Surfactant protein D is a biomarker of influenza-related pediatric lung injury.

BACKGROUND: Biomarkers that can risk-stratify children with influenza virus lower respiratory infection may identify patients for targeted intervention. Early elevation of alveolar-related proteins in the bloodstream in these patients could indicate more severe lung damage portending worse outcomes. METHODS: We used a mouse model of human influenza infection and evaluated relationships between lung pathophysiology and surfactant protein D (SP-D), SP-A, and Club cell protein 16 (CC16). We then measured SP-A, SP-D, and CC16 levels in plasma samples from 94 children with influenza-associated acute respiratory failure (PICFLU cohort), excluding children with underlying conditions explaining disease severity. We tested for associations between levels of circulating proteins and disease severity including the diagnosis of acute respiratory distress syndrome (ARDS), mechanical ventilator, intensive care unit and hospital days, and hospital mortality. RESULTS: Circulating SP-D showed a greater increase than SP-A and CC16 in mice with increased alveolar-vascular permeability following influenza infection. In the PICFLU cohort, SP-D was associated with moderate-severe ARDS diagnosis (p = 0.01) and with mechanical ventilator (r = 0.45, p = 0.002), ICU (r = 0.44, p = 0.002), and hospital days (r = 0.37, p = 0.001) in influenza-infected children without bacterial coinfection. Levels of SP-D were lower in children with secondary bacterial pneumonia (p = 0.01) and not associated with outcomes. CC16 and SP-A levels did not differ with bacterial coinfection and were not consistently associated with severe outcomes. CONCLUSIONS: SP-D has potential as an early circulating biomarker reflecting a degree of lung damage caused directly by influenza virus infection in children. Secondary bacterial pneumonia alters SP-D biomarker performance.

SRA gene knockout protects against diet-induced obesity and improves glucose tolerance.

We have recently shown that the non-coding RNA, steroid receptor RNA activator (SRA), functions as a transcriptional coactivator of PPARγ and promotes adipocyte differentiation in vitro. To assess SRA function in vivo, we have generated a whole mouse Sra1 gene knock-out (SRA(-/-)). Here, we show that the Sra1 gene is an important regulator of adipose tissue mass and function. SRA is expressed at a higher level in adipose tissue than other organs in wild type mice. SRA(-/-) mice are resistant to high fat diet-induced obesity, with decreased fat mass and increased lean content. This lean phenotype of SRA(-/-) mice is associated with decreased expression of a subset of adipocyte marker genes and reduced plasma TNFα levels. The SRA(-/-) mice are more insulin sensitive, as evidenced by reduced fasting insulin, and lower blood glucoses in response to IP glucose and insulin. In addition, the livers of SRA(-/-) mice have fewer lipid droplets after high fat diet feeding, and the expression of lipogenesis-associated genes is decreased. To our knowledge, these data are the first to indicate a functional role for SRA in adipose tissue biology and glucose homeostasis in vivo.

Using location, color, size, and depth to characterize and identify endometriosis lesions in a cohort of 133 women.

OBJECTIVE: To correlate histology with endometriosis characteristics. DESIGN: Secondary data analysis. SETTING: Government research hospital. PATIENT(S): One hundred thirty-three women with chronic pelvic pain and endometriosis who underwent laparoscopic surgery between 1999 and 2004. INTERVENTION(S): Laparoscopic excision of lesions, including recording of lesion characteristics and surgical impression of the lesions. MAIN OUTCOME MEASURE(S): All biopsies were sent for histological examination for endometriosis, and surgical and histological findings were compared. RESULT(S): Three hundred fifty-seven of 544 lesions believed to be endometriosis by the surgeon had positive histology. Mixed-color lesions most commonly contained endometriosis (76%), with the percentage of positive lesions being similar between single-color groups. Among subtle (red or white) lesions, 58% (164/283) were positive for endometriosis. Thirty women had only red or white lesions, and 18 (60%) had at least one lesion positive for endometriosis. Lesions were most commonly located in the cul-de-sac (64%), utero-sacral ligaments (68%), and ovarian fossa (70%). CONCLUSION(S): Wide, deep, mixed-color lesions in the cul-de-sac, the ovarian fossa, or the utero-sacral ligaments had the highest frequency of endometriosis. More than half of subtle lesions had endometriosis. These results should be considered when diagnosing endometriosis.

Endometriosis and the appendix: a case series and comprehensive review of the literature.

OBJECTIVE: To report the prevalence of appendiceal disease in women with chronic pelvic pain undergoing laparoscopy for possible endometriosis, summarize the literature, and more accurately estimate the prevalence of endometriosis of the appendix. DESIGN: Prospective case series and literature review. SETTING: Academic research institute. PATIENT(S): One hundred thirty-three patients with chronic pelvic pain and possible endometriosis undergoing laparoscopy. INTERVENTION(S): History, physical exam, and abdominopelvic laparoscopy. Endometriosis and adhesions were excised using selective Nd:YAG contact laser trabeculoplasty and pathologically evaluated. Only patients with visible abnormalities involving the appendix were treated via concurrent laparoscopic appendectomy. MAIN OUTCOME MEASURE(S): Appendiceal abnormalities at laparoscopy. RESULT(S): Of 133 patients, 13 had a previous appendectomy with unknown pathology. Of the remaining 120 patients, 109 reported right lower quadrant pain. Of this subgroup, six patients had appendiceal pathology: four with pathology-confirmed endometriosis, one with Crohn's disease suspected at laparoscopy, and one with chronic appendicitis. The prevalence of appendiceal endometriosis in patients with biopsy-proven endometriosis (n = 97) or with right lower quadrant pain (n = 109) was 4.1% and 3.7%, respectively. This rate was similar to the 2.8% prevalence confirmed by literature review in patients with endometriosis but was much higher than that reported in all patients (0.4%). CONCLUSION(S): Appendiceal endometriosis, while relatively uncommon in patients with endometriosis, is rare in the general population. In patients with right lower quadrant or pelvic pain, the appendix should be inspected for endometriosis and evidence of nongynecologic disease.