Serum adipocyte fatty acid-binding protein in the critically ill

Sepsis due to unabated inflammation is common. Increased production of pro-inflammatory cytokines, free radicals, and eicosanoids has been detected in sepsis and other critical illnesses but could also be due to decreased synthesis and release of anti-inflammatory molecules. Increased serum adipose-fatty acid-binding protein (A-FABP) levels can cause insulin resistance and have been reported in the critically ill, serve as a marker of prognosis, and thus link metabolic homeostasis and inflammation. A-FABP can be linked to the expression of Toll-like receptors, macrophage activation, synthesis and release of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, activation of cyclooxygenase 2 (COX-2) expression, and eicosanoid synthesis, events that can cause insulin resistance and initiation and progression of inflammation and sepsis. Unsaturated fatty acids and their anti-inflammatory products, such as lipoxins, resolvins, and protectins, may suppress A-FABP expression, inhibit macrophage and COX-2 activation, and decrease production of pro-inflammatory cytokines and ultimately could lead to a decrease in insulin resistance and resolution of inflammation and recovery from sepsis. Serial measurement of these pro- and anti-inflammatory molecules and correlation of their levels to the progression to or recovery from (or both) sepsis and other inflammatory processes may form a new approach to predict prognosis in inflammatory conditions and eventually could lead to the development of new therapeutic strategies.     

Role of the dorsolateral pontine nucleus in short-term adaptation of the horizontal vestibuloocular reflex

The dorsolateral pontine nucleus (DLPN) is a major component of the cortico-ponto-cerebellar pathway that carries signals essential for smooth pursuit. This pathway also carries visual signals that could play a role in visually guided motor learning in the vestibular ocular reflex (VOR). However, there have been no previous studies that tested this possibility directly. The aim of this study was to determine the potential role of the DLPN in short-term VOR gain adaptation produced by viewing a scene through lenses placed in front of both eyes. In control experiments, adaptation of VOR gain was achieved by sinusoidal rotation (0.2 Hz, 30 degrees /s) for 2 h while the monkey viewed a stationary visual surround through either magnifying (x2) or minifying (x0.5) lenses. This led to increases (23-32%) or decreases (22-48%) of VOR gain as measured in complete darkness (VORd). We used injections of muscimol, a potent GABA(A) agonist (0.5 microl; 2%), to reversibly inactivate the DLPN, unilaterally, in three monkeys. After DLPN inactivation, initial acceleration of ipsilateral smooth-pursuit was reduced by 35-68%, and steady-state gain was reduced by 32-61%. Despite these significant deficits (P < 0.01) in ipsilesional smooth pursuit, the VOR during lens viewing was similar to that measured in preinjection control experiments. Similarly, after 2 h of adaptation, VORd gain was not significantly different (P > 0.61) from control adaptation values for either ipsi- or contralesional directions of head rotation. This was the case even though a stable ipsilesional smooth pursuit deficit persisted throughout the full adaptation period. Our results suggest that visual error signals for short-term adaptation of the VOR are derived from sources other than the DLPN perhaps including other basilar pontine nuclei and the accessory optic system.     

Evaluation of autologous bone marrow in wound healing in animal model: a possible application of autologous stem cells

A study was conducted to evaluate the potential of autologous bone marrow-derived cells in comparison with buffy coat of autologous blood for rapid cutaneous wound healing in rabbit model. Three square full-thickness skin excisional wounds were created in 15 selected experimental animals (rabbit) divided randomly into three groups. The wound was treated with autologous bone marrow cells in plasma (group 1), buffy coat of blood in plasma (group 2) and autologous plasma as control (group 3). Wounds were observed for 30 days for granulation tissue formation, biochemical, histomorphological and histochemical evaluation. In this study, granulation tissue appeared significantly lesser in wounds of group 3 animals followed by group 2 and 1 animals. Neovascularisation, granulation tissue formation, denser, thicker and better arranged collagen fibres, reticulin fibres and elastin fibres formation was more in group 1 as compared with other groups. It was concluded that the application of bone marrow-derived nucleated cells into the wound margins resulted in early and significantly faster rate of complete healing as compared with buffy coat of autologous blood and autologous plasma (control). This approach may be beneficial in various surface wounds that heal at a slower rate and recommended for healing of various complicated wound in future.     

Synchronous Tricompartmental Benign CNS Tumors with Tonsillar Herniation, Cervicodorsal Syringomyelia and Hydrocephalus

In this study, three primary central nervous system tumors of different histological cell types occurring together without neurofibromatosis are reported. These included a sellar pituitary adenoma with apoplexy, a large torculo-tentorial meningioma in the posterior fossa, and a cervical spinal intramedullary schwannoma. Displacement of primitive multipotent cells in different central nervous system compartments or the oncogenic effects of activated signaling of growth factor receptors are the proposed pathophysiological mechanisms for the simultaneous genesis of different types of tumors. There was associated tonsillar herniation, cervicodorsal syringomyelia, and hydrocephalus. The radiological features and treatment strategy of these rare synchronous tumors are highlighted.     

Free radical scavenging alleviates the biomechanical impairment of gamma radiation sterilized bone tissue.

Terminal sterilization of bone allografts by gamma radiation is often essential prior to their clinical use to minimize the risk of infection and disease transmission. While gamma radiation has efficacy superior to other sterilization methods it also impairs the material properties of bone allografts, which may result in premature clinical failure of the allograft. The mechanisms by which gamma radiation sterilization damages bone tissue are not well known although there is evidence that the damage is induced via free radical attack on the collagen. In the light of the existing literature, it was hypothesized that gamma radiation induced biochemical damage to bone's collagen that can be reduced by scavenging for the free radicals generated during the ionizing radiation. It was also hypothesized that this lessening of the extent of biochemical degradation of collagen will be accompanied by alleviation in the extent of biomechanical impairment secondary to gamma radiation sterilization. Standardized tensile test specimens machined from human femoral cortical bone and specimens were assigned to four treatment groups: control, scavenger treated-control, irradiated and scavenger treated-irradiated. Thiourea was selected as the free radical scavenger and it was applied in aqueous form at the concentration of 1.5 M. Monotonic and cyclic mechanical tests were conducted to evaluate the mechanical performance of the treatment groups and the biochemical integrity of collagen molecules were assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native mechanical properties of bone tissue did not change by thiourea treatment only. The effect of thiourea treatment on mechanical properties of irradiated specimens were such that the post-yield energy, the fracture energy and the fatigue life of thiourea treated-irradiated treatment group were 1.9-fold, 3.3-fold and 4.7-fold greater than those of the irradiated treatment group, respectively. However, the mechanical function of thiourea treated and irradiated specimens was not to the level of unirradiated controls. The damage occurred through the cleavage of the collagen backbone as revealed by SDS PAGE analysis. Irradiated specimens did not exhibit a noteworthy amount of intact alpha-chains whereas those irradiated in the presence of thiourea demonstrated intact alpha-chains. Results demonstrated that free radical damage is an important pathway of damage, caused by cleaving the collagen backbone. Blocking the activity of free radicals using the scavenger thiourea reduces the extent of damage to collagen, helping to maintain the mechanical strength of sterilized tissue. Therefore, free radical scavenger thiourea has the potential to improve the functional life-time of the allograft component following transplantation.     

Morbidity and Mortality After Gastrectomy: Identification of Modifiable Risk Factors

Background

Morbidity after gastrectomy remains high. The potentially modifiable risk factors have not been well described. This study considers a series of potentially modifiable patient-specific and perioperative characteristics that could be considered to reduce morbidity and mortality after gastrectomy.

Methods

This retrospective cohort study includes adults in the ACS NSQIP PUF dataset who underwent gastrectomy between 2011 and 2013. Sequential multivariable models were used to estimate effects of clinical covariates on study outcomes including morbidity, mortality, readmission, and reoperation.

Results

Three thousand six hundred and seventy-eight patients underwent gastrectomy. A majority of patients had distal gastrectomy (N?=?2,799, 76.1 %) and had resection for malignancy (N?=?2,316, 63.0 %). Seven hundred and ninety-eight patients (21.7 %) experienced a major complication. Reoperation was required in 290 patients (7.9 %). Thirty-day mortality was 5.2 %. Age (OR?=?1.01, 95 % CI?=?1.01–1.02, p?=?0.001), preoperative malnutrition (OR?=?1.65, 95 % CI?=?1.35–2.02, p?<?0.001), total gastrectomy (OR?=?1.63, 95 % CI?=?1.31–2.03, p?<?0.001), benign indication for resection (OR?=?1.60, 95 % CI?=?1.29–1.97, p?<?0.001), blood transfusion (OR?=?2.57, 95 % CI?=?2.10–3.13, p?<?0.001), and intraoperative placement of a feeding tubes (OR?=?1.28, 95 % CI?=?1.00–1.62, p?=?0.047) were independently associated with increased risk of morbidity. Association between tobacco use and morbidity was statistically marginal (OR?=?1.23, 95 % CI?=?0.99–1.53, p?=?0.064). All-cause postoperative morbidity had significant associations with reoperation, readmission, and mortality (all p?<?0.001).

Conclusions

Mitigation of perioperative risk factors including smoking and malnutrition as well as identified operative considerations may improve outcomes after gastrectomy. Postoperative morbidity has the strongest association with other measures of poor outcome: reoperation, readmission, and mortality.