Intestinal lymphatic transport of halofantrine in rats assessed using a chylomicron flow blocking approach: The influence of polysorbate 60 and 80

The aim of the study was to examine the effects of polysorbate 60 and 80 on intestinal lymphatic transport of a poorly water-soluble compound, halofantrine, using a chylomicron flow blocking approach in rats. Male Sprague-Dawley rats were pretreated intraperitoneally with 3.0mg/kg cycloheximide or saline. One hour later, rats were dosed with 6.7mg/kg halofantrine in 0.4 or 1.0g/kg polysorbate 60 or 80, 0.33g/kg soybean oil or 0.33g/kg soybean oil+1.0g/kg polysorbate 80 by gavage, and plasma samples were collected. The fraction of halofantrine transported to the lymphatic system was determined as the difference between the bioavailability in saline-pretreated rats and cycloheximide-pretreated rats. No significant differences in halofantrine transport to the systemic blood and in the deduced lymphatic transport were observed between the two polysorbates, at the tested dosages. The lymphatic transport of halofantrine was the same whether dosing with polysorbate 60, polysorbate 80 or soybean oil; accordingly both surfactants can be used as lymphotropic carriers. Furthermore, there was a good correlation between the halofantrine transport to blood and lymphatics in the chylomicron flow blocking model and published results from the mesenteric lymph-cannulated model.     

Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study

BACKGROUND: Few longitudinal studies of dementia in Parkinson disease (PD) have been reported, and the proportion of patients with PD who eventually develop dementia is unknown. OBJECTIVE: To examine the 8-year prevalence, characteristics, and risk factors of dementia in patients with PD. METHODS: Patients were recruited from an epidemiological study of PD in the county of Rogaland, Norway, using explicit criteria for PD. Subjects with cognitive impairment at disease onset were excluded. A semistructured caregiver-based interview, cognitive rating scales, and neuropsychological tests were used to diagnose dementia according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition at baseline and 4 and 8 years later. A population-based sample of 3295 subjects in the municipality of Odense, Denmark, was used as a comparison group and examined at baseline and after 2 and 5 years. RESULTS: We included 224 patients with PD (116 women). At baseline, 51 patients (26%) had dementia. Fifty-five patients died, and 10 refused follow-up without their dementia status known. Forty-three and 28 new cases of dementia were identified at the 4- and 8-year evaluations, respectively. The 4-year prevalence of dementia in PD was nearly 3 times higher than in the non-PD group. The 8-year prevalence in PD was 78.2% (95% confidence interval [CI], 71.1-84.0). Risk factors for dementia were hallucinations before baseline (odds ratio [OR] = 3.1; 95% CI, 1.6-6.2) and akinetic-dominant or mixed tremor/akinetic PD (OR = 3.3; 95% CI, 1.2-8.5). CONCLUSIONS: More than three quarters of this representative PD cohort developed dementia during the 8-year study period. Early hallucinations and akinetic-dominant PD were associated with an increased risk of dementia.     

Outpatient psychotherapy for mothers--first empirical results

MOTHERHOOD is a vulnerable phase in the life of any woman, one that may be associated with an increased risk of mental illness. Despite the major clinical significance of this patient group, only a few psychotherapeutic treatment programs are tailored to the needs of mothers of infants. Even when treatment is urgently needed, many mothers of infants reject inpatient psychotherapy so as not to be separated from their children. The outcome may be chronification of disorders, in some cases with a negative impact on their children's development. A new psychotherapeutic outpatient treatment program adapted to the special needs of mothers and offering a substitute to inpatient treatment is presented. First empirical results show that the presented treatment concept led to significant improvements in the symptoms, whose stabilization continued up to the follow-up two years after the start of therapy.     

Melorheostosis with ipsilateral nevus sebaceus (didymosis melorheosebacea)

We report an unusual case of unilateral melorheostosis and ipsilateral extensive sebaceous nevus. Because the two conditions affected the same side of the body, we hypothesize that they originated from a common genetic mechanism. The temporal and spatial co-occurrence may represent a further example of non-allelic didymosis (twin spotting). The embryo would carry two different recessive mutations at one gene locus or at linked loci on either of a pair of homologous chromosomes. Postzygotic recombination occurring during early embryonic development would result in two different populations of cells homozygous for either mutation. If this concept holds true, the present case may be described as " didymosis melorheosebacea ".     

The prediction of defibrillation outcome using a new combination of mean frequency and amplitude in porcine models of cardiac arrest

We estimated the predictive power with respect to defibrillation outcome of ventricular fibrillation (VF) mean frequency (FREQ), mean peak-to-trough amplitude (AMPL), and their combination. We examined VF electrocardiogram signals of 64 pigs from 4 different cardiac arrest models with different durations of untreated VF, different durations of cardiopulmonary resuscitation, and use of different drugs (epinephrine, vasopressin, N-nitro-L-arginine methyl ester, or saline placebo). The frequency domain was restricted to the range from 4.33 to 30 Hz. In the 10-s epoch between 20 and 10 s before the first defibrillation shock, FREQ and AMPL were estimated. We introduced the survival index (SI; 0.68 Hz(-1). FREQ + 12.69 mV(-1). AMPL) by use of multiple logistic regression. Kruskal-Wallis nonparametric one-way analysis was used to analyze the different porcine models for significant difference. The variables FREQ, AMPL, and SI were compared with defibrillation outcome by means of univariate logistic regression and receiver operating characteristic curves. SI increased predictive power compared with AMPL or FREQ alone, resulting in 89% sensitivity and 86% specificity. The probabilities of predicting defibrillation outcome for FREQ, AMPL, and SI were 0.85, 0.89 and 0.90, respectively. FREQ, AMPL, and SI values were not sensitive in regard to the four different cardiac arrest models but were significantly different for vasopressin and epinephrine animals. IMPLICATIONS: We present a retrospective data analysis to evaluate the predictive power of different ventricular fibrillation electrocardiogram variables in pigs with respect to defibrillation outcome. We showed that our combination of variables leads to an improved forecast, which may help to reduce harmful unsuccessful defibrillation attempts.     

Treatment of excessive daytime sleepiness in patients with Parkinson's disease with modafinil

Excessive daytime sleepiness (EDS) may limit the symptomatic treatment of Parkinson's disease and can alter the patient's lifestyle significantly. Ten consecutive patients with Parkinson's disease on various dopaminergic drugs and EDS were recruited to a 4-week open-label trial of modafinil. Patients were evaluated using the Epworth Sleepiness Scale and Unified Parkinson's Disease Rating Scale part III. All but three patients, with previous history of intolerability of a dopamine agonist caused by EDS, remained on their baseline medications. Modafinil was titrated as needed to a maximum of 400 mg/day. The mean Epworth Sleepiness Scale score at baseline of patients completing the study (n = 9) was 14.22 (+/- 3.03). After completing the study on an average dose of 172 mg/day, the Epworth Sleepiness Scale score was 6.0 (+/- 4.87). Unified Parkinson's Disease Rating Scale scores were not affected by this medication. Side effects encountered were headache, generalized paresthesias, and hallucinations (n = 1 each, the patient developing hallucinations dropped out of the trial before completing 4 weeks of the study drug). The three patients who did not tolerate any increments of dopamine agonist before modafinil were able to tolerate further upward titration of the dopamine agonist. Modafinil may be effective in reducing EDS in patients with Parkinson's disease treated with dopaminergic drugs. It does not seem to worsen parkinsonian symptoms and may allow further increase in dopaminergic therapy in patients previously unable to tolerate this because of EDS.     

Therapeutic factors of outpatient group psychotherapy - the predictive validity of the Group Experience Questionnaire (GEQ)

It was the aim of the study to investigate different factors of group experience in relation to therapy effects and to prove the predictive validity of the Group Experience Questionnaire (GEQ); for this purpose for each scale of the GEQ the values of later "Responders" and "Non Responders" were compared. The sample consisted of 50 patients with psychosomatic diseases who where treated with outpatient integrated psychodynamic group therapy. We found that the GEQ is able to differentiate between successful and less successful patients. Especially the therapeutic factors "autonomy and optimism" as well as "well-being" are of high predictive value. Contrary to former investigations the therapeutic factor "cohesion" was less important, which could hint at the fact that a medium amount of cohesion might be sufficient for an effective process of treatment.     

Effect of ethnic background on Danish hospital utilisation patterns

The aim of the study is to examine possible ethnic differences in the utilisation patterns of hospitalised immigrants versus patients born in Denmark. Data were obtained from the Register of Prevention at Statistics Denmark. This register includes both clinical and socio-demographic data. All patients discharged as inpatients during 1997 at Bispebjerg Hospital (a major hospital in Copenhagen) were identified through the Register of Prevention and linked to data concerning diagnosis, place of birth, age and gender. To compare immigrants with patients born in Denmark, a study group and a reference group were formed. The final study group consisted of all patients characterised by 22 major diagnostic categories and born outside the five Nordic countries (altogether 858 persons accounting for 976 inpatient contacts). The reference group consisted of 2004 patients accounting for 2432 inpatient contacts characterised by the same diagnostic categories among a random sample of 10,000 patients born in Denmark. The measure of utilisation employed was length of inpatient stay determined by the total number of days that each admission lasted. Data were analysed by a multiple regression analysis controlling for age, gender, diagnosis and place of birth. The results show that for some diagnostic groups, native Danes have longer inpatient stay compared to immigrants, whereas for other diagnostic groups immigrants have longer inpatient stay than native Danes. There was no overall effect of ethnicity on duration of hospital stay and consequently the utilisation patterns of inpatient care seem to reflect equal care for equal needs.