Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

An association study of the cholesteryl ester transfer protein TaqI B polymorphism with late onset Alzheimer's disease

Cholesteryl ester transfer protein (CETP) is reportedly able to affect the amount of cholesterol available for deposition and/or removal from peripheral tissues, in its capacity to mediate the transfer of cholesterol from high density lipoprotein (HDL) to very low density lipoprotein, in exchange for triacylglycerols from the latter. The TaqI B polymorphism of the human CETP gene has been associated with decreased CETP mass and an increase in HDL-cholesterol. While many studies have addressed the atherogenic or anti-atherogenic potential of this polymorphism, little is known about its effect on neurodegeneration, despite the fact that CETP is expressed in the brain and the disturbance of cholesterol homeostasis appears to be an important factor in the pathogenesis of Alzheimer's disease (AD). In this report, we have compared the distribution of the TaqI B polymorphism in an independent population of 102 clinically diagnosed late onset AD patients and a spousal control group of 97 individuals. We have also examined the possible interaction between this polymorphism and two other polymorphisms suspected of affecting cholesterol flux, namely apolipoprotein E APOE epsilon4, and lipoprotein lipase LPLS447X. No statistically significant differences have emerged with respect to either genotype or allele frequencies between the AD and control populations. CETP TaqI B did not interact significantly with either APOE epsilon4 or LPLS447X, in this study.     

Testing normal older people three or four times at 1- to 2-year intervals: defining normal variance

Normative data were presented that defined the upper and lower standards for deciding if cognitive abilities show reliable change over 2 or more testing occasions when retesting occurs at 1- to 2-year intervals. The Mayo Cognitive Factor Scores (MCFS; G. E. Smith et al., 1994) were analyzed because they permit the quantitation of overall functioning in 5 clinically important cognitive domains: established verbal knowledge, nonverbal reasoning, attention and concentration, new learning, and delayed memory. To the authors' knowledge, this is the first report of both group-level and individual-level data analyses derived from a respectably sized sample of normal persons who have been tested 3 or more times at clinically common test-retest intervals.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Phorbol esters sensitize platelets to activation by physiological agonists

Phorbol esters such as phorbol 12, 13-dibutyrate (PdBu; 40 to 200 nmol/L) or 12-O-tetradecanoyl phorbol 13-acetate (20 to 80 nmol/L) added to aspirinized platelet-rich plasma (PRP) 5 to 15 seconds prior to various platelet stimuli (epinephrine, ADP, prostaglandin endoperoxide analog U44069, collagen, PAF, or vasopressin) potentiate the rate and extent of aggregation and ATP secretion induced by those agonists. Platelet aggregation, but not secretion, is potentiated at low concentrations of agonists; platelet secretion is potentiated at higher concentrations of the platelet stimuli. Potentiation of platelet responses was also observed when the preincubation time with PdBu was extended to 12 minutes and also occurred in washed platelets. The potentiating effect of phorbol esters is not mediated by formation of arachidonate metabolites or by released ADP. The sensitizing effect of PdBu on platelet aggregation induced by epinephrine is unique, since in contrast to the other platelet stimuli it is also found at maximal concentrations of epinephrine and does not diminish with prolonged preincubation of platelets with PdBu. Activation of protein kinase C ranges from 20% to 80% over control after 1 to 10 minutes of platelet pretreatment with PdBu but dramatically increases after subsequent addition of a stimulus such as vasopressin. In contrast, agonist- induced myosin light chain phosphorylation is reduced after platelet pretreatment with PdBu. The results indicate that protein kinase C activation enhances platelet aggregation and dense granule secretion triggered by physiologic stimuli, although it desensitizes agonist- induced myosin light chain phosphorylation.     

ApoE and Quality of Life in Nonagenarians

ObjectivesApoE ε4 is associated with adverse health conditions that negatively impact the quality of life (QOL). The relationship between ApoE ε4 and QOL has not been explored in the oldest old. Our study aimed to examine ApoE in the oldest old and explore its association with QOL.DesignCross-sectional cohort study.SettingA medium sized community in Olmsted County, Minnesota.ParticipantsIndividuals aged 90 to 99 years, living independently or in long term care environments.MeasurementsWe collected demographic information and measured cognitive function (Short Test of Mental Status, Mini-Mental State Examination, Mattis Dementia Rating Scale), QOL (Linear Analogue Self Assessment), and ApoE distribution. Subjects were classified as cognitively normal, mild cognitive impairment, dementia, or dementia with stroke and/or parkinsonism (DEMSP). Regression model was used to assess the predictors of QOL.ResultsA total of 121 subjects (45 cognitively normal, 13 with mild cognitive impairment, 34 with dementia, 29 DEMSP) aged 90–99 years, 106 (87.6 %) females, were included. Frequency of ApoE ε3 allele was highest (194 [80.2%]: ε2/3 18, ε3/3 77, ε3/4 22) followed by ApoE ε4 (25 [10.3%]: ε2/4 3, ε3/4 22) and ApoE ε2 (23 [9.5%; ε2/2 1, ε2/3 18, ε2/4 3). None of the subjects carried ApoE ε4/4 genotype. QOL was similar between ApoE ε4 carrier and noncarriers. Physical well-being, emotional well-being, intellectual well-being, social connectedness, and coping ability were positively associated with QOL, whereas male sex, DEMSP, pain frequency, and pain severity were negatively associated.ConclusionsThe most common ApoE in the oldest old was ε3/3 genotype and ε3 allele. No association was found between ApoE ε4 and QOL. However, those with high physical, emotional and intellectual well being, social connectedness, and coping ability had the highest overall QOL.     

Relationship of Height to Site‐Specific Fracture Risk in Postmenopausal Women

Height has been associated with increased risk of fracture of the neck of femur. However, information on the association of height with fractures at other sites is limited and conflicting. A total of 796,081 postmenopausal women, who reported on health and lifestyle factors including a history of previous fractures and osteoporosis, were followed for 8 years for incident fracture at various sites by record linkage to National Health Service hospital admission data. Adjusted relative risks of fracture at different sites per 10‐cm increase in height were estimated using Cox regression. Numbers with site‐specific fractures were: humerus (3036 cases), radius and/or ulna (1775), wrist (9684), neck of femur (5734), femur (not neck) (713), patella (649), tibia and/or fibula (1811), ankle (5523), and clavicle/spine/rib (2174). The risk of fracture of the neck of femur increased with increasing height (relative risk [RR] = 1.48 per 10‐cm increase, 99% confidence interval [CI] 1.39–1.57) and the proportional increase in risk was significantly greater than for all other fracture sites (p_{heterogeneity} < 0.001). For the other sites, fracture risk also increased with height (RR = 1.15 per 10 cm, CI 1.12–1.18), but there was only very weak evidence of a possible difference in risk between the sites (p_{heterogeneity} = 0.03). In conclusion, taller women are at increased risk of fracture, especially of the neck of femur. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease

Magnetic resonance (MR)-based volume measurements of atrophy are potential markers of disease progression in patients with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Longitudinal changes in (1)H MR spectroscopy ((1)H MRS) metabolite markers have not been characterized in MCI subjects. Our objective was to determine the longitudinal (1)H MRS metabolite changes in patients with MCI, and AD, and to compare (1)H MRS metabolite ratios and ventricular volumes in tracking clinical disease progression in AD. The neuronal integrity marker N-acetylaspartate/creatine ratio declined in MCI and AD patients compared to cognitively normal elderly. The change in (1)H MRS metabolite ratios correlated with clinical progression about as strongly as the rate of ventricular expansion, suggesting that (1)H MRS metabolite ratios may be useful markers for the progression of AD. Choline/creatine ratio declined in stable MCI, compared to converter MCI patients and cognitively normal elderly, which may be related to a compensatory mechanism in MCI patients who did not to progress to AD.     

White blood cell telomerase activity and incident respiratory illness among community-dwelling elderly vaccinated against seasonal influenza

Immune cell telomerase activity may impact vaccine response in the elderly. Fifty persons aged 60-100 years were tested for post-influenza vaccination telomerase RNA expression (TERT) in peripheral blood mononuclear cells to assess for an association with influenza antibody levels and influenza-like illness or incident respiratory infection (IRI) in the year following vaccination. High rates of seroprotective influenza antibody (> or = 1:40 titers) were observed post-vaccination (86-92% to vaccine viral strains), with no association to TERT. No IRI occurred among persons in the top quartile of TERT expression, whereas the IRI rate was 33% in the lower three quartiles (Kaplan-Meier P=0.028). TERT expression was also IRI significantly higher in those who did not experience IRI than those who did in the follow-up period (0.845 vs. 0.301, P=0.024). These data suggest that telomerase expression may correlate with immune capacity for vaccine response in the elderly and could represent a target for recognizing risk for vaccine failure.