Chasing Tics in the Human Brain: Development of Open,Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.     

Dose accuracy of new versus used novopen 4 insulin pens

Abstract Objective: To our knowledge, no studies have been performed testing dose accuracy in both new and used patient insulin injection pens. We hypothesized that the dose accuracy of used (>1 year) insulin pens to be less accurate than that of new insulin pens and investigated whether possible differences influence the treatment. This study compared the dosing accuracy of 11 new and 11 used (>1 year) Novopen(?) 4 pens (Novo Nordisk, Bagsvaerd, Denmark). Materials and Methods: Dosing accuracy differences between new and used pens were studied by weighing the volume of the dosage of 8 international units of insulin (IU) and 32?IU of 11 pens. Each measurement was repeated 15 times. Whether the pens complied with the International Organization for Standardization (ISO) limits of 10% for 8?IU and 5% for 32?IU was tested. The statistical analyses were performed using the Mann-Whitney rank sum test (within Sigmaplot version 12.0; Systat Software, Chicago, IL), and a P value of <0.05 was considered to be statistically significant. Results: For the 8?IU dose, the mean delivered dose was 8.04?IU in new pens and 7.91?IU in used insulin pens. For the 32?IU dose, the mean delivered dose was 31.90 in new pens and 31.68?IU in used insulin pens. The difference in the median values between the two groups was statistically significant (P<0.001). Three individual doses in the 32?IU dose exceeded the ISO range in the lower range. The difference in mean variation coefficient between the two groups was also statistically significant (P<0.001). Conclusions: There was a significant difference between the accuracy of new versus used insulin pens. More studies with larger sample sizes are necessary to confirm our findings and further elucidate the relationship between age of insulin pens and dose accuracy.     

Lower serum prohepcidin levels associated with lower iron and erythropoietn requirements in hemodialysis patients with chronic hepatitis C

ABSTRACT: BACKGROUND: Patients with chronic HCV infection have increased liver iron. Recently identified protein hepcidin synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. It was previously reported lower erythropoietin and iron supplementation requirement in HD patients with HCV infection. We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection. METHODS: Sixty patients (27 male, 33 female, mean age 50 +/-15 years) on chronic HD were included. Parameters related to iron metabolism (ferritin, serum iron and total iron binding capacity (TIBC)), inflammation (hs-CRP, TNF-alpha and IL-6) and prohepcidin levels were measured. The response to treatment (erythropoiesis-stimulating agent (ESA) resistance index) was assessed from the ratio of the weekly erythropoietin (rhuEPO) dose to hemoglobin (Hb) per unit weight. RESULTS: Serum prohepcidin levels of HCV positive patients (135+/-25 ng/mL) were significantly lower than HCV negative patients [148+/-18 ng/mL, (p=0.025)]. Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients (p=0.016). Serum prohepcidin levels was positively correlated with ferritin (r=0.405, p=0.001) and IL-6 (r=0.271, p=0.050) levels in HD patients. In the HCV positive group, serum prohepcidin levels significantly correlated with ferritin levels (r=0.514 p=0.004). In the HCV negative group, serum prohepcidin levels significantly correlated with serum IL-6 levels (r=0.418, p=0.027). In multiple regression analysis performed to predict prohepcidin in HCV positive patients, serum ferritin was found to be an independent variable (r=0.28, p=0.008). CONCLUSIONS: HCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation and/or lower iron and rhuEPO requirement in these patients.     

A Characterization of Aerosolized Sudan Virus Infection in African Green Monkeys,Cynomolgus Macaques,and Rhesus Macaques

Filoviruses are members of the genera Ebolavirus, Marburgvirus, and “Cuevavirus”. Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV) Boniface in non-human primates (NHP) belonging to three different species. Groups of cynomolgus macaques (cyno), rhesus macaques (rhesus), and African green monkeys (AGM) were challenged with target doses of 50 or 500 plaque-forming units (pfu) of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4–5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP.     

Cost analysis comparing ultrasonic fundus-first and conventional laparoscopic cholecystectomy using electrocautery

Background

Costs associated with laparoscopic fundus-first cholecystectomy using ultrasonic dissection versus a conventional laparoscopic cholecystectomy has not been compared.

Methods

Adult patients subjected to elective laparoscopic cholecystectomy between June 2002 and March 2004 were randomized to either an ultrasonic fundus-first dissection or dissection from the triangle of Calot with electrocautery. Differences in direct and indirect costs related to either technique were studied.

Results

The duration of the operation and hospitalization was longer when dissection was with the conventional technique. With the ultrasonic fundus-first technique, the direct cost was 1,190 SEK lower, and the total cost, taking also the cost for sick leave into account, was 5,370 SEK lower.

Conclusions

Both direct and indirect costs are lower with a laparoscopic fundus-first cholecystectomy using ultrasonic dissection than conventional laparoscopic cholecystectomy using electrocautery.     

Inhibition of vein graft intimal hyperplasia by periadventitial application of hyaluronic acid–carboxymethyl cellulose: An experimental study

Objective. Placement of an external support has been reported to prevent intimal hyperplasia of vein grafts. In this study, we investigated the effect of HA/CMC on intimal hyperplasia in a rabbit model. Design. Right jugular vein to common carotid artery bypass grafting was performed in 24 female New Zealand white rabbits (2.5–3.0 kg). Animals were divided into two groups: control group (n=12) and HA/CMC group (n=12). Absorbable membrane barrier was wrapped around vein grafts in HA/CMC group. In control group, no material was applied following venous graft bypass. Results. At 1 month, in the vein grafts supported with the HA/CMC membrane neointimal thickening was significantly less (109 µm [IQR, 78–166]) compared to the unsupported control grafts (220 µm [IQR; 101–312]; p<0.001). Medial thickening in the HA/CMC group (128 µm [IQR, 101–181]) compared to unsheathed control grafts (182 µm [IQR, 131–255] p<0.001) was also significantly less. Conclusion. Periadventitial placement of HA/CMC as an absorbable membrane inhibits intimal hyperplasia of vein bypass grafts in a rabbit model.     

Monitoramento dos efeitos da raquianestesia sobre a saturação de oxigênio cerebral em pacientes idosos com o uso de espectroscopia de luz próxima ao infravermelho

Objective

Central blockage provided by spinal anaesthesia enables realization of many surgical procedures, whereas hemodynamic and respiratory changes influence systemic oxygen delivery leading to the potential development of series of problems such as cerebral ischemia, myocardial infarction and acute renal failure. This study was intended to detect potentially adverse effects of hemodynamic and respiratory changes on systemic oxygen delivery using cerebral oxymetric methods in patients who underwent spinal anaesthesia.

Methods

Twenty‐five ASA I–II Group patients aged 65–80 years scheduled for unilateral inguinal hernia repair under spinal anaesthesia were included in the study. Following standard monitorization baseline cerebral oxygen levels were measured using cerebral oximetric methods. Standardized Mini Mental Test (SMMT) was applied before and after the operation so as to determine the level of cognitive functioning of the cases. Using a standard technique and equal amounts of a local anaesthetic drug (15 mg bupivacaine 5%) intratechal blockade was performed. Mean blood pressure (MBP), maximum heart rate (MHR), peripheral oxygen saturation (SpO₂) and cerebral oxygen levels (rSO2) were preoperatively monitored for 60 min. Pre‐ and postoperative haemoglobin levels were measured. The variations in data obtained and their correlations with the cerebral oxygen levels were investigated.

Results

Significant changes in pre‐ and postoperative measurements of haemoglobin levels and SMMT scores and intraoperative SpO₂ levels were not observed. However, significant variations were observed in intraoperative MBP, MHR and rSO2 levels. Besides, a correlation between variations in rSO2, MBP and MHR was determined.

Conclusion

Evaluation of the data obtained in the study demonstrated that post‐spinal decline in blood pressure and also heart rate decreases systemic oxygen delivery and adversely effects cerebral oxygen levels. However, this downward change did not result in deterioration of cognitive functioning.     

Simultaneous coronary artery bypass grafting and carotid endarterectomy can be performed with low mortality rates

There is controversy over the best approach for patients with concomitant carotid and coronary artery disease.1 Therapeutic strategies include isolated coronary artery bypass grafting (CABG), staged carotid endarterectomy (CEA) and CABG, reversed staged CEA and CABG, and simultaneous procedures under single anaesthesia.2Although reported experiences over three decades are available, combining CEA with CABG remains to be elucidated.3 Furthermore, risk of cerebrovascular accident (CVA), which is one of the major predictors of prognosis of CABG, has been reported to increase up to 14% in patients with severe carotid artery stenosis (> 80%).4-9Peri-operative neurological events such as stroke after CABG are the major neurological complications, which increase with age.10 The incidence of peri-operative stroke has been well documented at approximately 2% of all cardiac surgeries.11 Despite reduced overall complication rates over the years after CABG, the incidence of stroke remains relatively unchanged.10The aetiology of peri-operative stroke is multi-factorial including hypotension or hypoperfusion-induced reduced brain flow, atherosclerosis due to micro- or macro-embolisation, and intra- or extra-cranial vascular diseases.5 In addition, carotid artery disease is a critical factor; however, it is considered unlikely to be the only culprit for peri-operative strokes.12Although no consensus on the optimal management of patients with concomitant carotid and coronary artery disease has been reached,13 simultaneous CEA and CABG surgery is often associated with low rates of mortality and morbidity.14-17 In this study, we report our experience with simultaneous CEA and CABG surgery in our clinic in the light of data in the literature.