Muzaffar Ahmad

Pulmonary vasculitis (Wegener's granulomatosis): Immunohistochemical study of T and B cell markers

A case of pulmonary vasculitis (Wegeners granulomatosis) is reported in which immunoperoxidase studies demonstrated that the vascular lymphoid infiltrates were composed predominantly of T cells and monocytes. Occasional T cells, B cells and monocytes were identified in the alveolar septa. IgG, IgA, IgM, and C3 were not identified in pulmonary vessels, septa, or alveoli. These findings suggest that cellular rather than humoral-immune mechanisms predominate in pulmonary vasculitis.

Amyloidosis and Pleural Disease

Pleural involvement with systemic amyloidosis has been reported rarely in the literature. Diagnosis of this entity by percutaneous needle biopsy of the pleura has been described only in two prior case reports. We describe five patients in whom the diagnosis of pleural amyloidosis was established by Cope needle biopsy during evaluation of pleural effusions of indeterminate cause. Three patients presented with a history suggestive of multiorgan disease and a pleural biopsy performed despite a transudative effusion demonstrated amyloid infiltration of the pleura, obviating the need for other organ biopsies. We conclude that in patients with pleural effusions, if history suggests multiorgan involvement and there is suspicion for amyloidosis, then a closed pleural biopsy with special stains for amyloid should be performed even if the effusions are transudative. This may be the diagnostic procedure of choice in such patients.

Peripheral small cell undifferentiated carcinoma of the lung. Clinicopathologic features of 17 cases.

Seventeen cases of resectable peripheral small cell undifferentiated carcinoma of the lung were studied (average size, 2.1 cm; range, 0.9–3.5 cm). The carcinomas exhibited predominantly mixed intermediate and fusiform/spindle subtypes; in seven carcinomas there were at least some foci of oat cell subtype. There was no histologic evidence of typical carcinoid tumor. Seven cases were fixed in solutions appropriate for immunohistologic study; these exhibited prominent neuron‐specific enolase activity but less prominent and more variable staining for the carcinoembryonic antigen and cytokeratins. All 17 cases were deemed resectable and had no clinical or radiologic evidence of metastasis. Seven (41%) patients died with recurrent and/or metastatic carcinoma (average survival, 1.7 years); five of these patients had carcinomas with at least some foci of oat cell foci subtype.

Human alveolar macrophage function: differences between smokers and nonsmokers.

Human alveolar macrophages and peripheral blood monocytes were obtained from smoking and nonsmoking normal volunteers. The macrophages and monocytes were incubated in vitro with bacterial lipopolysaccaride (LPS). The oxidative metabolic response of these cells was measured by superoxide anion production. Macrophages from smokers were suppressed in their superoxide anion response to LPS activation as compared to macrophages from nonsmokers. Monocytes from smokers and nonsmokers were not different. The cytotoxic properties of these macrophages and monocytes were assessed by an in vitro 3H‐thymidine release assay against various allogeneic target cells. Macrophages and monocytes exposed to LPS were rendered tumoricidal. Macrophages from nonsmokers appeared to generate greater cytotoxic activity than macrophages from smokers. Macrophages from both smokers and nonsmokers were cytotoxic for three different tumorigenic cell lines but not for a nontumorigenic cell line. Monocytes from smokers and nonsmokers were not different in cytotoxic activity. We conclude that macrophages from both smokers and nonsmokers can be activated after exposure to LPS; however, macrophages from smokers may be slightly suppressed in their responses.

Excessive helper T-cell function in patients with idiopathic pulmonary fibrosis: Correlation with disease activity

Peripheral blood T lymphocytes from patients with idiopathic pulmonary fibrosis and matched normal controls were examined for their helper function in an in vitro antibody synthesis assay. This assay measures the dose-related T-cell regulation of antibody production by B cells in the presence of pokeweed mitogen. Eight patients of 14 expressed significantly increased helper T-cell activity, three exhibited no change, and three had depressed helper T-cell function. All of the patients with excessive helper T-cell function had an active neutrophilic alveolitis as determined by bronchoalveolar lavage on the day of study. Five of the 14 patients studied were determined to have a low percentage of neutrophils (less than 10%) in their BAL fluid. None of these were found to express excessive helper T-cell function; in fact three of the five had depressed helper T-cell function. No correlation between steroid therapy or smoking history and the expression of excessive helper function was observed. None of the peripheral blood T-cells from IPF patients were actively producing IL-2 in vitro without further stimulation, providing evidence against constitutive production in vivo. T cells were also examined for their ability to produce lymphokines promoting fibroblast proliferation. Enhanced stimulation of fibroblast proliferation was shown to positively correlate with disease activity as determined by the degree of neutrophilic alveolitis (r = 0.68). The significant correlation between neutrophilic alveolitis and excessive helper T-cell function observed here suggests that altered systemic immunoregulation accompanies local inflammation. The further participation of patient T cells in promoting fibroblast proliferation may contribute to the development of fibrosis, or to the contrary may be an attempt to limit the fibrotic process.

The immotile cilia syndrome: explanation for many a clinical mystery.

With the advent of electron microscopy, ciliary abnormalities could be detected, analyzed, and correlated with clinical problems. Kartageners syndrome, identified over 40 years ago as a triad of sinusitis, bronchiectasis, and situs inversus, was found to actually be a subset of a broader category of diseases: the immotile cilia syndrome. Two other subsets involving multiple organ systems have also been recognized.

Thalidomide-related eosinophilic pneumonia: A case report and brief literature review

Thalidomide has regained value in the multimodality treatment of leprosy, multiple myeloma, prostate, ovarian and renal cancer. Complications related to arterial and venous complications are well described. However, pulmonary complications remain relatively uncommon. The most common pulmonary side-effect reported is non-specific dyspnea. We report a patient with multiple myeloma, who developed an eosinophilic pneumonia, shortly after starting thalidomide. She had complete resolution of her symptoms and pulmonary infiltrates on discontinuation of the drug and treatment with corticosteroids. Physicians should be cognizant of this potential complication in patients receiving thalidomide who present with dyspnea and pulmonary infiltrates.

Photosensitizers as Diagnostic and Therapeutic Tools in Oncology

Photosensitizers are chemicals that can be activated in situ by penetrating light of a specific wavelength, leading either to fluorescence of a different wavelength; tissue necrosis or both. Most malignant and some premalignant tissues retain these photochemically active substances in higher concentrations and for longer durations than surrounding normal tissues. The exceptions are regenerating or embryonic tissue, inflammatory processes and organs rich in reticuloendothelial cells, such as liver, kidney, spleen, skin and, to some extent, muscles. Photosensitizers, which are relatively nontoxic and safe for humans and animals, are currently being studied for diagnostic and therapeutic applications.

Coronary stents: A health system perspective ☆ ☆☆ ★

The introduction and widespread application of coronary stenting is one of the most important developments in interventional cardiology.More than 400,000 Americans undergo coronary artery interventional procedures each year,and most estimates indicate that stents are deployed in more than half of these patients.1 This increase in stent deployment is accompanied by rapidly evolving techniques,new stent designs,and adjunctive therapy.Unfortunately,clinical practice has changed well ahead of supporting data regarding efficacy. The advent of managed, particularly capitated, care has placed a high premium on using only those therapeutic interventions that have a proven effect on outcome.This need to reduce unnecessary costs has increased the focus on evidence-based medical care and has led to widespread agreement, among both the medical profession and the public, that therapeutic measures cannot be justified on anecdotal experience alone. Coronary stenting provides a special challenge in this regard because its use is triggered by commonly used angiographic diagnostic studies.With the mergers, collaborations, and coalitions among health care institutions, the issue of the cost-effectiveness of coronary stenting has become sharply focused, especially as it relates to populations within regions, age groups, and health plans.The following questions and answers address the current status of coronary stenting from a health system perspective.

Management of COPD: a physiologic approach.

The main goal of therapy for COPD is to improve the patients quality of life. A rational approach to therapy requires improvement in pulmonary gas exchange by identification of the type or types of COPD present and tailoring of the therapeutic regimen to the severity and mechanism of obstruction. Other measures can be used to improve tissue oxygenation, including oxygen supplementation, maintenance of cardiac output and tissue perfusion, and reduction of metabolic demands. Complications of COPD are as important as the disease itself in terms of disability and require aggressive therapy.