Analysis of the axial flow field in stenosed carotid artery bifurcation models--LDA experiments

Laser Doppler anemometer (LDA) experiments were performed to gain quantitative information on the differences between the large-scale flow phenomena in a non-stenosed and a stenosed model of the carotid artery bifurcation. The influence of the presence of the stenosis was compared to the effect of flow pulse variation to evaluate the feasibility of early detection of stenosis in clinical practice. Three-dimensional Plexiglass models of a non-stenosed and a 25% stenosed carotid artery bifurcation were perfused with a Newtonian fluid. The flow conditions approximated physiological flow. The results of the velocity measurements in the non-stenosed model agreed with the results from previous hydrogen-bubble visualization. A shear layer separated the low-velocity area near the non-divider wall from the high-velocity area near the divider wall. In this shear layer, vortex formation occurred during the deceleration phase of the flow pulse. The instability of this shear layer dictated the flow disturbances. The influences of the mild stenosis, located at the non-divider wall, was mainly limited to the stability of the shear layer. No disturbances were found downstream of the stenosis near the non-divider wall. Using a pulse wave with an increased systolic deceleration time, the velocity distribution showed an extended region with reversed flow, a more pronounced shear layer and increased vortex strength. From these measurements it is obvious that the influence of the presence of a mild stenosis, mainly limited to the stability of the shear layer, can hardly be distinguished from the effects of a variation of the flow pulse. From this it can be concluded that methods for detection of mild stenosis, using solely the large-scale flow phenomena, as can be measured by ultrasound or MRI techniques, will hardly have any clinical relevance.     

Acetylcholine-activated chloride current in the T-84 colonic cell line

Plasma viral burden has proven valuable in predicting the future course of systemic HIV related disease and the response to treatment. It is not known whether plasma or cerebrospinal fluid (CSF) viral burden can be used to predict onset of or response to treatment of nervous system disease. We propose a model of viral load mediated neurotoxicity underlying peripheral and central HIV associated neurological disease. The objective of this preliminary study was to assess the relationship of HIV associated neurological disease to quantitative viral load in plasma and CSF. 47 subjects (HIV- = 10, HIV+ = 37) participated in the study. Plasma and CSF samples were collected within a 3 h window. RT-PCR (Roche Amplicor Monitor) was utilized to assess HIV-1 RNA viral load in both plasma and cell free (centrifuged) CSF. Subjects underwent concurrent comprehensive neurological and neuropsychological evaluations. In general, systemic viral load, as measured in plasma, was greater than that found in cell free CSF. Cell free CSF HIV RNA viral load was significantly correlated with neurological dysfunction, whereas plasma viral load was not. The sole subject with an elevated CSF viral load (> 5 Log 10), had HIV associated dementia (HAD) on clinical examination.     

Pitfalls in diagnosis of Lyme disease. What you need to know about serologic testing

Lyme disease can be difficult to recognize because not all patients have erythema migrans or other classic symptoms. Therefore, laboratory testing has become an important aid to clinical diagnosis. But the story doesn't end there-serologic testing presents another set of problems and concerns. Drs. Still and Ryan explain how aspects of the disease itself and various factors inherent in the available tests can affect laboratory results.     

Cerebral complications of murine monoclonal CD3 antibody (OKT3): CT and MR findings

Treatment of acute renal allograft rejection with mouse monoclonal antibody (OKT3) is associated with systemic and neurologic side effects. We describe cerebral abnormalities in a 13-year-old boy with steroid-resistant renal allograft rejection. After treatment with OKT3, an acute neurologic syndrome developed, including seizures, lethargy, and decreased mental function. CT and MR imaging revealed confluent cerebral lesions at the corticomedullary junction. Contrast-enhanced MR images showed patchy enhancement, indicating blood-brain barrier dysfunction. The diagnosis of OKT3-induced encephalopathy with cerebral edema and capillary leak syndrome was made. Although CT and MR findings are nonspecific, neuroradiologists should be aware of this condition in transplant patients treated with OKT3.     

Noradrenergic suppression of synaptic transmission may influence cortical signal-to-noise ratio

Norepinephrine has been proposed to influence signal-to-noise ratio within cortical structures, but the exact cellular mechanisms underlying this influence have not been described in detail. Here we present data on a cellular effect of norepinephrine that could contribute to the influence on signal-to-noise ratio. In brain slice preparations of the rat piriform (olfactory) cortex, perfusion of norepinephrine causes a dose-dependent suppression of excitatory synaptic potentials in the layer containing synapses among pyramidal cells in the cortex (layer Ib), while having a weaker effect on synaptic potentials in the afferent fiber layer (layer Ia). Effects of norepinephrine were similar in dose-response characteristics and laminar selectivity to the effects of the cholinergic agonist carbachol, and combined perfusion of both agonists caused effects similar to an equivalent concentration of a single agonist. In a computational model of the piriform cortex, we have analyzed the effect of noradrenergic suppression of synaptic transmission on signal-to-noise ratio. The selective suppression of excitatory intrinsic connectivity decreases the background activity of modeled neurons relative to the activity of neurons receiving direct afferent input. This can be interpreted as an increase in signal-to-noise ratio, but the term noise does not accurately characterize activity dependent on the intrinsic spread of excitation, which would more accurately be described as interpretation or retrieval. Increases in levels of norepinephrine mediated by locus coeruleus activity appear to enhance the influence of extrinsic input on cortical representations, allowing a pulse of norepinephrine in an arousing context to mediate formation of memories with a strong influence of environmental variables.     

Removal of the inferior olive abolishes myoclonic seizures associated with a loss of olivary serotonin

Several lines of clinical evidence suggest that myoclonus is caused by a reduction of serotonin in the brain and hyperactivity of the inferior olive. We determined whether a change in serotonin content within the olivocerebellar system accompanied a predisposition to myoclonus and investigated the necessity of the inferior olive for a myoclonic seizure. The experiments employed the genetically epilepsy-prone rat that exhibits a profound myoclonic seizure in response to an auditory stimulus. We found that these animals demonstrated a significant reduction in the serotonergic innervation of the inferior olive without a significant change in the serotonergic innervation at any other level of the olivocerebellar circuit. The deficit in olivary serotonin was verified physiologically and pharmacologically by a reduced sensitivity of the genetically epilepsy-prone rat to the tremorogenic effect of harmaline, which is known to produce tremor through a mechanism that requires serotonergic innervation of the inferior olive. We quantified the timing of the myoclonic seizure of the genetically epilepsy-prone rat and found that its large amplitude 2-6 Hz clonus was always preceded by 9-10 Hz tremor that was synchronized among limbs. Ablation of the inferior olive by 3-acetylpyridine abolished the myoclonic seizure. The specificity of the deficit in olivary serotonin, the timing of the seizure, and the demonstration of the necessity of the inferior olive for myoclonus suggest that pathological inferior olivary activity contributes to the genesis of a myoclonic seizure.     

Novel qualitative structure-activity relationships for the antinociceptive actions of H2 antagonists, H3 antagonists and derivatives

Recent studies have shown that cimetidine, burimamide and improgan (also known as SKF92374, a cimetidine congener lacking H2 antagonist activity) induce antinociception after intracerebroventricular administration in rodents. Because these substances closely resemble the structure of histamine (a known mediator of some endogenous analgesic responses), yet no role for known histamine receptors has been found in the analgesic actions of these agents, the structure-activity relationships for the antinociceptive effects of 21 compounds chemically related to H2 and H3 antagonists were investigated in this study. Antinociceptive activity was assessed on the hot-plate and tail-flick tests after intracerebroventricular administration in rats. Eleven compounds induced time-dependent (10-min peak) and dose-dependent antinociceptive activity with no observable behavioral impairment. ED50 values, estimated by nonlinear regression, were highly correlated across nociceptive assays (r2 = 0.98, n = 11). Antinociceptive potencies varied more than 6-fold (80-464 nmol), but were not correlated with activity on H1, H2 or H3 receptors. Although highly potent H3 antagonists such as thioperamide lacked antinociceptive activity, homologs of burimamide and thioperamide containing N-aromatic substituents retained H3 antagonist activity and also showed potent, effective analgesia. A literature review of the pharmacology of these agents did not find a basis for their antinociceptive effects. Taken with previous findings, the present results suggest: 1) these compounds act on the brain to activate powerful analgesic responses that are independent of known histamine receptors, 2) the structure-activity profile of these agents is novel and 3) brain-penetrating derivatives of these compounds could be clinically useful analgesics.     

Social support among African-American adults with diabetes, Part 2: A review

STUDY OBJECTIVE: To study differences in cardiovascular lifestyle risk factors and biological risk markers in early adult life, with special attention to age and sex differences. Lifestyle cardiovascular risk factors included dietary habits, physical inactivity, smoking, alcohol habits, psychosocial strain, and mental stress. Biological risk markers included anthropometric variables, arterial blood pressure, and serum cholesterol concentration. DESIGN: A combined individual and community based preventive programme, including health examinations. SETTING: All communities in the County of Skaraborg in south western Sweden. PARTICIPANTS: Altogether 12,982 men and women aged 30 or 35 years who underwent health examinations over seven years. MAIN RESULTS: In both sexes, biological risk markers studied were worse in 35 year old subjects than in 30 year olds. Furthermore, a larger proportion of men aged 35 years were smokers and were physically inactive compared with 30 year old men. However, dietary habits were better in both sexes in the upper age group. At both ages there were also significant differences between men and women. Women, compared with men, had better dietary habits and lower alcohol consumption but smoked more and experienced greater mental stress and psychosocial strain. All biological risk markers were worse in men than in women at both ages studied. During the observation period, some improvement of the health profile of the participants was observed, indicating a beneficial effect of the intervention programme. CONCLUSIONS: The results indicate that the risk of cardiovascular disease, as assessed from studying lifestyle and biological risk markers, increases early in life, suggesting that preventive measures should start early.     

Oral glucose ingestion increases endurance capacity in normal and diabetic (type I) humans

The effects of an oral glucose administration (1 g/kg) 30 min before exercise on endurance capacity and metabolic responses were studied in 21 type I diabetic patients [insulin-dependent diabetes mellitus (IDDM)] and 23 normal controls (Con). Cycle ergometer exercise (55-60% of maximal O2 uptake) was performed until exhaustion. Glucose administration significantly increased endurance capacity in Con (112 +/- 7 vs. 125 +/- 6 min, P < 0.05) but only in IDDM patients whose blood glucose decreased during exercise (70.8 +/- 8.2 vs. 82.8 +/- 9.4 min, P < 0.05). Hyperglycemia was normalized at 15 min of exercise in Con (7.4 +/- 0.2 vs. 4.8 +/- 0.2 mM) but not in IDDM patients (12.4 +/- 0.7 vs. 15.6 +/- 0.9 mM). In Con, insulin and C-peptide levels were normalized during exercise. Glucose administration decreased growth hormone levels in both groups. In conclusion, oral glucose ingestion 30 min before exercise increases endurance capacity in Con and in some IDDM patients. In IDDM patients, in contrast with Con, exercise to exhaustion attenuates hyperglycemia but does not bring blood glucose levels to preglucose levels.