Diastolic Function Study with Conventional and Pulsed Tissue Doppler Echocardiography Imaging in Acromegalic Patients

Acromegaly is associated with myocardial hypertrophy and it can progress to diastolic and systolic dysfunction. Purpose: To evaluate diastolic function in acromegalic patients through conventional echocardiography (CD) and tissue Doppler imaging (TDI). Methods: Seventeen acromegalic patients were submitted to CD and TDI, and early (E) and atriogenic (A) transmitral flow were evaluated in mitral, septal, and tricuspid regions. Results: In comparison with controls the means of conventional (1.06), septal (1.01), and tricuspid (0.98) E/A ratio were significantly lower in acromegalic patients. E/A ratio <1.0 was demonstrated in 41% and 49% of acromegalics by DC and TDI, respectively, with no statistical difference among the two methods. An inverse linear correlation was shown between mitral E/A ratio and acromegalic age (r =−0.7). Conclusion: In this study, DC and TDI were equally effective in demonstrating diastolic dysfunction, a common finding in acromegalic patients.     

Sleep-associated movement disorders and heart failure

Sleep-associated movement disorders are a broad group of sleep disorders characterized by involuntary movements that may disrupt sleep. Relatively little is known about the clinical consequences of sleep-associated movement disorders on cardiovascular health. Because these disorders manifest mostly during sleep, recognizing a movement disorder can be particularly difficult. Nevertheless, patients can have frequent arousals and suffer from similar sleep deprivation, fragmentation, and autonomic disruption as occurs in sleep-disordered breathing. Subsequently, these disorders may have a serious impact on daytime function and perception of health in patients with chronic heart failure.     

The natural progression of kidney injury in young type 1 diabetic patients

Diabetes is the most common cause of end-stage renal disease in industrialized countries. This article describes the structural changes in early diabetic nephropathy and the relationship with renal functional parameters, blood pressure, and albumin excretion. The detrimental influence of sustained hyperglycemia and/or glycemic fluctuations on renal structural change has been well documented. Tight glycemic control is paramount to preventing the development, and even the regression, of renal lesions. As much of the renal injury from diabetes occurs in clinical silence before symptoms or laboratory findings of renal injury are evident, finding early markers of risk is imperative so that nephropathy can be prevented. Currently, the only clinical surrogate marker of diabetic renal injury available is microalbuminuria. However, given the reports of regression of microalbuminuria back to normoalbuminuria, the reliability of this tool as an indicator of risk has been questioned. The need for alternative, noninvasive surrogate markers is described in this report.     

Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell–mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR–HLA-B*4405^EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.     

The Patient with Atrial Fibrillation

Atrial fibrillation is a frequently encountered arrhythmia, particularly affecting the elderly. Patients at significant risk for stroke should be considered for anticoagulation with warfarin. Management of atrial fibrillation revolves around either controlling the ventricular rate response or trying to maintain sinus rhythm with either pharmacologic or nonpharmacologic therapies. There are many treatment options to consider, based upon the patient's expectations, symptoms, and comorbid conditions. Therefore, the treatment of atrial fibrillation must be individualized.     

Oral Lichenoid Drug Eruption: A Report of a Pediatric Case and Review of the Literature

Abstract:   Lichenoid drug eruptions are seen most frequently on the skin and seldomly affect the mucosal surfaces. Oral involvement—known as oral lichenoid drug eruption—is more common in the adult population and has been associated with numerous medications. Pediatric-onset oral lichenoid drug eruption is an exceptionally rare finding with only isolated cases published in the literature. The nonspecific appearance and latent presentation of pediatric oral lichenoid drug eruption can cause confusion in diagnosis and treatment. We report a case of oral lichenoid drug eruption occurring in a 15-year-old and explore challenges in the clinical and histologic recognition of this condition.     

Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs

Highly purified cannabidiol (CBD) has demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome in randomized, double-blind, add-on, controlled phase 3 trials. It is important to consider the possibility of drug-drug interactions (DDIs). Here, we review six trials of CBD (Epidiolex/Epidyolex; 100 mg/mL oral solution) in healthy volunteers or patients with epilepsy, which investigated potential interactions between CBD and enzymes involved in drug metabolism of common antiseizure drugs (ASDs). CBD did not affect CYP3A4 activity. Induction of CYP3A4 and CYP2C19 led to small reductions in exposure to CBD and its major metabolites. Inhibition of CYP3A4 activity did not affect CBD exposure and caused small increases in exposure to CBD metabolites. Inhibition of CYP2C19 activity led to a small increase in exposure to CBD and small decreases in exposure to CBD metabolites. One potentially clinically important DDI was identified: combination of CBD and clobazam (CLB) did not affect CBD or CLB exposure, but increased exposure to major metabolites of both compounds. Reduction of CLB dose may be considered if adverse reactions known to occur with CLB are experienced when it is coadministered with CBD. There was a small increase of exposure to stiripentol (STP) when coadministered with CBD. STP had no effect on CBD exposure but led to minor decreases in exposure to CBD metabolites. Combination of CBD and valproate (VPA) did not cause clinically important changes in the pharmacokinetics of either drug, or 2-propyl-4-pentenoic acid. Concomitant VPA caused small increases in exposure to CBD metabolites. Dose adjustments are not likely to be necessary when CBD is combined with STP or VPA. The safety results from these trials were consistent with the known safety profile of CBD. These trials indicate an overall low potential for DDIs between CBD and other ASDs, except for CLB.     

Hippocampal‐striatal functional connectivity supports processing of temporal expectations from associative memory

The hippocampus and dorsal striatum are both associated with temporal processing, but they are thought to play distinct roles. The hippocampus has been reported to contribute to storing temporal structure of events in memory, whereas the striatum contributes to temporal motor preparation and reward anticipation. Here, we asked whether the striatum cooperates with the hippocampus in processing the temporal context of memorized visual associations. In our task, participants were trained to implicitly form temporal expectations for one of two possible time intervals associated to specific cue‐target associations, and subsequently were scanned using ultra‐high‐field 7T functional magnetic resonance imaging. During scanning, learned temporal expectations could be violated when the pairs were presented at either the associated or not‐associated time intervals. When temporal expectations were met during testing trials, activity in left and right hippocampal subfields and right putamen decreased, compared to when temporal expectations were not met. Further, psycho‐physiological interactions showed that functional connectivity between left hippocampal subfields and caudate decreased when temporal expectations were not met. Our results indicate that the hippocampus and striatum cooperate to process implicit temporal expectation from mnemonic associations. Our findings provide further support for a hippocampal‐striatal network in temporal associative processing.     

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4

Journal of Neurology - SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder...