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Biomedical subjects

J Lindeman

Publications and source records attributed to J Lindeman.

At least 37 records · Page 2Linked to original sources

Increase of Helicobacter pylori-associated corpus gastritis during acid suppressive therapy: implications for long-term safety.

OBJECTIVES: Helicobacter pylori causes chronic active gastritis with predominant localization in the gastric antrum. This predisposes to development of mucosal atrophy, intestinal metaplasia, and eventually, gastric cancer. The effects of acid suppression on H. pylori infection and associated gastritis are unclear. However rapid development of atrophic gastritis has been consistently observed in a number of studies during low acid output. We therefore studied the histological features of antrum and corpus of the stomach before and during acid suppressive therapy. METHODS: Fifty patients with either reflux esophagitis (n = 21), benign gastric ulcer (six patients), gastric erosions (three patients), or duodenal ulcer (20 patients) were treated for 8 wk with omeprazole 40 mg o.d. Esophagogastroduodenoscopy was performed pre-entry and at 8 wk. Biopsy specimens were sampled from the antrum and corpus for histology and cultures. RESULTS: Seventeen H. pylori-negative patients had no histological signs of active gastritis, before or after therapy. Thirty-three H. pylori-positive patients showed predominant colonization and associated inflammation in the antrum before therapy. After therapy, however, the infection predominantly affected the corpus. The inflammation and bacterial colonization in the antrum significantly decreased, leading to negative antral cultures in 61% (20 of 33 patients). In contrast, the inflammation of the corpus mucosa significantly increased despite stable bacterial counts. CONCLUSIONS: We conclude 1) that H. pylori testing in patients on profound acid suppressive therapy should be performed on combined corpus and antral specimens, and 2) that omeprazole therapy leads to a strong increase in corpus gastritis, which may explain the observed development of corpus atrophy in a substantial number of patients after several years of continuous acid suppressive treatment. Therefore, we suggest that patients in need of long-term acid suppressive therapy should receive bacterial eradication therapy if they are H. pylori positive.

Antacids↗

Syntactic context effects on word recognition: a developmental study.

In the present study, grammatical context effects on word recognition were examined among skilled and less skilled second and sixth grade readers. Of particular interest was how the word decoding ability may correlate with the grammatical context effect. For this purpose the rich case-marking system of the Finnish language was exploited. Recognition latencies for sentence-final nouns were measured as a function of their syntactic agreement with the preceding adjective. The naming and lexical decision tasks were used as critical measures. The study showed a clear syntactic context effect for each of the four experimental groups. The magnitude of the observed syntactic effect was substantially larger compared to earlier results. Furthermore, the effect emerged both in naming and lexical decision. In naming, less skilled 2nd grade decoders were more affected by grammatical incongruency than their more competent peers, whereas in lexical decision the skilled 6th graders differed from other groups by showing a smaller syntactic effect. The results are discussed in the light of Stanovich's interactive-compensatory model of word recognition.

Adolescent↗

Relation between IgG and IgA antibody titres against Helicobacter pylori in serum and severity of gastritis in asymptomatic subjects.

AIMS: To investigate whether the absorbance index of IgG and IgA antibodies against Helicobacter pylori is related to a semiquantitative assessment of the density of H pylori colonisation in gastric biopsy specimens and to the severity of gastritis. METHODS: The grade of gastritis was scored separately for antral and fundic mucosa using three different classifications. Serum IgA and IgG antibodies against H pylori were measured by ELISA. The density of gastric H pylori colonisation was graded semiquantitatively from 0 to 3. RESULTS: Among 48 healthy volunteers studied, 17 were found to have gastritis according to Whitehead's criteria. H pylori was present in the biopsy specimens of 14 of 17 subjects with gastritis. The IgG H pylori antibody absorbance index was significantly (p < 0.05) correlated not only with the density of antral H pylori colonisation, but also with the degree of gastritis of the antrum, as assessed by the Whitehead score, activity, and the Sydney system (p < 0.05). The IgA H pylori antibody absorbance index was significantly correlated with the Whitehead score and Sydney system, but not with the activity score of the antrum or with the density of antral gastric H pylori infection. There were no significant correlations between the IgG H pylori antibody absorbance index and the gastritis scores of the fundus mucosa and the density of H pylori infection of the gastric body. The IgA H pylori antibody absorbance index was only significantly (p < 0.05) correlated with the density of H pylori colonisation and the Sydney system gastritis score of the corpus. CONCLUSIONS: The serological absorbance index of IgG antibodies against H pylori is related to the severity of antral gastritis and the density of antral H pylori colonisation. Thus a high absorbance index of IgG antibodies against H pylori points to severe antral gastritis and dense H pylori colonisation of the antrum.

Adult↗

Flow cytometric DNA content of fresh tumor specimens using keratin-antibody as second stain for two-parameter analysis.

Studies concerning flow cytometric assessed DNA content reveal problems in interpretating DNA histograms of tumor specimens. The main problems are histograms with a broad coefficient of variation in the G0/G1 fraction; a high G2M fraction and samples with a low percentage of tumor cells. Therefore, in the present study, 382 fresh tumor specimens of carcinomas were analysed routinely, double labeled with, on the one hand, propidium-iodide for assessing DNA content and, on the other, a monoclonal keratin-antibody for marking epithelial and tumor cells. Of the 311 tumor samples, using single parameter analysis 165 (54%) were classified as DNA aneuploid and 146 (46%) as DNA "euploid." By double parameter analysis, 224 (72%) samples were keratin positive and 87 (27%) keratin negative and, of the 224 keratin positive tumors, 175 (78%) were DNA aneuploid and 49 (22%) DNA euploid. The DNA histograms of single and double parameter analysis were compared and it was concluded that in 24 cases (11%) keratin labeling was necessary to recognize DNA aneuploidy. In another 23 (10%) cases, keratin labeling was helpful in assessing DNA aneuploidy. Finally when the results of the 311 samples were combined, 215 (68%) were scored as DNA aneuploid and 99 (32%) DNA euploid. Thus the overall gain in assessing DNA aneuploidy using the double labeling technique is 14%. In conclusion, it is shown that keratin labeling on fresh tumor cell suspensions of epithelial tumors is of additional value in establishing DNA content. Because single parameter DNA assessment is adequate in approximately 60% of the tested samples, the double labeling technique can be performed routinely, or after initial single parameter DNA assessment. Histograms having a broad CV and/or a high G2M are good candidates for the double labeling technique. Using this technique, DNA-content assessment becomes more reliable.

Antibodies↗

Value of counting colonic mucosal Ig-containing cells in the differential diagnosis of chronic inflammatory bowel disease.

AIMS: To investigate whether counting cells containing immunoglobulin (Ig) subclass in colonic biopsy specimens of patients with chronic inflammatory bowel disease, in addition to conventional histological evaluation, can improve the differentiation of patients with Crohn's disease from those with ulcerative colitis. METHODS: The colonic and rectal biopsy specimens of 40 patients with chronic inflammatory bowel disease, comprising 20 patients with Crohn's disease and 20 with ulcerative colitis, were used and sections were stained specifically for IgA, IgM, and IgG heavy chains using an indirect immune peroxidase method. The immunoglobulin subclass containing cells were counted using an ocular grid counting method in a light microscope. A linear stepwise discriminant analysis was performed on Ig subclass containing cell counts in combination with 16 reproducible histological features. The results of this discriminant analysis were compared with the results of the discriminant analyses in which only the histological features were used. RESULTS: Applying stepwise discriminant analysis, two histological features (an excess of histiocytes in the lamina propria and the villous or irregular aspect of the mucosal surface) in combination with IgMax were selected as the most discriminatory parameters that distinguish Crohn's disease from ulcerative colitis. IgMmax was defined as the maximum value of the mean percentage of IgM containing cells over all the biopsy locations. The use of this combination resulted in a better classification in 20% of the patients with Crohn's disease and in 9% of the patients with ulcerative colitis compared with the use of histological features alone. CONCLUSIONS: Morphometric enumeration of Ig subclass containing cells in colonic mucosal biopsy specimens has diagnostic value as a means of differentiating individual patients with Crohn's disease from those with ulcerative colitis.

Adolescent↗

Human papillomavirus and the three group metaphase figure as markers of an increased risk for the development of cervical carcinoma.

In this study, the presence of atypical mitotic figures and human papilloma virus (HPV) genomes was related to the degree of cervical intraepithelial neoplasia (CIN) or microinvasive carcinoma (MIC) as found in 94 paraffin-embedded biopsies from cervical lesions. The results showed that the frequency of three group metaphase (TGM) figures, a special kind of atypical mitotic figure, as well as the presence of HPV 16 and 18 genomes increased with the degree of cervical intraepithelial neoplasia. TGM figures were observed in 24% of CIN2, up to 61% in CIN3 lesions, and in 83% of the microinvasive cervical carcinomas. HPV genomes were detected in 15% of CIN1, up to 75% in CIN3 lesions, and in 92% of the invasive carcinomas of the cervix. The combination of these two markers showed even a better association with a higher degree of cervical intraepithelial neoplasia. The results of these studies suggest that detection of particular HPV types, mainly HPV 16 and 18, and the presence of TGM figures can be considered as markers that indicate an increased risk for progression of cervical intraepithelial neoplasia to invasive carcinoma.

Carcinoma in Situ↗

Towards a quantitative grading of bladder tumors.

The histological inspection of tumor tissue for the purpose of reporting a tumor grade is a problem of significant clinical importance. The grading by a pathologist is only partly reproducible due to vaguely defined, subjective criteria. In this article we describe and evaluate a set of measurable features that quantitate the differences in tumor tissue. Different aspects of the reproducibility of the measurements under varying conditions of image selection, focus, and noise have been investigated. Three hundred thirty-three images were digitized from 111 bladder tissue sections (4 microns thick, Feulgen stained), using the ICAS microscope-camera platform. A segmentation routine was developed to segment the images into nuclei and background without any user interaction. Size, shape, optical density, and texture features were measured on and among the objects found by this segmentation routine using the image analysis package Acuity. The results of the measurements showed that there is a significant quantitative difference between grade 1 and grade 3 tumors. Grade 2 tumors can be described as "in between grade 1 and grade 3" and falling somewhere on an increasing scale between grades 1 and 3. Grade 2 tumors do not seem to represent a statistically distinct population. The procedure described here is shown to be quite reproducible in the presence of noise, reasonably reproducible in the event of a modest amount of defocusing (with grade 3 tumors exhibiting the most sensitivity), and less reproducible in the context of which fields-of-view are chosen for analysis.

Epithelium↗

Histopathological evaluation of colonic mucosal biopsy specimens in chronic inflammatory bowel disease: diagnostic implications.

In a prospective blind evaluation of multiple colonic mucosal biopsy specimens, 45 clinically well defined patients with chronic inflammatory bowel disease (21 Crohn's disease and 24 ulcerative colitis) and 16 control subjects (seven normal subjects and nine patients with diverticular disease) were studied to identify reproducible histopathological features which could distinguish chronic inflammatory bowel disease (CIBD) from non-CIBD and Crohn's disease from ulcerative colitis. Using kappa statistics 16 of 41 histological features were sufficiently reproducible for further stepwise discriminant analysis to differentiate between CIBD and non-CIBD, and between Crohn's disease and ulcerative colitis. Using the combination of three features (an increase of lymphocytes and plasma cells in the lamina propria, the presence of branching of crypts, and neutrophils in the crypt epithelium) we were able to distinguish CIBD from non-CIBD in 89% of the cases with high probability (p greater than 0.85). To separate Crohn's disease from ulcerative colitis three features (an excess of histiocytes in combination with a villous or irregular aspect of the mucosal surface and granulomas) had a high predictive value. Using these features 70% of Crohn's disease patients and 75% of ulcerative colitis patients were correctly classified with a high probability (p greater than 0.85). These findings indicate that the pathologist is dependent on the presence of only a few histological features for a reliable classification of Crohn's disease and ulcerative colitis.

Adult↗

Detection of Chlamydia trachomatis in clinical specimens by the polymerase chain reaction.

Sequences derived from the endogenous plasmid of Chlamydia trachomatis and from the genes coding for ribosomal 16S RNA of Chlamydia psittaci were used as primers and oligonucleotide probes for detection of chlamydiae by the polymerase chain reaction. The endogenous plasmid primers generated specific amplified products of 517 bp with all known Chlamydia trachomatis serovars. No specific products of Chlamydia psittaci and Chlamydia pneumoniae could be detected using these primers. With the rRNA primers specific amplified products of 208 bp were generated with Chlamydia psittaci, Chlamydia trachomatis and Chlamydia pneumoniae. No specific amplified products were detected with DNA isolated from a variety of microorganisms from the urogenital and the respiratory tract. Of 156 clinical specimens used for evaluation of the polymerase chain reaction, 26 were found to be positive for Chlamydia trachomatis on culture. All 26 culture positive samples were also found to be positive for Chlamydia trachomatis DNA by the polymerase chain reaction with both primer sets. Two culture negative samples were also found to be positive by this technique. The polymerase chain reaction thus seems to be a sensitive and reliable method for detection of Chlamydia trachomatis.

Base Sequence↗

Serodiagnosis of respiratory syncytial virus (RSV) infection in children as measured by detection of RSV-specific immunoglobulins G, M, and A with enzyme-linked immunosorbent assay.

The diagnostic value of an enzyme-linked immunosorbent assay for detection of respiratory syncytial virus (RSV)-specific immunoglobulin G (IgG), IgM, and IgA in sera from infants and children with proven RSV infection, from a control group, and from patients with symptoms of viral respiratory disease was analyzed. Compared to virus isolation and RSV antigen detection methods, the sensitivity of this assay was 87% and the specificity was 79%. For IgG alone, these were 45 and 92%, for IgM alone they were 48 and 92%, and for IgA alone they were 74 and 95%, respectively.

Antibodies, Viral↗

The Multivariate Prognostic Index and nuclear DNA content are independent prognostic factors in primary breast cancer patients.

The predictive value of a previously described Multivariate Prognostic Index (which incorporates weighted values of the mitotic activity index, tumor size, and the axillary lymph node status), and the nuclear DNA content (DNA) was evaluated in 156 patients with primary invasive ductal breast cancer, diagnosed between 1980 and 1983. The results were analysed with respect to the occurrence of distant recurrence and survival of the patients after at least 3 yr of follow-up (range 36-73 months; median 44 months). Known prognostic factors such as lymph node status, tumor size, and the mitotic activity index correlated independently with distant recurrence. Furthermore, in respect to survival, the investigated prognostic factors (except DNA content) were significantly correlated. The results indicate that the predictive value of the Multivariate Prognostic Index (MPI) is stronger (P less than 0.001) than of the nuclear DNA content (P less than 0.005) with respect to distant recurrence. In a Cox multivariate regression analysis DNA ploidy turned out to be an independent prognostic factor once the MPI was selected. Furthermore, in Cox's analysis, DNA ploidy was the fourth selected variable after lymph node status, mitotic activity index, and tumor size in individual parameter analysis. The results of this study indicate that, with respect to breast cancer screening programs, it seems worthwhile to integrate morphometric features, the MPI, and DNA ploidy in a new prognostic model.

Adult↗

Increased detection rate of human papillomavirus in cervical scrapes by the polymerase chain reaction as compared to modified FISH and southern-blot analysis.

Cervical scrapes from 80 women with a positive cytology result were tested for the presence of human papillomavirus (HPV) using the polymerase chain reaction (PCR) and compared to the results obtained with the modified filter in situ hybridisation (FISH) and the Southern-blot techniques. The sensitivity of the modified FISH and the Southern-blot was similar, and HPV was detected in 46% of the patients. The sensitivity of the PCR appeared to be higher, and HPV was detected in 70% of the patients. HPV-DNA could be detected in 46 of the 68 patients with mild dysplasia, in 6 of the 8 patients with severe dysplasia, and in all 4 patients with carcinoma in situ. In 18 patients (21%) more than one HPV type could be detected by the PCR. The control group consisted of 100 women involved in a triennial checkup programme, who had normal smear results and no history of cervical lesions. HPV was detected in 5% of the women by the PCR. The PCR technique detected HPV in a high proportion of the cervical scrapes from women with a positive cytology result. These results give further evidence for an important role of HPV in the pathogenesis of cervical cancer.

Biomarkers↗

Use of anticontamination primers in the polymerase chain reaction for the detection of human papilloma virus genotypes in cervical scrapes and biopsies.

A reliable application of the polymerase chain reaction (PCR) for detection of the human papilloma virus (HPV) genotypes in cervical smears and biopsies was developed. Primers flanking the HPV cloning site were used to avoid detection of cloned HPV plasmids. These anticontamination primers were used for the specific detection of HPV 6, 11, 16, 18, and 33 in cervical scrapes that had been tested previously for HPV with a combined modified filter in situ hybridization (modified FISH) and dot blotting procedure. The PCR appeared to be superior. Two groups of women were screened for HPV genotypes. Group A consisted of women belonging to a regularly screened population, and group B contained women attending a gynaecological clinic. It appeared that the overall prevalence of HPV in cytologically normal scrapes in the first group was 6%, whereas in the second group 12% was found. In scrapes with cytological dysplasia, the prevalence of HPV in group A and B was approximately 40% and 60%, respectively. HPV 16 was present predominantly. In biopsies of squamous cell carcinomas of the cervix uteri, an HPV prevalence rate of 90% was found, all of which contained only HPV 16 and 18. These data indicate an important role for HPV detection in the screening of cervical scrapes to identify women with an increased risk of cervical cancer.

Adult↗

Favourable effect of detergent on antigen detection and comparison of enzyme linked detection systems in an ELISA for Chlamydia trachomatis.

The influence of addition of detergents to the antigen on sensitivity of an ELISA for the detection of Chlamydia trachomatis was investigated. Of the detergents tested, only octyl-beta-d-glucopyranoside and sodiumdesoxycholate gave respectively a two- to fourfold and an eightfold increase in sensitivity. The effect was only present within a narrow range of detergent concentrations. The optimal detergent concentration was strongly dependent on the protein concentration in the antigen preparation. For optimal detection of the bound chlamydial antigen, enzyme and biotin labeled secondary antibodies were compared. The biotin labeled antibodies were combined with enzyme labeled streptavidin-biotin complex (SBC). Color development was obtained with both types of conjugates by using either o-phenylenediamine (OPD) or an enzyme amplification system. The best results were obtained with the SBC method and OPD.

Antigens, Bacterial↗

Optimization of human papillomavirus genotype detection in cervical scrapes by a modified filter in situ hybridization test.

Optimal conditions for the screening of cervical scrapes for human papillomavirus (HPV) were investigated by using filter in situ hybridization. Since integrated and episomal HPV can be found, cell lines containing viral DNA in an integrated form (HPV in CaSki) or in an episomal state (BK virus-induced hamster tumor cells) were used for optimization experiments. An increase in sensitivity was achieved by alkaline denaturation and neutralization before the specimens were spotted onto the membrane. This increase was 5-fold for the episomal virus and 16-fold for the integrated virus in the model system, as compared with other methods. To evaluate this method on clinical material, 1,963 cervical scrapes were screened for the presence of HPV 6/11 and HPV 16. Nineteen scrapes were positive for HPV 6/11 or HPV 16; and in 1,810 scrapes, no HPV 6/11 or HPV 16 could be detected by the modified filter in situ hybridization technique. Scrapes from which the interpretation of the modified filter in situ hybridization results were equivocal (n = 71, 3.6%) or in which positivity was detected for both HPV 6/11 and HPV 16 (n = 63, 3.2%) were further analyzed by the DNA dot spot technique. Eight scrapes with an equivocal result and only one scrape showing a double positivity by the modified filter in situ hybridization technique could be confirmed in the dot spot assay. In the total group 12 scrapes were positive for HPV 6/11 DNA, 15 were positive for HPV 16 DNA, and 1 was positive for both HPV 6/11 and HPV 16 DNA. Southern blot analysis on modified filter in situ hybridization-positive and -negative scrapes revealed a 100% correlation.

Adult↗

Human papillomavirus detection in urine samples from male patients by the polymerase chain reaction.

Human papillomavirus (HPV) detection was performed using the polymerase chain reaction technique on urine samples from 17 male patients with condylomata acuminata in the meatus urethrae. Urine samples from 14 male laboratory volunteers were analyzed as controls. The DNA was extracted and purified from urine sediments, centrifuged at 1,800 and 100,000 x g, and subjected to 40 cycles of amplification with HPV 6 and HPV 11 type-specific anticontamination primers and the heat-stable Taq DNA polymerase. HPV was detected in the urine of 15 (88%) patients. In all positive patients the urine sediments of both the 1,800 and 100,000 x g centrifugation steps contained HPV DNA. Eight patients were found to be positive for HPV 6 DNA, six were positive for HPV 11 DNA, and one was positive for both HPV 6 and HPV 11 DNA. None of the males in the control group was positive for either HPV 6 or HPV 11 DNA. The results demonstrate that HPV can be transported by the urine, probably in exfoliated HPV-infected cells. A similar mechanism may occur during ejaculation, allowing sexual transmission of HPV viruses harbored in the cells of the male genital tract.

Base Sequence↗

Chronic nonspecific duodenitis. A multiple biopsy study of the duodenal bulb in health and disease.

A clinical, endoscopic and histopathologic study on chronic nonspecific duodenitis was performed in 174 subjects, 124 patients (control patients, patients with gastric or duodenal ulcer and nonulcer dyspepsia) and 50 healthy volunteers without clinical history of gastro-intestinal disease. Chronic nonspecific duodenitis was found in 6 healthy volunteers (12%), 5 control patients (7%), one gastric ulcer patient (7%), all duodenal ulcer patients and in 15 patients with nonulcer dyspepsia (83%). Chronic non-specific duodenitis is a focal process affecting the duodenal bulb. It can be missed when only one biopsy is studied. Superficial gastric metaplasia was directly correlated to gastric acid secretion and was found in 32 healthy volunteers (64%), 23 control patients (34%), six gastric ulcer patients (43%), 20 duodenal ulcer patients (20%) and in 17 patients with nonulcer dyspepsia (94%). This study suggests that chronic nonspecific duodenitis is a stage of duodenal ulcer disease.

Adult↗

Human papillomavirus detection in paraffin-embedded cervical carcinomas and metastases of the carcinomas by the polymerase chain reaction.

The polymerase chain reaction (PCR) is used for human papillomavirus (HPV) detection in paraffin-embedded tissue. The specificity of the reaction is unaffected by the method of fixation used before embedding into paraffin. Five HPV 16, 18, 31, and 33 DNA in situ hybridization (DISH)-negative cervical carcinomas were subjected to the PCR. In two patients, HPV 16 DNA could be detected in the cervical squamous cell carcinomas and also in their lymph node metastases. One patient with an adeno-carcinoma of the cervix was found positive for HPV-18. A lymph node of this patient was HPV 18 positive as well. In the tumors of the remaining two patients, no HPV 16, 18, or 33 DNA was detected by the PCR. Both negative patients had cervical squamous cell carcinomas. One had a bladder metastasis, whereas the other had a lymph node metastasis and an additional distant metastasis in the lung. HPV DNA positivity in cervical carcinomas correlated with HPV prevalence in the metastases. This relationship can be of use for diagnostic purposes in the pathologic analysis of metastases.

Blotting, Southern↗