Pathological characteristics of a series of rare chronic histiocytic intervillositis of the placenta

Chronic histiocytic intervillositis of the placenta (CHI) is a rare and poorly understood pathology which may occur in all trimesters. The most conspicuous feature is a histiocytic infiltration of the intervillous space without involvement of the villous parenchyma. In this report on CHI, we re-evaluate a series of four cases and focus on histological, immunohistological and fluorescence in situ hybridisation-derived findings, fetal status and clinical data for previously unrecognised CHI-associated features. Our approach revealed that assisted reproduction-induced pregnancy had been performed in 2 of 4 CHI cases, but other factors and comorbidities are likely to contribute to CHI.     

Hyperpyrexia as the Presenting Symptom of Intracranial Hypotension

Introduction

Hyperpyrexia is a severely elevated core body temperature secondary to an elevated hypothalamic set thermo-regulatory threshold. Hyperthermia is an elevated core body temperature beyond the normal hypothalamic set thermo-regulatory threshold. Intracranial hypotension can present with a wide variety of symptoms ranging from orthostatic headache up to coma. We report a rare case of hyperpyrexia associated with intracranial hypotension.

Methods

A case report of a 55-year-old female patient with a history of angiogram-negative subarachnoid hemorrhage status post-ventriculoperitoneal (VP) shunt placement six years prior to admission who suddenly developed encephalopathy and high fever. Conventional management of the fever was unsuccessful.

Results and Management

Brain magnetic resonance imaging revealed signs of significant intracranial hypotension. When the VP shunt was tapped, no cerebrospinal fluid (CSF) could be obtained. Once the VP shunt settings were adjusted, the patient’s encephalopathy and hyperpyrexia resolved.

Conclusion

Hyperpyrexia might be a presenting symptom of intracranial hypotension, likely, secondary to hypothalamic dysfunction and compression. In our case, hyperpyrexia was reversible as the intracranial hypotension was emergently treated. Spontaneous intracranial hypotension might be difficult to diagnose, especially if it presented with non-classical symptoms like fever; thus, physicians should be aware of such association.

     

Functional glutamate transport in rodent optic nerve axons and glia

Recent findings suggest that synaptic-type glutamate signaling operates between axons and their supporting glial cells. Glutamate reuptake will be a necessary component of such a system. Evidence for glutamate-mediated damage of oligodendroglia somata and processes in white matter suggests that glutamate regulation in white matter structures is also of clinical importance. The expression of glutamate transporters was examined in postnatal Day 14-17 (P14-17) mouse and in mature mouse and rat optic nerve using immuno-histochemistry and immuno-electron microscopy. EAAC1 was the major glutamate transporter detected in oligodendroglia cell membranes in both developing and mature optic nerve, while GLT-1 was the most heavily expressed transporter in the membranes of astrocytes. Both EAAC1 and GLAST were also seen in adult astrocytes, but there was little membrane expression of either at P14-17. GLAST, EAAC1, and GLT-1 were expressed in P14-17 axons with marked GLT-1 expression in the axolemma, while in mature axons EAAC1 was abundant at the node of Ranvier. Functional glutamate transport was probed in P14-17 mouse optic nerve revealing Na+-dependent, TBOA-blockable uptake of D-aspartate in astrocytes, axons, and oligodendrocytes. The data show that in addition to oligodendroglia and astrocytes, axons represent a potential source for extracellular glutamate in white matter during ischaemic conditions, and have the capacity for Na(+)-dependent glutamate uptake. The findings support the possibility of functional synaptic-type glutamate release from central axons, an event that will require axonal glutamate reuptake.     

Synthesis of some novel quinoline-3-carboxylic acids and pyrimidoquinoline derivatives as potential antimicrobial agents

The synthesis and in vitro antimicrobial evaluation of several quinoline and pyrimidoquinoline derivatives are described. Treatment of 7-substituted quinolin-2(1H)-one-3-carboxylic acids 2a-c with phosphoryl chloride or thionyl chloride gave rise to the 7-substituted 2-chloroquinoline-3-carboxylic acids 3a-c and 7-substituted 2-chloro-3-chlorocarbonylquinolines 5a-c respectively. The 2-chloro function in compounds 3a-c was replaced by 2-aminothiazole or 2-aminopyridine to give 2-(thiazol-2-yl)aminoquinoline-3-carboxylic acids 4a-c or 2-(pyrid-2-yl)aminoquinoline-3-carboxylic acids 4d-f. Treatment of 5a-c with the same heterocyclic amines at room temperature furnished the corresponding 7-substituted 2-chloro-3-heteryl-aminocarbonylquinolines 6a-f. The tetracyclic 9-substituted thiazolo[3', 2':1, 2]-pyrimido[4, 5-b]quinolin-5-ones 7a-c and 10-substituted pyrido[1', 2':1, 2]-pyrimido[4, 5-b]quinolin-6-ones 7d-f were synthesized by heating 5a-c with the heterocyclic amines in toluene or by heating 6a-f under reflux in dimethylformamide. The products were evaluated in vitro for potential antimicrobial activity.     

Pharmacokinetics of high-dose buprenorphine following single administration of sublingual tablet formulations in opioid naïve healthy male volunteers under a naltrexone block

Sublingual buprenorphine formulations have been developed as treatments for opioid dependence. In three studies, opioid na?ve healthy male subjects received Subutex tablets (buprenorphine 2 and 8 mg [N=27] or 12 and 16 mg [N=27]) or Suboxone (two formulations) tablets (buprenorphine 8 mg/naloxone 2 mg [N=36]) sublingually, under a naltrexone block for assessment of buprenorphine pharmacokinetics and tablet disintegration times. Plasma buprenorphine was quantified up to 72 h post-dose using a sensitive LC-MS/MS assay. Mean Cmax values ranged from 1.6 to 6.4 ng/ml and tmax from 0.5 to 3 h. Concentrations declined bi-exponentially and fluctuations after a meal suggested enterohepatic recirculation of buprenorphine. The terminal half-life was approximately 26 h (range 9-69). Cmax and AUC appeared to increase in proportion to Subutex dose over 8-16 mg. The Suboxone formulations were bioequivalent. The least squares mean (90% CI) treatment ratio for Cmax was 1.00 (0.92-1.10) and AUC was 1.00 (0.95-1.06). Median times of disintegration were similar for all doses and formulations (range 6-12 min). Sublingual buprenorphine, up to 40 times the 400 microg analgesic dose, was well tolerated in these opioid na?ve subjects, as administration of naltrexone 50-150 mg was sufficient to attenuate anticipated adverse effects in this population of subjects.     

Toxicity, metabolism, and impact of mycotoxins on humans and animals

The worldwide contamination of foods and feeds with mycotoxins is a significant problem. Mycotoxins are secondary metabolites of molds that have adverse effects on humans, animals, and crops that result in illnesses and economic losses. Aflatoxins, ochratoxins, trichothecenes, zearelenone, fumonisins, tremorgenic toxins, and ergot alkaloids are the mycotoxins of greatest agro-economic importance. Some molds are capable of producing more than one mycotoxin and some mycotoxins are produced by more than one fungal species. Often more than one mycotoxin is found on a contaminated substrate. Factors influencing the presence of mycotoxins in foods or feeds include environmental conditions related to storage that can be controlled. Other extrinsic factors such as climate or intrinsic factors such as fungal strain specificity, strain variation, and instability of toxigenic properties are more difficult to control. Mycotoxins have various acute and chronic effects on humans and animals (especially monogastrics) depending on species and susceptibility of an animal within a species. Ruminants have, however, generally been more resistant to the adverse effects of mycotoxins. This is because the rumen microbiota is capable of degrading mycotoxins. The economic impact of mycotoxins include loss of human and animal life, increased health care and veterinary care costs, reduced livestock production, disposal of contaminated foods and feeds, and investment in research and applications to reduce severity of the mycotoxin problem. Although efforts have continued internationally to set guidelines to control mycotoxins, practical measures have not been adequately implemented.     

Electrocardiographic markers of increased risk of sudden cardiac death in patients with COVID‐19 pneumonia

BackgroundLittle is known about the role of ECG markers of increased risk of sudden cardiac death during the acute period of coronavirus disease 2019 ( COVID‐19) pneumonia.ObjectivesTo evaluate ECG markers of sudden cardiac death on admission, including the index of cardiac electrophysiological balance (iCEB) (QTc/QRS) and transmural dispersion of repolarization (TDR) (T from peak to end (Tp‐e) interval and Tp‐e/QTc), in patients with COVID‐19 pneumonia.Patients and methodsThis cross‐sectional study included 63 patients with newly diagnosed COVID‐19 pneumonia who presented to the outpatient clinic or admitted to the respiratory care unit between August 20 and September 15, 2020. Forty‐six persons matched for sex and age were selected from data collected before COVID‐19 pandemic.ResultsQRS and QTc showed a significant prolongation in patients with COVID‐19 pneumonia compared to the controls (87 vs. 78, p < .00, and 429 versus. 400, p < .00, respectively). After categorization of patients with COVID‐19 pneumonia into 3 groups according to the severity of pneumonia as mild‐moderate, severe, and critical groups, a decreased values of QRS were observed in the critical COVID‐19 pneumonia group compared to severe and mild‐moderate COVID‐19 pneumonia groups (p = .04) while increased values of QTc and iCEB(QTc/QRS) were noted in critical COVID‐19 pneumonia group compared to other 2 groups(p < .00).ConclusionsPatients with COVID‐19 pneumonia showed significant changes in repolarization and conduction parameters compared to controls. Patients with mild to severe COVID‐19 pneumonia may be at low risk for torsades de pointes development.     

Relative risk of acute pancreatitis in initiators of exenatide twice daily compared with other anti‐diabetic medication: a follow‐up study

Aims Previously, a retrospective cohort study found no increased risk of acute pancreatitis with current or recent use of exenatide twice daily compared with use of other anti‐diabetic drugs. This follow‐up study investigated incident acute pancreatitis, with the use of a different data source and analytic method, in patients exposed to exenatide twice daily compared with patients exposed to other anti‐diabetic medications. Methods A large US health insurance claims database was used. Eligible patients had ≥ 9 months continuous enrollment without a claim for pancreatitis and a claim for a new anti‐diabetic medication on or after 1 June 2005 to 31 March 2009. Cases of acute pancreatitis were defined as hospitalized patients with an Internation Classification of Disease 9 code of 577.0 in the primary position. A discrete time survival model was used to evaluate the relationship between exenatide twice daily and acute pancreatitis. Results Of 482 034 eligible patients, 24 237 initiated exenatide twice daily and 457 797 initiated another anti‐diabetic medication. Initiators of exenatide twice daily had more severe diabetes compared with initiators of other anti‐diabetic medications. After adjustments for propensity score, insulin and use of medication potentially associated with acute pancreatitis, the odds ratio with exenatide twice daily exposure was 0.95 (95% CI 0.65–1.38). A secondary analysis that examined current, recent and past medication exposure found no increased risk of acute pancreatitis with exenatide twice daily, regardless of exposure category. Conclusion This study indicates that exposure to exenatide twice daily was not associated with an increased risk of acute pancreatitis compared with exposure to other anti‐diabetic medications. These results should be interpreted in light of potential residual confounding and unknown biases.     

Predictive accuracy of serum hyaluronic acid as a non-invasive marker of fibrosis in a cohort of multi-transfused Egyptian children with β-thalassaemia major

Background and study aimLiver disease remains a major cause of morbidity and mortality in patients with β-thalassaemia major (β-TM); therefore, its identification at an early stage is of great significance. Serum hyaluronic acid (HA) is considered as a non-invasive marker that appears early before pathological changes occur. We aim to determine the predictive accuracy of HA in detecting and staging hepatic fibrosis in β-TM patients.Patients and methods30 Egyptian children with β-TM, and 15 age and sex-matched controls were studied. All had abdominal ultrasonography (US), measurement of serum amino-transferases (ALT, AST); hepatitis C, B and human immunodeficiency viruses (HCV, HBV, HIV) sero-markers, serum ferritin and HA. Liver biopsy was done for patients and fibrosis was scaled using Metavir scoring system and liver iron concentration (LIC) was measured.ResultsTwenty patients (67.7%) had sero-markers of HCV, none had HBV or HIV. Serum HA was significantly higher in patients (90.78 ± 28.79 ng/ml) compared to controls (21.1 ± 13.24 ng/ml) with p < 0.05. No difference between HCV infected and non-infected patients was detected. Positive significant correlation was detected between serum HA and stages of fibrosis by histopathology and US. No correlation was found between serum HA and age, sex, weight, height, haemoglobin level, platelet count, AST, serum ferritin, necro-inflammatory grade, and LIC.ConclusionsSerum HA is a valuable non-invasive marker that may contribute to the assessment of liver fibrosis in multi-transfused children and adolescents with β-TM, irrespective of concomitant HCV infection.