[Bacteria-killing viruses, Stalinists and "superbugs"]. / Bakteriedrepende virus, stalinister og "superbugs".

In June 2000, the WHO warned that the level of resistance to drugs used to treat common infectious diseases is now reaching a crisis point. If world governments do not control infections better in order to slow down the development of drug resistance, entire populations could be wiped out by superbugs against which there is no efficient treatment. Development of resistance is due to both underuse and overuse of drugs, and strategies have been worked out, to slow down the development of resistance for instance by the Norwegian Ministry of Health and Social Affairs. The present article deals with an old principle, mainly developed behind the Iron Curtain, which is now attracting renewed attention in the west: the application of bacterial viruses (bacteriophages) in the fight against bacteria. According to clinical trials in Eastern Europe, mostly uncontrolled, phages have been used successfully in treatments against antibiotic-resistant bacteria, for instance in suppurative wound infections, gastroenteritis, sepsis, osteomyelitis and pneumonia. These encouraging data are supported by recent findings in well-controlled animal models demonstrating that phages can rescue animals from a variety of fatal infections. The present review discusses possible advantages and limitations of phage treatment in humans.

Flunitrazepam versus placebo premedication for anxiety control in general dental practice.

Our objective was to examine the performance of sublingual administration of the short- to intermediate-acting benzodiazepine flunitrazepam on patients with dental anxiety. The study was designed as a randomized double-blind, placebo-controlled crossover trial with nearly identical dental interventions performed on two separate occasions in 24 adult patients. Flunitrazepam (1 mg) significantly reduced anxiety and was well tolerated. With few exceptions, both the patients and the dentist clearly favored the session with flunitrazepam. Most patients also preferred the remaining part of the day when they had been premedicated with flunitrazepam. They were apparently not particularly troubled by being somewhat drowsy. Dizziness was not reported as a problem. Flunitrazepam appears to be an effective, safe, and recommendable alternative for premedication of anxious dental patients.

Effect of homoeopathy on pain and other events after acute trauma: placebo controlled trial with bilateral oral surgery.

OBJECTIVE: To examine whether homoeopathy has any effect on pain and other inflammatory events after surgery. DESIGN: Randomised double blind, placebo controlled crossover trial with "identical" oral surgical procedures performed on two separate occasions in 24 patients. INTERVENTIONS: Treatment started 3 hours after surgery with either homoeopathy or placebo. MAIN OUTCOME MEASURES: Postoperative pain and preference for postoperative course assessed by patients on visual analogue scales. Measurements of postoperative swelling and reduction in ability to open mouth. Assessment of bleeding after surgery. RESULTS: Pain after surgery was essentially the same whether treated with homoeopathy or placebo. Postoperative swelling was not significantly affected by homoeopathy, but treatment tended to give less reduction in ability to open mouth. No noticeable difference was seen in postoperative bleeding, side effects, or complaints. Thirteen of the 24 patients preferred the postoperative course with placebo. CONCLUSIONS: No positive evidence was found for efficacy of homoeopathic treatment on pain and other inflammatory events after an acute soft tissue and bone injury inflicted by a surgical intervention. Differences in the order of 30% to 40% would have been needed to show significant effects.

Conscious sedation by rectal administration of midazolam or midazolam plus ketamine as alternatives to general anesthesia for dental treatment of uncooperative children.

The trial included 24 children (aged 2-7 yr) referred for dental treatment under general anesthesia, since conventional behavioral management methods had failed to achieve treatment acceptance. As an alternative, they received, on two separate occasions with "identical" dental treatment, conscious sedation by rectal administration of either midazolam (0.3 mg/kg body weight (bwt)) or midazolam (0.3 mg/kg bwt) plus ketamine (1.0 mg/kg bwt). This allowed a double-blind, crossover design. The aims were to assess conscious sedation, combined with local anesthesia, as an alternative to general anesthesia, and further to evaluate the effects obtained by addition of a low dose of ketamine to rectally administered midazolam. The feasibility of dental treatment was rated as excellent or good for 16 of the 24 children when premedicated with midazolam, and for 18 of the 24 children when ketamine was added to midazolam. At least some treatment could be given to all children. Verbal contact was maintained with all children throughout both treatment sessions. The children were significantly less anxious when they arrived for the second session. Amnesia and drowsiness were significantly increased when ketamine was added to midazolam. The combination also tended to be more efficient in relief of anxiety and prevention of pain, but there were large variations in the children's responses to the drugs. Midazolam significantly reduced the blood oxygen level, but not with ketamine added. For most children, both regimens proved to be appropriate as alternatives to general anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anti-inflammatory agents in acute tissue trauma. Choice and effects]. / Antiinflammatoriske midler ved akutte vevstraumer. Valg og virkninger.

The choice of drugs to reduce pain and excessive inflammatory reactions after surgery or accidental trauma is reviewed and discussed, with particular reference to a series of Norwegian studies based on bilateral oral surgery. In this model, paracetamol has proved capable of reducing post-operative swelling by about 30%, while acetylsalicylic acid (in common analgesic doses) failed to reduce or even tended to increase swelling. Paracetamol is a recommendable alternative for reducing acute post-traumatic pain and swelling, while acetylsalicylic acid should be avoided. Non-steroidal anti-inflammatory drugs which efficiently reduce rheumatoid swelling may provide good pain relief, but the effect on an acute post-operative swelling is less impressive. In the oral surgical model, glucocorticoids reduced post-traumatic swelling by about 50% and provided better or at least as good pain relief as any tested non-steroidal anti-inflammatory drug, including paracetamol. Single dose or short-term administration of a glucocorticoid is recommended as an efficient and valuable means of reducing both pain and excessive inflammation in surgery and traumatology. Of practical implication in traumatology is the finding that, for both paracetamol and glucocorticoids, almost the same reductions were recorded in swelling and pain whether the drug was administered prior to surgery or 2-3 hours afterwards.

[Gingival hyperplasia induced by calcium channel blockers. Rare or frequent in Norway?]. / Kalsiumkanalblokkerindusert gingival hyperplasi. Sjelden, eller tusener av tilfeller i Norge?

Sales statistics indicate that the number of Norwegians treated with calcium channel blockers increased from about 50,000 in 1986 to about 83,000 in 1991 (last year: nifedipine 39%, verapamil 27%, amlodipine 21%, diltiazem 10% and felodipine 3%). In spite of widespread use, only one report on gingival hyperplasia induced by calcium channel blockers has been received by the Norwegian Adverse drug reaction committee. The incidence of this adverse reaction is uncertain, but the few controlled studies that have been performed indicate that it may be as high as 15% in patients on long-term treatment, at least with nifedipine. This corresponds to nearly 5,000 cases among the about 32,000 users of nifedipine. Norwegian physicians and dentists are asked to report cases of gingival hyperplasia induced by calcium channel blockers. Although the voluntary report system is fraught with uncertainty, it is hoped that, in a relatively small and surveyable drug market as the Norwegian, the reporting may provide some relevant information, e.g. to allow comparison of the potential of the various calcium channel blockers to induce this adverse effect. A Norwegian controlled study on gingival conditions among long-term users of calcium channel blockers is in its initial stage. It may be of interest to compare the results of this study with the indications obtained from the spontaneous reporting on the incidence of this adverse effect, which is relatively easy to diagnose.

Fluorosis of deciduous teeth and first permanent molars in a rural Kenyan community.

The severity and distribution of fluorosis in the deciduous dentition of 76 children in a low-income community near Nairobi were studied. Seventeen children comprised a low-F (fluoride) group (water less than 0.7 ppm F) and 59 a high-F group (water approximately 9 ppm F). The high-F group had scores greater than or equal to 5 in the Thylstrup & Fejerskov classification system for 29% of the deciduous tooth surfaces, compared with 7% in the low-F group. Comparison between the scores of the second deciduous and the first permanent molars showed no significant difference in the high-F group (p greater than 0.001), whereas the deciduous molar was significantly less severely affected in the low-F group (p less than 0.001). The deciduous molars of the two groups differed significantly (p less than 0.002), but not the permanent molars (p greater than 0.10). Early introduction of tea might have been a major contributor to the distributions of fluorosis, particularly in the low-F group.

[Fluorosis due to fluoride in drinking water. A health risk even in Norway?]. / Fluorose på grunn av fluorid i drikkevann. En helserisiko også i Norge?

About 99% of the Norwegian population are supplied with surface water with very low fluoride levels. Accordingly, they need to use fluoride preparations to prevent dental caries. Groundwater with excess fluoride is a problem mainly in a few areas of South-Eastern Norway, where in some samples of borehole water the fluoride concentration has even exceeded 10 ppm. A warning is given against the use of high-fluoride water when preparing drinks and foods for children. Infants given dried milk formulas diluted with water are at particular risk of developing fluorosis. The recommended daily meals for a three month-old child contain 900 ml water. At a level of 2 ppm, the fluoride content of this volume will exceed the upper limit of the safe and adequate intake for a child this age by 3-4 times. Water used for this purpose should preferably not contain more than 0.5 ppm fluoride. While only few Norwegians are at risk of being exposed to high-fluoride water this problem affects many persons in other parts of the world. With reference to a joint Kenyan-Norwegian research project, the paper is illustrated by cases of dental fluorosis from a Kenyan village supplied with 9 ppm fluoride water. Dental fluorosis of such severity has never been encountered in Norway.

Intake of fluoride and excretion in mothers' milk in a high fluoride (9 ppm) area in Kenya.

In 27 nursing mothers a study was made on breast milk fluoride (F) levels and the 24-h intake of F through foods and beverages. The daily F intake averaged 22.1 mg (range 9.5-37.2 mg); cooked food contributed 11.7 mg, water 4.5 mg and tea 5.8 mg. The breast milk F concentration averaged 0.033 mg/l (range 0.011-0.073 mg/l). No significant correlation could be established between the milk F level and the intake of F. The milk F level was, however, correlated positively to mothers' age and negatively to mothers' weight. It is concluded that the milk fluoride level was only moderately increased by the high intake of F, and that the children's intake of F through mothers' milk was negligible compared to the very high F intake through complementary foods and beverages.

Acetylsalicylic acid or paracetamol?

Paracetamol, a widely used non-narcotic analgesic, has the same analgesic, and antipyretic efficacy as acetylsalicylic acid (ASA). In contrast to ASA, paracetamol has traditionally been claimed to have little or no anti-inflammatory effect. There is, however, increasing support for the view that paracetamol has anti-inflammatory activity and reduces pain and swelling in inflammatory conditions other than rheumatoid arthritis. Overall, paracetamol seems to be equally effective as ASA. Since ASA has a greater potential for adverse effects, paracetamol is increasingly preferred to ASA, particularly in children.

Effects of phenylbutazone and indomethacin on the post-operative course following experimental orthopaedic surgery in dogs.

Randomized placebo-controlled crossover studies were carried out in dogs to evaluate how two non-steroidal anti-inflammatory drugs (NSAID) might modulate an acute post-traumatic inflammatory reaction. Two "identical" surgical interventions were performed on the forelimbs of each animal with an interval of 28 days, to enable a paired comparison of the inflammatory signs and the wound/bone healing processes. At one operation 8 dogs received 300 mg phenylbutazone twice daily for 8 days starting on the day before surgery, and at the other operation matching placebo tablets were given. In a similar placebo-controlled trial another group of 8 dogs received 5 mg indomethacin twice daily. With phenylbutazone the post-operative swelling was not significantly reduced compared to placebo, but there was less pain and limping. With indomethacin the swelling was somewhat reduced, but there was no consistent difference to placebo in the pain and limping assessments. None of the drugs appeared to distinctly effect the wound or fracture healing, as evaluated by clinical inspection, comparison of radiographs and comparison of bone sections from the sites of surgery. It proved difficult to select an appropriate dosage of indomethacin due to its high potential to induce GI ulceration and bleeding in dogs. In this experimental surgical model with an acute inflammation, neither phenylbutazone nor indomethacin showed impressive anti-inflammatory or analgesic properties. In the same model paracetamol has proved to significantly and more efficiently, reduce both swelling and pain without any noticeable adverse effects, and appears to be a better alternative than the two presently tested NSAID.

Effects of paracetamol and acetylsalicylic acid on the post-operative course after experimental orthopaedic surgery in dogs.

In placebo-controlled cross-over trials in dogs, two 'identical' operations were performed on the forelimbs of each animal with an interval of 28 days, to evaluate how daily doses of 1.5 g paracetamol, 1.5 g acetylsalicylic acid (ASA) and 0.5 g ASA might modulate an acute post-operative inflammatory reaction. On the third post-operative day the reductions in swelling compared with placebo averaged 33% with 1.5 g paracetamol (P = 0.02), 24% with 1.5 g ASA (P = 0.03) and 15% with 0.5 g ASA (P = 0.18); while the reductions in pain estimates averaged 47% with 1.5 g paracetamol (P = 0.01), 32% with 1.5 g ASA (P = 0.07) and 28% with 0.5 g ASA (P = 0.21). There were no clinical signs of adverse drug effects, such as vomiting, haematochezia, cyanosis or depression. The results disagree with the traditional view that paracetamol has little or no anti-inflammatory effect, and demonstrate that paracetamol may reduce an acute inflammatory reaction, at least as efficiently as ASA. The potential pro-inflammatory effect of ASA in low doses is discussed. It is concluded that paracetamol appears to be a valuable drug against post-operative or post-traumatic sequelae in the veterinary as well as in the human clinic.