Egocentric disorientation following bilateral parietal lobe damage.

Aguirre and D'Esposito (1999) suggested a taxonomy and theoretical framework for understanding topographical disorders. One of the problems they described involved egocentric disorientation, in which deficits are not strictly confined to the topographical sphere but are seen on a wide variety of visuo-spatial paradigms. Here, we report a neuropsychological investigation of MU, a person with egocentric disorientation. To test the usefulness of Aguirre and D'Esposito's framework, we administered tests which were predicted to be easy or difficult for people with egocentric disorientation to show that MU was impaired on tasks sensitive to egocentric disorientation and that he showed adequate performance on tests sensitive to other types of topographical representation. Thus MU showed normal performance on a test of recognition of famous landmarks and he could identify photographs of personally familiar places in his home town, yet he could not say how to get from a recognised building to another place in his environment. His performance fulfils the criteria for egocentric disorientation and fits the predictions derived from Aguirre and D'Esposito's views.

Comparison of perioperative racemic methadone, levo-methadone and dextromoramide in cats using indicators of post-operative pain.

OBJECTIVE: To compare three opioid agonist drugs for perioperative analgesia in cats. STUDY DESIGN: Prospective, blind, controlled, randomised trial. ANIMALS: Ninety client-owned cats, weighing 3.1 (2.1-4.5) kg, aged 14.6 (6.0-84.0) months, were studied. METHODS: Seventy-six cats, scheduled for ovariectomy, received either 0.6 mg kg(-1) racemic methadone, 0.3 mg kg(-1) levo-methadone, 0.05 mg kg(-1) dextromoramide or a saline placebo IM. Behaviour and body position were assessed and scored 20 minutes later by a single 'blinded' observer. Anaesthesia was induced with propofol and maintained with halothane. Heart rate (HR), respiratory rate (RR), Fe'CO2 and SpO2 were recorded during anaesthesia. Post-operatively, pain was categorised as absent, moderate or severe, on the basis of appearance, behaviour and response to palpation of the surgical wound (pain score). Appearance, pain scores and physiological variables were monitored every 30 minutes, for a duration of 4 hours. Differences between time-dependent continuous variables were analysed using mixed models for repeated measurements. Differences in categorical, time-dependent variables were analysed using chi2-tests. Significance was set at p < or = 0.05. RESULTS: There were no significant changes in appearance after pre-anaesthetic medication. After surgery, there was no association between appearance and pain score with HR or RR. The assessment of pain depended on comparison with the placebo group, by comparing animals' reactions to wound palpation. Sixteen of the 18 cats in the placebo group and 14 of the 19 cats in the dextromoramide group showed signs of moderate-to-severe pain after surgery. In the levo-methadone group (n = 20), one animal showed pain after 60 minutes and two after 120 minutes. One cat in the racemic methadone group (n = 19) showed pain signs and behavioural changes at 60 minutes. Compared to the two methadone groups, 'rescue' analgesia was required more often in cats treated with dextromoramide or saline. CONCLUSION AND CLINICAL RELEVANCE: Dextromoramide (0.05 mg kg(-1)) was ineffective, while racemic methadone (0.6 mg kg(-1)) and levo-methadone (0.3 mg kg(-1)) provided effective analgesia in cats following ovariectomy, without behavioural, respiratory or cardiovascular side effects.

Improving the acceptability of the atrial defibrillator for the treatment of persistent atrial fibrillation: the atrial defibrillator sedation assessment study (ADSAS).

BACKGROUND: To compare the acceptability and effectiveness of three pre-medication regimens for manually activated cardioversion of recurrent persistent atrial fibrillation. METHODS: Eighteen patients implanted with the Jewel AF atrial defibrillator for drug-resistant persistent atrial fibrillation only were studied in an open-labelled randomised crossover study. Patients were assigned to sedation (S) with midazolam elixir, analgesia (A) with morphine sulphate or combination therapy (C) with dextromoramide and lorazepam. Pre-medication was taken up to 1 h before cardioversion. Patients rotated through each type of medication after undertaking at least one cardioversion. Visual analogue scales were completed immediately post-cardioversion and 24 h later for pain, anxiety and 'unpleasantness'. Higher scores represented a worse outcome. RESULTS: After 2 years' follow-up, 238 cardioversions were performed with S, 17 with A and 35 with C. The mean immediate combined score for S (10.9, 95% confidence interval (CI) 8.2-13.6) was significantly lower than for A (17.3, 95% CI 15.1-19.5, P = 0.01) and for C (15.9, 95% CI 12.3-19.6, P = 0.02). All patients who used S chose it as the most favourable pre-medicant. All patients who used A found it the least acceptable. CONCLUSION: Sedation rather than analgesia enhanced the acceptability of manually activated atrial defibrillation.

Chiral analysis of methylphenidate and dextromoramide by capillary electrophoresis.

Capillary electrophoretic methods have been developed to separate the enantiomers of methylphenidate (MPH) and dextromoramide. For MPH separation was achieved with heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMCD) as chiral selector in a 100 mM phosphoric acid buffer adjusted to pH 3.0 with triethanolamine. Commercial samples of D,L-erytho-MPH HCl and D,L-threo-MPH HCl were analysed using the method. There was no evidence of the presence of D,L-threo-MPH HCl in D,L-erytho-MPH HCl and vice versa. The ratio of the enantiomers was determined for each diastereoisomer. Hydroxypropyl-beta-cyclodextrin was the chiral selector of choice for the chiral separation of the enantiomers of moramide. The separation which gave a resolution of about 3.5 was achieved in 4 min using only a 6 cm of length of capillary. In a sample of dextro-R-moramide tartrate only a small quantity (4.9% w/w) of levo-S-moramide was detected with this method.

Craving patterns in methadone maintenance treatment with dextromoramide as adjuvant.

A study was performed to establish the effect on opiate craving among six long-term opiate-dependent subjects in methadone maintenance treatment. Subjects currently stabilised on methadone, received 5 or 10 mg dextromoramide besides methadone. During the study the usual methadone dose was diminished according to the individual subject's expectation of the effect of dextromoramide addition. A clear drug-effect relationship between the increment of dextromoramide plasma concentration and decrement of opiate craving could be seen. A craving increase before drug administration was seen in three cases. The results could imply beneficial effects of a short-acting opiate on diminishing craving in opiate addicts who are difficult to stabilise with methadone maintenance treatment.

Effect of electrolyte and solvent composition on capillary electrophoretic separation of some pharmaceuticals in non-aqueous media.

Non-aqueous capillary electrophoresis was used to study the separation selectivity of positively charged drug substances and negatively charged diuretics. Study was made of the effects of organic solvent composition and the background electrolyte on the separation. The separation selectivity could be altered considerably by varying the methanol/acetonitrile composition. In addition, the migration order and the resolution of the pharmaceuticals could be altered merely by changing the electrolyte cation or the anion. The electrolytes tested were alkali metal acetates, ammonium acetate, ammonium chloride and ammonium bromide. As with aqueous background electrolyte solutions, the electroosmotic flow was decreased with increasing size of the alkali metal cation of the electrolyte in methanol/acetonitrile 50:50 (v/v).

Determination and pharmacokinetics of dextromoramide in methadone maintenance therapy.

To study the pharmacokinetics of dextromoramide in long-term opiate addicts on methadone maintenance therapy (MMT) a reverse-phase HPLC technique was developed to monitor dextromoramide and methadone concentrations in plasma simultaneously. After liquid-liquid extraction from plasma, dextromoramide and methadone were determined using a Supelcosil LC-ABZ column and a mobile phase of KH2 phosphate buffer (25 mM, pH 2.5) mixed with acetonitrile (80:20, v/v) and UV detection at 206 nm. The method was found to be sufficiently sensitive, specific and reproducible to apply in six subjects on MMT for many years, receiving orally administered dextromoramide as adjuvant. Pharmacokinetic data sets for dextromoramide in each subject were conducted and analysed further, indicating short elimination half-life values (71 min, range 31-152 min). Contrary to previous studies, in all subjects tested the pharmacokinetics of dextromoramide are best described using an one-compartment model.

Case report of an unusual use of lidocaine during episodes of self mutilation.

We are reporting on a case of polyintoxication by cocaine, lidocaine, methadone, and dextromoramide. This conclusion is supported by the analysis of a strand of hair. We note for the first time the detection of dextromoramide as well as lidocaine and desethyl-lidocaine in hair. Concentrations in hair were: cocaine = 2.4 ng/mg, benzoylecgonine = 0.3 ng/mg, methadone = 10.2 ng/mg, EDDP = 1.5 ng/mg, dextromoramide = 1.6 ng/mg, lidocaine = 115.9 ng/mg and desethyl-lidocaine = 1.6 ng/mg. The victim who was seeking an anesthesia effect without the loss of consciousness ingested cocktails during episodes of self mutilation. The wounds were of two different types and with different morphological locations: long and deep without ablation of tissue, clean lacerations found on the neck, the pectoral region, and the left upper extremity; either round or discoid with deep excavation found on the head (ears, forehead, chin, and lips) and also, on the neck and on the left upper extremity. Near the most recent wounds, needle marks were noticed indicating probable local infiltration of lidocaine.

Analgesics in the management of chronic pain. Part four: Step 3 oral analgesic drug therapy.

Reluctance to commence treatment with a Step 3 drug on the Analgesic Stepladder is a common reason for failure to manage chronic severe pain in many situations. The fourth article in the series reviews the potent opioid analgesics for oral use and in doing so addresses the various prejudices that surface when such therapy is denied.

Knowing where and knowing what: a double dissociation.

We report a double dissociation between visuo-spatial abilities and semantic knowledge (knowledge of the names and attributes of objects and people), in two brain-injured people with longstanding stable impairments, using a wide range of tests to explore the extent of the dissociation, MU, who has bilateral lesions of occipito-parietal cortex, shows severe spatial disorientation with relatively well-preserved semantic knowledge. He is contrasted with JBR, who has bilateral temporal lobe damage and shows severe semantic problems and no impairment on visuo-spatial tasks. Our findings thus demonstrate a double dissociation between the performance of semantic and spatial tasks by MU and JBR. This pattern is consistent with Ungerleider and Mishkin's (1982) neurophysiological hypothesis of separable cortical visual pathways; one which is specialised for spatial perception and follows a dorsal route from occipital to parietal lobes, and the other following a more ventral route from occipital to temporal lobes, whose target is semantic information needed in specifying what an object is.

Dextromoramide pharmacokinetics following sublingual administration.

The extent of absorption and other pharmacokinetic parameters of dextromoramide following sublingual administration were assessed in five patients receiving chronic opioid analgesia. The use of the standard 5 mg tablet formulation was associated with negligible absorption in two patients, a prolonged time to peak concentration in the other three and substantial variability in clearance. The study concluded that the standard tablet formulation cannot be recommended for sublingual use where reliable, rapid onset analgesia is required.

Spinal clonidine fails to provide surgical anesthesia for transurethral resection of prostate. A dose-finding pilot study.

BACKGROUND AND OBJECTIVES: This study was designed to determine whether subarachnoid clonidine administration alone results in surgical anesthesia for transurethral resection of the prostate. METHODS: Blood pressure, heart rate, sedation, and sensory and motor blocks were assessed in 12 patients before and after lumbar subarachnoid injection of increasing doses of clonidine (three patients each received 75, 150, 300, and 450 micrograms doses). General anesthesia was induced at the request of the patient or surgeon, if conditions were unsatisfactory. RESULTS: Clonidine resulted in marked sedation within a mean of 19 minutes of spinal injection, and no motor block was observed. There was a 25% (range, 0-45%) reduction in mean arterial blood pressure. Although endoscopy was tolerated in all cases, general anesthesia was required when resection began, except in two patients who received 300 and 450 micrograms of clonidine, respectively. Postoperative analgesic requirements showed wide interindividual variability (mean, 6 hours; range 2-12 hours). CONCLUSIONS: Subarachnoid clonidine cannot be reliably used as the sole agent for spinal anesthesia, since general anesthesia is often required or deep sedation occurs. Increasing doses of clonidine do not prolong postoperative analgesia. Thus, clonidine could be used as a spinal analgesic but not as a spinal anesthetic.

Characterization of dextromoramide (Palfium) abuse by hair analysis in a denied case.

By providing information on exposure to drugs over time, hair analysis is useful in verifying the history of drug use. In a clinical case, where drug abuse was denied, it was possible to identify dextromoramide in the hair of the subject. After acid hydrolysis of the hair with 0.1 M HCl, in the presence of SKF 525A as an internal standard, the drug was extracted at pH 8.4 with chloroform-isopropanol-n-heptane (50:17:33 v/v) and quantified by gas chromatography/mass spectrometry. The hair strands were cut into 3 sections of 2.5 cm, corresponding to a growth period of 2 months. Concentrations were 1.09, 1.93 and 1.48 ng/mg from the root to the end, respectively. This is the first report on dextromoramide testing in human hair.

Simultaneous determination of dextromoramide, propoxyphene and norpropoxyphene in necropsic whole blood by liquid chromatography.

Dextromoramide, propoxyphene and its main metabolite, norpropoxyphene, were determined in blood after solid-liquid extraction by means of an HPLC method using photodiode-array detection. Two cases of fatal overdose resulting from abuse of the two drugs are presented. In case 1 the necropsic whole blood contained dextromoramide at toxic level (194 ng ml-1) and propoxyphene (614 ng ml-1) and norpropoxyphene (1100 ng ml-1) within the therapeutic range; the death could be due to the combined effect of the two analgesics and, perhaps, other associated drugs. In case 2, the necropsic whole blood concentrations of propoxyphene and norpropoxyphene were 4330 and 3800 ng ml-1, respectively, and could be considered as lethal.

Determination of dextromoramide in plasma and whole blood using high-performance liquid chromatography with ultraviolet absorbance detection.

Dextromoramide was determined in plasma and whole blood after solid-phase isolation by high-performance liquid chromatography using dextropropoxyphene as internal standard and ultraviolet detection at 215 nm. Owing to its good selectivity, sensitivity and reproducibility, the technique is available for forensic toxicology purposes as well as for clinical pharmacology. The concentrations of dextromoramide were determined in three cancer patients receiving intravenous treatment with one to three 5-mg daily doses. On the fourth day the plasma level was 13.85 +/- 3.27 ng ml-1 just before the first daily dose and 84.28 +/- 12.60 ng ml-1 30 min after dosing. The whole blood concentration, determined in one of the patients, was undetectable just before the dose and was 76 ng ml-1 30 min after dosing.

Transcranial electrical stimulation with high frequency intermittent current (Limoge's) potentiates opiate-induced analgesia: blind studies.

Transcutaneous cranial electrical stimulation (TCES) with high frequency (166 kHz) intermittent current (100 Hz: Limoge current) has been used for several years in cardiac, thoracic, abdominal, urological and micro-surgery. The main benefits are a reduced requirement for analgesic drugs, especially opiates, and a long-lasting postoperative analgesia. We have confirmed these clinical observations in rats using the tail-flick latency (TFL) test to measure pain threshold. TCES was not found to modify the pain threshold in drug-free rats, but it potentiated morphine-induced analgesia (systemic injection). To obtain a maximal effect, the stimulation must be initiated 3 h before the drug injection and be maintained throughout the duration of its pharmacological action. TCES potentitation was found to depend on the dose of the drug, the intensity of the current and the polarity of electrodes. These findings were confirmed by blind tests of the efficiency of TCES on several opiate analgesic drugs currently used in human surgery (morphine, fentanyl, alfentanil and dextromoramide). The analgesic effect of these 4 opiates (TFL as % of baseline without or with TCES) were respectively: 174%, 306%; 176%, 336%; 160%, 215%; and 267%, 392%. The results were obtained not only after systemic opiate treatment, but also after intracerebroventricular injection of morphine (10 micrograms; analgesic effect 152%, 207% with TCES) suggesting that TCES potentiation of opiate-induced analgesia is centrally mediated.