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M Salvatore

Publications and source records attributed to M Salvatore.

At least 55 records · Page 3Linked to original sources
PubMed2001

The diagnostic role of radionuclide imaging in evaluation of patients with nonhypersecreting adrenal masses.

UNLABELLED: The aim of this study was to evaluate the role of radionuclide imaging in the characterization of nonhypersecreting adrenal masses. METHODS: A total of 54 patients (19 men, 35 women; mean age, 50 +/- 16 y) with nonhypersecreting unilateral adrenal tumors that had been originally detected on CT or MRI underwent adrenal scintigraphy using different radiotracers. None of the patients showed specific symptoms of adrenal hypersecretion. Screening tests for excess cortical and medullary products showed normal adrenal hormone levels. Radionuclide studies (n = 73) included (131)I-norcholesterol (n = 24), (131)I-metaiodobenzylguanidine (MIBG) (n = 23), and (18)F-FDG PET (n = 26) scans. RESULTS: Histology after surgery (n = 31) or adrenal biopsy (n = 23) was obtained. Adrenal lesions were represented by 19 adenomas, 4 cysts, 1 myelolipoma, 1 neurinoma, 2 ganglioneuromas, 5 pheochromocytomas, 4 pseudotumors, 6 carcinomas, 2 sarcomas, and 10 metastases (size range, 1.5- to 5-cm diameter; mean, 4.9 +/- 3.1 cm). For norcholesterol imaging, diagnostic sensitivity, specificity, and accuracy were 100%, 71%, and 92%, respectively; the positive predictive value (PPV) of the norcholesterol scan to characterize an adrenal mass as an adenoma was 89%, whereas the corresponding negative predictive value (NPV) to rule out this type of tumor was 100%. For MIBG imaging, diagnostic sensitivity, specificity, and accuracy were 100%, 94%, and 96%, respectively; the PPV of the MIBG scan to characterize an adrenal mass as a medullary chromaffin tissue tumor was 83%, whereas the corresponding NPV to rule out this type of tumor was 100%. For FDG PET, diagnostic sensitivity, specificity, and accuracy were 100%, 100%, and 100%, respectively; the PPV of FDG PET to characterize an adrenal mass as a malignant tumor was 100%, whereas the corresponding NPV to rule it out was 100%. Furthermore, in 7 patients with malignant adrenal tumors, FDG whole-body scanning revealed extra-adrenal tumor sites (n = 29), allowing an accurate diagnosis of the disease's stage using a single-imaging technique. CONCLUSION: In patients with nonhypersecreting adrenal masses, radionuclide adrenal imaging, using specific radiopharmaceuticals such as norcholesterol, MIBG, and FDG, may provide significant functional information for tissue characterization. Norcholesterol and MIBG scans are able to detect benign tumors such as adenoma and pheochromocytoma, respectively. Conversely, FDG PET allows for recognition of malignant adrenal lesions. Therefore, adrenal scintigraphy is recommended for tumor diagnosis and, hence, for appropriate treatment planning, particularly when CT or MRI findings are inconclusive for lesion characterization.

19-Iodocholesterol↗
PubMed2001

[Morphological imaging of gastroenteropancreatic neuroendocrine tumours].

Biologically active neuroendocrine tumours produce early symptoms and are often difficult to diagnose owing to their small dimensions (<1 cm), whereas biologically inactive forms are often coarse and sometimes found by chance. As well as identifying the lesion, locoregional staging is also particularly important for therapeutic planning. Morphological imaging plays an important role in the identification of gastroenteropancreatic neuroendocrine tumours, providing an anatomic substrate for receptorial imaging which usually precede it in the diagnostic work-up, whereas it plays a primary role in the locoregional staging of these neoplasms for which surgery is the first and essential therapeutic approach. In the case of endocrine tumours of the pancreas alone, the most accurate method of diagnosis is currently echo-endoscopy using high-frequency probes. Two-phase spiral CT and dynamic MR have proved equally effective means of identifying endocrine tumours of the pancreas with slightly higher sensitivity for MR, both playing a role in the locoregional staging of biologically active and inactive tumours. Traditional radiology also plays a role in the identification of intestinal carcinoids.

Adenoma, Islet Cell↗
PubMed2001

[CT in findings intestinal carcinoids].

CT findings in intestinal carcinoids are various. While recognition of the primary tumour is a rare event, the contribution of CT in evaluating patients with suspected intestinal carcinoid is relevant, both for loco-regional staging and during long-term follow-up. Moreover, in the relatively frequent cases with an aspecific clinical onset, CT may be findings useful to direct diagnosis.

Carcinoid Tumor↗
PubMed2000

Influenza A and B viruses expressing altered NS1 proteins: A vaccine approach.

We propose a rational approach to the generation of live viral vaccines: alteration of virally encoded type I IFN antagonists to attenuate virulence while retaining immunogenicity. We have explored this concept by using the influenza virus. Previously we have shown that the NS1 protein of influenza A virus possesses anti-IFN activity. We now present evidence that influenza A and B viruses encoding altered viral NS1 proteins are highly attenuated in the mouse host, yet provide protection from challenge with wild-type viruses.

Animals↗
PubMed2000

Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma.

The regulatory mechanisms underlying the overexpression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in highly invasive breast carcinomas remain poorly understood. In this study, we have simultaneously determined the level of uPAR and the activity of the transcription factor Sp1 in 14 breast carcinomas and 5 benign lesions. We found that uPAR levels and Sp1-binding activity are coordinately elevated in malignant tumors (r, 0.94; P < 0.001). On the contrary, undetectable or only barely detectable levels of uPAR and Sp1 activity were found in benign breast lesions. Finally, the engagement of uPAR by catalytically inactive uPA in the MDA-MB-231 breast carcinoma cell line results in a rapid up-regulation of Sp1-binding activity followed by an increase of uPAR protein. These results, taken together, suggest the existence of a uPA-dependent positive regulatory loop that may progressively enhance malignant breast cell invasiveness.

Adult↗
PubMed2000

Automated segmentation and measurement of global white matter lesion volume in patients with multiple sclerosis.

A fully automated magnetic resonance (MR) segmentation method for identification and volume measurement of demyelinated white matter has been developed. Spin-echo MR brain scans were performed in 38 patients with multiple sclerosis (MS) and in 46 healthy subjects. Segmentation of normal tissues and white matter lesions (WML) was obtained, based on their relaxation rates and proton density maps. For WML identification, additional criteria included three-dimensional (3D) lesion shape and surrounding tissue composition. Segmented images were generated, and normal brain tissues and WML volumes were obtained. Sensitivity, specificity, and reproducibility of the method were calculated, using the WML identified by two neuroradiologists as the gold standard. The average volume of "abnormal" white matter in normal subjects (false positive) was 0.11 ml (range 0-0.59 ml). In MS patients the average WML volume was 31.0 ml (range 1.1-132.5 ml), with a sensitivity of 87.3%. In the reproducibility study, the mean SD of WML volumes was 2.9 ml. The procedure appears suitable for monitoring disease changes over time. J. Magn. Reson. Imaging 2000;12:799-807.

Adult↗
PubMed2000

Prediction of improvement in global left ventricular function in patients with chronic coronary artery disease and impaired left ventricular function: rest thallium-201 SPET versus low-dose dobutamine echocardiography.

Accurate assessment of myocardial viability permits selection of patients who would benefit from myocardial revascularization. Currently, rest-redistribution thallium-201 scintigraphy and low-dose dobutamine echocardiography are among the most used techniques for the identification of viable myocardium. Thirty-one consecutive patients (all men, mean age 60 +/- 8 years) with chronic coronary artery disease and reduced left ventricular ejection fraction (31% +/- 7%) were studied. Rest 201Tl single-photon emission tomography (SPET), low-dose dobutamine echocardiography and radionuclide angiography were performed before revascularization. Radionuclide angiography and echocardiography were repeated after revascularization. An a/dyskinetic segment was considered viable on 201Tl SPET when tracer uptake was >65%, while improvement on low-dose dobutamine echocardiography was considered a marker of viability. Increase in global ejection fraction was considered significant at > or = 5%. In identifying viable segments, rest 201Tl SPET showed higher sensitivity than low-dose dobutamine echocardiography (72% vs 53%, P<0.05), while specificity was not significantly different (86% vs 88%). In 17 patients, global ejection fraction increased > or = 5% (group 1) while in 14 it did not (group 2). A higher number of a/dyskinetic segments were viable on 201Tl SPET in group 1 than in group 2 (2.6 +/- 1.9 vs 0.6 +/- 1.2, P < 0.005), while no significant differences were observed on low-dose dobutamine echocardiography (1.7 +/- 1.6 vs 1.1 +/- 1.6). A significant correlation was found between the number of a/dyskinetic segments viable on 201Tl SPET and post-revascularization changes in ejection fraction (r = 0.52, P < 0.05), but such a correlation was not observed for low-dose dobutamine echocardiography. Using as the cut-off the presence of at least one viable a/dyskinetic segment, rest 201Tl SPET had a higher sensitivity (82% vs 53%, P = 0.07) and showed a trend towards higher accuracy and specificity (77% vs 58%, and 71% vs 64%, respectively) as compared with low-dose dobutamine echocardiography. In conclusion, these findings suggest that when severely reduced global function is present, rest 201Tl SPET evaluation of viability is more accurate than low-dose dobutamine echocardiography for the identification of patients who will benefit most from revascularization.

Adrenergic beta-Agonists↗
PubMed2000

Accuracy of enteroclysis in Crohn's disease of the small bowel: a retrospective study.

The aim of this study was to evaluate the accuracy of enteroclysis in the diagnosis of Crohn's disease of the small bowel in a group of consecutive patients. From January 1992 to December 1995, 165 patients with suspected Crohn's disease of the small bowel presented to our institution for enteroclysis. In 14 patients up to three enteroclysis exams were performed. Most patients (78%) underwent colonoscopy and retrograde ileoscopy. In the remaining patients clinical follow-up was used as gold standard. In 79 patients no radiographic abnormalities were found. Sixty-one patients (40 men and 21 women; mean age 34.2 years) had a radiological diagnosis of Crohn's disease. This involved the terminal ileum in 39 patients (64%) either alone (n = 25) or in association with the pelvic ileum (n = 14). In 12 of these patients retrograde ileoscopy was not feasible. Twenty-one patients underwent surgery. In 4 patients pathology revealed diseases other than Crohn's. These patients had all ileocecal diseases (tuberculosis = 2; non-Hodgkin's lymphoma = 1; adenocarcinoma = 1). One false-negative result was observed. Overall, enteroclysis showed a sensitivity of 98.2% and a positive predictive value of 93.4%. Enteroclysis is a sensitive technique in evaluating both the extent and the severity of small bowel involvement in Crohn's disease, although the overlap of radiographic findings may hamper its accuracy when the disease is confined to the ileocecal area.

Adolescent↗
PubMed2000

Prolactinomas in adolescents: persistent bone loss after 2 years of prolactin normalization.

OBJECTIVE: To evaluate the effect of hyperprolactinaemia and its treatment with dopamine-agonists on bone mass and turnover in adolescent patients compared to adults. PATIENTS: Forty patients with hyperprolactinaemia (20 with disease onset during adolescence and 20 during adulthood) and 40 healthy control subjects. DESIGN: Open transverse (in patients and controls) and open longitudinal (in the patients). MEASUREMENTS: Bone mineral density (BMD) at lumbar spine and femoral neck, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type-1 collagen (Ntx) levels were evaluated in patients and controls. In the 40 patients, bone mass and turnover were re-evaluated after 12 and 24 months of treatment with bromocriptine (BRC, dose 2.5-10 mg daily), quinagolide (CV, dose 0.075-0.3 mg daily) or cabergoline (CAB, dose 0.5-1.5 mg weekly). RESULTS: Transverse study: BMD values were significantly lower in hyperprolactinaemic patients than in controls, both at lumbar spine (0.81 +/- 0.01 vs. 1.010 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.71 +/- 0.01 vs. 0.873 +/- 0.03 g/cm2; P < 0.001). Thirty-two patients (80%) had osteoporosis and/or osteopenia at one or both skeletal sites. A significant inverse correlation was found between T score values measured at lumbar spine and femoral neck and the estimated disease duration. BMD was significantly lower in young than adult patients both at lumbar spine (T score, -2.4 +/- 0.1 vs. -1.4 +/- 0.3, P < 0.01) and at femoral neck (T score, -2.1 +/- 0.05 vs. -1.5 +/- 0.2, P < 0.05). Similarly, serum OC levels were significantly lower (2.0 +/- 0.11 vs. 9.1 +/- 2.4 micrograms/l, P < 0. 01) while Ntx levels were significantly higher in patients than in controls (129.2 +/- 1.7 vs. 80.7 +/- 2.9 nmol Bone collagen equivalent (BCE)/mmol creatinine; P < 0.001). A significant inverse correlation was found between prolactin (PRL) levels and OC levels, lumbar and femoral T score values, as well as between disease duration and OC levels, lumbar and femoral T score values. A significant direct correlation was also found between Ntx levels and PRL levels and disease duration. Longitudinal study: Normalization of serum PRL levels was obtained in all patients after 6-12 months of treatment. A significant increase of serum OC levels together with a significant decrease of Ntx levels was observed after 12 and 24 months of treatment (P < 0.01). Urinary and serum calcium, phosphorus, creatinine, and serum alkaline phosphatase and parathyroid hormone levels did not change during the study period in all patients. After 12 months of therapy OC and Ntx concentrations were restored to normal. A slight but not significant increase of BMD values was recorded after 12 and 24 months of treatment. After 12 months of treatment the percent increment of BMD values in the whole group of patients was 1.13 +/- 0.6% at lumbar spine and 1.2 +/- 0.4% at femoral neck level, whereas after 24 months, it was 2.8 +/- 0.7% at lumbar spine and 3.5 +/- 0.7% at femoral neck level. After 12 months of treatment, the percent increment of BMD values was 0.7 +/- 0.2% and 1.6 +/- 1.1% at lumbar spine and 0.9 +/- 0.5% and 1.6 +/- 0.5% at femoral neck level in the young and adult patients, respectively, whereas after 24 months, it was 2.1 +/- 0.8% and 3.4 +/- 1.3% at lumbar spine and 2.6 +/- 0.8% and 4.4 +/- 1.0% at femoral neck level in the young and adult patients, respectively. CONCLUSIONS: Adolescents with prolactinoma have osteopenia or osteoporosis, a finding that strengthens the need for a prompt diagnosis. Since normalization of PRL concentrations by dopamine agonist therapy is unable to restore the bone mass, other therapeutic approaches should be considered in order to prevent further long-term problems.

Adolescent↗
PubMed2000

Does the age of onset of growth hormone deficiency affect cardiac performance? A radionuclide angiography study.

BACKGROUND: GH and IGF-I seem to play a relevant role in cardiac development and performance. Long-standing GH deficiency (GHD) causes several abnormalities in cardiac structure and performance which ultimately determine an increased cardiovascular morbidity and mortality. OBJECTIVE: To investigate whether the age of onset of GHD plays a role in determining the negative effects on the heart. DESIGN: Open cross-sectional PATIENTS: 55 patients with adulthood-onset GHD and 36 healthy sex- and age-matched controls. Patients and controls were divided into 2 groups in line with age: 32 patients and 16 controls, were aged </= 35 years (young); while 23 patients and 20 controls were aged between 36 and 60 years (middle-aged). The estimated disease duration was similar in young (6.7 +/- 0.5 years) and middle-aged patients (8.1 +/- 1.2 years, P = 0.2). STUDY PROTOCOL: All subjects underwent ECG, blood pressure and heart rate measurement, plasma IGF-I level assay, and equilibrium radionuclide angiography. RESULTS: Plasma IGF-I levels were significantly lower in patients than in controls (P < 0.0001). When considered as a whole, no difference in systolic (SBP) and diastolic blood pressure (DBP) at peak exercise was found between patients and controls. However, a significant decrease of SBP at rest was found in young patients as compared to age-matched controls (P = 0.009), while a significant increase of DBP at rest was found in middle-aged patients as compared to age-matched controls (P = 0.03). In addition, in young patients, both resting (P = 0.02) and exercise heart rate (P = 0.01) were significantly lower than in controls. Diastolic filling when measured as end-diastolic volume (EVD/sec), was significantly reduced in middle-aged patients (P = 0.04). An impaired peak filling rate (PFR) (< 2.5 EDV/sec) was found in 30 patients (54.5%) and 10 controls (27.7%, chi2 = 5.3, P = 0.02): 17 young (53.1%) and 13 middle-aged patients (56.5%). A significant decrease of left ventricular (LV) ejection fraction (EF) at peak exercise was found in both patients groups (P < 0.0001) while LVEF at rest was lower only in middle-aged patients (P = 0.004). An impaired LVEF at rest (< 50%) was found in 13 patients (23.6%) and in none of controls (chi2 = 8.1, P = 0.004). The exercise induced changes in LVEF (DeltaEF) were significantly lower in both patients groups than in age-matched controls (P < 0.0001). Impaired LVEF response to exercise (< 5% increase vs. basal value) was found in 36 patients (65.4%) and in 5 controls (13.8%, chi2 = 21.3, P < 0.000): 21 young (65.6%) and 15 middle-aged patients (65.2%). The peak ejection rate (PER) was also significantly lower in young GHD patients than in controls (P < 0.001). Exercise duration and capacity were significantly reduced in both groups of GHD patients. In the patient group, age was significantly correlated with SBP and DBP levels both at rest (r = 0.612, and r = 0.516, respectively, P < 0.001) and at peak exercise (r = 0.4, P < 0.005 and r = 0.34, P < 0. 01, respectively), with exercise duration (r = - 0.383, P < 0.005) and capacity (r = - 0.355, P = 0.005). Disease duration was also correlated with IGF-I levels (r = - 0.319, P < 0.01), SBP levels at peak exercise (r = 0.352, P = 0.005), and LVEF at rest (r = - 0.254, P < 0.05). Finally, a significant correlation was found between IGF-I levels and DBP at peak exercise (r = 0.3, P < 0.05) and between GH peak at ARG + GHRH test and LVEF at rest (r = 0.232, P < 0.05). Exercise-induced changes in LVEF were significantly correlated with SBP levels at peak exercise (r = - 0.401, P < 0.005), PFR expressed as EDV/sec (r = - 0.306, P < 0.05) and SV/sec (r = - 0.292, P < 0.05). At multiple regression analysis in the patient group, age was the strongest predictor of SBP both at rest (t = 4.17, P < 0.0001) and at peak exercise (t = 2.32, P = 0.025), and capacity (t = - 2.84, P = 0.007). IGF-I levels were the strongest predictor of DBP at peak exercise (t = 2.2, P = 0.

Adult↗
PubMed2000

Scintigraphic detection of multidrug resistance in cancer.

One of the most extensively studied mechanisms of drug resistance involves the drug efflux pump P-glycoprotein (Pgp). The availability of radiolabeled substrates of Pgp such as 99mTc-MIBI and analogous 99mTc-labeled agents allows the clinical assessment of Pgp function in cancer patients. The consistency of the results from different institutions and trials strongly support the clinical application of this imaging technique for individual tailoring of chemotherapeutic regimens and for designing clinical trials with Pgp modulators.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Cardiac effect of thyrotoxicosis in acromegaly.

Cardiac structure and function are affected both by acromegaly and hyperthyroidism. Whereas the former is mainly characterized by ventricular hypertrophy as well as diastolic and systolic impairment, the latter frequently leads to increased heart rate and enhancement of contractility and cardiac output. To further investigate this issue, we designed this two-arm study. In the first cross-sectional study, we compared echocardiography and radionuclide angiography results obtained in eight hyperthyroid acromegalic patients, eight hyperthyroid nonacromegalic patients, and eight healthy subjects. All acromegalic patients were receiving treatment for acromegaly at the onset of hyperthyroidism. In the second longitudinal study, performed in the group of acromegalic patients, we compared the cardiovascular results obtained during hyperthyroidism with the retrospective data obtained at the initial diagnosis of acromegaly and after 1-yr treatment for this disease and those prospective data obtained during the remission of hyperthyroidism. In the cross-sectional study, hyperthyroid acromegalic patients showed an increase in the left ventricular (LV) mass index (LVMi) compared to healthy and hyperthyroid controls (P < 0.05), with evidence of LVMi hypertrophy in five of them (62.5%). A significant correlation was found between LVMi and GH levels (r = 0.785; P < 0.05). The LV ejection fraction (LVEF) at rest was higher in the control hyperthyroid population than in healthy controls (P < 0.05), whereas the LVEF response to exercise was reduced in acromegalic patients (P < 0.05 vs. healthy controls). In acromegalics, the exercise-induced change in LVEF was significantly reduced compared to that in healthy controls (P < 0.001), but not to that in hyperthyroid controls (P < 0.07), being abnormal (<5% increase vs. baseline values) in six patients. Four of these six patients (66%) had elevated GH and insulin-like growth factor I levels during the treatment of acromegaly. An inverse correlation between GH and LVEF at rest (r = -0.896;P < 0.05) and at peak exercise (r = -0.950; P < 0.001) was recorded. The peak filling rate was reduced in hyperthyroid acromegalic patients compared to those in both control populations (P < 0.05). In the longitudinal study, acromegalic patients showed an increased LVMi during hyperthyroidism compared to that observed after successful treatment of acromegaly (P < 0.05); resting LVEF was increased compared to both basal (P < 0.001) and posttreatment values (P < 0.05). However, the exercise-induced change in LVEF was reduced (P < 0.05 vs. previous follow-up values). Remission of hyperthyroidism led to significant reduction of LVMi (P < 0.05) and resting LVEF (P < 0.05) and an increase in exercise-induced LVEF (P < 0.05). In light of these findings, hyperthyroidism produces a detrimental effect on the cardiovascular system of acromegalic patients, particularly in those with uncontrolled disease. Thus, control of GH and insulin-like growth factor I should be a major objective, as cardiovascular risk persists in patients with ineffective hormonal suppression, and constant endocrine and cardiovascular surveillance remain crucial steps in patient follow-up.

Acromegaly↗
PubMed2000

Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly.

Cardiovascular disease is the most severe complication of acromegaly accounting for the increased mortality of these patients. Recently, the slow-release form of octreotide (OCT; Sandostatin LAR, OCT-LAR), for im injection every 28 days, was reported to induce suppression of GH levels below 7.5 mU/L (2.5 microg/L) in 39-75% of patients, and normalization of insulin-like growth factor (IGF)-I levels for age in 64-88% of patients, with an excellent patients' compliance. The aim of the present study was to investigate the early effect of OCT-LAR treatment on the left ventricular (LV) structure and performance in 15 somatostatin analog-naive patients with acromegaly (GH, 94.8 +/- 24.9 mU/L; IGF-I, 757.9 +/- 66.6 microg/L), focusing on the early effect of GH and IGF-I suppression on the heart. Cardiac structure was investigated by echocardiography, whereas LV performance was investigated by gated-blood-pool scintigraphy, before and after 3 and 6 months of treatment with OCT-LAR. OCT-LAR was initially administered im, at a dose of 20 mg every 28 days, for 3 months. In six patients, the dose was then increased to 30 mg every 28 days to achieve disease control, which was considered when fasting and/or glucose-suppressed GH values were below 7.5 and 3.0 mU/L, respectively, together with IGF-I values within the normal range for age. The treatment with OCT-LAR for 6 months induced a significant decrease of GH (to 12.9 +/- 3.0 mU/L) and IGF-I levels (to 340.3 +/- 40.2 microg/L) in all 15 patients. After 6 months of treatment, the percent IGF-I suppression was 52.8 +/- 4.4%, and serum GH/IGF-I levels were normalized in 9 patients. A significant decrease of LV mass index (LVMi), interventricular septum thickness, and LV posterior wall thickness was observed in all 15 patients after 3 and 6 months of OCT-LAR treatment: LVMi was decreased by 19.1 +/- 2.0% without any difference in patients with (19.9 +/- 2.7%) or without disease control (17.8 +/- 3.3%). Among the 11 patients with LV hypertrophy, 6 normalized their LVMi after treatment. At study entry, an inadequate LV ejection fraction (LVEF) at rest (<50%) was found in 5 patients (33.3%), whereas an impaired response of LVEF at peak exercise (<5% increase of basal value) was found in 9 patients (60%). A significant increase in LVEF, both at rest (from 51.6 +/- 2.6 to 58.1 +/- 1.7%, P < 0.01) and at peak exercise (from 51.6 +/- 2.3 to 60.2 +/- 2.4%, P < 0.001) was found in patients with (as compared with those without) disease control (from 55.2 +/- 3.8 to 58.0 +/- 4% and from 61.8 +/- 4.6 to 61.8 +/- 3.4%, respectively). Among the 5 patients with inadequate LVEF at rest, all but 1 regained a normal LVEF after 6 months of treatment; whereas, among the 9 patients with an impaired response of the LVEF at peak exercise, 3 patients normalized, 4 improved, and 2 impaired their responses after treatment. The percent of IGF-I suppression was significantly correlated with the percent increase of resting LVEF (r = 0.644, P < 0.01). Exercise duration (from 6.0 +/- 0.7 to 7.3 +/- 0.7 min) and capacity (from 69.0 +/- 8.2 to 80 +/- 7.8 watts) were increased in the 15 patients considered as a whole, but the improvement in the exercise response was significant only in patients with disease control (P < 0.01 and P < 0.05, respectively) who also had an increase in the peak ejection rate (P = 0.03). No change in hemodynamic parameters, either at rest or at peak exercise, was found after treatment with OCT-LAR in the 15 patients. In conclusion, the results of the present study demonstrate that OCT-LAR im injections every 28 days induces a sustained suppression of GH levels and IGF-I levels in all acromegalic patients, allowing achievement of disease control in 60% of patients after 6 months of treatment. The sustained suppression of IGF-I levels was followed by a significant reduction of LVMi in all patients already after 3 months of treatment, with recovery of LV hypertrophy in 6 of 11 patients. (ABSTRACT TRUN

Acromegaly↗
PubMed2000

[Relationship between exercise capacity and left ventricular function at rest in patients with heart insufficiency: radionuclide continuous monitoring of left ventricular function].

PURPOSE: To evaluate the relationship of systolic and diastolic function at rest to exercise capacity. MATERIAL AND METHODS: Seventeen patients with ischemic heart failure were included in the study. Ambulatory left ventricular monitoring at rest and during upright exercise with combined analysis of pulmonary gas exchange was performed. Ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, cardiac output, and peak filling rate were measured. RESULTS: Significant positive correlations were found between rest ejection fraction and peak oxygen consumption (r = .60, p < .01), peak cardiac output (r = .77, p < .0001), peak stroke volume (r = .67, p < .005), and peak ejection fraction (r = .69, p < .005). On the other hand, peak filling rate at rest showed a significant inverse correlation with peak end-diastolic (r = -.48, p < .05) and end-systolic (r = -.66, p < .005) volumes. The patients were then subgrouped into two groups according to their rest ejection fraction (lower or higher than 40%). In the group with ejection fraction less than 40% a significant correlation was observed between rest ejection fraction and both peak stroke volume (r = .66, p < .05) and peak ejection fraction (r = .69, p < .05). In the same group of patients an inverse correlation was found between peak filling rate and both end-diastolic (r = -0.65, p < .05) and end-systolic (r = -.82, p < .005) volumes. CONCLUSIONS: The results of the present study suggest that exercise capacity is related to left ventricular function at rest and that rest diastolic function might be a determinant of left ventricular function during exercise in patients with heart failure.

Exercise Tolerance↗
PubMed1999

Urokinase receptor interacts with alpha(v)beta5 vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer.

Perturbation of adhesive interactions at cell-substratum and cell-cell contact sites is a critical event in the multistep process of cancer invasion. Recent studies indicate that the urokinase receptor (uPAR) is associated in large molecular complexes with other molecules, such as integrins. To test the possibility that uPAR may physically and functionally interact with vitronectin (Vn) receptors, we determined the expression level of uPAR, alpha(v)beta3, and alpha(v)beta5 Vn receptors in 10 human breast carcinomas. Here, we show the ability of uPAR to physically associate with alpha(v)beta5 in the breast carcinomas examined. The functional effects of this interaction were studied using HT1080 human fibrosarcoma and MCF-7 human breast carcinoma cell lines, both exhibiting a urokinase-dependent physical association between uPAR and alpha(v)beta5. Both cell lines respond to urokinase or to its noncatalytic amino-terminal fragment by exhibiting remarkable cytoskeletal rearrangements that are mediated by alpha(v)beta5 and require protein kinase C activity. On the contrary, binding of Vn to alpha(v)beta5 results in the protein kinase C-independent formation of F-actin containing microspike-type structures. Furthermore, alpha(v)beta5 is required for urokinase-directed, receptor-dependent MCF-7 and HT1080 cell migration. These data show that uPAR association with alpha(v)beta5 leads to a functional interaction of these receptors and suggest that uPAR directs cytoskeletal rearrangements and cell migration by altering alpha(v)beta5 signaling specificity.

Adult↗
PubMed1999

Influence of left ventricular cavity size on clinical presentation in hypertrophic cardiomyopathy.

The aim of this study was to assess whether left ventricular (LV) cavity size relates to functional impairment and syncope in patients with hypertrophic cardiomyopathy (HC). LV diastolic dysfunction influences functional limitation in HC. A reduced LV end-diastolic dimension may underlie impaired diastolic properties and be implicated in hemodynamic syncope. Eighty-two consecutive patients with HC (off drugs, in sinus rhythm) underwent echocardiography to measure LV end-diastolic dimension in the short-axis view (indexed to the body surface area) and radionuclide angiography (n = 50) to calculate peak filling rate (normalized to stroke counts/s). Patients in New York Heart Association functional classes II to IV had smaller LV end-diastolic dimension (23.2 +/- 2.6 vs 25.5 +/- 2.5 mm/M2, p = 0.0001) and lower peak filling rate (4.3 +/- 1.4 vs 5.1 +/- 1.3 stroke counts/s, p = 0.036) than those in New York Heart Association class I. LV end-diastolic diameter was correlated to peak filling rate (r = 0.37; p = 0.008). The most potent predictors of functional limitation were LV end-diastolic dimension (relative risk [RR] 0.63, confidence interval [CI] 0.45 to 0.88; p = 0.008), age (RR 1.09, CI 1.03 to 1.17; p = 0.003), and LV thickness score (RR 1.08, CI 1.02 to 1.13; p = 0.003). LV cavity size was smaller in patients with functional limitation irrespective of obstruction and hypertrophy. Patients with differed from those without a history of syncope for a smaller LV end-diastolic dimension (23.2 +/- 2.5 vs 25.0 +/- 2.7 mm/M2, p = 0.008), which was the only independent predictor of syncope (RR 0.77, CI 0.63 to 0.95; p = 0.013). Thus, a small LV cavity size is associated with functional limitation and history of syncope in HC.

Adolescent↗
PubMed1999

The pituitary uptake of (111)In-DTPA-D-Phe1-octreotide in the normal pituitary and in pituitary adenomas.

The aim of this study was to compare the pituitary (111)In-DTPA-D-Phe1-octreotide uptake measured in 49 patients subjected to the scintigraphy for SS-R expressing tumors not located in the sellar region with that measured in 38 patients with pituitary adenomas. The 87 subjects enrolled in this study were divided into two groups: the first included SSR-expressing tumors (SS-ET), 10 thymomas, 13 differentiated thyroid carcinomas, 4 carcinoids, 5 neuroendocrine tumors, 5 insulinomas, 6 melanomas, 2 renal carcinomas, 2 pheocromocytomas, and 2 parathyroid tumors, while the second included pituitary adenomas, 25 GH-secreting, 4 GH/PRL-mixed and 9 clinically nonfunctioning adenomas (NFA). Planar and single-photon-emission tomography images of the head were obtained 2-4 and 24 hours after the injection of 77-103 MBq of (111)In-DTPA-D-Phe1-octreotide and pituitary uptake was measured by the region of interest method. A 4 point score was used to grade the pituitary-to-blood (T-to-B) ratios: 0=negative; 1 =faint (T-to-B=<1.5); 2=moderate (T-to-B=1.6-3.5); 3=intense (T-to-B=>3.5). In patients with pituitary adenomas, the percent suppression of GH and alpha-subunit levels after 6-12 months of octreotide treatment (0.3-0.6 mg/day) was correlated to T-to-B ratios. After 2-4 hr from injection, pituitary (111)In-DTPA-D-Phe1-octreotide uptake was moderate/intense in 2 out of 49 SS-ET (4%), 18 out of 29 acromegalics (62%) and 6 NFA (66.6%), while a faint uptake was detected in 4 SS-ET (8%), 8 GH-secreting adenomas (27.5%) and 3 NFA (33.3%). Negative scan was detected in the remaining 43 SS-ET (87.7%) and 3 GH-secreting microadenomas (10.3%). 24 hr after injection, pituitary (111)In-DTPA-D-Phe1-octreotide uptake was moderate/intense in SS-ET (10.2%), 21 GH-secreting adenomas (72.4%), and 9 NFA (100%) while a faint uptake was detectable in 15 SS-ET (30.6%), and 6 GH-secreting adenomas (20.7%). No uptake was visualized in 29 SS-ET, and 2 GH-secreting adenomas. By MRI a pituitary tumor was shown in the 2 SS-ET with early moderate tracer uptake. Normalization of circulating GH/IGF-I levels and suppression of alpha-subunit levels was achieved in 16 of 18 acromegalics (88.9%) and 5 of 6 NFA-bearing patients, respectively, with scan scored 2-3 at early images. Eleven acromegalics (37.9%) and 2 NFA (22.2%) displayed significant tumor shrinkage (> or =30% of baseline size) during long-term octreotide therapy. Both in GH-secreting and in NFA, a significant correlation was found between percent GH or alpha-subunit suppression after 6-12 months of octreotide therapy and T-to-B ratios both in early (r=0.626; p<0.0001 and r=0.738, p=0.003, respectively) and late images (r=0.569; p=0.002 and r=0.8, p=0.01, respectively). In conclusion, the (111)In-DTPA-D-Phe1-octreotide uptake in pituitary adenomas was significantly correlated to octreotide treatment. However, since pituitary (111)In-DTPA-D-Phe1-octreotide uptake was clearly detectable in 40% of patients with SS-ET not located in the pituitary region at 24 hr post-injection, (111)In-DTPA-D-Phe1-octreotide scintigraphy with late pituitary images can not be considered an useful method to predict the chronic responsiveness to octreotide in individual patients. Caution should also be taken in evaluating the results of the scintigraphy with early images in patients with scant uptake before excluding them from treatment.

Adenoma↗