Tip-of-the-Iceberg Fractures: Small Fractures That Mean Big Trouble.

Objective: Several small and seemingly unimportant fractures are associated with other more serious injuries, usually to adjacent soft tissues. The purpose of this article is to discuss 11 of these injuries, in each case describing the fracture (the tip) and the injuries that lie beneath the surface (the iceberg).

Conclusion: Some fractures should be considered analogous to the tip of an iceberg.

Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway.

The Hippo pathway is involved in the regulation of contact inhibition of proliferation and responses to various physical and chemical stimuli. Recently, several upstream negative regulators of Hippo signaling, including epidermal growth factor receptor ligands and lysophosphatidic acid, have been identified. We show that fibronectin adhesion stimulation of focal adhesion kinase (FAK)-Src signaling is another upstream negative regulator of the Hippo pathway.

Does correcting astigmatism with toric lenses improve driving performance?

Purpose: Driving is a vision-based activity of daily living that impacts safety. Because visual disruption can compromise driving safety, contact lens wearers with astigmatism may pose a driving safety risk if they experience residual blur from spherical lenses that do not correct their astigmatism or if they experience blur from toric lenses that rotate excessively. Given that toric lens stabilization systems are continually improving, this preliminary study tested the hypothesis that astigmats wearing toric contact lenses, compared with spherical lenses, would exhibit better overall driving performance and driving-specific visual abilities.

Regulation of L-type calcium channel by phospholemman in cardiac myocytes.

We evaluated whether phospholemman (PLM) regulates L-type Ca(2+) current (ICa) in mouse ventricular myocytes. Expression of α1-subunit of L-type Ca(2+) channels between wild-type (WT) and PLM knockout (KO) hearts was similar. Compared to WT myocytes, peak ICa (at -10 mV) from KO myocytes was ~41% larger, the inactivation time constant (τ(inact)) of ICa was ~39% longer, but deactivation time constant (τ(deact)) was similar.

Apoplexy of pituitary adenomas: the perfect storm.

Object: Pituitary adenomas occasionally undergo infarction, apoplexy, which often destroys much of the tumor. It is well known that apoplexy can be precipitated by several acute factors, including cardiac surgery, other types of surgery, trauma, insulin infusion, and stimulation with administration of hypothalamic releasing factors.

Methods: The prior focus on mechanisms underlying pituitary apoplexy has been on these acute events.

Different imaging characteristics of concurrent pituitary adenomas in a patient with Cushing's disease.

We report a patient with Cushing's disease (CD) and two pituitary adenomas that demonstrated different imaging characteristics and therefore suggest an alternative imaging strategy for these patients. A 42-year-old woman presented with signs and symptoms of CD. Biochemical evaluation confirmed hypercortisolemia and suggested CD.

Sorting nexin 5 and dopamine d1 receptor regulate the expression of the insulin receptor in human renal proximal tubule cells.

Sorting nexin 5 (SNX5) belongs to the SNX family, which is composed of a diverse group of proteins that mediate trafficking of plasma membrane proteins, receptors, and transporters. SNX5 is important in the resensitization of the dopamine D1-like receptor (D1R). D1R is uncoupled from its effector proteins in hypertension and diabetes, and treatment of diabetes restores D1R function and insulin receptor (IR) expression.

Role of saliva in esophageal defense: implications in patients with nonerosive reflux disease.

Background: It has been previously demonstrated that patients with reflux esophagitis exhibit a significant impairment in the secretion of salivary protective components versus controls. However, the secretion of salivary protective factors in patients with nonerosive reflux disease (NERD) is not explored. The authors therefore studied the secretion of salivary volume, pH, bicarbonate, nonbicarbonate glycoconjugate, protein, epidermal growth factor (EGF), transforming growth factor alpha (TGF-α) and prostaglandin E2 in patients with NERD and compared with the corresponding values in controls (CTRL).

Dr. Arvid Lindau and discovery of von Hippel-Lindau disease.

Arvid Lindau, MD, PhD, consolidated the disparate array of benign and malignant visceral and nervous system lesions into the neoplastic syndrome known as von Hippel-Lindau (VHL) disease. Based on this pioneering work, Dr. Lindau was awarded both a Rockefeller fellowship to work in Dr.

Common variants of the G protein-coupled receptor type 4 are associated with human essential hypertension and predict the blood pressure response to angiotensin receptor blockade.

Non-synonymous GRK4 variants, R65L, A142V and A486V, are associated with essential hypertension in diverse populations. This study replicated the association of GRK4 variants, including GRK4(142V), with human essential hypertension in a Japanese population (n=588; hypertensive, n=486 normotensive controls) and determined whether the presence of GRK4 variants predicted the blood pressure (BP) response to angiotensin receptor blockers (ARBs) in patients with essential hypertension. We analyzed 829 patients and compared the response to ARBs between individuals with no GRK4 variants (n=136) and those with variants at one or any of the three loci (n=693).

Neurological applications of transcranial high intensity focused ultrasound.

Advances in transcranial MRI-guided focused ultrasound have renewed interest in lesioning procedures in functional neurosurgery with a potential role in the treatment of neurological conditions such as chronic pain, brain tumours, movement disorders and psychiatric diseases. While the use of transcranial MRI-guided focused ultrasound represents a new innovation in neurosurgery, ultrasound has been used in neurosurgery for almost 60 years. This paper reviews the major historical milestones that have led to modern transcranial focused ultrasound and discusses current and evolving applications of ultrasound in the brain.

Identifying the right surface for the right patient at the right time: generation and content validation of an algorithm for support surface selection.

Support surfaces are an integral component of pressure ulcer prevention and treatment, but there is insufficient evidence to guide clinical decision making in this area. In an effort to provide clinical guidance for selecting support surfaces based on individual patient needs, the Wound, Ostomy and Continence Nurses Society (WOCN®) set out to develop an evidence- and consensus-based algorithm. A Task Force of clinical experts was identified who: 1) reviewed the literature and identified evidence for support surface use in the prevention and treatment of pressure ulcers; 2) developed supporting statements for essential components for the algorithm, 3) developed a draft algorithm for support surface selection; and 4) determined its face validity.

Does hugging provide stress-buffering social support? A study of susceptibility to upper respiratory infection and illness.

Perceived social support has been hypothesized to protect against the pathogenic effects of stress. How such protection might be conferred, however, is not well understood. Using a sample of 404 healthy adults, we examined the roles of perceived social support and received hugs in buffering against interpersonal stress-induced susceptibility to infectious disease.

Fcγ-receptor-mediated trogocytosis impacts mAb-based therapies: historical precedence and recent developments.

A specialized form of trogocytosis occurs when Fcγ receptors on acceptor cells take up and internalize donor cell-associated immune complexes composed of specific monoclonal antibodies (mAbs) bound to target antigens on donor cells. This trogocytosis reaction, an example of antigenic modulation, has been described in recent clinical correlative studies and in vitro investigations for several mAbs used in cancer immunotherapy, including rituximab and ofatumumab. We discuss the impact of Fcγ-receptor-mediated trogocytosis on the efficacy of cancer immunotherapy and other mAb-based therapies.

Oesophageal Doppler cardiac output monitoring: a longstanding tool with evolving indications and applications.

Much work has been done over the years to assess cardiac output and better grasp haemodynamic profiles of patients in critical care and during major surgery. Pulmonary artery catheterization has long been considered as the standard of care, especially in critical care environments, however this dogma has been challenged over the last 10-15 years. This has led to a greater focus on alternate, lesser invasive technologies.

Differential dopamine receptor subtype regulation of adenylyl cyclases in lipid rafts in human embryonic kidney and renal proximal tubule cells.

Dopamine D1-like receptors (D1R and D5R) stimulate adenylyl cyclase (AC) activity, whereas the D2-like receptors (D2, D3 and D4) inhibit AC activity. D1R, but not the D5R, has been reported to regulate AC activity in lipid rafts (LRs). We tested the hypothesis that D1R and D5R differentially regulate AC activity in LRs using human embryonic kidney (HEK) 293 cells heterologously expressing human D1 or D5 receptor (HEK-hD1R or HEK-hD5R) and human renal proximal tubule (hRPT) cells that endogenously express D1R and D5R.

Famotidine, a Histamine H Receptor Antagonist, Does Not Reduce Levodopa-Induced Dyskinesia in Parkinson's Disease: A Proof-of-Concept Study.

The neural mechanisms underlying levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) may involve histamine (H) receptors on striatopallidal pathways. We recently demonstrated that the clinically available oral histamine H receptor antagonist (H RA), famotidine, can reduce l-dopa-induced chorea in MPTP-lesioned macaques. We hypothesized that famotidine may be useful in the treatment of LID in PD patients.

Histone hypoacetylation-activated genes are repressed by acetyl-CoA- and chromatin-mediated mechanism.

Transcriptional activation is typically associated with increased acetylation of promoter histones. However, this paradigm does not apply to transcriptional activation of all genes. In this study we have characterized a group of genes that are repressed by histone acetylation.

Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells.

NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs) are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT) and hypertensive subjects (HT).

Pharmacodynamic evaluation of intragastric pH and implications for famotidine dosing in the prophylaxis of non-steroidal anti-inflammatory drug induced gastropathy-a proof of concept analysis.

Objective: Famotidine given at a dose of 80 mg/day is effective in preventing NSAID-induced gastropathy. The aim of this proof of concept study was to compare twice a day (BID) vs 3-times a day (TID) administration of this total dose of famotidine on intragastric pH in healthy volunteers.

Research Design And Methods: Two analyses were undertaken: (1) a 13 subject controlled cross-over 24-h intragastric pH evaluation of the BID and TID administration of 80 mg/day of famotidine, as well as measures for drug accumulation over 5 days (EudraCT, number 2006-002930-39); and (2) a pharmacokinetic (PK)/pharmacodynamic (PD) model which predicted steady-state famotidine plasma concentrations and pH of the two regimens.