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101.
Jane Farmer Patrick Dawson Elizabeth Martin Janet Tucker 《Health services management research》2007,20(1):59-68
There is a wealth of material on 'how to do' change plus empirical work revealing change process complexity. In health care, the relevance of context is highlighted, but studies of rural health-care change have focused on community impacts. There is little to inform health-care managers of how remoteness and rurality impact upon change processes. This study considered Scottish maternity units and aimed to identify issues in the change process associated with rurality and remoteness. Six units were purposively selected and 131 interviews were conducted with managers, staff and community members over 15 months. Analysis induced themes pertinent to remoteness and rurality. These included: perceived 'distance' between senior managers imposing change and the wider community of staff and residents; perceptions of community vulnerability; and tensions arising from working in small teams and living in small communities. The study provides useful insights for rural managers at a time of considerable service reconfiguration. 相似文献
102.
103.
Evidence from both experimental carcinogenesis and studies in human cirrhotic liver suggest that defective repair of the
promutagenic DNA base lesion, O
6-methylguanine, is a factor in the multistep process of hepatocellular carcinogenesis. Ubiquitous environmental alkylating
agents such as N-nitroso compounds can produce O
6-methylguanine in cellular DNA. Unrepaired, O
6-methylguanine can lead to the formation of G ? A transition mutations, a known mechanism of human oncogene activation and
tumour suppressor gene inactivation. Combined treatment of rodents with an agent producing O
6-methylguanine in DNA, and an agent promoting cell proliferation, leads to development of hepatic nodules and hepatocellular
carcinoma (HCC), cell division, hence DNA replication, being required for the propagation of tumorigenic mutation(s) in hepatocyte
DNA. The paramount importance of O
6-methylguanine in hepatocellular carcinogenesis is indicated by the observation that transgenic mice engineered to have increased
hepatic levels of repair enzyme O
6-methylguanine-DNA methyltransferase (MGMT) are significantly less prone to hepatocellular carcinogenesis following alkylating
agent treatment. Cirrhosis is a universal risk factor for development of human HCC, and a condition that is characterized
by increased hepatocyte proliferation as a result of tissue regeneration. Levels of the human repairing enzyme for O
6-methylguanine were found to be significantly lower in cirrhotic liver than in normal tissue. In accord with findings from
animal models, this suggested a mechanism in which persistence of O
6-methylguanine due to defective DNA repair by MGMT, together with increased hepatocyte proliferation, might lead to specific
gene mutation(s) and hepatocellular carcinogenesis. Screening for the presence and persistence of O
6-methylguanine in human DNA presently involves formidable technical difficulty. Indications are that such limitations might
be overcome by the use of an ultrasensitive method such as immuno-polymerase chain reaction (PCR). This approach should allow
parallel measurement of DNA adduct and repair enzyme in routine liver biopsy samples. It might also enable investigation of
O
6-methylguanine in human genes specifically associated with hepatocellular carcinogenesis. Given the wide variation in human
MGMT levels observed between individuals, tissues, and cells, this technology should be adapted to permit the ultrasensitive
localisation and measurement of adducts and repairing enzyme in liver biopsy tissue sections. Ability to ultrasensitively
measure O
6-methylguanine, and its repair enzyme, should prove valuable in the risk assessment of cirrhotic patients for developing hepatocellular
carcinoma.
Received for publication on July 6, 1998; accepted on Aug. 12, 1998 相似文献
104.
Cutaneous T-cell lymphoma 总被引:1,自引:0,他引:1
105.
Serotonin (5-HT) may be inhibitory to micturition at a spinal level. A potential mechanism of action for serotonergic inhibition of bladder function is a depression of the ascending limb of the supraspinal reflex mediating micturition. Ascending activity evoked by pelvic nerve stimulation was recorded in the thoracic spinal cord of anesthetized cats. For comparison, spinal reflex activity evoked by pelvic nerve stimulation was recorded on the pudendal nerve. The effects of intrathecal administration of serotonergic agents were examined to determine whether spinal and supraspinal responses to bladder afferent activation were modulated by 5-HT. Methysergide (60 nmol), a non-selective serotonergic antagonist, increased ascending activity by 61±7% and depressed spinal reflex activity by 38±6%. Zatosetron (10 nmol), a 5-HT3 antagonist had a similar effect on both activities (increased by 93±24% and decreased by 77±7%, respectively). The effect on ascending activity of blocking 5-HT3 receptors was also confirmed with ICS 205930 and MDL 72222. 2-Methyl-5-HT (800 nmol), a 5-HT3 agonist, depressed ascending activity to 46±9% of control, but enhanced spinal reflex activity by 73±92%. These results demonstrate that stimulation of 5-HT3 and methysergide-sensitive 5-HT receptors can inhibit ascending activity and facilitate spinal reflex activity elicited by activation of bladder afferents. It is suggested that descending serotonergic pathways may participate in the spinal coordination of urinary continence. 相似文献
106.
Helen E. Pearson Donna L. Smith-Harrison Nancy K. Rosenblatt Bertram R. Payne 《Experimental neurology》1993,119(2)
The short-term metabolic response of immature retinal ganglion cells to destruction of their target cells in the dorsal lateral geniculate nucleus (dLGN) was assessed in newborn cats. Retrograde degeneration of virtually all dLGN cells was induced by ablation of the 13 contiguous areas of visual cortex on the day of birth. The metabolic response of retinal ganglion cells to this loss of target cells in dLGN was determined by exposing the ganglion cell layer to tritiated uridine, a precursor of RNA. Control measurements were made from unoperated littermates. Following sectioning and processing of the retinae from both groups of kittens for autoradiography, silver grain densities overlying the cellular profiles in the ganglion cell layer were calculated. These calculations revealed levels of uridine incorporation at Postnatal Day 4 in both groups of kittens significantly higher than at either Postnatal Day 2 or 7, but no significant differences between the two groups on any day examined. These results show that the level of RNA synthesis in retinal ganglion cells increases temporarily during the first postnatal week and that this synthesis is unaffected by the death of target cells in the dLGN. The temporary increase may be related to the establishment of synaptic connections on retinal ganglion cells by their afferent bipolar and amacrine neurons in the inner nuclear layer. 相似文献
107.
Head injury mortality in two centers with different emergency medical services and intensive care 总被引:7,自引:0,他引:7
A R Colohan W M Alves C R Gross J C Torner V S Mehta P N Tandon J A Jane 《Journal of neurosurgery》1989,71(2):202-207
The authors report data collected prospectively on 551 cases of head injury in New Delhi, India, and 822 cases in Charlottesville, Virginia. The mortality rate, adjusted for initial severity of injury, was 11.0% in New Delhi versus 7.2% in Charlottesville (p less than 0.02). There was a striking similarity in mortality rates at both centers when comparing patients with the least severe head injuries and those with the most severe injuries according to the motor score of the Glasgow Coma Scale (GCS M). However, in the group with an abnormal but purposeful motor response (GCS M = 5), the mortality rate was 12.5% in New Delhi versus 4.8% in Charlottesville (p less than 0.01). The relative absence of prehospital emergency care and the delay in admission after head injury in New Delhi are cited as two possible causes for the differences in mortality rates in this subgroup of patients with "moderate" head injuries. 相似文献
108.
109.
Owens EB Hinshaw SP Kraemer HC Arnold LE Abikoff HB Cantwell DP Conners CK Elliott G Greenhill LL Hechtman L Hoza B Jensen PS March JS Newcorn JH Pelham WE Severe JB Swanson JM Vitiello B Wells KC Wigal T 《Journal of consulting and clinical psychology》2003,71(3):540-552
Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators. 相似文献
110.
Jane M Olson Sompong Vongpunsawad Helena Kuivaniemi Antti Ronkainen Juha Hernesniemi Markku Ryynänen Lee-Lian Kim Gerard Tromp 《BMC medical genetics》2002,3(1):7-7