Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI.

PURPOSE: The purpose of this study was to create an algorithm that combines multiple machine-learning techniques to predict the expanded disability status scale (EDSS) score of patients with multiple sclerosis at two years solely based on age, sex and fluid attenuated inversion recovery (FLAIR) MRI data. MATERIALS AND METHODS: Our algorithm combined several complementary predictors: a pure deep learning predictor based on a convolutional neural network (CNN) that learns from the images, as well as classical machine-learning predictors based on random forest regressors and manifold learning trained using the location of lesion load with respect to white matter tracts. The aggregation of the predictors was done through a weighted average taking into account prediction errors for different EDSS ranges. The training dataset consisted of 971 multiple sclerosis patients from the "Observatoire français de la sclérose en plaques" (OFSEP) cohort with initial FLAIR MRI and corresponding EDSS score at two years. A test dataset (475 subjects) was provided without an EDSS score. Ten percent of the training dataset was used for validation. RESULTS: Our algorithm predicted EDSS score in patients with multiple sclerosis and achieved a MSE=2.2 with the validation dataset and a MSE=3 (mean EDSS error=1.7) with the test dataset. CONCLUSION: Our method predicts two-year clinical disability in patients with multiple sclerosis with a mean EDSS score error of 1.7, using FLAIR sequence and basic patient demographics. This supports the use of our model to predict EDSS score progression. These promising results should be further validated on an external validation cohort.

Role of fungal trehalose and bacterial thiamine in the improved survival and growth of the ectomycorrhizal fungus Laccaria bicolor S238N and the helper bacterium Pseudomonas fluorescens BBc6R8.

The mycorrhiza helper bacterial strain Pseudomonas fluorescens BBc6R8 enhances the establishment of Laccaria bicolor S238N ectomycorrhizae by improving the pre-symbiotic growth and survival of the fungus. Nothing is known about the effect of the ectomycorrhizal fungus on the helper bacteria or the molecules that are involved in the interaction. In this study, we have monitored the population density of the helper strain P. fluorescens BBc6R8 in soils inoculated with L. bicolor and in control soils and found that the ectomycorhizal fungus improves the survival of the helper bacteria. We investigated the identity of the fungal and bacterial metabolites involved in this reciprocal growth-promoting effect using a combination of growth measurements, chemoattractant assays, HPLC and in silico genome analyses. We showed that trehalose, a disaccharide that accumulates to high levels in the fungal hyphae, chemoattracted and promoted the growth of the helper bacteria. Meanwhile, P. fluorescens BBc6R8 produced thiamine at concentrations that enhanced the fungal growth in vitro. Altogether our data indicate that the interaction between the two microorganisms is beneficial for both species and relies, at least in part, on trophic mutualism.

Metabotropic P2Y receptors inhibit P2X3 receptor-channels via G protein-dependent facilitation of their desensitization.

BACKGROUND AND PURPOSE: The aim of the present study was to investigate whether the endogenous metabotropic P2Y receptors modulate ionotropic P2X(3) receptor-channels. EXPERIMENTAL APPROACH: Whole-cell patch-clamp experiments were carried out on HEK293 cells permanently transfected with human P2X(3) receptors (HEK293-hP2X(3) cells) and rat dorsal root ganglion (DRG) neurons. KEY RESULTS: In both cell types, the P2Y(1,12,13) receptor agonist, ADP-beta-S, inhibited P2X(3) currents evoked by the selective agonist, alpha,beta-methylene ATP (alpha,beta-meATP). This inhibition could be markedly counteracted by replacing in the pipette solution the usual GTP with GDP-beta-S, a procedure known to block all G protein heterotrimers. P2X(3) currents evoked by ATP, activating both P2Y and P2X receptors, caused a smaller peak amplitude and desensitized faster than those currents evoked by the selective P2X(3) receptor agonist alpha,beta-meATP. In the presence of intracellular GDP-beta-S, ATP- and alpha,beta-meATP-induced currents were identical. Recovery from P2X(3) receptor desensitization induced by repetitive ATP application was slower than the recovery from alpha,beta-meATP-induced desensitization. When G proteins were blocked by intracellular GDP-beta-S, the recovery from the ATP- and alpha,beta-meATP-induced desensitization were of comparable speed. CONCLUSIONS AND IMPLICATIONS: Our results suggest that the activation of P2Y receptors G protein-dependently facilitates the desensitization of P2X(3) receptors and suppresses the recovery from the desensitized state. Hence, the concomitant stimulation of P2X(3) and P2Y receptors of DRG neurons by ATP may result both in an algesic effect and a partly counterbalancing analgesic activity.

A multi-approach study of the interaction of the Cu(II) and Ni(II) ions with alanylglycylhistamine, a mimicking pseudopeptide of the serum albumine N-terminal residue.

The protonation equilibria of alanylglycylhistamine (Ala-Gly-Ha) and the complexation of this ligand with Cu(II) and Ni(II) have been studied by pH-potentiometry, 1H and 14N NMR spectroscopy, electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), UV-Vis spectrophotometry and electron paramagnetic resonance (EPR). From pH approximately 2-12, the following complexes: MLH, MLH(-1), MLH(-2) and MLH(-3) are successively formed in aqueous solutions, the ligand under its neutral form being noted L. At physiological pH, the MLH(-2) complex is predominant. The coordination in this complex is assumed by one amino, two deprotonated peptide and one imidazole nitrogen atoms. The ESI-MS study confirmed the formation of the MLH(-1), MLH(-2) and MLH(-3) complexes. The structure of MLH(-2) was determined by single crystal X-ray analysis. CD and UV-Vis techniques allowed us to propose that the imidazole-N3 nitrogen acts as the anchor group for the coordination to the metal(II) ions rather than the amino group. At high pH values, the further deprotonation of the N-H imidazole group, leading to the formation of MLH(-3), occurs, as revealed by 1H NMR spectroscopy.

Somatic and axonal effects of ATP via P2X2 but not P2X7 receptors in rat thoracolumbar sympathetic neurones.

Excitatory ATP responses in rat cultured thoracolumbar sympathetic neurones are mediated by somatic P2X(2) receptors. The present study investigated a possible role of axonal P2X(2) as well as P2X(7) receptors on the same preparation. Confocal laser scanning microscopy demonstrated P2X(2) and P2X(7) immunoreactivity along the axons as well as P2X(7) immunoreactivity surrounding the cell nuclei. P2X(7) mRNA expression was detected in individual neurones using a single-cell RT-PCR approach. Adenosine triphosphate (ATP) caused a significant increase in axonal Ca(2+) concentration which was dependent on external Ca(2+) but insensitive to depletion of the cellular Ca(2+) pools by cyclopiazonic acid. Pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS; 30 micro m) virtually abolished the ATP response, whereas brilliant blue G (0.1 micro m), a selective P2X(7) receptor antagonist, had no effect. Dibenzoyl-ATP (BzATP; 100 micro m) induced a much smaller increase in axonal [Ca(2+)] concentration than ATP at equimolar concentrations. The response to BzATP was distinctly reduced by PPADS but not by brilliant blue G. The overall pharmacological profile of the axonal P2X receptors resembled closely that of the somatic P2X(2) receptors. In conclusion, the present data suggest the occurrence of axonal excitatory P2X(2) receptors in thoracolumbar sympathetic neurones. However, the functional significance of axonal and (peri)-nuclear P2X(7) receptors has still to be proven.

Interactions of aluminium(III) with glycerolphosphates and glycerophosphorylcholine.

The complexation of aluminium(III) with glycerol-1-phosphate (G1P) and glycerol-2-phosphate (G2P) in aqueous solutions has been studied as a function of pH, by pH-potentiometry, 31P NMR spectroscopy and ESI mass spectrometry. Various mononuclear complexes (MLH(2)(3+), MLH(2+), ML(+), ML(2)H, ML(2)(-)) and polynuclear species (M(3)L(3)H(-1)(2+), M(3)L(2)H(-n)((n-5)-) with n=5, 6, 7, M(2)L(2)H(-1)(+) ) are formed in the system where the full protonated ligands are noted LH(2). NMR experiments clearly show that G1P and G2P already interact with Al(III) at pH 1. The potentiometric results are confirmed by ESI measurements and 31P NMR studies. No metal ion-induced deprotonation and coordination of the alcoholic-OH functions seem to occur during the complexation. The situation is very different for the glycerophosphorylcholine ligand (GPC identical with LH). Only the complex ML(3+) is formed in aqueous solution with a relatively low formation constant (K=5 at 37 degrees C). This species is clearly identified in 31P and 27Al NMR spectra. The complexation study as a function of the temperature allowed us to determine the thermodynamic parameters of the complex formation. The complexation is not governed by the reaction enthalpy that is found to be positive but by the entropy that is largely positive.

Gallbladder injury in blunt abdominal trauma.

A 36-year-old woman was admitted to the hospital for an abdominal blunt trauma. At ultrasound (US) and computed tomography (CT), a gallbladder lesion was suspected, along with a tear of the liver. The patient was submitted to a diagnostic laparoscopy. The gallbladder was partially avulsed and bile was infiltrated in the hepatoduodenal ligament. Intraoperative cholangiography and Kocher's maneuver excluded other lesions. Laparoscopic cholecystectomy was performed, but due to severe hemorrhage from the liver tear, the operation was converted to an open procedure. Gallbladder lesions in blunt trauma are rare occurrences, but they are often associated with other organ injuries. US and CT scan are valuable for their diagnosis, but if a lesion is suspected, diagnostic laparoscopy is advisable in stable patients. It should be accompanied by a cystic duct cholangiography and a Kocher's maneuver to evaluate the integrity of the biliary tree. Laparoscopic cholecystectomy is generally feasible. Associated lesions require laparotomy when they are not amenable to laparoscopic treatment.

[Vascular homografts: clinical results]. / Omoinnesti vascolari: risultati clinici.

The authors review the results of clinical experiences regarding arterial and venous homografts. For the treatment of mycotic aneurysms and infected prostheses, in situ repair with vascular homografts represents a valuable alternative to conventional surgical treatments. In fact the large caliber arterial homografts allow safe in situ reconstruction, decrease early and midterm mortality and reinfection rates; the best results are achieved in case of infected grafts, whereas the prognosis of vasculo-enteric fistula remains very poor. The small caliber arterial homografts also have demonstrated satisfactory results in term of patency, although further experiences with longer follow-up are required. Vein homograft constitutes an alternative by-pass conduit for limb revascularisation in patients who lack adequate autogenous vein: although limb salvage rate is satisfactory, long term patency rate is poor when compared with autogenous veins. Improvement of preservation methodics, pharmacological control of rejection and tissue engineering represent the future perspectives in this field.

[Inflammatory abdominal aortic aneurysms]. / Aneurismi infiammatori dell'aorta addominale.

The authors present a review of the literature on inflammatory abdominal aortic aneurysms. These aneurysms represent from 3 to 10% of all abdominal aortic aneurysms. Progress has occurred in the technical approach to these aneurysms, and operative morbidity and mortality have been remarkably reduced. However, the pathogenesis remains poorly understood. Early reports have considered the inflammatory aneurysm as a distinct clinical and pathological entity, whereas recent evidences suggest a common etiopathogenetic mechanism for both atherosclerotic and inflammatory aneurysms. Finally, genetic and environmental factors, such as tobacco use, may predispose certain persons to the development of non-inflammatory aneurysms and others to a wide spectrum of inflammatory reactions until inflammatory aneurysms development. The most common clinical features of these aneurysms are represented by symptoms, such as abdominal or back pain, obstructive uropathy and by an elevated erythrocyte sedimentation rate. Computed tomography (CT) allows a specific diagnosis by the typical image of soft tissue surrounding the aortic wall enhancing with contrast administration. Ultrasonography is less sensitive whereas nuclear magnetic resonance (RNM) is a promising technique. Excretory urography may suggest the diagnosis by demonstration of ureter entrapment. Surgical therapy, by a technique of limited dissection represents the definitive treatment. Evolution of fibrosis after surgery is still debated because some studies have reported complete regression of inflammation and other partial regression or persistence of fibrotic process. At present, endovascular treatment of these aneurysms is occasionally reported, although preliminary results appear satisfactory.

[Prevalence of atherosclerosis in renal transplant recipients]. / Prevalenza dell'aterosclerosi nei pazienti portatori di trapianto renale.

BACKGROUND: Cardiovascular diseases are a major cause of morbidity and mortality after kidney transplantation. Renal transplant recipients have in fact accelerated atherosclerosis because of prolonged hemodialysis, arterial hypertension, dyslipidemia and other vascular risk factors. Studies concerning carotid and lower limb atherosclerotic changes in renal transplanted patients are at present scant. METHODS: In the present study the prevalence of carotid and iliac-femoro-popliteal atherosclerosis was evaluated by color flow Doppler in 99 patients 64 +/- 41 DS months after renal transplantation. Statistical analysis was used to correlate the presence and grade of atherosclerotic lesions with vascular risk factors and other clinical-laboratoristic parameters of the patients. RESULTS: The overall incidence of atherosclerotic lesions in the population studied was 54.5%; 46.5% of patients presented atherosclerotic plaques at carotid district, 43.4% at lower limb arteries and 35.4% at both districts. Two of these patients were symptomatic; one patient affected by claudicatio intermittens was submitted to conservative therapy, whereas another patient with abdominal aortic aneurysm underwent to surgical treatment. Univariate analysis showed a significant difference between males and females for lower limb atherosclerotic lesions (p=0.0013), whereas no correlation was found between carotid lesions and sex, or between smoke and atherosclerosis. Significant correlations were found by multiple correlations analisys between: the grade of atherosclerotic lesions in both districts and the patient age (p<0.0001); the grade of carotid atherosclerotic plaques and duration of pretransplantation dialysis (p<0.01); the grade of lower limb atherosclerosis and respectively glicemic (p<0.01), hematocrit (p<0.01), potassium (p<0.002) values, systolic blood pressure (p<0.02). CONCLUSIONS: Relevant rates of renal transplant recipients have carotid and peripheral atherosclerotic lesions. The study of aorto-iliac and lower extremity vascular atherosclerosis have important implications for the transplanted kidney functionality. Color flow Doppler represents a sensitive method for the follow-up examination of these patients.

[Laparoscopic fundoplication in gastroesophageal reflux disease: reflexions on a personal caseload]. / Fundoplicatio laparoscopica per malattia da reflusso gastroesofagea (MRGE): riflessioni su una casistica personale.

Ninety-two patients with severe, proton-pump-inhibitor-dependent gastro-oesophageal reflux disease were submitted to surgery and operated on by the same surgeon (SC) over the past 7 years (mean age: 42; range: 23-74 years). Partial fundoplication was performed in 14 patients with impaired oesophageal motility, while 78 total fundoplications were done in the others, 51 without, and 27 with division of the short gastric vessels. The mean follow-up was 29.5 months (range: 1-85 months). Conversion to open surgery was necessary in 6 patients (all in the first 40 cases). Perforation of the gastric fundus and early migration of the stomach into the mediastinum were the two most important complications observed. The mortality was nil. 39% of the patients complained of postoperative dysphagia but only five required endoscopic (4) or surgical (1) treatment. The percentages of dysphagia after partial fundoplication and total fundoplication with or without division of the short gastric vessels were 28%, 37% and 47%, respectively. In 83.7% the patients were satisfied with the clinical results and in 84% of cases medical treatment was avoided after surgery. On the basis of these data, laparoscopic surgery appears to be a good option for gastro-oeophageal reflux disease in selected patients with a poor response to, or dependent on medical treatment. However, the results of surgery may be subject to the limitations of a learning curve, as in all complex laparoscopic procedures.

Complexes of aluminium(III) with glucose-6-phosphate in aqueous solutions.

The interaction of aluminium(III) with glucose-6-phosphate (GP: LH2) in aqueous solutions has been studied from pH 1 to pH 8, by pH-potentiometry and multinuclear (31P, 27Al, 13C) NMR spectroscopy. Various mononuclear species (MLH2, MLH, ML, ML2H, ML2 and MLH(-3)) and dinuclear complexes M2L2H-n (n=1-4) are formed in the system. NMR clearly indicates that GP is already bound to Al(III) at pH 1. The potentiometric speciation results are confirmed and completed by spectroscopic experiments. Many peaks are observed in the 31P NMR spectra suggesting the formation of isomeric species. An attempt to assign the signals to the corresponding complexes is made, allowing a discussion about their structure. Interestingly enough no metal ion-induced deprotonation and coordination of the alcoholic-OH functions have been observed.

Human-dominated ecosystems and restoration ecology: Seveso today.

Seveso is a town (40,000 inhabitants) 16 km north of Milan, which from 10 July 1976 became synonymous with the chemically induced ecological catastrophe because of the large number of people affected by dioxin exposure and of the large area involved. The most polluted area (about 43 ha) was artificially reconstructed and transformed into a wood composed mainly of oaks with some scattered green fields and some bushy areas, the Bosco delle Querce urban park. A four-year survey monitoring the present ecological and biological risk parameters of the artificially reconstructed ecosystem shows its full ecological recovery as an urban park. Plant and animal coenoses are well composed and the park has been colonized by annelids, insects, amphibians, reptiles, birds and mammals. All these animals are useful biological reagents for risk-assessment because of their potential long-term exposure to TCDD. When some of the endpoints of the xenoestrogen-like molecules' action were studied (i.e., gametogenesis and the gross morphology of genital organs in rabbits and house mice), no signs of TCDD effects were detected. Mutagenicity tests and the house mouse sperm DNA COMET assay do not reveal the presence of any biological risk. The study of the carabidocoenosis and the housefly cytogenetics corroborates this last indication, thus guaranteeing the successful ecological recovery of the formerly most polluted Seveso area.

Potentiometric and spectroscopic studies on the dimethyltin(IV) complexes of 2-hydroxyhippuric acid.

Equilibrium and spectroscopic (1H, 13C NMR and 119Sn Mössbauer) studies in aqueous solution are reported for dimethyltin(IV) complexes of 2-hydroxyhippuric acid (Sal-Gly). Below pH 4, oxygen-coordinated complexes MLH and ML are formed. In the pH range 5-8.5, the species MLH(-1), predominates at any metal-to-ligand ratio. The ligand exchange of this species is slow on the NMR time scale, which allows its structural characterization by NMR spectroscopy: the coordination polyhedron around the tin atom is distorted trigonal bipyramidal, with tridentate [O-,N-,COO-] coordination of Sal-Gly, involving two equatorial methyl groups. The NMR results reveal that the main cause of the distortion of the polyhedron is the large CH3-Sn-CH3 angle of 136+/-4 degrees. The presented results supplement the data available on the dimethyltin(IV)-promoted amide deprotonation of peptides, and provide further arguments for the fundamental role of the carboxylate as an anchoring group in this process.

[Diagnosis and treatment of pheochromocytoma]. / Diagnosi e trattamento del feocromocitoma.

Early detection of a pheochromocytoma is necessary to avoid the cardiovascular complications of hypertension and to recognize the 10% of malignant neoplasms. Hypertensive changes, particularly hypertensive spikes and stable hypertension are the most common clinical features. A pheochromocytoma must be suspected in presence of various symptoms of which cephalea, tachycardia, diaphoresis are the most frequently encountered. Plasma catecholamines and 24-hours urine metabolites measurements have 60-100% and 72-99% sensitivity respectively. Radiologic procedures commonly used to locate a pheochromocytoma include CT and RM: they achieve 100% sensitivity for unilateral adrenal lesions and respectively 64% and 88% sensitivity for extra-adrenal lesions. Scintigraphic localization with MIBG provides functional informations and is recommended for follow-up of the recurrent or metastatic pheochromocytoma. Preoperative medical treatment using alpha and beta blocking agents or calcium channel blockers has contributed to reduce perioperative morbidity and mortality. Anterior transabdominal approach is advocated as the standard operative procedure; this approach allows ready access to any site where tumors are obviously present and permits thorough exploration of the abdominal cavity for additional contralateral adrenal or extra-adrenal lesions. An accurate preoperative localization of a sporadic, unilateral, of less than 7-10 cm, benign neoplasm constitutes the indication for the laparoscopic adrenalectomy. Pheochromocytoma-free survival were 92% and 80% at 5 and 10 years respectively; in living patients without recurrence, hypertension-free survival was 74% and 45% at 5 and 10 years respectively. Extra-adrenal pheochromocytomas are frequently malignant (36%) and are associated with a high incidence of persistent or recurrent disease (32%).

The radial artery: which place in coronary operation?

Previous long-term studies have shown unsatisfactory patency of saphenous vein grafts, compared with internal mammary artery grafts. Recently, the use of the radial artery as a coronary artery bypass graft has enjoyed a revival, on the basis of the belief that it will help improving long-term results of coronary operations. The recent report of encouraging 5-year patency rates, supports its continued use as a bypass graft. In this paper, we review the current knowledge about the radial artery as a bypass graft, with special emphasis on the clinical results.

Coronary and major vascular disease: aggressive screening and priority-based therapy.

It is well know that atherosclerosis can simultaneously affect different vascular subsystems, and patients with diffuse atherosclerosis can be a major management problem both for preoperative evaluation and for intraoperative management. The authors have conducted a prospective study to evaluate the prevalence of coronary artery disease in arteriopathic patients, and vice versa, to assess the effectiveness of aggressive screening together with a priority-based approach. Study 1 consisted of 1,000 consecutive non-emergent patients who were affected by abdominal aortic or carotid disease and were screened for the presence of coronary artery disease before surgery with a newly developed clinical risk assessment. They were stratified into three risk categories with different preoperative evaluation strategies. When coronary artery disease was concomitantly demonstrated in these patients, the choice of surgical method was based on priorities, and the use of combined surgical procedures as required. In study 2, 1,000 consecutive patients that required coronary angiography for suspected coronary artery disease were screened for the presence of carotid or abdominal aortic pathology, directly in the cardiac catheter laboratory during coronary angiography, by obtaining views of the aortic arch and abdominal aorta. Surgical approaches paralleled those of study 1. The results for study 1 showed that 720 patients (72%) were affected by abdominal aortic disease, 238 (24%) by carotid disease and 42 (4%) by both pathologies. Significant coronary artery disease was found in 152 patients (15%), of these 123 (81.5%) were affected by abdominal aortic disease and 29 (18.5%) by carotid artery disease. Abdominal aortic surgery was performed directly or after myocardial revascularization, with an overall mortality rate of 4/718 (0.6%), and a perioperative myocardial infarction rate of 10/718 (1.4%). For patients with carotid artery disease, the completed screening and possible therapy for coronary artery disease resulted in an in-hospital mortality rate of 2/238 (0.8%), and a perioperative myocardial infarction rate of 2/238 (0.8%). There were no significant differences in these rates between patients with or without coronary artery disease. Results for study 2 showed that of the 1000 consecutive patients enrolled for suspicion of coronary artery disease, 767 (77%) were affected by significant coronary artery disease. Among these, 38 (4.9%) had a surgically correctable aortic disease and 31 (4%) a surgically correctable carotid disease, which was monolateral and bilateral in 22 (74%) and nine (26%) patients, respectively, and four (0.5%) were diagnosed with both pathologies. These arteriopathic patients were treated for their coronary and vascular disease with no in-hospital mortality nor perioperative myocardial infarction. In patients with multiple vascular involvement, both coronary and vascular surgery can be performed with low risk when aggressive screening and priority-based therapy are adopted.

[Assessment and treatment of incidentally discovered adrenal tumors]. / Valutazione e trattamento degli incidentalomi del surrene.

An incidentally discovered adrenal mass involves two main questions: the first is the evaluation of the hormonal activity of incidentalomas, that by definition are considered clinically silent. The second problem is to establish preoperatively the biologic behaviour of the masses, whether they are benign or malignant. An essential endocrinological screening of these masses includes the 24 hour urine VMA determination, serum potassium level, and a 1 mg overnight dexamethasone suppression test. Furthermore, the recent observation of a possible partial deficit of 21-hydroxylase suggests the advantage of 17-hydroxyprogesterone dosage after ACTH stimulation. At present no biochemical or radiologic markers can reliably distinguish benign from malignant masses. For this reason the association of imaging study with scintigraphy seems to be helpful, providing "concordant" or "discordant" patterns with CT images. As regard to therapeutic indications, the resection of all hypersecretive masses, proved malignant or increased in diameter tumors is suggested. As regards to biochemically silent lesions, the tumor size has been deemed to be the most helpful determinant of the nature although controversy remains over the size cutoff below which the masses can safely be presumed to be benign and therefore observed. The threshold to proceed surgically has been based on the perceived risk of cancer balanced against the operative risk. However it seems reasonable to recommend excision or surgical exploration for hormonally silent tumors greater than 3 cm, particularly in younger patients. According to personal opinion the laparoscopic approach might represent the gold standard in the treatment of incidentally discovered adrenal masses.