Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations.

Helicobacter pylori possesses unusually high urease activity that lowers the urea concentration and raises the ammonium concentration of the gastric juice in infected people. The value of measuring urea and ammonium concentrations in gastric juice obtained during upper gastrointestinal endoscopy as a means of diagnosing the presence and eradication of the infection was assessed. Twenty four subjects with the infection and 14 in whom it had been eradicated were examined. Their H pylori status was confirmed by antral biopsy and 14C urea breath test. The median (range) gastric juice urea concentration in infected subjects was 0.8 mmol/l (0.5-2.9 mmol/l), which was lower than that in the uninfected subjects (2.1 mmol/l (1.0-3.7 mmol/l)) (p less than 0.001). The median gastric juice ammonium concentration in infected subjects was 3.4 mmol/l (1.0-13.0 mmol/l), which was higher than that in the uninfected subjects (0.64 mmol/l (0.02-1.4 mmol/l)) (p less than 0.001). Though the two groups overlapped in respect of their urea and ammonium concentrations, they were completely different when the urea: ammonium ratios were calculated--the ratios ranged from 0.04-0.7 (median 0.26) and from 1.1-113 (median 3.4) in infected and uninfected subjects respectively (p less than 0.001). Treatment with H2 antagonists did not change the concentrations of urea and ammonium or their ratio in gastric juice. Measurement of the urea: ammonium ratio in aspirated gastric juice obtained during routine upper gastrointestinal endoscopy may provide a rapid method of detecting H pylori infection and of confirming its eradication.     

Thymic function in adults: evidence derived from immune recovery patterns following myeloablative chemotherapy and stem cell infusion

We studied 45 patients aged 14–66 years who had undergone stem cell transplantation for a variety of malignant conditions at least 12 months previously. Compared to normal controls, they had significantly reduced absolute numbers of CD4⁺, CD4⁺CD45RA⁺ and CD4⁺CD45RO⁺ T cells and a reduced CD4⁺CD45RA⁺: CD4⁺CD45RO⁺ ratio. In all subsets T-cell numbers were significantly greater 24 months, compared to 12–24 months, after transplantation and there was a non-significant trend towards lower T-cell numbers with increasing age. We conclude that the thymus, or putative thymic-equivalent tissue, remains functional in older adults.     

Expression, localization, and signaling of PGE(2) and EP2/EP4 receptors in human nonpregnant endometrium across the menstrual cycle

This study was designed to elucidate the sites of synthesis and action of PGE(2) in the nonpregnant human uterus across the menstrual cycle. The sites of expression of PGE synthase and synthesis of PGE(2) were investigated by immunohistochemistry using full thickness uterine biopsies. Expression of PGE synthase and synthesis of PGE(2) were localized to glandular epithelial and endothelial cells in both basalis and functionalis regions of the human endometrium. By contrast, stromal staining was predominantly localized in the functionalis layer. Some cyclical variation in expression of PGE synthase and PGE(2) synthesis was observed, with reduced expression/synthesis detected in the stromal compartment of the functionalis during the late secretory phase of the menstrual cycle. Subsequently, we assessed the site of action of PGE(2) by investigating the expression of two PGE(2) receptor isoforms, namely EP2 and EP4. Cyclical variation in endometrial EP2 and EP4 receptor mRNA expression was quantified by TaqMan quantitative RT-PCR using RNA isolated from endometrial tissue collected across the menstrual cycle. No differences in EP2 receptor mRNA expression were detected; however, EP4 receptor mRNA expression was significantly higher in late proliferative stage (P < 0.05) than in early, mid, and late secretory stage endometrium. Expression patterns of EP2 and EP4 receptors were localized by nonradioactive in situ hybridization using fluorescein isothiocyanate end- labeled oligonucleotide probes. Expression of both receptors was observed in endometrial glandular epithelial and vascular cells, with no notable spatial or temporal variation. Finally, signaling of EP2/EP4 receptors was assessed by investigating cAMP generation in vitro after stimulation with PGE(2). Endometrial cAMP generation in response to PGE(2) was significantly greater in proliferative tissue compared with early and midsecretory stage tissue (3.77 +/- 0.85 vs. 1.96 +/- 0.28 and 1.38 +/- 0.23, respectively; P < 0.05). In conclusion, this study demonstrates glandular and vascular coexpression of PGE synthase, PGE(2), EP2, and EP4 receptors and suggests an autocrine/paracrine role for PGE(2) in epithelial/endothelial cell function in the human endometrium.     

Cardiac involvement in systemic lupus erythematosus detected by echocardiography

Cardiac involvement in patients with systemic lupus erythematosus (SLE) was assessed by full echocardiography and continuous wave Doppler in 50 consecutive patients and 50 age- and sex-matched control subjects in a prospective, blinded study. The left ventricular ejection fraction was decreased in patients compared to control subjects (61 +/- 9 vs 68 +/- 7%, p less than 0.001), whereas interventricular septum (12 +/- 3 vs 9 +/- 1 mm, p less than 0.001), and posterior wall dimension (9 +/- 2 vs 8 +/- 1 mm, p less than 0.001), left ventricular mass (186 +/- 54 vs 130 +/- 32 g, p less than 0.001) and mitral valve Doppler A:E ratio (0.8 +/- 0.2 vs 0.7 +/- 0.1, p less than 0.01) were increased. Pericardial effusion was detected in 27 patients and 5 control subjects, and valvular regurgitation was more frequent in the patients (aortic 2 vs 0; mitral 23 vs 5, p less than 0.001; tricuspid 34 vs 22, p less than 0.01 and pulmonary 28 vs 17, p less than 0.05). Mitral or aortic regurgitation was more common in patients with active SLE (60 vs 40%, difference not significant) but was not related to the duration of SLE (r = 0.02), duration of prednisone therapy (r = -0.13) or current dosage of prednisone (r = 0.01). This study demonstrates that pericardial effusion, valvular regurgitation and myocardial abnormalities are frequently present in patients with SLE.     

Plasticity in the organization and sequences of human KIR/ILT gene families

The approximately 1-Mb leukocyte receptor complex at 19q13.4 is a key polymorphic immunoregion containing all of the natural killer-receptor KIR and related ILT genes. When the organization of the leukocyte receptor complex was compared from two haplotypes, the gene content in the KIR region varied dramatically, with framework loci flanking regions of widely variable gene content. The ILT genes were more stable in number except for ILT6, which was present only in one haplotype. Analysis of Alu repeats and comparison of KIR gene sequences, which are over 90% identical, are consistent with a recent origin. KIR genesis was followed by extensive duplication/deletion as well as intergenic sequence exchange, reminiscent of MHC class I genes, which provide KIR ligands.     

Dietary inflammatory index or Mediterranean diet score as risk factors for total and cardiovascular mortality

Background and Aims

Dietary patterns are associated with risk of cardiovascular disease (CVD). We aimed to examine associations of the Dietary Inflammatory Index (DII) and the Mediterranean Diet Score (MDS) with total, cardiovascular disease (CVD) and coronary heart disease (CHD) mortality in the Melbourne Collaborative Cohort Study; and compare the strengths of the associations.

The Pediatric Studies Initiative: After 15 Years Have We Reached the Limits of the Law?

Background

Despite considerable disincentives for conducting drug studies in children, 15 years ago the Food and Drug Administration, pediatric health advocates and congressional sponsors created a carrot-and-stick policy approach of voluntary and mandatory programs to encourage the pharmaceutical industry to include children in the drug development process. After several rounds of reauthorization of the laws on a temporary basis, the enabling statutes have been made permanent.

Objective

The purpose of this analysis is to review the advances that resulted from the law and the areas where further progress is needed.

Methods

A brief review of the history and results of the pediatric studies initiative was conducted by the authors and a determination made about the accomplishments of the law and remaining challenges.

Results

Indicators of the changes that resulted from this pediatric studies initiative are both indirect, such as the increase in the number of indication supplements for new populations, and direct, such as the decrease in the percentage of medicines used off-label in children. Although the pediatric studies initiative has significantly improved therapeutic options for children, concern still exists that drug companies are reluctant to include children in drug development unless continuously incentivized, whether positively or negatively. Two challenges are particularly problematic: neonatal studies and child-friendly formulations.

Conclusion

Although the latest round of legislation should provide opportunities to address these problems, significantly more effort will be needed to achieve real culture change. Ultimately, the solution will require full program implementation by the Food and Drug Administration and close collaboration by many key stakeholders to ensure that pediatric studies become a routine part of the drug development process.