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BACKGROUND: Almost all (17/20) Swedish counties have pharmaceutical committees that establish recommendations for the use of antibiotic prophylaxis in oral healthcare.Objective To evaluate the evidence for the use of antibiotic prophylaxis in oral healthcare and the agreement between Swedish recommendations and evidence. MATERIAL AND METHODS: We conducted a systematic literature search in PubMed and the Cochrane Controlled Trials Register. The MeSH terms 'antibiotic prophylaxis' and 'dentistry' were used in the database search. Abstracts were reviewed according to specific inclusion and exclusion criteria. A total of 186 articles were read in full text by the four authors independently. Data extraction and interpretation of data was carried out using a pre-defined protocol. In the end, one case-control study was included for evaluation of evidence. RESULTS: The case-control study included patients with specific cardiac conditions. The study reported a 49% protective efficacy (odds ratio: 0.51) of antibiotic prophylaxis for first-time episodes of endocarditis within 30 days of procedure. This result was not statistically significant. The quality of the evidence was low. No studies were evaluated on patients with other medical conditions. The recommendations included several cardiac and other medical conditions for which there is a lack of evidence or no evidence to support the use of antibiotic prophylaxis. CONCLUSIONS: There is a lack of evidence to support the use of antibiotic prophylaxis. To avoid the risk of adverse events from antibiotics and the risk of developing resistant bacterial strains, the use of antibiotic prophylaxis should be minimised and recommendations in Sweden should be revised to be more evidence-based.

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Delayed neuroexcitatory symptoms after an uneventful anaesthesia are uncommon, although described in many reports. We want to report on two cases. The first patient developed muscle hypertonicity, jerky movements and unconsciousness after an uneventful anaesthesia with propofol, and later the same thing happened after anaesthesia with thiopentone. The second patient developed similar symptoms after an uneventful anaesthesia with propofol, but she never recovered completely after this and is now severely disabled. A search of the literature and the Swedish adverse drug reactions register revealed many similar cases. In both our patients the causal relationship between propofol and the neuroexcitatory symptoms remains uncertain, but we want to alert readers about this possible adverse reaction.

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Women's experiences and ideas about the climacteric are not in accord with the biomedical model, in which the climacteric and the menopause are characterized as being a risk factor for various diseases and a cause of "estrogen deficiency", a hormonal disease which is assumed to persist during the rest of life. The biomedical model may lead to medicalization and pathologizing, increasing the subordination of women and making them dependent on the health care system. Women who use hormonal therapy during the climacteric have many characteristics differentiating them from women who do not use such therapy. Thus, epidemiological studies will be difficult to interpret with respect to the long term effects of hormonal therapy. It is argued that the consultation for women of middle-age should be characterized by a holistic view of the woman taking account of her gender identity, life conditions and life situation. Such a view should focus on the woman's own ideas as to diagnostic procedures, treatment and solutions. In view of the lack of knowledge about the pros and cons of hormonal therapy, women themselves should make the decision, and such decisions should be encouraged. Also, the efforts directed towards women's compliance to hormonal therapy can be questioned. Women's climacteric symptoms should neither be medicalized, pathologized or minimized.

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In an effort to increase our knowledge of the optimal use of serum cystatin C and creatinine as glomerular filtration rate (GFR) markers, these variables, as well as lean tissue mass and GFR, were determined in a population of 42 healthy young adults (men and women with normal GFR). Dual-energy X-ray absorptiometry and measurement of the plasma clearance of iohexol were used to measure lean tissue mass and GFR, respectively. Serum creatinine was significantly correlated to lean tissue mass (r=0.65; p < 0.0001) but not to GFR (1/creatinine vs. GFR: r=0.11; p=0.106). In contrast, serum cystatin C correlated with GFR (1/cystatin C vs. GFR: r=0.32; p=0.0387), especially in men (1/cystatin C vs. GFR: r=0.64; p=0.0055), but not to lean tissue mass. These results might explain previous observations that serum cystatin C seems to be a better marker for GFR than serum creatinine, particularly for individuals with small to moderate decreases in GFR. However, the results also show that the serum concentrations of both creatinine and cystatin C are determined not only by GFR, but also by other factors. Since these additional factors differ for cystatin C and creatinine, it seems justified to use serum creatinine and cystatin C in conjunction to estimate GFR, at least until it is known in what situations serum creatinine or cystatin C is the preferable marker.

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BACKGROUND: Total knee replacement (TKR) has been associated with postoperative renal dysfunction. The use of monomeric methylmethacrylate (MMA) bone cement causes hypotension by several mechanisms. METHODS: In 30 patients undergoing TKR with (n = 16), or without (n = 14) bone cement, serum levels of creatinine, cystatin C and creatine kinase (CK) and urinary levels of creatinine and markers for glomerular (albumin, IgG) and tubular (protein HC) function were recorded preoperatively and on days 1, 2, 4 and 8 postoperatively. RESULTS: There were no changes in serum creatinine. Both groups had a transient, 5-fold rise in CK and a continuous increase in cystatin C. The urinary concentration of proteins increased postoperatively with a peak in the glomerular markers on day 1 and in the tubular marker on day 2. There were no significant differences in proteinuria between the groups. The 95% CIs for the difference in the means of the AUCs of the logarithmically transformed values for the proteins were never more than 19%. On day 8 all proteins had returned to their preoperative levels. CONCLUSION: Postoperatively, there was a transient increased leakage of proteins, indicating glomerular and tubular dysfunction. This was not influenced by the use of MMA bone cement.

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Findings in increasing numbers of clinical and epidemiological studies suggest gender-related differences to exist in the clinical efficacy and adverse effects of drug treatment. Pharmacokinetic studies have shown that the rate of systemic clearance adjusted for body mass may be significantly higher, or lower, in women than in men, which may partly be explained by sex differences in drug metabolism. However, sex differences have also been demonstrated in drug response at the receptor level, though few studies have been focused on this aspect. Many but not all, such gender-related differences can be explained by the effects of sex hormones. There is a need of more systematic analysis of gender-related differences in pharmacodynamics.

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Pregnancy is rare in Parkinson's disease (PD). In the literature on studies of antiparkinsonian drugs in animals during pregnancy, there are reports on malformations of the skeletal and circulatory system. However, the majority of studies in animals have not shown any teratogenicity. Amantadine has been teratogenic in rats and selegiline has caused neurochemical and behavioral alterations in rats when coadministered with clorgyline. The published experience with humans consists of 35 pregnancies among 26 women suffering from PD, including this report, and a number of cases treated with antiparkinsonian agents for other reasons. With the exception of the majority of the cases where amantadine was used, complications have been rare. However, there are indications that suggest a possible risk of a woman's parkinsonism worsening in connection with pregnancy. We also report the case of a woman with PD who was treated with L-dopa-benserazide during an uncomplicated pregnancy and gave birth to a healthy boy without experiencing any worsening of her PD.

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OBJECTIVE: To describe serum concentrations and clearance of sotalol after a massive overdose. CASE SUMMARY: A 37-year-old white man took 11.2 g of sotalol hydrochloride tablets in a suicide attempt. The first serum d,l-sotalol concentration 3 hours after taking the first tablet was 20.6 mg/L and the last measured concentration 59 hours later was 1.8 mg/L. Logarithmic transformation of the concentration data indicated two separate monoexponential phases in the elimination curve, with half-lives of 30.1 and 11.6 hours. DISCUSSION: The shorter serum half-life in the later phase is comparable with that in four previously reported sotalol intoxications and within the normal range. The elimination rate increased in a temporal manner with an increase in systolic blood pressure about 30 hours after the patient was admitted. Since the sotalol elimination rate depends principally on renal function, we believe the initially slow elimination is due to a temporary reduction of the renal function caused by the systolic hypotension. CONCLUSIONS: An initial phase of slow sotalol elimination may occur after severe overdoses. In our patient this was probably due to hypotension. Thus, blood pressure should be monitored carefully.

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We studied the influence of diclofenac on the pharmacokinetics of cloxacillin in healthy volunteers, 60 years or older, as well as the possible effect of cloxacillin and diclofenac on urinary protein excretion. In a randomized, double-blind, cross-over study 15 subjects were given 1 g cloxacillin, and placebo or 75 mg diclofenac, as single intravenous doses. Plasma concentrations of cloxacillin were followed over 10.5 hr, and urine excretion of cloxacillin over 24 hr. The effect of the drugs on urinary excretion of protein indicators of glomerular (albumin, IgG) and tubular (protein HC) function was also studied. Total plasma clearance of cloxacillin was with placebo 219 +/- 51 (mean +/- S.D.), and with diclofenac 212 +/- 39 ml/min./1.73 m2 (ns); renal clearance was 97 +/- 21 and 96 +/- 24 ml/min./1.73 m2, respectively (ns). The terminal t1/2 of cloxacillin was 1.03 +/- 0.42 hr with placebo, and 1.12 +/- 0.37 with diclofenac (ns). The mean ratio of AUC0-infinity's (cloxacillin plus diclofenac/cloxacillin plus placebo) was 1.03 (90% CI: 0.99, 1.08). Urinary excretion of the proteins was low and was not increased by cloxacillin or diclofenac. In healthy volunteers, 60 years or older, diclofenac does not alter cloxacillin pharmacokinetics, and neither cloxacillin nor diclofenac in single intravenous doses cause renal dysfunction.

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Valproic acid is an antiepileptic drug in widespread use. The possibility of various hematologic side effects with this drug is well recognized. We describe a breast-fed infant with thrombocytopenic purpura, anemia, and reticulocytosis, whose mother was treated with valproic acid. As the mother stopped breast-feeding, the infant recovered.

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We studied renal function during and after surgery in 38 patients undergoing total hip replacement (THR) and 21 patients undergoing total knee replacement (TKR). Serum creatinine and renal excretion of albumin, IgG, protein HC and creatinine were recorded preoperatively and on days 1, 2, 4, and 8. THR patients were randomized to treatment with (n 17) or without (n 21) prophylactic isoxazolyl penicillins, which all TKR patients had. In all 3 groups, the urinary concentration of proteins increased postoperatively with a peak in the glomerular markers (albumin, IgG) on days 1 and 2, and in the tubular marker (protein HC) on days 2 and 4. There were no statistically significant differences between the groups. On day 8, all urinary protein concentrations had essentially returned to their preoperative levels. Serum creatinine decreased by 10% in THR patients on day 1 and then returned to baseline levels, but there was a gradual increase up to 13% in TKR patients.

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OBJECTIVE: The pharmacokinetics of cloxacillin was investigated in 14 men and 24 women undergoing cemented hip (n = 19; age range 56-90) or knee replacement surgery (n = 19; age range 51-84) for osteoarthritis. Cloaxacillin 1 g was given intravenously as a bolus dose at the induction of anesthesia, and plasma samples and urine were collected for 6 h. Drug levels were determined using HPLC. RESULTS: Preoperative serum creatinine levels were 84 mumol.l-1 in hip patients and 72 mumol.l-1 in knee patients. The calculated values for creatinine clearance were 63 and 85 ml.min-1.1.73 m-2, respectively. Total clearance of cloxacillin was 134 ml.min-1.1.73 m-2 in eighteen evaluated patients undergoing hip replacement, and 162 ml.min-1.1.73 m-2 in eighteen patients undergoing knee surgery. Renal clearance was 72 and 79 ml.min-1.1.73 m-2, respectively. Non-renal clearance was 57 ml.min-1.1.73 m-2 in hip patients and 77 ml.min-1.1.73 m-2 in knee patients. Renal clearance of cloxacillin correlated with the estimated creatinine clearance (r = 0.652). Although women received higher doses than men (median 2.02 vs 2.32 mmol.1.73 m-2), there were no sex differences in clearance corrected for body surface area. CONCLUSION: Total clearance of cloxacillin was lower in patients undergoing hip replacement than in patients undergoing replacement of the knee, but there was no difference between men and women.

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OBJECTIVE: To report a case of neurologic adverse effects that developed during concomitant treatment with ciprofloxacin, nonsteroidal antiinflammatory drugs (NSAIDs), and chloroquine. Possible mechanisms for a drug interaction are discussed. CASE SUMMARY: A 68-year-old woman who was receiving chronic treatment with NSAIDs and chloroquine developed dizziness, anxiety, and tremors when ciprofloxacin 500 mg twice daily was begun for Salmonella osteitis. When she discontinued the antirheumatic treatment, there was a prompt relief of symptoms. After indomethacin was reintroduced, the patient developed signs and symptoms of peripheral neuropathy, which partially subsided when ciprofloxacin was discontinued. DISCUSSION: Enhanced neurologic adverse effects of ciprofloxacin when taken together with NSAIDs or chloroquine may result from reduced effects of gamma-aminobutyric acid. An alternative explanation could be that NSAIDs and chloroquine impair the elimination of ciprofloxacin, thereby contributing to toxic concentrations of the antibiotic. CONCLUSIONS: The possibility of interactions between ciprofloxacin and antirheumatic drugs should be considered.

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The calcium antagonistic properties of (+)-T-cadinol, some of its stereoisomers and related terpenes were investigated in both functional and radioligand binding studies, and the effects were compared with those of the dihydropyridine calcium antagonist (+/-)-nimodipine. In the isolated rat aorta, the terpenes relaxed contractions induced by 60 mM K+ more potently than those induced by phenylephrine. (+)-T-cadinol and its stereoisomers were the most potent among the terpenes to relax K(+)-induced contractions, whereas they were approximately 10,000 times less potent than (+/-)-nimodipine in this regard. Binding of the dihydropyridine radioligand [3H]-(+)-PN200-110 was studied on rat cerebral cortical membranes. Displacement and saturation studies indicated that (+)-T-cadinol caused a competitive inhibition of binding. The log Ki values for (+)-T-cadinol and (+/-)-nimodipine from displacement studies (-4.7 and -9.2) corresponded with the log RC50 values for relaxation of K(+)-contracted rat aortas (-5.0 and -9.0). For the terpenes, there was a significant correlation (P < 0.001, rs = 0.89) between displacement of dihydropyridine binding and the ability to relax K(+)-induced contractions. The structures of three terpenes were chemically modified by blocking hydroxyl groups. The potency of these derivatives, as well as the naturally occurring derivative-2-oxo-T-cadinol, to relax K(+)-induced contractions was not correlated to the lipophilicity of the compounds. Instead, other qualities appear to be of importance for the functional effects.(ABSTRACT TRUNCATED AT 250 WORDS)

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To identify factors that regulate the levels of immunoreactive digitalis-like substances (irEDLS) in body fluids, two studies were carried out. Plasma and urine levels of irEDLS were measured in uremic and normal subjects. Extracted material was fractionated (12 fractions) and assayed by digoxin radioimmunoassay. In four fractions, higher levels of irEDLS were found in uremic than in normal plasma. Urine from healthy subjects contained very high levels of irEDLS, but in urine collected from uremic patients irEDLS levels were similar to those in plasma. In another study, eight healthy subjects were given dexamethasone 1 mg orally and tetracosactide [an adrenocorticotropic hormone (ACTH) analogue] 0.25 mg i.v., on separate occasions. Dexamethasone suppressed the plasma and urine levels of cortisol and irEDLS. ACTH increased the levels of cortisol in plasma and urine, and of irEDLS in plasma. Taken together, these results support the hypothesis that irEDLS are of adrenal origin. However, decreased renal clearance, rather than increased production or release, may be the main cause of increased plasma levels of irEDLS in uremia.

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