Clonorchis-associated cholangiocarcinoma: a report of two cases with unusual manifestations.

Two cases of Clonorchis-associated cholangiocarcinoma are described along with their cholangiographic features to illustrate the spectrum of pathology ascribed to the injurious effects of the flukes on the bile duct epithelium. This includes adenomatous hyperplasia, extensive fibrosis, and carcinoma. The first case was also complicated by hepatic abscesses, left hepatic lobar atrophy, gastrobiliary and biliarocutaneous fistulae. The second case features an unusually dilated pancreatic duct containing pancreaticoliths that was found later to consist of hyperplastic bile duct epithelium, presumably carried by worm migration in the biliary tree. Liver sections from both patients showed typical features of hepatic clonorchiasis with the cancer. A knowledge of the wide spectrum of clinical presentation of clonorchiasis, particularly cholangiocarcinoma, might aid Western physicians in averting this serious sequela through prompt eradication of the helminthic infection and early recognition and treatment of its complications.     

Unexpected Recovery of Function After Severe Traumatic Brain Injury: The Limits of Early Neuroimaging-Based Outcome Prediction

Background

Prognostication in the early stage of traumatic coma is a common challenge in the neuro-intensive care unit. We report the unexpected recovery of functional milestones (i.e., consciousness, communication, and community reintegration) in a 19-year-old man who sustained a severe traumatic brain injury. The early magnetic resonance imaging (MRI) findings, at the time, suggested a poor prognosis.

Methods

During the first year of the patient’s recovery, MRI with diffusion tensor imaging and T2*-weighted imaging was performed on day 8 (coma), day 44 (minimally conscious state), day 198 (post-traumatic confusional state), and day 366 (community reintegration). Mean apparent diffusion coefficient (ADC) and fractional anisotropy values in the corpus callosum, cerebral hemispheric white matter, and thalamus were compared with clinical assessments using the Disability Rating Scale (DRS).

Results

Extensive diffusion restriction in the corpus callosum and bihemispheric white matter was observed on day 8, with ADC values in a range typically associated with neurotoxic injury (230–400 × 10^?6 mm²/s). T2*-weighted MRI revealed widespread hemorrhagic axonal injury in the cerebral hemispheres, corpus callosum, and brainstem. Despite the presence of severe axonal injury on early MRI, the patient regained the ability to communicate and perform activities of daily living independently at 1 year post-injury (DRS = 8).

Conclusions

MRI data should be interpreted with caution when prognosticating for patients in traumatic coma. Recovery of consciousness and community reintegration are possible even when extensive traumatic axonal injury is demonstrated by early MRI.     

Glyburide is Associated with Attenuated Vasogenic Edema in Stroke Patients

Background

Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known.

Methods

Using a case–control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the glyburide advantage in malignant edema and stroke-pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 (MMP-9) plasma level in large hemispheric stroke.

Results

We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level.

Conclusions

Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial.     

Periodontal disease and upper genital tract inflammation in early spontaneous preterm birth

OBJECTIVE: To estimate the relationship between maternal periodontal disease and both early spontaneous preterm birth and selected markers of upper genital tract inflammation. METHODS: In this case-control study, periodontal assessment was performed in 59 women who experienced an early spontaneous preterm birth at less than 32 weeks of gestation, in a control population of 36 women who experienced an early indicated preterm birth at less than 32 weeks of gestation, and in 44 women with an uncomplicated birth at term (>or = 37 weeks). Periodontal disease was defined by the degree of attachment loss. Cultures of the placenta and umbilical cord blood, cord interleukin-6 levels, and histopathologic examination of the placenta were performed for all women. RESULTS: Severe periodontal disease was more common in the spontaneous preterm birth group (49%) than in the indicated preterm (25%, P =.02) and term control groups (30%, P =.045). Multivariable analyses, controlling for possible confounders, supported the association between severe periodontal disease and spontaneous preterm birth (odds ratio 3.4, 95% confidence interval 1.5-7.7). Neither histologic chorioamnionitis, a positive placental culture, nor an elevated cord plasma interleukin-6 level was significantly associated with periodontal disease (80% power to detect a 50% difference in rate of histological chorioamnionitis, alpha = 0.05). CONCLUSION: Women with early spontaneous preterm birth were more likely to have severe periodontal disease than women with indicated preterm birth or term birth. Periodontal disease was not associated with selected markers of upper genital tract inflammation. LEVEL OF EVIDENCE: II-2     

Evolution of water diffusion and anisotropy in hyperacute stroke: significant correlation between fractional anisotropy and T2

BACKGROUND AND PURPOSE: We hypothesized that, in acute cerebral ischemic stroke, anisotropic diffusion increases if T2 signal intensity is not substantially elevated and decreases once T2 hyperintensity becomes apparent. Our purpose was to correlate fractional anisotropy (FA) measurements with the clinical time of stroke onset, apparent diffusion coefficients (ADC), and T2 signal intensity. METHODS: Tensor diffusion-weighted images (DWIs) of 25 patients were obtained within 12 hours of symptom onset. Trace DWIs, ADCs, FAs, and echo-planar T2-weighted images (T2WI) were generated. Stroke and contralateral normal volumes of interest (VOIs) were outlined on DWIs and projected onto the inherently coregistered ADC map, FA map, and echo-planar T2WI. Mean signal intensity of the ischemic and contralateral normal VOIs were compared for relatives change in ADC, FA, and signal intensity on T2WIs. RESULTS: A significant negative correlation was observed between FA and T2 signal-intensity change (r = -0.61, P =.00009). A trend of correlation between FA signal intensity and time of onset were found (r = -0.438, P =.025). No significant correlation was found between ADC and FA values (r = -0.302, P =.134). The mean ADC reduction in the ipsilateral ischemic volume was 31% +/- 11 compared with the contralateral normal side. CONCLUSION: Change in FA is inversely correlated with T2 signal intensity and, to a lesser extent, the time of onset, but it is not well correlated with ADC values in the acute stage.     

Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction

OBJECTIVE: Caspase-1 plays an important functional role mediating neuronal cell death and dysfunction after experimental traumatic brain injury (TBI) in mice. Minocycline, a derivative of the antibiotic tetracycline, inhibits caspase-1 expression. This study investigates whether minocycline can ameliorate TBI-mediated injury in mice. METHODS: Brains from mice subjected to traumatic brain injury underwent immunohistochemical analyses for caspase-1, caspase-3, and a neuronal specific marker (NeuN). Minocycline- and saline-treated mice subjected to traumatic brain injury were compared with respect to neurological function, lesion volume, and interleukin-1beta production. RESULTS: Immunohistochemical analysis revealed that activated caspase-1 and caspase-3 are present in neurons 24 hours after TBI. Intraperitoneal administration of minocycline 12 hours before or 30 minutes after TBI in mice resulted in improved neurological function when compared with mice given saline control, as assessed by Rotarod performance 1 to 4 days after TBI. The lesion volume, assessed 4 days after trauma, was significantly decreased in mice treated with minocycline before or after trauma when compared with saline-treated mice. Caspase-1 activity, quantified by measuring mature interleukin-1beta production by enzyme-linked immunosorbent assay, was considerably increased in mice that underwent TBI, and this increase was significantly diminished in minocycline-treated mice. CONCLUSION: We show for the first time that caspase-1 and caspase-3 activities localize specifically within neurons after experimental brain trauma. Further, these results indicate that minocycline is an effective pharmacological agent for reducing tissue injury and neurological deficits that result from experimental TBI, likely through a caspase-1-dependent mechanism. These results provide an experimental rationale for the evaluation of minocycline in human trauma patients.