Dual-head gamma camera coincidence imaging in pancreatic cancer.

OBJECTIVE: To assess the usefulness of dual-head camera imaging with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in the identification of malignant pancreatic lesions. MATERIAL AND METHODS: Fifteen (15) patients with pancreatic masses (7 females and 8 males, mean age 52 10 years) have been studied prospectively. After a 12-hour fasting patients received 120 MBq of FDG and were imaged in a dual-head camera equipped with coincidence detection. The final diagnosis was obtained by histology (biopsy or surgery in 13 patients) or follow-up (in 2 patients). RESULTS: Nine patients showed FDG uptake, all had pancreatic cancer proven on histological examination. Six patients had no tracer uptake: two had chronic pancreatitis, 1 had insulinoma, 1 had gastrinoma and two had pancreatic adenocarcinoma. Overall sensitivity was 69%, specificity was 100% and accuracy was 73%. CONCLUSION: Dual-head camera FDG images seem potentially useful in the characterization of the nature of pancreatic lesions. However, a negative study does not rule out malignancy in this patient population.

Imagen por coincidencia en gammacámara de doble cabezal en cáncer pancreático / Dual-Head gamma camera coincidence imaging in pancreatic cancer

Objetivo. Evaluar la utilidad de la realización de imagen con, 2-flúor-2 desoxi-D-glucosa-18F (FDG) em gammacámara de doble cabezal en la identificación de lesiones pancreáticas malignas. Materiales y métodos. Hemos estudiado en carácter prospectivo 15 pacientes con masas pancreáticas (7 mujeres y 8 hombres, edad promedio 52 ñ 10 años). Después de un ayuno de 12 horas los pacientes recibieron 120 MBq de FDG y se les realizó imágenes en una cámara de doble cabezal equipada con detección por coincidencia. El diagnóstico final se obtuvo por histología (biopsia o cirugía en 13 pacientes) o por seguimiento (en 2 pacientes).Resultados. Nueve pacientes mostraron captación de FDG, todos tuvieron cáncer pancreático probado con base en examen histológico. Seis pacientes no tuvieron captación del radiofármaco: dos pancreatitis crónicas, 1 insulinoma, 1 gastrinoma y dos adenocarcinomas pancreáticos. La sensibilidad global fue del 69 por ciento, la especificidad fue 100 por ciento y la exactitud fue del 73 por ciento. Conclusión. Las imágenes realizadas com FDG en cámara de doble cabezal equipada com detección por coincidencia parecen potencialmente útiles en la caracterización de lesiones pancreáticas, mientras que un estudio negativo no descarta totalmente malignidad (AU)

Symptoms, left ventricular function, and timing of valve replacement surgery in patients with aortic regurgitation.

BACKGROUND: Because cardiac decompensation is subtle, the best time to perform aortic valve replacement surgery may be difficult to determine. We investigated the relation of symptoms to left ventricular (LV) function and the timing of valve replacement in patients with aortic regurgitation (AR) of largely rheumatic origin. METHODS: Sixty-eight initially asymptomatic patients (mean age 29 years) with severe chronic AR were monitored for 36 months. Assessments included baseline and yearly echocardiograms and radioisotope ventriculography (resting and exercise) and clinical examinations every 6 months. RESULTS: Forty-seven patients (69%) remained asymptomatic and 21 (31%) had symptoms develop after 24 to 36 months. Compared with symptomatic patients, asymptomatic patients had significantly (P <.05) lower baseline LV end-diastolic diameter, end-systolic diameter, end-systolic stress, and volume/mass ratio but greater shortening fraction and ejection fraction (EF) at rest. These variables remained stable without statistically significant change until surgical correction in symptomatic patients. Percent variation of EF from rest to exercise increased in patients who remained asymptomatic (EF 2.8% +/- 10.6%) but decreased in those who became symptomatic (EF -4.2% +/- 13%; P <.05). Twenty symptomatic patients (New York Heart Association class III/IV, angina and/or syncope) had valve replacement surgery, after which all were in New York Heart Association class I/II and had significant decreases of LV end-diastolic and end-systolic diameters and an increase on percent variation of EF from rest to exercise (P <.0001). CONCLUSIONS: Development of symptoms did not correlate with change in any ventricular function indexes. Surgery on appearance of symptoms restored LV function to near normal.

[Myocardial perfusion study in patients with right bundle branch block]. / Estudo de perfusão miocárdica em portadores de bloqueio de ramo direito.

PURPOSE: To evaluate the sensitivity and specificity of myocardial perfusion scintigraphy in the detection of coronary artery disease in patients with right bundle branch block (RBBB). METHODS: Thirty one patients (24 male, 62.3 +/- 10.5 years) with RBBB, submitted to myocardial perfusion scintigraphy associated with exercise (n = 7) or dipyridamole (n = 24) and previous cinecoronariography were studied retrospectively. Left ventricle scintigraphic image was divided in three segments corresponding to the three main epicardic coronary territories in a total of 93 segments. Cineangiographic and scintigraphic data were then compared according to the different artery territories. RESULTS: Twenty three patients had significant lesions (> or = 60%) in one or more coronary arteries and eight had no obstruction. Forty nine segments were irrigated by normal coronary arteries and 44 were related to arteries that had significant lesions. Twenty out of twenty three patients showed alterations in perfusion (sensitivity = 87%). All patients without coronary obstructions showed normal perfusion scintigraphy (specificity = 100%). One of the segments perfused by normal coronaries showed abnormal scintigraphy. Scintigraphy showed perfusion defects in 29 out of 44 segments with coronary obstructions. Sensitivity and specificity of the method for each arterial territory were 72% and 100% (left descending coronary artery), 67% and 94% (right coronary artery), 55% and 100% (circunflex coronary artery), respectively. CONCLUSION: The presence of RBBB does not modify the sensitivity and specificity of the method in the detection of coronary artery disease.

[Assessment of the myocardial functional reserve in patients with left ventricular aneurysm by radionuclide ventriculography. Response to isotonic exercise]. / Avaliação da reserva funcional miocárdica em portadores de aneurisma de ventrículo esquerdo por ventriculografia radioisotópica. Resposta ao exercício isotônico.

PURPOSE: To evaluate global and regional left ventricular (LV) ejection fractions (EF) by radionuclide ventriculography in patients with LV aneurysm at rest and during isotonic exercise. METHODS: Twenty patients were studied by radionuclide ventriculography at rest and during exercise. All patients had been submitted to cineangiography and showed LV aneurysm post myocardial infarction. RESULTS: Patients were divided according to LV EF in two groups: one with EF > or = 40% and the other with < 40% EF. Both groups showed normal response of global EF to exercise: mean rest EF was 40 +/- 14% and mean exercise EF was 45 +/- 14% (p < 0.01). When groups were considered separately, EF values showed the same behavior. Half of the patients showed normal response to exercise and the other half showed abnormal response. These changes were not associated with resting EF values, but were due to regional EF of lateral wall, that changed from 44 +/- 7 to 48 +/- 7% in the group of patients with normal LV EF response to stress and from 50 +/- 5 to 46 +/- 5% in those with abnormal response (p < 0.01). CONCLUSION: The evaluation of regional ventricular EF by radionuclide ventriculography during exercise better discriminates functional reserve in patients with LV aneurysm than resting global EF. These findings could help the decision making of the therapeutic approach in this specific group of patients.

[Postoperative course of left ventricular function in aortic insufficiency]. / Evolução pós-operatória da função ventricular esquerda na insuficiência aórtica.

PURPOSE: To analyze the follow-up of left ventricular function (LVF) after surgical correction of severe chronic aortic insufficiency (AI). METHODS: Twenty-one out of 68 patients with AI, initially asymptomatic and that developed symptoms during the follow-up period of 24-36 months, were studied. Relationship between symptoms and LVF by echocardiogram and radioisotopic ventriculography at rest and in isotonic exercise were studied. Three clinical moments (CM) were assumed: CM-0- at the beginning of the study, when all patients were asymptomatic; CM-1- manifestation of the symptoms during 24-36 months; CM-2- corresponding to the late post-operative period of 8 months of 20 out of 21 patients (one refused the surgery). The analysis did not show any significant differences between the mean values of all echocardiographic variables (diastolic and systolic diameters, shortening fraction, final systolic stress, volume-mass ratio, contractility index) and the ejection fraction of the left ventricle (EF) obtained by the radioisotope ventriculography at rest and, including exercise, between clinical moments 0 and 1. RESULTS: In the CM-2, involution was verified for functional class I/II in all cases and absence of expressive complications or immediate or late postoperative mortality. Comparison between CM-2 and 0 showed expressive regression of the diameters at rest in the postoperative period and with significant improvement in the means mainly the percentual variation of the EF and total time of effort. CONCLUSION: Symptoms assembled patients with more advanced eccentric hypertrophy and did not coincide with any immediate change in findings studied at rest and at exercise. It represented a point of reference for surgical indication compatible with late postoperative involution of chronic adaptation of AI.

[The relationship between left ventricular function and the precipitation of symptoms in severe chronic aortic insufficiency]. / Relação entre função ventricular esquerda e desencadeamento de sintomas na insuficiência aórtica crônica severa.

PURPOSE: To study the relationship between symptoms and left ventricular function in 68 patients with severe chronic aortic regurgitation using echocardiogram and radionuclide left ventriculography at rest. METHODS: Three stages of natural history are assumed: the 1st, at the beginning of the study, when all patients were asymptomatic (clinical stage 0); the 2nd, at the end of 36 month persistence of asymptomatic (clinical stage 1), consisting of 45 patients (group AA); the 3rd, on occasion of manifestation of the symptoms during this period of time (clinical stage 2), consisting of 21 patients (group AS-PRE), with two fatalities not related to valvopathy. RESULTS: The comparison between the groups resulted in similarities in the mean ages, mean time of knowledge of the disease, predominance of males and rheumatic etiology. The profile analysis showed that the significant initial differences between the average of all echocardiographic variables (diastolic diameter, systolic diameter, shortening fraction, final systolic stress, volume-mass ratio, contractility index) and of the ejection fraction of the left ventricle obtained by the radionuclide ventriculography at rest, remained during the study. CONCLUSION: Development of symptoms grouped patients with more advanced excentric hypertrophy, did not coincide with any immediate change in the laboratory markers studied at rest and it was used as a referential for surgical therapy.

[Study of myocardial viability by thallium-201 SPECT. Conventional redistribution versus reinjection]. / Estudo da viabilidade miocárdica através do SPECT-Tálio-201. Redistribuição convencional versus reinjeção.

PURPOSE: To verify if a third series of images acquired by reinjection thallium-201, 24h after conventional myocardial perfusion with the radioisotope, improves the identification of myocardial viability segments. METHODS: We studied 30 patients, mean age 57.7 +/- 9.4 years, with old myocardial infarction using thallium (Tl)-201 SPECT (single-photon-emission computed tomography), and we obtained 3 series of images (stress, redistribution after 4h and reinjection after 24h. Cardiac images were divided in 5 segments (apical, lateral, anterior, septal and inferior) and each one received a value by a score system according to the Tl-201 myocardial uptake (0 = normal uptake; 1 = mild hypoperfusion; 2 = moderate hypoperfusion; 3 = severe hypoperfusion or no myocardial uptake). We considered viable myocardium when the uptake of Tl-201 in the segment related to the myocardial infarction increased at least 1 point in two different axis of Tl-201 SPECT. RESULTS: Seven (23.3%) patients demonstrated increase of Tl-201 uptake only at reinjection images, showing a higher efficacy of the method. Nine (30%) patients showed persistent hypoperfusion at all series of images suggesting only fibrosis in the area related to the infarction. Fourteen (46.7%) patients showed increase of Tl-201 concentration at redistribution images; among these patients, six showed improvement of myocardial uptake at reinjection. This condition were interpreted as regional chronic ischemic process: hibernating myocardium. CONCLUSION: Tl-201 hypoperfusion at redistribution images without significant changes in relation to the stress images do not represent fibrosis at all. The reinjection technic was better than conventional redistribution in the detection of viable myocardium. This data allows a better therapeutic orientation.

[Scintigraphy of myocardial perfusion combined with pharmacologic stress with dipyridamole]. / Cintilografia de perfusão miocárdica associada ao estresse farmacológico com dipiridamol.

PURPOSE: To analyze adverse reactions (AR), hemodynamic and electrocardiographic changes and thallium scintigraphy (TS) results, during pharmacological stress with dipyridamole (SD), correlating these data to the presence and extension of coronary artery disease (CAD). METHODS: We studied 126 patients, 66 had no evidence of cardiovascular disease (G1) and 60 had critical occlusive CAD > or = 70% stenosis (G2). Most of them were male, mean age 56.5 +/- 10.9 years old. All patients were submitted to TS after receiving 0.56 mg/kg of dipyridamole intravenously (0.14 mg/min during 4 min) followed by 111MBq of thallium-chloride-201. Conventional ECG was recorded before and after SD; heart rate (HR) and arterial pressure (AP) were monitored during dipyridamole infusion. All signals and/or symptoms were observed. RESULTS: Cine-coronarography showed 22 patients (37%) with one vessel disease (VD) (G2a), 26 (46%) with two VD (G2b) and 12 (20%) with three VD (G2c). Of the 126 patients 63% did not present symptoms. Flushing (25%) and sick-headache (12%) were most frequent AR. Typical angina was reported by one G1 patient (1.5%) and six G2 patients (10%) (p < 0.05). HR increased 18.09 +/- 12.27% and 12.40 +/- 4.90%, systolic blood pressure varied -5.2 +/- 7.5% and -4.3 +/- 6.5% in G1 and G2, respectively. These parameters are not correlated to CAD presence and extension. ST depression and ectopic beats occurred in 5% and 11% of G1 patients, in 15% and 30% of G2 patients, respectively (p < 0.05). Typical angina was more common in G2a and G2b; ST changes in G2b and G2c; and arrhythmia in G2c (not significant). Sensitivity of TS associated to SD was 84%, comparable to stress exercise thallium test. CONCLUSION: TS associated to SD, a noninvasive, safe with low morbidity and few collateral effects method is an option to patients with limitations to physical exercise tests.

[Clinical applications of CA 125 carcinoma of the ovary]. / Aplicações clínicas do CA 125 no carcinoma de ovário.

Cancer of the ovary is one of the most common causes of death among gynecologic neoplasms. As it is relatively "protected" by the peritoneal cavity, there is great need of methods to improve early diagnosis and to assist with the management of patients with this disease. An important advance was observed with the application of monoclonal antibodies. After 1983, most papers have mentioned CA 125 as a biochemical marker of ovarian non-mucinous cancer. The purpose of the authors is to discuss the controversial aspects of this important marker and its role in the diagnosis and follow-up of ovarian carcinoma. All being considered, clinical applications, post-treatment follow-up, and flaws can be established.

Partial purification of plasma and tissue kallikreins in psoriatic epidermis.

Human psoriatic scale extracts produced kinins from heated plasma (11.3 +/- 5.5 ng kinin/mg protein) and from purified low molecular weight (LMW) bovine kininogen (4.4 +/- 1.7 ng/mg). Sephacryl S-200 gel filtration of the extracts showed three peaks of kininogenase activity with Mr values of 90,000 (K-I), 65,000 (K-II), and 35,000 (K-III). Upon DEAE-Sepharose chromatography of the Sephacryl peaks, K-I activity was found in the nonadsorbed fraction and formed kinins only from heated plasma. Peak K-II activity was resolved into two peaks, K-IIa (in the nonadsorbed fraction), which formed kinins only from heated plasma, and K-IIb (in the adsorbed fraction), which formed kinins from both heated plasma and LMW bovine kininogen. K-III kininogenase activity appeared at the same position as K-IIb and also formed kinins from both substrates. Kininogenases K-I and K-IIa had the same Km value (0.3 mM) with Pro-Phe-Arg-p-nitroanilide(pNA), similar to that found with human plasma kallikrein. The Km value of K-IIb with Val-Leu-Arg-pNA (0.8 mM) was like that found for human salivary kallikrein, whereas K-III had a low affinity for this substrate. Like plasma kallikrein, K-I and K-IIa were inhibited by soybean trypsin inhibitor, but only weakly by aprotinin. In addition the kininogenase activity of both K-I and K-IIa was neutralized by adding antihuman prekallikrein immunoglobulin G (IgG). In contrast, K-IIb and K-III were strongly inhibited by aprotinin but not by soybean trypsin inhibitor, consistent with their being tissue kallikreins. It was confirmed that K-IIb and K-III shares antigenic determinant of urinary kallikrein.

Purification of epidermal plasminogen activator inhibitor.

A plasminogen activator inhibitor was purified from human cornified cell extract by DEAE-Sepharose, Sephacryl S-200, and high-performance liquid chromatographies on hydroxyapatite HPHT and anion-exchanger Mono Q at pH 7.2 and 8.0. The purified inhibitor showed Mr 43,000 and pI 5.2 50% inhibition of fibrinolytic activity (1.5 IU) of urokinase and tissue-type plasminogen activator was attained by 0.60 ng and 11.0 ng purified inhibitor, respectively. Synthetic substrate assay demonstrated slow tight-binding inhibition to both urokinase and tissue-type plasminogen activator. The inhibitor did not inactivate plasmin, thrombin, glandular kallikrein or trypsin.

Elastase activity in granulomatous inflammation in experimental murine leprosy.

Proteolytic activity for [3H]elastin, pyro-Glu-Pro-Val-pNA(S-2484), and Suc-(Ala)3-pNA(AAApNA) was demonstrated in the bound fraction extracted with 2 M KSCN + 0.1% Triton X-100 from hypersensitivity-type murine lepromas in C57BL/6N mice, while elastase-inhibitor activity was separately observed in the soluble fraction extracted with a Tris-saline buffer. Sephacryl S-200 gel chromatography showed a peak of elastolytic activity with approximately 20,000 in molecular weight. The following DEAE-Sepharose chromatography demonstrated three fractions of elastolytic activity (E-I, II, III). The inhibitory profile showed that E-I is a thiol proteinase, while E-II and E-III belong to serine proteinase-type elastases. Both E-II and E-III showed different properties with neutrophil elastase or elastase secreted from cultured macrophages, but identical characteristics to membrane bound-type elastase of monocytes. A lower level of elastolytic activity was detected in the bound fraction of nonhypersensitivity-type murine lepromas in CBA/N mice, suggesting a more involvement of membrane bound-type elastase from monocytes/macrophages during the tissue remodelings of hypersensitivity-type granulomas.

Plasminogen activator and plasminogen activator inhibitor associated with granulomatous inflammation: a study with murine leprosy.

Plasminogen activator that is associated with the development of hypersensitivity granulomas (gPA) was partially purified from a saline soluble fraction of murine lepromas elicited in "resistant" mice, C57BL/6N. The gPA was shown to consist of two subspecies (23,000 and 48,000 in molecular weight) with essentially identical enzymologic properties. The gPA was found to be a relatively heat stable weakly alkaline serine proteinase with trypsin-like characteristics in the specificity for synthetic substrates and proteinase inhibitors. It showed a high affinity for H-D-Ile-Pro-Arg-pNA (Km = 1.4 X 10(-4) M) H-D-Val-Leu-Lys-pNA (Km = 5.2 X 10(-4) M), and L-pyroGlu-Gly-Arg-pNA (Km = 9.3 X 10(-4) M). The gPA did not demonstrate antigenic cross reaction with urokinase-type or tissue-type plasminogen activator. Two distinct enzymatic regulators of the gPA were also demonstrated in the saline soluble fraction of the hypersensitivity granulomas. The gPA and its regulation are assumed to be correlated with macrophage activation in the hypersensitivity granulomas.

Fibrin and collagen deposition and fibroblasts proliferation in granuloma of murine leprosy. Comparison of two mouse strains with different immune reactions.

Comparative immunofluorescence study with murine lepromas induced in C57BL/6NJcl (immunologically high responder) and CBA/N (low responder) mouse strains revealed that fibrin formation was associated with cell-mediated immune resistance against invasive bacilli. Histochemistry on paraffin sections further elucidated fibroblast proliferation and formation of collagen fibers following fibrin deposition only in murine lepromas with positive host reactions.

Comparative study with two polar types of murine leprosy: an involvement of plasminogen activator and its possible regulating factor in the granulomatous tissue reaction.

Enzymatic activities in a saline-extractable fraction from two polar types of murine lepromas were investigated using pyroglutamyl-glycyl-arginine-p-nitroanilide and plasminogen-rich, as well as plasminogen-free, fibrin plates. An inhibitor activity for urokinase was also measured. C57BL/6NJcl (immunologically high responder strain) mice inoculated with 2 X 10(8) Mycobacterium lepraemurium developed a localized lepromatous lesion after 4 weeks. The tissue extracts obtained after 4-6 weeks exhibited inhibition for urokinase (8.8 IU/mg protein), but no enzymatic activity. After 8-11 weeks, when the lepromas showed an ulcerative change, prominent peptide hydrolytic activity (84.8 nmol/mg/protein/ min) was demonstrated. The fibrin plate assay confirmed that plasminogen activator is predominantly involved (26.4 IU/mg protein). The proteolytic activation was apparently correlated with discharge of purulent materials containing the bacilli and subsequent limitation of leproma development. However, similar modulation of the fibrinolytic enzyme-inhibitor system was not shown in CBA/N mice (immunologically low responders). The tissue extracts showed a low level of urokinase inhibitor activity (1.9 IU/mg protein), but no peptidolytic or plasminogen activator activity. Consequently, lepromas were developed progressively until 25 weeks after infection and dissemination from the lepromatous lesion took place thereafter. In comparison with histologic findings, which revealed accumulation of lymphocytes and mononuclear cells in the peripheral zone of lepromatous lesions in the C57BL/ 6NJcl, but not in the CBA/N mice, a controlling mechanism of plasminogen activator in tissue is assumed to be involved in the development of the granulomatous tissue reaction.