MR-determined hippocampal asymmetry in full-term and preterm neonates

Hippocampi are asymmetrical in children and adults, where the right hippocampus is larger. To date, no literature has confirmed that hippocampal asymmetry is evident at birth. Furthermore, gender differences have been observed in normal hippocampal asymmetry, but this has not been examined in neonates. Stress, injury, and lower IQ have been associated with alterations to hippocampal asymmetry. These same factors often accompany preterm birth. Therefore, prematurity is possibly associated with altered hippocampal asymmetry. There were three aims of this study: First, we assessed whether hippocampi were asymmetrical at birth, second whether there was a gender effect on hippocampal asymmetry, and third whether the stress of preterm birth altered hippocampal asymmetry. This study utilized volumetric magnetic resonance imaging to compare left and right hippocampal volumes in 32 full-term and 184 preterm infants at term. Full-term infants demonstrated rightward hippocampal asymmetry, as did preterm infants. In the case of preterm infants, hippocampal asymmetry was proportional to total hemispheric asymmetry. This study is the first to demonstrate that the normal pattern of hippocampal asymmetry is present this early in development. We did not find gender differences in hippocampal asymmetry at term. Preterm infants tended to have less asymmetrical hippocampi than full-term infants, a difference which became significant after correcting for hemispheric brain tissue volumes. This study may suggest that hippocampal asymmetry develops in utero and is maintained into adulthood in infants with a normal neurological course.     

Small molecule HIV entry inhibitors: Part II. Attachment and fusion inhibitors: 2004-2010

INTRODUCTION: The first US FDA approved HIV entry inhibitor drug Enfuvirdine belongs to the fusion inhibitor category. Earlier efforts in this area were focused on peptides and monoclonal antibodies; recently, the focus has shifted towards the development of small molecule HIV attachment and fusion inhibitors. They can be used for prophylactic purposes and also hold potential for the development of HIV microbicides. AREAS COVERED: In a previous paper ('Small molecule HIV entry inhibitors: Part I'), we reviewed patents and patent applications for small molecule chemokine receptor antagonists from major pharmaceutical companies. In this paper, the development of small molecule HIV attachment and fusion inhibitors is discussed in detail. It covers patents and patent applications for small molecule HIV attachment and fusion inhibitors published between 2004 and 2010 and related literature with a focus on recent developments based on lead generation and lead modification. EXPERT OPINION: To augment the potency of currently available antiretroviral drug combinations and to fight drug-resistant virus variants, more effective drugs which target additional steps in the viral replication cycle are urgently needed. HIV attachment and fusion processes are such targets. Inhibitors of these targets will provide additional options for the treatment of HIV drug-resistant strains. Small molecule HIV attachment inhibitors such as BMS-378806 and analogs from Bristol Myers Squibb, N-aryl piperidine derivatives from Propharmacon, and NBD-556 and NBD-557 from New York Blood Center may have potential as vaginal microbicidal agents and can be an economical alternative to monoclonal antibodies.     

Body mass index, prognosis and mode of death in chronic heart failure: results from the Valsartan Heart Failure Trial

AIMS: To assess the relationship between body mass index (BMI), mortality and mode of death in chronic heart failure (CHF) patients; to define the shape of the relationship between BMI and mortality. METHODS AND RESULTS: We performed a post-hoc analysis of 5010 patients from the Valsartan Heart Failure Trial. The end-points of the study were all-cause and cardiovascular mortality. Mortality rate was 27.2% in underweight patients (BMI<22 kg/m2), 21.7% in normal weight patients (BMI 22-24.9 kg/m2), 17.9% in overweight patients (BMI 25-29.9 kg/m2) and 16.5% in obese patients (BMI>30 kg/m2) (p<0.0001). The rates of non-cardiovascular death did not differ among groups. The risk of death due to progressive heart failure was 3.4-fold higher in the underweight than in the obese patients (p<0.0001). Normal weight, overweight and obese patients had lower risk of death as compared with underweight patients (p=0.019, HR 0.76, 95% CI 0.61-0.96; p=0.0005, HR 0.68, 95% CI 0.55-0.84; p=0.003, HR 0.67, 95% CI 0.52-0.88, respectively) independently of symptoms, ventricular function, beta-blocker use, C-reactive protein and brain natriuretic peptide levels. CONCLUSIONS: In CHF patients a higher BMI is associated with a better prognosis independently of other clinical variables. The relationship between mortality and BMI is monotonically decreasing.     

Repopulation of adult and neonatal mice with human hepatocytes: a chimeric animal model

We report the successful transplantation of human hepatocytes in immunodeficient, fumarylacetoacetate hydrolase-deficient (fah(-/-)) mice. Engraftment occurs over the entire liver acinus upon transplantation. A few weeks after transplantation, increasing concentrations of human proteins (e.g., human albumin and human C3a) can be measured in the blood of the recipient mouse. No fusion between mouse and human hepatocytes can be detected. Three months after transplantation, up to 20% of the mouse liver is repopulated by human hepatocytes, and sustained expression of lentiviral vector transduced gene can be observed. We further report the development of a hepatocyte transplantation method involving a transcutaneous, intrahepatic injection in neonatal mice. Human hepatocytes engraft over the entire injected lobe with an expansion pattern similar to those observed with intrasplenic transplantation.     

Reciprocity between phase shifts and amplitude changes in the mammalian circadian clock

Circadian rhythms help organisms adapt to predictable daily changes in their environment. Light resets the phase of the underlying oscillator to maintain the organism in sync with its surroundings. Light also affects the amplitude of overt rhythms. At a critical phase during the night, when phase shifts are maximal, light can reduce rhythm amplitude to nearly zero, whereas in the subjective day, when phase shifts are minimal, it can boost amplitude substantially. To explore the cellular basis for this reciprocal relationship between phase shift and amplitude change, we generated a photoentrainable, cell-based system in mammalian fibroblasts that shares several key features of suprachiasmatic nucleus light entrainment. Upon light stimulation, these cells exhibit calcium/cyclic AMP responsive element-binding (CREB) protein phosphorylation, leading to temporally gated acute induction of the Per2 gene, followed by phase-dependent changes in phase and/or amplitude of the PER2 circadian rhythm. At phases near the PER2 peak, photic stimulation causes little phase shift but enhanced rhythm amplitude. At phases near the PER2 nadir, on the other hand, the same stimuli cause large phase shifts but dampen rhythm amplitude. Real-time monitoring of PER2 oscillations in single cells reveals that changes in both synchrony and amplitude of individual oscillators underlie these phenomena.     

Clinical relevance of the nutcracker esophagus: suggested revision of criteria for diagnosis

BACKGROUND: Nutcracker esophagus (NE) is a manometric finding defined by peristaltic contractions with a mean distal esophageal amplitude (DEA) >180 mm Hg. This threshold has been selected as it exceeds the average DEA in healthy volunteers by 2 SDs. Since its introduction the clinical significance of this finding has been challenged, as many patients with NE are asymptomatic. AIM: To evaluate whether defining NE based on a different DEA threshold would be clinically more meaningful. METHODS: Retrospective review of prospectively collected manometry data between October 2001 and December 2003. Using previously published normal DEA values (mean and SD) patients with NE were stratified into 3 groups: group A (2 to 3 SD above mean): DEA 180 to 220 mm Hg; group B (3 to 4 SD above mean): DEA 220 to 260 mm Hg; and group C (>4 SD above mean): DEA >260 mm Hg. Symptoms, esophageal acid exposure, bolus transit data, and lower esophageal sphincter data were reviewed. RESULTS: The stratification of 56 NE patients into groups A, B, and C were 31, 16, and 9, respectively. The proportion of patients presenting with chest pain increased from 23% in group A to 69% in group B and 100% in group C. Patients in group C had significantly (P<0.05) higher mean lower esophageal sphincter pressure, shorter bolus transit time, and lower frequency of abnormal reflux. CONCLUSIONS: A revised definition of NE to include patients with a DEA >260 mm Hg, and possibly those with >220 may have greater clinical relevance.     

Percutaneous endoscopic gastrostomy sites infected by methicillin-resistant Staphylococcus aureus: impact on outcome

BACKGROUND: The impact of methicillin-resistant Staphylococcus aureus (MRSA) colonization of percutaneous endoscopic gastrostomy (PEG) sites on morbidity and mortality is uncertain. AIM: We investigated the impact of known prior MRSA colonization on the incidence of symptomatic PEG site wound infection and mortality. METHODS: Consecutive patients who had PEG tubes inserted recently at our hospital were identified. The presence or absence of MRSA colonization before PEG placement was noted. Patients were observed for wound infection, and swabs were taken from the site if there was clinical infection. Mortality within 30 days of PEG placement was determined. RESULTS: A total of 83 patients underwent PEG placement; 23 (28%) of these patients had known MRSA colonization before PEG placement. Of these, 13 (57%) developed symptomatic MRSA infection of the PEG site. The remaining 60 patients (72%) had no known prior MRSA colonization. In these patients, 9 (15%) developed symptomatic MRSA infection of the PEG site. The overall incidence of wound infection was 37% (31) of the total undergoing PEG placement, of whom 71% (22) had developed MRSA infection. The mortality of those with symptomatic MRSA infection of the PEG site was 9% (2/22), whereas the mortality from non-MRSA-infected PEGs was 20% (12/61). CONCLUSION: Patients with prior MRSA colonization had a significantly higher risk of developing symptomatic MRSA infection of the PEG site. However, there was still a significant risk (15%) of developing MRSA infection of the PEG site for patients with no known prior MRSA infection. MRSA infection of the PEG site did not affect mortality.     

Initiating buprenorphine treatment for hospitalized patients with opioid dependence: A case series

Background and Objectives

Opioid dependent patients are hospitalized frequently. We aimed to determine if initiation of buprenorphine treatment during hospitalization facilitates entry into treatment following discharge.

Methods

Retrospective case series (n = 47).

Results

Twenty‐two (46.8%) patients successfully initiated buprenorphine treatment within 2 months of discharge. Those patients obtaining a referral to a specific program were more successful in continuing treatment, but this difference did not reach statistical significance (59.1% vs 39.1%, p = 0.18).

Discussion and Conclusions

Hospitalization may be an important opportunity to engage opioid dependent patients to initiate buprenorphine treatment.

Scientific Significance

This study provides provisional support for utilizing buprenorphine for hospitalized patients. (Am J Addict 2015;24:10–14)