Trends in cervical squamous cell carcinoma incidence in 13 European countries: changing risk and the effects of screening.

Despite there being sufficient evidence for the effectiveness of screening by cytology in preventing cancer of the cervix uteri, screening policies vary widely among European countries, and incidence is increasing in younger women. This study analyzes trends in squamous cell carcinoma (SCC) of the cervix uteri in 13 European countries to evaluate effectiveness of screening against a background of changing risk. Age-period-cohort models were fitted and period and cohort effects were estimated; these were considered as primarily indicative of screening interventions and changing etiology, respectively. A unique set of estimates was derived by fixing age slopes to one of several plausible age curves under the assumption that the relation between age and cervical cancer incidence is biologically determined. There were period-specific declines in cervical SCC in several countries, with the largest decreases seen in northern Europe. A pattern emerged across Europe of escalating risk in successive generations born after 1930. In the western European countries, a decrease followed by a stabilization of risk by cohort was accompanied by period-specific declines. In southern Europe, stable period, but increasing cohort trends, were observed. Substantial changes have occurred in cervical SCC incidence in Europe and well-organized screening programs have been highly effective in reducing the incidence of cervical SCC. Screening and changing sexual mores largely explain the changing period- and cohort-specific patterns, respectively. The increasing risk in recent cohorts is of obvious concern particularly in countries where no screening programs are in place. Further investigation of the effectiveness of opportunistic screening is warranted as is the observation of differing risk patterns in young cohorts in countries with relatively similar societal structures.     

Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel.

PURPOSE: To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). EXPERIMENTAL DESIGN: A cohort of 97 Caucasian patients with cancer (median age, 57 years) received paclitaxel as an i.v. infusion (dose range, 80-225 mg/m(2)). Genomic DNA was analyzed using PCR RFLP or using Pyrosequencing. Pharmacokinetic variables for unbound paclitaxel were estimated using nonlinear mixed effect modeling. The effects of genotypes on typical value of clearance were evaluated with the likelihood ratio test within NONMEM. In addition, relations between genotype and individual pharmacokinetic variable estimates were evaluated with one-way ANOVA. RESULTS: The allele frequencies for the CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP3A4*3, CYP3A5*3C, and ABCB1 3435C>T variants were 0.7%, 9.2%, 2.1%, 0.5%, 93.2%, and 47.1%, respectively, and all were in Hardy-Weinberg equilibrium. The population typical value of clearance of unbound paclitaxel was 301 L/h (individual clearance range, 83.7-1055 L/h). The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated with unbound clearance of paclitaxel. Likewise, no statistically significant association was observed between the ABCB1 3435C>T variant and any of the studied pharmacokinetic variables. CONCLUSIONS: This study indicates that the presently evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes do not explain the substantial interindividual variability in paclitaxel pharmacokinetics.     

Retinal perfusion response to a slow multifocal M-sequence flicker stimulation

PURPOSE: To assess, if a slow multifocal stimulus (mfS) can provoke a perfusion response that can be measured with the Retinal Vessel Analyzer (RVA). METHODS: Seventeen eyes were examined. Pupils were dilated. A 120-second baseline recording was obtained with the RVA. The subject then turned to view an mfS for 56 s. The mfS consisted of 103 hexagons flickering according to an m-sequence with a stimulus base interval of 53.3 ms (L(max) = 100 cd/m(2), L(min) < 1 cd/m(2)). Immediately thereafter, the subject turned to the RVA, where measurements were resumed as soon as the same retinal vessel was targeted and continued for 104 s. Stimulation and recording was repeated twice. The diameter of a retinal vein and artery was measured for a length of at least 1 mm. The maximum vessel response was obtained by linear interpolation of the measured response within the 20 s following mfS. RESULTS: On average, veins dilated by 6.8% and arteries by 7% following mfS (p > 0.005). Such a dilatation could be observed in 9 veins and 7 arteries. Three venous and 2 arterial measurements did not show a dilatation following mfS. However, 13 of 34 measurements could not be analyzed due to signal problems or because the time from the end of mfS and the uptake of measurement exceeded 20 s. CONCLUSION: This slow multifocal ERG stimulus results in a dilatation of arteries and veins that can be measured with the RVA. Coupling an mfS to the RVA has the potential to topographically map changes in retinal perfusion in relation to the respective retinal area stimulated. When implementing the mfS into the RVA setup in order not to lose time due to the refixation in the RVA following mfS, one is required to take the transient nature of this perfusion change into consideration.     

Parkinson’s Disease and Sugar Intake—Reasons for and Consequences of a Still Unclear Craving

Lately, studies have shown that patients with Parkinson’s disease (PD) report a strong craving for sweets and consume significantly more fast-acting carbohydrates than healthy controls. Consuming food with a high-sugar content is assumed to lead to an increase in insulin concentration, which could positively influence dopamine concentration in the brain and unconsciously be used by patients as kind of “self-medication” to compensate for a lack of dopamine in PD. On the other hand, high-sugar intake could also lead to insulin resistance and diabetes, which is discussed as a causative factor for progressive neurodegeneration in PD. In this critical appraisal, we discuss the role of sugar intake and insulin on dopamine metabolism in patients with PD and how this could influence the potential neurodegeneration mediated by insulin resistance.     

Cytotoxic bastadin 24 from the Australian sponge Ianthella quadrangulata

A new cytotoxic bastadin, bastadin 24 ( 1), and the previously reported bastadins 4, 5, 6, 7, 12, 13, and 21 ( 2- 8) were isolated from a polar extract of the Australian marine sponge Ianthella quadrangulata. The planar structure of bastadin 24 ( 1) was elucidated as the 25-hydroxy derivative of bastadin 6 ( 4) by employing spectroscopic techniques (NMR, MS, UV, and IR). All isolated bastadins were evaluated for their cytotoxicity toward a panel of 36 human tumor cell lines and were found to be moderately cytotoxic. Bastadin 24 ( 1) exhibited selective cytotoxic activity toward five of the 36 investigated tumor cell lines. Bastadins 7 ( 5) and 12 ( 6) significantly inhibited the serum + hEGF-induced (human epithelial growth factor) tubular formation of human umbilical vein endothelial cells (HUVEC) at a concentration of 1 mug/mL.     

Prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy in 76 pregnancies at risk

OBJECTIVE: Evaluation of results in a consecutive series of 76 prenatal diagnoses for xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) made since 1977. METHODS: UV-induced DNA repair synthesis was assessed by the autoradiographic measurement of the incorporation of (3)H-thymidine. RESULTS: XP was diagnosed in 19 of the 76 investigated pregnancies at risk; cultured chorionic villus (CV) cells were used in 33 pregnancies with ten affected fetuses and cultured amniocytes in 43 pregnancies with nine affected fetuses. In four cases, CVS results were corroborated by subsequent investigation of amniocytes because maternal cell contamination in the CV cell culture was either present or could not be excluded. Uncertain results in two other cases with intermediate DNA repair capacity and severe maternal cell contamination required further investigation. Median time needed for cell culture and analysis was 25 days. To reduce intra-assay variations, a modification of the DNA repair synthesis assay has recently been developed. In this assay, patients and controls are investigated simultaneously in mixed cultures of cells labelled with polystyrene beads. CONCLUSION: Reliable prenatal diagnosis for XP and TTD can be made by the demonstration of clearly reduced UV-induced DNA repair synthesis due to defective global genome nucleotide excision repair.     

Rapid assessment of blood pressure in the obstetric day unit using Microlife MaM technology.

OBJECTIVE: To compare MaM technology with current methods of assessing blood pressure (BP) over time on the obstetric day unit. BACKGROUND: It is recommended that the average of repeated measures is used to confirm hypertension in pregnancy. The Microlife 3AC1 is a validated oscillometric device featuring "MaM" mode using the average of at least 3 BP readings 15 seconds apart. This allows rapid assessment of BP. The difference between each measurement is calculated and influences the percentage contribution to the final average reading. We compared MaM with readings taken in a conventional manner. METHODS: Blood pressure was measured in 30 hypertensive pregnant patients recruited from the obstetric day unit of a large teaching hospital. Single BP measurements were taken at 0, 15, 30, 60, and 90 minutes using the Microlife BP 3BT0-A[2]. Simultaneous measurements (in the opposite arm) were also taken at 0 and 90 minutes using MaM technology. RESULTS: Systolic BP fell over 90 minutes (p = 0.035) compared with the first single reading, but diastolic BP did not (p = 0.54). The difference between the first MaM and the first single reading was significantly different for systolic BP (5.6 mm Hg, p = 0.017), but not for diastolic (0.6 mm Hg, p = 0.39). The mean of all single readings and the first MaM reading were similar for both systolic and diastolic BP (SBP:0.3 mm Hg, p = 0.75, DBP: 0.2 mm Hg, p = 0.87). Conclusions: White-coat hypertension exists for systolic BP in the obstetric day unit. The MaM technology allows rapid and accurate characterization of blood pressure equivalent to repeated measures over 90 minutes.     

Altruistic acting caused by a touching hand: neural underpinnings of the Midas touch effect

Giving and receiving touch are some of the most important social stimuli we exchange in daily life. By touching someone, we can communicate various types of information. Previous studies have also demonstrated that interpersonal touch may affect our altruistic behavior. A classic study showed that customers give bigger tips when they are lightly touched by a waitress, which has been called the Midas touch effect. Numerous studies reported similar effects of touch on different kinds of helping or prosocial behaviors. Here, we aim to examine the neural underpinnings of this effect by employing a functional magnetic resonance imaging approach. While lying in the scanner, participants played different rounds of the dictator game, a measure of prosocial behavior. Before each round, participants were touched (or not touched in the control condition) by an experimenter. We found that touching the hand increased the likeliness to behave prosocial (but not the general liking of control stimuli), thereby confirming the Midas touch effect. The effect was predicted by activity in the primary somatosensory cortex, indicating that the somatosensory cortex here plays a causal role in prosocial behavior. We conclude that the tactile modality in social life may be much more important than previously thought.