Citations

AbstractPrevious studies indicate that moderate‐to‐high ethanol (EtOH) concentrations enhance dopamine (DA) neurotransmission in the mesolimbic DA system from the ventral tegmental area (VTA) and projecting to the nucleus accumbens core (NAc). However, voltammetry studies demonstrate that moderate‐to‐high EtOH concentrations decrease evoked DA release at NAc terminals. The involvement of γ‐aminobutyric acid (GABA) receptors (GABAARs), glycine (GLY) receptors (GLYRs) and cholinergic interneurons (CINs) in mediating EtOH inhibition of evoked NAc DA release were examined. Fast scan cyclic voltammetry, electrophysiology, optogenetics and immunohistochemistry techniques were used to evaluate the effects of acute and chronic EtOH exposure on DA release and CIN activity in C57/BL6, CD‐1, transgenic mice and δ‐subunit knockout (KO) mice (δ−/−). Ethanol decreased DA release in mice with an IC50 of 80 mM ex vivo and 2.0 g/kg in vivo. GABA and GLY decreased evoked DA release at 1–10 mM. Typical GABAAR agonists inhibited DA release at high concentrations. Typical GABAAR antagonists had minimal effects on EtOH inhibition of evoked DA release. However, EtOH inhibition of DA release was blocked by the α4β3δ GABAAR antagonist Ro15‐4513, the GLYR antagonist strychnine and by the GABA ρ1 (Rho‐1) antagonist TPMPA (10 μM) and reduced significantly in GABAAR δ−/− mice. Rho‐1 expression was observed in CINs. Ethanol inhibited GABAergic synaptic input to CINs from the VTA and enhanced firing rate, both of which were blocked by TPMPA. Results herein suggest that EtOH inhibition of DA release in the NAc is modulated by GLYRs and atypical GABAARs on CINs containing δ‐ and Rho‐subunits.

Objectives We analyzed growth rates of benign ovarian serous cystadenomas and cystadenofibromas to understand what percentage would show a volume doubling time (DT) of less than 3 years, between 3 and 5 years, or greater than 5 years. Methods We retrospectively reviewed pathology records (January 1, 2014, to June 30, 2019) to find all surgically excised ovarian serous cystadenomas and cystadenofibromas. Imaging records were then reviewed to identify those that had been confidently identified with ultrasound imaging, magnetic resonance imaging, or computed tomography at least twice before surgical removal, with at least a 60‐day interval between studies. Three orthogonal measurements were recorded on the first and last imaging studies on which the mass was detected, with volume calculations by the prolate formula (product of 3 measurements multiplied by 0.52). The volume DT was calculated and grouped into 1 of 5 categories: (1) DT of less than 1 year; (2) DT of 1 to 3 years; (3) DT of 3 to 5 years; (4) DT of 5 to 10 years; and (5) no growth (any mass with a DT >10 years or showing a decrease in volume). Results A total of 102 of 536 cystadenomas and 44 of 227 cystadenofibromas met inclusion criteria. Of the 146 tumors, 40 (27.4%) had a DT of less than 1 year; 38 (26.0%) had a DT of 1 to 3 years; 22 (15.1%) had a DT of 3 to 5 years; 10 (6.8%) had a DT of 5 to 10 years; and 36 (24.7%) showed no growth. Conclusions A total of 53.4% of ovarian serous cystadenomas/cystadenofibromas have a DT of less than 3 years; 15.1% have a DT between 3 and 5 years; and 31.5% have a DT of greater than 5 years or show no growth.

Parkinson’s disease is associated with degeneration of neuromelanin (NM)-containing substantia nigra dopamine (DA) neurons and subsequent decreases in striatal DA transmission. Dopamine spontaneously forms a melanin through a process called melanogenesis. The present study examines conditions that promote/prevent DA melanogenesis. The kinetics, intermediates, and products of DA conversion to melanin in vitro, and DA melanogenesis under varying levels of Fe3+, pro-oxidants, and antioxidants were examined. The rate of melanogenesis for DA was substantially greater than related catecholamines norepinephrine and epinephrine and their precursor amino acids tyrosine and l-Dopa as measured by UV-IR spectrophotometry. Dopamine melanogenesis was concentration dependent on the pro-oxidant species and Fe3+. Melanogenesis was enhanced by the pro-oxidant hydrogen peroxide (EC50 = 500 μM) and decreased by the antioxidants ascorbate (IC50 = 10 μM) and glutathione (GSH; IC50 = 5 μM). Spectrophotometric results were corroborated by tuning a fast-scan cyclic voltammetry system to monitor DA melanogenesis. Evoked DA release in striatal brain slices resulted in NM formation that was prevented by GSH. These findings suggest that DA melanogenesis occurs spontaneously under physiologically-relevant conditions of oxidative stress and that NM may act as a marker of past exposure to oxidative stress.

ObjectivesTo determine whether renal transplant diagnoses substantially change when 2 biopsy sites are chosen and whether contrast‐enhanced ultrasound (CEUS) has value for targeting the second site.MethodsWe prospectively enrolled 40 patients undergoing ultrasound‐guided renal transplant biopsy within 2 years of transplant: 20, surveillance; and 20, for cause. A CEUS examination was performed to identify cortical regions with subjectively altered flow. One biopsy was performed at the operator‐preferred (primary) site regardless of CEUS findings. Another biopsy was done at a second location, either targeted to an area in which CEUS perfusion findings differed from the primary site (targeted) or at a random location (secondary) if no other area differed. Specimens were randomly labeled A or B; pathologists were blinded to the CEUS result and biopsy location. Location‐specific CEUS assessments were recorded. Pathologic results were compared, including acute and chronic Banff scores and any new findings from the targeted or secondary biopsy.ResultsForty patients were enrolled between January 2016 and December 2018. No location‐specific pathologic differences correlated with differences in CEUS assessments. The second biopsy provided additional information that changed management in 4 of 40 patients (10.0% [95% confidence interval, 2.8%–23.7%]). Major bleeding complications occurred in 3 of 40 (7.5%) patients.ConclusionsContrast‐enhanced ultrasound targeting was not useful. Major bleeding complications were higher than expected, possibly due to the additional biopsy away from the operator‐preferred location. Obtaining a second renal transplant biopsy from a substantially different area than the initial operator‐preferred location provided additional clinically useful information in 10% of patients.

ObjectivesThe study aim was to evaluate the diagnostic performance of the uterine sliding sign in predicting deeply infiltrating endometriosis in the setting of non‐physician sonographers performing but not interpreting the maneuver. The impact of uterine sliding sign has not been previously demonstrated in this practice setting.MethodsPhysicians' remote interpretations of transvaginal ultrasound examinations in 2016, before uterine sliding sign, were compared to examinations in 2019 after addition of uterine sliding sign to determine the diagnostic rates. Surgical and histopathological results were reviewed to determine sensitivity and specificity of the respective exam techniques.ResultsTwo hundred eighty‐five transvaginal ultrasounds were performed in 2016 and 390 sliding sign ultrasounds in 2019. The number of deeply infiltrating endometriosis cases identified increased significantly from 2% to 6% during the study period (chi‐square, Fisher's exact test p = .012). The sensitivity and specificity of routine pelvic sonography for detecting deeply infiltrating endometriosis improved from 36%/94% to 68%/98%.ConclusionsUterine sliding sign videos should be included in the standard sonographic protocol for patients presenting with chronic pelvic pain, endometriosis history, or sonographic evidence of endometriosis in the setting of physicians interpreting sonographic images obtained by non‐physicians.

Intraoperative Transesophageal Echocardiography (TEE) during orthotopic liver transplant (OLT) is used to gather real-time information on cardiovascular function and intravascular volume status. We report a case where nonstandard TEE views were used to inspect the hepatic vasculature after allograft implantation. A 29-year-old male with secondary biliary cirrhosis with a MELD score of 20 underwent OLT using a liver from a 21-year-old brain-dead donor. Postreperfusion TEE, using the modified hepatic vein views, confirmed the presence of an inferior vena cava (IVC) suprahepatic anastomotic stenosis and hepatic vein and IVC thrombus resulting in hepatic venous outflow obstruction, allograft congestion, and hemodynamic instability. These nonstandard TEE images established the extent of suprahepatic caval outflow obstruction, in which intraoperative ultrasound was unable to definitively demonstrate. This guided real-time surgical decision-making in the postimplantation phase of the operation—ultimately leading to hepatic vein and IVC thrombectomy and revision of suprahepatic caval anastomosis.