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.

OBJECTIVETo study trough levels of metformin in serum and its intra-individual variation in patients using a newly developed assay.RESEARCH DESIGN AND METHODSTrough serum levels of metformin were measured once using liquid chromatography–tandem mass spectrometry (LCMSMS) in 137 type 2 diabetic patients with varying renal function (99 men) and followed repeatedly during 2 months in 20 patients (16 men) with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 body surface.RESULTSPatients with eGFR >60, 30–60, and <30 ml/min/1.73 m2 had median trough metformin concentrations of 4.5 μmol/l (range 0.1–20.7, n = 107), 7.71 μmol/l (0.12–15.15, n = 21), and 8.88 μmol/l (5.99–18.60, n = 9), respectively. The median intra-individual overall coefficient of variation was 29.4% (range 9.8–74.2).CONCLUSIONSDetermination of serum metformin with the LCMSMS technique is useful in patients on metformin treatment. Few patients had values >20 μmol/l. Metformin measurement is less suitable for dose titration.

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.

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.

Sixty consecutive patients with a ruptured supratentorial aneurysm underwent operation during the acute stage, 56 of them within 72 hours after the first bleed, one on the 4th day, and three on the 5th day. Six patients were classified preoperatively in Hunt and Hess neurological Grade I, 39 in Grade II, 11 in Grade III, and four in Grade IV or V. Nine patients had severe intracerebral hematomas, and one patient had a subdural hematoma. After the aneurysm was clipped, nimodipine was applied to the exposed arterial segments in a 2.5 X 10(-5)M solution for 10 minutes. Subsequently, all patients received a continuous intravenous nimodipine infusion (2 mg/hr) for 7 to 12 days, followed by oral treatment (270 mg/day). Forty-six patients (77%) made a good neurological recovery; the morbidity rate was 22%, and mortality rate 1.5%. Of the 45 patients in good condition (Grades I to II) preoperatively, 38 (84%) made a good neurological recovery. Two patients (3% of the total series) developed a typical picture of cerebral ischemic dysfunction of delayed onset with subsequent fixed neurological deficits. The results favor the opinion that early operative intervention is beneficial in patients in good condition rather than delaying surgery, and indicate that nimodipine provides an additional anti-ischemic effect. The appearance and severity of late angiographic vasospasm did not seem to be affected by nimodipine.

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Based on published reports of controlled double-blind studies, the efficacy of beta-receptor blockers and calcium antagonists in the prophylactic treatment of migraine is reviewed. Taking into consideration problems in trial design and evaluation of the effects of treatment, and the amount of documentation, it may be concluded that propranolol, metoprolol, timolol, nadolol and atenolol have been shown to reduce the frequency of migraine attacks in patients with common as well as classical migraine. The effect on duration and intensity of migraine attacks is less clear. Treatment effect is generally seen within 4 weeks, but seems to increase with time. Nonselective beta-receptor blockers as well as drugs selective for beta1-receptors may be effective, and their efficacy is comparable to that of other active antimigraine drugs. Available studies do not exclude the fact that beta-receptor blockers with partial agonist activity (intrinsic sympathomimetic activity) have an effect, but suggest that their efficacy is inferior to that of blockers lacking this property. Among the calcium antagonists tested for prophylactic effect in migraine, the effects of verapamil, nifedipine and diltiazem seem promising, but available documentation does not allow any definitive statements of efficacy to be made, particularly not for nifedipine and diltiazem. The ability of flunarizine to reduce the frequency of migraine attacks in patients with common and classical migraine is well documented; its effect on attack duration and intensity is less well established. The response rate is similar to that for beta-receptor blockers, and to that, for example, for pizotifen (pizotyline). Nimodipine also appears to reduce the frequency of migraine attacks, but the efficacy of this drug, compared with other alternatives, remains to be definitely established.

Patients with a ruptured supratentorial aneurysm undergoing early surgery after the subarachnoid haemorrhage were treated postoperatively with nimodipine to prevent delayed ischaemic dysfunction. It was given first as a continuous intravenous infusion 2 mg/h (mean dose 0.5 micrograms/kg/min) for at least 7 days, and then orally (45 mg X 6) for at least a further 7 days. During the i.v. infusion, the mean plasma concentration was 26.6 +/- 1.8 ng/ml. The plasma clearance ranged from 0.57 to 1.771/kg/h and was negatively correlated with the age of the patient. Immediately prior to successive oral doses, the mean plasma concentration was 13.2 ng/ml (range less than 3-38.8 ng/ml). The peak level was usually found after 1 h; it ranged from 7.0-96.0 ng/ml. Mean bioavailability was 15.9%. The nitropyridine metabolite was found in measurable concentrations only after oral treatment with nimodipine. In some cases, the concentration of metabolite exceeded that of the parent compound. The three patients investigated who developed delayed ischaemic dysfunction had plasma concentrations well within the range in patients who did not, so it seems unlikely that the therapeutic failure could be attributed to individual deviations in the pharmacokinetics of the drug.