Monday
Maternal Serum Ferritin Concentration Is Positively Associated with Newborn Iron Stores in Women with Low Ferritin Status in Late Pregnancy.
Abstract
Iron deficiency (ID) is common in pregnant women and infants, particularly in developing countries. The relation between maternal and neonatal iron status remains unclear. This study considered the issue in a large sample of mother-newborn pairs in rural southeastern China.
Hemoglobin (Hb) and serum ferritin (SF) were measured in 3702 pregnant women at ≥37 wk gestation and in cord blood of their infants born at term (37-42 wk gestation). Maternal anemia (Hb <110 27.5="27.5" 5.6="5.6" 86.9="86.9" 9.5="9.5" and="and" anemic="anemic" associated="associated" b="b" cord-blood="cord-blood" g="g" had="had" in="in" maternal="maternal" neonates="neonates" of="of" only="only" present="present" sf="sf" was="was" were="were" with="with">
There were low-order correlations between maternal and newborn iron measures (r = 0.07-0.10 for both Hb and SF; P ≤ 0.0001 due to the large number). We excluded 430 neonates with suggestion of inflammation [cord SF >370 μg/L, n = 208 and/or C-reactive protein (CRP) >5 mg/L, n = 233]. Piecewise linear regression analyses identified a threshold for maternal SF at which cord-blood SF was affected. For maternal SF below the threshold of 13.6 μg/L (β = 2.4; P = 0.001), cord SF was 0.17 SD lower than in neonates whose mothers had SF above the threshold (167 ± 75 vs. 179 ± 80 μg/L). T
he study confirmed that ID anemia remains common during pregnancy in rural southeastern China. Despite widespread maternal ID, however, iron nutrition seemed to meet fetal needs except when mothers were very iron deficient. The impact of somewhat lower cord SF on iron status later in infancy warrants further study.
Department of Child Health Care, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China J Nutr.2012 Sep 26.
Differences and similarities in binding of pyruvate and l-lactate in the active site of M4 and H4 isoforms of human lactate dehydrogenase
Abstract
We present QM/MM calculations that show differences in geometries of active sites of M4 and H4 isoforms of human LDH ligated with oxamate, pyruvate or l-lactate. As the consequence of these differences, binding isotope effects of the methyl hydrogen atoms of pyruvate and l-lactate may be used to experimentally distinguish these isoforms. Based on the FEP calculations we argue that l-lactate is a better candidate for the experimental studies. Our calculations of energies of interactions of ligands with the active site residues provide explanation for the observed experimentally sensitivity to inhibition of the M4 isoenzyme isoform and pinpoint the differences to interactions of the ligand with the histidine residue. We conclude that pyruvate interacts much stronger in the active site of H4 than M4 isoform and that the latter interactions are weaker than with water molecules in the aqueous solution
Research highlights
► Isoforms M4 and H4 of human lactate dehydrogenase exhibit different BIEs of pyruvate and l-lactate. ► Hydrogen BIEs of l-lactate and pyruvate can be used for differentiation of the LDH isoforms. ► Affinities of pyruvate toward active sites of M4 and H4 are different. ► l-lactate is a good candidate for experimental differentiation of LDH isoforms.
Conclusions
Studies presented herein explain the experimental observations where H4 isoform is much more sensitive to inhibition than the M4 isoenzyme. The studies of energies of interactions of ligands with the active site residues provide explanation to this problem and pinpoint the differences to interactions of pyruvate with the histidine residue. Our theoretical studies show that pyruvate interacts much stronger in the active site of H4 than M4 isoform. Moreover, the interactions of pyruvate with active site of M4 isoform are weaker that with water molecules in the aqueous solution.
Using QM/MM calculations it was shown that the geometries of the LDH active sites are significantly different when oxamate, pyruvate or l-lactate are ligated. Because of these differences M4 and H4 isoforms of human LDH may be distinguished on the basis of binding isotope effects of hydrogen atoms of the methyl group of pyruvate and l-lactate. FEP calculations indicate that pyruvate has low affinity to the active site of the M4 isoform thus it seems safer to use l-lactate as a ligand for experimental differentiation the LDH isoforms.
Archives of Biochemistry and Biophysics
Volume 505, Issue 1, 1 January 2011, Pages 33-41
Special Section: Trends in Enzymology 2010
We present QM/MM calculations that show differences in geometries of active sites of M4 and H4 isoforms of human LDH ligated with oxamate, pyruvate or l-lactate. As the consequence of these differences, binding isotope effects of the methyl hydrogen atoms of pyruvate and l-lactate may be used to experimentally distinguish these isoforms. Based on the FEP calculations we argue that l-lactate is a better candidate for the experimental studies. Our calculations of energies of interactions of ligands with the active site residues provide explanation for the observed experimentally sensitivity to inhibition of the M4 isoenzyme isoform and pinpoint the differences to interactions of the ligand with the histidine residue. We conclude that pyruvate interacts much stronger in the active site of H4 than M4 isoform and that the latter interactions are weaker than with water molecules in the aqueous solution
Research highlights
► Isoforms M4 and H4 of human lactate dehydrogenase exhibit different BIEs of pyruvate and l-lactate. ► Hydrogen BIEs of l-lactate and pyruvate can be used for differentiation of the LDH isoforms. ► Affinities of pyruvate toward active sites of M4 and H4 are different. ► l-lactate is a good candidate for experimental differentiation of LDH isoforms.
Conclusions
Studies presented herein explain the experimental observations where H4 isoform is much more sensitive to inhibition than the M4 isoenzyme. The studies of energies of interactions of ligands with the active site residues provide explanation to this problem and pinpoint the differences to interactions of pyruvate with the histidine residue. Our theoretical studies show that pyruvate interacts much stronger in the active site of H4 than M4 isoform. Moreover, the interactions of pyruvate with active site of M4 isoform are weaker that with water molecules in the aqueous solution.
Using QM/MM calculations it was shown that the geometries of the LDH active sites are significantly different when oxamate, pyruvate or l-lactate are ligated. Because of these differences M4 and H4 isoforms of human LDH may be distinguished on the basis of binding isotope effects of hydrogen atoms of the methyl group of pyruvate and l-lactate. FEP calculations indicate that pyruvate has low affinity to the active site of the M4 isoform thus it seems safer to use l-lactate as a ligand for experimental differentiation the LDH isoforms.
Archives of Biochemistry and Biophysics
Volume 505, Issue 1, 1 January 2011, Pages 33-41
Special Section: Trends in Enzymology 2010
Tuesday
Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis
Circulating lipopolysaccharides released from bacteria may activate both neutrophils and monocytes. The activated neutrophils release myeloperoxidase (MPO), a specific enzyme with strong oxidative activity. The aim of this study was to evaluate MPO enzyme activity in plasma of critically ill patients and to check the hypothesis that these concentrations in plasma would be higher in sepsis and systemic inflammatory conditions, as neutrophils release their contents before proliferating in response to stress.
Results
The plasma MPO enzyme activity in sepsis patients was significantly higher than that in the control group (mean, 2.4 ± 1.8 in sepsis and 1.86 ± 1.2 nmol per milligram protein per 10 minutes in systemic inflammatory response syndrome vs 0.32 ± 0.11 nmol per milligram protein per 10 minutes in healthy controls). Mean plasma lactate levels in sepsis (7.8 ± 1.2 mmol/L) and shock patients (9.5 ± 1.2 mmol/L) and cytokines like tumor necrosis factor–α, interleukin-8, and interleukin-1β were simultaneously evaluated to establish onset of inflammation and sepsis. These results show that neutrophil activation occurring during inflammation and sepsis could be detected by plasma MPO concentration
Conclusion : The plasma MPO concentrations may be a marker of the neutrophil proliferation and severity of inflammation
a Department of Anaesthesia, Chatrapati Shahuji Maharaj Medical University, Lucknow, UP, India
b Pharmacology Division, Central Drug Research Institute, Lucknow, UP, India
Results
The plasma MPO enzyme activity in sepsis patients was significantly higher than that in the control group (mean, 2.4 ± 1.8 in sepsis and 1.86 ± 1.2 nmol per milligram protein per 10 minutes in systemic inflammatory response syndrome vs 0.32 ± 0.11 nmol per milligram protein per 10 minutes in healthy controls). Mean plasma lactate levels in sepsis (7.8 ± 1.2 mmol/L) and shock patients (9.5 ± 1.2 mmol/L) and cytokines like tumor necrosis factor–α, interleukin-8, and interleukin-1β were simultaneously evaluated to establish onset of inflammation and sepsis. These results show that neutrophil activation occurring during inflammation and sepsis could be detected by plasma MPO concentration
Conclusion : The plasma MPO concentrations may be a marker of the neutrophil proliferation and severity of inflammation
a Department of Anaesthesia, Chatrapati Shahuji Maharaj Medical University, Lucknow, UP, India
b Pharmacology Division, Central Drug Research Institute, Lucknow, UP, India
Wednesday
"Contagious Yawning in Autistic and Typical Development"
Molly S. Helt, Inge-Marie Eigsti, Peter J. Snyder, Deborah A. Fein
Child Development Article first published online: 14 SEP 2010
If somebody yawns it is likely that half the people nearby will probably do the same - a occurrence we call contagious yawning. However, children with severe autism miss the subtle cues that elicit collective yawning, say researchers from the University of Connecticut in a study published in the medical journal Child Development. The writers say their findings may help experts determine why people with autism find it harder to form close emotional bonds with others.
The investigators also found that individuals with milder variants of ASD (autism spectrum disorder) were more likely to yawn contagiously that those with more severe autism. They also found that most children with or without autism under the age of four years are much less likely to be contagiously yawning.
Molly Helt, a doctoral student in the Department of Psychology, College of Liberal Arts and Sciences, University of Connecticut, and the study's primary author, wrote:
This lends support to the idea that the social mind develops over time through a process of mimicry and feedback. If we can identify a lack of mimicry of facial expressions early, it could be an identifier of potential neurodevelopment disorders such as autism.
Contagious yawning is a form of mimicry, something apparently unique to humans and chimpanzees - researchers believe we acquire it over time. It is different from spontaneous yawning, which all vertebrates do. Spontaneous yawning has been observed in fetuses in the womb.
Helt's study differs from previous ones in that it included live stimulis - human experimenters - as opposed to just exposing participants to videos of people yawning. The study compared children with severe autism, children diagnosed with a Pervasive Development Disorder, and kids with neither (typically developing children).
The study was divided into two parts:
The first study - including only typically developing children
120 typically developing children aged between 1 and 6 years were recruited from local daycare centers. They sat in a quiet room facing the experimenter who sat on the other side of the room. The experimenter read a story out loud, one of four stories which depended on the age of the children, for a total of 12 minutes. During the last 10 minutes of the reading the experimenter yawned four times, and recorded (discreetly) whether any child yawned within 90 seconds. About 40% of the reading sessions were randomly recorded on video and coded by two independent raters for reliability.
If a child yawned in response to one or more of the experimenter's stimulus yawns, he/she was considered a contagious yawner. The experimenter did not include in the analysis children who were not looking the experimenter most of the time.
The authors report that children under four years of age were much less likely to engage in contagious yawning, compared to the older kids.
There were 20 children aged just 1 year - none of them yawned.
There were 20 children aged 2 years - 1 of them yawned.
There were 20 children aged 3 years - 2 of them yawned. There were 20 children aged 4 years - 7 of them yawned.
There were 20 children aged 5/6 years - 8 of them yawned
We saw a major jump to adult levels of contagious yawning at age four. We thought that was the most surprising thing. We thought it would be quite a bit younger.
The second study - both children with autism and typically developing children This study involved 15 children with ASDs (autism spectrum disorders) and two control groups with typically developing children of the same age - a total of 28 children.
The test was identical to what was tried out in the first study.
The researchers found that:
Those with autism spectrum disorders yawned about half as often as the typically developing children did.
None of the children with severe autism got caught up in contagious yawning.
Helt believes that children with autism have a deficit in early social learning that impedes and undermines their ability to mimic the actions and emotions of others around them.
Helt added:
This lack of early mimicry could also impact feelings of psychological connection and opportunities for social learning. These changes could thus leave children with autism unable to recognize primitive socio-emotional clues that could otherwise serve to biologically and emotionally synchronize them with people around them.
The authors believe their findings may help people who work with children with ASDs develop approaches that focus more on social and emotional cues.
What is autism?
Autism is known as a complex developmental disability. Clinicians believe that Autism presents itself during the first three years of a child's life. The condition is the result of a neurological disorder that has an effect on normal brain function, affecting development of the person's communication and social interaction skills.
People with autism have problems with non-verbal communication, a wide range of social interactions, and activities that include an element of play and/or banter.
ASD stands for Autism Spectrum Disorder and can sometimes be referred to as Autistic Spectrum Disorder. ASDs are any developmental disabilities that have been caused by a brain abnormality. A person with an ASD typically has difficulty with social and communication skills.
A person with ASD will typically also prefer to stick to a set of behaviors and will resist any major (and many minor) changes to daily activities. Several relatives and friends of people with ASDs have commented that if the person knows a change is coming in advance, and has time to prepare for it; the resistance to the change is either gone completely or is much lower.
Click here to read about autism in more detail.
Source: University of Connecticut, Medical News Today (archives)
"Contagious Yawning in Autistic and Typical Development"
Molly S. Helt, Inge-Marie Eigsti, Peter J. Snyder, Deborah A. Fein
Child Development Article first published online: 14 SEP 2010
DOI: 10.1111/j.1467-8624.2010.01495.x
Child Development Article first published online: 14 SEP 2010
If somebody yawns it is likely that half the people nearby will probably do the same - a occurrence we call contagious yawning. However, children with severe autism miss the subtle cues that elicit collective yawning, say researchers from the University of Connecticut in a study published in the medical journal Child Development. The writers say their findings may help experts determine why people with autism find it harder to form close emotional bonds with others.
The investigators also found that individuals with milder variants of ASD (autism spectrum disorder) were more likely to yawn contagiously that those with more severe autism. They also found that most children with or without autism under the age of four years are much less likely to be contagiously yawning.
Molly Helt, a doctoral student in the Department of Psychology, College of Liberal Arts and Sciences, University of Connecticut, and the study's primary author, wrote:
This lends support to the idea that the social mind develops over time through a process of mimicry and feedback. If we can identify a lack of mimicry of facial expressions early, it could be an identifier of potential neurodevelopment disorders such as autism.
Contagious yawning is a form of mimicry, something apparently unique to humans and chimpanzees - researchers believe we acquire it over time. It is different from spontaneous yawning, which all vertebrates do. Spontaneous yawning has been observed in fetuses in the womb.
Helt's study differs from previous ones in that it included live stimulis - human experimenters - as opposed to just exposing participants to videos of people yawning. The study compared children with severe autism, children diagnosed with a Pervasive Development Disorder, and kids with neither (typically developing children).
The study was divided into two parts:
The first study - including only typically developing children
120 typically developing children aged between 1 and 6 years were recruited from local daycare centers. They sat in a quiet room facing the experimenter who sat on the other side of the room. The experimenter read a story out loud, one of four stories which depended on the age of the children, for a total of 12 minutes. During the last 10 minutes of the reading the experimenter yawned four times, and recorded (discreetly) whether any child yawned within 90 seconds. About 40% of the reading sessions were randomly recorded on video and coded by two independent raters for reliability.
If a child yawned in response to one or more of the experimenter's stimulus yawns, he/she was considered a contagious yawner. The experimenter did not include in the analysis children who were not looking the experimenter most of the time.
The authors report that children under four years of age were much less likely to engage in contagious yawning, compared to the older kids.
There were 20 children aged just 1 year - none of them yawned.
There were 20 children aged 2 years - 1 of them yawned.
There were 20 children aged 3 years - 2 of them yawned. There were 20 children aged 4 years - 7 of them yawned.
There were 20 children aged 5/6 years - 8 of them yawned
We saw a major jump to adult levels of contagious yawning at age four. We thought that was the most surprising thing. We thought it would be quite a bit younger.
The second study - both children with autism and typically developing children This study involved 15 children with ASDs (autism spectrum disorders) and two control groups with typically developing children of the same age - a total of 28 children.
The test was identical to what was tried out in the first study.
The researchers found that:
Those with autism spectrum disorders yawned about half as often as the typically developing children did.
None of the children with severe autism got caught up in contagious yawning.
Helt believes that children with autism have a deficit in early social learning that impedes and undermines their ability to mimic the actions and emotions of others around them.
Helt added:
This lack of early mimicry could also impact feelings of psychological connection and opportunities for social learning. These changes could thus leave children with autism unable to recognize primitive socio-emotional clues that could otherwise serve to biologically and emotionally synchronize them with people around them.
The authors believe their findings may help people who work with children with ASDs develop approaches that focus more on social and emotional cues.
What is autism?
Autism is known as a complex developmental disability. Clinicians believe that Autism presents itself during the first three years of a child's life. The condition is the result of a neurological disorder that has an effect on normal brain function, affecting development of the person's communication and social interaction skills.
People with autism have problems with non-verbal communication, a wide range of social interactions, and activities that include an element of play and/or banter.
ASD stands for Autism Spectrum Disorder and can sometimes be referred to as Autistic Spectrum Disorder. ASDs are any developmental disabilities that have been caused by a brain abnormality. A person with an ASD typically has difficulty with social and communication skills.
A person with ASD will typically also prefer to stick to a set of behaviors and will resist any major (and many minor) changes to daily activities. Several relatives and friends of people with ASDs have commented that if the person knows a change is coming in advance, and has time to prepare for it; the resistance to the change is either gone completely or is much lower.
Click here to read about autism in more detail.
Source: University of Connecticut, Medical News Today (archives)
"Contagious Yawning in Autistic and Typical Development"
Molly S. Helt, Inge-Marie Eigsti, Peter J. Snyder, Deborah A. Fein
Child Development Article first published online: 14 SEP 2010
DOI: 10.1111/j.1467-8624.2010.01495.x
Monday
High salivary alpha-amylase levels in patients with schizophrenia: A pilot study
Abstract
Previous studies have demonstrated the autonomic dysregulation in patients with schizophrenia using electrophysiological methods, such as electrodermal measures and heart rate analysis.
Several theories have been proposed to explain the underlying mechanisms of schizophrenia and its autonomic function. Recently, the measurement of salivary alpha-amylase has been considered to be a useful tool for evaluating the sympathetic-adrenal-medullary (SAM) system. Psychosocial stress increases the release of salivary alpha-amylase.
Although some studies have evaluated salivary alpha-amylase under psychosocial stress, no studies have demonstrated the change in the salivary alpha-amylase (sAA) activity level in schizophrenic patients. We examined the relationship between sAA level and psychiatric state in patients with schizophrenia (n = 54) using a portable and rapid hand-held monitor to investigate sAA. The sAA activity in the patients was significantly higher than that in the control subjects (n = 55) (p < 0.01). The correlation between amylase level and psychiatric symptoms was highly significant (r = 0.37, p < 0.01).
These findings indicate that higher increases in sAA may indicate severe psychiatric symptoms. These results indicate a predominant role of the sympathetic nervous system in the secretion of sAA, together with parasympathetic withdrawal, under psychosocial stress.
Takuji Inagakia, , , Tsuyoshi Miyaokab, Shihoh Okazakib, Hideaki Yasudab, Tetsuya Kawamukaib, Etsuko Utanib, Rei Wakeb, Maiko Hayashidab, Jun Horiguchib and Seiichi Tsujic
a Department of Psychology and Special Support Education, Faculty of Education, Shimane University, Matsue, Japan
b Department of Psychiatry, Faculty of Medicine, Shimane University, Izumo, Japan
c Tsuji Clinic, Hiroshima, Japan
Previous studies have demonstrated the autonomic dysregulation in patients with schizophrenia using electrophysiological methods, such as electrodermal measures and heart rate analysis.
Several theories have been proposed to explain the underlying mechanisms of schizophrenia and its autonomic function. Recently, the measurement of salivary alpha-amylase has been considered to be a useful tool for evaluating the sympathetic-adrenal-medullary (SAM) system. Psychosocial stress increases the release of salivary alpha-amylase.
Although some studies have evaluated salivary alpha-amylase under psychosocial stress, no studies have demonstrated the change in the salivary alpha-amylase (sAA) activity level in schizophrenic patients. We examined the relationship between sAA level and psychiatric state in patients with schizophrenia (n = 54) using a portable and rapid hand-held monitor to investigate sAA. The sAA activity in the patients was significantly higher than that in the control subjects (n = 55) (p < 0.01). The correlation between amylase level and psychiatric symptoms was highly significant (r = 0.37, p < 0.01).
These findings indicate that higher increases in sAA may indicate severe psychiatric symptoms. These results indicate a predominant role of the sympathetic nervous system in the secretion of sAA, together with parasympathetic withdrawal, under psychosocial stress.
Takuji Inagakia, , , Tsuyoshi Miyaokab, Shihoh Okazakib, Hideaki Yasudab, Tetsuya Kawamukaib, Etsuko Utanib, Rei Wakeb, Maiko Hayashidab, Jun Horiguchib and Seiichi Tsujic
a Department of Psychology and Special Support Education, Faculty of Education, Shimane University, Matsue, Japan
b Department of Psychiatry, Faculty of Medicine, Shimane University, Izumo, Japan
c Tsuji Clinic, Hiroshima, Japan
Relevance of declines in serum human chorionic gonadotropin levels to the management of persistent ectopic pregnancy
ABSTRACT
Aim: To evaluate postoperative declines in serum human chorionic gonadotropin (hCG) levels (percentages of preoperative hCG levels) to rule out persistent ectopic pregnancy (PEP).
Methods: A retrospective study was conducted on 50 patients who underwent laparoscopic salpingotomy between April 1995 and March 2008. The postoperative course was divided into four periods: (period A: days 1–2; period B: days 3–4; period C: days 5–6; and period D: days 7–8), and the postoperative serum human chorionic gonadotropin declines in the PEP and control groups (successfully treated patients) were compared. A cutoff value of serum hcg decline to rule out PEP was established by receiver operating characteristic (ROC) analysis.
Results: Ten of the 50 patients (20%) were diagnosed with PEP. There were no differences in clinical findings or preoperative serum hCG levels between the two groups. From period C, the serum hCG decline in the control group was significantly greater than in the PEP group, and all individual serum hCG declines in the PEP group were outside the 95% confidence interval of the control group. Furthermore, analysis by ROC using a 14% decline in postoperative serum hCG as a cutoff revealed that the specificity and sensitivity of the test were equal to 100% from period C.
Conclusion: Declines in serum hcg during period C (days 5–6) constitute an important marker of the presence or absence of PEP. Decisions regarding a second intervention for PEP should be made by this time postoperatively.
Journal of Obstetrics and Gynaecology Research
Volume 35 Issue 5, Pages 961 - 966
Published Online: 23 Oct 2009
Relevance of declines in serum human chorionic gonadotropin levels to the management of persistent ectopic pregnancy
Takashi Abe, Shigeo Akira, Yasuyuki Negishi, Masao Ichikawa, Akihito Nakai and Toshiyuki Takeshita
Aim: To evaluate postoperative declines in serum human chorionic gonadotropin (hCG) levels (percentages of preoperative hCG levels) to rule out persistent ectopic pregnancy (PEP).
Methods: A retrospective study was conducted on 50 patients who underwent laparoscopic salpingotomy between April 1995 and March 2008. The postoperative course was divided into four periods: (period A: days 1–2; period B: days 3–4; period C: days 5–6; and period D: days 7–8), and the postoperative serum human chorionic gonadotropin declines in the PEP and control groups (successfully treated patients) were compared. A cutoff value of serum hcg decline to rule out PEP was established by receiver operating characteristic (ROC) analysis.
Results: Ten of the 50 patients (20%) were diagnosed with PEP. There were no differences in clinical findings or preoperative serum hCG levels between the two groups. From period C, the serum hCG decline in the control group was significantly greater than in the PEP group, and all individual serum hCG declines in the PEP group were outside the 95% confidence interval of the control group. Furthermore, analysis by ROC using a 14% decline in postoperative serum hCG as a cutoff revealed that the specificity and sensitivity of the test were equal to 100% from period C.
Conclusion: Declines in serum hcg during period C (days 5–6) constitute an important marker of the presence or absence of PEP. Decisions regarding a second intervention for PEP should be made by this time postoperatively.
Journal of Obstetrics and Gynaecology Research
Volume 35 Issue 5, Pages 961 - 966
Published Online: 23 Oct 2009
Relevance of declines in serum human chorionic gonadotropin levels to the management of persistent ectopic pregnancy
Takashi Abe, Shigeo Akira, Yasuyuki Negishi, Masao Ichikawa, Akihito Nakai and Toshiyuki Takeshita
Tuesday
Efficacy and safety of sorafenib in patients
Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma (HCC): Asia-Pacific (AP) trial subgroup analyses by baseline transaminase (ALT/AST)/-alpha fetoprotein (AFP) levels
Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition).Vol 27, No 15S (May 20 Supplement), 2009: 4590
Background: Results of the phase III, randomized, double blind, placebo-controlled AP trial demonstrated that sorafenib is effective and safe for the treatment of advanced HCC in patients from the AP region (Cheng et al, Lancet Oncol, 2009). Hepatic function influences treatment as a measure of organ damage and tumor stage. We performed subset analyses of the AP study dataset according to baseline hepatic function, as indicated by levels of ALT/AST and AFP.
Methods: Patients (N=226) with advanced HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy were randomized 2:1 to receive sorafenib 400 mg BID or placebo. Endpoints included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for 28 days from first demonstration of response), time to progression (TTP) and safety. Patients were grouped by baseline levels of ALT/AST (normal, mild, or moderate) and AFP (normal or abnormal).
Results: Median TTP, OS and DCR by subset are shown in the table. The most common grade 3/4 adverse events in the sorafenib populations were hand-foot skin reaction and diarrhea.
Conclusions: Sorafenib was effective and safe in patients from the AP region with advanced HCC within a broad range of baseline hepatic enzyme and AFP levels. These results suggest that sorafenib is an effective treatment for HCC, irrespective of baseline ALT/AST or AFP levels
Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition).Vol 27, No 15S (May 20 Supplement), 2009: 4590
Background: Results of the phase III, randomized, double blind, placebo-controlled AP trial demonstrated that sorafenib is effective and safe for the treatment of advanced HCC in patients from the AP region (Cheng et al, Lancet Oncol, 2009). Hepatic function influences treatment as a measure of organ damage and tumor stage. We performed subset analyses of the AP study dataset according to baseline hepatic function, as indicated by levels of ALT/AST and AFP.
Methods: Patients (N=226) with advanced HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy were randomized 2:1 to receive sorafenib 400 mg BID or placebo. Endpoints included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for 28 days from first demonstration of response), time to progression (TTP) and safety. Patients were grouped by baseline levels of ALT/AST (normal, mild, or moderate) and AFP (normal or abnormal).
Results: Median TTP, OS and DCR by subset are shown in the table. The most common grade 3/4 adverse events in the sorafenib populations were hand-foot skin reaction and diarrhea.
Conclusions: Sorafenib was effective and safe in patients from the AP region with advanced HCC within a broad range of baseline hepatic enzyme and AFP levels. These results suggest that sorafenib is an effective treatment for HCC, irrespective of baseline ALT/AST or AFP levels
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