Role of Functional Imaging Techniques to Assess Motor and Language Cortical Plasticity in Glioma Patients: A Systematic Review.

Cerebral plasticity is the ability of the central nervous system to reorganize itself in response to different injuries. The reshaping of functional areas is a crucial mechanism to compensate for damaged function. It is acknowledged that functional remodeling of cortical areas may occur also in glioma patients. Principal limits of previous investigations on cortical plasticity of motor and language functions included scarce reports of longitudinal evaluations and limited sample sizes. This systematic review is aimed at elucidating cortical brain plasticity for motor and language functions, in adult glioma patients, by means of preoperative and intraoperative mapping techniques. We systematically reviewed the literature for prospective studies, assessing cortical plasticity of motor and language functions in low-grade and high-grade gliomas. Eight longitudinal studies investigated cortical plasticity, evaluated by motor and language task-based functional MRI (fMRI), motor navigated transcranial magnetic stimulation (n-TMS), and intraoperative mapping with cortical direct electrocortical stimulation (DES) of language and motor function. Motor function reorganization appeared relatively limited and mostly characterized by intrahemispheric functional changes, including secondary motor cortices. On the other hand, a high level of functional reshaping was found for language function in DES studies. Occurrence of cortical functional reorganization of language function was described focusing on the intrahemispheric recruitment of perilesional areas. However, the association between these functional patterns and recovery of motor and language deficits still remains partially clear. A number of relevant methodological issues possibly affecting the finding generalization emerged, such as the complexity of plasticity outcome measures and the lack of large longitudinal studies. Future studies are required to further confirm these evidences on cortical plasticity in larger samples, combining both functional imaging and intraoperative mapping techniques in longitudinally evaluations.

Efficacy of a new delivery system based on solid lipid microparticles for the oral administration of the non-conventional antioxidant IAC on a diabetes mouse model.

PURPOSE: We previously showed the positive effects of the new antioxidant molecule bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) in reducing basal hyperglycaemia and relieving glucose intolerance in a diabetes model. However, the chemical properties of IAC did not allow an efficient oral administration, thus representing the main failing of that study. Here, we tested the effect of a new oral delivery system based on solid lipid microparticles (SLMs) in a diabetes mouse model. METHODS: The diabetes model was induced in C57B1/6J mice using streptozotocin and nicotinamide. Only the animals that overcame the glycaemic threshold of 180 mg/dL were enrolled in the study. Diabetic animals were then randomly assigned to 4 groups (n = 9) and treated once a day for 5 consecutive weeks with IAC (50, 100, and 150 mg/kg b.w.). The control group was composed of (n = 7) healthy mice that received only the vehicle. Glucose level was weekly monitored during the treatment period and up to 3 weeks after the suspension of the treatment. Glucose tolerance and insulin-resistance test were carried out. RESULTS: Our results showed that SLMs maintained the IAC effect in reducing basal hyperglycaemia as well as improving the insulin sensitivity and glucose tolerance. CONCLUSION: The present study confirms that SLMs are promising drug carriers, which allow the oral administration of IAC ensuring its therapeutic efficacy. The concrete possibility to administer IAC per os represents a significant breakthrough in the putative consideration of this multi-radical scavenger in the diabetes therapeutic approach.

Whole-body MRI with diffusion-weighted imaging: a valuable alternative to contrast-enhanced CT for initial staging of aggressive lymphoma.

AIM: To compare the accuracy of whole-body magnetic resonance imaging (Wb-MRI) with diffusion-weighted imaging (DWI) to that of contrast-enhanced computed tomography (CE-CT) and 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron-emission tomography co-registered with low dose-CT (PET-CT) in defining lymphoma disease stage. MATERIALS AND METHODS: From February 2010 to May 2014, 41 lymphoma patients underwent Wb-MRI-DWI, CE-CT, and (18)F-FDG PET-CT. Histological subtypes included aggressive B-cell (n=11), follicular (n=13), mantle cell (n=3), and Hodgkin's (n=14) lymphoma. To compare the procedures, the reference standard (RS) assessment was defined by combining the results from (18)F-FDG PET-CT, CE-CT, and bone marrow (BM) histology, modifications after therapy, and histological re-assessments of uncertain lesions. RESULTS: Among 1025 nodal sites, 217 had disease involvement according to the RS. CE-CT yielded 23 false-negative and 11 false-positive errors. Wb-MRI-DWI failed to recognise 17 localisations and had six false-positive errors; (18)F-FDG PET-CT had no errors. Among 458 extranodal sites, 37 were positive according to the RS. (18)F-FDG PET-CT yielded four false-negative and two false-positive results. CE-CT yielded 17 false-negative errors. Wb-MRI-DWI yielded a single false-negative error. Wb-MRI-DWI was the most reliable imaging technique for BM evaluation. Considering each procedure alone, the final stage would have been missed in four cases using (18)F-FDG PET-CT, 12 cases using CE-CT, and none using Wb-MRI-DWI. CONCLUSION: The present data support Wb-MRI-DWI as a sensitive and specific imaging technique for lymphoma evaluation, supporting its use in place of CE-CT for staging.

Interictal cortical reorganization in episodic migraine without aura: an event-related fMRI study during parametric trigeminal nociceptive stimulation.

The aim of our study was to explore the pain processing network in patients with migraine during trigeminal nociceptive stimulation. Sixteen patients with episodic migraine without aura and 16 healthy controls performed functional magnetic resonance imaging during thermal stimuli (at 41, 51 and 53°C). Patients with migraine showed a greater activation in the perigenual part of anterior cingulate cortex at 51°C and less activation in the bilateral somatosensory cortex at 53°C compared to healthy controls. There were no differences in experimental pain perception between groups. Our findings demonstrate a functional reorganization of cerebral areas known to be involved in pain processing in patients with migraine.

Combined first-stage hepatectomy and colorectal resection in a two-stage hepatectomy strategy for bilobar synchronous liver metastases.

BACKGROUND: This study assessed the feasibility and outcomes of combined colorectal and hepatic resection as the first step of two-stage hepatectomy in patients with bilobar synchronous colorectal liver metastases. METHODS: All patients with bilobar synchronous colorectal liver metastases who were considered for two-stage hepatectomy, combining resection of the primary tumour with the first stage of hepatectomy, between 2000 and 2008 were selected from a prospectively collected database at two institutions. Data were analysed retrospectively on an intention-to-treat basis. RESULTS: Thirty-three patients were studied. Twenty patients received neoadjuvant chemotherapy. Combined colorectal resection and clearance of left-sided liver metastases was the first-stage procedure in all but one patient, in whom right clearance was performed. In 17 patients right portal vein ligation was undertaken at the same time. No patient died. Two patients had anastomotic leakage. Interval chemotherapy was given to 25 patients, five of whom also had percutaneous portal vein embolization. Twenty-five patients had the second-stage hepatectomy, but not eight patients with disease progression. There was one postoperative death after the second stage, and eight patients experienced morbidity. Median follow-up from the first stage was 28.7 months. Overall and disease-free survival rates for patients who completed the procedure were 80 and 44 per cent respectively at 3 years, and 48 and 22 per cent at 5 years. CONCLUSION: In patients with bilobar synchronous colorectal liver metastases who are candidates for two-stage hepatectomy, combined resection of the primary tumour and first-stage hepatectomy reduces the number of procedures, optimizes chemotherapy administration and may improve outcome.

Does the default-mode functional connectivity of the brain correlate with working-memory performances?

The "default-mode" network is an ensemble of cortical regions that are typically deactivated during demanding cognitive tasks in functional magnetic resonance imaging (fMRI) studies. Using functional connectivity analysis, this network can be studied as a "stand-alone" brain system whose functional role is supposed to consist in the dynamic control of intrinsic processing activities like attention focusing and task-unrelated thought generation and suppression. Independent component analysis (ICA) is the method of choice for generating a statistical image of the "default-mode" network (DMN) using a task- and seed-independent distributed model of fMRI functional connectivity without prior specification of node region extent and timing of neural activation. We used a standard graded working-memory task (n-back) to induce fMRI changes in the default-mode regions and ICA to evaluate to DMN functional connectivity in nineteen healthy volunteers. Based on the known spatial variability of the ICA-DMN maps with the task difficulty levels, we hypothesized the ICA-DMN may also correlate with the subject performances. We confirmed that the relative extent of the anterior and posterior midline spots within the DMN were oppositely (resp. positively in the anterior and negatively in the posterior cingulate cortex) correlated with the level of task difficulty and found out that the spatial distribution of DMN also correlates with the individual task performances. We conclude that the working-memory function is related to a spatial re-configuration of the DMN functional connectivity, and that the relative involvement of the cingulate regions within the DMN might function as a novel predictor of the working-memory efficiency.

Value of endorectal MRI and MRS in patients with elevated prostate-specific antigen levels and previous negative biopsies to localize peripheral zone tumours.

AIM: To evaluate prospectively the role of endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in detecting peripheral zone tumour in patients with total prostate-specific antigen (PSA) values>or=4 ng/ml and one or more negative transrectal ultrasound (TRUS) biopsy rounds. MATERIAL AND METHODS: Fifty-four consecutive men (mean age 65.4+/-5.2 years, mean total PSA 10.8+/-7.5 ng/ml), underwent a combined MRI-MRS examination with endorectal coil. MRI included transverse, coronal, and sagittal T2-weighted and transverse T1-weighted fast spin-echo sequences. MRS data were acquired using a double spin-echo point resolved spectroscopy (PRESS) sequence. A 10-site scheme was adopted to evaluate the prostate peripheral zone. A peripheral prostatic site was classified as suspicious if low intensity signal was present on T2-weighted images and/or if the choline+creatine/citrate ratio was >0.86. Following MRI-MRS all patients were submitted to a standard 10-core biopsy scheme to which from one to three supplementary samples were added from suspicious MRI and/or MRS sites. In per-patient analysis findings were considered true-positive if biopsy positive patients were classified as suspicious, irrespectively of lesion site indication. RESULTS: Prostate cancer (PC) was detected in 17 of 54 patients (31.5%); median Gleason score was 6 (range 4-8). On a per-patient basis sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were respectively 100, 64.9, 56.7, 100, and 75.9% for MRI; 82.2, 70.3, 57.7, 92.9, and 75.9% for MRS; and 100, 51.4, 48.6, 100, and 66.7% for combined MRI-MRS. In all the 17 PC patients, combined MRI-MRS correctly indicated the sites harbouring cancer, whereas both MRI and MRS gave erroneous indications in two patients. CONCLUSION: The results of the present study show that MRI alone might be able to select negative patients in whom further biopsies are unnecessary. The combination of MRI and MRS might be able to drive biopsies in suspicious sites and increase the cancer detection rate. Further studies are required to confirm these data.

Computer-aided cognitive rehabilitation improves cognitive performances and induces brain functional connectivity changes in relapsing remitting multiple sclerosis patients: an exploratory study.

To better understand the effects of short-term computer-based cognitive rehabilitation (cCR) on cognitive performances and default mode network (DMN) intrinsic functional connectivity (FC) in cognitively impaired relapsing remitting (RR) multiple sclerosis (MS) patients. Eighteen cognitively impaired RRMS patients underwent neuropsychological evaluation by the Rao's brief repeatable battery and resting-state functional magnetic resonance imaging to evaluate FC of the DMN before and after a short-term (8 weeks, twice a week) cCR. A control group of 14 cognitively impaired RRMS patients was assigned to an aspecific cognitive training (aCT), and underwent the same study protocol. Correlations between DMN and cognitive performances were also tested. After cCR, there was a significant improvement of the following tests: SDMT (p < 0.01), PASAT 3" (p < 0.00), PASAT 2" (p < 0.03), SRT-D (p < 0.02), and 10/36 SPART-D (p < 0.04); as well as a significant increase of the FC of the DMN in the posterior cingulate cortex (PCC) and bilateral inferior parietal cortex (IPC). After cCR, a significant negative correlation between Stroop Color-Word Interference Test and FC in the PCC emerged. After aCT, the control group did not show any significant effect either on FC or neuropsychological tests. No significant differences were found in brain volumes and lesion load in both groups when comparing data acquired at baseline and after cCR or aCT. In cognitively impaired RRMS patients, cCR improves cognitive performances (i.e., processing speed and visual and verbal sustained memory), and increases FC in the PCC and IPC of the DMN. This exploratory study suggests that cCR may induce adaptive cortical reorganization favoring better cognitive performances, thus strengthening the value of cognitive exercise in the general perspective of building either cognitive or brain reserve.

Supratracheal laryngectomy: current indications and contraindications.

Cancer of the larynx in the intermediate/advanced stage still presents a major challenge in terms of controlling the disease and preserving the organ. Supratracheal partial laryngectomy (STPL) has been described as a function-sparing surgical procedure for laryngeal cancer with sub-glottic extension. The aim of the present multi-institutional study was to focus on the indications and contraindications, both local and general, for this type of surgery based on the long-term oncological and functional results. We analysed the clinical outcomes of 142 patients with laryngeal cancer staged pT2-pT4a who underwent STPL. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and loco-regional control (LRC) rates were: glottic pT2 [71.4%, 95.2%, 76.0%, 76.0%], glottic-transglottic pT3 [85.3%, 91.1%, 86.4%, 88.7%], and pT4a [73.2%, 88.1%, 52.7%, 60.7%], respectively. DFS and LRC prevalences at 5 years were greatly affected by pT4a staging. Five-year laryngeal function preservation (LFP) and laryngectomy free survival (LFS) were: glottic pT2 [90.9%, 95.2%], glottic-transglottic pT3 [84.4%, 93.1%], and pT4a [63.7%, 75.5%], respectively, being affected by pT staging and age 65 ≥ years (LFP 54.1%). As a result of Type III open horizontal partial laryngectomies (OPHLs) (supratracheal laryngectomies), the typical subsites of local failure inside the larynx were the mucosa at the passage between the remnant larynx and trachea, the mucosa at the level of the posterior commissure and the contralateral cricoarytenoid unit as well as outside the larynx at the level of the outer surface of the remnant larynx. For patients with glottic or transglottic tumours and with sub-glottic extension, the choice of STPL can be considered to be effective, not only in prognostic terms, but also in terms of functional results.

Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly.

The effects of a 12- to 24-month treatment with depot long-acting octreotide (OCT-LAR) on hormone profile, tumor mass, and clinical symptoms were reported in 36 patients with active acromegaly [GH, 34.2 +/- 5.6 microg/L; insulin-like growth factor I (IGF-I), 784.5 +/- 40.4 microg/L]. Fifteen patients were de novo whereas 21 had previously undergone unsuccessful surgery. Serum GH (P < 0.0001) and IGF-I levels (P < 0.0001) significantly decreased as early as after the first injection of OCT-LAR and progressively declined during the 12-24 months of treatment both in de novo and in operated patients. At the last follow-up, GH hypersecretion was controlled (< or =2.5 microg/L) in 69.4% whereas normal IGF-I levels were achieved in 61.1% of patients. GH and IGF-I suppression during OCT-LAR treatment was similar in de novo and operated patients as shown by nadir GH (2.3 +/- 0.6 vs. 2.2 +/- 0.6 microg/L) and IGF-I (323.1 +/- 34.9 vs. 275.5 +/- 33.0 microg/L), percent suppression of GH (92.7 +/- 2.0 vs. 85.9 +/- 3.3%) and IGF-I (57.4 +/- 4.9 vs. 61.5 +/- 4.6%), and prevalence of GH (73.3 vs. 76.2%) and IGF-I (53.3 vs. 71.4%) control. A decrease in tumor volume was observed in 12 of 15 de novo patients, whereas no shrinkage was detected in 4 of 9 operated patients. No patient had tumor reexpansion during OCT-LAR treatment. Significant clinical improvement was obtained in all patients; heart rate, systolic blood pressure, and diastolic blood pressure significantly decreased in the entire population. A mild but significant increase of blood glucose levels, followed by a decrease of serum insulin levels, was observed after 3 months of treatment: this effect subsided with treatment continuation. OCT-LAR treatment was well tolerated by most patients. In conclusion, long-term treatment with OCT-LAR was effective in controlling GH and IGF-I hypersecretion in most patients with acromegaly, when applied either as primary therapy or as adjunctive therapy after surgery. Tumor shrinkage was observed in de novo patients during OCT-LAR treatment, suggesting that it can be successfully applied as primary therapy in patients bearing invasive tumors, who are less likely to be cured after surgery.

Effect of different dopaminergic agents in the treatment of acromegaly.

Medical treatment of acromegaly with dopamine agonists possesses 2 main advantages: the oral administration and the low costs. In this study, we reported on the results of chronic treatments with quinagolide (CV 205-502), cabergoline (CAB) and long-acting depot preparation of bromocriptine (BRC-LAR) in 34 acromegalics. Patients were divided into three groups on the basis of different treatment: CV 205-502 given to 16 patients at the dose of 0.3-0.6 mg/day for 6 months; CAB given to 11 patients at the dose of 1.0-2.0 mg weekly for 6 months; and BRC-LAR injected into 7 patients at the dose of 100 mg/month for 6-12 months. Basal and oral glucose tolerance test-stimulated serum GH levels, basal and TRH-stimulated PRL levels, plasma insulin-like growth factor I (IGF-I) levels, computed tomography scan, and/or magnetic resonance imaging were assessed before and quarterly during treatments. The chronic administration of CV 205-502, CAB, and BRC-LAR caused a significant decrease of circulating GH, IGF-I, and PRL levels (P < 0.005). Normalization of circulating GH and IGF-I levels was obtained in 7 of 16 (43.8%) patients treated with CV 205-502. Serum GH response to oral glucose tolerance test (oGTT) significantly improved (P < 0.005), and PRL levels were significantly suppressed during treatments. No correlation was found between basal and TRH-stimulated PRL levels and GH suppression during different therapies. Immunohistochemical staining revealed 19 GH-positive and 10 GH + PRL-positive adenomas. A significant association was found between GH/PRL staining and responsiveness to chronic treatments (chi 2 = 7.985, P < 0.005). Three patients had significant adenoma shrinkage. Slight nausea and hypotension which spontaneously disappeared within therapy progression, were referred by 5/16 patients during CV 205-502 and 2/7 during BRC-LAR. The results of this study indicate that CAB and BRC-LAR cannot be considered as useful medical approaches for acromegalics, whereas CV 205-502 normalized circulating GH and IGF-I levels in 47.8% of patients.

Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patients.

To investigate whether previous treatment with bromocriptine (BRC) or quinagolide (CV) impairs a subsequent response to long-term cabergoline (CAB) treatment, we prospectively studied 110 patients with macroprolactinoma. Four groups of patients were considered: 1) naive: 26 untreated patients with a mean serum PRL levels of 1013.4 +/- 277.7 microg/L (+/- SEM; range, 185.5-5611 microg/L); 2) intolerant: 19 patients previously shown to be intolerant of BRC treatment with a mean serum PRL level of 539.4 +/- 172.2 microg/L (range, 174-3564 microg/L); 3) resistant: 37 patients shown to be resistant/hyporesponsive to BRC, CV, or both, with a mean serum PRL level of 602.6 +/- 136.8 microg/L (range, 148-3511 microg/L); and 4) responsive: 28 patients previously treated with BRC or CV for 1-5 yr, achieving normoprolactinemia and restoration of gonadal function, but no longer treated with BRC or CV because of poor compliance or because the drug was not available. After a 15- to 30-day washout period, the serum PRL level was 397 +/- 43.1 microg/L (140-978 microg/L). CAB treatment was given at doses ranging 0.25-3.5 mg weekly for 1 yr to 110 patients, for 2 yr to 104 patients, and for 3 yr to 81 patients. Magnetic resonance imaging was performed before and after 12, 24, and 36 months of CAB treatment to evaluate significant tumor shrinkage (>80% reduction of pretreatment tumor volume). Among the 26 naive patients, normoprolactinemia was achieved in 21 (80.8%) after 1-6 months at 0.25-2 mg/week and in 5 patients after 24 months at 0.5-3 mg/week. Tumor volume was reduced from 1431.5 +/- 310.3 to 47.2 +/- 21.5 mm3 (P < 0.0001); average tumor shrinkage was 92.1 +/- 2.9%; significant tumor shrinkage was observed in 92.3% of patients, and tumor mass completely disappeared in 16 patients (61.5%). Among the 19 intolerant patients, normoprolactinemia was achieved in 18 (94.7%) after 1-6 months of CAB treatment at 0.25-1 mg/week. One patient remained mildly hyperprolactinemic. Tumor volume was reduced from 1925 +/- 423.1 to 842.0 +/- 330.7 mm3 (P < 0.001); average tumor shrinkage was 66.2 +/- 6.4%; significant tumor shrinkage was obtained in 42.1% of patients, and tumor mass completely disappeared in 4 patients (21%). Among the 37 resistant patients, normoprolactinemia was achieved in 19 (51.3%) after 6-12 months at 1-2 mg/week and in the remaining 18 patients after 18-24 months at 3-3.5 mg/week. Tumor volume was reduced from 1208.0 +/- 173.7 to 471.2 +/- 87.3 mm3 (P < 0.005); average tumor shrinkage was 58.4 +/- 4.9%; significant tumor shrinkage was obtained in 10 of 33 patients (30.3%), and in no patient did tumor mass completely disappear. Among the 28 responsive patients, normoprolactinemia was achieved in 23 (82.1%) after 1-6 months at 1-2 mg/week and in 5 patients after 12 months at 3 mg/week. Tumor volume was reduced from 1351.3 +/- 181.5 to 757.1 +/- 193.6 mm3 (P < 0.01); average tumor shrinkage was 59.2 +/- 6.2%; significant tumor shrinkage was obtained in 10 of 26 patients (38.4%), and tumor mass completely disappeared in 4 patients (15.4%). Nadir PRL levels and percent tumor shrinkage during CAB treatment in naive patients were significantly lower (P < 0.001) and higher (P < 0.001), respectively, than those in the remaining three groups, and the average weekly dose of CAB in resistant patients was significantly higher (P < 0.001) than that in the remaining three groups. A significant association was found between tumor shrinkage and previous treatments (chi2 = 27.1; P < 0.0001). At the multistep correlation analysis, nadir PRL levels were the strongest predictors of tumor shrinkage (r2 = 0.556; P < 0.0001), followed by CAB dose (r2 = 0.577; P < 0.0001). The tolerability was excellent in 105 patients (95.4%). In conclusion, the prevalence of macroprolactinoma shrinkage after CAB treatment at standard doses for 1-3 yr was higher in naive patients (92.3%) than in intolerant (42.1%), resistant (30.3%), and responsive patients (38.4%). Thus, C

Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage.

Cabergoline (CAB), a long-lasting dopamine-agonist, specific for the D2 receptor, is effective in normalizing serum PRL levels in most patients with microprolactinoma or idiopathic hyperprolactinemia. Because few data are presently available on the effects of CAB treatment in macroprolactinomas, the aim of this open-label study was to investigate whether this drug was effective in producing tumor shrinkage, as well as in normalizing PRL levels. Twenty-three patients with macroprolactinoma entered this study 15 patients had had no treatment, whereas the remaining 8 patients had been previously treated with bromocriptine, which was with-drawn because of intolerance. Three of 23 patients had undergone unsuccessful surgery. Pretreatment serum PRL levels ranged from 100-3860 micrograms/L. CAB was administered at a dose of 0.5-3 mg once or twice a week for 12-24 months. Magnetic resonance imaging (MRI) scans were performed before and 3, 6, 12, and 24 months after the beginning of treatment, to evaluate tumor shrinkage, defined as a decrease of at least 80% of baseline tumor volume. After 3-6 months of treatment with a low dose (0.5-1 mg/week), serum PRL levels normalized in 18 patients. In the remaining 5 patients, whose serum PRL levels were not normalized, the dose was increased to 2-3 mg/week. This schedule caused the normalization of PRL levels in 1 patient, whereas in the remaining 4 patients, PRL levels were reduced to 30-82 micrograms/L. A tumor volume reduction greater than 80% at MRI occurred in 14 of 23 patients (61%) after CAB treatment (from 2609.4 +/- 534.7 to 530.1 +/- 141.3 mm3 at the 12-24th month follow-up, P < 0.001). A volume reduction of 41.8 +/- 3.4% was already evident after 3 months (1436 +/- 285.9 mm3; P < 0.001). The complete disappearance of the tumor mass at MRI occurred after 6 months of treatment with CAB in 1 patient, and in 5 patients after 1 yr of treatment. An improvement of visual field defects was obtained in 9 of the 10 patients presenting visual impairment before CAB treatment. The drug was tolerated well by all patients. Only 1 patient experienced mild nausea, which disappeared spontaneously after the 2nd day of treatment. Long-term, a low dose of the D2 receptor agonist CAB significantly reduced tumor volume and normalized serum PRL levels in a great majority of patients bearing macroprolactinoma. This treatment met with excellent patient compliance. This study suggests that CAB can be used as a first choice drug treatment in macroprolactinomas, as already shown for microprolactinomas and idiopathic hyperprolactinemia.

A large false aneurysm of the right ventricle within a giant epicardial lipoma.

Lipomas, which account for approximately 10% of all neoplasms of the heart, may be detected in asymptomatic patients by chance during echocardiography, CT scan, or MRI scan. Occasionally, lipomas are complicated by arrhythmias. We describe a patient who presented with severe cardiomegaly and paroxysmal supraventricular tachycardia. An MRI scan showed a large intrapericardial lipoma with two large cavities inside communicating with each other and with the right ventricular chamber through a defect of the right ventricular wall. The mass was partially removed, and the right ventricle was patched. Surgery combined with antiarrhythmic therapy resulted in a good short-term result.

Development of a transposon mutagenesis system for Mycobacterium avium subsp. paratuberculosis.

Mycobacterium avium subspecies paratuberculosis, a slow-growing Mycobacterium, is the causative agent of Johne's disease. Although M. paratuberculosis is difficult to manipulate genetically, our laboratory has recently demonstrated the ability to introduce DNA into these bacteria by transformation and phage infection. In the current study we develop the first transposon mutagenesis system for M. paratuberculosis using the conditionally replicating mycobacteriophage phAE94 to introduce the mycobacterial transposon Tn5367. Southern blotting and sequence analysis demonstrated that the transposon insertion sites are distributed relatively randomly throughout the M. paratuberculosis genome. We constructed a comprehensive bank of 5620 insertion mutants using this transposon. The transposition frequency obtained using this delivery system was 1.0 x 10(-6) transposition events per recipient cell. Auxotrophic mutants were observed in this library at a frequency of 0.3%.

Plasma lipids and desogestrel and ethinyl estradiol: a meta-analysis.

OBJECTIVE: To review the literature to determine the magnitude of the effect of 150 micrograms desogestrel-30 micrograms ethinyl E2, an oral contraceptive (OC) formulation, on plasma lipid concentrations in healthy women using meta-analysis techniques. DATA SOURCES: All English-language published reports (1981 to 1991) on lipid parameters in women taking 150 micrograms desogestrel and 30 micrograms ethinyl E2 for up to 6 months obtained via an Embase database search and via a subsequent review of the reference lists. METHODS OF STUDY SELECTION: Of 98 articles, 18 met eligibility criteria and were included in the meta-analysis. DATA EXTRACTION AND SYNTHESIS: Data on total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were extracted. The change in each parameter from baseline to cycle 6 was estimated as a weighted mean of changes reported in each study; a standard error of the estimate was calculated. This procedure was validated by goodness-of-fit tests. RESULTS: The following statistically significant changes from baseline to cycle 6 were estimated (mean +/- SE): HDL-C: 0.15 +/- 0.02 mmol/L (5.80 +/- 0.62 mg/dL); triglycerides: 0.28 +/- 0.03 mmol/L (24.49 +/- 2.59 mg/dL); and LDL: - 0.12 +/- 0.04 mmol/L (-4.53 +/- 1.55 mg/dL). There was a nonsignificant trend toward an increase in total cholesterol. CONCLUSION: When given in combination with 30 micrograms ethinyl E2, desogestrel increased HDL-C and triglycerides and decreased LDL-C. The positive impact on HDL-C and LDL-C suggests that a potential cardioprotective benefit (rather than an atherosclerosis risk) may occur with prolonged use of such an OC, but this hypothesis will be difficult to prove.

Perfusion- and BOLD-based fMRI in the study of a human pathological model for task-related flow reductions.

In the present work, an arteriovenous malformation was taken as a pathological model for studying task-related flow decreases during a motor task. Combined Blood Oxygen Level Dependent (BOLD)-perfusion experiments were applied in order to evaluate the relative sensitivity of these techniques to task-related reductions in cerebral blood flow (CBF). Results shows that, by matching the sensitivity of the methods (which exhibit a different contrast-to-noise ratio) in the primary motor cortex, the spatial extent of the regions of decreased perfusion signal is larger than those of the BOLD signal reduction. The above finding suggests that perfusion imaging, that already represents a gold standard method in the detection of vascular phenomena, may estimate task-related flow decreases in a functional time-series better than BOLD.

Intracranial meningiomas: correlations between MR imaging and histology.

The authors have examined the relationship between magnetic resonance imaging (MRI) and histopathological features in 35 surgically verified intracranial meningiomas. Tumor signals on T1-weighted images were rather similar regardless of the histologic subtype of the tumors. On T2-weighted images, hypointense meningiomas were mainly fibroblastic and hyperintense tumors were mainly syncytial and angioblastic, and partly transitional. Isointense tumors were mainly transitional and partly fibroblastic and syncytial. The authors conclude that the signal intensity of the MRI may be useful in the preoperative characterization of intracranial meningiomas. T1-weighted images may predict the presence of cysts and intratumoral blood vessels; whereas T2-weighted images can give information about histological subtype, vascularity and consistency. Meningiomas hyperintense to the cortex on T2 are usually soft, more vascular and more frequently of syncytial or angioblastic subtype; tumors hypointense or hypo-isointense on T2 tend to have a more hard consistency and are more often of fibroblastic or transitional subtype.

High field functional MRI.

Functional magnetic resonance imaging (fMRI) has become the most widely used approach for studying brain functions in humans. The rapid and widespread diffusion of fMRI has been favoured by the properties this technique presents, and particularly by its sensitivity in analysing brain functional phenomena and by the lack of biological invasiveness, resulting in an unprecedented and unparalleled flexibility of use. These properties of fMRI brought the functional examination of the brain within the reach of the whole neuroscience community and have appreciably stimulated the research on the functional processes of the living brain. Among the main features of fMRI, its spatial and temporal resolution represents clear advantages compared with the other methods of functional neuroimaging. In fact, the high spatial resolution of fMRI permits to produce more precise and better localised information, and its temporal resolution provides the potential of a better understanding of neural dynamics at the level of single functional areas and of the neural constituents of functional patterns. A fundamental possibility of improving spatial and temporal resolution without excessively degrading signal-to-noise ratio consists in the use of high magnetic field intensity fMRI units. Besides, high field units make the use of more demanding fMRI paradigms, like single trial event related studies, much more compatible with the need of a solid statistical evaluation. This has notably promoted the diffusion of high field MRI units for human studies throughout the world, with very high field MRI units, up to 8 T, working in a few research centres, and a larger number of MRI units with field intensity ranging between 3 and 5 T.