Does the Holmium:Yag laser cause osteonecrosis?

Some authors have reported a few cases of paraarticular osteonecrosis following arthroscopic knee surgery in which laser was used to assist in the treatment of cartilage and meniscal pathology. We performed a prospective randomized clinical study to determine if osteonecrosis occurs after arthroscopic laser surgery. Fifty-five patients with cartilage problems in their knee joints were randomized into two groups: the laser group included 30 patients and the conventionally instrumented group consisted of 25 patients. Power settings for the Holmium:YAG laser were 0.5 to 1.5 joules per pulse and 5 and 25 Hertz. Total energy used for the procedures was 1 to 2 K joules. Magnetic resonance imaging was performed on all patients preoperatively and postoperatively (in third, sixth, and thirteenth months). None of the patients had osteonecrosis following arthroscopic laser surgery. When the Holmium:YAG laser is used at an optimal dosage (optimal joule and Hertz) with an optimal technique (keeping the handpiece at an appropriate angle and distance) and for an optimal time (avoiding overtreatment), it does not cause osteonecrosis.     

Covalent dimer species of beta-defensin Defr1 display potent antimicrobial activity against multidrug-resistant bacterial pathogens

Beta defensins comprise a family of cationic, cysteine-rich antimicrobial peptides, predominantly expressed at epithelial surfaces. Previously we identified a unique five-cysteine defensin-related peptide (Defr1) that, when synthesized, is a mixture of dimeric isoforms and exhibits potent antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa. Here we report that Defr1 displays antimicrobial activity against an extended panel of multidrug-resistant nosocomial pathogens for which antimicrobial treatment is limited or nonexistent. Defr1 fractions were collected by high-pressure liquid chromatography and analyzed by gel electrophoresis and mass spectrometry. Antimicrobial activity was initially investigated with the type strain Pseudomonas aeruginosa PAO1. All fractions tested displayed equivalent, potent antimicrobial activity levels comparable with that of the unfractionated Defr1. However, use of an oxidized, monomeric six-cysteine analogue (Defr1 Y5C), or of reduced Defr1, gave diminished antimicrobial activity. These results suggest that the covalent dimer structure of Defr1 is crucial to antimicrobial activity; this hypothesis was confirmed by investigation of a synthetic one-cysteine variant (Defr1-1cys). This gave an activity profile similar to that of synthetic Defr1 but only in an oxidized, dimeric form. Thus, we have shown that covalent, dimeric molecules based on the Defr1 beta-defensin sequence demonstrate antimicrobial activity even in the absence of the canonical cysteine motif.     

The Metabolic Effects of Omega-3 Plant Sterol Esters in Mixed Hyperlipidemic Subjects

Purpose

The aim of the current study was to evaluate the therapeutic effects of omega-3 plant sterol esters (n-3-PSE) on lipid profile and other coronary heart disease risk factors in subjects with mixed hyperlipidemia.

Methods

Ninety-one patients with mixed hyperlipidemia were randomized in a double blind fashion to receive either placebo (corn oil) or n-3-PSE. Twenty four patients dropped out or were excluded from the efficacy analysis due to protocol violation. The primary efficacy endpoint was mean change in plasma low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment. Other efficacy measures included plasma lipids, lipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels. Participants who completed the double-blind study were given the option to continue into an open-label, 12-weeks follow up phase.

Results

n-3-PSE treatment did not result in a significant change in LDL-C levels. Triglyceride levels were reduced significantly by 19% (51 mg/dL, p?<?0.0001) in the n-3-PSE group in comparison with the placebo group (p?=?0.025). Diastolic blood pressure and hsCRP were reduced by 7% (5.9 mmHg) and 7.8% (0.6 mg/L), respectively, and were significantly different from the placebo group (p?=?0.036 and p?=?0.018, respectively).

Conclusions

In patients with mixed hyperlipidemia, n-3-PSE treatment may offer a safe and effective therapy for triglyceride level reduction while avoiding the typical increase in LDL-C levels associated with n-3 fatty acid treatment. The observed reduction in blood pressure and inflammation markers warrants further evaluation. The positive effect of n-3-PSE treatment was preserved at the end of the follow up phase.     

The susceptibility of Aire(-/-) mice to experimental myasthenia gravis involves alterations in regulatory T cells

The autoimmune regulator (Aire) is involved in the prevention of autoimmunity by promoting thymic expression of tissue restricted antigens which leads to elimination of self-reactive T cells. We found that Aire knockout (KO) mice as well as mouse strains that are susceptible to experimental autoimmune myasthenia gravis (EAMG) have lower thymic expression of acetylcholine receptor (AChR- the main autoantigen in MG), compared to wild type (WT) mice and EAMG-resistant mouse strains, respectively. We demonstrated that Aire KO mice have a significant and reproducible lower frequency of CD4+Foxp3+ cells and a higher expression of Th17 markers in their thymus, compared to wild type (WT) mice. These findings led us to expect that Aire KO mice would display increased susceptibility to EAMG. Surprisingly, when EAMG was induced in young (2 month-old) mice, EAMG was milder in Aire KO than in WT mice for several weeks until the age of about 5 months. However, when EAMG was induced in relatively aged (6 month-old) mice, Aire KO mice presented higher disease severity than WT controls. This age-related change in susceptibility to EAMG correlated with an elevated proportion of Treg cells in the spleens of young but not old KO, compared to WT mice, suggesting a role for peripheral Treg cells in the course of disease. Our observations point to a possible link between Aire and Treg cells and suggest an involvement for both in the pathogenesis of myasthenia.     

Late evening brain activation patterns and their relation to the internal biological time, melatonin, and homeostatic sleep debt

Sleep propensity increases sharply at night. Some evidence implicates the pineal hormone melatonin in this process. Using functional magnetic resonance imaging, brain activation during a visual search task was examined at 22:00 h (when endogenous melatonin levels normally increase). The relationships between brain activation, endogenous melatonin (measured in saliva), and self-reported fatigue were assessed. Finally, the effects of exogenous melatonin administered at 22:00 h were studied in a double blind, placebo-controlled crossover manner. We show that brain activation patterns as well as the response to exogenous melatonin significantly differ at night from those seen in afternoon hours. Thus, activation in the rostro-medial and lateral aspects of the occipital cortex and the thalamus diminished at 22:00 h. Activation in the right parietal cortex increased at night and correlated with individual fatigue levels, whereas exogenous melatonin given at 22:00 h reduced activation in this area. The right dorsolateral prefrontal cortex, an area considered to reflect homeostatic sleep debt, demonstrated increased activation at 22:00 h. Surprisingly, this increase correlated with endogenous melatonin. These results demonstrate and partially differentiate circadian effects (whether mediated by melatonin or not) and homeostatic sleep debt modulation of human brain activity associated with everyday fatigue at night.     

Role of cortical cannabinoid CB1 receptor in conditioned taste aversion memory

The brain endocannabinoid system has been shown to play a role in memory, though the extent to which this role generalizes over different types and processes of memory is not yet determined. Here we show that the cannabinoid receptor 1 (CB1) plays differential roles in acquisition, extinction and reconsolidation of conditioned taste aversion (CTA) memory in the rat insular cortex, which contains the taste cortex. Activation of the CB1 receptor in the insular cortex inhibits acquisition and reconsolidation but not extinction, whereas blockade of the CB1 receptor promotes memory and blocks extinction of CTA, while having no apparent effect on reconsolidation. The CB1 ligands used in this study were incapable of substituting the unconditioned stimulus in CTA training. All in all, the data raise the possibility that the state of activity of the CB1 receptor in the insular cortex contributes to the encoding of hedonic valence that enters into association with taste items.     

Mitogen-activated protein kinases, inhibitory-kappaB kinase, and insulin signaling in human omental versus subcutaneous adipose tissue in obesity

MAPKs and inhibitory-kappaB kinase (IKK) were suggested to link various conditions thought to develop in adipose tissue in obesity (oxidative, endoplasmic reticulum stress, inflammation) with insulin resistance. Yet whether in obesity these kinases are affected in a fat-depot-differential manner is unknown. We assessed the expression and phosphorylation of these kinases in paired omental and abdominal-sc fat biopsies from 48 severely obese women (body mass index > 32 kg/m(2)). Protein and mRNAs of p38MAPK, ERK, c-Jun kinase-1, and IKKbeta were increased 1.5-2.5-fold in omental vs. sc fat. The phosphorylated (activated) forms of these kinases were also increased to similar magnitudes as the total expression. However, phosphorylation of insulin receptor substrate-1 on Ser312 (equivalent of murine Ser307) was not increased in omental, compared with sc, fat. Consistently, fat tissue fragments stimulated with insulin demonstrated that tyrosine phosphorylation and signal transduction to Akt/protein kinase B in omental fat was not inferior to that observable in sc fat. Comparison with lean women (body mass index 23.2 +/- 2.9 kg/m(2)) revealed similar ERK2 and IKKbeta expression and phosphorylation in both fat depots. However, as compared with lean controls, obese women exhibited 480 and 270% higher amount of the phosphorylated forms of p38MAPK and c-Jun kinase, respectively, in omental, but not sc, fat, and this expression level correlated with clinical parameters of glycemia and insulin sensitivity. Increased expression of stress-activated kinases and IKK and their phosphorylated forms in omental fat occurs in obesity, potentially contributing to differential roles of omental and sc fat in the pathophysiology of obesity.     

Nap and melatonin-induced changes in hippocampal activation and their role in verbal memory consolidation

Overnight sleep contributes to memory consolidation; even a short nap improves memory performance. Such improvement has been linked to hippocampal activity during sleep. Melatonin has been shown to affect the human hippocampus and to induce 'sleep like' changes in brain activation. We therefore conducted and compared two functional magnetic resonance imaging studies: the first study assessed the effect of a 2-hr mid-day nap versus an equal amount of wakefulness on a verbal memory task (unrelated word pair association); the second assessed the effect of melatonin versus placebo (both conditions without nap) on a similar task. We report that following a nap relative to wakefulness, successful retrieval-related activation in the parahippocampus is decreased. A smaller decrease is seen in wakefulness with melatonin but not placebo. In parallel, an improvement in verbal memory recall was found after a nap compared with wakefulness but not with melatonin during wakefulness compared with placebo. Our findings demonstrate effects of melatonin that resemble those of sleep on verbal memory processing in the hippocampus thus suggesting that melatonin, like sleep, can initiate offline plastic changes underlying memory consolidation; they also suggest that concomitant rest without interferences is necessary for enhanced performance.     

PTSD in Urban Primary Care: High Prevalence and Low Physician Recognition

BACKGROUND Posttraumatic stress disorder (PTSD) is associated with medical and psychological morbidity. The prevalence of PTSD in urban primary care has not been well described. OBJECTIVE To measure the prevalence of PTSD in primary care patients overall and among those with selected conditions (chronic pain, depression, anxiety, heavy drinking, substance dependence (SD), irritable bowel syndrome (IBS), and immigrant status). DESIGN Cross-sectional study. PARTICIPANTS English-speaking patients aged 18–65 years old, awaiting primary care appointments in an urban academic medical center, were eligible for enrollment to determine PTSD prevalence (N = 509). Additional eligible participants (n = 98) with IBS or SD were subsequently enrolled. MEASUREMENTS PTSD (past year) and trauma exposure were measured with Composite International Diagnostic Interview. We calculated the prevalence of PTSD associated with depression, anxiety, heavy drinking, SD, IBS, and chronic pain. Only the analyses on heavy drinking, SD, and IBS used all 607 participants. RESULTS Among the 509 adults in primary care, 23% (95% CI, 19–26%) had PTSD, of whom 11% had it noted in the medical record. The prevalence of PTSD, adjusted for age, gender, race, and marital and socioeconomic statuses, was higher in participants with, compared to those without, the following conditions: chronic pain (23 vs 12%, p = .003), major depression (35 vs 11%, p < .0001), anxiety disorders (42 vs 14%, p < .0001), and IBS (34 vs 18%, p = .01) and lower in immigrants (13 vs 21%, p = .05). CONCLUSIONS The prevalence of PTSD in the urban primary care setting, and particularly among certain high-risk conditions, compels a critical examination of optimal approaches for screening, intervention, and referral to PTSD treatment. Portions of this work were presented at the annual meeting of the Society of General Internal Medicine, May 2005, New Orleans, LA, at the annual meeting of the College on Problems of Drug Dependence, June 2005, Orlando, FL, and at the annual meeting of the American Public Health Association, November 2004, Washington, DC.     

Rosai-Dorfman disease with epidural and spinal bone marrow involvement: magnetic resonance imaging and diffusion-weighted imaging features

Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease, is a rare histiocytic disorder that typically presents with chronic, self-limiting cervical lymphadenopathy. Although this disease mainly affects histiocytes, there are a few reports of bone marrow infiltration. Diffusion-weighted imaging (DWI) is a promising technology in differentiating between various bone marrow pathologies. We here present conventional magnetic resonance imaging and DWI features of a patient with SHML and bone marrow involvement.