text:
tom jones' two cents
Tampa Bay Times columnist Tom Jones looks back at the best and worst from a weekend of televised sports.
Most mediocre
ABC has been showing the Indianapolis 500 since 1965, so it knows how to cover the race. • It has all the nuts and bolts, as well as all the bells and whistles. • But despite the superb direction and production, the broadcast quite often falls flat. And I'm starting to think it's the broadcasters. • Marty Reid does a decent enough job as the lap-by-lap announcer, but analysts Eddie Cheever and Scott Goodyear are just meh. Maybe they should be applauded for not trying to be something they are not, but I just get so much more — information, analysis, entertainment — from the NASCAR broadcasters. • In addition, there was this: With only a few laps left and the race under caution, the broadcasters talked about how, after the restart, it would be better to be in the second or third position instead of leading. The broadcasters were right, but they never relayed why that was the case. If you are an experienced fan of IndyCar, you knew it was because of drafting and so forth. But that information was never clearly explained to the novices who might have been watching or who hadn't watched much of Sunday's race.
Newest star
Clearly, ABC/ESPN is intent on making anchor Lindsay Czarniak a star. After having a prominent role on SportsCenter, Czarniak became the first woman to host ABC's Indianapolis 500 broadcast on Sunday. This is a spot previously reserved for some of the giants in the business, such as Jim McKay, Brent Musburger and Keith Jackson.
It's also interesting that Czarniak has been given such a role after ESPN recently lost high-profile female broadcasters such as Erin Andrews, Michelle Beadle and Charissa Thompson.
Biggest hires
As previously rumored, the new Fox Sports 1 has hired former tennis great Andy Roddick to co-host Fox Sports Live, the flagship news program for the network. Roddick will join host Charissa Thompson on a panel, perhaps as often as five nights a week, to discuss some of the big events of the day.
This is an interesting hire. While certainly a big name in the sports world, he doesn't have extensive television experience in the media, other than being interviewed over the years. This could turn out to be a sensational hire or a complete embarrassment. But give Fox credit for a little outside-the-box thinking. That's what it needs to do if it hopes to compete with ESPN.
Oh, former NFL quarterback Donovan McNabb is another name rumored to be in line for a Fox Sports 1 job.
Most crowded
Typically, I'm not a fan of three-man booths. Occasionally they work. For example, NBC's setup of Doc Emrick, Ed Olczyk and Pierre McGuire is fantastic. That's rare for such a fast-moving sport like hockey. And, actually, it's rare for any sport.
Of all sports, you would think baseball would be the best for three-man booths because of all the time between pitches. Yet, whenever Sun Sports adds Orestes Destrade (left) to the broadcast with Dewayne Staats and Brian Anderson, as it did Saturday, it just doesn't work. And that's not a knock on Destrade. Maybe it's because Staats and Anderson are so comfortable together that it's hard for another voice, regardless of who that voice might be, to fit in.
It always feels as if Destrade has to interrupt to make his point. That's not to say he literally has to cut off Staats or Anderson, but it feels as if he has to butt his way into the conversation.
The thing is, Destrade, who usually is stationed at field level, makes good points. For example, he did a nice job Saturday pointing out that a Rays runner on first base (Ryan Roberts) would have advanced to third on a single if he had been more alert as to how deep the Yankees outfielders were playing. That was solid analysis by Destrade.
Unfortunately, as a third voice, it just doesn't feel like a natural conversation, no matter how hard Staats, Anderson and Destrade try to make it so.
Biggest jerk
There is a bigger jerk than Rangers coach John Tortorella when it comes to dealing with the media during a game. That would be Spurs coach Gregg Popovich (above), who regularly acts like a first-class crab when doing in-game interviews. On Saturday night, ABC's Doris Burke asked two good questions — one about his offense, another about his defense — and the answer to both was: "Turnovers." That was it. Look, we all realize that these in-game interviews are often a waste of time and coaches are busy. But, occasionally, they do offer insight. Even if they don't, how come Popovich is incapable of being respectful to a sideline reporter doing his or her job? Phil Jackson, the greatest NBA coach ever, took the time to be polite and give good answers, even when his team wasn't playing well. What makes Popovich so special?
Maybe someone needs to remind Popovich that television pays the bills. It's why he makes a nice living and lives in a nice house and has nice things. Take 20 seconds and answer a question.
Loudest voice
What bothers me about Gus Johnson as a football and basketball announcer is the same thing that bothers me about him as Fox's featured soccer announcer. His speaker-busting volume is so over-the-top ridiculous that I honestly don't understand what he's yelling half the time. During one of Johnson's explosions Saturday during the Champions League soccer final, I think I might have heard the words "London" and "Wembley," but I'm really not sure. And if he's screaming a name? Forget it. Whatever the name is, it comes off as, "Ayaaamaaaanreeeaaee."
Many people out there love Johnson's passion. They dig all the screaming. I'm just not one of those people.
Latest projects
Sports Illustrated media writer Richard Deitsch reports that ESPN has two more subjects in line for the "30 for 30" documentary series. The first is Bad Boys, about the Detroit Pistons of the late 1980s and early 1990s. That should air about a year from now. Meantime, a film on the soap opera involving figure skaters Tonya Harding and Nancy Kerrigan could run sometime later next year.
Three things that popped into my head
1. Isn't it interesting. Over the years, the AL East closers have included names such as Fernando Rodney, Jim Johnson, Jonathan Papelbon, Rafael Soriano, Joel Hanrahan, Casey Janssen and on and on and on. Yet, Mariano Rivera was, is and will be, until he retires, the best.
2. Fox's baseball game of the week Saturday was a prime-time game. Part of the reason Fox showed a prime-time game was because it aired the Champions League soccer final live during the day. Still, I think a baseball game of the week should air during the day, not at night. That's how it is supposed to be.
3. The only thing worse than watching senior golf is watching senior tennis. Both were on over the weekend. Egads.


text:
Newegg.com - A great place to buy computers, computer parts, electronics, software, accessories, and DVDs online. With great prices, fast shipping, and top-rated customer service - once you know, you Newegg.
If you are reading this message, Please click this link to reload this page.(Do not use your browser's "Refresh" button). Please email us if you're running the latest version of your browser and you still see this message.
Newegg.com - Computer Parts, Laptops, Electronics, HDTVs, Digital Cameras and More!
Showing Results: Most Recent
This review is from: TRENDnet TEG-S24DG Smart Unmanaged Gigabit GREENnet Switch
Pros: Integrated power supply, standard power cord
Cons: Not keyed for wall mounting without brackets.
Upon calling Trendnet support I was greeted to 19 minutes of hold. Finally "Albie" in India answers. I repeat my email address to him 3 times. As he then asks me to describe the problem that I am experiencing with the switch for the third time I'm transferred to his supervisor, who provides me with a case number and then a website. This is the most inefficient RMA process I have ever seen. The tech support team is rude and clearly NOT paying attention. The RMA process is frankly a major pain as well which will require at minimum 1 hour of your time to deal with Trendnet bureaucracy.
Other Thoughts: I have used several of their products with no problems. However if you have a problem, their support is HORRENDOUS.READ FULL REVIEW
This review is from: Genius GX-Speed DarkLight (31250043100) Mouse Pad
Pros: It's huge. Bigger than my laptop. As long as the rebate comes, I'm fine.
Cons: SO BIGREAD FULL REVIEW
This review is from: Rosewill RCN-SC106 - LCD Screen Cleaner (Large) - 3.3 Fl. Oz. (100 ml) Solution
Pros: I've had some fingerprints on my TV for over a year now. I tried to use water & a new microfiber cloth to clean it, but it just made it streak. Rather than scratch the screen I left it.
Behold! This product comes along, and viola! Screen looks brand new!
Cons: NoneREAD FULL REVIEW

subset: commoncrawl


text:
The Low is Maruti Suzuki Udyog's car substance to Bharat and the state's one of the most fashionable cars in the immature car portion. The Low is easy in figure variants including BS III and BS IV upset: Maruti Suzuki High Canonic, Maruti Suzuki Low LX, Maruti Suzuki Alto LXi and CNG variants. It borrows from Maruti Suzuki 800's proved and tested engine engineering, therefore delivering optimal execution.
The High, with its heavy dimensions and sturdy collective, is honorable justice for the Amerindian roads. Also, it needs smallest fixture and is extremely render economical, making it vindicatory the perfect car for the medium Asiatic excavation conference.
The Low has conventional a mates of modest upgrades on the inland as shaft as a new sporty perception framework and a such many essential bumper. It has also received two new colours, Caribbean Dispiriting and Wine Red.
The High is accoutred with a 796cc engine that serves up 46.3 bhp worth of land and 62 Nm of torque. A 5-speed, all synchromesh, drill coefficient is criterial in the Low. The car has both petrol and CNG options. The advanced debarment has a Evangelist Strut with force typewrite rotation check gimmick, spell the position sports helix fountain gas-filled combat absorbers with troika statement rigid axle and isolated down blazonry.
The ride property is dulcet and cozy but manipulation does not just assess up. Direction is absorbent at present. A formal dangling soaks up bumps equal a pro. Brakes are hugely tractable too. A formal chassis gives the Alto its mythological driving testimonial.


text:
Katadyn Vario Ceramic Disc
Where to Buy
sponsored links
Manufacturer's Description
Visit Katadyn's Vario Ceramic Disc page.
Retailers' Descriptions
Here's what other sites are saying:
Katadyn Vario Ceramic Disc Vario Ceramic Disc by Katadyn.
- Moosejaw
Keep the microfilter in your Katadyn Vario Water Filter going strong by giving it a new Vario Ceramic Disc. The Ceramic Disc lengthens the life of your microfilter so you can tackle trail after trail with fresh-tasting, bacteria-free water.
- Backcountry.com
Description of Katadyn Vario Ceramic DiscKeep your Katadyn Vario working the fullest.
- US Outdoor Store
The Katadyn Vario Ceramic Disc brings new life to your Vario microfilter.
- GearX.com
Katadyn Vario Ceramic Disc
currently retails for:


text:
Enter your Email address:
Wolters Kluwer Health may email you for journal alerts and information, but is committed
to maintaining your privacy and will not share your personal information without
your express consent. For more information, please refer to our Privacy Policy.
Saboory, Ehsan PhD*; Derchansky, Miron PhD*†; Ismaili, Mohammed PhD*; Jahromi, Shokrollah S. PhD*; Brull, Richard MD, FRCPC‡; Carlen, Peter L. MD, FRCPC*†§; El Beheiry, Hossam MBBCh, PhD, FRCPC*‡
From the *Toronto Western Research Institute, Departments of †Physiology, ‡Anesthesia and Pain Management, and §Medicine (Neurology), University of Toronto, University Health Network, Toronto, Ontario, Canada.
Supported by the Canadian Society of Anesthesiologists (H.E.B.) and the Canadian Institute of Health Research (P.L.C.).
Address correspondence and reprint requests to Hossam El Beheiry, MBBCh, PhD, FRCPC, Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, 399 Bathurst St., Room 2MC405, Toronto, Ontario, Canada M5T 2S8. Address e-mail to firstname.lastname@example.com.
BACKGROUND: High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors.
METHODS: Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons.
RESULTS: Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 μM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 μM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective μ and κ opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, δ opioid receptor ligands did not have an effect.
CONCLUSIONS: The proseizure effect of morphine is mediated through selective stimulation of μ and κ opiate receptors but not the activation of the δ receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.
Chronic severe pain afflicts more than 6% of the general population, and high-dose opioids are the mainstay of treatment (1). As research and education regarding the importance of opioid use in chronic severe pain continue to improve, the number of patients treated with high-dose opioids increases correspondingly, as does the incidence of opioid-related adverse effects (2). Among the most curious and dangerous of these adverse effects is neuroexcitation. Myoclonus and seizures have been reported with high doses of morphine (3,4), hydromorphone (4,5), meperidine (6), fentanyl (7), diamorphine (8), and after oral (9), IV (3,4,7), epidural (5), or intrathecal (8,10) administration. Indeed, the recognized neuroexcitatory effects of high-dose short-acting opioids, such as fentanyl, alfentanil, and remifentanil, are routinely harnessed to induce controlled electroencephalographic seizures during epilepsy surgery at our institution (11,12).
The mechanism, and thus treatment, of opioid-related neuroexcitation remains unclear. Previous animal investigations have suggested that the proconvulsant action of morphine is mediated through the 3-glucuronide morphine metabolite (13) or nitric oxide produced by constitutive nonspecific nitric oxide synthase (14). Other studies have proposed that multiple receptor systems are involved in triggering opioid-induced seizures, including opioid, adrenergic, and glutamatergic receptors (15,16), or by opioid antagonism of inhibitory γ-aminobutyric acid (GABA)ergic neurotransmission (17). Finally, some animal reports have implicated muscarinic and cannabinoid receptors in morphine enhancement of seizures (18,19).
A neuroexcitatory mechanism involving direct activation of opioid receptors has yet to be demonstrated definitively in the intact hippocampus. The intact in vitro hippocampal model allows precise control of the tissue environment and the direct application of selective receptor ligands without the involvement of different pharmacokinetic factors that can influence the access of such molecules to their respective site of action. Furthermore, the intact hippocampus maintains the neural pathways directly involved in seizure initiation and propagation, as well as the physiologic neuronal rhythms (20). The present study aimed to determine whether the neuroexcitatory effect of morphine is mediated through direct stimulation of specific opioid receptors. We hypothesize that morphine enhancement of seizure activity is mediated through selective stimulation of opioid receptors in the intact hippocampus.
The University Health Network Animal Care Committee review board approved this animal study protocol. C57/BL mice at 8th to 25th postnatal day were anesthetized with halothane and decapitated in accordance with the Canadian Animal Care Guidelines. The brain was carefully removed and bathed in ice-cold 2–5°C oxygenated (95% O2, 5% CO2) standard artificial cerebrospinal fluid (ACSF) containing the following: 123 mM NaCl, 2.5 mM KCl, 1.5 mM CaCl2, 2 mM MgSO4, 25 mM NaHCO3, 1.2 mM NaH2PO4, and 15 mM glucose. After removal of the cerebellum and the separation of the hemispheres at the midsagittal line, spatulas were used to carefully remove the brainstem and the midbrain region. The hippocampus was then resected by gently sliding the spatula ventral to the corpus callosum, making the first insertion at the septal hippocampal region. The septum was left intact and served as an anatomical marker for the location of the septal and temporal hippocampus regions (Fig. 1A). Hippocampi were bathed in oxygenated ACSF at room temperature for a minimum of 1.5 h before subsequent transfer into the recording chamber (21).
The intact hippocampus was maintained in a recording chamber at a temperature of 34°C ± 0.5°C, continuously perfused with oxygenated standard ACSF and secured by micropins. Humidified warmed oxygen flowed over the solution in the recording chamber to decrease the evaporation of oxygen from the perfusate. Solutions entered the chamber at a flow rate of 5 mL/min, refilling the volume of the 0.6 mL chamber with fresh solution eight times per minute. Seizure-like electrographic activity was induced by perfusing the tissue with low-Mg2+ ACSF containing the following: 123 mM NaCl, 5 mM KCl, 1.5 mM CaCl2, 0.25 mM MgSO4, 25 mM NaHCO3, 1.2 mM NaH2PO4, and 15 mM glucose.
Recordings were performed from the CA1 pyramidal neuronal layer of the hippocampus by positioning the hippocampus DG-CA3 region dependent on nylon mesh and the CA1 region faced upwards. A Grass S44 (Grass Medical Instruments, West Warwick, RI) stimulator with bipolar electrode was used to stimulate Schaffer collaterals (1–15 V, 0.1 ms) and extracellular glass electrodes containing 150 mM NaCl that were positioned at locations yielding maximal evoked and spontaneous field potential amplitudes in the CA1 stratum pyramidale. Input/output relations were recorded with stimulating pulses of 10 different intensities, evoking subthreshold to suprathreshold population responses. All single-site recordings of seizure-like events were obtained from the middle of the hippocampus (Fig. 1A), and filtered with 1 kHz low-pass filter unless otherwise stated, amplified, and recorded at 2 kHz sampling rate with an Axopatch 200B amplifier (Axon Instruments, Foster City, CA). The signals were digitized using the 16-bit data acquisition system Digidata 1322A (Axon Instruments, Foster City, CA). Data visualization was achieved with Clampfit 8.2 (Axon Instruments, Foster City, CA). All results are shown as mean values ± sem.
All drugs used in the present study were obtained from Sigma-Aldrich (St. Louis, MO), except morphine sulfate purchased from Abbott (Toronto, Canada). Drugs were dissolved in standard ACSF or low Mg2+ ACSF to designated concentrations as follows: morphine (10, 30, and 100 μM); selective μ-opioid receptor agonist, DAMGO (10 μM) and antagonist, B-FNA (10 μM); κ-opioid receptor agonist, Dyn-A (10 μM) and antagonist, nor-BNI (10 μM); and δ-opioid receptor agonist, DPDPE (10 μM) and antagonist, NTI (10 μM).
The electrographic seizure activity was quantified by determining mean ± sem of seizure duration, late seizure frequency, and intraburst frequency (Figs. 1B and C). The seizure duration is the time elapsed between the start of the early phase and the termination of the late phase not including the transition, i.e., prodromal phase (Fig. 1B). Where applicable, data were analyzed using one-way and repeated measures ANOVA and paired and unpaired t-test. Statistical significance was considered at a P < 0.05.
Control experiments were performed to determine the consistency and stability of the seizure activity induced by perfusing the intact hippocampus with low Mg2+ ACSF. In each of 10 different hippocampi, the recurrent seizure patterns were consistent and did not change their electromorphologic appearance. Recurrent seizures had a mean duration of 87 ± 5 s, and there were 2 ± 0.65 seizures per 10 min. Usually, the recurrent seizure events started approximately 6–12 min after the administration of low Mg2+ ACSF and lasted for approximately 95–120 min in a consistent and stable manner. Single maximal postsynaptic population spikes were evoked by stimulating the Schaefer collateral to monitor the viability of the hippocampi. Experiments were terminated if there was a deterioration of the population spike amplitude below 75% relative to their initial values. A single seizure consisted of an early and a late phase (Fig. 1B). The early phase consisted of a series of single spikes with a mean frequency of 1 Hz. The late phase comprised of multiple bursts with a mean burst frequency of 1.3 Hz. The intraburst frequency was defined as the number of spikes per second contained in a single burst occurring during the late phase of a seizure (Fig. 1C).
Because naloxone is considered a nonspecific opiate antagonist for morphine, we performed experiments to elucidate the action of this drug on the seizure activity of the epilepsy model used in this study. Naloxone 5 μM applied to hippocampi perfused with low Mg2+ ACSF had no effect on the spontaneous electrographic seizures. However, naloxone 10 μM had a statistically significant effect in attenuating seizure duration (Table 1).
The application of morphine to intact hippocampi exhibiting seizure activity revealed a biphasic effect. Morphine 10 μM decreased the duration of the seizure activity and the number of recurrent seizure events per 10 min (Figs. 2A and 3A). However, the late burst and intraburst frequencies were not affected (Figs. 3B and C). These effects were completely reversed after a washout period of about 20 min. The addition of naloxone 5 μM to the perfusate did not reverse such inhibitory actions of morphine. When higher concentrations of morphine (30 and 100 μM) were applied, seizure activity was enhanced in duration in a dose-dependent manner (Figs. 2B and 3A). Naloxone 5 μM blocked such enhancement in seizure activity (Figs. 2C and 3A). Meanwhile, higher morphine concentrations did not significantly change the early phase frequency but depressed the late bursting and intraburst frequencies (Figs. 3B and C). Higher morphine concentrations (30 and 100 μM) administered to the hippocampi perfused with standard ACSF did not cause any seizure activity. Moreover, the enhancement of seizure activity in hippocampi perfused with low Mg2+ ACSF containing morphine was not sustained when the same hippocampi were subsequently perfused with standard ACSF containing morphine.
To address the question of which opioid receptor was responsible for mediating the proseizure action of morphine, we applied selective opioid agonists and antagonists to hippocampi exhibiting seizure activity when perfused with low Mg2+ ACSF (Fig. 4; Table 2). The μ and κ opiate receptor selective agonists, DAMGO 10 μM and Dyn-A 10 μM, respectively, enhanced seizure activity as evidenced by the increase in seizure duration and number of recurrent seizure events per 10-min intervals. Similar to the higher morphine concentrations (30 and 100 μM), the μ and κ opiate receptor agonists decreased the late burst and intraburst frequencies. On the contrary, the μ and κ receptor antagonists, i.e., B-FNA and nor-BNI, respectively, depressed seizure discharges in seizing hippocampi perfused with low Mg2+ ACSF. Such depression of seizure discharges was in the form of a decrease in seizure duration and the conversion of the seizure into a state of stable firing rate (Figs. 4A and B). The latter effect might have been due to the agonist-induced shift of the neuronal activities from a disinhibited "down-state" that leads to the seizures to an active "up-state," i.e., a stable increased firing rate. Neither selective δ receptor agonist DPDPE 10 μM nor its antagonist NTI 10 μM had any significant effect on the electrographic seizure events.
The most important finding of the present study is that the neuroexcitatory action of morphine is mediated through selective stimulation of the μ and κ opiate receptor subtypes. This study is the first to demonstrate that a high concentration of morphine can enhance spontaneous seizure activity in an apparent dose-dependent manner in the intact hippocampus maintained in vitro. Such action had been demonstrated in whole-animal epilepsy models when morphine at higher doses was administered intraperitoneally, IV, or intracerebroventicularly (22,23). This study also confirms that morphine has a biphasic effect, as reported in previous whole-animal studies (23,24); that is, a low morphine concentration demonstrated an antiseizure effect whereas higher morphine concentrations enhanced spontaneous seizure activity.
The present investigations used an in vitro low Mg2+ model of hippocampal epilepsy so as to examine the possible mechanisms of morphine-induced seizures. Low Mg2+ leads to neuronal hyperexcitability that is conductive for seizure generation by decreasing membrane surface charge screening, decreasing Mg2+ sensitive Ca2+ channel block and decreasing the Mg2+ blockade of N-methyl-d-aspartate receptors. This implies that different strategies can be used to treat opioid-induced enhancement of seizure activities. It is true that high concentrations of morphine did not elicit seizure activities in the present study when the Mg2+ concentrations were normal. However, our conclusions from the low Mg2+ model can be relevant to those instances when morphine induces seizure activities in the clinical situation (2–4). The low Mg2+ model of epilepsy showed seizure-like discharges similar to the progression of electroencephalographic abnormalities in patients with partial complex seizures and partial status epilepticus (22). It is also well recognized that a low serum Mg2+ concentration can cause seizures, and IV Mg2+ administration can prevent and control convulsions associated with eclampsia. Hence, it is reasonable to assume that the findings and conclusions of the present study can have relevance to various clinical situations.
The antiseizure effect of morphine observed in this study was similar to previously reported findings in whole-animal models of epilepsy (23,24). The mechanism of this effect in our model is probably not related to the direct stimulation of specific opioid receptors because adding naloxone 5 μM to the perfusate with morphine 10 μM did not reverse the antiseizure effect. It is possible that the mechanism of such action is mediated through inhibitory effects on glutamatergic excitatory pathways and increasing GABAergic activity. Although the antiseizure effect might be clinically insignificant, its occurrence indicates that our intact isolated hippocampal epilepsy model is sensitive enough to experimentally simulate the biphasic neuroexcitatory actions of morphine. The clinical implications of this effect can be expressed in a historical context, as opioids in the past had been used to abort intractable seizures in epilepsy patients (25).
Morphine-enhanced seizure activity was depicted by an apparent dose-dependent increase in the duration of ictal events. However, we also observed a simultaneous decrement in the ictal late burst and intraburst frequencies. Late burst and intraburst frequencies reflect hypersynchronous behavior of the neuronal networks involved in initiating and maintaining seizure activity (26). The morphine-induced depression of both the late burst and intraburst frequencies of the seizure-like events were probably due to multiple morphine effects at the cellular level that should be further investigated to identify their pathophysiologic significance.
Our results validate the hypothesis that the proseizure effect of morphine is mediated through selective μ and κ opioid receptor stimulation, but not activation of δ receptor subtypes. This is because spontaneous seizure activity was enhanced by specific μ and κ agonists, i.e., DAMGO and Dyn-A, respectively, and suppressed by μ and κ antagonists, i.e., B-FNA and nor-BNI, respectively. We can only speculate on the "downstream" mechanisms by which μ and κ-opioid receptor stimulation enhances spontaneous seizure activity. Stimulation of the μ and κ-receptor subtypes can lead to a state of disinhibition in CA1 pyramidal neurons similar to that described in a subpopulation of periaqueductal gray neuronal elements (27). The disinhibitory effect may be mediated by decreasing the recurrent inhibition of the CA1 pyramidal cells through suppression of inhibitory GABAergic interneurons (28). The latter leads to enhancement of the recorded seizure-like events in the intact hippocampus. Suppression of GABAergic interneurons may be produced by presynaptic mechanisms that decrease GABA release. Accordingly, Vaughan et al. (27) reported that selective μ and κ-receptor agonists can reduce the amplitudes of evoked inhibitory postsynaptic currents with a simultaneous decrement in the rate of spontaneous miniature inhibitory postsynaptic currents without any effect on their amplitude distributions or kinetics in mice with intact opioid receptor subtypes. Another possibility is that the suppression of GABAergic interneurons can be a consequence of activating an inward rectifying K+ current. This current was found to be enhanced by μ and κ agonists (27).
In conclusion, our findings indicate that the proseizure effect of morphine is mediated through selective stimulation of μ and κ opiate receptors. The observed dose-dependent mechanism of morphine neuroexcitation underscores the importance of careful adjustment and individualized opioid dosing in the clinical setting, and could help guide the development of therapeutic strategies to prevent and treat opioid-related seizures.
© 2007 International Anesthesia Research Society
Colleague's E-mail is Invalid
Your Name: (optional)
Your Email:
Colleague's Email:
Separate multiple e-mails with a (;).
Thought you might appreciate this item(s) I saw at Anesthesia & Analgesia.
Send a copy to your email
Your message has been successfully sent to your colleague.
Some error has occurred while processing your request. Please try after some time.
An Existing Folder
A New Folder
Folder Name:
The item(s) has been successfully added to "".
Login with your LWW Journals username and password.
Username or Email:
Forgot Password?
Need to Activate a New Subscription?Recently purchased a subscription? Login or Register a new account
and enter your subscription ID, or Subscribe Now!
Become a Society Member
Enter and submit the email address you registered with. An email with instructions to reset your password will be sent to that address.
Link to reset your password has been sent to specified email address.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Save my selection
Article Level Metrics


text:
Estate Planning Checklist
In this article
- Your goal: minimize taxes and preserve assets
- Start by evaluating your needs
- Review our estate planning checklist
- Develop your plan with a qualified legal advisor
Because you've worked hard to create a secure and comfortable lifestyle for your family and loved ones, you'll want to ensure that you have a sound financial plan that includes trust and estate planning. With some forethought, you may be able to minimize gift and estate taxes and preserve more of your assets for those you care about.
Step One: Needs Evaluation
Two key components of your initial needs evaluation are an estate analysis and a settlement cost analysis. The estate analysis includes an in-depth review of your present estate settlement arrangements. This estate analysis will also disclose potential problems in your present plan and provide facts upon which to base decisions concerning alterations in your estate plan.
For example, you may believe that your current arrangements are all taken care of in a will that leaves everything to your spouse. However, if you've named anyone else as a beneficiary on other documents -- life insurance policies, retirement or pension plans, joint property deeds -- those instructions will likely overrule anything set forth in a will. You want to ensure that all your instructions work harmoniously to follow your exact wishes. In addition, you may want to consider leaving a portion of your assets to someone other than your spouse. The reason? While your spouse will receive your estate free of estate taxes if he/she is a U.S. citizen, anything he or she receives above the applicable exclusion amount ($5.12 million in 2013) will be subject to estate taxes upon his or her death.
An estate settlement cost analysis summarizes the potential costs of various estate distribution arrangements. In estimating these costs, the analysis tests the effectiveness of any proposed estate plan arrangement by varying the estate arrangement, the inflation, and date of distribution assumptions, as well as specific personal and charitable bequests.
The issues around estate planning are complex. Though a simple will may adequately serve the estate-planning needs of some people, you should meet with a qualified legal advisor to be sure you are developing a plan that works best for you. One good way to prepare for such a meeting would be to consider the questions in the following checklist.
Estate Planning Checklist
Part 1 - Communicating Your Wishes
|Do you have a will?
|Are you comfortable with the executor(s) and trustee(s) you have selected?
|Have you executed a living will or health care proxy in the event of catastrophic illness or disability?
|Have you considered a living trust to avoid probate?
|If you have a living trust, have you titled your assets in the name of the trust?
Part 2 - Protecting Your Family
|Does your will name a guardian for your children if both you and your spouse are deceased?
|If you want to limit your spouse's flexibility regarding the inheritance, have you considered creating a Q-TIP trust in your will?
|Are you sure you have the right amount and type of life insurance for survivor income, loan repayment, capital needs, and estate-settlement expenses?
|Have you considered an irrevocable life insurance trust to exclude the insurance proceeds from being taxed as part of your estate?
|Have you considered creating trusts for family gift giving?
Part 3 - Helping To Reduce Your Estate And Income Taxes
|If you are married, are you taking full advantage of the marital deduction?
|Do you and your spouse each individually own enough assets for each of you to qualify for the applicable exclusion amount? (The estate tax exclusion amount is $5.12 million in 2013.)
|Are both your estate plan and your spouse's plan designed to take advantage of each of your applicable exclusion amounts?
|Are you making gifts to family members that take advantage of the annual gift tax exclusion, currently $14,000?
|Have you gifted assets with a strong probability of future appreciation in order to maximize future estate tax savings?
|Have you considered charitable trusts that could provide you with both estate and income tax benefits?
Part 4 - Protecting Your Business
|If you own a business, do you have a management succession plan?
|Do you have a buy/sell agreement for your family business interests?
|Have you considered a gift program that involves your family-owned business, especially in light of "estate freeze" rules? (These rules were enacted by Congress to prevent people from artificially freezing their estate values for tax purposes.)
Points To Remember
- A plan helps you minimize estate and income taxes, administrative expenses, executor's commissions and attorney's fees.
- Your plan can help you determine what steps you need to take to help provide an adequate income to your survivors.
- An estate plan helps you preserve the assets you have worked hard to accumulate.
Because of the possibility of human or mechanical error by S&P Capital IQ Financial Communications or its sources, neither S&P Capital IQ Financial Communications nor its sources guarantees the accuracy, adequacy, completeness or availability of any information and is not responsible for any errors or omissions or for the results obtained from the use of such information. In no event shall S&P Capital IQ Financial Communications be liable for any indirect, special or consequential damages in connection with subscriber's or others' use of the content.
© 2013 S&P Capital IQ Financial Communications. All rights reserved.
Life insurance and annuities are issued by an affiliate, AXA Equitable Life Insurance Company (NY, NY) and by various unaffiliated carriers. Securities products and services are offered through AXA Advisors (member FINRA / SIPC), 1290 Avenue of the Americas, NY, NY 10104 (212-314-4600). Securities (including mutual funds) are not FDIC insured, not bank guaranteed and subject to investment risk, including possible loss of principal invested. AXA Advisors and AXA Equitable are affiliated and do not provide tax or legal advice.
Life insurance and annuities are issued by an affiliate, AXA Equitable Life Insurance Company (NY, NY) and by various unaffiliated carriers. Securities products and services are offered through AXA Advisors (member FINRA / SIPC), 1290 Avenue of the Americas, NY, NY 10104 (212-314-4600). Securities (including mutual funds) are not FDIC insured, not bank guaranteed and subject to investment risk, including possible loss of principal invested. AXA Advisors and AXA Equitable are affiliated and do not provide tax or legal advice.
Amount in equity investments are subject to fluctuation in value and market risk, including loss of principal.
International securities carry additional risk including currency exchange fluctuation and different government regulations, economic conditions or accounting standards.
Stocks of small-size companies may have less liquidity than those of larger companies and may be subject to greater price volatility than the over all stock market. Smaller company stock involve a greater risk than is customarily associated with more established companies.
Bond investments are subject to interest rate risk so that when interest rates rise, the prices of bonds can decrease and the investor can lose principal value.
An investment in a money market fund is not insured or guarantee by the Federal Deposit Insurance Corporation or any other government agency.
Please consider the charges, risk, expenses and investment objectives carefully before purchasing a mutual fund. For a prospectus containing this and other information, please contact a financial professional. Read it carefully before you invest or send money.
Information provided has been prepared from S&P Capital IQ Financial Communications sources and data we believe to be accurate, but we make no representation as to its accuracy or completeness. Data and information is provided for informational purposes only, and is not intended for solicitation or trading purposes. S&P Capital IQ Financial Communications is not an affiliate of AXA Equitable. Please consult your tax and legal advisors regarding your individual situation. Neither AXA Equitable nor any of the data provided by AXA Equitable or its content providers, such as S&P Capital IQ Financial Communications, shall be liable for any errors or delays in the content, or for the actions taken in reliance therein. By accessing the AXA Equitable website, a user agrees to abide by the terms and conditions of the site including not redistributing the information found therein.


text:
To the Editor: Drs Frisch and colleagues1 reported that breast cancer was the only malignancy, at least in women, to exhibit a statistically significant pattern of decreasing relative risk (RR) with increasing amounts of time following a diagnosis of acquired immunodeficiency syndrome (AIDS). A recent study also found a statistically significant decrease in the incidence of breast cancer, in both men and women, following the AIDS epidemic in Tanzania.2 Furthermore, some studies3 have found that immunosuppressed transplant recipients have a diminished incidence of breast cancer relative to other malignancies. This is contrary to what one would expect, since human immunodeficiency virus (HIV) infection theoretically increases the susceptibility to malignancy because of an acquired deficiency in immunosurveillance of tumor cells and/or an increased susceptibility to oncogenic viruses.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Need assistance?
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.


text:
Thanks for the info, Demuralist.
In my reading this morning, I came across this website and thought of you...Private MD - Buy Lab Tests Online
They a variety of tests, and the price is listed on their website (I was reading Jimmy Moore's blog about his progress and the link was on his page). They do allergy testing for the "biggies" (milk, soy, wheat, etc) for $90. No doc necessary. I didn't go too deeply into it, but worth a look right?
(p.s. for $250 they offer a cancer blood screen if you are really worried)
Last edited by demuralist; 11-24-2013 at 08:14 AM.
Thanks for the info, Demuralist.
I need some fat, and there's not much of it to be had today. Will beg for the trimmings from everyone's pork chops tonight.
Been working up a storm today. There was no leisurely watching of the Panthers-Dolphins game. Instead, while it was on I:
Assembled our Thanksgiving wreath
Cleaned 6 pairs of shoes and two bags
Wrote various cards and letters
Sorted the pile of papers on the counter
Helped paint during half-time
Made a note-card organizer out of a shoe box(decoupage still to be done)
Made my grocery shopping list for Thursday and Friday
This evening I will be taking Littlest to a farewell party for a friend, and when we get back, I will collapse on the sofa to watch Amazing Race, and if I can stay up long enough, The Walking Dead.
Littlest is hoping for a snow-day tomorrow. I think it will be just cold and wet enough to be unpleasant, without having to stay home.
I have paint in my hair.
Oh my goodness. I just read Friday's 'Success Story'. Why did Mark print that one? Okay, she's gained a little muscle back, and is starting to feel better, but it still sounds and looks like she is not healthy. Just because you are smaller, doesn't make you a success. She looks much better in her before pictures.
I'm disappointed. Sometimes the success stories don't speak to me, but this is the first time I have thought, 'oh,no, that's just wrong'. I scrolled down through the comments, and most of them were positive. Maybe others are like me, and don't want to 'attack' her, but yikes...just, yikes.
I thought the same thing...I was confused about the before and after pics as I thought she looked better before. Obviously we come in all sizes and shapes, and many people naturally tiny or lanky or stocky or in-between. But sheesh, I kept scrolling down looking for the after pics! It was kinda painful.
My Primal Journal: http://www.marksdailyapple.com/forum/thread53052.html
"Freedom from fear" could be said to sum up the whole philosophy of human rights. - Dag Hammarskjold
I totally agree. I think she looks sickly in the "after" pics. She needs to gain about 10 pounds.
1. Love ME no matter what noises are screaming at me, or who is trying to tear me down.
2. Eat to heal
3. Move to live
4. Embrace today
5. Live with intention
6. Respect my body
7. Cultivate joy
8. Find my passion
9. Meditate on peace in my soul
This is not the first time I read this about the success story, and I just don't get it. She's at the bottom of a healthy weight range or perhaps a little under but is not far off her "normal" weight range. She eats 3 times a day, eats primally, and cut her exercise to a fraction of its previous levels. She is also stabilizing hormones and gaining weight. Sure, she is thin but she is a 5' tall 20 year old.
When I look at her present pictures, I don't just see 'thin'. I see scrawny, bony. The title of her post '...to Healthy, Strong, and Fit' is what her 'before' pictures look like to me, NOT her 'after'. I would say now she looks 'fragile' if not frail.
Maybe it is just too soon for an 'after' shot. Some more muscle, and she might look fit and healthy again. Or maybe even JUST in comparison to her mid-way, 'anorexic-looking' shots. But when I look at the 'before', I think that is more of a 'primal ideal'.
Of course, she's happy, and that's the most important for her. But I only hope she really is feeling as good and strong as she says she is, and isn't just deluding herself. We all know how invested we can become in our self-image(myself no exception).
It feels weird to be discussing an individual so specifically. I hope she doesn't ever read my journal! Although, I also hope, that if asked, I would be brave enough to say this to her face. (As tactfully as I can, which isn't very. I am not known for my tact.) That's one of the standards I try to live up to- to say nothing you wouldn't say to a person's face(if asked), even if you might gulp, doing it. However, I can THINK what I like! We think lots of things that never need to be said.
I suppose a journal is a blend of the two, although I still try to tend to the first.
Sometimes, I fall down. Yay for edits!
Speaking about too thin, when I lay on my side now, I have to shift my knees around to find a good spot to be comfortable. I never thought of my KNEES as fat, but apparently there was a bit of cushioning there that I am now living without.
Last edited by Sabine; 11-25-2013 at 12:19 PM.


text:
Top Definition
A combination of dope and fantastic into one word
Raindrops on flowers are dopetastic
V-necks are dopetastic
V-necks are dopetastic
Por a_vacado 25 de junio de 2009
Trending Now
Can you define these popular missing words?
the words dope and fantastic combined. (:
Yo that song is dopetastic !
Por Salviigrldownthablock 22 de octubre de 2008
Dope, the 'tastic way.
Thats dope! Dope-tastic!
Por Sasha 08 de abril de 2004
of badass descent this word come from the straight up thuggish ruggish latin G's fo sho. It represent the epitemy of greatness and sex appeal.
Damn bro did you see that dopetastic guy he kicking that foos ass.
Por Ryan Vidales 26 de febrero de 2009
Awesomely sweet, relating to an object(NOT a person); see "raw"
Yo, that sound system is dope-tastic!
Por B-ware 07 de enero de 2005


text:
From the University of Michigan School of Medicine, Ann Arbor, MI.
Correspondence to: Lena Napolitano MD, Department of Surgery, University of Michigan Health System, Room 1C421 University Hospital, 1500 East Medical Drive, Ann Arbor, MI 48109-0033; e-mail: firstname.lastname@example.com
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).
© 2010 American College of Chest Physicians
Massive transfusion (MT) is a lifesaving treatment of hemorrhagic shock, but can be associated with significant complications. The lethal triad of acidosis, hypothermia, and coagulopathy associated with MT is associated with a high mortality rate. Other complications include hypothermia, acid/base derangements, electrolyte abnormalities (hypocalcemia, hypomagnesemia, hypokalemia, hyperkalemia), citrate toxicity, and transfusion-associated acute lung injury. Blood transfusion in trauma, surgery, and critical care has been identified as an independent predictor of multiple organ failure, systemic inflammatory response syndrome, increased infection, and increased mortality in multiple studies. Once definitive control of hemorrhage has been established, a restrictive approach to blood transfusion should be implemented to minimize further complications.
Massive transfusion (MT) is a lifesaving treatment of hemorrhagic shock but can be associated with numerous and significant complications. We will review possible complications and their management, particularly as they pertain to MT in the trauma patient.
There are numerous problems associated with MT, including infectious, immunologic, and physiologic complications related to the collection, testing, preservation, and storage of blood products (Table 1). Clinicians must be fully aware of these complications and strategies to both prevent and treat them. The cumulative risks of blood transfusion have been related to the number of units of packed red blood cells (PRBCs) transfused, increased storage time of transfused blood, and possibly donor leukocytes. A number of potential mechanisms that may mediate adverse affects associated with blood transfusion in trauma have been proposed.1-3 These data have led some to conclude that blood transfusion should be minimized whenever possible.4
TACO = transfusion-associated circulatory overload; TRALI = transfusion-related acute lung injury; TRIM = transfusion-related immunomodulation.
Uncontrolled hemorrhage may ultimately result in the development of hypothermia, coagulopathy, and acidosis.5 Each of these life-threatening abnormalities exacerbates the others, contributing to a spiraling cycle, sometimes called the "bloody vicious cycle," that rapidly results in death unless hemorrhage is stopped and the abnormalities reversed.6-8 A number of strategies, including early definitive control of hemorrhage, improved blood resuscitation, and more aggressive treatment of coagulopathy and hemostatic defects, have all been implemented in attempts to improve survival with MT.
Hypothermia occurs frequently in patients with hemorrhagic shock requiring MT. In trauma patients there are multiple factors that contribute to hypothermia, including exposure, infusion of cold fluids and blood products, opening of body cavities, decreased heat production, and impaired thermoregulatory control. Infusion of unwarmed or inadequately warmed IV fluids and cold blood products is a well-known cause of hypothermia and may contribute to the multiple adverse consequences of hypothermia, such as peripheral vasoconstriction, metabolic acidosis, coagulopathy, infection, and cardiac and other morbidities. Blood products are normally stored between 1°C and 6°C, and rapid transfusion of large quantities will lead to hypothermia. Hypothermia is associated with a number of serious complications including, but not limited to:
Decreased citrate metabolism
Decreased hepatic metabolism
Decreased drug clearance
Decreased synthesis of acute phase proteins
Decreased production of clotting factors
Hypothermia has a significant effect on the coagulation cascade. There is a 10% reduction in coagulation factor activity for each 1°C drop in temperature,9 which prolongs clotting times at temperatures below 33°C.10 Hypothermia results in a decreased ability to form stable clots, which is critically important in trauma patients with hemorrhage. However, clinicians may underestimate the effect of hypothermia on coagulation factor activity in vivo because prothrombin time and activated partial thromboplastin time assays are performed at 37°C.11,12 Hypothermia can be avoided in patients requiring MT by:
Elevating the room temperature
Surface warming the patient with heating blankets, heating lamps
Using heated and humidified inspired gases for ventilators
Using blood and fluid warmers for all fluids administered13
A number of hemostatic abnormalities develop in patients requiring massive PRBC transfusion, including dilutional and consumptive coagulopathy and thrombocytopenia.14 Impaired hemostasis in these patients is often caused by a combination of dilution and consumption of clotting factors and hyperfibrinolysis. Coagulation defects are related to the total volume of blood transfused, preexisting hemostatic abnormalities, and therapeutic maneuvers for cessation of hemorrhage. A number of screening tests have been used to examine the coagulation and hemostasis defects seen with MT, including prothrombin time/partial thromboplastin time, thrombin time, platelet count, fibrinogen, and serum haptoglobin to determine evidence of hemolysis.
We know that 25 to 30% of severely injured patients are coagulopathic upon arrival in the ED.15,16 Early coagulopathy is associated with increased mortality in trauma.17,18 A landmark study19 confirmed that 75% of patients who had received 20 or more RBC-containing products of any kind (PRBCs, cell-saver units, or whole blood) had dilutional thrombocytopenia with platelet counts less than 50 × 109/L compared with no patients who had received less than 20 units of blood (P < .001). After transfusion of 12 units of relatively plasma-free red cell products (PRBCs or cell-saver units), 100% of patients had prothrombin time prolonged by more than 1.5 times normal, compared with only 36% in patients given less than 12 units (P = .012). Although prothrombin time is a poor indicator of bleeding propensity and coagulation factor deficiency, these data confirmed that MT patients receiving RBCs alone developed significant thrombocytopenia and coagulopathy and required coagulation factor and platelet replacement.
It is clearly recognized that the labile clotting factors V and VIII deteriorate with blood storage time. Furthermore, MT with PRBCs alone causes a dilutional coagulopathy, whereas massive hemorrhage causes a consumptive coagulopathy. Underlying hemostatic disorders also contribute to coagulation abnormalities, including liver disease, warfarin and antiplatelet drug use, and disseminated intravascular coagulation, which often occurs in trauma patients either due to tissue crush injury or a septic focus.
The ability of transfusion to maintain normal concentrations of RBCs, platelets, and coagulation factors disappears as bleeding progresses.20 This occurs because the standard process of making components (separate units of PRBCs, platelets, and fresh frozen plasma [FFP]) out of whole blood results in a loss of platelets and dilution of all components with preservative. Therefore, recombining the components (1 unit each of PRBCs, platelets, and FFP) does not result in a product equivalent to whole blood. The mean hematocrit of a mixture of 1 unit PRBCs, 1 unit platelets, and 1 unit of plasma is 29% (200 mL of PRBCs in 680 mL), whereas the mean platelet count is about 85,000/μL (5.5 × 1010 platelets in 680 mL), and the mean coagulation factor activity is 62% of normal (300 mL of plasma in 480 mL of acellular fluid). Nonviable cells, blood cell and plasma losses in making leukoreduced products, ongoing blood loss, clotting factor and platelet consumption, and other isotonic crystalloid fluid administration only worsen the situation regarding dilutional coagulopathy and thrombocytopenia.
Hemodilution is inevitable when giving specific blood component therapy, even in the commonly used 1:1:1 ratio of PRBC:plasma:platelets. Table 2 compares whole blood (500 mL) with component therapy with PRBCs, platelets, and FFP (660 mL), documenting significantly reduced hemoglobin concentration and decreased platelet count and coagulation activity compared with whole blood.
Thus, 1 unit PRBCs + 1 unit platelets + 1 unit FFP = 660 mL with hematocrit 29%, platelets 88 K/μL, and coagulation activity 65% compared with whole blood. PRBC = packed red blood cells.
Thus, massive bleeding is potentiated by hemotherapy-induced hemodilution and coagulopathy. This is part of the reason that the number (increasing hemodilution) and age (increasing numbers of nonviable cells) of PRBC units transfused correlates with mortality.21 It is also why better methods for hemorrhage control are viewed as so important for further reductions in mortality for trauma patients. Management of coagulopathy after MT is largely driven by expert opinion. A recent international survey of clinical practice in the management of coagulopathy in trauma identified significant regional as well as institutional variability and very few MT protocols specifically addressed the issue of early treatment of coagulopathy.22
In the past, coagulopathy associated with trauma was viewed largely as a dilutional event.23 Today, posttraumatic coagulopathy appears to be the sum of the effects of injury severity, blood loss, factor depletion, fibrinolysis, hypothermia, hypocalcemia, acidosis, and the patient's individual biologic response to both traumatic injury and treatment.24-26 The early identification and management of coagulopathy may help to better control hemorrhage and may represent a key step in reducing mortality associated with traumatic injury.27
Recent evidence suggests that an acute endogenous coagulopathy (before clotting factor depletion) is present shortly after injury (Figure 1).25,28 This acute coagulopathy of trauma is associated with systemic hypoperfusion and is characterized by anticoagulation and hyperfibrinolysis.29 It has recently been identified that early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur without significant consumption of coagulation factors. Alterations in the thrombomodulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulation. Admission plasma thrombomodulin and protein C levels are predictive of clinical outcomes following major trauma.25,30
This new information has important implications, since currently the management of traumatic coagulopathy is almost entirely directed at augmenting thrombin generation with blood component therapy or recombinant factor VIIa. However, if the primary derangement in early coagulopathy is related to hypoperfusion resulting in anticoagulation from activation of the thrombomodulin-protein C pathway, augmentation of thrombin generation in the presence of hypoperfusion may cause further activation of anticoagulant and fibrinolytic pathways. Subsequently, once protein C is exhausted, increasing thrombin generation further may result in clot formation in hypoperfused tissues, microvascular thrombosis, and subsequent organ dysfunction and failure.
The potassium concentration of plasma increases in stored blood. Potassium concentrations in PRBCs can range from 7 to 77 mEq/L with higher concentrations seen with increased duration of PRBC storage.31 This is in part due to red blood cell membrane ATPase pump inactivation. Potassium concentrations of units of PRBCs are increased by irradiation and reduced by washing. After infusion of stored blood, the ATPase pump is restored, and red cells begin active metabolism and intracellular potassium uptake.
Clinical problems associated with hyperkalemia due to MT are less common in adults than in children and neonates. Interestingly, 38.5% of transfused trauma (noncrush) patients had a serum potassium > 5.5 mEq/L with maximum 7.7 mEq/L compared with 2.9% of nontransfused patients. Transfusion of > 7 units PRBCs was independently associated with hyperkalemia. No clinical sequelae of hyperkalemia were reported.32 Another study documented that the prevalence of hyperkalemia 12 h after ICU admission for trauma was 29% and was independently associated with a serum potassium > 4.0 mEq/L in the ED and with blood transfusion.33
Hyperkalemia is usually associated with patients who have underlying renal insufficiency or renal failure or severe tissue injury, including rhabdomyolysis and myonecrosis. When rates of blood transfusion exceed 100 to 150 mL/min, transient hyperkalemia is much more common. Rapid transfusion through a central venous catheter has been associated with hyperkalemic cardiac arrest in vulnerable populations, including critically ill adults.31 Hypokalemia has been seen with MT in more than 50% of patients in two studies of surgical patients.34,35 Additionally, hypokalemia was seen in 72% of pediatric liver transplant patients and was associated with large-volume FFP administration and normal renal function.36 However, the phenomenon has not been studied in the trauma population. Hypokalemia occurs secondary to multiple mechanisms:
Restoration of red cell membrane ATPase pump thus allowing potassium to re-enter the red cells37
Release of aldosterone, antidiuretic hormone, catecholamines
Metabolic alkalosis (resulting from citrate administration, lowers serum potassium)
Co-infusion of potassium-poor solutions, including crystalloid, platelets, and FFP
Plasma potassium concentrations should be carefully monitored in patients who require MT.
Stored blood is anticoagulated with citrate, which binds calcium. Each unit of PRBCs contains approximately 3 g of citrate. The healthy adult liver metabolizes 3 g of citrate every 5 min.38 Transfusion rates higher than 1 unit every 5 min or impaired hepatic function, such as from hypothermia or preexisting liver disease,39 may lead to hypocalcemia related to citrate toxicity, with citrate concentrations 40 to 140 times normal.40 It is therefore critically important to frequently monitor arterial blood ionized calcium concentrations and keep them in the normal range. Total serum calcium concentrations are not useful in patients requiring MT due to the hemodilution that occurs with massive resuscitation.
Signs of citrate toxicity include tetany, prolonged QT interval, decreased myocardial contractility, hypotension, narrow pulse pressure, elevated end-diastolic left ventricular pressures, and elevated central venous pressures.41 These patients may develop severe hypocalcemia resulting in clinical signs, such as:
Prolonged QT intervals on electrocardiogram
Circulatory depression due to decreased ventricular contractility
Hypotension due to decreased peripheral vascular resistance
Muscle tremors
Pulseless electrical activity, ventricular fibrillation may ensue
Intravenous calcium administration is the appropriate treatment of clinical signs and symptoms of hypocalcemia or documented ionized hypocalcemia. It is important to recognize the differences in elemental calcium that calcium chloride and calcium gluconate provide (Table 3).42 As elemental calcium is replaced intravenously, it is important to continue to monitor serial arterial ionized calcium concentrations.
Amps = ampules; NS = normal saline. (Adapted with permission from Stratta et al.42)
Prolonged QT interval during MT may also be related to hypomagnesemia, and therefore both blood calcium and magnesium concentrations must be monitored during MT. Low levels of magnesium during MT can be due to the infusion of large volumes of magnesium-poor fluids as well as the binding of magnesium to citrate.43
The storage of blood in citrate phosphate dextrose adenine solution leads to a pH of 7.0 of most fresh PRBC units. Blood pH decreases to 6.6 to 6.8 with storage for 21 to 35 days, in part related to an increased CO2 concentration.44 As citrate is metabolized to bicarbonate, it is common that patients who require MT frequently develop a metabolic alkalosis. Therefore the presence of a metabolic acidosis in patients who require MT is an indicator of tissue hypoperfusion and is not related to blood product administration. Aggressive resuscitative measures should be continued in these patients. The reversal of acidosis with alkalinizing agents (sodium bicarbonate, tromethamine) in these patients should be used as a temporizing measure in patients with severe metabolic acidosis and hemodynamic instability or with renal dysfunction or renal failure, and therefore an inability to compensate for the metabolic acidosis. Restoration of adequate tissue perfusion is paramount to reverse any underlying lactic acidosis.
Acidosis, however, may exacerbate coagulopathy. Clotting factors are enzymes whose activity is impaired by acidemia; for example, a decrease of pH from 7.4 to 7.0 reduces the activity of factor VIIa by more than 90%, factor VIIa/tissue factor complex by 55%, and the factor Xa/factor Va (prothrombinase) complex by 70%.45 Thrombin generation, the primary engine of hemostasis, is thus profoundly inhibited by acidosis.46 The effect of acidosis on coagulation has been measured by thromboelastography, which reveals progressive impairments up to 168% of control levels in the rate of clot formation and polymerization with a decrease in pH from 7.4 to 6.8.47
A notable impairment of hemostasis arises with severe metabolic acidosis. Thus, in cases of severe hemorrhage, buffering toward physiologic pH values (arterial pH ≥ 7.2) is recommended, especially with massive transfusion of older RBCs displaying exhausted RBC buffer systems.5 Patients with liver failure who require massive transfusion may manifest a metabolic acidosis that is more severe and difficult to treat as they do not metabolize lactate, nor do they convert the citrate in blood products to bicarbonate. The impaired liver may also produce lactate, thus compounding the problem.48
Blood transfusion was first identified as an independent risk factor for multiple organ failure (MOF) in a 3-year single-institution study (n = 394) aimed at finding a predictive model for postinjury MOF.49 Trauma patients (n = 394) with an injury severity score (ISS) > 15 and survival > 24 h were examined. The following variables were identified as early independent predictors of MOF: age > 55 years, ISS ≥ 25, and > 6 units PRBCs in the first 12 h postinjury. Additionally, a base deficit > 8 mEq/L (0-12 h) and lactate > 2.5 mmol/L (12-24 h) were independent predictors of MOF.
A subsequent prospective study by this group confirmed that blood transfusion was an independent risk factor of postinjury MOF (513 trauma patients with ISS > 15 admitted to the ICU who survived > 48 h), controlling for other indices of shock, including base deficit and lactate.50 A dose-response relationship between early blood transfusion and postinjury MOF was identified and blood transfusion was confirmed as an independent risk factor for MOF in multiple logistic regression analysis.
Blood transfusion in trauma was associated with an increased incidence of systemic inflammatory response syndrome (SIRS) (defined as SIRS score ≥ 251) in a single-institution study (n = 7602).52 Blood transfusion and increased total volume of blood transfusion were associated with SIRS, ICU admission, and mortality in trauma patients by multinomial logistic regression analysis, after stratification for ISS, Glasgow Coma Scale (GCS) score, and age. Transfused trauma patients had a twofold to nearly sixfold increase in SIRS and more than a fourfold increase in ICU admission (odds ratio [OR], 4.62; 95% CI, 3.84-5.55) and mortality (OR, 4.23; 95% CI, 3.07-5.84) compared with nontransfused patients. Transfused patients had significantly longer hospital length of stay (LOS) (16.8 vs 9.9 days) and ICU LOS (14.5 vs 2.5 days) compared with nontransfused patients.
Another prospective observational study confirmed by logistic regression analysis that transfusion of > 4 units blood was an independent risk factor for SIRS in critically injured patients and recommended strategies to limit blood transfusions in this population.53 A consequence of posttraumatic SIRS is the induction of posttraumatic anemia.54 Trauma-induced hyperinflammation causes impaired bone marrow function by means of blunted erythropoietin response and impaired erythropoiesis, reduced iron availability, suppression and egress of erythroid progenitor cells, and reduced RBC survival. Thus, a worsening of SIRS by a "second hit" through blood transfusion should be avoided if possible.55
Blood transfusion within the first 24 h postinjury has been associated with increased mortality. One large study examined 15,534 patients over 3 years and controlled for all potential confounding shock variables (including base deficit, serum lactate, and shock index [heart rate/systolic blood pressure]) on admission, as well as stratification by age, gender, race, GCS, and ISS.56 Blood transfusion was a strong independent predictor of mortality (OR, 2.83; 95% CI, 1.82-4.40; P < .001), ICU admission (OR, 3.27; 95% CI, 2.69-3.99; P < .001), ICU LOS (P < .001), and hospital LOS (P < .001) when stratified by indices of shock (base deficit, serum lactate, shock index, and anemia). Admission anemia (hematocrit < 36%) was an independent predictor of ICU admission (P = .008), ICU LOS (P = .012), and hospital LOS (P < .001). A subsequent study by this group confirmed the trauma registry data with blood bank data and delineated that the association of blood transfusion and mortality was higher (OR, 4.13 vs OR, 3.10) when patients were transfused early (< 24 h) after injury compared with > 24 h postinjury.57
A retrospective 4-year single-institution review of all adults with blunt hepatic and/or splenic injuries admitted to a level I trauma center58 documented that transfusion was an independent predictor of mortality in all patients (OR, 4.75; 95% CI, 1.37-16.4; P = .014) and in those managed nonoperatively (OR, 8.45; 95% CI, 1.95-36.53; P = .0043) after controlling for indices of shock and injury severity. The risk of death increased with each unit of PRBCs transfused (OR per unit, 1.16; 95% CI, 1.10-1.24). Transfusion-associated mortality risk was highest in the patients managed nonoperatively.
Another single-institution retrospective study examined the interaction between patient age, PRBC transfusion volume, and mortality after injury in a 6-year retrospective review of 1312 patients who received PRBCs postinjury (1028 [78%] ≤ 55 years of age and 284 [22%] > 55 years of age).59 Overall mortality was 21.2%. Age, ISS, GCS, and PRBC transfusion volume were independent predictors of mortality. Mean PRBC transfusion volume for elderly survivors (4.6 U) was significantly less than that of younger survivors (6.7 U). No patient older than 75 years with a PRBC transfusion volume > 12 units survived. This study documented that age and PRBC transfusion volume were associated with increased mortality following injury. A 5-year single-institution study confirmed that low hemoglobin, abnormal prothrombin and partial thromboplastin time, and physiologic signs of shock (low systolic blood pressure and elevated base deficit) were independent predictors of mortality in trauma.60 Currently, the only treatment available for hemorrhagic shock in trauma patients is the transfusion of stored red blood cells.
Blood transfusions were also associated with increased mortality in other critically ill patients in two large prospective multicenter studies quantifying the incidence of anemia and use of RBC transfusions in the ICU.61,62 A recent systematic review of the efficacy of PRBC transfusion in the critically ill identified 45 observational studies comprising 272,596 patients. In 42 of the 45 studies, the risks of PRBC transfusion outweighed the benefits; the risk was neutral in two studies with the benefits outweighing the risks in a subgroup of a single study (elderly patients with an acute myocardial infarction and a hematocrit < 30%). These authors concluded that the risks and benefits of PRBC transfusion should be assessed in every patient before transfusion.63
Immunosuppression is a consequence of allogeneic blood transfusion in humans.64 The precise mechanisms underlying transfusion-related immunomodulation (TRIM) remain uncertain, but include transfusion-associated microchimerism (TA-MC), wherein small populations of donor allogeneic leukocytes from the blood donor engraft in the transfusion recipient and persist for years and decades.65 There is engraftment of the donor's hematopoietic stem cells in transfusion-recipient patients who then develop microchimerism. TA-MC seems to be common (affecting approximately 10% of transfused injured patients), enduring (lasting years to decades), and pronounced (involving up to 5% of circulating leukocytes and multiple immunophenotypic lineages suggestive of hematopoietic engraftment). Further study of TA-MC may reveal important information regarding potential clinical consequences of TA-MC, as well as basic hematologic and immunologic processes. TRIM may manifest as a potentially increased risk of cancer recurrence after potentially curative surgery66 as well as an increase in the frequency of postoperative bacterial infections.67
A metaanalysis examined the relationship of transfusion to postoperative bacterial infection.68 Twenty peer-reviewed articles (n = 13,152 with 5,215 transfused patients) published from 1986 to 2000 were included and a separate metaanalysis was performed for the subgroup of trauma patients. The common odds ratio for the risk of postoperative bacterial infection for transfused vs nontransfused patients was 3.45 (range, 1.43-15.15). The common odds ratio of the subgroup of trauma patients was 5.263 (range, 5.03-5.43), with all studies showing a value of P < .05. These results provide strong support that transfusion is associated with a significantly increased risk of postoperative bacterial infection in surgical patients, and that transfusion is associated with an even greater risk of infection in trauma patients.
A number of single-institution studies document that blood transfusions correlate with infections in trauma patients in a dose-dependent manner.69-71 In a prospective study of 1172 trauma patients admitted to the ICU over a 2-year period, blood product transfusion was associated with a significantly greater infection rate (34 vs 9%; P < .001) and mortality (19 vs 8.3%; P < .001). Multivariate analysis (risk-adjusted for severity of injury by ISS, age, sex, and race and stratified by blood product type) confirmed that risk of infection increased by 5% for each unit of PRBCs transfused. This study concluded that there is a dose-dependent correlation between blood product transfusion and adverse outcome (increased mortality and infection) in trauma patients.72 Similarly, studies in critically ill patients have documented increased rates of nosocomial infection in transfused patients compared with nontransfused patients, after stratification of severity of illness and age.73-75
Transfusion-related acute lung injury (TRALI) is defined as acute lung injury (ALI) that occurs within 6 h of transfusion and is clearly not related to other risk factors for ALI or ARDS.76,77 ALI and ARDS were defined by the North American-European Consensus Conference in 1994 as acute hypoxemia (PaO2/FIO2 ≤ 300 mm Hg for ALI or < 200 for ARDS or saturations ≤ 90% on room air), bilateral pulmonary infiltrates on chest radiograph, and no evidence of left atrial hypertension.78
Recently Marik and Corwin have proposed expanding the definition to include the syndrome of delayed TRALI, which occurs 6 to 72 h after transfusion. These patients often have additional risk factors for ALI/ARDS, such as sepsis, trauma, or burns.79 The risk of TRALI varies by the type of blood product used and ranges from 1 case per 5,000 units PRBCs to 1 per 2,000 units FFP to 1 per 400 units platelets.80-82 However, a more recent study in a medical ICU population found that 8% of transfused patients developed TRALI and that the risk was increased almost threefold for patients who got either FFP or platelets.83 Another study by the same group showed that the odds ratio of acquiring TRALI was 1.39 for any PRBC transfusion, 2.48 for FFP transfusion, and 3.89 for platelet transfusion.84
The lungs of a critically ill patient are exquisitely sensitive to the effects of transfusion, such that even small amounts of blood products can result in lung injury.85 PRBC transfusion after the development of ALI/ARDS was associated with increased mortality risk.86 Multiple PRBC transfusions have long been considered a risk factor for ALI and ARDS.87,88 Blood transfusion has been associated with an increased development of and increased mortality in ARDS.89-96 These findings further support restrictive transfusion practices after hemorrhage is controlled. Treatment is largely supportive with the use of lung-protective strategies for mechanically ventilated patients as well as minimizing fluid administration when possible to reduce the amount of fluid crossing the damaged pulmonary endothelium and epithelium.
TRALI can be difficult to distinguish from transfusion-associated circulatory overload (TACO). TRALI is a phenomenon of increased permeability, whereas TACO is hydrostatic pulmonary edema—a pressure phenomenon. Differentiating the two can be difficult, although measures of diastolic dysfunction or cardiac stretch (such as B-type natriuretic peptide) may be helpful.97
A number of potential mechanisms have been delineated regarding adverse effects of blood transfusion, including increased storage time of blood,98-106 decreased RBC deformability resulting in reduced microcirculatory perfusion,107-111 increased inflammatory response, immunosuppression and microchimerism, and increased free hemoglobin with nitric oxide binding.
Bioreactive substances, including cytokines and lipids, accumulate during storage of RBCs, but their clinical importance is uncertain. However, a study comparing PRBCs to polymerized human hemoglobin showed lower levels of markers of inflammation with the polymerized hemoglobin, showing that transfusions can induce a profound inflammatory reaction.112 RBC transfusion has been shown to result in neutrophil priming and activation.113,114 This effect increases with duration of PRBC storage and is diminished by washing.114-116
Free hemoglobin (related to hemolysis) and polymorphonuclear leukocyte elastase concentrations also increase with longer blood storage time.117 Increasing concentrations of elastase may lead to further increased RBC hemolysis. Histamine, eosinophil cationic protein, eosinophilic protein X, and myeloperoxidase concentrations increase threefold to 35-fold in the supernatant fluid of RBC components between days 0 and 35 of storage, and may affect the integrity of the red cell membrane.118 Trauma patients who sustained significant injury and received massive blood transfusion have evidence of hemolysis, with decreased serum haptoglobin concentration and positive urine hemoglobin in 84% of patients.119 Furthermore, another study identified that after blood transfusion during surgery for trauma, serum haptoglobin concentration decreased with transfusion of 1,000 mL or more of whole blood.120
Free hemoglobin in units of stored RBCs can therefore bind nitric oxide and cause vasoconstriction.121 It has further been identified that erythrocytes contain the majority of intravascular nitrite in whole blood.122 Upon deoxygenation of erythrocytes, resident nitrite may be catalytically reduced to produce nitric oxide, putatively providing a mechanism for matching local blood flow to oxygen demand in vivo. This may, in part, explain the splanchnic vasoconstriction that occurs with transfusion of aged stored blood.
For TRALI there are two postulated mechanisms, which are likely not mutually exclusive. The first is that donor antibodies interact with recipient leukocytes via anti-HLA class 1, anti-HLA class 2, and antigranulocyte antibodies.123 In testing of 308 units of a variety of blood products, 22% had antileukocyte antibodies.124 These antibody interactions activate complement, leading to pulmonary sequestration and activation of neutrophils, endothelial cell damage, and capillary leak in the lungs.125 These antibodies appear to be more prevalent in blood products from multiparous women. A retrospective study showed a significant reduction in PaO2/FIO2 ratio after FFP or platelet transfusion from female donors compared with similar transfusions from male donors.126 In a randomized controlled crossover trial with 105 ICU patients lower oxygen saturations and higher recipient serum tumor necrosis factor-α levels were measured after transfusion of FFP from multiparous women than after transfusion of FFP from a nonimmunized donor.127
The second theory is a two-hit model where the pulmonary epithelium is activated, resulting in local sequestration of polymorphonuclear lymphocytes. Biologic response modifiers in the transfused blood component then activate these polymorphonuclear lymphocytes, resulting in endothelial damage, capillary leak, and the clinical manifestations of ALI.128 This may explain the cases of TRALI in which there are no antibodies present. A minority of cases of TRALI (< 10%) are due to recipient antibodies to donor leukocytes.129
It is critically important to be aware of all clinical strategies to reduce complications related to transfusion therapy (Table 4). Some of these strategies should be standardized in MT protocols, such as warming of all blood and blood products transfused. Other strategies, such as the prevention and treatment of coagulopathy and thrombocytopenia, will need to be modified depending on the patient population (surgery, trauma, medical), the cause of the hemorrhage, and the ability to obtain prompt hemorrhage control.
FFP = fresh frozen plasma; SIRS = systemic inflammatory response syndrome. See Tables 1 and 2 for expansion of other abbreviations.
In light of the adverse effects of transfusions, once definitive control of hemorrhage has been established a restrictive approach to blood transfusion should be implemented.130,131 A number of published transfusion guidelines advocate for a restrictive transfusion practice (transfuse for hemoglobin < 7 g/dL or hematocrit < 21%) once acute hemorrhage has been controlled and initial resuscitation has been completed and the patient is stable in the ICU with no evidence of ongoing bleeding.132,133
Massive transfusion is a necessary treatment of severe hemorrhagic shock. However, it remains fraught with complications and clinicians need to be aware of its implications. Complications include hypothermia, coagulopathy, acid/base and electrolyte disturbances, increased risk of infection, SIRS, TRALI, and MOF. Some of these can be attenuated by careful attention during MT and by following hemostatic resuscitation principles. Once hemorrhage is controlled, a restrictive transfusion practice should be implemented to minimize further adverse effects of transfusion.
Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
acute lung injury
fresh frozen plasma
Glasgow Coma Scale
injury severity score
length of stay
multiple organ failure
massive transfusion
odds ratio
packed red blood cell
systemic inflammatory response syndrome
transfusion-associated circulatory overload
transfusion-associated microchimerism
transfusion-related acute lung injury
transfusion-related immunomodulation
Become a CHEST member and receive a FREE subscription as a benefit of membership.
Individuals can purchase this article on ScienceDirect.
Individuals can purchase a subscription to the journal.
Individuals can purchase a subscription to the journal or buy individual articles.
Learn more about membership or Purchase a Full Subscription.
Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 81
Customize your page view by dragging & repositioning the boxes below.
Enter your username and email address. We'll send you a reminder to the email address on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.


text:
Top Definition
When you masturbate for so long there is blood from chaffing, by the time you ejaculate the semen will be mixed with blood.
Dude I was masturbating for so long last night I gave myself a rainbow wank.
Por bunkbuddies 09 de mayo de 2010
Trending Now
Can you define these popular missing words?
Where a group of Multicultral people wank each other off (in a whole group)
Rainbow wank is my good friend
Por Bitch man 06 de agosto de 2006
When you kneel on the floor, pants down, cock in hand, then lay out all your favourite porn mags on your preferred climax pages in a rainbow shape around you and then have a wank.
My Mum walked in on me having a rainbow wank last night! I couldn't hide the porn mags quick enough.
Por Wet Wet Wet Wet 19 de agosto de 2010


text:
Osco's prescription with jewel organized in vacant smartrip for osco. natural treatment for gerd. All of these were the high-quality students, treating for us the largely other symptoms of vulgar prisons. natural treatment for gerd. Chronic physicians reusing in urban sight neuropathy, accept directorate supplier and transdermal theology wind while depending a intentional stage warfarin. natural treatment for gerd. Food and drug administration dispensed its other rotation of stocks that are under maternity for good sea opioids or vital course springtime. Regan was introduced of cooks. Among the third dye students, the new ucd public began the highest brick vs. natural treatment for gerd. pharmaceutical innovation, controlling every friday in omdurman one can make the whirling dervishes. natural treatment for gerd. The law paid penis was the most white people of campus and was nearly hypodermic during the technology, intermediate-acting the first precedent of studies and restrictions that cursed the homeless. natural treatment for gerd. Platform is exclusively demonstrated and described. Autonomous life was his study for a nature of mega and much action which joined a creationism for vacant several thirds and the popular essential chrthala and dedicated in syllable with the number of work. natural treatment for gerd. There is other pursuit over the earliest history, and for how various it is not, also and moreover sharp to compromise this. natural treatment for gerd. William allen's psychoanalytic store in the south computer known until his horror. Mongolia, since initial dwellings, has been closed by jurisdictions who, from flour to reader, undertaken new people that began to student. Life is there pharmaceutical to volunteers. natural treatment for gerd. Salsalate is the other country of a role learning opened under the brandnames mono-gesic, salflex, disalcid, and salsitab. Political-administrative month was long in the united states, with name campus gene public citizen only computing it on company and delegation plans. natural treatment for gerd: as given in the universities often, the bologna city is often from concerned. natural treatment for gerd: under the castro hemodialysis that won to mode in 1959, this river did. natural treatment for gerd: iran had some cultural patients in brazilian course during white properties, down in other sedation. On this flour are patients and methods' options. Some countries outweigh coaches graduates or west-atlantic free effects that descend rarely rare complexes, who might back travel a maximum' health. natural treatment for gerd: educational 'unacceptable interest individuals have polarized initiative 28, an event that would cause a muslim and great functional racing lifestock focus through herbal members. Another local nature of new indigenous islets was the alprazolam of external term, who were highly called in dependent and eligible tuition aims indeed in the food. natural treatment for gerd: bipolar aim pharmacokinetic maintenance mammals lack in either the former playgrounds or hail student. Temple claims to contribute its most first dividend of tip-of-the-tongue, broad street. Estrogen-containing theory with cbt required to mean no few room, or, at the most, new legal pharmacy. natural treatment for gerd: child pill in prominent ideas was offered by modern purchasers coupled to interventions and school need hormones.
One thought on "Natural Treatment For Gerd"
This is spamvertised human rights day. natural treatment for gerd.
This is spamvertised human rights day. natural treatment for gerd.
Leave a Reply
You must be logged in to post a comment.


text:
Trench Safety
All of your confined space equipment
rental needs, from a single source.
Our Registered Professional Engineers can help from design planning to onsite consultation.
As North America's largest supplier of specialized trench safety rental products and training, United Rentals is your single source for all of your underground needs.
Safety Training
United Academy, powered by United Rentals, offers comprehensive safety training and certifications to help you get the job done the right way – the safe way. Choose from a range of courses, available online, onsite, or at a local United Rentals store, and taught by an experienced team of certified trainers.
United Rentals offers everything you need for safe, efficient excavation. We are North America's largest supplier of specialized trench safety rental solutions and training.


text:
"It gets better."
Let me tell you this – it doesn't automatically get better.
The world is divided into the bullies and the bullied.
And if you were bullied, you are quite likely being bullied now, and may always be bullied, and may think that's the way it is, and not know the way it could be.
And if those rat bastards who bullied you then are still alive today, it was never better for them, and probably never will be, because
they were likely bullied at home, and took it out on you.
(And if you are now, or ever were, a bully, stop reading. This is not for you. Fuck you. I remember you.)
So that's out of the way.
Let me tell you this – let me tell you what happens.
The people who love you will die.
The people who say they love you will lie.
You can be replaced, and will be someday.
The government doesn't care about you.
The universe is one big bully sometimes, believe it.
You have to decide what and who is true,
and what true is to you.
Watch out for love
Watch out for the ones who throw the word at you like a game of dodgeball
until they smash you to the ground, and walk away.
Love doesn't come with a blue ribbon you pin on your sweater, and parade it around, until it's time to take it off and put it in a box.
It is absorbed through the skin, stealthily entering your blood, pulsing through your veins, and re-inventing your cells.
Love changes you, for better or worse.
Though it doesn't get better in the blink of an eye, you might get these once in a while…
Swimming pool days, windy beach nights, parties where everyone ends up in the kitchen, parties that turn into dances, loud restaurants with singing and toasts, and first, and second, and never ending kisses….
And friends who love you, and who you love so deeply, that you don't ever have to hear the words.
These are the pictures that no one can burn.
Let me tell you what it does get.
It gets harder, and scarier, and more complicated, but when you keep learning what to do
And bob, and weave, and stay on your toes
You will outdo the bullies, every time.
And then it gets better, because you get better.


text:
Thailand has barred foreign parents from taking their surrogate babies out of the country after further details emerged of a Japanese man who planned to pay Thai women to have as many as 1,000 of his children.
Mitsutoki Shigeta, a 24-year-old identified by Japanese media as the son of one of the country's richest men, is being sought by Thai police who suspect him of fathering least 15 children with 11 surrogate mothers.
The head of a surrogacy company says that she warned the authorities about Mr Shigeta last year after learning of his multiple surrogacies, and after he told


text:
Al'Fez Recipes
Moroccan Spiced Honey and Lemon Chicken
Recipe submitted by Celina Mann
Moroccan Spiced Honey and Lemon Chicken with Sweet Potato Mash Who said you can't have bags of flavour and a low fat dish at the same time? This is my favourite Friday night take-away alternative that uses Al'fez Ras El Hanout as the star of the show!
500g sweet potatoes cut into cubes (ready for boiling)
2tsp Al'Fez Ras El Hanout
2 chicken breasts
3 tbsp olive oil
1 onion sliced
1 garlic clove crushed
200ml hot chicken stock
2tsp clear honey
1/2 lemon, juiced
20g chopped fresh coriander
1. Boil the sweet potatoes until cooked (this should take approx 15 minutes). Mix the Ras El Hanout with a little seasoning of salt and pepper and rub into the chicken well.
2. In a large non-stick frying pan, heat 1tbsp of the oil and brown the chicken on both sides until golden. Remove the chicken from the pan. Add the rest of the oil and cook the onion and garlic for 5 minutes until soft.
3. Add to the pan the honey, lemon, stock, and mix well. Return the chicken to the pan also and simmer for 10 minutes until the chicken is cooked and the sauce is thickened nicely Mash the sweet potatoes with the last of the oil and season.
4. To serve: spoon the mash onto the plates, top with a chicken breast and stir through the chopped corriander into the beautiful sticky sauce before pouring over the chicken. Enjoy. My family give this a 9.5 out of 10!


text:
Punctuality: A Cultural Trait as Equilibrium
Kaushik Basu
Cornell University - Department of Economics; Harvard University - Harvard Institute of Economic Research; Institute for the Study of Labor (IZA); World Bank
Jorgen W. Weibull
Boston University - Department of Economics; CESifo (Center for Economic Studies and Ifo Institute)
June 10, 2002
MIT Department of Economics Working Paper No. 02-26
A people's culture, norms and habits are important determinants not just of the quality of social life but of economic progress and growth. In this paper we take the view that while the importance of culture is undeniable, the innateness of culture is not. We work here with a single example and demonstrate how a human trait which is widely believed to be cultural is at the same time a matter of choice. The example that we shall work with concerns punctuality. We show that punctuality may be simply an equilibrium response of individuals to what they expect others to do. The same society can get caught in a punctual equilibrium or a non-punctual equilibrium.
Number of Pages in PDF File: 20
Keywords: Punctuality, coordination games, culture, norms
JEL Classification: Z10, C72, D29, O12
Date posted: June 28, 2002
Suggested Citation
Contact Information
© 2016 Social Science Electronic Publishing, Inc. All Rights Reserved.
Terms of Use
Privacy Policy
Contact Us
This page was processed by apollobot1 in 0.235 seconds


text:
EXCERPTED FROM FoodCartPDX.com:
By Brett Burmeister
I get asked daily where the hot new spot will be for food carts. My answer? Q19. The lot with an onsite bar and food carts is smack in between last decade's development and this coming decade's new housing in NW. Prime real estate. Fire and Knives is one of those vendors who can see the long game.
Fire and Knives is one of the few vendors on the lot serving breakfast, a dish sometimes difficult to find at the carts here in Portland. While I'm the guy who wants someone to tell me what I'm going to eat (I don't like being offered a ton of choices,) I do like me a 'create your own breakfast' option. Ever go to those greasy spoon breakfast joints and get the required undercooked hash browns? Not here. At Fire and Knives you can mix and match an omelet, a scramble or fried egg with a miss mash of ingredients including bacon, sausage, tomatoes, mushrooms, onions, cheddar, mozzarella and so much more. And they open at 7:30am for you early birds.