Adductor canal versus femoral triangle anatomical locations for continuous catheter analgesia after total knee arthroplasty: a multicentre randomised controlled study.

BACKGROUND: Adductor canal (AC) catheters are being used to provide continuous postoperative analgesia after total knee arthroplasty (TKA) surgery. There are anatomical arguments that most AC catheters are being inserted into the femoral triangle (FT) compartment of the thigh rather than the AC compartment. The clinical relevance of this is unknown with respect to motor weakness, quality of analgesia, and opioid consumption. We hypothesised that AC catheters provide superior functional mobilisation on postoperative Day 1 after TKA as measured using the Timed Up and Go (TUG) test. METHODS: In this multinational, multicentre, double-blinded RCT, catheters were inserted under ultrasound guidance into the anatomical AC and FT compartments. The standardised protocol included spinal anaesthesia without intrathecal morphine, fixed catheter infusion rates, and oral analgesia. RESULTS: Of 151 subjects recruited, 75 were in the AC group and 76 in the FT group. There was no statistically significant difference in TUG on postoperative Day 1 between AC (38 [29-55] s) and FT subjects (44 [32-64] s) (median [inter-quartile range]); P=0.11). There was no difference in TUG Day 2, AC (38 [27-53] s) vs FT (42 [31-59] s); P=0.66. There were no statistically significant differences for secondary endpoints of pain level, effectiveness of pain relief, interference of functional activities and interpersonal relationships by pain, and opioid consumption between groups. CONCLUSIONS: There were no differences in immediate postoperative functional mobility, analgesia, and opioid consumption provided by catheters inserted into the AC vs FT locations for TKA surgery. CLINICAL TRIAL REGISTRATION: ANZCTR12617001421325.

[Use of a medical discharge sheet for medication reconciliation in an internal medicine department: Assessment of general practitioners' opinion]. / Conciliation médicamenteuse avec remise d'une fiche de conciliation de sortie dans un service de Médecine Interne : évaluation de la perception des médecins généralistes.

BACKGROUND: Medication reconciliation (MR) is a systematic and comprehensive review of all medication a patient is taking. In this study, a discharge medication sheet (DMS) is given to patients upon discharge: it contains discharge prescription and any changes made to admission prescription with justifications. The aim of this study is to explore general practitioners' (GP) perceptions of this DMS in order to suggest improvements. METHODS: In this prospective observational study, individual semi-directed interviews were conducted with GPs who received a DMS following the hospitalization of one of their patients. Answers were grouped by topic and subjected to descriptive analysis. RESULTS: Between October 2015 and July 2016, 33 DMS were completed. Among the 33 GPs, 16 had seen their patients with their DMS and agreed to be interviewed. The DMS was very appreciated and improved care pathway. However, this study highlights transmission difficulties for this sheet, attributed in particular to a lack of information of practitioners and patients and to the paper format, which appears to be inadequate. The main suggested improvement is real-time transmission of the DMS via email. CONCLUSION: Practitioners' opinion is in favor of the use of a DMS. Certain specific points need to be improved, such as better information of practitioners and patients, and transmission of the DMS via a secure email system.

Proctolin-like immunoreactivity in dorsal paired median neurons generating plateau action potentials in cockroach Periplaneta americana.

The proctolinergic nature of dorsal paired median (DPM) neurons generating plateau action potentials (PAPs) of the cockroach CNS has been demonstrated using a double labelling technique (lucifer yellow staining and proctolin-like immunochemistry). Electrophysiological results support morphological evidence that a direct pathway exists from axons passing throughout the proctodeal nerves to electrically active DPM neuron somata. However, the occurrence of spike failure along the neuritic membrane and the existence of a neuritic spike initiating site has been postulated because spontaneous PAPs recorded intracellularly were not associated on a one-to-one basis with peripheral axon spikes.

Neuritic GABAergic synapses in insect neurosecretory cells.

The localization of synaptic gamma-aminobutyric acid (GABA) receptors on cockroach dorsal unpaired median (DUM) neurons of the last abdominal ganglion was investigated. These neurosecretory cells, mainly octopaminergic, possess a soma located on the dorsal midline of the ganglion, from which emerges a short primary neurite dividing into two symmetrical lateral branches on both lateral edges of the ganglion. GABA pressure ejections onto the soma and onto the neuritic arborization elicited hyperpolarizations. Moreover, electrical stimulation of the anterior connectives evoked a postsynaptic potential, mainly inhibitory. This response and the GABA hyperpolarization of the neuritic field are antagonized by lateral application of picrotoxin while soma GABA hyperpolarization remained unchanged. This suggests that there are two kinds of GABA receptors located (i) onto the soma membrane of the DUM neurons and called extrasynaptic receptors, (ii) on the neuritic arborization, called synaptic receptors and implicated in the connection between neurons coming from the anterior part of the nervous system and the DUM cells. Immunohistological double staining technique reinforced the electrophysiological results by showing the presence of GABA-like immunoreactive processes next to octopamine-like immunoreactive ones.

Synaptic currents recorded from the dendritic field of an insect giant interneurone.

A method is described enabling the recording of synaptic currents from an isolated interganglionic interneurone in the central nervous system of the cockroach, Periplaneta americana, using an oil-gap recording system. The circuitry contains a Wheatstone bridge in which the preparation is the unknown resistance. Using a voltage-clamp technique, both excitatory and inhibitory postsynaptic currents together with currents induced by metabolic changes can be detected.

Sensitive nicotinic and mixed nicotinic-muscarinic receptors in insect neurosecretory cells.

Short-term cultured dorsal unpaired median neurones from adult cockroach, Periplaneta americana, have been used to study alpha-bungarotoxin-resistant cholinergic receptors. Both acetylcholine and nicotine applied by pressure ejection to the neuronal soma induced depolarizing responses recorded with the patch-clamp technique in the whole cell recording configuration. Nicotine was more potent than acetylcholine and developed a dose-dependent biphasic depolarization including a fast and a slow component. The slow component was sensitive to alpha-bungarotoxin, d-tubocurarine, pirenzepine and gallamine, whereas the fast component was resistant to these nicotinic and muscarinic antagonists. These results demonstrate that two distinct functional receptors exist: a sensitive nicotinic and a 'mixed' (nicotinic muscarinic) receptor governing a nicotine-induced biphasic response.

BIDN, a bicyclic dinitrile convulsant, selectively blocks GABA-gated Cl- channels.

BIDN (3,3-bis(trifluoromethyl)bicyclo[2,2,1]heptane-2,2-dicarbonitrile) at 10(-5) M blocked GABA-induced inhibitory postsynaptic potentials (IPSPs) recorded from an identified, giant interneuron (G12) of the cockroach (Periplaneta americana). The same concentration of this bicyclic dinitrile also blocked Cl- -mediated responses of G12 to GABA applied by pressure microinjection into the terminal abdominal ganglion neuropile containing dendrites of G12. BIDN (10(-5) M) was without effect on a response of G12 to GABA known to be mediated by a GABAB type receptor. In studies of the cell body of an identified motor neurone, the fast coxal depressor (Df) in the cockroach metathoracic ganglion, BIDN (10(-5) M) blocked reversibly an extrasynaptic GABA-gated Cl- channel, but not an extrasynaptic L-glutamate-gated Cl- channel. Glycine-gated Cl- channels observed when rat brain messenger RNA was expressed in Xenopus laevis oocytes were unaffected by BIDN at concentrations up to 10(-4) M, whereas this same concentration of BIDN completely blocked GABA-gated Cl- responses recorded from the same preparations. Unlike picrotoxin, which antagonises a variety of ligand-gated Cl- channels, to date BIDN has been found to block only Cl- channels gated by GABA, both in insect and vertebrate preparations.

Postsynaptic effects of 4-aminopyridine in the sixth abdominal ganglion of the cockroach.

The synaptic action of 4-aminopyridine (4-AP) was studied in the sixth abdominal ganglion of the cockroach Periplaneta americana L. The drug 4-AP did not modify the affinity of cholinergic receptors. At concentrations above 10(-4)M, 4-AP depolarized the postsynaptic membranes even after blockage of muscarinic and nicotinic receptors by antagonistic substances.

Effects of McN-A-343 on insect neurosecretory cells: evidence for muscarinic-like receptor subtypes.

The muscarinic agonist McN-A-343 has been used to characterize the muscarinic receptors on somata of adult cockroach dorsal unpaired median (DUM) neurones maintained in short-term culture. Pressure application of McN-A-343 onto isolated DUM neurones induced a dose- and voltage-dependent biphasic response composed of a fast initial hyperpolarization followed by a slow depolarizing phase, recorded with the patch-clamp technique in the whole-cell recording configuration. The fast hyperpolarization reversed at an extrapolated potential value of -91.04 mV and was fully antagonized by the M2 muscarinic antagonist methoctramine. The slow depolarizing component reversed at an extrapolated value of -28.33 mV and was inhibited by the M1 muscarinic antagonist pirenzepine. These results demonstrate both a specific effect for McN-A-343 on DUM neurones and the existence of two functionally distinct muscarinic-like receptor subtypes governing this McN-A-343-induced biphasic response.

Effects of a centipede venom fraction on insect nervous system, a native Xenopus oocyte receptor and on an expressed Drosophila muscarinic receptor.

Centipede venoms are complex protein mixtures; very few is known about their pharmacological actions. Application of a Scolopendra sp. venom fraction (SC1) on the cockroach giant axon induced an increase in the leak current correlated with a decrease in the membrane resistance, suggesting the presence in SC1 of components opening non-specific pores in the axonal membrane. On a cockroach central cholinergic synapse, microinjection of SC1 induced a small transient depolarization of the postsynaptic membrane, followed by a slow stable depolarization and a drastic decrease in the evoked subthreshold excitatory postsynaptic potential amplitude. A pretreatment of the ganglion with atropine or scopolamine reduced the amplitude of the SC1-induced depolarizing wave, suggesting a possible cholinergic muscarinic target. On control Xenopus oocytes, SC1 induced an inward oscillatory Ca2(+)-dependent Cl- current mediated through the activation of native lysophosphatidic acid receptors (LPAr). Indeed, pretreatment of oocytes with 1 microM N-palmitoyl-tyrosine phosphoric acid, a selective competitive antagonist of LPAr, decreased responses to SC1 by 70%. Application of SC1 to oocytes expressing a cloned Drosophila muscarinic receptor (Dml) induced a biphasic response comprising: (1) a large fast Cl- current that was abolished by pretreatment with atropine and scopolamine and (2) a slow and small oscillating Cl- current corresponding to the response observed in control oocytes. These observations confirm the presence of muscarinic agonists in SCI and reveal their direct action on an insect muscarinic receptor subtype homologous to mammalian M1-M3 receptors.

Clonazepam in acute mania: time-blind evaluation of clinical response and concentrations in plasma.

This study was performed to evaluate the optimal doses and clinical efficacy of clonazepam as a first-line drug in acute mania, as well as to determine its effective plasma concentrations. Clonazepam was administered orally to 11 newly admitted inpatients. On day 0, the loading dose was titrated upward according to the clinical global impression; the maintenance dose was calculated with intent to maintain the plasma level that had been achieved after initial dose escalation. Clinically based dose adjustments were allowed on days 4 and 7. Manic symptoms were scored on days 0, 4 and 14 according to a time-blind procedure; clonazepam plasma levels were measured by HPLC. On day 14, there was a significant decrease in manic symptoms and 66.7% of the patients who completed the trial were markedly improved. Steady-state plasma levels of clonazepam were significantly correlated with daily doses (rs = 0.795, P < 0.005) and therapeutic concentrations ranged between 6.5-83.9 micrograms/l. At the onset of therapy, the clinically titrated loading dose resulted in plasma concentrations within the narrow range of 18.9-34.0 micrograms/l. These results support the potential value of clonazepam in the short-term management of acute mania; the initial control of agitation was achieved with plasma drug levels in a remarkably narrow range as compared with the further control of mania.

A double-blind comparison of clonazepam and placebo in the treatment of neuroleptic-induced akathisia.

The present study was designed to investigate the efficacy of clonazepam in neuroleptic-induced akathisia. Twelve patients were treated during 2 weeks with clonazepam or placebo in a double-blind randomized design. Akathisia was scored by an independent rater before and after treatment, as well as 1 week after medication withdrawal. Clonazepam (0.5-2.5 mg/day) induced a significantly higher reduction in the akathisia scores than placebo (p < 0.05). One week after stopping the drug, there was a partial but significant relapse in the treated group as compared with controls, in whom the symptoms remained stable. In addition, the clinical improvement was significantly correlated with the daily dose of clonazepam (rs = 0.827; p < 0.002). These results support the potential usefulness of clonazepam in the treatment of neuroleptic-induced akathisia and suggest an optimal daily dose in the range of 10-40 micrograms/kg.

Pilot investigation of thyrotropin-releasing hormone-induced thyrotropin and prolactin release in anxious patients treated with diazepam.

Benzodiazepines have been reported to inhibit thyrotropin (TSH) and prolactin (PRL) secretion in response to stressful and pharmacologic stimuli in experimental animals. The current study investigates basal and thyrotropin-releasing hormone (TRH)-stimulated TSH and PRL release in anxious patients treated with diazepam. Six hospitalized patients having generalized anxiety or adjustment disorder with anxious mood (DSM III-R criteria) were treated during 1 week with diazepam (mean daily dose 33.3 mg). TRH testing was performed comparatively before and after 7 days of diazepam administration (with 250 micrograms protirelin and blood sampling at 15-min intervals over 60 min). Steady-state plasma levels of diazepam and its metabolite nordazepam (desmethyldiazepam) were determined by high-performance liquid chromatography. After 7 days of diazepam treatment, basal plasma levels of TSH and PRL were not affected compared with pretreatment values. Similarly, the time-course of TRH-induced TSH release was not modified by the treatment. By contrast, there was a trend to decrease in the TRH-induced PRL release, and the decrease in the PRL response to TRH on day 7 was significantly correlated with plasma nordazepam concentrations (rs = 0.943, p = 0.02). These preliminary results suggest that benzodiazepines, at therapeutic doses for the treatment of anxiety, may alter TRH-induced PRL release in humans.

Therapeutic isoniazid monitoring using a simple high-performance liquid chromatographic method with ultraviolet detection.

Simultaneous measurement of isoniazid and its main acetylated metabolite acetylisoniazid in human plasma is realized by high-performance liquid chromatography. The technique used is evaluated by a factorial design of validation that proved to be convenient for routine drug monitoring. Plasma samples are deproteinized by trichloroacetic acid and then the analytes are separated on a microBondapak C18 column (Waters). Nicotinamide is used as an internal standard. The mobile phase is 0.05 M ammonium acetate buffer (pH 6)-acetonitrile (99:1, v/v). The detection is by ultraviolet absorbance at 275 nm. The validation, using the factorial design allows one to: (a) test the systematic factors of bias (linearity and matrix effect); (b) estimate the relative standard deviations (RSDs) related to extraction, measure and sessions assay. The linearity is confirmed to be within a range of 0.5 to 8 microg/ml of isoniazid and 1 to 16 microg/ml of acetylisoniazid. This method shows a good repeatability for both extraction and measurement (RSD INH=3.54% and 3.32%; RSD Ac.INH=0.00% and 5.97%), as well as a good intermediate precision (RSD INH=7.96%; RSD Ac.INH=15.86%). The method is also selective in cases of polytherapy as many drugs are associated (rifampicin, ethambutol, pyrazinamide, streptomycin). The matrix effect (plasma vs. water) is negligible for INH (3%), but statistically significant for Ac.INH (11%). The application of this validation design gave us the possibility to set up an easy and suitable method for INH therapeutic monitoring.

Pre- and postsynaptic effects of taurine and GABA in the cockroach central nervous system.

Taurine resembles GABA in its synaptic effects in the cockroach cercal nerve giant fiber synapse where it exerts a depressant action upon synaptic transmission. Both taurine and GABA produce an increased conductance of pre- and postsynaptic membranes through changes in the permeability of chloride ions.

Determination of the acetylator phenotype in Moroccan tuberculosis patients using isoniazid as metabolic probe.

A large interindividual variability in drug acetylation is associated with genetic polymorphism of the polymorphic Type 2 N-acetyltransferase (NAT2), and an important interethnic difference has been frequently observed. However, few data on this polymorphism in the Moroccan population are available. In the present study the acetylator phenotype in 89 Moroccan patients with tuberculosis has been determined using isoniazid (INH) as metabolic probe. The subjects (69 women and 20 men between 18 and 77) were each given a 5 mg/kg oral dose of INH. Plasma concentration of INH and its metabolite, acetylisoniazid (ac.INH), were measured by high-performance liquid chromatography at 3 hours post dose. The plasma level ratio of acetylisoniazid to isoniazid (Rm), and the plasma level of acetylisoniazid as a percentage (%ac.INH) were used to express the activity of the polymorphic NAT2. The distribution of these 2 parameters in the studied population was clearly bimodal resulting in 2 distinct groups: slow acetylators (Rm < or = 0.84, %ac.INH < or = 45.64%), and fast acetylators (Rm > or = 1.29, %ac.INH > or = 56.26%) who accounted respectively for 61.8% and 38.2% of the population. The 2 approaches used showed a complete concordance.

Neurite regeneration of long-term cultured adult insect neurosecretory cells identified as DUM neurons.

A distinctive group of neurons having cell bodies located along the midline of the dorsal surface of the sixth abdominal (A6) ganglion of the adult cockroach Periplaneta americana has been characterized by direct anterogradc cobalt chloride staining. These neurons identified as dorsal unpaired median (DUM) neurons, present a T-shaped morphology. The soma gives rise to a single primary neurite running anteriorly in the ganglion before dividing into two lateral neurites which run into the left and the right side of the ganglion. A characteristic dendritic arborization arises from the lateral neurites within the ganglion. This major branching pattern is mainly located at the periphery of the A6 ganglion and forms a symmetrical complicated network. A new culture procedure of these same adult DUM neurons has been developed from the dissociation of the median parts of the A6 ganglia. In our experimental conditions, we show that cultured adult DUM neurons can survive for several weeks, and regenerate a single primary neurite dividing into two symmetrical lateral neurites with a number of fine processes radiating from the endings. This corresponds to the typical DUM neuron morphology revealed in situ on the same preparation using the cobalt chloride staining technique. This culture system developed for the first time on A6 ganglia adult DUM neurons will allow a better understanding of the physiological intracellular mechanisms involved in the neurosecretory functions of DUM neurons, which are currently unknown.

[Subconjunctival localization of a Wuchereria bancrofti adult female]. / Localisation sous-conjonctivale d'une femelle adulte de Wuchereria bancrofti.

The authors describe a case of conjunctival localization of a living adult Wuchereria bancrofti female observed in a 6 year old native Haitian girl, two years after her arrival in France. The adult was surgically removed from the conjunctiva. Microfilariae were evidenced in blood samples obtained at midnight. This is the first case of sub-conjunctival localization of W. bancrofti. This case stresses the necessity to identify the filaria by studying the microfilariae in blood samples obtained at different times of the nycthemere and/or by observing the adult after surgical extraction. The presence of a Loa, a Dirofilaria, a Mansonella, or a Wuchereria calls for different medical therapies.

[Comparative study of 2 classifications of glaucomatous perimetric deficits]. / Etude comparative de deux classifications des déficits périmétriques glaucomateux.

The purpose of this retrospectively study is to compare the results obtained using the unquestionable criteria, recommended by American Academy of Ophthalmology versus the minimum criteria proposed by HODAPP. The first are founded on the degree of the depth of the deficits in dB, the second take into account the statistically significant loss. One hundred glaucomatous visual fields screened with the Humphrey perimeter, with program 24-2, are retained for their correct indices of reliability, a MD better than -12 dB, and experience of the automated perimetry. This population was divided into two groups of 50:index MD greater than -6 dB. And index MD between -6 and -12 dB. The deficits were analyzed on the graph of individual deviation. Arcuate scotoma and nasal step were the majority of defects: 86 to 90% at the stage of mild deficit; 98% at the stage of moderate deficit. The deficits prevailed in the superior hemifield in 60% of cases. Nasal projection accounted for less than half of the deficits when MD was > -6 dB its frequency fell to less than 10% when MD worsened. Conversely the frequency of arcuate scotoma increased. The isolated deficits decreased with the MD aggravation, but even when the deficit was mild, they accounted for already less than half of the cases. Most of the associated deficits were located in the hemifield opposite to the principal defect. Defects were larger and more frequently multiple with the AAO classification than with the HODAPP. The minimum criteria of the classification of glaucomatous visual field defects proposed by HODAPP appear more specific than the unquestionable criteria of the AAO, and also appear easier to use.