Jon Fulford

Myometrial and placental artery reactivity alone cannot explain reduced placental perfusion in pre‐eclampsia and intrauterine growth restriction

Objectives (1) To investigate a possible association between myometrial and placental artery vasoreactivity and perfusion at the basal and chorionic plates, respectively. (2) To confirm that myometrial arteries from women with pre‐eclampsia and intrauterine growth restriction exhibit an attenuated endothelium‐dependent vasodilatory response.

Age‐ and sex‐related differences in muscle phosphocreatine and oxygenation kinetics during high‐intensity exercise in adolescents and adults

The aim of this investigation was to examine the adaptation of the muscle phosphates (e.g. phosphocreatine (PCr) and ADP) implicated in regulating oxidative phosphorylation, and oxygenation at the onset of high intensity exercise in children and adults. The hypotheses were threefold: primary PCr kinetics would be faster in children than adults; the amplitude of the PCr slow component would be attenuated in children; and the amplitude of the deoxyhaemoglobin/myoglobin (HHb) slow component would be reduced in children. Eleven children (5 girls, 6 boys, 13 ± 1 years) and 11 adults (5 women, 6 men, 24 ± 4 years) completed two to four constant work rate exercise tests within a 1.5 T MR scanner. Quadriceps muscle energetics during high intensity exercise were monitored using 31P‐MRS. Muscle oxygenation was monitored using near‐infrared spectroscopy. The time constant for the PCr response was not significantly different in boys (31 ± 10 s), girls (31 ± 10 s), men (44 ± 20 s) or women (29 ± 14 s, main effects: age, p = 0.37, sex, p = 0.25). The amplitude of the PCr slow component relative to end‐exercise PCr was not significantly different between children (23 ± 23%) and adults (17 ± 13%, p = 0.47). End‐exercise [PCr] was significantly lower, and [ADP] higher, in females (18 ± 4 mM and 53 ± 16 µM) than males (23 ± 4 mM, p = 0.02 and 37 ± 11 µM, p = 0.02), but did not differ with age ([PCr]: p = 0.96, [ADP]: p = 0.72). The mean response time for muscle tissue deoxygenation was significantly faster in children (22 ± 4 s) than adults (27 ± 7 s, p = 0.01). The results of this study show that the control of oxidative metabolism at the onset of high intensity exercise is adult‐like in 13‐year‐old children, but that matching of oxygen delivery to extraction is more precise in adults. Copyright

The emerging role of functional MRI for evaluating fetal brain activity.

Although functional magnetic resonance imaging is a technique that is widely used in adult populations, its use within a fetal environment has been extremely limited. Problems associated with movement and technical scanning issues have limited its effectiveness in providing reliable and spatially accurate details of fetal brain activity. However, initial research has indicated that it is a viable tool for assessing functional maturation in the fetus, and recent advances in echo-planar imaging sequences on the abdomen at 3-T provide the potential for more reliable activation detection and higher resolution spatial information. If the technique can be further developed such that a similar reliability in activity patterns is observed as in conventional functional MRI, then fetal functional MRI could offer a useful contribution at a clinical level as well as at a research one in the assessment of brain development and maturation.

Bilateral redundancy gain and callosal integrity in a man with callosal lipoma: a diffusion-tensor imaging study.

We investigated whether abnormalities in the structural organization of the corpus callosum in the presence of curvilinear lipoma are associated with increased facilitation of response time to bilateral stimuli, an effect known as the redundancy gain (RG). A patient (A.J.) with a curvilinear lipoma of the corpus callosum, his genetically-identical twin, and age-matched control participants made speeded responses to luminant stimuli. Structural organization of callosal regions was assessed with diffusion-tensor imaging. A.J. was found to have reduced structural integrity in the splenium of the corpus callosum and produced a large RG suggestive of neural summation.

Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1β–associated renal disease and can be symptomatic

Abstract Background Heterozygous mutations in the HNF1B gene are the most common monogenic cause of developmental kidney disease. Extrarenal phenotypes frequently occur, including diabetes mellitus and pancreatic hypoplasia; the latter is associated with subclinical exocrine dysfunction. We measured faecal elastase-1 in patients with HNF1B-associated disease regardless of diabetes status and assessed the degree of symptoms associated with pancreatic exocrine deficiency. Methods Faecal elastase-1 was measured in 29 patients with a known HNF1B mutation. We defined a low faecal elastase-1 concentration based on the 2.5 percentile of 99 healthy control individuals (410 μg/g stool). Symptoms related to pancreatic exocrine dysfunction were assessed and a subset of the HNF1B cohort (n  =  6) underwent pancreatic imaging. Results Faecal elastase-1 was below the 2.5 percentile of the control cohort in 18/29 (62%) patients with HNF1B-associated renal disease. A total of 8/29 (28%) had a measurement suggestive of exocrine pancreatic insufficiency at  <200 μg/g stool; of these, 3 suffered with abdominal pain, loose stools and/or unintentional weight loss. All three experienced symptomatic improvement and weight gain after commencing pancreatic enzyme replacement therapy. Faecal elastase-1 was low in 7/15 (47%) HNF1B patients without diabetes compared with 11/14 (79%) of those with diabetes (P  =  0.1). Conclusions Faecal elastase-1 deficiency is a common feature of HNF1B-associated renal disease even when diabetes is not present and pancreatic exocrine deficiency may be more symptomatic than previously suggested. Faecal elastase-1 should be measured in all patients with known HNF1B-associated disease complaining of chronic abdominal pain, loose stools or unintentional weight loss. The discovery of a low faecal elastase-1 concentration in individuals with developmental kidney disease of uncertain cause should prompt referral for HNF1B genetic testing.

Two protocols to measure mitochondrial capacity in women and adolescent girls: a 31P-MRS preliminary study.

The phosphocreatine (PCr) recovery time constant (τ) following exercise provides a measure of mitochondrial oxidative capacity. The purpose of this investigation was to use 2 different protocols to determine τ in adolescent females. 31P-MR spectra were collected during 2 exercise tests in 6 adolescent girls (13.8 ± 0.3 y) and 7 women (23.2 ± 3.4 y). The first test consisted of 23 repeated 4 seconds maximal isometric calf contractions separated by 12-second recovery; PCr recovery between the final 18 contractions was used to calculate τ. The second test was a sustained 20-second maximal contraction; recovery was fitted with an exponential function to measure τ. PCr τ did not significantly differ between groups: (gated exercise: 4 girls: 16 ± 5 s, 7 women: 17 ± 5 s, p; sustained exercise: 6 girls: 19 ± 6 s, 7 women: 19 ± 4 s). Bland-Altman analysis demonstrated a close agreement between sustained and gated exercise. Both gated and sustained exercise appear feasible in a pediatric population, and offer a noninvasive evaluation of mitochondrial oxidative capacity.