Somatostatin receptor scintigraphy patterns in patients with sarcoidosis.

PURPOSE: Sarcoidosis is a multisystem granulomatous disorder, most frequently involving the lungs, skin, or eyes. Somatostatin receptor scintigraphy (SRS) can visualize sarcoid granulomas through binding of a radionuclide-coupled somatostatin analog to somatostatin receptors that are expressed in sarcoidosis. Uptake and patterns on SRS were studied and correlated to clinical and conventional findings. PATIENTS AND METHODS: Data of 218 SRSs undertaken for the analysis of potential sarcoidosis were studied. These scintigraphies were retrospectively studied on intensity uptake degrees and localization of sarcoidosis-associated lesions, and compared with conventional radiological techniques (chest x-ray and CT). RESULTS: In all but 1 of the 175 evaluable patients, SRS demonstrated uptake. In patients with thoracic sarcoidosis-associated lesions, SRS improved the yield of visualization of chest x-ray in 20 (36%) and CT in 7 (32%) of histologically unproven patients, and in 31 (30%) and 8 (14%) of the histologically proven patients, respectively. Mediastinal lesions together with either eye, salivary glands, clavicular, or hilar localizations were most frequent demonstrated on SRS and constituted characteristic patterns. Exclusive extrapulmonary disease was found in 6% of the patients. CONCLUSIONS: Somatostatin receptor scintigraphy enhances the yield of investigations in sarcoidosis patients and therefore provides a useful and sensitive imaging technique to monitor organ involvement and therapeutic efficacy in patients with sarcoidosis.

Electrical remodeling reflected by QRS and T vector changes following cardiac resynchronization therapy is related to survival in heart failure patients with left bundle branch block.

INTRODUCTION: We investigated changes in electrocardiographic spatial QRS and T vectors as markers of electrical remodeling before and after cardiac resynchronization therapy (CRT) and their association with altered outcome. METHODS AND RESULTS: In 41 patients with LBBB, ECGpost was recorded during intrinsic rhythm after interrupting CRT pacing and compared to the pre-implant ECGpre and the ECG during CRT (ECGCRT). Mean spatial angles between QRS and T vectors were determined with the Kors matrix conversion. Left ventricular ejection fraction (LVEF) was determined with nuclear isotope ventriculography before CRT implantation (LVEFpre) and at inclusion (LVEFpost). Following CRT, LVEF improved significantly from 26 ± 10 to 36 ± 14% (p=0.01). Duration of QRSpre (168 ± 15 ms) was not different from QRSpost (166 ± 15 ms). A smaller angle between QRSCRT and Tpost was related to a greater angle between Tpre and Tpost (Pearson's R -0.61 - p<0.001). During follow-up (30 ± 2 months) 9 patients (22%) died. Univariate Cox regression revealed higher mortality in the patients with lower LVEFpost (HR 1.10, p=0.01), a larger angle QRSCRTTpost (HR 1.03, p=0.03), a smaller angle QRSpreQRSpost (HR 0.97, p=0.03) and smaller angle TpreTpost (HR 0.95, p<0.01). After adjusting for LVEFpost, only smaller angle TpreTpost was associated with mortality (HR 0.96, p=0.03). CONCLUSIONS: Electrical remodeling can be quantified by measuring the angles between spatial QRS and T vectors before, during and after CRT. In absence of QRS duration changes, more extensive electrical remodeling is associated with a significantly better survival. QRS and T vector changes deserve further investigation to better understand the individual response to CRT.

Stress and excitatory synapses: from health to disease.

Individuals are exposed to stressful events in their daily life. The effects of stress on brain function ranges from highly adaptive to increasing the risk to develop psychopathology. For example, stressful experiences are remembered well which can be seen as a highly appropriate behavioral adaptation. On the other hand, stress is an important risk factor, in susceptible individuals, for depression and anxiety. An important question that remains to be addressed is how stress regulates brain function and what determines the threshold between adaptive and maladaptive responses. Excitatory synapses play a crucial role in synaptic transmission, synaptic plasticity and behavioral adaptation. In this review we discuss how brief and prolonged exposure to stress, in adulthood and early life, regulate the function of these synapses, and how these effects may contribute to behavioral adaptation and psychopathology.

Cellular localization of metabotropic glutamate receptors in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder associated with cortical malformations (cortical tubers) and the development of glial tumors (subependymal giant-cell tumors, SGCTs). Expression of metabotropic glutamate receptor (mGluR) subtypes is developmentally regulated and several studies suggest an involvement of mGluR-mediated glutamate signaling in the regulation of proliferation and survival of neural stem-progenitor cells, as well as in the control of tumor growth. In the present study, we have investigated the expression and cell-specific distribution of group I (mGluR1, mGluR5), group II (mGluR2/3) and group III (mGluR4 and mGluR8) mGluR subtypes in human TSC specimens of both cortical tubers and SGCTs, using immunocytochemistry. Strong group I mGluR immunoreactivity (IR) was observed in the large majority of TSC specimens in dysplastic neurons and in giant cells within cortical tubers, as well as in tumor cells within SGCTs. In particular mGluR5 appeared to be most frequently expressed, whereas mGluR1alpha was detected in a subpopulation of neurons and giant cells. Cells expressing mGluR1alpha and mGluR5, demonstrate IR for phospho-S6 ribosomal protein (PS6), which is a marker of the mammalian target of rapamycin (mTOR) pathway activation. Group II and particularly group III mGluR IR was less frequently observed than group I mGluRs in dysplastic neurons and giant cells of tubers and tumor cells of SGCTs. Reactive astrocytes were mainly stained with mGluR5 and mGluR2/3. These findings expand our knowledge concerning the cellular phenotype in cortical tubers and in SGCTs and highlight the role of group I mGluRs as important mediators of glutamate signaling in TSC brain lesions. Individual mGluR subtypes may represent potential pharmacological targets for the treatment of the neurological manifestations associated with TSC brain lesions.

Mode switching failure during atrial flutter: the '2:1 lock-in' phenomenon.

AIMS: To evaluate incidence and mechanism of a special form of automatic mode switching (MS) failure in patients with atrial flutter. METHODS AND RESULTS: Retrospectively the charts of 134 patients implanted with dual chamber pacemakers with MS algorithms were reviewed. Seven patients (5.2%) were identified that presented with sustained rapid ventricular pacing resulting from atrial flutter with failure of automatic MS. Since this form of MS failure implies 2:1 tracking of atrial flutter, it was coined '2:1 lock-in'. A theoretical timing model was developed to clarify the mechanism of this special form of MS failure. Prerequisites for the '2:1 lock-in' phenomenon are: (1). the sum of the AV delay and the post ventricular blanking (PVAB) must be longer than the cycle length of the atrial flutter, (2). the tachycardia detection rate must be higher than half the atrial flutter rate and (3). the maximum tracking rate (MTR) must be higher than half the atrial flutter rate. Recommendations for programming in order to avoid this specific form of MS failure are made accordingly and parallel algorithms for flutter detection are discussed. CONCLUSION: '2:1 lock-in' is a typical form of MS failure in patients with atrial flutter and the mechanism is closely linked to the typical atrial sensing windows.

Inappropriate rate response in a VVI-R pacemaker.

The search for a pacemaker that accurately and easily mimics normal physiology is a continuing effort. Present pacing developments include AV synchrony and rate adaptiveness. The usefulness and clinical value of some of the new pacing systems remain unclear. Although the hemodynamic advantages of rate responsive pacing over classical ventricular pacing are well established (Kristensson et al., 1985), an ideal sensor for physiological demands has not been established. We report a case of apparently unequivocal increase in heart rate during upper limb movements in a patient with a VVI-R pacemaker using minute ventilation as a sensor. Inappropriate heart rate acceleration may result from changes in transthoracic impedance due to upper limb exercise and it does not necessarily represent sensor malfunction. Although this complication is well-known in VVI-R pacemakers using respiratory rate or minute ventilation as sensor (Santomauro et al., 1992), one must remain aware of this sensor-related problem. In this particular patient the problem could be solved by implanting the pacemaker can more medially.