Regional cerebral blood flow was measured in 35 patients with organic dementia (Alzheimer's disease, n = 13, vascular dementia, n = 17, frontotemporal dementia, n = 5) and orthostatic hypotension. Measurements were performed during supine rest and during head-up tilt (60 degrees). Despite marked blood pressure falls, few patients had symptoms of orthostatic hypotension. All three dementia groups had a decrease in regional cerebral blood flow in the frontal lobes during head-up tilt, but no change in mean hemispheric flow. All patients had a consistent drop in their systolic blood pressure upon head-up tilt, with a wide variation over time. The findings suggest that orthostatic hypotension needs to be considered, and actively sought for, in organic dementia as many patients may lack the typical symptoms of orthostatic hypotension, despite a marked fall in blood pressure.
Regional cerebral blood flow was measured in 21 normotensive subjects during supine rest and during head-up tilt to 70 degrees. The results showed significant and consistent regional cerebral blood flow changes in the frontal areas with lower relative flow distribution values (percentage of mean flow) during head-up tilt than during supine rest. The lower frontal flow distribution values during tilt were not related to habituation, to repeated measurements, or to the estimated level of arterial CO2 which was derived from expired end-tidal CO2 levels. None of the subjects had orthostatic hypotension and there was no significant difference in mean hemispheric blood flow between lying down and standing up. There was no significant gender difference in regional cerebral blood flow, although female subjects tended to have higher mean hemispheric flow than males in both postures. It remains to be established whether the flow decreases in the frontal cortex are caused by cerebral functional factors or by haemodynamic mechanisms.
Eight patients meeting Leonhard's criteria for cycloid psychosis were investigated on repeated occasions during a psychotic episode, with regional cerebral blood flow measurements and clinical ratings. The results showed that, at admission to the hospital, when the patients were clinically exacerbated, the mean hemispheric blood flow was significantly elevated compared with values from a normal control group. The hemispheric blood flow level covaried significantly with the degree of clinical symptoms, such that the more elevated the cortical blood flow was, the more behaviorally disturbed was the patient. At discharge from the hospital, the patients had no residual symptoms and the cortical blood flow was normal. These findings differ distinctly from those commonly made in other psychoses, such as schizophrenia.
Background
Acute retroviral syndrome (ARS) is associated with HIV-1 subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS.
Methods
Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive from Kenya, Rwanda, Uganda, Zambia and Sweden were analysed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on eleven symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS.
Results
Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n=36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% CI: 1.7–28.8], p=0.003). IP-10 was fourteen-fold higher during hAHI, elevated in seven of the eleven symptoms, and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4–96.6) and specificity of 100.0% (95% CI: 90.3–100.0).
Conclusions
A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.
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