Premature infants exhibit neurodevelopmental delay and reduced growth of the cerebral cortex. However, the underlying mechanisms have remained elusive. Therefore, we hypothesized that neurogenesis in the ventricular and subventricular zones of the cerebral cortex would continue in the third trimester of pregnancy, and that preterm birth would suppress neurogenesis. To test our hypotheses, we evaluated autopsy materials from human fetuses and preterm infants of 16–35 gestational weeks (gw). We noted that both cycling and non-cycling Sox2+ radial glial cells as well as Tbr2+ intermediate progenitors were abundant in human preterm infants until 28 gw. However, their densities consistently decreased from 16 through 28 gw. To determine the effect of premature birth on neurogenesis, we employed a rabbit model and compared preterm (E29, 3 days old) and term pups (E32, <2h age) at an equivalent post-conceptional age. Glutamatergic neurogenesis was suppressed in preterm rabbits, as indicated by reduced number of Tbr2+ intermediate progenitors and increased number of Sox2+ radial glia. Additionally, hypoxia inducible factor-1α, vascular endothelial growth factor, and erythropoietin were higher in term than preterm pups, reflecting the hypoxic intrauterine environment of just-born term pups. Proneural genes, including Pax6, Neurogenin-1 and -2, were higher in preterm rabbit pups compared to term pups. Importantly, neurogenesis and associated factors were restored in preterm pups by treatment with dimethyloxallyl glycine—a hypoxia mimetic agent. Hence, glutamatergic neurogenesis continues in the premature infants, preterm birth suppresses neurogenesis, and hypoxia-mimetic agents might restore neurogenesis, enhance cortical growth, and improve neurodevelopmental outcome of premature infants.
Background and Purpose-Prenatal glucocorticoids prevent germinal matrix hemorrhage in premature infants. The underlying mechanism, however, is elusive. Germinal matrix is enriched with angiogenic vessels exhibiting paucity of pericytes and glial fibrillary acidic protein-positive astrocyte end feet. Therefore, we asked whether glucocorticoid treatment would suppress angiogenesis and enhance periendothelial coverage by pericytes and glial fibrillary acidic protein-positive end feet in the germinal matrix microvasculature. Methods-We treated pregnant rabbits with intramuscular betamethasone and delivered pups prematurely by cesarean section at E29 (termϭ32 days). Endothelial turnover, vascular density, pericyte coverage, glial fibrillary acidic protein-positive end feet, cell death, and growth factors orchestrating angiogenesis, including vascular endothelial growth factor, angiopoietins, transforming growth factor-, and platelet-derived growth factor-B, were compared between betamethasone-treated and untreated pups. Similar comparisons were done between autopsy materials from premature infants exposed and unexposed to prenatal glucocorticoids. Results-Antenatal glucocorticoid treatment reduced endothelial proliferation, vascular density, and vascular endothelial growth factor expression in the germinal matrix of both rabbits and humans. The pericyte coverage was greater in glucocorticoid-treated rabbit pups and human infants than in controls, but not the glial fibrillary acidic protein-positive end feet coverage. Transforming growth factor-, but not angiopoietins and platelet-derived growth factor-B, were elevated in glucocorticoid-treated rabbit pups compared with controls. Betamethasone treatment induced apoptosis, neuronal degeneration, and gliosis in rabbit pups. However, there was no evidence of increased cell death in glucocorticoid-exposed human infants. Conclusions-Prenatal glucocorticoid suppresses vascular endothelial growth factor and elevates transforming growth factor- levels, which results in angiogenic inhibition, trimming of neovasculature, and enhanced pericyte coverage. These changes contribute to stabilizing the germinal matrix vasculature, thereby reducing its propensity to hemorrhage. Prenatal glucocorticoid exposure does not induce neural cell death in humans, unlike rabbits. (Stroke. 2010;41:1766-1773.)
Patient: Male, 67Final Diagnosis: Recurrent metastatic eccrine porocarcinomaSymptoms: Skin lesionMedication: —Clinical Procedure: —Specialty: DermatologyObjective:Rare diseaseBackground:Eccrine porocarcinoma, or malignant eccrine poroma, is a rare primary skin tumor that develops in the sixth and seventh decades of life, and can present as a painless and solitary nodule. Histopathology is required to confirm the diagnosis. A rare case is presented of metastatic eccrine porocarcinoma, occurring four years after surgical excision of the primary scalp tumor, and includes a review of the literature.Case Report:A 67-year-old man initially presented with a scalp lesion that was non-painful, exophytic, and pigmented. Following complete excision, histopathology confirmed the diagnosis of eccrine porocarcinoma with clear resection margins. Four years later, he presented with discrete erythematous patches and plaques, in a zosteriform distribution, in the skin of the right neck, shoulder, and chest. A biopsy and histopathology of the skin rash confirmed metastatic eccrine porocarcinoma. A positron-emission tomography-computed tomography (PETCT) scan identified areas of hypermetabolic activity, with a standardized uptake value (SUV) of 12, and an infiltrating soft tissue tumor in the right suboccipital region. Surgical resection of the suboccipital mass, followed by histopathology, confirmed metastatic eccrine porocarcinoma. During a postoperative ear, nose, and throat (ENT) examination, he was found to have metastases in the right ear canal. The patient received five cycles of chemotherapy, but later developed renal failure and eventually chose palliative care.Conclusions:A rash-like presentation of skin metastasis to the trunk and metastasis to the ear from a primary eccrine porocarcinoma is rare. Early diagnosis and adequate surgical resection are recommended to reduce patient mortality.
Lung cancer has the highest mortality of all cancers in the United States. The incidence of lung cancer with metastases to the skin varies between 1–12%, with the highest incidence seen in men. Here, we present two cases of lung cancer presenting as skin metastasis. The first patient was an 80-year-old African American male who presented to the hospital for evaluation of a right upper back mass. A few months prior to admission, he was found to have a left lung mass on CT scan of the chest, he underwent biopsy which showed poorly differentiated SCC of the lung. He also had a skin biopsy which showed poorly differentiated carcinoma in the dermis consistent with metastatic SCC. He was started on chemotherapy, but could not tolerate it. He was accepted to hospice. The second patient was a 78-year-old Hispanic female who presented to the hospital with dyspnea, and a dry cough. Upon physical examination, a 2 × 2 cm ulcerated, wart-like nodule on the right palm was noted. Subsequent CT scan of the chest showed a partial collapse of the right middle lobe. A biopsy of the hand mass revealed well-to-moderately differentiated metastatic SCC favoring lung origin. A bronchoscopy biopsy showed invasive SCC. Subsequently her condition worsened and she passed away. Metastasis to the skin is an unusual presenting symptom of lung cancer. It is therefore essential to consider metastasis as a diagnosis in a patient with both a skin lesion and a smoking history.
Granulocyte colony-stimulating factor (G-CSF) is a recombinant human glycoprotein that promotes proliferation and differentiation of granulocytic-committed progenitors. It is commonly used to treat neutropenia and is generally well tolerated. Occurrences of rare but serious adverse events in association with the use of G-CSF have been described. We report the case of a 54-year-old male with squamous cell carcinoma of the lung who developed abdominal aortitis following the use of G-CSF. Other possible aetiological conditions were excluded based on laboratory and radiological evaluations. To our knowledge, this represents the second case report demonstrating an association between aortitis and the use of G-CSF.
Patient: Male, 63Final Diagnosis: Sarcomatoid carcinoma of the lung with spine metastasisSymptoms: Back pain • coughMedication: —Clinical Procedure: Lung biopsy • laminectomySpecialty: PulmonologyObjective:Rare diseaseBackground:Sarcomatoid carcinoma is a rare, aggressive, malignant cancer composed of sarcoma and sarcoma-like components, and can occur in different organs such as the thyroid gland, bone, skin, breast, pancreas, liver, urinary tract, and lung. Pulmonary sarcomatoid carcinoma accounts for only a small percentage of lung cancers and has histological variants that include pleomorphic carcinoma, giant cell carcinoma, spindle cell carcinoma, carcinosarcoma, and pulmonary blastoma.Case Report:Here, we present a case of sarcomatoid carcinoma in a 63-year-old HIV-positive Hispanic male who presented with back pain, dry cough, and weight loss. A CT scan of his chest showed an ovoid mass in the lower lobe of the left lung, and an MRI of the spine showed a left lateral paraspinal soft tissue mass causing central canal stenosis and mild cord compression. The patient underwent laminectomy and resection of the spinal mass. A transthoracic needle biopsy of the lung and spinal masses had similar histopathology, and were indicative of sarcomatoid carcinoma.Conclusions:We report a rare case of sarcomatoid carcinoma involving both the lung and spinal cord in the same patient. Sarcomatoid carcinomas of the lung have poor prognosis and are aggressive cancers. Moreover, our case also had the co-occurrence of HIV and sarcomatoid carcinoma.
FFG and FOLFOX4 were generally well tolerated. Based on ORR, FOLFOX4 was superior to FFG. However, differences in TTP and OS comparing regimens were inconclusive. General use of gemcitabine as a biomodulator of 5-fluorouracil in CRC cannot be recommended at this time and the regimen remains investigational.
Traditionally, typographers and designers have relied on variations in the shape and form of letters and text to enhance textual meaning. It is hypothesized that animated text may be used to recreate a broader range of paralinguistic meaning and emotion than is possible with the use of static text alone. This pilot study was conducted to provide conceptual validation for the hypothesis that animated text can communicate certain emotions such as anger, sadness, happiness and fear. Animations were subjected to pre-testing and refined as needed. Subjects were tested for their understanding of the emotional content of a sample set of animated sentences. There was strong support for the animations created to measure ‘sadness’ and ‘happiness’. Findings also indicated that certain textual motions are associated with the intensity of certain emotions.
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