Search

Acute exercise induced compartment syndrome is a rare clinical diagnosis with serious long-term ramifications if not diagnosed in a timely fashion. We present a case of acute exercise induced compartment syndrome of the right lower extremity in a 22-year-old active-duty man that occurred during a physical fitness assessment. He was treated with a two incision four compartment fasciotomy, however required debridement of muscle from the anterior compartment on subsequent washouts of the wound that led to significant foot drop postoperatively. We reviewed the literature for published cases of acute exercise induced compartment syndrome and provide some information from the 47 patients identified in our review. This case highlights a unique pathology for which military providers should have a strong index of suspicion. It additionally stresses the importance of adequate hydration and musculoskeletal conditioning in the setting of military fitness assessments.

This manuscript aims to determine if there is a difference in performance outcomes after initial training with either animals or simulators. Volunteers without prior experience performing emergency procedures were randomly assigned to receive training in cricothyroidotomy on either a pig model or on an artificial simulator. Volunteers were given identical lectures and trained to proficiency. Two weeks after training, trainees were tested using human cadavers as to their performance with time, incision size, incision start location, initial placement attempt, and final accuracy. Overall success rate of the animal-trained group was 64 per cent and in the artificial simulator group, 73 per cent ( P = 0.431). Median time to completion in the animal group and artificial simulator group was 143 s and 105 s ( P = 0.482), and incision lengths 4.0 cm and 3.2 cm ( P = 0.173), respectively. Accuracy of initially attempted incision placement and final cricothyroidotomy tube placement was also compared. Initially attempted site accuracy in the animal-trained group was 93 per cent and correct final position 79 per cent, and in the artificial group, 100 per cent ( P = 0.452) and 88 per cent ( P = 0.782), respectively. There was no statistically significant, objective difference in any metric between animal- and simulator-trained groups after cricothyroidotomy training. For initial training, there is no objective benefit of animal training.

The objective of this study is to compare post-training self-efficacy between artificial simulators and live animal training for the performance of emergency medical procedures. Volunteer airmen of the 81st Medical Group, without prior medical procedure training, were randomly assigned to two experimental arms consisting of identical lectures and training of diagnostic peritoneal lavage, thoracostomy (chest tube), and cricothyroidotomy on either the TraumaMan (Simulab Corp., Seattle, Washington) artificial simulator or a live pig (Sus scrofa domestica) model. Volunteers were given a postlecture and postskills training assessment of self-efficacy. Twenty-seven volunteers that initially performed artificial simulator training subsequently underwent live animal training and provided assessments comparing both modalities. The results were first, postskills training self-efficacy scores were significantly higher than postlecture scores for either training mode and for all procedures (p0.0001). Second, post-training self-efficacy scores were not statistically different between live animal and artificial simulator training for diagnostic peritoneal lavage (p = 0.555), chest tube (p = 0.486), and cricothyroidotomy (p = 0.329). Finally, volunteers undergoing both training modalities indicated preference for live animal training (p0.0001). We conclude that artificial simulator and live animal training produce equivalent levels of self-efficacy after initial training, but there is a preference in using a live animal model to achieve those skills.

Spontaneous pneumothorax is a commonly encountered problem in the Emergency Department. Patients are often treated without further investigation for an underlying etiology. We present a patient who was unable to completely resolve a pneumothorax and was found to have lymphangioleiomyomatosis (LAM), a rare cystic lung disease. In the past, LAM was difficult to diagnose and had a mortality of 100% after 10 years, but now there is a 71% survival after 10 years. Recent research has led to increased characterization of the pathology and radiographic findings. This article briefly presents the case and discusses the etiology, diagnosis, and treatment of LAM.

APPL1 is an adaptor protein that plays a critical role in regulating adiponectin and insulin signaling. However, how APPL1 is regulated under normal and pathological conditions remains largely unknown. In this study, we show that APPL1 undergoes phosphorylation at Ser(430) and that this phosphorylation is enhanced in the liver of obese mice displaying insulin resistance. In cultured mouse hepatocytes, APPL1 phosphorylation at Ser(430) is stimulated by phorbol 12-myristate 13-acetate, an activator of classic PKC isoforms, and by the endoplasmic reticulum (ER) stress inducer, thapsigargin. Overexpression of wild-type but not dominant negative PKCα increases APPL1 phosphorylation at Ser(430) in mouse hepatocytes. In addition, suppressing PKCα expression by shRNA in hepatocytes reduces ER stress-induced APPL1 phosphorylation at Ser(430) as well as the inhibitory effect of ER stress on insulin-stimulated Akt phosphorylation. Consistent with a negative regulatory role of APPL1 phosphorylation at Ser(430) in insulin signaling, overexpression of APPL1(S430D) but not APPL1(S430A) impairs the potentiating effect of APPL1 on insulin-stimulated Akt phosphorylation at Thr(308). Taken together, our results identify APPL1 as a novel target in ER stress-induced insulin resistance and PKCα as the kinase mediating ER stress-induced phosphorylation of APPL1 at Ser(430).

Patellar tendon rupture is a rare occurrence usually associated with chronic degeneration within the tendon, systemic illness, and fluoroquinolone therapy as mentioned previously. However in healthy adults, overweight men in their 3rd or 4th decade of life may be at increased risk when partaking in athletic activities, especially jumping activities. Patella alta is a key finding on physical exam and on radiographs as was evident in our case. Imaging can also be performed with ultrasound and MRI to confirm tendon rupture and rule out other concurrent injuries. Prompt surgical management and early rehabilitation are key to regaining normal function of the extensor mechanism. Preventive medicine education may be important for those at increased risk of injury.

Clinical, epidemiological, and biochemical studies have highlighted the role of obesity-induced insulin resistance in various metabolic diseases. However, the underlying molecular mechanisms remain to be established. In the present study, we show that palmitate-induced serine phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1) negatively regulates insulin signaling. PDK1-mediated Akt phosphorylation at Thr308 in the activation loop is reduced in C2C12 myotubes treated with palmitate or overexpressing protein kinase C theta (PKCtheta), a kinase that has been implicated in hyperlipidemia-induced insulin resistance. Palmitate treatment also inhibited platelet-derived growth factor-stimulated Akt phosphorylation, suggesting that the inhibition could occur at a site independent of IRS1/2. The inhibitory effect of palmitate on PDK1 and Akt was diminished in PKCtheta-deficient mouse embryonic fibroblasts (MEFs) by treating C2C12 myotubes with PKCtheta pseudosubstrates. In vivo labeling studies revealed that PDK1 undergoes palmitate-induced phosphorylation at two novel sites, Ser504 and Ser532. Replacing Ser504/532 with alanine disrupted PKCtheta-catalyzed PDK1 phosphorylation in vitro and palmitate-induced PDK1 phosphorylation in cells. PDK1-deficient MEFs transiently expressing PDK1S504A/S532A but not PDK1S504E/S532D showed increased basal and insulin-stimulated Akt phosphorylation at Thr308 when compared with MEFs expressing wild-type PDK1. Taken together, our results identify PDK1 as a novel target in free fatty acid-induced insulin resistance and PKCtheta as the kinase mediating the negative regulation.

3-Phosphoinositide-dependent protein kinase-1 (PDK1) mediates phosphorylation and activation of members of the AGC protein kinase family and plays an essential role in insulin signaling and action. However, whether and how PDK1 activity is regulated in cells remains largely uncharacterized. In the present study, we show that PDK1 undergoes insulin-stimulated and phosphatidylinositol 3-kinase-dependent phosphorylation at Ser244 in the activation loop and at a novel site: Ser163 in the hinge region between the two lobes of the kinase domain. Sequence alignment studies revealed that the residue corresponding to Ser163 of PDK1 in all other AGC kinases is glutamate, suggesting that a negative charge at this site may be important for PDK1 function. Replacing Ser163 with a negatively charged residue, glutamate, led to a 2-fold increase in PDK1 activity. Molecular modeling studies suggested that phosphorylated Ser163 may form additional hydrogen bonds with Tyr149 and Gln223. In support of this, mutation of Tyr149 to Ala is sufficient to reduce PDK1 activity. Taken together, our results suggest that PDK1 phosphorylation of Ser163 may provide a mechanism to fine-tune PDK1 activity and function in cells.

Phosphorylation of Thr(308) in the activation loop and Ser(473) at the carboxyl terminus is essential for protein kinase B (PKB/Akt) activation. However, the biochemical mechanism of the phosphorylation remains to be characterized. Here we show that expression of a constitutively active mutant of mouse 3-phosphoinositide-dependent protein kinase-1 (PDK1(A280V)) in Chinese hamster ovary cells overexpressing the insulin receptor was sufficient to induce PKB phosphorylation at Thr(308) to approximately the same extent as insulin stimulation. Phosphorylation of PKB by PDK1(A280V) was not affected by treatment of cells with inhibitors of phosphatidylinositol 3-kinase or by deletion of the pleckstrin homology (PH) domain of PKB. C(2)-ceramide, a cell-permeable, indirect inhibitor of PKB phosphorylation, did not inhibit PDK1(A280V)-catalyzed PKB phosphorylation in cells and had no effect on PDK1 activity in vitro. On the other hand, co-expression of full-length protein kinase C-related kinase-1 (PRK1/PKN) or 2 (PRK2) inhibited PDK1(A280V)-mediated PKB phosphorylation. Replacing alanine at position 280 with valine or deletion of the PH domain enhanced PDK1 autophosphorylation in vitro. However, deletion of the PH domain of PDK1(A280V) significantly reduced PDK1(A280V)-mediated phosphorylation of PKB in cells. In resting cells, PDK1(A280V) localized in the cytosol and at the plasma membrane. However, PDK1(A280V) lacking the PH domain localized predominantly in the cytosol. Taken together, our findings suggest that the wild-type PDK1 may not be constitutively active in cells. In addition, activation of PDK1 is sufficient to phosphorylate PKB at Thr(308) in the cytosol. Furthermore, the PH domain of PDK1 may play both positive and negative roles in regulating the in vivo function of the enzyme. Finally, unlike the carboxyl-terminal fragment of PRK2, which has been shown to bind PDK1 and allow the enzyme to phosphorylate PKB at both Thr(308) and Ser(473), full-length PRK2 and its related kinase PRK1/PKN may both play negative roles in PKB-mediated downstream biological events.