SUBACUTE NEUROTOXICITY OF 5-FLUOROURACIL and ITS DERIVATIVE, CARMOFUR, IN CATS

The subacute neurotoxicity of 5-fluorouracil (FU) and its derivative, carmofur (HCFU), in cats was morphologically examined; both these drugs were orally administered once daily for a maximum of three months. The dosis of FU and HCFU was 2 mg/kg/day and 10 mg/kg/day, respectively. Both FU and HCFU induced two sorts of changes in the brain, i.e., vacuolation and softening-like change. The former was distributed in the white matter of the cerebrum and cerebellum and in areas of the gray matter such as the tectum and tegmentum of the brain stem, while the latter was distributed exclusively in the gray matter of the tectum and tegmentum of the brain stem. The tectum, especially the inferior colliculus, was most frequently affected by both types of change. Ultrastructurally, vacuolation was found to be due to lamellar splitting or separation between the axon and innermost myelin layer. These findings were compared with those in dogs and as the etiopathogenesis vacuolation due to direct toxic effect of FU or its metabolites to myelin and softening-like change due to local circulatory disturbance caused by vacuolation were proposed. ACTA PATHOL JPN 38: 1255-1266, 1988.     

Attitudes, subjective norms and models of use for smokeless tobacco among college athletes: implications for prevention and cessation programming

Data from a sample of 338 male university varsity and intramuralfootball and baseball players were used to specify a model ofsmokeless tobacco (SLT) use based on the Theory of ReasonedAction. Differences between athletes who did and did not intendto use SLT within the next 2 weeks were found for nine of 12outcome beliefs, nine of 12 outcome evaluations, seven of sevennormative beliefs and four of seven items measuring motivationto comply. Principal components analysis of the attitude itemsresulted in four components: health, immediate effects, healtheffects relative to smoking and addiction. Likewise, three componentswere found for subjective norms: family, peers and advertisingfigures. Stepwise hierarchical multiple regression indicatedthat immediate effects were most strongly related to intention,followed by siblings' and teams' use of SLT and advantage ofuse relative to smoking. Implications for prevention and cessationprogramming from the findings are discussed.     

Motor neuron disease with dementia and ophthalmoplegia

Ophthalmoplegia and dementia are not usually observed in patients with amyotrophic lateral sclerosis. We report the case of a 60-year-old female with ophthalmoplegia and frontal-type dementia which appeared at an early stage of her illness that presented with dysarthria and weakness in the upper extremities. Notable autopsy findings in the central nervous system were, in addition to the degeneration of upper and lower motor neurons, moderate neuronal loss and spongy degeneration in layer II of the frontal cortex with prominent astrocytosis, and moderate neuronal loss with astrocytosis in both the substantia nigra and the red nucleus. Central chromatolysis of a few neurons in the oculomotor nucleus was seen. This case is considered to be a new subtype of motor neuron disease.     

Causality of parenchymal and vascular changes in rats with experimental thiamine deficiency encephalopathy

The causality of vascular and parenchymal damage to the central nervous system (CNS) was examined In rats with thiamine deficiency. Male Sprague Dawley rats were divided Into two groups; one was given a thiamlne-deficient diet ODD) and Injected Intraperitoneally with 10μg/100g bodyweight pyrithlamine (PT) In order to analyze morpho-metrically the topographical and sequential relationship between vascular and parenchymal changes and vase dilatation, and the other was given a TDD and 50 μg/100 g bodyweight PT in order to determine hemorrhagic sites using serial dons. Histological examination showed that sponglotic change occurred selectively in the Interior colllculus (100%) from day 19, and thereafter In the thalamus (95%), mammlllary body (50%) and nuclei olivaris and vestlbularls of the pons (25%), with or without hemorrhage. Simultaneously, glycogen accumulation was also observed In these regions at a frequency similar to that of hemorrhage. Ultrastructurally, however, hydroplc swelling of astrocytic and neuronal processes without glycogen accumulation was observed as early as day 9 In the inferior cofliculus, at which time an Increase of glial fibrillary acldic protein-positive processes was also recognized. The Superior colllculus was completely spared. From day 22 vasodilatation of the Inferior colliculus occurred, concomltantly with bodyweight loss and neurological symptoms. Twenty-two examined hemorrhages, which occurred in the thalamus and Inferior colliculus, were distributed along the arterioles or capillarles on the arterial side. In conclusion, the morphological CNS changes caused by thiamine deficiency with administration of low-dose PT in rats begin as hydropic swelling of neuronal and astrocytic processes, followed by hemorrhage and, thereafter, by vasodllatatlon. The predilectlon for hemorrhage on the arterial side without parenchymal changes suggests that petechial hemorrhage Is not simply secondary to parenchymal changes, but Is due to hemadynamlc change resulting from thlamfne deficiency-Induced vascular dysfunction.     

A case report of intrapulmonary schwannoma

A 38-year-old man without any symptoms was admitted to our institution because of an abnormal shadow found incidentally on a chest X-ray. Chest computed tomography showed a round mass in the lingular segment of the left upper lobe. Lingular segmentectomy was performed, and the histopathological diagnosis was intrapulmonary schwannoma. Immunohistochemical staining revealed a positive result for S-100 protein and negative results for CD34 and desmin. We report this case of intrapulmonary schwannoma, which is extremely rare.     

First implication of STRA6 mutations in isolated anophthalmia, microphthalmia, and coloboma: a new dimension to the STRA6 phenotype

Microphthalmia, anophthalmia, and coloboma (MAC) are structural congenital eye malformations that cause a significant proportion of childhood visual impairments. Several disease genes have been identified but do not account for all MAC cases, suggesting that additional risk loci exist. We used single nucleotide polymorphism (SNP) homozygosity mapping (HM) and targeted next-generation sequencing to identify the causative mutation for autosomal recessive isolated colobomatous microanophthalmia (MCOPCB) in a consanguineous Irish Traveller family. We identified a double-nucleotide polymorphism (g.1157G>A and g.1156G>A; p.G304K) in STRA6 that was homozygous in all of the MCOPCB patients. The STRA6 p.G304K mutation was subsequently detected in additional MCOPCB patients, including one individual with Matthew-Wood syndrome (MWS; MCOPS9). STRA6 encodes a transmembrane receptor involved in vitamin A uptake, a process essential to eye development and growth. We have shown that the G304K mutant STRA6 protein is mislocalized and has severely reduced vitamin A uptake activity. Furthermore, we reproduced the MCOPCB phenotype in a zebrafish disease model by inhibiting retinoic acid (RA) synthesis, suggesting that diminished RA levels account for the eye malformations in STRA6 p.G304K patients. The current study demonstrates that STRA6 mutations can cause isolated eye malformations in addition to the congenital anomalies observed in MWS.     

Perspectives of Expectant Women and Health Care Providers on Birth Plans

ObjectiveA birth plan is a document detailing a woman's preferences and expectations related to labour and delivery. Empirical research exploring the value of birth plans has shown conflicting findings about whether birth plans have a positive or negative effect on labour and delivery, suggesting a need for further study. This study aimed to understand the perspectives of women, health care providers, and support persons regarding the use of birth plans.MethodsA cross-sectional questionnaire was distributed to a convenience sample of expectant or postpartum women, health care providers, and support persons from January 2012 to March 2012 in British Columbia.ResultsIn total, 122 women and 110 health care providers and support persons completed the questionnaire. Both women and their attendants viewed the birth plan as being valuable for acting as both a communication and education tool. However, the respondents noted that women may be disappointed or dissatisfied if a birth plan cannot be implemented. The most important elements of a birth plan identified included pain management, comfort measures (e.g., mobility during labour), postpartum preferences (e.g., breastfeeding), atmosphere (e.g., privacy), and birthing beliefs (e.g., cultural views).ConclusionThis is the first study to identify advantages and disadvantages of using a birth plan as well as the most important aspects of a birth plan from the perspectives of both women and their attendants in Canada. The findings could be applied to optimize the efficacy of birth plans in Canada and potentially internationally as well.     

Effects of Family and Friend Support on LGB Youths' Mental Health and Sexual Orientation Milestones

This study examined the effects of social support components and providers on mental health and sexual orientation (SO) milestones of lesbian, gay, and bisexual (LGB) youths. Data were collected on 461 self‐identified LGB adolescents and young adults. Family acceptance and support yielded the strongest positive effect on self‐acceptance of SO, whereas friends' support and acceptance yielded the strongest positive effect on disclosure of SO. Family support had the strongest negative effect on youth's mental distress, whereas friends' and family support had the strongest positive effect on well‐being. These findings highlight the importance of the daily perceptions of LGB youth within social and familial settings, indicating that both positive and negative aspects of support affect youths' mental health and identity development.     

Possible relationship between the stress‐induced synaptic response and metaplasticity in the hippocampal CA1 field of freely moving rats

Hippocampal long‐term potentiation (LTP) is suppressed not only by stress paradigms but also by low frequency stimulation (LFS) prior to LTP‐inducing high frequency stimulation (HFS; tetanus), termed metaplasticity. These synaptic responses are dependent on N‐methyl‐D ‐aspartate receptors, leading to speculations about the possible relationship between metaplasticity and stress‐induced LTP impairment. However, the functional significance of metaplasticity has been unclear. The present study elucidated the electrophysiological and neurochemical profiles of metaplasticity in the hippocampal CA1 field, with a focus on the synaptic response induced by the emotional stress, contextual fear conditioning (CFC). The population spike amplitude in the CA1 field was decreased during exposure to CFC, and LTP induction was suppressed after CFC in conscious rats. The synaptic response induced by CFC was mimicked by LFS, i.e., LFS impaired the synaptic transmission and subsequent LTP. Plasma corticosterone levels were increased by both CFC and LFS. Extracellular levels of γ‐aminobutyric acid (GABA), but not glutamate, in the hippocampus increased during exposure to CFC or LFS. Furthermore, electrical stimulation of the medial prefrontal cortex (mPFC), which caused decreases in freezing behavior during exposure to CFC, counteracted the LTP impairment induced by LFS. These findings suggest that metaplasticity in the rat hippocampal CA1 field is related to the neural basis of stress experience‐dependent fear memory, and that hippocampal synaptic response associated stress‐related processes is under mPFC regulation. Synapse 63:549‐556, 2009. © 2009 Wiley‐Liss, Inc.