Apolipoprotein E polymorphism in elderly east Africans

Current advances have shown the apolipoprotein E (APOE)-epsilon 4 allele to be highly associated with late-onset familial and sporadic Alzheimer's disease (AD) in Western populations. The association of APOE allele frequencies and dementia remain unknown in populations from developing countries. We recently initiated a project to examine APOE frequencies in non-demented and demented elderly East Africans. Blood DNA collected from two hospital-based populations showed that the APOE allele frequencies in a group of non-demented 67 Tanzanians over the age of 65 years were found to be 14% for epsilon 2, 61% for epsilon 3 and 25% for epsilon 4. By comparison, the frequency of APOE-epsilon 4 in an age-matched demented group was also 25%. Assessment of APOE genotypes in the group of elderly Kenyan subjects from Nairobi also revealed high frequencies of the epsilon 4 allele with no clear difference in frequency between demented and non-demented subjects. Our preliminary observations suggest that elderly East Africans with no apparent clinical AD possess relatively high APOE-epsilon 4 allele frequencies compared to normal ageing subjects from Western countries including African-Americans. These results appear similar to those reported in a recent study in Nigerian Africans where a lack of correlation between APOE-epsilon 4 allele frequency and Alzheimer type of dementia was noted, and imply that APOE-epsilon 4 allele may not necessarily be a risk factor in some populations of Africa.     

Non-smoking as risk factor for Alzheimer''s disease?

The short-term effect of dexamethasone, a synthetic glucocorticoid, on both fatty acid and cholesterol synthesis has been investigated in rat hepatocyte cultures. Within 4h following hormone addition to the cultures, a noticeable stimulation of labelled acetate incorporation into fatty acids was observed. Similar behaviour was noticed when [3H]H2O was used as an independent index of the lipogenic activity. In the same cultures, however, cholesterol synthesis from both [14C]acetate or [3H]H2O was significantly reduced by dexamethasone addition. In these conditions, no significative variation of cholesterol synthesis starting from labelled mevalonate was observed.     

Bioavailability and pharmacokinetic disposition of tacrine in elderly patients with Alzheimer''s disease

PURPOSE: The Baerveldt glaucoma implant is an aqueous shunting device with large surface area that is installed through a single-quadrant conjunctival incision. A rabbit model of the Baerveldt implant was created to obtain serial histology and clinical information over 1 year. METHODS: Modified versions of the Baerveldt implant (110 or 160 mm2) were implanted in 18 normal New Zealand white rabbit eyes. The rabbits were examined periodically and their intraocular pressures (IOPs) recorded. They were killed at monthly intervals to obtain histology of the bleb capsules. RESULTS: Thin capsules were present at 1 month, which consisted of lamellar collagen deposition surrounded by a granulomatous reaction with multinucleate giant cells. Inflammatory cells (probably macrophages) were scattered on the inner bleb surface. The granulomatous reaction resolved after 4 months. Subsequently, capsule thickness and cellularity remained relatively stable, although the collagen stroma became less compact over time. Sixteen rabbit eyes had initial IOP reductions of > or = 3 mm Hg compared with fellow eyes, which persisted up to 4 weeks postoperatively. Seven eyes (39%) exhibited a hypertensive phase (IOP exceeded that of fellow eye by > or = 3 mm Hg) from 2 weeks to 3 months postoperatively. CONCLUSION: The Baerveldt explant is surrounded by a fibrous capsule that matures over time. The bleb histology in the rabbit model is similar to that described with the Molteno implant in primates and humans, except for the eventual development of a fibroblastic inner lining in the rabbit model. This contrasts with primate and human models, in which the inner lining remains an open mesh.     

Macronutrient intake and cardiovascular risk factors in older coloured South Africans

A cross-sectional analytical study was undertaken to investigate the macronutrient intake and cardiovascular risk factor profile of community-dwelling older coloured (mixed descent) South Africans. A sample of 200 subjects aged 65 years and above in Cape Town was randomly drawn using a two-stage cluster design. Trained field workers interviewed subjects to obtain demographic, dietary and life-style data, to draw fasting blood samples for the analysis of plasma lipids, and to take anthropometric measurements. Nutrient intake was assessed using a validated quantified food frequency questionnaire. Blood pressure was measured according to the guidelines of the American Heart Association. The mean daily energy intake was 7984 (3245) kJ and 6979 (2219) kJ for men and women, respectively. Twenty-nine per cent of the subjects had energy intakes less than two-thirds of the RDA. Dietary fat intake comprised 32.4% of total energy intake, which is in line with the prudent dietary guidelines. The inadequate fibre intake (mean = 17(8) g/day) was attributed to the low consumption of fruit and vegetables. Anthropometric assessment indicated that the women tended towards overnutrition, while the men appeared to be undernourished. Lipid profiles fell within the lower end of the moderate risk band for cardiovascular disease and a high prevalence of hypertension (71.7%) was identified. The survey findings indicate a need for health promotion activities to encourage increased physical activity levels and an increased consumption of vegetables, fruit, wholegrain cereals and low fat dairy products in this population.     

Tau in Alzheimer''s disease

The effects on goats of Calotropis procera latex given by different routes of administration were investigated. The administration of latex at 1 ml/Kg body weight via the oral route or at 0.005 ml/Kg body weight/day via the intravenous or intraperitoneal route caused death of the goats between 20 minutes and 4 days. When the small dose of latex (0.005 ml/Kg body weight/day) was given by the oral route or intramuscular route no death among the goats occurred. Nervous signs, frequent urination, frothing at the mouth, dyspnoea and diarrhoea were the main features in goats given latex by the oral, intravenous or intraperitoneal route. Lameness was observed in goats given latex via the intramuscular route. Lesions were widespread congestion and haemorrhage, pulmonary cyanosis, enterohepatonephropathy, peritonitis (in goats receiving latex via i.p. route) and haemorrhagic myositis at the site of latex injection. These changes were accompanied by increases in the activities of serum GDH, LDH, ALP, GGT and AST and in the concentrations of cholesterol, urea and creatinine and decreases in the level of total protein.     

Cardiovascular risk factors in the elderly

Although a number of risk factors for cardiovascular morbidity and mortality have been identified in young and middle-aged adults, their prevalence and importance are less known in the elderly. Elderly people have a risk profile different from that of younger subjects, but representative data on risk factors for cardiovascular disease in the elderly are difficult to find in the literature. Some typical 'major' risk factors, like blood pressure (BP), total cholesterol or left ventricular hypertrophy, do not have a clear predictive role for cardiovascular mortality in the elderly, especially in the extreme ages, while risk indicators usually labelled as 'minor' (serum uric acid, ventilatory function or proteinuria), do have a strong predictive value in these individuals. This must be taken into account when evaluating the cumulative risk of the elderly, in order to avoid overtreatment of subjects with mildly elevated BP or cholesterol.     

Cholesterol and lipoprotein(a) as risk factors for coronary heart disease in elderly subjects

The changes in lipoprotein(a) concentration that occur with age as a result of its association with an increased risk of coronary artery disease were investigated. Lipoprotein(a) concentrations were measured in serum samples from healthy volunteers, individuals with premature coronary artery disease, individuals with hyperlipidaemia but without evidence of premature coronary artery disease, and also in elderly men and women who had hyperlipidaemia. Concentrations in individuals with premature coronary artery disease were the same as those of the healthy volunteers, while in both these groups they were lower than those found in hyperlipidaemic elderly men and women, and those found in hyperlipidaemic women aged 36-68 years. No association between raised lipoprotein(a) concentration and mortality as a result of premature coronary artery disease was demonstrated. Raised lipoprotein(a) levels found in the hyperlipidaemic individuals also suggested that it may not be an independent risk factor.     

Postprandial hypotension in Alzheimer''s disease

The degree of postprandial hypotension in patients with Alzheimer's disease (AD) is not known. We therefore studied ten AD patients and 23 controls before and after a meal. Seven AD patients but only six controls showed a fall in blood pressure (BP) of 20 mmHg or more. Maximum BP fall in AD patients was observed between 20 and 120 min after food ingestion. This differed from the time course in other groups with primary chronic autonomic failure. Postural hypotension occurred in two controls, but not in AD patients. Abnormalities in cardiac vasomotor regulation, gut peptide liberation or both could be responsible for postprandial hypotension in AD.     

Delirium risk factors in elderly hospitalized patients

BACKGROUND: The relation of parental smoking to wheezing and asthma occurring after the first year of life was assessed by a systematic quantitative review of case-control and longitudinal studies, complementing earlier reviews of cross sectional surveys and wheezing in early childhood. METHODS: Fifty one relevant publications were identified after consideration of 1593 abstracts selected by electronic search of the Embase and Medline databases using keywords relevant to passive smoking in children. The search was completed in April 1997 and identified six studies of asthma incidence, seven of prognosis, 22 case-control studies, and 10 case series addressing disease severity. RESULTS: Maternal smoking was associated with an increased incidence of wheezing illness up to age 6 (pooled odds ratio 1.31, 95% CI 1.22 to 1.41), but less strongly thereafter (1.13, 95% CI 1.04 to 1.22). The long term prognosis of early wheezing illness was better if the mother smoked. The pooled odds ratio for asthma prevalence from 14 case-control studies was 1.37 (95% CI 1.15 to 1.64) if either parent smoked. Four studies suggest that parental smoking is more strongly associated with wheezing among non-atopic children. Indicators of disease severity including symptom scores, attack frequency, medication use, hospital attendance, and life threatening bronchospasm were in general positively related to household smoke exposure. CONCLUSIONS: The excess incidence of wheezing in smoking households appears to be largely non-atopic "wheezy bronchitis" with a relatively benign prognosis, but among children with established asthma, parental smoking is associated with more severe disease. This apparent paradox may be reconciled if environmental tobacco smoke is considered a co-factor provoking wheezing attacks, rather than a cause of the underlying asthmatic tendency.     

Motor performance in Alzheimer''s disease

A 47-year-old man with Hirayama's disease who developed cervical spondylotic amyotrophy (CSA) is presented. The patient had noted weakness and atrophy of hand and forearm muscles bilaterally at the age of 16. At the age of 40, he developed proximal muscle atrophy and weakness bilaterally after 20 years of a non-progressive state. Myelography and computed tomography (CT)-myelography revealed that ventral cord compression at multiple levels of C4-7 vertebral bodies was increased when the neck was extended. The clinical diagnosis was CSA associated with Hirayama's disease. To our knowledge, this is the first such case to be reported.     

Glial cells in Alzheimer''s disease: preferential effect of APOE risk on scattered microglia

HumD21S11 is a short tandem repeat DNA polymorphic system with a complex basic structure of (TCTA)4-6 (TCTG)5-6 (TCTA)3 TA (TCTA)3 TCA (TCTA)2 TCCA TA (TCTA)n. Using the allelic ladder prepared by us, the distribution of alleles among Japanese and Chinese was investigated, and four new alleles 28.2, 34, 35.2, and 36.2, were discovered. DNA sequencing was performed on the newly found alleles as well as on family samples and led to the discovery of different gene structures within alleles 28 and 32. Forensic materials, including hairs and seminal stains, were tested in parallel with blood samples from the same individual and were successfully typed for D21S11.     

Object decision priming in Alzheimer''s disease

The ability to effectively define disease status in ovarian cancer after initial therapy or to selectively screen high-risk populations remains a major challenge for in vivo monoclonal antibody (mAb)-targeted approaches. Antitumour murine mAbs (HMFG1, HMFG2, H317, and H17E2) and the reshaped human antibody Hu2PLAP (against placental alkaline phosphatase; PLAP), labelled with indium-111 and iodine-123, were evaluated for their ability to localise ovarian tumours in sequential studies of our group. Thirty patients with ovarian cancer, aged 40-78 years (median 60 years) were studied with HMFG1/G2: 11, and H317/H17E2: 19 murine mAbs. Six patients with ovarian cancer aged between 36 and 65 years (median 49 years) were studied with the reshaped human Hu2PLAP mAb (5 patients) or the murine H17E2 mAb (2 patients) labelled with 111In via a new macrocyclic chelating agent (DOTA). One of these was imaged twice, with H17E2- and Hu2PLAP-DOTA-111In, respectively. In 20 out of 22 patients with radiologically measurable ovarian cancer, the presence of tumour was confirmed by the murine mAb scan and correlated well with the findings of conventional radiology diagnostic methods. One of these patients with a negative H17E2 scan and a large abdominal mass at laparotomy was found to have a PLAP-negative tumour on immunohistochemistry. Additionally, the antibody scan revealed the presence of active disease, confirmed at laparotomy/laparoscopy, in 6 out of 8 patients considered to be in clinical complete remission. Best images were obtained at 24 and 48 h after the 123I and 111In mAbs, respectively. Successful imaging with the reshaped human antibody, Hu2PLAP, was seen in 2 patients with PLAP-positive tumours. Antibodies to DOTA developed in 2 patients. In conclusion, immunolocalisation of ovarian tumours is feasible with both murine and reshaped human mAbs. The sensitivity and specificity of the method appear very high in this pilot study, and in view of the absence of toxicity, the diagnostic contribution of this approach should be evaluated prospectively. Given the low number of patients without surgically detectable disease in the present study, future investigations should include more patients with no evidence of disease in order to provide more meaningful estimates of specificity.     

Evaluation of risk factors for fatal neonatal sepsis

OBJECTIVE: To evaluate risk factors for fatal neonatal sepsis. DESIGN: Prospective study. SETTING: Referral neonatal unit of a teaching hospital. SUBJECTS: 171 neonates admitted with sepsis. METHODS: Clinical examination and investigations on the day of admission were recorded and the neonates followed up to determine the final outcome. RESULTS: The overall fatality was 48.5%. In the univariate analysis, the factors significantly associated with death were weight, gestational age, age at onset of sepsis, hypothermia, requirement of IPPV, presence of refractory septic shock, neutropenia, metabolic acidosis and raised prothrombin time. However, in the multivariate analysis, only neutropenia, metabolic acidosis, increased prothrombin time and refractory septic shock retained their significance. The adjusted odd's ratio (95% confidence interval) were 0.095 (0.04 = 0.22), 1.14 (1.04-1.25), 1.04 (1.002-1.08) and 11.82 (5.47-69.40), respectively. CONCLUSION: Even in a setting with high fatality rates, high risk of mortality in neonatal sepsis can be identified and targeted for intensive intervention.     

Biological markers of Alzheimer''s disease

A 49-year-old woman presented with splenic lymphoma with villous lymphocytes (SLVL) that showed a clonal abnormality of del(7)(q22q32) in addition to inv(10)(p13q23), the latter being a previously undescribed abnormality in chronic lymphoproliferative disorders. A review of the literature on cytogenetic abnormalities of SLVL indicates that del(7q) is strongly associated with SLVL and may be important in the pathogenesis of this disorder.     

Neurochemical studies of Alzheimer''s disease

Age differences in the representation of semantic information may underlie the cognitive decline observed in aging. The objective of the present study was to determine to what extent elderly and young subjects agreed in the representations of semantic categories. Ninety elderly (77 women, 13 men) and 90 young (74 women, 16 men) participants wrote down the first four associations evoked by each of 30 semantic category names. Results showed differences between the two groups in items selected as most common responses (MCRs); frequency of occurrence of the MCRs differed between the two groups in 21 semantic categories. Results suggest that young and elderly subjects hold different representations of semantic categories and also highlight the importance of using age-appropriate norms in the evaluation of cognitive functions in aging.     

Mitochondrial DNA mutations in Alzheimer''s disease

A rapid, simple, and efficient chloroform/methanol-free method of isolating gangliosides is described. The nonionic polyoxyethylene detergent, hexaethyleneglycol mono-n-tetradecyl ether (C14EO6), forms clear micellar solutions in water, but two-phase separation can be achieved by centrifugation in the presence of ammonium sulfate at room temperature. A mixture of pure gangliosides, metabolically labeled gangliosides obtained from cultured hippocampal neurons, and gangliosides from rat cerebellar tissue were quantitatively recovered in the detergent-rich upper (coacervate) phase, with a partition coefficient K > 60. Gangliosides were subsequently separated from the detergent using an Iatrobead column prior to analysis by thin-layer chromatography. The procedure described here is as efficient as other methods of ganglioside extraction, such as that using chloroform/methanol/water/pyridine, but is less time-consuming inasmuch as extraction, purification, and TLC analysis can be completed within 1 day.     

Peripheral artery disease and cardiovascular risk factors in the elderly. The Honolulu Heart Program

Peripheral vascular disease as measured by the ankle/brachial blood pressure index (ABI) is associated with increased risk of mortality and morbidity. Few sources of data on the relationship of risk factors to ABI are available for the elderly, especially those > 80 years of age, and minority populations. ABI measurements from the Honolulu Heart Program's fourth reexamination of 3450 ambulatory, elderly Japanese American men indicate that the prevalence of an abnormal ABI, defined as a ratio of < 0.9, was 13.6%, increasing from 8.0% in those 71 to 74 years of age to 27.4% in those 85 to 93 years. Associations that were U or J shaped were present for a number or risk factors (higher rates of abnormality [ABI < 0.9] in those in the lowest and highest risk factor quintiles) in a cross-sectional analysis. Risk factors measured at baseline were also predictive of an abnormal ABI 25 years later, even after adjustment for multiple risk factors. The odds ratio (OR) for an ABI < 0.9 at the 80th percentile of cholesterol compared with that at the 20th percentile was 1.4; the OR for 1-hour postload glucose was 1.3, and for alcohol intake 1.2. The OR associated with hypertension was 1.8 and that for smoking, 2.9 (P < .05 for all ORs). These findings are consistent with ABI being a marker for generalized atherosclerotic disease in old and very old Japanese American men.     

Loss of dopamine D2 receptors in Alzheimer''s disease with parkinsonism but not Parkinson''s or Alzheimer''s disease

Qualitative analyses of midfoot stabilization in triple arthrodeses utilizing bone staple versus 4.5-mm cannulated cancellous screw fixation, with and without washers, were performed in fresh cadaveric specimens. Twenty-two trials (11 matched-pair feet) were used for direct comparison. Stiffness, defined as force/displacement, was determined at each talonavicular and calcaneocuboid joint. Ultimate load failure points of each specimen were also calculated. Trial results showed no statistically significant difference in stiffness or ultimate failure between these two forms of midfoot fixation for triple arthrodeses.     

Determinants of carer stress in Alzheimer''s disease

Ovarian cancer is the fifth most common malignancy among American women and the fourth leading cause of cancer death. The rapid advances in molecular genetic analysis, presymptomatic detection, and treatment of ovarian cancer are staggering. In this review, both the genetic component and the molecular biology of ovarian cancer are discussed, as well as current recommendations for genetic counseling. It is important for the practicing obstetrician and gynecologist to become familiar with these concepts, for it is he or she who will likely serve as a primary resource of information for these patients.