Stimulus Generalization in Mice during Pavlovian Eyeblink Conditioning.

Here, we investigate stimulus generalization in a cerebellar learning paradigm, called eyeblink conditioning. Mice were conditioned to close their eyes in response to a 10-kHz tone by repeatedly pairing this tone with an air puff to the eye 250 ms after tone onset. After 10 consecutive days of training, when mice showed reliable conditioned eyelid responses to the 10-kHz tone, we started to expose them to tones with other frequencies, ranging from 2 to 20 kHz. We found that mice had a strong generalization gradient, whereby the probability and amplitude of conditioned eyelid responses gradually decreases depending on the dissimilarity with the 10-kHz tone. Tones with frequencies closest to 10 kHz evoked the most and largest conditioned eyelid responses and each step away from the 10-kHz tone resulted in fewer and smaller conditioned responses (CRs). In addition, we found that tones with lower frequencies resulted in CRs that peaked earlier after tone onset compared with those to tones with higher frequencies. Together, our data show prominent generalization patterns in cerebellar learning. Since the known function of cerebellum is rapidly expanding from pure motor control to domains that include cognition, reward-learning, fear-learning, social function, and even addiction, our data imply generalization controlled by cerebellum in all these domains.

In vivo 3 T MR diffusion tensor imaging for detection of the fibre architecture of the human uterus: a feasibility and quantitative study.

OBJECTIVE: The aim of this study was to investigate the feasibility of depicting fibre architecture of human uteri in vivo using 3 T MR diffusion tensor imaging (MR-DTI) with a three-dimensional (3D) tractography approach. Quantitative results were provided. METHODS: In vivo 3 T MR-DTI was performed on 30 volunteers (9 Caesarean delivery). Main diffusion directions reflecting the fibre orientation were determined using sensitivity-encoding single-shot echo planar imaging with diffusion-sensitised gradients (b=600 mm(2) s(-1)) along 32 directions. A deterministic fibre-tracking algorithm was used to show in vivo fibre architecture, compared with ex vivo histological slides of cadaveric uteri. The number of fibres, the fibre density, the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were measured in 13 volunteers. RESULTS: Anisotropy was found in most regions of normal uteri and the preferential order of uterine fibres depicted, consisting of two representative fibre directions: circular and longitudinal, as in ex vivo studies. Two-thirds of uteri with a Caesarean scar did not have the same orientation of fibres in the anterior isthmus when compared with non-scarred myometrium. Quantitative data were obtained from 13 volunteers: Caesarean-scarred uteri (n=5) showed lower fibre number and density in the scarred anterior isthmus than the nulliparous uteri (n=8). No significant differences were found in FA (0.42 ± 0.02, 0.41 ± 0.02; p=0.25) and ADC (1.82 ± 0.18 × 10(-3) mm(2) s(-1), 1.93 ± 0.25 × 10(-3) mm(2) s(-1); p=0.20). CONCLUSION: Fibre architecture of the human uterus can be depicted in vivo using 3 T MR-DTI. Advances in knowledge 3 T MR-DTI can help to provide an in vivo insight of uterine anatomy non-invasively, especially in females with previous Caesarean surgery, in order to provide better management of subsequent deliveries.

Role of diffusion-weighted magnetic resonance imaging in prostate cancer evaluation.

PURPOSE: The authors analysed the role of diffusion-weighted imaging (DWI) as an additional tool in magnetic resonance (MR) evaluation of prostate cancer. MATERIALS AND METHODS: Forty-one patients with suspected prostate cancer underwent MR imaging (1.5 Tesla). A DWI sequence was added to the standard morphological protocol, with a maximum b value of 1,000 s/mm(2). Diffusion maps were obtained, and the apparent diffusion coefficient (ADC) was calculated by drawing a region of interest (ROI) over healthy tissue and areas suspicious for malignancy. Histology was considered the gold standard. RESULTS: The areas correctly classified by MR imaging (42/51) had a low signal intensity on T2-weighted imaging and low ADC value (0.99 ± 0.15 mm(2)/s; p<0.01) compared with the healthy peripheral zone (PZ) (1.73 ± 0.27 mm(2)/s; p<0.01). Nine areas classified as suspicious for malignancy on T2-weighted sequences showed high ADC (1.44 ± 0.06 mm(2)/s; p<0.01) and were confirmed to be disease free by subsequent histological examination. The accuracy of morphofunctional MR imaging was 81.6% compared with 73.7% of the morphological analysis alone. CONCLUSIONS: The addition of DWI to the standard protocol increases the overall diagnostic performance of MR imaging in detecting prostatic cancer. Thus, DWI can help the clinician determine the most appropriate management strategy for the patient.

FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer.

BACKGROUND: In patients with colorectal liver metastases (CLM) R0 resection significantly improves overall survival (OS). METHODS: In this report, we present the results of a phase II trial of FOLFOX6+bevacizumab in patients with non-optimally resectable CLM. Patients received six cycles of FOLFOX6+ five of bevacizumab. Patients not achieving resectability received six additional cycles of each. A PET-CT was performed at baseline and again within 1 month after initiating treatment. RESULTS: From September 2005 to July 2009, 21 patients were enrolled (Male/Female: 15/6; median age: 65 years). An objective response (OR) was documented in 12 cases (57.1%; complete responses (CRs): 3, partial response (PR): 9); one patient died from toxicity before surgery. Thirteen patients underwent radical surgery (61.9%). Three (23%) had a pathological CR (pCR). Six patients (46.1%) experienced minor postsurgical complications. After a median 38.8-month follow-up, the median OS was 22.5 months. Patients achieving at least 1 unit reduction in Standard uptake value (SUV)max on PET-CT had longer progression-free survival (PFS) (median PFS: 22 vs 14 months, P=0.001). CONCLUSIONS: FOLFOX6+bevacizumab does not increase postsurgical complications, yields high rates of resectability and pCR. Early changes in PET-CT seem to be predictive of longer PFS.

Contrast-enhanced MRI and PET-CT in the evaluation of patients with suspected local recurrence of rectal carcinoma.

PURPOSE: This study aimed to evaluate the role of contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) in the assessment of local recurrence of rectal cancer. MATERIALS AND METHODS: Among 200 patients scheduled for CT follow-up, 60 (48 low risk; 12 high risk) were selected due to CT findings suspicious for or suggestive of local recurrence. Patients underwent contrast-enhanced MRI and PET-CT within 2 weeks. Biopsy was considered the gold standard in 39 cases and follow-up at 6 and 12 months in the remaining 21. RESULTS: Local recurrence was confirmed by histology in 15 cases (7 low risk; 8 high risk) and was excluded in 21 cases by long-term follow-up and in 24 by histology. Sensitivity, specificity, positive and negative predictive value and accuracy were 86.7%, 68.9%, 48.1%, 93.9% and 73.3% for contrast-enhanced MRI and 93.3%, 68.9%, 50%, 96.9% and 75% for PET-CT. CONCLUSIONS: Contrast-enhanced MRI and PET-CT can help in the detection of local recurrence of rectal cancer, even though their roles in early detection remains debatable, as the value of these techniques in current surveillance protocols is still to be defined.

Chronic total coronary occlusion in patients with intermediate viability: value of low-dose dobutamine and contrast-enhanced 3-T MRI in predicting functional recovery in patients undergoing percutaneous revascularisation with drug-eluting stent.

PURPOSE: Myocardial viability was evaluated by magnetic resonance imaging (MRI) in patients with chronic total coronary occlusion (CTO) treated with a drug-eluting stent. Change in left ventricular ejection fraction (LVEF) was analysed. MATERIALS AND METHODS: Twenty-three patients with CTO underwent delayed-enhancement (DE) and low-dose dobutamine MRI (LD). Diastolic wall thickness (DWT), dobutamine-induced systolic wall thickening (SWT) and DE transmural extension were quantitatively assessed in vessel-related segments, calculating the contribution of viable tissue to SWT, expressed as viability index (VI)=[SWTx(100 - DE)]/100. Patients with transmural enhancement were excluded from revascularisation. At 6 months follow-up, patients underwent coronary angiography (CA) and MRI. Functional recovery was defined as a 2-mm increase in SWT. RESULTS: Transmural enhancement (mean DE 62.88+/-37.18] was present in three patients. Mean DWT, SWT, VI and DE of recanalised patients were 8.03+/-2.35, 2.64+/-1.56, 1.77+/-1.48 mm and 41.97+/-30.32. Revascularisation was successful in 14/16. Follow-up CA showed patency of treated vessels. Functional recovery was achieved in 13 patients. Functional recovery showed significant correlation with SWT (beta 1,779, p=0.015), and even higher correlation with VI (beta 2.032, p=0.011). LVEF improved significantly [Delta 95% confidence interval (CI) -4.47, p=0.0203). CONCLUSIONS: Invasive CTO treatment has beneficial effects on myocardial contractility that can be predicted by VI, and on LVEF.

3-Tesla MRI for the evaluation of myocardial viability: a comparative study with 1.5-Tesla MRI.

PURPOSE: We compared 3-Tesla (3-T) and 1.5-Tesla (1.5-T) cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability in nearly identical experimental conditions. MATERIALS AND METHODS: Thirty-five patients (mean age 63+/-11; 94.2% men) submitted to primary coronary angioplasty underwent both 3-T and 1.5-T cardiac MRI, which was considered the gold standard. Comparison was performed on the basis of the same viability imaging protocol, which included resting cine-MR [balanced fast-field echo (B-FFE) sequence] followed by contrast-enhanced MR to evaluate perfusion and delayed enhancement (DE). We then performed functional index measurements and visual estimation of kinesis, perfusion and DE referring to a 5-point scale. Image quality was assessed on the basis of signal to noise ratio (SNR) and contrast to noise ratio (CNR). RESULTS: We found nonsignificant differences between the two scanners (P=NS) in measuring the functional and viability parameters. Myocardial SNR was significantly higher with 3-T MRI compared with 1.5-T MRI (61.3% gain). Even though a loss of CNR was recorded in B-FFE and in first-pass perfusion sequences (12.4% and 23.7%, respectively), on DE images, we quantified the increase of SNR and CNR of infarction of 387.8% and 330%, respectively. CONCLUSIONS: We found that 3-T MRI showed high concordance with 1.5-T MRI in the evaluation of functional and viability parameters and provided better evidence of damaged myocardium.

How to quantify infarct size on delayed-enhancement MR images: a comparison between visual and quantitative approach.

PURPOSE: Our aim was to evaluate the reliability of visual quantification of infarct extent on delayed enhanced magnetic resonance images. MATERIALS AND METHODS: Eighty patients with previous myocardial infarction underwent cine and contrast-enhanced cardiac magnetic resonance imaging. The gadolinium-enhanced images were evaluated using a segmental model with two different methods: a visual score on a 5-point scale (0 no hyperenhancement, 4 hyperenhancement>76% of myocardial wall) and a quantitative analysis based on the manual tracing of infarct contours with automatic threshold analysis. Each segment was also assigned a wall-motion score ranging from 0 (normokinesia) to 4 (dyskinesia). Statistical evaluation was performed. RESULTS: Out of 1,280 segments, 322 (25.1%) showed wall-motion abnormalities with enhancement in 327 (25.5%) evaluated with visual score and in 414 (32.3%) quantitatively. Among segments with normal or mild hypokinesia, 89.2% had a delayed-enhancement scoreor=3. Mean time required for the visual and quantitative approach was 7+/-3 and 18+/-9 min, respectively. There was strong agreement between the visual and quantitative method (k=0.92; p<0.01). CONCLUSIONS: Visual analysis of delayed enhancement is a timesaving approach that is sufficient to assess the transmural extent of infarction. Moreover, it has high correlation with wall-motion abnormalities.

Treatment retention and birth outcomes of crack users enrolled in a substance abuse treatment program for pregnant women.

This study examined characteristics of pregnant crack users that were associated with their retention in a residential treatment program and the outcomes of their pregnancies. The participant characteristics were assessed when the women were admitted to the program, and were related to their demographic status, physical health, psychological functioning, substance use, and pregnancy. In general, the findings point to the importance of early interventions with this population. Implications and limitations of this study, as well as suggestions for future research, are discussed.

Maternal serum markers. Estimation of the risk of Down's syndrome: a prospective study.

The risk of Down's syndrome pregnancies can be estimated by quantitation of maternal serum markers, namely alpha-fetoprotein, unconjugated estriol and human chorionic gonadotropin (triple test). A prospective study of 2892 pregnant women (median age 33.5 years) is reported. The detection rate of Down's syndrome pregnancies was 80% (confidence intervals 45%-100%) when a risk of 1:380 or greater was considered "screen positive", the false positive rate was 13.3% (confidence intervals 12.0%-14.5%). The importance of the accurate assessment of gestational age and the time of blood sampling are emphasized. Our findings are compared with similar studies performed in other laboratories.

Chromosome 22 monosomy in a radiation-induced meningioma.

We report for the first time on the cytogenetics of a radiation-induced meningioma, in a patient without neurofibromatosis. Chromosome 22 monosomy was found in more than 50% of the cells examined. These findings seem to suggest that the same kind of chromosomal aberrations are found in both "idiopathic" and radiation-induced meningiomas and that a common etiopathogenetic mechanism might be at work in meningiomas of whatever origin.

Comparison between monocomponent human insulin U-40 and U-100 in CSII treatment of type 1 diabetics.

A multicentric study has been carried out to compare the efficacy and the safety of monocomponent human insulins of different concentration (Novo Actrapid HM U-40 and U-100) in CSII-treated Type 1 diabetics. 15 males, all of whom had been diabetic for at least 2 yr, had been treated by CSII and were skillful in the self-monitoring of diabetes were selected for observation at 3 different clinical centres (Bologna, Chieti and Torino). After a 1-week period of insulin dose optimization, the patients were asked not to modify either basal or pre-prandial insulin infusion during the following 2 weeks in which they were treated alternately by U-40 or by U-100 insulin (7 days for each treatment in random sequence). Each day or at least every other day, patients recorded at home a 9-point blood glucose profile by means of glucose-sensitive strips and photometric reading (Reflocheck System-BOEHRINGER MANNHEIM, FRG). The patients used the microinfuser Miles Microjet Bolus 2 for the U-40 infusion and the same model with appropriate modifications for the U-100 infusion. On the last day of each study period, blood samples were drawn after the pre-breakfast insulin bolus. Paired Student's t-test analyses between blood glucose values obtained with different regimens did not show a significant difference in metabolic control. Similarly no difference could be observed in insulin absorption after an identical bolus of U-40 or U-100 insulin. In conclusion human U-100 insulin seems to be as effective and safe as U-40 and is recommended in order to reduce the size of microinfusers.

Influence of physical training on blood glucose control, glucose tolerance, insulin secretion, and insulin action in non-insulin-dependent diabetic patients.

This study has been designed to investigate, in five non-insulin-dependent diabetic patients, the influence of physical training (1 h a day, 7 days a wk for 6 wk, at 50-60% maximum oxygen uptake) on blood glucose control, glucose tolerance, insulin secretion, and insulin action. Physical training resulted in a significant improvement in blood glucose control, glucose tolerance, and insulin action. These results suggest that short-term intense physical training ameliorates the main metabolic derangements of non-insulin-dependent diabetes mellitus.