Endotypes of difficult-to-control asthma in inner-city African American children.

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6-17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population.

Using corticosteroids during pregnancy. Are topical, inhaled, or systemic agents associated with risk?

QUESTION: I am concerned about use of corticosteroids during pregnancy. Some of my women patients of reproductive age are using topical, inhaled, or oral preparations, and I am not sure what to advise. ANSWER: Both topical and systemic corticosteroids are used for a variety of autoimmune and inflammatory conditions. Results of first-trimester studies were inconclusive and underpowered. Recent meta-analyses suggest a small but significant association between use of systemic corticosteroids during the first trimester and oral clefts. This is consistent with results of animal studies. No similar evidence exists for topical or inhaled corticosteroids, probably because of much lower systemic exposure.

Eigen value analysis of HIV-1 integrase inhibitors.

A three-dimensional quantitative structure activity relationship using the eigen value analysis (EVA) paradigm applied to 41 HIV-1 integrase inhibitors that inhibit integrase mediated cleavage (3'-processing step) and integration (3'-strand transfer step) in vitro was performed. The training set consisted of 35 molecules from five structurally diverse classes: salicylhydrazines, lichen acids, coumarins, quinones, and thiazolothiazepines. Models derived using semiempirical (MOPAC AM1 and PM3) calculated normal-mode frequencies were compared. The predictive ability of each resultant model was evaluated using a test set comprised of six molecules belonging to a different structural class: hydrazides. Models derived using AM1 method showed considerable internal as well as external predictivity (r(2)(cv) = 0.806, r(2)(pred) = 0.761 for 3'-processing and r(2)(cv) = 0.677, r(2)(pred) = 0.591 for 3'-strand transfer).

Molecular electrostatic potentials as input for the alignment of HIV-1 integrase inhibitors in 3D QSAR.

Comparative molecular similarity indices analysis (CoMSIA), a three-dimensional quantitative structure activity relationship (3D QSAR) paradigm, was used to examine the correlations between the calculated physicochemical properties and the in vitro activities (3'-processing and 3'-strand transfer inhibition) of a series of human immunodeficiency virus type 1 (HIV-1) integrase inhibitors. The training set consisted of 34 molecules from five structurally diverse classes: salicylpyrazolinones, dioxepinones, coumarins, quinones, and benzoic hydrazides. The data set was aligned using extrema of molecular electrostatic potentials (MEPs). The predictive ability of the resultant model was evaluated using a test set comprised of 7 molecules belonging to a different structural class of thiazepinediones. A CoMSIA model using an MEP-based alignment showed considerable internal as well external predictive ability (r2(cv) = 0.821, r2(pred) = 0.608 for 3'-processing; and r2(cv) = 0.759, r2(pred.) = 0.660 for 3'-strand transfer).

Metastatic prostatic carcinoma presenting as an anterior mediastinal mass on gallium imaging.

A great majority of mediastinal lymph node metastases originate from primary neoplasms within the thorax. Mediastinal metastases from other malignancies are not infrequently encountered but are uncommon from a prostatic primary site. Since prostatic metastases may mimic lymphomatous nodes, it is important to be aware that mediastinal adenopathy occurring in a patient with prostatic carcinoma may be caused by metastases from that site rather than from lymphoma, or be secondary to some unknown primary malignancy elsewhere in the body. The author presents a case of metastatic prostatic carcinoma in the anterior mediastinum that was detected on Ga-67 citrate imaging and confirmed on a CT scan.

Hemangioma, a rare cause of photopenic lesion on skeletal imaging.

In searching for disease on skeletal images it is important to identify areas of increased activity and cold lesions, which are usually more difficult to identify. Focal photon-deficient lesions are due to metastatic disease in over 80% of cases. They may occur if the tumor is extremely aggressive, if there is disruption of the blood supply to the bone, or if there is significant marrow involvement, particularly in a vertebral body. Some of the common causes of a photopenic lesion are avascular necrosis, malignant bone tumors such as multiple myeloma, metastasis, radiation therapy, attenuation artifacts such as prosthesis or pacemaker, and early osteomyelitis. A case of hemangioma of the dorsal vertebra, a rare cause of photopenic lesion, is reported here.

Scintigraphy of bile leakage following cholecystectomy.

Biloma resulting as a complication of cholcecystectomy is rarely reported. Infection and rupture of biloma into the peritoneal cavity is a reported complication that may need aggressive surgical management. A case of infected biloma is presented in which an active biliary leak was demonstrated on a hepatobiliary scan with Tc-99m DISIDA.

Imaging of an actively bleeding aortoduodenal fistula.

Diagnosis of gastrointestinal bleeding remains a difficult problem. Radionuclides have been used widely to detect active GI bleeding. A case of actively bleeding aortoduodenal fistula detected on radionuclide imaging is presented.

Gallium-67 imaging in pulmonary eosinophilic granuloma.

Gallium-67 citrate has been known to localize in the lungs in a variety of pulmonary diseases. Abnormal lung activity implies active underlying disease. Serial Ga-67 lung scans may be helpful when steroids are used as therapeutic agents. A case of pulmonary eosinophic granuloma is reported here with diffuse bilateral Ga-67 pulmonary activity.