Urine cytologic monitoring for rejection after vascularized pancreas transplantation.
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Biomedical subjects
Publications and source records attributed to J Linder.
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Technologies emerging and evolving in the 1990s, particularly in molecular biology, therapeutics, computerization, and information management, will alter the type of work and work load of the pathologist. In general, new technologies will increase the work load of pathologists. However, the extent to which new medical technologies affect pathology will be modulated by socioeconomic factors, given the relationship between new technology and increased medical costs. Pathologists may choose to embrace many new technologies and should play an active role in technology assessment to ensure the appropriate use of new diagnostic procedures.
A comprehensive panel of monoclonal antibodies that mark R-S/H cell, T- and B-cell, monocyte/histocyte was tested in paraffin sections of 107 cases of Hodgkin's disease (HD) including 21 cases of lymphocyte predominance (LP) and 86 cases of Non-LP HD. Thirty cases each of peripheral T-cell lymphoma and B-cell lymphoma were also tested for comparison. R-S/H cells were not stained with T-cell marker (UCHL-1) or monocyte/histocyte marker (Mac387) in all of these cases of HD. The results showed presence of certain difference in the phenotype of LP from non-LP. The H+L type of R-S/H cells of LP often reacted with B-cell markers including L26, LN2, LN1 and MB2 (93.3%-100%), LCA (83.3%) and EMA (92.3%), but rarely with LeuM1,T mü 9, or BerH2. On the contrary, most of the R-S/H cells of non-LP reacted with LeuM1 (80%), T mu 9(84%), BerH2(65%) but not with B-cell markers, LCA or EMA. Our study suggests a B-cell (probably the follicular center cell) derivation for L+H type of R-S/H cells in LP. The fact that 1 case of LP in this group transformed to a large cell B-cell lymphoma also supports this consideration. PNA is a sensitive marker of R-S/H cells but is not a specific one, since PNA stains 43.3% of the peripheral T-cell lymphoma and 20% of the B-cell lymphomas. Our findings indicate that using a panel of antibodies which mark R-S/H cells, T- and B-cells in paraffin sections will be helpful in the diagnosis and subtyping of Hodgkin's disease.
Prenatally acquired cytomegalovirus infection in twins was temporally associated with a discordant development of neonatal hepatitis and extrahepatic biliary atresia. This case presents evidence suggesting an association between perinatal cytomegalovirus infection and selected extrahepatic biliary atresia and neonatal hepatitis. Congenital cytomegalovirus infections and cytomegalovirus hepatitis are also discussed.
Using an antibody to the nerve growth factor receptor (NGFR), we examined dendritic reticulum cells (DRCs) immunohistochemically in 62 formalin-fixed, paraffin-embedded lymph nodes from patients with reactive follicular hyperplasia or with various types of lymphoma. A dendritic staining pattern within germinal centers was present in 25 of 26 routinely processed lymph nodes with reactive follicular hyperplasia. In contrast, dendritic staining with anti-NGFR was present within neoplastic follicles in only three of 28 follicular lymphomas. Staining of benign, residual germinal centers with anti-NGFR was present in mantle zone lymphoma and Hodgkin's disease. These findings suggest a possible role for the NGFR in the maturation and/or activation of normal DRCs. The loss of NGFR expression in most follicular lymphomas indicates that DRCs are altered as part of the neoplastic process. The possibility that DRCs may play a role in the pathogenesis of follicular lymphoma is suggested.
Results are reported of a blind rediagnosis of a consecutive series of parent-child pairs hospitalized with a diagnosis of schizophrenia or mood disorder. Patterns of illness in pairs meeting DSM-III-R criteria for either disorder were examined by contrasting the two generations on their respective distributions of diagnoses, and means of age at onset and severity of illness. While no case of mood disorder was found in the children of schizophrenic parents, 50% of the children of parents with psychotic mood disorders presented with schizophrenia. The offspring also had an earlier age at onset of illness than did their parents.
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To evaluate the possibility that bronchoalveolar lavage could provide sufficient respiratory epithelial cells to quantify changes in epithelial cell types associated with chronic inflammation, we examined the epithelial cells obtained in the first infused (20 ml) aliquots that were processed separately from later aliquots, a process known to enrich for bronchial contents. Epithelial cells, including ciliated cells, goblet cells, and fragments of desquamated epithelium, were easily identified after preparation by cytocentrifugation and staining with a modified Giemsa stain. Quantification of the columnar cell types revealed that those with chronic bronchitis and asymptomatic smokers have increased goblet cells as a percentage of the total columnar epithelial cells (chronic bronchitics 36 +/- 2 percent, asymptomatic smokers 22 +/- 2 percent) compared with normal subjects (9 +/- 1 percent, p less than 0.001, ANOVA). Significantly, the goblet cell percentage was strongly correlated with other measures of bronchitis and measures of airflow obstruction such as the bronchitis index, a visually derived score at bronchoscopy of airway inflammation (r = 0.72, p less than 0.001), the percent neutrophils in the first infused aliquots (r = 0.44, p less than 0.05), and the FEV1 percent (r = -0.74, p less than 0.001). Thus, bronchoalveolar lavage is capable of providing sufficient bronchial epithelial cells for analysis, and the changes seen in the spectrum of columnar epithelial cells may reflect important underlying pathologic changes.
Pulmonary failure is a major contributor to morbidity and mortality during marrow aplasia following high-dose antineoplastic therapy. For this reason, we initiated a pulmonary surveillance program for patients undergoing high-dose chemotherapy for leukemia or bone marrow transplantation. As part of this program, bronchoscopy with BAL was performed prior to therapy and at the onset of granulocytopenia. Thirty-three of the first 57 patients managed in this program developed some evidence of pulmonary complications. Twelve patients died in aplasia; all had pulmonary failure. Forty patients had clinically significant abnormalities on the bronchoscopy before treatment including 12 of 19 patients who had normal findings on chest x-ray films, physical examination, and pulmonary function testing, and no fever. Twenty-seven patients had clinically significant abnormal bronchoscopy or BAL at the onset of granulocytopenia. Thirteen patients required additional bronchoscopy. No patient required an open lung biopsy. Pulmonary surveillance using bronchoscopy with BAL is useful in the detection of pulmonary disease prior to the initiation of and following high-dose antineoplastic therapy.
Diffuse alveolar hemorrhage is a life-threatening complication after bone marrow transplantation. We investigated the radiographic abnormalities that occurred in 39 transplantation patients with a diagnosis of diffuse alveolar hemorrhage and correlated the findings with the patients' clinical course. The initial radiographic abnormalities after diffuse alveolar hemorrhage developed an average of 11 days after bone marrow transplantation, and the radiographic abnormalities preceded the clinical diagnosis by an average of 3 days. Twenty-seven patients initially had bilateral radiographic abnormalities; 10 initially had unilateral abnormalities (seven in the right lung, three in the left lung). Two patients had normal chest radiographs throughout their clinical course. All 37 patients with radiographic abnormalities had abnormalities involving the central portion of the lung, primarily the middle and lower lung zones. The initial radiographic pattern was interstitial in 27 and alveolar in 10. In 24 patients, radiographic abnormalities were initially judged to be mild; three were severe from the onset. Radiographic abnormalities rapidly worsened in most patients over 6 days. In 30 patients, diffuse bilateral radiographic abnormalities involving all lung zones developed. Eleven patients persisted in having only interstitial radiographic abnormalities; 26 had a confluent alveolar pattern. At the height of radiographic abnormalities, 27 cases were judged to be severe, and only one case was judged to be mild. The mortality rate in patients with diffuse alveolar hemorrhage was 77%. The radiographic abnormalities of diffuse alveolar hemorrhage are nonspecific and usually precede the clinical diagnosis. The clinical course after hemorrhage is short, often resulting in death.
Cytomegalovirus (CMV) is a common cause of lower respiratory tract infections in immunocompromised individuals. Bronchoalveolar lavage (BAL) is a noninvasive means to procure large numbers of bronchial and alveolar cells from the lung. To assess various methods of detecting CMV in the lavage specimen, 26 BAL specimens from 16 patients at high risk for CMV infection were evaluated. The methods and time required for analysis were the following: cytologic examination of Papanicolaou-stained membrane filters (1 h); viral cytopathic effects in tissue culture (days to weeks); spin amplification followed by staining with a monoclonal antibody for detection of CMV early nuclear antigen (18 h); and in situ hybridization (IH) with a biotinylated complementary DNA (cDNA) CMV probe (5 h). CMV was detected in 11 of 26 (42%) specimens by the early antigen assay, ten of 26 (38%) by in situ hybridization, five of 26 (19%) by tissue culture, and three of 26 (12%) by routine cytology. The absence of diagnostic CMV nuclear and/or cytoplasmic inclusions in many specimens positive by in situ hybridization and/or early antigen detection assay may be in part due to low levels of viral replication, insufficient for the development of diagnostic inclusions. These data show that techniques using in situ hybridization or fluorescent anti-CMV antibodies are rapid and are more sensitive for CMV identification than both cytomorphological examination and traditional tissue culture methods. Additional studies are required to determine the clinical significance of early CMV detection by in situ hybridization and early nuclear antigen detection assays.
Iron, by catalyzing the generation of the hydroxyl radical via the Haber-Weiss reaction, may participate in oxidant tissue injury. To determine whether iron might contribute to cigarette smoke-induced lung injury, we estimated the iron content of the lower respiratory tract by measuring intracellular iron content of pulmonary macrophages and extracellular iron content of bronchoalveolar lavage fluid from cigarette smokers and nonsmokers. Bronchoalveolar lavage was performed by using methods that allow for recovery of samples enriched for bronchial and alveolar contents. The intracellular iron content of the alveolar macrophages was determined by staining cytocentrifuged, air-dried pulmonary macrophages with a modified Prussian blue stain and assigning a score of 0 to 3 (0 = no stain, 3 = dense staining throughout the cytoplasm) to 100 macrophages. The extracellular iron level of bronchoalveolar lavage fluid was determined by using modifications of the Ferrozine method of Carter. Macrophage intracellular iron content was measured in a group of cigarette smokers with chronic bronchitis (n = 17), in smokers without chronic bronchitis (n = 15), and in normal volunteers (n = 15). Extracellular iron concentration was determined in a subset of the subjects with chronic bronchitis (n = 12) and in a separate group of normal volunteers (n = 5). The intracellular iron score was elevated in the bronchial sample lavage fluid in both the smokers with chronic bronchitis (45.3 +/- 13.9) and the asymptomatic smokers (26.6 +/- 8.0) compared with the normal individuals (8.1 +/- 1.7, p less than 0.03, both comparisons), but did not differ between the two groups of cigarette-smoking subjects (p = 0.68).(ABSTRACT TRUNCATED AT 250 WORDS)
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A clinicopathologic analysis of 22 cases of mantle zone lymphoma (MZL) was performed. In lymph node sections, MZL was characterized by the proliferation of neoplastic small lymphoid cells in wide mantles around benign germinal centers. Eighteen cases were of the intermediate lymphocytic type and four cases were of the small lymphocytic type. Immunohistologic analysis of paraffin sections revealed the following characteristic immunophenotype of MZL: L26, LN2, NUB1 and T2/48 positive, and LN5, LN1, AF6 and UCHL1 negative. The immunophenotype of MZL was identical to that of normal primary lymphoid follicles and the mantle zones of secondary follicles, except for the absence of staining with LN5 in MZL. The median age of the patients was 63 years, and the male-to-female ratio was 1.2:1. B symptoms were present in 55% of the patients, and 81% had splenomegaly. An absolute lymphocytosis was present at the time of initial diagnosis in 13% of the patients, and 67% had bone marrow involvement by lymphoma. Thirteen percent of the patients had Stage II disease, 23% had Stage III disease, and 64% had Stage IV disease. All 22 patients received some form of therapy, with 73% receiving multiagent chemotherapy. Eleven patients achieved a complete remission at some time during their course. The overall median survival of the entire group was 88 months. Clinical features which appeared to influence survival adversely included an absolute lymphocyte count above 4000/microliters, a platelet count less than 100,000/microliters, and male sex. Achievement of a complete remission at any time favorably influenced survival. Pathologic features which appeared to influence survival adversely were a mitotic rate of 10 or more per 10 high-power fields (HPF) and the presence of 40 or more large lymphoid cells per 10 HPF. These findings lead the authors to conclude that MZL is a distinctive form of low-grade non-Hodgkin's lymphoma.
Advanced T-cell non-Hodgkin's lymphoma in adults has been found to have a poor outlook with conventional chemotherapy. To see if this extends to patients treated with high dose therapy and autologous hematopoietic stem cell transplantation, we reviewed the results with this treatment approach at our institution. From October, 1983, to May, 1988, 41 patients who underwent high-dose therapy and autologous hematopoietic stem cell transplant for recurrent non-Hodgkin's lymphoma were re-biopsied before transplantation to determine their immunophenotype. Seventeen of these patients were found to have a T-cell lymphoma, and 24 had a B-cell lymphoma. All patients were included in the intermediate or high grade non-Hodgkin's lymphoma categories, and none were histologically transformed from a low grade lymphoma. Analysis of the response to autologous transplantation in these two patient populations revealed a slightly better complete response rate for patients with T-cell lymphoma (ie, 59% versus 42%, P = NS). The actuarial 2-year survival was 35% in the T-cell group compared with 30% in the B-cell group (P = NS). The 2-year disease-free survival was 28% for the T-cell and 17% for the B-cell patients. Our results with autologous transplantation for salvage therapy revealed equivalent long-term survival and disease-free survival in both relapsed T- and B-cell non-Hodgkin's lymphoma.
Bronchoalveolar lavage has been widely used to sample the lower respiratory tract. Most of the material recovered with this technique represents alveolar contents. A number of modifications have been suggested in order to obtain samples relatively enriched for bronchial material. In order to be able to use a standard technique for bronchoalveolar lavage to sample both airways and "routine" alveolar material, a simple modification of the technique as described by Reynolds and Newball was used: five sequential 20-ml aliquots were infused into the lower respiratory tract, and each aliquot was immediately aspirated. The return from the first aliquot was processed separately from the return from the subsequent four aliquots. These last four aliquots were pooled. Analysis of the first aliquot revealed it to be enriched for ciliated epithelial cells when compared with the subsequent aliquots. There were also differences in inflammatory cell composition with the bronchial sample containing relatively more neutrophils and relatively less lymphocytes. Aspiration during transoral bronchoscopy was documented by quantifying salivary amylase in the bronchial and alveolar lavage fluids. It was estimated, however, that the aspiration was not of quantitative significance in the vast majority of subjects studied. Finally, with the technique of fractional processing of bronchoalveolar lavage samples, it was possible to compare the protein concentrations in bronchial and alveolar lavages. Most prominent among the differences was a marked relative enrichment in the bronchial samples for immunoglobulin A. The technique of fractional processing of bronchoalveolar lavage samples provides a simple means to obtain samples enriched for bronchial and alveolar components. This should facilitate analysis of lower respiratory tract specimens in airway disease.
Bronchial mucosal injury initiates a complex series of repair mechanisms, one of which is reepithelialization of a denuded lumenal surface. This suggests the hypothesis that bronchial epithelial cells, the cells initially affected by bronchial injury, might be able to initiate repair of an injured area by producing a chemotactic activity for intact bronchial epithelial cells. To evaluate this, bronchial epithelial cells were prepared from bovine lung by protease digestion and cultured in medium 199 (M199) with 10% fetal calf serum (FCS) until confluence, after which the cells were rinsed with Hanks' balanced salt solution, and serum-free fresh M199 was added. This conditioned medium was then collected and used to test the chemotactic response of bronchial epithelial cells using a blindwell chamber technique. Target cells for this assay were isolated from airways by protease digestion, grown to confluence in M199 with 10% FCS, and then harvested with trypsin. Bronchial epithelial cell-conditioned medium harvested after 3 days attracted more cells (197.0 +/- 5.7 cells/10 high power fields) than did M199 without FCS alone (4.3 +/- 0.9) (p less than 0.01). Checkerboard analysis showed that the migration was chemotactic. The chemotactic activity was nondialyzable, pepsin-labile, acid-stable, heat-labile, and lipid-inextractable. The chemotactic activity accumulated in the culture medium with time. The addition of 25 micrograms/ml of cycloheximide inhibited this accumulation. Column chromatography with Sephadex G-150 revealed a single peak of chemotactic activity in the high molecular weight range. The chemotactic activity was bound to gelatin-Sepharose 4B and was eluted with 6 M urea.(ABSTRACT TRUNCATED AT 250 WORDS)