(111)In-octreotide SPECT-CT in head and neck paragangliomas.

Head and neck paragangliomas are rare neuroendocrine tumors expressing somatostatin receptors on their cell surface, particularly subtype 2. Due to this distinctive feature, images can be obtained in Nuclear Medicine using synthetic analogues of somatostatin, mainly octreotide, which allow selective display by planar scintigraphy, SPECT-CT or PET-CT imaging after radiolabeling with (111)In or (68)Ga. Three cases have been selected and presented from a series of patients that illustrate the utility of SPECT-CT studies with (111)In-octreotide in the diagnosis and monitoring of this type of tumor. These are characterization at initial diagnosis, staging, and detection of local recurrence or metastasis, with added value with respect to anatomical images (nuclear magnetic resonance, computed axial tomography, angiography), for example in the differentiation between functional tissue or scar in patients who had previously undergone surgery.

[Chronic infections multifocal osteomyelitis vs chronic recurrent multifocal osteomyelitis: with reference to one case]. / Osteomielitis crónica multifocal séptica vs osteomielitis crónica multifocal recurrente: a propósito de un caso.

We present a rare case of chronic infectious multifocal osteomyelitis with affectation symmetric in the both femures in a patient with spondyarthropathic secondary Inflammatory Bowel Disease. The diagnosis was confirmed with culture of the bone biopsy. The aim of this work is the revision of the Chronic Infectious Multifocal Osteomyelitis and the Chronic Recurrent Multifocal Osteomyelitis into SAPHO syndrome that both were the possibilities diagnoses.

Disturbed synthesis of insulinlike growth factor I and its binding proteins may influence renal function changes in liver cirrhosis.

Insulinlike growth factor-1 (IGF-1) is an anabolic hormone synthesized by the liver upon stimulation by growth hormone (GH). IGF-1 exerts important effects on renal hemodynamics and renal sodium handling. The bioactivity of this hormone is influenced by its binding proteins (BP) of which IGF-BP3 favors retention in the capillary lumen while IGF-BP1 facilitates the transport to the target tissues. IGF-BP1 modulates the actions of IGF-1 on target cells including renal tubules. Although a number of reports have dealt with disturbances of the IGF-1/IGF-BP system in cirrhosis, no studies have yet addressed the relationship between alterations in this system and renal function changes in cirrhosis. In the present study we have included 20 patients with cirrhosis and 10 healthy subjects (control group). As compared with the controls, patients showed lower circulating levels of IGF-1 and IGF-BP3, higher IGF-BP1 levels, and a tendency to higher insulinemia and GH values. The index IGF-1 x IGF-BP1/IGF-BP3 (IGF-1-IGF-BP index, reflecting the accessibility of circulating IGF-1 to target cells) was higher in patients with ascites. IGF-1 directly correlated with renal blood flow (P < 0.05), with IGF-BP3 (P < 0.001) and inversely with the Pugh's score (P < 0.02). A negative correlation was found between IGF-1-IGF-BP index and fractional sodium excretion (P < 0.01) and between IGF-BP1 and urinary sodium excretion (P < 0.02). Our findings support the hypothesis that the disturbance of the IGF-1/IGF-BP axis may be related to the degree of renal vasodilation and renal sodium retention in cirrhotic patients.

[The capacity of the rest-dobutamine gated SPECT protocol to predict contractile recovery after revascularization of myocardial dysinergic areas]. / Capacidad del protocolo de gated-SPECT reposo/dobutamina para predecir la recuperación contráctil posrevascularización de áreas miocárdicas disinérgicas.

INTRODUCTION AND AIM: Gated-SPECT is a promising method to analyze myocardial viability. We have assessed the accuracy of a new protocol of rest/Dobutamine gated-SPECT, based on the evaluation of contractile reserve induced by 10 microg/kg/min of Dobutamine, to predict contractile recovery after revascularization of dysinergic myocardial territories. PATIENTS AND METHODS: In a group of 36 patients submitted to percutaneous revascularization, we selected 40 vascular territories (21 left descending artery, 19 right coronary-circumflex) with severely depressed contractility (contrast ventriculography, center line method). Follow up evaluation at 6 months showed the absence of angiographic restenosis and control contrast ventriculography assessed the contractile changes of the selected territories, considering those with contractile restoration as viable. Before revascularization, rest/Dobutamine gated-SPECT study was applied and viability was defined as the presence of contractile reserve (positive or improvement [n = 21] and negative or impairment [n = 7]) with non viability being the absence of contractile reserve (n = 12). We analyzed the evolution of the ejection fraction in a group of 27 patients with impaired ventricular function and complete revascularization. RESULTS: Gated-SPECT showed a sensitivity of 0.96 (95% CI 0.78-0.99) and a specificity of 0.78 (95% CI 0.48-0.94) in the diagnosis of viability. The ejection fraction (median [interquartile range]) increased after revascularization: 0.42 (0.15) vs 0.55 (0.22), Z = -3.9; p < 0. 001. The diagnosis of viability by gated-SPECT (p < 0.001) and the extent of severely depressed myocardium (p = 0.04) independently predicted the increase of the ejection fraction after revascularization. CONCLUSIONS: The analysis of contractile reserve by rest/Dobutamine gated-SPECT is adequate to diagnose viability in territories with severely depressed contractility and independently predicts the increase of ejection fraction after revascularization.

[Validation of the three-dimensional method of sestamibi gated-SPECT in the calculation of the left ventricular ejection fraction in patients with ischemic heart disease. Comparison with contrast ventriculography]. / Validación del modelo tridimensional de gated-SPECT con sestamibi para el cálculo de la fracción de eyección ventricular izquierda en pacientes con cardiopatía isquémica. Comparación con la ventriculografía de contraste.

INTRODUCTION AND OBJECTIVE: Tomography with acquisition synchronized with electrocardiography, gated-tomography, allows the assessment of left ventricular contractile function. The accuracy of a new method of gated-tomography, based on the three dimensional representation of the left ventricle to calculate the ejection fraction was validated by means of comparison with contrast ventriculography. METHODS: We studied 85 patients with ischemic cardiopathy, and ejection fraction was calculated by contrast ventriculography and sestamibi-gated-tomography, at rest and throughout 10 micrograms/kg/min of dobutamine. Furthermore, we assessed the extent of perfusion defect, as well as the number of segments with activity below 50% of the total 13 segments in which the tomographic slices were divided. RESULTS: Gated-tomography was significantly correlated to contrast ventriculography in the calculation of ejection fraction, both with acquisition at rest (r = 0.80) and throughout Dobutamine (r = 0.82). The average underestimation of gated-tomography calculation of ejection fraction was significantly greater for the rest study (-0.12 [IC 95% 0.04, -0.30]) than the dobutamine study (-0.07 [IC 95% 0.09, -0.24]). Patients with greater perfusion defects (4 o more segments) had no differences in underestimation of ejection fraction (-0.13 [IC 95% 0.03, -0.30] versus -0.11 [IC 95% 0.07, -0.29]). CONCLUSIONS: The three-dimensional method of gated-tomography accurately assesses the ejection fraction. The underestimation determined by this method was lower in the study done with viable doses of dobutamine. The extent of perfusion defect had no deleterious effect on gated-tomography in the calculation of ejection fraction.

Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes.

OBJECTIVE: To study the effect of steroidal and nonsteroidal antiinflammatory drugs (NSAID) on cyclooxygenase (COX-1 and COX-2) activity in human articular chondrocytes. METHODS: Chondrocytes were isolated from articular cartilage of donors with no articular disease. Unstimulated and interleukin 1 (IL-1) stimulated chondrocytes were used as models to study the effects of drugs on COX-1 and COX-2. Cells were incubated with vehicle or drugs; supernatants were removed and the level of prostaglandin E2 (PGE2) in each sample was determined by enzyme immunoassay. IC50 were calculated from the reduction in PGE2 content by different concentrations of the test substance by linear regression analysis. RESULTS: COX- mRNA was detected in unstimulated cells, but stimulation with IL-1 for up 12 h did not modify the levels of COX-1 mRNA. In contrast, COX-2 mRNA was not detectable in unstimulated cells, but it was induced by IL-1. Dexamethasone inhibited COX-2 mRNA expression induced by IL-1. COX-2 protein levels correlated with mRNA expression. Dexamethasone was the strongest drug inhibitor of COX-2 (IC50 = 0.0073 microM). However, it did not inhibit COX-1 activity. Among all NSAID tested, meloxicam and aspirin were the least potent inhibitors of COX-1 (IC50 = 36.6 microM and 3.57 microM, respectively). Indomethacin and diclofenac were the most potent inhibitors of COX-1 (IC50 = 0.063 microM and 0.611 microM, respectively) and COX-2 isoforms (IC50 = 0.48 microM and IC50 = 0.63 microM, respectively). Meloxicam was a more potent inhibitor of COX-2 (IC50 = 4.7 microM) than aspirin (IC50 = 29.3 microM) and similar to piroxicam (IC50 = 4.4 microM). Among all drugs tested dexamethasone showed the greatest selectivity for COX-2 and meloxicam was the NSAID with the best COX-2/COX-1 ratio (r = 0.12). Aspirin and piroxicam were about 8 times more active against COX-1 than COX-2, indomethacin was 7 times more active, and diclofenac was an equipotent inhibitor of COX-1 and COX-2. CONCLUSION: We found that COX-1 and COX-2 isoforms are expressed in human chondrocytes at rest and in IL-1 stimulated cells, respectively. Antiinflammatory drugs have different capacities to inhibit COX enzyme in human articular chondrocytes.

Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology.

OBJECTIVE: To determine which kind of cell death occurs in cartilage from patients with osteoarthritis (OA). METHODS: Seven normal and 16 OA cartilage samples were collected at autopsy or during joint replacement surgery, respectively. A piece of cartilage was cryopreserved until histologic studies were done. The rest of the cartilage was used to isolate chondrocytes. Apoptotic chondrocytes were analyzed by light and fluorescence microscopy using nuclear 4',6-diamidino-2-phenylindole dihydrochloride stain. Apoptotic chondrocytes were quantified by fluorescence-activated cell sorter (FACS) analysis. The TUNEL technique was used to study histologic apoptosis in situ. Superficial cartilage was processed for ultrastructural study by electron microscopy. RESULTS: OA chondrocytes displayed nuclear and cytoplasmic changes consistent with apoptotic cell death. FACS analysis showed that the OA cartilage had a higher proportion of apoptotic chondrocytes than did normal tissue (51% versus 11%; P < 0.01). In situ study of DNA fragmentation in the cartilage showed that apoptotic cells were located in the superficial and middle zones. Ultrastructural analysis of the superficial OA cartilage revealed some empty lacunae, lysosomal-like structures, matrix vesicle-like structures, fragmented chondrocytes, and nuclear condensation. CONCLUSION: Chondrocytes in OA cartilage demonstrated morphologic changes that are characteristic features of apoptosis. This mechanism of cell death plays an important role in the pathogenesis of OA and could be targeted for new treatment strategies.

Activating and inhibitory mutations in adjacent tyrosines in the kinase domain of ZAP-70.

ZAP-70 is an 70-kDa protein tyrosine kinase, expressed exclusively in T cells and NK cells, and plays a critical role in mediating T cell activation in response to T cell receptor engagement. The strong correlation between tyrosine phosphorylation of ZAP-70 and its acquisition of increased kinase activity suggests that is is positively regulated by tyrosine phosphorylation. Previously, we identified tyrosines 492 and 493 of ZAP-70 as being sites of in vivo phosphorylation in response to T cell receptor engagement. To determine the role of phosphorylation in regulating ZAP-70 activity, we mutated each of these tyrosines individually to phenylalanine. When expressed in COS cells, Y493F-mutated ZAP-70 demonstrated normal basal kinase activity, but, unlike wild type ZAP-70, could not be activated by tyrosine phosphorylation induced by incubation with pervanadate or by co-expression of constitutively activated Lck. This suggests that Tyr-493 phosphorylation is required for the tyrosine phosphorylation-induced activation of ZAP-70. The Y492F mutation resulted in 4-fold higher basal kinase activity, which could be stimulated further by tyrosine phosphorylation. These results reveal that critical tyrosine residues in the kinase domain of ZAP-70 are important in regulation of its catalytic activity.

Arteriovenous shunting, hemodynamic changes, and renal sodium retention in liver cirrhosis.

BACKGROUND: Arterial vasodilation has been postulated to initiate sodium retention in cirrhosis. This work was designed to analyze whether arteriovenous shunting underlies vasodilation and influences renal function in cirrhosis. METHODS: The femoral arteriovenous difference in oxygen content (Ca-VO2) was measured in 10 healthy subjects (control group) and 31 cirrhotic patients: 9 without ascites (group 1), 10 with ascites and a urinary sodium excretion rate (UNaV) of > 10 mEq/24 h (group 2), and 12 with ascites and UNaV of < or = 10 mEq/24 h (group 3). In 8 subjects from each group, femoral blood flow and the cardiac output were determined by duplex-Doppler ultrasonography. In 9 cases arteriovenous shunting in the femoral territory was estimated using 30 +/- 5-microns radiolabeled microspheres. RESULTS: Ca-VO2 was lower in group 3 than in controls or group 1. Ca-VO2 correlated inversely with femoral blood flow, plasma renin activity, plasma aldosterone concentration, and degree of shunting measured by microspheres. Ca-VO2 correlated directly with systemic vascular resistance and prothrombin index. CONCLUSIONS: In decompensated cirrhotic patients, there is an increased arteriovenous shunt for oxygen in the lower extremities that is associated with increased arterial blood flow, decreased systemic vascular resistance, and worsening of liver function. This shunt is due partly to opening of arteriovenous precapillary connections.

Primary adrenocortical nodular dysplasia presented as adrenal adenoma by functional scintigraphy.

This is a report of a case of a 12-year-old boy with Cushing's syndrome in which high doses of dexamethasone failed to suppress glucocorticoid secretion. Neither CT nor MRI (morphologic studies) revealed any adrenal abnormality. Functional images with NP-59 (I-131 beta-iodomethyl-norcholesterol) clearly revealed intense unilateral uptake in the right adrenal gland. A right adrenalectomy was performed, and the pathologic diagnosis was primary adrenocortical nodular dysplasia. One year later, the cushingoid signs had virtually disappeared and urinary steroid excretion and serum cortisol levels were within the normal range. Nevertheless, primary adrenocortical nodular dysplasia is essentially a bilateral disease. In this case, a remission in the adrenocortical hyperfunction was observed. Although there was confusion in the etiological diagnosis, functional scintigraphy correctly indicated the status of adrenal function.