MR imaging, flow and motion.

The present work is intended as a nonmathematical review of the role of flow and motion in nuclear magnetic resonance (MR) imaging. A historical review of MR flow measurement techniques is given, followed by a short overview of flow models in vitro and in vivo. The theory behind the influence of motion on the modulus and phase MR signal information is discussed and effects such as washin/washout, flow-induced signal void, phase offset, and phase dispersion are defined. A simple approach to the concept of MR angiography is given, and methods for quantitative flow measurements such as the phase mapping technique, are surveyed. Aspects of the measurement of diffusion and microcirculation are given, and finally, an overview of the role of MR flow imaging in present and future clinical application is given.     

Prevalence and correlates of arthritis‐attributable work limitation in the US population among persons ages 18–64: 2002 National Health Interview Survey Data

Objective

To estimate the national prevalence of arthritis‐attributable work limitation (AAWL) among persons ages 18–64 with doctor‐diagnosed arthritis and examine correlates of AAWL.

Methods

Using the 2002 National Health Interview Survey, we estimated the prevalence of AAWL (limited in whether individuals work, the type of work they do, or the amount of work they do) and correlates of AAWL in univariable and multivariable‐adjusted logistic regression analyses. Survey data were analyzed in SAS and SUDAAN to account for the complex sample design.

Results

A total of 5.3% of all US adults ages 18–64 reported AAWL; in this age group, AAWL is reported by ～30% of those who report arthritis. The prevalence of AAWL was highest among people ages 45–64 years (10.2%), women (6.3%), non‐Hispanic blacks (7.7%), people with less than a high school education (8.6%), and those with an annual household income <$20,000 (12.6%). AAWL was substantially increased among people with arthritis‐attributable activity limitations (multivariable‐adjusted odds ratio [OR] 9.1, 95% confidence interval [95% CI] 7.1–11.6). The multivariable‐adjusted likelihood of AAWL was moderately higher among non‐Hispanic blacks (OR 1.6, 95% CI 1.2–2.3), Hispanics (OR 1.8, 95% CI 1.2–2.6), and people with high levels of functional/social/leisure limitations (OR 1.8, 95% CI 1.4–2.3) and was decreased among those with a college education (OR 0.6, 95% CI 0.4–0.8).

Conclusion

AAWL is highly prevalent, affecting millions of Americans and one‐third of adults with doctor‐diagnosed arthritis. Findings suggest the need for more targeted research to better understand the natural history, success of interventions, and effects of policy on AAWL. Public health interventions, including self‐management education programs, may be effective in countering AAWL.     

Relation between tobacco use and urinary excretion of thromboxane A2 and prostacyclin metabolites in young men

BACKGROUND. Cigarette smoking is a risk factor for cardiovascular disease. The present study addressed the effect of tobacco use on the formation of two eicosanoids, thromboxane A2 and prostacyclin, which have been implicated in both acute and chronic cardiovascular disorders. METHODS AND RESULTS. In 577 randomly sampled 18-19-year-old men, the urinary excretion of the 2,3-dinor metabolites of thromboxane A2 and prostacyclin (Tx-M and PGI-M, respectively) was analyzed and related to the subjects' self-reported use of tobacco. Sixty-five percent of the subjects used no tobacco, 7.5% were cigarette smokers, 22% used wet (oral) snuff, and the rest reported a mixed use of tobacco. The urinary excretion of Tx-M was higher (p less than 0.001) in cigarette smokers than in those not using tobacco (180 versus 128 pg/mg creatinine) and was correlated (r = 0.35, p less than 0.05) with the daily cigarette consumption. Snuff users had no increase in their urinary excretion of Tx-M, despite urinary cotinine levels comparable to those in the cigarette smokers (1,210 and 1,560 ng/ml, respectively). The excretion of PGI-M did not differ between non-tobacco users, cigarette smokers, and snuff users. CONCLUSIONS. We conclude that cigarette smoking, but not the use of snuff, facilitates the formation of thromboxane A2. We propose that such an increased formation reflects platelet activation in the absence of vascular injury and that it may be of significance for the subsequent development of cardiovascular disease.     

Tubulointerstitial nephritis caused by the antiviral agent foscarnet

The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymorphonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.     

Tears of the medial meniscus associated with increased radionuclide activity of the proximal tibia

Summary Three patients who presented with long-standing medial knee pain and normal radiographs had an isotope bone scan in an attempt to arrive at a diagnosis. In each case there was a well-defined area of increased uptake over the medial tibial condyle and arthroscopy subsequently revealed meniscal damage. After arthroscopic menisectomy each patient became asymptomatic and the bone scan returned to normal. We suggest that patients with incapacitating knee pain, normal radiographs and a positive bone scan undergo an arthroscopy even in the absence of clinical signs of meniscal damage.

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Résumé Trois malades qui présentaient depuis longtemps des douleurs de la partie interne du genou et dont les radiographies étaient normales ont bénéficié d'une scintigraphie afin d'essayer d'ðablir un diagnostic. Dans tous les cas il y avait une zone bien limitée d'hyperfixation au niveau de la partie interne de l'extrémité supérieure du tibia, et l'arthroscopie ultérieure découvrit une lésion méniscale. Après méniscectomie arthroscopique tous les malades furent soulagés et la scintigraphie redevint normale. Nous proposons que l'on pratique une arthroscopie, même en l'absence de signes cliniques d'atteinte méniscale, chez les sujets présentant des douleurs notables du genou, avec des radiographies normales et une scintigraphie positive.

     

Pharmacokinetics of ketanserin in patients with essential hypertension

Summary The pharmacokinetics of ketanserin and its main metabolite ketanserin-ol, and the antihypertensive effects of intravenous, single oral and chronic oral (40 mg once daily) administration of ketanserin, have been investigated in a single blind study of 10 patients with uncomplicated mild hypertension. Ketanserin had a terminal half-life of 29.2 h, a plasma clearance of 518 ml/min and a volume of distribution of 18.0 l/kg. Chronic oral intake of 40 mg ketanserin (tablet formulation) gave a peak concentration of unchanged ketanserin of 88 ng/ml after 1.1 h. Its absolute bioavailability was 48%.During chronic therapy the maximal concentration of ketanserin-ol was 208 ng/ml and its half-life of elimination was 35.0 h. As this metabolite can be oxidized back to ketanserin, it contributes to the prolonged half-life of unchanged ketanserin seen during chronic therapy.The blood pressure was reduced by approximately 15% by oral ketanserin. The maximal reduction in blood pressure coincided with the peak concentration of unchanged ketanserin. During chronic therapy with 40 mg once daily blood pressure was reduced over 24 h. The heart rate was slightly reduced and the cardiovascular responses and the plasma noradrenaline concentrations during isometric exercise were only slightly influenced by ketanserin therapy.Thus, unchanged ketanserin has a relatively long half-life during chronic oral therapy and its pharmacokinetics in middle-aged hypertensive patients is similar to that in normal young volunteers.     

Kainic acid-mediated increase of preprotachykinin-A messenger RNA expression in the rat hippocampus and a region-selective attenuation by dexamethasone.

The hippocampus contains the highest number of glucocorticoid-sensitive neurons in the rat brain and excessive exposure to glucocorticoids can cause damage to hippocampal neurons and impair the capacity of the hippocampus to survive neuronal insults. In this study in situ hybridization combined with quantitative image analysis was used to study preprotachykinin-A mRNA levels after administration of a toxic dose of kainic acid in animals pretreated with glucocorticoids. Kainic acid was injected into dorsal hippocampus CA3 region in animals pretreated with the synthetic glucocorticoid receptor agonist dexamethasone and in control animals. Preprotachykinin-A mRNA was not detected in the hippocampus of untreated animals or in animals analysed 30 min after a kainic acid injection. However, 4 h after injection of kainic acid, the level of preprotachykinin-A mRNA increased to 20-times above the detection limit both in the dentate gyrus and the CA3 region of the hippocampus. Treatment of kainic acid-injected animals with dexamethasone 30 min before and 2 h after the injection attenuated the increase in the granule cells of the dentate gyrus by 50%. In contrast, dexamethasone pretreatment had no significant effect on the kainic acid-induced increase of preprotachykinin-A mRNA in pyramidal cells in regions CA3 or CA1. These results show that an excitatory stimulus within the hippocampus causes a substantial increase in the level of preprotachykinin-A mRNA in hippocampal granule and pyramidal cells and suggest that in granule cells of the dentate gyrus this increase can be modulated by glucocorticoids.     

Chemical monitoring of neurosurgical intensive care patients using intracerebral microdialysis.

The authors have used intracerebral microdialysis to develop a method for routine monitoring of disturbances in brain energy metabolism in patients in the neurosurgical intensive care unit. Microdialysis was conducted for periods ranging from 2.3 to 8.3 days in four patients (three with severe head injuries and one with severe subarachnoid hemorrhage). Altogether, 4447 chemical analyses from 587 dialysis samples were carried out. Concentrations of the energy-related metabolites lactate, pyruvate, and hypoxanthine were measured, and the lactate:pyruvate ratio was calculated. In addition, the acids glutamate, aspartate, taurine, glutamine, asparagine, and glycine were measured in one patient. The microdialysis data were matched with various clinical events, including intracranial hypertension and therapeutic interventions such as initiation or withdrawal of barbiturates and cerebrospinal fluid drainage. The present study shows that microdialysis can be used for long-term measurement of extracellular fluid (ECF) energy-related metabolites and amino acids in the frontal cortex of neurosurgical patients in a clinical setting. Fluctuations of the measured ECF energy-related substances corresponded to various clinical events presumably involving hypoxia/ischemia. The authors found a 25-fold increase in ECF glutamate, aspartate, and taurine under conditions of energy perturbation, as indicated by high levels of the lactate:pyruvate ratio, lactate, and hypoxanthine. The use of long-term intracerebral microdialysis in patients opens a new field of clinical research, with many possibilities for improving insight into intracranial dynamics in acute cerebral conditions.     

Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals

JC virus (JCV) infection is regularly asymptomatic in healthy individuals. In contrast, in immunocompromised individuals, highly activated virus replication may lead to PML. Peripheral blood cells (PBCs) are found to habor JCV DNA in healthy and diseased individuals and it is discussed that they might be responsible for dissemination of the virus to the central nervous system (CNS) during persistence. To better understand the role of JCV DNA in PBCs for persistent infection and pathogenesis, the authors characterized the extent of JCV infection in Ficoll-gradient purified blood cells (peripheral blood mononuclear cells [PBMCs]) of healthy and human immunodeficiency virus type 1 (HIV-1)-infected individuals. Virus activation in PBMCs from healthy JCV-infected individuals was found at a rate of 0% to 38% at low polymerase chain reaction (PCR) sensitivity. In progressive multifocal leukoencephalopathy (PML) patients, a stronger signal was found, indicating increased virus activation. JCV DNA was regularly detected in T and B lymphocytes and in monocytes at low levels. However, granulocytes were shown to be the predominant reservoir of JCV DNA harboring high copy numbers. Although the overall distribution of viral genomes holds true for the population studied, in the individual, a markedly changed pattern of distribution can be found.     

Systemic Absorption and Block after Epidural Injection of Ropivacaine in Healthy Volunteers

Background: For local anesthetics, the process of removal from the site of administration influences the duration of anesthesia and the risk for systemic toxicity to develop. The systemic absorption of epidural ropivacaine and the time profile of sensory and motor block were studied in healthy volunteers.

Methods: Nine persons simultaneously received 150 mg ropivacaine hydrochloride (7.5 mg/ml) epidurally and 40 mg deuterium-labeled (sup 2 H sub 3)ropivacaine hydrochloride (0.25 mg/ml) intravenously. Peripheral arterial and venous plasma samples were collected, and assessments of sensory and motor block were made.

Results: The arterial plasma concentrations increased faster than the venous concentrations, with 50% higher maximum concentrations after both intravenous and epidural administration. The absorption was biphasic. A correlation was seen between the duration of sensory block and the slower absorption half-life; that is, the longer the half-life, the longer the duration. The extent of spread varied among the volunteers, with the median upper block level not exceeding T12. The motor block (Bromage score 1) was of slower onset (median, 0.4 h) and of shorter duration (median, 4.1 h) than the sensory block (onset, 0.2 h; duration, 6.5 h at L2 medians).