on gastroduodenal motility in healthy volunteers

Enteric-coated preparations containing a fixed peppermint oil/caraway oil combination (e.g. Enteroplant(R)) are widely used in patients with functional dyspepsia. The effect of a separate intraduodenal application of the active ingredients of Enteroplant(R) (90 mg peppermint oil (WS(R) 1340), 50 mg caraway oil (WS(R) 1520) per capsule) and of a hydrophobic phase galenic auxiliary material contained in the Enteroplant(R) formulation (dose as contained per capsule) on gastroduodenal motility were studied with stationary manometry in healthy volunteers. The carrier demanded by the experimental setup also served as a control. The results showed that: (1) during phase III of the migrating motor complex (MMC) the frequency and duration of contractions showed a significant decrease in the duodenum for WS(R) 1340; (2) WS(R) 1520 significantly reduced the contraction amplitudes in the duodenum during phase I and II of the MMC; (3) trends for decreased values were seen for WS(R) 1340 in the gastric corpus and duodenum and for WS(R) 1520 in the gastric antrum; (4) in the gastric corpus the duration of contractions was significantly reduced after application of WS(R) 1340 during phases I and II of the MMC; (5) WS(R) 1520 significantly reduced the contraction amplitudes and the duration of contractions in the gastric corpus during phase III of the MMC; (6) for the hydrophobic phase a moderate but significant decrease of duration of contractions in the duodenum and of frequency of contractions in the gastric corpus was seen. No adverse events were observed during the study. In conclusion, it could be shown that both WS(R) 1340 and WS(R) 1520 contribute to the efficacy of Enteroplant(R). They act locally in the stomach and duodenum to produce smooth-muscle relaxation. The effects of the active ingredients WS(R) 1340 and WS(R) 1520 substantially exceed the effects observed with the galenic auxiliary material and the carrier, respectively.     

Cutaneous manifestations in inflammatory bowel disease

Numerous extraintestinal manifestations in various organ systems have been reported to be associated with inflammatory bowel disease (IBD). Aim of the present paper was to evaluate the frequency of cutaneous manifestations in Crohn's disease (CD) and ulcerative colitis (UC) with respect to their location, the activity and location of the underlying disease, the treatment options and the time to remission. METHODS: The medical records of 1043 inpatients with CD and UC were screened retrospectively for extraintestinal symptoms with special regard to cutaneous manifestations. RESULTS: The prevalence of cutaneous manifestations in IBD was 22/1043 (2.1%; 18 women, 4 men; age: 31.41 +/- 9.9 [21-51] yrs.). In 15/22 patients (68.2%) the cutaneous manifestations were associated with CD, in 7/22 patients (31.8%) UC was confirmed. In 6/22 patients (27.3%) pyoderma gangrenosum (PG) was diagnosed, in 16/22 patients (72.7%) erythema nodosum (EN). EN and PG predominately occurred at the lower legs: in 68.1% the tibia was the main affection site. Other locations like breast or anus were rare. In 16/22 patients (72.7%) an acute phase of the underlying disease was evident, in 6/22 patients (27.3%) CD or UC were in remission. In patients with CD a colonic involvement was found in 86.7%. Arthritis was the most frequent coexisting extraintestinal manifestation in CD (53.3%) and UC (28.8%). Drug treatment was performed with high doses of glucocorticoids and salicylates. The time to remission in patients with EN was significantly shorter as compared to PG (5.3 +/- 1.8 vs. 19.6 +/- 14.2 weeks; p < 0.001). In 5/22 patients (22.7%) cutaneous manifestations reoccurred after a symptom-free interval. All efflorescenses reoccurred during an active phase of the underlying disease at the same manifestation site as the initial presentation. CONCLUSION: In this series the prevalence of cutaneous manifestations in IBD was 22/1043 (2.1%). EN and PG were more frequent in women with IBD, in CD, and during the acute phases of the underlying disease. EN and PG predominately affect the lower legs. Cutaneous manifestations respond well to an acute phase therapy of the underlying disease. The time to remission was significantly shorter in EN as compared to PG. However, relapses have to be considered in a relevant subgroup of patients.