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Biomedical subjects

F Clayton

Publications and source records attributed to F Clayton.

At least 37 records · Page 2Linked to original sources

Refractile mycobacteria in Romanowsky-stained bone marrow smears. A comparison of acid-fast-stained tissue sections and Romanowsky-stained smears.

The appearance of mycobacteria was studied in Wright-stained bone marrow preparations of human immunodeficiency virus-infected patients and compared with acid-fast-stained trephine biopsy sections and culture results. Mycobacterium avium complex in Romanowsky-stained preparations may be seen as extracellular and intracellular clear or red refractile beaded rods and nonrefractile "negative images." Refractile mycobacteria were seen in 17 of 20 culture-positive cases. Acid-fast stain of the trephine biopsy demonstrated organisms in only 11 of the 20 cases. Thus, six cases were culture positive and contained refractile rods but had no acid-fast organisms on the trephine biopsy. No false-positive results were seen with Romanowsky stain; the three false-negative results for refractility also were negative with acid-fast stain. Examination of Romanowsky-stained smears or imprints for refractile mycobacteria provides a reliable and sensitive method to identify mycobacteria in this population. Romanowsky-stained bone marrow aspirate and imprint smears should be examined for refractile bacilli when mycobacterial infection is suspected.

Acquired Immunodeficiency Syndrome↗

Pathologic correlates of survival in 378 lymph node-negative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor.

Pathologic features of 378 breast carcinomas without axillary lymph node metastases were correlated with long-term prognosis. Mitotic count, the feature best predicting prognosis, was most useful at lower mitotic count levels than usually studied. Cases with less than 4.5 mitotic figures per ten high-power fields had a 20-year tumor-related survival of 73% versus 48% for those with higher mitotic counts. Low and high mitotic count groups had significantly different prognoses for T1c, T2, and T3 tumors. Multivariate analysis showed that the best combination of features predicting tumor-related death were high mitotic count (relative risk, x 2.8), large tumor size (relative risk, x 1.7), lymphatic invasion (relative risk, x 1.7), and skin or subjacent muscle or chest wall invasion (relative risk, x 2.5). Nuclear grade, Bloom-Richardson grade, modified Scarff-Bloom-Richardson grade, Fisher's grade, and necrosis correlated well with survival but had no significant additional predictive value when adjusted for the mitotic count.

Breast Neoplasms↗

Small intestinal injury and parasitic diseases in AIDS.

OBJECTIVES: To examine jejunal biopsies from patients with the acquired immunodeficiency syndrome (AIDS), chronic diarrhea, and weight loss, and to correlate the presence of small intestinal injury with pathogens, histopathologic changes, and absorption. DESIGN: Prospective analysis of jejunal biopsies from 43 patients with AIDS, 10 patients with AIDS-related complex, and 6 heterosexual control volunteers. The biopsies were examined for pathogens; electron microscopy was used in 22 patients. The results of quantitative histologic measurements were correlated with histopathologic features and D-xylose absorption. SETTING: A university-affiliated teaching hospital with many AIDS patients of varying demographic characteristics. MEASUREMENTS AND MAIN RESULTS: Jejunal biopsies in 62% of the patients with AIDS had partial villus atrophy with or without crypt hyperplasia unlike those of controls, a result implying small intestinal injury. Small intestinal injury was associated with lymphoplasmacytic infiltration and cytopathic change of the villus epithelium. Light and electron microscopic examination detected cryptosporidia or microsporidia in 19 of 27 patients with small intestinal injury. The presence of these parasites was associated with significantly diminished D-xylose absorption when compared with absorption in controls or in patients with AIDS, diarrhea, weight loss, and no parasites. CONCLUSION: A significant proportion of patients with AIDS with severe small intestinal injury have enterocyte infections. Like cryptosporidiosis, intestinal microsporidiosis may be an important cause of enteropathy in patients with AIDS.

AIDS-Related Complex↗

Correlation of in situ hybridization with histology and viral culture in patients with acquired immunodeficiency syndrome with cytomegalovirus colitis.

Endoscopic colonic biopsy specimens from 34 patients with acquired immunodeficiency syndrome and six patients without acquired immunodeficiency syndrome (3 were human immunodeficiency virus-seropositive and 3 were human immunodeficiency virus-seronegative) were examined by in situ hybridization for evidence of cytomegalovirus colitis and the results were compared with histologic examinations and viral cultures. In situ hybridization was positive in 22 of 25 patients with acquired immunodeficiency syndrome with histologic evidence of cytomegalovirus colitis. By our interpretation, 15 patients without cytomegalovirus colitis histologically all had negative hybridization studies. No correlation was found between in situ hybridization and viral culture results. In situ hybridization is a useful confirmatory test when the histologic changes are suspicious for cytomegalovirus but not considered diagnostic; it will only rarely demonstrate staining in a case considered negative histologically.

Acquired Immunodeficiency Syndrome↗

Non-Hodgkin's lymphoma in bone. Pathologic and radiologic features with clinical correlates.

Thirty-seven lymphomas of bone were studied, including 33 diffuse large cell lymphomas, three undifferentiated (small noncleaved cell) lymphomas, and one well-differentiated (small) lymphocytic lymphoma. The large cell lymphomas were subclassified as large cleaved, large noncleaved, multilobated cell, and immunoblastic sarcoma (large cell lymphoma, immunoblastic type). Eleven of 26 large cell lymphoma patients with adequate follow-up were long-term survivors (free of disease for more than 5 years). Nineteen of the 33 large cell lymphomas were localized to one bone. The stage and histologic pattern significantly correlated with long-term survival among large cell lymphomas. Seventy-three percent of patients with localized lymphoma were long-term survivors, in contrast to 9% of those with disseminated disease. Sixty-seven percent of patients with large cleaved and multilobated cell lymphoma were long-term survivors, but only 21% of those with large noncleaved cell and immunoblastic sarcoma were. The tumors had a blastic, lytic, or mixed radiographic appearance and had either sclerotic, lytic, or permeative borders; none of the radiologic findings were diagnostically useful.

Adolescent↗

Human alpha-fetoprotein and albumin: differences in zinc binding.

The binding of zinc to both human alpha-fetoprotein (AFP) and albumin isolated from cord serum was studied by Sephadex G-50 gel-filtration chromatography. We found that the total number of binding sites for zinc on AFP and albumin were approximately 16 and 12, respectively. Both graphical analysis and the computer program 'LIGAND' indicate that there are at least two major classes of binding sites for both proteins. Both methods of analysis suggested that there are four to five high-affinity sites for zinc on AFP and only two to three similar sites on albumin. The affinity of zinc for AFP (dissociation constant, Kd, 6-8 X 10(-6) mol/l) was higher than for albumin (Kd, 1-3 X 10(-5) mol/l) for the high-affinity sites. The estimates for the zinc low-affinity binding sites were more uncertain, and several classes of low-affinity binding sites of different affinities might be present in both proteins. The results of our inhibition studies suggest that calcium, copper and lead might also bind with AFP at the zinc-binding sites.

Binding Sites↗

Bronchioloalveolar carcinomas. Cell types, patterns of growth, and prognostic correlates.

Forty-five bronchioloalveolar carcinomas were studied, including 27 cases by electron microscopy. Bronchioloalveolar carcinomas can be classified by routine sections or by diastase-digested periodic acid-Schiff (PAS) stains, but electron microscopy is useful in confirming Clara cell or type II pneumocyte (nonmucinous) differentiation and excluding metastases. Mucinous bronchioloalveolar carcinoma can mimic metastatic adenocarcinoma histologically and ultrastructurally. Of the nine tumors with mucinous differentiation, eight had aerogenous dissemination (multifocal or with pneumonic spread), and seven of those eight were fatal. Twenty-four of 36 nonmucinous bronchioloalveolar tumors had aerogenous spread; all of the 24 patients died or were living with distant metastases. The 12 nonmucinous tumors without aerogenous dissemination had a 5-year survival rate of 61%. Among these, the smaller tumors had a better prognosis. The presence of alveolar spread, rather than cell type, was the most important feature predicting survival.

Actuarial Analysis↗

Analysis of microvascular changes in frostbite injury.

Reported here is the characterization of the hairless mouse ear as a model system for defining the microvascular effects of minimal frostbite injury by means of gross, in vivo microscopic, histologic, and electron microscopic analysis. Initial efforts, using controlled temperatures and time of freezing, defined the minimum conditions necessary to produce consistent tissue necrosis to be -4 degrees C for 3 min. In vivo observation, after rapid thaw, showed a return of blood flow to apparent normal prefreeze rates, followed by a gradual sludging of blood 15 to 20 min post-thaw and eventually in cessation of blood flow. No vascular spasm was observed. Histologic and electron microscopic examination, unexpectedly, did not reveal evidence of early platelet or fibrin thrombi. However, marked vasodilatation and circulatory congestion began 2-3 hr after thawing. Subsequently, prominent discontinuities between damaged endothelial cells and breaks in the microvascular basement membranes were found at the light and ultrastructural level. Interstitial edema and extravasated erythrocytes occurred shortly thereafter, preceding gross tissue necrosis evident at post-freeze Day 3. We conclude that in this animal system thrombus formation is not an initial event, but rather that vascular injury in the form of endothelial cell damage predominates in early frostbite injury.

Animals↗

Pure mucinous carcinomas of breast: morphologic features and prognostic correlates.

Fifty-three pure mucinous carcinomas of breast were studied, with long-term follow-up evaluation (average, 15 years) for 37. The mean age of the patients was 63 years. Long-term survival (Kaplan-Meier method) was 68 per cent, excluding non-tumor-related deaths. Median survival for the patients with fatal carcinomas was 11.3 years. Fatal and disseminated carcinomas were best predicted by the presence of axillary metastases and by tumor cellularity and size. Only five of the patients had axillary metastases at mastectomy, but in four of these five patients distant metastases developed later. The diameters of all ten of the fatal and disseminated carcinomas were at least 2.5 cm, while 17 of the 27 long-term survivors had smaller tumors. All ten of the fatal and disseminated carcinomas had cellularity of more than 10 per cent, while 12 of 27 long-term survivors had less cellular tumors. Tumor cellularity did not correlate with tumor size; these features were entirely independent. Thus, in contrast to the findings of some prior studies with shorter follow-up periods, pure mucinous carcinomas were seen to be slowly growing, but fully malignant, tumors warranting standard breast carcinoma treatment.

Adenocarcinoma, Mucinous↗

Pancreatoblastoma in an adult.

A 37-year-old man with a history of abdominal pain, diarrhea, and weight loss was found to have an 8-cm-diameter tumor in the head of the pancreas, a biopsy specimen of which revealed histologically and ultrastructurally typical pancreatoblastoma. The tumor was unresectable and demonstrated no response to chemotherapy; however, substantial tumor shrinkage resulted from intraoperative and external beam radiation therapy. This rare tumor, to our knowledge not previously reported in an adult, should be considered in the differential diagnosis of adults as well as children with pancreatic epithelial tumors.

Adenoma, Islet Cell↗

A simple radial immunodiffusion method for assay of beta 2-microglobulin in serum.

In this method for clinical measurement of beta 2-microglobulin, a 10 g/L agarose gel containing anti-beta 2-microglobulin is used, with subsequent staining with Coomassie Blue. Although the method is slow (requiring 30 h), it is inexpensive, reliable, and accurate over the range of 1 to 10 mg/L, and is useful in the determination of beta 2-microglobulin in serum and cerebrospinal fluid. A modified procedure in which staining with silver is used may be sufficiently sensitive for the clinical assay of urine.

Humans↗

The lability of estrogen receptor: correlation of estrogen binding and immunoreactivity.

We compared the Abbott enzyme immunoassay method for estrogen receptor with a standard dextran-coated charcoal method, and studied the effects of treatments causing denaturation. Estrogen receptor values were slightly higher by the Abbott method, but the methods agreed with regard to receptors being present or absent in 94-98% of 50 cases. Heat lability of immunoreactivity by the Abbott enzyme immunoassay is comparable to the lability of estrogen binding by the estrogen receptor. Estrogen and molybdate substantially stabilized estrogen receptor during the assay, but improper handling of tissue before the assay may cause similar, substantial decreases in estrogen receptor by either method. The Abbott method is easier to use than the dextrancoated charcoal method, requires less tissue, and measures receptor with or without endogenously bound estrogen, but reagent cost is high.

Breast Neoplasms↗

Open lung biopsy in Mycoplasma pneumoniae pneumonia.

Pathologic descriptions of Mycoplasma pneumoniae pneumonia in humans are scarce, and most descriptions are from autopsy studies. We studied open lung biopsy specimens from six patients with proved or probable M pneumoniae pneumonia and reviewed the findings on M pneumoniae pneumonia that have been reported in the literature, as well as the electron microscopic characteristics of the organism, to document the morphologic spectrum. Five of our six cases showed a typical but nonspecific polymorphonuclear leukocyte-rich exudate in the bronchiolar lumina, metaplastic cells that lined the bronchioles, a lymphoplasmacytic bronchiolar wall infiltrate, peribronchiolar septal widening, and adjacent hyperplasia of type II pneumocytes. In one patient, diffuse alveolar damage was superimposed on the above bronchiolar lesion, and the sixth patient had a nonspecific organizing pneumonia.

Adolescent↗

Electron microscopy of body fluids.

Transmission electron microscopy and scanning electron microscopy are complementary techniques; the former is useful for examining the fine internal structural detail of tissue and cell surfaces and the latter is useful for studying three-dimensional configurations. The methods and findings of transmission and scanning electron microscopic study of effusions are summarized, and their practical application in routine clinical work is assessed.

Adenocarcinoma↗

Argyrophilic breast carcinomas: evidence of lactational differentiation.

Twenty unselected breast carcinomas were examined for argyrophilia by the Sevier-Munger stain and for dense-core secretory granules by electron microscopy. All cases were examined for lactalbumin and five cases were also studied for gastrin, insulin, calcitonin, somatostatin, glucagon, ACTH, prolactin, and pancreatic polypeptide by an immunoperoxidase technique; two cases were further analyzed for lactalbumin by ultrastructural immunoperoxidase stain. Focal or diffuse argyrophilia was present in ten cases. Intracytoplasmic lactalbumin was present in seven of these cases, but immunoperoxidase staining for the neuroendocrine hormones was negative. Fine structural examination demonstrated varying numbers of 95 to 450-nm-diameter, round, membrane-bound, dense-core secretory granules in 13 cases. Nine of the granule-containing cases were also argyrophilic, and seven of these contained intracytoplasmic lactalbumin. Both the argyrophilia and the dense-core secretory granules thus correlated with the presence of intracytoplasmic lactalbumin. None of the 20 patients had clinical evidence of carcinoid syndrome or showed evidence of other hormone secretion. Argyrophilia and granular lactalbumin staining in a somewhat similar pattern was found in pregnant and lactating breast controls. Argyrophilia and ultrastructural dense-core granules are common in breast carcinomas and might represent lactational differentiation. These findings do not indicate the presence of a carcinoid tumor because in most of these tumors the secretory granules appear to contain milk protein secretory product rather than neuroendocrine polypeptides, and most argyrophilic tumors do not morphologically or clinically resemble carcinoid tumors.

Adenoma↗