Amyloid β 38, 40, and 42 species in cerebrospinal fluid: More of the same?

Various C-terminally truncated amyloid beta peptides (Abeta) are linked to Alzheimer's disease (AD) pathogenesis. Cerebrospinal fluid (CSF) concentrations of Abeta38, Abeta40, and Abeta42 were measured by enzyme-linked immunosorbent assay in 30 patients with AD and 26 control subjects. CSF Abeta42 levels was decreased in patients with AD, whereas CSF Abeta38 and Abeta40 levels were similar in patients with AD and control subjects. All three Abeta peptides were interrelated, particularly CSF Abeta38 and Abeta40. Diagnostic accuracy of CSF Abeta42 concentrations was not improved by applying the ratios of CSF Abeta42 to Abeta38 or Abeta40.     

Radical radiotherapy compared with surgery for advanced squamous cell carcinoma of the base of tongue

PURPOSE: This study reports on T3/T4 base of tongue (BOT) tumors treated at the Erasmus MC (Rotterdam) with external beam radiotherapy (EBRT) and brachytherapy (BT). Local control, survival, and functional outcome are compared to results obtained in similar patients treated at the Vrije University Medical Center (VUMC, Amsterdam) by surgery and postoperative RT (PORT). METHODS AND MATERIALS: At Rotterdam 46/2 Gy was given to the primary and bilateral neck, followed by an implant using low-dose-rate (LDR 24-35 Gy; median 27 Gy), or fractionated high-dose-rate (fr. HDR 20-28 Gy; median 24 Gy). A neck dissection (ND) was performed in case of N+ disease. 67% of BOT tumors had a T4 cancer. At Amsterdam surgery (S) followed by PORT 40-70 Gy (median 60 Gy) was performed; 26% BOT tumors were T4. Sex, age and nodal distribution were similar. Actuarial local control and survival were computed. Performance Status Scale (PSS) scores were established. Xerostomis was determined on visual analog scales (VAS). RESULTS: Local failure at 5-years was 37% (Rotterdam) vs. 9% (Amsterdam) (p < 0.01). The overall survival was not significantly different (median 2.5 years vs. 2.9 years, respectively [p = 0.47]). The PSS favored brachytherapy. Both groups were equally affected by xerostomia. CONCLUSIONS: The 5-year local control was 65% with EBRT and BT. This result is strongly affected by 4 patients with residual disease after implantation. The Rotterdam patients had more advanced BOT tumors (67% vs. 26% T4), explaining the higher local failure rate. Given the organ preservation properties of radiotherapy-only and the better PSS scores, the jury is still out on the optimal treatment for BOT tumors.     

Dietary phylloquinone intake as a potential marker for a heart-healthy dietary pattern in the Framingham Offspring cohort

Abstract Associations were evaluated among self-reported dietary intakes of phylloquinone (vitamin K-1), lifestyle characteristics, and intermediary markers of cardiovascular disease risk in a population-based cohort of men and women. Dietary phylloquinone intakes were assessed by food frequency questionnaire in 1,338 men and 1,603 women (mean age, 54 years) participating in the Framingham Heart Study. Cross-sectional associations with lifestyle characteristics and lipid profiles, including total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, and triglyceride concentrations, were estimated across increasing quintile categories of phylloquinone intakes. Participants in the highest quintile category of phylloquinone intake consumed more fruit, vegetables, fish, dietary fiber, and dietary supplements ( P <.001), and consumed less meat and less saturated fat ( P <.001). Higher phylloquinone intakes were also associated with lower triglyceride concentrations ( P <.001). In conclusion, a high phylloquinone intake may be a marker for an overall heart-healthy dietary pattern.     

Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families

Germline mutations in succinate dehydrogenase subunits B, C and D (SDHB, SDHC and SDHD), genes encoding subunits of mitochondrial complex II, cause hereditary paragangliomas and phaeochromocytomas. In SDHB (1p36)- and SDHC (1q21)-linked families, disease inheritance is autosomal dominant. In SDHD (11q23)-linked families, the disease phenotype is expressed only upon paternal transmission of the mutation, consistent with maternal imprinting. However, SDHD shows biallelic expression in brain, kidney and lymphoid tissues (Baysal et al., 2000). Moreover, consistent loss of the wild-type (wt) maternal allele in SDHD-linked tumours suggests expression of the maternal SDHD allele in normal paraganglia. Here we demonstrate exclusive loss of the entire maternal chromosome 11 in SDHD-linked paragangliomas and phaeochromocytomas, suggesting that combined loss of the wt SDHD allele and maternal 11p region is essential for tumorigenesis. We hypothesize that this is driven by selective loss of one or more imprinted genes in the 11p15 region. In paternally, but not in maternally derived SDHD mutation carriers, this can be achieved by a single event, that is, non-disjunctional loss of the maternal chromosome 11. Thus, the exclusive paternal transmission of the disease can be explained by a somatic genetic mechanism targeting both the SDHD gene on 11q23 and a paternally imprinted gene on 11p15.5, rather than imprinting of SDHD.     

Flexibility in spatial and non-spatial feature grouping: an event-related potentials study

Early perceptual grouping was studied using 256-channels event-related potentials in a choice response task. The task involved the detection of a triangle configuration of Gabor patches among patches of different spatial frequencies. The influence of two task-irrelevant factors was compared. One was the spatial proximity relation between the target patches and the other their relative orientation, a non-spatial relationship. Non-spatial effects were predominant in early peaks N64 and P100 in the occipital areas, and were reduced in size for later peaks. Spatial effects started from N180 in the occipital areas and continued in P250 and P430 in the central areas, increasing in size with time. These findings constitute a case of reversal of the usual order of spatial and non-spatial feature processing, illustrating that the flexibility in the early visual system may be greater than previously assumed.     

Truth telling and truthfulness in the care for patients with advanced dementia: an ethnographic study in Dutch nursing homes

The purpose of this study was to investigate and analyze the moral tension that exists in the care for demented nursing home patients, between the principle of respect for autonomy and the value that is attached to respect for the subjective world of the patient. To this end an ethnographical field study was carried out by two researchers in two Dutch nursing homes. Among the central topics that evolved were the different moral problems that nurses experience concerning truth telling and acting truthfully in relation to demented patients. In situations unrelated to the dementia and its diagnosis, the right to be informed is in principle respected, even if the information is sometimes painful. More specific questions of demented patients about their situation are a regular cause of embarrassment for their carers, who rely on various treatment strategies to deal with such questions. These strategies are often successful. However, when they fail, the nurses are faced with a problem they cannot solve, namely the loss of a common shared world and the resulting unmentionable truth about the diagnosis of dementia, as objective basis and legitimization for their approach to the demented patient. We conclude that in the training and professional support given to nurses, more attention should be paid to (awareness of) the moral problems that arise from this loss of a common shared world, so that they can react to the subjective world of demented patients without feeling that they are deceiving them.     

Changing education,changing assessment,changing research?

BACKGROUND: In medical education, assessment of medical competence and performance, important changes have taken place in the last 5 decades. These changes have affected the basic concepts in all 3 domains. DEVELOPMENTS IN EDUCATION AND ASSESSMENT: In education constructivism has provided a completely new view on how students learn best. In assessment the change from trait-orientated to competency- or role-orientated thinking has given rise to a whole range of new approaches. Certain methods of education, such as problem-based learning (PBL), and assessment, however, are often seen as almost synonymous with the underlying concepts, and one tends to forget that it is the concept that is important and that a particular method is but 1 way of using a concept. When doing this, one runs the risk of confusing means and ends, which may hamper or slow down new developments. LESSONS FOR RESEARCH: A similar problem seems to occur often in research of medical education. Here too, methods--or, rather, methodologies--are confused with research questions. This may lead to an overemphasis on research that fits well known methodologies (e.g. the randomised controlled trial) and neglect of what are sometimes even more important research questions because they do not fit well known methodologies. CONCLUSION: In this paper we advocate a return to the underlying concepts and a careful reflection of their use in various situations.     

Bye-bye urinary gonadotrophins? Reply to debate

Dear Sir, Drs Matorras and Crosignani have recently published a debateon urinary gonadotrophins: ‘Bye-bye gonadotrophins,’(Matorras et al., 2002; Crosignani, 2002) in which both authorssuggested a potential risk of prion infectivity to which I wouldlike to respond. Discouraging the use of urinary gonadotrophinssolely on the grounds of potential risks associated with prion     

Effects of oral and transdermal low-dose estrogen therapy on echocardiographic parameters of cardiac function

OBJECTIVE: To investigate the effects of transdermal 17 beta-estradiol (E(2)) compared with oral unopposed as well as opposed E(2) on echocardiographic parameters of left ventricular (LV) systolic and diastolic function. DESIGN: A prospective, randomized, double-blind, placebo-controlled, multi-center study. SETTING: Gynecologic and cardiologic outpatient departments. PATIENT(S): One hundred fifty-two healthy hysterectomized postmenopausal women. INTERVENTION(S): Participants received daily placebo (n = 49) or transdermal E(2) (50 microg; tE(2) group, n = 33), or oral E(2) (1 mg; oE(2) group, n = 37), or oral E(2) (1 mg) combined with gestodene (25 microg; oE(2)+G group, n = 33) for thirteen 28-day treatment cycles. MAIN OUTCOME MEASURE(S): M-mode, quantitative two-dimensional, and Doppler echocardiographic measurements were performed at baseline and after 1 year. RESULT(S): Compared with placebo, tE(2) and oE(2) showed no statistically significant changes in LV function. oE(2)+G resulted in a statistically significant favorable increase in peak flow velocity, flow velocity integral, and mean acceleration. Furthermore, a favorable decrease was observed in interventricular septum thickness and ejection time. CONCLUSION(S): After 1 year of unopposed E(2), LV function remained unchanged. The oE(2)+G treatment showed a potential beneficial influence on LV systolic function.