Bilateral inferior petrosal sinus sampling in adrenocorticotropin-dependent hypercortisolism: always, never, or sometimes?

http://bit.ly/2RkVorD

Bioleaching of heavy metals from harbor sediment using sulfur-oxidizing microflora acclimated from native sediment and exogenous soil

Abstract

The harbor sediment containing high concentration of heavy metals may pose serious impacts on the marine ecosystem and environmental quality. The bioleaching process has been considered as an environmentally friendly and cost-effective alternative for removing heavy metals from contaminated sediments. In this study, a series of experiments were performed to investigate the feasibility of bioleaching process for removing heavy metals from the contaminated harbor sediments. The performance of the bioleaching process inoculated with sulfur-oxidizing microflora acclimated from the native harbor sediment was compared with that acclimated from the exogenous soil. In the bioleaching experiment with inoculants from native sediment, the efficiency of Zn, Cu, Cr, Pb, and Ni (30 days) reached 39–100%, 21–94%, 8–63%, 5–74%, and 19–77%, respectively. While 59–100% of Zn, 22–100% of Cu, 0–95% of Cr, 0–100% of Pb, and 22–100% of Ni were respectively removed in the bioleaching experiment with inoculants from exogenous soil after 30 days of reaction time. The results show that the rate and efficiency of metal removal in the bioleaching process decreased with an increase of sediment solid content from 10 to 40 g/L. The efficiency of metal removal in the bioleaching process with inoculants from the native sediment was lower than those from the exogenous soil due to the bacterial activity. By the fractionation of metal in the harbor sediment, exchangeable, carbonate-bound, and Fe/Mn oxide-bound metals (mobile fractions) were found to be apparently reduced and even organic matter/sulfide-bound and residual metals (stable fractions) were slightly removed after the bioleaching experiment.

http://bit.ly/2RICgmV

Magnetic Resonance Imaging

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select article MRI visualization of shiitake mycelium growing in woodchip blocks used for shiitake mushroom cultivation

Research articleAbstract only

MRI visualization of shiitake mycelium growing in woodchip blocks used for shiitake mushroom cultivation

Kuniyasu Ogawa, Takeshi Yashima

In Press, Accepted Manuscript, Available online 11 January 2019

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Abstract

Abstract

In order to eliminate woodchip blocks where unwanted fungi have grown and select only blocks where shiitake mycelium are growing well, there is a need to develop a visualization technique for shiitake mycelium growing in woodchip blocks, and MRI is an obvious candidate technique. From the results of measurements of the woodchip bed in a small bottle (26 mm inside diameter) where shiitake mycelium was growing, the T1 relaxation time constant immediately after inoculation was 77.9 ± 5.5 ms, and the value after about 10 to 20 days increased to 135.0 ± 9.8 ms (the increase rate was 73%). The T1 maps of the wood-chip block (130 mm length, 75 mm height and 55 mm thickness) in which shiitake mycelium grew were calculated from T1 weighted images measured by changing TR from 28 to 400 ms. From the T1 maps of time series, it was found that the shiitake mycelium extended from the right-hand side to the left-hand side of the woodchip block in a planar manner. Furthermore, in a woodchip block in which penicillium was generated, since the T1 relaxation time constant of only the shiitake mycelium became longer, it was possible to visualize the shiitake mycelium distinctly from penicillium.

select article Quantification of pathophysiological alterations in venous oxygen saturation: A comparison of global MR susceptometry techniques

Short communicationAbstract only

Quantification of pathophysiological alterations in venous oxygen saturation: A comparison of global MR susceptometry techniques

Paula L. Croal, Jackie Leung, Charly L. Phillips, Malambing G. Serafin, Andrea Kassner

In Press, Accepted Manuscript, Available online 11 January 2019

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Abstract

Abstract

The purpose of this study was to compare the Infinite Cylinder and Forward Field methods of quantifying global venous oxygen saturation (Yv) in the superior sagittal sinus (SSS) from MRI phase data, and assess their applicability in systemic cerebrovascular disease.15 children with sickle cell disease (SCD) and 10 healthy age-matched controls were imaged on a 3.0 T MRI system. Anatomical and phase data around the superior sagittal sinus were acquired from a clinically available susceptibility weighted imaging sequence and converted to Yv using the Infinite Cylinder and Forward Field methods. Yv was significantly higher when calculated using the Infinite Cylinder method compared to the Forward Field method in both patients (p = 0.003) and controls (p < 0.001). A significant difference in Yv was observed between patients and controls for the Forward Field method only (p = 0.006). While various implementations of Yv quantification can be used in practice, the results can differ significantly. Simplistic models such as the Infinite Cylinder method may be easier to implement, but their dependence on broad assumptions can lead to an overestimation of Yv, and may reduce the sensitivity to pathophysiological changes in Yv.

select article The use of a binary chelate formulation: Could gadolinium based linear contrast agents be rescued by the addition of zinc selective chelates?

Research articleAbstract only

The use of a binary chelate formulation: Could gadolinium based linear contrast agents be rescued by the addition of zinc selective chelates?

Wendell Gibby, Wes Parish, Ray M. Merrill, Diego Fernandez, ... Ryan Parr

In Press, Accepted Manuscript, Available online 10 January 2019

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Abstract

Abstract

Tissue and bone retention of gadolinium based contrast agents (GBCAs) has become a clinical concern because of the potential short and long term toxic effects of free gadolinium. This is a critical problem for most open-chain agents that more readily transmetallate in vivo, in comparison to macrocyclic compounds. Gadoliniumdiethylene tri-aminepentaacetic acid bis-glucosamide (Gd-DTPA-BIGA) is an experimental, open-chain contrast agent which has a significantly increased relaxivity coefficient in comparison to other GBCAs. This results in greater signal intensity and improved contrast enhancement. These superior imaging qualities initiated a search for a solution to the transmettalation of this agent. Plasma zinc is a well-known GBCA transmettalation agent. Since the base chelate of Gadodiamide (Gd-DPTA-Bis-Methylamide or Omniscan), DTPA-Bis-Methylamide (DTPA-BMA), readily transmettalates with and binds serum zinc, we hypothesized that a plasma "zinc sink," may significantly reduce transmettalation of linear agents. 5% DTPA-BMA was added to a formulation of Gd-DTPA-BIGA, which was tested against the original formulation of Gd-DTPA-BIGA with 0.2% of the base chelate DTPA-BIGA. These formulations, including gadodiamide, were labeled with 153GdCl3 followed by infusion into cohorts of Sprague Dawley rats which were sacrificed at 1, 30 and 60 days. Internal organs were harvested, along with blood, skin and femur, and analyzed for residual gadolinium. A subset of tissues were also interrogated with ICP-MS. Labeled Gadodiamide and saline where used as controls.

Conclusion: The addition of 5% DTPA-BMA, as a zinc binding agent, reduced the transmetallation of the linear agent Gd-DTPA-BIGA, in comparison to its original formulation supplemented with 0.2% BIGA. This result indicates that supplementing linear GBCAs with ancillary chelates may hold promise for reducing, or eliminating the biological archiving of gadolinium in tissues. In addition, this paper provides valuable animal data on the long term retention of gadolinium from linear based contrast agents.

select article NMR-based analysis of shear strength of weakly expansive clay in sodium chloride solution

Research articleAbstract only

NMR-based analysis of shear strength of weakly expansive clay in sodium chloride solution

Haihao Yu, De'an Sun, Huihui Tian

In Press, Accepted Manuscript, Available online 7 January 2019

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Abstract

Abstract

A series of direct shear and nuclear magnetic resonance (NMR) tests were performed on a compacted weakly expansive clay saturated by sodium chloride (NaCl) solutions with different concentrations to study the effect of NaCl solution on the shear strength and its mechanism. Results from the direct shear tests show that the shear strength decreases slightly with increasing the NaCl solution concentration when the concentration is less than 1.0 mol/L. The results of NMR tests show that the smaller transverse relaxation times (T2) of specimens saturated by NaCl solutions with concentrations of 0.5 and 1.0 mol/L are less than that of the specimen saturated by deionized water. This means that the amount of smaller pores in the specimens saturated by deionized water is greater than that in specimens by NaCl solutions. That is, the specimen saturated by deionized water is denser than those by NaCl solutions under the same vertical pressure, and thus the shear strength of weakly expensive clay decreases with increasing the NaCl solution concentration.

select article Slow component apparent diffusion coefficient for prostate cancer: Comparison and correlation with pharmacokinetic evaluation from dynamic contrast-enhanced MR imaging

Research articleAbstract only

Slow component apparent diffusion coefficient for prostate cancer: Comparison and correlation with pharmacokinetic evaluation from dynamic contrast-enhanced MR imaging

Akio Ogura, Fumie Maeda, Seiji Yahata, Daisuke Koyama, ... Kenichiro Yamamura

In Press, Accepted Manuscript, Available online 7 January 2019

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Abstract

Abstract

Purpose

Dynamic contrast enhancement (DCE)-MRI has high diagnostic performance of prostate cancer. However, it is preferable to avoid the use of MRI contrast media. A study reported that the diagnosability of the wash-in index of DCE-MRI was equivalent to the intravoxel incoherent motion of the diffusion weighted image.

The purpose of this study was to examine the correlation between the slow component apparent diffusion coefficient (ADC) and the wash-out index of the DCE.

Materials and methods

Thirty-eight patients diagnosed with prostate cancer by biopsy were enrolled in this study. The fast and slow component ADCs of the DWI were calculated for 76 points of the tumor and the contralateral normal parts. Furthermore, the wash-in and wash-out indices of the DCE-MRI were calculated. The correlations for each calculated index were compared.

Results

There was a significant difference between the tumor and the contralateral normal parts for both fast (p = 0.03) and slow component (p < 0.01) ADCs. In addition, the slow component ADC was correlated with the wash-out index (r = 0.64).

Conclusion

The slow component ADC was correlated with the wash-out index, and may, therefore, be a suitable substitute for DCE-MRI.

select article Using functional magnetic resonance imaging to evaluate an acute allograft rejection model in rats

Research articleAbstract only

Using functional magnetic resonance imaging to evaluate an acute allograft rejection model in rats

Song Zeng, Lu Liang, Qiang Zhang, Yue Xu, ... Xiaopeng Hu

In Press, Accepted Manuscript, Available online 7 January 2019

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Abstract

Abstract

Purpose

To assess the longitudinal changes of allograft pathophysiology by intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) MRI in a rat model of acute renal allograft rejection.

Materials and methods

Acute rejection (AR) was induced by transplantation of Dark Agouti donor kidneys into Lewis recipients (n = 18). A Lewis-Lewis rat syngeneically transplanted (sTX) model served as the control (n = 6). Acute tubular necrosis (n = 6) and acute calcineurin inhibitor toxicity (n = 6) groups were established using Lewis rats. MRI was performed on postoperative day (POD) 1, 4 and 7 in the allogeneically transplanted (aTX) group and on POD4 in the other groups. Histological evaluation and PCR were performed.

Results

After the allogenic transplantation, all MRI parameters of allograft further decreased until POD7, and the D and ADC values in the cortex were significantly lower than that in the sTX group (1.03 ± 0.09 vs 1.52 ± 0.09 × 10−3 mm2/s, Padj < 0.05; 1.21 ± 0.03 vs 1.78 ± 0.07 × 10−3 mm2/s, Padj < 0.05). The D*, f and R2* values of the aTX group in the cortex and medulla were significantly lower than those in the sTX group on POD7 (cortex, D*: 25.60 ± 4.78 vs 69.32 ± 9.79 × 10−3 mm2/s, Padj < 0.05; f: 7.84 ± 1.83 vs 20.34 ± 3.08%, Padj < 0.05; R2*: 16.61 ± 4.18 vs 31.48 ± 6.43 1/s, Padj < 0.05; medulla, D*: 13.59 ± 6.08 vs 62.75 ± 9.20 × 10−3 mm2/s, Padj < 0.05; f: 7.46 ± 1.62 vs 14.68 ± 2.05%, Padj < 0.05; R2*: 21.59 ± 3.45 vs 39.53 ± 4.34 1/s, Padj < 0.05). AR grafts presented serve interstitial inflammation, tubulitis and infiltration of T-lymphocytes and macrophages. The MRI parameters, including D, ADC, D*, f and R2*, were significantly correlated with the histological changes, cell infiltration and inflammatory cytokine mRNA levels.

Conclusions

IVIM coupled with BOLD MRI allows longitudinal assessment of allograft diffusion, perfusion and oxygen consumption impairment caused by acute renal allograft rejection in rat model.

select article Water mobility spectral imaging of the spinal cord: Parametrization of model-free Laplace MRI

Research articleAbstract only

Water mobility spectral imaging of the spinal cord: Parametrization of model-free Laplace MRI

Dan Benjamini, Peter J. Basser

In Press, Corrected Proof, Available online 22 December 2018

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Abstract

Abstract

Diffusion magnetic resonance imaging (dMRI) of biological systems most often results in non-monoexponential signal, due to their complexity and heterogeneity. One approach to interpreting dMRI data without imposing tissue microstructural models is to fit the signal to a multiexponential function, which is sometimes referred to as an inverse Laplace transformation, and to display the coefficients as a distribution of the diffusivities, or water mobility spectra. Until recently, this method has not been used in a voxelwise manner, mainly because of heavy data requirements. With recent advancements in processing and experimental design, voxelwise Laplace MRI approaches are becoming feasible and attractive. The rich spectral information, combined with a three-dimensional image, presents a challenge because it tremendously increases the dimensionality of the data and requires a robust method for interpretation and analysis. In this work, we suggest parameterizing the empirically measured water mobility spectra using a bimodal lognormal function. This approach allows for a compact representation of the spectrum, and it also resolves overlapping spectral peaks, which allows for a robust extraction of their signal fraction. We apply the method on a fixed spinal cord sample and use it to generate robust intensity images of slow- and fast-diffusion components. Using the parametric variables, we create novel image contrasts, among them the information entropy of the water mobility spectrum, which pack unique features of the individual diffusion regimes in the investigated system.

select article Two-dimensional nuclear magnetic resonance method for wettability determination of tight sand

Research articleAbstract only

Two-dimensional nuclear magnetic resonance method for wettability determination of tight sand

Can Liang, Lizhi Xiao, Cancan Zhou, Yan Zhang, ... Zijian Jia

In Press, Corrected Proof, Available online 5 December 2018

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Abstract

Abstract

The wettability of reservoir rocks is important for oil recovery and reserve calculations. However, current methods for evaluating the wettability of rocks are time-consuming and expensive. Previous work has shown that low-field nuclear magnetic resonance (NMR) is a potentially useful and non-invasive technique for rock wettability determination. However, for rocks with strong internal magnetic field gradients, the current method is less efficient. In this study, the bipolar pulsed field gradient (PFG)-Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence was applied to the study of rock wettability. This method can suppress the effect of the internal magnetic field gradient in rocks and accurately extract wettability information. The diffusion-transverse relaxation time (D-T2) method was employed to quantitatively estimate the wettability of rocks. Results of Amott wettability tests and NMR T1-T2 maps were combined to provide a more complete wettability characterization of tight sand. The results demonstrate the feasibility of the new method for characterizing wettability. The proposed method and workflow is of significance to the development of oil fields.

select article Influence of excess ligand on Nephrogenic Systemic Fibrosis associated with nonionic, linear gadolinium-based contrast agents

Research articleAbstract only

Influence of excess ligand on Nephrogenic Systemic Fibrosis associated with nonionic, linear gadolinium-based contrast agents

Richard C. Semelka, John P. Prybylski, Miguel Ramalho

In Press, Accepted Manuscript, Available online 22 November 2018

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Abstract

Abstract

Background

The molecular structure, charge, thermodynamic and kinetic stability are approximately the same for gadodiamide and gadoversetamide, the main substantive difference is that gadodiamide is manufactured with 5% free ligand to form Omniscan® and gadoversetamide with 10% free ligand to form OptiMARK®.

Purpose

To determine the relative risk of Nephrogenic Systemic Fibrosis (NSF) between gadodiamide (Omniscan®) and gadoversetamide (OptiMARK®) and to explore the potential contribution of the amount of excess ligand added to their commercial formulations.

Materials and methods

In this retrospective observational study, the number of doses and NSF cases associated with these agents were calculated based on two different approaches: the number of doses was determined based on pharmaceutical companies' information, and the number of unconfounded NSF cases was obtained from the previously published literature based on a legal database. A second analysis estimates the number of doses and NSF cases from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Results

Approximately 87 million and 12 million doses of Omniscan® and OptiMARK®, respectively, have been administered worldwide since their original approval for use in the various countries throughout the world. A total of 197 and 8 unconfounded cases of NSF have been reported with Omniscan® and OptiMARK®, rendering an incidence of 2.3/million and 0.7/million for these agents, respectively. The FAERS analysis suggested reported incidences of 13.1/million and 5.0/million.

Conclusion

There is an approximately 3-fold greater incidence of NSF from Omniscan® than OptiMARK®. The difference in incidence might reflect the lesser quantity of added free ligand to the formulation of Omniscan®.

select article Optimising sampling patterns for bi-exponentially decaying signals

Research articleAbstract only

Optimising sampling patterns for bi-exponentially decaying signals

A. Reci, M.I. Ainte, A.J. Sederman, M.D. Mantle, L.F. Gladden

In Press, Corrected Proof, Available online 6 November 2018

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Abstract

Abstract

A recently reported method, based on the Cramér-Rao Lower Bound theory, for optimising sampling patterns for a wide range of nuclear magnetic resonance (NMR) experiments is applied to the problem of optimising sampling patterns for bi-exponentially decaying signals. Sampling patterns are optimised by minimizing the percentage error in estimating the most difficult to estimate parameter of the bi-exponential model, termed the objective function. The predictions of the method are demonstrated in application to pulsed field gradient NMR data recorded for the two-component diffusion of a binary mixture of methane/ethane in a zeolite. It is shown that the proposed method identifies an optimal sampling pattern with the predicted objective function being within 10% of that calculated from the experiment dataset. The method is used to advise on the number of sampled points and the noise level needed to resolve two-component systems characterised by a range of ratios of populations and diffusion coefficients. It is subsequently illustrated how the method can be used to reduce the experiment acquisition time while still being able to resolve a given two-component system.

select article Editorial: The Fourteenth International Bologna Conference on Magnetic Resonance in Porous Media (MRPM14)

EditorialNo access

Editorial: The Fourteenth International Bologna Conference on Magnetic Resonance in Porous Media (MRPM14)

Clifford R. Bowers, Sergey Vasenkov

In Press, Corrected Proof, Available online 1 November 2018

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select article High temperature/pressure MAS-NMR for the study of dynamic processes in mixed phase systems

Research articleOpen access

High temperature/pressure MAS-NMR for the study of dynamic processes in mixed phase systems

Ali Chamas, Long Qi, Hardeep S. Mehta, Jesse A. Sears, ... David W. Hoyt

In Press, Corrected Proof, Available online 25 October 2018

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Abstract

Abstract

A new MAS-NMR rotor (the WHiMS rotor) has been developed which can reach pressures of 400 bar at 20 °C or 225 bar at 250 °C. These rotors are ideal for mixed phase systems such as a reaction using a solid catalyst with a liquid/supercritical solvent topped with high pressure gas in the head space. After solid and liquid portions of the sample are loaded, the rotor is capped with an o-ring equipped polymer bushing that snaps into a mating groove in the rotor. The bushings incorporate a check valve into the sealing mechanism which allows for pressurization without mechanical manipulation – they will allow gas to flow in but not out. This WHiMS rotor design has enabled experiments on a wide variety of biotic and abiotic mixed-phase systems. Geochemical systems have also been studied, for example, adsorption and confinement studies of supercritical methane/CO2 in clays and other minerals which display pressure dependent 13C chemical shifts. Example data from other mixed-phase chemical and microbial systems are reported. These include monitoring metabolite conversion of extremophilic bacteria found in subsurface systems at elevated pressures and real-time operando reactions in catalysis systems - with liquid-quality resolution for 1H and 13C NMR spectra.

select article Preliminary evaluation of accelerated microscopic diffusional kurtosis imaging (μDKI) in a rodent model of epilepsy

Research articleAbstract only

Preliminary evaluation of accelerated microscopic diffusional kurtosis imaging (μDKI) in a rodent model of epilepsy

Yang Ji, Dongshuang Lu, Limin Wu, Bensheng Qiu, ... Phillip Zhe Sun

In Press, Corrected Proof, Available online 20 October 2018

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Abstract

Abstract

Purpose

Our study aimed to develop accelerated microscopic diffusional kurtosis imaging (μDKI) and preliminarily evaluated it in a rodent model of chronic epilepsy.

Methods

We investigated two μDKI acceleration schemes of reduced sampling density and angular range in a phantom and wild-type rats, and further tested μDKI method in pilocarpine-induced epilepsy rats using a 4.7 Tesla MRI. Single slice average μDapp and μKapp maps were derived, and Nissl staining was obtained.

Results

The kurtosis maps from two accelerated μDKI sampling schemes (sampling density and range) are very similar to that using fully sampled data (SSIM > 0.95). For the epileptic models, μDKI showed noticeably different contrast from those obtained with conventional DKI. Specifically, the average μKapp was significantly less than that of the average of Kapp (0.15 ± 0.01 vs. 0.47 ± 0.02) in the ventricle.

Conclusions

Our study demonstrated the feasibility of accelerated in vivo μDKI. Our work revealed that μDKI provides complementary information to conventional DKI method, suggesting that advanced DKI sequences are promising to elucidate tissue microstructure in neurological diseases.

select article A novel MRI phantom to study interstitial fluid transport in the glymphatic system

Research articleAbstract only

A novel MRI phantom to study interstitial fluid transport in the glymphatic system

M.E. Komlosh, D. Benjamini, N.W. Williamson, F. Horkay, ... P.J. Basser

In Press, Corrected Proof, Available online 19 October 2018

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Abstract

Abstract

The glymphatic system is a recently discovered transport system, mediated by cerebral spinal fluid (CSF), that clears metabolic and cellular waste products in the brain. This system's function in the brain is analogous to that of the lymphatic system in the rest of the mammalian body. It is hypothesized that CSF clears harmful chemicals from the brain by flowing through interstitial spaces in the brain during sleep. While there is growing recognition of the critical role the glymphatic system plays in maintaining normal brain health and in explaining pathology, there are few noninvasive imaging methods that measure and characterize the efficacy of glymphatic transport in vivo. In this study we designed, constructed, and tested a glymphatic transport magnetic resonance imaging (MRI) flow phantom, which combines regions that mimic CSF-filled ventricles and brain interstitial space. We tested high- and low-q space diffusion MRI and diffusion tensor imaging (DTI) acquisitions to determine if they could detect, measure, and map interstitial glymphatic flows. The results suggest that, under certain flow conditions, diffusion-weighted MRI can detect the enhanced mixing that occurs during glymphatic clearance.

select article The downhole circumferential scanning magnetic resonance imaging tool

Research articleAbstract only

The downhole circumferential scanning magnetic resonance imaging tool

Wei Liu, Lizhi Xiao, Guangzhi Liao, Yan Zhang, Sihui Luo

In Press, Corrected Proof, Available online 19 October 2018

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Abstract

Abstract

The downhole circumferential scanning magnetic resonance logging is able to image saturation distribution and fluid properties of stratum around a borehole, thus providing relevant and abundant information for formation evaluation. The device employs a phase-controlled excitation device based on combined array structure to accomplish three dimensional data acquisition from axial, radial and circumferential directions. This paper focuses on the design principle of device and the structure of electronic control system. A mutual coupling analysis with array antenna was carried out using inductance coupling principle, and realize the decoupling and energy discharge compensation of array antennas. The circumferential scanning nuclear magnetic resonance technique has a potential of overcoming the weakness of two dimensional measurements and raising new applications that it determines the azimuth of the fluid in the borehole and realizes the imaging measurement of the pore structure and the reservoir fluid.

select article Characterization of porous media by <em>T</em>₂-<em>T</em>₂ correlation beyond fast diffusion limit

Research articleAbstract only

Characterization of porous media by T2-T2 correlation beyond fast diffusion limit

Zhou Yu, Yan Zhang, Lizhi Xiao, Guangzhi Liao

In Press, Corrected Proof, Available online 19 October 2018

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Abstract

Abstract

Pore size distribution and surface relaxivity are two important properties of porous media such as rock samples and can be obtained by NMR methods. However, it is difficult to obtain these information beyond the fast diffusion limit. Here we present a new method to directly characterize the averaged pore size of a porous sample with a narrow pore size distribution. This method is based on the parallel plates pore model and the T2-T2 correlation sequence. The pore size (a) - surface relaxivity (ρ) correlation maps were obtained using the non-negative least squares method. Three kinds of glass bead samples were measured and the averaged pore size and surface relaxivity were extracted.

select article Credit-card sized field and benchtop NMR relaxometers using field programmable gate arrays

Research articleAbstract only

Credit-card sized field and benchtop NMR relaxometers using field programmable gate arrays

J. Beau W. Webber, Pavel Demin

In Press, Corrected Proof, Available online 18 October 2018

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Abstract

Abstract

The tools for developing systems for NMR improve each year. Some firmware based designs based on Field Programmable Gate Arrays (FPGAs) have been developed to implement both the core and peripheral apparatus for NMR Relaxometers and NMR Cryoporometers. Hand held in size they are particularly suitable for desktop, mobile and field use.

Software tools now enable the writing of firmware that enable the rapid design of digital and digitised R.F. data and control systems. This firmware can then be loaded into and run on hardware that often is only the size of a credit-card. These devices can include a single-chip Linux computer with an FPGA capable of processing digital RF on the same chip. These can generate RF signals digitally, process RF signals for up- and down-conversion, and can provide an on chip NMR pulse sequencer.

An extremely well tested NMR digital transmitter has been upgraded to use the latest surface-mount Bipolar and Field Effect Transistors. The circuitry is now the size of a book of matches, and interfaces to credit-card sized FPGA modules for RF generation, phase shifting and drive signals. This NMR transmitter design uses digital logic principles rather than conventional tuned R.F. techniques Offering both active-damping and active-quench, a very square R.F. Pulse with fast turn off is achieved, with Mark 1 giving 2.6 μs π/2 and 4.8 μs π pulses into a 5 mm diameter NMR sample (2.7 mT B1) at 20 MHz for Protons. T1ρ pulses are stable and consistent.

select article New magnet array design for downhole NMR azimuthal measurement

Research articleAbstract only

New magnet array design for downhole NMR azimuthal measurement

Sihui Luo, Lizhi Xiao, Xin Li, Guangzhi Liao, ... Yangyang Xu

In Press, Corrected Proof, Available online 16 October 2018

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Abstract

Abstract

In low-field NMR, depth information and radial profile information of downhole formation can be easily acquired with the help of static gradient magnetic field produced by permanent magnets, called downhole NMR imaging. Based on the hypothesis that the formation is homogeneous, average signals detected by centralized or decentralized sensors can provide enough information for petrophysical parameters. In fact, the inhomogeneity of formation may have serious impact on description of the characteristics of formation and oil/gas location which is rarely studied in NMR well-logging. To improve this, we design and implement a new quadrupolar magnet array aimed at achieving azimuthal measurement in this paper. A new quadrupolar magnet array is consisted of four bread-shaped magnets combined with additional small hexangular magnets to produce enough strength and high homogeneity of static field along with circumferential direction at deeper DOI (depth of investigation). Azimuthal measurements are achieved by using coil array combined with quadrupolar magnet array.

select article Investigating mobility of crude oil adsorbates on mineral surfaces by NMR

Research articleAbstract only

Investigating mobility of crude oil adsorbates on mineral surfaces by NMR

Henrik N. Sørgård, Christian Totland, Willy Nerdal, John Georg Seland

In Press, Corrected Proof, Available online 15 October 2018

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Abstract

Abstract

We have applied diffusion and relaxation Nuclear Magnetic Resonance experiments to investigate the translational and rotational mobility of adsorbents on quartz and calcite mineral surfaces. On both surfaces it was found that water is the dominant molecule. On the quartz surface the majority of water molecules have a relatively high degree of both rotational and translational mobility, while a minor fraction of water molecules, and all hydrocarbon molecules, have a significantly lower mobility. On the calcite surface the translational mobility is very low for all the adsorbed molecules, while there is a large diversity in rotational mobility, indicating that the hydrocarbon molecules are strongly attached to the surface, but that some part of each molecule still have a large degree of rotational mobility. Diffusion and relaxation experiments give a detailed description of both the molecular mobility of adsorbed species on these mineral surfaces, which leads to new insight with respect to aging processes on a molecular level.

select article Under-sampling and compressed sensing of 3D spatially-resolved displacement propagators in porous media using APGSTE-RARE MRI

Research articleAbstract only

Under-sampling and compressed sensing of 3D spatially-resolved displacement propagators in porous media using APGSTE-RARE MRI

Daan W. de Kort, Stefan A. Hertel, Matthias Appel, Hilko de Jong, ... Lynn F. Gladden

In Press, Corrected Proof, Available online 15 October 2018

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Abstract

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Osteosarcoma of the mandible

: A case report and short literature review p. 193
Niharika Bisht, Sankalp Singh, Samir Gupta, Harinder Pal Singh, Prabha Shankar Mishra, Deepak Mulajker
DOI:10.4103/ccij.ccij_6_18  
Osteosarcomas comprise of a heterogeneous group of tumors with a predilection for involving long bones commonly. The jaw remains a rare site of involvement, and these tumors can be considered a distinct entity. The key for managing them lies in histological and radiological correlation for an early diagnosis. Surgery and chemotherapy remain the main modalities of treatment. We present a case of osteogenic sarcoma of the mandible that after radical treatment had local recurrence and distant metastasis.
http://www.ccij-online.org/currentissue.asp?sabs=y

Psammomatoid juvenile ossifying fibroma of maxilla

: An uncommon neoplasm p. 191
Jyotsna Naresh Bharti, Ashok Singh, Jitendra Singh Nigam
DOI:10.4103/ccij.ccij_8_18  
Juvenile ossifying fibroma (JOF) is a rare variant of ossifying fibroma. JOF is classified into two distinct clinicopathological variants: Trabecular and psammomatoid JOF. Based on the age group involved, most common site of occurrence and clinical behavior, JOF differs from the larger group of ossifying fibromas. We report a case of psammomatoid JOF of maxilla in a 10-year-old female who presented with a swelling over the right side of the face.
http://www.ccij-online.org/currentissue.asp?sabs=y

Carcinosarcoma of the submandibular gland with a rhabdomyosarcoma component

: A case report and review of the literature p. 187
Suma M Narayana, Smrita Singh, Rekha V Kumar
DOI:10.4103/ccij.ccij_83_18  
Carcinosarcoma of the salivary gland is a rare and aggressive malignancy with a poor prognosis. These neoplasms are composed of malignant epithelial and mesenchymal elements. This report describes a new case of carcinosarcoma arising in the submandibular gland, which had a rhabdomyosarcoma component, without clinical or histological evidence of a preexisting pleomorphic adenoma. Till date, only two case reports have described the occurrence of carcinosarcoma with a rhabdomyosarcoma component in the salivary gland, to the best of our knowledge. Histological and immunohistochemical results are presented. The literature is reviewed, and the possible histogenesis and pathogenesis of carcinosarcoma (true malignant mixed tumor) of the salivary gland are briefly discussed.
http://www.ccij-online.org/currentissue.asp?sabs=y

Years with anxiety and headache

Recurrent pilocytic astrocytoma after 5 years with anxiety and headache p. 184
Mazaher Ramezani, Shima Jalalvandi, Zahra Torkchin, Masoud Sadeghi
DOI:10.4103/ccij.ccij_66_18  
Pilocytic astrocytomas (PAs) account for 25% of all pediatric brain tumors and commonly occur in the first two decades of life. Recurrence and/or regrowth of residual tumors are not common and mostly occur within 4–5 years of the first surgery. Herein, we reported a 16-year-old male adolescent with neurological symptoms and signs that pathologic specimens confirmed the diagnosis of PA. The patient underwent 27 sessions of radiotherapy without surgery. After 5 years, at the age of 21, the patient readmitted with anxiety and headache and the recurrence of the same tumor with the same grade. We suggest follow-up of the patient after initial treatment for at least 5 years with considering any neurological symptoms including behavioral changes.
http://www.ccij-online.org/currentissue.asp?sabs=y

Apoptotic indices are useful in distinguishing between benign and malignant squamous lesions

Operational role of apoptotic index in premalignant and malignant squamous lesions: An apprise p. 180
Sheetal Arora, Deepshikha Rana, Indrani Dhawan, Rashmi Arora
DOI:10.4103/ccij.ccij_80_17  
Background: The aim of the study was to evaluate the role of apoptotic index (AI) in premalignant and malignant squamous lesions of different sites on light microscopy. Materials and Methods: Retrospective study of 75 cases of premalignant and malignant squamous epithelial lesions of different sites was done. All slides were H and E stained, screened for apoptosis under ×40. AI was calculated as the number of apoptotic cells and apoptotic bodies, expressed as percentage of total number of tumor cells counted in each case. Results: On statistical analysis, it was found that the difference in the apoptotic indices in all the subgroups of dysplasia was not statistically significant. However, the significant statistical difference was found within the malignant group, P value between well-differentiated squamous cell carcinoma (SCC) and moderately differentiated SCC (MDSCC) was <0.0001. P value obtained between MDSCC and poorly differentiated SCC was 0.0006. Conclusion: We conclude that apoptotic indices are useful in distinguishing between benign and malignant squamous lesions. Several indices such as proliferating index (Ki-67) and AgNOR count are not routinely available in various hospitals, especially in developing countries. The advantage of this technique is that it can be calculated in routine H and E stained sections, and so it saves time. Although it is labor-intensive, it is cost-effective method which can benefit the patient as it correlates well with tumor aggressiveness and thereby increasing the prognosis of the patients.
http://www.ccij-online.org/currentissue.asp?sabs=y

Computed tomography-guided fine-needle aspiration and concurrent core biopsy

 in diagnosis of intrathoracic mass: An evaluation of 54 cases in a tertiary care hospital p. 176
Rajashree Pradhan, Sajeeb Mondal, Subrata Pal, Mrinal Sikder, Biswajit Biswas
DOI:10.4103/ccij.ccij_81_17  
Introduction: Fine-needle aspiration cytology (FNAC) is a simple, safe, and effective tool for cytological diagnosis of different neoplastic lesions. Computed tomography (CT)-guided core biopsy is also essential for tissue diagnosis. Aims and Objectives: The aim of this study is to assess the diagnostic value and limitations of fine-needle aspiration and core biopsy in diagnosis of intrathoracic lesions; we have done this retrospective study. Materials and Methods: In all 54 cases with mean age of 57.37 years, CT-guided FNAC and core biopsy were performed on same sittings. 20–22 G Chiba needle was used for FNAC, and core biopsy was performed by 18–20 G coaxial automated cutting needle. The cytological and histological evaluations were done in our cytology and histopathology laboratory. Complications were managed by pulmonologists. Results: On the evaluation of FNAC smears, diagnosis was done in 44 cases and 10 cases were inconclusive. In core biopsy, five cases were inconclusive. Most of the tumors were of epithelial origin (43 cases, 87.75%) and 95.59% cases were malignant in our series. Sensitivity and diagnostic accuracy of core biopsy (90.38% and 90.74, respectively) were higher than FNAC (84.62% and 85.18%, respectively). Conclusion: CT-guided core biopsy was more effective and accurate in diagnosis and tumor classification than FNAC in spite of higher complication rate.
http://www.ccij-online.org/currentissue.asp?sabs=y

Ultrasound-guided fine-needle aspiration cytology of head and neck masses

: Experience in Ado-Ekiti, Southwestern Nigeria p. 171
Abidemi Emmanuel Omonisi, Olufunso Simisola Aduayi, John Adetunji Omotayo, Ganiyu Olusola Akanbi, Olusola Olusoga Akute
DOI:10.4103/ccij.ccij_87_17  
Background: A multidisciplinary approach to the evaluation of head and neck masses is crucial to achieving optimum patient care and enhancing diagnostic accuracy for definitive treatment. This is exemplified by the clinical and radiopathologic correlation of head and neck masses subjected to diagnostic evaluation using ultrasound-guided fine-needle aspiration cytology (FNAC) in a tertiary health institution. Subjects and Methods: A prospective study was carried out on 51 patients with head and neck lesions referred to the FNAC Clinic of the Department of Anatomic Pathology of Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria. The study was conducted over a period of 2 years between February 2014 and January 2016. The FNAC was done under imaging guidance with a 7.5 MHz ultrasound probe. Clinical, radiological, and pathological findings were correlated. The data were analyzed using SPSS version 15. Results: The study population consisted of 12 (23.5%) males and 39 (76.5%) females. The age range was 2–80 years with a mean age of 44.7 ± 18.4 years. A significant proportion (80.4%) of the masses was located in the anterior neck. Multinodular goiter (n = 22, 43.1%) was the predominant clinical diagnosis. On ultrasonography, the predominant echotexture of the masses was heterogeneous (n = 29, 56.9%), only 4 (7.84%) of the masses had internal calcifications while the predominant composition of the masses was a mixture of solid and cystic portions (n = 30, 58.8%). There was a strong radiopathologic correlation (Spearman correlation value of 0.910). Conclusion: Ultrasound-guided FNAC of head and neck masses provides a synergistic approach to patient care and should be encouraged in our setting for optimum diagnostic yields.
http://www.ccij-online.org/currentissue.asp?sabs=y

Latex-related symptoms and sensitization

Prevalence and associated factors of latex-related symptoms and sensitization at a multispecialty hospital: A cross-sectional study p. 122
Jandhyala Sridhar, Rahul Ray
DOI:10.4103/jmms.jmms_58_18  
Background and Aim: Upsurge in usage of latex gloves over the last few decades, coupled with the proliferation of medical latex products at the workplace, has led to a higher incidence of latex-related symptoms among health-care workers (HCWs). This study aimed to assess the prevalence and associated factors of latex glove-related symptoms and sensitization among HCW at a multispecialty hospital. Materials and Methods: The study included all the paramedical personnel and nurses employed at a multispecialty hospital where powdered latex gloves were in use. Consenting participants were evaluated by a questionnaire for symptoms of latex allergy, followed by a skin prick test (SPT) for evaluating sensitization to latex allergen. Statistical Analysis Used: Mean, standard deviation, and Student's t-test were used for continuous data. Categorical data were analyzed using the Chi-square test. Odds ratios and 95% confidence intervals were calculated. Results: Latex glove-related symptoms were present in 25 (10.91%) HCWs. Symptoms suggestive of Type I latex allergy were reported in 11 (4.8%), while those of contact dermatitis were reported in 17 (7.42%) HCWs. Of the 229 HCWs, 37 (16.16%) had a personal history of atopy; 14 (6.11%) were SPT positive to latex allergen. Conclusions: In this study among Indian HCW, there was a significant correlation of latex glove-related symptoms with the duration of glove use, personal atopy, and SPT positivity to latex allergen. Questionnaire-based evaluation of allergic symptoms along with SPT positivity was found to be a useful identifier of true latex allergy.
http://www.marinemedicalsociety.in/currentissue.asp?sabs=y

Role of kisspeptin and Kiss1R in the regulation of prolactin gene expression in rat somatolactotroph GH3 cells

Abstract

Hypothalamic kisspeptin is a known principal activator of gonadotropin-releasing hormone neurons and governs the hypothalamic-pituitary-gonadal axis. Previous reports have shown that kisspeptin is also released into the hypophyseal portal circulation and directly affects the anterior pituitary. In this study, we examined the direct effect of kisspeptin on pituitary prolactin-producing cells. The rat pituitary somatolactotroph cell line GH3 expresses the kisspeptin receptor (Kiss1R); however, in these cells, kisspeptin failed to stimulate prolactin-promoter activity. When GH3 cells overexpressed Kiss1R, kisspeptin clearly increased prolactin-promoter activity, with a concomitant increase in extracellular signal-regulated kinase (ERK) and cAMP/protein kinase A (PKA) signaling pathways. In the experiments using GH3 cells overexpressing Kiss1R, kisspeptin did not potentiate thyrotropin-releasing hormone (TRH)-induced prolactin-promoter activity, but it potentiated the pituitary adenylate cyclase-activating polypeptide-induced prolactin-promoter activity, with a concomitant enhancement of ERK and PKA signaling pathways. Although the basal and TRH-induced prolactin-promoter activities were not modulated by increasing amounts of Kiss1R expression in GH3 cells, kisspeptin-stimulated prolactin-promoter activity was increased by the amount of Kiss1R overexpression. Endogenous Kiss1r mRNA expression in GH3 cells was significantly increased by treatment with estradiol (E2) but not by TRH. In addition, kisspeptin's ability to stimulate prolactin-promoter activity was restored after E2 treatment in non-transfected GH3 cells. Our current observations suggest that kisspeptin might have a direct effect on prolactin expression in the anterior pituitary prolactin-producing cells under the influence of E2, which may regulate Kiss1R expression and function.

http://bit.ly/2M5hdG7

Reply to “Predictors of surgical outcome and early criteria of remission in acromegaly—some controversial issues”

http://bit.ly/2suIPLT

Analysis of risk factors of metabolic syndrome using a structural equation model: a cohort study

Abstract

Purpose

We aimed to use a structural equation model (SEM) to determine the interrelations between various risk factors, including latent variables, involved in the development of metabolic syndrome(MetS).

Methods

This study used data derived from the MJ Longitudinal Health Check-up Population Database for participants aged 20 to 70 years, who were asymptomatic for MetS at enrollment and were followed up for 5 years. A SEM was applied to investigate the attributions of MetS and the interrelations between different risk factors.

Results

Socioeconomic status (SES), living habits, components of metabolic syndrome (COMetS), and blood pressure had a diverse impact on the onset of MetS, directly and (or) indirectly. When investigating the latent risk factors and the interrelations between different risk factors. The standardized total effect (the sum of the direct and indirect effects, β_t) of SES, living habits, blood pressure and COMetS on the onset of MetS was 0.084, −0.179, 0.154, and 0.353, respectively. SES, as a distal risk factor, directly influenced living habits, blood pressure, and COMetS with standardized regression coefficients (β_r) of −0.079 (P < 0.001), 0.200 (P < 0.001), and −0.163 (P < 0.001) respectively. Unfavorable living habits exerted an inverse effect on blood pressure and COMetS (β_r = −0.101, P < 0.001; β_r = −0.463, P < 0.001), which was an important path way for developing MetS.

Conclusions

These results demonstrate that individuals with a higher level of SES are susceptible to high blood pressure and are at increased risk for MetS. Additionally, there is a decrease in exercise and an increase in smoking and consumption of alcohol corresponded to an increase in metabolic risk factors.

http://bit.ly/2M69dV9

Correction to: Signs and symptoms of acromegaly at diagnosis: the physician’s and the patient’s perspectives in the ACRO-POLIS study

The original version of this article unfortunately contained a mistake in corresponding author name as Philippe Chanson in the affiliation section.

http://bit.ly/2sjtiyj

Adult individuals with congenital, untreated, severe isolated growth hormone deficiency have satisfactory muscular function

Abstract

Purpose

While growth hormone (GH) and the insulin-like growth factor type I (IGF-I) are known to exert synergistic actions on muscle anabolism, the consequences of prolonged GH deficiency (GHD) on muscle function have not been well defined. We have previously described a large cohort of subjects with isolated GHD (IGHD) caused by a mutation in the GH-releasing hormone receptor gene, with low serum levels of GH and IGF-I. The aim of this study was to assess muscular function in these IGHD subjects.

Methods

A total of 31 GH-naïve IGHD (16 males) and 40 control (20 males) subjects, matched by age and degree of daily physical activity, were enrolled. Fat free mass was measured by bioelectrical impedance; muscle strength by dynamometry of handgrip, trunk extension, and knee extension; myoelectric activity and muscle fatigue by fractal dimension; conduction velocity in vastus medialis, rectus femoris, and vastus lateralis muscles by surface electromyography.

Results

The IGHD group showed higher knee extension strength both when corrected for weight and fat free mass, and higher handgrip and trunk extension strength corrected by fat free mass. They also exhibit higher conduction velocity of the muscles vastus medialis, rectus femoris, and vastus lateralis, but lower free fat mass and myoelectric activity of the vastus medialis, rectus femoris and vastus lateralis. There were no differences between the two groups in fractal dimension in all studied muscles.

Conclusion

Individuals with untreated IGHD have better muscle strength parameters adjusted for weight and fat free mass than controls. They also exhibit greater peripheral resistance to fatigue, demonstrating satisfactory muscle function.

http://bit.ly/2M2PdCH

Signs and symptoms of acromegaly at diagnosis: the physician’s and the patient’s perspectives in the ACRO-POLIS study

Abstract

Purpose

Acromegaly is characterized by a broad range of manifestations. Early diagnosis is key to treatment success, but is often delayed as symptomatology overlaps with common disorders. We investigated sign-and-symptom associations, demographics, and clinical characteristics at acromegaly diagnosis.

Methods

Observational, cross-sectional, multicenter non-interventional study conducted at 25 hospital departments in France that treat acromegaly (ClinicalTrials.gov: NCT02012127). Adults diagnosed with acromegaly < 5 years were enrolled. Demographic and clinical data were obtained from medical reports and patient questionnaires. Sign-and-symptom associations were assessed by multiple correspondence analysis (MCA).

Results

Overall, 472 patients were included in the analyses. MCA was unsuccessful in identifying sign-and-symptom associations at diagnosis. Endocrinologists (29.5% patients) and other clinical specialists (37.2% patients) were commonly first to suspect acromegaly. Morphologic manifestations (83.7–87.9% patients), snoring syndrome (81.4% patients), and asthenia (79.2% patients) were frequently present at diagnosis; differences were found between sexes for specific manifestations. Rates of discrepancy between patient- and physician-reported manifestations were highest for functional signs. Earliest manifestations prior to diagnosis, according to how they were detected, were enlarged hands and feet (6.4 ± 6.8 and 6.2 ± 6.9 years, functional signs), hypertension (6.6 ± 7.5 years, complementary examination) and carpal/cubital tunnel syndrome (5.7 ± 6.7 years, functional signs with complementary examination).

Conclusions

Results confirm the broad range of manifestations at diagnosis and delay in recognizing the disease. We identified early manifestations and sex differences that may aid physicians in diagnosing acromegaly. Discrepancy rates suggest physicians should obtain the patient's perspective and seek functional signs during diagnosis.

http://bit.ly/2sjWZPF

18F-FDG PET reveals an adrenocortical carcinoma in a bilateral adrenal multinodular disease

http://bit.ly/2M5h9pR

The relationship between anti-Müllerian hormone serum level and body mass index in a large cohort of infertile patients

Abstract

Purpose

To evaluate the relationship between serum Anti-Müllerian hormone (AMH) level and body mass index (BMI) in infertile patients.

Methods

Medical records of patients with infertility evaluated between January 2013 and February 2018 in the Reproductive Medicine Department of a private hospital were reviewed. Patients with the following criteria were excluded from the study: polycystic ovary syndrome, primary ovarian insufficiency, AMH values > 10 ng/mL, current oral contraceptive users and previous ovarian surgery or endometriosis, and anovulation of other causes, except decreased ovarian reserve.

Results

A total of 2204 infertile patients were included (mean age 34.58 ± 4.3 years, mean BMI 22.35 ± 3.6 kg/m², and mean serum AMH 2.44 ± 2.17 ng/ml). In the entire group of patients, serum AMH level was positively correlated with BMI after adjustment for age (beta = 0.059, p < 0.005). When the association between serum AMH level and BMI was analysed in subgroups of patients, after adjustment for age, we found a positive correlation between the two parameters in patients ≤ 35 years old (< 0.05), of normal weight (p < 0.05) and with normal ovarian reserve (p < 0.05). After adjustment for age, BMI ≥ 25 kg/m² was significantly associated with higher AMH values in comparison to normal weight patients.

Conclusions

In infertile patients, AMH is positively correlated with BMI, especially in patients younger than 35 years, of normal weight and with normal ovarian reserve. Moreover, the presence of mild excess adiposity seems to be associated with higher AMH values. Our data contradict the previous studies showing a negative impact of excess adiposity on AMH serum levels.

http://bit.ly/2skQwUw

Surgical outcomes and predictors of glucose metabolism alterations for growth hormone-secreting pituitary adenomas: a hospital-based study of 151 cases

Abstract

Purpose

The surgical outcome on glucose metabolism in acromegaly patients is not fully understood. We aimed to investigate the impact of surgery on glucose metabolism and identify key factors that influence alterations of glucose metabolic status in acromegaly patients.

Methods

Oral glucose tolerance test was performed in 151 newly diagnosed acromegaly patients before and 3–12 months after surgery. Insulin resistance and insulin secretion was assessed. Patients were grouped as cured, discordant, and having active disease according to postoperative growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. Receiver-operating characteristic curves were generated to determine the optimal cut-off points to predict the impact of surgery on glucose metabolism.

Results

At baseline, 32.5%, 41.7%, and 25.8% patients were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM), respectively. After surgery, improved glucose tolerance was observed in 87.3% patients with IGT and 66.7% patients with DM. Deterioration was observed in 14.3% patients with NGT. Glucose tolerance improved in patients with lower preoperative FBG, 2 h-BG, and HbA1c and higher HOMA-β and IGI/IR. The proportion of NGT was significantly increased in surgically cured patients (28.3% vs. 79.2%, P < 0.001) and those with normal GH but elevated IGF-1 levels (25.6% vs. 79.5%, P < 0.001), but not in patients with active disease (42.9% vs. 57.1%, P = 0.131). Baseline FBG < 6.35 mmol/l predicted improved glucose metabolism after surgery.

Conclusions

Glucose metabolic status improved in patients with preserved β-cell function. Preoperative FBG was an independent predictor for improved glucose tolerance status after surgery.

http://bit.ly/2M5h5X9

Alterations in hypothalamic-pituitary-adrenal function immediately after resection of adrenal adenomas in patients with Cushing’s syndrome and others with incidentalomas and subclinical hypercortisolism

Abstract

Background

Patients with cortisol secreting adrenal adenomas present with Cushing's syndrome (CS), while 5–15% of subjects with adrenal incidentalomas have subclinical hypercortisolism (SH) as they have biochemical abnormalities suggesting autonomous cortisol secretion without associated clinical features of CS.

Goals

Examine HPA function immediately after resection of either of these adenomas and utilize the data to decide on initiating glucocorticoid replacement.

Methods

ACTH, cortisol, and DHEA-S levels were measured frequently for 8 h after adrenalectomy in 14 patients with CS and 19 others with incidentalomas + SH. Glucocorticoids were withheld before/during surgery and administered 6–8 h postoperatively to those who had cortisol levels of <3 ug/dL (83 nmol/L).

Results

Preoperatively, incidentalomas + SH patients had larger tumors, higher ACTH, and DHEA-S but lower dexamethasone-suppressed serum cortisol levels than those with CS. Postoperatively, ACTH levels increased in both groups: (90.1 ± 31.6; 24.1 ± 14.4 ng/L, respectively; P < 0.001). Postoperative ACTH levels correlated negatively with preoperative Dexamethasone-suppressed cortisol concentrations in both groups. Patients with CS had steeper decline in cortisol concentrations than those with incidentalomas + SH. All patients with CS had hypocortisolemia requiring glucocorticoid therapy for several months, while only 5/19 with incidentalomas + SH had cortisol levels <3 ug/dL;(83 nmol/L) 6–8 h after adrenalectomy and received hydrocortisone replacement therapy for ≤4 weeks.

Conclusions

Surgical stress stimulates HPA function even in patients with hypercortisolemia. Patients with incidentalomas + SH have incomplete HPA suppression that allows more robust response to surgical stress than that observed in patients with CS. HPA assessment immediately after surgical resection of adrenal incidentalomas identified those requiring glucocorticoid replacement before discharge.

http://bit.ly/2slgasl

Intravenous (IV) fluid resuscitation

Intravenous fluid resuscitation in sepsis and critical illnesses  p. 148
Prabhakar Gupta, Kuldeep Kumar Ashta
DOI:10.4103/jmms.jmms_9_18  
Intravenous (IV) fluid resuscitation, pioneered in 1832, is now one of the most common medical interventions in hospitalized patients. Up until the end of the 20th century, IV fluid prescriptions have been considered ancillary, benign interventions and rarely tested in good-quality randomized clinical trials (RCTs). Robust clinical research evidence emerging in the past decade and a half, however, has revealed counterintuitive findings. The emerging research has consistently demonstrated harm, including higher mortality, and questionable clinical benefits associated with protocolized aggressive fluid resuscitation, as espoused in the early goal-directed therapy. Conservative fluid management has been shown to be associated with better outcomes in most clinical settings. Recent RCTs have also revealed clinically relevant pharmacological differences between types of IV fluids, especially pertaining to predictable harms associated with some commonly used IV fluids. Concerns have emerged over risks of metabolic acidosis and renal failure associated with the use of normal saline. Balanced solutions have been found to be safe across a wide spectrum of conditions. Better understanding of the complex pathophysiology of sepsis and critical illnesses and recognition of newer concepts such as profound disruption of the endothelial glycocalyx layer leading to profound leakiness of vessels question the basic premise of injection of large quantities of IV fluids during resuscitation.
http://www.marinemedicalsociety.in/currentissue.asp?sabs=y

Introduction

During the course of the past two centuries, due to a general absence of robust evidence, intravenous (IV) fluid use in resuscitation was largely guided by empirical institutional protocols or prescriber preferences.^[1]

A major inflection point in the history of IV fluid resuscitation was the publication of early goal-directed therapy (EGDT) model of IV fluid resuscitation as incorporated in the Surviving Sepsis Campaign Guidelines (SSCG).^[2] Although intended for use in sepsis, due to widespread popularity and endorsements, EGDT became a standard of care not just in sepsis but also in other critical illnesses necessitating fluid resuscitation.^[3] EGDT popularized infusions of large quantities (in some instances measurable in gallons) of crystalloids, in an effort to achieve, untested, arbitrarily predetermined, fixed metrics such as 8 mmHg of central venous pressure (CVP).^[4] Till date, there is no upper cutoff limit of dose of IV fluid to be infused within the first 6 h, prescribed in EGDT or SSCG.

Over the last decade, EGDT has been tested in several large, high-quality clinical trials and the results have been counterintuitive and consistent across various studies and diverse settings.^[5],[6],[7]

In a patient-level meta-analysis of ProMISe, ARISE, and ProCESS, which analyzed data of 3723 patients at 138 centers, in seven countries spread over three continents, the use of EGDT versus usual care did not result in any difference in mortality at 90 days. EGDT was also associated with greater use of intensive care and cardiovascular support and treatment costs. Moreover, EGDT was not beneficial even in specific subgroups of more severely ill patients such as those with hyperlactatemia, hypotension with hyperlactatemia, or higher predicted risk of death.^[8]

A review of basic research and clinically relevant newer insights into the complex pathophysiology of circulatory system and transmembrane fluid shifts during acute illnesses may tender some explanations and may help us understand the consistent, counterintuitive results of harm from aggressive IV fluid resuscitation as shown in recent high-quality randomized clinical trials (RCTs) and meta-analyses.

Resuscitation Physiology

Classic model

Classic model of resuscitation physiology envisages (a) a circulatory system with "physical or mechanical plumbing" characteristics defined by forward and backward hydrostatic pressures, (b) the cardiac activity serving as the "motor" of the pump, (c) sympathetic activity, which may increase cardiac output and arterial and venous tones and pressures, and (d) compartment model of diffusion of fluids which presumes that only the capillaries and postcapillary venules permit transmembrane fluid flow.

These mechanisms were postulated to explain circulatory and fluid physiology in health and/or simplified deviations from healthy state. Clinical conditions meriting IV fluid resuscitation such as sepsis, burns, and trauma, however, have an exceedingly complex, dynamically changing circulatory, hemodynamic, endothelial, and neurohormonal pathophysiology.^[9]

Current Approaches to Resuscitation Physiology

Aggressive fluid resuscitation may have been predicated on the rather reductionist premise that hypotension in critical illnesses is a consequence of volume loss and that mechanically pumping large quantities of IV fluid on the venous side of the circulation may faithfully and incrementally be transformed into raised hydrostatic pressure and forward flow in the arterial circulation.

Robust RCTs in the past two decades have shown that this is not the case and a closer examination of certain key aspects of resuscitation physiology may illustrate the mechanisms of potential harm and lack of intended therapeutic gains of aggressive fluid therapy in resuscitation. A focused discussion of key aspects of resuscitation physiology specifically relevant to bolus IV fluid resuscitation is attempted below.

Venous system

The arterial system and the left side of the heart are usually the focus of deliberations in ischemic heart disease. Due to certain unique characteristics, however, the venous system acquires more significance in resuscitation physiology and critical illnesses. During resuscitation, for example, large quantities of fluids are directly injected into the venous system. Compliance of veins is 30-fold higher than arteries and the venous system accommodates 70% of the total blood volume as compared to only 18% in the arteries.^[10]

Unstressed volume, stressed volume

The blood volume which can be accommodated in the venous system without exerting any hydrostatic pressure is the unstressed volume. The volume of blood, over and above the unstressed volume, which stretches the veins and results in the emergence of positive hydrostatic pressure in the venous system is called the stressed volume.^[4]

Theoretically, when the heart is stopped (zero flow), the hydrostatic pressure exerted by the intravascular volume on the vasculature is called the mean circulatory filling pressure (MCFP).

Stressed volume in the venous system is the major contributor for the MCFP, which in turn is the major determinant of venous return. Venous return occurs when the MCFP, which normally is 8–10 mmHg, exceeds the CVP.^[4]

Circulatory hemodynamic effects of intravenous fluid boluses

Due to a large capacitance and a constant compliance, the venous system can accommodate large IV infusion volumes resulting in relatively small increases in MCFP. Conversely, due to restraining effects of the pericardium and the cardiac cytoskeleton, the diastolic compliance of both ventricles rapidly reduces with increasing distending volumes resulting in relatively large and rapid increases in the CVP.^[11]

Therefore, with bolus infusions, the CVP increases disproportionately faster than the MCFP, thereby reducing the gradient of blood flow from the venous system to the right atrium (the venous return).

The driving force for organ blood flow is the pressure difference between the mean arterial pressure and the CVP. Thus, a rapidly rising CVP (as might happen during IV bolus) not only reduces the gradient for venous return but also reduces forward blood flow through the organs.^[11]

CVP is the major determinant of capillary blood flow. The higher the CVP, the lesser the capillary flow.^[11]

Thus, we see that rapid infusion of fluid boluses may not improve circulatory hemodynamics and, on the contrary, may actually impede forward flow in the circulation and venous return.

Vasoplegia

A primary pathology in severe sepsis, septic shock, and critical illnesses is vasoplegia and not dehydration which may or may not be present as an epiphenomenon.^[12]

Vasoplegia leads to arterial dilatation resulting in systemic hypotension. More importantly, there is profound venodilation, especially in the splanchnic and cutaneous vascular beds.

There is no mechanism by which IV fluid infusion can improve vasoplegia. Bolus IV fluid infusions in the setting of profound vasoplegia can however rapidly increase the unstressed volume and CVP, thereby reducing venous return and cardiac output. Vasoplegia improves either with vasopressors or with spontaneous homeostasis over time.

Cardiac Physiology

Fluid administration will only result in increase of stroke volume (SV) when both of two conditions are met, namely (i) the fluid bolus increases the MCFP more than the CVP. We have seen in the preceding discussion that rapid fluid boluses are likely to raise the CVP more than the MCFP^[13] and (ii) both ventricles are functioning on the ascending limb of the Frank–Starling curve.

Sepsis-associated myocardial dysfunction tends to flatten the Frank–Starling curve. Up to 50% of patients with sepsis may have systolic dysfunction.^[14]

Furthermore, due to high prevalence of lifestyle diseases in the hospitalized population, left ventricular diastolic dysfunction is emerging as an important finding in patients with severe sepsis and septic shock.^[15] Patients with diastolic dysfunction respond very poorly to fluid loading. In such patients, fluid challenges will result in increased cardiac filling pressures, increased pulmonary and venous hydrostatic pressures, increased release of natriuretic peptides, with minimal, if any rise in SV.^[4],[16]

Endothelial and Microcirculatory Dysfunction

There is a marked endothelial dysfunction in sepsis characterized by increased expression and activation of endothelial adhesion molecules, resulting in increased adhesion and activation of leukocytes and platelets, and the net effect is marked leakiness and heterogeneous abnormalities in microcirculatory blood flow.^{[9],[17],[18],[19]}

Furthermore, aggressive fluid therapy leads to increased cardiac filling pressures which results in release of natriuretic peptides. Natriuretic peptides profoundly disrupt the glycocalyx structure and function, leading to increased vascular leakiness.^[18],[19] Increased natriuretic peptides also reduce lymphatic drainage by reducing lymphatic propulsive motor activity.^[20]

Fluid Responsiveness

A significant finding from fluid resuscitation studies over the years is that only 50% of the patients are fluid responders.

Here, three key concepts need to be emphasized.

1. There is no physiologic rationale for bolus IV fluid infusions in fluid nonresponders
2. Even in the fluid responders, once the optimal preload is achieved, any additional increase in preload does not result in any appreciable increase in SV and results in harm, in that, right atrial pressure (RAP) rapidly increases resulting in increased pulmonary and venous hydrostatic pressures, release of natriuretic peptides resulting in shift of fluid into the interstitial tissue causing pulmonary and tissue edema. In addition, due to sepsis-associated myocardial dysfunction, these adverse hemodynamic effects may appear at a lower fluid dose, even before the optimal preload is achieved^[20]
3. Disproportionately large fraction of the infused fluid will promptly leak out into the extravascular space. In healthy volunteers, of the infused volumes of crystalloids, only 15% remains in the intravascular space at 3 h. Due to endothelial disruption, in sepsis, less than 5% of a crystalloid bolus remains in the intravascular space at 1 h^[21]

Thus, the intended hemodynamic gains of IV fluid bolus, even in fluid responders, are short-lived, and most of the infused bolus will rapidly accumulate in the interstitial space leading to tissue edema.

Implications on Intravenous Fluid Therapeutics

It is obvious from the above discussion that aggressive, goal-directed IV fluid resuscitation algorithmized to meet externally decided static metrics such as CVP is fraught with pitfalls. It may be noted that while residents and house officers may have a liking for customized algorithms, these, as is the case of EGDT, have been proven to be harmful. Rather, under the following subheadings, we propose suggestions, based on the emerging evidence, on caution and discretion in the use of volumes and types of IV fluids in day-to-day settings with an aim to reduce harm arising from individual fluid prescriptions.

Dose of Fluid Therapy

Initial bolus

Ideally, the initial fluid bolus should aim to replace the extant volume lost and the anticipated ongoing losses in the next few hours.

Many conditions with hypotension, however, may not be fluid depleted states. In sepsis, the dominant physiology is of profound vasoplegia, vascular leakiness, and fluid redistribution, rather than dehydration, unless there are other associated causes of fluid loss such as fever and poor oral intake.

Till date, the best trial comparing the effects of IV fluid boluses with no boluses in critical illness is the landmark Fluid Expansion as Supportive Therapy trial (FEAST). In this multicenter RCT involving 3141 children with severe sepsis and demonstrated evidence of fluid depletion, any fluid boluses, when compared to no fluid bolus, were strongly associated with higher mortality and morbidity. The statistical significance was of such magnitude that the trial had to be stopped on ethical grounds.^[22] These findings are congruent with other high-quality clinical research in fluid therapeutics emerging over the past decade.^{[5],[6],[7],[8]}

The fact that, in the FEAST trial subjects, even in patients with proven volume depletion, IV fluid boluses, when compared to no bolus resulted in higher mortality, should compel us to revisit the widely held premise that IV fluid therapy is a central pillar of management of critical illnesses.^[4]

Considering the above, a reasonable approach may be using a therapeutic trial of a small bolus, approximately 250–500 mL of a crystalloid, in the setting of systolic hypotension and oliguria. If the blood pressure does not respond, consideration should be given for addressing possible concomitant vasoplegia with vasopressors. If the initial bolus has failed, repeat "fluid challenges" have no role and may prove counterproductive.^[4],[23]

Maintenance fluids

After initial fluid resuscitation, a subset of patients, especially those who have poor oral intake, may need maintenance fluids, with an aim to preserving the extracellular volume while maintaining a normal electrolyte balance.

However, in actual practice, maintenance fluids are often routinely prescribed. Some of these patients may have already received a large positive balance in the acute resuscitation period. Subjecting them to further daily prescriptions of maintenance fluids without compelling indications may lead to a large cumulative fluid balance over several days.^[24],[25]

In a high-quality, prospective RCT, conservative late fluid management was associated with lesser morbidity and mortality as compared to liberal fluid policy.^[26]

Maintenance fluids should only be prescribed if there are clear indications. Maintenance fluids should be actively stopped if there is no compelling indication for ongoing fluid administration. The quantity of maintenance fluids should be estimated individually in each patient with an emphasis on frequent audits of cumulative fluid balance since admission, aiming to avoid positive balance.^[1],[26]

Type of Fluid Therapy

The composition of IV fluids may have a bearing on context-specific outcomes, especially related to potential harm. Different types of IV fluids should be prescribed after factoring in patient-specific and context-specific differences.^[1],[23]

Colloids

The findings of the landmark saline versus albumin fluid evaluation (SAFE) and FEAST studies assuaged concerns about safety of albumin raised in a Cochrane review. However, the data did not reveal any significant advantage of albumin over saline, thereby challenging long-held concepts about the advantages of albumin as a resuscitation solution.^[27],[28]

In volume-depleted states requiring resuscitation, it appears that albumin, which is more expensive and less easily available, offers no distinct advantages over saline in patient-centered outcomes.

Semisynthetic colloids

A range of semisynthetic colloids including HES solutions, succinylated gelatin, and dextran solutions were developed to offset the constraints of cost and availability of albumin. However, research has revealed clinically relevant safety concerns with the use of semi-synthetic colloids.^{[29],[30],[31]}

In view of the lack of clinical benefit, evidence of potential nephrotoxicity, decreased availability, and higher costs, the inclusion of semisynthetic colloids in fluid resuscitation protocols in critically ill patients is questionable.

Crystalloids

Normal saline

Worldwide, sodium chloride (normal saline) is the most commonly used crystalloid solution.

Due to the strong ion difference of 0.9% saline being zero, administration of large quantities of normal saline leads to hyperchloremic metabolic acidosis.

The hyperchloremic metabolic acidosis related to large volume bolus infusion of normal saline may lead to immune and renal dysfunction, including reduced renal blood flow, electrolyte disturbances, acute kidney injury, renal replacement therapy utilization, postoperative infections, acidosis investigations, and costs.^[32],[33]

Hence, normal saline should not be the first choice of IV fluid in most critical illnesses necessitating IV fluid resuscitation. Normal saline may be an appropriate choice in conditions associated with alkalosis such as dehydration resulting from protracted emesis. To avoid the potential hypotonicity associated with balanced solutions, normal saline may be the preferred choice among maintenance fluids.^[23]

Balanced solutions

Crystalloids designed to have a pH and chemical composition similar to extracellular fluid are called "balanced" or "physiologic" solutions. The most widely used of such solutions are Hartmann's and Ringer's solutions and their derivatives. However, none of these solutions achieve the true composition of extracellular fluid.

Due to a sodium concentration lower than the extracellular fluid, balanced solutions are hypotonic. To offset the instability of bicarbonate-containing balanced solutions in plastic containers, other anions, such as lactate, acetate, gluconate, and malate are used.

Administration of large quantities of balanced solutions may theoretically lead to hyperlactatemia, metabolic alkalosis, and hypotonicity (with compounded sodium lactate) and cardiotoxicity (with acetate). The calcium contained in some balanced solutions may lead to production of microthrombi when co-administered with citrate-containing red-cell transfusions.^[23]

However, when tested in a wide spectrum of clinical settings, among all IV fluids, balanced solutions have shown the best safety profile including burns, diabetic ketoacidosis, and trauma and patients undergoing surgery.^{[34],[35],[36],[37]}

Conclusions

The physiology of sepsis and other similar critical illnesses is dynamically dysfunctional and dominated by marked vascular leakiness, myocardial depression, and profound vasoplegia. Most of the injected IV fluid rapidly leaks into the interstitial compartment, even in healthy individuals, and more promptly and profoundly so in critically ill patients.

The findings of FEAST, ProMISe, ProCESS, ARISE, PRISM, and CHEST are particularly important because they reveal potential harm or lack of benefit of widely practiced and advocated aggressive fluid resuscitation policies such as espoused in the EGDT protocol. The evidence is relatively robust, congruent across various studies, and in line with newer understanding of the complex, biologically dynamic physiology of acute illnesses.

These vital findings of high-quality clinical research emerging in the preceding two decades represent a paradigm change in our understanding of fluid therapeutics and critical illness physiology. This paradigm shift should be discussed widely so that the newly recognized potential harms related to the extant practice of algorithmized aggressive fluid resuscitation may be mitigated and patients may benefit with a more informed and judicious use of IV fluids in sepsis and critical illnesses.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

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