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PubMed2003

Urinary actin, interleukin-6, and interleukin-8 may predict sustained ARF after ischemic injury in renal allografts.

BACKGROUND: Cellular damage and inflammation after ischemia contribute to sustained acute renal failure (ARF). METHODS: To quantify cellular damage and inflammation in postischemic ARF and identify markers of renal functional outcome, urine specimens from 40 renal allograft recipients, including 30 cadaveric (9 "sustained ARF" and 21 "recovery" subjects) and 10 living donor allografts ("LD"), were analyzed for actin, gamma-glutamyl transpeptidase (GGTP), lactate dehydrogenase (LDH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) during the first posttransplant week. RESULTS: On day 0, urinary actin, GGTP, IL-6, and IL-8 were elevated in recipients destined to have sustained ARF compared with those destined to recover. Median values per gram of urine creatinine in the sustained ARF, recovery, and LD groups were 263.9, 0.0, and 0.0 microg for actin; 5000.0, 892.9, and 5555.6 U for GGTP; 193.1, 27.2, and 10.5 ng for IL-6; and 382.0, 17.8, and 18.5 ng for IL-8, respectively. In contrast, urinary LDH and TNF-alpha increased in recipients with recovering function compared with those who had sustained ARF. The corresponding median values were 36.7 and 16.3 U (recovery versus sustained ARF) for LDH, and 18.4 and 7.6 ng (LD versus sustained ARF) for TNF-alpha. Computational analyses using the Receiver Operating Characteristic Curve found that elevated urinary actin, IL-6, and IL-8 on day 0 were strong predictors of sustained ARF, where the calculated areas under the curve were 0.75, 0.91, and 0.82, respectively. CONCLUSION: Increased urinary actin, IL-6, and IL-8 may be useful markers for the prediction of sustained ARF after ischemia.

Actins↗
PubMed2000

Distribution of glutamate and preproenkephalin messenger RNAs following transient focal cerebral ischemia.

Middle cerebral artery occlusion may result in increased activation of N-methyl-D-aspartate- or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type receptors by glutamate and lead to neuronal cell death. To characterize molecular events that precede cell death following transient focal ischemia, in situ hybridization histochemistry was used to measure levels of glutamate receptor subunit 1 (GluR1), GluR2, GluR3, N-methyl-D-aspartate receptor subunit 1 (NR1) and preproenkephalin messenger RNAs in adult rats at various recirculation times (1.5, 3 and 24 h) following a 90-min period of middle cerebral artery occlusion. At 1.5 and 3 h recirculation, autoradiography showed pronounced but differential decreases in AMPA, NR1 and preproenkephalin messenger RNA expression throughout the infarcted ipsilateral striatum. Non-uniform patterns of in situ hybridization grains emerged such that many striatal neurons were depleted of AMPA and preproenkephalin messenger RNAs, while others retained control levels. In cortical regions destined to undergo infarction, GluR2 and NR1 messenger RNAs were preferentially reduced relative to the contralateral side (to 75+/-8.5% and 66+/-4.5%, respectively); GluR1, GluR3 and preproenkephalin messenger RNAs were unaltered. At 24 h recirculation, depletion of striatal and cortical messenger RNAs became less selective. GluR3 and preproenkephalin messenger RNAs were up-regulated in ipsilateral spared regions of the striatum, and GluR1 and GluR2 messenger RNAs increased bilaterally in the cingulate cortex and in selective nuclei of the amygdala. Histological cell death or neurodegeneration was not detected in areas of reduced glutamate and preproenkephalin messenger RNA expression in either the ipsilateral striatum or cortex before 24 h. These findings suggest that complex and long-lasting decreases in messenger RNA expression occur prior to significant cell loss in regions destined to undergo infarction. Increased formation of Ca2+-permeable AMPA receptor assemblies may occur in "unspared" and "spared" regions via different mechanisms and contribute to alterations in post-ischemic synaptic activity. The possibility arises that there may be altered relationships between glutamatergic and enkephalin synapses, since the dorsolateral striatum, where preproenkephalin messenger RNA expression is acutely reduced, receives innervation by the affected ipsilateral cortical region.

Animals↗
PubMed2003

Indications for long-term assist device placement as bridge to transplantation.

The current indications for long-term mechanical support as bridge to transplantation first require the patient to be a transplant candidate. Often times a patient presents with limited history and refractory cardiogenic shock, where a full transplant work-up for contraindications cannot be safely performed. The use of short-term mechanical support can be used to help filter out many patients who have easily identifiable contraindications to heart transplant. Nevertheless, patients need to be listed for a heart transplant before the implantation of some of these devices. This paradigm needs to be altered, because there are many instances where mechanical support can be used to support a patient for an intervention to "make" them a transplant candidate where they otherwise would not have been. Long-term mechanical support can overcome the cardiac contraindication to the surgical/interventional therapy to "cure" them of the process that would have prevented them from being a good cardiac transplant candidate in the first place. Noncardiac surgical procedures are well tolerated in these patients [11]. The FDA is currently evaluating the Vented Electric Heartmate system for use as destination therapy for patients who are not transplant candidates. Approval for this indication (with a device that is already approved for bridge to transplantation) will allow this paradigm shift. This system could be used in the group who may be good candidates, but not determined. If they were subsequently determined to not be a good surgical candidate, they would be chronically supported with the LVAD as destination therapy.

Equipment Design↗
PubMed2001

Stability of hibernating myocardium in pigs with a chronic left anterior descending coronary artery stenosis: absence of progressive fibrosis in the setting of stable reductions in flow, function and coronary flow reserve.

OBJECTIVES: This study was performed to determine whether hibernating myocardium is adaptive or is destined to undergo progressive irreversible injury. BACKGROUND: Previous studies have suggested that hibernating myocardium eventually results in progressive dysfunction. Since serial studies cannot be performed in humans, the temporal progression of physiologic and structural adaptations was evaluated in pigs with hibernating myocardium. METHODS: Pigs were instrumented with a left anterior descending coronary artery (LAD) stenosis (1.5 mm) and underwent physiologic studies three to five months later to quantify regional function, perfusion and 18F-2-deoxyglucose (FDG) uptake. Viability was confirmed by histology and contractile reserve. RESULTS: Hibernating myocardium was characterized by severe regional dysfunction (centerline score, -1.9+/-0.1), reduced resting subendocardial flow (LAD: 0.85+/-0.03 vs. normal: 1.02+/-0.03 ml/min/g, p < 0.01), critically reduced subendocardial flow reserve (adenosine flow: 1.04+/-0.09 ml/min/g, p = NS vs. rest; epinephrine flow: 0.88+/-0.07 ml/min/g, p = NS vs. rest) and increased FDG uptake (0.022+/-0.002 vs. 0.014+/-0.001 ml/g/min, p < 0.01). Physiologic parameters were not different among animals studied at three (93+/-1 days, n = 27), four (118+/-2 days, n = 26) or five months (150+/-6 days, n = 9). Pathology revealed a small increase in LAD connective tissue (6.4+/-0.4% vs. 4.0+/-0.2%, p < 0.001), with no change over this time frame. CONCLUSIONS: Thus, physiologic and structural features of hibernating myocardium remain constant for at least two months. The absence of functional deterioration or progressive fibrosis suggests that hibernation is adaptive rather than an unstable physiology destined to progress to irreversible injury. The stability of this model appears ideally suited for interventions targeted to improve flow and function in chronically dysfunctional myocardium.

Animals↗
PubMedDate not supplied

Effect of point of care testing on length of stay in an adult emergency department.

Devices are now available that are practical for point of care testing (PCT) in hospital settings. Previous studies in clinical settings, however, have failed to demonstrate a reduction in patients' length of stay (LOS) associated with the use of PCT. This randomized controlled study compared PCT with central laboratory testing in a hospital Emergency Department to assess the difference in patients' LOS. Patients randomized to PCT (n = 93) had a median stay of 3 h, 28 min (interquartile range [IR] 2:28 to 5:30), while those allocated to the central laboratory (n = 87) had a median stay of 4 h, 22 min (IR 3:04 to 5:47). The median stay associated with PCT was significantly shorter. Among patients who were destined to be discharged home, there was also a significantly shorter stay, but not among those who were destined to be admitted. It was concluded that the use of PCT can achieve significant time savings in an Emergency Department.

Adolescent↗
PubMed1996

Dopaminergic and GABAergic interneurons of the olfactory bulb are derived from the neonatal subventricular zone.

Earlier studies in our laboratory have demonstrated that a discrete region of the anterior part of the neonatal subventricular zone (SVZa) contains exclusively neuronal progenitor cells. The descendants of the SVZa progenitor cells are destined for the granule cell and glomerular layers of the olfactory bulb, where they differentiate into granule and periglomerular cells, the interneurons of the olfactory bulb, respectively. In the present set of experiments we examined the neurotransmitter phenotype of the SVZa-derived cells. In order to label SVZa-derived cells, the cell proliferation marker bromodeoxyuridine (BrdU) was injected into the SVZa of postnatal day 2 (P2) rats. After 3 weeks, by which time most of the SVZa-derived cells have migrated to their final destination in the bulb, the animals were perfused and their brains processed for immunohistochemistry. To identify the neurotransmitter phenotype of the SVZa-derived cells, sagittal sections of the forebrain, including the olfactory bulb, were double-labeled with an antibody to BrdU in conjunction with an antibody to gamma-amino-butyric acid (GABA) or tyrosine hydroxylase (TH), the rate limiting enzyme in the synthesis of dopamine. Using simultaneous indirect immunofluorescence to detect the presence of single- and double-labeled cells, we found that 59% and 51% of the BrdU-positive cells were immunoreactive for GABA in the granule cell and glomerular layers, respectively. In addition, 10% of the BrdU-positive periglomerular cells were immunoreactive for TH. The presence of double-labeled (BrdU-positive/GABA-positive and BrdU-positive/TH-positive) cells in the olfactory bulb, demonstrates that the SVZa is a source of the GABAergic and dopaminergic interneurons of the olfactory bulb during postnatal development.

Animals↗
PubMed1998

Immunizations for international travel.

Immunization recommendations for international travelers is a complex subject that takes into consideration the geographic destination, planned activities during travel, health conditions at destination, length of trip, and underlying health status of the traveler. The final immunization program is also determined by how much time is available before departure and the worldwide availability of vaccines and their cost. In some cases, preventive behaviors and chemoprophylaxis may protect against the risk of infection when immunizations are unavailable or unobtainable.

Bacterial Vaccines↗
PubMed1997

The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate targeted migration of branchial neural crest cells.

BACKGROUND: During vertebrate head development, neural crest cells migrate from hindbrain segments to specific branchial arches, where they differentiate into distinct patterns of skeletal structures. The rostrocaudal identity of branchial neural crest cells appears to be specified prior to migration, so it is important that they are targeted to the correct destination. In Xenopus embryos, branchial neural crest cells segregate into four streams that are adjacent during early stages of migration. It is not known what restricts the intermingling of these migrating cell populations and targets them to specific branchial arches. Here, we investigated the role of Eph receptors and ephrins-mediators of cell-contact-dependent interactions that have been implicated in neuronal pathfinding-in this targeted migration. RESULTS: Xenopus EphA4 and EphB1 are expressed in migrating neural crest cells and mesoderm of the third arch, and third plus fourth arches, respectively. The ephrin-B2 ligand, which interacts with these receptors, is expressed in the adjacent second arch neural crest and mesoderm. Using truncated receptors, we show that the inhibition of EphA4/EphB1 function leads to abnormal migration of third arch neural crest cells into second and fourth arch territories. Furthermore, ectopic activation of these receptors by overexpression of ephrin-B2 leads to scattering of third arch neural crest cells into adjacent regions. Similar disruptions occur when the expression of ephrin-B2 or truncated receptors is targeted to the neural crest. CONCLUSIONS: These data indicate that the complementary expression of EphA4/EphB1 receptors and ephrin-B2 is involved in restricting the intermingling of third and second arch neural crest and in targeting third arch neural crest to the correct destination. Together with previous work showing that Eph receptors and ligands mediate neuronal growth cone repulsion, our findings suggest that similar mechanisms are used for neural crest and axon pathfinding.

Animals↗
PubMed2003

Acquired commissural fusion of aortic valves in patients with left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) currently are used as bridges for patients who deteriorate clinically while awaiting cardiac transplantation. At the time of transplantation or subsequent death, we can assess the effect of long-term device implantation on cardiac structural changes. We have noted, in our years of experience, that aortic valve commissures may fuse in patients supported by LVADs. These observations may be important in the use of these pumps as long-term destination therapy. METHODS: We examined 33 hearts (both explants and autopsy specimens) from patients supported either with vented-electric (VE) HeartMates (n = 21) or with implantable pneumatic HeartMates (n = 12). We noted commissures involved, fusion length (mm), duration of LVAD support, and type of LVAD. As controls, we examined 49 explanted hearts from patients with heart failure who were not supported by LVADs. RESULTS: We found commissural fusion in 17 of the 33 hearts. Of those 17 hearts, 4 (23.5%) had 2 commissural fusions, and 13 (76.5%) had only 1 fusion. Fusion length ranged from 5 mm to 17 mm (mean, 9.9 mm). The lesion was more common in patients fitted with VE HeartMates (p < 0.0002). We found small amounts of commissural fusion in 8 of the 49 control hearts. CONCLUSIONS: Acquired commissural fusion is common in patients supported by LVADs, particularly the VE HeartMate. The lesion also occurs occasionally in failing hearts of patients not supported by LVADs. The significance of the lesion in patients who require long-term LVAD support either as a bridge to transplantation or as destination therapy is unclear.

Aortic Valve↗
PubMed2003

Recovery from heart failure with circulatory assist: a working group of the National, Heart, Lung, and Blood Institute.

BACKGROUND: Over the past decade, mechanical circulatory support has been beneficial as a bridge to cardiac transplantation, and anecdotal evidence suggests that heart failure patients fitted with mechanical assist devices experience direct cardiac benefits. Moreover, recent trials on limited numbers and subpopulations of patients--notably the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH)--support earlier observations of improved cardiac function and point towards the use of assist devices as destination therapy. Methods and results To investigate this phenomenon, on August 2-3, 2001, the National Heart, Lung, and Blood Institute convened the working group, "Recovery from Heart Failure with Circulatory Assist" in Bethesda, Maryland. The team included cardiac surgeons, cardiologists, and experts in experimental research. The goal was to prioritize recommendations to guide future programs in: (1). elucidating the mechanisms leading to reverse remodeling associated with a left ventricular assist device (LVAD); (2). exploring advanced treatments, including novel pharmacologies, tissue engineering, and cell therapies, to optimize recovery with LVAD therapy; and (3). identifying target genes, proteins, and cellular pathways to focus on for production of novel therapies for myocardial recovery and cardiovascular disease. CONCLUSIONS: The working group also made research and clinical recommendations to eventually translate findings into improved therapeutic strategies and device design: (1). support collaborations among clinical and basic scientists with an emphasis on clinical/translational research that might eventually lead to clinical trials; (2). identify candidate patients most likely to benefit from LVAD as a destination therapy; (3). explore potential biomarkers indicating when patients could most successfully be weaned from devices; and (4). promote clinical and experimental study of mechanically assisted organs and the tissue derived from them.

Adrenergic beta-Antagonists↗
PubMed1999

What do proteins need to reach different vacuoles?

Vacuolar proteins begin their life in the endoplasmic reticulum (ER) where they enter the secretory pathway. The information necessary for the correct delivery of soluble proteins to vacuoles has been found in propeptides that might be located at the N-terminus or the C-terminus of the protein, or might be internal. Without these propeptides, vacuolar proteins are secreted. For membrane proteins, both the transmembrane domains and the cytosolic tails are important for sorting to the tonoplast. Available information suggests that soluble proteins destined for the lytic vacuoles are transported through the Golgi complex and then sorted by a receptor that delivers them to a prevacuolar compartment. Proteins destined for the storage vacuoles might or might not travel through the Golgi complex and are packed into large, dense vesicles before being delivered to the storage vacuoles. Sorting of storage proteins occurs along the Golgi complex or in the ER itself and appears to involve self-aggregation.

Journal Article↗
PubMed1998

A practical method for simultaneous multiple intracerebral implantations for microdialysis in rats.

Many experimental designs require the chronic implantation of different elements destined to act as channels that facilitate the information conveyance between the brain and some external devices or vice versa. Electrodes for electrophysiological or electrochemical recording or brain stimulation, and guide shafts for drug administration or chemical monitoring of the extracellular space are the most common examples of channels serving those purposes. The stereotaxic implantation of one or more of those experimental tools in the same antero-posterior plane is relatively easy, but surgery is nonetheless more complicated when two or more elements have to be placed using totally different coordinates. In those cases the current strategy consists in the successive implantation of the elements, waiting for the hardening of the dental acrylic destined to fix one of them in place before dealing with the next. This procedure takes time, is considerably more laborious than surgery for single elements and is particularly difficult when the elements have to be implanted in close proximity. The present report describes a method that simplifies surgery for multiple intracerebral implantation and allows the simultaneous and exact placement of as many electrodes or guide shafts as is practical in any experimental design. The method requires the previous construction of a jig or template designed to temporarily hold the elements to be implanted, allowing them to assume and keep the same positional relationship that they should have when definitively in place within the skull. The design may vary according to the type of elements to be implanted and the coordinates required for each particular experiment, but here it is illustrated describing the assembly of a particular jig for the simultaneous implantation of guide shafts for ulterior microdialysis in the prefrontal cortex (PFC), nucleus accumbens (NAC) and striatum (STR). Some rules can be derived from this particular case to make the method a more general one and suitable for any combination of elements and stereotaxic coordinates.

Animals↗
PubMed2004

An update of recent evidence of the relationship between objective and self-report measures of the physical environment and physical activity behaviours.

The physical environment has the potential to influence the physical behaviours of large numbers of people; hence creating supportive environments has the potential to increase physical activity (PA). During the last decade, there has been growing interest in how the physical environment shapes PA behaviour. This area of research is important given that levels of PA participation are declining globally. Literature was reviewed that examined the association between physical environmental attributes and PA behaviours. The environmental attributes were grouped into four categories based on a conceptual framework of environmental factors that might influence PA and included functionality, safety, aesthetics and destinations. Positive associations were found between both perceived and objectively measured environmental factors and PA behaviour. The availability, accessibility and convenience of destinations and facilities, as well as the general functionality of the neighbourhood (eg, the presence of sidewalks, traffic conditions) and aesthetics were positively associated with various levels of PA. The review highlights the need for future studies: to examine behaviour-specific environmental attributes, to collect objectively-measured environmental data and to include both objective and perceived environmental data in the same studies, and to adopt prospective study designs to allow causal relationships to be established.

Environment↗
PubMed2005

Traveller's diarrhoea.

Traveller's diarrhoea affects over 50% of travellers to some destinations and can disrupt holidays and business trips. This review examines the main causes and epidemiology of the syndrome, which is associated with poor public health infrastructure and hygiene practices, particularly in warmer climates. Although travellers may be given common sense advice on avoidance of high-risk foods and other measures to prevent traveller's diarrhoea, adherence to such advice is sometimes difficult and the evidence for its effectiveness is contradictory. However, non-antimicrobial means for prevention of traveller's diarrhoea are favoured in most settings. A simple stepwise approach to the management of traveller's diarrhoea includes single doses or 3-day courses of antimicrobials, often self administered. The antibiotics of choice are currently fluoroquinolones or azithromycin, with an emerging role for rifaximin. In the long term, there will be greater benefit and effect on the health of local inhabitants and travellers from improving public health and hygiene standards at tourist destinations.

Anti-Bacterial Agents↗
PubMed2003

The treatment of Alzheimer's disease: success short of cure.

Metaphor has an important role in the discussion of scientific discovery because it enables researchers to talk about things of which their understanding is incomplete. Alzheimer's disease (AD) can be seen as a journey down a path, which becomes steadily less pleasant and ends in a wholly undesirable destination. To further the metaphor, treatments can be seen as attempts to help the patient return to the starting point, to slow the journey, or to stop at some point on the path. However, treatment may be successful but may not return the patient to their starting point or slow disease progression. We argue that treatments that steer the patient down a different path, to a destination preferable to that at the end of the AD path, can also be seen as successful. This metaphor has practical implications for clinical trials. It highlights the importance of individualised outcome measures that incorporate patients' preferences and should encourage us to develop better means of enabling the recovery of self. To understand how there can be treatment success short of cure, without knowing at the outset what form that success may take, will require systematic observation and careful description of patients' experiences.

Alzheimer Disease↗
PubMedDate not supplied

Gender influences on spine loads during complex lifting.

BACKGROUND CONTEXT: Previous research has documented differences in spine loading between genders when the imposed load is normalized relative to the size of the person. However, under realistic work conditions the magnitude of the load handled is seldom adjusted relative to worker anthropometry. Thus, there is a void in our knowledge in that we do not understand how material handling influences spine loading and potential risk of injury as a function of gender under realistic lifting situations. PURPOSE: To evaluate the differences in spine loading between men and women when exposed to similar workplace demands. STUDY DESIGN: A laboratory study was conducted to investigate the biomechanical responses during realistic free-dynamic lifting tasks when subjects lifted from origins and destinations that were either fixed or set relative to the subject's anthropometry. PATIENT SAMPLE: Twenty men and 20 women asymptomatic for low back pain were recruited to participate in the study. OUTCOME MEASURES: The three-dimensional spine loads were predicted from a well-established electromyography-assisted model. METHODS: Both genders completed a series of symmetric and asymmetric (60-degree clockwise) lifts that originated from two shelf heights ("relative" to knee height and "set" at 35 cm from floor) and terminated at one of two destination heights ("relative" to waist and "set" 102 cm from the floor). Three levels of box weight were investigated (6.8, 13.6 and 22.7 kg). RESULTS: Men had significantly greater compression forces than women (about 640 N). Loading differences between genders were further magnified by several of the workplace factors. The differences between men and women were even greater when lifting either of the heavier loads from the lower fixed shelf (more than 50% greater). CONCLUSIONS: It is apparent that men produce the greater loads on their spines during lifting. However, engineering controls, such as adjustable workplace layout or less weight lifted, may reduce or eliminate gender-specific differences in spine loads. Furthermore, the differences in spine loads appear to be a result of kinematic trade-offs and muscle coactivity differences in combination with unequal body masses between genders. However, when the loads were put into context of the expected tolerances of the spine, women were found to be at increased risk of injury, especially when lifting heavy loads or under asymmetric lifting conditions. Collectively, the results indicate the need to account for differences between the genders when designing the workplace.

Adult↗
PubMed2005

Reproductive health status, knowledge, and access to health care among female migrants in Shanghai, China.

As the largest labour flow in human history, the recent rise in migration in China has opened up unprecedented opportunities for millions of Chinese to rearrange their lives. At the same time, this process has also posed great challenges to Chinese migrants, especially female migrants, who not only face a bias against 'outsiders' but also have a greater need for reproductive health-related services in their migratory destinations. Based on data collected via multiple sources in Shanghai, China's largest metropolis, this study profiles the changing characteristics of female migrants, presents data on self-reported symptoms of reproductive health-related problems and knowledge on reproductive health issues, compares maternal and child health measures between migrants and local residents, and examines factors related to reproductive health knowledge and migrants' access to health care in urban China. Results of this study show a relatively low level of self-reported reproductive health problems among female migrants, coupled with a relatively high level of ignorance in knowledge related to STD. Both self-reported health status and knowledge of reproductive health are related to migrants' educational attainment and length of stay in the urban destination. This study also finds ample evidence that female migrants' access to urban health care is limited by a number of institutional barriers.

Adolescent↗
PubMed1977

Isolation of myxoviruses from dead birds arriving at Heathrow Airport, London.

Forty-four haemagglutinating viruses were isolated from the pooled tracheal/cloacal swabs of the dead birds from 170 consignments of caged birds arriving at Heathrow Airport over a period of 6 months. Two isolates were identified as Newcastle disease virus but the remaining 42 were all identified as influenza viruses with Hav 7 Neq 2 antigens. All the consignments from which influenza viruses were isolated originated in India but had widespread destinations. The NDV isolates were from birds originating in central America and destined for Japan.

Animals↗