Interaction pharmacokinetics of pegylated liposomal doxorubicin (Caelyx) on coadministration with paclitaxel or docetaxel

Purpose To investigate the pharmacokinetics of polyethylene glycol-coated liposomal doxorubicin (PLD, Caelyx) when given as a single agent and in combination with the taxanes paclitaxel or docetaxel in humans.Methods The plasma kinetics of PLD were studied in 19 cancer patients treated with PLD every 4 weeks combined with either paclitaxel (on a weekly basis in seven and as a single infusion in three patients) or docetaxel (weekly in seven and as a single infusion in two). Plasma concentrations of PLD were quantified in two sets of samples per patient to compare the same pharmacokinetic parameters in each subject when treated with single-agent PLD and again with the combination. Total doxorubicin concentrations in plasma were quantified by HPLC. Pharmacokinetics were evaluated by noncompartmental analysis and the data obtained were compared for differences by a matched-pairs nonparametric test.Results Coadministration of paclitaxel produced a median/mean 54/80% increase in PLD AUC_inf (95% confidence interval 23% to 136%, P=0.002). The observed increase was consistent among all subjects. PLD clearance was also decelerated in the presence of paclitaxel (P=0.013) while other pharmacokinetic parameters were affected modestly. A small increase in the AUC of PLD was observed in the docetaxel/PLD arm (mean increase 12%, P=0.039) while PLD clearance decreased marginally and other pharmacokinetic parameters remained unaffected. AUC extrapolated to infinity was below 8% in both arms.Conclusions This study showed the presence of a pharmacokinetic interaction that led to higher plasma concentrations of PLD when combined with paclitaxel and to a minor extent when combined with docetaxel. This pharmacokinetic information may be of value when planning combination therapies of PLD with taxanes.     

Retrospective study of febrile seizures: subsequent electroencephalogram findings,unprovoked seizures and epilepsy in adolescents

A retrospective questionnaire to determine the prevalence of febrile seizures was given to adolescents (16- and 17-year-olds) in the final 2 years of secondary school at the five schools in Alexandroupolis, Greece. Parents were interviewed, and clinical and electroencephalographic examinations were performed in all adolescents with a history of febrile seizures. Of 1708 adolescents, 56 (3.3%) had experienced at least one febrile seizure. Of these, 44 (78.6%) were simple and 12 (21.4%) were complex febrile seizures. Recurrent seizures occurred in 22 cases (39.3%), and the mean age at onset was 25.1 months. There was a positive first-degree family history in eight cases (14.3%) and this increased to 27.3% in cases with recurrent seizures. Two of the adolescents (3.6%) had had one unprovoked seizure before the age of 3 years, and another two children developed epilepsy. Epileptiform electroencephalogram discharges were observed in only one case (1.8%) with generalized tonic-clonic epilepsy.     

Flapping of the dissected intima in a case of traumatic carotid artery dissection in a jackhammer worker

We present the sonographic finding of flapping of the dissected intima inside the carotid artery in a 48‐year‐old man who suffered an acute stroke after vigorous use of a jackhammer. The dissected intima was seen to flap inside the lumen regularly and in synchrony with the vessel's pulse. There was no distal segmental stenosis. The extracranial blood flow velocities were within normal limits and transcranial Doppler examination did not reveal any velocity alteration. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2009     

Association of demographic, clinical and treatment variables with quality of life of patients with epilepsy in Greece

PURPOSE: The aim was to study the influence of patients' age, frequency and type of seizures, disease duration, number of AEDs and use of benzodiazepines on the quality of life of patients with epilepsy. PATIENTS AND METHODS: We consecutively identified 223 patients with epilepsy who attended the epilepsy outpatient clinics at three university hospitals in Greece. Quality of life was evaluated by QOLIE-31. One-way analysis was used to assess the association of the studied factors and QOLIE-31 subscales. After checking for co-linearity, we performed multivariate stepwise linear regression analysis with all the variables that on univariate analysis showed a statistically significant effect on each subscale of QOLIE-31 to explore which of the studied factors affect independently on QOLIE-31 scores. RESULTS: Of a total of 223 patients, 118 (52.95%) were men; mean age was 35.18 +/- 13.22; mean duration of the disease was 13 years; 58 (26%) patients had generalized seizures, 93 (41.7%) had PS, and 72 (32.3%) of the patients had PsG; 85 (38.1%) were on polytherapy and 38 (17%) were taking benzodiazepines. Independent factors affecting QoL were: seizure frequency (Overall QoL P = 0.0001, Seizure worry and Emotional well-being P < 0.0001, Energy/fatigue and Social functioning P = 0.01); duration of the disease (Overall QoL and Energy/fatigue P = 0.01, Seizure worry P = 0.008, Cognitive functioning P < 0.0001); polytherapy only for the Emotional well-being P < 0.0001; and use of benzodiazepines (Overall QoL, Energy/fatigue, Social functioning P = 0.002, Cognitive functioning P < 0.0001). CONCLUSION: Our findings suggest that QoL in epileptic patients might be affected, in addition to the other established factors (high frequency of seizures and polytherapy), by the daily use of benzodiazepines as adjunctive therapy. Change of medical strategy concerning this medication may lead to improving the QoL of these patients.     

Sensitivity and specificity of a new indicator test (Neuropad) for the diagnosis of peripheral neuropathy in type 2 diabetes patients: a comparison with clinical examination and nerve conduction study

OBJECTIVE: The objective of this study was to evaluate the sensitivity and specificity of a new indicator test (Neuropad) for the diagnosis of peripheral neuropathy in type 2 diabetes patients as compared with clinical examination and nerve conduction study (NCS). PATIENTS AND METHODS: This study included 120 type 2 diabetes patients (58 men) with a mean age of 67.3 +/- 5.9 years and a mean diabetes duration of 13.1 +/- 3.2 years. Diabetic neuropathy was diagnosed through the Neuropathy Disability Score. An NCS was performed on radial, ulnar, sural, and common and deep peroneal nerves. Patients were also examined with the new indicator test. The "time to complete color change of the test" from blue to pink was recorded. The test was considered abnormal in patients who exhibited a time to complete color change of the test exceeding 600 s in at least one foot. RESULTS: Neuropathy was diagnosed by clinical examination in 83 (69.2%) patients. The sensitivity of the indicator test for clinical neuropathy was 95.2%, and its specificity was 67.6%. The sensitivity of NCS for clinical neuropathy was 94%, and its specificity was 62.1%. The sensitivity of the indicator test for abnormal NCS was 97.8%, and its specificity was 96.4%. CONCLUSIONS: The new indicator test has a very high sensitivity not only for the diagnosis of clinical neuropathy but also for the diagnosis of neurophysiological neuropathy. Specificity is moderately high for the diagnosis of clinical neuropathy, while it is particularly high for the diagnosis of neurophysiological neuropathy. The indicator test has a validity comparable to that of NCS for the diagnosis of diabetic neuropathy. Finally, the time to complete color change of the test is associated with the severity of nerve conduction impairment.     

Sleep architecture in stroke and relation to outcome

The aim of this study was to investigate sleep architecture in stroke patients, and correlate possible disturbances with the topography, severity and outcome of stroke and the presence of sleep-disordered breathing (SDB). In total, 62 acute stroke patients and 16 age- and gender-matched hospitalised controls underwent polysomnographic studies. Sleep architecture was analysed according to the topography of lesion, severity (National Institutes of Health Stroke Scale) and outcome (Barthel Index) of stroke. We found that sleep architecture is disturbed in stroke patients, regardless of SDB. Stroke patients (without SDB) have reductions in total sleep time and sleep efficiency, reduced stage II and slow wave sleep, increased wakefulness during sleep and increased sleep latency. Rapid eye movement (REM) sleep is reduced when SDB is also present. REM sleep is relatively preserved in cerebellar strokes, as opposed to other topographies. Sleep stages I and REM are negatively associated with stroke severity, and the latency to REM sleep is positively correlated with a good outcome. Sleep architecture is impaired in stroke patients (with fragmentation, increased wakefulness and reduced slow wave sleep), and this correlates with severity and outcome. Sleep disturbances should be investigated and addressed in these patients. Further studies are needed to confirm these findings and assess the clinical and therapeutic implications.     

Feasibility study and pharmacokinetics of low-dose paclitaxel in cancer patients with severe hepatic dysfunction

The aim of this study is to investigate the feasibility and determine the pharmacokinetics of low-dose paclitaxel in cancer patients with severe hepatic dysfunction. This was a prospective study. Patients with liver metastases who had either transaminase serum levels higher than 10 times the upper normal limit or bilirubin serum levels higher than 5 times the upper normal limit were eligible. All patients underwent pharmacokinetic evaluation during the first course of treatment. Pharmacokinetics in severe hepatic dysfunction patients were compared with data from a reference group of patients with normal hepatic function who participated in a phase I study. Nine severe hepatic dysfunction patients were treated with paclitaxel 70 mg/m administered as a 1-h infusion every 2 weeks. They received a median three treatment courses (range 1-9) without clinically relevant toxicity. The area under the concentration-time curve of paclitaxel was markedly higher in severe hepatic dysfunction patients when compared with the normal hepatic function control group treated with the same dose (98% increase, P<0.001). Area under the concentration-time curve and the time above 0.1 micromol/l (T>0.1) concentration threshold in the severe hepatic dysfunction patients who received paclitaxel 70 mg/m approximated pharmacokinetics of paclitaxel in patients with normal liver function who received 130 mg/m. Maximum plasma concentration (Cmax) did not differ between the two groups. In conclusion, paclitaxel 70 mg/m was safely delivered every 2 weeks in patients with severe hepatic dysfunction and resulted in adequate plasma concentrations. Paclitaxel at this dosage can be taken as an option for severe hepatic dysfunction patients who are expected to get clinical benefits from taxanes.     

Neurogenic vestibular evoked potentials using a tone pip auditory stimulus

OBJECTIVES: To obtain neurogenic vestibular evoked potentials (NVESTEPs) with surface scalp recording using a tone pip auditory stimulus. METHODS: Fourteen neurologically normal volunteers (Age range 26-45 years, 10 females and 4 males), and two patients with sensorineural hearing loss and possible multiple sclerosis respectively, were examined. Two channel recordings were obtained, the first channel being P3 referred to Fpz, and the second channel being P4 referred to Fpz. A 1 kHz tone pip stimulus with two cycles was delivered via headphones monoaurally with contralateral masking noise. RESULTS: A consistent negative wave with a mean absolute latency of 4.72 msec was obtained, which we have named N5. 25% of the ears tested had better responses at the ipsilateral parietal electrode. In the patient with bilateral sensorineural hearing loss, NVESTEPs was present, suggesting that the NVESTEP is not a cochlear response. In the patient with possible multiple sclerosis, an abnormal NVESTEP response and a normal BAEP response were found. CONCLUSION: Use of a tone-pip rather than a click auditory stimulus allows a lower click intensity to be used in the production of NVESTEP responses, leads to a shorter testing time, and is therefore more comfortable for the patient. This study adds to our impression that the NVESTEP may be a physiological response that can be used to assess the vestibular system and is different from the BAEP response. Further testing in patients with symptoms of dizziness and with disorders specific for the vestibular nerve is required.     

Stroke recurrence and mortality in northeastern Greece: the Evros Stroke Registry

Journal of Neurology - Up to date there is no population-based study from Greece providing long-term data on incidence of both all-cause mortality and stroke recurrence for patients with first ever...