Exaggerated blood pressure response to dynamic exercise despite chronic refractory hypotension: results of a human case study.

BACKGROUND: Chronic refractory hypotension is a rare but significant mortality risk in renal failure patients. Such aberrant physiology usually deems patient unfit for renal transplant surgery. Exercise stimulates the mechano-chemoreceptors in the skeletal muscle thereby modulating the sympathetic effects on blood pressure regulation. The haemodynamic response to dynamic exercise in such patients has not been previously investigated. We present a case with severe chronic hypotension who underwent exercise testing before and after renal transplantation, with marked differences in blood pressure response to exercise. CASE PRESENTATION: A 40-year old haemodialysis-dependent patient with a 2 year history of refractory hypotension (≤80/50 mmHg) was referred for living donor renal transplantation at our tertiary centre. Each dialysis session was often less than 2 h and 30 min due to symptomatic hypotension. As part of the cardiovascular assessment, she underwent haemodynamic evaluation with cardiopulmonary exercise testing. Blood pressure normalized during unloaded pedalling but was exaggerated at maximal workload whereby it rose from 82/50 mmHg to a peak of 201/120 mmHg. Transthoracic echocardiography, tonometric measure of central vascular compliance and myocardial perfusion scan were normal. She subsequently underwent an antibody-incompatible renal transplantation and was vasopressor reliant for 14 days during the post-operative period. Eight weeks following transplant, resting blood pressure was normal and a physiological exercise-haemodynamic response was observed during a repeat cardiopulmonary exercise testing. CONCLUSION: This case highlights the potential therapeutic role of unloaded leg cycling exercise during dialysis session to correct chronic hypotension, allowing patients to have greater tolerance to fluid shift. It also adds to existing evidence that sympathetic dysfunction is reversible with renal transplant. Furthermore chronic hypotension with preserved exercise-haemodynamic response and cardiovascular reserve should not preclude these patients from renal transplant surgery.

Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

BACKGROUND: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. METHODS: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. RESULTS: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. CONCLUSIONS: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.

Four Social Brain Regions, Their Dysfunctions, and Sequelae, Extensively Explain Autism Spectrum Disorder Symptomatology.

Autism spectrum disorder (ASD) is a challenging neurodevelopmental disorder with symptoms in social, language, sensory, motor, cognitive, emotional, repetitive behavior, and self-sufficient living domains. The important research question examined is the elucidation of the pathogenic neurocircuitry that underlies ASD symptomatology in all its richness and heterogeneity. The presented model builds on earlier social brain research, and hypothesizes that four social brain regions largely drive ASD symptomatology: amygdala, orbitofrontal cortex (OFC), temporoparietal cortex (TPC), and insula. The amygdala's contributions to ASD largely derive from its major involvement in fine-grained intangible knowledge representations and high-level guidance of gaze. In addition, disrupted brain regions can drive disturbance of strongly interconnected brain regions to produce further symptoms. These and related effects are proposed to underlie abnormalities of the visual cortex, inferior frontal gyrus (IFG), caudate nucleus, and hippocampus as well as associated symptoms. The model is supported by neuroimaging, neuropsychological, neuroanatomical, cellular, physiological, and behavioral evidence. Collectively, the model proposes a novel, parsimonious, and empirically testable account of the pathogenic neurocircuitry of ASD, an extensive account of its symptomatology, a novel physiological biomarker with potential for earlier diagnosis, and novel experiments to further elucidate the mechanisms of brain abnormalities and symptomatology in ASD.

Effects of time and concentration of sodium ascorbate on reversal of NaOCl-induced reduction in bond strengths.

The use of NaOCl as an endodontic irrigant lowers the bond strength of resin cements but this can be reversed by the use of 10% sodium ascorbate for 10 min. The objective of this study was to evaluate the effect of time and concentration of ascorbate at restoring the bond strength. Group 1 roots were prepared using 0.9% NaCl as an irrigant; group 2 roots were irrigated with 5.25% NaOCl; group 3 roots were irrigated with 5.25% NaOCl followed by 10% ascorbate for 10 min; group 4 roots were irrigated with 5.25% NaOCl followed by 10% ascorbate for 3 min; group 5 roots were irrigated with 5.25% NaOCl followed by 10% ascorbate for 1 min; and group 6 roots were irrigated with 5.25% NaOCl followed by 20% ascorbate for 1 min. All roots were then filled with C&B Metabond, stored 1 day in water, and then cross-sectioned into 6 slabs, 1 mm thick, that were trimmed and tested for tensile bond strength. The results demonstrated that 5.25% NaOCl irrigation produced (p < 0.05) significant reduction in resin-dentin bond strengths, but this can be reversed by 10% ascorbate treatment for 1 min.

Posttraumatic stress disorder: a theoretical model of the hyperarousal subtype.

Posttraumatic stress disorder (PTSD) is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper) is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms) is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC), and medial orbitofrontal cortex (mOFC), to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framework.

An unusual presentation of atrial myxoma with haematuria and proteinuria.

Myxomas are uncommon primary cardiac tumours, usually affecting the left atrium. We describe an unusual presentation of cardiac myxoma with asymptomatic proteinuria and haematuria. Surgical excision of the tumour resulted in complete resolution of the urinary abnormalities. The production of antiendothelial cell antibodies and interleukin-6 by cardiac myxomas may be relevant as these substances have been implicated with the development of renal injury and proteinuria.

Comparison of preparation design and material thickness on microbial leakage through Cavit using a tooth model system.

Few studies have compared Cavit thickness and access design as factors in microbial leakage. The present study used an acrylic tooth model to measure leakage of Streptococcus mutans. Pilot studies confirming the sterility of Cavit showed it will inhibit microbial growth for 2 days. The experiments compared class I preparations where Cavit thickness was 4 mm with class II preparations where thickness was 2-3 mm. Accesses sealed with cotton pellets were compared with those without cotton. Results of the study showed no bacterial contamination in any of the class I samples (up to 14 days). Some class II samples showed contamination at day 1 (3 out of 14), with all contaminated at day 7 (14 of 14), yet only 1 contaminated at day 14 (1 out of 14). The results suggest that a 4-mm thickness of Cavit should prevent bacterial ingress for at least 2 weeks, but microbial leakage may occur if temporary thickness is less than 3 mm or in a complex access preparation.

Effects of EGF and IGF-1 on proliferation of cultured human proximal tubule cells after oxidant stress.

BACKGROUND: Both insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) stimulate proliferation of various renal tubule epithelial cells in culture including proximal tubule cells. In some epithelial cells, the effects of EGF and IGF-1 are additive or synergistic. The effects of EGF and IGF-1 in cultured tubule epithelial cells following injury are limited. METHODS: Immortalized human proximal tubules cultured in serum-free defined medium were exposed to 0.3-1.5 mM peroxide for 1 h then washed and growth factors were added. ATP was measured by chemiluminescence, proliferation by [3H]thymidine uptake, and receptor expression by flow cytometry. RESULTS: Immediately after 1.5 mM peroxide exposure, ATP levels were depressed to as low as approximately 15% of normal but had recovered to near normal levels by 4 h. Proliferation was depressed in a dose-dependent manner by peroxide. At the lowest doses of peroxide both EGF (20 ng/mL) and IGF-1 (390 ng/mL) stimulated proliferation. As the concentration of peroxide increased, EGF lost its ability to stimulate proliferation and in fact antagonized IGF-1 which when added alone remained effective at stimulating proliferation even at the highest levels of peroxide exposure. EGF and peroxide depressed EGF receptor expression but there were no changes in IGF-1 receptor expression with any maneuver. CONCLUSION: The effects of EGF to antagonize IGF-1 are distal to IGF-1 receptor expression. The effects of these growth factors under control conditions do no translate to effects after injury.