Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smo...Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence, addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. In addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However, there is a large degree of between-study variability that demonstrates the need for larger, well-controlled casecontrol studies to identify target genes and deduce mechanisms that account for the genetic basis of interindividual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.展开更多
Objective. All- terrain vehicle (ATV) injuries among children represent a significant and growing problem. Although state level analyses have characterized some aspects of pediatric ATV- related injuries, little infor...Objective. All- terrain vehicle (ATV) injuries among children represent a significant and growing problem. Although state level analyses have characterized some aspects of pediatric ATV- related injuries, little information on the national impact on hospitalization is available. This study was designed to characterize more fully the patterns of injury, hospital length of stay, and hospital charges associated with ATV- related injuries, with a nationally representative sample. Methods. Analyses were based on the 1997 and 2000 Healthcare Cost and Utilization Project Kids’ Inpatient Database (KID). The KID is the only national, all- payer database of hospital discharges for children. KID data were weighted to represent all discharges from general hospitals in the United States. Discharges with external cause- of- injury codes consistent with off- road ATV related injuries were selected, and the affected population was described. Nationally representative rates of ATV- related injuries were calculated, and changes between 1997 and 2000 were documented. Results. An estimated 5292 children were hospitalized because of ATV- related injuries during the 2- year period, and hospitalizations increased 79.1% between 1997 and 2000. Rates of ATV- related hospitalization were highest among adolescent white male subjects, consistent with previous studies. Most patients had hospital lengths of stay of < 4 days (68% ), but 10% had stays of > 8 days. Injury severity varied considerably, with more than one third of patients sustaining moderate to severe injuries. Approximately 1% of hospitalizations resulted in in- hospital deaths. Total hospital charges for this injury mechanism were ＄ 74 367 677 for the 2- year study period. Most of these charges were paid by private insurers. Conclusions. This study provides evidence supporting recent substantial increases in childhood ATV- related injuries. The hospitalization impact of ATV- related injuries among children is considerable. Our data support the need for ongoing creative attempts to identify effective strategies to decrease ATV injuries among children.展开更多
There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two bi...There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two biogenic amine systems were selected as examples of biomarkers for neurotoxicity. To investigate these neurochemical endpoints, two prototype neurotoxicants were evaluated in experimental animals. One agent, reserpine, was used to assess developmental neurotoxicity and administered prenatally, while the other, MDMA, was used in the adult animal. The neurochemical biomarkers measured were dopamine, serotonin, and their metabolite (DOPAC and 5-HIAA) concentrations by HPLC/EC and dopamine receptor binding by radioligand receptor techniques. A review of the background, experimental design, and results are presented in this article. Our findings indicate that components of the biogenic amine systems can be used as sensitive neurochemical biomarkers of neurotoxicity. These neurochemical biomarkers can be correlated with neuropathological and behavioral biomarkers to aid in the understanding of mechanisms of neurotoxicity.展开更多
Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. Neurotoxic effects may be permanent or reve...Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. Neurotoxic effects may be permanent or reversible, produced by neuropharmacological or neurodegenerative properties of a neurotoxicant, or the result of direct or indirect actions on the nervous system (ICON, 1990). Adverse effects include side effects (unwanted effects) or effects due to overdosing; functional or structural responses that promote compensation to restore normal function; or any展开更多
IGF-I and IGF-II are ubiquitously expressed growth factors that have profoun d effects on the growth and differentiation of many cell types and tissues, incl uding cells of the CNS. In biologic fluids, most IGFs are b...IGF-I and IGF-II are ubiquitously expressed growth factors that have profoun d effects on the growth and differentiation of many cell types and tissues, incl uding cells of the CNS. In biologic fluids, most IGFs are bound to one of six IG F binding proteins (IGFBPs 1-6). Increasing evidence strongly supports a role f or IGF-I in CNS development, as it promotes neuronal proliferation and survival . However, little is known about IGF-I and its homolog IGF-II and their carrie r proteins, IGFBPs, during the neonatal period in which brain size increases dra matically, myelination takes place, and neurons show limited capacity to prolife rate. Herein, we have determined the concentrations of IGF-I, IGF-II, IGFBP-I , and IGFBP-3 in cerebral spinal fluid (CSF) samples that were collected from children who were 1 wk to 18 y of age. The concentrations of IGF-I, IGFBP-I, and IGFBP-3 in CS F from children < 6mo of age were significantly higher than in older children, w hereas IGF-II was higher in the older group. This is in contrast to what is obs erved in the peripheral circulation, where IGF-I and IGFBP-3 are low at birth and rise rapidly during the first year, reaching peak levels during puberty. Hig her concentrations of IGF-I, IGFBP-I, and IGFBP-3 in the CSF of very young ch ildren suggest that these proteins might participate in the active processes of myelination and synapse formation in the developing nervous system. We propose t hat IGF-I and certain IGFBPs are likely necessary for normal CNS development du ring critical stages of neonatal brain growth and development.展开更多
Background/Purpose: Lipoblastoma/lipoblastomatosis, a rare benign pediatric tumor composed of embryonic fat, most often presents as a rapidly growing mass in children younger than 3 years. This benign tumor locally re...Background/Purpose: Lipoblastoma/lipoblastomatosis, a rare benign pediatric tumor composed of embryonic fat, most often presents as a rapidly growing mass in children younger than 3 years. This benign tumor locally recurs up to 25%of the time.This retrospective review was done to emphasize problems with diagnosis, management, and the approach to follow-up care.Methods: Sixteen cases of pathologically proven lipoblastoma presenting to a single institution over a 16-year period (1988-2004) were reviewed retrospectively for clinical features and outcome. Results: There were 11 males and 5 females ranging in age from 18 days to 12.75 years. Preoperative diagnoses were accurate in only 3 cases. Two lesions recurred locally over a period of 10 months and 5 years. One lesion presented with local infiltration. Six lesions were right-sided, 5 were left-sided,and 5 were midline. Conclusions: It is important to consider lipoblastoma in the diagnosis of a rapidly enlarging fatty mass in children. Complete resection is the only definitive treatment and should not be delayed when impingement on surrounding structures is imminent. There is a tendency for these lesions to recur despite presumed complete excision. Therefore, followup for a minimum of 5 years is recommended.展开更多
Foot ulceration is one of the most debilitating complications associated with diabetes,but its cause remains poorly understood.Several studies have been undertaken to understand healing kinetics or find possible thera...Foot ulceration is one of the most debilitating complications associated with diabetes,but its cause remains poorly understood.Several studies have been undertaken to understand healing kinetics or find possible therapies to enhance healing.However,few studies have been directed at understanding the immunological alterations that could influence wound healing in diabetes.In this study,we analysed the T-cell receptor(TCR)repertoire diversity in TCR-αβ^(+)T cells.We also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot ulcers.Our results showed that diabetic individuals,especially those with foot ulcers,have a significantly lower naive T-cell number and a poorer TCR-Vβrepertoire diversity.We also showed that the reduced TCR-Vβrepertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells,the major source of tumour necrosis factor-αproduction,which was even more pronounced in patients with acute foot ulceration.Moreover,the expression of several inflammatory chemokine receptors was significantly reduced in diabetic patients.In conclusion,effector T-cell accumulation and TCR repertoire diversity reduction appear to precede the development of foot ulcers.This finding may open new immunological therapeutic possibilities and provide a new prognostic tool in diabetic wound care.展开更多
Burn patients experience anxiety and pain in the course of their injury, treatment, and recovery. Hence, treatment of anxiety and pain is paramount after burn injury. Children, in particular, pose challenges in anxiet...Burn patients experience anxiety and pain in the course of their injury, treatment, and recovery. Hence, treatment of anxiety and pain is paramount after burn injury. Children, in particular, pose challenges in anxiety and pain management due to their unique physiologic, psychologic, and anatomic status. Burn injuries further complicate pain management and sedation as such injuries can have effects on medication response and elimination. Burn injuries further complicate pain management and sedation as such injuries can have effects on medication response and elimination. The purpose of this review is to describe the challenges associated with management of anxiety, pain, and sedation in burned children and to describe the different options for treatment of anxiety and pain in burned children.展开更多
Antibiotic-impregnated ventricular shunt catheters(AIVSCs)with 0.15%clindamycin and 0.054%rifampin are commonly used to prevent ventriculo-peritoneal(VP)shunt infections.Initially approved by the United States Food an...Antibiotic-impregnated ventricular shunt catheters(AIVSCs)with 0.15%clindamycin and 0.054%rifampin are commonly used to prevent ventriculo-peritoneal(VP)shunt infections.Initially approved by the United States Food and Drug Administration in 2003(https://www.integralife.com/file/general/1561404015.pdf),they have antimicrobial activity documented for minimum 31 days(https://www.accessdata.fda.gov/cdrh_docs/pdf11/K110560.pdf).These antibiotics were chosen as they cover the majority of Staphylococcus aureus and may provide some activity against coagulase negative staphylococci.1 These normal skin flora account for the majority of VP shunt infections.In the largest randomized controlled trial(RCT)to date,AIVSCs significantly reduced the risk of infection compared with standard shunts(cause-specific hazard ratio(HR)0.38).2 This effect was mainly due to a reduction in staphylococcal infections;the number of gram-negative infections was similar in both groups.Observational studies3–5 and a meta-analysis6 in children support the findings of this RCT.The objective of this study was to examine the spectrum of pathogens,time to infection,and outcomes with AIVSCs vs standard shunts.展开更多
文摘Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence, addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. In addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However, there is a large degree of between-study variability that demonstrates the need for larger, well-controlled casecontrol studies to identify target genes and deduce mechanisms that account for the genetic basis of interindividual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.
文摘Objective. All- terrain vehicle (ATV) injuries among children represent a significant and growing problem. Although state level analyses have characterized some aspects of pediatric ATV- related injuries, little information on the national impact on hospitalization is available. This study was designed to characterize more fully the patterns of injury, hospital length of stay, and hospital charges associated with ATV- related injuries, with a nationally representative sample. Methods. Analyses were based on the 1997 and 2000 Healthcare Cost and Utilization Project Kids’ Inpatient Database (KID). The KID is the only national, all- payer database of hospital discharges for children. KID data were weighted to represent all discharges from general hospitals in the United States. Discharges with external cause- of- injury codes consistent with off- road ATV related injuries were selected, and the affected population was described. Nationally representative rates of ATV- related injuries were calculated, and changes between 1997 and 2000 were documented. Results. An estimated 5292 children were hospitalized because of ATV- related injuries during the 2- year period, and hospitalizations increased 79.1% between 1997 and 2000. Rates of ATV- related hospitalization were highest among adolescent white male subjects, consistent with previous studies. Most patients had hospital lengths of stay of < 4 days (68% ), but 10% had stays of > 8 days. Injury severity varied considerably, with more than one third of patients sustaining moderate to severe injuries. Approximately 1% of hospitalizations resulted in in- hospital deaths. Total hospital charges for this injury mechanism were ＄ 74 367 677 for the 2- year study period. Most of these charges were paid by private insurers. Conclusions. This study provides evidence supporting recent substantial increases in childhood ATV- related injuries. The hospitalization impact of ATV- related injuries among children is considerable. Our data support the need for ongoing creative attempts to identify effective strategies to decrease ATV injuries among children.
文摘There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two biogenic amine systems were selected as examples of biomarkers for neurotoxicity. To investigate these neurochemical endpoints, two prototype neurotoxicants were evaluated in experimental animals. One agent, reserpine, was used to assess developmental neurotoxicity and administered prenatally, while the other, MDMA, was used in the adult animal. The neurochemical biomarkers measured were dopamine, serotonin, and their metabolite (DOPAC and 5-HIAA) concentrations by HPLC/EC and dopamine receptor binding by radioligand receptor techniques. A review of the background, experimental design, and results are presented in this article. Our findings indicate that components of the biogenic amine systems can be used as sensitive neurochemical biomarkers of neurotoxicity. These neurochemical biomarkers can be correlated with neuropathological and behavioral biomarkers to aid in the understanding of mechanisms of neurotoxicity.
文摘Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. Neurotoxic effects may be permanent or reversible, produced by neuropharmacological or neurodegenerative properties of a neurotoxicant, or the result of direct or indirect actions on the nervous system (ICON, 1990). Adverse effects include side effects (unwanted effects) or effects due to overdosing; functional or structural responses that promote compensation to restore normal function; or any
文摘IGF-I and IGF-II are ubiquitously expressed growth factors that have profoun d effects on the growth and differentiation of many cell types and tissues, incl uding cells of the CNS. In biologic fluids, most IGFs are bound to one of six IG F binding proteins (IGFBPs 1-6). Increasing evidence strongly supports a role f or IGF-I in CNS development, as it promotes neuronal proliferation and survival . However, little is known about IGF-I and its homolog IGF-II and their carrie r proteins, IGFBPs, during the neonatal period in which brain size increases dra matically, myelination takes place, and neurons show limited capacity to prolife rate. Herein, we have determined the concentrations of IGF-I, IGF-II, IGFBP-I , and IGFBP-3 in cerebral spinal fluid (CSF) samples that were collected from children who were 1 wk to 18 y of age. The concentrations of IGF-I, IGFBP-I, and IGFBP-3 in CS F from children < 6mo of age were significantly higher than in older children, w hereas IGF-II was higher in the older group. This is in contrast to what is obs erved in the peripheral circulation, where IGF-I and IGFBP-3 are low at birth and rise rapidly during the first year, reaching peak levels during puberty. Hig her concentrations of IGF-I, IGFBP-I, and IGFBP-3 in the CSF of very young ch ildren suggest that these proteins might participate in the active processes of myelination and synapse formation in the developing nervous system. We propose t hat IGF-I and certain IGFBPs are likely necessary for normal CNS development du ring critical stages of neonatal brain growth and development.
文摘Background/Purpose: Lipoblastoma/lipoblastomatosis, a rare benign pediatric tumor composed of embryonic fat, most often presents as a rapidly growing mass in children younger than 3 years. This benign tumor locally recurs up to 25%of the time.This retrospective review was done to emphasize problems with diagnosis, management, and the approach to follow-up care.Methods: Sixteen cases of pathologically proven lipoblastoma presenting to a single institution over a 16-year period (1988-2004) were reviewed retrospectively for clinical features and outcome. Results: There were 11 males and 5 females ranging in age from 18 days to 12.75 years. Preoperative diagnoses were accurate in only 3 cases. Two lesions recurred locally over a period of 10 months and 5 years. One lesion presented with local infiltration. Six lesions were right-sided, 5 were left-sided,and 5 were midline. Conclusions: It is important to consider lipoblastoma in the diagnosis of a rapidly enlarging fatty mass in children. Complete resection is the only definitive treatment and should not be delayed when impingement on surrounding structures is imminent. There is a tendency for these lesions to recur despite presumed complete excision. Therefore, followup for a minimum of 5 years is recommended.
基金financed by FEDER funds by the operational program Factors of Competitivity–COMPETEthe Portuguese Foundation for Science and Technology(FCT)-EXCL/DTP-PIC/0069/2012,PEst-C/SAU/LA0001/2013 and UID/NEU/04539/2013+1 种基金the EFSD European Research Programme in Microvascular Complications of Diabetes supported by Novartis,and Forum Hematológico do Norte,PortugalEugénia Carvalho is partly funded by the Arkansas Biosciences Institute,the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000,NIH P30AG028718,and NIH RO1 AG033761.
文摘Foot ulceration is one of the most debilitating complications associated with diabetes,but its cause remains poorly understood.Several studies have been undertaken to understand healing kinetics or find possible therapies to enhance healing.However,few studies have been directed at understanding the immunological alterations that could influence wound healing in diabetes.In this study,we analysed the T-cell receptor(TCR)repertoire diversity in TCR-αβ^(+)T cells.We also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot ulcers.Our results showed that diabetic individuals,especially those with foot ulcers,have a significantly lower naive T-cell number and a poorer TCR-Vβrepertoire diversity.We also showed that the reduced TCR-Vβrepertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells,the major source of tumour necrosis factor-αproduction,which was even more pronounced in patients with acute foot ulceration.Moreover,the expression of several inflammatory chemokine receptors was significantly reduced in diabetic patients.In conclusion,effector T-cell accumulation and TCR repertoire diversity reduction appear to precede the development of foot ulcers.This finding may open new immunological therapeutic possibilities and provide a new prognostic tool in diabetic wound care.
文摘Burn patients experience anxiety and pain in the course of their injury, treatment, and recovery. Hence, treatment of anxiety and pain is paramount after burn injury. Children, in particular, pose challenges in anxiety and pain management due to their unique physiologic, psychologic, and anatomic status. Burn injuries further complicate pain management and sedation as such injuries can have effects on medication response and elimination. Burn injuries further complicate pain management and sedation as such injuries can have effects on medication response and elimination. The purpose of this review is to describe the challenges associated with management of anxiety, pain, and sedation in burned children and to describe the different options for treatment of anxiety and pain in burned children.
文摘Antibiotic-impregnated ventricular shunt catheters(AIVSCs)with 0.15%clindamycin and 0.054%rifampin are commonly used to prevent ventriculo-peritoneal(VP)shunt infections.Initially approved by the United States Food and Drug Administration in 2003(https://www.integralife.com/file/general/1561404015.pdf),they have antimicrobial activity documented for minimum 31 days(https://www.accessdata.fda.gov/cdrh_docs/pdf11/K110560.pdf).These antibiotics were chosen as they cover the majority of Staphylococcus aureus and may provide some activity against coagulase negative staphylococci.1 These normal skin flora account for the majority of VP shunt infections.In the largest randomized controlled trial(RCT)to date,AIVSCs significantly reduced the risk of infection compared with standard shunts(cause-specific hazard ratio(HR)0.38).2 This effect was mainly due to a reduction in staphylococcal infections;the number of gram-negative infections was similar in both groups.Observational studies3–5 and a meta-analysis6 in children support the findings of this RCT.The objective of this study was to examine the spectrum of pathogens,time to infection,and outcomes with AIVSCs vs standard shunts.
