Biomedical subjects
Publications and source records attributed to T A Godwin.
Diffuse lung injury can either heal normally or progress to fibrosis. Calcification in the setting of fibrosis is common. The appearance of mature woven bone is not. We report a patient with extensive diffuse pulmonary ossification and discuss some of the theories relating to the development of this phenomenon.
Infrared spectra were obtained from exfoliated cervical cells from 156 females, of whom 136 were normal, 12 had cervical cancer, and 8 had dysplasia. The spectra of the normal women, essentially identical, differed from those obtained from patients with either cancer or dysplasia. In malignant samples we noted (i) significant changes in the intensity of the glycogen bands at 1025 cm-1 and 1047 cm-1, the bands at 1082 cm-1 and 1244 cm-1, the C--O stretching band at 1155 cm-1, and the band at 1303 cm-1, (ii) significant shifts of the peaks normally appearing at 1082 cm-1, 1155 cm-1, and 1244 cm-1, and (iii) an additional band at 970 cm-1. Further study of several of these bands, including the pressure dependence of their frequencies, revealed that in the malignant cervical tissue there were extensive changes in the degree of hydrogen bonding of phosphodiester groups of nucleic acids and C--OH groups of proteins, as well as changes in the degree of disorder of methylene chains of lipids. The IR spectra of samples with dysplasia demonstrated the same changes with cancer samples, except that the changes were of lesser magnitude and the phosphodiester peak normally appearing at 1082 cm-1 did not shift. These spectroscopic changes appear to progress in tandem with the morphological changes that lead normal cervical epithelium to cancer through the premalignant stage of dysplasia. The diagnostic potential of IR spectroscopy is discussed.
A retrospective study was performed to determine the ploidy of superficial (above muscularis propria) and deep (below muscularis propria) biopsy specimens from the primary colorectal cancer of 88 patients with Dukes Stage C2 and D colorectal tumors. The ploidy of lymph node and liver metastases was compared with that of the superficial and deep specimen from the corresponding primary tumor. Among the tumors studied, 78% exhibited nondiploid stemlines. In 19% of the tumors, the ploidy of the superficial biopsy differed from that of the deep biopsy. Among these discordant tumors, all of the deep biopsy specimens corresponded in ploidy to the liver metastases, whereas most of the superficial specimens were similar in ploidy to the lymph node metastases. Our observations suggest that measurement of a single site may not be sufficient to detect nondiploid stemlines within a tumor. They also suggest that measurement of deeper parts of invasive tumors may be more reflective of the phenotype of distant metastases than measurement of superficial specimens.
The pathologic changes associated with human cryptosporidiosis have not been well characterized. In this report, 15 cases of cryptosporidiosis in acquired immunodeficiency syndrome patients are described. Organisms were found in autopsy tissue specimens in 13 cases, and only in antemortem stool samples in two. Gastrointestinal/hepatobiliary distribution of organisms was as follows: small intestine (13 cases), extrahepatic bile ducts (eight), intrahepatic bile ducts (seven), large intestine (six), pancreas (five), stomach (three), and esophagus (one). At all sites, infection was usually associated with nonspecific reactive epithelial changes, architectural abnormalities such as villous flattening in the small intestine, and interstitial edema with mixed inflammatory cell infiltrates. Presence of organisms and associated mucosal injury were patchy and of variable severity in the intestine. In the biliary tract, injury was commonly diffuse and severe. Pancreatic duct injury was generally mild and often limited to hyperplastic squamous metaplasia. In late-stage acquired immunodeficiency syndrome patients with cryptosporidiosis, widespread infection in the gastrointestinal and biliary systems by this coccidian was more common and severe than previously suggested. Although the mechanisms have yet to be determined, infection usually is accompanied by pathologic changes that may be causally related to pathophysiologic abnormalities, such as diarrhea and malabsorption, and may account for other clinical manifestations of pancreatitis, cholangitis, and obstructive cholestasis.
One hundred fifty-two cases (155 specimens) of lymphoproliferative disorders were studied by immunohistochemistry and gene rearrangement analysis. Ninety-five of 96 B-cell lymphomas (99%) showed genotypic B-cell monoclonality. Of these, five cases had rearranged T-cell receptor (TCR) beta chain gene in addition to immunoglobulin heavy chain (IgH) and kappa light chain (Ig-K), one case had rearranged IgH and TCR-gamma chain but not Ig-K or TCR-beta, and two cases had only Ig-K rearrangement. One exceptional case in the B-cell lymphoma group had unrearranged, germline genotypes. In contrast, only 10 of 19 (53%) phenotypic T-cell lymphomas had rearranged TCR-beta, eight with concurrent TCR-gamma rearrangement. Of the remaining nine cases, six had germline configuration, two had rearranged Ig-K only, and one had both IgH and Ig-K rearrangement. This last case was reclassified as T-cell predominant, B-cell lymphoma. Thirteen of 16 cases of Hodgkin's disease had germline configuration; three cases had rearranged IgH and Ig-K, of which two were lymphocyte predominant with light chain monoclonality and one was a recurrence. Among 21 reactive lesions, 17 had germline configuration and four had rearranged IgH and Ig-K genes. Of these four cases, two were orbital lesions, one was a partially involved lymph node, and one developed a nodular lymphoma 9 months later. Our results indicate that almost all B-cell lymphomas have IgH and/or Ig-K rearrangement. In contrast, peripheral T-cell lymphomas have greater genotypic heterogeneity, and germline patterns for TCR genes are not uncommon. Reactive lesions and Hodgkin's disease tend to retain germline configuration, and any exception is often associated with an unusual clinical setting and/or histology. Genotypic analysis is thus most indicated in B-cell lymphomas with equivocal immunohistochemistry findings, T-cell lymphomas, and atypical cases of Hodgkin's disease and reactive lesions.
In 16 cases of human immunodeficiency virus-associated Mycobacterium avium-intracellulare complex (MAC) infection, 7 were diagnosed after finding intracytoplasmic negatively staining linear inclusions within histiocytes using Romanowsky-stained bone marrow aspirate smears. Four patients had inclusions within monocytes and neutrophils in the peripheral blood smear. The authors believe these cases represent the first reported examples of MAC inclusions observed within leukocytes in Wright's-stained peripheral blood smears. Inclusions usually were found in the setting of prominent toxic changes in leukocytes such as large Dohle bodies, marked granulation, and vacuolation. These inclusions are characteristic of mycobacteria and can be confirmed by acid fast stains and mycobacteriologic culture. The authors present the clinical and laboratory setting in which identification of inclusions in peripheral blood smears may be a rapid, minimally invasive, and cost-effective method of diagnosing mycobacterial infection.
Cryptosporidiosis of the biliary system was studied retrospectively in 13 patients with acquired immunodeficiency syndrome (AIDS). The diagnosis was made by means of histologic examination (n = 9) or imaging studies and the presence of intestinal cryptosporidiosis (n = 4). Imaging studies were done in 10 patients. Ultrasound (US) and computed tomography (CT) showed dilatation of the biliary ducts, some with wall thickening, thickening of the gallbladder wall and pericholecystic fluid. Cholangiograms showed attenuation and pruning of the intrahepatic bile ducts, some with beading and dilatation of the common bile duct. Three patients had papillary stenosis. Numerous Cryptosporidium organisms were found in three resected gallbladders and in the biliary ducts of seven patients in whom autopsy was performed, accompanied by an exuberant inflammatory response. Correlation of the radiologic and pathologic findings establishes a direct etiologic role of Cryptosporidium as one of the major infectious agents in cholangitis associated with AIDS.
Embolization of intestinal contents to the lung is an exceedingly rare event, which to our knowledge, has never been reported as a cause of death. Equally rare is duodenocaval fistula resulting from a penetrating duodenal peptic ulcer. We present the case of a 51-year-old man whose duodenal ulcer led to a fistulous tract with the inferior vena cava and subsequently to progressive pulmonary embolization of intestinal contents, ultimately resulting in death from respiratory failure.
Patients with systemic lupus erythematosus and with antiphospholipid antibody are subject to sudden occlusion of multiple blood vessels. We describe two patients with systemic lupus erythematosus with acute, catastrophic, widespread non-inflammatory visceral vascular occlusions associated with high-titer antiphospholipid antibody. The histopathologic features clearly distinguished these patients from classic systemic lupus erythematosus vasculitis. We further suggest that, based on a probable pathogenesis related to the presence of antiphospholipid antibody, and based on the non-inflammatory vascular occlusion, steroids and other immunosuppressive medications are of limited value. Plasmapheresis along with anticoagulant therapy should be considered.
Superficial colonic cells were taken from normal-appearing mucosa at 2, 5, and 10 cm proximal and distal to colorectal cancer margins in 37 patients. The DNA ploidy and proliferative pattern of each sample were determined using flow cytometry. In 11 patients, histology of mucosal sections from the same sites also was analyzed. We found a higher frequency of aneuploidy than previously reported in mucosa up to 10 cm from a colorectal cancer; 62% (23/37) of the primary cancers were aneuploid, and of these, 48% (11/23) were associated with adjacent aneuploid mucosa. The mucosa adjacent to the 14 diploid cancers had only diploid characteristics. The proliferative activity (as reflected by synthetic (S) phase fraction) of aneuploid cancers (21.1 +/- 2.0% SEM) and aneuploid mucosa as far as 10 cm away (21.2 +/- 2.1% SEM) was higher than in normal controls (10.2 +/- 0.7% SEM) (P less than 0.0005). Parallel cytology excluded shed cancer cells as an explanation for these findings. Histology showed diffuse, generally mild and reactive, mucosal abnormalities in eight of 11 patients. Ploidy did not correlate with histologic abnormalities. The findings of aneuploidy and high S-phase fraction in uninvolved superficial mucosa provide evidence for a field defect in mucosa adjacent to colorectal cancer and support the concept that the large bowel mucosa behaves as a unit in carcinogenesis.
Necropsy findings in 101 adult patients with the acquired immunodeficiency syndrome (AIDS) from two metropolitan hospitals were compared retrospectively with the antemortem clinical diagnoses. 94% of the patients were male and 68% were homosexual or bisexual. 75 (74%) patients had AIDS-related diseases at necropsy that were not suspected clinically. The commonest of the unsuspected AIDS-related diseases were cytomegalovirus infection (49% of all cases), systemic fungal infection (20%), systemic Kaposi's sarcoma (14%), Mycobacterium avium intracellulare infection (11%), and systemic herpes infection (9%). Cryptococcal infection and cytomegalovirus retinitis were always diagnosed antemortem; and Pneumocystis carinii pneumonia went undiagnosed in only 5 of 58 (9%) patients who had proven infection either clinically or at necropsy. 8 patients who died with fungal pneumonia had undergone bronchoscopy; however, in only 1 patient was it diagnosed antemortem. Tuberculosis was undiagnosed in 4 patients. 4 cases of central nervous system lymphoma diagnosed only at necropsy had been treated empirically for toxoplasmosis. Bacterial pneumonias contributed considerably to mortality in 30% of the patients.
Chemotherapy-related pneumonitis developed in eight patients during treatment for breast cancer. Six were receiving adjuvant therapy and two were being treated for metastatic disease. Fever, chills, dyspnea, and dry cough were the initial symptoms. Observations from chest roentgenograms varied from normal to bilateral interstitial-alveolar infiltrates. Results of pulmonary function tests were markedly abnormal, with a decreased diffusing capacity being the most characteristic abnormality. The pneumonitis developed in six patients while receiving 20 mg or less per day of prednisone and appeared temporarily related to tapering of steroid therapy in four patients. All patients recovered clinically, although prednisone therapy of 60 mg/day or its equivalent was required in three cases. Mild pulmonary function abnormalities persisted. Drug-induced pneumonitis should be considered in the differential diagnoses of patients with breast cancer in whom unexplained fever, dyspnea, or infiltrates develop during multidrug chemotherapy.
We describe a rare variant of schwannoma characterized by a interconnecting multinodular growth mimicking a plexiform neurofibroma. The schwannoma recurred twice. The second recurrence was not excised and has not increased in size for 1 1/2 years. The patient is alive and well, 3 years and 4 months after the first excision with no clinical evidence of metastasis.
A phase I study of tricyclic nucleoside phosphate was conducted in 20 adults with advanced cancer. Tricyclic nucleoside phosphate was given as an iv infusion over 15 minutes once every 3 weeks; the doses ranged from 25 to 350 mg/m2. Beginning at a dose of 250 mg/m2, hyperglycemia and elevation of hepatocellular enzymes were observed; at a dose of 350 mg/m2, two patients developed irreversible liver damage. Patients at all dose levels experienced reduction in serum phosphorus; reduction of serum calcium was noted only with the two highest doses. Nausea and vomiting occurred occasionally. Myelosuppression was not a prominent toxic effect. No major therapeutic responses were noted. Further clinical trials employing this schedule are probably not warranted.
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Fourteen cellular schwannomas, a variety of peripheral nerve sheath tumor showing a predominantly compact cellular growth, no formed cellular palisades or Verocay bodies, but the ultrastructure of schwannomas, are reported. A presumed nerve of origin was identified in three instances. The tumor had no sex predeliction; the mean age was 48. The neoplasm is usually well encapsulated and most commonly presents in the neck, posterior mediastinum, or pelvis. Because of a variety of confusing histologic features, including dense cell bundles and fascicles, storiform areas, a moderate mitotic activity and moderate nuclear atypia, six of 14 cases were mistaken for either fibrous histiocytoma, leiomyoma, malignant peripheral nerve sheath tumor, or sarcoma of uncertain type. In two instances the false impression of a malignant tumor was reinforced by clinical evidence of bony erosion and destruction. Follow-up thus far has shown the tumor to be benign.
Nodular regenerative hyperplasia was found in nine patients who had hematological disease including polycythemia vera, agnogenic myeloid metaplasia, primary thrombocythemia, rheumatoid arthritis with thrombocytosis, multiple myeloma, and erythrocytosis associated with polycystic renal disease. Portal hypertension was suspected in three and features of hypersplenism were present in four. 2. Nodular regenerative hyperplasia occurred in livers which had widespread obliteration of portal vein radicals (obliterative portal venopathy). Morphometric analysis indicated that the portal vein lesions were predominately located in veins up to 0.2 mm in diameter and were significantly more frequent than similar lesions occurring in elderly persons. 3. The following pathogenesis of nodular regenerative hyperplasia is proposed: Thrombi, perhaps largely composed of platelet aggregates formed in the portal venous circulation or spleen, embolize to the liver and results in obliterative vascular lesions. Atrophy and regenerative nodule formation occur in response to the interruption of the portal blood supply.
BACKGROUND: Carcinoembryonic antigen (CEA) is an oncofetal glycoprotein involved in cell recognition and adhesion. Serum CEA has been extensively studied as a potential chemical marker for malignancy, most notably in patients with colon carcinoma. Serum CEA measurements have not been reported for patients with salivary gland carcinomas. METHODS: Serum CEA was measured in a case study using enzyme immunoassay with monoclonal antibody specific for CEA. Tissue was examined with standard histologic and immunohistologic methods. RESULTS: A patient was initially seen with adenoid cystic carcinoma (ACC) of the trachea and had a markedly elevated serum CEA level which declined after surgical resection. The serum CEA level became elevated again when the patient developed abdominal metastases and then declined after debulking of the tumor. Immunohistochemical study of the tumor was positive for CEA. CONCLUSIONS: The measurement of serum CEA levels may play a role in the management of patients with ACC. Clinical investigation utilizing monoclonal antibodies against CEA, for imaging and for the delivery of chemotherapy and radiotherapy may be worthwhile.