Dare to Care for the Elderly: Five Insights.

Care is often limited by patient age due to societal forces concerning expense and successful outcome. A mother's critical illness yields insights into care that worked despite advanced age. The five subsequent insights are viewed against data from randomized clinical trials illustrating how we know what we think we know. From this a healthcare model is proposed that insures a healthier elderly population.

Maximum carotid artery wall thickness and risk factors in a young primary prevention population.

Maximum carotid artery wall thickness was utilized in a primary prevention population and compared with baseline risk factors. Carotid wall thickness was measured between the blood-intima and media-adventitia interfaces by B-mode ultrasonography using software calipers at points of protrusion. Long-axis measures were confirmed by short-axis assessment. The maximum carotid wall thickness for each subject was divided by age in years to yield an annual accretion rate (called carotid intima-media thickness accretion rate [CIMTAR]). The entire study population was then divided by median CIMTAR to investigate the association with baseline variables used in standard risk assessments with the bifurcated groups. Traditional risk factors such as age, diabetes, smoking, hyperlipidemia, and obesity were not associated with greater than median CIMTAR. Only male gender (P = 0.02) and systolic blood pressure (P = 0.002) in baseline variables were associated with an elevated CIMTAR for the entire population. Among those not taking lipid-lowering therapy at baseline, only systolic blood pressure remained significant (P = 0.0002). Correlations between low-density lipoprotein (LDL) cholesterol level and maximum carotid wall thickness/CIMTAR were weak for the entire population (r = -0.17/r = -0.12, respectively). Measure of maximum carotid wall thickness may select patients earlier for treatment than traditional risk factors. The addition of CIMTAR to risk algorithms may permit a single-point assignation of subsequent vascular risk that is more efficacious than traditional risk factors.

Vascular pleiotropy of statins: clinical evidence and biochemical mechanisms.

The ability of statins to lower serum cholesterol and reduce coronary heart disease endpoints has confirmed portions of the lipid hypothesis. However, the time to benefit and increased benefit in overlapping populations have suggested that nonlipid or pleiotropic effects of statins may be present. The apparent benefit of statins in cerebrovascular disease may imply a similar final common pathway among the diverse mechanisms of vascular diseases. Statins' inhibition of isoprenoid intermediates may modify GTP binding proteins such as Rho. The augmentation of collateral blood flow downstream of activated plaque through endothelial cell nitric oxide synthase may be the biochemical basis of statins' vascular pleiotropy. Eventual clinical paradigms of statin use may include higher doses to enhance pleiotropic effects and treatment, even when lipid markers are within guidelines.

Possible short-term amelioration of basilar plaque by high-dose atorvastatin: use of reductase inhibitors for intracranial plaque stabilization.

Regression of symptomatic intracranial atherostenosis is not known to be a common occurrence. In this case, delay of basilar reconstruction by endovascular means permitted serial angiographic assessment of plaque change. The use of high-dose atorvastatin over a 2-week period was associated with marked angiographic improvement. Medical programs of plaque stabilization may provide adjunctive benefit in patients with symptomatic intracranial disease.

Basilar artery endoprosthesis placement: rescue therapy for recurrent thrombosis.

Hyperacute thrombosis of the basilar artery accompanied urgent treatment of basilar thrombosis with local thrombolytics and arterial reconstruction by balloon angioplasty. Successful placement of an endoprosthesis into the basilar artery permitted sustained restoration of blood flow. To the authors' knowledge, this is the first successful report of intracranial endoprosthesis deployment.

Balloon angioplasty of intracranial arteries for stroke prevention.

Stroke from surgically inaccessible intracranial atherostenosis remains a formidable clinical challenge. While antithrombotic or antiplatelet therapy may prevent distal embolism, there is no effective program for plaque stabilization preventing progression of atherosclerotic stenosis. In patients with isolated circulations (single vertebral with absent posterior communicating arteries, single carotid with contralateral internal carotid artery occlusion, or single carotid with an absent anterior communicating artery), occlusion of the stenotic vessel may produce a low flow-mediated stroke. Fifteen patients with atherosclerotic intracranial stenoses were treated by balloon angioplasty after medical therapy with warfarin failed. Treated territories included the distal internal carotid, proximal middle cerebral, distal vertebral, and basilar arteries. Dilation was successful in all vessels, with residual stenoses averaging less than 30%. Two complications included one paramedian pontine stroke and a single vessel rupture that proved fatal. There was no recurrence of transient ischemic attacks and no restenosis at the angioplasty site over a follow-up period of more than 24 months. In this small series, balloon angioplasty of intracranial vessels provided a therapeutic option for secondary stroke prevention in highly selected patients. Further studies will be necessary to establish the efficacy and safety of endovascular treatment in larger series.

Adenylate cyclase and histopathological changes in the gerbil brain following prolonged unilateral ischemia and recirculation.

This study was designed to correlate histopathological changes in gerbil brain following unilateral primary and secondary ischemia to enzymatic-adenylate cyclase damage. At three hrs permanent occlusion of the right common carotid artery only minimal histological changes were evident in cerebrum, hippocampus, striatum and olfactory tubercle while the enzyme responses were unremarkable. Severe histological and enzymatic alterations were present at one hour of recirculation subsequent to 3 hrs of unilateral occlusion. Similar damage was evident at 6 and 24 hrs permanent occlusion. Principal enzyme damage was directed toward basal activity, as well as stimulation of the catalytic (forskolin-sensitive) sites on the enzyme complex. For the most part the transducer (GTP-sensitive) site was unaffected by ischemia until 24 hr ligation. These changes were observed in only those gerbils developing severe symptoms of stroke.

Classification of ischemic-induced damage to Na+, K+-ATPase in gerbil forebrain. Modification by therapeutic agents.

The activity of three forms of ATPase were examined in fractions of the brain of the gerbil treated with ethylene glycol-N-N-tetra-acetic acid (EGTA) under a variety of conditions of primary and secondary (reflow) ischemia. In animals which were unilateral ischemic (ligation of the right common carotid), damage to Na+, K+-ATPase alone was observed only after at least 6 hr of ischemia had elapsed. The phenomenon occurred in only symptomatic gerbils and was absent in animals which were either asymptomatic or only displayed partial neurological symptoms. Under conditions of bilateral cerebral ischemia, in which both carotid arteries were clamped, only irreversible ischemia (60 min) followed by reflow, was associated with highly significant damage to cerebral Na+, K+-ATPase. In regional studies of the forebrain involving ischemia for 60 min plus 30 min reflow, damage to Na+, K+-ATPase was evident in the cerebrum, hippocampus, striatum and thalamus, while the hypothalamus and olfactory bulb were spared. Pretreatment of gerbils with allopurinol, clonazepam or combinations of thiopental plus either indomethacin or methylprednisolone offered protection to cerebral Na+, K+-ATPase subsequent to secondary ischemia. With only minor exceptions (striatum) neither Ca2+, Mg2+- nor Mn2+-ATPase were altered by stroke or treatment with drugs.

Regional cyclic AMP systems during secondary ischemia in gerbils: influence of anesthetic agents.

The effect of three modes of anesthesia was evaluated with regard to regional damage to central cyclic nucleotide systems in the gerbil brain as a consequence of bilateral ischemia (clamping the common carotids) followed by various periods of recirculation. The injection of thiopental as much as 90 min before stroke prevented damage to chemical activation [catecholamines, guanosine triphosphate (GTP), or forskolin] of adenylate cyclase. However, the basal enzyme activity was lower in all brain regions whether thiopental was administered to stroke or sham-operated animals. Injection of ketamine drastically shortened the survival times of gerbils undergoing stroke followed by recirculation. About 90% of the animals could tolerate a maximum of only 15 min stroke with 15 min recirculation. At this time frame the patterns of activation of adenylate cyclase in only the olfactory tubercle and hippocampus were altered. When procaine was used as a local anesthetic agent during surgery, damage to catecholamine-, GTP-, or forskolin-activated adenylate cyclase was evident to varying degrees in the frontal cortex, hippocampus or olfactory tubercle, but not in the nucleus accumbens and olfactory bulb of gerbils subjected to 60-min stroke followed by 15 or 150 min of recirculation. The degree of enzyme damage was neither correlated with the fed vs. fasted state of the animal nor with the whole blood concentration of glucose. A depression in the amplitude of visually evoked potentials correlated to neurological signs and to enzyme damage. During anesthesia, ketamine increased steady-state concentrations of cyclic AMP in the frontal cortex and hippocampus from gerbil brains that had been rapidly inactivated by microwave irradiation. Thiopental increased steady-state cyclic AMP in only the olfactory tubercle. Cyclic GMP concentrations were unchanged by any anesthetic agent. In animals completely recovering from anesthesia and occluded for a brief period followed by 10 min of reflow, steady-state concentrations of only cyclic AMP were augmented.

Protective action by methylprednisolone, allopurinol and indomethacin against stroke-induced damage to adenylate cyclase in gerbil cerebral cortex.

Adenylate cyclase activity was investigated in either homogenate or particulate fractions from the frontal cerebral cortex of the gerbil following five experimental conditions of bilateral ischemia. After periods of 15 min ischemia, 15 min ischemia plus 15 min of recirculation or 60 min ischemia the enzyme generally displayed enhanced responses to GTP, norepinephrine (NE), dopamine (DA), NE + GTP and DA + GTP. Pretreatment of the gerbils with methylprednisolone, allopurinol or indomethacin did not significantly influence the outcome of these findings. When the animals were subjected to 60 min ischemia plus 15 min of reflow, enzyme responses to the stimulatory agents including forskolin and NaF were all reduced. Pretreatment with methylprednisolone, allopurinol or indomethacin prevented the damage to adenylate cyclase in the 60 min ischemia plus 15 min reflow animals. When animals were made ischemic for 15 min followed by one week of recovery, enzyme sensitivity to GTP, calmodulin-Ca++, NE, combinations thereof and forskolin were reduced in only the particulate fractions. Enzyme damage was reversed following methylprednisolone. Enzyme damage may result from generation of free radicals during reflow and drugs that either inhibit synthesis pathways generating free radicals, stabilize cell membranes or act as free radical scavengers may be therapeutically beneficial under specific conditions of stroke.

Kinetics of GTP-modulation of adenylate cyclase in gerbil cerebral cortex after bilateral ischemia.

Changes in the sensitivity of adenylate cyclase and steady-state levels of cyclic AMP (adenosine 3',5'-monophosphate) occur in mammalian brain during ischemic episodes. In our previous investigation with the gerbil model of bilateral ischemia there was an indication that ischemic conditions produced an enhancement of GTP sensitivity of adenylate cyclase within the cerebral cortex. The present study employed a kinetic analysis to evaluate further the role of this GTP modulation of adenylate cyclase in the gerbil frontal cortex during periods of bilateral ischemia and recirculation. In general, after either 15-min (with or without 15-min reflow) or 60-min ischemia the Vmax to GTP (alone or with dopamine and norepinephrine) was increased. Under these conditions the ED50 for half-maximal enzyme activation was decreased, indicating a greater affinity of the transducer site for GTP during ischemia. However, if irreversible 60-min ischemia was followed by 15-min reflow the enzyme responses to GTP were now absent. An unexpected observation showed that the ED50 for GTP activation of cortical adenylate cyclase was likewise attenuated when sham-operated animals were compared to normal gerbils.

Erotomania or de Clérambault syndrome.

De Clérambault focused attention on a syndrome in which a woman has the delusional belief that a man, usually of higher social status and considerably older, is much in love with her. If the patient's romantic ideas shaped private fantasies instead of determined public behavior, there would be little cause for concern. The situation becomes critical when the fantasies are dramatized in real life with an unsuspecting and usually unwilling man cast in the role of the lover. The woman dwells on the feelings she ascribes to her "suitor." Such delusional thinking, resulting from an ego defect and producting bizarre actions, may be shaped largely by feelings of being unloved or even unloveable; a narcissistic blow is overcome by a grandiose fantasy. Cases in which erotomania is prominent are usually diagnosed as paranoid state or paranoid schizophrenia.