BriXS, a new X-ray inverse Compton source for medical applications.

MariX is a research infrastructure conceived for multi-disciplinary studies, based on a cutting-edge system of combined electron accelerators at the forefront of the world-wide scenario of X-ray sources. The generation of X-rays over a large photon energy range will be enabled by two unique X-ray sources: a Free Electron Laser and an inverse Compton source, called BriXS (Bright compact X-ray Source). The X-ray beam provided by BriXS is expected to have an average energy tunable in the range 20-180 keV and intensities between 1011 and 1013 photon/s within a relative bandwidth ΔE/E=1-10%. These characteristics, together with a very small source size (~20 µm) and a good transverse coherence, will enable a wide range of applications in the bio-medical field. An additional unique feature of BriXS will be the possibility to make a quick switch of the X-ray energy between two values for dual-energy and K-edge subtraction imaging. In this paper, the expected characteristics of BriXS will be presented, with a particular focus on the features of interest to its possible medical applications.

Diagnostic accuracy and interobserver agreement of Quasistatic Ultrasound Elastography in the diagnosis of thyroid nodules.

PURPOSE: To assess the best technique and the diagnostic accuracy of Quasistatic Ultrasound Elastography (QUE) in thyroid nodules. Interobserver agreement was also evaluated. MATERIALS AND METHODS: A preliminary study of 50 patients with 54 thyroid nodules was performed with quantitative software in order to define the best cut-off value of different imaging methods. All patients underwent total thyroidectomy and histopathology findings served as the standard of reference. Thereafter, 154 nodules in 137 consecutive patients were prospectively evaluated by three operators. Findings at fine-needle aspiration cytology and histopathology (N = 60) served as the standard of reference. RESULTS: The most accurate technique was the axial peri-intranodular measurement method which achieved an area under the ROC curve of 0.961 (95 %CI 0.848 - 1.00) and had an optimal cut-off value of 3.00. QUE in the differentiation of thyroid nodules showed for operator 1: sensitivity 90 % (95 %CI 73.5 - 97.9 %), specificity 92.7 % (95 %CI 86.7 - 96.6 %), LR+ 12.40 (6.54 - 23.50), LR- 0.11 (0.04 - 0.32) and accuracy 91.4 % (95 %CI 85.4 - 97.3 %); for operator 2: sensitivity 86.7 % (95 %CI 69.3 - 96.2 %), specificity 87.1 % (95 %CI 79.9 - 92.4 %), LR+ 6.72 (4.16 - 10.80), LR- 0.15 (0.06 - 0.38) and accuracy 86.9 % (95 %CI 80.0 - 93.7 %); for operator 3: sensitivity 80 % (95 %CI 61.4 - 92.3 %), specificity 83.9 % (95 %CI 76.2 - 89.9 %), LR+ 4.96 (3.20 - 7.70), LR- 0.24 (0.12 - 0.49) and accuracy 81.9 % (95 %CI 74.0 - 89.9 %). Interobserver agreement values between operator 1 and operator 2 (k = 0.79) (p < 0.05, 95 %CI 0.684 - 0.904), between operator 1 and operator 3 (k = 0.73, 95 %CI: 0.607 - 0.854) and between operator 2 and operator 3 (k = 0.71, 95 %CI: 0.584 - 0.835) were significant. CONCLUSION: QUE provides accurate quantitative evaluation of thyroid nodules with low interobserver variability.

Is ionized calcium a reliable predictor of hypocalcemia after total thyroidectomy? A before and after study.

Wanting to find a way of identifying patients suitable for early discharge after thyroidectomy, we set out to establish whether ionized calcium concentration is a better predictor of post-surgical hypocalcemia than total serum calcium. Data were analyzed to establish whether serum ionized calcium concentrations are correlated with total serum calcium levels and symptomatic hypocalcemia after thyroidectomy. Sixty-two patients undergoing total thyroidectomy at the Department of Surgical Sciences of the "Sapienza" University of Rome, Italy, in 2010. Ionized calcium was measured before (day 0) and after surgery (days 1, 2 and 60) in all the patients. These measurements were compared with preoperative (day 0) and postoperative total serum calcium levels (days 1, 2 and 60). The preoperative ionized calcium levels differed from the ionized calcium levels recorded on days 1 and 2; this pattern was not observed for the total calcium concentrations. Conversely, total calcium on days I and II correlated significantly with the various ionized calcium measurements. The presence of parathyroid glands in the surgical specimen did not seem to affect suitability for discharge. The statistical analysis showed that ionized calcium measurements are more reliable than total calcium measurements in the immediate and long-term follow-up of total thyroidectomy patients. Applying a 95% confidence interval we established reference values for both total serum calcium and ionized calcium, below which all patients develop postoperative symptomatic hypocalcemia. In conclusion, measurement of ionized calcium, as opposed to total calcium, should be strongly recommended in the immediate and longterm follow-up of total thyroidectomy patients.

Double ileo-ceco-colic invagination due to right colon carcinoma: clinical presentation and management.

Intestinal intussusceptions represent a rare cause of intestinal obstruction in adults (about 1% of intestinal obstructions). The principle causes are benign or malignant tumors. In adults, the most frequent localizations of intestinal invaginations are the ileo-cecal segment, ileum and colon as exclusive localization. We report the case of a 56 year-old Caucasian male admitted in our Department complaining with diffuse abdominal pain and severe anemia. The colonoscopy revealed a vegetant, stenosing and ulcerated mass in the hepatic flexure. The computed tomography suggested the additional diagnosis of intestinal intussusception with no evidence of intestinal obstruction. In our experience, surgery is always indicated for the treatment of intussusceptions in adults, especially for the almost constant underlying neoplasm.

Transmesenteric hernia after right nephrectomy: diagnostic and therapeutic management.

Internal abdominal hernias are a rare cause of intestinal obstruction (0.2-0.9%). Transmesenteric hernia is a rare type of internal hernia and usually in adult people is acquired. We report the case of a 44 year-old caucasian female with a small bowel occlusion after right nephrectomy for clear cell renal carcinoma caused by an acquired transmesenteric hernia. We emphasize the role of CT scanning for a prompt diagnosis and a quick surgical treatment in order to avoid intestinal gangrene.

Two-years follow-up of low-dose methotrexate and 6-methylprednisolone therapy in a patient with idiopathic retroperitoneal fibrosis.

Retroperitoneal fibrosis (RPF), also known as Ormond's disease, is a rare fibroinflammatory disease with uncertain etiology. RPF is characterized by the presence of a particular retroperitoneal fibrotic tissue which is white, woody and involving retroperitoneal structures such as the great vessels, ureters and psoas muscle. The main complication of RPF is the obstruction of local structures such as the ureters due to the fibrosis and the treatment of this aspect represents the main challenge for this pathology. RPF medical treatment consists of corticosteroids or/and immunosuppressive therapy. We report a case of a patient affected by idiopathic RPF treated with low-dose methotrexate (MTX) and 6-methylprednisolone (6-MP) for two years, describing and confirming the effectiveness and safety of a long-term low-dose MTX and 6-MP treatment associated to ureteral Double-J stenting avoiding more invasive surgical approaches.

[Association between thyroiditis and cancer. Our experience]. / Associazione tra tiroidite e cancro tiroideo: nostra esperienza.

We analyzed a homogeneous sample of 671 patients underwent total thyroidectomy for various pathologies evaluating the final histological diagnosis and seeking the association between thyroiditis and cancer. As is known to the literature the incidence of association between autoimmune disease and cancer is not exceptional. In our experience, we have shown it in 39 cases (18.6%). We also considered the genetic background RET/PTC which is more prevalent in cases of papillary carcinoma in an inflammatory environment; could be stimulant the study of specific molecular markers to identify targets to inhibit the inflammatory status in thyroid cancer prevention.

2,6-Diketopiperazines from amino acids, from solution-phase to solid-phase organic synthesis.

A method to prepare 1,3-disubstituted 2,6-diketopiperazines (2,6-DKP) as useful heterocyclic library scaffolds in the search of new leads for drug discovery is described. The method can be used in solution-phase and solid-phase conditions. In the key step of the synthesis, the imido portion of the new molecule is formed in solution through intramolecular cyclization, under basic conditions, of a secondary amide nitrogen on a benzyl ester. A Wang resin carboxylic ester is used as the acylating agent under solid-phase conditions, allowing the cyclization to take place with simultaneous cleavage of the product from the resin ("cyclocleavage"). The synthetic method worked well with several couples of amino acids, independently from their configuration, and was used for the parallel synthesis of a series of fully characterized compounds. The use of iterative conditions in the solid phase (repeated addition of fresh solvent and potassium carbonate to the resin after filtering out the product-containing solution) allowed us to keep diastereoisomer content below the detection limit by HPLC and (1)H NMR (200 MHz).

Gender-related differences in body dysmorphic disorder (dysmorphophobia).

Body Dysmorphic Disorder (BDD), which consists of pathological preoccupations with defects in different body parts, has been systematically studied only in the last decade. We hypothesized that gender would differentially influence the localization of the preoccupations as well as the extent and type of comorbidity with other psychiatric disorders. With the use of a specially constructed semistructured interview, we evaluated 58 consecutive outpatients with DSM-III-R BDD (women = 41.4%, men = 58.6%). Women had significantly more preoccupations with breast and legs, checking in the mirror and camouflaging, as well as lifetime comorbidity with panic, generalized anxiety, and bulimia. Men had significantly higher preoccupations with genitals, height, excessive body hair, as well as higher lifetime comorbidity with bipolar disorder. Although BDD is almost never found without comorbidity, it does appear to be an autonomous syndrome, and gender tends to influence the nature and extent of this comorbidity.

Prevalence, phenomenology and comorbidity of body dysmorphic disorder (dysmorphophobia) in a clinical population.

Dysmorphophobia (body dysmorphic disorder), defined as a preoccupation with an imaginary or minimal defect in appearance, has been known for more than a century but has received relatively little empirical study. The authors investigated the demographics, phenomenology, course, associated psychopathology and family history in a series of 58 patients (34 men and 24 women) with the disorder. The patients were assessed with the Hopkins Symptom Checklist and two specially constructed instruments developed by the authors. The mean age at onset of body dysmorphic disorder was 17 (sd = 3.8) years and the average duration was 9 (sd = 5.3) years. The most common preoccupations were defects of the face, nose, genitals and legs. Seventy-nine percent of the patients reported excessive mirror checking and 53% reported attempts to camouflage their 'deformities'. As a result of their symptoms, 89.6% avoided the usual social activities, 51.7% showed an impairment of their academic or job performance, 45% experienced suicidal ideation and 36% showed aggressive behaviour. Seventy-two percent of the patients had an associated lifetime diagnosis of a major mood disorder and 74% of an anxiety disorder. Body dysmorphic disorder has a generally chronic course, causes considerable distress and a serious impairment in many areas, and shows strong links with mood and obsessive-compulsive disorders.

Fluvoxamine in the treatment of body dysmorphic disorder (dysmorphophobia).

Fifteen consecutive patients with a DSM-III-R diagnosis of body dysmorphic disorder (BDD) were included in a 10-week open clinical trial of fluvoxamine. Treatment began at 100 mg/day fluvoxamine and was increased to a maximum of 300 mg/day or until intolerable side effects developed or a complete or nearly complete resolution of symptoms occurred. At baseline and at weeks 2, 6 and 10, patients completed the Hopkins Symptoms Check-List (HSCL-90) and a specific rating scale for BDD symptoms (BDDSS), and clinicians completed a Clinical Global Improvement Scale. Twelve of the 15 patients completed the trial. Of the three patients who did not complete the study, one improved moderately during the placebo phase, one showed a marked worsening of the depressive symptoms during the wash-out phase and one showed adverse side effects, such as nausea and diarrhoea, after the first week of treatment and was unable to continue the trial. After 10 weeks, of the 12 remaining patients, 10 were considered to be markedly improved, one minimally improved and one unchanged. Several outcome measures showed a significant improvement from baseline to week 10. Our findings suggest that fluvoxamine may be effective in the treatment of BDD. Double-blind studies will be required to investigate these findings further.

New arylpyrido-diazepine and -thiodiazepine derivatives are potent and highly selective HIV-1 inhibitors targeted at the reverse transcriptase.

A series of pyridobenzothiodiazepindioxides such as the 11-ethyl-6,8,9-trimethyl-6,11-dihydro-pyrido[2,3-f] [2,1,5]benzothiodiazepine-5,5-dioxide and arylpiridodiazepines such as the 6,7-dihydro-7-methyl-12-ethyl-pyrido[2,3-b] pyrido(2',3'-4,5]furo[2,3-f][1,4]diazepin-6(12H)-thio and the 6,7-dihydro-7-methyl-12-ethyl-pyrido[2,3-b]pyrido- [2,3-4,5]thieno[2,3-f][1,4] diazepin-6(12H)-thione were found to inhibit human immunodeficiency virus type 1 [HIV-1(IIIB)] replication at a concentration of 0.003-0.04 microM without being cytotoxic at a 3,000- to 15,000-fold higher concentration. These compounds proved effective against a variety of HIV-1 strains, including those that are resistant to 3'-azido-3' deoxythymidine (AZT), but not against HIV-2, simian immunodeficiency virus or herpes simplex virus. An HIV-1 strain containing the 188 Tyr-->His mutation in the reverse transcriptase displayed severely reduced sensitivity to the compounds. The specificity of these compounds is due to an interaction with the reverse transcription process. The 6,7-dihydro-7-methyl-12-ethyl-pyrido[2,3-b]pyrido [2,3-4,5]thieno[2,3-f][1,4]diazepin-6(12H)-thione (MEN 10979) enhanced the anti-HIV-1 activity of AZT and dideoxyinosine (ddI) in a synergistic manner. The new arylpyrido-diazepine and -thiodiazepine derivatives appear to be drug candidates for the treatment of HIV-1 infection.

Psychotic symptom patterns and the diagnosis of schizophrenia.

In comparing 101 psychotic patients subtyped by DSM-III criteria into paranoia, schizophrenia, schizoaffective, and affective disorders, we failed to distinguish them on the basis of delusional and hallucinatory experiences. These 'productive', 'positive' or 'irritative' symptoms--which the literature tends to link with temporolimbic dysfunction--did not appear specifically linked to schizophrenia. By contrast, 'negative' or 'deficit' symptoms--which the literature tends to relate to frontal lobe dysfunction--appeared more specific--especially for the disorganized subtype of schizophrenia. Although these data tend to support Bleulerian over Schneiderian conceptualization of schizophrenia, the heterogeneity of neuropsychological deficits implied in the negative symptom complexes limits the nosologic utility of the rubric of schizophrenia so defined.

New dibenzothiadiazepine derivatives with antidepressant activities.

A new series of 11-[(aminoalkyl)carbonyl] derivatives of 6,11-dihydrodibenzo[c,f][1,2,5]thiadiazepine 5,5-dioxide (10-39) were synthesized and evaluated for potential antidepressant activity in the apomorphine-induced hypothermia (Apo 16) test. Effects on reserpine-induced hypothermia and toxicity for the most potent antagonists of Apo 16 hypothermia were also studied. Structure-activity relationships are reported. Anticholinergic effects were evaluated for compound 12, identified as the most potent and least toxic in this series, by assessing physostigmine lethality. Compound 12 was also subjected to X-ray analysis.

New benzofuran-imidazoles as antimycotic agents. I. Synthesis and characterization.

With the aim of obtaining new drugs having antimycotic activity together with antibacterial and fewer side effects, we synthesized ten new benzofuran-2-yl-imidazoles.

New benzofuran-imidazoles as antimycotic agents. II. In vitro studies.

Ten new imidazole derivatives, benzofuran-imidazoles, were studied in vitro to establish their antimycotic activity against 70 fungal strains, in comparison with three known imidazoles and, for the dermatophytes only, griseofulvin. A very high inhibitory activity against dermatophytes was shown by five of the new substances. The other filamentous fungi and yeasts showed a more marked variation in their susceptibility. However a good sensitivity of some isolates of Candida albicans and other yeasts was seen.