The antidepressant efficacy of citalopram.

Depression is a long-term illness requiring psychopharmacological treatment over long periods of time. Treatments need to be effective and safe, but in an illness requiring long-term medication, acceptability to patients must also be addressed. Data from eight placebo-controlled studies addressing short-term efficacy and two placebo-controlled studies of long-term (6 months) treatment have demonstrated the antidepressant efficacy of citalopram. Fourteen studies comparing citalopram with a reference antidepressant have provided supporting evidence of efficacy. In all, 3905 patients have been included in clinical efficacy studies, in which 2579 patients have been treated with citalopram, 486 with placebo and 840 with a reference antidepressant. The recommended dose of 20 mg appears appropriate for most patients, with the option of raising the dose in non-responders, particularly if they have more severe depression.

Anesthesia with alfentanil and methohexitone for short gynecological surgery. A comparison with thiopentone/nitrous oxide.

An anesthetic technique in which alfentanil hydrochloride, an ultra-short-acting opioid, was used as a substitute for N2O/O2 was evaluated in outpatient gynecological surgery. Methohexitone was used as a hypnotic agent. The following parameters were studied: blood pressure (BP) and heart rate before, during and at the end of surgery; the incidence of apnea longer than 20 s at induction; the awakening phase; immediate postoperative complications and later postoperative complications according to a questionnaire, including signs of thrombophlebitis. Eighty-nine patients were randomly allocated to three groups. Twenty-nine patients received alfentanil 7 micrograms/kg plus methohexitone plus O2/air (Group A7). Thirty patients received alfentanil 15 micrograms/kg plus methohexitone plus O2/air (Group A15). Thirty patients received thiopentone 5 mg/kg plus N2O/O2 (Group P, reference group). Neither in the A7-group, nor in the A15-group was there any increase in peroperative BP, while in the P-group both systolic and diastolic BP rose. The awakening phase was significantly shorter in both the A7- and A15-groups compared to the P-group. Apnea of clinical importance was only seen in the A15-group. There were few immediate postoperative complications in all groups, but the incidence of dizziness was significantly higher in the P-group. According to the questionnaire, the overall incidence of complaints the day after surgery was somewhat higher in the P-group. On the other hand, there was a somewhat higher incidence of thrombophlebitis in both A-groups. We may thus recommend the use of a combination of alfentanil 7 micrograms/kg plus methohexitone and air/oxygen for anesthesia in patients subjected to short gynecological procedures.

The role of calcium channels and serotonin (5-HT2) receptors for tumour cell lodgement in the liver.

The effect of blockade of calcium channels and/or 5-HT receptors on the hepatic lodgement of intraportally injected fibrosarcoma cells was studied in rats. The calcium channel blocker verapamil and the 5-HT2 antagonist ketanserin each had a significant lodgement reducing effect. The pure 5-HT2 antagonist R 56413 was most effective and dose-dependent in its tumour cell lodgement reducing effect. At the highest dose tested (2.5 mg/kg body weight) R 56413 was as effective as thrombocytopenia, indicating that 5-HT is the most important platelet-released product that influences tumour cell lodgement.

A comparative study of loperamide and diphenoxylate in the treatment of chronic diarrhoea caused by intestinal resection.

A double-blind cross-over study of the antidiarrhoeal effects of loperamide and diphenoxylate in 29 patients with chronic diarrhoea due to intestinal resection is presented. Most of these subjects had had surgery for Crohn's disease which was in a stable and nonactive phase during the study. Loperamide and diphenoxylate were presented as identical capsules. Each was administered for a minimum duration of 25 days. The number of capsules required to control diarrhoea was significantly smaller in the loperamide group than in the diphenoxylate group. Loperamide was also statistically superior to diphenoxylate at reducing the number of stools and improving the faecal consistency. Nineteen of the 29 patients considered loperamide to be the most effective antidiarrhoeal drug, five preferred diphenoxylate and five did not notice any difference.

Solubility of antimycotics: a problem in in vitro experiments.

An investigation of how miconazole nitrate dissolved in dimethylformamide in initial concentrations of 1,000, 500, and 100 microgram/ml may alter its concentration with storage time, is presented. The determination of miconazole nitrate was performed with high pressure liquid chromatography. After 8 hours the 1,000 microgram/ml solution was milky and the concentration of miconazole had fallen significantly. It was concluded that test agar plates or agar tubes must be made with freshly prepared and clear stock solutions, otherwise false MIC's may be obtained.

Tension and cyclic GMP changes in potassium depolarized rabbit colon muscle.

Potassium depolarization of rabbit colon muscle elicited a contraction consisting of 2 distinct phases, an initial rapid phasic contraction and a tonic contracture. The tonic contraction was, in contrast to the phasic contraction, dependent on the extracellular calcium for its development. There was a correlation between the tension development and the increase of the cyclic GMP level in the K+-depolarized muscle. Experimental conditions which abolished the tonic contracture, viz glucose omission and treatment with Ca2+-antagonists (verapamil, SKF 525A) also inhibited the cyclic GMP response. The changes of the cyclic GMP levels were Ca2+-dependent. K+-ions also changes the cyclic AMP content an effect which was atropine sensitive. From the experimental data obtained in this investigation we suggest that the co-variation of the tension and the cyclic GMP level in the depolarized colon muscle might depend on oscillations in a common intracellular factor, probably Ca2+.

Contraction of glycerol extracted fibres of smooth muscle by acetylcholine and imidazole in the presence of a Ca-binding microsomal fraction from rabbit colon.

Microsomal and mitochondrial fractions were isolated from rabbit colon muscle homogenate by differential centrifugation. The calcium content of these fractions were rather similar. The microsomes were divided into subfractions by gradient centrifugation and tested on glycerol treated colon muscle. Acetylcholine and imidazole elicited an EGTA-sensitive contraction of glycerinated colon muscles in the presence of microsomal subfractions and Mg-ATP. The glycerinated colon muscle constitute a rapid system for qualitative drug tests on Ca-metabolism in subcellular fractions of smooth muscle.