Comparison of headache parameters using headache type and emotional status.

Objective: The literature on the impact of headache has traditionally focused on the relationship of subject variables to specific headache types. Recently, increasing attention is being paid to the impact on disease of emotional distress. The current study was designed to determine whether differences in subject variables arose when comparing them by headache type vs.

Grapefruit-felodipine interaction: effect of unprocessed fruit and probable active ingredients.

Objectives: To determine whether unprocessed grapefruit can cause a drug interaction, whether the active ingredients are naturally occurring, and whether specific furanocoumarins or flavonoids are involved.

Methods: The oral pharmacokinetics of felodipine and its dehydrofelodipine metabolite were determined after administration of felodipine 10 mg extended-release tablet with 250 mL commercial grapefruit juice, homogenized grapefruit segments, or extract of segment-free parts equivalent to one unprocessed fruit or water in a randomized four-way crossover study. Inhibition of recombinant CYP3A4 by furanocoumarins (bergamottin, 6',7'-epoxybergamottin, 6',7'-dihydroxybergamottin) and flavonoids (naringenin optical isomers) was determined.

EEG and clinical associations with mortality in comatose patients in a general intensive care unit.

The authors examined EEG findings and clinical factors for their association with outcome in comatose patients in their general intensive care unit. The following individual and combinations of factors were strongly related to mortality, with positive predictive values of >0.80 and odds ratios >2.

Grapefruit juice-felodipine interaction: effect of naringin and 6',7'-dihydroxybergamottin in humans.

Objective: To test whether naringin or 6',7'-dihydroxybergamottin is a major active substance in grapefruit juice-felodipine interaction in humans.

Methods: Grapefruit juice was separated by means of centrifugation and filtration into supernatant and particulate fractions, which were then assayed for naringin and 6',7'-dihydroxybergamottin. The effect of these fractions, grapefruit juice (containing comparable amounts of both fractions), and water on the pharmacokinetics of oral felodipine were assessed in 12 healthy men in a randomized, 4-way crossover study.

An electroencephalographic classification for coma.

Background: The assessment of thalamocortical function in comatose patients in the intensive care unit (ICU) can be difficult to determine. Since the electroencephalogram (EEG) affords such assessment, we have developed an EEG classification for comatose patients in our general ICU.

Methods: One hundred EEGs were classified in a blinded fashion by two EEGers, using our method and that of Synek.

Computed tomography evaluation of patients with chronic headache.

Objective: To determine whether the rate of detecting a tumour, arteriovenous malformation (AVM) or aneurysm with the use of enhanced or unenhanced computed tomography (CT) is significant in patients with chronic headache and to calculate the cost.

Design: Case series.

Setting: Chronic headache clinic at a tertiary care referral centre.

Ataxia in institutionalized patients with epilepsy.

Fifty-four per cent of 41 chronically institutionalized adult patients with epilepsy had ataxia of gait (wide mean stride width). None of the following correlated with stride width: serum phenytoin, previous phenytoin toxicity, seizure frequency, or status epilepticus. Seventeen of the 41 patients had computed tomographic head scans.

Quinidine interaction with nifedipine and felodipine: pharmacokinetic and pharmacodynamic evaluation.

Conflicting findings suggest that serum quinidine concentrations may be decreased or increased by nifedipine. We performed a double-blind, placebo-controlled trial of Latin-square design. Twelve healthy men received 3 days of pretreatment with nifedipine prolonged action (20 mg twice a day) or felodipine extended release (10 mg every day), another dihydropyridine calcium antagonist, followed by coadministration of quinidine (400 mg).

Comparison of the efficacy and safety of flunarizine to propranolol in the prophylaxis of migraine.

This study was designed to compare flunarizine, a cerebro-specific calcium channel antagonist, and propranolol in the prophylaxis of migraine with or without aura. Following a 1 month single-blind placebo baseline period, 94 patients were equitably randomised under double-blind conditions to take flunarizine 10 mg daily or propranolol 80 mg twice daily for 4 months. Both treatments led to a significant reduction in the frequency of migraines and use of rescue analgesics with a significantly greater decrease in number of attacks for flunarizine after 1 and 4 months.

Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain.

To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa.

Comparative efficacy of dietary treatments on renal function in rats with sub-total nephrectomy: renal polyunsaturated fatty acid incorporation and prostaglandin excretion.

The efficacy of dietary intervention with either 6% protein restriction, fish oil or safflower oil was assessed in the remnant nephron model. Female Munich Wistar rats were prefed for one week prior to 5/6 nephrectomy and followed for the ensuing 28 days. Fish oil, safflower oil and protein restriction prevented the gammaglobulinuria but only fish oil lessened the albuminuria in this model.

A comparative analysis of two dosing strategies of flurbiprofen in rheumatoid arthritis: an application of sequential trial design.

Forty patients with classic or definite rheumatoid arthritis were entered into a double-blind, randomized, multiple crossover, sequential trial comparing two doses (300 mg vs 150 mg per day) and two dosing schedules (b.i.d.

The effects of a thromboxane synthase inhibitor, a prostacyclin analog and PGE1 on the nephritis of the NZB/W F1 mouse.

One hundred NZB/W F1 female mice were studied to compare the effects of a thromboxane synthase inhibitor (TSI), a stable prostacyclin analog (iloprost) and prostaglandin E1 (PGE1) in the evolution of the nephritis. At 10 weeks of age mice were randomly assigned to cohorts of 20 to receive either no treatment, vehicle control, PGE1, iloprost or TSI. Proteinuria, mortality, systemic blood pressure, renal immune complex deposition, urinary TX B2 and 6 keto PGF1 alpha levels were measured.

Calcium and the Fc receptor on human platelets.

We have described the calcium dependence of the IgG Fc receptor (Fc-R) on human platelets by analyzing the direct binding of radiolabelled Fc fragments, monomers and dimers of IgG. Specific binding to platelets was undetectable at 37 degrees C in a calcium-free preparation but readily detected when calcium was restored. Scatchard analysis of the binding data for the calcium-restored platelets permitted calculation of the available Fc-R and the Ka of binding for the different IgG ligands.

Midazolam: kinetics and effects on memory, sensorium, and haemodynamics.

This study aimed not only to compare the pharmacokinetics of oral and intravenous doses of the new water-soluble benzodiazepine, midazolam, but also to study the effects on haemodynamics, sensorium, and memory performance. Eight normal human volunteers each received a single 15 mg dose of midazolam base orally and intravenously in randomized sequence 2 weeks apart. Serial venous samples were obtained for 12 h after dosing.

Efficient pharmacokinetic modeling of complex clinical dosing regimens: the universal elementary dosing regimen and computer algorithm EDFAST.

Dosing regimens used in clinical practice are often complex, involving several different routes of administration, dose sizes, dosing rates, and dosing intervals and durations. A novel universal elementary dosing regimen (uedr), that allows general pharmacokinetic modeling of these clinical regimens, is presented and developed mathematically. The uedr concept is computationally efficient, mathematically exact, and logically simple, and can replace the disparate standard concepts and equations of elementary infusion, "bolus" injection, multiple injection, oral dosing, zero-order-release dosing, etc.

Lidocaine therapy with an exponentially declining infusion. Clinical evaluation of an optimized dosing technique.

A novel technique to achieve rapidly and continually maintain therapeutic lidocaine concentrations was designed according to known pharmacokinetic properties of the drug and was tested in 12 patients who required immediate lidocaine prophylaxis because of suspected acute myocardial infarction. The serum lidocaine concentrations achieved by this method remained within the therapeutic range (1.2 to 5.

Comparative trial of indapamide and hydrochlorothiazide in essential hypertension, with forearm plethysmography.

Seventeen patients (11 males) 34-66 years in age with uncomplicated essential hypertension completed a randomized, placebo-controlled, double-blind cross-over study comparing indapamide (IND) 2.5 mg q am with hydrochlorothiazide (HCT) 50 mg q am. The lead-in placebo period of 2 months was followed by two active drug phases of 3 months' duration separated by a 2-month placebo-washout period.

Kinetic disposition of intravenous ceftriaxone in normal subjects and patients with renal failure on hemodialysis or peritoneal dialysis.

The kinetic disposition of a single intravenous dose of ceftriaxone (250 to 665 mg) was studied in six normal subjects and nine patients with renal insufficiency and normal hepatic function. In normal subjects, ceftriaxone was eliminated with a t1/2 beta of 5.2 h (range, 4.

Factors influencing the long-term prognosis of treated patients with variant angina.

To determine the prognosis of variant angina and the factors influencing it, 169 consecutive patients hospitalized in our coronary unit were followed for a mean of 15.3 months (range 1 to 68). Survival at 1, 2, and 3 years was 95%, 90%, and 87%, respectively; survival without myocardial infarction was 80%, 78%, and 75%.

Biologic activity of metronidazole in plasma and urine of volunteers with normal or impaired renal function.

In this study, we have compared a bioassay procedure with high-pressure liquid chromatography (HPLC) for the determination of metronidazole levels in serum and urine. Plasma and urine of volunteers with normal or impaired renal function were obtained at various intervals after a single intravenous dose of 500 mg metronidazole. In plasma of normal volunteers 30 hours after dosing, the bioassay gave results comparable to the total values of the parent compound plus metabolites.

Metronidazole kinetics in dialysis patients.

Five volunteers with normal renal function (NOR) and eight patients with renal insufficiency (REN) were given a single dose of 500 mg metronidazole (MET) intravenously over 26 minutes. Serial venous plasma samples were taken at certain intervals for 30 hours. Four of the eight REN patients were also given the drug at the start of hemodialysis and four simultaneous inflow-outflow samples were taken over 4 hours of dialysis.