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Biomedical subjects

J K Boitnott

Publications and source records attributed to J K Boitnott.

At least 37 records · Page 2Linked to original sources

Resection of hepatic duct bifurcation and transhepatic stenting for sclerosing cholangitis.

Thirty-one patients with sclerosing cholangitis underwent reconstruction of their hepatic duct bifurcation and long-term stenting between 1980 and 1987. Indications for surgery were persistent jaundice in 29 and recurrent cholangitis in two. The mean serum bilirubin level before surgery was 10.4 mg/dl. Liver biopsy revealed that 26 patients had varying degrees of hepatic fibrosis, and five patients had progressed to secondary biliary cirrhosis. In 29 patients the major obstructive duct disease was at or near the hepatic duct bifurcation, and in two patients it was in the distal common duct. The operative procedure consisted of: (1) excision of the hepatic duct bifurcation and extrahepatic biliary tree, (2) dilatation of the intrahepatic ducts, (3) insertion of Silastic transhepatic biliary stents, and (4) bilateral hepaticojejunostomies. Two of the five patients (40%) with cirrhosis died after surgery. In contrast, only one of 26 patients (3.9%) with hepatic fibrosis died after operation. The 1-, 3-, and 5-year actuarial survival rates for patients with cirrhosis were 20%, 20%, and 20%, respectively. The only long-term survivor underwent a liver transplant. The 1-, 3-, and 5-year actuarial survival rates for patients with hepatic fibrosis were 92%, 87%, and 71%, respectively. In addition, the mean serum bilirubin levels of patients with hepatic fibrosis at 1, 2, 3, 4, and 5 years were 3.4 mg/dl, 2.9 mg/dl, 4.0 mg/dl, 5.4 mg/dl, and 4.3 mg/dl, respectively. Two of the long-term survivors subsequently underwent a liver transplant. Patients with sclerosing cholangitis, persistent jaundice, and biliary cirrhosis should be referred for consideration of liver transplantation. However, in the absence of biliary cirrhosis, if the major obstructive disease is at the hepatic duct bifurcation, primary biliary reconstruction and long-term stenting should be considered.

Adult↗

Pseudo-graft-versus-host disease in heart and heart-lung recipients.

Autopsies from nine patients who had received a cardiac allograft transplant and one with a combined heart-lung transplant were assessed for histologic evidence of pseudo-graft-versus-host disease (pseudo-GVHD). Five of the ten patients had GVHD-like changes in two or more tissues, including prominent lymphocyte-associated bile duct injury consistent with marked hepatic pseudo-GVHD and mild cutaneous changes resembling GVHD. A sixth recipient had marked changes in the liver, but autopsy restrictions prevented examination of the skin. A seventh recipient had only mild pseudo-GVHD changes limited to the skin. In contrast, a series of six patients who were candidates for cardiac transplant had no specific pathologic changes suggesting pseudo-GVHD. The majority of those with pseudo-GVHD had received nonirradiated blood product transfusions, raising the possibility of posttransfusion engraftment and GVHD. Unlike the posttransfusion GVHD, however, two of the six developed GVHD-related complications late with a latent period of five and 9.5 months, and two recipients received no transfusions. All were receiving only modest doses of immunosuppressive agents at the time they developed liver function abnormalities, including low or tapering doses of cyclosporine (CsA). In some of these recipients, therefore, the pseudo-GVHD changes may well represent an autoimmune reaction resembling the post-CsA model of autoimmune disease.

Adult↗

Integrated pathology reporting, indexing, and retrieval system using natural language diagnoses.

Pathology computer systems are making increasing use of natural language diagnoses. The Johns Hopkins Medical Institutions integrated pathology reporting system, a commercial product with extensive, locally added enhancements, covers all information management functions within autopsy and surgical pathology divisions and has on-line linkages to clinical laboratory reports and the medical library's Mini-MEDLINE system. All diagnoses are written in natural language, using a word processor and spelling checker. A security system with personal passwords and different levels of access for different staff members allows reports to be signed out with an electronic signature. The system produces financial reports, overdue case reports, and Boolean searches of the database. Our experience with 128,790 consecutively entered pathology reports suggests that the greater precision of natural language diagnoses makes them the most suitable vehicle for follow-up, retrieval, and systems development functions in pathology.

Artificial Intelligence↗

Farber disease: pathologic diagnosis in sibs with phenotypic variability.

We describe new pathologic findings in two sibs with Farber lipogranulomatosis. The first child, a 3-month-old boy, presented with only hepatosplenomegaly and had a fulminant clinical course suggestive of malignant histiocytosis. The second child, a 5 1/2-month-old girl, had the typical clinical presentation of Farber disease, with hoarseness and painful swollen joints. At autopsy, storage material was demonstrated in the second child at laryngeal and periarticular subcutaneous sites. Visceral involvement was prominent in both sibs, although not typical of the disease, and included a newly described nephropathy with elevated urine ceramide levels. Liver and spleen contained massive histiocytic infiltrates in association with elevated ceramide levels. Lymph nodes also contained histiocytic infiltrates but without the sinusoidal involvement typical of proliferative histiocytic disorders. These two cases demonstrate new pathologic anomalies in Farber disease, indicating that biochemical analyses of biopsy specimens may be necessary to establish the diagnosis of Farber disease when atypical clinical and morphologic anomalies are present.

Amidohydrolases↗

Primary lymphomas of the liver. Report of six cases and review of the literature.

Six cases of diffuse large cell lymphoma (DLCL) of the liver were studied with immunohistochemistry for common leukocyte antigen (CLA), lysozyme, alpha-1-antitrypsin (AAT), and kappa and lambda light chains on paraffin-embedded tissues. All six cases were positive for CLA. Four of the six cases showed staining for lysozyme and AAT (three focal and one diffuse staining). In three cases, frozen tissue for monoclonal antibodies and glutaraldehyde-fixed tissue for electron microscopic examination were available. Two of these showed B-cell phenotypes with monoclonal antibody studies. Electron microscopic examination on these two B-cell lymphomas showed scant cytoplasm and a paucity of cytoplasmic organelles. The third case did not show definite B- or T-cell surface markers but did show strong Leu-M1 and OKM1 staining. Electron microscopic examination of the tumor cells showed a prominent Golgi apparatus, abundant cytoplasm with numerous cytoplasmic organelles and phagolysosomes. However, DNA hybridization studies on this tumor showed immunoglobulin heavy and kappa light chain gene rearrangements typical of a B-cell lymphoma. All six lymphomas were solitary liver masses without evidence of disease elsewhere. The mean age for the six patients was 56.2 years (four males, two females).

Aged↗

A neoplasm with pancreatic and hepatocellular differentiation presenting with subcutaneous fat necrosis.

A neoplasm demonstrating both pancreatic and hepatic phenotypes is described. The tumor, from a 53-year-old woman with the syndrome of subcutaneous fat necrosis and arthropathy, was studied histologically, immunohistochemically, ultrastructurally, and biochemically. The clinical features of this case can be explained by the production of large amounts of lipase by the tumor. The hepatocellular properties of the tumor included characteristic morphology and the synthesis of catalase. The pancreatic properties of the tumor included the production of pancreatic lipase. This neoplasm would appear to be analogous to animal models in which the transdifferentiation of pancreatic acinar cells and hepatocytes has been demonstrated. Although the bulk of the tumor was present in the liver, the authors believe the tumor arose from the pancreas. The distinction between differentiation and site of origin of tumors is discussed.

Adipose Tissue↗

Clip-ablation. A model of experimental hypertension in the rat.

A model of experimental hypertension has been developed in which the features of the two kidney-one clip and renal ablation models are combined in a single rat. It has been designated the clip-ablation model. It is produced by the placement of a silver clip with an opening of 0.13 mm on a branch of the left renal artery supplying one-third of that kidney, followed by right nephrectomy. In this way the effects of renin-dependent hypertension may be studied in glomeruli which are undergoing compensatory changes in response to reduction in renal mass. Clip-ablation rats were compared to rats with 1 1/3 reduction of renal mass at various intervals up to 28 days after operation. Systolic blood pressure rose with increasing time after operation in both groups with the increase being greater in the clip-ablation rats (177 +/- 10 mm Hg) as compared to the ablation rats (153 +/- 6 mm Hg) at 28 days. Plasma renin activity was increased slightly at 3 days in the ablation rats but had returned to normal levels by 28 days. By contrast, the plasma renin activity rose throughout the experimental period in the clip-ablation rats and attained a level of 32.3 +/- 8.0 ng/ml/hour by 28 days. Urine protein was significantly higher than normal only in the 28-day clip ablation rats (71.2 +/- 23.9 mg/24 hour). Glomerular damage index (GDI), a measure of glomerular injury, increased with longer intervals from operation in both experimental groups, paralleling the rise in systolic blood pressure. Beginning on day 14 and onward the GDI was always numerically higher in the clip-ablation rats than in the ablation rats. Stepwise multiple regression analysis indicated that the strongest predictor of GDI was the change in blood pressure. Plasma renin activity had an additional independent effect on GDI in the clip-ablation rats. The finding of more glomerular damage in the clip-ablation rats than in those with simple removal of comparable amounts of renal tissue is in contrast to the lesser amount of damage found in the two kidney-one clip model when compared with the model of removal of renal substance. It is likely that the compensatory hemodynamic changes in response to reduction in renal mass in the glomeruli of clip-ablation rats make them more vulnerable to injury when exposed to a renin-angiotensin induced hypertension.

Animals↗

Diet and other risk factors for cancer of the pancreas.

The findings of a case - control study of cancer of the pancreas, which was conducted in the Baltimore metropolitan area, are reported. Two hundred one patients with pancreatic cancer were matched on age (+/- 5 years), race, and sex to hospital and non-hospital controls, the latter selected by random-digit-dialing (RDD). All subjects were interviewed regarding diet, beverage consumption, occupational and environmental exposures, and medical and surgical history. Significantly decreased risks were associated with consumption of raw fruits and vegetables and diet soda, and significantly increased risks were associated with consumption of white bread when cases were compared with hospital and RDD controls. A significantly reduced risk was associated with consumption of wine when cases were compared to RDD controls. Risk ratios for consumption of coffee were not significantly different from one, although there appeared to be a dose - response relationship in women. A moderate but statistically nonsignificant increase in relative odds was found for cigarette smoking, and cessation of smoking was associated with a marked reduction in risk. No significant associations were found with particular occupational exposures. Tonsillectomy was associated with a significantly reduced risk, a finding that has been observed for other cancers as well. The current evidence indicates that pancreatic cancer is likely to result from a complex interaction of factors and suggests that the study of its etiology requires a multidisciplinary approach involving both laboratory and epidemiologic components.

Aged↗

Effects of carcinogen dosage on experimental colonic carcinogenesis by azoxymethane: an ultrastructural study of grossly normal colonic mucosa.

The transmission electron microscopic features of grossly normal colonic mucosa in the azoxymethane [(AOM) CAS: 25843-45-2]-treated rat model of colonic carcinogenesis were studied by the method of concomitant variation. Ten-week-old male F344 rats were given 10 weekly sc injections of AOM at doses of 3, 7, or 14 mg/kg body weight and were killed 1 week or 15 weeks after the last AOM dose. Grossly normal distal left colon was examined using transmission electron microscopy. Three transient dose-dependent features of colonic epithelial cells were identified: a) mitochondrial injury, b) nuclear pleomorphism and loss of polarity, and c) increased numbers of mitotic figures in the lower third of the crypts. Because these dose-dependent features were present only shortly after AOM administration, they appeared to be manifestations of carcinogen toxicity and associated reactive, regenerative epithelial changes. By contrast, four persistent dose-dependent features were identified: a) increased numbers of epithelial cells with enlarged nucleoli, b) increased numbers of mitotic figures in the middle third of crypts, c) reduced numbers of goblet cells, and d) reduced numbers of apical cytoplasmic vacuoles in the upper third of the crypts. Because these features persisted in a dose-dependent manner for many weeks after the last dose of AOM and were present after the latent period to tumor formation, they appear to be morphologic precursors to colonic carcinogenesis in the model.

Animals↗

The role of resection margin frozen section in the surgical management of Crohn's disease.

The use of frozen section examination of resection margins in selecting the site for an ileocolonic anastomosis was evaluated in patients with Crohn's disease. Seventy-nine patients with ileitis or ileocolitis who underwent first resection with removal of all apparent disease and primary ileocolonic anastomosis were studied. The patients with a resection margin examined by frozen section (FS group, n = 38) and those with margins chosen on the basis of visual inspection alone (NO-FS group, n = 41) were compared. Frozen section examination was found to be poor at detecting margin involvement: although 60 of 61 margins examined by frozen section were reported as negative at the time of operation, 20 of 61 were actually involved by Crohn's disease. Furthermore, despite the use of frozen section examination, the prevalence and severity of margin involvement in the FS and NO-FS groups were not statistically significantly different. Short term and long term clinical outcome were also not statistically different; the incidence of postoperative anastomotic leakage and obstruction was 13 per cent in the FS group and 5 per cent in the NO-FS groups (p NS). Clinical recrudescence rates by life table analysis in the FS and NO-FS groups were 37 +/- 9 per cent and 50 +/- 8 per cent, respectively, at five years, and 60 +/- 12 per cent and 66 +/- 9 per cent at ten years (p NS). Reoperation rates were 18 +/- 8 per cent at five years in both groups and 36 +/- 13 per cent in the FS group and 32 +/- 12 per cent in the NO-FS group at ten years. The findings support conservative resection to achieve grossly uninvolved margins rather than sacrifice of functional intestine in an attempt to achieve histopathologically uninvolved margins on frozen section.

Actuarial Analysis↗

Cholestatic hepatitis from erythromycin ethylsuccinate. Report of two cases.

Cholestatic hepatitis developed in two patients while they were receiving erythromycin ethylsuccinate. Both patients had received the drug without apparent problem within two months of the episode of drug-related cholestatic injury. In both, there was complete resolution of the hepatic injury upon withdrawal of the drug. Erythromycin ethylsuccinate should be added to the list of drugs causing cholestatic hepatitis.

Chemical and Drug Induced Liver Injury↗

The spectrum of carcinoma arising in Barrett's esophagus. A clinicopathologic study of 26 patients.

The clinical and pathologic features of carcinoma arising in Barrett's esophagus were studied in resection specimens from 26 patients. White males predominated (73%). A history of symptomatic gastroesophageal reflux was frequently absent, being elicited in only eight of 14 patients (57%) with a carefully obtained history at the time of presentation with carcinoma. Survival was relatively short with a median survival of 23 +/- 5 months, and only three patients had a disease-free survival longer than 2 years. A pathologic spectrum of carcinoma was found: differentiation ranged from well to poorly differentiated in the 20 patients with a single adenocarcinoma; two separate carcinomas were found in four patients; and a spectrum of differentiation in a single tumor was found in the other two cases, one an adenocarcinoid tumor and the other an adenosquamous carcinoma. The tumors were generally far advanced, with extension through the esophageal wall in 23 of 26 cases (88%) and metastases to lymph nodes in 17 of 24 cases (71%). Epithelial dysplasia, including carcinoma in situ in some cases, was found in Barrett's mucosa adjacent to the tumor in all 26 patients. Our findings suggest that a surveillance program for dysplasia in patients known to have Barrett's esophagus is warranted in an attempt to improve the outcome. However, the impact of surveillance on the incidence of Barrett's carcinoma may be lessened by its frequent occurrence in patients with asymptomatic gastroesophageal reflux.

Adenocarcinoma↗

Endothelial cell activity in experimental hypertension. Effects of hemodynamic factors.

The cause of the increased endothelial cell proliferative activity found in experimental hypertension in the rat is not clear. In this experiment the part played by altered vascular hemodynamics was explored in a model in which part of the aorta was subjected to a high blood pressure and the other not. Hypertension was produced by the application of a tight ligature to the aorta between the levels of the two renal arteries, the mechanism being interference with the blood supply to the more distally placed kidney. Because the aorta is constricted, the segment above the ligature is subjected to high blood pressure and the segment below it to lowered pressure, although both segments are exposed to humoral factors such as renin and angiotensin II. Aortic endothelial cells were labeled with tritiated thymidine and cell replication and cell density studies carried out using en face monolayer preparations of endothelium. It was found that endothelial cell replication was considerably increased at 7 days following induction of hypertension in segments of aorta above the ligature but not in the segment below the ligature. The increased activity was short-lived and had returned to normal levels at 4 weeks. Cell density was increased above the ligature at both 1 and 4 weeks following induction of hypertension. The changes are consistent with the idea that the increased cell replication and consequent increased cell density above the ligature were initiated by the increased stretching of the aortic wall attending the development of hypertension.

Animals↗

Aortic endothelial cell activity in high renin and normal renin models of hypertension in the rat.

To determine whether renin or angiotensin might have an effect on endothelial cell activity, we studied cell replication and cell density in two models of hypertension in the rat. The first was a model in which the plasma renin activity was high during the three time periods studied (1, 2, and 4 weeks after renal artery constriction) and the second, a model with elevated plasma renin activity only during the initial period (1 weeks). Aortic endothelial cells were labeled with tritiated thymidine period to killing, and en face endothelial cell monolayers were prepared. The ratio of labeled cells to total cells (thymidine index) and the ratio of total number of cells to number of fields observed (cell density) were calculated for the whole aorta, segments of the aorta, and zones within the segments. In both hypertensive models, an elevation of the thymidine index (indicative of increased endothelial cell replication) was observed at 1 week but not at subsequent times when the levels had returned to those of the controls. Cell density was increased at all time periods studied and like the thymidine index showed no significant differences between the two hypertensive models. Although renin or angiotensin (or other humoral factors) could have been responsible for the increased thymidine index after 1 weeks, it is considered that hypertension itself it a more likely cause, taking into account the decreased indices at later time periods when one model has high renin levels and the other does not. The increased cell density at all time periods studied in both models is regarded as an adaptive reaction to the increased blood pressure.

Animals↗

Pathological factors that influence prognosis in stage A prostatic cancer: the influence of extent versus grade.

To determine the pathologic factors useful in predicting prognosis in patients with stage A prostatic cancer we studied 117 patients followed for 2 to 15 years. Since no patient was treated until progression of disease occurred we were able to correlate pathologic findings with the natural history of the disease in an untreated population of patients. In 14 patients (12 per cent) extensive local (2) or metastatic (12) disease developed. Because 12 of the 14 patients had progression of the disease within 4 years we thought than an analysis of all patients followed for 4 years would be useful. Extent and grade of disease were the 2 factors that most accurately predicted progression. No patient with a low grade lesion (Hopkins grade 1 or Gleason total score 2 to 4) had progression and only 2 per cent of patients with less than 5 per cent cancer had progression. These patients were classified as stage A1 and 60 per cent of all patients were in this category. We believe that these patients require no further therapy. Of the patients with more than 5 per cent cancer 32 per cent had progression and 17 per cent of the patients with either Hopkins grade 2 to 3 disease or Gleason total score more than 4 had progression. These patients were classified as stage A2 and their optimal management remains to be determined.

Adenocarcinoma↗