New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by...New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage of 800 mg,threetimes a day,was compared to 2400 mg given once a day.Under ideal conditions,the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3%between single and multiple doses.Despite changes in motility and defection rates,the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10%between dosing regimens.Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate.In active colitis,sigmoid 5-ASA concentration becomes negligible.Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.展开更多
The Chandipura vesiculovirus(CHPV),a single-stranded,negative sense RNA arbovirus with five structural proteins-the G,N,M,P,and L proteins-is the source of Chandipura virus infection.Children between the ages of 9 mon...The Chandipura vesiculovirus(CHPV),a single-stranded,negative sense RNA arbovirus with five structural proteins-the G,N,M,P,and L proteins-is the source of Chandipura virus infection.Children between the ages of 9 months and 14 years old are the most common recipients of CHPV infection,which is primarily spread by sand flies(Sergentomyia,Phlebotomus species).The potential advantages of black seeds(N.sativa)in the treatment of patients with CHPV infection are the main topic of our current review.The majority of patients infected with CHPV experience neurological complications such as encephalitis and other neurological complications.Since there is currently no approved antiviral treatment,supportive care and symptomatic therapy are the primary methods used to manage CHPV-infected patients.Herbal candidates possessing antioxidant,immunomodulatory,antiviral,and anti-inflammatory qualities may aid in the treatment of CHPV infection.The antiviral,anti-inflammatory,antioxidant,and immunomodulatory qualities of black seeds(N.sativa)have been shown in a number of preclinical and clinical investigations;these attributes could be helpful in the treatment of CHPV infection.Black seeds(N.sativa)may help treat CHPV-infected patients in the early stages of their illness when used in conjunction with symptomatic therapy and supportive care.In patients infected with CHPV,additional randomized controlled clinical trials would assess the efficacy and safety of black seeds(N.sativa).展开更多
Identifying the presence of cognitive impairment in patients admitted for inpatient rehabilitation is important as it may impact on their ability to participate in a rehabilitation program. The Folstein Mini Mental St...Identifying the presence of cognitive impairment in patients admitted for inpatient rehabilitation is important as it may impact on their ability to participate in a rehabilitation program. The Folstein Mini Mental State Examination (MMSE) has been used by clinicians as a cognitive screening tool for its convenience, even though it is not sensitive, and often fails to detect cognitive impairment. Recently, the Montreal Cognitive Assessment (MoCA) has been developed as a brief cognitive screening tool to detect mild-moderate cognitive impairment. We performed a longitudinal study to compare the utility of the MMSE and MoCA in an inpatient rehabilitation setting. A total of 50 consecutive patients were studied with an average age of 71.7 years of age. The mean test score for MMSE was 26.5 and 22.2 for the MoCA. The Pearson’s correlation coefficient between the scores was 0.695 (p < 0.003). The mean performance time for the MMSE was 7.4 minutes and 14.8 minutes for the MoCA. MMSE did not perform well as a screening instrument for mild cognitive impairment as there were 43 patients who scored 24 or more on MMSE, and 25 patients (58%) scored 25 or less on MoCA, indicating the presence of cognitive impairment. Even though the MoCA takes longer to administer, the additional important information provided indicates that the MoCA should be used rather than the MMSE as a cogni-tive screening tool.展开更多
Casals et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weigh...Casals et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weight and hyperphosphatemia with these preparations, although our study was not quoted by Casals. We performed a pharmacokinetic study involving 13 volunteers who were divided into two groups on the basis of body weight： group I consisting of seven women with a median weight of 60 kg and group Ⅱ consisting of five men and one woman with a median weight of 119.2 kg. Group Ⅰdeveloped higher peak phosphate levels and maintained these levels above the subjects in Group Ⅱ for a prolonged time period despite adequate hydration being ensured with frequent monitoring of weight, fluid intake and total body weight. Our studydemonstrated that adequate hydration does not protect against the secondary effects of hyperphosphatemia. In the study by Casais et al, 66% of the study subjects were women, the correlation between serum phosphate and gender in their data also appears to be important. Women are at higher risk of acute phosphate nephropathy due to a diminished volume of distribution of the high dose of ingested phosphate. Decreased volume of distribution in women is due to diminished body weight. This is further compounded by decreased creatinine clearance in females.展开更多
AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-...AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-treatment,single dose cross-over bioequivalence study,under non-fed condition to compare the pharmacokinetic prof iles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd.,India using an indigenously developed active pharmaceutical ingredient(API) and the commercially available Stogra formulation,of UCB Japan Co.,Ltd.,Japan.The two treatments were separated by a washout period of 5 d.After an overnight fasting period of 10 h,the subjects were administered either the test or the reference medication as per the randomization schedule.Blood samples were collected at intervals up to 24 h,as per the approved protocol.Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry(LC/MS/MS) method,and a non-compartmental model was used for pharmacokinetic analysis.The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence,subjects,period and treatment.Statistical significance was evaluated at 95% conf idence level(P ≥ 0.05).RESULTS:The mean(±SD) values of the pharmacokinetic parameters(test vs reference) were Cmax(265.15±49.84 ng/mL vs 246.79±29.30 ng/mL,P<0.05),Area under the curve(AUC)(0-t)(1033.13±298.74 ng.h/mL vs 952.93±244.07 ng.h/mL,P < 0.05),AUC(0-∞)(1047.61±301.22 ng.h/mL vs 964.21±246.45 ng.h/mL,P<0.05),and tv2(1.92±0.94 h vs 2.05±1.01 h,P<0.05).The 90% conf idence intervals(CI) for the test/reference ratio of mean Cmax,AUC(0-t),and AUC(0-∞) were within the acceptable range of 80.00 to 125.00.The mean times(± SD) to attain maximal plasma concentration(tmax) of lafutidine were 0.95±0.24 h vs 1.01±0.29 h(P<0.05) for the test and the reference formulations respectively.Both the formulations were well tolerated.展开更多
Primary sclerosing cholangitis(PSC)is a chronic,progressive,hepatobiliary disease characterized by inflammation and fibrosis of the intra-and extra-hepatic bile ducts.Its natural history is one that generally progress...Primary sclerosing cholangitis(PSC)is a chronic,progressive,hepatobiliary disease characterized by inflammation and fibrosis of the intra-and extra-hepatic bile ducts.Its natural history is one that generally progresses towards cirrhosis,liver failure,cholangiocarcinoma,and ultimately disease-related death,with a median liver transplantation-free survival time of approximately 15-20 years.However,despite its lethal nature,PSC remains a heterogenous disease with significant variability in outcomes amongst different regions of the world.There are also many regions where the outcomes of PSC have not been studied,limiting the overall understanding of this disease worldwide.In this review,we present the geoepidemiologic variations in outcomes of PSC,with a focus on survival pre-and post-liver transplantation as well as the concurrence of inflammatory bowel disease and hepatobiliary neoplasia.展开更多
Introduction: Rupture of unscarred uterus (primary uterine rupture) is a rare peripartum complication often associated with catastrophic maternal and neonatal outcomes. Case presentation: A 27-year-old primigravid lad...Introduction: Rupture of unscarred uterus (primary uterine rupture) is a rare peripartum complication often associated with catastrophic maternal and neonatal outcomes. Case presentation: A 27-year-old primigravid lady, previously healthy, at 40 weeks + 2 days presented to a midwife’s clinic for routine antenatal consultation. She was advised to have induction of labor. This was initiated with 2 tablets of Misoprostol (400 mcg) vaginally. Twelve hours later, and after remaining at full cervical dilation for 4 hours, she was referred to our maternity service for alleged failure to descend. On arrival, she was apprehensive, exhausted but hemodynamically stable. Pelvic exam disclosed a fully dilated cervix with the vertex at S + 1 and a caput reaching the introitus. No fetal heart rate could be elicited by the CTG monitor and this was verified by a bedside ultrasonography. Operative vaginal delivery was performed due to maternal exhaustion. This was complicated by transient shoulder dystocia. Manual revision of the birth canal and the uterine cavity disclosed a suspicion of left vaginal vault gapping together with a left fundal uterine rupture. Consequently, the patient was rushed to the operating room for an urgent exploratory laparotomy. The rupture sites were identified and repaired while a large broad ligament hematoma on the same side was explored and hemostasis secured with ipsilateral uterine artery ligation of the fundal and cervical branches. The postoperative course was smooth and the patient left the hospital on the 5th day postpartum. Conclusion: Cases of unscarred uterine rupture are limited. One of the most frequent risk factor is the injudicious use of Misoprostol for labor induction. Sudden arrest of progress of labor or failure to descend might mask uterine rupture. We recommend that all birth attendants be familiar with the guidelines issued by FIGO, ACOG and other societies for the safe use of these potent uterotonics.展开更多
Objective： The treatment of multi- fragmentary, intraarticular fractures of the distal humerus is difficult, even in young patients with bone of good quality. Small distal fragment, diminished bone mineral quality an...Objective： The treatment of multi- fragmentary, intraarticular fractures of the distal humerus is difficult, even in young patients with bone of good quality. Small distal fragment, diminished bone mineral quality and increased trauma-associated joint destruction make stable joint reconstruction more problematic. The anatomically preshaped locking plates allow angular stable fixation for these complex fractures. We evaluated functional results of patients treated with open reduction and internal fixation with distal humerus locking plates for complex distal hu- merus fractures. Methods： Forty-three consecutive patients with ar- ticular fractures of the distal humerus were treated by open reduction and internal fixation with AO distal humerus plate system and locking reconstruction plates. Forty patients were available for the final outcome analysis. According to AO/ASIF classification, there were 2 cases of type A2, 4 cases of type A3, 1 case of type B1, 1 case of type B2, 14 cases of type C1, 7 cases of type C2 and 11 cases of type C3. Open reduction with triceps splitting technique was used in all patients. The clinical and radiographic follow-up was performed and outcome measures included pain assessment,range of motion, and Mayo elbow performance score. Results： Forty patients were available for the final outcome analysis. There were 29 males and 11 females with an average age of 38.4 years （18-73 years）. Clinical and ra- diological consolidation of the fracture was observed in all cases at an average of 11.6 weeks （9-14 weeks）. The average follow-up was 12 months （10-18 months）. Using the Mayo elbow performance score the results obtained were graded as excellent or good results in 33 patients （82.5%）. One pa- tient had superficial infection, and 4 had myositis ossificans. There were no cases of primary malposition or secondary displacement, implant failure or ulnar neuropathy. Conclusion： Anatomically preshaped distal humerus locking plate system is useful in providing stable fixation for complex distal articular fracture and facilitating early post- operative rehabilitation. The low rate of implant failure in the present study indicates that the technique is promising and warrants further investigation.展开更多
文摘New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage of 800 mg,threetimes a day,was compared to 2400 mg given once a day.Under ideal conditions,the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3%between single and multiple doses.Despite changes in motility and defection rates,the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10%between dosing regimens.Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate.In active colitis,sigmoid 5-ASA concentration becomes negligible.Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.
文摘The Chandipura vesiculovirus(CHPV),a single-stranded,negative sense RNA arbovirus with five structural proteins-the G,N,M,P,and L proteins-is the source of Chandipura virus infection.Children between the ages of 9 months and 14 years old are the most common recipients of CHPV infection,which is primarily spread by sand flies(Sergentomyia,Phlebotomus species).The potential advantages of black seeds(N.sativa)in the treatment of patients with CHPV infection are the main topic of our current review.The majority of patients infected with CHPV experience neurological complications such as encephalitis and other neurological complications.Since there is currently no approved antiviral treatment,supportive care and symptomatic therapy are the primary methods used to manage CHPV-infected patients.Herbal candidates possessing antioxidant,immunomodulatory,antiviral,and anti-inflammatory qualities may aid in the treatment of CHPV infection.The antiviral,anti-inflammatory,antioxidant,and immunomodulatory qualities of black seeds(N.sativa)have been shown in a number of preclinical and clinical investigations;these attributes could be helpful in the treatment of CHPV infection.Black seeds(N.sativa)may help treat CHPV-infected patients in the early stages of their illness when used in conjunction with symptomatic therapy and supportive care.In patients infected with CHPV,additional randomized controlled clinical trials would assess the efficacy and safety of black seeds(N.sativa).
文摘Identifying the presence of cognitive impairment in patients admitted for inpatient rehabilitation is important as it may impact on their ability to participate in a rehabilitation program. The Folstein Mini Mental State Examination (MMSE) has been used by clinicians as a cognitive screening tool for its convenience, even though it is not sensitive, and often fails to detect cognitive impairment. Recently, the Montreal Cognitive Assessment (MoCA) has been developed as a brief cognitive screening tool to detect mild-moderate cognitive impairment. We performed a longitudinal study to compare the utility of the MMSE and MoCA in an inpatient rehabilitation setting. A total of 50 consecutive patients were studied with an average age of 71.7 years of age. The mean test score for MMSE was 26.5 and 22.2 for the MoCA. The Pearson’s correlation coefficient between the scores was 0.695 (p < 0.003). The mean performance time for the MMSE was 7.4 minutes and 14.8 minutes for the MoCA. MMSE did not perform well as a screening instrument for mild cognitive impairment as there were 43 patients who scored 24 or more on MMSE, and 25 patients (58%) scored 25 or less on MoCA, indicating the presence of cognitive impairment. Even though the MoCA takes longer to administer, the additional important information provided indicates that the MoCA should be used rather than the MMSE as a cogni-tive screening tool.
文摘Casals et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weight and hyperphosphatemia with these preparations, although our study was not quoted by Casals. We performed a pharmacokinetic study involving 13 volunteers who were divided into two groups on the basis of body weight： group I consisting of seven women with a median weight of 60 kg and group Ⅱ consisting of five men and one woman with a median weight of 119.2 kg. Group Ⅰdeveloped higher peak phosphate levels and maintained these levels above the subjects in Group Ⅱ for a prolonged time period despite adequate hydration being ensured with frequent monitoring of weight, fluid intake and total body weight. Our studydemonstrated that adequate hydration does not protect against the secondary effects of hyperphosphatemia. In the study by Casais et al, 66% of the study subjects were women, the correlation between serum phosphate and gender in their data also appears to be important. Women are at higher risk of acute phosphate nephropathy due to a diminished volume of distribution of the high dose of ingested phosphate. Decreased volume of distribution in women is due to diminished body weight. This is further compounded by decreased creatinine clearance in females.
文摘AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-treatment,single dose cross-over bioequivalence study,under non-fed condition to compare the pharmacokinetic prof iles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd.,India using an indigenously developed active pharmaceutical ingredient(API) and the commercially available Stogra formulation,of UCB Japan Co.,Ltd.,Japan.The two treatments were separated by a washout period of 5 d.After an overnight fasting period of 10 h,the subjects were administered either the test or the reference medication as per the randomization schedule.Blood samples were collected at intervals up to 24 h,as per the approved protocol.Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry(LC/MS/MS) method,and a non-compartmental model was used for pharmacokinetic analysis.The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence,subjects,period and treatment.Statistical significance was evaluated at 95% conf idence level(P ≥ 0.05).RESULTS:The mean(±SD) values of the pharmacokinetic parameters(test vs reference) were Cmax(265.15±49.84 ng/mL vs 246.79±29.30 ng/mL,P<0.05),Area under the curve(AUC)(0-t)(1033.13±298.74 ng.h/mL vs 952.93±244.07 ng.h/mL,P < 0.05),AUC(0-∞)(1047.61±301.22 ng.h/mL vs 964.21±246.45 ng.h/mL,P<0.05),and tv2(1.92±0.94 h vs 2.05±1.01 h,P<0.05).The 90% conf idence intervals(CI) for the test/reference ratio of mean Cmax,AUC(0-t),and AUC(0-∞) were within the acceptable range of 80.00 to 125.00.The mean times(± SD) to attain maximal plasma concentration(tmax) of lafutidine were 0.95±0.24 h vs 1.01±0.29 h(P<0.05) for the test and the reference formulations respectively.Both the formulations were well tolerated.
文摘Primary sclerosing cholangitis(PSC)is a chronic,progressive,hepatobiliary disease characterized by inflammation and fibrosis of the intra-and extra-hepatic bile ducts.Its natural history is one that generally progresses towards cirrhosis,liver failure,cholangiocarcinoma,and ultimately disease-related death,with a median liver transplantation-free survival time of approximately 15-20 years.However,despite its lethal nature,PSC remains a heterogenous disease with significant variability in outcomes amongst different regions of the world.There are also many regions where the outcomes of PSC have not been studied,limiting the overall understanding of this disease worldwide.In this review,we present the geoepidemiologic variations in outcomes of PSC,with a focus on survival pre-and post-liver transplantation as well as the concurrence of inflammatory bowel disease and hepatobiliary neoplasia.
文摘Introduction: Rupture of unscarred uterus (primary uterine rupture) is a rare peripartum complication often associated with catastrophic maternal and neonatal outcomes. Case presentation: A 27-year-old primigravid lady, previously healthy, at 40 weeks + 2 days presented to a midwife’s clinic for routine antenatal consultation. She was advised to have induction of labor. This was initiated with 2 tablets of Misoprostol (400 mcg) vaginally. Twelve hours later, and after remaining at full cervical dilation for 4 hours, she was referred to our maternity service for alleged failure to descend. On arrival, she was apprehensive, exhausted but hemodynamically stable. Pelvic exam disclosed a fully dilated cervix with the vertex at S + 1 and a caput reaching the introitus. No fetal heart rate could be elicited by the CTG monitor and this was verified by a bedside ultrasonography. Operative vaginal delivery was performed due to maternal exhaustion. This was complicated by transient shoulder dystocia. Manual revision of the birth canal and the uterine cavity disclosed a suspicion of left vaginal vault gapping together with a left fundal uterine rupture. Consequently, the patient was rushed to the operating room for an urgent exploratory laparotomy. The rupture sites were identified and repaired while a large broad ligament hematoma on the same side was explored and hemostasis secured with ipsilateral uterine artery ligation of the fundal and cervical branches. The postoperative course was smooth and the patient left the hospital on the 5th day postpartum. Conclusion: Cases of unscarred uterine rupture are limited. One of the most frequent risk factor is the injudicious use of Misoprostol for labor induction. Sudden arrest of progress of labor or failure to descend might mask uterine rupture. We recommend that all birth attendants be familiar with the guidelines issued by FIGO, ACOG and other societies for the safe use of these potent uterotonics.
文摘Objective： The treatment of multi- fragmentary, intraarticular fractures of the distal humerus is difficult, even in young patients with bone of good quality. Small distal fragment, diminished bone mineral quality and increased trauma-associated joint destruction make stable joint reconstruction more problematic. The anatomically preshaped locking plates allow angular stable fixation for these complex fractures. We evaluated functional results of patients treated with open reduction and internal fixation with distal humerus locking plates for complex distal hu- merus fractures. Methods： Forty-three consecutive patients with ar- ticular fractures of the distal humerus were treated by open reduction and internal fixation with AO distal humerus plate system and locking reconstruction plates. Forty patients were available for the final outcome analysis. According to AO/ASIF classification, there were 2 cases of type A2, 4 cases of type A3, 1 case of type B1, 1 case of type B2, 14 cases of type C1, 7 cases of type C2 and 11 cases of type C3. Open reduction with triceps splitting technique was used in all patients. The clinical and radiographic follow-up was performed and outcome measures included pain assessment,range of motion, and Mayo elbow performance score. Results： Forty patients were available for the final outcome analysis. There were 29 males and 11 females with an average age of 38.4 years （18-73 years）. Clinical and ra- diological consolidation of the fracture was observed in all cases at an average of 11.6 weeks （9-14 weeks）. The average follow-up was 12 months （10-18 months）. Using the Mayo elbow performance score the results obtained were graded as excellent or good results in 33 patients （82.5%）. One pa- tient had superficial infection, and 4 had myositis ossificans. There were no cases of primary malposition or secondary displacement, implant failure or ulnar neuropathy. Conclusion： Anatomically preshaped distal humerus locking plate system is useful in providing stable fixation for complex distal articular fracture and facilitating early post- operative rehabilitation. The low rate of implant failure in the present study indicates that the technique is promising and warrants further investigation.
