Bridge Technology with TSH Receptor Chimera for Sensitive Direct Detection of TSH Receptor Antibodies Causing Graves' Disease: Analytical and Clinical Evaluation.

Graves' disease is caused by stimulating autoantibodies against the thyrotropin receptor inducing uncontrolled overproduction of thyroid hormones. A Bridge Assay is presented for direct detection of these thyroid-stimulating immunoglobulins using thyrotropin receptor chimeras. A capture receptor, formed by replacing aa residues 261-370 of the human thyrotropin receptor with residues 261-329 from rat lutropin/choriogonadotropin receptor and fixed to microtiter plates, binds one arm of the autoantibody. The second arm bridges to the signal receptor constructed from thyrotropin receptor (aa 21-261) and secretory alkaline phosphatase (aa 1-519) inducing chemiluminescence. The working range of the assay is from 0.3 IU/l to 50 IU/l with a cutoff of 0.54 IU/l and functional sensitivity of 0.3 IU/l. Sensitivity and specificity are 99.8 and 99.1%, respectively, with a diagnostic accuracy of 0.998. The low grey zone is from 0.3-0.54 IU/l. The stimulatory character of the assayed antibodies is shown through a good correlation (r=0.7079, p<10(-7)) to serum T4 levels of untreated patients. In Graves' disease, titers are increased in associated eye disease. In 3 hypothyroid patients with sera positive in the thyrotropin receptor competition assay and in the blocking bioassay, antibodies are not detected by the Bridge Assay, while the monoclonal blocking antibody K1-70 was detected. In Hashimoto disease thyrotropin receptor autoantibodies are detected in some patients, but not in goiter. This Bridge Assay delivers good diagnostic accuracy for identification of Graves' disease patients. Its high sensitivity may facilitate early detection of onset, remission, or recurrence of Graves' disease enabling timely adaption of the treatment.Human genes: TSHR, Homo sapiens, acc. no. M31774.1.

Hemodynamic effects of alinidine (ST 567) at rest and during exercise in patients with chronic congestive heart failure.

Selective inhibition of sinus node function offers the possibility to decrease heart rate and reduce myocardial oxygen consumption in patients with impaired cardiac function, if myocardial contractility is not further attenuated. To study the influence of a specific sinus node inhibitor on myocardial function, alinidine was given to 10 patients with chronic congestive heart failure and stable sinus rhythm. Radionuclide ventriculography was used to monitor left ventricular function at rest and during a standardized exercise protocol. After a bolus injection of 45 mg of alinidine followed by infusion of 10 mg/hr, radionuclide studies were repeated 1.5 and 3 hours later. The results show that left ventricular ejection fraction, stroke volume, and end-diastolic volume index were essentially unchanged, whereas cardiac index decreased by 10% at rest and during exercise. Heart rate decreased markedly by 14% at rest and by 13% during exercise. Systolic blood pressure was reduced by 6% at rest and by 14% during exercise. As a result of the marked decrease of these two parameters, a pronounced effect was seen on rate-pressure product with a 19% decrease at rest and a 24% decrease during exercise. No significant side effects were observed. Alinidine might be given to patients with chronic congestive heart failure and sinus rhythm in doses up to 45 mg without exerting a clinically relevant negative inotropic effect. Therefore it may represent an alternative to other drugs when a decrease in heart rate is desired to reduce myocardial oxygen consumption.

Lack of tolerance after chronic administration of controlled-release isosorbide-5-mononitrate. Interaction of nitrate and gallopamil.

The effect of a controlled-release formulation of isosorbide-5-mononitrate (IS-5-MN) was studied in patients with coronary heart disease (CHD), with the aim of comparing the acute effect with that after chronic administration on parameters of ischemia. To determine whether any tolerance developed, several aspects of ischemia were observed: ECG signs, clinical parameters, and left ventricular function. Fifteen patients with angiographically proven CHD were examined with 12-lead exercise ECG before, 2 h and 4 h after the first dose and after 10 days of therapy with 60 mg IS-5-MN (Coleb-Duriles) once daily. After 7 days, three radionuclide ventriculographies were performed: control, 2 h after nitrate and 2 h after 75 mg gallopamil. Plasma concentrations of IS-5-MN were measured before every exercise test. The results showed a reduction of total ST-segment depression from 0.59 mV to 0.29 mV after 2 h (NS) and 4 h (P less than 0.05) on the 1st day and from 0.48 mV to 0.32 mV (P less than 0.05) and 0.31 mV (NS) after 10 days. The severity of angina pectoris was diminished by about 50%. The effect on exercise duration and time to ST-segment depression by more than 0.1 mV remained unchanged after 10 days, whereas the effect on blood pressure, heart rate and time to onset of angina was attenuated. The mean decrease in ejection fraction (EF) from rest to exercise was reduced from--5.9% to -1.9% (P less than 0.05) after nitrate, while an increase of +1.4% was seen after gallopamil (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Duplex sonography in postoperative monitoring of pancreatic transplants--initial experiences]. / Die Duplexsonographie in der postoperativen Uberwachung von Pankreastransplantaten--erste Erfahrungen.

Duplex ultrasound has gained importance in postoperative monitoring of renal transplants; however, there is no published data on its value in pancreatic transplants. The present study reports on simultaneous pancreatic and renal transplantation of two patients submitted to Duplex scan and conventional ultrasound. During intervals without clinical evidence of complications continuous systolic/diastolic flow was observed. In one case of acute pancreatic rejection Duplex sonography delineated significant reduction of diastolic flow paralleling morphological changes in US. Therefore, relevance of clinical exploration and diagnostic US may be increased by supplementary use of duplex ultrasound.

Acute renal vein thrombosis in renal allografts: detection with duplex Doppler US.

Renal allograft recipients were routinely monitored by means of duplex Doppler ultrasound. In a 20-month survey period, four instances of acute renal vein thrombosis were detected among 75 patients. All episodes occurred within the first 3 postoperative days. The examinations disclosed peaked, abruptly dropping systolic frequency shifts and retrograde plateaulike frequency shifts during diastole at the level of the main renal artery and its proximal branches. A venous Doppler signal could not be recorded. The findings are interpreted as indicating renal impedance exceeding diastolic pressure with nonpropulsive blood flow within the arterial vasculature.

Differentiation between infarction and cardiomyopathy in left bundle branch block by parametric radionuclide imaging.

In LBBB the diagnosis of the underlying disease, i.e. infarction (MI) or cardiomyopathy (CMP), is still a challenge. In this study, the usefulness of radionuclide ventriculography (RNV) for solving this problem noninvasively was tested. The hypothesis was that quantitation of the space-time sequence of left ventricular (LV) contraction by Fourier analysis may differentiate among MI, CMP, and LBBB-specific wall motion abnormalities (WMA). Forty-seven patients (pts) with LBBB were divided into 3 groups: 1) 20 pts with MI, 2) 7 pts with CMP, 3) 20 pts without MI or CMP. Regional parametric amplitude and phase data of eight LV sectors were calculated and expressed in standard deviation units (SDU) of normal. Out of the many regional data only the values of the mean amplitude and the standard deviation of the mean phase shift showed high discriminative power for separating the three groups, with an average squared canonic correlation of 0.5 and a Wilks lambda of 0.22, respectively. In other words, 17 of 20 pts in group 1, 6 of 7 pts in group 2, and 19 of 20 pts in group 3 were truly diagnosed by RNV alone. Such a separation also seems reasonable physiologically, since the mean amplitude reflects global left ventricular function and standard deviation of phase is a measure of time homogeneity of contraction. Furthermore, there was a significant septal phase delay of -4.92 +/- 5.3 SDU in 15 pts with septal MI compared to group 3 pts, who had a subtle premature septal motion of +0.75 +/- 2.64 SDU, whereas the septal amplitude was not different and slightly decreased in both.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluating transplant kidneys: nuclear magnetic resonance tomography in comparison with sonography]. / Beurteilung von Transplantatnieren: Kernspintomographie und Sonographie im Vergleich.

In a prospective study we compared the results of MRI and ultrasound in assessing renal dysfunctions in 22 patients with renal allografts. The current diagnostic criteria are presented and the range of indications is evaluated in relation to perfusion scans.