Confidentiality and serious harm in genetics - preserving the confidentiality of one patient and preventing harm to relatives

Genetics can pose special challenges to the principle of confidentiality within the health professional-patient relationship, since genetic information is by its nature both individual and familial. Most professional guidelines allow confidentiality to be broken in rare circumstances, where it will prevent a 'serious', 'imminent' and 'likely' harm. We argue that the types of harms that may result from genetic medicine are particularly diverse. Using clinical examples, we explore ethical issues that arise when balancing individual and family member interests. As genetic testing becomes more, widespread situations will arise where clinicians are faced with a choice between preserving the confidentiality of one patient and preventing harm to another. Professionals need to incorporate the notion of familial implications in their counseling of individuals. Since such dilemmas have been relatively rare in the pre-genetic age, we call for a wider debate on the balance between confidentiality and harm to others.     

8OHdG levels in brain do not indicate oxidative DNA damage in Alzheimer''s disease

Accumulation of oxidative DNA damage has been proposed to underlie aging and neurodegenerative diseases such as Alzheimer's Disease (AD). The DNA adduct 8-hydroxy-2′-deoxyguanosine (8OHdG) is considered a good indicator of oxidative DNA damage. To investigate whether this type of DNA damage is involved in AD etiology, 8OHdG levels were determined in postmortem human brain tissue of controls and AD patients (in frontal, occipital, and temporal cortex and in hippocampal tissue). Parametric studies in rat revealed no influences of postmortem delay, repeated freezing/thawing or storage time. In human brain, approximately two 8OHdG molecules were present per 10⁵ 2′-deoxyguanosines. In AD patients and controls, 8OHdG-levels were not related to age, sex, or brain region. Also, no differences were found between controls and AD patients. It was concluded that 8OHdG in nuclear DNA, although present throughout the brain in fairly high amounts, does not accumulate with age, nor does it appear to be involved in AD. More detailed studies are required to extend this conclusion to other types of oxidative damage.     

Laser energy threshold for thermal vascular injury in a port-wine stain skin model

Monte Carlo simulation of laser energy deposition in a port-wine stain (PWS) skin model and numerical solution of the thermal diffusion equation have been used to calculate threshold energies for thermal injury of PWS blood vessels for different vessel sizes and laser pulse durations. It has been assumed that an average vessel temperature rise of 65 C causes thermal injury to the blood vessel. The result is that for a certain combination of wavelength, pulse duration and incident energy density, only a limited range of blood vessel sizes can be injured optimally. Higher energy densities are required to injure smaller vessels with the same pulse duration, spot size and wavelength. This gives support to the mechanisms of selective photothermolysis suggested previously by Anderson and Parrish, although their model was based on the cooling behaviour of instantaneously heated vessels. The authors hypothesize that different laser parameter settings that match the individual PWS vessel anatomy during treatment will be used in the future, instead of many treatments with the same laser parameters. This could lead to less treatment sessions and to an improved predictability of clinical results.     

Therapeutic angiogenesis as a new experimental treatment for vascular disease

Currently, our treatment modalities for patients with severe coronary artery disease consist of combinations of medication, percutaneous transluminal coronary angioplasty (PTCA) and coronary revascularization operations. Still, the number of patients who cannot be treated adequately in these ways is growing. In recent years progress has been made in the field of angiogenesis: the process of the development of new capillaries. It is now known that blood vessel growth is an essential phenomenon in a range of disease. It is possible to inhibit or stimulate this process, offering hope for new treatments in a wide array of diseases. Stimulation of angiogenesis has already been successful in animal models of chronic peripheral and myocardial ischaemia. Results of experimental treatments of coronary patients have been reported since 1998. 'Therapeutic angiogenesis' may evolve as our fourth treatment modality for the treatment of coronary artery insufficiency.     

α-葡萄糖苷酶抑制剂治疗2型糖尿病的系统评价

目的评价α-葡萄糖苷酶抑制剂治疗2型糖尿病患者的效果。方法检索Cochrane图书馆、MEDLINE、EMBASE、CurrentContents、LILACS在研试验数据库,主题为α-葡萄糖苷酶抑制剂的综述的参考文献,并联系纳入试验的专家与实施者。最近检索日期为2003年月12月(CurrentContents)和2003年4月(其他数据库)。纳入α-葡萄糖苷酶抑制剂单一疗法与其它干预比较,治疗2型糖尿病疗程至少12周的随机对照试验,并且试验至少包括以下结局之一:病死率、患病率、生活质量、血糖控制、血脂、胰岛素水平、体重、不良事件。两名评价者独立阅读所有摘要,评价质量并提取数据,分歧通过协商解决或由第三位评价者裁决。由一位统计学家在对提取数据输入数据库时进行检查。我们尽量联系所有作者以核实数据。结果共纳入41个试验、8130例受试者,其中30个针对阿卡波糖,7个针对米格列醇,1个针对优格列波糖,还有3个为不同α-葡萄糖苷酶抑制剂间的比较。绝大多数研究疗程为24周,仅有2个研究超过1年。与安慰剂相比,阿卡波糖血糖控制效果更好:糖化血红蛋白–0.8%[95%CI(–0.9,–0.7)],空腹血糖–1.1mmol/L[95%CI(–1.4,–0.9)],负荷血糖–2.3mmol/L[95%CI(–2.7,–1.9)],阿卡波糖对糖化血红蛋白的作用呈非剂量依赖。我们发现其可降低负荷胰岛素,但对血脂和体重未见临床相关的作用。不良反应主要来自胃肠道且与剂量相关。相对于磺脲,阿卡波糖将空腹和负荷胰岛素水平分别降低至–24.8pmol/L[95%CI(–43.3,–6.3)]和–133.2pmol/L[95%CI(–184.5,–81.8)],但阿卡波糖引起的不良反应更多。结论关于α-葡萄糖苷酶抑制剂是否影响2型糖尿病患者的病死率和患病率仍不清楚。相反,其对血糖控制或胰岛素水平作用明显,对血脂和体重的作用差异无统计学意义。α-葡萄糖苷酶抑制剂更长疗程的效果仍不确定。阿卡波糖剂量超过50mg(TID)时不能进一步影响糖化血红蛋白水平,不良反应反而更多,与磺脲相比,α-葡萄糖苷酶抑制剂降低了空腹和负荷胰岛素水平,但在血糖控制和不良反应方面存在不利影响。     

Early childhood internalizing problems,externalizing problems and their co-occurrence and (mal)adaptive functioning in emerging adulthood: a 16-year follow-up study

Purpose

A vast amount of studies suggest that internalizing or externalizing problems are related to individual functioning, and often co-occur. Yet, a focus on their additive and interactive effects is scarce. Furthermore, most research has focused on a limited number of developmental domains and mostly on maladaptive functioning. Therefore, the current prospective study examined whether early childhood (ages 4–8) internalizing and externalizing problems and their interaction were related to a broad range of (mal)adaptive functioning outcomes in emerging adulthood (ages 20–24).

Methods

Data from the Flemish Study on Parenting, Personality and Development were used. At Time 1 (1999) mothers of 374 children (45% boys) and fathers of 357 children (46% boys) rated internalizing and externalizing problems through the Child Behavior Checklist. Outcomes in emerging adulthood were measured through self-reports 16 years later across the following domains: psychological functioning, social functioning, work, physical health, and self-concept.

Results

Early externalizing problems were related to maladaptive outcomes on the psychological and social domains. With regard to adaptive functioning, externalizing problems were associated with lower satisfaction regarding general health on the physical domain. Early internalizing problems were not associated with any emerging adulthood outcomes. The interaction of (father reported) internalizing and externalizing problems was related to aggressive behavior.

Conclusion

Early childhood externalizing problems were associated with maladaptive and adaptive functioning over a time span of 16 years. The results add to studies on the implementation of prevention and intervention programs in early childhood and to the value for developing personalized interventions.

     

Increased Amoeboid Microglial Density in the Olfactory Bulb of Parkinson's and Alzheimer's Patients

The olfactory bulb (OB) is affected early in both Parkinson's (PD) and Alzheimer's disease (AD), evidenced by the presence of disease‐specific protein aggregates and an early loss of olfaction. Whereas previous studies showed amoeboid microglia in the classically affected brain regions of PD and AD patients, little was known about such changes in the OB. Using a morphometric approach, a significant increase in amoeboid microglia density within the anterior olfactory nucleus (AON) of AD and PD patients was observed. These amoeboid microglia cells were in close apposition to β‐amyloid, hyperphosphorylated tau or α‐synuclein deposits, but no uptake of pathological proteins by microglia could be visualized. Subsequent analysis showed (i) no correlation between microglia and α‐synuclein (PD), (ii) a positive correlation with β‐amyloid (AD), and (iii) a negative correlation with hyperphosphorylated tau (AD). Furthermore, despite the observed pathological alterations in neurite morphology, neuronal loss was not apparent in the AON of both patient groups. Thus, we hypothesize that, in contrast to the classically affected brain regions of AD and PD patients, within the AON rather than neuronal loss, the increased density in amoeboid microglial cells, possibly in combination with neurite pathology, may contribute to functional deficits.     

DIetary ASSessment (DIASS) Study: Design of an Evaluation Study to Assess Validity,Usability and Perceived Burden of an Innovative Dietary Assessment Methodology

During recent years, the integration of technology has substantially improved self-reported dietary assessment methods, such as food frequency questionnaires (FFQ), food records, and 24-h recalls. To further reduce measurement error, additional innovations are urgently needed. Memory-related measurement error is one of the aspects that warrants attention, which is where new smartphone technologies and ecological momentary assessment (EMA) approaches provide a unique opportunity. In this article, we describe the DIASS study, which was designed to evaluate an innovative 2-h recall (2hR) smartphone-based methodology, against traditional 24-h recalls, FFQ, and biomarkers, to assess both actual and habitual dietary intake. It is hypothesized that a 2-h reporting window decreases reliance on memory and reporting burden, and increases data accuracy. We included 215 men (28%) and women (72%), with a mean ± SD age of 39 ± 19 years and a mean ± SD BMI of 23.8 ± 4.0. Most participants were highly educated (58%). Response rates for the various dietary assessment methods were >90%. Besides the evaluation of the accuracy, usability, and perceived burden of the 2hR methodology, the study set-up also allows for (further) evaluation of the other administrated dietary assessment tools.     

Branching of calyceal afferents during postnatal development in the rat auditory brainstem

Cells in the anteroventral cochlear nucleus (aVCN) send out calyceal axons that form large excitatory somatic terminals, the calyces of Held, onto principal cells of the contralateral medial nucleus of the trapezoid body (MNTB). It is unclear which fraction of these axons might form more than one calyx and whether this fraction changes during development. We combined in vitro anterograde tracing, stereological cell counts, analysis of apoptosis, and immunohistochemistry to study the development of calyceal afferents in rats of different postnatal ages. We found that some principal cells were contacted by multiple large axosomatic inputs, but these invariably originated from the same axon. Conversely, at least 18% of traced afferents branched to form multiple calyces, independently of age. Calyces from the same axon generally innervated nearby principal cells, and most of these branch points were <50 microm away from the synaptic terminals. Our results show that the projection from the aVCN to the MNTB is divergent, both when calyces have just been formed and in the adult. Cell counts did not provide evidence for principal cell loss during development, although analysis of apoptosis showed a large increase in nonneuronal cell death around the onset of hearing. Our data suggest that, once a calyceal synapse forms in the MNTB, it stays.