Fetal abdominal hyperechoic mass: diagnosis and management.

In the last 2 years, we have had the opportunity to follow 12 cases diagnosed with hyperechoic abdominal masses. Four of the cases ended with a fetal demise, while 7 resulted in the birth of an anomalous or medically ill neonate. Only 1 case has shown spontaneous resolution of the hyperechoic mass with the birth of a normal neonate. The in utero diagnosis of a hyperechoic abdominal mass should encourage the clinician to further investigation since the differential diagnosis is quite diverse. Appropriate counselling for the patient is a necessary part of prenatal care.     

Right ventricular function in early septic shock states

Objectives To define a variable which could reliability predict when fluid resuscitation as monotherapy is not expected to improve organ perfusion pressure, owing to limitations in cardiac output responsiveness in patients with severe sepsis.Design Prospective controlled trial.Setting Anesthesiological ICU in a university hospital.Patients Twenty seven patients in early septic shock states (MAP<60 mmHg).Interventions Infusion therapy was titrated until no further increase in cardiac index and mean arterial pressure could be achieved. Fluid resuscitation as monotherapy was deemed unsuccessful at the end of 2 h if inotropic or vasoactive pharmacologic support was required to maintain a mean arterial pressure > 60 mmHg.Measurements and results We investigated the hemodynamic course during fluid resuscitation (2850±210 ml crystalloids) with special emphasis on right heart function using the thermodilution technique. Eleven patients (group A) had a right ventricular (RV) ejection fraction below 45%. In this group positive inotropic and/or vasoactive drugs were obligatory to achieve and maintain a sufficient perfusion pressure (MAP>60 mmHg) after fluid challenge.Conclusions In 27 septic shock patients investigated, we diagnosed right ventricular dysfunction in 41%. In this specific patient population fluid replacement alone did not succeed in stabilizing hemodynamic variables, therefore necessitating catecholamine therapy.     

Renin inhibitors based on dipeptide analogues. Incorporation of the hydroxyethylene isostere at the P2/P3 sites

The synthesis of a series of renin inhibitors in which the P2 and P3 amino acids are replaced with the hydroxyethylene dipeptide isostere is reported. In vitro evaluation of the inhibitors has revealed that this isostere is an acceptable amide-bond replacement in which activity is maintained and stability is enhanced. Structure-activity relationships of this series resemble but do not parallel those of the corresponding dipeptide-containing inhibitors.     

Should combined pharmaco- and psychotherapy be offered to depressed patients?

Focusing on recent publications from the 1990s, this article qualitatively reviews the comparative efficacy of the combination of pharmaco- and psychotherapy (COMBI) vs either modality alone. There is only a weak empirical basis recommending the routine use of both psychotherapy and pharmacotherapy in acute treatment of Major Depressive Disorders (MDD). Concerning long-term treatment of MDD patients, the methodologically sophisticated study from Frank et al. shows that a COMBI is superior to interpersonal psychotherapy but not superior to medication alone. However, certain subgroups of patients might benefit substantially from COMBI compared to both psychotherapy and pharmacotherapy alone: 1) acute and long-term treatment of more severe forms of chronic depression, and 2) long-term treatment of older MDD patients. Compared to psychotherapy alone, severely depressed MDD patients profit more and faster when treated with combined psycho-pharmacotherapy.     

Improved reversal learning and altered fear conditioning in transgenic mice with regionally restricted p25 expression

Cleavage of the cyclin-dependent kinase 5 activator p35 generates the protein fragment p25, which accumulates in the forebrain of patients with Alzheimer's disease. Although p25 expression has been suggested to affect learning and memory, this hypothesis has not been tested to date. To investigate the role of p25 in hippocampus-dependent learning and memory we have generated transgenic mice expressing p25 preferentially in postnatal forebrain. p25 expression was highest in hippocampus where it averaged approximately 33% of endogenous p35 expression. This low level of p25 expression did not seem to result in hyperphosphorylation of tau, but increased the phosphorylation of neurofilament M and enhanced the expression of tau protein. These molecular changes did not correlate with neurodegeneration or motor abnormalities. In the Morris water maze the p25 mutants were normal in learning an initial platform location, but surprisingly reversal learning was improved when the platform position was changed. The p25 mutants were normal in contextual fear conditioning. However, when trained with a tone presentation the mutants showed reduced contextual conditioning and enhanced tone fear conditioning. We conclude that low p25 expression has pleiotropic effects on learning and memory. As p25 expression can improve learning and memory, p25 formation could be a compensatory mechanism for learning and memory deficits in Alzheimer's disease.     

Dissociative symptoms in posttraumatic stress disorder: diagnosis and treatment

This article explores the complex relationship between dissociation and psychiatric trauma. Dissociation is described as a defense reaction, a risk factor for the development of posttraumatic stress disorder, and as a set of syndromal disturbances. The authors discuss various models proposed for the relationship between these. They outline developmental considerations in diagnosis and treatment and end by discussing further needed research.     

Novel erythromycin derivatives with aryl groups tethered to the C-6 position are potent protein synthesis inhibitors and active against multidrug-resistant respiratory pathogens.

A novel series of erythromycin derivatives has been discovered with potent activity against key respiratory pathogens, including those resistant to erythromycin. These compounds are characterized by having an aryl group tethered to the C-6 position of the erythronolide skeleton. Extensive structural modification of the C-6 moiety led to the discovery of several promising compounds with potent activity against both mef- and erm-mediated resistant Streptoccoccus pneumoniae. Preliminary mechanistic studies indicated that the new macrolides are potent protein synthesis inhibitors, which interact with methylated ribosomes isolated from resistant organisms. In experimental animal models, these compounds exhibited excellent in vivo efficacy and balanced pharmacokinetic profiles.     

Aggressive breast cancer cells are dependent on activated Abl kinases for proliferation, anchorage-independent growth and survival

Mutant Abl kinases (such as BCR-Abl) drive the development of leukemia; however little is known regarding whether Abl kinases contribute to the development or progression of solid tumors. We recently demonstrated that endogenous Abl kinases (c-Abl, Arg) are activated by deregulated ErbB receptors and Src kinases, and drive invasion of aggressive breast cancer cells. In this study, we examined whether activation of endogenous Abl kinases affects transformation, proliferation and survival, which are major contributors to breast cancer development and metastatic progression. Using a pharmacological inhibitor and RNAi, we demonstrate that activation of endogenous Abl kinases dramatically promotes breast cancer cell proliferation and anchorage-independent growth in serum, as well as survival following nutrient deprivation. Activation of Abl kinases mediates phosphorylation of STAT3, and promotes proliferation by accelerating G(1) --> S progression. Moreover, we identify IGF-1R as a novel upstream activator of endogenous Abl kinases, and demonstrate that Abl kinase activation is required for IGF-1-stimulated cell cycle progression in breast cancer cells. Since activation of Abl kinases affects multiple steps of breast cancer development and progression, Abl kinase inhibitors are likely to be effective agents for the treatment of breast cancers containing highly active Abl kinases.     

Early effect of hyaluronic acid intra-articular injections on serum and urine biomarkers in patients with knee osteoarthritis: An open-label observational prospective study

The aim of the study was to investigate the effect of hyaluronic acid (HA) intra articular injections (IA) on osteoarthritis (OA) biomarkers in patients with knee OA. Prospective open label study. Fifty‐one patients with unilateral symptomatic K‐OA received IA injections of 2mL of HA on days (D) 1, 7, 14 and were followed 3 months. At D‐15 patients were examined and X‐rays performed, to exclude patients with bilateral K‐OA, or those with more than three symptomatic OA joints. From 15 days (D‐15) before the first injection to D90 concomitant therapies were unchanged. Walking pain (WP) on VAS was obtained at each visit. Urine (U) and serum (S) samples were obtained at D‐15, D1, D30, and D90. S‐C2C, S‐Cartilage oligomeric matrix protein, S‐HA, S‐CS 846 epitope, S‐type II collagen propeptide, and U‐type II collagen C telopeptide (U‐CTX II/creatinin) were assayed. Predictive factors of response were analyzed using logistic regression. Correlations between variables were obtained using Spearman test. Forty‐five patients were analyzed. Between D‐15 and D1 there was no difference for any biomarkers At D1, WP (SD) was correlated with U‐CTX II/creat (p = 0.006). Between D1 and D90: U‐CTX II/creat decreased significantly. After adjustment for confounding variables there was a significant correlation between clinical response and U‐CTX II/creat variation. U‐CTX II and S‐HA at baseline were independently predictive of clinical response. This study showed that 90 days after HA IA injections, U‐CTX II levels significantly decrease compared to baseline, suggesting a slowdown of type II collagen degradation. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:679–685, 2012