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1.
Colorectal Dis ; 9(5): 412-9, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17504337

ABSTRACT

OBJECTIVE: The aims were to determine agreement between staging of rectal cancer made by magnetic resonance imaging (MRI) and histopathological examination and the influence of MRI on choice of radiotherapy (RT) and surgical procedure. METHOD: In this retrospective audit, preoperative MRI was performed on 91 patients who underwent bowel resection, with 93% having total mesorectal excision. Tumour stage according to mural penetration, nodal status and circumferential resection margin (mCRM) involvement was assessed and compared with histopathology. RESULTS: Five radiologists interpreted the images. Overall agreement between MRI and histopathology for T stage was 66%. The greatest difficulty was in distinguishing between T1, T2 and minimal T3 tumours. The accuracy for mCRM (MRI) was 86% (78/91),with an interobserver variation between 80% and 100%. In the 13 cases with no agreement between mCRM and pCRM (pathological), seven had long-term RT and nine en bloc resections, indicating that the margins initially were involved with an even higher accuracy for mCRM. Preoperative short-term RT was routine, but based on MRI findings, choice of RT was affected in 29 cases (32%); 17 patients had no RT and 12 long-term RT. The surgical procedure was affected in 17 cases (19%) with planned perirectal en bloc resections in all. CRM was involved (< or = 1 mm) in 14.7% of the 34 cases in which MRI had an effect upon choice of RT and/or surgery compared with 8.8% of the remaining 57 cases where it had no impact. CONCLUSION: Magnetic resonance imaging predicted CRM with high accuracy in rectal cancer. MRI could be used as a clinical guidance with high reliability as indicated by the low figures of histopathologically involved CRM.


Subject(s)
Colorectal Neoplasms/pathology , Magnetic Resonance Imaging , Neoplasm Staging/methods , Radiotherapy, Adjuvant/methods , Adult , Aged , Aged, 80 and over , Colectomy/methods , Colorectal Neoplasms/diagnosis , Female , Humans , Male , Middle Aged , Observer Variation , Predictive Value of Tests , Prognosis , Retrospective Studies
2.
Colorectal Dis ; 9(8): 706-12, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17535279

ABSTRACT

OBJECTIVE: Circumferential resection margin (CRM) involvement has been correlated with a high risk of developing local recurrence. The aim of this study was to examine the prognostic significance of the CRM involvement after curative resection of rectal cancer in patients treated with preoperative radiotherapy and postoperative chemotherapy where indicated. METHOD: All patients with rectal cancer treated in a regional central unit from 1996 to 2004 were identified. A surgical resection was performed on 257 patients, and in 229 of these this was assessed as potentially curative. The CRM was examined in all patients. A CRM of < or = 1 mm was considered positive. RESULTS: A positive margin was seen in 19 (8%) patients. At a median follow up of 40 months, only four (1.7%) patients had developed local recurrence, one of whom had a positive CRM. In the four patients the tumour was 5 cm or less from the anal verge. There were no significant differences regarding local recurrence and survival between CRM positive and negative tumours. CONCLUSION: Rectal cancer managed by combined radiochemotherapy and surgery resulted in a low positive CRM rate and a low local recurrence rate. An involved CRM was not a predictor of local recurrence.


Subject(s)
Neoplasm Recurrence, Local , Rectal Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Preoperative Care , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , Survival Rate
3.
Eur J Surg Oncol ; 31(4): 381-5, 2005 May.
Article in English | MEDLINE | ID: mdl-15837044

ABSTRACT

AIMS: Lymphatic mapping and sentinel node biopsy entails better staging in malignant melanoma and breast cancer and we used this technique in patients with colon cancer to possibly improve detection of lymphatic spread. METHODS: Thirty patients with invasive adenocarcinomas were investigated. The tumour status in identified sentinel node(s) was compared with the status in all other harvested regional nodes for each patient. Patients were followed at regular visits for more than 30 months. RESULTS: Sentinel nodes were identified in all cases, either per-operatively (28 cases) or at dissection of the formalin-fixed specimen (2 cases). The sentinel nodes were diagnostic for the entire lymphatic field in 28 patients and the false negative rate was 2/12. In four cases, the sentinel nodes were the only metastatic nodes. After at minimum 30 months, three patients had died of colon cancer metastases. CONCLUSION: This method improved the identification of patients with lymph-node metastases, especially those with only few metastatic nodes. Patients dying from metastatic disease had lymph-node metastases at diagnosis.


Subject(s)
Adenocarcinoma/pathology , Colonic Neoplasms/pathology , Lymphatic Metastasis , Sentinel Lymph Node Biopsy/methods , Adenocarcinoma/mortality , Aged , Aged, 80 and over , Colonic Neoplasms/mortality , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Staining and Labeling , Survival Analysis
4.
Scand J Gastroenterol ; 37(8): 884-90, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12229961

ABSTRACT

BACKGROUND: The exact role of Helicobacter pylori as a causative agent of gastric cancer is still under debate. The aim of this study was to determine how the use of different diagnostic methods for detection of H. pylori influences the measures of prevalence of the infection and thus the association with risk of gastric adenocarcinoma. METHODS: We included 72 cases and 324 controls in an endoscopy clinic-based matched case-control study. Culture of H. pylori and immunohistochemical staining were performed on gastric biopsies. Serum samples were tested for H. pylori IgG by conventional ELISA and by immunoblotting. RESULTS: The overall prevalence of H. pylori was 68% based on all 4 diagnostic methods, 79% in the cases and 66% in the controls. Highest agreement, 91%, was observed between culture and immunohistochemistry with a Kappa value of 0.81. Immunoblotting detected the highest number of H. pylori-positive subjects in both cases and controls. The association of H. pylori positivity with gastric cancer was generally weaker and statistically non-significant using culture and immunohistochemistry compared with the serological tests, of which IgG ELISA yielded the higher odds ratio (OR 2.5, 95% confidence interval 1.4-4.4). CONCLUSION: The study shows that relative risk estimates for the association between H. pylori and gastric cancer risk are to some extent determined by the diagnostic method used to detect H. pylori infection.


Subject(s)
Adenocarcinoma/microbiology , Helicobacter Infections/diagnosis , Helicobacter pylori , Stomach Neoplasms/microbiology , Aged , Antibodies, Bacterial/analysis , Antigens, Bacterial/analysis , Bacterial Proteins/analysis , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastritis/microbiology , Helicobacter Infections/complications , Helicobacter pylori/immunology , Helicobacter pylori/isolation & purification , Humans , Immunoblotting , Immunoglobulin G/analysis , Immunohistochemistry , Male , Models, Statistical , Multivariate Analysis , Odds Ratio , Risk Factors , Sensitivity and Specificity
5.
J Clin Microbiol ; 38(10): 3555-60, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11015363

ABSTRACT

In this study we report on the isolation and characterization of the intestinal spirochete Brachyspira aalborgi using human mucosal biopsy specimens taken from the colon of a young adult male with intestinal spirochetosis. A selective medium, containing 400 microg of spectinomycin/ml and 5 microg of polymyxin/ml was used for the isolation procedure. A high degree of similarity, in terms of phenotypic properties and 16S ribosomal DNA sequence, was observed between the isolated strain, named W1, and the type strain, 513A, of B. aalborgi. A similarity of 99.7% in the nucleotide sequence was found between W1 and 513A(T), based on the almost-complete gene. A short segment of the 16S rRNA gene was amplified by PCR using genetic material enriched from paraffin-embedded biopsy specimens, which were taken from the patient on two occasions. The products showed 16S rRNA gene sequences virtually identical to that of strain 513A(T) in the actual region. Immunohistochemistry was performed on the colonic biopsy specimens with a polyclonal antibody raised against an intestinal spirochete isolated in a previous case of human intestinal spirochetosis. The antibody reacted strongly with the spirochete on the luminal epithelium. No immune reaction was seen within or below the surface epithelium. Routine histology did not reveal signs of colitis. Electron microscopy showed spirochetes attached end-on to the colonic mucosal surface. The isolate grew poorly on a commonly used selective medium for intestinal spirochetes, which may explain previous failures to isolate B. aalborgi.


Subject(s)
Intestinal Mucosa/microbiology , Spirochaetaceae , Spirochaetales Infections/diagnosis , Adult , Biopsy , Colon/microbiology , Colon/pathology , DNA, Ribosomal/genetics , Humans , Intestinal Mucosa/pathology , Male , Microscopy, Electron , Microvilli/microbiology , Microvilli/pathology , Microvilli/ultrastructure , Phenotype , RNA, Ribosomal, 16S/genetics , Spirochaetaceae/classification , Spirochaetaceae/isolation & purification , Spirochaetales Infections/pathology
6.
Cancer Epidemiol Biomarkers Prev ; 9(9): 981-5, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11008919

ABSTRACT

The aim of this novel endoscopy clinic-based case-control study was to explore the influence of different Helicobacter pylori strain types on the risk of gastric adenocarcinoma using isolated bacterial strains, tissue samples, and sera. We included 72 cases with gastric adenocarcinoma and 324 age- and sex-matched controls. Histological characterization, culture, molecular typing of H. pylori genes by PCR (cagA/vacA), conventional IgG ELISA, and immunoblotting (Western blot) for the CagA and VacA proteins were performed. With four tests combined, H. pylori infection was detected in 57 (79%) cases and 213 (66%) controls. A positive association between H. pylori infection and gastric cancer risk was found [odds ratio (OR), 2.1; 95% confidence interval, 1.1-3.9]. Type I (OR, 1.8), intermediate (OR, 2.0), and type H (OR, 0.2) strains of H. pylori presented different serum antibody levels and different levels of association with gastric cancer. Our case-control study, based on molecular characterization and serology, provides further evidence that infection by more virulent strains of H. pylori and the presence of antibodies toward the CagA protein can be used as markers for an increased risk of gastric adenocarcinoma and that the strain types of H. pylori could be used in the future to determine disease outcome.


Subject(s)
Adenocarcinoma/microbiology , Antigens, Bacterial , Helicobacter pylori/pathogenicity , Stomach Neoplasms/microbiology , Adenocarcinoma/etiology , Aged , Bacterial Proteins/analysis , Bacterial Typing Techniques , Biomarkers, Tumor , Case-Control Studies , Female , Gastric Mucosa/microbiology , Helicobacter Infections/complications , Helicobacter pylori/classification , Humans , Logistic Models , Male , Odds Ratio , Risk Factors , Stomach Neoplasms/etiology , Virulence
7.
Int J Cancer ; 86(3): 337-43, 2000 May 01.
Article in English | MEDLINE | ID: mdl-10760820

ABSTRACT

Regulation of cell differentiation is most often impaired in malignant tumors and may represent a key mechanism for the progression of the disease. CCAAT-enhancer binding protein (C/EBP) is a family of transcription factors involved in the regulation of embryonic gut development in rodents, which has also been detected in various malignancies, e.g., liposarcomas and breast and ovarian epithelial tumors. We studied the relationship between C/EBP and tumor histology (Duke's invasive stage and pathological grade) in colorectal cancer. Immunoblotting techniques were used on microdissected fresh frozen tumor specimens, and expression of C/EBPalpha, C/EBPbeta and C/EBPzeta (CHOP) was analyzed in addition to that of the cell-cycle regulator p53 and the proliferation marker PCNA. Expression of C/EBPbeta (LAP isoforms) was markedly increased in all tumors compared with normal colon mucosa. Although the inter-patient variability was large, we found that LIP, the isoform of C/EBPbeta known to inhibit transcription, was expressed at higher levels in Duke's stage B tumors compared with Duke's stage A, whereas Duke's C tumors had the lowest LIP expression. A similar relationship was seen for CHOP. The cell-cycle regulator gene p53 was the only factor that clearly correlated with pathological grade: a decrease in p53 expression was demonstrated. Our data suggest that genetic and cellular events involving C/EBPbeta and CHOP are important for tumor invasion and that these events do not appear to be related to the pathological grade of the tumor.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Neoplasm Invasiveness/genetics , Nuclear Proteins/genetics , Transcription Factors/genetics , Aged , Aged, 80 and over , CCAAT-Enhancer-Binding Proteins , Cell Division/genetics , Colorectal Neoplasms/metabolism , DNA-Binding Proteins/biosynthesis , Female , Humans , Male , Middle Aged , Nuclear Proteins/biosynthesis , Transcription Factor CHOP , Transcription Factors/biosynthesis , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
8.
Br J Dermatol ; 142(1): 44-51, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10651693

ABSTRACT

In a previous screening study, 16% of patients with psoriasis had IgA and/or IgG antibodies to gliadin (AGA). The aim of the present study was to evaluate the effect of a gluten-free diet (GFD) in 33 AGA-positive and six AGA-negative psoriasis patients. Of the 33 AGA-positive patients, two had IgA antibodies to endomysium (EmA) and 15 an increased number of lymphocytes in the duodenal epithelium, but in some this increase was slight. Two patients had villous atrophy. A 3-month period on a GFD was followed by 3 months on the patient's ordinary diet. The severity of psoriasis was evaluated with the psoriasis area and severity index (PASI). The examining dermatologists were unaware of the EmA and duodenal biopsy results throughout the study. Thirty of the 33 patients with AGA completed the GFD period, after which they showed a highly significant decrease in mean PASI. This included a significant decrease in the 16 AGA-positive patients with normal routine histology in duodenal biopsy specimens. The AGA-negative patients were not improved. After GFD, the AGA values were lower in 82% of those who improved. There was a highly significant decrease in serum eosinophil cationic protein in patients with elevated AGA. When the ordinary diet was resumed, the psoriasis deteriorated in 18 of the 30 patients with AGA who had completed the GFD period. In conclusion, psoriasis patients with raised AGA might improve on a GFD even if they have no EmA or if the increase in duodenal intraepithelial lymphocytes is slight or seemingly absent.


Subject(s)
Antibodies/analysis , Gliadin/immunology , Glutens/therapeutic use , Psoriasis/diet therapy , Adolescent , Adult , Aged , Arthralgia/etiology , Arthritis/etiology , Biopsy , Celiac Disease/diet therapy , Celiac Disease/pathology , Female , Glutens/blood , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Male , Middle Aged , Psoriasis/immunology
9.
FEMS Immunol Med Microbiol ; 23(3): 253-7, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10219598

ABSTRACT

The gastric bacterial flora and its influence on the 13C-urea breath test (UBT) for detection of Helicobacter pylori infection was studied in a pig model. Seven SPF minipigs were used. H. pylori or a mix of other urease positive bacteria were administered orally. UBT, serum and biopsies for histology and culture were collected. Our results show that UBT is not specific for H. pylori in pigs as the gastric bacterial flora is responsible for the high UBT values observed. Furthermore, the Ellegaard Göttingen SPF minipigs are not useful in an animal model for H. pylori studies.


Subject(s)
Helicobacter Infections/microbiology , Helicobacter pylori/enzymology , Helicobacter pylori/isolation & purification , Urea , Urease/biosynthesis , Animals , Carbon Isotopes , Female , Swine
10.
Med Oncol ; 15(4): 255-61, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9951689

ABSTRACT

In this study the entire p53 complementary DNA has been sequenced in 20 non-small cell lung carcinomas (NSCLC) and the results correlated with chemosensitivity, immunohistochemistry and clinical data. Ten patients had mutations in p53, 8 missense mutations and 2 nonsense mutations. The method discovered two mutations never described previously and two other mutations that have never been described before in connection with NSCLC tumours. Chemosensitivity data, according to a short-term assay (FMCA), indicated that tumours with p53 mutation were more resistant to cisplatin and cyclophosphamide. Immunohistochemical studied demonstrated a 70% concordance between over-expression of p53 protein and mutation in p53. No conclusions or trends could be drawn from the immunohistochemical studies of Bcl-2 and Bax.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Genes, p53/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Sequence Analysis, DNA/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , DNA, Complementary , Drug Resistance , Drug Resistance, Neoplasm , Female , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Male , Middle Aged , Mutation , Tumor Suppressor Protein p53/metabolism
11.
Acta Derm Venereol ; 77(5): 343-6, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9298124

ABSTRACT

The aim of this work was to study tryptase+ mast cells and CD3+ T lymphocytes in non-involved skin in psoriasis and their possible relation to mast cells and lymphocytes in the duodenal mucosa. Skin biopsy specimens were obtained from 43 patients with psoriasis of variable severity and from 10 healthy subjects. Compared with the reference subjects, the number of mast cells in non-involved skin was clearly increased, most markedly in the papillary dermis. The increase was present both in mild, moderate and severe psoriasis. CD3+ lymphocytes were increased in non-involved skin in moderate and severe psoriasis. Patients with an increased number of duodenal intraepithelial lymphocytes had significantly more mast cells in non-involved skin than those without such an increase, and there was a significant correlation between the number of mast cells in non-involved skin and score for intraepithelial lymphocytes. However, when the 14 patients with increased intraepithelial duodenal lymphocytes were excluded-as they may represent a separate type of psoriasis-another type of correlation between the skin and the duodenal mucosa was found, namely a highly significant inverse correlation between the number of CD3+ lymphocytes in non-involved skin and the number of duodenal mast cells, which is highly elevated in psoriasis. The results might indicate an interplay between skin and intestinal mast cells and lymphocytes in a hitherto unknown way.


Subject(s)
CD3 Complex/analysis , Duodenum/pathology , Mast Cells/pathology , Psoriasis/pathology , Skin/pathology , T-Lymphocytes/pathology , Adult , Aged , Biopsy/methods , Cell Count , Epithelium/pathology , Female , Gastroscopy , Humans , Immunohistochemistry , Intestinal Mucosa/pathology , Male , Middle Aged , Probability , Reference Values , T-Lymphocytes/chemistry
12.
Radiology ; 204(2): 533-8, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9240549

ABSTRACT

PURPOSE: To investigate whether endosonography is reliable in making radiation therapy decisions in rectal cancer, with possible downstaging taken into consideration. MATERIALS AND METHODS: Ninety patients (52 men, 38 women; median age, 69 years) with rectal adenocarcinoma underwent endosonography within 2 weeks before surgery and radiation therapy (performed in 54 patients). The tumor invasive edge was used for radiation therapy decision making. RESULTS: The local stage was accurately assessed in 65 patients (39 with and 26 without irradiation). The tumor invasive edge was accurately assessed in 63 patients. Overstaging was present in 19 patients; the tumor had grown almost through the muscularis propria in six. The invasive edge (P = .1) and lymph node status were overstaged more often in the patients with than in the patients without irradiation. Tumor was understaged in eight patients: The invasive edge did not penetrate but there was budding beyond the muscularis propria in five; the invasive edge penetrated the muscularis propria in two. In seven of the eight patients, growth beyond the muscularis propria was smaller than the endosonographic resolution. Three patients with understaged, nonirradiated tumors developed pelvic recurrence. None of the patients with irradiation and none of the 16 patients without irradiation but with correct assessment developed pelvic recurrence. CONCLUSION: Preoperative irradiation decision making on the basis of endosonographic findings is uncertain. Downstaging after preoperative irradiation must be considered.


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/pathology , Rectum/pathology , Adenocarcinoma/therapy , Aged , Combined Modality Therapy , Endosonography , Female , Humans , Male , Neoplasm Invasiveness , Neoplasm Staging , Rectal Neoplasms/therapy , Rectum/diagnostic imaging
13.
Br J Dermatol ; 136(6): 866-70, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9217818

ABSTRACT

We have shown that the number of tryptase-positive mast cells in the duodenal mucosa in psoriasis is increased and that a subgroup of psoriasis patients showed elevated levels of antibodies to gliadin (some of whom also had increased lymphocytes in the duodenal epithelium). Duodenal biopsy specimens from 37 patients with psoriasis (eight mild, 13 moderate and 16 severe) and 22 patients with irritable bowel syndrome (IBS) were examined regarding the presence of tryptase + mast cells. Intraepithelial infiltration by lymphocytes was evaluated and scored from 0 to 3. Patients with psoriasis had 131 +/- 58 mast cells/mm2 (mean +/- SD) and those with IBS 28 +/- 18. Only in four of the 37 psoriasis patients was the number within the range of that in the IBS group. There were no signs of stromal inflammation except in one psoriasis patient. No relationship was found between degree of severity of psoriasis and number of mast cells. In 25 of the 37 specimens from psoriasis patients there was no increase in intraepithelial lymphocytes, whereas seven showed a slight increase (score 1-2) and five a moderate increase (score > or = 2-3). The number of tryptase + mast cells was similar in patients with or without increased intraepithelial lymphocytes. The number of mast cells showed no relation to the presence or absence of antibodies to gliadin. We hypothesize that there are at least two types of abnormalities in the duodenal mucosa in psoriasis, one type that is present in most psoriasis patients and characterized by an increase in mast cells and eosinophils, and another that is present in a subgroup of patients with antibodies to gliadin and an increased number of duodenal intraepithelial lymphocytes. The mechanisms underlying the increase in the number of mast cells and its relevance are not yet known.


Subject(s)
Duodenum/enzymology , Inflammation Mediators/analysis , Mast Cells/enzymology , Mitogens/analysis , Psoriasis/immunology , Serine Endopeptidases/analysis , Adult , Aged , Antibodies/analysis , Cell Count , Chymases , Duodenum/pathology , Eosinophils/pathology , Female , Gliadin/immunology , Humans , Immunoglobulin A/analysis , Intestinal Mucosa/enzymology , Intestinal Mucosa/pathology , Lymphocyte Count , Male , Mast Cells/pathology , Middle Aged , Tryptases
14.
Pediatr Res ; 41(4 Pt 1): 554-9, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9098859

ABSTRACT

Problems in the diagnosis of celiac disease are that a long time is needed between challenge with gluten and the appearance of the typical diagnostic morphologic signs in gut mucosa. Furthermore, local immunity to gliadin is only slowly and often incompletely mirrored by serum IgA anti-gliadin antibody (AGA) levels. It is known that a local IgA-associated immune response in the gut may be better and more quickly mirrored by an increase of circulating IgA-producing cells against the immunogen than by IgA serum antibodies. We have therefore used an enzyme-linked immunospot (ELISPOT) assay to enumerate IgA AGA spot-forming cells (SFC) in peripheral blood in 82 children with suspected celiac disease or with other gastrointestinal symptoms. The numbers of IgA AGA SFC/10(6) mononuclear cells were markedly increased in 17 patients with untreated (and later biopsy-verified) celiac disease compared with healthy children, children with nonceliac disease, and patients treated for celiac disease (p < 0.0001). In 20 children with celiac disease the numbers of IgA AGA SFC increased rapidly (p < 0.0001) after gluten challenge. As early as 2 wk after gluten challenge, 15/20 of these patients had abnormal levels of IgA AGA SFC, 6/20 patients had increased levels of serum IgA AGA, and 7/20 had IgA anti-endomysium antibodies. Our results indicate that analysis of IgA AGA production in peripheral blood cells may in further clinical studies provide a sensitive method for the diagnosis of celiac disease after a short time of gluten challenge.


Subject(s)
Celiac Disease/immunology , Enzyme-Linked Immunosorbent Assay/methods , Gliadin/immunology , Immunoglobulins/biosynthesis , Lymphocytes/immunology , Mass Screening/methods , Adolescent , Case-Control Studies , Celiac Disease/diagnosis , Child , Child, Preschool , Female , Follow-Up Studies , Glutens , Humans , Immunoglobulin A/biosynthesis , Immunoglobulin G/biosynthesis , Immunoglobulin M/biosynthesis , Infant , Male , Sensitivity and Specificity , Time Factors
15.
Br J Dermatol ; 135(3): 371-8, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8949428

ABSTRACT

The occurrence of EG2-positive (EG2+) eosinophils and IgE in biopsy specimens of duodenal mucosa and skin from 39 psoriasis patients was studied, with emphasis on the relation to serum eosinophil cationic protein (ECP), serum IgE and the presence or absence of serum IgA and IgG antigliadin antibodies. Psoriasis patients had significantly elevated serum levels of ECP even after exclusion of five of 37 sera which were Phadiatop positive. The elevated serum ECP was not associated with the presence of IgA or IgG antibodies to gliadin. After exclusion of Phadiatop positive sera the serum IgE values did not differ from those of a group of healthy blood donors. Patients with psoriasis had a pronounced increase of EG2+ cells in their duodenal stroma. Patients without antibodies to gliadin tended to have even more EG2+ cells than those with such antibodies and those with increased duodenal intraepithelial lymphocytes. IgE+ cells were present in most duodenal specimens, and in some specimens there were > 100 IgE+ cells/section. The number of EG2+ cells was increased in lesional skin and, in some patients, also in non-involved skin, but there was a more pronounced increase in EG2 reactivity in the duodenal than in the skin specimens. IgE reactivity was increased both in non-involved and involved skin and was significantly related to the number of IgE-positive cells in the duodenal stroma. The results of this study indicate that the gastrointestinal tract and the eosinophil granulocyte might be involved in psoriasis in a hitherto unknown way.


Subject(s)
Blood Proteins/analysis , Duodenum/immunology , Eosinophils/immunology , Inflammation Mediators/blood , Psoriasis/immunology , Ribonucleases , Adult , Aged , Eosinophil Granule Proteins , Female , Gliadin/immunology , Humans , Immunoenzyme Techniques , Immunoglobulin A/blood , Immunoglobulin E/analysis , Immunoglobulin G/blood , Intestinal Mucosa/immunology , Leukocyte Count , Male , Middle Aged , Skin/immunology
16.
Lancet ; 348(9026): 515-7, 1996 Aug 24.
Article in English | MEDLINE | ID: mdl-8757154

ABSTRACT

BACKGROUND: An epidemiological association between Crohn's disease and measles virus exposure in early life has been suggested in case-control studies. METHODS: To determine absolute risk estimates for in-utero measles virus exposure and Crohn's disease, maternity charts for all 25000 deliveries at University Hospital, Uppsala, between 1940-49 were reviewed: four cases of measles infection in the mother during pregnancy were identified. The children and two of their mothers were interviewed and case records reviewed. Three offspring had undergone multiple intestinal resections; tissue from these cases were examined by routine histology, and for measles-virus nucleoprotein antigen by immunohistochemistry and immunogold electronmicroscopy. FINDINGS: Three of the four children had Crohn's disease. In each the disease was preceded by recurrent, antibiotic-resistant pneumonia. They had extensive ileal and colonic disease; two patients required intravenous feeding. The only offspring to have had measles as a child did not develop Crohn's disease. Measles virus antigen was detected in foci of granulomatous and lymphocytic inflammation in all children with Crohn's disease. INTERPRETATION: The data indicate that exposure of mothers to measles virus in utero is a risk factor for Crohn's disease in their children. Exposure at this time may lead to persistent infection, or modify the response to infection in later life, leading to persistence of measles virus.


Subject(s)
Crohn Disease/virology , Measles virus/isolation & purification , Measles/complications , Pregnancy Complications, Infectious , Adult , Child , Female , Humans , Ileum/virology , Male , Pregnancy , Risk Factors
17.
Sex Transm Dis ; 23(4): 293-8, 1996.
Article in English | MEDLINE | ID: mdl-8836023

ABSTRACT

BACKGROUND AND OBJECTIVES: Guidelines for the histopathologic diagnosis of human papillomavirus (HPV) infection have been drawn from changes seen in cervical specimens not necessarily applicable to penile epithelium. GOAL: To evaluate histopathologic examination as a means of diagnosing HPV infection of the male genital tract. STUDY DESIGN: Ninety-two consecutive male patients seen at the sexually transmitted diseases clinic. Twelve had condyloma acuminatum, and 80 had papular lesions, macular lesions, or both. Fifteen men without signs of HPV infection served as controls. Biopsy specimens were evaluated morphologically by light microscopy, and HPV DNA detection was performed by in situ hybridization and polymerase chain reaction. RESULTS: All acuminate lesions were HPV DNA positive with in situ hybridization. Forty papular and/or macular lesions harbored HPV DNA, 28 (35%) of them positive with in situ hybridization and the other 12 (15%) positive with polymerase chain reaction. Morphologic signs attributed to HPV infection were found in HPV-positive and HPV-negative penile lesions, as well as in normal epithelium. In papular and macular lesions, the only criterion associated with HPV DNA positivity was neoplastic changes, which was present in 16 (40%) HPV DNA-positive specimens, compared to 4 (10%) HPV DNA-negative specimens (P < 0.01). Of the 16 lesions with neoplasia, 15 (94%) had detectable HPV DNA of a potentially oncogenic type. CONCLUSIONS: Histopathologic signs of HPV infection other than neoplasia seem to be of limited value. Detection of the infectious agent, in this case HPV, should be the gold standard for the diagnosis as it is for other infectious diseases. The strong association between neoplasia and potentially oncogenic HPV types makes this issue even more important.


Subject(s)
Condylomata Acuminata/pathology , DNA, Viral/analysis , Papillomaviridae , Penile Diseases/pathology , Adult , Aged , Biopsy , Case-Control Studies , Condylomata Acuminata/virology , Humans , In Situ Hybridization , Male , Middle Aged , Penile Diseases/virology , Polymerase Chain Reaction , Reproducibility of Results
18.
Br J Dermatol ; 133(6): 896-904, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8547041

ABSTRACT

In a screening study concerning IgA and IgG antibodies to gliadin (IgA AGA and IgG AGA, respectively) in psoriasis, raised levels of IgA and AGA were found to be more common than in a reference group. To determine whether elevated AGA levels were associated with an increased number of intraepithelial lymphocytes, 33 patients with IgA AGA (n = 28) or IgG AGA (n = 5) values above 90% of the reference values (> 50 units/ml IgA AGA and < 12 units/ml IgG AGA) underwent gastroduodenoscopy and duodenal biopsy in a prospective study. For comparison, six patients with low levels of both IgA AGA and IgG AGA were included. Five biopsy specimens were taken in each patient. Paraffin-embedded specimens were examined with regard to the degree of intraepithelial lymphocyte infiltration, and scored from 0 to 3. Biopsy specimens with a score of 0 had one mononuclear cell or less per four epithelial cells. The specimens were also examined with regard to the presence of intraepithelial CD3+ T lymphocytes and gamma/delta+ T lymphocytes. In the six patients with low IgA AGA and low IgG AGA, the biopsy score was 0. Fourteen of the 33 patients with raised AGA had a score of > or = 1; of these, 12 had raised IgA AGA and two had slightly raised IgG AGA. Two of the patients with raised IgA AGA had partial villous atrophy, but the majority had normal villous architecture. There was a significant correlation both between the biopsy score and the number of intraepithelial CD3+ cells and between the score and the number of intraepithelial gamma/delta+ positive T lymphocytes. The serum IgA AGA levels were significantly correlated with the duodenal biopsy score, the number of intraepithelial gamma/delta+ T lymphocytes, and the number of CD3+ intraepithelial T lymphocytes. Most patients had no, or only mild, gastrointestinal symptoms. Of the 14 patients with biopsy scores > or = 1, seven had severe psoriasis and five moderately severe psoriasis, whereas only two had mild psoriasis. There was no relationship between the duodenal score and haemoglobin, folate, whole blood selenium or serum zinc levels. Some of these patients improve on a gluten-free diet, but it is still too early to draw any definite conclusions concerning the type of relationship between the skin lesions, the increased number of intraepithelial lymphocytes in the duodenal mucosa and gluten hypersensitivity.


Subject(s)
Duodenum/immunology , Gliadin/immunology , Intestinal Mucosa/immunology , Lymphocytes/immunology , Psoriasis/immunology , Adult , Aged , Antibodies, Anti-Idiotypic/blood , Duodenum/pathology , Female , Histocytochemistry , Humans , Immunoglobulin A/blood , Intestinal Mucosa/pathology , Lymphocyte Count , Male , Middle Aged , Prospective Studies , Psoriasis/diet therapy , Psoriasis/pathology
19.
Gynecol Obstet Invest ; 40(4): 265-70, 1995.
Article in English | MEDLINE | ID: mdl-8586310

ABSTRACT

BACKGROUND AND OBJECTIVES: To assess the presence of human papillomavirus (HPV) DNA in vulvar papillomatosis, since some women with this complaint have symptoms associated with HPV infection, such as itching, burning, and dyspareunia. GOAL: To reassure the patients that they do not have a transmissible viral disease, by excluding a HPV origin of their condition. STUDY DESIGN: Vulvar biopsy specimens from 22 females with vulvar papillomatosis, from 10 females with prominent aceto-white vulvar lesions, and from 14 healthy controls were analyzed histologically for signs of HPV infection and by in situ hybridization and polymerase chain reaction for the presence of HPV DNA. RESULTS: Specimens from women with vulvar papillomatosis showed some histological signs associated with HPV infection, but no koilocytotic atypia or dysplasia and thus resembled normal-looking vulvar mucosa. Aceto-white lesions frequently displayed histological features suggestive of HPV infection, including dysplasia. HPV DNA was detected in 6 of 10 patients with aceto-white lesions, but only in 1 of 22 patients with papillomatosis and in no healthy controls. CONCLUSIONS: According to our results, HPV DNA, which is generally found in cervical lesions and subclinical infections, is not present in vulvar papillomatosis even though symptoms associated with HPV infection are frequent complaints.


Subject(s)
DNA, Viral/analysis , Papilloma/pathology , Papillomaviridae/genetics , Vulva/pathology , Vulvar Neoplasms/pathology , Adult , Biopsy , DNA Probes, HPV , DNA, Neoplasm/analysis , DNA, Neoplasm/genetics , DNA, Viral/genetics , Female , Humans , In Situ Hybridization , Incidence , Middle Aged , Mucous Membrane/pathology , Mucous Membrane/virology , Papilloma/virology , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Polymerase Chain Reaction , Tumor Virus Infections/diagnosis , Tumor Virus Infections/epidemiology , Vulva/virology , Vulvar Neoplasms/virology
20.
Gastroenterology ; 103(3): 934-42, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1323500

ABSTRACT

The presence of autoimmune gastritis was investigated in 54 women with postpartum thyroiditis. Parietal cell antibodies (PCA) specific against H+, K(+)-adenosine triphosphatase (EC 3.6.1.36) were found in 18 women during pregnancy; in 10 of them, a 2-9-fold increase in the PCA level was observed in the postpartum period. At a 5-year follow-up, the initially PCA-positive women still had elevated antibody levels. Hypergastrinemia and low pepsinogen levels were noted in 4 women. In 2 of these women low serum vitamin B12 levels had developed. In 6 of 9 PCA-positive women examined by gastroscopy, biopsy specimens from the gastric body mucosa contained mononuclear cells, mainly T lymphocytes (CD3+) and macrophages (Leu-M3+) combined with an aberrant epithelial expression of HLA-DR. In four patients with chronic gastritis, all parietal cells, as defined by a specific monoclonal antibody, were found to have immunoglobulin G (IgG) deposits by a double-immunostaining method. Three of them had microscopic evidence of atrophy, whereas in 1 patient the body mucosa was intact. In 1 further patient with intact glands at histological examination, the basolateral membrane of some oxyntic glands was coated with IgG. The selective in situ deposition of antibodies associated with histologically intact parietal cells may support the concept that specific autoantibodies participate in the early pathogenesis of parietal cell destruction.


Subject(s)
Adenosine Triphosphatases/immunology , Antibodies/analysis , Autoimmune Diseases/immunology , Gastrins/blood , Gastritis/immunology , Puerperal Disorders/immunology , Thyroiditis, Autoimmune/immunology , Adult , Autoimmune Diseases/blood , Autoimmune Diseases/pathology , Biopsy , Female , Fluorescent Antibody Technique , Follow-Up Studies , Gastric Mucosa/pathology , Gastritis/blood , Gastritis/pathology , H(+)-K(+)-Exchanging ATPase , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Iron/blood , Pepsinogens/blood , Pregnancy , Puerperal Disorders/blood , Thyroiditis, Autoimmune/blood , Vitamin B 12/blood
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