Two cases of intestinal spirochetosis (IS) with acquired immunodeficiency syndrome are reported. ... more Two cases of intestinal spirochetosis (IS) with acquired immunodeficiency syndrome are reported. In case 1, a 48-year-old homosexual black man presented with a 1-month history of alternating watery diarrhea and constipation, which dissipated following the removal of two colonic hyperplastic polyps containing IS. In case 2, a 26-year-old homosexual black man presented with a 3-month history of persistent bloody diarrhea and was found to have chronic shigellosis and IS. Pathologic findings of IS were similar in both cases. Basophilic fringes typical of IS covered the surfacing colonic epithelium and consisted of dense growths of spirochetes adherent to and oriented perpendicular to the plasma membranes of the surfacing epithelium. The spirochetes measured 3 to 5 microns in length and 0.2 micron in width, contained four to eight axial fibrils, and closely resembled Brachyspira aalborgi ultrastructurally. These cases are notable because the histopathologic changes of IS were more extensive than generally described. There was involvement of both the right colon and rectum by IS in case 2, and in both cases there was extension of the IS down into the crypts of Lieberkühn, spirochetal invasion of the colonic mucosa, and a conspicuous inflammatory response by macrophages in the underlying lamina propria.
Spirochete infestations occur in man and monkeys and have previously been studied in our laborato... more Spirochete infestations occur in man and monkeys and have previously been studied in our laboratory. The purpose of this paper is to compare the topography of colonic mucosa of the rhesus monkey in the presence and in the absence of spirochete infestations. The scanning electron microscope (SEM) observations were made at magnifications varying from 100 to 10 000. At identical magnifications, both light (LM) and transmission electron microscope (TEM) observations were made on sections. Mucosal structures were compared by these three methods. In addition, colonic mucosa observed by SEM was later sectioned and examined by TEM. The polygonal pattern and the central crypt of the normal mucosa seen at magnification 100–300 by SEM are not altered by the presence of spirochete infestations, At 1 000 magnifications, the normal surface seen as convoluted ridges under SEM is replaced by the granular surface representing multiple spirochetes at brush border. At 10 000 magnifications, the normal surface is divided into multiple hemispherical elevations. Normal colonic epithelium first studied by SEM was reembedded and sectioned for TEM in order to determine the nature of hemispherical elevations. This method demonstrates that these elevations do not represent the tip of microvilli but are the uneven distribution of metal deposits over the glycocalyx and microvilli. At the identical magnification, individual spirochetes are well distinguished and are oriented perpendicular to the mucosal surface. They are 5 μ long and 0.5 μ wide. As many as 1 800 organisms are present per square millimeter. The combined use of SEM, TEM, and LM has provided a new interpretation of normal colonic mucosal topography and its distinctive alteration by spirochete infestations.
Formaldehyde, acetaldehyde, malondialdehyde, glutaraldehyde and paraldehyde, when added in vitro ... more Formaldehyde, acetaldehyde, malondialdehyde, glutaraldehyde and paraldehyde, when added in vitro to platelet-rich plasma, generate a similar distinct platelet aggregation response which is dose dependent when measured with a manual visual microscopic technique and by computerized image analysis, 'computerized platelet aggregation analysis'. Light transmission aggregometry did not measure this aggregation in a reliable manner. The aggregating reaction was specific to the aldehyde group and was not seen when the aldehyde was replaced by an alcohol, ketone, or acetate group in the case of acetaldehyde. The maximal aggregating effect of these aldehydes was directly proportional to the number of aldehyde groups per molecule. Aggregation was found to require the presence of plasma, but not von Willebrand's factor.
Original Article from The New England Journal of Medicine Fatal Pneumonia Associated with Adeno... more Original Article from The New England Journal of Medicine Fatal Pneumonia Associated with Adenovirus Type 7 in Three Military Trainees.
American Journal of Clinical Pathology, Apr 1, 1981
Physicians can play an important role as consultants in the utilization of laboratory data by pro... more Physicians can play an important role as consultants in the utilization of laboratory data by providing interpretation, recommending action, and presenting rationale. These activities have been quantitated in 382 consecutive consultations provided by pathologists in the coagulation laboratory, and their statistical interrelationships have been analyzed. Quantitative characterization of the consultation is important, since the pathologist's professional role in patient care may no longer remain informal and undocumented. However, analogous evaluations can be applied to expose, evaluate, and improve the properties of clinical consultation in general.
Journal of the American College of Cardiology, Mar 1, 1993
We examined the relation between the level of urinary fibrinopeptide A and the presence of angiog... more We examined the relation between the level of urinary fibrinopeptide A and the presence of angiographic intracoronary thrombus in patients with unstable angina to determine whether this marker predicts active thrombus formation. Although it is known that thrombus plays a role in acute ischemic syndromes, a noninvasive method to predict its presence in individual patients with unstable angina has not been determined. Fibrinopeptide A is a polypeptide cleaved from fibrinogen by thrombin and thus is a sensitive marker of thrombin activity and fibrin generation. Angiographic thrombus, graded 0 to 4, and the presence of ST segment depression or T wave inversions, or both, on the electrocardiogram (ECG) were related to fibrinopeptide A levels in 24 patients with rest angina of new onset, 18 with crescendo angina, 19 with stable angina and 9 with chest pain but without coronary artery disease. All patients had chest pain within the 24 h of sample acquisition. The angiographic incidence of thrombus was significantly higher in patients with new onset of rest angina (67%, p < 0.001) and crescendo angina (50%, p < 0.001) as were fibrinopeptide A levels (p = 0.002). Fibrinopeptide A levels correlated significantly (p < 0.001) with the presence of a filling defect (grade 4 intracoronary thrombus) or contrast staining (grade 3). All patients with fibrinopeptide A > or = 8 ng/mg creatinine showed grade 3 to 4 thrombus and 15 of 16 patients with levels > or = 6.0 ng/mg creatinine exhibited angiographic evidence of thrombus (13 with grades 3 to 4). Patients with reversible ST changes on the ECG had significantly higher levels of fibrinopeptide A (p < 0.001), and ST changes correlated significantly with the presence of angiographic thrombus (p < 0.001). Nonetheless, a significant minority of patients with unstable angina had neither angiographic nor biochemical evidence of thrombus. Elevated fibrinopeptide A levels in unstable angina reflected active intracoronary thrombus formation and were present in patients with angina of new onset as well as crescendo angina. Reversible ST changes are accompanied by thrombin activity and angiographic thrombus formation. However, a sizable percentage of patients with unstable angina had no evidence of thrombus and these patients may have had transient platelet aggregation without fibrin thrombus formation.
Proceedings of the Annual Symposium on Computer Application in Medical Care, Nov 5, 1980
Page 1. EXAMINATION OF TiE DYNAMICS OF PLATELET AGGREGATION AND DISAGGREGATION USING COMPUTERIZED... more Page 1. EXAMINATION OF TiE DYNAMICS OF PLATELET AGGREGATION AND DISAGGREGATION USING COMPUTERIZED IMAGE ANALYSIS Ruth E. Dayhoff, MD, Jack A. Zeller, MD, Robert S. Ledley, DDS, Louis S. Rotolo ...
American Journal of Obstetrics and Gynecology, Aug 1, 1970
Abstract Plasminogen activator fibrinolytic activity and nonspecific protease fibrinolytic activi... more Abstract Plasminogen activator fibrinolytic activity and nonspecific protease fibrinolytic activity in uterine tissue controls and neoplasias were studied by the histochemical fibrin film method of Kwaan and Astrup. The frozen tissue sections of 2 to 3 μ thick were mounted on fibrin-plasminogen films and incubated at 37° C. for 60 minutes for demonstration of plasminogen activator fibrinolytic activity. Plasminogeninactivated control films by incubating at 80° C. for 45 minutes were used for nonspecific protease fibrinolytic activity. Plasminogen activator fibrinolytic activity was found not only in intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix, but also in areas of squamous metaplasia of the cervix and invasive endometrial adenoacanthoma. Nonspecific protease fibrinolytic activity was seen in endometrial carcinoma cells and in cervical intraepithelial neoplasia.
Platelet aggregation is a critical event in hemostasis and thrombosis, and therefore requires acc... more Platelet aggregation is a critical event in hemostasis and thrombosis, and therefore requires accurate measurement. Aggregometry, the most popular in vitro method for measurement of platelet aggregation, measures changes in light transmission as stimulated free platelets combine to form aggregates. However, it does not provide detailed information about the size and number of platelet aggregates and free platelets. The TEXAC image analyzer, using whole picture texture analysis, provides this information and is able to detect the presence of platelet aggregates in unstimulated and minimally stimulated conditions, which would otherwise be missed. Quantitative information may be of critical importance in the control of platelet behavior in patients with atherosclerotic and thrombotic disease.
VIIIth International Congress on Thrombosis and Haemostasis, 1981
Formaldehyde causes platelet aggregation (or agglutination) which varies with dosage. Aggregation... more Formaldehyde causes platelet aggregation (or agglutination) which varies with dosage. Aggregation was studied in ten blood samples drawn from normal volunteers. A small volume of formaldehyde was added to platelet rich plasma in a light transmission aggregcmeter to produce final formaldehyde concentrations between 0.1% and 8%. Measurements were made by three methods: (1) light transmission aggregometry, (2) visual semi-quantitative microscopic analysis, and (3) quantitative image analysis (Computerized Platelet Aggregation Analysis) . Using the visual semi-quantitative microscopic method, the dose response curve (expressed as the percentage of platelets involved in aggregates) increased from 11% at a formaldehyde concentration of 0.1% to 41% at a 0.5% formaldehyde concentration; it then decreased to 11% at a formaldehyde concentration of 8%. This curve may reflect the influence of two different formaldehyde effects: an aggregating effect which increases until about 0.5% concentratio...
Thromboembolic disease is a major cause of death in the United States today. Because platelet agg... more Thromboembolic disease is a major cause of death in the United States today. Because platelet aggregation plays an important role in thrombus formation, many attempts have been made to study it in vitro. The dynamics of platelet aggregation and disaggregation are of especial interest but are presently not well understood because the most commonly used method of study (light transmission aggregometry) is inadequate. Using the TEXAC whole picture image analyzer, a quantitative method has been developed for measuring platelet aggregation which provides a complete distribution of platelet aggregate sizes. Development of this new method called Computerized Platelet Aggregation Analysis (C.P.A.A.) required multi-stage removal of background noise, image enhancement of low contrast unstained particles (platelets), and derivation of a correction factor for chance adjacency of platelets. Platelets from four healthy volunteers were studied to determine the degree of aggregation and disaggregat...
Two cases of intestinal spirochetosis (IS) with acquired immunodeficiency syndrome are reported. ... more Two cases of intestinal spirochetosis (IS) with acquired immunodeficiency syndrome are reported. In case 1, a 48-year-old homosexual black man presented with a 1-month history of alternating watery diarrhea and constipation, which dissipated following the removal of two colonic hyperplastic polyps containing IS. In case 2, a 26-year-old homosexual black man presented with a 3-month history of persistent bloody diarrhea and was found to have chronic shigellosis and IS. Pathologic findings of IS were similar in both cases. Basophilic fringes typical of IS covered the surfacing colonic epithelium and consisted of dense growths of spirochetes adherent to and oriented perpendicular to the plasma membranes of the surfacing epithelium. The spirochetes measured 3 to 5 microns in length and 0.2 micron in width, contained four to eight axial fibrils, and closely resembled Brachyspira aalborgi ultrastructurally. These cases are notable because the histopathologic changes of IS were more extensive than generally described. There was involvement of both the right colon and rectum by IS in case 2, and in both cases there was extension of the IS down into the crypts of Lieberkühn, spirochetal invasion of the colonic mucosa, and a conspicuous inflammatory response by macrophages in the underlying lamina propria.
Spirochete infestations occur in man and monkeys and have previously been studied in our laborato... more Spirochete infestations occur in man and monkeys and have previously been studied in our laboratory. The purpose of this paper is to compare the topography of colonic mucosa of the rhesus monkey in the presence and in the absence of spirochete infestations. The scanning electron microscope (SEM) observations were made at magnifications varying from 100 to 10 000. At identical magnifications, both light (LM) and transmission electron microscope (TEM) observations were made on sections. Mucosal structures were compared by these three methods. In addition, colonic mucosa observed by SEM was later sectioned and examined by TEM. The polygonal pattern and the central crypt of the normal mucosa seen at magnification 100–300 by SEM are not altered by the presence of spirochete infestations, At 1 000 magnifications, the normal surface seen as convoluted ridges under SEM is replaced by the granular surface representing multiple spirochetes at brush border. At 10 000 magnifications, the normal surface is divided into multiple hemispherical elevations. Normal colonic epithelium first studied by SEM was reembedded and sectioned for TEM in order to determine the nature of hemispherical elevations. This method demonstrates that these elevations do not represent the tip of microvilli but are the uneven distribution of metal deposits over the glycocalyx and microvilli. At the identical magnification, individual spirochetes are well distinguished and are oriented perpendicular to the mucosal surface. They are 5 μ long and 0.5 μ wide. As many as 1 800 organisms are present per square millimeter. The combined use of SEM, TEM, and LM has provided a new interpretation of normal colonic mucosal topography and its distinctive alteration by spirochete infestations.
Formaldehyde, acetaldehyde, malondialdehyde, glutaraldehyde and paraldehyde, when added in vitro ... more Formaldehyde, acetaldehyde, malondialdehyde, glutaraldehyde and paraldehyde, when added in vitro to platelet-rich plasma, generate a similar distinct platelet aggregation response which is dose dependent when measured with a manual visual microscopic technique and by computerized image analysis, 'computerized platelet aggregation analysis'. Light transmission aggregometry did not measure this aggregation in a reliable manner. The aggregating reaction was specific to the aldehyde group and was not seen when the aldehyde was replaced by an alcohol, ketone, or acetate group in the case of acetaldehyde. The maximal aggregating effect of these aldehydes was directly proportional to the number of aldehyde groups per molecule. Aggregation was found to require the presence of plasma, but not von Willebrand's factor.
Original Article from The New England Journal of Medicine Fatal Pneumonia Associated with Adeno... more Original Article from The New England Journal of Medicine Fatal Pneumonia Associated with Adenovirus Type 7 in Three Military Trainees.
American Journal of Clinical Pathology, Apr 1, 1981
Physicians can play an important role as consultants in the utilization of laboratory data by pro... more Physicians can play an important role as consultants in the utilization of laboratory data by providing interpretation, recommending action, and presenting rationale. These activities have been quantitated in 382 consecutive consultations provided by pathologists in the coagulation laboratory, and their statistical interrelationships have been analyzed. Quantitative characterization of the consultation is important, since the pathologist's professional role in patient care may no longer remain informal and undocumented. However, analogous evaluations can be applied to expose, evaluate, and improve the properties of clinical consultation in general.
Journal of the American College of Cardiology, Mar 1, 1993
We examined the relation between the level of urinary fibrinopeptide A and the presence of angiog... more We examined the relation between the level of urinary fibrinopeptide A and the presence of angiographic intracoronary thrombus in patients with unstable angina to determine whether this marker predicts active thrombus formation. Although it is known that thrombus plays a role in acute ischemic syndromes, a noninvasive method to predict its presence in individual patients with unstable angina has not been determined. Fibrinopeptide A is a polypeptide cleaved from fibrinogen by thrombin and thus is a sensitive marker of thrombin activity and fibrin generation. Angiographic thrombus, graded 0 to 4, and the presence of ST segment depression or T wave inversions, or both, on the electrocardiogram (ECG) were related to fibrinopeptide A levels in 24 patients with rest angina of new onset, 18 with crescendo angina, 19 with stable angina and 9 with chest pain but without coronary artery disease. All patients had chest pain within the 24 h of sample acquisition. The angiographic incidence of thrombus was significantly higher in patients with new onset of rest angina (67%, p < 0.001) and crescendo angina (50%, p < 0.001) as were fibrinopeptide A levels (p = 0.002). Fibrinopeptide A levels correlated significantly (p < 0.001) with the presence of a filling defect (grade 4 intracoronary thrombus) or contrast staining (grade 3). All patients with fibrinopeptide A > or = 8 ng/mg creatinine showed grade 3 to 4 thrombus and 15 of 16 patients with levels > or = 6.0 ng/mg creatinine exhibited angiographic evidence of thrombus (13 with grades 3 to 4). Patients with reversible ST changes on the ECG had significantly higher levels of fibrinopeptide A (p < 0.001), and ST changes correlated significantly with the presence of angiographic thrombus (p < 0.001). Nonetheless, a significant minority of patients with unstable angina had neither angiographic nor biochemical evidence of thrombus. Elevated fibrinopeptide A levels in unstable angina reflected active intracoronary thrombus formation and were present in patients with angina of new onset as well as crescendo angina. Reversible ST changes are accompanied by thrombin activity and angiographic thrombus formation. However, a sizable percentage of patients with unstable angina had no evidence of thrombus and these patients may have had transient platelet aggregation without fibrin thrombus formation.
Proceedings of the Annual Symposium on Computer Application in Medical Care, Nov 5, 1980
Page 1. EXAMINATION OF TiE DYNAMICS OF PLATELET AGGREGATION AND DISAGGREGATION USING COMPUTERIZED... more Page 1. EXAMINATION OF TiE DYNAMICS OF PLATELET AGGREGATION AND DISAGGREGATION USING COMPUTERIZED IMAGE ANALYSIS Ruth E. Dayhoff, MD, Jack A. Zeller, MD, Robert S. Ledley, DDS, Louis S. Rotolo ...
American Journal of Obstetrics and Gynecology, Aug 1, 1970
Abstract Plasminogen activator fibrinolytic activity and nonspecific protease fibrinolytic activi... more Abstract Plasminogen activator fibrinolytic activity and nonspecific protease fibrinolytic activity in uterine tissue controls and neoplasias were studied by the histochemical fibrin film method of Kwaan and Astrup. The frozen tissue sections of 2 to 3 μ thick were mounted on fibrin-plasminogen films and incubated at 37° C. for 60 minutes for demonstration of plasminogen activator fibrinolytic activity. Plasminogeninactivated control films by incubating at 80° C. for 45 minutes were used for nonspecific protease fibrinolytic activity. Plasminogen activator fibrinolytic activity was found not only in intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix, but also in areas of squamous metaplasia of the cervix and invasive endometrial adenoacanthoma. Nonspecific protease fibrinolytic activity was seen in endometrial carcinoma cells and in cervical intraepithelial neoplasia.
Platelet aggregation is a critical event in hemostasis and thrombosis, and therefore requires acc... more Platelet aggregation is a critical event in hemostasis and thrombosis, and therefore requires accurate measurement. Aggregometry, the most popular in vitro method for measurement of platelet aggregation, measures changes in light transmission as stimulated free platelets combine to form aggregates. However, it does not provide detailed information about the size and number of platelet aggregates and free platelets. The TEXAC image analyzer, using whole picture texture analysis, provides this information and is able to detect the presence of platelet aggregates in unstimulated and minimally stimulated conditions, which would otherwise be missed. Quantitative information may be of critical importance in the control of platelet behavior in patients with atherosclerotic and thrombotic disease.
VIIIth International Congress on Thrombosis and Haemostasis, 1981
Formaldehyde causes platelet aggregation (or agglutination) which varies with dosage. Aggregation... more Formaldehyde causes platelet aggregation (or agglutination) which varies with dosage. Aggregation was studied in ten blood samples drawn from normal volunteers. A small volume of formaldehyde was added to platelet rich plasma in a light transmission aggregcmeter to produce final formaldehyde concentrations between 0.1% and 8%. Measurements were made by three methods: (1) light transmission aggregometry, (2) visual semi-quantitative microscopic analysis, and (3) quantitative image analysis (Computerized Platelet Aggregation Analysis) . Using the visual semi-quantitative microscopic method, the dose response curve (expressed as the percentage of platelets involved in aggregates) increased from 11% at a formaldehyde concentration of 0.1% to 41% at a 0.5% formaldehyde concentration; it then decreased to 11% at a formaldehyde concentration of 8%. This curve may reflect the influence of two different formaldehyde effects: an aggregating effect which increases until about 0.5% concentratio...
Thromboembolic disease is a major cause of death in the United States today. Because platelet agg... more Thromboembolic disease is a major cause of death in the United States today. Because platelet aggregation plays an important role in thrombus formation, many attempts have been made to study it in vitro. The dynamics of platelet aggregation and disaggregation are of especial interest but are presently not well understood because the most commonly used method of study (light transmission aggregometry) is inadequate. Using the TEXAC whole picture image analyzer, a quantitative method has been developed for measuring platelet aggregation which provides a complete distribution of platelet aggregate sizes. Development of this new method called Computerized Platelet Aggregation Analysis (C.P.A.A.) required multi-stage removal of background noise, image enhancement of low contrast unstained particles (platelets), and derivation of a correction factor for chance adjacency of platelets. Platelets from four healthy volunteers were studied to determine the degree of aggregation and disaggregat...
Uploads
Papers by Jack A Zeller