Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke,seizures and sensorimotor gating deficit

Background and purpose:

Abnormal glutamatergic activity is implicated in neurologic and neuropsychiatric disorders. Selective glutamate receptor antagonists were highly effective in animal models of stroke and seizures but failed in further clinical development because of serious side effects, including an almost complete set of symptoms of schizophrenia. Therefore, the novel polyvalent glutamatergic agent 3,5-dibromo-L-phenylalanine (3,5-DBr-L-Phe) was studied in rat models of stroke, seizures and sensorimotor gating deficit.

Experimental approach:

3,5-DBr-L-Phe was administered intraperitoneally as three boluses after intracerebral injection of endothelin-1 (ET-1) adjacent to the middle cerebral artery to cause brain injury (a model of stroke). 3,5-DBr-L-Phe was also given as a single bolus prior to pentylenetetrazole (PTZ) injection to induce seizures or prior to the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) to cause disruption of prepulse inhibition (PPI) of startle (sensorimotor gating deficit).

Key results:

Brain damage caused by ET-1 was reduced by 52%, which is comparable with the effects of MK-801 in this model as reported by others. 3,5-DBr-L-Phe significantly reduced seizures induced by PTZ without the significant effects on arterial blood pressure and heart rate normally caused by NMDA antagonists. 3,5-DBr-L-Phe prevented the disruption of PPI measured 3 days after the administration of ET-1. 3,5-DBr-L-Phe also eliminated sensorimotor gating deficit caused by MK-801.

Conclusion and implications:

The pharmacological profile of 3,5-DBr-L-Phe might be beneficial not only for developing a therapy for the neurological and cognitive symptoms of stroke and seizures but also for some neuropsychiatric disorders.     

Safety and Feasibility of Percutaneous Tracheostomy Performed by Neurointensivists

Introduction  We evaluated the effects of a change from routine surgical tracheostomy (ST), performed primarily by ENT surgeons, to bedside percutaneous tracheostomy (PT) performed by neurointensivists. Methods  The first 67 PT procedures performed by neurointensivists were retrospectively reviewed, and compared with 68 consecutive ST procedures performed during the previous year. Demographics, severity of illness, procedural complications, incidence of ventilator-associated pneumonia (VAP), duration of mechanical ventilation (DMV), length of stay (LOS), and hospital charges were evaluated. Results  Age, race, gender, neurological diagnoses, comorbid illnesses, and Glasgow coma scale on admission and the day of tracheostomy were similar. Procedural complications occurred in 8% of PT patients and 9% of ST patients, including clinically significant bleeding, transient loss of the airway, ICP rise requiring treatment, or acute lung injury (P = 0.3). PT was performed earlier than ST (median [interquartile range] ventilator day 8 [4–11] vs. 12 [8–18], P = 0.001). Median DMV was shorter in the PT cohort (19 [10–27] vs. 24 [16–33] days, P = 0.02), as was median ICU LOS (15 [9–21] vs. 19 [12–27] days, P = 0.01). ICU charges (US dollars) were lower in the PT cohort (median $123,404 vs. $156,311, P = 0.01). Trends toward less VAP, shorter hospital LOS, and lower total hospital charges among patients receiving PT did not achieve significance. Conclusions  PT performed by neurointensivists was safe compared to ST. Timely PT by neurointensivists may offer significant advantages in terms of ventilator weaning, ICU LOS, and the cost of care.     

Predicting long-term outcome in poor grade aneurysmal subarachnoid haemorrhage patients utilising the Glasgow Coma Scale

The Glasgow Coma Scale (GCS) is the most universally accepted system for grading level of consciousness. Predicting outcome is particularly difficult in poor grade aneurysmal subarachnoid haemorrhage (aSAH) patients. We hypothesised that the GCS and individual examination components would correlate with long-term outcome and have varying prognostic value depending on assessment time points. GCS scores of 160 aSAH patients presenting in stupor or coma were prospectively recorded on admission and each subsequent day until hospital day 14. Early treatment was planned for each patient unless the patient’s family refused aggressive intervention or the patient died before surgery. Outcomes were assessed by the modified Rankin scale (mRS) at 14 days, 3 months, and one year.All patients who did not receive surgical treatment died within one year. Of the 104 patients who received surgical treatment, 13.5% of them had a favourable outcome at 14 days, 38.5% at 3 months, and 51% at one year (p < 0.0001). Admission GCS scores significantly correlated with outcome (Spearman rank test, rs = 0.472, p < 0.0001). On admission, motor examination correlated best with one-year outcome (rs = 0.533, p < 0.0001). Each point increase in motor examination predicted a 1.8-fold increased odds of favourable long-term outcome (95% confidence interval [CI], 1.4–2.3). At discharge, eye examination (rs = 0.760, p < 0.0001) correlated best with one-year outcome, and a one point increase in eye examination predicted a 3.1-fold increased odds of favourable outcome (95% CI, 1.8–5.4). During hospitalisation, the best eye exam (rs = 0.738, p < 0.0001) and worst motor exam (rs = 0.612, p < 0.0001) were the most highly correlated with the one-year outcome.Long-term follow-up is necessary when evaluating recovery after aSAH, as outcomes improve significantly during the first year. The GCS and its individual components correlate well with long-term outcome. Admission motor examination and spontaneous eye opening during hospitalisation are most predictive of favourable recovery.     

Increased prevalence of temporary cardiac pacing in people with epilepsy

IntroductionEven though ictal tachyarrhythmias are more common, ictal brady-asystole is more likely to be fatal, and yet is potentially preventable with pacemaker (PM) implantation. We sought to quantify the degree of association of PM placement in people with and without epilepsy, including neurological and cardiovascular cohorts.MethodsRetrospective cross-sectional analysis of the National Hospital Discharge database using International Classification of Diseases Clinical Modification (ICD-9-CM) codes. We identified people with and without epilepsy between 1990 and 2006. The epilepsy cohort was compared to patients without epilepsy and other cardiovascular and central nervous system (CNS) disease cohorts.ResultsPeople with epilepsy had higher odds of temporary PM (TPM; OR 1.6) than patients without epilepsy, especially amongst males (OR 2.0), young- (OR 4.6) and middle-aged (OR 4.3) patients. The epilepsy cohort had significantly higher odds of TPM than demyelinating disease (OR 7.9) and migraine (OR 9.1) cohorts. Compared to stroke, people with epilepsy had higher odds of TPM in the male (OR 1.6) and middle-age (OR 2.4) subgroups. No significant association was seen with permanent PM (PPM).ConclusionsOur study demonstrates the high likelihood of TPM placement in epilepsy patients as compared to cohorts without epilepsy. Significant associations were seen especially in males and young- and middle-aged patients. Since demyelinating and migraine cohorts are somewhat similar to epilepsy patients in age and sex characteristics, the higher odds of TPM in epilepsy patients may be related to the disease mechanism causing brady-asystole; however this requires further study.     

Expression of antimicrobial peptides in diabetic foot ulcer

Background

Foot ulcers are one of the main diabetes complications due to its high frequency and difficulty of complete healing. There are several factors that participate in diabetic ulcers development and limited information exists about the role of antimicrobial peptides (AMP) in its pathogenesis.

Objective

The aim of this study was to analyze the expression pattern of the main AMPs: Human Neutrophil Peptide (HNP)-1, Human β-defensin (HBD)-1, HBD-2, HBD-3, HBD-4 and cathelicidin LL-37 in biopsies from diabetic foot ulcers (DFU).

Methods

20 biopsies from DFU grade 3 according to Wagner's classification and 20 biopsies from healthy donors were obtained. Real time PCR, immunohistochemistry and primary cell cultures were performed.

Results

β-Defensins were overexpressed in DFU, whereas LL-37 has low or none expression in comparison with healthy skin. When primary cell culture from these biopsies were performed and infected with Staphylococcus aureus, epidermal cell from diabetic ulcers showed lower LL-37 expression compared with cell cultures from healthy donors skin.

Conclusion

These results suggest that though most AMPs are expressed in DFU, this production is not appropriate to promote wound healing and contain secondary infections.     

An investigation into the numbers of dentists from 19 European Economic Area (EEA) member states currently registered to work in the United Kingdom and key differences between the practise of dentistry in the UK and their member states of origin

The aim of this short communication is to highlight the numbers of non-UK EEA qualified dentists currently registered with the General Dental Council (GDC) and to present a brief overview of the systems for the provision of oral healthcare in the non-UK EEA member states identifying differences in practise. The relevant data were gathered for the National Clinical Assessment Service (NCAS) as part of a wider project. It was found that at 31 December 2010, 28% of dentists registered with the GDC had not qualified in the UK. Of these more than 6,300 were European Economic Area (EEA) dentists with non-UK qualifications. The nature of their practise varied widely from member state to member state. The implications of these findings are discussed briefly.     

Prevalence and risk factors for diabetic peripheral neuropathy,neuropathic pain and foot ulceration in the Arabian Gulf region

Aims/IntroductionThis study determined the prevalence and risk factors for diabetic peripheral neuropathy (DPN), painful DPN and diabetic foot ulceration (DFU) in patients with type 2 diabetes in secondary healthcare in Qatar, Kuwait and the Kingdom of Saudi Arabia.Materials and MethodsAdults aged 18–85 years with type 2 diabetes were randomly enrolled from secondary healthcare, and underwent clinical and metabolic assessment. DPN was evaluated using vibration perception threshold and neuropathic symptoms and painful Diabetic Peripheral Neuropathy was evaluated using the Douleur Neuropathique 4 questionnaire.ResultsA total of 3,021 individuals were recruited between June 2017 and May 2019. The prevalence of DPN was 33.3%, of whom 52.2% were at risk of DFU and 53.6% were undiagnosed. The prevalence of painful DPN was 43.3%, of whom 54.3% were undiagnosed. DFU was present in 2.9%. The adjusted odds ratios for DPN and painful DPN were higher with increasing diabetes duration, obesity, poor glycemic control and hyperlipidemia, and lower with greater physical activity. The adjusted odds ratio for DFU was higher with the presence of DPN, severe loss of vibration perception, hypertension and vitamin D deficiency.ConclusionsThis is the largest study to date from the Middle East showing a high prevalence of undiagnosed DPN, painful DPN and those at risk of DFU in patients with type 2 diabetes, and identifies their respective risk factors.