Interstitial Lung Disease in Relatives of Patients with Pulmonary Fibrosis.

Rationale: Although relatives of patients with familial pulmonary fibrosis (FPF) are at an increased risk for interstitial lung disease (ILD), the risk among relatives of sporadic idiopathic pulmonary fibrosis (IPF) is not known.Objectives: To identify the prevalence of interstitial lung abnormalities (ILA) and ILD among relatives of patients with FPF and sporadic IPF.Methods: Undiagnosed first-degree relatives of patients with pulmonary fibrosis (PF) consented to participate in a screening study that included the completion of questionnaires, pulmonary function testing, chest computed tomography, a blood sample collection for immunophenotyping, telomere length assessments, and genetic testing.Measurements and Main Results: Of the 105 relatives in the study, 33 (31%) had ILA, whereas 72 (69%) were either indeterminate or had no ILA. Of the 33 relatives with ILA, 19 (58%) had further evidence for ILD (defined by the combination of imaging findings and pulmonary function testing decrements). There was no evidence in multivariable analyses that the prevalence of either ILA or ILD differed between the 46 relatives with FPF and the 59 relatives with sporadic IPF. Relatives with decrements in either total lung or diffusion capacity had a greater than 9-fold increase in their odds of having ILA (odds ratio, 9.6; 95% confidence interval, 3.1-29.8; P < 0.001).Conclusions: An undiagnosed form of ILD may be present in greater than 1 in 6 older first-degree relatives of patients with PF. First-degree relatives of patients with both familial and sporadic IPF appear to be at similar risk. Our findings suggest that screening for PF in relatives might be warranted.

TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia.

AIMS/HYPOTHESIS: Common DNA variants of the transcription factor 7-like 2 gene (TCF7L2) are associated with type 2 diabetes. Familial combined hyperlipidaemia (FCHL) is characterised by hypertriacylglycerolaemia, hypercholesterolaemia, or both. Additionally, disturbances in glucose metabolism are commonly seen in FCHL. Therefore, we hypothesised that TCF7L2 may contribute to the genetic susceptibility for this common dyslipidaemia. METHODS: We investigated the effect of the TCF7L2 variants, rs7903146 and rs12255372, on FCHL and its component traits triacylglycerol (TG), total cholesterol (TC) and apolipoprotein B (ApoB) in 759 individuals from 55 Mexican families. As a replication sample, 719 individuals from 60 Finnish FCHL families were analysed. We also used quantitative RT-PCR to evaluate the transcript levels of TCF7L2 in 47 subcutaneous fat biopsies from unrelated Mexican FCHL and normolipidaemic participants. RESULTS: Significant evidence for association was observed for high TG for the T alleles of rs7903146 and rs12255372 (p = 0.005 and p = 0.01) in Mexican FCHL families. No evidence for association was observed for FCHL, TC, ApoB or glucose in Mexicans. When testing rs7903146 and rs12255372 for replication in Finnish FCHL families, these single nucleotide polymorphisms were associated with TG (p = 0.01 and p = 0.007). Furthermore, we observed statistically significant decreases in the mRNA levels (p = 0.0002) of TCF7L2 in FCHL- and TG-affected individuals. TCF7L2 expression was not altered by the SNP genotypes. CONCLUSIONS/INTERPRETATION: These data show that rs7903146 and rs12255372 are significantly associated with high TG in FCHL families from two different populations. In addition, significantly decreased expression of TCF7L2 was observed in TG- and FCHL-affected individuals.

The validity of the static-charge-sensitive bed in the detection of fentanyl-induced respiratory depression.

BACKGROUND: Only a few methods for the measurement of breathing are non-invasive and do not interfere with measured parameters. The static-charge-sensitive bed (SCSB) could be such a monitor. The aim of this study was to evaluate the validity of the SCSB compared with the respiratory inductive plethysmograph (RIP) using a fentanyl-induced respiratory depression model. METHODS: Eight healthy male volunteers were infused with intravenous (i.v.) fentanyl (15 microg/kg/h) until a decrease in SpO2 below 90% for 1 min emerged. Breathing was continuously and simultaneously measured with SCSB and RIP. Oxygenation, hemodynamics, arterial blood gas analysis, and subjective opioid-related effects were monitored. Fentanyl concentration was measured from an arterial blood sample. The respiratory rate data of the SCSB (automated analysis and manual calculation) were compared with the corresponding RIP data, using analysis of variance for repeated measures. The validity of the SCSB compared with RIP was evaluated using an intra-class correlation coefficient. RESULTS: Mean fentanyl dose was 629 microg. A statistically significant association was found between the RIP and SCSB data in the manual SCSB analysis (P < 0.0001), but not in the automated SCSB analysis (P = 0.91). After adjusting for the effect of time and the SCSB method, an intra-class correlation coefficient between the manually calculated SCSB values and the RIP values was 0.66. CONCLUSION: Clinically significant changes in respiratory rate were detected with the SCSB, but the results had to be analyzed manually. The SCSB best suits situations, where comprehensive data are needed. It is not suitable for on-line respiratory monitoring, as the automated analysis did not calculate the respiratory rate correctly.

Fetal oxygen saturation during epidural and paracervical analgesia.

BACKGROUND: We wanted to assess changes in fetal oxygenation during maternal epidural or paracervical analgesia in labor. METHODS: A prospective, open and non-randomized study. Twenty healthy parturients were enrolled before they asked for pain relief. Informed consent was obtained. Fetal and maternal oxygen saturations were measured before and up to 1 h after the initiation of analgesia. Fetal oximetry was performed with the Nellcor N-400 oximeter+FS-14B fetal oxygen sensor (Nellcor Puritan Bennett, Pleasanton, California, USA). Maternal oximetry was done with Datex Satlite portable monitor (Datex, Finland). Visual analog scale was used for assessing pain relief. Two-way analysis of variance and students t-test were used for statistical analyses. RESULTS: Fetal oxygenation initially improved in both groups. The saturation then returned to baseline in both groups. In the epidural group, the values remained at baseline or slightly below, while in the paracervical group the saturation remained a little higher than baseline (p=0.009). No change was seen in maternal oxygenation or heart rate. No change in fetal heart rate was found either. Epidural block was superior to paracervical block with respect to pain relief (p=0.002). CONCLUSIONS: There was a small but significant difference in fetal oxygenation between epidural and paracervical groups during the observation period. The magnitude of the difference is hardly clinically significant. A larger, randomized study is needed to elucidate the mechanisms behind this finding.

Neonatal monitoring after maternal fentanyl analgesia in labor.

OBJECTIVE: To characterize different methods of monitoring neonatal effects associated with maternal opioid analgesia. Special focus was on the static-charge-sensitive bed (SCSB), which could potentially serve as a non-invasive neonatal monitor. METHODS: 12 healthy, term newborns from normal pregnancies were included in this prospective, randomized, controlled study. Maternal labor analgesia was either intravenous fentanyl (n = 5) or paracervical bupivacaine blockade (n = 7). Neonatal recording from delivery to the age of 12 hours included continuous SCSB monitoring with ECG and oximeter for sleep states, respiration, oxygenation, heart rate, and body movements. In addition, umbilical blood pH, Apgar, Amiel-Tison's Neurologic and Adaptive Capacity Scoring (NACS), skin cyanosis scoring, blood pressure, rectal and skin temperatures, and skin blood flow measurements were performed. RESULTS: The study was interrupted, because one baby in the fentanyl group had a significant decrease in oxyhemoglobin saturation (SpO2) to 59%. This was considcred to be residual effect of fentanyl and was treated with naloxone. SpO2 was generally lower in the fentanyl group. Epochs with SpO2 < 90% were more frequent in the fentanyl group, especially during active sleep (mean +/- SD 11.9 +/- 10.7% vs. 2.0 +/- 1.7% of epochs, p = 0.034). Mean heart rate values were lower in the fentanyl group (121.1 +/- 6.4 vs. 132.6 +/- 6.8 beats per minute, p = 0.02), and this difference was seen during wake and all sleep states. Maximum heart rate values were lower in the fentanyl group, too. The opiate group had less quiet sleep than controls (9.6 +/- 2.8% vs. 18.3 +/- 8.3%, p = 0.05). NACS after birth was lower in the fentanyl group (median [range] 15 [13-26] vs. 22 [20-25], p = 0.004). CONCLUSIONS: Several differences were seen between the fentanyl and the control group babies. The SCSB method proved sensitive enough to find neonatal effects of maternal analgesia. Together with ECG and SpO2 monitoring, SCSB gives plentiful information on neonatal well-being in a non-invasive way. Results of this study emphasize the importance of neonatal monitoring after maternal opiate use in labor.

Intravenous fentanyl PCA during labour.

PURPOSE: To evaluate the usefulness of intravenous patient-controlled analgesia (PCA) fentanyl for labour analgesia, its effectiveness for maternal pain and safety for the fetus and newborn. METHODS: Twenty primigravidas were randomised to receive intravenous PCA fentanyl or epidural analgesia for labour pain. Maternal pain, heart rate and arterial oxyhaemoglobin saturation (SpO2) were monitored. Fetal and neonatal monitoring included cardiotocogram (CTG), APGAR, neurological scoring and static-charge-sensitive bed (SCSB) recording for 12 hr postnatally with ECG and SpO2. Fentanyl concentrations and pH of umbilical artery and vein were analysed. RESULTS: Initially, epidural analgesia was more effective (P = 0.01), and three patients in the fentanyl group were given epidural due to unsatisfactory pain relief. Overall satisfaction for analgesia did not differ between the groups. Maternal side-effects were more frequent in the fentanyl group (dizziness and tiredness most often, P = 0.0001). Severe side-effects were not reported. In CTG there were no differences between groups. All the newborns were healthy, APGAR and pH were normal. Naloxone was not used. Neurological scoring was similar in both groups. In 12 hr monitoring heart rate, breathing frequency and movement time were similar in both groups, but SpO2 was lower in the fentanyl group (P < 0.001). Umbilical cord fentanyl concentrations were low or beyond the detection limit. CONCLUSION: Intravenous fentanyl can be used for labour analgesia with the doses reported here as an alternative to epidural analgesia. However, the fetus and neonate must be appropriately monitored. Naloxone and oxygen should be available if neonatal distress occurs.

Sleep in multiple pregnancy: breathing patterns, oxygenation, and periodic leg movements.

OBJECTIVES: Our goal was to study whether multiple pregnancy at the third trimester predisposes to breathing disturbances and arterial oxyhemoglobin desaturation during sleep. STUDY DESIGN: Nocturnal breathing, oxygenation, and movement activity were studied in 10 mothers: 8 with twins, 1 with triplets, and 1 with quadruplets. RESULTS: No obstructive and few central sleep apnea episodes were observed. Four subjects had episodes of increased respiratory resistance, but only one, the mother with quadruplets, was significantly affected. Arterial oxyhemoglobin saturation was always maintained above 90%. Periodic leg movements were present in all mothers, with a frequency range of 3.7 to 49.7 movements per hour. CONCLUSIONS: In spite of the large uterus in multiple pregnancy, nocturnal breathing and oxygenation are well maintained. Increased motor activity and frequent awakenings suggest poor sleep quality, which may be further compromised by intensive periodic leg movements.

Growth hormone mediates zone-specific gene expression in liver.

The CYP2B1/2 gene pair is an example of many liver genes that exhibit a characteristic zonated expression pattern in the liver. The factors governing this zonation are poorly understood. We observed that after hypophysectomy the expression of CYP2B1/2 protein and mRNA in the normally silent periportal (upstream) region was high, in both male and female rats. Treatment with growth hormone counteracted the effect of hypophysectomy, limiting expression to the perivenous (downstream) region, completely in females and partially in males. This shows that a hormone zone-specifically regulates gene expression in the liver.