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Biomedical subjects

D W McCloskey

Publications and source records attributed to D W McCloskey.

11 recordsLinked to original sources

Immunophenotyping of cytologic specimens by flow cytometry.

Immunophenotyping by flow cytometry is well established as an ancillary technique in the diagnosis of hematopoietic neoplasms. However, flow cytometry is rarely performed on cytologic specimens because most cytologist are more comfortable with direct microscopy and believe that there is inadequate cellularity for analysis. Paradoxically, cytologic material is usually cell suspensions making it ideal for flow cytometry. In order to evaluate the usefulness of immunophenotyping cytologic specimens by flow cytometry, we retrospectively reviewed all cytologic specimens submitted to our flow cytometry unit from 1988 to 1991. Thirty-one cerebrospinal fluid specimens were analyzed. There were inadequate cells for analysis in 15 cases. Five showed a monoclonal proliferation; 11 were nondiagnostic. A range (r) of one to six cell surface markers were performed. Thirty-two body cavity fluids were analyzed: 7 peritoneal, 19 pleural, 2 pericardial, and 4 bronchoalveolar lavage. There were cells to analyze in all cases. Seven had a monoclonal proliferation; 25 were nondiagnostic (r = 4-21 markers performed). One hundred eighteen fine needle aspirates (FNA) were reviewed; 58 FNA were radiologically guided, 60 were superficial lesions. There were inadequate cells for analysis in two cases. Sixty-one demonstrated a monoclonal proliferation; 55 were nondiagnostic (r = 1-22 markers performed). We conclude that immunophenotyping by flow cytometry is of limited value for cerebrospinal fluid analysis and that knowledge of previous immunophenotyping studies is essential for correct analysis; analysis of body cavity fluids is easily performed but less often demonstrates a monoclonal proliferation. Immunophenotyping by flow cytometry is a valuable adjunctive technique for FNA and yields adequate cells for analysis.

Antigens, Surface↗

Diagnosis of metastatic thymoma using flow cytometry.

Thymomas are cytologically benign epithelial neoplasms of the thymus gland. They compose 10% of mediastinal tumors, and are most common in the anterosuperior compartment. Seven to 36% of thymomas are malignant, as determined by tissue invasion, yet they metastasize in less than 3% of cases. Distinguishing lymphoma from lymphocyte-predominant thymoma is imprecise due to their histologic similarities. We present a 45-year-old man with intracranial metastatic thymoma. The lesion was interpreted radiographically as meningioma, and as possible lymphoma by frozen section. Flow cytometry proved this neoplasma to be a metastatic thymoma. Sixteen monoclonal antibodies were used to immunophenotype the CD45+ component of this tumor. Coexpression of CD4 and CD8 along with CD1 demonstrated lymphocytes of late cortical thymocyte origin; a second component was cytokeratin positive. This is the first reported case of extrathoracic metastases of thymoma diagnosed using flow cytometry. We propose this method as an invaluable technique to diagnose these histologically difficult neoplasms.

Aneuploidy↗

Processing surgically removed lymph nodes.

Delicate lymph nodal tissue must be processed accurately and evaluated for proper patient management. In more than 125 cases at Methodist Hospital of Indiana, we devised a procedure that has allowed accurate diagnosis in 98% of cases. The pathologist's approach and the variety of studies necessary to confirm the diagnosis are presented, as well as important procedural considerations.

Diagnosis↗

Immunologic monitoring of the cardiac transplant patient.

Peripheral blood lymphocyte morphology and cell surface markers were repeatedly evaluated in 49 orthotopic cardiac transplant patients over a period of three years to determine the utility of these parameters in predicting an episode of acute cardiac rejection. Lymphocytes were measured with a calibrated microscope and termed "activated" if greater than 10 mu in diameter. If a patient demonstrated greater than 30 activated lymphocytes/cu mm, the same lymphocytes were stained with monoclonal antibodies directed to T-cell subsets and B cells. These findings were retrospectively correlated with endomyocardial biopsy results. Absolute numbers of T-cell subsets and B cells were analyzed via Student's t test to identify significant differences during acute cardiac rejection. Of 347 biopsy specimens, 47 demonstrated histologic features of acute cardiac rejection. Simultaneous immune activation of lymphocytes occurred with 33 of 47 samples, while another 51 episodes of lymphocyte activation were detected without acute rejection. No statistically significant differences in absolute numbers of T-lymphocyte subsets were noted at the time of acute rejection.

Acute Disease↗

Endoscopic argon laser photocoagulation of small sessile colonic polyps.

The availability of flexible quartz wave ¿uides allowing introduction of argon laser energy through endoscopes suggests the possibility of ablation of colonic mucosal lesions by this technique. To ascertain the effects of the argon laser on the colon, penetration depth and perforation studies were conducted in dogs. At 250 joules/cm2 energy density, less than 50% muscularis externa injury was noted in 29 of 42 lesions. No perforation was noted. Healing was complete in 8 days. The time required for deliberate perforation with the catheter firmly pressed against the wall of a distended inflated colon using 2 W argon laser applied continuously was 41 +/- 13 sec, N = 53. In a human study of 15 small sessile polyps ablated by laser and the colon examined 4 days later at colectomy, no penetration of the laser beneath the submucosa was noted. In 11 patients with Gardner's syndrome 211 polyps have been removed in 18 treatments without complication. These encouraging results suggest the continued study of this endoscopic modality in the treatment of mucosal lesions of the colon.

Animals↗

A comparison of the He Ne laser and ultrasound Doppler systems in the determination of viability of ischemic canine intestine.

One of the most challenging intraoperative dilemmas continues to be determination of viability of ischemic bowel. Many techniques and devices are available to help the surgeon, probably the most useful of which is the ultrasound Doppler. A more recently developed system, the laser Doppler, has a flexible optical fiber and fine tip probe that can be approximated onto or endoscopically passed into the gastrointestinal tract. This study was undertaken to experimentally compare the He Ne laser and ultrasound Doppler systems in predicting viability of ischemic canine intestine. Twenty ischemic bowel zones were created in dogs by division of the mesenteric blood supply. Determination of the last site of antimesenteric serosal nor fusion was then marked with each Doppler. Additionally, the fine tip probe was endoscopically passed across the ischemic zone and mucosal perfusion determined. Thus, each zone was marked three times, each indicating the anticipated site of necrosis by each method. The animals were killed 24 hours later and the tissues studied histologically. The results demonstrated that both the serosally applied and endoscopically placed laser Doppler were closer to predicting the point of total transmural necrosis. The possible clinical advantage of this device in prevention of short gun syndromes is readily apparent. The additional asset of a flexible optical fiber than can be endoscopically or laparoscopically passed make it an even more attractive modality. The findings of this study attested to the superior sensitivity, ease of use, and objectivity of the laser Doppler when compared with the ultrasound system.

Animals↗

Hodgkin disease as the terminal malignancy in Richter syndrome.

A case of Richter syndrome in which autopsy revealed typical infiltrates of Hodgkin disease, including Reed-Sternberg cells, is reported. Previous reports of this association have met with skepticism. Clinical findings in patients with Hodgkin infiltrates do not differ from those with histiocytic lymphoma, except for the more frequent occurrence of a declining lymphocyte count. The present case is further evidence that Hodgkin disease does occur as a terminal malignancy in Richter syndrome.

Autopsy↗

Neodymium-yag laser treatment of experimental canine gastric bleeding. Acute and chronic studies of photocoagulation, penetration, and perforation.

Determination of the efficacy and safety of endoscopic laser photocoagulation to control upper gastrointestinal bleeding is prerequisite to the general application of this treatment in humans. We studied photocoagulation hemostasis, penetration, and perforation produced by a 55-W neodymium-yag (Nd:YAG) laser to control standardized experimental gastric bleeding lesions in a heparinized canine model. Photocoagulation of bleeding lesions was 100% successful with an application time of 3.56 +/- 1.65 sec (mean +/- SD). Histologic examintion of the gastric wall revealed a depth of injury to the muscularis externa of 40-100% with greater than 2 sec photocoagulation. Continuous photocoagulation exceeding 4 sec produced an 80-100% depth of muscle injury. Perforation of the gastric wall occurred after 9.6 +/- 1.5 sec, and all dogs studied after perforation survived. These studies indicate that Nd:YAG photocoagulation is an effective method to control experimental gastric bleeding lesions with a ratio between mean photocoagulation hemostasis and perforation times of approximatley 1:3. Further studies are required to define the implications of photocoagulation injury to muscle and the role of the gastric serosa in laser applications.

Animals↗

Cell proliferation in esophageal columnar epithelium (Barrett's esophagus).

In order to correlate histopathology and cell turnover in esophageal tissue in patients with esophageal columnar epithelium, biopsy specimens from 11 patients were studied. Two of the patients had adenocarcinoma of the esophagus not present in the specimens studied. In the heterogeneous esophageal columnar epithelium, the DNA synthesis phase averaged 10.4 +/- 0.3 hr; labeling index of cells in the crypt-like structures was 23.3 +/- 0.3%; generation time was 44.6 +/- 1.2 hr, and the mitotic index was 1.82 +/- 0.07%. Significant differences were not present among specimens with columnar epithelium but they differed from cell proliferation in adjacent squamous epithelium where S phase was similar but labeling and mitotic indexes were lower and generation time increased to 105 +/- 6 hr. In the 2 patients with adenocarcinoma of the esophagus, and in 1 of 9 without adenocarcinoma, labeling of surface columnar cells after brief exposure to [3H]thymidine was present suggests that this may be a manifestation of early malignant change.

Adenocarcinoma↗

Pneumonia in the neonate associated with group B streptococcal septicemia.

Fifteen newborns referred to the University of Utah Neonatal Intensive Care Unit (NICU) between 1971 and 1974 had septicemia and bronchopneumonia caused by streptococci of Lancefield group B. Eight of these infants could not be distinguished from others with idiopathic respiratory distress syndrome. All eight died and at autopsy were found to have bronchopneumonia. At autopsy, five of the ten subjects had bilateral pleural effusions. Eight of these early onset infections were caused by type III strains, three by type II strains, and four by Ia strains. The three survivors were infected by Ia organisms; two of these patients received antimicrobial therapy within one hour of birth and the other was treated at 20 hours of age. Among the 12 patients who died, six received no antibiotics and five were treated 12 or more hours after delivery. Earlier recognition may lead to more efficacious therapy of this most fulminant infection of the newborn.

Bronchopneumonia↗

Hodgkin's disease variant of Richter's syndrome. Report of a case with diagnosis by fine needle biopsy.

BACKGROUND: Chronic lymphocytic leukemia (CLL) with transformation into large cell lymphoma (Richter's syndrome) is a well-documented phenomenon. Only rarely does CLL terminate in Hodgkin's disease (HD) as Richter's syndrome. Reports of Hodgkin's variant of Richter's syndrome proven by histologic and immunohistologic evaluation have been published, but no cytologic reports of this entity exist. Distinguishing between large cell lymphoma and HD as variants of Richter's syndrome is essential because of recent reports of improved prognosis in HD. CASE: We report a case of a 65-year-old male previously diagnosed with CLL who subsequently developed fever, fatigue, an intraabdominal mass and enlarged periaortic lymph nodes. Fine needle biopsy (FNB) and immunophenotyping by flow cytometry of the mass revealed cytologic and immunophenotypical cells of CLL admixed with binucleate and multinucleate cells with prominant eosinophilic nucleoli consistent with Reed-Sternberg cells. CONCLUSION: This is the first reported case of HD variant of Richter's syndrome diagnosed by FNB. As FNB becomes more common in the follow-up of lymphoreticular diseases, cytologists should be aware of this unusual HD variant of Richter's syndrome.

Aged↗