Background:Vasovagal syncope(VVS)greatly impairs quality of life.The therapeutic efficacy of oral rehydration saline(ORS)for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease.Bod...Background:Vasovagal syncope(VVS)greatly impairs quality of life.The therapeutic efficacy of oral rehydration saline(ORS)for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease.Body mass index(BMI)was demonstrated to reflect blood volume to a certain extent.Therefore,the present study explored the capability of BMI to predict the therapeutic response of children with VVS to ORS treatment.Methods:Seventy-four children with VVS who visited the Syncope Unit of Pediatrics at Peking University First Hospital from November 2010 to June 2019 receiving ORS treatment were enrolled for this retrospective case-control study.A comparison of demographic,clinical,and hemodynamic characteristics was performed between responders and non-responders.The correlation between baseline BMI and response time was analyzed.To determine the value of baseline BMI in predicting the therapeutic efficacy of ORS in children with VVS,a receiver operating characteristic curve analysis was performed.Results:Fifty-two children were identified as responders,and the remaining 22 children were identified as non-responders.The baseline BMI of the responders was much lower than that of the non-responders(16.4[15.5,17.8]kg/m2vs.20.7±3.6 kg/m2,P<0.001),and baseline BMI was positively correlated with response time in the head-up tilt test after adjusting for sex(r=0.256,95%confidence interval[CI]:0.067-0.439,P=0.029).The area under the receiver operating characteristic curve of baseline BMI was 0.818(95%CI:0.704-0.932,P<0.001),and an optimal cut-off value of 18.9 kg/m2 yielded a sensitivity of 83%and a specificity of 73%to predict the efficacy of ORS in VVS.Conclusion:Prior to treatment,baseline BMI is a promising predictor of response to ORS in children with VVS.展开更多
AIM: To investigate the effect of carbachol on gastrointestinal function in a dog model of oral resuscitation for burn shock. METHODS: Twenty Beagle dogs with intubation of the carotid artery, jugular vein and jejunum...AIM: To investigate the effect of carbachol on gastrointestinal function in a dog model of oral resuscitation for burn shock. METHODS: Twenty Beagle dogs with intubation of the carotid artery, jugular vein and jejunum for 24 h were subjected to 35% total body surface area fullthickness burns, and were divided into three groups: no fluid resuscitation (NR, n = 10), in which animals did not receive fluid by any means in the first 24 h postburn; oral fluid resuscitation (OR, n = 8), in which dogs were gavaged with glucose-electrolyte solution (GES) with volume and rate consistent with the Parkland formula; and oral fluid with carbachol group (OR/CAR, n = 8), in which dogs were gavaged with GES containing carbachol (20 μg/kg), with the same volume and rate as the OR group. Twenty-four hours after burns, all animals were given intravenous fluid replacement, and 72 h after injury, they received nutritional support. Hemodynamicand gastrointestinal parameters were measured serially with animals in conscious and cooperative state. RESULTS: The mean arterial pressure, cardiac output and plasma volume dropped markedly, and gastrointestinal tissue perfusion was reduced obviously after the burn injury in all the three groups. Hemodynamic parameters and gastrointestinal tissue perfusion in the OR and OR/CAR groups were promoted to pre-injury level at 48 and 72 h, respectively, while hemodynamic parameters in the NR group did not return to pre-injury level till 72 h, and gastrointestinal tissue perfusion remained lower than pre-injury level until 120 h post-burn. CO 2 of the gastric mucosa and intestinal mucosa blood flow of OR/CAR groups were 56.4 ± 4.7 mmHg and 157.7 ± 17.7 blood perfusion units (BPU) at 24 h postburn, respectively, which were significantly superior to those in the OR group (65.8 ± 5.8 mmHg and 127.7 ± 11.9 BPU, respectively, all P < 0.05). Gastric emptying and intestinal absorption rates of GES were significantly reduced to the lowest level (52.8% and 23.7% of pre-injury levels) in the OR group at about 2 and 4 h post-burn, and did not return to 80% of pre-injury level until 24 h. In the first 24 h postburn, the rate of gastric emptying and intestinal water absorption were elevated by a mean 15.7% and 11.5%, respectively, in the OR/CAR group compared with the OR group. At 5 days, the mortality in the NR group was 30% (3/10), 12.5% in the OR group (1/8), and none in the OR/CAR group. CONCLUSION: Carbachol had a beneficial effect on oral resuscitation of burn shock by promoting gastric emptying and intestinal absorption in our canine model.展开更多
BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented...BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.展开更多
Management of acute diarrhea remains a global challenge, particularly in resource-limiting countries. Oral rehydration solution (ORS), a passive rehydrating therapy developed approximately 40 years ago, remains the ma...Management of acute diarrhea remains a global challenge, particularly in resource-limiting countries. Oral rehydration solution (ORS), a passive rehydrating therapy developed approximately 40 years ago, remains the mainstay treatment. Although ORS is effective for hydration, since it does not inhibit enterotoxin-mediated excessive secretion, reduced absorption and compromised barrier function - the primary mechanisms of diarrhea, ORS does not offer a rapid relief of diarrhea symptom. There are a few alternative therapies available, yet the use of these drugs is limited by their expense, lack of availability and/or safety concerns. Novel anti-diarrheal therapeutic approaches, particularly those simple affordable therapies, are needed. This article explores intestinal calcium-sensing receptor (CaSR), a newly uncovered target for therapy of diarrhea. Unlike others, targeting this host antidiarrheal receptor system appears “all-inclusive”: it is anti-secretory, pro-absorptive, anti-motility, and anti-inflammatory. Thus, activating CaSR reverses changes of both secretory and inflammatory diarrheas. Considering its unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators, it is possible that through targeting of CaSR with a combination of specific nutrients, novel oral rehydrating solutions that are inexpensive and practical to use in all countries may be developed.展开更多
AIM:To investigate the frequency,etiology,and current management strategies for diarrhea in newborn.METHODS:Retrospective,nationwide study involving 5801 subjects observed in neonatal intensive care units during 3 yea...AIM:To investigate the frequency,etiology,and current management strategies for diarrhea in newborn.METHODS:Retrospective,nationwide study involving 5801 subjects observed in neonatal intensive care units during 3 years.The main anamnesis and demographic characteristics,etiology and characteristics of diarrhea,nutritional and therapeutic management,clinical outcomes were evaluated.RESULTS:Thirty-nine cases of diarrhea(36 acute,3 chronic) were identified.The occurrence rate of diarrhea was 6.72 per 1000 hospitalized newborn.Etiology was defined in 29 of 39 newborn(74.3%):food allergy(20.5%),gastrointestinal infections(17.9%),antibiotic-associated diarrhea(12.8%),congenital defects of ion transport(5.1%),withdrawal syndrome(5.1%),Hirschsprung's disease(2.5%),parenteral diarrhea(2.5%),cystic fibrosis(2.5%),and metabolic disorders(2.5%).Three patients died due to complications related to diarrhea(7.7%).In 19 of 39 patients(48.7%),rehydration was performed exclusively by the enteral route.CONCLUSION:Diarrhea in neonates is a challenging clinical condition due to the possible heterogeneous etiologies and severe outcomes.Specific guidelines are advocated in order to optimize management of diarrhea in this particular setting.展开更多
Remote,rural ethnic-minority communities face greater disaster-related public health risks due to their lack of resources and limited access to health care.The Ethnic Minority Health Project(EMHP) was initiated in 200...Remote,rural ethnic-minority communities face greater disaster-related public health risks due to their lack of resources and limited access to health care.The Ethnic Minority Health Project(EMHP) was initiated in 2009 to work with remote,disaster-prone ethnic-minority villages that live in extreme poverty.One of the project's aims is to develop and evaluate bottom-up health risk reduction efforts in emergency and disaster risk management(HealthEDRM).This article shares project updates and describes field intervention results from the Yi ethnic community of Hongyan village in China's Sichuan Province,an area that experiences recurrent floods.It was found that 64% of the village respondents had never considered any form of disaster preparation,even with the recurrent flood risks.Health intervention participants showed sustained knowledge retention and were nine times more likely to know the correct composition of oral rehydration solution(ORS) after the intervention.Participants also retained the improved knowledge on ORS and disaster preparedness kit ownership12 months after the intervention.展开更多
Objective: To observe the therapeutic effect of Zhixie Buye mixture (止泻补液合剂, ZXBYM) on infantile diarrhea patients with mild or middle degree of dehydration. Methods: Controlled observation method was adopted in...Objective: To observe the therapeutic effect of Zhixie Buye mixture (止泻补液合剂, ZXBYM) on infantile diarrhea patients with mild or middle degree of dehydration. Methods: Controlled observation method was adopted in the clinical and experimental study. Results: There was no significant difference in the treatment of dehydration between the ZXBYM group and oral rehydration solution (ORS) group (P>0.05), at the same time it was more effective for ZXBYM to eliminate such symptoms as vomiting and abdominal distension (P<0.01). In addition, it was confirmed that the ion concentration of sodium, potassium, chlorine, glucose and osmotic pressure in the mixture was similar to those in ORS. Animal experiment showed that ZXBYM has the effect of rat intestine peristalsis suppression and water absorption promotion in colon. And there was statistical difference in antidiarrhea effect between the mixture and ORS (P<0.01). Conclusion: ZXBYM is an effective mixture in the treatment of diarrhea with dehydration. It has a good prospect for the development and application.展开更多
基金This work was supported by grants from the Peking University Medicine Fund of Fostering Y oung Scholars'Scientifie&Technological Innovation,Peking University Clinical Medicine Plus X-Young Scholars Project(PKU2019LCXQ011)the Peking University Clinical Scientist Program(No.BMU2019LCKXJ001)and the Fundamental Research Funds for the Central Universities.
文摘Background:Vasovagal syncope(VVS)greatly impairs quality of life.The therapeutic efficacy of oral rehydration saline(ORS)for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease.Body mass index(BMI)was demonstrated to reflect blood volume to a certain extent.Therefore,the present study explored the capability of BMI to predict the therapeutic response of children with VVS to ORS treatment.Methods:Seventy-four children with VVS who visited the Syncope Unit of Pediatrics at Peking University First Hospital from November 2010 to June 2019 receiving ORS treatment were enrolled for this retrospective case-control study.A comparison of demographic,clinical,and hemodynamic characteristics was performed between responders and non-responders.The correlation between baseline BMI and response time was analyzed.To determine the value of baseline BMI in predicting the therapeutic efficacy of ORS in children with VVS,a receiver operating characteristic curve analysis was performed.Results:Fifty-two children were identified as responders,and the remaining 22 children were identified as non-responders.The baseline BMI of the responders was much lower than that of the non-responders(16.4[15.5,17.8]kg/m2vs.20.7±3.6 kg/m2,P<0.001),and baseline BMI was positively correlated with response time in the head-up tilt test after adjusting for sex(r=0.256,95%confidence interval[CI]:0.067-0.439,P=0.029).The area under the receiver operating characteristic curve of baseline BMI was 0.818(95%CI:0.704-0.932,P<0.001),and an optimal cut-off value of 18.9 kg/m2 yielded a sensitivity of 83%and a specificity of 73%to predict the efficacy of ORS in VVS.Conclusion:Prior to treatment,baseline BMI is a promising predictor of response to ORS in children with VVS.
基金Supported by The Special Foundation of the 11th five-yearPlan for Military Medical Projects, No. 06Z055
文摘AIM: To investigate the effect of carbachol on gastrointestinal function in a dog model of oral resuscitation for burn shock. METHODS: Twenty Beagle dogs with intubation of the carotid artery, jugular vein and jejunum for 24 h were subjected to 35% total body surface area fullthickness burns, and were divided into three groups: no fluid resuscitation (NR, n = 10), in which animals did not receive fluid by any means in the first 24 h postburn; oral fluid resuscitation (OR, n = 8), in which dogs were gavaged with glucose-electrolyte solution (GES) with volume and rate consistent with the Parkland formula; and oral fluid with carbachol group (OR/CAR, n = 8), in which dogs were gavaged with GES containing carbachol (20 μg/kg), with the same volume and rate as the OR group. Twenty-four hours after burns, all animals were given intravenous fluid replacement, and 72 h after injury, they received nutritional support. Hemodynamicand gastrointestinal parameters were measured serially with animals in conscious and cooperative state. RESULTS: The mean arterial pressure, cardiac output and plasma volume dropped markedly, and gastrointestinal tissue perfusion was reduced obviously after the burn injury in all the three groups. Hemodynamic parameters and gastrointestinal tissue perfusion in the OR and OR/CAR groups were promoted to pre-injury level at 48 and 72 h, respectively, while hemodynamic parameters in the NR group did not return to pre-injury level till 72 h, and gastrointestinal tissue perfusion remained lower than pre-injury level until 120 h post-burn. CO 2 of the gastric mucosa and intestinal mucosa blood flow of OR/CAR groups were 56.4 ± 4.7 mmHg and 157.7 ± 17.7 blood perfusion units (BPU) at 24 h postburn, respectively, which were significantly superior to those in the OR group (65.8 ± 5.8 mmHg and 127.7 ± 11.9 BPU, respectively, all P < 0.05). Gastric emptying and intestinal absorption rates of GES were significantly reduced to the lowest level (52.8% and 23.7% of pre-injury levels) in the OR group at about 2 and 4 h post-burn, and did not return to 80% of pre-injury level until 24 h. In the first 24 h postburn, the rate of gastric emptying and intestinal water absorption were elevated by a mean 15.7% and 11.5%, respectively, in the OR/CAR group compared with the OR group. At 5 days, the mortality in the NR group was 30% (3/10), 12.5% in the OR group (1/8), and none in the OR/CAR group. CONCLUSION: Carbachol had a beneficial effect on oral resuscitation of burn shock by promoting gastric emptying and intestinal absorption in our canine model.
基金Supported by Eunice Kennedy Shriver National Institute of Child Health&Human Development of the National Institutes of Health,No.1K08HD079674-01 and 1R41HD092133-01National Institute of Allergy and Infectious Diseases,No.1A21AI169282and VA Research Career Scientist Award,No.1IK6BX004835.
文摘BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.
基金Supported by The National Institute of Health NICHD,award No.K08HD079674the CDNHF/NASPGHAN foundation,award No.00102979the Children’s Miracle Network
文摘Management of acute diarrhea remains a global challenge, particularly in resource-limiting countries. Oral rehydration solution (ORS), a passive rehydrating therapy developed approximately 40 years ago, remains the mainstay treatment. Although ORS is effective for hydration, since it does not inhibit enterotoxin-mediated excessive secretion, reduced absorption and compromised barrier function - the primary mechanisms of diarrhea, ORS does not offer a rapid relief of diarrhea symptom. There are a few alternative therapies available, yet the use of these drugs is limited by their expense, lack of availability and/or safety concerns. Novel anti-diarrheal therapeutic approaches, particularly those simple affordable therapies, are needed. This article explores intestinal calcium-sensing receptor (CaSR), a newly uncovered target for therapy of diarrhea. Unlike others, targeting this host antidiarrheal receptor system appears “all-inclusive”: it is anti-secretory, pro-absorptive, anti-motility, and anti-inflammatory. Thus, activating CaSR reverses changes of both secretory and inflammatory diarrheas. Considering its unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators, it is possible that through targeting of CaSR with a combination of specific nutrients, novel oral rehydrating solutions that are inexpensive and practical to use in all countries may be developed.
文摘AIM:To investigate the frequency,etiology,and current management strategies for diarrhea in newborn.METHODS:Retrospective,nationwide study involving 5801 subjects observed in neonatal intensive care units during 3 years.The main anamnesis and demographic characteristics,etiology and characteristics of diarrhea,nutritional and therapeutic management,clinical outcomes were evaluated.RESULTS:Thirty-nine cases of diarrhea(36 acute,3 chronic) were identified.The occurrence rate of diarrhea was 6.72 per 1000 hospitalized newborn.Etiology was defined in 29 of 39 newborn(74.3%):food allergy(20.5%),gastrointestinal infections(17.9%),antibiotic-associated diarrhea(12.8%),congenital defects of ion transport(5.1%),withdrawal syndrome(5.1%),Hirschsprung's disease(2.5%),parenteral diarrhea(2.5%),cystic fibrosis(2.5%),and metabolic disorders(2.5%).Three patients died due to complications related to diarrhea(7.7%).In 19 of 39 patients(48.7%),rehydration was performed exclusively by the enteral route.CONCLUSION:Diarrhea in neonates is a challenging clinical condition due to the possible heterogeneous etiologies and severe outcomes.Specific guidelines are advocated in order to optimize management of diarrhea in this particular setting.
基金funded by the CCOUC field research fundthe Chow Tai Fook Charitable Foundation+1 种基金the I-CARE Programme (The Chinese University of Hong Kong)Wu Zhi Qiao Charitable Foundation
文摘Remote,rural ethnic-minority communities face greater disaster-related public health risks due to their lack of resources and limited access to health care.The Ethnic Minority Health Project(EMHP) was initiated in 2009 to work with remote,disaster-prone ethnic-minority villages that live in extreme poverty.One of the project's aims is to develop and evaluate bottom-up health risk reduction efforts in emergency and disaster risk management(HealthEDRM).This article shares project updates and describes field intervention results from the Yi ethnic community of Hongyan village in China's Sichuan Province,an area that experiences recurrent floods.It was found that 64% of the village respondents had never considered any form of disaster preparation,even with the recurrent flood risks.Health intervention participants showed sustained knowledge retention and were nine times more likely to know the correct composition of oral rehydration solution(ORS) after the intervention.Participants also retained the improved knowledge on ORS and disaster preparedness kit ownership12 months after the intervention.
文摘Objective: To observe the therapeutic effect of Zhixie Buye mixture (止泻补液合剂, ZXBYM) on infantile diarrhea patients with mild or middle degree of dehydration. Methods: Controlled observation method was adopted in the clinical and experimental study. Results: There was no significant difference in the treatment of dehydration between the ZXBYM group and oral rehydration solution (ORS) group (P>0.05), at the same time it was more effective for ZXBYM to eliminate such symptoms as vomiting and abdominal distension (P<0.01). In addition, it was confirmed that the ion concentration of sodium, potassium, chlorine, glucose and osmotic pressure in the mixture was similar to those in ORS. Animal experiment showed that ZXBYM has the effect of rat intestine peristalsis suppression and water absorption promotion in colon. And there was statistical difference in antidiarrhea effect between the mixture and ORS (P<0.01). Conclusion: ZXBYM is an effective mixture in the treatment of diarrhea with dehydration. It has a good prospect for the development and application.