Apolipoprotein E and Alzheimer's disease

Genetic variation in apolipoprotein E (APOE) influences Alzheimer's disease (AD) risk. APOE ε4 alleles are the strongest genetic risk factor for late onset sporadic AD. The AD risk is dose dependent, as those carrying one APOE ε4 allele have a 2-3-fold increased risk, while those carrying two ε4 alleles have a 10-15-fold increased risk. Individuals carrying APOE ε2 alleles have lower AD risk and those carrying APOE ε3 alleles have neutral risk. APOE is a lipoprotein which functions in lipid transport, metabolism, and inflammatory modulation. Isoform specific effects of APOE within the brain include alterations to Aβ, tau, neuroinflammation, and metabolism. Here we review the association of APOE with AD, the APOE isoform specific effects within brain and periphery, and potential therapeutics.

Epidural Blood Patch Performed for Severe Intracranial Hypotension Following Lumbar Cerebrospinal Fluid Drainage for Intracranial Aneurysm Surgery. Retrospective Series and Literature Review

Intracranial hypotension (IH) can occur following lumbar drainage for clipping of an intracranial aneurysm. We observed 3 cases of IH, which were all successfully treated by epidural blood patch (EBP). Herein, the authors report our cases.

A Comparative Review of the Hemodynamics and Pathogenesis of Cerebral and Abdominal Aortic Aneurysms: Lessons to Learn From Each Other

OBJECTIVE: Cerebral aneurysms (CAs) and abdominal aortic aneurysms (AAAs) are degenerative vascular pathologies that manifest as abnormal dilations of the arterial wall. They arise with different morphologies in different types of blood vessels under different hemodynamic conditions. Although treated as different pathologies, we examine common pathways in their hemodynamic pathogenesis in order to elucidate mechanisms of formation. MATERIALS AND METHODS: A systematic review of the literature was performed. Current concepts on pathogenesis and hemodynamics were collected and compared. RESULTS: CAs arise as saccular dilations on the cerebral arteries of the circle of Willis under high blood flow, high wall shear stress (WSS), and high wall shear stress gradient (WSSG) conditions. AAAs arise as fusiform dilations on the infrarenal aorta under low blood flow, low, oscillating WSS, and high WSSG conditions. While at opposite ends of the WSS spectrum, they share high WSSG, a critical factor in arterial remodeling. This alone may not be enough to initiate aneurysm formation, but may ignite a cascade of downstream events that leads to aneurysm development. Despite differences in morphology and the structure, CAs and AAAs share many histopathological and biomechanical characteristics. Endothelial cell damage, loss of elastin, and smooth muscle cell loss are universal findings in CAs and AAAs. Increased matrix metalloproteinases and other proteinases, reactive oxygen species, and inflammation also contribute to the pathogenesis of both aneurysms. CONCLUSION: Our review revealed similar pathways in seemingly different pathologies. We also highlight the need for cross-disciplinary studies to aid in finding similarities between pathologies.

Perceptions of Door-to-Door HIV Counselling and Testing in Botswana

Prevalence of HIV infection in Botswana is among the highest in the world; at 23.9 of 15 - 49-year-olds. Most HIV testing is conducted in voluntary counselling and testing centres or medical settings. Improved access to testing is urgently needed. This qualitative study assessed and documented community perceptions about the concept of door-to-door HIV counselling and rapid testing in two of the highest-prevalence districts of Botswana. Community members associated many positive benefits with home-based; door-to-door HIV testing; including convenience; confidentiality; capacity to increase the number of people tested; and opportunities to increase knowledge of HIV transmission; prevention and care through provision of correct information to households. Community members also saw the intervention as increasing opportunities to engage and influence family members and to role model positive behaviours. Participants also perceived social risks and dangers associated with home-based testing including the potential for conflict; coercion; stigma; and psychological distress within households. Community members emphasised the need for individual and community preparation; including procedures to protect confidentiality; provisions for psychological and social support; and links to appropriate services for HIV-positive persons

Prevalencia del suicidio en la Región de Tarapacá, años 1990-2008 / Prevalence of suicide in the Region of Tarapacá, years 1990-2008

Hemos llevado a cabo un estudio epidemiológico descriptivo de las muertes de tipo suicida en Tarapacá, Chile, entre los años 1990 y 2008, obteniéndose interesantes datos acerca del comportamiento de este fenómeno en una zona extrema, con indicios de una compleja adaptación social y dificultades en la integración individual. En un total de 432 casos, por ejemplo, la tasa de suicidio varió de un 6,11 por 100.000 hab. en 1990 a 13,32 por 100.000 hab. en 2008; se observó que el suicidio fue más frecuente entre los 20 a 44 años, especialmente en hombres, con una proporción cercana a 6:1, siendo el mecanismo más utilizado el ahorcamiento, tanto entre hombres como mujeres. Otro punto interesante lo constituye el hecho de que la tasa de suicidio a partir de 1996 se duplica respecto a los años precedentes, excediendo las tasas de otras regiones del país, la tasa nacional de suicidio y la de muchos países de la región y de Europa, constituyéndose en la segunda causa de muerte violenta en la provincia, lo cual nos retrotrae al complejo fenómeno biopsicosocial involucrado en la génesis del suicidio.

We carried out an epidemiological descriptive study of suicidal type deaths in Tarapacá, Chile, between 1990 and 2008, collecting interesting information about the behavior of this phenomenon in an extreme zone, with indicators of a complex social adjustment and difficulties in individual integration. In a whole of 432 cases, for example, the rate of suicide changed from 6.11 for 100.000 hab. in 1990 to 13.32 for 100.000 hab. in 2008; we observe that the suicide was more frequent in ages between 20 to 44 years, especially in men with a nearby proportion of 6:1, being the mechanism most used in both sexes, the hanging. Another interesting point constitutes the fact that the rate of suicide from 1996 doubled in relation to previous years, exceeding the rates of other regions of the country, the national rate and the rate of many American countries and even some European countries, being constituted in the second cause of violent death in our province, which makes us think about the complex phenomenon biopsicosocial involved in the genesis of the suicide.

Brain abscesses - the Groote Schuur experience; 1993 - 2003 : neurosurgery

Objective. To review management and outcome of patients with brain abscess treated at Groote Schuur Hospital (GSH) between 1993 and 2003. Patients and methods. Case notes; radiological results and laboratory records were reviewed retrospectively for 121 patients at GSH who underwent a neurosurgical procedure for treatment of a brain abscess between 1993 and 2003. Patients not treated surgically were excluded. Follow-up with serial computed tomography (CT) scans; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels and the temperature chart were used to determine the duration of parenteral antibiotic treatment and the need for repeat surgical evacuation of pus by either aspiration or excision of the capsule. Results. The mean patient age was 33 years; with a male-to-female ratio of 5:1. Headache; depressed level of consciousness and pyrexia were the commonest presenting symptoms. Other symptoms included seizures and hemiparesis. The frontal lobe was the commonest site (44); the majority of abscesses occurred as a result of infection following trauma. Mastoiditis (21) and sinusitis (8) were the second and third most common causes. Organisms were identified in 81of cases; polymicrobial infections occurred in half of these. Thirty-three different organisms were identified; the majority of which were Gram-positive bacteria. Anaerobes were present in 23; while methicillin-resistant Staphylococcus aureus was identified in 1 patient. Nocardia was seen in 3 patients; 2 of whom were diabetic. The average duration of parenteral antibiotic therapy was 15 and 19 days for excision and aspiration respectively. Accurate ESR records were available in 75of cases; with a positive predictive value in 81; while CRP (in use since 1999) was helpful in 92of cases. Outcome. Sixteen patients (13) died; 12 of whom had been admitted with a Glasgow Coma Score (GCS) of less than 4T/15. Thirteen patients developed epilepsy. On discharge; patients continued to take oral antibiotics for another 4 weeks; at the end of which they were reviewed at the neurosurgery outpatient department. Conclusion. Compared with previous studies from this hospital; mortality and morbidity have been diminishing progressively. GCS at the time of admission remains the most important prognostic factor

Impact of the prehospital trauma life support programme in Trinidad and Tobago

The impact of the Prehospital Trauma Life Support (PHTLS) programme, introduced in Trinidad and Tobago in 1992, was assessed by questionnaires completed by 26 medical personnel (MP); 71 ambulance personnel (AP); and 50 non ambulance paramedical personnel (NAP). Of the 23 MP, 45 AP and 38 NAP who were aware of the programme, 19 (82.6) MP, 40 (88.9) AP and 25 (65.8) NAP were able to differentiate personnel that had taken the PHTLS programme based on their performance. 32 (71.1) of the AP were PHTLS trained. 24 (53.3) and 4 (9) of the AP identified poor equipment and poor supervision, respectively, as reasons for difficulty in applying PHTLS principles. Improvements observed among those completing the PHTLS programme were: improved resuscitation techniques by 20 (86.9) MP, 38 (84.4) AP and 27 (71.1) NAP; better vital signs recording by 8 (34.8) MP, 27 (60) AP and 8 (21.1) NAP; improved immobilization by 23 (100) MP, 40 (88.9) AP and 33 (86.8) NAP; better haemorrhage control by 22 (95.6) MP, 40 (88.9) AP and 24 (63.2) NAP; appropriate splinting of fractures by 23 (100) MP, 40 (88.9) AP and 32 (84.2) NAP; and increased utilization of oxygen by 15 (65.2) MP, 31 (68.9) AP and 21 (55.3) NAP. 32 (71.1) AP with PHTLS training indicated improvement in their ability to resuscitate and transport trauma victims, with 42 (93.3) reporting improvement in overall prehospital care. Medical, paramedical and ambulance personnel all perceive a significant positive impact of PHTLS training on prehospital trauma care. Although improvements in supervision, documentation and equipment are still required, improved trauma resuscitative techniques after PHTLS training should improve trauma patient outcome in Trinidad and Tobago.

The effect of diazepan and exercise training on selected biochemical and histochemical properties of rat skeletal muscle

The effects of chronic diazepan (D) treatment and exercise training on total body mass (TBM), microsomal protein yield (MPY), calcium uptake by fragmented sarcoplasmic reticulum (SR), muscle fibre cross-sectional area, and both PFK and SDH activities were investigated in the tibialis anterior (TA), soleus (Sol), and plantaris (Plt) muscles of 50 male albino Sprague-Dawley rats. Rats were assigned randomly to control (C), sprint-trained (S), or endurance-trained (E) groups. Training was of 12 weeks duration. One-half of each group received daily intraperitoneally D doses of 5 mg kg(-1) of TBM. Exercise reduced TBM (p<0.05); increased the relative BM of the TA (E=2.02+0.02, p<0.01) and Plt (E=1.15+0.02, p<0.01; S=1.13+0.03, p<0.01), as well as the Ca++ uptake of the Sol SR (C=0.08+0.02, E=0.16+01, p<0.05). MPY was elevated in S-Sol (C=1.12+0.6, S=1.52+0.1, p<0.01). Delevated Sol MPY as well as TA PFK. S-trained animals had lower mean fibre areas than the E-trained (D-treated and untreated) animals. The elevated relative masses of TA and Plt are explained by a decreased TBM with exercise. The increased Ca++ uptake of the Sol indicates that E enhances this function, and the increased MPY probably implies an increased SR. The D could be responsible for the D-elevated Sol MPY as well as the TA PFK. El D did not reduce neuromuscular activity to a level adversely affecting oxidative enzyme activity, but in the case of PFK activity in the TA muscle, such a reduction was evident.

A serological survey of scrub, tick, and endemic typhus in Sabah, East Malaysia.

A seroepidemiological survey of 837 people and 383 febrile patients was performed in rural areas of Sabah. We determined that the rickettsial diseases scrub typhus and endemic typhus were uncommon causes of febrile illness, as was tick typhus, except in forest dwelling peoples. The rate of occurrence of SFGR specific antibody was 16.5% among 412 forest dwellers, indicating that tick typhus may be a frequent cause of illness in this population.