Atypical Presentations of Spinal Cord Tumors in Children

Pain is a frequent presenting symptom of spinal cord tumors in children and usually manifests as local spinal pain in the bony segments overlying the tumor. Two pediatric patients are presented in whom the diagnosis of intramedullary spinal cord tumors was delayed for many months because their pain was atypical. One had recurrent abdominal pain diagnosed as irritable bowel syndrome. The other had very abrupt paroxysmal but infrequent attacks of arm pain and no neurologic abnormalities. Possible mechanisms of their pain, as well as the other features that might have suggested the diagnosis, are discussed. (J Child Neurol 1992;7:360-363).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66988/2/10.1177_088307389200700405.pd

Brief Communication

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67313/2/10.1177_088307389801300308.pd

Phosphoinositide metabolism and prostacyclin formation in retinal microvascular endothelium: Stimulation by adenine nucleotides

Phosphoinositide lipid metabolism and prostacyclin production are implicated in endothelium dependent vascular relaxation in large blood vessels. To determine if these biochemical pathways might be involved in the regulation of microvascular tone in the retina, we measured the formation of 6-keto-prostaglandin-F1[alpha], the stable end product of prostacyclin, and inositol phosphates from 3H-labeled phosphoinositide lipids, in endothelial cells prepared from bovine retinal microvessels and maintained in long-term culture. We found that adenosine 5'-triphosphate and adenosine 5'-diphosphate both stimulated a dose-dependent accumulation of inositol phosphates and of 6-keto-prostaglandin-F1[alpha] in these cells. The agonist specificity of the responses, with stimulation by adenosine 5'-triphosphate and adenosine 5'-diphosphate, and inactivity of adenosine 5'-monophosphate and adenosine, suggest that they are mediated through P2 purinergic receptors. The similar early time courses of 6-keto-prostaglandin-F1[alpha] and inositol triphosphate production support the hypothesis that prostacyclin formation could result from the mobilization of intracellular calcium by inositol triphosphate, which activates phospholipase A, and thereby releases arachidonic acid to form prostacyclin. These findings point to a role for these cells in the regulation of normal retinal vascular tone. Because phosphoinositide lipid metabolism is altered in diabetes, dysfunction of these biochemical pathways in retinal endothelium could underlie the pathophysiology of diabetic retinopathy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28775/1/0000607.pd

8‐Year‐Old Boy with Progressive Headache

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99694/1/bpa12074.pd

Improved prognosis of intracranial non-germinoma germ cell tumors with multimodality therapy

The 5 year survival for patients with malignant intracranial non-germinoma germ cell tumors (NGGCT) which include endodermalsinus tumors, embryonal carcinomas, choriocarcinomas and immatureteratomas is less than 25% following a small resection and radiotherapy. In an effort to improve the survival of these patients, an approach using an attempt at radical resection wherefeasible, followed by multi-modality ’sandwich‘ therapy (chemotherapy-radiation-chemotherapy) was used to treat 18 newly diagnosed patients between 1986 and 1994 in a multi-institution study. Fourteen patients had histologically proven NGGCT andfour were presumed NGGCT because of markedly elevated concentrations of serum and/or CSF alpha fetoprotein (AFP) and/or beta human chorionic gonadatrophin (b-HCG). The primary tumor was confined to thepineal region in 12 patients, the suprasellar region in five, and acerebral hemisphere in one. None of the patients had central nervoussystem metastases at diagnosis by MRI imaging of the spine and CSF cytology. Radical surgical resection was performedinitially in 11 patients (gross total — 6, subtotal — 5);four had a biopsy and three had no surgery. All patients then received3 or 4 cycles of neoadjuvant chemotherapy with cisplatin (100 mg/m 2 /cycle) and VP-16 (500 mg/m 2 /cycle)/cycle). Of the 12 patients with evaluabledisease there were 9 responses to the neoadjuvant chemotherapy (5 CR,4 PR); 2 patients had stable disease and 1 progressed duringchemotherapy. Six patients with no evaluable disease after a grosstotal resection had a continuous complete response. Seventeen patientsreceived radiation therapy (involved field — 11, involved field + craniospinal — 4, involved field+ whole brain — 2). Twelve patients received 4 cycles post-radiation chemotherapy with vinblastine (6.5 mg/m 2 /cycle), bleomycin (15 U/m 2 /cycle),VP-16 (300 mg/m 2 /cycle, carboplatin (450 mg/m 2 /cycle). A total of four patients have died (3 — progressive/recurrent disease, 1 — metabolic). Four year actuarialevent-free and total survival rates are 67% and 74%. This multi-modality adjuvant therapy approach appears to dramatically improve the outcome of malignant intracranialNGGCT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45385/1/11060_2004_Article_110512.pd

The Role of CD 133+ Cells in a Recurrent Embryonal Tumor with Abundant Neuropil and True Rosettes ( ETANTR )

Embryonal tumor with abundant neuropil and true rosettes ( ETANTR ) is a recently described embryonal neoplasm of the central nervous system, consisting of a well‐circumscribed embryonal tumor of infancy with mixed features of ependymoblastoma (multilayer ependymoblastic rosettes and pseudorosettes) and neuroblastoma (neuroblastic rosettes) in the presence of neuropil‐like islands. We present the case of a young child with a very aggressive tumor that rapidly recurred after gross total resection, chemotherapy and radiation. Prominent vascular sclerosis and circumscribed tumor led to the diagnosis of malignant astroblastoma; however, rapid recurrence and progression of this large tumor after gross total resection prompted review of the original pathology. ETANTR is histologically distinct with focal glial fibrillary acid protein ( GFAP ) and synaptophysin expression in the presence of neuronal and ependymoblastic rosettes with focal neuropil islands. These architectural features, combined with unique chromosome 19q13.42 amplification, confirmed the diagnosis. In this report, we describe tumor stem cell ( TSC ) marker CD 133, CD 15 and nestin alterations in ETANTR before and after chemotherapy. We found that TSC marker CD 133 was richly expressed after chemotherapy in recurrent ETANTR , while CD 15 is depleted compared with that expressed in the original tumor, suggesting that CD 133+ cells likely survived initial treatment, further contributing to formation of the recurrent tumor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102077/1/bpa12079.pd

Angiogenesis in developing rat brain: An in vivo and in vitro study

Brain capillary proliferation in postnatal rats was measured in vivo by [3H]thymidine autoradiography. Maximal capillary proliferation occurred between 5 and 9 postnatal days, and was 40 times greater than in the adult. To test the hypothesis that soluble angiogenesis factors play a role in this developmental vascularization of brain, we prepared extracts from the brains of 6-day-old rats at the peak of proliferative activity, and from adults when it was lowest. We assayed them using an in vitro growth system measuring [3H]thymidine incorporation into cultured brain capillary endothelial cells. Extracts prepared from either 6-day or adult rats and containing 150 [mu]g/ml protein caused more than a 4-fold stimulation of the endothelial cells, increasing to 8-fold at a concentration of 1500 [mu]g/ml. The presence of growth-promoting activity in brain extracts from both adult and immature rats suggests that soluble angiogenesis factors may be present in the brain throughout life, but are unavailable for stimulation of in vivo capillary growth unless released or activated by an appropriate stimulus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25473/1/0000013.pd

a4-Containing GABA _A Receptors on DRD2 Neurons of the Nucleus Accumbens Mediate Instrumental Responding for Conditioned Reinforcers and Its Potentiation by Cocaine

Extrasynaptic GABA A receptors (GABA ARs) composed of a4, b, and d subunits mediate GABAergic tonic inhibition and are potential molecular targets in the modulation of behavioral responses to natural and drug rewards. These GABA ARs are highly expressed within the nucleus accumbens (NAc), where they influence the excitability of the medium spiny neurons. Here, we explore their role in modulating behavioral responses to food-conditioned cues and the behavior-potentiating effects of cocaine. a4-Subunit constitutive knock-out mice (a4 /) showed higher rates of instrumental responding for reward-paired stimuli in a test of conditioned reinforcement (CRf). A similar effect was seen fol-lowing viral knockdown of GABA AR a4 subunits within the NAc. Local infusion of the a4b d-GABA AR-preferring agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; Gaboxadol) into the NAc had no effect on responding when given alone but reduced cocaine potentiation of responding for conditioned reinforcers in wild-type, but not a4 / mice. Finally, specific deletion of a4-subunits from dopamine D2, but not D1, receptor-expressing neurons (DRD2 and DRD1 neurons), mimicked the phenotype of the constitutive knockout, potentiating CRf responding, and blocking intra-accumbal THIP attenuation of cocaine-potentiated CRf responding. These data demonstrate that a4-GABA AR-mediated inhibition of DRD2 neurons reduces instrumental responding for a conditioned reinforcer and its po-tentiation by cocaine and emphasize the importance of GABAergic signaling within the NAc in mediating the effects of cocaine.</p

Female and male Leach\u27s Storm Petrels (Hydrobates leucorhous) pursue different foraging strategies during the incubation period

Reproduction in procellariiform birds is characterized by a single egg clutch, slow development, a long breeding season and obligate biparental care. Female Leach\u27s Storm Petrels Hydrobates leucorhous, nearly monomorphic members of this order, produce eggs that are between 20 and 25% of adult bodyweight. We tested whether female foraging behaviour differs from male foraging behaviour during the ~ 44-day incubation period across seven breeding colonies in the Northwest Atlantic. Over six breeding seasons, we used a combination of Global Positioning System and Global Location Sensor devices to measure characteristics of individual foraging trips during the incubation period. Females travelled significantly greater distances and went farther from the breeding colony than did males on individual foraging trips. For both sexes, the longer the foraging trip, the greater the distance. Independent of trip duration, females travelled farther, and spent a greater proportion of their foraging trips prospecting widely, as defined by behavioural categories derived from a hidden Markov Model. For both sexes, trip duration decreased with date. Sex differences in these foraging metrics were apparently not a consequence of morphological differences or spatial segregation. Our data are consistent with the idea that female foraging strategies differed from male foraging strategies during incubation in ways that would be expected if females were still compensating for egg formation