[Severe anaemia caused by Human Parvovirus B19 infection in a patient with autoimmune haemolytic anaemia and a B-cell non-Hodgkin lymphoma]. / Ernstige anemie door infectie met het Humaan parvovirus B19 bij een patiënt met een auto-immuun-hemolytische anemie en een B-cel-non-hodgkinlymfoom.

A 65-year-old man with a 15-year history of 'leukemicised' low-grade lymphocytic B-cell non-Hodgkin lymphoma with a low-titre of IgM kappa paraprotein was admitted with severe anaemia and reticulocytopenia. Treatment with prednisone and chlorambucil had been started two weeks earlier because of a recently diagnosed Coombs-positive haemolytic anaemia. He also received a blood transfusion at that time. During his stay in the hospital, a crista biopsy was performed that revealed no signs of bone marrow suppression but markedly enlarged pro-erythroblasts. Although a serologic test for Human Parvovirus-B19 was negative, PCR showed a sharply increased viral load with more than 1 x 10(11) copies/ml, compatible with a primary parvovirus infection. In retrospect, an earlier transfusion of blood that had not been screened for parvovirus was probably the culprit. Treatment with human immunoglobulin was effective in lowering the viral load and normalising the haemoglobin. This case illustrates that reticulocytopenia in a patient with a haematologic disorder accompanied by a shortened erythrocyte life-span is suggestive for a primary parvovirus infection, especially following a recent transfusion. To prevent transmission of Human Parvovirus B19 via blood transfusion, the Health Council of the Netherlands published a guideline indicating that patients at high risk for a complicated infection with Human Parvovirus B19 should be given 'virus-free' blood products.

The fate of poly(2-dimethyl amino ethyl)methacrylate-based polyplexes after intravenous administration.

Poly(2-dimethyl amino ethyl) methacrylate (pDMAEMA) cationic polymers have been shown to be efficient vectors for gene delivery in vitro. This contribution deals with the in vivo properties of polyplexes based on this polymer. In mice, pDMAEMA/[32P]-pLuc complexes distributed primarily to the lungs. The gene expression profile matched the biodistribution profile. In vitro turbidity experiments in serum showed severe aggregation upon addition of cationic polyplexes, pointing out the involvement of aggregates in the dominant lung uptake of the positively charged polyplexes. Incubations of polyplexes with albumin yielded a decline of the zeta potential of the complexes to negative values, making an electrostatic mechanism in the dominant lung uptake less likely. Hemagglutination experiments showed that the polyplexes induce the formation of extremely large structures when incubated with washed erythrocytes. Altogether, the present data indicate that aggregate formation and trapping of the formed aggregates in the lung capillary bed is probably responsible for the dominant lung uptake and transfection. Poly(ethylene)glycol (PEG) of the polymeric structures prevented the increase in the observed turbidity in serum seen with polyplexes and was also able to reduce interactions with erythrocytes. Currently, the in vivo fate of the PEGylated polyplexes is under investigation.

The influence of heart rate and age on diastolic blood flow velocity in the left ventricular inflow tract.

To investigate the relationship between age-related blood flow velocity and heart rate in the left ventricular inflow tract, we studied 118 healthy volunteers (age greater than 15 years). The maximal velocity (Vmax) of the transmitral diastolic flow during early ventricular filling (E) and during filling due to atrial contraction (A) was measured at 3 sites in the left ventricle with pulsed Doppler echocardiography. At all these sites a significant positive correlation was found between the VmaxA and the EA ratio and the interaction of heart rate and age. VmaxA increases if age and heart rate increase. The influence of the interaction of age and heart rate on VmaxA is most pronounced near the mitral annulus. VmaxA is only related to age and decreases with advancing age. Our observations contribute to the explanation of the more important role of the atrial contraction in the elderly.

The effect of respiration on diastolic blood flow velocities in the human heart.

This study was performed to evaluate the effects of respiration on diastolic blood flow velocity and its relevance for the determination of pulsed Doppler reference values from diastolic blood flow. Doppler signals were recorded from both the atrial and ventricular sides of the mitral valve and the tricuspid valve in 215 healthy volunteers (120 males and 95 females, with ages ranging from 1-65 years). Respiratory signals were recorded simultaneously by a mercury strain gauge around the thorax. From the medians of Doppler spectra the maximum velocity during early diastole (VmaxE), during atrial contraction (VmaxA) and the ratio between VmaxE and VmaxA (EA ratio) were obtained. On the atrial side of the tricuspid valve, VmaxE and VmaxA were significantly higher during inspiration than during expiration. On the ventricular side of the tricuspid valve, this was only found for VmaxE. On the atrial side of the mitral valve, VmaxE and VmaxA were significantly lower during inspiration than during expiration. At the ventricular side of the mitral valve, this was found only for VmaxE. No significant effect of respiration was found on the EA ratio. We conclude that there is a respiration-related effect on VmaxE and VmaxA. However, no significant effect is found on the EA ratio. Thus, for the determination of the EA ratio in intersubject studies, information about the respiratory cycle is not relevant.

Effects of aging on cardiac blood flow velocities.

The effects of aging on cardiac blood flow velocities are important as a description of the natural history of the aging process and as a reference for evaluation of the aging cardiovascular system. We therefore studied these effects in 215 healthy volunteers, 120 males and 95 females, between 1 and 65 years old. Pulsed Doppler signals were recorded proximal and distal to the mitral (M) and tricuspid (T) valves, in the left ventricular outflow tract (LVOT), in the ascending aorta (AAO), in the right ventricular outflow tract (RVOT), and in the pulmonary artery (PA). Systolic (S) flow velocity patterns consist mainly of one peak. Diastolic blood flow velocity is characterized by two peaks: one due to early filling (E) of the ventricle and a second as a result of atrial contraction (A). All peaks are characterized by the maximum of the median velocity curve (Vmax). With age increasing from 1 to 65 years, VmaxS decreases in the AAO (40%) and PA (10%), VmaxE decreases on both sides of the M valve (proximal-50%; distal-30%), and the T valve (proximal-20%; distal-30%). However, with increasing age VmaxS increases in the LVOT (25%), and VmaxA increases on both sides of the M valve (proximal-20%; distal-50%) and proximal to the T valve (30%). VmaxS in the RVOT and VmaxA distal to the T valve did not show a relation with age. These observations demonstrate that in a normal population Vmax in the heart and great vessels is age dependent at most sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Limits of reproducibility of mitral pulsed Doppler spectra.

The total intrinsic variability of pulsed Doppler spectra of mitral blood flow was evaluated in this study. Doppler examinations were performed in 10 normal volunteers (7 men, 3 women), ages 29 to 57 years (mean 41) with an interval period of 3 months. The recordings were made in the apical 4-chamber view, using a 2.25-MHz transducer. The sample was placed approximately 1 cm proximal (left atrium) and 1 cm distal (left ventricle) from the middle of the anulus of the mitral valve at the onset of diastole. Processing of the raw Doppler spectra was done in a way that avoided subjective manipulation by the investigators. Mitral peak velocities, accelerations and spectral widths were measured in early diastole and late diastole. From the parameters under investigation, maximal velocities showed the best reproducibility with a range of coefficients of variation of 9 to 13%. Peak acceleration in early diastole and spectral widths showed rather large coefficients of variation, ranging from 19 to 30 and 14 to 24%, respectively. Mitral pulsed Doppler spectra in the left atrium were more reproducible than in the left ventricle.

Reference values for pulsed Doppler signals from the blood flow velocity on both sides of the pulmonary valve.

Pulsed Doppler signals were recorded from the pulmonary artery and the right ventricular outflow tract in 215 healthy subjects (120 males, 95 females; 1-65 years). Amplitude spectra from these Doppler signals were stored in digital form together with adjustment data for the instrument and the simultaneously recorded ECG. From these Doppler spectra the median of the maximal velocity (Vmax), the maximal acceleration (Amax) and the dispersion of the velocity distribution around Vmax (width) were calculated. These three median values were used to characterize the Doppler spectra and to define normal values for bloodflow velocities. Thus, calculations were made without observer interacting using a well-defined computer program. The effect of age, gender, body surface area and heart rate were studied. Reference ranges were calculated. There is a slight decrease of the median value of Vmax and Amax in the pulmonary artery during lifetime from 80 to 70 cm s-1 and from 1,200 to 800 cm s-2, respectively. On the other hand, there is no correlation between age and Vmax and Amax in the right ventricular outflow tract. The width of the spectra increases with age at both sites. No significant changes with age were seen with the other variables.

Normal diastolic filling patterns of the left ventricle.

Pulsed Doppler measurements on both sides of the mitral valve and M-mode left ventricular echocardiograms were performed in 215 healthy subjects, 120 males and 95 females, between one and 65 years old, in order to evaluate normal diastolic filling patterns of the left ventricle. The relation between the maximum blood velocity during early passive filling (E wave) and during atrial contraction (A wave) was computed from the Doppler spectra obtained proximal and distal to the mitral valve, resulting in the EA ratio. The influence on the EA ratio of age, gender, body surface area, blood pressure, heart rate, PR interval, respiration, wall thickness and basal wall mass of the left ventricle was investigated. The study showed that the EA ratio measured proximal to the mitral valve (in the left atrium) was significantly smaller than the EA ratio measured distal (in the left ventricle) and that the only prominent relations with the EA ratio were those with age and heart rate. The EA ratio declines with age: proximal to the mitral valve from approximately (medians) 2.5 to 1 and distal to it from 3.5 to 1.5. All other physiological variables are weakly related or unrelated to the EA ratio in this group of healthy subjects.

Reference values for pulsed Doppler signals from the blood flow on both sides of the aortic valve.

Pulsed Doppler signals were recorded in 215 healthy subjects, 120 males and 95 females, between 1 and 65 years of age. The measurements were performed in the left ventricular outflow tract (LVOT) and in the ascending aorta (AAO). Amplitude spectra from the Doppler signals were stored in digital form together with adjustment data for the instrument, the simultaneously registered ECG and respiration signal. The maximum velocity (Vmax), the maximum acceleration (Amax) and the width of the velocity distribution around Vmax (width) were derived from these spectra and used for the characterization of the signals. These parameters were computed without observer interaction using a computer program. Effects of age, sex, body surface area, heart rate and respiration were studied. Reference ranges were calculated. The following conclusions can be drawn: Vmax and Amax in the AAO decrease clearly with increasing age from approximately 100 to 60 cm s-1 and from 2000 to 1000 cm s-2 (medians), respectively. The variation of the width in the AAO is greater for people over 45 years. Vmax, Amax and width in the LVOT increase slightly with advancing age from approximately 60 to 80 cm s-1, 800 to 1000 cm s-2 and 12 to 15 cm s-1 (medians), respectively. These parameters of flow were either unrelated or only weakly related to other physiological variables in this study group.

Left atrial enlargement: an electrocardiographic misnomer? An electrocardiographic-echocardiographic study.

The agreement between electrocardiography and echocardiography for diagnosing left atrial (LA) enlargement has been studied in 100 unselected consecutive adult patients with a variety of cardiac diseases. In only 4 did both methods agree with respect to the diagnosis of LA enlargement. Mainly as a result of supraventricular arrhythmia, the P wave of the ECG could not be analyzed in 19 patients. In 13 of these, the echocardiogram showed enlargement of the LA. Four of the remaining 81 patients had positive ECG criteria for LA enlargement and 20 patients showed LA enlargement on their echocardiogram. It appears from our results that there is no agreement between the ECG diagnosis of LA enlargement and the LA cavity size as measured from the echocardiogram. Echocardiography may be considered as a reference method for assessing left atrial size.

The vibratory innocent heart murmur studied by echo-Doppler.

So-called innocent heart murmurs are thought to be originated by a possible physiologic narrowing of the left ventricular outflow tract, accentuated by a higher contractibility of the myocardium in some children. The aim of our studies was to evaluate this theory with pulsed Doppler echocardiography in order to detect possible local bloodstream disturbances. In a study of 20 children, with or without a vibratory innocent heart murmur no statistical difference was found in either peak-velocity, acceleration or width of the Doppler spectra, read out in an objective computed digital way. The hypothetic location of the origin of the vibratory innocent heart murmur in the left ventricular outflow tract has not yet been confirmed with Doppler echocardiography.