Despite the fact that glutamine is not considered to be an essential amino acid, it is the amino acid found in the greatest concentration both in plasma (26%) as in skeletal muscle (75%). These levels may decrease in post-operative, trauma, or critical patients. Glutamine performs many functions in which its demand may be increased, such as: it is a precursor of the synthesis of nucleotides; it is an activator of the protein synthesis and at the same time it inhibits the degradation; it is an activator of glycogen synthesis; it is a metabolic substrate for rapidly replicating cells; it is an energy source for the enterocyte which is so important for maintaining the integrity and the function of the intestinal barrier, and the consumption thereof may be increased under conditions of stress. The administration of glutamine intravenously leads to two physical-chemical problems; the first is its low solubility in water; at 20 degrees C this is only 36 g/l, and the second problem is its low chemical stability in an aqueous solution at 22-24 degrees C, this being 11 days. This problem has led the industry to research two dipeptides of glutamine; L-alanyl-glutamine, and L-glycyl L-glutamine, both of which are much more soluble and much more stable. At present there is still a controversy regarding the dosage of glutamine and its dipeptides, with the dose being 0.19-0.29 g/kg/day of L-glutamine or its dipeptide forms, in surgical post-operative periods or to prevent bacterial translocation, and in patients who are candidates for bone marrow transplants, the administered dose has been 0.37-0.57 g/kg/day. The purpose of this study is to review the existing bibliography regarding the efficacy of L-glutamine or its dipeptides in four possible indications for its application in the daily clinical practice, such as: a) In post-operative surgical patients of major or medium surgery, glutamine or its dipeptides reduces the losses of muscular glutamine and its catabolism, showing a less negative nitrogen balance. b) Whether it avoids bacterial translocation. c) Whether it favors the response of the immunological system. d) Whether in patients who are candidates for bone marrow transplants this decreases the side effects due to chemotherapy and radiotherapy such as mucositis, or whether it decreases the number of days of neutrophil recovery. At present, on the European market there are two commercially available brands of glutamine dipeptides: Dipeptiven, by Fresenius Laboratories, Germany. A 100 ml vial which corresponds to 20 g of L-alanyl L-glutamine (8.2 g of alanine + 13.46 g of L-glutamine). This is added to the standard amino acid solution. Glamin, Pharmacia and Upjohn Laboratory, Sweden. This is an amino acid solution with 13.4% essential and non-essential amino acids which are equivalent to 22.4 g of nitrogen/l, and which contain 30.27 g L-glycyl-L-glutamine (10.27 g of glycine + 20 g of L-glutamine).
Calcium antagonists are widely used in the treatment of hypertension. However, few endpoint studies with calcium antagonists have been done to prove reduction in hypertensive complications. Results of the STONE, SYST-EUR and SYST-CHINA studies show that long-acting calcium antagonists are effective compared to placebo, especially in patients with isolated systolic hypertension and diabetes. Ongoing prospective and randomized trials like STOP II, INSIGHT, NORDIL, ALLHAT and ASCOT will clarify whether calcium antagonists are more effective than well-proven diuretics and betablockers. ASCOT will test the hypothesis that amlodipine is more efficacious than atenolol in preventing cardiac complications in 18,000 hypertensive patients with high coronary risk including diabetes (among them, 2,000 in Norway). The study is also randomizing the patients in a factorial design to either atorvastatin or placebo, testing the so-called lipid hypothesis.
BACKGROUND: Brachytherapy is increasingly used in the treatment of early prostate cancer, but has not been implemented as a treatment option in Norway. Recent advances in imaging techniques and the radiation technology itself has facilitated improvements in and better standardisation of brachytherapy. MATERIAL AND METHODS: An group of expert assisted the Norwegian Centre for Health Technology Assessment (SMM) in a systematic review of the evidence on the clinical effectiveness of prostate brachytherapy. The literature was identified by a defined search strategy, and assessed for relevance and validity. Only controlled or comparative studies were included in the review. RESULTS: There were no randomized controlled trials or large prospective studies. Many of the relevant studies were of poor validity. None of the included studies had sufficient follow-up for overall or disease free survival. There were no differences between brachytherapy, external beam therapy or radical prostatectomy in disease free survival (PSA measures) or in rates of complications. INTERPRETATION: There is a lack of valid data from large prospective studies on the clinical effectiveness of brachytherapy. On the other hand, the clinical effectiveness of radical prostatectomy and external beam radiotherapy is also poorly documented. Results from one large randomized controlled trial comparing radical prostatectomy with brachytherapy in the USA will not be available within the next ten years.
Ethical problems are quoted as a reason not to perform clinical trials in children. Little is known about the views of researchers regarding ethics.
A pilot study was conducted to assess the applicability of a questionnaire design containing trial scenarios to examine views regarding the use of children in drug trials and to elicit possible international differences.
Paediatricians and researchers in the United Kingdom and Canada.
Responders were presented with a questionnaire containing direct questions and six trial scenarios, each containing an ethical dilemma. Responders were asked regarding their own approval and their perceived opinion of whether an ethical review board (ERB) would approve.
One hundred questionnaires (50 each country) were received. Few responders had research ethics training (14% United Kingdom and 8% Canada). Most (80 and 88%) felt children could be harmed by participation in trials and half (47 and 59%) felt children should only participate if they receive direct benefit. Many (58 and 61%) disagreed with payments beyond travel expenses. In the trial scenarios, 34% of responders were willing to enter healthy children in a pharmacokinetics study of an antibiotic for cystic fibrosis and 22% considered their ERBs would approve. Only a third (33%) would enter children in an analgesia trial that was placebo-controlled.
Using healthy children and placebos in trials caused concern. Similar views were found between the two countries. The majority had no training in research ethics. The study highlights the usefulness of a questionnaire with clinical trial scenarios to try to elicit views on the ethics of conducting research in children.