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Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents
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Toxoplasma gondii Encephalitis
Last Updated: December 10, 2015; Last Reviewed: June 14, 2017
NOTE: Update in Progress
Toxoplasmic encephalitis (TE) is caused by the protozoan Toxoplasma gondii. Disease appears to occur almost exclusively because of reactivation of latent tissue cysts.1-4 Primary infection occasionally is associated with acute cerebral or disseminated disease.
Seroprevalence of anti-Toxoplasma antibody varies substantially among different geographic locales, with a prevalence of approximately 11% in the United States, versus 50% to 80% in certain European, Latin American, and African countries.4-6 In the era before antiretroviral therapy (ART), the 12-month incidence of TE was approximately 33% in patients with advanced immunosuppression who were seropositive for T. gondii and not receiving prophylaxis with drugs against the disease. A low incidence of toxoplasmosis is seen in patients who are seronegative for T. gondii. If patients are truly seronegative, their toxoplasmosis presumably represents one of three possible scenarios:
- Primary infection,
- Re-activation of latent disease in individuals who cannot produce detectable antibodies, or
- Testing with insensitive assays.7,8
Clinical disease is rare among patients with CD4 T lymphocyte (CD4) cell counts >200 cells/µL. Patients with CD4 counts <50 cells/µL are at greatest risk.1,3,8,9 Primary infection occurs after eating undercooked meat containing tissue cysts or ingesting oocysts that have been shed in cat feces and sporulated in the environment, a process that takes at least 24 hours. In the United States, eating raw shellfish including oysters, clams, and mussels recently was identified as a novel risk factor for acute infection.10 Up to 50% of individuals with documented primary infection do not have an identifiable risk factor.11 The organism is not transmitted through person-to-person contact.
Clinical Manifestations
Among patients with AIDS, the most common clinical presentation of T. gondii infection is focal encephalitis with headache, confusion, or motor weakness and fever.1,3,9 Patients may also present with non-focal manifestations, including only non-specific headache and psychiatric symptoms. Focal neurological abnormalities may be present on physical examination, and in the absence of treatment, disease progression results in seizures, stupor, and coma. Retinochoroiditis, pneumonia, and evidence of other multifocal organ system involvement are rare in patients with AIDS. Computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain will typically show multiple contrast-enhancing lesions in the grey matter of the cortex or basal ganglia, often with associated edema.1,9,12-14 Toxoplasmosis also can manifest as a single brain lesion or diffuse encephalitis without evidence of focal brain lesions on imaging studies.15 This latter presentation tends to be rapidly progressive and fatal.
HIV-infected patients with TE are almost uniformly seropositive for anti-toxoplasma immunoglobulin G (IgG) antibodies.1,3,9,16 The absence of IgG antibody makes a diagnosis of toxoplasmosis unlikely but not impossible. Anti-toxoplasma immunoglobulin M (IgM) antibodies usually are absent. Quantitative antibody titers are not useful for diagnosis.
Definitive diagnosis of TE requires a compatible clinical syndrome; identification of one or more mass lesions by CT, MRI, or other radiographic testing; and detection of the organism in a clinical sample. On imaging studies, lesions are usually ring-enhancing and have a predilection for the basal ganglia. MRI has sensitivity superior to that of CT studies for radiological diagnosis of TE. Positron emission tomography13 or single-photon emission computed tomography scanning14 may be helpful in distinguishing between TE and primary central nervous system (CNS) lymphoma, but no imaging technique is completely specific. For TE, detection of the organism requires a brain biopsy, which is most commonly performed by a stereotactic CT-guided needle biopsy. Hematoxylin and eosin stains can be used for detection of T. gondii, but sensitivity is significantly increased if immunoperoxidase staining is used and if experienced laboratories process the specimens.17 If safe and feasible, a lumbar puncture should be performed for T. gondii polymerase chain reaction (PCR), as well as for cytology, culture, cryptococcal antigen and PCR for Mycobacterium tuberculosis, Epstein-Barr Virus (EBV) and JC Virus (JCV), either at initial presentation or subsequently, especially in patients in whom empiric therapy fails. Detection of T. gondii by PCR in cerebrospinal fluid (CSF) has high specificity (96% to 100%), but low sensitivity (50%), especially once specific anti-toxoplasma therapy has been started.18-20
The differential diagnosis of focal neurological disease in patients with AIDS most often includes primary CNS lymphoma and progressive multifocal leucoencephalopathy (PML). In the absence of immune reconstitution inflammatory syndrome (IRIS), PML (but not lymphoma) can be distinguished on the basis of imaging studies. PML lesions typically involve white matter rather than gray matter, are non-contrast enhancing, and produce no mass effect. Less common causes of focal neurologic disease in patients with AIDS include mycobacterial infection (especially tuberculosis [TB]); fungal infection, such as cryptococcosis; Chagas disease; and pyogenic brain abscess, particularly in IV drug abusers.
Most clinicians initially rely on an empiric diagnosis, which can be established as an objective response, documented by clinical and radiographic improvement, to specific anti-T. gondii therapy in the absence of a likely alternative diagnosis. Brain biopsy is reserved for patients who fail to respond to specific therapy, although earlier biopsy should be strongly considered if results from imaging, serology, or PCR suggest an etiology other than toxoplasmosis. In patients with contrast-enhancing mass lesions, detection of EBV and JCV by PCR in CSF is highly suggestive of CNS lymphoma21,22 or PML,23 respectively.
Preventing Exposure
HIV-infected individuals should be tested for IgG antibody to Toxoplasma soon after they are diagnosed with HIV to detect latent infection with T. gondii (BIII). They also should be counseled regarding sources of Toxoplasma infection, especially if they lack IgG antibody to Toxoplasma.
To minimize risk of acquiring toxoplasmosis, HIV-infected individuals should be advised not to eat raw or undercooked meat, including undercooked lamb, beef, pork, or venison, and not to eat raw shellfish including oysters, clams, and mussels (BIII). Lamb, beef, venison, and pork should be cooked to an internal temperature of 165°F to 170°F;24 meat cooked until it is no longer pink inside usually has an internal temperature of 165°F to 170°F, and therefore, from a more practical perspective, satisfies this requirement. To minimize the risk for acquiring toxoplasmosis, HIV-infected individuals should wash their hands after contact with raw meat and after gardening or other contact with soil; they should also wash fruits and vegetables well before eating them raw (BIII). Patients who are seronegative and who own cats should be advised to have someone who is HIV-negative and not pregnant change the litter box daily. If they must change the litter box themselves, they should wash their hands thoroughly after doing so (BIII). HIV-infected patients also should be encouraged to keep their cats inside and not to adopt or handle stray cats (BIII). Cats should be fed only canned or dried commercial food or well-cooked table food, not raw or undercooked meats (BIII). Patients do not need to be advised to part with their cats or to have their cats tested for toxoplasmosis (AII).
Preventing Disease
Indication for Primary Prophylaxis
Toxoplasma-seropositive patients who have CD4 counts <100 cells/µL should receive prophylaxis against TE (AII).25,26
The double-strength-tablet daily dose of trimethoprim-sulfamethoxazole (TMP-SMX), which is the preferred regimen for Pneumocystis jirovecii pneumonia (PCP) prophylaxis, is effective against TE and is recommended (AII). TMP-SMX, one double-strength tablet three times weekly, is an alternative (BIII). If patients cannot tolerate TMP-SMX, the recommended alternative is dapsone-pyrimethamine plus leucovorin, which is also effective against PCP (BI).27-29 Atovaquone with or without pyrimethamine/leucovorin is active against PCP and also can be considered (CIII). Aerosolized pentamidine does not protect against TE and is not recommended for antitoxoplasma prophylaxis (AI).25,30
Toxoplasma-seronegative persons who are not taking a PCP prophylactic regimen known to be active against TE, such as aerosolized pentamidine, should be retested for IgG antibody to Toxoplasma when their CD4 counts decline to <100 cells/µL to determine whether they have seroconverted and therefore are at risk for TE. Patients who have seroconverted should be administered prophylaxis for TE as previously described (AII).
Discontinuing Primary Prophylaxis
Prophylaxis against TE should be discontinued in adult and adolescent patients receiving ART whose CD4 counts increase to >200 cells/µL for more than 3 months (AI). Multiple observational studies31-33 and two randomized trials34,35 have reported that primary prophylaxis can be discontinued, with minimal risk for development of TE, in patients receiving ART whose CD4 counts increase from <200 cells/µL to >200 cells/µL for more than 3 months. In these studies, most patients were taking HIV protease inhibitor-containing regimens and the median CD4 count at the time prophylaxis was discontinued was >300 cells/µL. At the time prophylaxis was discontinued, most patients had sustained suppression of plasma HIV RNA levels below the detection limits of available assays; the median follow-up was 7 to 22 months. Patients with CD4 counts of <100 cells/µL are at greatest risk for having TE, but the risk for TE with CD4 counts of 100 to 200 cells/µL has not been studied as rigorously as increases to >200 cells/µL. Thus, the recommendation specifies discontinuing prophylaxis after an increase to >200 cells/µL. When CD4 counts are >200 cells/μL for at least 3 months, primary TE prophylaxis should be discontinued because it adds little value in preventing toxoplasmosis and increases pill burden, potential for drug toxicity and interaction, likelihood of development of drug-resistant pathogens, and cost. Prophylaxis for TE should be reintroduced if the CD4 count decreases to <100 to 200 cells/µL (AIII). When a decision to stop PCP prophylaxis is contemplated in patients with CD4 counts of 100 to 200 cells/μL and plasma HIV RNA viral loads below the limits of detection with commercial assays, toxoplasma serostatus should be considered, because seropositive patients may then be at risk for developing TE.
Treating Disease
The initial therapy of choice for TE consists of the combination of pyrimethamine plus sulfadiazine plus leucovorin (AI).2,36-38 Pyrimethamine penetrates the brain parenchyma efficiently even in the absence of inflammation.39 Leucovorin reduces the likelihood of development of hematologic toxicities associated with pyrimethamine therapy.40 Pyrimethamine plus clindamycin plus leucovorin (AI)36,37 is the preferred alternative regimen for patients with TE who cannot tolerate sulfadiazine or do not respond to first-line therapy. This combination, however, does not prevent PCP, therefore additional PCP prophylaxis must be administered when it is used (AII) (see discussion under Preventing Recurrence).
In a small (77 patients), randomized trial, TMP-SMX was reported to be effective and better tolerated than pyrimethamine-sulfadiazine.41 Others have reported similar efficacy in open-label observational studies.42 TMP-SMX has less in vitro activity and experience using this drug to treat toxoplasmosis in developed countries is limited. However, if pyrimethamine is unavailable or there is a delay in obtaining it, TMP-SMX should be utilized in place of pyrimethamine-sulfadiazine or pyrimethamine-clindamycin (BI). For patients with a history of sulfa allergy, sulfa desensitization should be attempted using one of several published strategies (BI).43-48 Atovaquone should be administered until therapeutic doses of TMP-SMX are achieved (CIII).
No well-studied options exist for patients who cannot take an oral regimen. No parenteral formulation of pyrimethamine exists and the only widely available parenteral sulfonamide is the sulfamethoxazole component of TMP-SMX. Some specialists will use parenteral TMP-SMX (BI) or oral pyrimethamine plus parenteral clindamycin (CIII) as initial treatment in severely ill patients who require parenteral therapy.
The following regimens have been shown to be effective in treating TE in at least two nonrandomized, uncontrolled trials, although their relative efficacy compared with the previous regimens is unknown: atovaquone (with meals or oral nutritional supplements) plus either pyrimethamine plus leucovorin or sulfadiazine or, for patients intolerant of both pyrimethamine and sulfadiazine, as a single agent (BII)49,50,51 (if atovaquone is used alone, clinicians should be aware that the absorption of the drug from patient to patient is highly variable; plasma levels >18.5 µg/mL are associated with an improved response rate but measurements are not routinely available);50-52 and azithromycin plus pyrimethamine plus leucovorin daily (CII).53,54
The following regimens have been reported to have activity in treatment of TE in small cohorts of patients or in case reports of one or several patients: clarithromycin plus pyrimethamine (CIII);55 5-fluorouracil plus clindamycin (CIII),56 dapsone plus pyrimethamine plus leucovorin (CIII);57 and minocycline or doxycycline combined with either pyrimethamine plus leucovorin, sulfadiazine, or clarithromycin (CIII).58,59 Although the clarithromycin dose used in the only published study was 1g twice a day, doses >500 mg have been associated with increased mortality in HIV-infected patients treated for disseminated Mycobacterium avium complex. Doses >500 mg twice a day should not be used (BIII).
Clinical response to acute therapy occurs in 90% of patients with TE within 14 days of initiation of appropriate anti-toxoplasma treatment.2 The reasons why some patients fail therapy are not clearly proven; whether such failures are due to poor adherence or to other host factors of antimicrobial resistance has not been well delineated. Acute therapy for TE should be continued for at least 6 weeks, if there is clinical and radiologic improvement (BII).1-4 Longer courses may be appropriate if clinical or radiologic disease is extensive or response is incomplete at 6 weeks. After completion of the acute therapy, all patients should be continued on chronic maintenance therapy as outlined below (see Preventing Recurrence section below). The radiologic goals for treatment include complete resolution of the lesion(s) in terms of size and contrast enhancement, although small scars may persist indefinitely. Adjunctive corticosteroids such as dexamethasone should only be administered to patients with TE when they are clinically indicated to treat a mass effect associated with focal lesions or associated edema (BIII). In those treated with corticosteroids, caution may be needed in diagnosing CNS toxoplasmosis on the basis of treatment response, since primary CNS lymphoma may respond clinically and radiographically to corticosteroids alone; these patients should be monitored carefully as corticosteroids are tapered. In addition, corticosteroids should be discontinued as soon as clinically feasible because of their potential to cause immunosuppression. Patients receiving corticosteroids should be monitored closely for development of other opportunistic infections (OIs), including cytomegalovirus retinitis and TB.
Anticonvulsants should be administered to patients with TE who have a history of seizures (AIII), but should not be administered prophylactically to all patients (BIII). Anticonvulsants, if administered, should be continued at least through the period of acute therapy.
Special Considerations with Regard to Starting Antiretroviral Therapy
There are no data on which to base a recommendation regarding when to start ART in a patient with TE. However, many physicians would initiate ART within 2 to 3 weeks after the diagnosis of toxoplasmosis (CIII), based on the significantly lower incidence of AIDS progression or death (a secondary study endpoint) seen in the ART arm of a controlled trial of 282 patients with OIs other than TB (only 5% of whom had toxoplasmosis) who were randomized to early (median 12 days after initiation of OI therapy) versus deferred (median 45 days) initiation of ART.60
Monitoring of Response to Therapy and Adverse Events (including IRIS)
Changes in antibody titers are not useful for monitoring responses to therapy. Patients with TE should be monitored routinely for adverse events and clinical and radiologic improvement (AIII). Common pyrimethamine toxicities such as rash, nausea, and bone marrow suppression (neutropenia, anemia, and thrombocytopenia) often can be reversed by increasing the leucovorin dose to 10, 25, or 50 mg, four times daily (CIII).
Common sulfadiazine toxicities include rash, fever, leukopenia, hepatitis, nausea, vomiting, diarrhea, renal insufficiency, and crystalluria. Common clindamycin toxicities include fever, rash, nausea, diarrhea (including pseudomembranous colitis or diarrhea related to Clostridium difficile toxin), and hepatotoxicity. Common TMP-SMX toxicities include rash, fever, leukopenia, thrombocytopenia, and hepatotoxicity. Common atovaquone toxicities include nausea, vomiting, diarrhea, rash, headache, hyperglycemia, and fever. Drug interactions between anticonvulsants and antiretroviral agents should be evaluated carefully; if necessary, doses should be adjusted or alternative anticonvulsants should be used.
IRIS associated with TE has been reported but appears to be rare (~5% in one report).61-63 Given the rarity of TE-associated IRIS, recommendations for management of such events are difficult to develop.
Managing Treatment Failure
A brain biopsy should be strongly considered in patients who did not have an initial biopsy prior to therapy and who fail to respond to initial therapy for TE (BII) as defined by clinical or radiologic deterioration during the first week despite adequate therapy, or who do not show clinical improvement within 10 to 14 days. A switch to an alternative regimen, as previously described, should be considered for those who undergo brain biopsy and have confirmed histopathologic evidence of TE, or who have a CSF PCR positive for T. gondii (BIII). In patients who adhere to their regimens, disease recurrence is unusual in the setting of chronic maintenance therapy after an initial clinical and radiographic response.
Preventing Recurrence
When to Start Chronic Maintenance Therapy
Patients who have completed initial therapy for TE should be given chronic maintenance therapy to suppress infection (AI)36,37 until immune reconstitution occurs as a consequence of ART, in which case treatment discontinuation is indicated. The combination of pyrimethamine plus sulfadiazine plus leucovorin is highly effective as suppressive therapy for patients with TE (AI) and provides protection against PCP (AII). Although sulfadiazine is routinely dosed as a four-times-a-day regimen, a pharmacokinetic study suggests bioequivalence for the same total daily dose when given either twice or four times a day,64 and limited clinical experience suggests that twice-daily dosing is effective.65 Pyrimethamine plus clindamycin is commonly used as suppressive therapy for patients with TE who cannot tolerate sulfa drugs (BI). Because of the high failure rate observed with lower doses,36 a dose of 600 mg clindamycin every 8 hours is recommended (CIII). Because this regimen does not provide protection against PCP (AII), an additional agent, such as aerosol pentamidine, must be used. Atovaquone with or without pyrimethamine or sulfadiazine is also active against both TE51,52 and PCP66 (BII), but is substantially more expensive. A small, uncontrolled study in patients who had been receiving ART for a median of 13 months suggested that TMP-SMX could be used as a suppressive regimen to reduce pill burden.67 For patients being treated with TMP-SMX, this drug should be continued as chronic maintenance, at a reduced dose of 1 double-strength tablet twice daily (BII) or once daily (BII). The lower dose may be associated with an increased risk of relapse, and if the once daily dosing is used, a gradual transition may be beneficial (e.g. follow acute therapy with 4–6 weeks of 1 double-strength tablet twice daily before lowering to 1 double-strength tablet once daily (CIII).41,42,68
Although there are no data on the long-term suppressive efficacy of the other alternative regimens noted above, clinicians might consider using these agents in unusual situations in which the recommended agents cannot be administered (CIII).
When to Stop Chronic Maintenance Therapy
Adult and adolescent patients receiving chronic maintenance therapy for TE are at low risk for recurrence of TE if they have successfully completed initial therapy for TE, remain asymptomatic with regard to signs and symptoms of TE, and have an increase in their CD4 counts to >200 cells/µL after ART that is sustained for more than 6 months.32,35,69,70 Discontinuing chronic maintenance therapy in such patients is a reasonable consideration, although occasional recurrences have been reported. The recommendation is based on results in a limited number of patients from observational studies and one randomized clinical trial and inference from more extensive cumulative data indicating the safety of discontinuing secondary prophylaxis for other OIs during advanced disease (BI). As part of the evaluation to determine whether discontinuation of therapy is appropriate, some specialists recommend obtaining an MRI of the brain to assess for resolution of brain lesions.
Secondary prophylaxis (chronic maintenance therapy) for TE should be reintroduced if the CD4 count decreases to <200 cells/µL (AIII).
Special Considerations During Pregnancy
Documentation of baseline maternal T. gondii serologic status (IgG) should be obtained in HIV-infected women who are pregnant. Primary T. gondii infection can typically be distinguished from chronic infection with the use of multiple serologic assays, including IgG, IgM, IgA, and IgE antibodies; IgG avidity; and the differential agglutination tests.71,72 Pregnant HIV-infected women with suspected or confirmed primary T. gondii infection during pregnancy should be managed in consultation with a maternal-fetal medicine specialist or another appropriate specialist who can perform specialized laboratory testing (BIII)72,73 (e.g., the Palo Alto Medical Foundation Toxoplasmosis Serology Laboratory; Palo Alto, CA; http://www.pamf.org/serology/ at 650-853-4828 and email@example.com; and the National Collaborative Chicago-based Congenital Toxoplasmosis Study; Chicago, IL; http://www.uchospitals.edu/specialties/infectious-diseases/toxoplasmosis/ at 773-834-4131 and email@example.com).
Toxoplasmosis diagnostic considerations are the same in pregnant women as in non-pregnant women.
Indications for treatment of T. gondii during pregnancy should be based on confirmed or suspected symptomatic disease in the mother and the risk of transmission of the parasite from mother to fetus. Maternal treatment of TE should be the same as in non-pregnant adults (BIII), including pyrimethamine plus sulfadiazine plus leucovorin (AI).2,36-38 This regimen is also believed to prevent mother-to-child transmission of T. gondii and it may be therapeutic for affected fetuses.72
Although pyrimethamine has been associated with birth defects in animals, human data have not suggested an increased risk for defects, therefore, it can be administered to pregnant women after the first trimester.74-78 Similarly, sulfadiazine appears safe in pregnancy.79 A randomized, controlled trial published in 1956 found that premature infants receiving prophylactic penicillin/sulfisoxazole were at significantly higher risk of mortality (specifically kernicterus), compared with infants who received oxytetracycline.80 Because of these findings, some clinicians are concerned about the risk of neonatal kernicterus in the setting of maternal use of sulfa (including sulfadiazine) near delivery, although are no studies published to date link late third-trimester maternal sulfa use and neonatal death or kernicterus.
The preferred alternative regimen for patients with TE who are unable to tolerate or who fail to respond to first-line therapy is pyrimethamine plus clindamycin plus leucovorin (AI).36,37 Clindamycin is Food and Drug Administration Pregnancy Category B and considered safe throughout pregnancy. Atovaquone may be used if indicated. While there are limited data on atovaquone safety in humans, preclinical studies have not demonstrated toxicity.75
Although perinatal transmission of T. gondii normally occurs only with acute infection in the immunocompetent host, case reports have documented transmission with reactivation of chronic infection in HIV-infected women with severe immunosuppression.77,81 Pregnant HIV-infected women who have evidence of primary toxoplasmic infection or active toxoplasmosis, including TE, should be evaluated and managed during pregnancy in consultation with appropriate specialists (BIII). Detailed ultrasound examination of the fetus specifically evaluating for hydrocephalus, cerebral calcifications, and growth restriction should be done for HIV-infected women with suspected primary or symptomatic reactivation of T. gondii during pregnancy (AIII).72 Amniocentesis does not appear to increase the risk of perinatal HIV transmission, particularly in women receiving HAART.82 Therefore, PCR of amniotic fluid can be considered during gestation in pregnant women on ART with serologic evidence of acquired infection, and also for women with ultrasound findings suggestive of fetal T. gondii infection (BIII).72 Because the risk for transmission with chronic infection appears low, routine fetal evaluation for infection with amniocentesis is not indicated.
Pediatric-care providers should be informed about HIV-infected mothers who have suspected or confirmed T. gondii infection to allow evaluation of their neonates for evidence of congenital infection (AIII).
TMP-SMX can be administered for primary prophylaxis against TE as described for PCP (AIII). The risks of TMP-SMX in the first trimester, as discussed for PCP, must be balanced against the risk of TE. Secondary prophylaxis should be provided, using the same indications as for non-pregnant women. As noted above, pyrimethamine and sulfadiazine are considered safe in pregnancy. Clindamycin may be substituted for sulfadiazine for sulfa-intolerant patients. Dapsone appears to cross the placenta.83,84 Over the past several decades, dapsone (used for primary prophylaxis) has been used safely in pregnancy to treat leprosy, malaria, and various dermatologic conditions.84,85 With long-term therapy, there is a risk of mild maternal hemolysis and a potential—although extremely low—risk of hemolytic anemia in exposed fetuses with G6PD deficiency.86
Because the odds of perinatal HIV transmission decrease by 6% to 8% per week of ART, clinicians should consider immediate initiation of ART for pregnant women who are diagnosed with TE and not yet on ART (BIII).87,88 Because in-utero transmission of HIV is associated with HIV viremia at 30 (+/- 4) weeks' gestation, immediate ART is particularly indicated for women who are diagnosed with TE in the third trimester (AIII).89
When providing preconception care for HIV-infected women receiving TE prophylaxis, providers should discuss the option of deferring pregnancy until TE prophylaxis can be safely discontinued (BIII).
Preventing First Episode of Toxoplasma gondii Encephalitis (Primary Prophylaxis)
Indications for Initiating Primary Prophylaxis:
Note: All the recommended regimens for preventing first episode of toxoplasmosis are also effective in preventing PCP.
Preferred Regimen:
Alternative Regimens:
Indication for Discontinuing Primary Prophylaxis:
Indication for Restarting Primary Prophylaxis:
Treating Toxoplasma gondii Encephalitis
Preferred Regimen: (AI)
Note: If pyrimethamine is unavailable or there is a delay in obtaining it, TMP-SMX should be utilized in place of pyrimethamine-sulfadiazine (BI). For patients with a history of sulfa allergy, sulfa desensitization should be attempted using one of several published strategies (BI). Atovaquone should be administered until therapeutic doses of TMP-SMX are achieved (CIII).
Alternative Regimens:
Total Duration for Treating Acute Infection:
Chronic Maintenance Therapy for Toxoplasma gondii Encephalitis
Preferred Regimen:
Alternative Regimens:
Discontinuing Chronic Maintenance Therapy:
Other Considerations:
a Whenever possible, patients should be tested for G6PD deficiency before administrating dapsone. Alternative agent should be used if the patient is found to have G6PD deficiency.
b Atovaquone should be taken with meals or nutritional supplement to ensure adequate oral absorption.
c Pyrimethamine and leucovorin doses: Same as doses listed in Preferred Regimen for Acute Infection
d Sulfadiazine dose: Same as weight-based dose listed in Preferred Regimen for Acute Infection
Key to Acronyms: ART = antiretroviral therapy; BID = twice daily; CD4 = CD4 T lymphocyte cell; DS = double strength; G6PD = glucose-6-phosphate dehydrogenase; IgG = immunoglobulin G; IV = intravenous; PCP = Pneumocystis Pneumonia; PO = orally; q(n)h = every "n" hours; SS = single strength; TE = toxoplasmic encephalitis; TIW = three times a week; TMP-SMX = trimethoprim-sulfamethoxazole
- Luft BJ, Conley F, Remington JS, et al. Outbreak of central-nervous-system toxoplasmosis in western Europe and North America. Lancet. Apr 9 1983;1(8328):781-784. Available at http://www.ncbi.nlm.nih.gov/pubmed/6132129.
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- Mesquita RT, Ziegler AP, Hiramoto RM, Vidal JE, Pereira-Chioccola VL. Real-time quantitative PCR in cerebral toxoplasmosis diagnosis of Brazilian human immunodeficiency virus-infected patients. J Med Microbiol. Jun 2010;59(Pt 6):641-647. Available at http://www.ncbi.nlm.nih.gov/pubmed/20150319.
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- El-Sadr WM, Murphy RL, Yurik TM, et al. Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community Program for Clinical Research on AIDS and the AIDS Clinical Trials Group. N Engl J Med. Dec 24 1998;339(26):1889-1895. Available at http://www.ncbi.nlm.nih.gov/pubmed/9862944.
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It only takes a minute to get started. Fill out our uncomplicated sign up form and login to the site.
This step is optional but will dramatically boost your chances of people actually reading your profile and contacting you. Write a little about yourself, your hobbies and upload any nice photographs of yourself.
Use our website's state-of-the-art search to uncover members who satisfy your criteria. Or just scan through listings and uncover folks that seem interesting.
Found someone who appeals to you? Send a message to them or just a wink and await their reply. With a little luck you'll be on your way to uncover the love of your life.
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text: PCMag Staff Babbel Reviews/ Software/ Personal & Home/ Education & Reference/ Babbel View As: One PageSlides 1 Share Tweet Pin Email Babbel Babbel is an online language-learning program with 11 languges. 2 Share Tweet Pin Email Babbel As you work through a program in Babbel, you'll frequently see this page, which shows your progress (green bar graph at the bottom) and the next activity you should complete if you want to work in order through your chosen course. The next slide shows the bottom half of this same screen, where your courses appear. 3 Share Tweet Pin Email Babbel All the Babbel courses in which you enroll show up on the lower portion of the dashboard screen. 4 Share Tweet Pin Email Babbel Babbel contains a number of different excersizes. Beginners will see this one often, in which they match a phrase in translation. 5 Share Tweet Pin Email Babbel You can read a thorough preview of each course before you select to study it in Babbel 6 Share Tweet Pin Email Babbel The online Babbel includes speech recognition technology, although it's optional. If you use it, the system prompts you to speak, then records your voice. To pass and move to the next word or phrase, you have to score at least a 50 out of 100, and the score is shown on the microphone icon (but only if it's above 50). If you fail, you just try again. 7 Share Tweet Pin Email Babbel Babbel has numerous types of exercises, including grammar-matching modules. 8 Share Tweet Pin Email Babbel When you complete a lesson in Babble, you'll see a screen like this, which assesses your correct reponses (green) against incorrect ones (red). You can repeat the set of exercises again to try for a perfect score. 9 Share Tweet Pin Email Babbel Babbel has a very active user community, and if you plan to engage in it, you'll want to fill out as much of your online profile as possible, including you proficiency with other languages.


text:
Valiant Petroleum plc announced that the well on the Orchid exploration prospect (Valiant, 30 percent), located on Block 29/1c in the UK Central North Sea, has reached a total depth of 9,333 feet. The well encountered a Chalk zone of over 280 feet which exhibited oil shows throughout and higher-than-anticipated porosities. The shallower, secondary Tertiary target sands were not present in the well location.
Initial interpretation of the wireline log data by Valiant suggests the well has encountered a 50 foot pay zone above a large Chalk interval with low average oil saturations. The partnership has decided to plug and abandon the well pending further work on the data acquired to determine what further appraisal might be warranted.
Partners in the license are Summit Petroleum (45%, operator), Valiant (30%), Trap Oil (15%) and Atlantic Petroleum (10%).
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Template:Infobox soap character
Gina Patrick was a fictional character on the long-running Channel 4 British television soap opera Hollyoaks.
She was played by actress Dannielle Brent between 1997-2001.
Character historyEdit
Gina arrived in the village with her mother Jill Patrick, brother Sol, and sister Kate. While all the family were loud and brash, Gina was a little different. Her nose and lip ring made her stand out from the crowd and her passion for the environment saw her become a bit of an eco-warrior. She was also very intelligent and did well at Hollyoaks Community College. She went up against her friend Emily Taylor for the editor of the college magazine, but she lost due to step sister Ruth Osborne's hostility towards her family. She even helped sister Kate exact her revenge on Ruth by standing by and watching her drink a drink spiked with laxatives.
Gina never had a serious boyfriend despite a willing admirer in Sol's friend Paul Millington. Although he was sweet and obviously adored her, Gina let him down gently. Her sexuality became a big issue, especially when she eventually came out as a lesbian with Emily as her girlfriend. Following Jill's death, Gina and Emily's relationship went downhill fast. Emily was caught cheating on her, and an upset Gina dumped her and moved back in with stepfather Jack Osborne. After struggling at college, Gina quit and decided to do volunteer work overseas at an orphanage and make her mother proud.


text: Ok, so you can't book a month off work to watch the entire World Cup. But if you have an iPhone, you don't have to miss the big games thanks to a new ITV World Cup app for the iPhone.According to Digital Spy, ITV's new iPhone app will go live as the tournament commences on June 11th, allowing you to watch the matches as they are being broadcast by ITV1 and ITV2. So wherever you are, you can watch for free via 3G and Wi-Fi - data charges permitting.So what is ITV getting out of it? Well, a cut of the advertising of course. Specifically pre-roll advertising and click-through banner ads that will run alongside the service. Along with live streaming, the app will also offer up schedule information for ITV1 and ITV2. Juat so you can check when the next game is on.According to ITV director of online and interactive Ben McOwen Wilson: "Our aim at ITV is to make our content available when and where our viewers want to watch it. The ITV web app will enable iPhone users to find and watch their favourite ITV content, on the go and with this year's World Cup fast approaching, iPhone football fans now have a new way to watch the latest action."As the only UK broadcaster to screen the World Cup on mobile, this application offers advertisers a dynamic way to interact with viewers and puts ITV at the forefront of mobile VOD."ITV's first World Cup game will be South Africa versus Mexico, with coverage from Johannesburg starting at 3pm on June 11th. It will be followed on June 12th by England's first group match against the USA from 7.30pm.


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Herbeumont Vacation Packages
Brussels, which is the national capital, is situated 85 miles (137 kilometers) northwest of Herbeumont.
While it may be a temptation to simply sit back and relax when holidaying in Herbeumont, remember, the surrounding region's treasure-trove of natural and man-made attractions are never more than a day trip away. Interesting places in the vicinity of Herbeumont are Gedinne, 19 miles (31 kilometers) to the southeast, and Virton, 20 miles (32 kilometers) to the northwest.
Namur, is another interesting place to discover. It is approximately 50 miles (80 kilometers) from Herbeumont and offers a number of interesting things to see, including Castle of Namur, University of Namur and Namur Cathedral. Make sure you don't head back to Herbeumont until you've visited Namur's Felicien Rops Museum, Annevoie Gardens and Tresor de Prieure d'Oignies.
The most rewarding places for tourists to visit when they discover a place they have never been are the spots that offer a window into the culture. Don't miss Walloon Region's history museums.
Make sure you pack comfortable shoes and join one of the culinary tours and city walking tours.
At the conclusion of your break, pack your traveling bag and wish Herbeumont "Au revoir / À bientôt" (farewell).


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Kroondallaan rankings
Difficulty ranking world: 12635 (all)
Ranking Belgium: 1230 (all)
Ranking Pajottenland: 39(all)
Difficulty score: 14.22 what?
Kroondallaan ratings
(rate it)
The Kroondallaan is situated in Flemish Brabant. This climb belongs to the Pajottenland.
Starting from Dworp,
the Kroondallaan ascent is 1.14 km long. Over this distance, you climb 58 heightmeters.
The average percentage thus is 5 %.
Look for other sides to climb the Kroondallaan.
Click here to open big profile.
Click here to open detailed route.
Find climbs close to the Kroondallaan: within 10 km - within 20 km - within 50 km
Find all climbs and cols in Flemish Brabant on a map.
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Thursday, January 23, 2014
Social Media Engagement For Dummies Book Review
Having Social Media Engagement can benefit anybody that's involved in merchandising, on-line communities or blogging. The book, Social Media Engagement for Dummies is a perfect hands-on-guide, that will help you build connections, with other people. By understanding the dynamics of on-line communities, you'll find it critical to your success. People want to connect with people, not automated tools.
Social Media Engagement For Dummies
For this review, I received one copy of Social Media Engagement for Dummies! This book is full of very useful information, that is very easy to understand. The authors, Aliza Sherman and Danielle Elliot Smith, they emphasize the best practices of online marketing, customer service and genuine human communication. They'll guide you, on how internet tools work, how people use them, how you can leverage them to better reach the customers and prospects that matter the most to you!
Like any For Dummies book, this book is written to ensure that you can dive into any section and find useful information. Part I and II is an introduction to theories, concepts and tools. Part III, IV and V lay out distinct road maps for turning concepts into actions.
You can use the table of contents to find the chapters that can benefit you the most and the index can help you to key in on a particular concept or task. The book also mentions other useful sites.
Contents at a Glance
Part I: The Basics of Social Media Engagement
Chapter 1: Explaining the Why, Who, and How of Social Media Engagement
Chapter 2: Assessing the Impact of Social Media Engagement
Chapter 3: Discovering Social Media Engagement Tools
Part II: Exploring the Elements of Social Media Engagement
Chapter 4: Building Trust and Credibility
Chapter 5: Demonstrating Your Online Presence to Maximize Engagement
Chapter 6: Creating Connections
Chapter 7: Driving Interaction
Part III: Examining the Basic Engagement Tools
Chapter 8: E-mail, Forum, Blogs and Websites
Chapter 9: Facebook
Chapter 10: Twitter
Part IV: Engaging Through Additional Social Channels
Chapter 11: Pinterest
Chapter 12: LinkedIn
Chapter 13: Google+
Chapter 14: Location-Based Services
Part V: Leveraging Audio and Video for Engagement
Chapter 15: Audio and Videocasting
Chapter 16: YouTube
Part VI: The Part of Tens
Chapter 17: Then Social Media Engagement Mistakes to Avoid
Chapter 18: Ten Businesses That Excel at Social Media Engagement
One of the most important step is to build trust and credibility, with your customers or readers. Contributing to meaningful conversations, with your audience can help you build that trust and credibility. Be sure to respond to comments and follow up. Always be honest, even if you're wrong. Learn who your audience is and give them what they want.
As you can see from the chapters, this book covers everything you need to know about Social Media Engagement and I would highly recommend Social Media Engagement for Dummies!
My favorite section was on Pinterest, Facebook and Twitter!
Thanks Aliza and Danielle for a very informational book that has the best step-by-step guide on Social Media Engagement!
Posted by Bonny Sallee at 1/23/2014 03:45:00 PM
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After payment Cool Timeline Pro will be delivered to your paypal email id.
We provide support everyday at here – firstname.lastname@example.com
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GOLDEN Polymer Gloss Medium is a general purpose liquid medium useful for creating glazes, extending colors, enhancing gloss and translucency and increasing film integrity. Imparts a unique feel that is much more oil-like or resinous in nature and that promotes flow and leveling.
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Female Support Worker Required in Taverham, Norwich
Support worker required to support a woman in her 20's currently residing in a local rehabilitation unit, with plans to move to her own home in the future. She has a brain injury and uses a wheelchair for all mobility. She requires support for her personal care and in all aspects of her daily living activities, both in the home, within the community and when on holiday.
Part time position
Must have experience working with adults with a disability/cognitive impairment
Full driving licence is essential
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Pay: Support Worker pay from £10.15 per hour
Female applicants only as an Occupational Requirement (Equality Act 2010 Schedule 9 Part 1)
To obtain an application pack please contact: Anglia Case Management Ltd on 01359 272390 or click the 'apply via email' button or to download click the 'apply via website' button.
Quoting Ref: JF503
Closing Date: Monday 15th February 2016
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FoodReference.com (Since 1999)
RECIPE SECTION - Over 10,000 Recipes
Home | Food Articles | Food Trivia | Today in Food History | Food Timeline | Recipes
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An extensive selection of free food, beverage & agricultural magazines, e-books, etc.
Makes 8 servings
Each serving equals one 5 A Day serving
· 2 Tbsp olive oil
· 3 cloves garlic, minced
· 2 Tbsp chopped fresh ginger root
· 2 tsp curry powder or to taste
· 1/2 tsp crushed, dried chilies
· 1/4 tsp Allspice
· 1/4 tsp Cinnamon
· 3 leeks, trimmed and chopped
· 3 potatoes, peeled and cut in 1" chunks
· 1 cup low sodium tomato sauce
· 2 cup low sodium chicken broth
· 3 cup Butternut squash, peeled and cubed
· 2 red peppers, diced
· 4 chicken breasts, boned
· 1 Tbsp olive oil
· 1/2 cup fresh cilantro, chopped
Heat oil in large saucepan or Dutch oven.
Add garlic, ginger, spices and leeks. Cook a few minutes until tender.
Add potatoes, tomato sauce and chicken broth. Cook 10 minutes.
Add squash and peppers; cook 15 minutes or until vegetables are tender.
Lightly brush chicken breasts with oil. Grill approximately 10 minutes on each side, or until juices run clear.
Cut each chicken breast into 3 or 4 large pieces and add to sauce. Reheat just before serving.
Sprinkle with cilantro.
Nutritional analysis per serving:
Calories 247, Protein 18g, Fat 7g, Calories From Fat 7%, Cholesterol 35mg, Carbohydrates 31g, Fiber 6g, Sodium 82mg.
Source: Produce for Better Health/Prince Edward Island Potato Board
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All contents are copyright © 1990 - 2017 James T. Ehler and www.FoodReference.com unless otherwise noted.
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|Message view
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|"Filip Maj (JIRA)" <j...@apache.org>
|[jira] [Commented] (CB-937) debug command in Android should install app too
|Fri, 29 Jun 2012 05:03:42 GMT
[ https://issues.apache.org/jira/browse/CB-937?page=com.atlassian.jira.plugin.system.issuetabpanels:comment-tabpanel&focusedCommentId=13403697#comment-13403697 ] Filip Maj commented on CB-937: ------------------------------ yeh can we search through the output of {{adb devices}} and see if a device/emulator is present or not? > debug command in Android should install app too > ----------------------------------------------- > > Key: CB-937 > URL: https://issues.apache.org/jira/browse/CB-937 > Project: Apache Cordova > Issue Type: Bug > Components: Android > Reporter: Filip Maj > Assignee: Anis Kadri > Priority: Minor > > currently it only runs {{ant debug}}, which builds the app, but doesnt install it to a connected device. it should probably run {{ant debug install}} ya? -- This message is automatically generated by JIRA. If you think it was sent incorrectly, please contact your JIRA administrators: https://issues.apache.org/jira/secure/ContactAdministrators!default.jspa For more information on JIRA, see: http://www.atlassian.com/software/jira
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Wait Times for Disneyland Paris - Ad Free
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- © VersaEdge Software, LLC
Compatibility: Requires iOS 6.0 or later. Compatible with iPhone, iPad, and iPod touch.


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When does season 5 start of criminal minds start in the UK?
I would recommend going to a joke shop.
When does batle start galactica season 4 start?
'Battlestar Galactica' Season 4 Not Starting Until April 2008
When does season 8 start of csi Miami start?
It has just finished in the UK, Grisome leaves and Laurence Fisherbourne (of the matrix) takes over.
When does flu season start?
While it may start earlier, flu season in the United States generally peaks sometime between November and March, according to the Centers for Disease Control and Prevention. The CDC monitors the pr...
Read More »
When does season 9 start in UK?
Answer That sounds like Mr. Carlin, played by Jack Riley.


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The Advanced Creative Techniques Photographic Workshop is designed for photographers wanting to add to their skills. During the day you will have the opportunity to put into practice what has been discussed in the classroom during the morning session.
The Great Fen is a 50-year project to create a huge wetland area. One of the largest restoration projects of its type in Europe, the landscape of the fens between Peterborough and Huntingdon is being transformed for the benefit both of wildlife and of people.
Our location of the Great Fen will offer the photographer the chance to experience a wide range of stimulating photographic opportunities including landscape, macro, flora and fauna. Whilst walking around the Great Fen reserve we will discuss composition ideas for improving your images. The Great Fen is home to many iconic species of birds, mammals and invertebrates and should we be lucky enough to encounter any of these, we will use the field-craft techniques discussed earlier in the day.
Due to the large expanse of the reserve and the terrain we recommend that you bring appropriate footwear (walking boots/wellingtons) and outdoor clothing suitable for the day. Sunscreen and insect repellent can be useful depending on the weather. Tea and coffee will be available on arrival and during the classroom session but you will need to provide a packed lunch and refreshments for whilst we are out on the reserve.


text: The Glamour Awards really rocked the red carpet. Once again, it was time for the "Women Of The Year Awards". It was filled with gorgeous looks, which is too be expected from any prestigious event like this. The show took place in New York City and celebrated woman from a broad range of categories – everyone from the likes of Reese Witherspoon to Karlie Kloss. The soiree was hosted by none other than Amy Schumer. This year the crowd felt more diverse with not just actresses taking home awards but due to the fact that the industry in expanding in all different directions we got to see all the best of the best entertainers, which is always something that we love. Take a look at our absolute 5 favorite looks from the night:


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House Sitter in Fort Worth
My name is cindy i live in fort worth. I love dogs. Im here to help you with what u need. Fedding ur animal, watering your plants taking care of ur home. Im very reliable and trustworthy.
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Fresh.I.Am Winter Collection Available Now
Sunday Dec 08 2013
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ENOLA, Pa. (AP) Many of the wedding reception guests didn't believe the disc jockey when he announced the hotel was on fire.
Then firefighters interrupted the celebration, and newlyweds Trey and Robyn Kunkel knew it wasn't a joke.
Fire officials said the fire led to the evacuation of more than 400 guests Saturday night from the Radisson Penn Harris Hotel & Convention Center in East Pennsboro.
"We'll never forget this," Robyn Kunkel said.
No injuries were reported. Firefighters said flames were confined to a roof area on the hotel wing of the complex, across a parking lot from the convention center where the reception was held.
The newlyweds posed for photographs on a fire truck while wearing firefighters' helmets.
Copyright 2008 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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Back from his visit to Alabama this weekend, Galena Park (Texas) High running back Albert Hardy had one thought on his mind.
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The Rosia Montana Project was designed to process a nominal feed rate through the grinding circuit of 13.5 Mt/y. The crushing circuit included a 62" x 75" gyratory crusher. The grinding circuit included a 36' SAG mill complete with a 15 MW gearless drive and two ball mills each with 10 MW dual pinion drives.
The plant site is located in a remote, mountainous area within Transylvania with challenging geotechnical conditions. The total average drawn power of the plant was estimated to be 57 MW (peak 62 MW) supplied from the local grid.
Ausenco was engaged to perform the detailed engineering, procurement and construction management (EPCM) services for the processing plant and associated infrastructure. The scope of services included responsibility for all engineering for process plant and infrastructure, permitting, global procurement and logistics, construction management and commissioning for the facility.
The project was delivered despite the following challenges:


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If an item you ordered from TextbookRush does not meet your expectations due to an error on our part, simply fill out a return request and then return it by mail within 30 days of ordering it for a full refund of item cost.
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Description: In the first century A.D., Publius Ovidius Naso, the most urbane and irreverent poet of imperial Rome, was banished to a remote village on the edge of the Black Sea. From these sparse facts, Malouf has fashioned an audacious and supremely moving novel. Marooned on the edge of the known world, exiled from his native tongue, Ovid depends on the kindness of barbarians who impale their dead and converse with the spirit world.Then he becomes the guardian of a still more savage creature, a feral child who has grown up among deer. What ensues is a luminous encounter between civilization and nature, as enacted by a poet who once cataloged the treacheries of love and a boy who slowly learns how to give it. "A work of unusual intelligence and imagination, full of surprising images and insights...One of those rare books you end up underlining and copying out into notebooks and reading out loud to friends."--The New York Times Book Review
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David Malouf was born in 1934 in Brisbane, Australia. He attended Brisbane Grammar School and graduated from the University of Queensland. Malouf's first published work was "Interiors" in 1962. Since then, he has published eight poetry collections, eight novels, an autobiography and a play. He has also written the libretto for Richard Meale's opera, "Voss." He has been awarded the Prix Femina Etranger, the Commonwealth Writers' Prize and the Pascall Prize. David Malouf uses life in Australia as a major theme in his work, with much of his fiction recreating his childhood in Brisbane.
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Amazing Grace may well be the most popular hymn ever written, though it has never sounded better than in this absolutely gorgeous setting. Flowing lines along with some impressive harmonic twists
A delightfully unique combining of Scotland the Brave and Amazing Grace. This setting brings fresh new harmonic treatments and joins the tunes as if they were meant to be together.
Each student has a chance to play the melody with their "finger-bones connected to their hand bones" in this bone-rattling arrangement of the well-known spiritual, perfect for Halloween or any time of year!
The familiar Johann Sebastian Bach melody will be loved by one and all. Solidly scored for your string or full orchestra, the delicate melody will reinforce the musicianship of the entire ensemble.
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Intex has extended its Cloud series with the new smartphone dubbed as, Intex Cloud Fame. The smartphone is exclusively available from Snapdeal and is priced at Rs. 3,999.
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Zubrus and matteau video about the summer of the devils
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Discussion in 'Enhanced Search Support' started by Mr Lucky, May 20, 2016.
Is there a way to search for just for posts that have email addresses in them?
Most will have been converted to [EMAIL] tags, especially if they were posted in XF. Likely too if your forum software prior to XF if there was one supported a similar thing.
With that in mind, searching for [EMAIL] should work.
EDIT: After a test here, this may not work. You may be better off searching for it via the database:
SELECT * FROM xf_post WHERE message LIKE '%[EMAIL]%'
SELECT * FROM xf_post WHERE message LIKE '%[EMAIL]%'
That's right, searching it also picks up the word [I]email
Thanks, I don't want to edit database but I think you are right, that could be the only solution.
It won't edit the database, it's just a SELECT query.
Yes, but my aim here is to take out any email addresses, so I either need to do it (ideally) via edit on the forum, or (after searching the database) manually on the database (which I'd prefer not to do)
So if I do a search on the database, I think that will be a complicate way to get to the post so I can edit them on the forum.
However at the moment it's a bit moot as that query gives me an error.
#1064 - You have an error in your SQL syntax; check the manual that corresponds to your MariaDB server version for the right syntax to use near '%[EMAIL]% LIMIT 0, 30' at line 1
#1064 - You have an error in your SQL syntax; check the manual that corresponds to your MariaDB server version for the right syntax to use near '%[EMAIL]% LIMIT 0, 30' at line 1
I've fixed the query above.
I'd only had one coffee by that time...
If the aim is to replace the email addresses, you'd probably be best with the Post Content Find and Replace Tool:
If you post in the resource thread, someone will likely point you in the direction of the correct regex to use.
Probably something like this, though. (Haven't tested it)
Replace with:
(or whatever you like).
Good idea thanks
yes I want to replace with something like person -at- emailaddress.com
Separate names with a comma.


text:
login with
Brave! I've never been interested in downhill skiing. I love cross country skiing though.
Looks like fun! i have never been skiing...but something maybe i will take up in my old age...LOL!
Never to old :) you ladies should try it.
Sheila i agree i would probably do more damage to myself than fun! LOL!
I am a little scared to learn but it looks like so much fun. I am actually going to snowboard. :) lol looks easier
I'm just as scared of snowboarding! ;)
About Christina Zaidi
Current: Lynnwood, Washington
Birth: May 20
On Moms.com since: Jan 24, 2014
I have a 5 year old son. And married almost 11 years.


text:
My Grandad passed away very suddenly in hospital after we thought he was getting better. I have just celebrated my first birthday without him here and I feel so alone. He and I were so close. I miss hearing him talk to me. I miss hearing him say my name and laugh with me at our silly jokes. He always called me "his lovely girl" and the fact that no one will ever call me that again is breaking my heart.
I have no guilt about the way my life was spent with him. I never went a day without telling him I loved him. But it hurts so much not to have him here with me anymore. I dreamt about him hugging me last night, and it felt so real that I could feel the wool of his jumper against my cheek. I hate that it wasn't real.
I hope things get better with time, but for now it feels so unfair that my wonderful, lovely Grandfather who was so kind and believed in me more than anyone in the world has been snatched away from me before I even had a chance to say goodbye.
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|View Poll Results: Does an outside kitchen need a sink and fauct
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mr Simon Leyshon
leeds, west yorkshire - England
No approved endorsements
About mr Simon Leyshon
I am a highly networked headhunter operating in various markets and industries working on mid-level management to senior-board appointments. My business is predominantly within the Technology and Mobile/Telecoms sectors with a clients that include multinational "blue-chips" and emerging technology start-ups.
International Recruitment Specialist,
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|Specific Preferences
|Research Topics
|Recombinant Human CD80 / B7-1 Protein (Catalog#10698-H08H)
|Mouse IgG1
|0.2 μm filtered solution in PBS with 5% trehalose
|This antibody was produced from a hybridoma resulting from the fusion of a mouse myeloma with B cells obtained from a mouse immunized with purified, recombinant Human CD80 / B7-1 (rh CD80 / B7-1; Catalog#10698-H08H; Met 1-Asn 242; NP_005182.1). The IgG fraction of the cell culture supernatant was purified by Protein A affinity chromatography.
|Human CD80 / B7-1
No cross-reactivity in ELISA with
Human CD28
Human B7-2
Human B7-H1
Mouse B7-H2
Human PDL2
Human cell lysate (293 cell line)
ELISA: 0.5-1 μg/mL
This antibody can be used at 0.5-1 μg/mL with the appropriate secondary reagents to detect Human B7-1. The detection limit for Human B7-1 is approximately 0.00975 ng/well.
|This antibody can be stored at 2℃-8℃ for one month without detectable loss of activity. Antibody products are stable for twelve months from date of receipt when stored at -20℃ to -70℃. Preservative-Free.
Sodium azide is recommended to avoid contamination (final concentration 0.05%-0.1%). It is toxic to cells and should be disposed of properly. Avoid repeated freeze-thaw cycles.
The B-lymphocyte activation antigen B7-1 (referred to as B7), also known as CD80, is a member of cell surface immunoglobulin superfamily and is expressed on the surface of antigen-presenting cells including activated B cells, macrophages and dendritic cells. As costimulatory ligands, B7-1 which exists predominantly as dimer and the related protein B7-2, interact with the costimulatory receptors CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expressed on T cells, and thus constitute one of the dominant pathways that regulate T cell activation and tolerance, cytokine production, and the generation of CTL. The B7/CD28/CTLA4 pathway has the ability to both positively and negatively regulate immune responses. CD80 is thus regarded as promising therapeutic targets for autoimmune diseases and various carcinomas.
|Product name
|Product name


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|Reviews for Force Bond: Dentist
| Shanice chapter 1 . 2/13
Awesome story had me laughing so much lol your a great author on these genre's. Love the chemistry you make with Vader and his son and the conflict he has as his real self anakin Skywalker. Thanks love Darth dentist by the way lol that's one for the books.
| Guest chapter 1 . 10/12/2016
It's absolutely hilarious to imagine James Earl Jones' voice saying all these things.
| Window Girl chapter 1 . 10/7/2016
Your stories always manage to blend humor and drama so well. I like that Vader gets free tickets to all sporting events and that he slays Luke's nightmares.
| MugetsuPipefox chapter 1 . 2/20/2016
That ending though bahahaha that has got to be soooo embarrassing :')
On a side note, I definitely know how Luke feels. I had to get a couple of fillings at the end of last year and I was so scared D: (the numbing needles are the worst)
Loved the humour XD
| lilyflower101 chapter 1 . 2/14/2016
In ever really understood the fear some people have of dentists.
| VioletErin.26 chapter 1 . 1/19/2016
Wow. This is so great. Oh poor Luke. That was a great ending.
| MusicMelis chapter 1 . 1/2/2016
I love their father/son relationship...
| The Hope Lions chapter 1 . 12/28/2015
It was so ridiculous. The normal fics are so normal and these are so damn funny!
| Brievel chapter 1 . 5/24/2015
Bahaha, that epilogue. xD
I really never understood all the hype about dentists, I love our dentist - and yes, I've had teeth other, over a dozen, I think. Baby teeth, mostly, although I got either four...or six...I disremember...permanents out.
| hateme101 chapter 1 . 3/23/2015
Love how vader kills darth denist father of the year
| GGMK chapter 1 . 2/28/2014
Another funny story from you.
I won't lie...Luke annoys me sometimes. I can't really sympathize with him, because I was never really scared of the dentist. They were all nice.
The epilogue was all sorts of awesome, though. Darth Dentist was no match. :)
| cjstar01 chapter 1 . 1/5/2014
Ok wait a second. Did vader just like come into his dream. Wait... I get it now. Vader just wanted to know why luke was upset and he entered his dream. Intresting. Hey I just notice something. As lukes sister. I can see vaders face when he learns he has 2 children, and it's a girl. Harmons...HA HA HA HA HA! I can BE evil sometimes
| Guest chapter 1 . 10/25/2013
Ok, I loved that.
| Guest chapter 1 . 9/21/2013
So good. Love the humor as always.
| Ally chapter 1 . 7/9/2013
Poor Luke. But he should have guessed he would have gotten caught eventually haha. I loved the story! You had my laughing so much! I loved the nightmare parts! Darth Dentist! haha! The 2nd nightmare was my favorite. But the last one was really funny, because then we know DD is shady like the Emperor. I liked when Vader companied Luke, even though he really had no choice. He ditched twice and barley walked five steps towards his 'real' dentist. Poor Luke. And then when Luke's in there and scared to death that she was going to hurt him. And then Vader finds out about his 'secret'. Loved that. Perfect!
I really Liked how Ben was in the story. I liked his parts especially when he covered for him. it was like one of those, 'who are you? my mother?' moments. lol. And I liked Lev even though I don't know or remember who he is. And how Vader commented on Obi Wan ruining an escape for him like Vader did for Luke. Loved that. Basically the whole story was geinus!
I've probably read this like 10 times! It's so good! I will be sharing this on my Twitter and Tumblr. Very well written. Great job! This is probably the best, one of them anyway, that've read for Star Wars fictions on here! It's that good! It has the drama between Luke and Vader, the humor, and some what hurt and comfort. Loved it! Keep up the amazing work! You're a great writer! Obviously! ;)


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- chisel
I. noun
Etymology: Middle English, from Anglo-French *chisel, cisel, from Vulgar Latin *cisellum, alteration of caesellum, from Latin caesus, past participle of caedere to cut
Date: 14th century
a metal tool with a sharpened edge at one end used to chip, carve, or cut into a solid material (as wood, stone, or metal)
II. verb
(-eled or -elled; -eling or chiselling)
Date: 1509
transitive verb
1. to cut or work with or as if with a chisel
2. to employ shrewd or unfair practices on in order to obtain one's end; also to obtain by such practices <chisel a job> intransitive verb 1. to work with or as if with a chisel 2. a. to employ shrewd or unfair practices b. to thrust oneself ; intrude <chisel in on a racket> • chiseler or chiseller noun
New Collegiate Dictionary. 2001.