Evaluation of various attenuation corrections in lung SPECT in healthy subjects

The effect of increasingly more sophisticated attenuation correction methods on image homogeneity has been studied in seven healthy subjects. The subjects underwent computed tomography (CT), single photon emission computed tomography (SPECT) and transmission computed tomography (TCT) of the thorax region in the supine position. Density maps were obtained from the CT and TCT studies. Attenuation corrections were performed using five different methods: (1) uniform correction using only the body contour; (2) TCT based corrections using the average lung density; (3) TCT based corrections using the pixel density; (4) CT based corrections using average lung density; and (5) CT based corrections using the pixel density. The isolated attenuation effects were assessed on quotient images generated by the division of images obtained using various attenuation correction methods divided by the non-uniform attenuation correction based on CT pixel density (reference method). The homogeneity was calculated as the coefficient of variation of the quotient images (CV(att)), showing the isolated attenuation effects. Values of CV(att) were on average 12.8% without attenuation correction, 10.7% with the uniform correction, 8.1% using TCT map using the average lung density value and 4.8% using CT and average lung density corrections. There are considerable inhomogeneities in lung SPECT slices due to the attenuation effect. After attenuation correction the remaining inhomogeneity is considerable and cannot be explained by statistical noise and camera non-uniformity alone.     

Day-to-day variation of bronchodilatory response to an inhaled beta-2-stimulant in asthmatics

The effect of inhaling 0.25 and 2.0 mg of terbutaline sulphate, a beta-2-stimulant, from a metered dose aerosol was studied in five asthmatic patients during two periods of five days each. During the first period, the patients used a good spontaneous inhalation technique; during the second period, the inhalation technique was optimized and controlled. The variation of basal FEV1 and of the increase (delta FEV1) caused by 0.25 mg of inhaled terbutaline was considerable. The effect was only slightly better and the variation only slightly smaller when the controlled inhalation technique was used. The differences were not significant. In individual patients, there was no or negative correlation between delta FEV1 and the corresponding basal FEV1 value. Accordingly, the most commonly used way of expressing delta FEV1 as a percentage of basal FEV1 value was found to be insensitive. Delta FEV1, expressed as a percentage of the maximum available FEV1 increase on the same day after 2.25 mg terbutaline sulphate, was found to be most sensitive. This way of expressing delta FEV1 will increase the possibilities of detecting differences between treatments in clinical trials.     

Does digital chest radiography assess regional ventilation?

Summary. Digital radiography of the chest was evaluated for estimation of regional ventilation disturbances. Thirty-three patients with suspected bronchial carcinomas were examined. Objective measurements of regional density changes during breathing correlated significantly with standardized regional lung function tests (¹³³Xe ventilation scintigraphy), but did not permit reliable individual estimations of regional ventilation. About 35% of the density variations could be explained by regional ventilation. Thus, factors other than ventilation, e.g. changes in the geometry of the thorax, have a major impact on the density variation at digital radiography.,     

Improved red cell survival in patients with chronic subclinical haemolysis due to artificial heart valve. Observations after in vitro treatment of the cells with potassium cyanate

Red cell survival was studied with use of Chromium-51 isotope and standard haematologic tests of haemolysis. The study comprised 30 patients with normally functioning single artificial heart valves of various types. They were investigated on 2 or 3 occasions. Red cells labelled with Cr-51 were treated for 30 min with potassium cyanate (0.5 mg/100 ml) in 5% invertose or with only 5% invertose. The mean red cell survival without cyanate treatment was 25 (+/- 4.2) days. Following cyanate treatment this figure improved to 31 (+/-4.8) days. Low-grade chronic intravascular haemolysis was associated with all the valve types. Abnormal results were found in 67% and 62% of the tests in patients with ball-type valve (deBakey and Starr-Edwards, respectively). The figures for tilting disc values (Lillehei-Kaster and Bj?rk-Shiley) were 51 and 45.5%, while Carpentier-Edwards bioprosthetic valves gave 15.5% abnormal test results. The findings thus suggested that ball valves are more haemolytic than tilting disc valves, which in turn are more haemolytic than tissue valves.     

Nasal mucosal blood flow after intranasal allergen challenge

The nasal mucosal blood flow in patients with allergic rhinitis was determined at nasal allergen challenges with the 133Xenon washout method. Determinations were made in 12 subjects before and 15 minutes after challenge with diluent and increasing doses of allergen. The time course was followed in eight subjects by means of repeated measurements during 1 hour after a single allergen dose. Finally, the blood flow was measured after unilateral allergen challenge in the contralateral nasal cavity. A dose-dependent decrease in blood flow was found after nasal challenge with increasing doses of allergens, whereas challenge with diluent alone did not induce any changes. The highest allergen dose, which also induced pronounced nasal symptoms, resulted in a decrease in blood flow of 25% (p less than 0.001). The time-course study demonstrated a maximum decrease in blood flow 10 to 20 minutes after challenge and then a gradual return to baseline. Unilateral allergen challenge resulted in a decrease in blood flow in the contralateral, unchallenged nasal cavity, suggesting that part of the allergen-induced changes in blood flow were reflex mediated.     

Effects of topical treatment with H1 and H2 antagonists on clinical symptoms and nasal vascular reactions in patients with allergic rhinitis

Fifteen asymptomatic subjects with allergic rhinitis participated in a double-blind, randomized, crossover, placebo-controlled study. The subjects were pretreated intranasally with a single dose of a selective H1 receptor antagonist, levocabastine, and/or selective H2 receptor antagonist, ranitidine, prior to a nasal allergen challenge. The nasal symptoms obtained at the challenge were assessed using a scoring technique 15 min after the allergen exposure. The nasal airway resistance was determined twice prior to and once after the allergen challenge using anterior rhinomanometry. The nasal mucosal blood flow was determined before and 15 min after allergen challenge using the 133Xe wash-out technique. After pretreatment with the H1 antagonist there was a statistically significant reduction in the number of sneezes and rhinorrhea compared to pretreatment with placebo. Pretreatment with the H2 receptor significantly decreased the rhinorrhea but not the sneeze. The nasal blockage was unaffected by both the H1 and the H2 antagonists. Pretreatment with the H1 and/or the H2 antagonists inhibited the reduction in the nasal mucosal blood flow induced by the allergen challenge to a significant degree. The present findings suggest that topical treatment with the highly selective histamine antagonist, levocabastine, inhibits allergen-induced reflex-mediated symptoms. H1 and H2 receptors do not appear to be involved in the regulation of the tone of the capacitance vessels. This indicates that a more complex mechanism participates in the induction of nasal blockage than the direct effect of histamine on H1 and H2 receptors on the capacitance vessels of the nasal mucosa alone. Both H1 and H2 receptors are of importance for the regulation of nasal mucosal blood flow during the allergic reaction.     

Secretory immunoglobulin A (IgA) responses in IgA nephropathy patients after mucosal immunization, as part of a polymeric IgA response

Secretory immunoglobulin A (SIgA), although generated at mucosal surfaces, is also found in low concentrations in the circulation. Recently, SIgA was demonstrated in mesangial deposits of patients with immunoglobulin A nephropathy (IgAN), suggesting a role in the pathogenesis. This finding is in line with the belief that high molecular weight (HMW) immunoglobulin A (IgA) is deposited in the kidney. However, there is little information on the size distribution of antigen-specific IgA in circulation upon mucosal challenge. In this study we measured antigen-specific IgA, including SIgA, in serum following challenge of IgAN patients and controls via intranasal vaccination with a neoantigen, cholera toxin subunit B (CTB). We size-fractionated serum and nasal washes to study the size distribution of total IgA, SIgA and CTB-specific IgA. Finally, we compared the size distribution of antigen-specific IgA after mucosal immunization with the distribution upon systemic immunization. A significant induction of antigen-specific SIgA was detectable in serum of both patients with IgAN and controls after mucosal immunization with CTB. Independent of the route of immunization, in both groups the antigen-specific IgA response was predominantly in the polymeric IgA fractions. This is in contrast to total IgA levels in serum that are predominantly monomeric. We conclude that mucosal challenge results in antigen-specific SIgA in the circulation, and that the antigen-specific IgA response in both IgAN patients and in controls is of predominantly HMW in nature. No differences between IgAN patients and controls were detected, suggesting that the size distribution of antigen-specific IgA in the circulation is not disturbed specifically in IgAN patients.     

Generalized hexokinase deficiency in the blood cells of a patient with nonspherocytic hemolytic anemia

In a patient with nonspherocytic hemolytic anemia, a hexokinase deficiency was detected in the red cells (residual activity about 25% of normal) and in blood platelets (20%-35% of normal activity). Although the total hexokinase activity in lymphocytes was normal, the amount of hexokinase type I was decreased to about 50% of normal. However, the deficiency was compensated for by the appearance of type III hexokinase. Compartmentation studies with controlled digitonin- induced cell lysis showed that this type III enzyme was localized in the cytosol, while almost all hexokinase activity in normal lymphocytes is particulate. No abnormal lymphocyte functions could be detected. The patient was homozygous for the defect. The parents and three of five sibs of the patient were apparently heterozygous with residual activities of 50%-67% of normal in their red cells, but did not show any clinical signs of hexokinase deficiency. The variant enzyme had a slightly decreased affinity for MgATP2- and a strongly increased inhibition constant for glucose-1,6-P2. Affinity for glucose, heat stability, and pH optimum were normal. In the electrophoretic pattern of red cell hexokinase, only one subtype of hexokinase I could be detected, while in normal red cells, at least three subtypes are present. In the heterozygous individuals, no enzymatic abnormalities could be detected, except for an aberration in the electropherogram of one sib.