Prescrire Int. 2002 Feb;11(57):21-3.
Highlights of the 22nd French pharmacovigilance meeting.

[No authors listed]

(1) The 22nd French pharmacovigilance meeting, held in July 2001, presented data on adverse effects notified by health professionals to regional pharmacovigilance centres in France. (2) Non specific "immunostimulants" are not harmless placebos, as might be concluded from the relative lack of data. There have been 315 notifications of severe adverse effects, some with positive rechallenge, reporting cutaneous, gastrointestinal, respiratory, haematological and other disorders. Attributability was considered "likely" in 68% of cases. Three deaths occurred. (3) Other well known adverse effects continue to occur: convulsions with camphor, visual hallucinations with oxybutynin, headache with antimigraine drugs, liver damage with dextropropoxyphene, neuropsychological disorders after buflomedil overdose (especially in patients with renal failure), hyperkalaemia during spironolactone combination with an angiotensin-converting-enzyme inhibitor (ACE inhibitor), and severe infections after intravesical BCG. (4) Rare adverse effects of old drugs were identified, such as oedema with valproic acid, interstitial pneumonia with flecainide, and a bleeding risk due to tramadol interaction with oral anticoagulants. (5) The adverse effects of new drugs are better documented: celecoxib is now implicated in visual disorders. (6) Overall, the meeting confirmed that only a small proportion of adverse drug reactions are notified, that a large number of hospitalised patients suffer from drug induced complications, and that summaries of product characteristics (SPC) are often too brief or reassuring regarding pharmacovigilance data. The poor risk-benefit ratios of some drugs call for their immediate market withdrawal.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11985373&dopt=Abstract tramadol Ultram




J Chromatogr B Analyt Technol Biomed Life Sci. 2002 May 25;772(1):11-8.
Advanced fibre optical scanning in thin-layer chromatography for drug identification.

Ahrens B, Blankenhorn D, Spangenberg B.

Institute of Legal Medicine, Friedrich-Schiller-Universitat, Furstengraben 23, D-07743, Jena, Germany.

A systematic toxicological analysis procedure using high-performance thin layer chromatography in combination with fibre optical scanning densitometry for identification of drugs in biological samples is presented. Two examples illustrate the practicability of the technique. First, the identification of a multiple intake of analgesics: codeine, propyphenazone, tramadol, flupirtine and lidocaine, and second, the detection of the sedative diphenhydramine. In both cases, authentic urine specimens were used. The identifications were carried out by an automatic measurement and computer-based comparison of in situ UV spectra with data from a compiled library of reference spectra using the cross-correlation function. The technique allowed a parallel recording of chromatograms and in situ UV spectra in the range of 197-612 nm. Unlike the conventional densitometry, a dependency of UV spectra by concentration of substance in a range of 250-1000 ng/spot was not observed.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12016011&dopt=Abstract tramadol Ultram

sgpgi.ac.in

BACKGROUND AND PURPOSE: Because of the prohibitive cost of laparoscopic disposable instruments such as the PneumoSleeve, Endocatch, and vascular staples, laparoscopic live-donor nephrectomy has not gained wide acceptance in many developing countries. To circumvent this problem, we have developed a cost-saving approach, which is described herein and compared with the open method. PATIENTS AND METHODS: Forty-nine patients underwent laparoscopic live-donor nephrectomy at our institute, of which two were performed by the hand-assisted technique, five by the technique described by Fabrizio et al and forty-two by our modified cost-saving laparoscopy-assisted technique (LD). The latter patients were compared with 50 patients who had a standard open donor nephrectomy (OD) through a rib-resecting (12th rib) flank incision. Our technique is similar to the procedure described by Fabrizio et al except for a 6- to 8-cm incision placed in the subcostal region to retrieve the kidney after the renal vessels are cut and ligated as in the open procedure. The costs of the various techniques at our institute were compared. RESULTS: The LD and OD groups were similar in terms of age, weight, side of nephrectomy, and number of renal vessels. The operative time was longer in the LD group than in the OD group (180.7 +/- 18 minutes v 101.5 +/- 10.4 minutes), whereas the mean intraoperative blood loss was less (85.5 +/- 21.35 v 220 +/- 22.5 mL; P < 0.001). Warm ischemia time and recipient outcomes were comparable in the two groups. Patients in the LD group had lower postoperative narcotic (tramadol hydrochloride) requirement (155.3 +/- 53.3 mg v 251.8 +/- 63.1 mg; P < 0.001) and earlier discharge from the hospital (3.14 v 5.7 days; P < 0.001). The mean expense incurred was US$175 v US$160 in the LD and OD groups, respectively. The cost of the hand-assisted and standard laparoscopic techniques was significantly higher than that of our modified technique. CONCLUSIONS: Our modified technique of laparoscopy-assisted live-donor nephrectomy avoids the use of costly disposables yet offers the advantages of lesser morbidity and small incision of LD. It is cost effective and is an alternative to open nephrectomy in the developing world.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12028624&dopt=Abstract tramadol Ultram

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Two simple and sensitive kinetic methods for the determination of tramadol hydrochloride are described. The first method is based upon a kinetic investigation of the oxidation reaction of the drug with alkaline potassium permanganate at room temperature for a fixed time at 20 min. The absorbance of the colored manganate ions was measured at 610 nm. The second method is based on the reaction of tramadol hydrochloride with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in presence of 0.1 M sodium bicarbonate. The spectrophotometric measurements were recorded by measuring the absorbance at 467 nm, at fixed time at 25 min on thermostated water bath at 90+/-1 degrees C. All variables affecting the development of the colour have been investigated and the conditions were optimised. The absorbance concentration plots in both methods were rectilinear over the range 5-25 and 50-250 microg ml(-1), for the first and second methods, respectively. The two methods have been applied successfully to commercial capsule and ampoule dosage form. The results obtained are compared statistically with those given by the reference spectrophotometric method. The determination of tramadol hydrochloride by the fixed concentration and rate constant methods is feasible with the calibration equations obtained, but the fixed time method proves to be more applicable.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12093516&dopt=Abstract tramadol Ultram




Unfallchirurg. 2002 Jun;105(6):527-31.
[Modification of human osteoblasts by various analgesics]

[Article in German]

Matziolis G, Rau HM, Klever P, Erli HJ, Paar O.

Universitatsklinikums der RWTH Aachen, Berlin.

Analgesia plays a major role in the therapy of fractures. This raises the question whether frequently used analgetics as Tramadol and Diclofenac have negative effects on the healing of fractures. Human osteoblasts were isolated from human spongiosa and incubated with Diclofenac, Tramadol and without analgetic substance in an in vitro experiment. After 9 days the absolute number of cells as a marker for proliferation and their mitochondrial activity were quantified. The mitochondrial activity was measured using the metabolisation of XTT (sodium-3'-(1-[phenylamino-carbonyl]-3,4-tetrazolium)-bis(4- methoxy-6-nitro) benzene-sulfonic acid hydrate). Both drugs led to a concentration-dependent decrease of cell proliferation. Tramadol showed a significant effect at a concentration of 20 micrograms/ml, which is much higher than the therapeutical concentration of 0.25 microgram/ml in serum. Diclofenac decreased cell proliferation at a concentration of 6 micrograms/ml, having a therapeutical concentration of 1.5 micrograms/ml in serum. Vitality of cells had constant correlation to absolute number of cells (R = 0.95). Our results don't suggest any negative effects of Tramadol on the osteoblast activities in vitro. Diclofenac significantly decreased the proliferation of human osteoblasts at concentrations probably reachable in vivo. A prolonged healing of fractures under treatment with Diclofenac may be possible in critical situations (pseudarthrosis revision, callus distraction).

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12132192&dopt=Abstract tramadol Ultram