Regional cerebral blood flow (CBF), oxygen extraction ratio (OER), oxygen utilization (CMRO2) and blood volume (CBV) were measured in a group of 34 healthy volunteers (age range 22-82 yrs) using the 15O steady-state inhalation method and positron emission tomography. Between subjects CBF correlated positively with CMRO2, although the interindividual variability of the measured values was large. OER was not dependent on CMRO2, but highly negatively correlated with CBF. CBV correlated positively with CBF. When considering the values of all the regions of interest within a single subject, a strict coupling between CMRO2 and CBF, and between CBF and CBV was found, while OER was constant and independent of CBF and CMRO2. In 'pure' grey and white matter regions CMRO2, CBF and CBV decreased with age approximately 0.50% per year. In other regions the decline was less evident, most likely due to partial volume effects. OER did not change or showed a slight increase with age (maximum in the grey matter region 0.35%/yr). The results suggest diminished neuronal firing or decreased dendritic synaptic density with age.

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An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed. These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.

OBJECTIVE -The aim of our study was to assess the prevalence of clinical hypogonadism, based on both symptoms and biochemical available measures of testosterone deficiency, in men with type 2 diabetes.RESEARCH DESIGN AND METHODS -In a cross-sectional study of 355 type 2 diabetic men aged Ͼ30 years, total and bioavailable testosterone, sex hormone-binding globulin, BMI, and waist circumference were measured and free testosterone was calculated. Overt hypogonadism was defined as the presence of clinical symptoms of hypogonadism and low testosterone level (total testosterone Ͻ8 nmol/l and/or bioavailable testosterone Ͻ2.5 nmol/l). Borderline hypogonadism was defined as the presence of symptoms and total testosterone of 8 -12 nmol/l or bioavailable testosterone of 2.5-4 nmol/l. RESULTS -A low blood testosterone level was common in diabetic men, and a significant proportion of these men had symptoms of hypogonadism. Overt hypogonadism was seen in 17% of men with total testosterone Ͻ8 nmol/l and 14% with bioavailable testosterone Ͻ2.5 nmol/l. Borderline hypogonadism was found in 25% of men with total testosterone 8 -12 nmol/l and bioavailable testosterone between 2.5 and 4 nmol/l; 42% of the men had free testosterone Ͻ0.255 nmol/l. BMI and waist circumference were both significantly negatively correlated with testosterone levels in men, with the association being stronger for waist circumference.CONCLUSIONS -Testosterone levels are frequently low in men with type 2 diabetes, and the majority of these men have symptoms of hypogonadism. Obesity is associated with low testosterone levels in diabetic men. Diabetes Care 30:911-917, 2007

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