Does the one-leg rise test reflect quadriceps strength in individuals following anterior cruciate ligament reconstruction?

OBJECTIVE: To explore if one-leg rise test performance is associated with quadriceps strength following anterior cruciate ligament reconstruction (ACLR). DESIGN: Cross-sectional. PARTICIPANTS: 100 individuals (50 females, 50 males) aged 18-40 years, 9-36 months post-ACLR with ongoing knee symptoms (KOOS4 <80/100). MAIN OUTCOME MEASURES: Number of one-leg rise repetitions (using an adjustable-height plinth) and isometric quadriceps strength using isokinetic dynamometry (60° flexion, normalised to body mass). Multivariable fractional polynomial regression models adjusted for sex explored relationships between one-leg rise performance (repetitions) and quadriceps strength (Nm/kg) for each limb. RESULTS: A non-linear, increasing association between one-leg rise performance and quadriceps strength was observed, with the rate of increase attenuating at higher values of one-leg rise performance. Similar relationships were observed in the ACLR (ß = 0.15, 95%CI 0.10 to 0.20; adjusted r2 = 0.51) and contralateral limb (ß = 0.14, 95%CI 0.08 to 0.19; r2 = 0.42). CONCLUSION: The one-leg rise test can be an indicator of quadriceps strength in individuals after ACLR, enabling clinicians to easily monitor quadriceps strength recovery without specialised equipment. With the relationship between one-leg rise performance and quadriceps strength attenuating with a larger number of one-leg rises achieved, other factors (e.g., motivation, endurance) likely contribute to one-leg rise performance at higher values.

Kinetic interactions between 4-methylpyrazole and ethanol in healthy humans.

4-Methylpyrazole (4-MP), a potent inhibitor of alcohol dehydrogenase activity, is a candidate to replace ethanol as the antidote for methanol and ethylene glycol intoxications, because it has a longer duration of action and apparently fewer adverse effects. To study a probable mutual inhibitory effect between ethanol and 4-MP on their elimination, two studies were performed in healthy human volunteers using double-blind crossover designs. In study A1 4-MP in the presumed therapeutic dose range of 10 to 20 mg/kg caused a 40% reduction in the rate of elimination of ethanol in 12 subjects given 0.5 to 0.7 g/kg of ethanol. These data suggest that such doses of 4-MP inhibit alcohol dehydrogenase activity in humans in vivo and would be effective at blocking methanol or ethylene glycol metabolism. In study B, ethanol (0.6 g/kg followed by 0.2 g/kg twice) significantly decreased the rate of elimination of 4-MP (5 mg/kg, given intravenously to four subjects). These moderate doses of ethanol also inhibited the rate of urinary excretion of 4-carboxypyrazole, the primary metabolite of 4-MP in humans. Data suggest that ethanol inhibits 4-MP metabolism, thereby increasing the duration of therapeutic blood levels of 4-MP in the body. This mutual interaction may have clinical implications, because most self-poisoned patients have also ingested ethanol. Theoretically, methanol and ethylene glycol might also show such interactions with 4-MP.

Serum sodium stabilizing effect of enalapril after standard water load in a patient with a history of self-induced water intoxication.

1. A 21 day prospective placebo controlled double blind cross over trial of enalapril was studied in a normonatremic patient with a known history of SIWI. 2. At the end of each prophylactic treatment, the patient was challenged with a water load of 20 ml/kg. 3. The mean serum sodium of 140.111 mmol/L on prophylactic enalapril was significantly higher than the 137.6 mmol/L on placebo (p = 0.0015). 4. After a water load, the mean serum sodium on enalapril was 137.6 mmol/L, compared to 133.833 mmol/L (p = 0.0015) on placebo.

Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans.

4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, may be useful for the treatment of methanol and ethylene glycol intoxications. A placebo-controlled, double blind, multiple dose, sequential, ascending-dose study has been performed to determine the tolerance of 4-MP in healthy volunteers. Oral loading doses of 4-MP were followed by supplemental doses every 12 h through 5 days, producing plasma levels in the therapeutic range. A slight, transient elevation in one or both serum transaminase values was observed in 6 of the 15 subjects treated with 4-MP. This effect was not dose related nor apparently mediated through a hypersensitivity reaction. Serum triglyceride levels were increased in 30% of 4-MP treated subjects, but also in 25% of the placebo subjects. 4-MP treatment did not produce any other significant changes in objective clinical parameters nor in subjective side effects. The results suggest that a mild, transient increase in liver function tests might be observed in some subjects treated with multiple doses of 4-MP. Nevertheless, the slower elimination rate and lesser degree of toxicity of 4-MP would make it preferable to ethanol in therapy of these poisonings.

Effects of d-amphetamine on human aggressive responding maintained by avoidance of provocation.

Male subjects were administered placebo and three doses of d-amphetamine (5, 10 and 20 mg per 70 kg of body weight) under double-blind conditions in a laboratory setting which provided both aggressive and nonaggressive response options. the nonaggressive response was button pressing maintained by the presentation of points which were exchanged for money. The aggressive response was pressing another button which ostensibly resulted in the subtraction of points from a fictitious person. Aggressive responding was initiated by subtracting points from the subject. Point subtractions were attributed to the other person. Aggressive responding was maintained by an avoidance contingency between aggressive responses and scheduled provoking point subtraction presentations. d-Amphetamine increased nonaggressive responding, while aggressive responding was increased at the 10 mg dose and 20 mg resulted in significant decreases in aggressive responding relative to the 10 mg dose. Comparisons with previous research indicate that the contingency relationship between aggressive responses and presentation of provoking point subtractions can alter the effects of d-amphetamine on aggressive responding.

Non-linear kinetics of 4-methylpyrazole in healthy human subjects.

In order to evaluate the pharmacokinetic profile of the alcohol dehydrogenase inhibitor 4-methylpyrazole 4-MP, a placebo-controlled, double-blind, single-dose, randomized, sequential, ascending-dose "Phase-I study" was performed in healthy male volunteers at dose levels of 10 (n = 4), 20 (n = 4), 50 (n = 4) and 100 mg.kg-1 (n = 3). In the 10 and 20 mg.kg-1 group, the elimination of 4-MP from the plasma followed non-linear kinetics with mean rates of concentration decline of 3.66 and 5.05 mumol.l-1.h-1, respectively. In the two highest dose groups, the elimination also appeared to be non-linear although the patterns were not followed long enough to confirm this. The mean rates of concentration decline at the higher doses were significantly increased, up to 14.9 mumol.l-1.h-1 at 100 mg.kg-1. The average renal clearance of 4-MP was low, 0.016 ml.min-1.kg-1, and only 3% of the administered dose was excreted unchanged in the urine, indicating metabolism as the major route of elimination. Because of the apparently unusual kinetics following single dose treatment, thorough multiple dose studies need to be carried out to determine a safe dosage regimen for 4-MP.

Duration of the suppressive effect of tricyclic antidepressants on histamine-induced wheal-and-flare reactions in human skin.

The antihistaminic properties of the tricyclic antidepressants have been recognized since these compounds were first developed. Antidepressants, which are equally effective for treating depression or used in the treatment of chronic urticaria, have varying in vitro antihistaminic properties. We compared the duration of H1-receptor blockade by two tricyclic antidepressants, doxepin (the most potent antihistamine) and desipramine (the least potent antihistamine), in a single dose, double-blind, noncrossover study. After baseline prick test with histamine phosphate 1:1000 by Multitest (Lincoln Diagnostics, Decatur, Ill.), the suppression of cutaneous histamine-induced wheal-and-flare responses were measured daily for 7 days in 33 healthy volunteers who were randomly administered a single 25 mg dose of oral desipramine or doxepin. Significant differences in the suppression of the wheal-and-flare responses to histamine between the two drugs were noted (p less than 0.05) during the first 3 days. Desipramine suppressed the wheal for 2 days and flare for 1 day. Doxepin suppressed the wheal for 4 days and flare for 6 days. Our results suggest doxepin should be withheld for at least 7 days before allergy skin testing.

4-Methylpyrazole: a controlled study of safety in healthy human subjects after single, ascending doses.

4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, is a possible future drug for the treatment of methanol and ethylene glycol intoxications and the severe ethanol-disulfiram reaction. Therefore a placebo-controlled, double-blind, single-dose, randomized, sequential, ascending-dose "Phase I study" was performed in healthy volunteers in order to determine the tolerance of 4-MP at dose levels of 10 (n = 4), 20 (n = 4), 50 (n = 4), and 100 mg/kg (n = 3). Along with each dose group, there were two placebos except with the 100 mg/kg group where there was only one placebo. In the 10 and 20 mg/kg group there were no side-effects in any subject. At the 50 mg/kg level, three out of four subjects experienced slight to moderate nausea and dizziness from 0 to 2.5 h after dosing. In the 100 mg/kg group all three subjects reported side-effects like nausea, dizziness, and vertigo, that were short-lived in two subjects, but lasted up to 30 h in one subject. The study was stopped after evaluation of the latter subject, so fewer subjects were completed in this last group. Despite these subjective side-effects, there were no significant changes in objective clinical parameters like pulse, blood pressure, body temperature, or blood and urine chemistries. We conclude that at a single dose of 4-MP (10-20 mg/kg) producing plasma levels within a probable therapeutic range, no side-effects were attributed to 4-MP.

Alternative treatments for withdrawing the long-term benzodiazepine user: a pilot study.

Anxiolytic therapy with benzodiazepines and their potential for dependence are reviewed. Relaxation training and biofeedback have been used for chemically dependent anxious patients. These techniques have been recommended for benzodiazepine-dependent patients, but not investigated. Previous withdrawal studies offer only limited follow-up data. Stress management treatment was based on a successful case study. Recruitment difficulties were encountered. However, seven patients were randomly assigned to stress management or brief psycho-therapy. All showed improvement, but three of four patients available for 1 year follow-up had returned to pretreatment dependence. These withdrawal difficulties suggest the need for more effective treatments and more adequate follow-up studies.