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Background: Over the last decade, clinical interest to evaluate human 25-hydroxy-vitamin D (25[OH]D) serum levels has increased exponentially. In the present study, four chemiluminescence immunoassays (CLIA), one radioimmunoassy (RIA), and one high performance liquid chromatography (HPLC) method were compared and also with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in view of 25(OH)D serum level determination. Methods: For the method comparison, blood samples from 133 consecutive patients were prospectively collected. All participants gave written informed consent for their blood samples to be used in this study. They came to the Department of Nuclear Medicine of the Central Hospital Steyr (Austria) for osteodensidometric measurement as part of their preventive medical check-up. Pearson's correlation coefficients, Bland-Altman plots, and paired t-tests were calculated. Assay-specific reference ranges were considered using blood samples from persons with normal parathormone, calcium, and total-protein values (n = 97). Results: The highest correlation was between the HPLC and the LC-MS/MS method (r = 0.96). The lowest correlation was between the cobas Vitamin D3 assay (Roche) and any of the evaluated assays (r = 0.46 - 0.63). Bland-Altman plots revealed a big negative mean bias in three assays (cobas Vitamin D3 assay [Roche]: -22.8; DiaSorin LIAISON [25[OH]D total CLIA [Diasorin]: -18.4; Diasorin 25[OH]D125 I RIA [Diasorin]: -23.8 [nmol/L]) and a much smaller positive mean bias in the other assays (ClinRep complete 25[OH]D2/D3 HPLC kit [Recipe]: 2.7; ADVIA Centaur Vitamin D total assay [Siemens]: 8.2; IDS total vitamin D assay [Immunodiagnostic Systems]: 12.1 [nmol/L]) compared to the LC-MS/MS method. Meanwhile, the manufacturer has withdrawn the cobas Vitamin D3 assay from the market. Conclusions: Poor antibody specificity with cross-reactivity to other vitamin D metabolites, incomplete extraction of the 25(OH)D analyte from the vitamin D-binding protein (DBP), and confounding matrix substances such as lipids could be potential reasons for the unacceptable performance of the cobas Vitamin D3 assay (Roche) and also the significant differences in the 25(OH)D determination between various assays. Standardization and harmonization of 25(OH)D measurements are therefore urgently needed. The widespread introduction of well standardized assays in clinical laboratories is the challenge in the next years. (Clin. Lab. 2014;60:1541-1550. DOI: 10.7754/Clin.Lab.2014.131114)

Fatty acids are promptly taken up, metabolised and eliminated by healthy cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are known to be associated with an impaired fatty acid metabolism. It was the aim of this study to investigate fatty acid metabolism in a rat heart transplant model and to correlate scintigraphic findings with histological changes. After right-side nephrectomy of Lewis recipients Brown Norway cardiac allografts were anastomosed to the renal vessels. Animals were given no immunosuppression. The metabolism of carrier-free 17-123 jodo-heptadecanoic acid (123J-HDA) with a specific activity of2 x 10(17) Bq/ml was scintigraphically measured between days 1 and 11. An increase in the grade of rejection was observed over time. Fifty-six frames of 30 s duration each were recorded. For the region of interest (native heart, transplanted heart, left kidney) frames 10-56 were superimposed, time-activity curves generated and monoexponentially fitted. Furthermore, elimination half-life and intercepts were calculated. Following scintigraphic evaluation the animals were killed and graft as well as native hearts excised for histological examination. The uptake of the tracer identified severe grades of rejection. Elimination half-life of the tracer was twice as long from hearts with mild rejection and more than 14 times as long in severe rejection compared with no rejection. Elimination half-life and amplitude did not permit discrimination between grades 1, 2 and 3 a, but significantly decreased in groups 3 b and 4. This method therefore seems to be a valuable tool for the noninvasive detection of severe acute cardiac allograft rejection. Since fatty acid metabolism is clearly stress-dependent it remains to be seen whether this method allows detection of earlier rejection in loaded hearts.

The long-term efficacy of physiologic dual-chamber (DDD) pacing in the treatment of end-stage idiopathic dilated cardiomyopathy was evaluated in a longitudinal study of up to 5 years in 17 patients. The considerable clinical improvement achieved after implantation of a pacemaker programmed for DDD pacing at an atrioventricular delay of 100 ms was maintained throughout the follow-up period or until death and was associated with a consistent decrease in New York Heart Association class and an increase in left ventricular ejection fraction. Cardiothoracic ratio, heart rate and echocardiographic dimensions progressively decreased, and systolic and diastolic blood pressures increased. Median survival time was 22 months. During follow-up, 4 patients received donor hearts, 9 had a sudden death at home without defined cause or after a thromboembolic event, and 1 died from adenocarcinoma. Three patients survived the follow-up. No patient needed rehospitalization owing to a worsening of heart failure after pacemaker implantation. An interruption of pacing in DDD mode for 2 to 4 hours was followed within the first months by a marked decrease in left ventricular ejection fraction and an increase in cardiothoracic ratio and echocardiographic dimensions, but this response consistently decreased during follow-up. The data indicate that DDD pacing can be recommended as a useful tool in the long-term treatment of end-stage idiopathic dilated cardiomyopathy, with progressive improvement in cardiac function and a reduction of the dilatation of the left ventricle.

Because hepatocyte transplantation into the spleen or the peritoneal cavity, although successful in rats, is more difficult and less successful in larger animals, the lung was chosen for its accessibility and its high oxygen content as a new site for hepatocyte implantation for treatment of acute hepatic failure. Acute hepatic failure was induced by a combination by a portocaval side-to-side shunt and an 80% liver resection, which was associated with a greater than 90% mortality. Hepatocyte transplantation was performed either by injection of 1 x 10(7) cells via the jugular vein (100% mortality) or 5-7 x 10(7) cells transcutaneously into the right lung (92% survival). After injection of the cell-free supernatant into the lung, 53.3% of the animals survived. If more than 90% of the liver was resected, none of the animals survived despite hepatocyte or supernatant injection. From these findings, it is concluded that the lung is a suitable home for hepatocytes. However, the hepatocytes survived only in cases of acute hepatic failure with some remaining vital liver parenchyma.

In 53 patients with COPD and precapillary pulmonary hypertension, we investigated the effect of three typical calcium antagonists on hemodynamics at rest and during bicycle ergometer exercise. In the responders, the decrease in pulmonary vascular resistance following nifedipine was 23 percent at rest (p less than 0.0005) and 35 percent during exercise (p less than 0.0005); following diltiazem, it was 10 percent at rest (p less than 0.05) and 23 percent during exercise (p less than 0.025); following verapamil, it was 22 percent at rest (p less than 0.005) and 11 percent during exercise (p less than 0.025). The cardiac index rose significantly at rest and under exercise only after the administration of nifedipine (+16 percent and +8 percent, resp). Nifedipine caused the most distinctive peripheral vasodilation. The heart rate increased slightly following nifedipine and decreased slightly following diltiazem and verapamil. After long-term therapy with nifedipine (13 +/- 5 months), the decrease in pulmonary artery pressure and pulmonary vascular resistance was no longer significant. In our opinion, the different hemodynamic action profiles will have consequences for the differential therapy in patients with COPD and pulmonary hypertension.

Standard bone scintigraphy [using technetium-99m methylene diphosphonate (MDP)] is widely held to be the most sensitive method for the early detection of psoriatic arthropathy. Preliminary results of this study reveal that 99mTc human immunoglobulin (HIG) scintigraphy demonstrates a typical premature pattern of extradermal psoriatic disease in digits indicative of the early stage of psoriatic arthritis. This pattern was also found in a rare case of psoriatic arthropathy without skin lesions. 99mTc-HIG scintigraphy appears to reveal the initial inflammatory characteristics of later bone lesions. In the advanced stage of psoriatic arthritis, 99mTc-MDP and 99mTc-HIG scans were found to be equally sensitive in the detection of the affected joints. Thus 99mTc-HIG scintigraphy seems to be useful in the early detection of psoriatic arthropathy and also in advanced psoriatic arthritis, as well as for the detection of psoriatic arthropathy without skin lesions.

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a doubleblind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2·4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2·39±0·02 vs 2·32±0·02 mmol/l, P=0·037) and phosphate (0·97±0·06 vs 0·75±0·05 mmol/l, P=0·011) increased and the index of phosphate excretion (0·03±0·03 vs 0·19±0·02, PPP=0·026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8·9±1·2 vs 3·3±0·5 ng/ml, PP=0·009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306·5±45·3 vs 88·7±22·5 ng/ml, P An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1·194±0·058 vs 1·133±0·046 g/cm2, P=0·015), femoral neck (1·009±0·051 vs 0·936±0·034 g/cm2, P=0·004), Ward's triangle (0·801±0·055 vs 0·816±0·04 g/cm2, P=0·019) and the trochanteric region (0·869±0·046 vs 0·801±0·033 g/cm2, P=0·005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < −1·0 s.d.) increased more than in those with normal bone mass (lumbar spine 11·5 vs 2·1%, P=0·030, and femoral neck 9·7 vs 4·2%, P=0·055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk. European Journal of Endocrinology 136 282–289

BACKGROUND This study compared clinical-chemical estimates of infarct size with scintigraphic estimates of myocardial scar in patients with first-time acute myocardial infarction (AMI). METHODS Levels of the cardiac isoform of the contractile protein troponin T (TnT), of creatine kinase (CK), and of the isoenzyme MB of CK (CK MB) were tested in serially drawn blood samples from 21 patients (two females and 19 males; median age, 55 years). Of these 21 patients, five had anterior- and 16 had inferior-wall AMI; all patients received intravenous thrombolytic therapy. Single-photon emission computed tomography (SPECT) with technetium-99m-isonitrile (Tc-sestamibi) was performed at rest after the onset of AMI (median time, 5 weeks). Scintigraphic defects were calculated using "bull's-eye" polar coordinate maps. All patients had an uncomplicated course between discharge and myocardial scintigraphy. RESULTS Scintigraphic defect sizes ranged from 3.2% to 47.8% of the left ventricle (median, 27.3%). Cardiac TnT and CK MB release correlated closely with each other and with scintigraphic estimates of myocardial scar. Significant correlates were found between cardiac TnT and CK MB peak values (r = 0.87, P = 0.0001), CK MB peaks and Tc-sestamibi defect sizes (r = 0.73, P = 0.0014), and TnT peaks and scintigraphic defect sizes (r = 0.73, P = 0.0011). CONCLUSIONS Because animal studies have already shown a very close correlation between histologic infarct size and SPECT Tc-sestamibi defect size, our results indicate that cardiac TnT is a useful marker to assess infarct size noninvasively in man.

A 17-year-old male patient with aplastic anemia underwent bone marrow transplantation and succumbed 4 days after marrow infusion from sudden myocardial failure. Fever of unknown origin (FUO) had accompanied the patients course from admission until death. The cause of death was fungus myocarditis, which had escaped detection in vivo, in spite of a daily culture program for bacteria and fungi, and a close monitoring of the patients circulation and ventricular performance. Commonly applied diagnostic criteria for systemic mycosis, such as topical colonization, malfunction of invaded organs and positive fungus cultures failed to provide a timely diagnosis. With regard to the problems in diagnosing systemic mycosis, the potential stem cell toxicity of antifungal drugs and the need for immunosuppressive therapy prior to marrow infusion, we strongly recommend not to start the transplantation procedure unless FUO has been treated successfully.

A total of 240 survivors of one or more myocardial infarctions were consecutively admitted to perform supine exercise radionuclide ventriculography. Within 3 years after the test, 22 died; this group was compared to an age-matched control group of 22 survivors for left and right ventricular function during rest, exercise, and simultaneously assessed exercise performance as well as ECG variables. Evaluation of 3-year survival by linear discriminant analysis revealed an accuracy of 82% for discriminant models using ECG and exercise performance variables. Implementation of resting left ventricular ejection fraction and change of right ventricular ejection fraction during exercise, as well as scintigraphic presence or absence of dyskinesia, improved the accuracy of the model to 91% of correctly classified patients.

Radionuclide ventriculography (RNV) indices of regurgitation, Fourier amplitude ratio (FAR) and additional RNV variables were prospectively compared to Doppler echocardiography (DE) in 108 consecutive patients with no or mild left ventricular regurgitation, to assess RNV accuracy in detecting regurgitation in patients with different cardiac disorders. Exclusion of left ventricular or tricuspid regurgitation allowed investigation of the FAR range at rest and during exercise in a sufficiently large appropriate reference group without regurgitation. FAR, as well as other RNV variables, failed to provide more information for the diagnosis of mild (clinically irrelevant) left ventricular regurgitation than the diagnosis upon admission alone. Despite the superiority of DE as a gold standard in the detection of mild regurgitation, at present evaluation of RNV regurgitation indices might be the only method to discover regurgitation arising during dynamic exercise.

Dipyridamole stress is favorable in patients unable to exercise maximally for 201Tl myocardial scintigraphy. Aside from an analysis of uptake defects, proper washout analysis can be limited by heart rate variations when isolated dipyridamole stress is used. Heart rate standardized 201Tl washout kinetics after a combined dipyridamole and submaximal exercise stress protocol (CDSE), feasible in elderly patients as well as in patients with peripheral artery disease, were therefore studied to investigate the 201Tl washout after CDSE in differently defined patient groups: Group I comprised 19 patients with documented heart disease and angiographically excluded coronary artery disease (CAD); group II contained 17 patients with a very low likelihood of CAD determined by both normal exercise radionuclide ventriculography and normal 201Tl uptake. Group III comprised 56 patients with a 50% pretest likelihood of CAD but normal 201Tl uptake. Mean washout values were nearly identical in all groups. Despite similar uptake patterns, however, washout standardized by CDSE was significantly lower than the normal washout values after maximal treadmill exercise. Thus an obviously lower 201Tl washout after CDSE than after maximal treadmill exercise must be considered if washout analysis criteria after dipyridamole are applied to evaluate ischemic heart disease. Nevertheless, heart rate elevation achieved by additional submaximal exercise stress seems necessary, adequate and clinically safe for standardisation of washout analysis in dipyridamole 201Tl scintigraphy.

In an attempt to evaluate the dynamics of fatty acid metabolism after aortocoronary bypass grafting (ACBG), ten patients were investigated after ACBG by 123I-HDA myocardial scintigraphy. Tracer kinetics were followed for 90 min and compared to those of 36 nongrafted patients with different underlying heart diseases, including healthy volunteers. Regional analysis and monoexponential curve fitting were used to evaluate t1/2 (half-life of the early period of tracer elimination); biexponential curve analysis was used to calculate Ca/Cb, the ratio of a fast and a slow component of tracer elimination. Rest and stress MUGA-RNV served as discriminating parameters to discern between patient groups with normal and abnormal ventricular function. Group I (normal controls) encompassed ten patients with normal ventricular function, including three after ACBG, and group II seven patients after ACBG and with abnormal ventricular function. Group III had coronary artery disease (CAD) documented by angiography, and group IV by prior myocardial infarction (MI). Group V included patients with cardiomyopathy (CMP). Regional analysis of group II revealed no significant differences to control regions (Gr I) for t1/2 or Ca/Cb, but showed for Ca/Cb a nonsignificant shift toward group III values. However, group II differed significantly from group III and V. Three patients with normal ventricular function after ACBG showed elimination values that were all well within the range of completely normal individuals. Thus our data support the assumption that a normal function is indicative of a normal metabolism. Following myocardial fatty acid metabolism during rest might be a helpful noninvasive tool for etiologic differentiation of disturbed ventricular function.

The concentration of atrial natriuretic peptide was measured in order to evaluate its importance in patients suffering from a variety of cardiac diseases. There was a correlation between plasma concentrations of atrial natriuretic peptide and its "second messenger" cyclic guanosine monophosphate (cGMP) in all of the cases examined. We investigated the relationship between atrial natriuretic peptide and cGMP plasma concentrations during rest and exercise in comparison with the scintigraphically assessed left- and right-ventricular ejection fraction in patients with chronic heart disease (n = 20), and after orthotopic heart transplantation (n = 16); plasma concentrations were also measured in healthy controls (n = 14). Atrial natriuretic peptide and cGMP concentrations showed a similar correlation during rest and exercise with r = 0.74 and r = 0.81, respectively. With the exception of patients after heart transplantation, a significant negative correlation was seen between the left ventricular ejection fraction and atrial natriuretic peptide or cGMP plasma concentrations during rest conditions (r = 0.76 or 0.58, respectively). No correlation was apparent between plasma concentrations of atrial natriuretic peptide or cGMP and the left- or right ventricular ejection fraction during exercise. The concentrations of atrial natriuretic peptide and cGMP in plasma differed significantly between healthy controls and patients during rest and exercise. It is noteworthy that atrial natriuretic peptide and cGMP concentrations were markedly higher in patients after heart transplantation than in patients suffering from chronic heart disease. Our results indicate that plasma atrial natriuretic peptide and cGMP concentrations are sensitive markers of cardiac impairment.