Interobserver and within-subject variances of T2-relaxation time and 1H-metabolite ratios in the normal hippocampus.

PURPOSE: To investigate the magnetic resonance (MR) reproducibility of normal hippocampal volume (HV), temporal lobe volume (TLV), transversal relaxation time (T(2)) and (1)H-MR spectroscopy ((1)H-MRS) metabolite ratios. MATERIALS AND METHODS: Two sets of HV, TLV, T(2) and MR spectroscopic metabolite signal ratios were determined in 27 healthy volunteers. HV and TLV were measured with a T(1)-weighted MR sequence; whereas T(2) measurements were performed with conventional spin-echo (CSE) and fast spin-echo (FSE) MR imaging sequences. The interobserver and within-subject variances of T(2) measurements were estimated. RESULTS: Estimated right and left HV coefficients of variation (CV)=0.13. FSE T(2) measurements showed no significant differences in the interobserver (CV=0.02) and within-subject variances (CV=0.02). Measurements showed no differences in the interobserver (CV=0.02) and within-subject (CV=0.04) variances for the CSE T(2) of the right and left hippocampi. Metabolite ratios between N-acetyl aspartate (NAA) and creatine (Cr), choline (Cho) and creatine, and NAA and choline plus creatine (Cho + Cr) for the right hippocampus were 2.29+/-0.19, 1.52+/-0.14 and 0.91+/-0.05, respectively. Metabolite ratios for the left hippocampus were 2.18+/-0.10, 1.48+/-0.10 and 0.88+/-0.06, respectively. CONCLUSIONS: HV, TLV, T(2) and (1)H MRS metabolite ratio measurements showed fair reproducibility with small CVs, and no differences in the interobserver and within-subject variances, including no differences between right and left TLV, and in the right and left T(2).

Quantitative assessment of Gd-DTPA contrast agent from signal enhancement: an in-vitro study.

Quantitative determination of in-vivo gadolinium diethylenetriamine-pentaacid (Gd-DTPA) concentration is attractive in various studies involving perfusion, tracer kinetics and permeability constants. Using a 1.5 T clinical system and a 7 T small-bore system, we evaluated a method for absolute determination of Gd-DTPA concentrations in plasma solutions. Different solutions of Gd-DTPA and (99m)Tc-DTPA were mixed in human plasma and concentrations in the range of 0-5.0 mmol/l (1.5 T system) or 0-3.0 mmol/l (7 T system) of Gd-DTPA were divided into thirteen tubes. All MRI measurements were carried out using conventional sequences (SE, FLASH and GRASS). The MR measured intensity was converted to Gd-DTPA concentration by mathematical interpretation of the sequences. All MRI sequences showed, that the measured concentrations of Gd-DTPA revealed a slight non-linear difference compared with the calculated Gd-DTPA concentrations determined by the plasma (99m)Tc-DTPA using gamma counting. This non-linearity was most pronounced at high Gd-DTPA concentrations, suggesting that the discrepancy could be a result of an increased plasma relaxivity at higher concentrations. Adjustment of measured Gd-DTPA concentration was therefore performed using a selected power function, A[Gd-DTPA](a), which yielded the best linear relationship. Regression analysis showed that the scaling constant (A) varied from 0.11 to 97.45 and the power constant (a) varied from 0.83 to 1.6. Based on these constants, the MRI measured concentrations of Gd-DTPA did not differ from the calculated concentrations of Gd-DTPA obtained from reference measurements of (99m)Tc-DTPA. In the 1.5 T system, a linear relationship (r(2) > or = 0.95) was demonstrated in the range of 0-5.0 mmol/l Gd-DTPA, and in the 7 T system, a linear relationship (r(2) > or = 0.92) was demonstrated in the range of 0-3.0 mmol/l Gd-DTPA. Additionally, the effect of signal-to-noise on measured concentrations of Gd-DTPA was simulated using MR data of the mixed solutions of Gd-DTPA in plasma and the analytical expression of the pulse sequences. The simulations showed that the concentrations were most sensitive to noise in the GRASS sequence. In conclusion, this study demonstrates a novel approach to quantify accurately the Gd-DTPA concentration directly from MRI signal data using different routine sequences.

[Is visual assessment of MRI adequate in the investigation of patients with temporal lobe epilepsy? Evaluation of the diagnostic accuracy of the visual assessment of MRI in mesial temporal sclerosis]. / Er visuel bedømmelse af MR-scanning tilstraekkelig ved udredning af patienter med temporallapsepilepsi? Vurdering af den diagnostiske sikkerhed ved visuel bedømmelse af mesial temporal sklerose på MR-scanninger.

INTRODUCTION: Is visual assessment of MRI adequate in patients with temporal lobe epilepsy? Visual versus quantitative MRI assessment of mesial temporal sclerosis (hippocampal gliosis (HG) and hippocampal atrophy (HA)). MATERIAL AND METHODS: The MRIs of 25 patients with temporal lobe epilepsy were assessed visually by three radiologists with different levels of neuroradiological MRI experience (expert, trained, and inexperienced). Diagnosis obtained earlier by T2-relaxometry and volume measurements were considered to be the gold standard. RESULTS: The diagnostic accuracy of visual assessment was high for unilateral HA, but low for bilateral HA and unilateral and bilateral HG, and it was not better for the expert eye than for the inexperienced. Interobserver agreement on the visual diagnosis of HG and HA (Cohen's Kappa coefficient): 0.49 (HG) and 0.84 (HA). Intraobserver reliability for the expert/trained/inexperienced observer for visual diagnosis (Kappa): 0.83/0.64/0.47 (HG) and 0.88/0.69/0.73 (HA). DISCUSSION: Reproducibility and diagnostic accuracy of visual assessment varied unacceptably from the quantitative MRI-based diagnosis. Quantitative measurements are recommended in patients suspected of MTS.

Flextube reflectometry for determination of sites of upper airway narrowing in sleeping obstructive sleep apnoea patients.

The aim of this study was to examine a new technique based on sound reflections in a flexible tube for identifying obstructive sites of the upper airway during sleep. There was no significant difference between two nights in seven obstructive sleep apnoea (OSA) patients regarding the level distribution of pharyngeal narrowings, when the pharynx was divided into two segments (retropalatal and retrolingual). We also compared the level distribution determined by magnetic resonance imaging (MRI) with the level distribution found by flextube reflectometry in seven OSA patients. There was no significant difference between flextube and MRI level distributions during obstructive events, but due to few subjects the power of the test was limited. We found a statistically significant correlation between the number of flextube narrowings per hour of sleep and the number of obstructive apnoeas and hypopnoeas per hour of sleep determined by polysomnography (PSG) in 21 subjects (Spearman's correlation coefficient r = 0.79, P < 0.001). In conclusion, the flextube reflectometry system seems to be useful for level diagnosis in OSA before and after treatment.

Indirect evidence for the potential ability of magnetic resonance imaging to evaluate the myocardial iron content in patients with transfusional iron overload.

The purpose of this study was to evaluate the potential ability of magnetic resonance imaging (MRI) for evaluation of myocardial iron deposits. The applied MRI technique has earlier been validated for quantitative determination of the liver iron concentration. The method involves cardiac gating and may, therefore, also be used for simultaneous evaluation of myocardial iron. The tissue signal intensities were measured from spin echo images and the myocardium/muscle signal intensity ratio was determined. The SI ratio was converted to tissue iron concentration values based on a modified calibration curve from the liver model. The crucial steps of the method were optimized; i.e. recognition and selection of the myocardial slice for analysis and positioning of the regions of interest (ROIs) within the myocardium and the skeletal muscle. This made the myocardial MRI measurements sufficiently reproducible. We applied this method in 41 multiply transfused patients. Our data demonstrate significant positive linear relationships between different iron store parameters and the MRI-derived myocardial iron concentration, which was significantly related to the serum ferritin concentration (rho=0.62, P<0.0001) and to the MRI-determined liver iron concentration (rho=0.36, P=0.02). The myocardial MRI iron concentrations demonstrated also a significant positive correlation with the number of blood units given (rho=0.45, P=0.005) and the aminotransferase serum concentration (rho=0.54, P=0.0008). Our data represents indirect evidence for the ability of MRI techniques based on myocardium/muscle signal intensity ratio measurements to evaluate myocardial iron overload.

Expression of CD2 and activation markers on blood T-helper cell subsets in patients with transfusional iron overload.

The aim of the present study was to investigate the relationship between different measures of iron status, and the expression of CD2, and the activation markers CD25, CD71, CD45RO, HLADR CD38 within the Th-cell subset in patients with progressive transfusional iron overload. We estimated the expression of the activation surface markers on the Th cells of peripheral blood by flow cytometry from 22 multiply transfused patients. The number of CD2 binding sites (BS) on Th cells was significantly higher in the patients (82 917 +/- 30 801) than in age-matched normal controls (41 145 +/- 6989, P < 0.0001). When investigating whether this difference could be due to the iron overload we found the number of CD2 BS closely related to the iron saturation of serum transferrin (TfS) (R2 = 0.78, P < 0.001). The relationship to the serum ferritin concentration and to the number of blood units given was weaker, but also significant (R2 = 0.22, P < 0.027, respectively, R2 = 0.21, P < 0.032). Also the fraction of mature memory Th cells which express CD45RO at a high level was directly related to the TfS (R2 = 0.57, P < 0.0001), while the expression of CD38 within the Th cell fraction was inversely related to the TfS (R2 = - 0.43, P = 0.009). The expression of HLA-DR (but not of CD25 and CD71) was also directly related to the TfS (R2 = 0.29, P = 0.01). Our results show a clear, statistical relationship between the iron status and the expression of surface markers within Th cells in multiply transfused patients.

Unbiased and efficient estimation of left ventricular volumes by three-dimensional echocardiography with coaxial sections. Validation with magnetic resonance imaging.

The objective of this study was to investigate the degree of bias with coaxial three-dimensional echocardiography in an experimental animal setup and to establish the minimum number of sections needed for estimation of left ventricular (LV) volume. Epicardial coaxial echocardiography and magnetic resonance imaging (MRI) was used to measure LV volume in 14 pigs, with chronic remodeled left ventricles induced by repeated intracoronary microembolizations. In addition, six animals underwent serial MRI at baseline, immediately after intracoronary microembolization, and after 119-165 days (mean 129 days). Coaxial echocardiography was performed by rotational acquisition of long-axis sections starting from an arbitrary angle. Planimetered MRI contours of LV endocardial borders were analyzed to investigate the relationship between the number of coaxial sections, and the precision of volume estimates. The mean +/- 2SD of the differences between coaxial epicardial echocardiography with six sections and MRI were -2.5 +/- 16.4 ml, 0.8 +/- 13.1 ml, and 2% +/- 14% for end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF), respectively. Numerical analysis conducted on MRI contours of LV endocardial borders showed that with six coaxial sections the average coefficient of error was < 1% for the EDV and ESV. Three-dimensional echocardiography with six coaxial sections provides unbiased LV volume estimation with minimal geometric error.

In vivo measurements of relaxivities in the rat kidney cortex.

The aim of this study was to implement a novel noninvasive method to derive the in vivo T1 relaxivity (R1) and T2 relaxivity (R2) in the rat kidney cortex. A two-compartment gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) distribution model was established to estimate the bolus and infusion dosages of Gd-DTPA necessary for obtaining the required steady-state concentration levels. After a single bolus injection of (99m)Tc-DTPA, several blood samples were collected. Based on considerations from the applied two-compartment model, a steady-state concentration was predicted approximately 5-10 minutes after the bolus injection. The plasma concentration levels of Gd-DTPA were measured by simultaneous injection of (99m)Tc-DTPA. Three regions in the cortex (upper, central, and lower) of both rat kidneys were used. A statistical evaluation resulted in the following in vivo relaxivities found at 7 T: R1 = 1.04 +/- 0.08 mM(-1)s(-1) and R2 = 10.78 +/- 0.83 mM(-1)s(-1). Using a 95% confidence interval, no intracortical differences were detected. The relaxivities R1 and R2 calculated in the intact rat kidney cortex were distinctly different from relaxivities found in human plasma: (22 degrees C) 4.42 +/- 0.07 mM(-1)s(-1) (r2> 0.98) and R2 = 5.75 +/- 0.17 mM(-1)s(-1) (r2> 0.98), respectively. The measurements showed a marked difference between in vitro and in vivo relaxivities. Comparison of the distribution rates in pig, human, and rats shows a distinct proportionality between size and renal function.

Differences in blood-tumour-barrier leakage of human intracranial tumours: quantitative monitoring of vasogenic oedema and its response to glucocorticoid treatment.

PURPOSE: To study differences in tumour capillary permeability as expressed by the unidirectional transport rate constant Ki, extracellular distribution volume Vd and relaxation time T1 in human intracranial tumours using a recently described MRI method, and apply the model to study differences in these parameters after glucocorticoid (GC) treatment. PATIENTS AND METHODS: Seventeen brain tumour patients were studied. There were seven glioblastoma (GLI), four metastasis (MET), and six meningioma (MM) patients. Nine patients were studied before and after an average of 6 days of GC treatment. A 1.5 Tesla MR imaging scanner was used, and a two compartment diffusion model for Gd-DTPA was applied. RESULTS: There was a significant difference between pre-treatment Ki in GLI's and MM's, MM's having the highest permeability. There were no significant differences between pre-treatment Vd or T1 among the different tumour types. After GC treatment Ki decreased 15% on average (52% in GLI's and MET's, but only 4% in MM's). Vd decreased 14% on average in all tumours, but 47% in GLI's and MET's (p < 0.04), but increased 2% during treatment of MM's. T1 decreased 9% in all tumours (p < 0.04), but 11% in GLI's and MET's (p < 0.003), and only 6% in MM's. CONCLUSIONS: It is possible to estimate Ki, Vd and T1 simultaneously in brain tumour patients in a clinical MRI system. Ki was significantly higher in MM's compared to GLI's and MET's suggesting that MM's differ in some physiological parameter at the blood-tumour interface. MM's did not respond to GC treatment, neither in Ki, Vd nor in T1, whereas GLI's and MET's primarily decreased their extracellular distribution volume, suggesting that this may be an important effect in GC's mode of action in these tumour types.

Myocardial structure as a determinant of pre- and postoperative ventricular function and long-term prognosis after valve replacement for aortic stenosis.

BACKGROUND: Long-term results after aortic value replacement for aortic stenosis can be correlated to a cardiac-related pre-operative risk profile. This predictability indicates that there is a common basis in subtle or overt structural abnormalities of left ventricular myocardium. METHODS AND RESULTS: Forty-nine patients aged 24-82 (mean 61) years, with aortic stenosis had a full wall thickness transmural biopsy of the left ventricular antero-lateral free wall during aortic valve replacement. Echocardiography and radionuclide ventriculography were performed prior to, and 18 months (n = 41) after, the operation. Postoperative follow-up to a maximum of 7.7 years was 100% complete. Pre-operatively, all patients had an increase in both the left ventricular mass index (202 +/- 67 g.m-2) and the muscle cell diameter (41 +/- 8 microns); other morphological data included a muscle cell nucleus volume of 752 +/- 192 microns3, a muscle cell mass index of 163 +/- 54.m-2, and a fibrous tissue mass index of 39 +/- 16 g.m-2. Patients with a pre-operative episode of clinical left ventricular failure (n = 19) had significantly greater morphological variables than those without. Pre-operative ejection fraction and other measures of systolic function correlated inversely with the morphological data, except for the fibrous tissue mass index; diastolic function indices correlated inversely with all the morphological variables. At the 18-month re-study, the same general picture was noted, but with an underlying strengthening, especially of the muscle cell mass index. Overall, the mass index dropped to 152 +/- 51 g.m-2 (P < 0.0001), but in 17% of the patients it became normal; the mass index at 18 months was directly correlated to morphological variables. A high muscle cell nucleus volume was identified as an independent predictor of early and late mortality. CONCLUSIONS: Abnormalities of the hypertrophied left ventricular muscle cell and the degree of muscle hypertrophy are, to some degree, underlying determinants of pre-operative symptomatology, pre- and postoperative ventricular function, and early and late mortality after valve replacement for aortic stenosis. Incomplete hypertrophy impaired results, was related to pre-operative myocardial structural abnormalities.

[Mortality and worsening of prognosis for patients with aortic stenosis while on the waiting list]. / Mortalitet og prognoseforringelse for patienter med aortastenose på kirurgisk venteliste.

In a prospective study, 99 consecutive patients with an operative indication due to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting time to aortic valve replacement (AVR) averaged 6.3 months (0.5-19 months). There were 58 men and 41 women with a mean age of 61 years (21-82 years). The patients were divided into three groups: group 1 (N = 81) with an uneventful stay on the waiting list; group 2 (N = 11) with significant worsening of a prognostic index; and group 3 (N = 7) with patients who died during the waiting time. The waiting list death rate was 13.5%/patient-year compared with a post-AVR death rate of 4.9% patient-year (p < 0.05) with a mean post-AVR follow-up of 5.7 years. According to a prognostic index (Cox regression model) at inclusion, group 2 patients had a predicted 7-year post-AVR survival probability of 72%, but only of 61% according to their prognostic index immediately preoperatively; their observed 7-year post-AVR survival was 60%. Logistic regression analysis identified high age, short duration of symptoms, signs of severe hypertrophy and strain in the ECG, female gender, and deranged left ventricular diastolic function (related to severely increased left ventricular muscle mass) as independent predictors of prognostic worsening and death while on the waiting list. The predictive models did not allow sufficiently accurate identification of the patients at risk during the waiting period. The consequences of a surgical waiting period averaging 6 months are serious for AS patients. The death rate is high and a subgroup worsens its prognostic profile with a significantly reduced post-AVR long-term survival as the result.

[Quantification of iron level in the liver by MR imaging in patients treated for transfusion siderosis]. / Kvantitering af jernindholdet i levern ved MR-billeddannelse hos patienter i behandling for transfusionssiderose.

Patients with chronic blood transfusion requirements develop progressive iron overload, which is followed by organ damage in severe cases. Chemical determination of the liver iron concentration in liver biopsies is still regarded as the gold-standard for a precise determination of the degree of iron overload, but cannot be performed just for determination of the liver iron concentration alone due to the possible harmful side effects due to percutaneous liver biopsies. We have therefore validated a non-invasive MRI-technique based on the calculation of the ratio between the signal intensity (SIR) of the liver and skeletal muscle. We found a good correlation between the chemically determined liver iron concentration and the corresponding SIR-values (r2 = 0.98, p < 0.0001) low inter-day variation (2.9 +/- 2.7 mumol Fe/g) indicating that our non-invasive method is applicable for the determination of the liver iron concentration and may also be used for monitoring the efficacy of iron chelation by repeated measurements.

Cardiac function during iron chelation therapy in adult non-thalassaemic patients with transfusional iron overload.

It is well-documented that iron chelation by desferrioxamine protects/improves the cardiac function in blood transfusion-dependent children suffering from beta-thalassaemia. In patients who do not become dependent upon blood transfusion until adulthood (ANT-patients), iron chelation by desferrioxamine may affect the cardiac function in unknown ways, presumably because age-related changes in the heart may cause iron chelation to affect the cardiac function in different ways. We therefore followed the left ventricular ejection fraction (LVEF) by multigated radionuclide angiography in 16 iron-loaded ANT-patients during iron chelation alone and after increasing the efficacy of chelation by vitamin C supplementation. During 12 months of iron chelation the mean LVEF fell significantly from 63.3% to 58.0% (p=0.04). Individual changes in LVEF did not correlate significantly with age but with the pretreatment liver iron concentration. After initiation of vitamin C supplementation, the mean LVEF increased from 55.9% to 65.3% (p=0.01). Our data suggest that in ANT-patients prolonged desferrioxamine treatment without vitamin C supplementation may be associated with reduced LVEF, whereas vitamin C supplementation seems to benefit the cardiac function. Similar findings have not been described in beta-thalassaemia and may hence be specific for ANT-patients. However, our findings have to be confirmed by controlled studies.

Impact of size mismatch and left ventricular function on performance of the St. Jude disc valve after aortic valve replacement.

BACKGROUND: The hemodynamic function of the St. Jude valve may change relative to changes in left ventricular function after aortic valve replacement for aortic stenosis. From theoretical reasons one may hypothesize that prosthetic valve hemodynamic function is related to left ventricular failure and mismatch between valve size and patient/ventricular chamber size. METHODS: Forty patients aged 24 to 82 years who survived aortic valve replacement for aortic stenosis with a standard St. Jude disc valve (mean size, 23.5 mm; range, 19 to 29 mm) were followed up prospectively with Doppler echocardiography and radionuclide left ventriculography preoperatively and 9 days, 3 months, and 18 months after the operation with assessment of intravascular hemolysis at 18 months. Follow-up to a maximum of 7.4 years (mean, 6.3 years) was 100% complete. RESULTS: Left ventricular muscle mass index decreased from 198 +/- 62 g.m-2 preoperatively to 153 +/- 53 g.m-2 at 18 months (p < 0.001), paralleled by a significant increase in left ventricular ejection fraction, peak ejection rate, and peak filling rate; only 18% of the patients had normal left ventricular muscle mass index and only 32% normal ventricular function (normal left ventricular ejection fraction, peak ejection rate, peak filling rate, early filling fraction, and late filling fraction during atrial contraction) at 18 months. Prosthetic valve peak Doppler gradient dropped from 20 +/- 6 mm Hg at 9 days to 17 +/- 5 mm Hg at 18 months (p < 0.05). Reduction of left ventricular muscle mass index was unrelated to peak gradient and size of the valve. Peak gradient at 18 months rose with valve orifice diameter of 17 mm or less (by 6 mm Hg), orifice diameter/body surface area of 9 mm.m-2 or less (by 5 mm Hg), left ventricular enddiastolic dimension (by 23 mm Hg per 10 mm increase), and impaired ventricular function (by 3 mm Hg). All but 2 patients (5%) had intravascular hemolysis; none had anemia. Two patients with moderate paravalvular leak had the highest serum lactic dehydrogenase levels; 4 patients with trivial leak had higher serum lactic dehydrogenase levels than those without leak. Serum lactic dehydrogenase levels rose with moderate paravalvular leak, impaired ventricular function, and valve orifice diameter. Six patients with trivial or moderate paravalvular leak had a cumulative 7-year freedom from bleeding and thromboembolism of 44% +/- 22% compared with 87% +/- 5% for those without leak (p < 0.05). CONCLUSIONS: The peak gradient of the St. Jude aortic valve dropped marginally over the first 18 postoperative months in association with incomplete left ventricular hypertrophy regression and marginal improvement of ventricular function. Mismatch between valve size and ventricular cavity size or patient size and impaired function of a dilated ventricle significantly compromised the performance of the St. Jude valve. Probably explained by platelet destruction or activation, paravalvular leak was related to bleeding and thromboembolic complications.

Left ventricular systolic and diastolic function in aortic stenosis. Prognostic value after valve replacement and underlying mechanisms.

AIMS: The aims of the study were to examine the prognostic value of pre-operative left ventricular systolic and diastolic function on early, and late mortality after valve replacement for aortic stenosis, and to identify possible underlying mechanisms. METHODS AND RESULTS: Ninety-one prospectively recruited consecutive patients with a mean age of 61 years underwent valve replacement for aortic stenosis with concomitant coronary artery bypass grafting in 32 and a minimum postoperative observation period of 5.4 years. There were six early (< or = 30 days postoperatively) and 19 late deaths, and 18 deaths from specific causes (cardiac and prosthetic valve related). Early mortality occurred exclusively among patients with a combined subnormal left ventricular systolic function (subnormal ejection fraction or peak ejection rate, or supranormal time-to-peak ejection--duration of systole ratio) and a subnormal fast filling fraction. In Cox regression models on crude mortality and specific deaths, a subnormal ejection fraction and a fast filling fraction of < or = 45% were the only independent risk factors. Patients with none of these risk factors had normal sex- and age-specific survival, those with any one factor had an early, and those with both factors a massive early and a late excess mortality, with 5-year crude survival of 92%, 77%, and 50%, respectively (P < 0.0001). Systolic wall stress was without prognostic value. Further analyses indicated that impairment of left ventricular function occurred with increasing muscle mass over two phases: (1) diastolic dysfunction characterized by a pattern of severe relative concentric hypertrophy; (2) the addition of systolic dysfunction characterized by a more dilated, less concentric chamber geometry. Coronary artery disease seemed to provoke the latter development sooner. CONCLUSIONS: Impaired systolic and diastolic left ventricular function, irrespective of afterload, were decisive independent pre-operative risk factors for early as well as late mortality after aortic valve replacement for aortic stenosis. The adverse influence of concentric hypertrophy was the main underlying mechanism. Operative intervention, before impairment of diastolic and systolic function, should be advocated.

Mortality and worsening of prognostic profile during waiting time for valve replacement in aortic stenosis.

In a prospective study 99 consecutive patients with operative indication due to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting-time to aortic valve replacement (AVR) averaged 6.3 months (0.5-19 months). There were 58 men and 41 women with a mean age of 61 years (21-82 years). The patients were divided into three groups: group I (n = 81) with an uneventful stay on the waiting list (including one patient who declined the AVR offer); group II (n = 11) with significant worsening of a prognostic index; and group III (n = 7) with patients who died during the waiting-time. The waiting-list death rate was 13.5 +/- 5.0% patient-year-1 compared with a post-AVR death rate of 4.9 +/- 0.9%. patient-year-1 (p < 0.05) with a mean post-AVR follow-up of 5.7 years. According to their prognostic index at inclusion, group II patients had a predicted (by a Cox model) 7-year post-AVR survival probability of 72%, but only of 61% according to their prognostic index immediately preoperatively; their observed 7-year post-AVR survival was 60%. Logistic regression analysis identified high age, short duration of symptoms, severe hypertrophy and strain in the ECG, female sex, and deranged left-ventricular diastolic function (related to severely increased left-ventricular muscle mass) as independent predictors of death on the waiting-list and prognosis worsening. From a clinical viewpoint, the predictive models did not allow sufficiently accurate identification of the patients at risk during the waiting-time. The consequences of a surgical waiting-time averaging 6 months are serious for AS patients. The death rate is high and a subgroup worsen their prognostic profile, with significantly reduced post-AVR long-term survival as the result.

[MR-scanning in complex partial epilepsy]. / MR-skanning ved kompleks partiel epilepsi.

In a prospective investigation concerning 50 consecutive patients suffering from complex partial epilepsy who all had a normal CT investigation pathological findings were recognized in 80% using MRI. The MRI examination included volume estimation of the hippocampus. The volume estimations were compared to a reference material. In 24% a focal pathology was recognized, that was suspected of being responsible for the epileptic condition. Only 20% of the examinations were evaluated as normal. Hippocampal atrophy was recognized in 50%. In the latter group a diagnosis of hippocampal sclerosis was established in 16%. It is concluded that MRI is the investigation of choice in complex partial epilepsy and that volume estimation of the hippocampus is important.

The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload.

Long-term follow-up data are presented on changes in peripheral blood counts and Hb requirements of 11 patients with myelodysplastic syndromes (MDS) during iron chelation treatment with desferrioxamine for up to 60 months. The erythroid marrow activity was indirectly evaluated by repeated determinations of the serum transferrin receptor concentration. The efficacy of iron chelation was evaluated by repeated quantitative determination of the liver iron concentration by magnetic resonance imaging. Reduction in the Hb requirement ( > or = 50%) was seen in 7/11 (64%) patients. Five patients (46%) became blood transfusion independent. Platelet counts increased in 7/11 (64%) patients and the neutrophil counts in 7/9 (78%) evaluable patients. All patients in whom iron chelation was highly effective showed improvement of erythropoietic output accompanied by an increase in the serum transferrin receptor concentration. It is concluded that reduction in cytopenia in MDS patients may be accomplished by treatment with desferrioxamine, if the iron chelation is efficient and the patients are treated for a sufficiently long period of time. Exactly how treatment with desferrioxamine works remains a challenge for further investigation.

Serum procollagen III peptide concentration in iron overload.

Patients with severe iron overload may develop hepatic fibrosis due to iron toxicity. Unfortunately, the follow-up of the fibrogenic activity during treatment by histological examination of tissue biopsies carries potential side effects, and may therefore not be justified ethically. Recently, the serum concentration of procollagen type III peptide (S-PIIINP) has been shown to be a valid serum marker of the activity of collagen metabolism in conditions with hepatic fibrosis unrelated to iron overload. In order to evaluate the potential usefulness of this test in patients with fibrosis due to iron overload, we investigated the relationship between the PIIINP serum concentration and the size of iron overload in 18 patients with hereditary haemochromatosis (HH) and in 14 patients with transfusional iron overload. A close correlation was found between S-ferritin and S-PIIINP (r = 0.73, p < 0.0001). Follow-up of 6 patients during iron depletion treatment revealed a normalization of the serum aminotransferase concentration before normalization of S-PIIINP was found. This may indicate that excess iron directly induces an increase in fibrogenesis rather than the increased fibrogenesis is secondary to hepatocellular injury caused by iron excess. Thus, serial measurements S-PIIINP may be useful in follow-up of the fibrogenic process due to iron overload.

Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassaemic patients.

The ability to quantitate transfusional iron overload is crucial for determining the need for and the efficacy of chelation therapy in patients with long-standing transfusion-dependent anaemias. We evaluated the usefulness of some indirect measures of iron overload in estimating the iron concentration in the liver--the most important iron storage organ--in 26 non-chelated adult non-thalassaemic patients. Liver iron concentration was determined non-invasively by magnetic resonance imaging (MRI). The standard error of the estimated liver iron concentration was 80 mumol Fe/g dried liver tissue when using the number of transfused blood units, and 93 mumol Fe/g when using a serum ferritin assay. Follow-up in 11 patients (12-48 months) revealed that serum ferritin is a poor measure of the liver iron concentration during iron chelation. However, this discrepancy was individually different and seemed to be dependent on the erythropoietic marrow activity. By monitoring the liver iron concentration by MRI, we compared the efficacy of chelation with desferrioxamine given either by subcutaneous continuous infusions or by bolus injections. Depletion of liver iron stores could be achieved efficiently by both regimens.