Furoxan derivatives demonstrated in vivo efficacy by reducing Mycobacterium tuberculosis to undetectable levels in a mouse model of infection.

OBJECTIVES: The most recent survey conducted by the World Health Organization described Tuberculosis (TB) as one of the top 10 causes of death and the leading cause of death from a single infectious agent. The increasing number of TB-resistant cases has contributed to this scenario. In light of this, new strategies to control and treat the disease are necessary. Our research group has previously described furoxan derivatives as promising scaffolds to be explored as new antitubercular drugs. RESULTS: Two of these furoxan derivatives, (14b) and (14c), demonstrated a high selectivity against Mycobacterium tuberculosis. The compounds (14b) and (14c) were also active against a latent M. tuberculosis strain, with MIC90 values of 6.67 µM and 9.84 µM, respectively; they were also active against monoresistant strains (MIC90 values ranging from 0.61 to 20.42 µM) and clinical MDR strains (MIC90 values ranging from 3.09 to 42.95 µM). Time-kill experiments with compound (14c) showed early bactericidal effects that were superior to those of the first- and second-line anti-tuberculosis drugs currently used in therapy. The safety of compounds (14b) and (14c) was demonstrated by the Ames test because these molecules were not mutagenic under the tested conditions. Finally, we confirmed the safety, and high efficacy of compounds (14b) and (14c), which reduced M. tuberculosis to undetectable levels in a mouse aerosol model of infection. CONCLUSION: Altogether, we have identified two advanced lead compounds, (14b) and (14c), as novel promising candidates for the treatment of TB infection.

Image-aided estimate of tumor burden in Hodgkin's disease: evidence of its primary prognostic importance.

PURPOSE: To explore a more direct method for evaluating tumor burden (TB) in Hodgkin's disease (HD) and to verify its prognostic importance. PATIENTS AND METHODS: The volume of TB at diagnosis was directly and retrospectively measured in 121 HD patients through images of the lesions recorded by computed tomographic (CT) scan of the thorax, abdomen, and pelvis for all deep sites of involvement and many superficial ones, and by ultrasonography (US) for the remaining superficial lesions. RESULTS: The TB, which was obtained from the sum of the volumes of all the lesions measured on CT scans and US and normalized to body-surface area (relative TB [rTB]), showed a median value of 102.6 cm(3)/m(2) (range, 2.2 to 582.8). At multivariate analysis for prognostic value, rTB was the parameter that statistically correlated best with time to treatment failure (P = 2.2 x 10(-6)), followed by erythrocyte sedimentation rate (ESR) (P =.0003), and serum fibrinogen (P =.0112). The prognostic discrimination allowed by rTB alone proved to be clearly superior to that obtained with the score of the International Prognostic Factor Project. The rTB was found to be correlated with many clinical staging parameters (bulky disease, number of involved lymph node regions, serum lactate dehydrogenase, ESR, hemoglobin, Karnofsky index), but its predictability from these variables was low (R(2) =.668). CONCLUSION: Relative TB is emerging as a strong prognostic factor in HD, more powerful than and largely independent of those hitherto known and used. Further studies are needed to confirm these results and exploit their clinical value, particularly the relationship among rTB, drug doses, and response.

Treatment of Budd-Chiari syndrome with transjugular intrahepatic portosystemic shunt (TIPS).

PURPOSE: This study was performed to evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of patients affected by Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: From January 1999 to December 2006, 15 patients (seven male and eight female subjects, age range 7-52 years) with BCS uncontrolled by medical therapy were treated with TIPS placement. In seven cases BCS was idiopathic, in four it was caused by myeloproliferative disorders and in four by other disorders. One patient also had portal vein thrombosis. In 5/15 cases TIPS was created through a transcaval approach. Eight patients (53.4%) received a bare stent, and seven (46.6%) received a stent graft. The follow-up lasted a median of 29.4 (range 3.2-68) months. RESULTS: Technical success was achieved in all patients without major complications. TIPS was very effective in decreasing the portosystemic pressure gradient from 26.2+/-5.8 to 10+/-6.2 mmHg. All patients but two were alive at the time of writing. Acute leukaemia was the cause of the single early death and was unrelated to the procedure. The patient with portal vein thrombosis underwent thrombolysis before TIPS, but the vein occluded again after 3 weeks, and the patient died 6 months later. The other patients showed significant improvements in liver function, ascites and symptoms related to portal hypertension. Primary patency was 53.3%, and primary assisted patency was 93.3%. No patient required or was scheduled for liver transplantation. CONCLUSIONS: TIPS is an effective and safe treatment for BCS and may be considered a valuable alternative to traditional surgical portosystemic shunting or liver transplantation.

Power Doppler ultrasound of gallbladder wall vascularization in inflammation: clinical implications.

We investigated the role of Power Doppler US in the diagnosis and follow-up of cholecystitis. We reviewed the examinations of 21 surgical patients aged 27-48 years with US findings of cholecystitis. We performed B-mode and then Power Doppler US. Wall thickness and US structure, the presence/absence of stones, and US Murphy's sign were assessed at B-mode US, whereas only the presence/absence of wall vascularization was studied with Power Doppler. B-mode and Power Doppler changes post treatment were also investigated. Ultrasound showed wall thickening in all patients. In addition, positive Murphy's sign and/or gallbladder stones were seen in 6 patients each at B-mode US and wall vascularization in 7 patients with Power Doppler. Acute cholecystitis was diagnosed in these patients. The other 14 patients presenting wall thickening but no vascularization and negative US Murphy's sign were diagnosed as having chronic cholecystitis; 10 of them had gallbladder stones. Two of seven acute cholecystitis patients were operated on in the acute stage for the onset of complications and histologic findings confirmed the US diagnosis. As for the remaining patients, histology diagnosed chronic cholecystitis in 17, whereas wall thickening was not inflammatory in 2 cases. All the cases with early wall vascularization were eventually diagnosed as cholecystitis. Power Doppler US permits confirmation of the diagnosis of acute cholecystitis and distinguishing of chronic disease, which helps in planning of surgery.

[Assessment of varicocele recurrence with ultrasonography, color and power Doppler]. / Valutazione delle recidive del varicocele con ecografia, color e power doppler.

To study the postoperative recurrences of varicocele and the relationship between recurrences and sperm variables, we reexamined postoperatively 48 patients aged 14-56 years (mean: 25 years); the patients returned within a time range of 4 to 36 months. All the patients underwent physical examination, B-mode, color and power Doppler sonography (US); the images were acquired with the patient both supine and upright, both at rest and during Valsalva maneuver. We studied the incidence of recurrences and their bilaterality, the presence of reflux with or without functional maneuvers, associated conditions, surgical complications and the improvement of sperm variables; color and power Doppler findings were compared. The incidence of recurrences (28) and that of major complications (2) were related to the type of surgery: thus, no complications but 26 recurrences were found in the patients with spermatic vein ligation, versus only 2 recurrences but also 2 major complications (1 testicular ischemia and 1 hydrocele) in the patients with ligation of the spermatic cord venous channels. A right varicocele was found in 12 patients, which confirmed the frequent bilaterality of this condition; 8 patients with recurrences had improved sperm variables and 6 presented associated conditions. Our trial confirms that B-mode US, combined with color and power Doppler, can show recurrences, bilaterality, surgical complications and associated conditions and emphasize the role of these exams in the postoperative follow-up of varicocele. However, no method alone, without the evaluation of sperm variables, permits to select the patients to be reoperated on.

Spiral CT findings in a case of pulmonary sequestration.

Pulmonary sequestration has always been diagnosed by direct demonstration of the vessels tributary to the lesion, usually by angiography. Conventional CT can identify the arterial supply in only two thirds of cases. We report a case of pulmonary sequestration diagnosed using Spiral CT, based on the demonstration of both arterial supply and venous drainage. The capabilities of Spiral CT to detect subtle vessel abnormalities and to yield reliable multiplanar imaging enabled us to show the whole course of both the artery and the vein tributary to the lesion. Axial images were the most useful ones to diagnose pulmonary sequestration; 2D and 3D reconstructions were useful for a detailed and immediate spatial depiction of the parenchymal abnormality and of its vascular pedicle.

[Vein patency in patients with pacemaker implanted via subclavian vein: digital phlebography assessment]. / Pervietà venosa nei pazienti con pacemaker impaintati per via succlavia: controlli con flebografia digitalizzata.

Venous thrombosis is a well-known complication of permanent cardiac pacemaker implantation, particularly, chronic occlusion of the subclavian vein is reported to occur in 20-33% of the cases where the percutaneous approach is performed. We examined 135 asymptomatic patients with digital venography to asses the frequency of venous thromboses causing stenosis and occlusion of the subclavian or anonymous arteries in pacemaker carriers. We considered both one- (44) and two-chamber (91) pacemakers and investigated a possible statistically significant difference between them: we found 21 venous thromboses (15%), seven of them in one-chamber pacemakers (15.9%) and 14 two-chambers pacemakers (15.3%). None of our 94 male and 41 female patients was on anticoagulants or had any evidence of coagulation disorders. Venography was performed 39.3 months (mean) after pacemaker implantation (range: 3-120 months). We conclude that digital venography is a simple and relatively noninvasive method permitting better depiction of subclavian, anonymous and caval veins than Doppler US and also showing some vascular abnormalities which may complicate pacemaker implantation.

[The use of spiral computerized tomography in the study of pancreatic insulinoma: preliminary results]. / Uso della Tomografia Computerizzata spirale nella ricerca degli insulinomi panreatici: risultati preliminari.

Insulinomas are usually benign tumors originating in the pancreatic islets: since they are biologically active tumors, insulinomas present at clinics with hypoglycemia caused by increased insulin production. We examined 7 patients with clinically suspected insulinomas with spiral CT to investigate its capabilities in identifying and characterizing this type of lesion. Four patients had abnormal spiral CT findings (true positives); the diagnosis was confirmed at surgery in 3 patients and at instrumental follow-up in the other. The tumors were 12.2 mm in average diameter. CT showed no tumor mass in 3 cases, which was confirmed at angiography and MRI (true negatives). We observed a typical contrast pattern in 50% of cases, namely a ring-like enhancement changing into homogeneous enhancement. Multiplanar and 3D reconstructions were not necessary for lesion identification, but we used them for regional vascular mapping. In our experience, which is limited to few cases and dose not allow any statistically significant conclusion, spiral CT exhibited high sensitivity in the detection and characterization of pancreatic insulinomas which permits to reduce the resort to more invasive angiographic techniques.

Use of spiral computed tomography for multiplanar dental reconstruction.

OBJECTIVE: To compare spiral with conventional CT for multiplanar reconstruction (MPR) prior to dental implant placement. METHODS: Ten patients underwent conventional and then Spiral CT at 1 mm slice thickness. In six patients (Group A) the pitch was 1:1; the other four (Group B) it was 2:1. Image quality and clinical features were evaluated separately on axial and reconstructed images by two experienced radiologists who scored each parameter from 1 (poor, non-diagnostic) to 3 (good, diagnostic). RESULTS: Loss of spatial resolution with spiral CT was not significant and the diagnostic yield poorer only for trabecular bone structure. The MPRs were better and depiction of the mandibular canal more reliable. CONCLUSIONS: We recommend the use of spiral CT instead of conventional CT for dental MPR because examination time is shorter and patient comfort is improved. Use of a pitch of 2:1 permits a marked reduction in X-ray dose with no loss of image quality.

Nonbiodegradable expanded polytetrafluoroethylene-covered stent implantation in porcine peripheral arteries: histologic evaluation of vascular wall response compared with uncoated stents.

PURPOSE: To test the vascular wall response to an expanded polytetrafluoroethylene-covered stent, compared with conventional stenting, up to 6 months after deployment in the vascular district of a swine model. METHODS: Fourteen minipigs underwent implantation of expanded polytetrafluoroethylene-covered stents (CS) and bare stents (BS) in five peripheral arteries. Animals were killed at different time points (from 1 to 180 days). Histopathologic assessment by morphologic and morphometric analysis and by scanning electron microscopy (SEM) were used to assess the incorporation characteristics and re-endothelialization extent of the two types of stents. RESULTS: A total of 70 stents (14 CS and 14 BS in the renal arteries; 28 CS in the iliac arteries, and 14 CS in the aorta) were implanted. Microscopic examination confirmed the absence of occlusive thrombi in both the CS and BS groups. Microthrombi were observed in 10 of 13 CS (77% of cases) and in four of four BS (100% of cases, p < 0.05). Inflammation was mild in 69% of segments in which a CS was implanted and in 74% of segments in which a BS was implanted (p = NS), while a severe inflammatory reaction was observed in 6% of CS segments and in 8% of BS segments (p = NS). No differences were detected at the long-term analysis between neointimal thickness in CS compared with BS segments (0.46 +/- 0.18 mm vs 0.42 +/- 0.26 mm at 90 days and 0.36 +/- 0.08 mm vs 0.35 +/- 0.04 mm at 180 days; p = NS, respectively). At SEM analysis, re-endothelization was evident 15 days after the implant in both CS and BS starting from the stent edges. CONCLUSION: CS implantation did not elicit a more severe thrombotic deposition compared with that of BS. A similar inflammatory reaction of the arterial wall was present in the two stent groups 3 and 6 months following the implant. In addition, CS implantation did not stimulate excessive neointimal formation when compared with BS.

Spiral CT angiography and surgical correlations in the evaluation of intracranial aneurysms.

We investigated the accuracy of spiral computed tomography angiography (CTA) in the detection and study of intracranial aneurysms by comparing CTA with selective angiograms and surgical findings. Twenty-six patients (9 men and 17 women; mean age 53.1 +/- 1.8 years) with suspected intracranial aneurysms were submitted to CTA (1- to 2-mm slices, pitch 1:1, 24 s, RI = 1) after a conventional CT examination showing subarachnoid hemorrhage (SAH) in 19 cases and during neuroradiological investigations performed for other reasons in 7 cases. One hundred twenty to 150 ml iodate contrast agent (0.3-0.4 gI/ml) were injected intravenously at 5 ml/s rate and with 12- to 25-s delay calculated with a preliminary test bolus. Three-dimensional shaded surface display (3D SSD) and maximum intensity projection (MIP) reconstructions were obtained from axial images. Then, within 48 h, all patients were submitted to digital subtraction angiography (DSA), with separate assessment of CTA and DSA findings. Twenty-two aneurysms shown by CTA were confirmed at DSA and surgery (true positives), whereas the vascular lesion was not confirmed at DSA in 2 cases (false positives). The presence of intracranial aneurysms was excluded at both CTA and subsequent DSA in 7 cases (true negatives) and there were no false negatives; sensitivity was 100 %, specificity 77.8 %, and diagnostic accuracy 93.5 %. Computed tomography angiography aneurysm location was confirmed at surgery in all cases, with very high accuracy in assessing the presence of an aneurysm neck (100 %). Computed tomography angiography accurately depicted the aneurysm shape in 20 of 22 cases, but failed to depict its multilobed nature in 2 cases. The mean aneurysm diameter calculated at CTA was 0.99 +/- 0.12 cm vs 1.09 +/- 0.11 cm at surgery (p < 0.01). The present results suggest that the high sensitivity of CTA, if confirmed by further studies, might help in avoiding having to resort to arteriography after negative CTA in SAH patients.