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1.
BMJ Case Rep ; 20102010 Aug 26.
Article in English | MEDLINE | ID: mdl-22767479

ABSTRACT

A 64-year-old woman was referred with a short history of abdominal pain, anorexia and weight loss. Investigations revealed a probable enteropathy associated T-cell lymphoma (EATL). Further investigations revealed evidence of what appeared to be a myocardial infarction. After going through laparoscopy to obtain diagnostic tissue, the patient developed cardiogenic shock which proved refractory to medical therapy. Postmortem examination revealed diffuse abdominal lymphoma consistent with EATL. Surprisingly, there was extensive infiltration of the myocardium. This report demonstrates an unusual pathology resulting from EATL and discusses the limited evidence relating to cardiac involvement of this disease.


Subject(s)
Cardiomyopathy, Restrictive/diagnosis , Celiac Disease/diagnosis , Enteropathy-Associated T-Cell Lymphoma/diagnosis , Myocardial Infarction/diagnosis , Autopsy , Biopsy, Needle , Cardiomyopathy, Restrictive/pathology , Celiac Disease/pathology , Coronary Angiography/methods , Diagnosis, Differential , Disease Progression , Echocardiography, Doppler/methods , Electrocardiography/methods , Enteropathy-Associated T-Cell Lymphoma/pathology , Enteropathy-Associated T-Cell Lymphoma/surgery , Fatal Outcome , Female , Humans , Immunohistochemistry , Laparotomy/methods , Middle Aged , Myocardial Infarction/diagnostic imaging , Postoperative Complications/physiopathology , Postoperative Complications/therapy
2.
J Clin Pathol ; 60(5): 487-91, 2007 May.
Article in English | MEDLINE | ID: mdl-16731598

ABSTRACT

BACKGROUND: The risk of encountering tuberculosis (TB) has reduced with the decreased incidence of the disease; however, it still can be found at autopsy. AIM: To assess the magnitude of exposure to Mycobacterium tuberculosis at autopsy in a large general hospital setting, in a country with low incidence. METHODS: Retrospective search of the autopsy records from 1991 to 2004. Patients' records and histological slides were reviewed, and medical personnel interviewed. RESULTS: 15 cases of active TB were identified in the 14-year period, during which 4930 autopsies were performed (1 case per 329 autopsies); of these, 10 cases were unsuspected (67%). Five of these cases contained abundant acid-fast bacilli. Patients tended to be middle aged and males with complex clinical histories; two were HIV positive. Two patients were brought in dead to hospital, with no clinical indication of TB. Of 15 autopsy staff, 1 required chemoprophylaxis but none contracted TB. CONCLUSION: The risk of unexpectedly encountering TB at autopsy continues even in a low-risk European setting. It has implications for the health of autopsy room staff, autopsy room design and ventilation, choice of protective equipment and for the public health service. Protective strategies include assessment of the risk of a case being infected, early recognition of gross lesions, use of methods for reducing the production of infected aerosols and protection against any aerosols created.


Subject(s)
Autopsy , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Mycobacterium tuberculosis/isolation & purification , Occupational Exposure/adverse effects , Tuberculosis/transmission , Adult , Aged , Female , Follow-Up Studies , Hospitals, General , Humans , Male , Middle Aged , Occupational Exposure/prevention & control , Personnel, Hospital , Retrospective Studies , Safety Management/methods , Tuberculosis/prevention & control
3.
Heart ; 91(3): e19, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15710690

ABSTRACT

A 60 year old woman presented with chest pain. An ECG showed ST depression across the anterior leads and lateral T wave inversion and angiography showed a significant proximal circumflex lesion. After percutaneous intervention to the circumflex artery she had a cardiac arrest and died. Postmortem examination found a stent blocked with a combination of thrombus and a tangle of translucent material. Embolic coronary artery occlusion is well described but this is the first report of embolisation of material arising from the lining of the guiding catheter as the cause.


Subject(s)
Arterial Occlusive Diseases/diagnostic imaging , Stents/adverse effects , Arterial Occlusive Diseases/etiology , Arterial Occlusive Diseases/therapy , Catheterization/methods , Coronary Angiography/methods , Coronary Vessels/pathology , Fatal Outcome , Female , Humans , Middle Aged
5.
J Urol ; 166(1): 255-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11435881

ABSTRACT

PURPOSE: To our knowledge innervation of the upper urinary tract and its role in motility and sensation are not clearly understood. The whole mount preparation technique provides 3-dimensional (D) morphology of the innervation and its relationship of branching and interconnecting nerve fibers to each other and to the neighboring tissues. Confocal laser scanning microscopy provides dramatic optical advantages for detecting 3-D structures in thick specimens. We investigated the distribution and morphology of the neuronal structures in the human upper urinary tract using the whole mount preparation technique and confocal laser scanning microscopy. MATERIALS AND METHODS: Whole mount preparations of the human renal pelvis and ureter were stained by standard immunohistochemical method using various neuronal markers (protein gene product 9.5, neuron specific enolase and neurofilament). The 3-D architecture of the specimens was investigated with the help of confocal laser scanning microscopy. RESULTS: We detected 2 mesh-like neuronal networks or plexus in the human upper urinary tract. The first and more prominent plexus was located in the submucosa between the lamina propria and tunica muscularis, and the second neuronal network was found between the smooth muscle fibers of the ureteral wall. There were frequent interconnections between the 2 networks in the ureteral wall. CONCLUSIONS: To our knowledge our study shows for the first time that there are 2 well formed mesh-like neuronal plexus in the human upper urinary tract. Our findings suggest that the autonomic nervous system of the human upper urinary tract may have a significant role in the propagation, coordination and modulation of ureteropelvic peristalsis.


Subject(s)
Kidney Pelvis/innervation , Kidney Pelvis/pathology , Nerve Net/pathology , Ureter/innervation , Ureter/pathology , Adolescent , Adult , Autopsy , Child , Culture Techniques , Female , Humans , Male , Microscopy, Confocal , Middle Aged , Sensitivity and Specificity
6.
Pediatr Surg Int ; 17(4): 299-303, 2001 May.
Article in English | MEDLINE | ID: mdl-11409166

ABSTRACT

Hirschsprung's disease (HD) is characterised by the absence of ganglion cells and the presence of hypertrophic nerve trunks in the distal bowel. It has been suggested that aganglionosis may be caused by failure of differentiation as a result of microenvironmental change after neuronal migration has occurred. Recently, it was reported that cell-adhesion molecules (CAMs) and fibroblast growth factors (FGFs) stimulate neurite outgrowth through activation of FGF receptors (FGFRs) in neurons. The aim of this study was to investigate the expression of CAMs FGFs, and FGFRs in ganglionic (NG) and aganglionic (AG) segments of HD in order to understand the role of CAM-FGF signalling in the pathogenesis of HD. Specimens from NG and AG segments of bowel from 11 patients with HD were obtained at the time of definitive pull-through operation, snap-frozen in OCT compound, and stored at -70 degrees C. Aganglionosis was confirmed by Haematoxylin and eosin staining and acetylcholinesterase histochemistry; 8-micron cryosections were immunostained using the standard streptavidinbiotin-immunoperoxidase method. The following antibodies were used as the first antibody; FGF2 and FGF7 for FGFs, FGFR1 and FGFR2 for FGFRs, NCAM, L1CAM, and N-cadherin for CAMs. FGF2, FGF7, and FGFR2 were expressed in neuronal tissue of NG segments as well as in hypertrophic nerves of AG segments. There was a lack of FGFRI expression in neuronal tissue of both NG and AG bowel. Immunoreactivity with all three CAMs was detected in ganglion cells in NG bowel and in hypertrophic nerve trunks in AG bowel. In contrast the numbers of CAM-positive nerve fibres in muscle layers were markedly decreased in AG bowel compared to NG bowel. The markedly decreased expression of CAMs on nerve fibres within the muscle of AG bowel suggests that CAM-FGF signalling is altered in HD, resulting in failure of enteric neuroblast migration.


Subject(s)
Fibroblast Growth Factors/physiology , Hirschsprung Disease/physiopathology , Neural Cell Adhesion Molecules/physiology , Receptors, Fibroblast Growth Factor/physiology , Signal Transduction/physiology , Cadherins/physiology , Child , Child, Preschool , Colon/pathology , Colon/physiopathology , Female , Fibroblast Growth Factor 7 , Ganglia/pathology , Ganglia/physiopathology , Hirschsprung Disease/pathology , Humans , Infant , Infant, Newborn , Leukocyte L1 Antigen Complex , Male , Membrane Glycoproteins/physiology , Receptor Protein-Tyrosine Kinases/physiology , Receptor, Fibroblast Growth Factor, Type 1 , Receptor, Fibroblast Growth Factor, Type 2
7.
Arch Pathol Lab Med ; 125(6): 759-64, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11371227

ABSTRACT

BACKGROUND: Appendices removed from patients with suspected appendicitis often appear normal on histologic examination. OBJECTIVE: To study appendix specimens for the expression of inflammatory markers as an indicator of presence of an inflammatory response in this subgroup of patients. METHODS: Cyclooxygenase 1 and 2, prostaglandin E(2), inducible nitric oxide synthase, and major histocompatibility complex class II were investigated by immunofluorohistochemistry using confocal laser microscopy in 15 acutely inflamed appendix specimens, 39 histologically classified "normal" appendices, and 11 negative control specimens. RESULTS: Strong expressions of all the inflammatory mediators were found in the mucosa of inflamed appendices, in approximately 50% of histologically normal appendices from patients with a clinical diagnosis of appendicitis, and in none of the normal control specimens. CONCLUSION: This study confirms the existence of a subgroup of appendicitis within the so-called histologically normal appendices in which evidence of an inflammatory pathologic condition is only obvious at a molecular level. The initiating signal for this and all other forms of clinical appendicitis still remains elusive.


Subject(s)
Appendicitis/pathology , Appendicitis/surgery , Appendix/pathology , Appendectomy , Appendicitis/diagnosis , Appendix/immunology , Appendix/metabolism , Case-Control Studies , Cyclooxygenase 1 , Cyclooxygenase 2 , Dinoprostone/metabolism , Emergencies , Histocompatibility Antigens Class II/metabolism , Humans , Immunohistochemistry , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Inflammation Mediators/metabolism , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Isoenzymes/metabolism , Membrane Proteins , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , Prostaglandin-Endoperoxide Synthases/metabolism
8.
Hematology ; 6(1): 65-8, 2001.
Article in English | MEDLINE | ID: mdl-27419606

ABSTRACT

Thrombotic thrombocytopenic purpura (TTP) is a systemic disease characterised by the presence of microvascular thrombi resulting from endothelial injury and platelet activation. Vascular occlusion leads to the clinical manifestations of ischaemicorgan damage, microangiopathic haemolytic anaemia and thrombocytopenia. Pancreatitis has rarely been described in association with TTP and has not been reported with TTP in pregnancy. We describe a case of pancreatic necrosis due to TTP which presented in the third trimester of pregnancy and we review the literature relating to this rare complication.

9.
J Am Coll Cardiol ; 36(7): 2257-62, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11127470

ABSTRACT

OBJECTIVES: We studied the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial selectin (E-selectin) on aortic valve endothelium in patients undergoing valve replacement. We also assessed the relation between serum levels and endothelial expression and also the changes in serum levels following surgery. BACKGROUND: Nonrheumatic aortic valve disease is believed to be a degenerative condition. Increased tissue and soluble adhesion molecule levels are described in inflammatory conditions. METHODS: Aortic valves from 22 surgical (16 bicuspid, 6 tricuspid) and 6 autopsy (4 normal, 2 thickened) cases were studied by immunohistochemistry. Soluble adhesion molecules were measured in peripheral blood preoperatively, and at 6 and 18 months postoperatively, and compared with controls. RESULTS: The majority of the surgically removed tricuspid and bicuspid valves expressed adhesion molecules (E-selectin, 75% and 100%; ICAM-1, 75% and 80%; VCAM-1, 69% and 60%, respectively). The normal postmortem valves did not express these, while the diseased ones did. Endothelial expression of E-selectin correlated strongly with serum levels (r = 0.695, p = 0.004). Soluble E-selectin levels were significantly higher at baseline compared with controls (p = 0.017) and fell significantly at 18 months postoperatively (p = 0.005). CONCLUSIONS: Adhesion molecule expression on diseased valves supports an inflammatory component in "degenerative" aortic valve disease. The diseased valves may be the main source of elevated soluble E-selectin in this condition as blood levels correlate with endothelial expression and blood levels fall at 18 months postoperatively.


Subject(s)
Aortic Valve , E-Selectin/blood , Endothelium, Vascular/metabolism , Heart Valve Diseases/blood , Intercellular Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/blood , Aged , Aortic Valve/surgery , Enzyme-Linked Immunosorbent Assay , Female , Heart Valve Diseases/surgery , Humans , Immunohistochemistry , Male , Middle Aged
10.
Arch Pathol Lab Med ; 124(10): 1429-33, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11035570

ABSTRACT

OBJECTIVE: The pathogenesis of appendicitis remains poorly understood. However, there is increasing evidence of involvement of the enteric nervous system in immune regulation and in inflammatory responses. This study was set up to characterize the status of the enteric nervous system in normal and in inflamed appendixes. METHODS: S100- and 2',2'-cyclic nucleotide 3' phosphodiesterase-positive Schwann cells, synaptophysin, and neuron-specific, enolase-positive nerve fibers and tryptase-positive mast cells were evaluated with immunohistochemical staining in surgically resected appendixes from 20 children with histologically proven acute appendicitis (HA), 10 histologically normal appendixes (HN) from patients with a clinical diagnosis of appendicitis, and 10 normal appendixes from patients undergoing elective abdominal surgery. Immunostained sections were subjected to quantitative image analysis. The number and size of ganglia and the number of nerve fibers, Schwann cells, and mast cells in each tissue compartment was quantitatively or semiquantitatively measured. RESULTS: Increased numbers of fibers, Schwann cells, and enlarged ganglia, widely distributed in the muscularis externa and submucosa, were seen in all HA appendixes and in 4 of 10 HN appendixes. The number and size of ganglia in muscularis externa and in the submucosa of appendixes with HA were significantly greater compared with those in control appendixes (P <.001). A significantly increased number of individually stained nerve fibers and Schwann cells (P <.05) were present in the muscularis externa in HA appendixes compared with control appendixes. Significantly increased numbers of tryptase-positive mast cells (P <.05) were present in the submucosa, muscularis, and especially in the lamina propria in HA specimens, compared with that of control tissue. CONCLUSIONS: The significant increase in neural components and mast cells in acute appendicitis is unlikely to develop during a single acute inflammatory episode. This suggests an underlying chronic abnormality as a secondary reaction to repeated bouts of inflammation, obstruction, or both. These results challenge our current understanding of the pathophysiological processes that give rise to acute appendicitis.


Subject(s)
Appendicitis/complications , Enteric Nervous System/pathology , Peripheral Nervous System Diseases/complications , 2',3'-Cyclic-Nucleotide Phosphodiesterases/metabolism , Acute Disease , Appendicitis/metabolism , Appendicitis/pathology , Child , Chymases , Enteric Nervous System/metabolism , Female , Humans , Hypertrophy , Immunoenzyme Techniques , Male , Nerve Fibers/metabolism , Nerve Fibers/pathology , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/pathology , Phosphopyruvate Hydratase/metabolism , S100 Proteins/metabolism , Schwann Cells/metabolism , Schwann Cells/pathology , Serine Endopeptidases/metabolism , Synaptophysin/metabolism , Tryptases
11.
Arch Pathol Lab Med ; 124(9): 1314-9, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10975929

ABSTRACT

OBJECTIVE: Hypertrophic nerves have long been considered a histopathologic feature of the aganglionic segment in Hirschsprung disease, but they remain incompletely explained. The purpose of this study was to define the nature and diagnostic importance of hypertrophic nerves in Hirschsprung disease and to clarify their relation to nearby smaller nerve fibers. METHODS: We used an immunoperoxidase staining technique to compare the distribution of 2 nerve markers-erythrocyte-type glucose transporter (GLUT-1), a marker of perineurium, and nerve growth factor receptor, a marker of both nerve fibers and perineurium-in aganglionic tissue (12 resected specimens and 4 rectal biopsies) and control tissue (6 autopsy specimens and 17 rectal biopsies) of children. RESULTS: In control ganglionic tissue, the myenteric and submucosal areas contained only occasional GLUT-1-positive nerves (usually less than 50 microm in diameter), but extramural extrinsic (serosal) nerves were invariably positive for GLUT-1. In aganglionic tissue, GLUT-1-positive nerves in the myenteric and submucosal areas were frequent and included both large (50-150 microm) and small (<50 microm) diameter nerves. Nerve growth factor receptor-positive fibers were frequent in all layers of all tissue studied. In aganglionic bowel, a distinct perineurium could be identified in the largest nerves, but nerve growth factor receptor had poor discrimination for small perineurium-sheathed nerves. CONCLUSION: Most nerves, of both large and small diameter, in the myenteric and submucosal plexus of aganglionic bowel are GLUT-1 positive. Serosal extrinsic nerves stain identically, supporting the interpretation that the mural nerves are of extrinsic origin. Mural GLUT-1-positive nerves, when they are multiple and especially when they are greater than 50 microm in diameter (a figure which may be used as a threshold for hypertrophic nerves), are suggestive of Hirschsprung disease.


Subject(s)
Colon/innervation , Hirschsprung Disease/metabolism , Hirschsprung Disease/pathology , Monosaccharide Transport Proteins/analysis , Nervous System/pathology , Biopsy , Glucose Transporter Type 1 , Hirschsprung Disease/surgery , Humans , Hypertrophy , Immunoenzyme Techniques , Nervous System/chemistry , Receptor, Nerve Growth Factor/analysis , Rectum/pathology , Rectum/surgery
12.
Gut ; 47(4): 514-9, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10986211

ABSTRACT

BACKGROUND: There is concern that the incidence of non-Hodgkin's lymphoma (NHL) will rise with increasing use of immunosuppressive therapy. AIMS: Our aim was to determine the risk of NHL in a large cohort of patients with inflammatory bowel disease (IBD), and to study the association between IBD, NHL, and immunosuppressive therapy. METHODS: We studied 782 IBD patients (238 of whom received immunosuppressive therapy) who attended our medical centre between 1990 and 1999 (median follow up 8.0 years). Standardised incidence ratios (SIRs) and 95% confidence intervals (CI) were calculated. Expected cases were derived from 1995 age and sex specific incidence rates recorded by the National Cancer Registry of Ireland. RESULTS: There were four cases of NHL in our IBD cohort (SIR 31.2; 95% CI 2.0-85; p=0.0001), all of whom had received immunosuppressive therapy: azathioprine (n=2), methotrexate (n=1), and methotrexate and cyclosporin (n=1). Our immunosuppressive group had a significantly (59 times) higher risk of NHL compared with that expected in the general population (p=0.0001). Three cases were intestinal NHL and one was mesenteric. Mean age at NHL diagnosis was 49 years, mean duration of IBD at the time of NHL diagnosis was 3.1 years, and mean duration between initiation of immunosuppressive therapy and diagnosis of NHL was 20 months. CONCLUSIONS: Although underlying IBD may be a causal factor in the development of intestinal NHL, our experience suggests that immunosuppressive drugs can significantly increase the risk of NHL in IBD. This must be weighed against the improved quality of life and clinical benefit immunosuppressive therapy provides for IBD patients.


Subject(s)
Colonic Diseases, Functional/drug therapy , Immunosuppressive Agents/adverse effects , Intestinal Neoplasms/epidemiology , Lymphoma, Non-Hodgkin/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Colonic Diseases, Functional/diagnosis , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Incidence , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/etiology , Ireland/epidemiology , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/etiology , Male , Middle Aged , Risk Factors , Severity of Illness Index
13.
Am J Forensic Med Pathol ; 21(4): 380-4, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11111802

ABSTRACT

Fracture and dislocation of major joints may be caused by the forceful tonic muscular contractions of seizure activity. A 77-year-old man who was found dead in bed with no sign of external trauma had bilateral central fracture dislocations of the femoral head through the acetabular floor with fatal pelvic hemorrhage and extensive pulmonary fat and bone marrow embolism. He had epilepsy, but the last seizure was 6 years earlier, and he had long discontinued medication. The fractures were attributed to a new unwitnessed seizure. This is the twentieth case of central fracture dislocation of the hip since 1970, when better anesthesia eliminated convulsive therapy-induced fractures. The authors review these 20 cases. Seizures followed inflammation, infarction or neoplasia of the brain, eclampsia, metabolic or iatrogenic causes, or epilepsy (6 cases, 2 of which had no prior seizures for 5 years). There were 11 men (mean age, 64 years) and 9 women (mean age, 47 years). Fractures were unilateral in 13 and bilateral in 7. Additional fractures (in vertebrae, shoulders, or femur) were present in eight. Only eight had prior bone disease. Local symptoms led to diagnosis in most, but two were identified incidentally on imaging. The current patient was the only one to die suddenly, but six other patients presented with shock and three died (one of whom had injuries that led to a suspicion of manslaughter). Central fracture-dislocation of the hip is a rare and little known consequence of seizures, with strong potential for misdiagnosis and lethal complications.


Subject(s)
Death, Sudden/etiology , Epilepsy/complications , Hemorrhage/etiology , Hip Fractures/complications , Acetabulum/injuries , Aged , Embolism, Fat/complications , Female , Femur Head/injuries , Hip Fractures/etiology , Humans , Male
15.
J Rheumatol ; 26(9): 1869-76, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10493664

ABSTRACT

OBJECTIVE: To examine the gastrointestinal (GI) immune system in rheumatoid arthritis (RA) for evidence of activation. METHODS: Duodenal biopsies from 25 patients with RA were obtained by endoscopy. Single cell suspensions from the epithelial layer and lamina propria were prepared. Flow cytometry was used to examine the expression of CD4, CD8, T cell receptor-gammadelta (TCR-gammadelta), TCR-alphabeta, HLA-DR, CD44, and interleukin 2 receptor on gut T lymphocytes. Fifteen disease control (DC) individuals and 6 patients with osteoarthritis (OA) taking longterm nonsteroidal antiinflammatory drug (NSAID) therapy were also investigated. Peripheral blood T lymphocytes from all individuals were examined for the expression of these surface molecules. RESULTS: HLA-DR expression was significantly increased on intraepithelial lymphocytes (IEL) and enterocytes from patients with RA (n = 13) compared with the 2 control groups (p<0.01). Immunohistochemistry also revealed increased expression of HLA-DR on enterocytes from patients with RA. RA IEL (n = 6) expressed significantly higher levels of CD44 (p<0.02). In the lamina propria, a small but significant gammadelta T lymphocyte population (mean 5.5%, range 2-12%) was detected in rheumatoid factor positive RA patients (n = 8) compared with RF negative RA patients (n = 8, mean 2%, range 0.4-6%; p<0.01) and the disease control group (n = 15, mean 2%, range 0.5-5%; p<0.01). None of these changes were detectable in peripheral blood lymphocytes from patients with RA. CONCLUSION: This study demonstrates evidence of activation of specific components of the GI immune system in RA. Peripheral blood T lymphocytes from patients with RA did not show increased expression of activation markers, suggesting that changes in the RA GI tract are not systemic but localized. Moreover, these changes appear to be independent of NSAID therapy.


Subject(s)
Arthritis, Rheumatoid/immunology , Digestive System/immunology , HLA-DR Antigens/analysis , Hyaluronan Receptors/analysis , Intestinal Mucosa/immunology , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/pathology , Biomarkers/analysis , Biopsy, Needle , Digestive System/pathology , Duodenoscopy , Duodenum/immunology , Duodenum/pathology , Female , Flow Cytometry , Humans , Immunohistochemistry , Intestinal Mucosa/pathology , Male , Middle Aged , Monocytes/immunology , Reference Values , Sensitivity and Specificity
16.
Pediatr Surg Int ; 15(3-4): 243-7, 1999.
Article in English | MEDLINE | ID: mdl-10370035

ABSTRACT

Wilms' tumor (WT) usually has a good outcome, although a poor prognosis is often related to more advanced stages and anaplastic features. Apoptosis occurs with variable frequency in malignant tumors, and may have a role in reducing their growth rate. The bcl-2 proto-oncogene inhibits apoptosis, and the consequent increase in the number of cells may play a role in the development of tumors. The aim of this study was to analyze the role of apoptosis and bcl-2 expression in WT. Twenty-six resected WT specimens were studied; 12 patients had stage I tumor, 4 stage II, 5 stage III, 3 stage IV, and 2 stage V. Twenty-three tumors were classified as favorable histology (FH) and 3 as unfavorable (UH). The mean follow-up was 34 months; 22 patients were alive and 4 were dead (2 with FH: 1 stage III and 1 stage IV, and 2 with UH stages 4). Apoptosis was detected by the in-situ end-labelling technique; bcl-2 expression was detected by immunohistochemistry. An apoptotic index (AI) was calculated as the ratio of apoptotic to normal cells in each specimen. The AI was lower in higher tumor stages, with a significant difference between stages I and IV (P < 0.05). In cases with UH, Al was lower than in tumors with FH (P < 0.01). The AI was also lower in patients who died than in those who survived (P < 0. 01). In all specimens no correlation between AI and bcl-2 expression was observed. Progression to advanced stages of WT and a poor prognosis f anaplastic tumors may be linked with disruption of the mechanisms that control apoptosis. Bcl-2 does not play a role as a regulator of apoptosis in WT, other oncogenes and tumor-suppression genes may be more involved in inhibiting apoptosis in WT.


Subject(s)
Apoptosis , Genes, bcl-2/genetics , Kidney Neoplasms/genetics , Wilms Tumor/genetics , Child, Preschool , Female , Follow-Up Studies , Humans , Immunohistochemistry , Male , Proto-Oncogene Mas
17.
Gut ; 44(5): 666-74, 1999 May.
Article in English | MEDLINE | ID: mdl-10205203

ABSTRACT

BACKGROUND: Nitric oxide is the most important transmitter in non-adrenergic non-cholinergic nerves in the human gastrointestinal tract. Impaired nitrergic innervation has been described in Hirschsprung's disease, hypertrophic pyloric stenosis, and intestinal neuronal dysplasia (IND). Recent findings indicate that hyperganglionosis, one of the major criteria of IND, is age dependent. However, information is scanty regarding the neurone density in normal human bowel in the paediatric age group. AIMS: To determine neurone density, morphology, and nitric oxide synthase distribution of the normal myenteric plexus at different ages during infancy and childhood. METHODS: Specimens were obtained from small bowel and colon in 20 children, aged one day to 15 years, at postmortem examination. Whole mount preparations were made of the myenteric plexus, which were subsequently stained using NADPH diaphorase histochemistry (identical to nitric oxide synthase) and cuprolinic blue (a general neuronal marker). The morphology of the myenteric plexus was described and the neurone density estimated. RESULTS: The myenteric plexus meshwork becomes less dense during the first years of life. The density of ganglion cells in the myenteric plexus decreases significantly with age during the first three to four years of life. The NADPH diaphorase positive (nitrergic) subpopulation represents about 34% of all neurones in the myenteric plexus. CONCLUSIONS: The notable decrease in neurone density in the myenteric plexus during the first years of life indicates that development is still an ongoing process in the postnatal enteric nervous system. Applied to the clinical situation, this implies that interpretation of enteric nervous system pathology is dependent on the age of the patient.


Subject(s)
Intestines/innervation , Myenteric Plexus/growth & development , Adolescent , Age Factors , Cell Count , Child , Child, Preschool , Coloring Agents , Humans , Indoles , Infant , Infant, Newborn , Intestines/enzymology , Myenteric Plexus/anatomy & histology , Myenteric Plexus/enzymology , NADPH Dehydrogenase/metabolism , Neurons/cytology , Nitric Oxide Synthase/metabolism , Organometallic Compounds
19.
Pediatr Surg Int ; 13(8): 581-3, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9799380

ABSTRACT

We examined immunohistochemically the expression and localisation of synapse-associated proteins, syntaxin (SNT) and synaptotagmin (STG) in the entire resected specimens of colon obtained at the time of pull-through operation from 15 patients with Hirschsprung's disease (HD) and 6 age-matched controls. Both antibodies showed a similar pattern of staining. In the normal colon and ganglionic colon from HD, there was strong reactivity in the submucous and myenteric plexuses in addition to staining of nerve fibres in the smooth-muscle layers. In the aganglionic colon, there was an absence or marked decrease in SNT and STG-positive nerve fibres in the smooth-muscle layers and in hypertrophic nerve trunks. Our data indicate that important proteins necessary for the docking of synaptic vesicles at the presynaptic plasma membrane are lost in fibres innervating the smooth muscle of HD and suggest that abnormal neurotransmission may have a role in the maintenance of muscle spasticity.


Subject(s)
Calcium-Binding Proteins , Colon/innervation , Hirschsprung Disease/metabolism , Membrane Glycoproteins/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Case-Control Studies , Child , Child, Preschool , Colon/metabolism , Hirschsprung Disease/surgery , Humans , Immunohistochemistry , Infant , Infant, Newborn , Qa-SNARE Proteins , Synaptotagmins
20.
Eur Urol ; 34(3): 233-6, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9732200

ABSTRACT

OBJECTIVE: Polytetrafluoroethylene (PTFE) paste has been used for over 30 years to treat urinary incontinence and for 14 years to treat vesicoureteral reflux with little reported morbidity. Some investigators have been concerned by the use of PTFE as the implanted substance, because migration of PTFE particles from the site of injection in the periurethral and periureteral regions to the lungs and brain has been reported in animal studies. We injected PTFE paste intravascularly in dogs in order to investigate its effect on brain parenchyma. METHODS: A total of 12 mongrel dogs, weighing 11.5-17.5 kg, were divided into four groups. Group 1 (n = 3): injection of 0.5 ml of PTFE paste suspended in 50 ml of saline into a peripheral vein once a week for 4 weeks. Group 2 (n = 3): injection of 50 ml of saline into a peripheral vein once a week for 4 weeks as controls. Group 3 (n = 3): one injection of 0.1 ml of PTFE paste suspended in 20 ml of saline into the right carotid artery. Group 4 (n = 3): one injection of 20 ml of saline into the right carotid artery as controls. After an interval of 6 months, all animals were sacrificed and the lungs and brain removed. Brain from 1 animal in each group was dissolved in sodium hypochlorite solution, the resulting organ suspension was centrifuged, and the smear preparations of the precipitate examined by polarized light microscopy, scanning electron microscopy, and X-ray microanalysis. Brains from 2 animals in each group were fixed in formalin solutions, 6-micrometer sections were cut and stained with haematoxylin and eosin, Cajal stain for Purkinje fibre, and Luxol fast blue stain for myelin, and glial fibrillary acidic protein immunohistochemistry was carried for astrocytes using monoclonal mouse anti-GFAP (glial fibrillary acidic protein) at a dilution of 1:50 with an avidin-biotin-peroxidase complex method. RESULTS: PTFE particles were seen in the cerebral vessels in only those animals who had PTFE injected into the right carotid artery. The haematoxylin and eosin staining showed PTFE particles in vessels with focal foreign-body reaction, but no infarction. Luxol fast blue staining showed no demyelination around vessels containing the particles and the parenchyma. Cajal staining demonstrated no abnormality of nerve fibres, and there was no astrocytosis using GFAP immunohistochemical staining. CONCLUSIONS: Our findings indicate that following intravenous injection, there was no evidence of migration of PTFE to the brain. Small quantities of PTFE injected into the carotid arteries were associated with local foreign-body reaction, but no brain parenchymal tissue damage was found.


Subject(s)
Brain/pathology , Foreign-Body Migration/pathology , Polytetrafluoroethylene/toxicity , Animals , Brain/drug effects , Carotid Arteries , Dogs , Foreign-Body Reaction/pathology , Injections, Intra-Arterial , Injections, Intravenous , Lung/drug effects , Lung/pathology , Polytetrafluoroethylene/administration & dosage
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