Nomifensine and imipramine in endogenous depression. A double-blind Scandinavian multicentre study.
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Biomedical subjects
Publications and source records attributed to K Jensen.
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20 patients with cystic fibrosis and chronic pulmonary Pseudomonas aeruginosa infection underwent a total of 23 courses of treatment with a new cephalosporin, cefsulodin. The patients were given 100-150 mg/kg/day in 3 divided doses for 14 days, alone or in combination with tobramycin. Maximum serum levels were around 150 microgram/ml and 6-h levels above 5 micrograms/ml. 90% of the infecting strains were sensitive to 5 micrograms/ml in vitro. Apart from discomfort in direct relation to intravenous bolus injection the drug was well tolerated. Clinical improvement was pronounced, and in 5 cases. P. aeruginosa disappeared from bronchial secretions. Patients allergic to carbenicillin tolerated cefsulodin without signs of allergy. Cefsulodin thus appears to be an effective alternative to carbenicillin in the treatment of severe P. aeruginosa infections.
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The kinetics of citalopram were studied in a group of volunteers after oral (8 subjects) and intravenous (4 subjects) single doses and repeated oral administration (7 subjects). Inter- and intraindividual variation was limited and linearity of kinetics indicated. Systemic and apparent oral clearance estimates (mean 0.42 l plasma/min.) were similar, indicating roughly complete systemic availability. The presence of unchanged drug in urine, corresponding to 1/7 of the dose, suggests elimination by renal as well as hepatic processes. The data from the intravenous test revealed two compartment kinetics; the total volume of distribution was estimated to about 1150 l and that of the central compartment to 175 l. Upon repeated administration steady-state conditions were generally achieved after one week in agreement with the 33 hrs half-life of elimination. Citalopram peak concentrations were reached within 2-4 hours after the daily dose and maximally two-fold variation was recorded in the 24 hrs dose interval. The levels of a main pharmacodynamically active metabolite were roughly half as high as the drug levels.
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In crude water-soluble extracts of Pseudomonas aeruginosa 64 antigens can be demonstrated by crossed immunoelectrophoresis in agarose with polyvalent Pseudomonas-immunoglobulin. One of these antigens cross-reacts with antigens prepared from bacteria of a wide range of taxonomic groups. Monospecific immunoglobulins to this antigen (Common Antigen) were produced by immunization with the appropriate immunocomplex extracted from agarose. Common Antigen was purified by the combination of two fractionation methods: Precipitation of the crude extract with 18% (w/v) sodium sulfate, followed by gel filtration of the supernatant on a Sephadex G-200 column. By this method, 35% of Common Antigen from the crude extract was recovered, more than half of the fractions electrophoretically pure. Electrophoresis of reduced Common Antigen on a dodecyl sodium sulfate polyacrylamide gel revealed two protein bands with apparent molecular weights of 59-62 000 and 62-65 000, respectively. The untreated antigen, however, passed a column of Sephadex G-200 with the void volumen, indicating a substance of high molecular weight (> 4-600 000).
Common Antigen (CA) of Pseudomonas aeruginosa has been shown to be a protein composed of polypeptide subunits of a molecular weight (MW) of about 62 000. The MW of this protein was estimated to 665 000 by gel filtration on sepharose CL-6B, to 800 000 by electrophoresis on polyacrylamide gradient gels and to about 900 000 by ultracentrifugation, on a sucrose gradient. By analytical ultracentrifugation with Schlieren optics a sedimentation coefficient (S20 degrees, W) of 22.65 was calculated. The isoelectrical point was determined to pH 4.4. The antigen was decomposed on exposure to proteolytic enzymes. Polysaccharide, lipid, deoxyribonucleic acid or ribonucleic acid were not demonstrated in CA. The amino acid content of CA was determined, and no hexosamine or abnormal residues were observed. The amino acid content of CA was determined, and no hexosamine or abnormal residues were observed. The antigen was degraded when heated to 100 degrees C for 4 min or when exposed to pH below 4 or above 11 at 4 degree C. CA has been isolated from the cytoplasmic water-soluble fraction of disintegrated bacteria and only trace-amounts could be obtained from envelope fractions after solubilization with Triton X-100.
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Thirty-eight in-patients with endogenous- and 20 in-patients with non-endogenous depression, took part in a multi-centre 3-week double-blind trial where patients were randomly allocated to treatment with either 6 g L-tryptophan or 150 mg imipramine daily. Item analysis of Hamilton ratings, before the investigation and weekly during the trial period demonstrated few statistically different mean scores on individual items between the two treatment groups. After 3 weeks' treatment a statistically significant item mean reduction on the 0.1% level was found in the item Agitation in favour of imipramine-treated, and in the item Work and Activities in favour of L-tryptophan-treated endogenously depressed patients. After 3 weeks' treatment a statistically significant item mean reduction on the 5% level was found in the item Suicide in favour of imipramine-treated non-endogenously depressed patients. The present study has shown that, after 3 weeks' treatment, imipramine and L-tryptophan has decreased the mean score on individual items of HRS in about the same degree.
From Nov. 15 to Dec. 17, 1977, Pseudomonas cepacia was isolated from the blood of 16 patients in Odense, Denmark, and Nijmegen, Holland, 2--5 days after an operation with general anaesthesia. The fever started 14--70 h after operation and lasted 2--4 days. All patients recovered. 14/15 patients examined 7--51 days later had agglutinating antibody titres of 400-3,200 against the epidemic strain. Ps. cepacia with identical biochemical characters and sensitivity pattern was isolated from unbroken vials containing the anaesthetic fentanyl, which had been given to all 16 patients. Two batches were contaminated, one heavily so (10(4)--10(5) cfu/0.1 ml). Seven other batches examined yielded no growth. The preservative added to the vials was a mixture of methyl- and propyl-p-hydroxybenzoates which not only allowed growth of the Ps. cepacia strain but could also serve as a carbon source as did citric and malonic acids. The concentration of preservative was not reduced in contaminated vials. The vials had not been sterilized after closure; too much reliance had been placed on an aseptic technique and insufficient preservatives.
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