Effects of ketamine on brain function during smooth pursuit eye movements

The uncompetitive NMDA receptor antagonist ketamine has been proposed to model symptoms of psychosis. Smooth pursuit eye movements (SPEM) are an established biomarker of schizophrenia. SPEM performance has been shown to be impaired in the schizophrenia spectrum and during ketamine administration in healthy volunteers. However, the neural mechanisms mediating SPEM impairments during ketamine administration are unknown. In a counter‐balanced, placebo‐controlled, double‐blind, within‐subjects design, 27 healthy participants received intravenous racemic ketamine (100 ng/mL target plasma concentration) on one of two assessment days and placebo (intravenous saline) on the other. Participants performed a block‐design SPEM task during functional magnetic resonance imaging (fMRI) at 3 Tesla field strength. Self‐ratings of psychosis‐like experiences were obtained using the Psychotomimetic States Inventory (PSI). Ketamine administration induced psychosis‐like symptoms, during ketamine infusion, participants showed increased ratings on the PSI dimensions cognitive disorganization, delusional thinking, perceptual distortion and mania. Ketamine led to robust deficits in SPEM performance, which were accompanied by reduced blood oxygen level dependent (BOLD) signal in the SPEM network including primary visual cortex, area V5 and the right frontal eye field (FEF), compared to placebo. A measure of connectivity with V5 and FEF as seed regions, however, was not significantly affected by ketamine. These results are similar to the deviations found in schizophrenia patients. Our findings support the role of glutamate dysfunction in impaired smooth pursuit performance and the use of ketamine as a pharmacological model of psychosis, especially when combined with oculomotor biomarkers. Hum Brain Mapp 37:4047–4060, 2016. © 2016 Wiley Periodicals, Inc .     

Race and Health Disparities in Patient Refusal of Surgery for Early-Stage Non-Small Cell Lung Cancer: A SEER Cohort Study

Introduction  

Several factors, including race, age, stage, comorbid conditions, social support, and socioeconomic status, have been linked to the likelihood of a patient having surgery for early-stage non-small cell lung cancer (NSCLC). The aim of the present study is to determine the influence of race and health disparities on refusal of recommended potentially curative surgery.     

The history of pituitary surgery for Cushing disease

Although he never performed a pituitary operation for the disease, Harvey Cushing was the first to describe and treat patients with Cushing disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas at autopsy in patients without premorbid endocrinopathy. They concluded that the adrenal gland was the cause of CD, which resulted in a 3-decade abandonment of pituitary surgery for CD. Jules Hardy in 1963 used the operating microscope to perform the first selective removal of an adrenocorticotropic hormone (ACTH)-secreting microadenoma, which established a pituitary cause and defined the modern treatment of CD. Subsequent reports by Hardy, Laws, and Wilson resulted in widespread acceptance of pituitary surgery for CD. Initial reluctance to operate on the pituitary for CD was multifaceted and included general uncertainty surrounding the etiology of Cushing syndrome as well as a lack of early surgical success, both due to the small size of ACTH-secreting adenomas. Selective removal of ACTH-secreting adenomas identified the source of CD and ended the delay in acceptance of pituitary surgery for CD.     

Sagittal spinopelvic parameters in children with achondroplasia: identification of 2 distinct groups

Imatinib mesylate has become the treatment of choice for gastrointestinal stromal tumors (GISTs) and has made a revolutionary impact on survival rates. Bone marrow necrosis is a very rare adverse event in malignant GIST. Bone metastases are also rarely encountered in the setting of this disease. The authors report on a patient with malignant GIST who developed a bone lesion, mimicking spinal metastasis on both MR imaging and FDG-PET/CT. Corpectomy and anterior fusion was performed, but the pathology report was consistent with bone marrow necrosis. Radiological and clinical similarities made the distinction between metastasis and bone marrow necrosis challenging for the treating physicians. Instead of radical surgical excision, more conservative methods such as percutaneous or endoscopic bone biopsies may be more useful for pathological confirmation, even though investigations such as MR imaging and FDG-PET/CT indicate metastatic disease.     

Biplanar flap reconstruction for pressure ulcers: experience in patients with immobility from chronic spinal cord injuries

BackgroundSurgical therapy for advanced-stage pressure ulcers recalcitrant to healing is a widely accepted practice. The present study examined the incidence of wound recurrence after reconstruction with fasciocutaneous versus combined (biplanar) muscle and fasciocutaneous flaps.MethodsA retrospective review identified 90 nonambulatory patients with spinal cord injury who underwent reconstruction for persistent decubitus ulcers from 2002 to 2008. Electronic medical records were surveyed for patient comorbidities and postoperative complications. Statistical methods included the Fisher exact test and the Mann–Whitney U test with a 2-sided P value of less than .05.ResultsAmong 90 patients reviewed, 33% (n = 30) received fasciocutaneous flaps and 66% (n = 60) underwent biplanar reconstruction. Comorbidities were the same between cohorts with the exception of a greater prevalence of diabetes in the biplanar group (27% vs 50%; P < .05). The incidence of recurrence for biplanar flaps (25%) was significantly lower than for fasciocutaneous reconstruction (53%; P < .01).ConclusionsBiplanar flap reconstruction should be considered for chronically immobilized patients at high risk for recurrent decubitus ulceration.     

Recurrence of kyphosis and its functional implications after surgical stabilization of dorsolumbar unstable burst fractures

Background contextTreatment of unstable burst fractures in the dorsolumbar spine still remains controversial. Surgical stabilization has been aimed to prevent long-term back pain and progression of deformity.PurposeThis study was aimed to analyze the degree of loss of correction of the angle of kyphosis with pedicle screw instrumentation in place and the components responsible for the recurrence of kyphosis after surgical stabilization of dorsolumbar A3 fractures and to assess the return of functional capacity in these patients.Study designRetrospective study.Patient sampleThis study involves 26 patients who had dorsolumbar unstable burst fractures (Arbeitsgemeinschaft für Osteosynthesefragen type A3).Outcome measuresRadiological assessment at injury, immediate postoperative period, and most recent follow-up along with functional assessment using short form 36 (SF-36) and return to work.MethodsAll the patients had posterior pedicle screw instrumentation without fusion for unstable dorsolumbar burst compression (A3) fractures. The mean follow-up period was 25.5 months. All of them had their fractures stabilized with Universal Spinal System (Synthes, Welwyn Garden City, UK) Fracture System. Serial standing lateral radiographs were taken from the immediate postoperative period to the most recent follow-up. The angle of kyphosis; the heights of the discs above and below the fractured vertebra; and the heights of the vertebral bodies above, at, and below the fractured level were measured. The height at each level was measured in three segments (anterior, middle, and posterior). The values were normalized to avoid discrepancies while comparing radiographs. The difference in the height of each segment measured between the immediate postoperative period and the most recent follow-up was computed.ResultsThe mean angle of kyphosis was 6.3±8.9 in the immediate postoperative period and 15.7±6.7 at the most recent follow-up (p<.001). The mean patient function score from SF-36 was 52.3%, and the mean pain score was 44.9%. There was no relationship to the loss of correction angle of kyphosis to the patient function score (r=0.06, p=.76) and the pain score (r=0.11, p=.58). The correlation between the corresponding difference in the height of each segment and the degree of loss of correction of the angle of kyphosis showed positive correlation to the decrease in the anterior and middle segment heights at the fractured vertebral level.ConclusionThere is a progressive loss of correction of the angle of kyphosis after posterior stabilization with instrumentation even without implant removal that mainly corresponds to the decrease in the anterior segment height of the fractured vertebral body.     

Gene Profiling of Human Adipose Tissue During Evoked Inflammation In Vivo

OBJECTIVE

Adipose inflammation plays a central role in obesity-related metabolic and cardiovascular complications. However, few human adipose-secreted proteins are known to mediate these processes. We hypothesized that microarray mRNA profiling of human adipose during evoked inflammation could identify novel adipocytokines.

RESEARCH DESIGN AND METHODS

Healthy human volunteers (n = 14) were treated with intravenous endotoxin (3 ng/kg lipopolysaccharide [LPS]) and underwent subcutaneous adipose biopsies before and after LPS. On Affymetrix U133Plus 2.0 arrays, adipose mRNAs modulated >1.5-fold (with P < 0.00001) were selected. SignalP 3.0 and SecretomeP 2.0 identified genes predicted to encode secreted proteins. Of these, 86 candidates were chosen for validation in adipose from an independent human endotoxemia protocol (N = 7, with 0.6 ng/kg LPS) and for exploration of cellular origin in primary human adipocytes and macrophages in vitro.

RESULTS

Microarray identified 776 adipose genes modulated by LPS; 298 were predicted to be secreted. Of detectable prioritized genes, 82 of 85 (96% [95% CI 90–99]) were upregulated (fold changes >1.0) during the lower-dose (LPS 0.6 ng/kg) validation study and 51 of 85 (59% [49–70]) were induced greater than 1.5-fold. Treatment of primary adipocytes with LPS and macrophage polarization to M1 proinflammatory phenotype increased expression by 1.5-fold for 58 and 73% of detectable genes, respectively.

CONCLUSIONS

We demonstrate that evoked inflammation of human adipose in vivo modulated expression of multiple genes likely secreted by adipocytes and monocytes. These included established adipocytokines and chemokines implicated in recruitment and activation of lymphocytes, adhesion molecules, antioxidants, and several novel genes with unknown function. Such candidates may represent biomarkers and therapeutic targets for obesity-related complications.Activation of innate and adaptive immunity is a crucial link between adiposity and its metabolic complications (1–4). In rodents, modulation of toll-like receptor-4 (5), tumor necrosis factor (TNF) receptors (6), chemokines, and downstream kinases (7) attenuate diet-induced obesity and insulin resistance. Further, cross talk between immune cells and adipocytes promotes an inflammatory, insulin-resistant state in obesity. A key initiating event in adipose inflammation is recruitment of T-lymphocytes (8,9) and monocyte/macrophages (10,11) with elaboration of inflammatory adipocytokines that modulate metabolic signaling (12–15). Despite experimental evidence in rodent models, most evidence supporting these concepts in humans derives from observational and correlative studies (16–18). Indeed, validated adipokines that mediate, or serve as biomarkers for, complications of human adiposity remain limited.Expression of inflammatory, insulin-signaling, and lipid genes are perturbed in adipose of obese humans (19–21). Recently, the in vitro secretome of subcutaneous and visceral primary human adipocytes was described and includes many unexplored proteins modulated during adipogenesis (1,22). Remarkably, less than half of genes found in the human subcutaneous adipocyte secretome were previously found in the murine 3T3-L1 preadipocyte secretome (22), underscoring the importance of studies in human tissue.Experimental human endotoxemia can provide unique insights into the relationship of inflammation to metabolic disturbance in man (23,24). Others and we have shown that endotoxemia induces acute metabolic, lipoprotein, and oxidant responses that resemble the chronic changes in insulin resistance and metabolic syndrome (25,26). Notably, endotoxemia induces adipose inflammation (27) with activation of several adipose inflammatory cascades, including cytokines, chemokines, and suppressor of cytokine signaling (SOCS) molecules (26) that attenuate insulin signaling and are implicated in obesity and type 2 diabetes (28).We applied microarray mRNA profiling of human adipose during endotoxemia to identify novel inflammation-induced adipose genes. We focused on genes predicted to be secreted and validated our findings in vivo through independent experiments of low-grade human inflammation. Finally, we identified in vitro the likely human adipose cellular source of these top candidates.     

Bilateral infraorbital nerve blocks decrease postoperative pain but do not reduce time to discharge following outpatient nasal surgery

Purpose

While infraorbital nerve blocks have demonstrated analgesic benefits for pediatric nasal and facial plastic surgery, no studies to date have explored the effect of this regional anesthetic technique on adult postoperative recovery. We designed this study to test the hypothesis that infraorbital nerve blocks combined with a standardized general anesthetic decrease the duration of recovery following outpatient nasal surgery.

Methods

At a tertiary care university hospital, healthy adult subjects scheduled for outpatient nasal surgery were randomly assigned to receive bilateral infraorbital injections with either 0.5% bupivacaine (Group IOB) or normal saline (Group NS) using an intraoral technique immediately following induction of general anesthesia. All subjects underwent a standardized general anesthetic regimen and were transported to the recovery room following tracheal extubation. The primary outcome was the duration of recovery (minutes) from recovery room admission until actual discharge to home. Secondary outcomes included average and worst pain scores, nausea and vomiting, and supplemental opioid requirements.

Results

Forty patients were enrolled. A statistically significant difference in mean [SD] recovery room duration was not observed between Groups IOB and NS (131 [61] min vs 133 [58] min, respectively; P = 0.77). Subjects in Group IOB did experience a reduction in average pain on a 0–100 mm scale (mean [95% confidence interval]) compared to Group NS (?11 [?21 to 0], P = 0.047), but no other comparison of secondary outcomes was statistically significant.

Conclusions

When added to a standardized general anesthetic, bilateral IOB do not decrease actual time to discharge following outpatient nasal surgery despite a beneficial effect on postoperative pain.     

Health related quality of life patterns in patients treated with interstitial prostate brachytherapy for localized prostate cancer--data from CaPSURE

PURPOSE: We measured the impact brachytherapy monotherapy (BMT) has on general and disease specific health related quality of life (HRQOL) compared to patients treated with radical prostatectomy (RP). MATERIALS AND METHODS: We studied 419 men with newly diagnosed prostate cancer who enrolled in CaPSURE (Cancer of the Prostate Strategic Urological Research Endeavor) data base whose primary treatment was brachytherapy monotherapy (92) or radical prostatectomy (327). The validated RAND 36-Item Health Survey and the UCLA Prostate Cancer Index were used to measure HRQOL before treatment and at 6-month intervals during the first 2 years after treatment. RESULTS: Patients treated with BMT or RP did not differ greatly in general HRQOL after treatment. Both treatment groups showed early functional impairment in most general domains with scores returning to or approaching baseline in most domains 18 to 24 months after treatment. Patients treated with BMT had significantly higher urinary function scores at 0 to 6 months after treatment (84.5, SD 18.7) than patients treated with RP (63.3, SD 26.6). Urinary bother scores at 0 to 6 months after treatment were not significantly different between patients treated with BMT (67.7, SD 31.2) and those treated with RP (67.4, SD 29.1). Both treatment groups had decreases in sexual function that did not return to pretreatment levels. CONCLUSIONS: Overall BMT and RP are well tolerated procedures that cause mild changes in general HRQOL. Disease specific HRQOL patterns are different in patients treated with BMT or RP. Baseline and serial HRQOL measurements after treatment can provide valuable information regarding expected quality of life outcome after treatment for localized prostate cancer.