Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic con...Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic control of various diseases. Crigler-Najjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma. The patient is at permanent risk for irreversible brain damage. The goal of liver cell transplantation is to reduce serum bilirubin levels within safe limits and to alleviate phototherapy requirements to improve quality of life. Preliminary data on Gunn rats, the rodent model of the disease, were encouraging and have led to successful clinical trials. Herein we report on two additional patients and describe the current limits of the technique in terms of durability of the response as compared to alternative therapeutic procedures. We discuss the future developments of the technique and new emerging perspectives.展开更多
AIM： To determine the incidence, clinical characteristics and outcomes of patients with metformin associated lactic acidosis （MALA）.METHODS： Auckland City Hospital drains a population of just over 400000 people. A...AIM： To determine the incidence, clinical characteristics and outcomes of patients with metformin associated lactic acidosis （MALA）.METHODS： Auckland City Hospital drains a population of just over 400000 people. All cases presenting with metabolic acidosis between July 2005 and July 2009 were identifed using clinical coding. A retrospective case notes review identifed patients with MALA. Prescribing data for metformin was obtained from the national pharmaceutical prescribing scheme.RESULTS： There were 42 cases of metabolic lactic acidosis over 1718000 patient years. There were 51000 patient years of metformin prescribed to patients over the study period. There were thirty two cases of lactic acidosis due to sepsis, seven in patients treated with metformin. Ten cases of MALA were identified. The incidence of MALA was estimated at 19.46 per 100000 patient year exposure to metformin. The relative risk of lactic acidosis in patients on metformin was 13.53 （95%CI： 7.88-21.66） compared to the general population. The mean age of patients with MALA was 63 years, range 40-83 years. A baseline estimated glomerular fltration rate was obtained in all patients and ranged from 23-130 mL/min per 1.73 m^2. Only two patients had chronic kidney disease G4.Three patients required treatment with haemodialysis. Two patients died.展开更多
Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited dis...Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.展开更多
Femoral neck stress fractures （FNSFs） are rare, constituting only 5% of all stress fractures in young adults. These fractures are usually seen in athletes, military recruits and patients with underlying metabolic di...Femoral neck stress fractures （FNSFs） are rare, constituting only 5% of all stress fractures in young adults. These fractures are usually seen in athletes, military recruits and patients with underlying metabolic diseases. The treatment of FNSFs is still controversial because of the inherent complications associated with the treatment procedure. We came across 4 cases of bilateral FNSFs in non-athletic individuals who were manual labourers with- out underlying bony disorders. Two patients with FNSFs and coxa vara deformity on both sides were managed by subtrochanteric valgus osteotomy and dynamic hip screw fixation. One of the remaining two patients was treated by cannulated cancellous screw fixation on one side and sub- trochanteric valgus osteotomy on the other side. The fourth patient received subtrochanteric valgus osteotomy on oneside and bipolar hemiarthroplasty on the other side after failed cannulated screw fixation. All the fractures healed without any complications. No evidence of avascular ne- crosis or arthritis was noted in our series. Subtrochanteric valgus osteotomy restores normal neck-shaft angle in pa- tients suffering from FNSFs combined with coxa vara deformity. Moreover, it helps to bring the forces acting around the hip to normal biomechanical levels, leading to fracture union and better results. Replacement arthroplasty is recommended to patients who fail to achieve bony union after fixation.展开更多
Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three pr...Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three presumable mechanisms involved in the development of POI,namely apoptosis acceleration,follicular maturation blocking and premature follicle activation,through the following studied causes:(i) chromosomal abnormalities or gene mutations:mostly involve X chromosome,such as FMR1 premutation;more and more potentially causal genes have been screened recently;(ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency;(iii) autoimmune mediated ovarian damage:observed alone or with some certain autoimmune disorders and syndromes;but the specificity and sensitivity of antibodies towards ovary are still questionable;(iv) iatrogenic:radiotherapy or chemotherapy used in cancer treatment,as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function;(v) virus infection such as HIV and mumps;(vi) toxins and other environmental/lifestyle factors:cigarette smoking,toxins(e.g.,4-vinylcyclohexene diepoxide),and other environmental factors are associated with the development of POI.The etiology of a majority of POI cases is not identified,and is believed to be multifactorial.Strategies to POI include hormone replacement and infertility treatment.Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women.Embryo cryopreservation,ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments.展开更多
文摘Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic control of various diseases. Crigler-Najjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma. The patient is at permanent risk for irreversible brain damage. The goal of liver cell transplantation is to reduce serum bilirubin levels within safe limits and to alleviate phototherapy requirements to improve quality of life. Preliminary data on Gunn rats, the rodent model of the disease, were encouraging and have led to successful clinical trials. Herein we report on two additional patients and describe the current limits of the technique in terms of durability of the response as compared to alternative therapeutic procedures. We discuss the future developments of the technique and new emerging perspectives.
文摘AIM： To determine the incidence, clinical characteristics and outcomes of patients with metformin associated lactic acidosis （MALA）.METHODS： Auckland City Hospital drains a population of just over 400000 people. All cases presenting with metabolic acidosis between July 2005 and July 2009 were identifed using clinical coding. A retrospective case notes review identifed patients with MALA. Prescribing data for metformin was obtained from the national pharmaceutical prescribing scheme.RESULTS： There were 42 cases of metabolic lactic acidosis over 1718000 patient years. There were 51000 patient years of metformin prescribed to patients over the study period. There were thirty two cases of lactic acidosis due to sepsis, seven in patients treated with metformin. Ten cases of MALA were identified. The incidence of MALA was estimated at 19.46 per 100000 patient year exposure to metformin. The relative risk of lactic acidosis in patients on metformin was 13.53 （95%CI： 7.88-21.66） compared to the general population. The mean age of patients with MALA was 63 years, range 40-83 years. A baseline estimated glomerular fltration rate was obtained in all patients and ranged from 23-130 mL/min per 1.73 m^2. Only two patients had chronic kidney disease G4.Three patients required treatment with haemodialysis. Two patients died.
文摘Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.
文摘Femoral neck stress fractures （FNSFs） are rare, constituting only 5% of all stress fractures in young adults. These fractures are usually seen in athletes, military recruits and patients with underlying metabolic diseases. The treatment of FNSFs is still controversial because of the inherent complications associated with the treatment procedure. We came across 4 cases of bilateral FNSFs in non-athletic individuals who were manual labourers with- out underlying bony disorders. Two patients with FNSFs and coxa vara deformity on both sides were managed by subtrochanteric valgus osteotomy and dynamic hip screw fixation. One of the remaining two patients was treated by cannulated cancellous screw fixation on one side and sub- trochanteric valgus osteotomy on the other side. The fourth patient received subtrochanteric valgus osteotomy on oneside and bipolar hemiarthroplasty on the other side after failed cannulated screw fixation. All the fractures healed without any complications. No evidence of avascular ne- crosis or arthritis was noted in our series. Subtrochanteric valgus osteotomy restores normal neck-shaft angle in pa- tients suffering from FNSFs combined with coxa vara deformity. Moreover, it helps to bring the forces acting around the hip to normal biomechanical levels, leading to fracture union and better results. Replacement arthroplasty is recommended to patients who fail to achieve bony union after fixation.
文摘Primary ovarian insufficiency(POI) occurs in about 1% of female population under the age of 40,leading to reproductive problems,an earlier encounter with menopausal symptoms,and complicated diseases.There are three presumable mechanisms involved in the development of POI,namely apoptosis acceleration,follicular maturation blocking and premature follicle activation,through the following studied causes:(i) chromosomal abnormalities or gene mutations:mostly involve X chromosome,such as FMR1 premutation;more and more potentially causal genes have been screened recently;(ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency;(iii) autoimmune mediated ovarian damage:observed alone or with some certain autoimmune disorders and syndromes;but the specificity and sensitivity of antibodies towards ovary are still questionable;(iv) iatrogenic:radiotherapy or chemotherapy used in cancer treatment,as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function;(v) virus infection such as HIV and mumps;(vi) toxins and other environmental/lifestyle factors:cigarette smoking,toxins(e.g.,4-vinylcyclohexene diepoxide),and other environmental factors are associated with the development of POI.The etiology of a majority of POI cases is not identified,and is believed to be multifactorial.Strategies to POI include hormone replacement and infertility treatment.Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women.Embryo cryopreservation,ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments.
