Efficient pulse sequence for multisection dual-repetition time MR image acquisition

A magnetic resonance imaging pulse sequence was developed in which multisection spin-echo image data are simultaneously acquired for two repetition time (TR) intervals (TR1 and TR2) in one imaging sequence. In a conventional multisection image at a single TR, the number of sections is limited to TR/TS, where TS is the readout time. With this new sequence, the number of sections that can be imaged at both TRs in one acquisition is equal to (TR1 + TR2)/(TS1 + TS2), where TS1 and TS2 may be different for the two TRs. Imaging time is equal to that for a single image at a TR of TR1 + TR2. Clinical images were obtained with the new sequence from 15 patients and compared with images acquired at the same TR/TE by means of standard multisection single-TR methods. Relative image quality was assessed by three radiologists in 37 comparisons. In general, the dual-TR results at the long TR were judged equivalent to those from a single-TR image. Dual-TR results at the short TR had a modest reduction in contrast, but in none of 15 cases were any pathologic features missed.     

A Translational Rodent Assay of Affective Biases in Depression and Antidepressant Therapy

The subjective measures used to study mood disorders in humans cannot be replicated in animals; however, the increasing application of objective neuropsychological methods provides opportunities to develop translational animal tasks. Here we describe a novel behavioral approach, which has enabled us to investigate similar affective biases in rodents. In our affective bias test (ABT), rats encounter two independent positive experiences—the association between food reward and specific digging substrate—during discrimination learning sessions. These are performed on separate days under either neutral conditions or during a pharmacological or affective state manipulation. Affective bias is then quantified using a preference test where both previously rewarded substrates are presented together and the rat''s choices recorded. The absolute value of the experience is kept consistent and all other factors are counterbalanced so that any bias at recall can be attributed to treatment. Replicating previous findings from studies in healthy volunteers, we observe significant positive affective biases following acute treatment with typical (fluoxetine, citalopram, reboxetine, venlafaxine, clomipramine) and atypical antidepressants (agomelatine, mirtazapine), and significant negative affective biases following treatment with drugs associated with inducing negative affective states in humans (FG7142, rimonabant, 13-cis retinoic acid). We also observed that acute psychosocial stress and environmental enrichment induce significant negative and positive affective biases, respectively, and provide evidence that these affective biases involve memory consolidation. The positive and negative affective biases induced in our test also mirror the antidepressant and pro-depressant effects of these drugs in patients suggesting our test has both translational and predictive validity. Our results suggest that cognitive affective biases could contribute to drug- or stress-induced mood changes in people and support the hypothesis that a cognitive neuropsychological mechanism contributes to antidepressant drug efficacy.     

Multidetector CT and histological features of benign mesenchymoma of the infratemporal space: a rare case report

Benign mesenchymoma is a soft tissue neoplasm composed of an admixture of two or more benign mesenchymal components in addition to fibrous tissue. A rare case of benign mesenchymoma of the infratemporal space in a 14-year-old boy is presented. In this case report we discuss the salient imaging and histopathological features of this rare entity.     

A Pharmacokinetic-Pharmacodynamic Study of Intravenous Midazolam and Flumazenil in Adult New Zealand White—Californian Rabbits (Oryctolagus cuniculus)

Flumazenil, a competitive GABA_Areceptor antagonist, is commonly used in rabbits to shorten sedation or postanesthetic recovery after benzodiazepine administration. However, no combined pharmacokinetic (PK) and pharmacodynamic (PD) data are available to guide its administration in this species. In a prospective, randomized, blinded, crossover study design, the efficacy of IV flumazenil (FLU; 0.05 mg/kg) or saline control (SAL; equal volume) to reverse the loss of righting reflex (LORR) induced by IV midazolam (1.2 mg/kg) was investigated in 15 New Zealand white rabbits (2.73 to 4.65 kg, 1 y old). Rabbits were instrumented with arterial (central auricular artery) and venous (marginal auricular vein) catheters. After baseline blood sampling, IV midazolam was injected (T0). Flumazenil or saline (FLU/SAL) was injected 30 s after LORR. Arterial blood samples were collected at 1 and 3 min after midazolam injection, and at 1, 3, 6, 10, 15, 21, 28, 36, 45 and 60 min after injection with flumazenil. Plasma samples for midazolam, 1-OH-midazolam and flumazenil were analyzed using high performance liquid chromatography-high-resolution mass spectrometry and the time to return of righting reflex (ReRR) was compared between groups (Wilcoxon test). FLU terminal half-life, plasma clearance and volume of distribution were 26.3 min [95%CI: 23.3 to 29.3], 18.74 mL/min/kg [16.47 to 21.00] and 0.63 L/kg [0.55 to 0.71], respectively. ReRR was 25 times faster in rabbits treated with FLU (23 [8 to 44] s) compared with SAL (576 [130 to 1141] s; 95%CI [425 to 914 s]). Return of sedation (lateral recumbency) occurred in both groups (7/13 in FLU; 12/13 in SAL) with return of LORR in a few animals (4/13 in FLU; 7/13 in SAL) at 1540 [858 to 2328] s. In the population and anesthesia protocol studied, flumazenil quickly and reliably reversed sedation induced by midazolam injection. However, the potential return of sedation after flumazenil administration warrants careful monitoring in the recovery period.

Benzodiazepines (BZD) are a class of sedatives-hypnotics commonly used in exotic companion and laboratory animals (birds, reptiles, and small mammals).^10,18 Their mechanism of action is mediated by enhancing γ-aminobutyric acid (GABA) affinity for the GABA_A receptor, and results in sedation, anxiolysis, and muscle relaxation with minimal cardiorespiratory depression.¹⁷ The short-acting BZD, midazolam, is frequently used in rabbits as a sole agent, or in a premedication combination.^11,23,24 The ability to deliver midazolam by the intramuscular route (in contrast to diazepam) is useful in rabbits, as their temperament often means that sedation is required for noninvasive procedures such as radiography or intravenous catheterization.¹¹The increasing popularity of rabbits, both as pets and in research, has created a greater demand for rabbit anesthesia.¹⁴ Unfortunately, the risk of perianesthetic mortality remains higher in rabbits as compared with dogs or cats, with the majority of deaths occurring during the recovery period.^12,34 This tendency toward death during recovery is likely multifactorial, with possible causative factors including the continued depressive effects of sedative and anesthetic drugs during recovery, a period when physiologic monitoring and surveillance is frequently decreased.¹² Therefore, shortening the recovery period through pharmacological antagonism of drugs is an attractive approach that has already shown benefits in other animals and in humans.^26,30Flumazenil (FLU) is a selective GABA_A receptor antagonist that antagonizes the clinical effects of midazolam through competitive inhibition at the benzodiazepine allosteric site of the GABA_A receptor.³¹ Its use reduces both recovery and discharge times after benzodiazepine sedation in humans.³⁹ However, the potential for return of sedation after FLU antagonism has been reported.^7,21,39 The available literature on the use of FLU in rabbits is very limited, with the only data found in reports that used considerable variations in dose (0.02 to 0.1 mg/kg IV, IM or SC).^5,16,44 Furthermore, the quality and duration of recovery and the potential for resedation, is rarely described or quantified, making the frequent use of FLU in clinics largely anecdotal rather than evidence-based.The objectives of this study were to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of FLU and midazolam in rabbits, including the risk of resedation after FLU administration. A secondary objective was to assess the degree of sedation using a modified sedation scale in rabbits. Our hypotheses were that: 1) PK of FLU in rabbits will allow a dose of 0.05 mg/kg to fully and safely reverse the sedative effects of midazolam; and 2) The modified sedation scale will allow differentiation of sedated and unsedated rabbits.     

Management of adult Langerhans cell histiocytosis based on the characteristic clinical features

To find out the most appropriate management, clinical features of 18 cases of adult multisystem langerhans cell histiocytosis (LCH) have been analyzed. The patients comprising of 9 males and 9 females were median age of 36 years, ranging from 18-53 years at diagnosis. Regarding the initial symptoms, 7 patients (2 males and 5 females) showed central diabetes insipidus (CDI) and other endocrine symptoms with thickened pituitary stalk or a mass at the hypothalamic region. Additional 2 patients initiated the disease with CDI with no immediate diagnosis. In the remaining patients, the disease begun with single (n = 3) or multiple (n = 1) spinal bone lesion(s) in 4 patients (all males), with multiple bone lesions in 3 patients (1 male and 2 females), with single skull lesion in one female patient and with ambiguous symptoms including hypothyroidism in the remaining one male patient. We also recognized the correlation between pregnancy/childbirth and LCH in 4 patients. In terms of treatment, 9 patients received systemic immuno-chemotherapy alone, of which the majority received vinblastine-based chemotherapy while 4 received 2-chlorodeoxyadenosine. Five had a combination of immuno-chemotherapy with surgical resection or radiotherapy, 2 had immunotherapy alone, 2 had surgical resection followed by observation alone to date. Three patients received hematopoietic stem cell transplantation after extensive chemotherapy. In terms of outcome, 15 patients are alive (9 with active disease, 6 without active disease), with a median of 66 mo (range 17-166 mo), two died of disease while the remaining 1 lost to follow-up. Based on these results, we think that early diagnosis and rapid introduction of appropriate treatment are essential, in order to overcome the problems relevant to adult LCH.     

Recombinant human erythropoietin ameliorated endothelial dysfunction and macrophage infiltration by increasing nitric oxide in hypertensive 5/6 nephrectomized rat aorta

Recombinant human erythropoietin (rHuEPO), used clinically for renal anemia, reportedly exhibits pleiotropic properties in various tissues. To test whether it ameliorates vascular injury, rHuEPO (75U/kg) was administered subcutaneously every 3days for 10days to 5/6 nephrectomized hypertensive rats (5/6Nx) treated with 1% NaCl. rHuEPO had no effect on increased systolic blood pressure or decreased hematocrit values, but normalized levels of proteinuria and creatinine clearance. Vasodilation in response to acetylcholine in the aortic ring was impaired in the 5/6Nx, and improved by treatment with rHuEPO. Immunohistochemical analysis revealed that the infiltration of adventitial areas by macrophages and expression of osteopontin were enhanced in the 5/6Nx aorta and the overexpression was suppressed by rHuEPO. rHuEPO also attenuated medial hyperplasia. Akt signaling was activated by the increased expression of phosphorylated Akt and GSK-3β in aorta from rHuEPO-treated 5/6Nx. rHuEPO restored plasma NOx (NO(2)(-)+NO(3)(-)) levels and endothelial nitric oxide synthase (eNOS) content in the 5/6Nx aorta. Treatment with an eNOS substrate, l-arginine, which caused a similar increase in plasma NOx levels as the rHuEPO treatment, resulted in a normalization of endothelial dysfunction and vascular inflammation. These results suggest that a low dose of rHuEPO exerted vasoprotective effects in rats with hypertensive renal failure.     

The effect of hypercapnia and hypertension on cerebral oxygen balance during one-lung ventilation for lung surgery during propofol anesthesia

Study objectiveTo investigate whether jugular bulb venous oxygen saturation (SjO₂) values increased with induced hypercapnia or induced hypertension during propofol-based anesthesia for one-lung ventilation (OLV).DesignProspective clinical study.SettingOperating room at University hospital.Participants15 adult patients scheduled for elective thoracic procedures in the lateral position.InterventionsGeneral anesthesia was maintained with propofol combined with epidural anesthesia. During OLV, hypercapnia (PaCO₂ = 50 mmHg) and hypertension (20% increase in mean arterial pressure) were applied.MeasurementsSjO2 values were measured.Main resultsWith hypercapnia, SjO₂ values increased 30 ± 18% (from 54.3 ± 8.8% to 69.3 ± 6.3%). With hypertension, SjO₂ values were increased by 9 ± 18% (from 54.4 ± 9.0% to 58.5 ± 8.8%). These changes were significantly different. No significant differences regarding SaO₂ were observed during OLV in the experimental period.ConclusionHypercapnia, not hypertension, significantly improved cerebral oxygen balance without observed side effects during propofol anesthesia.