Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory diarrhoea with ... more Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory diarrhoea with onset either in the first 72 hours of life (early onset) or at 6-8 weeks after birth (late onset). To date over 30 cases have been reported worldwide. The prognosis for this life threatening condition continues to be poor. Therapeutic agents like somatostatin and epidermal growth factor are either ineffective or of marginal benefit. Overall five year survival after small bowel transplantation is currently approximately 50%. The following brief review is aimed towards helping neonatologists/perinatologists in the early diagnosis, and management of CMVA and in counselling the parents appropriately.
Suboptimal fetal growth has been associated with an increased risk of adult disease, which may be... more Suboptimal fetal growth has been associated with an increased risk of adult disease, which may be exacerbated by an increased placental weight–to–fetal weight ratio. Placental weight is a summary measure of placental growth and development throughout pregnancy. However, measures of placental structure, including the chorionic disk surface area and thickness and eccentricity of the umbilical cord insertion, have been shown to account for additional variance in birth weight beyond that explained by placental weight. Little is known of the variability of these placental parameters in low-risk populations; their association with maternal, pregnancy, and neonatal characteristics; and the agreement between manual and digital measures. This study used manual and digital image analysis techniques to examine gross placental anatomy in 513 low-risk, singleton, term, first-born infants. Parametric methods compared groups and examined relationships among variables. Maternal birth weight, prepre...
Posterior urethral valves are the main cause of bladder outflow obstruction in human fetuses. Thi... more Posterior urethral valves are the main cause of bladder outflow obstruction in human fetuses. Thirty per cent of boys with valves develop end-stage renal disease, despite intervention in the postnatal period. The timing and mechanisms of renal damage in bladder outflow obstruction are unknown. We investigated the timing of changes in morphology and apoptosis in the fetal sheep kidney in response to obstruction. Thirty-three fetal lambs at day 70 of gestation underwent surgical creation of bladder outflow obstruction. Twenty-nine fetal lambs had sham surgery. Fetal kidneys were collected 2, 5, 10, 20 and 30 days after surgery. Renal histology was examined. Real-time PCR was used to quantify the renal cortical expression of the pro-apoptotic gene Bax and anti-apoptotic gene Bcl-X. The TUNEL technique was used to assess regional renal apoptosis in response to obstruction. Changes in renal morphology were evident as early as 2 days after surgery in fetuses with bladder outflow obstruction, and progressed over 20-30 days to cystic renal dysplasia. Bladder outflow obstruction increased the renal cortical expression of Bax relative to Bcl-X. Tubular apoptosis peaked after 2 days of obstruction. Blastemal apoptosis peaked after 5 days of obstruction. Changes in pro- and anti-apoptotic gene expression in the fetal renal cortex, and alterations in the number of apoptotic cells and renal morphology are evident soon after the onset of bladder outflow obstruction. These findings suggest that damage to the developing fetal kidney begins to occur at the onset of obstruction. Attempts to preserve renal function by antenatal interventions may best be achieved by early treatment.
Using in vitro model for studying the induction and inhibition of spontaneous apoptosis in human ... more Using in vitro model for studying the induction and inhibition of spontaneous apoptosis in human first trimester placental villi, mediated by the free radical scavenger SOD, we have examined the expression of bcl-xL, bax, Caspase-3 and PARP (Poly ADP-ribosyl). An increase in apoptosis was associated with activation of PARP and an increase and activation of Caspase-3. There was no significant change in bcl-x or bax. Therefore bcl-x and bax do not appear to have a significant role in apoptosis in the first trimester in vitro. Cleavage of Caspase-3 rather than transcriptional regulation appears to be the main determinant of Caspase-3 activity in first trimester placental villi.
Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory diarrhoea with ... more Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory diarrhoea with onset either in the first 72 hours of life (early onset) or at 6-8 weeks after birth (late onset). To date over 30 cases have been reported worldwide. The prognosis for this life threatening condition continues to be poor. Therapeutic agents like somatostatin and epidermal growth factor are either ineffective or of marginal benefit. Overall five year survival after small bowel transplantation is currently approximately 50%. The following brief review is aimed towards helping neonatologists/perinatologists in the early diagnosis, and management of CMVA and in counselling the parents appropriately.
Suboptimal fetal growth has been associated with an increased risk of adult disease, which may be... more Suboptimal fetal growth has been associated with an increased risk of adult disease, which may be exacerbated by an increased placental weight–to–fetal weight ratio. Placental weight is a summary measure of placental growth and development throughout pregnancy. However, measures of placental structure, including the chorionic disk surface area and thickness and eccentricity of the umbilical cord insertion, have been shown to account for additional variance in birth weight beyond that explained by placental weight. Little is known of the variability of these placental parameters in low-risk populations; their association with maternal, pregnancy, and neonatal characteristics; and the agreement between manual and digital measures. This study used manual and digital image analysis techniques to examine gross placental anatomy in 513 low-risk, singleton, term, first-born infants. Parametric methods compared groups and examined relationships among variables. Maternal birth weight, prepre...
Posterior urethral valves are the main cause of bladder outflow obstruction in human fetuses. Thi... more Posterior urethral valves are the main cause of bladder outflow obstruction in human fetuses. Thirty per cent of boys with valves develop end-stage renal disease, despite intervention in the postnatal period. The timing and mechanisms of renal damage in bladder outflow obstruction are unknown. We investigated the timing of changes in morphology and apoptosis in the fetal sheep kidney in response to obstruction. Thirty-three fetal lambs at day 70 of gestation underwent surgical creation of bladder outflow obstruction. Twenty-nine fetal lambs had sham surgery. Fetal kidneys were collected 2, 5, 10, 20 and 30 days after surgery. Renal histology was examined. Real-time PCR was used to quantify the renal cortical expression of the pro-apoptotic gene Bax and anti-apoptotic gene Bcl-X. The TUNEL technique was used to assess regional renal apoptosis in response to obstruction. Changes in renal morphology were evident as early as 2 days after surgery in fetuses with bladder outflow obstruction, and progressed over 20-30 days to cystic renal dysplasia. Bladder outflow obstruction increased the renal cortical expression of Bax relative to Bcl-X. Tubular apoptosis peaked after 2 days of obstruction. Blastemal apoptosis peaked after 5 days of obstruction. Changes in pro- and anti-apoptotic gene expression in the fetal renal cortex, and alterations in the number of apoptotic cells and renal morphology are evident soon after the onset of bladder outflow obstruction. These findings suggest that damage to the developing fetal kidney begins to occur at the onset of obstruction. Attempts to preserve renal function by antenatal interventions may best be achieved by early treatment.
Using in vitro model for studying the induction and inhibition of spontaneous apoptosis in human ... more Using in vitro model for studying the induction and inhibition of spontaneous apoptosis in human first trimester placental villi, mediated by the free radical scavenger SOD, we have examined the expression of bcl-xL, bax, Caspase-3 and PARP (Poly ADP-ribosyl). An increase in apoptosis was associated with activation of PARP and an increase and activation of Caspase-3. There was no significant change in bcl-x or bax. Therefore bcl-x and bax do not appear to have a significant role in apoptosis in the first trimester in vitro. Cleavage of Caspase-3 rather than transcriptional regulation appears to be the main determinant of Caspase-3 activity in first trimester placental villi.
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