Laterality of deep white matter hyperintensities correlates with basilar artery bending and vertebral artery dominance

AimTo investigate whether vertebrobasilar geometry contributes to the presence, severity, and laterality of white matter hyperintensities (WMH).MethodsWe retrospectively reviewed 290 cerebral scans of patients who underwent time-of-flight and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) between 2017 and 2018. WMH were counted, localized, and grouped according to laterality on the FLAIR sequence. A 3D mesh of the posterior circulation was reconstructed (with ITK SNAP software) and the morphology of the vertebrobasilar system analyzed with an in-house software written in Python.ResultsPatients were assigned into a group with WMH (n = 204) and a group without WMH (n = 86). The severity of WMH burden was mainly affected by age and hypertension, while the localization of the WMH (or laterality) was mainly affected by the vertebrobasilar system morphology. Basilar artery morphology only affected the parieto-occipital region significantly if both posterior communicating arteries were hypoplastic or absent. The dominant vertebral artery and basilar artery curve had an opposite directional relationship.ConclusionsAn unequal vertebral artery flow is an important hemodynamic contributor to basilar bending. Increased basilar artery curvature and increased infratentorial WMH burden may signal inadequate blood flow and predict cerebrovascular events.

Cerebrovascular diseases, predominantly stroke, remain the leading cause of death and functional disability worldwide (1). White matter hyperintensities (WMH) on cerebral T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences have been linked to cerebrovascular disease outcomes and ischemic stroke (2,3) (Figure 1). WMH, subclinical cerebral alterations caused by changes in cerebral vascular morphology, may lead to cerebral histological changes long before the manifestation of neurological deficits or cognitive decline (4). Multiple studies suggested that ischemia plays a crucial role in the development of tortuous arterioles and reduced cerebral blood flow. Despite the two decades of advancements in the understanding of the etiology of these processes, much uncertainty remains (2). Chronic hypoperfusion and arteriolosclerosis are considered key features in the development of WMH. The presence of WMH triples the risk of stroke and doubles the risk of dementia (5). Previous publications showed a significant correlation between cerebral artery morphology and stroke localization (6). However, the connection between WMH and large cerebral artery morphology is not yet fully understood.Open in a separate windowFigure 1White matter hyperintensity on T2 fluid-attenuated inversion recovery magnetic resonance imaging sequence (scale bar, 5 cm; source: Medical Imaging Centre, Semmelweis University). Based on our white matter hyperintensities evaluation protocol, this patient was categorized as posterior cerebral artery region right dominant.Approximately 20% of strokes occur in the region supplied by the vertebrobasilar system. Unlike most systemic arteries, which are characterized by a tree-like branching pattern, the basilar artery is unique as it is created from the confluence of the two vertebral arteries. The vertebral arteries are mostly asymmetric and left-dominant. The varying vessel morphologies may cause asymmetrical blood flow in the basilar artery, which over time possibly leads to bending. This phenomenon, named basilar curve or basilar bending, may create microvascular damage to the surrounding brain areas.Therefore, our first aim was to investigate if basilar artery geometry affected the existence and laterality of WMH. Our second aim was to investigate the influence of the vertebral artery dominance on basilar artery geometric indices.     

Natural orifice translumenal endoscopic surgery (NOTES?): a technical review

Introduction  

The clinical NOTES literature continues to grow. This review quantifies the published human NOTES experience to date, examines instrument use in detail, and compiles available perioperative outcomes data.     

A review of the Transitional Emergency Nurse Practitioner

Introduction

A retrospective exploratory study was conducted to (i) explore the practice patterns of a Transitional Emergency Nurse Practitioner (TENP) working across two urban Emergency Departments (ED); (ii) identify the demographic characteristics of the TENP patient cohort; and (iii) identify if TENP patients were appropriately and timely managed.

Method

The study was conducted across two hospital sites over two consecutive years for a 3-month period. Data collection occurred during the months of December through to February. TENP patients were identified by hospital electronic medical record and were then grouped into a model that included ‘Fast Track’ or ‘See and Treat’ cohort. The cohorts were then analysed for diagnostic groups, age, sex, length of stay, triage category, and re-presentations.

Results

The TENP worked a total of 600 h (Site 1 252 h; Site 2 348 h) across the study period. The TENP managed a total of 481 patients (262 Site 1; 220 Site 2) during the study period. The majority of patients (412; 84%) were managed in the ‘See and Treat’ cohort (Site 1 246, 94%; Site 2 166, 75%) and 70 patients (16%) were managed in the ‘Fast Track’ cohort (Site 1 16, 4%; Site 2 54, 25%). The median length of stay for TENP managed patients was 143 min, with 96% of patients leaving the ED in less than 8 h. There were no TENP unplanned re-presentations at either site. The TENP managed more male patients across both sites. The majority (75%) of patients the TENP managed had musculoskeletal and/or wound conditions or injuries.

Conclusion

TENP practice across the two Sydney metropolitan ED sites was similar. The model adapted for Tertiary Referral centres was appropriate for smaller urban EDs. The study supports existing evidence of timely and appropriate care being delivered by TENPs across Australian EDs. Given the work practice similarities, the study demonstrates that State and/or National standards and policies could be developed for emergency advanced practice roles.     

Structural abnormalities of ventrolateral and orbitofrontal cortex in patients with familial bipolar disorder

Objectives: Abnormalities of ventral prefrontal function have been widely reported in bipolar disorder, but reports of structural abnormalities in the same region are less consistent. We examined the presence and location of ventral prefrontal abnormalities in a large sample of individuals with bipolar disorder and their relationship to gender, psychotic symptoms, and age. Methods: Structural magnetic resonance imaging brain scans were carried out on 66 individuals with bipolar disorder, type I, and 66 controls. Voxel‐based morphometry was used to examine differences in grey and white matter density between the groups and their relationship with a lifetime occurrence of psychotic symptoms and age. Results: Reductions in grey matter density were seen in the left and right lateral orbital gyri and the right inferior frontal gyrus, while white matter density reductions were seen in the corona radiata and the left temporal stem. In contrast, hallucinations and positive symptoms were associated with grey matter reduction in the left middle temporal gyrus. Age was more strongly associated with the right inferior frontal gyrus grey matter reductions in the bipolar group than in the controls, but not with any other finding. Conclusion: Abnormalities of the ventral prefrontal cortex are likely to be involved in the aetiopathology of bipolar disorder, while hallucinations appear to be more closely associated with temporal lobe abnormality, extending earlier work in schizophrenia. Further prospective studies are required to comprehensively address the trajectory of these findings.     

A comprehensive review of laparoscopic redo fundoplication

Background  

The last decade has seen the publication of multiple case series investigating the feasibility of performing reoperative fundoplications using laparoscopic techniques. Most of these studies are small and reflect initial experiences with the procedure. To examine the collective experience with laparoscopic redo fundoplications, a systematic review was conducted.     

Donor cell leukemia developing six years after marrow grafting for acute leukemia

A patient who developed recurrent leukemia more than six years after marrow grafting from an HLA-identical same-sex sibling is reported. Difference in DNA restriction fragment length polymorphisms between donor and host demonstrated that the DNA in the recurrent leukemia sample was probably of donor origin. Possible mechanisms that could explain the long latent period between transplantation and expression of leukemic transformation are discussed. We conclude that future cases of late leukemic recurrence after marrow grafting should be studied to determine whether, in contrast to early relapses, late relapses occur in donor cells in most or all instances.     

The mechanism of white cell reduction by synthetic fiber cell filters

The mechanism of white cell (WBC) retention by synthetic fiber-based WBC filters was studied. Filters were made of nonwoven fleece prepared from polyester, surface-modified polyester, or polypropylene fibers. Human platelet concentrates were filtered through experimental filters consisting of 8 to 54 layers of nonwoven fleece with mean pore sizes from 7.3 to 14.2 microns. Filters made of fleece of smaller pore size removed WBCs less effectively than filters with larger-pore fleece. Retention of lymphocytes and granulocytes gradually dropped to 0 percent as increasing loads were applied to the filters. The maximal retention capacity for these cell types (i.e., the number of cells retained when "saturating" numbers of WBCs were applied) was proportional to the number of layers of filter material used. Platelet retention did not correlate with WBC retention. Depth filtration, rather than mechanical sieving, seems to be the principal means of WBC removal by nonwoven fiber filters. A low initial number of WBCs in the component to be filtered is important for successful WBC filtration.     

An inhibitory effect of veratridine during tetanic stimulation of the rat diaphragm

The membrane ‘labilizer’ veratridine (3.7 ± 10^-6 m) which potentiates the contractions at twitch (0.1 Hz) stimulation due to multiple discharges, inhibited the tetanic contractions (50 Hz in 10 s) and the simultaneously recorded electromyogram in a use-dependent way, leading to fading of tetanic tension. The effect was equal during indirect and direct stimulation, and could therefore be localized to the excitable sarcolemma. This was confirmed by intracellular recording of action potentials, showing a marked veratridine-induced fallout of action potentials during continuous 50 Hz stimulation, whereas endplate potentials were unaffected. Accordingly, veratridine probably caused a use-dependent inhibition of the Na⁺ channels of the excitable sarcolemma. The tetanic fade was unaffected by K⁺ depolarization, increased by hyperpolarization in K⁺-free solution, and decreased by high Ca²⁺. All these changes of the ionic concentrations inhibited the twitch potentiating effect of veratridine. Since hyperpolarization and increasing the electric field in the membrane with high Ca^,+ had opposite effects on the tetanic fade, the field change was probably not the cause of the antagonism in high Ca²⁺. Instead, a membrane stabilizing effect of high Ca²⁺ is suggested, since the neutral local anaesthetic benzocaine (1.5 ± 10^-4 m), which is also a membrane stabilizing drug, had the same effects as high Ca²⁺ on the veratridine-induced tetanic fade. The effect of veratrine during tetanic stimulation was partly reversible upon washing. The reversibility was enhanced by high Ca²⁺ or benzocaine.     

IMPROVED TOLERABILITY OF FELODIPINE COMPARED WITH AMLODIPINE IN ELDERLY HYPERTENSIVES: A RANDOMISED,DOUBLE-BLIND STUDY IN 535 PATIENTS,FOCUSING ON VASODILATORY ADVERSE EVENTS

SUMMARY The primary aim of this double-blind, parallel group trial was to compare incidence of newly occurring vasodilatory adverse events in elderly patients treated with recommended once-daily doses of felodipine extended release (ER) or amlodipine. A total of 535 patients over 65 years old with a sitting diastolic blood pressure of 90-115 mmHg and/or systolic blood pressure 160-220 mmHg, were recruited at 46 centres worldwide. Patients were randomised to felodipine ER 2.5 mg or amlodipine 5 mg. If blood pressure was >160/90 mmHg after three or six weeks, felodipine ER was increased to 5 and 10 mg and amlodipine to 10 mg. After nine weeks, average doses of felodipine ER and amlodipine were 5.5 mg and 7.3 mg, respectively. Newly occurring vasodilatory adverse events were reported by 32% of felodipine ER patients and 43% of amlodipine patients (p=0.007). Both treatments effectively reduced blood pressure 24 hours post-dose. Using a low starting dose and individual titration, felodipine ER achieves good control of blood pressure with few vasodilatory side-effects.     

Reconciling scientific and religious discourse about madness during the age of reason: lessons for today?

Reconciling scientific and religious discourse about madness during the age of reason: lessons for today? This paper argues that the secularization of madness, during the seventeenth and eighteenth centuries, occurred as a consequence of cultural change that accompanied the social upheavals of the age. In examining the reconciliation of competing explanations for madness, from theological and empirical viewpoints, it is suggested that these paradigms were never totally separated and argued that developments during this period were a consequence of continual interaction and dialogue between these contrasting views. Furthermore, it is suggested that an understanding of these changing times can illuminate present debates surrounding mental illness.