Growing Region Segmentation Software (GRES) for quantitative magnetic resonance imaging of multiple sclerosis: intra- and inter-observer agreement variability: a comparison with manual contouring method

Lesion area measurement in multiple sclerosis (MS) is one of the key points in evaluating the natural history and in monitoring the efficacy of treatments. This study was performed to check the intra- and inter-observer agreement variability of a locally developed Growing Region Segmentation Software (GRES), comparing them to those obtained using manual contouring (MC). From routine 1.5-T MRI study of clinically definite multiple sclerosis patients, 36 lesions seen on proton-density-weighted images (PDWI) and 36 enhancing lesion on Gd-DTPA-BMA-enhanced T1-weighted images (Gd-T1WI) were randomly chosen and were evaluated by three observers. The mean range of lesion size was 9.9-536.0 mm(2) on PDWI and 3.6-57.2 mm(2) on Gd-T1WI. The median intra- and inter-observer agreement were, respectively, 97.1 and 90.0% using GRES on PDWI, 81.0 and 70.0% using MC on PDWI, 88.8 and 80.0% using GRES on Gd-T1WI, and 85.8 and 70.0% using MC on Gd-T1WI. The intra- and inter-observer agreements were significantly greater for GRES compared with MC ( P<0.0001 and P=0.0023, respectively) for PDWI, while no difference was found between GRES an MC for Gd-T1WI. The intra-observer variability for GRES was significantly lower on both PDWI ( P=0.0001) and Gd-T1WI ( P=0.0067), whereas for MC the same result was found only for PDWI ( P=0.0147). These data indicate that GRES reduces both the intra- and the inter-observer variability in assessing the area of MS lesions on PDWI and may prove useful in multicentre studies.     

Local staging of pancreatic carcinoma with multi-detector row CT: use of curved planar reformations initial experience

PURPOSE: To evaluate the utility of curved planar reformations compared with standard transverse images in the assessment of pancreatic tumors. MATERIALS AND METHODS: Forty-three patients suspected of having pancreatic tumors underwent contrast material-enhanced biphasic multi-detector row computed tomography (CT). Curved planar reformations were generated along the pancreatic duct, common bile duct, and major mesenteric vessels. Three blinded independent readers assessed the curved planar reformations and transverse images separately for the presence of tumor, resectability, and vascular involvement. The results were compared with those of a consensus panel who evaluated the curved planar reformations and transverse images together along with clinical data and surgical findings. RESULTS: Of 43 patients, 20 had pancreatic malignancies as judged by the consensus panel and proven at biopsy and/or clinical follow-up. For tumor detection, transverse images and curved planar reformations had an average sensitivity of 95.0% and 98.4% (P >.05), respectively, and an average specificity of 90.9% and 91.3% (P >.05), respectively. For tumor resectability, transverse images and curved planar reformations had an average sensitivity of 85.7% and 71.4% (P >.05), respectively, and an average specificity of 85.2% and 84.3% (P >.05), respectively. Average interpretation time was 6.4 minutes with transverse images and 4.1 minutes with curved planar reformations. CONCLUSION: Curved planar reformations are equivalent to transverse images in the detection of pancreatic tumors and determination of surgical resectability.     

Lateral parabrachial lesions disrupt paraoxon-induced conditioned flavor avoidance.

Preliminary clinical evidence obtained in Gulf War veterans and patients suffering multiple chemical sensitivity points to the existence of a potential link between environmental exposure to organosphosphates (OPs) and the emergence of unspecific sickness syndromes in which associative Pavlovian conditioning might be partly involved. A laboratory animal model might be a useful tool for analyzing the involvement of conditioning in sickness syndromes potentially linked to OP poisoning. The first objective in the present study was to determine if paraoxon (PX), the neuroactive metabolite of the OP parathion, elicits a conditioned avoidance response to a novel stimulus (a taste-odor compound) in a conditioned flavor aversion procedure. Data obtained in Experiment 1 show conditioned flavor avoidance, demonstrative of the associative nature of the sickness properties of PX. The second objective was to characterize the nature of the specific physiological cue serving as the unconditioned stimulus in PX-induced conditioned avoidance. Despite PX administration did induce cholinergic hyperactivity, as measured by body hypothermia and increased jaw movements, lesions of the lateral parabrachial area (lPB) disrupted PX-elicited flavor avoidance responses, indicating that cholinergic signs were not sufficient as unconditioned stimuli supporting avoidance responses. Given that lPB neural integrity is necessary to process aversive interoceptive information, disruption of conditioned flavor avoidance as a result of lPB lesions is consistent with a central interruption of interoceptive processing in PX-poisoned animals. Data are discussed under the light of the hypothesis claiming the importance of associative processes and noncholinesterase targets in sickness syndromes potentially induced by OP exposure.     

Irinotecan (CPT-11) as first-line monotherapy in patients with advanced, metastatic colorectal cancer refractory to 5-fluorouracil adjuvant chemotherapy: a multicenter phase II study

Irinotecan (CPT-11) is active against colorectal cancer (CRC) refractory to 5-fluorouracil. Further information is needed to confirm whether CPT-11 monotherapy is more effective against tumors than 5-FU monotherapy or if there is cross-resistance of CPT-11 with 5-FU. This study assessed the efficacy and toxicity of CPT-11 350 mg/m² iv, once every 3 weeks, in patients with unsuccessfully pretreated advanced CRC. Thirty-two patients were enrolled and overall 152 cycles were administered. The total objective response rate was 17.9% and the disease stabilized in 11 patients (39.3%). Median time to progression was 3.8 months and me-dian survival was 8.2 months. Grade 3/4 diarrhea was observed in 9 cycles (5.9%) and 6 patients (18.8%), and grade 3/4 neutropenia in 5 cycles (3.3%) and 4 patients (12.5%). CPT-11 monotherapy is an active and well-tolerated first-line chemotherapy for CRC in 5-FU pretreated patients.     

Influence of initial neck node biopsy on the incidence of recurrence in the neck and survival in patients who subsequently undergo curative resectional surgery

During a period of 23 years, 57 patients who had an initial neck node biopsy elsewhere, with the diagnosis of metastatic squamous cell carcinoma established, underwent curative resection by our department after the site of head and neck primary was found. Ten patients free of disease died of other causes, leaving 47 patients who were eligible for at least 3 years of follow-up. Nineteen patients are aliye after 3 or more years. The incidence of recurrence in the neck was 57% (27/47). The 3-year survival in this group of Stage III was 40% (19/47) and 5-year survival was 34% (16/47). Compared with historical data, it appears from the present study that a previous biopsy of a neck node did not adversely affect the incidence either of neck recurrence or survival when appropriate surgery is performed.     

Manometric study of the anal sphincter during haemorrhoidectomy using posterior perineal block

Minor anorectal diseases affect 4-5% of the adult western population. Operations are performed on an ambulatory or 24-hour-stay basis. The aim of our study was to assess the physiology of anal sphincter relaxation by anal manometry after posterior perineal block during haemorrhoidectomy. We recruited 15 patients with third and fourth degree hemorrhoids in a manometric study of the anal sphincter during haemorrhoidectomy with regional anaesthesia. The patients underwent anal manometry before and 15 minutes after the posterior perineal block to determine the resting and squeeze anal pressures. Differences were considered significant at p < 0.05. We observed mean reductions of 34.6% and 37.1% in resting and squeeze pressure values, respectively, after posterior perineal block (p < 0.005). Our manometric study demonstrated that anal sphincter relaxation after posterior perineal block correlates with a significant reduction in resting and squeeze pressures because the block anaesthesia not only the somatic, but also the sympathetic fibres. We believe that posterior perineal block allows the surgeon to perform radical haemorrhoidectomy in the overnight stay setting with optimal intra- and postoperative analgesia, safe sphincter relaxation, lower postoperative complications, and lower costs to the public health service.     

Spread of T lymphocyte immune responses to myelin epitopes with duration of multiple sclerosis

Although the primary cause of multiple sclerosis (MS) is unclear, evidence supports a role for autoimmune attack of myelin by T lymphocytes. However, it has been difficult to relate patterns of autoimmunity to pathogenesis. In mouse models, the case has been made for relapsing and remitting disease driven by epitope spread: an initial lesion leads to presentation of central nervous system antigens, in turn triggering the next wave of autoimmune T cells of different specificity, the response thus broadening. Few studies have been done to determine whether these events could be important over the longer time scale of human disease. We compared T cell responses with a panel of myelin epitopes in clinically isolated syndrome patients with a first attack, patients with MS with a mean disease duration of 0.95 years, and patients with MS having a mean disease duration of 15.9 years. T cells from patients with long-term disease recognize more myelin epitopes than patients with recent-onset disease. The epitope myelin basic protein 131-149, in particular, was more commonly recognized by patients with long-term disease. The data support the notion that the T cell response in MS broadens with time and is thus implicated in the ongoing pathogenic process. However, there was no clear correlation between disease severity and number of epitopes recognized. This may argue against a simple causal role of epitope spread in driving progression, as has been suggested in experimental allergic encephalomyelitis.     

Paradoxical CD4+ T-cell decline in HIV-infected patients with complete virus suppression taking tenofovir and didanosine

BACKGROUND: Tenofovir (TDF) and didanosine (ddI) are both adenosine analogues with convenient posology, strong potency and a relatively high genetic barrier for resistance. The popularity of this combination, however, has been questioned due to concerns about pharmacokinetic interactions and increased risk of pancreatitis and hyperglycemia. Less information is available about other possible side effects. PATIENTS AND METHODS: HIV-infected individuals who initiated a protease inhibitor-sparing regimen between September 2002 and June 2003 at five hospitals, and had at least one subsequent visit within the next 12 months, always with complete virus suppression, were retrospectively assessed. Only drug-naive individuals and patients who simplified a prior successful antiretroviral regimen were analysed. RESULTS: Outcomes were analysed in 570 individuals according to treatment modality (98 drug-naive versus 472 simplified); the nucleoside analogue (NA) backbone (298 with TDF + ddI, 88 with ddI, 44 with TDF, and 140 with neither ddI nor TDF); and the third agent used (378 with non-nucleoside analogues versus 192 with NA). Significant CD4+ T-cell declines were seen in patients taking ddI + TDF with respect to all other NA combinations, including ddI or TDF separately. Patients exposed to high ddI doses or taking a third NA showed more pronounced CD4 declines. Plasma levels of ddI correlated with the extent of CD4+ T-cell loss. CONCLUSION: Patients receiving ddI + TDF-based combinations show CD4+ T-cell declines despite achieving complete virus suppression. This effect generally progresses with time. An imbalance in adenosine metabolites within CD4+ T lymphocytes may explain this phenomenon, which resembles the genetic purine nucleoside phosphorylase deficiency syndrome.     

Dilated perivascular spaces: hallmarks of mild traumatic brain injury

BACKGROUND AND PURPOSE: Recent animal and human studies have shown an increased frequency of enlarged, high-convexity Virchow-Robin spaces (VRS) in several neurologic diseases, suggesting their role as neuroradiologic markers of inflammatory changes. The aim of this study was to determine the prevalence of high-convexity dilated VRS in mild traumatic brain injury (TBI). METHODS: T2-weighted, T1-weighted, fluid-attenuated inversion recovery, and T2*-weighted gradient-echo brain MR images were acquired in 24 patients with TBI (10 women, 14 men; mean age, 33.6; range, 18.1-50.8 years) and 17 age- and sex-matched healthy control subjects (nine women, eight men; mean age, 32.8; range, 18.4-47.8 years). The mean interval after TBI was 3.6 days (range, 1-9 days) in 15 patients and 3.7 years (range, 0.6-13.4 years) in nine patients. Axial T2-weighted images were used to identify dilated VRS and to measure CSF volume; T1-weighted images were used to measure brain volume. Dilated VRS were identified as punctuate areas with CSF-like signal intensity in the high-convexity white matter. RESULTS: Mean (+/- standard deviation) number of VRS was significantly higher in patients (7.1 +/- 4.6) than in controls (3.0 +/- 3.0, P = 0.002) [corrected] In controls, VRS were associated with age (R = 0.69, P < .001) whereas in patients, they neither correlated with brain and CSF volumes nor with age and the elapsed time from injury. CONCLUSION: Our results suggest that the increased number of dilated VRS is a radiologic marker of mild head injury that is readily detectable on T2-weighted images. Because their number does not vary with time from injury, VRS probably reflect early and permanent brain changes.