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Biomedical subjects

G N Gephardt

Publications and source records attributed to G N Gephardt.

At least 19 recordsLinked to original sources

Pseudo-gamma heavy chain (IgG4 lambda) deposition disease.

Two patients with Ig deposition disease presented with acute renal failure, moderate proteinuria, and hematuria. A plasmacytoid lymphocytic infiltrate was identified in bone marrow that produced IgG4 lambda and free lambda light chains. One patient developed an anaplastic plasmacytoma (secreting only lambda light chains) 1 yr after renal biopsy. Renal biopsy in both patients demonstrated a nodular intercapillary glomerulopathy and electron dense granular deposits, associated with a linear pattern of IgG4 heavy chain deposition in vascular, tubular, and glomerular basement membranes (VBM, TBM, and GBM). In one patient this entrapped IgG4 was unassociated with detectable kappa or lambda light chains. In the second patient, lambda light chains (1+) were detected only in the GBM, but IgG4 (4+) was identified in GBM/TBM. Neither circulating (peripheral blood and bone marrow serum) nor cellular free gamma chains were present. We propose the term "pseudo-gamma heavy chain deposition disease" for the process.

Aged

Hypersensitivity pneumonitis versus invasive pulmonary aspergillosis: two cases with unusual pathologic findings and review of the literature.

Two brothers simultaneously exposed to moldy hay, who developed differing forms of Aspergillus-related lung disease, are presented. Patient 1 developed a true case of hypersensitivity lung disease, whereas his brother developed invasive aspergillosis with bronchoalveolar lavage eosinophilia and unusual pathologic features including tissue eosinophilia. The possible overlap between hypersensitivity pneumonitis and invasive aspergillosis in the immunocompetent host is discussed.

Adult

Columnar papilloma of the bronchus. Case report and literature review.

Solitary papillomas are rare endobronchial neoplasms that are most commonly lined by a squamous epithelium (i.e., squamous papillomas). Papillomas exhibiting nonsquamous epithelium are even more unusual; only seven solitary papillomas lined by columnar epithelium (i.e., columnar papillomas) have been previously described. The current report presents the eighth patient with a columnar papilloma and demonstrates some features common to solitary papillomas (i.e., central location in the airways, associated atelectasis), but distinctive from squamous papillomas (i.e., absence of malignant potential).

Aged

A prospective comparison of DNA quantitation by image and flow cytometry.

Advances in computer and video technology suggest that image analysis may be practical method of measuring DNA that also allows visual confirmation of cell type. The purpose of this study was to prospectively compare DNA quantitation from 92 solid tumors in which DNA indices had been measured by image analysis of touch preparations (CAS 100) and flow cytometry of cell suspensions (FACScan). For 81 cases, there was excellent correlation between the two methods. For nine cases, however, an aneuploid population, usually near tetraploid, was identified by image but not by flow cytometry. Three cases had aneuploid peaks by flow cytometry that were not identified by image. Although these methods show good correlation, rare populations may be missed by CAS, presumably because of sampling errors in the touch preparation. Aneuploid populations may also be missed by flow cytometry, either because of cell loss during processing or because visual identification by image can increase sensitivity.

Adenocarcinoma

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.

Aged

Wegener's granulomatosis. Immunomicroscopic and ultrastructural study of four cases.

Four cases of Wegener's granulomatosis involving lung are reported in which immunomicroscopy demonstrated that the parenchymal and vascular infiltrates were composed primarily of T cells and monocytes. No IgG, IgA, IgM, or C3 was identified in pulmonary vessels or alveolar septa. Ultrastructural studies failed to demonstrate dense deposits in alveolar septal capillaries or interstitium. These findings indicate that a cellular immune mechanism is active in these forms of pulmonary vasculitis and that immune complex deposition does not play a role.

Adult

Utility of frozen-section evaluation of lymph nodes in the staging of bronchogenic carcinoma at mediastinoscopy and thoracotomy.

We conducted a retrospective analysis of the utility of frozen-section diagnoses in determining lymph node status at mediastinoscopy in 122 consecutive patients with bronchogenic carcinoma. Thirty-five of 122 patients had one or more lymph nodes with frozen-section evaluation positive for metastatic carcinoma. Subsequent nodal sections not in the original frozen-section study revealed metastatic carcinoma in two additional patients. The false-negative rate was 1.6%. Sensitivity was 94.6%. Predictive value of negative frozen-section evaluation results was 97.7%. Because there were no false-positive frozen-section results, specificity and predictive value for positive results of frozen-section evaluation were 100%. The statuses of individual lymph nodes from these 122 patients were also evaluated. Six hundred twenty lymph nodes were sampled from the mediastinum at mediastinoscopy. Frozen-sections in 47 lymph nodes were positive. Subsequent nodal sections not in the original frozen-sections examination revealed metastatic carcinoma in four additional lymph nodes. The false-negative rate was 0.6%. Sensitivity was 92.2%. Predictive value of negative results from frozen-section evaluation was 99.3%. Because there were no false-positive frozen-section results, specificity and predictive value for positive results of frozen-section examination were 100%. We conclude that frozen-section evaluation of lymph nodes at mediastinoscopy reliably indicates lymph node status, thus enabling the physician to decide whether to proceed to thoracotomy. Thus staging of the carcinoma and definitive surgery can be accomplished during a single anesthetic procedure. Combining mediastinoscopy and thoracotomy with frozen-section diagnostic control also reduces both the length and cost of hospitalization.

Biopsy

Clinical outcome of three discrete histologic patterns of injury in severe lupus glomerulonephritis.

There is a spectrum of glomerular pathology in patients with severe lupus glomerulonephritis (GN) that includes (1) severe segmental GN (SEG) with greater than or equal to 50% of glomeruli involved by active segmental inflammation, (2) diffuse GN, and (3) membranous GN with associated severe SEG or diffuse GN (MGN + PGN). The clinical and laboratory characteristics at entry and at follow-up of 85 patients in a prospective therapeutic trial of plasmapheresis were examined to determine if these morphologic variants had prognostic implications. Addition of plasmapheresis to the therapeutic regimen did not affect outcome, and the two treatment groups were analyzed together. Patients with the three patterns of lupus GN were similar demographically and clinically, and they had similar serum creatinines at entry (SEG, 1.87 +/- 0.28 mg/dL [mean +/- SE], v diffuse GN, 2.11 +/- 0.21, v MGN + PGN, 2.12 +/- 0.26; P = 0.75). Although significant differences were found in the initial serum C3 (SEG, 46 +/- 5 mg/dL, v diffuse GN, 34 +/- 3, v MGN + PGN, 45 +/- 3; P = 0.02) and urinary protein excretion (SEG, 3.6 +/- 0.6 g/24 h, v diffuse GN, 6.0 +/- 0.7, v MGN + PGN, 6.7 +/- 0.9; p = 0.03), none of the clinical or laboratory data predicted the morphologic pattern of the glomerular lesion. Adverse outcomes included defined clinical stop points, nonfatal renal failure, and death. One half of the patients with MGN + PGN (13/26) had an adverse outcome, compared with 5/24 patients with SEG and 11/35 patients with diffuse GN. This trend was supported by actuarial analysis of outcomes showing that patients with MGN + PGN had the lowest cumulative proportion without adverse outcome after 175 weeks of follow-up (MGN + PGN, 0.40, v SEG, 0.77, v diffuse GN, 0.64; P = 0.04). We concluded that (1) at presentation, the specific glomerular lesion in severe lupus GN cannot be predicted on clinical or serological criteria alone; (2) on the basis of morbidity and mortality, cases with all three morphologic variants should be classified as severe lupus GN; and (3) patients with MGN + PGN appear to experience more adverse outcomes than patients with SEG or diffuse GN.

Actuarial Analysis

Diffuse panbronchiolitis preceding ulcerative colitis.

To expand the clinical spectrum of ulcerative colitis-associated lung disease, we describe a patient with panbronchiolitis associated with ulcerative colitis. In addition to his having a distinctive pulmonary manifestation of this bowel disease, other noteworthy aspects of this patient's course include the onset of pulmonary symptoms several years prior to bowel manifestations and the partial resolution of his pulmonary symptoms following colectomy.

Adult

Transbronchial needle aspiration for histology specimens.

Fine-gauge (22-G) transbronchial needle aspiration (TBNA) has significantly added to the diagnostic yield of FOB, and in some institutions has become routine in staging bronchogenic carcinoma. Cytologic examination of the specimen obtained by n228G TBNA, however, has several limitations. The mediastinal aspirate can be contaminated by tumor cells from respiratory secretions, giving false positive diagnoses of unresectability. The diagnosis of benign conditions can seldom be made. Using 18-G TBNA, we can obtain specimens for histologic examination from paratracheal, peribronchial, and carinal areas by FOB. Both 18-G and 22-G TBNA were performed in 34 patients with radiographic abnormalities involving mediastinal or hilar areas. Tissue for histologic examination was obtained in 17 patients (50 percent) using 18-G TBNA and was diagnostic in 11 (32 percent), including three patients with benign conditions. The overall diagnostic yeild of 18-G TBNA was 41 percent (14/34 patients), increasing the yield of FOB from 50 percent to 58 percent. There were no false positive results and few minor complications. 18-G TBNA is effective in obtaining tissue for histologic examination and diagnosing benign conditions. In selected cases this technique increases the diagnostic yield of FOB.

Adenocarcinoma

Atheroembolic renal disease: association with renal arterial stenosis.

In elderly patients with generalized atherosclerosis and longstanding hypertension, progressive renal insufficiency should suggest renal artery occlusive disease and/or renal cholesterol embolization. Renal cholesterol embolization is not an absolute contraindication to successful surgical revascularization. Renal cholesterol emboli were identified in biopsy specimens obtained in 24 cases at the Cleveland Clinic from 1978 to 1986, and renal artery stenosis was an associated finding in 19. Clinical manifestations of generalized atherosclerosis were common, including ileofemoral atherosclerosis (18), coronary artery disease (16), carotid occlusive disease (15), and carotid occlusive disease with a history of stroke (8). Evidence of embolic events in other organs was common. Hypertension worsened before biopsy in 21 patients with and without renal artery stenosis. Surgery or angiography definitely or probably contributed to renal failure in 16. Of 12 who underwent surgical revascularization of a renal artery, renal function improved in five, remained stable in five, and worsened in one. Renal function improved in the three patients undergoing dialysis before revascularization, and two were able to discontinue dialysis.

Aged

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.

Adult

Nephrotic range proteinuria with "minimal change glomerulopathy" in human renal allografts: report of four cases.

Four patients who received renal allografts developed nephrotic range proteinuria 2 to 16 months after renal transplantation. Twenty-four-hour urine protein excretion at the time of renal allograft biopsy ranged from 5.9 to 17.0 g/24 hours. The serum creatinine at the time of renal allograft biopsy ranged from 2.0 to 3.9 mg/dl (180 to 350 mumol/L). Biopsies of the allografts demonstrated minimal glomerular abnormalities by light microscopy, immunomicroscopy, and electron microscopy. Two biopsies exhibited severe interstitial fibrosis. These four cases illustrate the unusual finding of "minimal change glomerulopathy" in renal allograft recipients exhibiting nephrotic range proteinuria. All four patients progressed to dialysis 4, 36, 46, and 53 months after transplantation. Transplant nephrectomy was performed in three patients. One showed acute cortical necrosis. Two showed glomerular, vascular, and tubular-interstitial features of chronic rejection.

Adult

Chronic glomerular microangiopathy complicating metastatic carcinoma.

Six cases of metastatic carcinoma associated with chronic glomerular microangiopathy and renal failure are reported. All had prominent subendothelial lucent zones and double-contoured glomerular basement membranes. There was no immunohistologic or ultrastructural evidence for immune complex entrapment in glomeruli. By immunohistology, material antigenically related to fibrin or fibrinogen was identified in glomerular basement membranes despite a paucity of typical fibrillar fibrin. Four patients received mitomycin C before the onset of renal disease, and one patient received chemotherapy other than mitomycin C before development of renal failure. One patient had no chemotherapy but was given radiotherapy, which did not include the kidneys in the irradiated field. These six cases emphasize the diverse pathophysiologic mechanisms by which glomerular microangiopathy may arise in metastatic carcinoma.

Adenocarcinoma

Pulmonary lymphoid neoplasms. Role of immunohistology in the study of cellular immunotypes and in differential diagnosis.

Seven cases of lymphoid neoplasms presenting in the lung were evaluated by immunohistology for T and B cell antigens and immunoglobulin light chains in frozen tissue sections. Although follow-up was short or inconclusive in some patients with lymphoma and pseudolymphoma, it was concluded that evaluation of T and B cell antigens and immunoglobulin light chains in frozen tissue is helpful in classifying lymphocytic neoplasms, especially in cases without definite cytologic evidence of malignancy. As demonstrated in two additional cases, lymphocyte/leukocyte markers in paraffin-embedded tissue are important in the differential diagnosis of lesions with cytologic features of malignancy.

Adult

Focal and segmental glomerulosclerosis. Immunohistologic study of 20 renal biopsy specimens.

To evaluate the deposition of immunoglobulins and complement and their relationship to sclerotic and nonsclerotic glomerular segments, immunoperoxidase without periodic acid-Schiff counterstain (IMP) and with periodic acid-Schiff counterstain (IMPAS) for IgG, IgA, IgM, and C3 was performed on cryostat-frozen sections using the direct method, along with routine light microscopy and electron microscopy, in a series of 20 renal biopsy specimens from 20 patients with the final diagnosis of focal and segmental glomerulosclerosis. Neither diffuse mesangial nor diffuse glomerular basement membrane deposits were detected by IMP, IMPAS, or electron microscopy. In 18 biopsy specimens, IMPAS demonstrated focal and segmental granular to globular deposits of IgM and/or C3 in sclerotic glomerular segments. In eight biopsy specimens, small granular deposits of IgM and/or C3 deposits were identified in optically normal glomeruli, suggesting that these deposits may precede segmental sclerosis.

Adolescent