Subtalar arthrodesis using a single compression screw: a comparison of results between anterograde and retrograde screwing.

INTRODUCTION: The primary objective of this study was to compare the radiological and clinical results of anterograde and retrograde screwing in subtalar arthrodesis using a single compression screw. The secondary objective was to evaluate the subjective results and consolidation of this procedure. The hypotheses were that isolated screw fixation was sufficient to achieve good consolidation and that there was no difference between the two techniques with a similar rate of bone fusion. METHODS: This is a monocentric, retrospective, radio-clinical study based on 99 patients (101 feet), 58 males and 41 females, with an average age of 64 years. The main aetiology was post-traumatic osteoarthritis, which represented 51% of cases. Two groups were formed: group A (52 feet) consisting of fixed arthrodesis with ascending (retrograde) screwing and group D (49 feet) consisting of fixed arthrodesis with descending (anterograde) screwing. The two groups were statistically comparable in terms of demographic data as well as aetiologies and comorbidities. Arthrodeses which were not fused at 6 months were reassessed at one year and in the event of any radio-clinical doubt regarding consolidation, an additional CT scan was prescribed. Average post-operative follow-up was 11 ± 5 years (2-27 years). RESULTS: Ninety-two arthrodeses (93%) were fused at one year and 9 were considered to be in non-union, 5 (9.8%) in group A, and 4 (8.3%) in group D. We recorded 30 complications, 22 of which were due to a conflict with the screw head, 18 (34.5%) in group A and 4 (8.3%) in group D (p = 0.03). Conflict between the screw head and the heel led to the removal of the screw after consolidation of the arthrodesis. The clinical results were evaluated using Odom's criteria. Nine per cent of patients described their results as excellent, 29% as good, 51% as satisfactory and 11% found the result to be poor. CONCLUSION: The fusion rate for isolated compression screw arthrodesis is good, and there is no difference between anterograde and retrograde screws. However, the discomfort caused by the screw head being insufficiently embedded in the retrograde group led to a non-negligible number of additional surgeries to remove the screw.

Are Schatzker and AO classifications accurate enough to classify tibial plateau fractures in alpine skiers?

PURPOSE: The aims of this study were (1) to collect prospectively all tibial plateau fractures admitted to our department, over two ski seasons, and to classify them according to the Schatzker and AO classifications; (2) to assess if these classifications are accurate enough to include all types of fractures; and (3) to compare theses fractures with the series found in the literature, which included very few or no skiing accidents. METHODS: During the 2016-2017 and 2017-2018 ski seasons, we prospectively included 116 tibial plateau fractures caused by downhill skiing accidents. All patients underwent standard X-rays and 2D and 3D CT scans. The fractures were classified according to the AO and Schatzker revisited classifications. RESULTS: The full series consisted of 56 males (48%) and 60 females (52%), aged 49 ± 16 years (18-77). There were 60 type B (52%) and 56 type C fractures (48%) for AO classification and 45.5% types I, II and III and 54.5% types IV, V and VI for Schatzker classification. Thirty-five frontal fractures (30%) were not differentiated under the AO classification and, likewise, associated tibial spine fractures (28.5%) were not differentiated in the Schatzker classification. We were also unable to classify anterior tibial tuberosity fractures (14.5%) and fibula head fractures (8%). The anatomo-pathological types were not so different from road traffic accidents. CONCLUSION: Contrary to our hypothesis, the anatomical-pathological damage in tibial plateau fractures resulting from downhill skiing accidents was barely any different from those found in road traffic accidents. However, despite progress in classifications with the emergence of 3D CT scans, it is still not always possible to categorise all fractures within a given classification.

Malunion of the Acetabulum Treated by Intra-articular Buttress.

Acetabulum malunions are extremely difficult to treat, and for many years, surgical indications have been dominated by total hip replacement. We treated a protruding acetabular malunion, 20 years ago, using an intra-articular buttress, by means of an allograft corresponding to a femoral head fragment which had been cryopreserved. The radiological and clinical result with this extended follow-up is quite remarkable, which has motivated us to present this original technique.

Posterior cruciate ligament reconstruction for chronic lesions: clinical experience with hamstring versus ligament advanced reinforcement system as graft.

PURPOSE: The aim of this study was to compare clinical and laximetric results in chronic, isolated posterior cruciate ligament (PCL) rupture repairs, using either a hamstring graft or an artificial ligament (ligament advanced reinforcement system (LARS®)). METHODS: Sixteen patients presenting with an isolated unilateral PCL rupture were included in this retrospective study. Initially, eight underwent a PCL reconstruction using a hamstring tendon autograft (hamstring group), and over a later period, eight further patients underwent a reconstruction using an artificial ligament with a new procedure. RESULTS: Fifteen patients were male and one female, with an average age of 29.3 years. All patients were operated on within an average time of 18 months post-injury. Pre-operative posterior laxity was equivalent (p = 0.309), 18.25 mm on average for the hamstring group and 18.75 mm for the LARS group. With an average follow-up of 24 months, residual posterior laxity was significantly improved, decreasing from 18.25 to 7.37 mm for the hamstring group (p < 0.05) with a median at 7.5 mm and from 18.75 to 5.25 mm for the LARS group (p < 0.05) with a median at 5 mm. The improvement in laxity for the hamstring group was 60% and 71.5% for the LARS group. The LARS group compares favourably (p = 0.003 and 0.01). Tegner activity level improved significantly following ligamentoplasty, with no difference between the two groups (p = 0.4). Likewise, there was no significant difference in the Lysholm and IKDC scores between the two groups (p = 0.4). CONCLUSION: The initial hypothesis of this study was proven correct. Nevertheless, a longer term study is necessary to assess the consequences of residual laxity in hamstring grafts and the long-term behaviour and tolerance of the LARS artificial ligament.

Independent clinical appraisal of the Tape Locking Screw (TLS®) anterior cruciate ligament reconstruction technique compared with the hamstring graft technique with a minimum of 12-month follow-up.

INTRODUCTION: The aim of this study was to assess the differential laxity after reconstruction of the anterior cruciate ligament (ACL) by the TLS® technique using a single tendon, the semitendinosus in four-strand graft, compared with the hamstring technique which uses both the gracilis and semitendinosus. We hypothesised that this surgical technique would provide post-surgical differential laxity measurements at least as good as those of the hamstring technique. MATERIALS AND METHODS: We carried out a prospective monocentric study on patients undergoing unilateral anterior cruciate ligament repair between December 2014 and June 2016. All patients were followed up for at least 12 months. The series compares 61 patients operated on using the TLS® technique by the same surgeon, with 33 patients operated on using the hamstring technique by a second surgeon. The main objective of the study was to compare the post-operative differential laxity, measured using the KT1000, between the two techniques. RESULTS: There was no significant difference in the patients' epidemiological characteristics and pre-operative scores between the two groups. Average pre-operative differential laxity was 6.5 mm ± 2.1 (min 3; max 12) in the TLS group and 6.4 mm ± 2.0 (min 0; max 11) in the hamstring group, with no statistically significant difference. The average post-operative difference in laxity was - 0.1 mm ± 1.9 (min - 5; max 4) in the TLS group and 0.3 mm ± 2.0 (min - 7; max 5) in the hamstring group. Again, no significant difference was observed between groups. DISCUSSION: This study demonstrates a level of post-operative differential laxity control using TLS comparable with that of the ACL reconstruction technique using a hamstring graft with preserved tibial insertion. LEVEL OF EVIDENCE: II, prospective cohort study.

Pharmacokinetic and pharmacodynamic study of suriclone imipramine interaction in man.

Suriclone is a novel cyclopyrrolone exhibiting anxiolytic activity. Twelve healthy Caucasian male volunteers participated in the study. A single dose of suriclone 0.4 mg, imipramine 75 mg, suriclone 0.4 mg + imipramine 75 mg, or placebo was given according to a 4 x 4 Latin-square design in order to assess the effect of drug association on pharmacokinetics and psychomotor performances. Visual analogue scale ratings, critical flicker frequency, choice visual reaction time, and Pauli, picture memory and Sternberg tests were performed before and 1.5, 6 and 9 h after drug administration. Suriclone, with the exception of the Pauli test, had no effect on psychomotor performances. The imipramine-suriclone association appeared to disturb some performances (no statistical significance), probably due to the effect of imipramine. Blood samples were collected for determination of imipramine and suriclone plasma levels respectively by high-performance liquid chromatography and radioimmunoassays. Suriclone AUC, Cmax and Tmax were not affected by imipramine, and reciprocally.

Inhibition of ex-vivo PAF-induced platelet aggregation by the PAF-antagonist RP 48740: relationship to plasma concentrations in healthy volunteers.

RP 48740, 3-(3-pyridyl)-1H,3H-pyrrolo [1,2-c] thiazole-7-carboxamide, a specific competitive PAF-receptor antagonist in vitro, was given to 29 healthy male volunteers for 7 days. Plasma drug concentrations and ex-vivo PAF-induced platelet aggregation were assessed on Days 1, 4, and 7. RP 48740 had linear pharmacokinetics after single and repeated doses. It caused stable inhibition of PAF-induced platelet aggregation in a dose-dependent manner. The effect disappeared within 24 h, even after 7 days of repeated doses. The effect of RP 48740 displayed a sigmoidal relation to the plasma drug concentration; I50 2.3 (0.3) mg.l-1. There were no clinical or biological adverse reactions to RP 48740 during the study.

Pharmacokinetics of pyrimethamine in healthy young volunteers using a new solid phase extraction/HPLC method.

The single dose pharmacokinetics of pyrimethamine were determined in 12 healthy young volunteers using a newly developed fully automated analytical system which combines liquid solid extraction on disposable extraction columns and high performance liquid chromatography. This technique is highly sensitive (detection 1 ng/ml) and reproducible. Following a 50mg dose of the drug, the plasma concentration peaked at 0.48 0.13 g/ml (msd) and was attained 2.5 hours (median value) post dosing. Thereafter, the plasma level of pyrimethamine decreased slowly, the level at 336 hours after administration being still about 40 ng/ml. The area under the plasma concentration-time curve (AUC0-inf) was 56.8 18.4 h.mg/ml. The volume of distribution Vd was: 2.42 1.25 l/kg and the total clearance: 15.55 4.48 ml/h/kg. Urinary excretion represented about 20% to 40% of the dose after seven days of the administered dose.

Evaluation of Bayesian estimation to discriminate subpopulations of patients with altered pharmacokinetics using fragmentary data: a pilot study with pefloxacin.

Bayesian estimation of individual pefloxacin pharmacokinetic parameters was evaluated in patients with renal (n = 34) or hepatic (n = 16) impairments who participated in experimental pharmacokinetic studies during pefloxacin development. The trials involved singly intravenous dosing (300 to 850 mg as 0.5 to 1h-infusion) and serial pefloxacin plasma level measurements (n = 10-18 over 72-96 h). Bayesian estimation used only 2 measured plasma levels (end of infusion and either 12 hour (BE 12h) or 48 hour (BE 48h) levels) and a priori information obtained in a reference population of healthy volunteers (n = 19). The performance of Bayesian estimation in predicting total plasma clearance (Cl), elimination half-life (t1/2) and steady state volume of distribution (Vss) was evaluated with respect to weighted nonlinear least-square estimates using all the data points and a two-compartment model. Pharmacokinetic parameters (and their inter-individual variability) in patients differed significantly from those of healthy volunteers (e.g. t1/2 of 22 +/- 14 h, range 6-81 h vs. 11 +/- 2 h, range 8-17, p less than 0.001). BE 12h provided biased estimates of Cl and t1/2 (24 and 28% respectively) and poor precision (30 and 53% respectively), Vss being well estimated. The BE 48h estimator had good performance with unsignificant bias (less than 1%) and good precision (extremes 13 and 27% for Cl and t1/2 respectively). Patients with hepatic impairment had the more pronounced pharmacokinetics modifications and could even be discriminated from healthy volunteers using the biased BE 12h estimates. These results suggest that Bayesian estimation is quite robust to the a priori information.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of fluoroquinolones in hepatic failure.

In patients with alcoholic cirrhosis, the pharmacokinetics of the fluoroquinolones were variously altered. The kinetics of ciprofloxacin were slightly modified in patients with mild or moderate impairment. Ofloxacin kinetics were influenced by renal dysfunction encountered in patients with ascites. Pefloxacin kinetics were markedly modified with wide variations in elimination among patients. Ascitic penetration of ofloxacin and pefloxacin was excellent. Since no relationship between ofloxacin or pefloxacin kinetics and the usual liver function tests was found, recommended dosage regimens in cirrhotic patients have to be controlled by monitoring plasma drug levels during treatment.

The excretion of zopiclone into breast milk.

1. The excretion of zopiclone into breast milk was studied in 12 lactating women in the early postpartum period following the oral administration of a single zopiclone tablet (7.5 mg). 2. The milk/plasma AUC ratio of zopiclone was 0.51 +/- 0.09 (mean +/- s.d.). Individual mean milk/plasma concentration ratios of zopiclone showed significant interindividual variation (range 0.41-0.70). 3. A comparison of pharmacokinetic parameters in the postpartum women with those reported previously in non-pregnant women, showed significantly higher Cmax values in the lactating mothers; tmax occurred later in milk than in maternal plasma. 4. Assuming a daily milk intake of 0.15 l kg-1 and 100% absorption the average infant dose of zopiclone in milk would be 1.4% of the weight adjusted dose ingested by the mother.

Steady state pharmacokinetics of zopiclone during multiple oral dosing (7.5 mg nocte) in patients with severe chronic renal failure.

Zopiclone is a new hypnotic cyclopyrrolone with a short elimination half-life (5.3 h). The pharmacokinetic profile of this drug was studied in 7 chronic renal failure (CRF) patients given 7.5 mg nocte for 7 consecutive nights. The pharmacokinetic values obtained were compared with the corresponding values found in healthy young volunteers given the same repeated dosage regimen. C max and T max were not significantly different between the two groups but the C min of unchanged zopiclone (at 24 h) post-dosing was significantly (p less than 0.001) higher in CRF patients (8.16 +/- 5.34 ng/ml) than in healthy volunteers (1.90 +/- 0.82 ng/ml). The AUC values in CRF patients were also significantly increased during the seventh day (742 +/- 212 h ng/ml) compared to healthy subjects (408 +/- 66.5 h ng/ml) and the elimination half-life of zopiclone was also longer in CRF patients (about 8 h) than in the reference group (about 5 h). Nevertheless, the accumulation ratios remained similar in the two groups (1.09 +/- 0.18 in CRF patients and 1.02 +/- 0.2 in healthy subjects). Thus no evident accumulation of zopiclone appeared in the CRF patients. As in the healthy subjects, no metabolites were detected in the plasma of the CRF patients although at steady state the urinary excretion of zopiclone and its N-oxide and N-desmethyl derivatives (2.03% +/- 1.52% and 1.99 +/- 0.65% of the dose, respectively) was significantly decreased compared to healthy subjects (3.7% +/- 2.1% and 32.6% +/- 4.5%, respectively). Zopiclone thus represents a safe alternative to benzodiazepine hypnotic therapy in patients with renal impairment.

Interaction of suriclone with central type benzodiazepine receptors in living baboons.

The interaction of suriclone and two of its main metabolites with central type benzodiazepine receptors, which had been labeled in vivo with the radioligand [11C]RO 15-1788, was investigated in living baboons. The concentration of radioligand bound to the receptors, as measured in brain transverse sections by positron emission tomography, decreased rapidly after the i.v. administration of suriclone at doses known to induce pharmacological effects. The rate and extent to which [11C]RO 15-1788 binding was displaced increased with increasing doses of suriclone. The half-inhibitory dose (ID50) was determined to be 0.08 mg/kg in vivo. The rapid inhibitory effect of suriclone on the in vivo binding of [11C]RO 15-1788 in the brain seems to reflect its ability to act at the GABA-benzodiazepine receptor complex, at or near to the benzodiazepine binding site, to induce its pharmacological activity. The i.v. injection of the demethylated metabolite of suriclone, RP 35,489, only caused a slight displacement of [11C]RO 15-1788 binding even at a dose of 2 mg/kg. Thus, suriclone appears to be more potent than RP 35,489 to displace the benzodiazepine 11C antagonist in vivo. The sulfoxide metabolite, RP 46,166, did not significantly change the kinetics of [11C]RO 15-1788 binding in the brain. The slight effects produced by high doses of RP 35,489 and RP 46,166 on [11C]RO 15-1788 binding in the brain suggest that these metabolites are probably not responsible for the expression of biological activity of suriclone mediated by benzodiazepine receptors.

[Pharmacokinetics of cefixime in healthy volunteers after a single oral administration of 200 mg]. / Pharmacocinétique du céfixime chez le volontaire sain après administration orale unique à la dose de 200 mg.

The antibacterial activity of cefixime is identical with that of parenteral third generation cephalosporins. Its kinetics were studied in 24 healthy male volunteers who received one single 200 mg tablet. Cmax was 3.25 mg/l and Tmax was 4 h. After 12 hours, serum concentrations were still as high as 0.70 mg/l. Half-life was 3.3 h and urinary excretion was not predominant. Thus, cefixime was characterized by its relatively long serum half-life as compared with other cephalosporins. Despite some degree of individual variations, serum and urine concentrations of the antibiotic remained for 12 hours above the MIC of susceptible pathogens.

Chronopharmacokinetic and bioequivalence studies of two formulations of trimipramine after oral administration in man.

The bioavailability of two oral formulations of trimipramine, tablets and solution, was performed in twelve healthy volunteers, in a cross-over study. Each formulation was administered in the morning after a fasted period, and in the evening after a meal, in order to evaluate the role of both administration time and food consumption on the plasma kinetic parameters, under usual therapeutic conditions. A high interindividual variability of data was found. First, the extent of bioavailability was identical for the two formulations but the rate of bioavailability seemed to be different, with the p.o. solution, being more rapidly absorbed (tmax = 1.50 h). The effect of administration time was more obvious for the solution as shown by a lower quantitative absorption as well as a delay in time to reach the maximal concentration. Regardless of formulation and administration time, the t1/2 beta was about 10 hours and the mean MRT value was 11 hours.

Pharmacokinetics of spiramycin in man.

The pharmacokinetics of spiramycin were studied after single and repeated administration by iv and oral routes. Following iv administration of a 500-mg dose in a one-hour infusion, peak serum concentrations were 1.54-3.10 mg/l. These concentrations are higher than MICs of spiramycin for various infectious agents. Eight hours after the end of infusion, the mean serum concentration was close to 0.25 mg/l. Spiramycin is rapidly and widely distributed throughout the body and achieves high ratios of tissue to serum concentrations in bucco-dental, pulmonary and prostatic tissues and skin. The distribution half-life of spiramycin was 10 min. The steady-state volume of distribution (Vdss) and the tissue distribution volume were 5.6 and 4.5 l/kg. The absolute bioavailability of spiramycin was 36% (S.D. +/- 14). Oral doses of spiramycin between 1 and 2 g resulted in linear increase in the peak serum levels and areas under the serum concentration-time curve. Spiramycin does not appear to undergo important metabolic conversion and is mainly excreted via the biliary route. Indeed, in man, the urinary excretion of active compounds represents only 7.6 to 20% of the administered dose. Spiramycin had a terminal elimination half-life of approximately 5 h. Renal clearance (144 ml/min) was much lower than non-renal clearance (887 ml/min). The total body clearance of spiramycin in young adults was 1.42 l/min (S.D. +/- 0.5) but only 0.53 l/min (S.D. +/- 14) in elderly subjects. During repeated iv administration (500 mg tid), steady state was achieved after four doses. Cmax and Cmin were 3.0 and 0.5 mg/l in young adults and 4.5 and 1.75 mg/l in elderly patients. Spiramycin's kinetics differ in several important respects from erythromycin's, notably the larger volume of distribution of spiramycin which reflects the higher tissue concentration. The reduced spiramycin clearance in elderly subjects requires further investigation.

Simultaneous determination of zopiclone and its two major metabolites (N-oxide and N-desmethyl) in human biological fluids by reversed-phase high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of zopiclone and its main metabolites (N-oxide and N-desmethyl derivatives) in biological fluids. After selective extraction (dichloromethane-2-propanol) these compounds are chromatographed on a column packed with Spherisorb ODS-2 (5 micron) using monobasic sodium phosphate-methanol (45:55, v/v). The eluted compounds are measured by fluorescence detection. The limit of detection of the method is 5 ng/ml for zopiclone in plasma and urine and 10 ng/ml for its two main metabolites (coefficient of variation less than 10%). This method has been successfully applied to pharmacokinetic studies of zopiclone and its two main metabolites in healthy subjects and patients with chronic renal failure.

Critical factors for pharmacokinetics of zopiclone in the elderly and in patients with liver and renal insufficiency.

Zopiclone, a new hypnotic cyclopyrrolone, undergoes extensive hepatic metabolism. The carrier of hypnotic activity is the parent compound; however, knowledge of its metabolic profile is essential for the understanding of pharmacokinetic changes in various pathophysiological conditions. In 45 healthy young volunteers, zopiclone had a Tmax of 0.5. A first-pass effect of 20% resulted in an absolute bioavailability, F, of 77%. The volume of distribution ratio Vdc/Vdt was 3.2. The plasma half-life (t1/2) was 5.1 h. A metabolic ratio of 3.7 and 4.6 was found for the two main urinary metabolites, N-oxide and N-desmethyl derivatives. No modifications of kinetics were seen after chronic treatment. In eight patients with liver insufficiency, the main changes (delayed Tmax, 3.5 h, higher plasma concentrations with an increased F of 97%, prolonged t1/2 of 8.4 h) were essentially due to a reduced hepatic metabolic clearance, as shown by a decreased metabolic ratio for the two main metabolites. In 18 patients with renal insufficiency, the only major modification was an increased bioavailability (F of 115%) probably due to a relative decrease of the Vdc. In 19 elderly subjects, the main findings were a decreased metabolic clearance, as shown by decreased metabolic ratios, and an inversion of the Vdc/Vdt ratio, evoking the changes seen in renal insufficiency. The increase in F (168%) and the age-dependent increase in plasma t1/2 (8.1 h) in the oldest subjects (over 74 years of age) can be explained by this double mechanism. On the basis of these findings, a reduction of the initial zopiclone dose from 7.5 to 3.5 mg/day is recommended for patients with severe liver insufficiency and patients over 70 years of age with liver insufficiency.

Isosorbide dinitrate: relationship between pharmacokinetics and brachial artery hemodynamics in essential hypertension.

Pharmacokinetics of isosorbide dinitrate (ISDN) and brachial arterial hemodynamics have been studied in 15 patients with sustained essential hypertension. The hemodynamic study was performed by using a pulsed Doppler device enabling evaluation of the diameter of the brachial artery with an error of less than 10%. After intravenous administration until plateau concentrations were reached, the ISDN infusion was stopped in order to study the disappearance curve of the drug and the pharmacokinetic parameters. ISDN caused a significant decrease in systolic pressure, a significant increase in arterial diameter, and no change in heart rate. Brachial hemodynamics were not correlated with the plasma concentration in the steady state or the area under the disappearance curve. In contrast, the changes in arterial diameter during perfusion were significantly correlated with the apparent distribution volume, a finding that might indirectly reflect the affinity of ISDN for vascular tissues.