Sub-calcaneal plantar fat pad assessment using dual-energy computed tomography: First experience in the diabetic foot.

BACKGROUND: This study assessed the use of dual-energy computed tomography (CT) to evaluate sub-calcaneal plantar fat pad changes in people with diabetic neuropathy. METHODS: Dual-energy CT scans of people with diabetic neuropathy and non-diabetic controls were retrospectively included. Average CT values (in Hounsfield Units) and thickness (in centimeters) of the sub-calcaneal plantar fat pad were measured in mono-energetic images at two energy levels (40 keV and 70 keV). The CT values measured in patients with diabetic neuropathy were correlated to barefoot plantar pressure measurements performed during walking in a clinical setting. FINDINGS: Forty-five dual-energy CT scans of people with diabetic neuropathy and eleven DECT scans of non-diabetic controls were included. Mean sub-calcaneal plantar fat pad thickness did not significantly differ between groups (diabetes group 1.20 ± 0.34 cm vs. control group 1.21 ± 0.28 cm, P = 0.585). CT values at both 40 keV (-34.7 ± 48.7 HU vs. -76.0 ± 42.8 HU, P = 0.013) and 70 keV (-11.2 ± 30.8 HU vs. -36.3 ± 27.2 HU, P = 0.017) were significantly higher in the diabetes group compared to controls, thus contained less fatty tissue. This elevation was most apparent in patients with Type 1 diabetes. CT values positively correlated with the mean peak plantar pressure. INTERPRETATION: Dual-energy CT was able to detect changes in the plantar fat pad of people with diabetic neuropathy.

Sagittal sinus blood flow in the ovine fetus as a continuous measure of cerebral blood flow: relationship to behavioural state activity.

Superior sagittal sinus blood flow (Q(ss)) was studied over a 6-h period in nine chronically catheterized fetal sheep as a continuous measure of cerebral blood flow to determine the change in blood flow values and in measures of blood flow variability in relation to behavioural state activity. Mean Q(ss) was increased during the low voltage (LV)/rapid eye movement (REM) state compared to the high voltage (HV)/NREM state by approximately 25%, and was further increased during periods of LV/REM with fetal breathing movements. The increase in Q(ss) was abrupt and began at the transition to LV/REM, with the rate of change 2-fold greater than that during transition to HV/NREM, where the decrease in Q(ss) was gradual and began prior to the evident state change. Q(ss) showed considerable fluctuation, which tended to be greater during the HV/NREM state compared to the LV/REM state when analyzed using measures of longer term variability. Q(ss) thus provides for a continuous measure of cerebral blood flow in the ovine fetus, with the approximately 25% increase with change from the HV/NREM to LV/REM state similar to that previously reported using radioactive microspheres. The abrupt increase in Q(ss) at the transition to LV/REM versus the gradual decrease in Q(ss) before transition to HV/NREM would suggest that the state-related change in brain blood flow is better linked to the presence of the LV electrocorticogram and favours its active generation.

The adenosine A(1)-receptor antagonist 8-CPT reverses ethanol-induced inhibition of fetal breathing movements.

Administration of either ethanol or adenosine inhibits fetal breathing movements (FBM), eye movements, and low-voltage electrocortical activity (LV ECoG). The concentration of adenosine in ovine fetal cerebral extracellular fluid increases during ethanol-induced inhibition of FBM. The purpose of this study was to determine the effect of a selective adenosine A(1)-receptor antagonist, 8-cyclopentyltheophylline (8-CPT) on the incidence of FBM during ethanol exposure. After a 2-h control period, seven pregnant ewes received a 1-h intravenous infusion of ethanol (1 g/kg maternal body wt), followed 1 h later by a 2-h fetal intravenous infusion of either 8-CPT (3.78 +/- 0.08 microg. kg(-1). min(-1)) or vehicle. Ethanol reduced the incidence of FBM from 44.0 +/- 10.4 to 2.7 +/- 1.3% (P < 0.05) and 51.2 +/- 7.6 to 11.9 +/- 5.0% (P < 0.05) in fetuses destined to receive 8-CPT or vehicle, respectively. In the vehicle group, FBM remained suppressed for 7 h. In contrast, during the first hour of 8-CPT infusion, FBM returned to baseline (31 +/- 11%) and was not different from control throughout the rest of the experiment. Ethanol also decreased the incidence of both low-voltage electrocortical activity and eye movements, but there were no differences in the incidences of these behavioral parameters between the 8-CPT and vehicle groups throughout the experiment. These data are consistent with the hypothesis that adenosine, acting via A(1) receptors, may play a role in the mechanism of ethanol-induced inhibition of FBM.

Increased cerebral extracellular adenosine and decreased PGE2 during ethanol-induced inhibition of FBM.

Adenosine and PGE2 are neuromodulators, both of which inhibit fetal breathing movements (FBM). Although circulating PGE2 has been implicated as a mediator of ethanol-induced inhibition of FBM in the late-gestation ovine fetus, a role for adenosine has not been examined. The objective of this study was to determine the effect of maternal ethanol infusion on ovine fetal cerebral extracellular fluid adenosine and PGE2 concentrations by using in utero microdialysis and to relate any changes to ethanol-induced inhibition of FBM. Dialysate samples were obtained from the fetal parietal cortex over 70 h after surgery to determine steady-state extracellular fluid adenosine and PGE2 concentrations. On each of postoperative days 3 and 4, after a 2-h baseline period, ewes received a 1-h infusion of ethanol (1 g/kg maternal body wt) or an equivalent volume of saline, and the fetus was monitored for a further 11 h with 30-min dialysate samples collected throughout. Immediately after surgery, dialysate PGE2 and adenosine concentrations were 3.7 +/- 0.7 and 296 +/- 127 nM, respectively. PGE2 did not change over the 70 h, whereas adenosine decreased to 59 +/- 14 nM (P < 0.05) at 4 h and then remained unchanged. Ethanol decreased dialysate PGE2 concentration for 2 h (3.3 +/- 0.3 to 1.9 +/- 0.4 nM; P < 0.05) and increased adenosine concentration for 6 h (87 +/- 13 to a maximum of 252 +/- 59 nM, P < 0.05). Ethanol decreased FBM incidence from 47 +/- 7 to 16 +/- 5% (P < 0.01) for 8 h. Saline infusion did not change dialysate adenosine or PGE2 concentrations or FBM incidence. These data are consistent with the hypothesis that fetal cerebral adenosine, and not PGE2, is the primary mediator of ethanol-induced inhibition of FBM at 123 days of gestation in sheep.

Prostaglandin E2 inhibition of fetal breathing movements is not sustained during prolonged reduced uterine blood flow in sheep.

Fetal breathing movements (FBM) are inhibited by both exogenous prostaglandin E2 (PGE2) and ethanol in sheep. Maternal ethanol exposure in late-gestation sheep also increases fetal [PGE2]. However, during prolonged reduced uterine blood flow (RUBF) when [PGE2] in fetal plasma is already elevated, FBM are not inhibited by ethanol. These experiments were designed, therefore, to test the hypothesis that the FBM response to PGE2 is also diminished during RUBF. PGE2 (594+/-19 ng.min(-1).kg(-1) fetal body weight) was infused for 6 h into the jugular vein of RUBF (PO2 = 14+/-1 mmHg (1 mmHg = 133.3 Pa); n = 7) and control (PO2 = 22+/-1 mmHg (p < 0.01); n = 7) ovine fetuses, and the effect on FBM, electrocortical (ECoG), and electroocular activities was determined. The infusion of PGE2 increased plasma [PGE2] from 881+/-162 to 1189+/-114 pg.mL(-1) in RUBF fetuses and from 334+/-72 to 616+/-118 pg.mL(-1) (p < 0.05) in control fetuses. FBM were initially inhibited by PGE2 from 22.5+/-9.4 and 17.9+/-6.5% of the time to 6.9+/-2.4 and 0.5+/-0.4% (p < 0.01) in RUBF and control fetuses, respectively. FBM remained inhibited in control fetuses throughout the infusion but returned to baseline incidence in RUBF fetuses in the last 2 h of the infusion. These results are consistent with the hypothesis that one component of the adaptative mechanisms of the fetus to prolonged RUBF is an altered response of FBM to exogenous PGE2. We speculate that the lack of a sustained inhibition in FBM during RUBF with infusion of PGE2 may be a result of an alteration in brainstem receptor function or number or local PGE2 removal.

Failure of magnesium sulfate infusion to inhibit uterine activity in pregnant sheep.

OBJECTIVES: Our purpose was to determine the effect of magnesium sulfate infusion on nonlabor uterine contractures and corticotropin-induced preterm uterine contractions in pregnant sheep. STUDY DESIGN: Fetal and maternal vascular catheters and uterine electromyographic electrodes were surgically placed in 15 pregnant sheep between 118 and 125 days' gestation. After 3 to 5 days of recovery, magnesium sulfate was infused into 7 ewes with a 0.11 gm/kg bolus over 20 minutes, followed by 0.08 gm/kg/hr. In 8 animals labor was induced with use of an intrafetal corticotropin infusion, after which 4 ewes received magnesium sulfate and 4 received saline solution. Continuous recordings of uterine electromyographic activity, amniotic pressure, fetal heart rate, blood pressure, and tracheal pressure were made. Maternal and fetal magnesium, calcium, albumin concentrations, and blood gases were determined before and during the infusion. RESULTS: Maternal magnesium concentrations increased from an average of 0.94 +/- 0.03 mmol/L to 2.73 +/- 0.1 mmol/L at the end of the bolus, remaining elevated (2.44 +/- 0.17 mmol/L) for 8 hours. Fetal magnesium concentrations (0.89 +/- 0.03 mmol/L before the bolus) did not change with the maternal infusion. In ewes not in labor, uterine contractures occurred 3.7 +/- 0.7 times per 2 hours before and did not change significantly with the infusion of magnesium sulfate. During corticotropin-induced preterm labor uterine contractions were present 13 +/- 3.2 times per hour before infusions and were unchanged by infusion of magnesium sulfate to the ewes. CONCLUSIONS: Magnesium sulfate infusion in pregnant sheep has no effect on either nonlabor uterine contractures or on corticotropin-induced preterm uterine contractions.