Nutritional Supplementation Reduces Lesion Size and Neuroinflammation in a Sex-Dependent Manner in a Mouse Model of Perinatal Hypoxic-Ischemic Brain Injury

Perinatal hypoxia-ischemia (HI) is a major cause of neonatal brain injury, leading to long-term neurological impairments. Medical nutrition can be rapidly implemented in the clinic, making it a viable intervention to improve neurodevelopment after injury. The omega-3 (n-3) fatty acids docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3), uridine monophosphate (UMP) and choline have previously been shown in rodents to synergistically enhance brain phospholipids, synaptic components and cognitive performance. The objective of this study was to test the efficacy of an experimental diet containing DHA, EPA, UMP, choline, iodide, zinc, and vitamin B12 in a mouse model of perinatal HI. Male and female C57Bl/6 mice received the experimental diet or an isocaloric control diet from birth. Hypoxic ischemic encephalopathy was induced on postnatal day 9 by ligation of the right common carotid artery and systemic hypoxia. To assess the effects of the experimental diet on long-term motor and cognitive outcome, mice were subjected to a behavioral test battery. Lesion size, neuroinflammation, brain fatty acids and phospholipids were analyzed at 15 weeks after HI. The experimental diet reduced lesion size and neuroinflammation specifically in males. In both sexes, brain n-3 fatty acids were increased after receiving the experimental diet. The experimental diet also improved novel object recognition, but no significant effects on motor performance were observed. Current data indicates that early life nutritional supplementation with a combination of DHA, EPA, UMP, choline, iodide, zinc, and vitamin B12 may provide neuroprotection after perinatal HI.     

A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants

This study was carried out to assess the feasibility of late cord clamping of 45 s in preterm infants delivered mainly by caesarean section and the effects on post-partal adaptation and anaemia of prematurity. Prior to delivery, 40 infants of <33 gestational weeks were randomised to either 20 s or 45 s of late cord clamping. After the first shoulder was delivered, oxytocin was given intravenously to the mother in order to enhance placento-fetal transfusion while the infant was held below the level of the placenta. The 20 infants in group 1 (20 s) had a mean birth weight of 1070 g and a mean gestational age of 29 + 4/7 weeks versus 1190 g and 30 weeks in group 2 (45 s). On day 42 of life there were ten infants without transfusions in group 2 versus three in group 1 (P < 0.05). Out of the 20 infants in group 1, 19 and 15/19 in group 2 were delivered by caesarean section. There were no significant differences in Apgar scores, temperature on admission, heart rate, blood pressure and requirements for artificial ventilation. Conclusion Delayed cord clamping of 45 s is feasible and safe in preterm infants below 33 weeks of gestation. It is possible to perform the procedure at caesarean section deliveries and it should be performed whenever possible. It reduces the need for packed red cell transfusions during the first 6 weeks of life. Received: 10 February 2000 / Accepted: 12 April 2000     

Granular cell tumor of the penis: clinicopathologic evaluation of 9 cases

The occurrence of granular cell tumor (GCT) in penile tissue is very rare, with only 9 examples reported to date in the English-language literature. Herein, we describe the clinicopathologic and immunohistochemical findings in 9 additional cases. The patients ranged in age from 20 to 60 years (mean, 42 years; median, 40 years) at time of diagnosis. All penile tumors were solitary and arose in the dermis of the penile shaft (n=4), prepuce (n=3), and corona (n=2). A patient had a history of multiple cutaneous GCTs. Duration of symptoms before surgery ranged from 5 days to 2 years with the presence of an asymptomatic nodule representing the most common tumor-related complaint (n=8). The lesions ranged in size from 0.6 to 2.5 cm (mean, 1.5 cm; median, 1.5 cm). Microscopically, the tumors were moderate to highly cellular and were composed of oval to polygonal-shaped cells with abundant coarsely granular eosinophilic cytoplasm. Tumor cells grew in infiltrating nests, cords, and trabeculae and showed neural (n=2) and vessel wall (n=1) invasion or formed a relatively well-marginated solid nodule. Bland cytological features with only rare cells showing nucleomegaly (n=7) or spindling (n=3) were exhibited by 8 tumors. A tumor demonstrated diffuse nuclear atypia and was classified as "atypical." Mitotic activity ranged from 0 to 8 mitoses (mean, 1.4 mitoses) per 50 high-powered fields with no atypical division figures identified. All tumors tested showed moderate to strong immunohistochemical expression of S100 protein (n=6) and low-affinity nerve growth factor receptor (n=5), which was useful for detecting small deposits of tumor and helpful in evaluating surgical margins. Focal tumor cell immunoreactivity was observed for calretinin (4/6 cases) and glial fibrillary acidic protein (1/6 cases). All patients underwent simple (local) excision of their tumor. Complete follow-up data (mean, 21 years; interval range, 0.5-28 years) were available for 6 patients. No patient experienced recurrence or metastatic spread of tumor although surgical margins were microscopically involved by tumor in 5 cases. Benign GCT involving superficial soft tissue of the penis can be adequately managed by a simple excision. Patients with microscopically involved surgical margins can be clinically followed without immediate additional surgery.     

Epithelioid hemangioma of the penis: a clinicopathologic and immunohistochemical analysis of 19 cases, with special reference to exuberant examples often confused with epithelioid hemangioendothelioma and epithelioid angiosarcoma

Epithelioid hemangiomas of the penis are very rare. To date, less than 10 examples have been reported in the English language literature. In this report, we describe the clinical, histopathologic, and immunohistochemical findings in 19 cases retrieved from our files. The patients ranged in age from 23 to 75 years (median age, 45 years) at the time of initial surgical resection. Seventeen patients presented with a solitary mass, and two presented with two separate, but closely approximated, lesions. The process involved the glans penis (n = 3), shaft (n = 11), base of the penis (n = 2), or penis, not otherwise specified (n = 3). The lesions ranged in size from <0.5 to 2.5 cm (median size, approximately 1.2 cm) in greatest dimension. Eleven examples were specifically noted to be dorsally located, and only one was stated to be ventral. Localized pain or tenderness was the most common complaint, documented in 12 cases. The preoperative duration of the lesions ranged from 5 days to 1 year (median 4.5 months). Microscopically, all examples contained a tumefactive proliferation of epithelioid endothelial cells, often in a nodular or lobular configuration and associated with an inflammatory infiltrate containing lymphocytes and eosinophils. In 14 cases, the vascular proliferation was associated with a small arterial segment, sometimes with mural damage and frequently (n = 13) with intraluminal epithelioid endothelial cells. Based on the growth pattern of the epithelioid endothelial cells, 13 cases were considered "typical," and six were considered exuberant or "atypical." The latter examples had a prominent centrally located zone where nests or sheet-like aggregates of epithelioid endothelial cells did not form discrete vessels. Immunohistochemical data are available for 15 tumors. The epithelioid endothelial cells usually had strong reactivity for CD31, lesser reactivity for factor VIIIrAg, and minimal reactivity for CD34. In 9 of 12 cases, a small number of epithelioid endothelial cells expressed keratins. In all cases tested, at least focal muscle-specific actin-positive myopericytic cells were present bordering the endothelial cells, and this was especially notable peripherally. Initial surgical intervention consisted of either a shave biopsy (n = 1), excisional biopsy (n = 2), or local excision (n = 16). A complete follow-up history is available for 12 patients, and incomplete follow-up information is available for an additional four patients. One patient developed a new epithelioid hemangioma at a site within the penis separate from the initial lesion, but no patient is known to have experienced a true metastasis or to have died of complications of this process. Optimal management appears to be complete local excision with periodic follow-up visits to monitor for local recurrence.     

An fMRI study of simple ethical decision-making

Recent functional neuroimaging studies suggest that ventromedial prefrontal cortex (vmPFC), left posterior superior temporal sulcus (pSTS) and posterior cingulate cortex are engaged during moral decision-making on complex dilemmatic or salient emotional stimuli. In this fMRI study we investigated which of these brain regions are activated during simple ethical decision-making about unambiguous scenarios not containing direct bodily harm or violence. Simple moral decisions compared to semantic decisions resulted in activation of left pSTS and middle temporal gyrus, bilateral temporal poles, left lateral PFC and bilateral vmPFC. These results suggest that pSTS and vmPFC are a common neuronal substrate of decision-making about complex ethical dilemmas, processing material evocative of moral emotions and simple ethical decision-making about scenarios devoid of violence and direct bodily harm.