Glucocorticoids and lymphocytes. III. Effects of glucocorticoid administration on lymphocyte glucocorticoid receptors

To determine the effects of glucocorticoid administration on the number of measured lymphocyte glucocorticoid receptor sites and the duration of such effects, seven normal volunteers were studied. Glucocorticoid receptor levels of the lymphocytes circulating in the blood of each volunteer were determined. Glucocorticoid was then administered in a regimen of a total of four doses of dexamethasone 4 mg p.o. every 6 hr. Determinations of the number of receptors were performed at 6 hr and at various subsequent times after the end of dexamethasone administration. When compared to baseline receptor numbers, six volunteers showed a decrease in receptor number after glucocorticoid administration (median maximum decrease 2,046 sites/cell). The fall in receptor number occurred rapidly, reaching a nadir within 30 hr from the end of glucocorticoid administration. The return of receptor number to baseline was more gradual, requiring from 3 to as long as 17 days in one subject. Our results suggest that in order to accurately interpret glucocorticoid receptor numbers in human lymphoid cells, glucocorticoid should not have been administered for 3 wk prior to determinations of receptor levels.     

Palmoplantar keratoderma of Sybert

A 13-year-old boy and a 7-year-old boy, who are brothers, presented with a life-long history of erythema, hyperkeratosis, and desquamation of the hands and feet. Symptoms improved with the use of topical glucocorticoids and keratolytics. PPK of Sybert is characterized by palmoplantar hyperkeratosis with transgrediens, autosomal dominant inheritance, and the absence of associated systemic features.     

Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells

Two monoclonal antibodies (To15 and 4KB128) specific for the B cell- associated CD22 antigen (135,000 mol wt) are described. On immunoenzymatic analysis of cryostat tissue sections, these antibodies strongly label both mantle zone and germinal center B lymphoid cells in secondary lymphoid follicles (and also scattered extrafollicular lymphoid cells) but are unreactive with other cell types (with the exception of weak reactivity with some epithelioid histiocytes). These reactions differ from those of monoclonal antibodies B1 and B2 (anti- CD20 and CD21) but are similar to those of the pan-B antibody B4 (anti- CD19). One of the anti-CD22 antibodies (To15) has been tested extensively by immunoenzymatic labeling on greater than 350 neoplastic lymphoid and hematological samples. The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative). In cell smears, the antigen could be found on neoplastic cells in most B cell lymphoproliferative disorders, including common acute lymphoblastic leukemia (ALL) (90% positive) and B cell chronic lymphocytic leukemia (CLL) (89% positive). We conclude that anti-CD22 antibodies are of value for identification of human B cell lymphoproliferative disorders (especially when used in conjunction with anti-CD19 antibodies). Previous reports that the CD22 antigen is absent from many B cell neoplasms are probably due to its being expressed within the cytoplasm of immature B cells rather than on their surface.     

中国汉族帕金森病人群 SLC18A2 基因 P387L 突变的遗传学分析

目的：SLC18A2基因的P387L突变在中国汉族散发性帕金森病人群的关联研究。方法：在931例汉族人群 中(包括455例散发性帕金森病患者和476例正常对照者)应用飞行时间质谱分析(matrix-assisted laser desorption/ionization- time-of-fl ight mass spectrometry,MALDI-TOF MS)技术测定P387L基因型,并应用Sanger测序的方法对结果进一步验证。 同时采用病例-对照研究,探索该突变与散发性帕金森病的关联。结果：在本组931个研究个体中均未发现该突变位 点。结论：该突变位点在中国汉族人群中很罕见,可能并非中国汉族散发性帕金森病人群的致病突变位点,该突变 位点与帕金森病之间的关联尚需扩大样本及在其他种族人群中进行验证。     

Effectiveness of first-line antiretroviral therapy in the IPEC cohort,Rio de Janeiro,Brazil

Background

While Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need, the epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income country has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine the socio-demographic, behavioral, clinical and structural factors associated with virologic suppression.

Methods

Virologic suppression on first-line ART at 6, 12, and 24 months from start of ART was defined as having a viral load measurement ≤400 copies/mL without drug class modification and/or discontinuation. Drug class modification and/or discontinuation were defined based on the class of a particular drug. Quasi-Poisson regression was used to quantify the association of factors with virologic suppression.

Results

From January 2000 through June 2010, 1311 patients started first-line ART; 987 (75%) patients used NNRTI-based regimens. Virologic suppression was achieved by 77%, 76% and 68% of patients at 6, 12 and 24 months, respectively. Factors associated with virologic suppression at 12 months were: >8 years of formal education (compared to <4 years, risk ratio (RR) 1.13, 95% confidence interval (95% CI) 1.03-1.24), starting ART in 2005-2010 (compared to 2000-2004, RR 1.25 95% CI 1.15-1.35), and clinical trial participation (compared to no participation, RR 1.08 95% CI 1.01-1.16). Also at 12 months, women showed less virologic suppression compared to heterosexual men (RR 0.90 95% CI 0.82-0.99). For the 24-month endpoint, in addition to higher education, starting ART in the later period, and clinical trial participation, older age and an NNRTI-based regimen were also independently associated with virologic suppression.

Conclusions

Our results show that in Brazil, a middle-income country with free access to treatment, over three-quarters of patients receiving routine care reached virologic suppression on first-line ART by the end of the first year. Higher education, more recent ART initiation and clinical trial participation were associated with improved outcomes both for the 12-month and the 24-month endpoints, suggesting that further studies are needed to understand what aspects relating to these factors lead to higher virologic suppression.

     

Cost-Effectiveness of Chemoprevention with Proton Pump Inhibitors in Barrett’s Esophagus

Background

Proton pump inhibitors (PPIs) may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus. PPIs are prescribed for virtually all patients with Barrett’s esophagus, irrespective of the presence of reflux symptoms, and represent a de facto chemopreventive agent in this population. However, long-term PPI use has been associated with several adverse effects, and the cost-effectiveness of chemoprevention with PPIs has not been evaluated.

Aim

The purpose of this study was to assess the cost-effectiveness of PPIs for the prevention of EAC in Barrett’s esophagus without reflux.

Methods

We designed a state-transition Markov microsimulation model of a hypothetical cohort of 50-year-old white men with Barrett’s esophagus. We modeled chemoprevention with PPIs or no chemoprevention, with endoscopic surveillance for all treatment arms. Outcome measures were life-years, quality-adjusted life years (QALYs), incident EAC cases and deaths, costs, and incremental cost-effectiveness ratios.

Results

Assuming 50 % reduction in EAC, chemoprevention with PPIs was a cost-effective strategy compared to no chemoprevention. In our model, administration of PPIs cost $23,000 per patient and resulted in a gain of 0.32 QALYs for an incremental cost-effectiveness ratio of $12,000/QALY. In sensitivity analyses, PPIs would be cost-effective at $50,000/QALY if they reduce EAC risk by at least 19 %.

Conclusions

Chemoprevention with PPIs in patients with Barrett’s esophagus without reflux is cost-effective if PPIs reduce EAC by a minimum of 19 %. The identification of subgroups of Barrett’s esophagus patients at increased risk for progression would lead to more cost-effective strategies for the prevention of esophageal adenocarcinoma.