Idiopathic myointimal hyperplasia of mesenteric veins: a rare mimic of idiopathic inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood disease that occurs in the rectosigmoid colon of predominantly young, previously healthy male patients. IMHMV typically requires segmental resection due to complications after a relatively protracted clinical course. This disease presents a challenging diagnostic dilemma for the clinician because it is initially often confused with chronic idiopathic inflammatory bowel disease. We report a case of IMHMV, illustrate endoscopic and histopathologic features, and review key characteristics of this rare entity.     

Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation

Caspase-3 is a major cell death effector protease in the adult and neonatal nervous system. We found a greater number and higher density of cells in the cortex of caspase-3(-/-) adult mice, consistent with a defect in developmental cell death. Caspase-3(-/-) mice were also more resistant to ischemic stress both in vivo and in vitro. After 2 h of ischemia and 48 h of reperfusion, cortical infarct volume was reduced by 55%, and the density of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells was decreased by 36% compared with wild type. When subjected to oxygen-glucose deprivation (2 h), cortical neurons cultured from mice deficient in caspase-3 expression were also more resistant to cell death by 59%. Mutant brains showed caspase-specific poly(ADP-ribose) polymerase cleavage product (85-kDa fragment) in vivo and in vitro, suggesting redundant mechanisms and persistence of caspase-mediated cell death. In the present study, we found that caspase-8 mediated poly(ADP-ribose) polymerase cleavage in caspase-3(-/-) neurons in vivo and in vitro. In addition, mutant neurons showed no evidence of compensatory activation by caspase-6 or caspase-7 after ischemia. Taken together, these data extend the pharmacological evidence supporting an important role for caspase-3 and caspase-8 as cell death mediators in mammalian cortex and indicate the potential advantages of targeting more than a single caspase family member to treat ischemic cell injury.     

Thrombopoietin stimulates megakaryocytopoiesis, myelopoiesis, and expansion of CD34+ progenitor cells from single CD34+Thy-1+Lin- primitive progenitor cells

Thrombopoietin (TPO) or MpI ligand is known to stimulate megakaryocyte (MK) proliferation and differentiation. To identify the earliest human hematopoietic cells on which TPO acts, we cultured single CD34+Thy- 1+Lin- adult bone marrow cells in the presence of TPO alone, with TPO and interleukin-3 (IL-3), or with TPO and c-kit ligand (KL) in the presence of a murine stromal cell line (Sys1). Two distinct growth morphologies were observed: expansion of up to 200 blast cells with subsequent differentiation to large refractile CD41b+ MKs within 3 weeks or expansion to 200-10,000 blast cells, up to 25% of which expressed CD34. The latter blast cell expansions occurred over a 3- to 6-week period without obvious MK differentiation. Morphological staining, analysis of surface marker expression, and colony formation analysis revealed that these populations consisted predominantly of cells committed to the myelomonocytic lineage. The addition of IL-3 to TPO-containing cultures increased the extent of proliferation of single cells, whereas addition of KL increased the percentage of CD34+ cells among the expanding cell populations. Production of multiple colony- forming unit-MK from single CD34+Thy-1+Lin- cells in the presence of TPO was also demonstrated. In limiting dilution assays of CD34+Lin- cells, TPO was found to increase the size and frequency of cobblestone areas at 4 weeks in stromal cultures in the presence of leukemia inhibitory factor and IL-6. In stroma-free cultures, TPO activated a quiescent CD34+Lin-Rhodamine 123lo subset of primitive hematopoietic progenitor cells into cycle, without loss of CD34 expression. These data demonstrate that TPO acts directly on and supports division of cells more primitive than those committed to the MK lineage.     

Concurrent validity of the Neurobehavioural Assessment for Pre-term Infants (NAPI) at term age

Background: Accurate measurement of neonatal neurological integrity is critical for early identification of pre-term and full-term infants at-risk for developmental disability. The Neurobehavioural Assessment for Pre-term Infants (NAPI) was developed to measure the progression of neurobehavioural development in pre-term infants born between 32 weeks post-conceptional age (PCA) and term. This instrument has many unique advantages; however, criterion validity is unknown and results are subsequently difficult to interpret. Objectives: This study examined the concurrent validity of the NAPI against a criterion instrument, the Einstein Neonatal Neurobehavioural Assessment Scale (ENNAS), which measures similar constructs and has demonstrated excellent reliability and validity. Methods: A sample of 41 pre-term and full-term infants (40?±?2 weeks) was assessed with the NAPI and ENNAS on the same day. Results: The findings demonstrated that correlations between similar NAPI clusters and ENNAS clusters ranged from 0.35–0.65 and correlations between many similar individual NAPI and ENNAS items ranged from 0.40–0.60. Two NAPI clusters also discriminated between normal, abnormal and suspect performance on the ENNAS. Conclusion: The NAPI has many unique advantages as a tool. It examines neonates serially, has established weekly normative data and requires minimal infant handling. This study provides new validation of the NAPI instrument.     

Postoperative fluid collections after colon resection: the utility of clinical assessment

Background

Computed tomography (CT) scans often identify postoperative fluid collections of uncertain clinical relevance.

Methods

Consecutive adult patients undergoing colorectal resection and postoperative CT scan from January 1, 2000 to December 31, 2008, at a university teaching hospital were identified from a prospective database. A host of clinical and CT findings were recorded. Fisher's exact test and logistic regression with univariate and multivariate analysis were used to assess the predictive value of clinical and radiologic variables.

Results

Nine hundred six patients had a colon resection during the study period. Fifty-four patients had a postoperative fluid collection, of which 36 were found to be abscesses. Only high clinical suspicion of an abscess predicted the presence of an abscess (P = .009); of the radiologic criteria, only proximity to the anastomosis was predictive (P = .05).

Conclusions

Clinical judgment is superior to radiologic and individual clinical parameters. This finding has the potential to prevent many unnecessary procedures.     

Synaptic alterations in the rTg4510 mouse model of tauopathy

Synapse loss, rather than the hallmark amyloid‐β (Aβ) plaques or tau‐filled neurofibrillary tangles (NFT), is considered the most predictive pathological feature associated with cognitive status in the Alzheimer's disease (AD) brain. The role of Aβ in synapse loss is well established, but despite data linking tau to synaptic function, the role of tau in synapse loss remains largely undetermined. Here we test the hypothesis that human mutant P301L tau overexpression in a mouse model (rTg4510) will lead to age‐dependent synaptic loss and dysfunction. Using array tomography and two methods of quantification (automated, threshold‐based counting and a manual stereology‐based technique) we demonstrate that overall synapse density is maintained in the neuropil, implicating synapse loss commensurate with the cortical atrophy known to occur in this model. Multiphoton in vivo imaging reveals close to 30% loss of apical dendritic spines of individual pyramidal neurons, suggesting these cells may be particularly vulnerable to tau‐induced degeneration. Postmortem, we confirm the presence of tau in dendritic spines of rTg4510‐YFP mouse brain by array tomography. These data implicate tau‐induced loss of a subset of synapses that may be accompanied by compensatory increases in other synaptic subtypes, thereby preserving overall synapse density. Biochemical fractionation of synaptosomes from rTg4510 brain demonstrates a significant decrease in expression of several synaptic proteins, suggesting a functional deficit of remaining synapses in the rTg4510 brain. Together, these data show morphological and biochemical synaptic consequences in response to tau overexpression in the rTg4510 mouse model. J. Comp. Neurol., 521:1334–1353, 2013. © 2012 Wiley Periodicals, Inc.     

Corpora amylacea in a leiomyoma of soft tissue

A case of myxoid leiomyoma of deep soft tissue is described. The patient was a 42-year-old woman who presented with menorrhagia, and an ischiorectal mass was identified. A total hysterectomy was performed, and the mass was removed. On gross examination, the mass was 6cm x 5cm x 4cm and had a mucoid cut surface. Histologic examination revealed a myxoid leiomyoma with abundant intracellular corpora amylacea (CA). An infarcted leiomyoma was present in the hysterectomy specimen. The patient remains well, with no evidence of recurrence 3 years after surgery. Leiomyomas of deep soft tissue are rare, and, to our knowledge, none have been described containing CA.