First 60 fetal in-utero myelomeningocele repairs at Saint Louis Fetal Care Institute in the post-MOMS trial era: hydrocephalus treatment outcomes (endoscopic third ventriculostomy versus ventriculo-peritoneal shunt).

INTRODUCTION: The published results of the Management of Myelomeningocele Study (MOMS) trial in 2011 showed improved outcomes (reduced need for shunting, decreased incidence of Chiari II malformation, and improved scores of mental development and motor function) in the fetal prenatal repair group compared to the postnatal group. Historically, endoscopic third ventriculostomy (ETV) remains as a controversial hydrocephalus treatment option with high failure rates in pediatric patients with a history of myelomeningocele (MMC). We report hydrocephalus treatment outcomes in the fetal in-utero myelomeningocele repair patients who underwent repair at our Saint Louis Fetal Care Institute following the MOMS trial. We looked carefully at ETV outcomes in this patient population and we identified risk factors for failure. METHODS: At our Saint Louis Fetal Care Institute, we followed the maternal and fetal inclusion and exclusion criteria used by the MOMS trial. The records of our first 60 fetal MMC repairs performed at our institute between 2011 and 2017 were examined. We retrospectively reviewed the charts, prenatal fetal magnetic resonance imaging (MRI) and ultrasound (US) imaging findings, postnatal brain MRI, and Bayley neurodevelopment testing results for infants and children who underwent surgical treatment of symptomatic hydrocephalus (VP shunt versus ETV). Multiple variables possibly related to ETV failure were considered for identifying risk factors for ETV failure. RESULTS: Between May 2011 and March 2017, 60 pregnant female patients underwent the prenatal MMC repair for their fetuses between 20 and 26 weeks' gestational age (GA) utilizing the standard hysterotomy for exposure of the fetus, and microsurgical repair of the MMC defect. All MMC defects underwent successful in-utero repair, with subsequent progression of the pregnancy. At the time of this study, 58 babies have been born, 56 are alive since there were 2 mortalities in the neonatal period due to prematurity. One patient was excluded given lack of consent for research purposes. From the remaining 55 patient included in this study, a total of 30 infants and toddlers underwent treatment of hydrocephalus (ETV and VPS groups). Twenty-five patients underwent ETV (24 primary ETV and 1 after shunt failure). Nineteen patients underwent shunt placements (6 primary/13 after ETV failure). Mean GA at time of MMC repair for the ETV group was 24 + 6/7 weeks (range 22 + 4/7 to 25 + 6/7). Mean follow up for patients who had a successful ETV was 17.25 months (range 4-57 months). Bayley neurodevelopmental testing results were examined pre- and post-ETV. Overall ETV success rate was 11/24 (45.8%) at the time of this study. The total number of patients who underwent shunt placement was 19/55 (34.5%), while shunting rate was 40% in the MOMS trial. Using a simple logistic regression analysis to identify predictors of ETV failure, ETV age ≤6 months and gestational age ≥23 weeks at repair of myelomeningocele were significant predictors for ETV failure while in-utero ventricular stability ≤4 mm and in-utero ventricular size post-repair ≤15.5 mm were significant predictors for ETV success. None of the listed variables independently predicted classification into ETV success versus ETV failure groups when entered into multiple logistic regression analysis. CONCLUSIONS: ETV, as an alternative to initial shunting, may continue to show promising results for treating fetal MMC repair patient population who present with symptomatic hydrocephalus during infancy and early childhood. Although our overall CSF diversion rate (ETV and VPS groups) in our fetal MMC group is higher than the MOMS trial, our shunting rate is lower given our higher incidence of patients with successful ETV. To our knowledge, this is the largest reported ETV series in patients who underwent fetal MMC repair. ETV deserves a closer look in the setting of improved hindbrain herniation in fetal in-utero MMC repair patients. In our series, young age (less than 6 months) and late GA at time of fetal MMC repair (after 23 weeks GA) were predictors for ETV failure, while in-utero stability of ventricular size (less than 4 mm) and in-utero ventricular size post-repair ≤15.5 mm were predictors for ETV success. Larger series and potential prospective randomized studies are required for further evaluation of risk factors for ETV failure in the fetal MMC patient population.

Reproductive strategy, spawning induction, spawning temperatures and early life history of captive sicklefin chub Macrhybopsis meeki.

Macrhybopsis reproduction and propagule traits were studied in the laboratory using two temperature regimes and three hormone treatments to determine which methods produced the most spawns. Only sicklefin chub Macrhybopsis meeki spawned successfully although sturgeon chub Macrhybopsis gelida released unfertilized eggs. All temperature and hormone treatments produced M. meeki spawns, but two treatments had similar success rates at 44 and 43%, consisting of a constant daily temperature with no hormone added, or daily temperature fluctuations with hormone added to the water. Spawns consisted of multiple successful demersal circular swimming spawning embraces interspersed with circular swims without embraces. The most spawns observed for one female was four and on average, 327 eggs were collected after each spawn. The water-hardened eggs were semi-buoyant and non-adhesive, the first confirmation of this type of reproductive guild in the Missouri River Macrhybopsis sp. From spawn, larvae swam vertically until 123 accumulated degree days (° D) and 167° D for consumption of first food. Using average water speed and laboratory development time, the predicted drift distance for eggs and larvae could be 468-592 km in the lower Missouri River. Results from this study determined the reproductive biology and early life history of Macrhybopsis spp. and provided insight into their population dynamics in the Missouri River.

Reconstitution of Fusion Proteins in Supported Lipid Bilayers for the Study of Cell Surface Receptor-Ligand Interactions in Cell-Cell Contact.

Bioactive molecules such as adhesion ligands, growth factors, or enzymes play an important role in modulating cell behavior such as cell adhesion, spreading, and differentiation. Deciphering the mechanism of ligand-mediated cell adhesion and associated signaling is of great interest not only for fundamental biophysical investigations but also for applications in medicine and biotechnology. In the presented work, we developed a new biomimetic platform that enables culturing primary neurons and testing cell surface-receptor ligand interactions in cell-cell contacts as, e.g., in neuronal synapses. This platform consists of a supported lipid bilayer modified with incorporated neuronal adhesion proteins conjugated with the Fc-domain of IgG (ephrin A5 Fc-chimera). We extensively characterized properties of these protein containing bilayers using fluorescence recovery after photobleaching (FRAP), quartz crystal microbalance with dissipation (QCM-D), and immunostaining. We conclude that the Fc-domain is the part responsible for the incorporation of the protein into the bilayer. The biomimetic platform prepared by this new approach was able to promote neuronal cell adhesion and maintain growth as well as facilitate neuronal maturation as shown by electrophysiological measurements. We believe that our approach can be extended to insert other proteins to create a general culture platform for neurons and other cell types.

The impact and recovery of asteroid 2008 TC(3).

In the absence of a firm link between individual meteorites and their asteroidal parent bodies, asteroids are typically characterized only by their light reflection properties, and grouped accordingly into classes. On 6 October 2008, a small asteroid was discovered with a flat reflectance spectrum in the 554-995 nm wavelength range, and designated 2008 TC(3) (refs 4-6). It subsequently hit the Earth. Because it exploded at 37 km altitude, no macroscopic fragments were expected to survive. Here we report that a dedicated search along the approach trajectory recovered 47 meteorites, fragments of a single body named Almahata Sitta, with a total mass of 3.95 kg. Analysis of one of these meteorites shows it to be an achondrite, a polymict ureilite, anomalous in its class: ultra-fine-grained and porous, with large carbonaceous grains. The combined asteroid and meteorite reflectance spectra identify the asteroid as F class, now firmly linked to dark carbon-rich anomalous ureilites, a material so fragile it was not previously represented in meteorite collections.

PLTP regulates STAT3 and NFκB in differentiated THP1 cells and human monocyte-derived macrophages.

Phospholipid transfer protein (PLTP) plays an important role in regulation of inflammation. Previously published studies have shown that PLTP binds, transfers and neutralizes bacterial lipopolysaccharides. In the current study we tested the hypothesis that PLTP can also regulate anti-inflammatory pathways in macrophages. Incubation of macrophage-like differentiated THP1 cells and human monocyte-derived macrophages with wild-type PLTP in the presence or absence of tumor necrosis factor alpha (TNFα) or interferon gamma (IFNγ) significantly increased nuclear levels of active signal transducer and activator of transcription 3, pSTAT3(Tyr705) (p<0.01). Similar results were obtained in the presence of a PLTP mutant without lipid transfer activity (PLTP(M159E)), suggesting that PLTP-mediated lipid transfer is not required for activation of the STAT3 pathway. Inhibition of ABCA1 by chemical inhibitor, glyburide, as well as ABCA1 RNA inhibition, reversed the observed PLTP-mediated activation of STAT3. In addition, PLTP reduced nuclear levels of active nuclear factor kappa-B (NFκB) p65 and secretion of pro-inflammatory cytokines in conditioned media of differentiated THP1 cells and human monocyte-derived macrophages. Our data suggest that PLTP has anti-inflammatory capabilities in macrophages.

Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in Type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications.

AIMS: The Michigan Neuropathy Screening Instrument (MNSI) is used to assess distal symmetrical peripheral neuropathy in diabetes. It includes two separate assessments: a 15-item self-administered questionnaire and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes. The purpose of this study was to evaluate the performance of the MNSI in detecting distal symmetrical peripheral neuropathy in patients with Type 1 diabetes and to develop new scoring algorithms. METHODS: The MNSI was performed by trained personnel at each of the 28 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications clinical sites. Neurologic examinations and nerve conduction studies were performed during the same year. Confirmed clinical neuropathy was defined by symptoms and signs of distal symmetrical peripheral neuropathy based on the examination of a neurologist and abnormal nerve conduction findings in ≥ 2 anatomically distinct nerves among the sural, peroneal and median nerves. RESULTS: We studied 1184 subjects with Type 1 diabetes. Mean age was 47 years and duration of diabetes was 26 years. Thirty per cent of participants had confirmed clinical neuropathy, 18% had ≥ 4 and 5% had ≥ 7 abnormal responses on the MNSI questionnaire, and 33% had abnormal scores (≥ 2.5) on the MNSI examination. New scoring algorithms were developed and cut points defined to improve the performance of the MNSI questionnaire, examination and the combination of the two. CONCLUSIONS: Altering the cut point to define an abnormal test from ≥ 7 abnormal to ≥ 4 abnormal items improves the performance of the MNSI questionnaire. The MNSI is a simple, non-invasive and valid measure of distal symmetrical peripheral neuropathy in Type 1 diabetes.

Identification of molecular markers for articular cartilage.

OBJECTIVE: The aim of the current study was to identify molecular markers for articular cartilage (AC) that can be used as tools for the quality control of tissue engineered (TE) cartilage. DESIGN: A genome-wide expression analysis was performed using RNA isolated from articular and growth plate (GP) cartilage, both extracted from the knee joints of 6 weeks old minipigs. After confirming the specific expression for selected genes by RT-PCR, these were used as molecular markers for the quality control of TE cartilage. RESULTS: Albeit several known chondrocyte markers were expressed to a similar extent in articular and GP cartilage, our genome-wide expression analysis led us to identify genes being selectively expressed in either GP or articular chondrocytes. These findings led us to perform a RT-PCR expression analysis for the corresponding genes to demonstrate the absence of GP-specific markers in TE cartilage, while common or AC markers were expressed. CONCLUSIONS: Taken together, these results provide important novel insights into chondrocyte biology in general and AC in particular. In addition, it is reasonable to speculate, that some of the identified genes play distinct roles in the regulation of articular chondrocyte differentiation and/or function, thereby raising the possibility that they may serve as targets for non-operative therapies of osteoarthritis (OA).

Preproenkephalin (Penk) is expressed in differentiated osteoblasts, and its deletion in Hyp mice partially rescues their bone mineralization defect.

Although our understanding of the molecular mechanisms controlling osteoblast differentiation and function is steadily increasing, there are still many open questions, especially regarding the regulation of bone matrix mineralization. For instance, while there is hallmark evidence for the importance of the endopeptidase Phex, whose inactivation in Hyp mice or human patients causes X-linked hypophosphatemic rickets, it is still largely unknown how Phex controls bone mineralization since a physiological substrate for its endopeptidase activity has not been identified yet. Using a genome-wide expression analysis comparing primary calvarial osteoblasts, we have identified preproenkephalin (Penk) as a gene that is selectively expressed in mineralized cultures. Since a role of enkephalin in the regulation of bone remodeling has been suggested previously and since Leu-enkephalin is known to be cleaved by Phex, we analyzed whether Penk expression in osteoblasts is physiologically relevant. Through skeletal analysis of a Penk-deficient mouse model, we found that Penk expression is dispensable for bone development and remodeling since we could not detect any defect following nondecalcified bone histology and histomorphometry compared to wild-type littermates. When Penk was deleted in Phex-deficient Hyp mice, however, we observed a significant reduction of the osteoid enrichment at 24 weeks of age, whereas their disturbance of mineral homeostasis was not affected by the additional absence of the Penk gene. Taken together, our data provide the first in vivo analysis concerning the role of Penk in osteoblasts.

Chest wall pain following lung stereotactic body radiation therapy using 48Gy in three fractions: A search for predictors.

PURPOSE: Chest wall pain is an uncommon but bothersome late complication following lung stereotactic body radiation therapy. Despite numerous studies investigating predictors of chest wall pain, no clear consensus has been established for a chest wall constraint. The aim of our study was to investigate factors related to chest wall pain in a homogeneous group of patients treated at our institution. PATIENTS AND METHODS: All 122 patients were treated with the same stereotactic body radiation therapy regimen of 48Gy in three fractions, seen for at least 6 months of follow-up, and planned with heterogeneity correction. Chest wall pain was scored according to the Common Terminology Criteria for Adverse Events classification v3.0. Patient (age, sex, diabetes, osteoporosis), tumour (planning target volume, volume of the overlapping region between planning target volume and chest wall) and chest wall dosimetric parameters (volumes receiving at least 30, 40, and 50Gy, the minimal doses received by the highest irradiated 1, 2, and 5cm3, and maximum dose) were collected. The correlation between chest wall pain (grade 2 or higher) and the different parameters was evaluated using univariate and multivariate logistic regression. RESULTS: Median follow-up was 18 months (range: 6-56 months). Twelve patients out of 122 developed chest wall pain of any grade (seven with grade 1, three with grade 2 and two with grade 3 pain). In univariate analysis, only the volume receiving 30Gy or more (P=0.034) and the volume of the overlapping region between the planning target volume and chest wall (P=0.038) significantly predicted chest wall pain, but these variables were later proved non-significant in multivariate regression. CONCLUSION: Our analysis could not find any correlation between the studied parameters and chest wall pain. Considering our present study and the wide range of differing results from the literature, a reasonable conclusion is that a constraint for chest wall pain is yet to be defined.

Maximizing Sacral Chordoma Resection by Precise 3-Dimensional Tumor Modeling in the Operating Room Using Intraoperative Computed Tomography Registration with Preoperative Magnetic Resonance Imaging Fusion and Intraoperative Neuronavigation: A Case Series.

INTRODUCTION: The primary treatment for patients with sacral chordoma is en bloc surgical resection with negative margins, which has been shown to reduce local recurrence and tumor-related morbidity. Here we describe the use of intraoperative neuronavigation using preoperative spine magnetic resonance imaging fused to intraoperative computed tomography (CT) to create 3-dimensional tumor reconstructions in the operating room for intraoperative identification of bone and soft-tissue margins for maximal safe tumor resection. METHODS: A single-institution retrospective chart review was completed to encompass our experience of 6 consecutive patients who had sacral chordoma resections using our described navigation protocol. We collected data on patient demographics, previous surgeries, radiation therapy, preoperative examination, spinal levels involved, dural involvement, estimated blood loss, surgery time, tissue diagnosis, follow-up, postoperative examination, complications, and recurrence. Primary outcome was en bloc resection with negative margins as planned preoperatively. RESULTS: Negative surgical margins were achieved in 5 of 5 patients, who were preoperatively planned for en bloc resection with negative margins. The most common levels involved were S4-S5. All patients had a stable or improved neurologic examination after en bloc surgical resection. The average follow-up was 5.4 months ± 84.6 days. No patient had residual or recurrent tumor at last follow-up. CONCLUSIONS: Magnetic resonance imaging-CT fusion and 3-dimensional reconstruction techniques using an intraoperative CT scanner with image-guided navigation to aid preoperative planning and surgical resection of sacral chordomas are not well represented in the literature. This technique can be used for planning en bloc surgical resections and for more precisely identifying tumor margins intraoperatively.

Free propagation phase-contrast breast CT provides higher image quality than cone-beam breast-CT at low radiation doses: a feasibility study on human mastectomies.

In this study we demonstrate the first direct comparison between synchrotron x-ray propagation-based CT (PB-CT) and cone-beam breast-CT (CB-CT) on human mastectomy specimens (N = 12) including different benign and malignant lesions. The image quality and diagnostic power of the obtained data sets were compared and judged by two independent expert radiologists. Two cases are presented in detail in this paper including a comparison with the corresponding histological evaluation. Results indicate that with PB-CT it is possible to increase the level of contrast-to-noise ratio (CNR) keeping the same level of dose used for the CB-CT or achieve the same level of CNR reached by CB-CT at a lower level of dose. In other words, PB-CT can achieve a higher diagnostic potential compared to the commercial breast-CT system while also delivering a considerably lower mean glandular dose. Therefore, we believe that PB-CT technique, if translated to a clinical setting, could have a significant impact in improving breast cancer diagnosis.

Initial results from the New Horizons exploration of 2014 MU69, a small Kuiper Belt object.

The Kuiper Belt is a distant region of the outer Solar System. On 1 January 2019, the New Horizons spacecraft flew close to (486958) 2014 MU69, a cold classical Kuiper Belt object approximately 30 kilometers in diameter. Such objects have never been substantially heated by the Sun and are therefore well preserved since their formation. We describe initial results from these encounter observations. MU69 is a bilobed contact binary with a flattened shape, discrete geological units, and noticeable albedo heterogeneity. However, there is little surface color or compositional heterogeneity. No evidence for satellites, rings or other dust structures, a gas coma, or solar wind interactions was detected. MU69's origin appears consistent with pebble cloud collapse followed by a low-velocity merger of its two lobes.

SAA and PLTP activity in plasma of periodontal patients before and after full-mouth tooth extraction.

OBJECTIVE: To assess whether treatment of advanced periodontal disease affects plasma levels of serum amyloid A (SAA) and phospholipid transfer protein (PLTP) activity. DESIGN: We measured the levels of SAA and PLTP activity in plasma of 66 patients with advanced periodontal disease before and after treatment by full-mouth tooth extraction (FME). RESULTS: At baseline, median SAA levels in our study population were within the normal range (2.7 microg ml(-1)) but SAA was elevated (>5 microg ml(-1)) in 18% of periodontitis patients. Three months after FME, SAA levels were significantly reduced (P = 0.04). SAA did not correlate with any of the periodontal disease parameters. PLTP activity was elevated in patients with periodontitis, compared to the PLTP activity reference group (age-matched systemically healthy adults, n = 29; 18 micromol ml(-1) h(-1)vs 13 micromol ml(-1) h(-1), respectively, P = 0.002). PLTP activity inversely correlated with average periodontal pocket depth (PPD) per tooth (r(s) = -0.372; P = 0.002). Three months after FME, median PLTP activity did not change significantly. CONCLUSIONS: Full-mouth tooth extraction significantly reduces SAA, a marker of inflammation, while it does not affect plasma PLTP activity. However, the inverse correlation between PLTP activity and average PPD suggests that increased PLTP activity may limit periodontal tissue damage.

X-ray-Based 3D Virtual Histology-Adding the Next Dimension to Histological Analysis.

Histology and immunohistochemistry of thin tissue sections have been the standard diagnostic procedure in many diseases for decades. This method is highly specific for particular tissue regions or cells, but mechanical sectioning of the specimens is required, which destroys the sample in the process and can lead to non-uniform tissue deformations. In addition, regions of interest cannot be located beforehand and the analysis is intrinsically two-dimensional. Micro X-ray computed tomography (µCT) on the other hand can provide 3D images at high resolution and allows for quantification of tissue structures, as well as the localization of small regions of interest. These advantages advocate the use of µCT for virtual histology tool with or without subsequent classical histology. This review summarizes the most recent examples of virtual histology and provides currently known possibilities of improving contrast and resolution of µCT. Following a background in µCT imaging, ex vivo staining procedures for contrast enhancement are presented as well as label-free virtual histology approaches and the technologies, which could rapidly advance it, such as phase-contrast CT. Novel approaches such as zoom tomography and nanoparticulate contrast agents will also be considered. The current evidence suggests that virtual histology may present a valuable addition to the workflow of histological analysis, potentially reducing the workload in pathology, refining tissue classification, and supporting the detection of small malignancies.

Awake Microvascular Decompression for Trigeminal Neuralgia: Concept and Initial Results.

BACKGROUND: In this initial series, we evaluated the use of microvascular decompression (MVD) under an awake anesthesia protocol ("awake" MVD) to assess whether intraoperative pain evaluation can identify and mitigate insufficient decompression of the trigeminal nerve, improving surgical outcomes, and possibly expand the indications of MVD in patients with comorbidities that would preclude the use of general endotracheal anesthesia (GEA). METHODS: An Institutional Review Board-approved prospective study of 10 consecutive adults who underwent MVD for trigeminal neuralgia (TN) was conducted. The primary outcome measure was postoperative TN pain quantified on the Barrow Neurological Institute (BNI) Pain Severity Scale. RESULTS: The median patient age was 65.5 years, with a female:male ratio of 6:4. All 10 patients tolerated the procedure well and did not require GEA intraoperatively or postoperatively. Nine patients had a successful surgical outcome (BNI score I, n = 5; BNI score II, n = 4). One patient did not have pain relief (BNI score IV). This same patient also developed a pseudomeningocele, which was the sole surgical complication observed in this series. One patient experienced recurrence of pain at 11 months, with BNI score increasing from I to II. The median duration of follow-up was 16.5 months. Two patients did not experienced resolution of evoked pain during intraoperative awake testing following decompression. Further intraoperative exploration revealed secondary offending vessels that were subsequently decompressed, leading to resolution of pain. CONCLUSIONS: Intraoperative awake testing for treatment efficacy may increase the success rate of MVD by rapidly identifying and mitigating insufficient cranial nerve V decompression.

Effects of repetitive prolonged breath-hold in elite divers on myocardial fibrosis and cerebral morphology.

BACKGROUND: Prolonged apnea by breath-hold (BH) divers leads to hypoxemia and compensatory mechanisms of the cardiovascular system (i.e. increase of total peripheral resistance, increase of systolic blood-pressure, left-ventricular enlargement) to maintain oxygen supply to oxygen sensitive organs such as the brain. All these changes may result in structural myocardial or subclinical brain alterations. Therefore, the aim of this study was to investigate mid-term effects of repetitive prolonged apnea using cardiac magnetic resonance imaging (CMR) and magnetic resonance imaging of the brain. MATERIALS AND METHODS: 17 elite BH divers (15 males) were investigated at baseline, from whom 9 (7 males) were investigated again at follow-up one year later. CMR included functional imaging and tissue characterization using T1- and T2-mapping as well as late gadolinium enhancement. Results were compared intra-individually and with 50 age matched controls. RESULTS: Mean BH time were 297 ±â€¯52 s (entire cohort) and 315 ±â€¯56 s (sub-cohort) at initial, and 334 ±â€¯104 s at follow-up examination. Apnea resulted in a progressive increase of the left ventricle and impaired function, whichfully resolved after cessation of apnea. At rest, no dilation of the left ventricle was notable (LV-EDV: 106.7 ±â€¯28.8 ml; LV-EDV/BSA: 52.2 ±â€¯12.7 ml/m2). Compared to controls, the apnea group showed significantly lower volumes (LV-EDV: 106.7 ±â€¯28.8 ml vs. 140.9 ±â€¯36.3 ml, p = .008; LV-EDV/BSA: 52.2 ±â€¯12.7 ml/m2 vs. 73.7 ±â€¯12.8 ml/m2). In contrast, LV-EF showed no significant differences between both groups (61.0 ±â€¯7.0% vs. 60.9 ±â€¯3.6%). T1- and T2-mapping revealed no significant differences, neither intra-individually nor in comparison with age matched controls. (T1 pre-contrast: 974.1 ±â€¯12.9 ms vs. 969.4 ±â€¯29.0 ms, p = .2; T1 post-contrast: 368.9 ±â€¯38.5 ms vs. 966.7 ±â€¯40.5 ms, p = .4; ECV: 29.2 ±â€¯1.5% vs. 29.8 ±â€¯1.6%, p = .3; T2. 52 ±â€¯2 ms vs. 52 ±â€¯3 ms; p = .4). Except for one old embolic lesion no structural changes were found in brain imaging. CONCLUSION: Although, prolonged apnea leads to impressive adaptions of the cardiovascular system (i.e. dilation of the left ventricle) and hypertension due to peripheral vasoconstriction no mid-term morphological changes could be observed in both, the myocardium and the brain. BH divers are suitable as a model to investigate acute physiological changes of prolonged apnea and hypoxemia, but not as a model for chronic alterations.

The measurement of apolipoprotein A-I and A-II levels in men and women by immunoassay.

To study apolipoprotein A-II, a simple, precise, and accurate immunodiffusion assay was developed and applied in a population sample of industrial employees. Apolipoprotein A-II (A-II) did not increase with age in men (r = -0.20, n = 172), but showed a slight increase with age in women (0.1 mg/dl per yr, r = 0.20, n = 188). A-II correlated significantly with apolipoprotein A-I (A-I) (r = 0.71) and high density lipoprotein (HDL) cholesterol (men, r = 0.64; women, r = 0.49). The A-I/A-II ratio was significantly related to HDL cholesterol (men, r = 0.29; women, r = 0.44). Women on no medication (n = 92) had A-II levels similar to men (34+/-5 and 33+/-5 mg/dl, mean+/-SD, respectively), whereas women on oral contraceptives or estrogens had significantly higher levels (39+/-6 mg/dl, n = 75, P < 0.01). The plasma A-I/A-II weight ratio was 3.6+/-0.4 for men and 3.8+/-0.5 for women. In the d = 1.10-1.21 subfraction, both males and females had similar A-I, A-II, and HDL cholesterol levels (men: mean, 97, 27, and 32 mg/dl, respectively; women: mean, 104, 28, and 36 mg/dl, respectively). Women had approximately twice the amount of A-I, A-II, and HDL cholesterol than men in the d = 1.063-1.10 fraction (men: mean, 10, 2, and 10 mg/dl, respectively; women: mean, 24, 4, and 19 mg/dl, respectively). The A-I/A-II weight ratio in the d = 1.063-1.10 fraction (men, 5.1+/-0.7; women, 6.1+/-1.3) was significantly greater (P < 0.01) than that in the d = 1.10-1.21 fraction (men, 3.7+/-0.2; women, 3.8+/-0.2). Furthermore, the weight ratio of cholesterol to total apoprotein A in the d = 1.063-1.10 fraction (men, 0.75+/-0.09; women, 0.67+/-0.05) was significantly higher (P < 0.01) than that found in the d = 1.10-1.21 fraction (men, 0.26+/-0.04, women, 0.28+/-0.05). Thus, the compositions of HDL hydrated density subclasses are significantly different from each other. These results suggest that the differences in HDL between men and women are due primarily to differences in the relative proportions of HDL subclasses rather than to the intrinsic differences in HDL structure.

Low-density lipoprotein receptor activity in cultured human skin fibroblasts. Mechanism of insulin-induced stimulation.

Low-density lipoproteins (LDL) receptor activity, as reflected by LDL degradation, was stimulated by the addition of insulin to cultures of human skin fibroblasts. These changes occurred independently of the glucose concentration of the incubation medium and occurred whether or not LDL receptor activity was suppressed. A comparison of the saturation kinetics of LDL receptor activity in the presence and absence of insulin indicated that insulin produced a 35% increase in Vmax with no difference in "apparent Km". These results suggest that insulin enhances LDL receptor activity by increasing the number of LDL receptors rather than by influencing binding affinity. In confirmation, LDL degradation by receptor negative cells was not enhanced by insulin. Sterol synthesis from [14C]acetate was also stimulated by insulin, but egress of cholesterol and cellular cholesterol content were unaffected by the hormone. The effect of insulin on LDL receptors was not dependent on its known ability to enhance cellular DNA synthesis and proliferation, because insulin stimulated LDL receptor activity in cells kept quiescent by maintenance in plasma-derived serum that was devoid of platelet derived growth factor. Nevertheless, the effect of insulin in enhancing LDL receptor number, coupled with stimulation of endogenous cholesterol synthesis, provides a mechanism whereby the cell could theoretically increase its supply of cholesterol during times of additional need.

Radioimmunoassay of human plasma lecithin-cholesterol acyltransferase.

A sensitive and precise competitive-displacement double-antibody radioimmunoassay was developed for the human plasma enzyme lecithin-cholesterol acyltransferase (LCAT; Ec 2.3 1.43). The ability of plasma from various animal species to displace labeled human LCAT from goat anti-human LCAT could be ranked in the following order: man and sheep > nonhuman primates > cat or dog > pig > rabbit or guinea pig > mouse > rat. Normolipidemic subjects had levels of LCAT of 6.14 +/- 0.98 micrograms/ml (mean +/- SD, n = 66). Subjects with dysbeta-lipoproteinemia had the highest plasma LCAT levels (7.88 +/- 0.39 micrograms/ml, n = 7, P < 0.05), followed by hypercholesterolemic subjects (7.00 +/- 1.30, n = 41) and hypertriglyceridemic subjects (6.96 +/- 1.3, n = 10). LCAT-deficient subjects had the lowest enzyme levels (0.89, 0.83, and 0.05 micrograms/ml, respectively, and two subjects with no detectable enzyme). Males had lower LCAT levels (6.42 +/- 1.05 micrograms/ml, n = 90, for all subjects; 5.99 +/- 1.03, n = 44, for normolipidemics) than females (7.01 +/- 1.14, n = 34, for all subjects P < 0.01; 6.44 +/- 0.79, n = 22, for normolipidemics, P < 0.01). LCAT levels correlated significantly with total cholesterol (males, r = 0.384, P < 0.001; females, r = 0.519, P < 0.002); and total triglyceride (only in females, r = 0.512, P < 0.002). LCAT levels in females correlated inversely with HDL cholesterol (r = 0.341, P < 0.05) and apoprotein D (r = 0.443, P < 0.02), but no such relationship existed in males.