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An inborn term neonate weighing 2600 g developed meconium aspiration syndrome at birth. Baby had respiratory failure requiring high-frequency oscillatory ventilation support at 15 hours of life. He additionally developed hypotension with left ventricular dysfunction noted on point-of-care echocardiography (POCE), which required dopamine and epinephrine infusions. At 28 hours of life, he was started on inhaled nitric oxide (iNO), followed by milrinone due to hypoxaemic respiratory failure and the POCE revealed severe pulmonary artery hypertension (PAH). As PAH was refractory to iNO and milrinone, vasopressin was added which resulted in rapid improvement in oxygenation and normalisation of pulmonary artery pressures. Baby was weaned off from vasoactive support in the next 120 hours. Vasopressin proved to be the rescue agent in this case of iNO refractory PAH without any side effects during therapy. Baby was successfully extubated on day 18 and was discharged with a normal neurological examination finding.

Increased antibacterial resistance (ABR) and limited drug discovery warrant optimized use of available antibiotics. One option is to rationally combine two antibiotics (fixed dose combination (FDC)) that may delay or prevent emergence of ABR in notorious pathogen. Major concern with FDC is the mutual interaction of its components that might influence their pharmacokinetic (PK) profile, requiring reassessing of whole formulation (adding cost and time). The interaction can be identified by comparing PK profile of a drug present in FDC with its independent entity. An open-label, crossover, single-dose comparative PK study of FDC (ceftriaxone and sulbactam) with their individual reference formulations was performed in 24 healthy adult subjects. No mutual PK interactions between ceftriaxone and sulbactam were observed. Pharmacokinetic data was used to develop a population-PK model to understand between-subject variability (BSV). Pharmacokinetics of ceftriaxone/sulbactam was explained by one and two compartment models, respectively. The subject's "weight" was identified as a covariate explaining BSV. Both internal and external validations (healthy/infected subjects) were done. The model-derived population-PK parameters of FDC's active components in infected subjects were similar to literature reported values of individual components. Efficacies of various FDC dosage regimens over a range of minimum inhibitory concentrations (MICs) were assessed by Monte Carlo simulations using population-PK parameters of infected/healthy subjects. In infected subjects, 3 g FDC/24 h can treat bacteria with MIC ≤8 μg/mL, while for MIC 8-32 μg/mL, 3 g FDC/12 h is recommended. Lastly, the developed population-PK model was successfully used to predict drug exposure in pediatric population.

Our previous work suggests that pharmacological induction of oxidative stress causes anxiety-like behavior in rats. Interestingly, sleep deprivation is reported to cause oxidative damage in the brain and is also reported to be anxiogenic. Minimal mechanistic insights are available. In this study, using a behavioral and biochemical approach, we investigated involvement of oxidative stress mechanisms in sleep deprivation-induced anxiety-like behavior of rats and the protective role of treadmill exercise in this process. We report that acute sleep deprivation (SD) increases oxidative stress in the cortex, hippocampus and amygdala while prior treadmill exercise prevents this increase. Serum corticosterones also increase with SD but its levels are normalized in exercised sleep-deprived rats. Also, anxiety-like behavior of rats significantly increases with SD while prior treadmill exercise prevents this increase. Protein expression of two enzymes involved in antioxidant defense, glyoxalase (GLO)-1 and glutathione reductase (GSR)-1 increased after 24h SD in the hippocampus, cortex and amygdala while their levels were normalized in exercised sleep-deprived rats. It is plausible that oxidative stress via regulation of GLO1 and GSR1 is involved in sleep deprivation-induced anxiety-like behavior of rats.

Introduction: Cone beam computed tomography (CBCT) is a relatively new technological innovation that utilises flat-panel detector technology to obtain CT-like images. The key strength of a CBCT system is that cross-sectional imaging can be obtained using the angiographic flat panel unit without having to move the patient, allowing the radiologist to obtain soft tissue imaging during the procedure. This allows treatment planning, guidance, and assessment of outcome to be performed in one interventional suite. Materials and Methods: From December 2008 to June 2009, 24 CBCT scans were performed during vascular interventional procedures on our department’s newly installed multi-axis flat panel angiographic unit. Results: Ten cases were performed for hepatic trans-arterial chemoembolisation, 9 cases for hepatic arterial Yttrium-90 infusion, while 5 cases were for other indications. CBCT was found to be useful in 20 of the 24 cases. Conclusion: Our early experience showed that CBCT was useful in impacting decisions during selected vascular interventional procedures. As CBCT technology improves, we can foresee wider applications of this technology. Key words: Angiogram, C-arm, CBCT, Embolisation

Atherosclerotic disease accounts for 20%-30% of strokes in the general population. In young adults, it is an unexpected event and its causes involve diverse pathologies. Herein, we describe a unique case of acute embolic stroke in a young adult patient due to the presence of a large clot in the right common and internal carotid arteries, as a result of an extrinsic cause. Surgical clot retrieval was considered unsafe at that point in time in view of the active inflammatory changes surrounding the affected vessels. This was eventually treated with a novel endovascular technique, a unique alternative to open surgery, with excellent clinical outcome. To our knowledge, the penumbra system has never been used for thrombus removal in a nonacute setting.

We recently reported involvement of oxidative stress in anxiety-like behavior of rats. Others in separate studies have demonstrated a link between oxidative stress and hypertension as well as with type 2 diabetes/insulin resistance. In the present study, we have tested a putative role of oxidative stress in anxiety-like behavior, hypertension and insulin resistance using a rat model of oxidative stress. Oxidative stress in rats was produced by xanthine (0.1%; drinking water) and xanthine oxidase (5 U/kg; i.p.). X+XO-treated rats had increased plasma and urinary 8-isoprostane levels (a marker of oxidative stress) and increased malondialdehyde (MDA) levels in the hippocampus and amygdala as compared to control rats. Serum corticosterone (a systemic marker of stress and anxiety) levels also increased with X+XO treatment. Moreover, anxiety-like behavior measured via open-field and light-dark exploration behavior tests significantly increased in X+XO-treated rats. Mean arterial blood pressure measured in anesthetized rats increased in X+XO-treated compared to control rats. Furthermore, plasma insulin but not glucose levels together with homeostasis model assessment (HOMA), an index of insulin resistance, were higher in X+XO-treated rats. Our studies suggest that oxidative stress is a common factor that link anxiety-like behavior, hypertension and insulin resistance in rats.

Purpose To evaluate our experience of limb salvage with bare nitinol stent enabled recanalization of long length occlusions of superficial femoral artery (SFA) and adjacent proximal popliteal artery (PPA) in diabetic patients. Methods A total of 573 patients underwent 842 lower limb interventions from August 2006 to September 2008 at our institute. A retrospective review was done of diabetic patients undergoing recanalization of long length SFA/adjacent PPA (>10 cm) occlusions with self expanding bare nitinol stents evaluating their impact on limb salvage. Results Forty-four patients (mean age 65.2 years, M:F 25:19) underwent 49 long-length (>10 cm) SFA/PPA stenting procedures over a period of 26 months. Diabetics comprised 66% of patients ( n =29, mean age: 63.7 years, M: F 19:10). The infrapopliteal distal run-off in this diabetic subgroup comprised one vessel ( n =14/29, 48%), two vessels ( n =12/29, 41%), and three vessels ( n =3/29, 10%). The spectrum of critical limb ischemia included rest pain ( n =8), ulcer ( n =7) and gangrene ( n =14). The lengths of occlusions recanalized were 10–39 cm. A total of 58 stents (individual length 10–17 cm, average diameter 6 mm, mean 2 stents per patient) were placed with average length of stented segment being 23.8 cm. Four patients had stents placed through ipsilateral popliteal artery approach with rest placed through femoral artery approach. Significant complications of the procedure included distal embolization ( n =3) successfully managed with thrombolysis and popliteal arteriovenous fistula in one patient undergoing recanalization through popliteal approach, managed with covered stent placement. No procedure related mortality occurred during thirty-day follow-up period. All were followed up over an average duration of twelve months post-procedure. Three patients died due to associated medical conditions during this period. The following amputations were done on follow-up (three toe amputations, five forefoot amputations, three below-knee amputations, two above-knee amputations). The overall limb salvage rate was 80%. Conclusion Our study shows beneficial result of SFA/PPA stent placement in diabetic occlusions with significant concomitant infrapopliteal disease.

Purpose To assess the efficacy of endovenous laser therapy (EVLT) in the treatment of lower-limb venous ulcers secondary to venous reflux. Materials and Methods Forty-four of 139 patients referred for EVLT from January 2004 to August 2007 had nonhealing venous ulcers. Preprocedural duplex ultrasound (US) was performed to document saphenous venous reflux secondary to saphenofemoral/saphenopopliteal junction incompetence, deep venous insufficiency, and deep vein thrombosis. Follow-up intervals were within 1 week, monthly until ulcer healing, and every 6 months thereafter. Mean follow-up period was 35.8 months (range, 8.1–59.3 months). Results Mean great saphenous vein (GSV) diameter and length treated were 9.9 mm (range, 5.5–16.0 mm) and 36.7 cm (range, 20.0–60.0 cm). Mean laser energy used was 3,292 J (range, 1,392–4,971 J). Mean energy deposited per centimeter of vein was 93.6 J/cm (range, 45.2–182.0 J/cm). Mean laser time was 232 seconds (range, 99–347 sec). Fifteen patients with follow-up duplex US had no GSV flow at 6 months, with nonvisualization indicating complete obliteration. Ulcer healing occurred as early as 1 week after the procedure in some patients. Cumulative healing rates at 1, 3, 6, and 12 months were 82.1%, 92.5%, 92.5%, and 97.4%, respectively. No ulcer had recurred at 1 year, but ulcers recurred in five patients at 14, 14, 23, 35, and 52 months after EVLT, respectively. One patient with a nonhealing ulcer 2 years after treatment developed well differentiated squamous cell carcinoma. Conclusions Ulcer epithelization occurred with continued GSV occlusion and loss of flow. Most ulcers healed within 3 months with no recurrence at 1 year. Nonhealing ulcers should undergo biopsy to exclude malignant transformation.

Recent work has suggested correlation of oxidative stress with anxiety-like behavior. There also is evidence for anxiolytic effects of physical exercise. However, a direct role of oxidative stress in anxiety is not clear and a protective role of physical exercise in oxidative stress-mediated anxiety has never been addressed. In this study, we have utilized rats to test direct involvement of oxidative stress with anxiety-like behavior and have identified oxidative stress mechanisms likely involved in anxiolytic effects of physical exercise. Intraperitoneal injections at non-toxic dose of l-buthionine-(S,R)-sulfoximine (BSO), an agent that increases oxidative stress markers, increased anxiety-like behavior of rats compared to vehicle-treated control rats. Prior 2 weeks treatment with the antioxidant, tempol attenuated BSO-induced anxiety-like behavior of rats suggesting a role of oxidative stress in this phenomenon. Moreover, moderate treadmill exercise prevented BSO-induced anxiety-like behavior of rats and also prevented BSO-mediated increase in oxidative stress markers in serum, urine and brain tissue homogenates from hippocampus, amygdala and locus coeruleus. Thus increasing oxidative stress increases anxiety-like behavior of rats. Moreover, antioxidant or treadmill exercise training both reduce oxidative stress in the rat brain regions implicated in anxiety response and prevent anxiety-like behavior of rats.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To present our institution’s experience of selective embolization of renal angiomyolipomas with alcohol and the long-term follow up data. PATIENTS AND METHODS This retrospective study included 34 patients treated between October 1997 and October 2007 (29 women and five men, mean age 44 years). Of these patients, nine had tuberous sclerosis, 14 were bilateral and 16 were multifocal. Indications for treatment were previous haemorrhage (14), size >4 cm (19) and increasing size over a short period (one). The largest treated lesion was 24.4 cm, and the mean (range) size was 11.9 (2.9–24.4) cm. All patients were treated by selective embolization using a mixture of alcohol and lipiodol. Three patients also had coiling of aneurysms and two patients had additional embolization with polyvinyl alcohol particles. The follow-up was both radiological and clinical, with recurrence defined as growth by >2 cm or symptoms requiring further treatment. RESULTS The technical success rate was 100%, with only one significant complication of non-target renal embolization, with self-limiting effects. Minor complications included 11 patients with post-embolization syndrome, all of which settled with conservative measures. The mean (range) combined radiological and clinical follow-up was 44.2 (12–116) months, with all patients having a follow-up of >1 year. Radiological success was achieved in 97%, with only one lesion growing by >2 cm. The combined clinical and radiological success rate was 85%, with two patients undergoing surgery, two having repeat embolization and one currently offered surgery due to a recent increase in size. CONCLUSION Our study provides long-term evidence that selective arterial embolization with alcohol is a safe and effective method for improving clinical symptoms (85%) and preventing tumour progression (97%) in patients with renal angiomyolipoma.

We report the case of a 74-year-old man with post-percutaneous-nephrostomy venous hemorrhage from an iatrogenic fistula between the renal pelvis and a large tributary of the renal vein. Conservative management failed to contain the hemorrhage. Hence the fistula was occluded by coil embolization through the renal vein. This endovascular approach enabled rapid and effective stoppage of the venous bleed.There was no recurrence of the bleed or any pertinent complication at 3-month follow-up.

Fistulous communication between the renal artery stump and inferior vena cava following nephrectomy is rare. We describe the case of a 52-year-old man with a fistula detected on investigation for hemolytic anemia in the postoperative period. The patient had had a nephrectomy performed 2 weeks prior to presentation for blunt abdominal trauma. The fistula was successfully occluded percutaneously using an Amplatzer vascular plug. The patient recovered completely and was discharged 2 weeks later.

Introduction: Liver biopsy is considered the definitive investigation in the diagnosis and management of liver disease. This study describes the experience of performing transjugular liver biopsy (TJLB) over the last 9 years in a local single centre. Materials and Methods: A retrospective review of consecutive TJLB procedures performed at our institution was conducted. A total of 152 patients (74 males and 78 females), with a mean age of 47.4 years (range, 13 to 83 years) underwent a total of 154 TJLB procedures at our institution between March 2003 and November 2011. The principal indication for TJLB was severe coagulopathy in over 80% of patients. The technical success, number of passes, histological adequacy and complication rates were analysed. Results: The procedural success rate was 98.7% (152 out of 154 procedures). Adequate material for diagnosis was obtained in 149 out of 152 (98.0%) technically successful procedures. There was procedure related morbidity in 8 patients (5.2%) of which all but one were self-limiting requiring no further intervention. We also performed hepatic venous pressure gradient (HVPG) measurements in 19% of patients at the time of TJLB. Conclusion: TJLB performed at our institution is a safe and reliable technique in patients in whom traditional percutaneous liver biopsy may be hazardous. TJLB has a high technical success rate as well as a high diagnostic yield with a low complication rate. TJLB also has the added benefit of performing HVPG, which is of increasing importance in management and prognostication of chronic liver disease. Key words: Indications, Safety, Singapore, Transjugular Liver Biopsy

A 78-year-old man with end-stage renal disease and a right brachial-cephalic upper arm direct hemodialysis access presented with symptomatic central venous occlusion. The right brachiocephalic vein occlusion in this patient was refractory to wire traversal. Sharp recanalization of the central venous occlusion was done with an Outback LTD re-entry catheter (Cordis Corporation, a Johnson & Johnson Company, Miami, Fla). The track was balloon dilated and stented. When the conventional management options fail, this technique may be used to salvage a precious dialysis access and to relieve the patient from symptoms of central venous hypertension.

Fistulous communication between the renal artery stump and the inferior vena cava is a rare complication of nephrectomy. We report a case of an adult male in whom a fistula was detected on investigation for persistent postoperative anemia. The fistula was initially identified with Doppler sonography and subsequently confirmed on a catheter angiogram. It was successfully occluded percutaneously with an Amplatzer vascular plug. The plug had a distinctive appearance on subsequent sonographic studies that was useful for follow-up evaluation. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008

The management of hyperleukocytosis currently involves intensive supportive care for preventing tumor lysis syndrome (TLS)-associated metabolic abnormalities as well as cytoreduction procedures to reduce the white blood cell (WBC) count. These procedures are often equipment-intensive and may not be practised in developing countries with limited resources. Hence, it is not clear what would be the most effective strategy to manage hyperleukocytosis and prevent TLS.All children ≤12 years, diagnosed with acute lymphoblastic leukemia (ALL) and hyperleukocytosis (WBC count100 × 10(9)/l) were administered L-asparginase (L-asp, 6,000 U/m(2), i.m.) along with standard supportive care consisting of hydration, oral allopurinol administration and alkalization. The complete blood counts and biochemical parameters were monitored for 72 h. After 48 h, if the WBC count was100 × 10(9)/l, a repeat dose of L-asp was administered.Twenty-one children (9 boys and 12 girls) with hyperleukocytic ALL were treated with L-asp. The median age of the children was 5.3 years (range 2-11 years). The median initial WBC count was 249 × 10(9)/l (range 151-476 × 10(9)/l). Twenty children received only one dose of L-asp. The mean reduction in WBC count achieved by treatment was 15.7, 42.0, 61.0, 76.4, 85.5 and 90.8% at 12, 24, 36, 48, 60 and 72 h, respectively. None of the patients developed TLS.Chemical cytoreduction by administering L-asp is an effective means of managing hyperleukocytosis and preventing TLS.

Previously, we have published that pharmacological induction of oxidative stress causes anxiety-like behavior in rats and also is associated with hypertension in these animals. Here, we report that sub-chronic induction of oxidative stress via pharmacological induction leads to i) reduction in glyoxalase (GLO)-1 and glutathione reductase (GSR)-1 expression; ii) calpain mediated reduction of brain derived neurotrophic factor (BDNF) levels; iii) NFκB mediated upregulation of proinflammatory factors interleukin (IL)-6 and tumor necrosis factor (TNF)-α and elevated angiotensin (AT)-1 receptor levels in hippocampus, amygdala and locus coeruleus regions of the brain. Acute oxidative stress has opposite effects. We speculate that regulation of GLO1, GSR1, BDNF, NFκB and AT-1 receptor may contribute to anxiety-like behavior and hypertension in rats.

Carotid-cavernous fistulas (CCFs) are anomalous connections between the carotid circulation and the cavernous sinus, and may cause significant morbidity. Endovascular treatment of these lesions can be challenging if typical transvenous routes are inaccessible. We describe a case of a Barrow type D carotid-cavernous fistula in which transvenous embolization was attempted via the inferior petrosal sinus (IPS). No connection was found to the fistula, and the superior ophthalmic vein (SOV) was thrombosed. A novel direct percutaneous puncture of the IOV was performed with ultrasound guidance showing that this is a safe alternative route of CCF access and embolization when the IPS and SOV are inaccessible.

Exposure of rats to unpredictable, inescapable stress results in two distinct behaviors during subsequent escape testing. One behavior, suggestive of lack of stress resilience, is prolonged escape latency compared to non-stressed rats and is labeled learned helplessness (LH). The other behavior suggestive of stress resilience is normal escape latency and is labeled non-helpless (NH). This study examines the effects of unpredictable, inescapable tail-shock stress (TSS) on alpha(2)-adrenoceptor (α(2A)-AR) and corticotropin-releasing factor 1 receptor (CRF(1)-R) regulation as well as protein levels of G protein-coupled receptor kinase 3 (GRK3), GRK2, tyrosine hydroxylase (TH) plus carbonylated protein levels in locus coeruleus (LC), amygdala (AMG), cortex (COR) and striatum (STR). In NH rats, α(2A)-AR and CRF(1)-R were significantly down-regulated in LC after TSS. No changes in these receptor levels were observed in the LC of LH rats. GRK3, which phosphorylates receptors and thereby contributes to α(2A)-AR and CRF(1)-R down-regulation, was reduced in the LC of LH but not NH rats. GRK2 levels were unchanged. In AMG, GRK3 but not GRK2 levels were reduced in LH but not NH rats, and receptor regulation was impaired in LH rats. In STR, no changes in GRK3 or GRK2 levels were observed. Finally, protein carbonylation, an index of oxidative stress, was increased in the LC and AMG of LH but not NH rats. We suggest that reduced stress resilience after TSS may be related to oxidative stress, depletion of GRK3 and impaired regulation of α(2A)-AR and CRF(1)-R in LC.

Background: To describe modification of the sandwich technique to preserve flow in the hypogastric artery after endovascular repair of aortoiliac aneurysmal disease in patients with challenging anatomy. Methods and Results: The sandwich technique has been proposed as an option in patients with aortoiliac aneurysmal disease, in whom standard iliac branch device may not be technically feasible. We feel that even with the sandwich technique, there are issues with adequately treating these aneurysms in patients with short common iliac arteries with critical landing zones and in those with narrow-caliber external iliac arteries. We describe our experience with two patients we operated on using a modification of the originally described technique and their follow-up. Conclusions: The modification of the sandwich technique is a promising alternative technique that would be useful in situations where standard endovascular grafts cannot be used in patients with challenging anatomy.