If these myocytes could talk,they would speak the language of metabolites

Cardiac wound healing following ischemic injury requires a well-described spatiotemporal progression of events involving multiple cell types and cell-cell interactions. While cellular crosstalk among immune cell, endothelial cell, and fibroblast populations is known to regulate these progressive phases, the role of cardiac myocytes in controlling the wound-healing program is unclear. In this issue of the JCI, Li et al. describe a mechanism of cellular crosstalk between cardiac myocytes and fibroblasts that disrupts nonmyocyte cell function and worsens wound healing outcomes following myocardial infarction (MI). This tour de force study used an arsenal of multidisciplinary approaches to identify a central role for the ectonucleotidase ENPP1 in this process. These findings have clear therapeutic implications, as the authors identified a small molecular inhibitor of ENPP1 that improved post-MI outcomes in mice. These exciting data provide impactful mechanistic information that advance the field’s understanding of cardiac repair and remodeling.     

Prospective study of lower respiratory tract infections in an extended-care nursing home program: potential role of oral ciprofloxacin

PURPOSE: Infections of the lower respiratory tract pose an important problem in nursing homes. Despite the magnitude of this problem, few, if any, antibiotic studies have been targeted specifically at nursing home-acquired bronchopulmonary infections. Following the establishment of a teaching Extended-Care Nursing Home Program, which facilitated the early diagnosis and therapy of bronchopulmonary infections, a comparative trial of oral ciprofloxacin and intramuscular cefamandole was initiated in elderly patients with lower respiratory tract infections. In addition to assessing the relative efficacy and safety of ciprofloxacin and cefamandole, our goals were to identify problems and pitfalls associated with conducting clinical research in this nursing home setting, evaluate selected clinical and laboratory features of lower respiratory tract infection in this patient population, and measure outcomes in all study groups. PATIENTS and METHODS: During a 20-month period, 40 patients with pneumonia and 20 patients with acute bronchitis were enrolled in this randomized study. Sixty-three patients with pneumonia who were ineligible for the randomized study were also followed prospectively. The mean age of the 111 participants (123 cases) was 80.8 years; all patients had at least one chronic medical condition. RESULTS: Although Streptococcus pneumoniae was the single most common isolate, gram-negative bacteria were cultured from 81 percent of the cases that yielded pathogens from a satisfactory sputum specimen. The in-hospital mortality rate was strikingly low (6.5 percent), and a large majority of patients in all study groups were discharged safely back to their nursing homes well within the Diagnosis-Related Group length of stay. CONCLUSION: Ciprofloxacin appeared to be as safe and effective as cefamandole in this nursing home program; however, additional studies are needed to determine its role in the treatment of elderly patients with bronchopulmonary infections.     

Synthesis and separation in the history of "nature" and "nurture"

For much of the 20th century scientific psychology treated the relative contributions of nature and nurture to the development of phenotypes as the result of two quite separate sources of influence. One, nature, was linked to biological perspectives, often manifest as "instinct", while the other, nurture, was taken to reflect psychological influences. We argue that this separation was contingent on historical circumstance. Prior to about 1920, several perspectives in biology and psychology promoted the synthesis of nature and nurture. But between 1930 and 1980 that synthetic consensus was lost in America as numerous influences converged to promote a view that identified psychological and biological aspects of mind and behavior as inherently separate. Around 1960, during the hegemony of behaviorism, Daniel Lehrman, Gilbert Gottlieb, and other pioneers of developmental psychobiology developed probabilistic epigenesis to reject predeterminist notions of instinct and restore a synthesis. We describe the earlier and later periods of synthesis and discuss several influences that led to the separation of nature and nurture in the middle of the 20th century.     

A novel strategy for the treatment of cocaine addiction

Cocaine's addictive liability has been linked to its pharmacologic actions on mesotelencephalic dopamine (DA) reinforcement/reward pathways in the central nervous system (CNS). Dopaminergic transmission within these pathways is modulated by gamma-aminobutyric acid (GABA). With this knowledge, we examined the utility of gamma vinylGABA (GVG), a selective and irreversible inhibitor of GABA-transaminase (GABA-T) known to potentiate GABAergic inhibition, to alter cocaine's biochemical effects as well as its effects on behaviors associated with these biochemical changes. GVG significantly attenuated cocaine-induced increases in neostriatal synaptic DA in the non-human primate (baboon) brain as assessed by positron emission tomography (PET) and abolished both the expression and acquisition of cocaine-induced conditioned place preference (CPP). It had no effect on CPP for a food reward, the delivery of cocaine to the brain or locomotor activity. These findings suggest the possible therapeutic utility in cocaine addiction of a pharmacologic strategy targeted at the GABAergic neurotransmitter system, a system distinct from but functionally linked to the DA mesotelencephalic reward/reinforcement system. However, rather than targeting the GABA receptor complex with a direct GABA agonist, this novel approach with GVG takes advantage of the prolonged effects of an irreversible enzyme inhibitor that raises endogenous GABA levels without the addictive liability associated with GABA agonists acting directly at the receptor itself. Human trials with GVG are currently being developed to directly examine the utility of this novel strategy for the treatment of cocaine addiction. Synapse 30:119–129, 1998. © 1998 Wiley-Liss, Inc.     

Variant slips of psoas and iliacus muscles,with splitting of the femoral nerve

In bilateral dissections of 68 cadavers, four examples were found unilaterally of variant slips of iliacus and psoas major muscles. In three of them the femoral nerve was pierced by the variant slip. One of these variants was a previously undocumented accessory slip of iliacus, originating from the iliolumbar ligament, passing inferiorly anterior to iliacus, and traversing the femoral nerve; its tendon split to be attached proximally to the lesser trochanter of the femur and distally to an unknown insertion. Such anomalies might cause tension on the femoral nerve resulting in referred pain to the hip and knee joints and to the lumbar dermatomes L2,3 and 4. © 1996 Wiley-Liss, Inc.     

Prevalence,management, and outcomes of patients with coagulopathy after acute nonvariceal upper gastrointestinal bleeding in the United Kingdom

BACKGROUND: Coagulopathy after major hemorrhage has been found to be an independent risk factor for mortality after traumatic bleeding. It is unclear whether similar associations are present in other causes of major hemorrhage. We describe the prevalence, use of plasma, and outcomes of patients with coagulopathy after acute nonvariceal upper gastrointestinal bleeding (NVUGIB). STUDY DESIGN AND METHODS: This study was a multicenter UK national audit. Data were collected prospectively on consecutive admissions with upper gastrointestinal bleeding over a 2‐month period to 212 UK hospitals. Coagulopathy was defined as an international normalized ratio (INR) of at least 1.5. Logistic regression was used to examine the relationship between coagulopathy and patient‐related outcome measures of mortality, rebleeding, and need for surgery and/or radiologic intervention. RESULTS: A total of 4478 patients were included in the study. Coagulopathy was present in 16.4% (444/2709) of patients in whom an INR was recorded. Patients with coagulopathy were more likely to present with hemodynamic shock (45% vs. 36%), have a higher clinical Rockall score (4 vs. 2), receive red blood cell transfusion (79% vs. 48%) and have high‐risk stigmata of hemorrhage at endoscopy (34% vs. 25%). After adjustment for confounders the presence of a coagulopathy was associated with a fivefold increased in the odds of mortality (odds ratio, 5.63; 95% confidence interval, 3.09‐10.27; p < 0.001). Only 35% of patients with coagulopathy received fresh‐frozen plasma transfusion. CONCLUSIONS: Coagulopathy was prevalent in 16% of patients after NVUGIB and independently associated with more than a fivefold increase in the odds of in‐hospital mortality. Wide variation in plasma use exists indicates clinical uncertainty regarding optimal practice.     

Sleeve gastrectomy: 5-year outcomes of a single institution

BackgroundLaparoscopic sleeve gastrectomy (SG) is the most recent bariatric surgical procedure to gain universal acceptance by providers and payers. Long-term clinical data on outcomes is limited at this time.MethodsWe retrospectively examined 5-year outcomes (weight loss, complications, and resolution of co-morbid conditions) of patients undergoing SG at our institution.ResultsOur initial SG was performed in 2005, and we operated on 55 consecutive patients who are 5 years out from surgery. Six patients were excluded from the long-term results. Four patients underwent conversion to a duodenal switch, and 2 patients died in the first year outside the perioperative period. Average starting body mass index was 65 kg/m². Five-year average percent excess weight loss was 86% (range 50%–103%). Percentage of co-morbidities resolved: hypertension (95%), type 2 diabetes mellitus (100%), hyperlipidemia (100%), and obstructive sleep apnea (100%). Gastroesophageal reflux disease (GERD) was resolved in 53%, and new GERD symptoms developed in 11% of patients. There was 1 staple line leak (1.9%), no strictures, no gastrointestinal bleeding, and no perioperative deaths.ConclusionIn this study, SG is a well-tolerated and effective bariatric surgical procedure with good long-term weight loss and resolution of co-morbid medical conditions.     

In-vitro methods for testing dermal absorption and penetration of toxic gases

This technical note provides details of an experimental technique for in-vitro skin studies with atmospheric chemical challenge. There appear to be major evidence gaps in relation to dermal exposure of gases. We describe a modification of standard OECD protocols for an atmospheric delivery system which can be used to understand interaction of toxic gases and the skin. The system can be used to examine the mechanisms by which skin uptake occurs. Auxiliary components which allow for parameter variation such as temperature and relative humidity are also described. Methodology presented in this technical note uses examples of gas challenges (ammonia, chlorine) to illustrate its application to gases of differing physicochemical properties. This adapted protocol can be applied in the context of HAZMAT scenarios involving atmospheric toxic chemical release and dermal absorption potential under variable exposure conditions.