BACKGROUND Hip resurfacing arthroplasty(HRA)is an alternative to total hip arthroplasty(THA)that is typically reserved for young active patients because it preserves bone.However,the benefits of HRA only hold true if ...BACKGROUND Hip resurfacing arthroplasty(HRA)is an alternative to total hip arthroplasty(THA)that is typically reserved for young active patients because it preserves bone.However,the benefits of HRA only hold true if conversion THA after failed HRA provides acceptable outcomes.AIM To compare patient reported outcomes for conversion THA after HRA failure to primary THA.METHODS A retrospective review of 36 patients(37 hips)that underwent conversion THA for failed HRA between October 2006 and May 2019 by a single surgeon was performed.Patient reported outcomes[modified Harris Hip Score(mHHS),University of California Los Angeles(UCLA)activity score]were obtained via an email-based responder-anonymous survey.Outcomes were compared to normative data of a primary THA cohort with similar demographics.Subgroup analysis was performed comparing outcomes of conversion THA for adverse local tissue reaction(ALTR)vs all other causes for failure.RESULTS The study group had a lower mHHS than the control group(81.7±13.8 vs 90.2±11.6,P<0.01);however,both groups had similar UCLA activity levels(7.5±2.3 vs 7.2±1.6,P=0.51).Patients that underwent conversion for non-ATLR causes had similar mHHS(85.2±11.5 vs 90.2±11.6,P=0.11)and higher UCLA activity levels(8.5±1.8 vs 7.2±1.6,P<0.01)compared to the control group.Patients that underwent conversion for ATLR had worse mHHS(77.1±14.5 vs 90.2±11.6,P<0.01)and UCLA activity levels(6.1±2.3 vs 7.2±1.6,P=0.05)when compared to the control group.CONCLUSION Patient outcomes equivalent to primary THA can be achieved following HRA conversion to THA.However,inferior outcomes were demonstrated for ALTR-related HRA failure.Patient selection and perhaps further studies examining alternative HRA bearing surfaces should be considered.展开更多
Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally ...Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements （glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC） were upregulated when rats fed alcohol were treated with a low dose of PS-34Z （Bortezomib, Velcade）. This is an important finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease are related to proteasome inhibitor reversibility and the rebound of proteasome activity 72 h post PS-341 administration.展开更多
We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients dem onst...We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients dem onstrated f indings consistent with drug-induced acute liver injury. To our knowledge, we are the fi rst instit ute to report acute liver injury from both of these two typ es of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supp lements for the purpose of weight loss.展开更多
AIM To investigate the hypothesis that exposure to guanidinoacetate(GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver path...AIM To investigate the hypothesis that exposure to guanidinoacetate(GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage.METHODS Adult male Wistar rats were fed the control or ethanolLieber De Carli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macroand micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol.CONCLUSION To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.展开更多
It has been shown that preneoplastic liver cell foci and hepatic nodules generated by thioacetamide(TAA)in drug-primed mice,which were first fed diethyl 1,4-dihydro,1,4,6-trimethyl 3,5-pyridine decarboxylate(DDC)or gr...It has been shown that preneoplastic liver cell foci and hepatic nodules generated by thioacetamide(TAA)in drug-primed mice,which were first fed diethyl 1,4-dihydro,1,4,6-trimethyl 3,5-pyridine decarboxylate(DDC)or griseofulvin(GF)for 5 months were resistant to protoporphyrin accumulation.[1]DDC or GF are potent porphyrinogenic drugs and accumulate protoporphyrin in the mouse liver.Although DDC or GF are withdrawn for 1 month,when treated with TAA,the nodules formed on the 5th or 7th day of treatment were devoid of protoporphyrin deposits.Feeding DDC or GF for 8 months induced liver tumors which were devoid of protoporphyrin deposits.In contrast,the surrounding liver tissue contained numerous protoporphyrin deposits.This could be attributed to the decreased activity of delta-aminolevulinate synthase,the first rate-limiting enzyme in protoporphyrin synthesis.展开更多
文摘BACKGROUND Hip resurfacing arthroplasty(HRA)is an alternative to total hip arthroplasty(THA)that is typically reserved for young active patients because it preserves bone.However,the benefits of HRA only hold true if conversion THA after failed HRA provides acceptable outcomes.AIM To compare patient reported outcomes for conversion THA after HRA failure to primary THA.METHODS A retrospective review of 36 patients(37 hips)that underwent conversion THA for failed HRA between October 2006 and May 2019 by a single surgeon was performed.Patient reported outcomes[modified Harris Hip Score(mHHS),University of California Los Angeles(UCLA)activity score]were obtained via an email-based responder-anonymous survey.Outcomes were compared to normative data of a primary THA cohort with similar demographics.Subgroup analysis was performed comparing outcomes of conversion THA for adverse local tissue reaction(ALTR)vs all other causes for failure.RESULTS The study group had a lower mHHS than the control group(81.7±13.8 vs 90.2±11.6,P<0.01);however,both groups had similar UCLA activity levels(7.5±2.3 vs 7.2±1.6,P=0.51).Patients that underwent conversion for non-ATLR causes had similar mHHS(85.2±11.5 vs 90.2±11.6,P=0.11)and higher UCLA activity levels(8.5±1.8 vs 7.2±1.6,P<0.01)compared to the control group.Patients that underwent conversion for ATLR had worse mHHS(77.1±14.5 vs 90.2±11.6,P<0.01)and UCLA activity levels(6.1±2.3 vs 7.2±1.6,P=0.05)when compared to the control group.CONCLUSION Patient outcomes equivalent to primary THA can be achieved following HRA conversion to THA.However,inferior outcomes were demonstrated for ALTR-related HRA failure.Patient selection and perhaps further studies examining alternative HRA bearing surfaces should be considered.
基金Supported by NIH/NIAAA 8116 and by a Pilot Project Funding from the Alcohol Center Grant on Liver and Pancreas P50-011999
文摘Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements （glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC） were upregulated when rats fed alcohol were treated with a low dose of PS-34Z （Bortezomib, Velcade）. This is an important finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease are related to proteasome inhibitor reversibility and the rebound of proteasome activity 72 h post PS-341 administration.
基金Supported by Harbor UCLA Medical Center and The Division of Gastroenterology
文摘We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients dem onstrated f indings consistent with drug-induced acute liver injury. To our knowledge, we are the fi rst instit ute to report acute liver injury from both of these two typ es of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supp lements for the purpose of weight loss.
基金Supported by a Merit Review grant BX001155(to Kharbanda KK)from the Department of Veterans Affairs,Office of Research and Development(Biomedical Laboratory Research and Development)
文摘AIM To investigate the hypothesis that exposure to guanidinoacetate(GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage.METHODS Adult male Wistar rats were fed the control or ethanolLieber De Carli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macroand micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol.CONCLUSION To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.
文摘It has been shown that preneoplastic liver cell foci and hepatic nodules generated by thioacetamide(TAA)in drug-primed mice,which were first fed diethyl 1,4-dihydro,1,4,6-trimethyl 3,5-pyridine decarboxylate(DDC)or griseofulvin(GF)for 5 months were resistant to protoporphyrin accumulation.[1]DDC or GF are potent porphyrinogenic drugs and accumulate protoporphyrin in the mouse liver.Although DDC or GF are withdrawn for 1 month,when treated with TAA,the nodules formed on the 5th or 7th day of treatment were devoid of protoporphyrin deposits.Feeding DDC or GF for 8 months induced liver tumors which were devoid of protoporphyrin deposits.In contrast,the surrounding liver tissue contained numerous protoporphyrin deposits.This could be attributed to the decreased activity of delta-aminolevulinate synthase,the first rate-limiting enzyme in protoporphyrin synthesis.
