Publications

A rapidly progressive, fatal recrudescence of pulmonary Kaposi sarcoma developed in an HIV-infected man who was receiving corticosteroids for treatment of an immune reconstitution syndrome secondary to Mycobacterium avium complex pulmonary infection. We discuss the implications for current diagnosis and management of HIV-associated pulmonary diseases.

Tryptases and chymases are the major proteins stored and secreted by mast cells. The types, amounts, and properties of these serine peptidases vary by mast cell subtype, tissue, and mammal of origin. Membrane-anchored gamma-tryptases are tryptic, prostasin-like, type I peptidases that remain membrane attached on release and act locally. Soluble tryptases, including their close relatives, mastins, form inhibitor-resistant oligomers that act more remotely. Befitting their greater destructive potential, chymases are quickly inhibited after release, although some gain protection by associating with proteoglycans. Most chymase-like enzymes, including mast cell cathepsin G, hydrolyze chymotryptic substrates, an uncommon capability in the proteome. Some rodent chymases, however, have mutations resulting in elastolytic activity. Secreted tryptases and chymases promote inflammation, matrix destruction, and tissue remodeling by several mechanisms, including destroying procoagulant, matrix, growth, and differentiation factors and activating proteinase-activated receptors, urokinase, metalloproteinases, and angiotensin. They also modulate immune responses by hydrolyzing chemokines and cytokines. At least one chymase protects mice from intestinal worms. Tryptases and chymases can also oppose inflammation by inactivating allergens and neuropeptides causing inflammation and bronchoconstriction. Thus, like mast cells themselves, mast cell serine peptidases play multiple roles in host defense, and any accounting of benefit versus harm is necessarily context specific.

Everolimus (40-O-(2-hydroxyethyl)rapamycin, Certican) is a 31-membered macrolide lactone. In lymphocytes, it inhibits the mammalian target of rapamycin (mTOR) and is used as an immunosuppressant after organ transplantation. Due to its instability in pure organic solvents and insufficient HPLC separation, NMR spectroscopy analysis of its metabolite structures is nearly impossible. Therefore, structural identification based on tandem mass spectrometry (MS/MS) and MS(n) fragmentation patterns is critical. Here, we have systematically assessed the fragmentation pattern of everolimus during liquid chromatography (LC)-electrospray ionization (ESI)-MS/MS and validated the fragment structures by (1) comparison with structurally identified derivatives (sirolimus), (2) high-resolution mass spectrometry, (3) elucidation of fragmentation pathways using ion trap mass spectrometry (up to MS(5)) and (4) H/D exchange. In comparison with the structurally related immunosuppressants tacrolimus and sirolimus, our study was complicated by the low ionization efficiency of everolimus. Detection of positive ions gave the best sensitivity, and everolimus and its fragments were mainly detected as sodium adducts. LC-ESI-MS/MS of everolimus in combination with collision-induced dissociation (CID) resulted in a complex fragmentation pattern and the structures of 53 fragments were identified. These detailed fragmentation pathways of everolimus provided the basis for structural elucidation of all everolimus metabolites generated in vivo und in vitro.

INTRODUCTION

Although physician discussion with patients regarding fertility preservation (FP) options prior to cancer treatment can provide important information for survivors concerning their future fertility, little is known about the extent to which physicians discuss FP with patients. This qualitative study sought to identify current physician FP communication practices and determine factors that may impact communication efforts regarding FP.

MATERIALS AND METHODS

Qualitative data were collected using semi structured interviews with 16 physicians practicing at a major cancer center in the South.

RESULTS

All providers were board certified in medical oncology, radiation oncology or surgical oncology. The main factors that emerged from qualitative analysis included distinct variations in quality of discussion about FP, knowledge of FP resources, attitudes, practice behaviors and perceptions of patient characteristics.

DISCUSSION

While most physicians discussed potential fertility loss as a side effect of cancer treatment, few provided information to patients about preserving fertility. Patient characteristics such as gender and cancer site may impact the discussion, as well as system factors such as costs of procedures and access to FP resources. Education and training for physicians about FP options for cancer patients, particularly females, may promote discussion of FP. In addition, system barriers related to availability and affordability of FP resources must also be addressed.

IMPLICATIONS FOR CANCER SURVIVORS

Physicians should consider providing patients with timely, understandable information related to their FP options, prior to the administration of treatment. Such discussions may lead to improved quality of life for individuals as they transition from patients to survivors.

High resolution CT (HRCT) scanning has contributed significantly to the evaluation of patients with interstitial lung disease and is particularly useful in the diagnosis of idiopathic pulmonary fibrosis (IPF). The characteristic radiographic features of the idiopathic interstitial pneumonias on HRCT scans have been increasingly analysed and are now fairly well described. Based on current data, HRCT scanning can provide a confident, highly specific diagnosis of IPF in many patients with diffuse lung disease. This article reviews an organised approach to HRCT scanning and identifies the features that allow an accurate diagnosis of the idiopathic interstitial pneumonias to be made. The role of surgical lung biopsy is discussed in the diagnosis of cases when a definite HRCT diagnosis cannot be made.

BACKGROUND

Certain hospitals play a central role in ensuring Medicaid-insured patients' access to care. Their quality of care is critical to evaluate.

OBJECTIVE

To determine whether hospitals for which Medicaid patients represent a high percentage of total discharges provide a different quality of care than other hospitals.

RESEARCH DESIGN

Cross-sectional analysis.

SUBJECTS

Acute care hospitals participating in the first Hospital Compare public report (released November 2004) and the 2004 American Hospital Association hospital survey.

MEASURES

Hospitals serving 1 standard deviation above the national mean percentage of Medicaid patients were designated high Medicaid hospitals. Performance was assessed using percent compliance with 10 processes of care for 3 conditions: myocardial infarction, congestive heart failure, and community-acquired pneumonia.

RESULTS

Among the 2874 nonteaching hospitals, high Medicaid hospitals had lower adherence (P < 0.01) than other nonteaching hospitals on all 10 indicators. Of particular clinical importance, high Medicaid nonteaching hospitals less frequently prescribed beta-blockers (83% vs. 90%%, P < 0.0001) and aspirin at discharge in myocardial infarction (85% vs. 91%%, P < 0.0001), and administered antibiotics on time in CAP (68% vs. 75%, P < 0.0001). Among teaching institutions, there were few differences between high Medicaid and other hospitals.

CONCLUSIONS

Among hospitals publicly reporting on the Hospital Compare Web site, nonteaching hospitals treating a high percentage of Medicaid patients had lower adherence to quality indicators than other nonteaching hospitals on 10 indicators. Further research is needed to determine what factors contribute to differences in reported quality.