Biomedical subjects
Publications and source records attributed to P Eriksson.
A 36 year old man with Down's syndrome developed group B streptococcal (subtype Ia) mitral endocarditis, which was complicated by widespread abscess formation. He was given antibiotics for one year, and no surgery was performed. Despite the underlying condition, the IgM response and the production of specific antibodies against the bacteria were normal.
A patient with familial amyloid polyneuropathy and congestive heart failure underwent myocardial imaging using technetium-99m pyrophosphate. Planar scintigraphy showed an intense, diffuse biventricular uptake of the radiotracer. Single-photon emission computed tomography demonstrated an unevenly distributed uptake of the isotope. The greatest activity corresponded to regions with marked echocardiographic changes. Emission tomography may aid in assessing the degree and distribution of the infiltrative lesions in cardiac amyloidosis.
To assess the severity of outlfow obstruction in patients with aortic valve disease, the aortic valvar area was noninvasively determined in 22 patients with isolated aortic stenosis or combined stenosis and regurgitation. The ejection time (ET), maximal velocity (Vmax), and systolic velocity integral (SVI) of the aortic flow was obtained by continuous wave Doppler ultrasound. Left ventricular stroke volume (SV) was determined by radionuclide angiography, using a counts-based nongeometric technique with individual attenuation correction. Aortic valve area (AVA) was calculated using a modified Gorlin formula; AVA = SV/(71.2 X ET X Vmax), and also by dividing the stroke volume by the systolic velocity integral; AVA = SV/SVI. The two noninvasive determinations correlated closely with the valve areas obtained by invasive measurements; r = 0.95, SEE = +/- 0.13 cm2 by the modified Gorlin formula, and r = 0.94, SEE = +/- 0.14 cm2 by the integration method. The two noninvasive calculations showed almost uniform results; r = 0.98, SEE = +/- 0.09 cm2. In conclusion, aortic valve area can be determined with reasonable accuracy by combining Doppler echocardiography and radionuclide angiography. This noninvasive approach may reduce the need for invasive measurements in patients with suspected aortic valve disease. In addition, radionuclide angiography provides important information about left ventricular function.
It has been suggested that a higher cardiac stimulation threshold reduces the applicability of pacemaker therapy in cardiac amyloidosis. We therefore reviewed threshold data in patients with familial amyloidosis with polyneuropathy (FAP), which is an inherited type of systemic amyloidosis, invariably involving the heart. Fourteen FAP patients treated with a pacemaker were studied. The mean (+/- SD) voltage stimulation threshold during implantation was 1.0 +/- 0.5 V, and noninvasive follow-up 6 months later revealed a mean Vario threshold of 1.9 +/- 0.5 V. Beyond this time, the threshold tended to be stable, and high threshold exit block did not occur in any patient. Several FAP patients did show a moderately elevated threshold, and a multiprogrammable pulse generator with a high output capability is recommended when pacemaker therapy is considered in these patients.
The clinical and echocardiographic features of cardiac amyloidosis may closely resemble those of hypertrophic cardiomyopathy, and the disorders may thus be mixed up. The present study was undertaken in an attempt to identify features separating the two conditions by analysis of electro- and echocardiographic findings in patients with familial amyloid polyneuropathy and hypertrophic cardiomyopathy. Twenty-nine patients with familial amyloidosis and 22 with hypertrophic cardiomyopathy were studied. Particular attention was given to the sum of the S wave in V1 and R wave in V5 or V6, the echocardiographic left ventricular mass and cross-sectional area, the presence or absence of asymmetrical septal thickening, granular and sparkling myocardial appearance, thickened heart valves, systolic anterior motion of the mitral valve, and pericardial effusion. A granular and sparkling appearance of the myocardium and thickened heart valves were found to be the best predictors of cardiac amyloidosis, while low QRS amplitudes in relation to echocardiographic left ventricular mass and a pericardial effusion seemed less important. The presence of systolic anterior movement of the mitral valve, a large left ventricular mass and a sum of S in V1 and R in V5 or V6 greater than 35 mm indicated hypertrophic cardiomyopathy. When the four strongest predictors (left ventricular mass, thickened heart valves, a granular sparkling myocardial appearance, and systolic anterior movement of the mitral valve) were used to reclassify the present patients, 28 of 29 amyloidosis patients and 21 of 22 patients with hypertrophic cardiomyopathy were correctly categorized. Noninvasive methods may thus be useful for detecting the myocardial infiltrative process, and cardiac amyloidosis may be confidently diagnosed by typical noninvasive findings together with histopathological documentation of amyloid in an organ other than the heart.
Ten-day-old NMRI mice were given a single peroral dose of 1.4 mumol/kg body wt of either of the substances of DDT (0.5 mg), DDOH-PA (a DDT metabolite conjugated to palmitic acid; 0.7 mg), or polychlorohexadecane (PCHD, a synthesized chlorinated paraffin; 1.0 mg). The mice were killed either 24 hr or 7 days after treatment, and crude synaptosomal fractions (P2) were prepared from the cerebral cortex and hippocampus. The density of the muscarinic receptors was assayed by measuring quinuclidinyl benzilate ([3H]QNB) specifically bound in the P2 fraction. A significant increase in the specific [3H]QNB binding was observed in the cerebral cortex in DDT- and DDOH-PA-treated mice 7 days after treatment, compared to control. These results were further explored by determining the ratio of high- and low-affinity binding sites by using an agonist (carbachol)-antagonist ([3H]QNB) competition assay. A significant decrease in the percentage of high-affinity binding sites and a corresponding increase in the percentage of low-affinity binding sites, compared to control, were observed after DDT and DDOH-PA treatment. The presynaptically sodium-dependent choline uptake system also was studied. In mice receiving PCHD there was a significant decrease (65%) in the Vmax value 7 days after treatment, but no change was observed in mice receiving DDT or DDOH-PA. This study shows that the sensitivity of the cholinergic system to persistent xenobiotics acting over a long period of time may be higher in the immature mouse.
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Involvement of the heart is common in the various types of amyloidosis. Little attention has, however, been paid to the presence and significance of amyloid in cardiac valves. We examined the heart valves of twelve autopsy cases with familial amyloidosis with polyneuropathy. All leaflets showed more or less abundant amyloid infiltration with significant valvular aortic stenosis due to degenerative calcification in two cases. In familial amyloidosis with polyneuropathy, amyloid deposits are thus invariably present in the valves, but the valvular function is often preserved. Amyloid may, however, produce hemodynamically significant valvular lesions, and the importance of valvular involvement in the various types of amyloidosis may still be underestimated.
Amyloid infiltration of the heart may frequently masquerade as other cardiac disorders. The extended use of echocardiography may contribute to an erroneous diagnosis of hypertrophic cardiomyopathy, as both conditions show several features in common. This was the case with the patient reported below. A low QRS amplitude, an increased right ventricular wall thickness, thickened cardiac valves, and a pericardial effusion may, however, indicate amyloid infiltration. The diagnosis of systemic amyloidosis of immunocytic origin was subsequently established in our patient. A definitive diagnosis of amyloid heart disease requires endomyocardial biopsy, but it is suggested that typical noninvasive findings together with demonstration of amyloid in an organ other than the heart is sufficient for a reliable diagnosis. In addition, systemic manifestations may contribute to a correct diagnosis in generalized amyloidosis. Our patient had features consistent with the rare muscle pseudohypertrophy syndrome, which is associated with immunocytic amyloidosis.
There is an increased risk of anaesthetic complications in patients with myocardial disorders. The present paper concerns seven patients with familial amyloid polyneuropathy, who developed severe bradycardia or heart block during anaesthesia. Amyloid infiltration of the cardiac conducting tissues probably increases their susceptibility to anaesthetic agents. Dysfunction of autonomic nerves may also diminish cardiac impulse formation and conduction. In addition, the possibility of contributing succinylcholine-induced hyperkalaemia cannot be excluded. There was a prompt response to infusion of isoproterenol in all patients so treated, but the insertion of a temporary pacemaker prior to anaesthesia should, nevertheless, be seriously considered in this group of patients.
The mean pressure difference across the valve in aortic stenosis is an indicator of the severity of the obstruction to flow. Non-invasive determination of the mean pressure gradient by Doppler ultrasonography is, however, complicated by the squared relation between instantaneous velocities and pressure differences. The validity of a new simple formula for calculation of the mean pressure difference from the peak pressure difference was evaluated in 26 patients with aortic stenosis. The formula is: delta pmean = 0.64 delta ppeak, where delta pmean is the mean pressure gradient and delta ppeak the peak pressure gradient. There was a close correlation between the mean pressure differences determined by application of the formula to the peak pressure differences measured at catheterisation and the mean pressure differences obtained by planimetry (r = 0.97, SEE = 4.7 mm Hg). The correlation between mean pressure differences determined by continuous wave Doppler ultrasound and the formula and those measured by planimetry was also close (r = 0.91, SEE = 7.6 mm Hg) and only three patients showed a difference between the two methods of greater than 10 mm Hg. The new formula is a simple and reliable means of estimating the mean pressure difference from Doppler recordings and it facilitates the comparison of Doppler and catheterisation data.
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The uptake of L-[3H]glutamate, L-[3H]aspartate, gamma-[3H]aminobutyric acid (GABA), [3H]dopamine, DL-[3H]norepinephrine and [3H]5-hydroxytryptamine (5-HT) was studied in astrocytes cultured from the cerebral cortex, striatum and brain stem of newborn rat and grown for 2 weeks in primary cultures. The astrocytes exhibited a high-affinity L-glutamate uptake with Km values ranging from 11 to 110 microM. Vmax values were 4.5 in cerebral cortex, 39.1 in striatum, and 0.4 in brain stem, nmol per mg cell protein per min. There was a less prominent high-affinity uptake of L-aspartate with Km values from 88 to 187 microM. Vmax values were 7.4 in cerebral cortex, 37.1 in striatum, and 3.1 in brain stem, nmol per mg cell protein per min. The high-affinity GABA uptake exhibited Km values ranging from 5 to 17 microM and Vmax values were 0.01 for cerebral cortex, 0.04 for striatum, and 0.1 for brain stem, nmol per mg cell protein per min. No high-affinity, high-capacity uptake was found for the monoamines. The results demonstrate a heterogeneity among the astroglial cells cultivated from the different brain regions concerning the uptake capacity of amino acid neurotransmitters. Furthermore, amino acid transmitters and monoamines are taken up by the cells in different ways.
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The transvalvular pressure difference in 58 consecutive patients with valvular aortic stenosis was calculated from maximal aortic jet velocity measured by continuous wave Doppler ultrasound within 24 hr of cardiac catheterization. An adequate Doppler registration was obtained in 50 patients (86%), and no patient was excluded from the study because of a non-ideal registration. For the total series of patients, a correlation coefficient r = 0.85 between Doppler-calculated and invasively measured pressure differences was obtained, and for the 6 patients examined simultaneously by the two methods a correlation coefficient r = 0.91 was obtained. These results confirm that Doppler ultrasound is a useful method for quantification of the pressure difference across the valve in aortic stenosis. Together with other non-invasive measures, Doppler ultrasound is a valuable aid in the evaluation of patients with suspected aortic stenosis.
In a quantitative retaining study and a whole-body autoradiographic study 5 14C-labelled compounds, bis-(4-chlorophenyl)trichloroethane (DDT), 2,2',4,4',5,5'-hexachlorobiphenyl (6-CB), hexachlorophene (HCP), polychlorohexadecane (PCHD) and diethylhexylphthalate (DEHP) were each administered to mice at the age of 3, 10 and 20 days. The mice were killed 24 h or 7 days after treatment and the amount of radioactivity in the whole brain was measured and its distribution studied. The retention of radioactivity was most pronounced in mice receiving DDT, PCHD, and 6-CB during the tenth day of life. Here the level of radioactivity 7 days after treatment was nearly as high as that observed after 24 h (ratio between 0.86 and 0.74). In contrast, HCP showed a rapid elimination from the brain and was hardly retained at all in the 20-day-old mouse brain. The retention of DEHP in the brain was minimal. Some of the autoradiographic sections were also subjected to myelin staining. Large amounts of radioactivity were found in the myelinated areas of the brain after HCP and PCHD administration. DDT and 6-CB showed a more even distribution within the brain and were not particularly concentrated in the myelin. There was no obvious relationship between the lipophilicity of the parent compounds and their retention in the brain.
Two-dimensional echocardiography in systemic amyloidosis has in most cases shown highly refractile myocardial echoes. The morphological basis for this finding has so far been little examined. In the present study, echocardiographic examinations were performed in vitro on autopsied hearts from ten patients with familial amyloidosis with polyneuropathy (FAP). An ultrasonically visible needle was used to localize the abnormal echoes, and samples were taken for histological analysis of the region of the echocardiographic abnormality. Our results indicate that the highly refractile myocardial echoes in FAP are due to nodules composed of collagen and amyloid.
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