Mechanisms of nasal hyper-reactivity

Hyper-reactivity to non-specific challenges has been considered a hallmark of asthma and is defined as an abnormal responsiveness of the bronchial airways to a variety of provocative agents. The mechanisms underlying hyper-reactivity in the upper and lower airways are not known. By using the nose to study the inflammatory response possible abnormalities can be investigated carefully and pathophysiology of specific airway hyper-reactivities can be better understood. Other factors than merely constriction of the bronchial smooth muscles can cause narrowing of the free lumen to airflow. Functionally different and very distinct mucosal end-organ reactivities may also be increased. If these reactivities can be well assessed, specific airway hyper-reactivity can be defined. In the present report, specific mucosal end-organ hyper-reactivites in the allergic nasal mucosa are presented. Certain widespread hypotheses, such as the role of the eosinophil and the “increased absorption permeability theory”, are disputed.     

Retrospective versus original information on diet: implications for epidemiological studies

The aim of this study was to evaluate the use of retrospective information on diet in relation to the information originally reported. Hospital controls (n = 131) who participated in a case-control study on diet and pancreatic cancer in Stockholm, Sweden, answered a second postal questionnaire four years later about their current and previous food consumption. The food consumption was dichotomized for the purpose of the analysis. In relation to the original information, the use of retrospective information overestimated previous food consumption among subjects with increased intake, while retrospective information underestimated previous food consumption among subjects with decreased intake. These tendencies were slightly more pronounced in the age group 60-79 years than in the age group 40-59 years. For subjects with unchanged food consumption, there was a high agreement between original and retrospective information. Considerable differential misclassification could be introduced in an epidemiological study if cases and non-cases differ with regard to changes in food consumption.     

No persistent effect of angiotensin converting enzyme inhibitor treatment in Milan hypertensive rats despite regression of vascular structure.

Milan hypertensive rats were treated, from ages 4 to 24 weeks, with the angiotensin converting enzyme (ACE) inhibitor, perindopril, in doses of 1.5 mg/kg per day or 0.4 mg/kg per day. Controls were untreated Milan hypertensive rats. At age 24 weeks, a mesenteric biopsy was taken, from which two resistance vessels were taken out and mounted on a myograph for structural and functional analysis. Thereafter, treatment was withdrawn and the blood pressure of the rats was followed until age 36 weeks. Perindopril treatment had a dose-dependent effect on blood pressure as well as on both structural (media thickness, media: lumen ratio) and functional (estimated pressure against which vessels could contract) parameters of the resistance vessels. However, when treatment was withdrawn, blood pressure rose to (low-dose perindopril group) or above (high-dose perindopril group) control levels. The results contrast with previous studies using spontaneous hypertensive rats (SHR) where, using the same protocol, blood pressure remains low after withdrawal of treatment with ACE inhibitors, including perindopril, although the effect on resistance vessel parameters is similar. The results show that the persistent effect of ACE inhibitor therapy which has been seen in SHR is not a general feature of genetic hypertension. Furthermore, these results raise doubts as to whether the persistent effect seen in SHR is due to a general effect of ACE inhibitor treatment on vascular structure.     

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.     

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.