Descriptive assessment of adverse events associated with midazolam-etomidate versus saline-etomidate in healthy hydromorphone premedicated dogs.

OBJECTIVES: To determine the frequency, severity and duration of adverse events including myoclonus, pain on injection, hypersalivation, regurgitation and apnoea after administration of midazolam or saline followed by etomidate in hydromorphone premedicated dogs. MATERIALS AND METHODS: Dogs undergoing elective dental prophylaxis or soft tissue surgeries were enrolled in this randomised trial. Dogs were premedicated with hydromorphone 0.1 mg/kg IV. Sixty seconds later, midazolam 0.3 mg/kg or saline at an equivalent volume was administered IV. Sixty seconds after that, etomidate 1.5 mg/kg IV was administered over 60 seconds. Additional doses of 0.5 mg/kg etomidate were administered until endotracheal intubation was successful. Observers were blinded to the treatment. Frequency, duration and a severity score of 0 to 3 were recorded for myoclonus, pain on injection, hypersalivation and regurgitation. Duration of apnoea and frequency of any additional complications was recorded. RESULTS: Forty variable breed healthy dogs were enrolled in the study. Myoclonus, pain on injection, regurgitation, hypersalivation, gagging, tachypnoea and pigmenturia occurred, respectively, in 10%, 40%, 0%, 15%, 35%, 25% and 5% of dogs in the saline group and 0%, 65%, 0%, 10%, 45%, 15% and 5% of dogs in the midazolam group. Apnoea occurred for 115 seconds (range 0 to 660 seconds) and 160 seconds (range 0 to 600 seconds) in the saline and midazolam groups, respectively. Two dogs developed pigmenturia. The trial was stopped early due to the occurrence of pigmenturia. CLINICAL SIGNIFICANCE: Due to early stopping of the trial, the predefined sample size was not reached. Further investigation is needed to determine if midazolam reduced the incidence of adverse events or improved the induction quality when combined with hydromorphone and etomidate.

Microglial contribution to synaptic uptake in the prefrontal cortex in schizophrenia.

Microglia in human post-mortem tissue in schizophrenia patients' brains engulf synaptic material, but not differently to age-matched non-neurological control brains. Also, schizophrenia brains display similar levels of microgliosis to control brains.

Fluctuating asymmetry of the normal facial skeleton.

The purpose of this study was to produce reliable estimations of fluctuating facial asymmetry in a normal population. Fifty-four computed tomography (CT) facial models of average-looking and symmetrical Chinese subjects with a class I occlusion were used in this study. Eleven midline landmarks and 12 pairs of bilateral landmarks were digitized. The repeatability of the landmark digitization was first evaluated. A Procrustes analysis was then used to measure the fluctuating asymmetry of each CT model, after all of the models had been scaled to the average face size of the study sample. A principal component analysis was finally used to establish the direction of the fluctuating asymmetries. The results showed that there was excellent absolute agreement among the three repeated measurements. The mean fluctuating asymmetry of the average-size face varied at each anthropometric landmark site, ranging from 1.0mm to 2.8mm. At the 95% upper limit, the asymmetries ranged from 2.2mm to 5.7mm. Most of the asymmetry of the midline structures was mediolateral, while the asymmetry of the bilateral landmarks was more equally distributed. These values are for the average face. People with larger faces will have higher values, while subjects with smaller faces will have lower values.

Complications following arthroscopic surgery of the hip: a systematic review of 36 761 cases.

AIMS: The number of patients undergoing arthroscopic surgery of the hip has increased significantly during the past decade. It has now become an established technique for the treatment of many intra- and extra-articular conditions affecting the hip. However, it has a steep learning curve and is not without the risk of complications. The purpose of this systematic review was to determine the prevalence of complications during and following this procedure. MATERIALS AND METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in designing this study. Two reviewers systematically searched the literature for complications related to arthroscopy of the hip. The research question and eligibility criteria were established a priori. Pertinent data were abstracted and analysed. RESULTS: We found 276 relevant studies with a total of 36 761 arthroscopies that met the inclusion criteria. The mean age of the patients was 36.7 years (1.7 to 70) and the mean body mass index was 25.7 kg/m2 (20.2 to 29.2). Femoroacetabular impingement and labral tears were the most common indications for the procedure. The total number of complications was 1222 (3.3%). Nerve injury (0.9%), mainly involving the pudendal and lateral femoral cutaneous nerves, and iatrogenic chondral and labral injury (0.7%), were the two most common complications. There were 58 major complications (0.2%), the most common being intra-abdominal extravasation of fluid, which was found in 13 cases (0.04%). There were three deaths (0.008%). CONCLUSION: Arthroscopic surgery of the hip is a procedure with a relatively low rate of complications, although some may be significant in this young cohort of patients. This study relied on the reported complications only and the results should be interpreted with caution. Cite this article: Bone Joint J 2017;99-B:1577-83.

Delineation of gliomas using radial metabolite indexing.

(1) H MRSI has demonstrated the ability to characterise and delineate brain tumours, but robust data analysis methods are still needed. In this study, we present an objective analysis method for MRSI data to delineate tumour abnormality regions. The presented method is a development of the choline-to-N-acetylaspartate index (CNI), which uses perpendicular distances in a choline versus N-acetylaspartate plot as a measure of abnormality. We propose a radial CNI (rCNI) method that uses the choline to N-acetylaspartate ratio directly as an abnormality measure. To avoid problems with small or zero denominators, we perform an arctangent transformation. CNI abnormality contours were evaluated using a z-score threshold of 2 (CNI2) and 2.5 (CNI2.5) and compared with rCNI2. Simulations modelling low-grade (LGG) and high-grade (HGG) gliomas with different tissue compartments and partial volume effects suggest improved specificity of rCNI2 (LGG 92%/HGG 91%) over CNI2 (LGG 69%/HGG 69%) and CNI2.5 (LGG 74%/HGG 75%), whilst retaining a similar sensitivity to both CNI2 and CNI2.5. Our simulation results also confirm a previously reported increase in specificity of CNI2.5 over CNI2 with little penalty in sensitivity. The analysis of MRSI data acquired from 10 patients with low-grade glioma at 3 T suggests a more robust delineation of the lesions using rCNI with respect to conventional imaging compared with standard CNI. Further analysis of 29 glioma datasets acquired at 1.5 T, together with previously published estimated tumour proportions, suggests that rCNI has higher sensitivity and specificity for the identification of abnormal MRSI voxels.

Neurologic melioidosis in an imported pigtail macaque (Macaca nemestrina).

Burkholderia pseudomallei is the cause of melioidosis in humans and other animals. Disease occurs predominately in Asia and Australia. It is rare in North America, and affected people and animals typically have a history of travel to (in human cases) or importation from (in animal cases) endemic areas. We describe the gross and histopathologic features and the microbiologic, molecular, and immunohistochemical diagnoses of a case of acute meningoencephalomyelitis and focal pneumonia caused by B. pseudomallei infection in a pigtail macaque that was imported from Indonesia to the United States for research purposes. This bacterium has been classified as a Tier 1 overlap select agent and toxin; therefore, recognition of pathologic features, along with accurate and timely confirmatory diagnostic testing, in naturally infected research animals is imperative to protect animals and personnel in the laboratory animal setting.

A quick guide to survey research.

Questionnaires are a very useful survey tool that allow large populations to be assessed with relative ease. Despite a widespread perception that surveys are easy to conduct, in order to yield meaningful results, a survey needs extensive planning, time and effort. In this article, we aim to cover the main aspects of designing, implementing and analysing a survey as well as focusing on techniques that would improve response rates.

RNAi screening identifies TAK1 as a potential target for the enhanced efficacy of topoisomerase inhibitors.

In an effort to develop strategies that improve the efficacy of existing anticancer agents, we have conducted a siRNA-based RNAi screen to identify genes that, when targeted by siRNA, improve the activity of the topoisomerase I (Top1) poison camptothecin (CPT). Screening was conducted using a set of siRNAs corresponding to over 400 apoptosisrelated genes in MDA-MB-231 breast cancer cells. During the course of these studies, we identified the silencing of MAP3K7 as a significant enhancer of CPT activity. Follow-up analysis of caspase activity and caspase-dependent phosphorylation of histone H2AX demonstrated that the silencing of MAP3K7 enhanced CPT-associated apoptosis. Silencing MAP3K7 also sensitized cells to additional compounds, including CPT clinical analogs. This activity was not restricted to MDA-MB-231 cells, as the silencing of MAP3K7 also sensitized the breast cancer cell line MDA-MB-468 and HCT-116 colon cancer cells. However, MAP3K7 silencing did not affect compound activity in the comparatively normal mammary epithelial cell line MCF10A, as well as some additional tumorigenic lines. MAP3K7 encodes the TAK1 kinase, an enzyme that is central to the regulation of many processes associated with the growth of cancer cells (e.g. NF- κB, JNK, and p38 signaling). An analysis of TAK1 signaling pathway members revealed that the silencing of TAB2 also sensitizes MDA-MB-231 and HCT-116 cells towards CPT. These findings may offer avenues towards lowering the effective doses of Top1 inhibitors in cancer cells and, in doing so, broaden their application.

An extended role for CT in the emergency diagnosis of malignant spinal cord compression.

AIM: To evaluate the usefulness of computed tomography (CT) for triaging between urgent transfer to a neurosurgical unit and delayed magnetic resonance imaging (MRI) in the local hospital. MATERIALS AND METHODS: Radiologists blinded to the MRI findings scored CT images from 1-5 using a novel grading system based on the degree of cord compression observed in 44 patients. Seventy separate levels were scored. The observers' CT scores were compared with the MRI findings. All scoring radiologists were specialist registrars at different stages of training. RESULTS: Agreement between CT and MRI scores for metastatic spinal cord compression (MSCC) were high with Cohen's weighted Kappa score 0.70 (p<0.001, 95% CI 0.65 to 0.75). CT has a sensitivity of 89% and specificity of 92% for MSCC. Half the false-positive and false-negative results came from a single junior radiologist who would not normally report CT or MRI studies unsupervised. The best CT-MRI agreement was from the most senior trainee radiologist. CONCLUSIONS: Spinal findings on routine staging whole-body CT combined with clinical findings are sufficient to determine which patients with MSCC can safely wait for MRI the next working day at the local hospital and those who need emergency transfer to a neurosurgical unit for MRI and possible surgical decompression.

Anaesthesia for caesarean section in a patient with Budd-Chiari syndrome and hepatopulmonary syndrome post liver transplantation.

Hepatopulmonary syndrome is characterised by hypoxaemia and intrapulmonary shunting in the presence of portal hypertension. It is uncommon in the obstetric population but may occur in patients with Budd-Chiari syndrome in the absence of severe liver dysfunction. We discuss the management of a primigravida with Budd-Chiari syndrome and persistent hepatopulmonary syndrome post liver transplantation. A literature review revealed only one report of a successful pregnancy in association with hepatopulmonary syndrome. We discuss its recognition in patients with liver disease and anaesthetic considerations in its presence.

The natural history of interferon-alpha2b-induced thyroiditis and its exclusivity in a cohort of patients with chronic hepatitis C infection.

BACKGROUND: Interferon-alpha2b (IFN-alpha2b) is well known to cause both hyper- and hypo-thyroidism. In the former, the commonest aetiology is thyroiditis. As there is no previous data to fully characterize the entity of IFN-related thyroiditis, the aim of this study is to document in detail its evolution in a cohort of hepatitis C patients treated with pegylated IFN-alpha2b and Ribavirin (RBV). METHODS: A prospective observational study was conducted in patients who developed thyroid diseases whilst receiving combination of pegylated IFN-alpha2b and RBV for hepatitis C. The patients were followed with monthly thyrotropin (TSH). Where TSH was undetectable, free tetra- (fT4) and tri-iodothyronine (fT3) were added. Anti-thyroperoxidase (TPO), anti-thyroglobulin (Tg) and thyroid stimulating immunoglobulin (TSI) levels were also performed at diagnosis, during and at the end of IFN therapy. All patients were assessed and followed up closely with monthly TSH, fT4 and fT3 levels until the completion, after 6 and 12 months of treatment. RESULTS: There were seven females and four males over a 30-month period. All patients were found to have thyroiditis. On average, the time to the development of thyroid disease was 10 weeks and duration of disease 9 weeks. All patients eventually recovered normal biochemical thyroid function although two required short-term supplementation. CONCLUSION: Thyroiditis was found exclusively in our patients. Both the hyper- and hypo-thyroid phase can be short lived, extreme and transient in nature which warrants strict monthly TSH monitoring. Careful follow-up of all patients is mandatory as complete recovery is expected.

Anaesthesia for caesarean section in a patient with Ehlers-Danlos syndrome associated with postural orthostatic tachycardia syndrome.

We report the use of regional anaesthesia for elective caesarean section in a primigravida with hypermobility type Ehlers-Danlos syndrome (type III) associated with postural orthostatic tachycardia syndrome. Single-shot spinal anaesthesia was performed after failed epidural anaesthesia. This genotype, although generally associated with fewer antenatal and peripartum complications, is more likely than other types to display dysautonomia and orthostatic intolerance. This requires careful management for delivery.

The protracted Holocene extinction of California's flightless sea duck (Chendytes lawi) and its implications for the Pleistocene overkill hypothesis.

Bones of the flightless sea duck (Chendytes lawi) from 14 archaeological sites along the California coast indicate that humans hunted the species for at least 8,000 years before it was driven to extinction. Direct (14)C dates on Chendytes bones show that the duck was exploited on the southern California islands as early as approximately 11,150-10,280 calendar years B.P., and on the mainland by at least 8,500 calendar years B.P. The youngest direct date of 2,720-2,350 calendar years B.P., combined with the absence of Chendytes bones from hundreds of late Holocene sites, suggests that the species was extinct by approximately 2,400 years ago. Although the extinction of Chendytes clearly resulted from human overhunting, its demise raises questions about the Pleistocene overkill model, which suggests that megafauna were driven to extinction in a blitzkrieg fashion by Native Americans approximately 13,000 years ago. That the extermination of Chendytes was so protracted and archaeologically visible suggests that, if the terminal Pleistocene megafauna extinctions were primarily the result of human exploitation, there should also be a long and readily detectable archaeological record of their demise. The brief window now attributed to the Clovis culture ( approximately 13,300-12,900 B.P.) seems inconsistent with an overhunting event.

Hispanic ethnicity, race and blood donation in the United States.

The aim of this study was to assess the hypothesis that blood donation rates vary with Hispanic ethnicity (family origin in Spanish-speaking countries) in addition to race in the United States. Lower blood donation rates have been reported among African Americans (AAs) compared with non-Hispanic European Americans (EAs). Adequate published reports on donation rates are not available for Hispanic Americans (HAs). Using data from a 2002 national survey, which included 4923 men and 7600 women aged 15-44 years with complete data, we tested the hypothesis using weighted bivariate and multivariate statistics. Among men aged 25-44 years, the percentage [95% confidence limits (95% CL)] with a history of blood donation since 1985 was similar at ages 25-34 years (46%, 42-49) and 35-44 years (41%, 37-45). It was highest in non-Hispanic EA (49%, 45-52%), intermediate in AA (35%, 30-40%) and lowest in HA (30%, 25-36%) (P < 0.001). Other variables significantly (P < 0.01) associated with history of blood donation in bivariate analyses were nativity (United States/other), education (<12/>or=12 years), poverty (<200%/>or=200% poverty limit) and married (yes/no). Variables that are not significantly associated were age, metropolitan residence (yes/no), receipt of public assistance (yes/no), current labour-force participation (yes/no) and religion raised. Compared with non-Hispanic EA, the adjusted odds ratios were essentially the same for Hispanics 0.66 (95% CL 0.47-0.92) and AAs 0.64 (95% CL 0.49-0.84). Only 34% of women had donated blood, but the association with race/ethnicity was similar. Similar patterns were also seen at ages 15-24 years. HAs and AAs have similar low blood donation rates compared with non-Hispanic EAs. The difference is not explained by sociodemographic variables.

Laparoscopic staging of pancreatic tumors induces increased invasive capacity in vitro.

INTRODUCTION: Laparoscopy and laparoscopic ultrasound have a well-defined role in staging patients with pancreatic malignancy. The effect of the hypoxic pneumoperitoneum induction on tumor biology is unknown. The authors investigated whether an in vitro pneumoperitoneum augments the invasive capacity of pancreatic tumors and elucidate a mechanism by which this may occur. METHODS: A pancreatic (PSN-1) adenocarcinoma cell line was exposed to an in vitro pneumoperitoneum (carbon dioxide (CO2) or helium) for a maximum of 2 h or left in normal growth conditions (control). Cells were nonenzymatically harvested and placed in invasion assays. These were performed over 72 h using Matrigel coated 8-mm Transwell filters and analyzed using MTS colorimetric assay. Gelatin zymography was employed to assess the level of matrix metalloproteases (MMP) 2 and 9 (gelatinase A and B) secretion. Expression of tissue inhibitor of metalloproteases 1 (TIMP-1) was assessed using ELISA (Biotrak). Inhibition of invasion assays was performed using a specific gelatinase inhibitor (MMPI; Calbiochem). RESULTS: The invasive capacity of pancreatic tumour cells is augmented versus control in both helium (p <0.05) and CO2 (p <0.001) groups. Concomitant significant upregulation of the gelatinase activity was demonstrated with both insufflants (p <0.05; 0.001, respectively). Enhanced invasion was attenuated by the addition of a specific gelatinase inhibitor (p <0.05). CONCLUSIONS: These results indicate the invasive capacity of pancreatic tumor cells is augmented by laparoscopic staging in vitro. This is in part mediated by increased gelatinase activity and may be attenuated by the addition of specific inhibitors.

Pneumoperitoneum augmented tumor invasiveness is abolished by matrix metalloproteinase blockade.

BACKGROUND: Certain surgical strategies, including Helium (He) and carbon dioxide (CO2) insufflation in laparoscopy, have been shown to induce a hypoxic environment. This may have a significant effect on the invasive capacity of tumor cells and may be a factor in the incidence of port-site metastases seen in patients following laparoscopic resection for malignancy. METHODS: A colon adenocarcinoma cell line (SW1222) was exposed to an in vitro pneumoperitoneum of CO2 or He at 3 mmHg or left in normal growth conditions (control). After a 4-hour exposure to an in vitro pneumoperitoneum, the ability of the cells to invade through 8.0-microm Transwell filters coated with Matrigel was analyzed by colorimetric MTS assay and by direct staining of the filters. The effect of the addition of a known blocker of matrix metalloproteinases (MMPs), 1,10-phenanthroline (1,10-P), was investigated. RESULTS: Cells exposed to an in vitro pneumoperitoneum demonstrate significantly increased invasive capacity compared to the control set, without loss of viability (He vs control, p <0.001; CO2 vs control, p <0.001). This augmented capacity is abolished by the addition of 1,10-P (p <0.01). CONCLUSION: Exposure of a colonic adenocarcinoma cell line to either a CO2 or He pneumoperitoneum causes an increase in tumor cell invasiveness, which is abolished by the presence of a known inhibitor of MMPs. This suggests that MMPs have an important role in the metastatic potential of tumors exposed to a hypoxic operative environment.