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Biomedical subjects

R Holland

Publications and source records attributed to R Holland.

At least 55 records · Page 3Linked to original sources

Nationwide breast cancer screening programme fully implemented in The Netherlands.

The period 1990-1997 saw the implementation of a nationwide breast cancer screening programme in the Netherlands, which provided biennial mammography for all women aged 50-69 years (50-75 years at present). The National Evaluation Team monitors the programme annually collecting regional data on screening outcomes; regional cancer registries provide data on interval cancers and on breast cancers in unscreened women by linkage of cancer registry data to data on screened women. Of 4 million women invited, 78.5% attended for screening. Screening resulted in 13.1 referrals, 9.2 biopsies and 6.1 breast cancers detected per 1000 women screened initially (6.9, 4.5 and 3.5 per 1000 in subsequently screened women, respectively). Within the first 2 years following screening 0.95 interval cancers per 1000 women-years were diagnosed. The stage distribution of screen-detected cancers was more favourable than that of interval cancers and of those diagnosed in unscreened women. The results are largely consistent with expectations. Results may nonetheless be further improved, particularly the detection rate in subsequent screens.

Journal Article↗

Macrolide resistance in Streptococcus pyogenes isolates from throat infections in the region of Aachen, Germany.

Macrolide-resistance was assessed in 216 consecutive Streptococcus pyogenes isolates from throat infections in the region of Aachen, Germany. Seventeen isolates were resistant to erythromycin: 12 isolates revealed a macrolide (M) phenotype and harbored mefA, and five strains expressed an inducible macrolide-lincosamide-streptogramin B (MLSB) phenotype of which four strains harbored ermA(TR) and one strain contained ermB(AM). Telithromycin (HMR 3647) and quinupristin/dalfopristin remained active particularly against the ermA(TR)-containing S. pyogenes isolates studied. Random amplified polymorphic DNA analysis identified multiple clones among erythromycin-resistant strains, but did not discriminate beyond the emm-type. mefA was present in three isolates either with emm2, emm12, or emm75, and in nine isolates with emm4. All four strains with ermA(TR) contained emm77, and the single strain with ermB(AM) harbored emm1. Despite the relative low rate of macrolide-resistance, these data suggest that at least three different macrolide-resistance determinants are prevalent in Germany and that mefA has spread rapidly into multiple clones of S. pyogenes.

Anti-Bacterial Agents↗

Mineral trioxide aggregate repair of lateral root perforations.

This study was conducted to observe the healing process of intentional lateral root perforation repaired with mineral trioxide aggregate (MTA). Forty-eight root canals of dogs' teeth were instrumented and filled. After partial removal of the filling, an intentional perforation was made with a bur in the lateral area of the root. The perforations were repaired with MTA or Sealapex (control group). Histological analysis occurred 30 and 180 days after treatment. Results showed no inflammation and deposition of cementum over MTA in the majority of the specimens. In the 180-day period, Sealapex exhibited chronic inflammation in all the specimens and slight deposition of cementum over the material in only three cases. In conclusion, MTA exhibited better results than the control group.

Aluminum Compounds↗

Identification and expression of cephamycinase bla(CMY) genes in Escherichia coli and Salmonella isolates from food animals and ground meat.

Twenty-one Salmonella and 54 Escherichia coli isolates, recovered from food animals and retail ground meats, that exhibited decreased susceptibilities to ceftiofur and ceftriaxone were shown to possess a bla(CMY) gene. The bla(CMY-4) gene was identified in an E. coli isolate recovered from retail chicken and was further shown to be responsible for resistance to cephalothin, ampicillin, and amoxicillin-clavulanic acid and elevated MICs of ceftriaxone, cefoxitin, and ceftiofur.

Animals↗

Reaction of rat connective tissue to implanted dentin tube filled with mineral trioxide aggregate, Portland cement or calcium hydroxide.

The subject of this study was to observe the rat subcutaneous connective tissue reaction to implanted dentin tubes filled with mineral trioxide aggregate, Portland cement or calcium hydroxide. The animals were sacrificed after 7 or 30 days and the undecalcified specimens were prepared for histological analysis with polarized light and Von Kossa technique for mineralized tissues. The results were similar for the studied materials. At the tube openings, there were Von Kossa-positive granules that were birefringent to polarized light. Next to these granulations, there was an irregular tissue like a bridge that was Von Kossa-positive. The dentin walls of the tubes exhibited in the tubules a structure highly birefringent to polarized light, usually like a layer and at different depths. The mechanism of action of the studied materials has some similarity.

Aluminum Compounds↗

Healing process of dog dental pulp after pulpotomy and pulp covering with mineral trioxide aggregate or Portland cement.

Considering several reports about the similarity between the chemical compositions of the mineral trioxide aggregate (MTA) and Portland cement (PC), the subject of this investigation was to analyze the behavior of dog dental pulp after pulpotomy and direct pulp protection with these materials. After pulpotomy, the pulp stumps of 26 roots of dog teeth were protected with MTA or PC. Sixty days after treatment, the animal was sacrificed and the specimens removed and prepared for histomorphological analysis. There was a complete tubular hard tissue bridge in almost all specimens. In conclusion, MTA and PC show similar comparative results when used in direct pulp protection after pulpotomy.

Aluminum Compounds↗

Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana.

Arabidopsis thaliana is an important model system for plant biologists. In 1996 an international collaboration (the Arabidopsis Genome Initiative) was formed to sequence the whole genome of Arabidopsis and in 1999 the sequence of the first two chromosomes was reported. The sequence of the last three chromosomes and an analysis of the whole genome are reported in this issue. Here we present the sequence of chromosome 3, organized into four sequence segments (contigs). The two largest (13.5 and 9.2 Mb) correspond to the top (long) and the bottom (short) arms of chromosome 3, and the two small contigs are located in the genetically defined centromere. This chromosome encodes 5,220 of the roughly 25,500 predicted protein-coding genes in the genome. About 20% of the predicted proteins have significant homology to proteins in eukaryotic genomes for which the complete sequence is available, pointing to important conserved cellular functions among eukaryotes.

Arabidopsis↗

[Alterations of stage distribution for breast cancer since the implementation of national screening program in the Netherlands during 1989-1995].

OBJECTIVE: To determine the results of the nation-wide breast cancer screening on the basis of the stage distribution of diagnosed breast cancer 1989-1995. DESIGN: Descriptive, inventory. METHOD: At the University of Nijmegen data concerning the numbers of diagnosed breast cancer cases and age and stage at diagnosis were obtained from the Netherlands Cancer Registry for the years 1989-1995. Population data were provided by Statistics Netherlands. With these data incidence figures were calculated. RESULTS: The number of invasive breast cancers rose from almost 8,000 in 1989 to almost 10,500 in 1994. In 1995, a small decrease was visible. The increase was largest in women aged 50-69 years, the target population of the screening programme (introduced in 1988), and less in older women. In women aged 50-69 years, the incidence of stage I tumours doubled, stage II tumours increased but had returned to original levels in 1995, whereas stage III and IV had decreased by more than 24%. The number of carcinomas in situ rose from 336 in 1989 to 829 in 1995 in all age categories, but most in women aged 50-69 years. CONCLUSION: When the implementation scheme of the national screening programme is taken into account, the results are indicative of a reduction in breast cancer mortality. Whether such a mortality reduction actually will follow, has to be awaited.

Adult↗

Correlation of high-resolution breast MR imaging with histopathology; validation of a technique.

A high-resolution three-dimensional surface gradient coil set was used to obtain magnetic resonance (MR) images of breast specimens, using a gradient-echo pulse sequence (TR/TE 1000/8 msec, flip angle 75 degrees), with 117 micrometer in-plane resolution and 1 mm slice thickness. Breast tissues were obtained from one autopsy and three surgical specimens. High-resolution breast MR images and histopathology sections (7 micrometer thickness) were acquired in the same anatomical plane. Radiographs were acquired of the sliced specimens (approximately 5 mm thick) so that images from all three methods could be correlated. It was found that in vitro high-resolution breast MRI correlated well with low-resolution microscopic histology, demonstrating normal anatomy (lobules, ducts, connective tissue strands, blood vessels) and pathology (tumor content, margins, and presence of microcalcifications) of the breast more clearly than conventional pre-gadolinium breast MRI. High-resolution breast MRI may improve specificity, when added to a conventional breast MRI protocol.

Biopsy↗

Malignant adenomyoepithelioma of the breast with metastasis in the thyroid gland 12 years after excision of the primary tumor. Case report and review of the literature.

We describe a patient who was admitted to our hospital with an enlarged left lobe of the thyroid gland. Since fine-needle aspiration showed atypical follicular cells, a surgical exploration followed. Owing to extensive tumor infiltration into the surrounding tissues curative surgery was not possible, and only an incisional biopsy was taken. Histological examination of this biopsy revealed a mixed tumor composed of epithelial and myoepithelial cells. A primary thyroid tumor, metastasis of a salivary gland, and a skin appendage tumor could be excluded based on clinical examination, conventional histology, and immunohistochemistry. A tumor of the left breast treated 12 years earlier had originally been classified as an intraductal/intracystic carcinoma with focal invasion, but was re-examined. Using immunohistochemistry, the breast tumor was reclassified as a malignant adenomyoepithelioma. The current tumor was apparently a metastasis from this primary breast tumor. An updated review of the literature is given, including current knowledge on histological and immunohistochemical features of adenomyoepithelioma of the breast, with special attention to the reported pathological characteristics of recurrent and malignant tumors. Based on the reported pathological characteristics of recurrent and metastatic tumors we offer a diagnostic tool for identifying potentially malignant and recurrent tumors.

Biomarkers, Tumor↗

Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology.

It is now widely recognised that classifying ductal carcinoma in situ (DCIS) of the breast and diagnosing atypical ductal hyperplasia are associated with significant interobserver variation. Two possible reasons for this inconsistency are differences in the interpretation of specified histological features and field selection where morphology is heterogeneous. In order to investigate the relative contribution of these two factors to inconsistent interpretation of intraductal proliferations, histological sections of 32 lesions were sent to 23 European pathologists followed 3 years later by images of small parts of these sections. Kappa statistics for diagnosing hyperplasia of usual type, atypical ductal hyperplasia and ductal carcinoma in situ were 0.54, 0.35 and 0.78 for sections and 0.47, 0.29 and 0.78 for images, respectively, showing that most of the inconsistency is due to differences in morphological interpretation. Improvements can thus be expected only if diagnostic criteria or methodology are changed. In contrast, kappa for classifying DCIS by growth pattern was very low at 0.23 for sections and better at 0.47 for images, reflecting the widely recognised variation in the growth pattern of DCIS. Higher kappa statistics were obtained when any mention of an individual growth pattern was included in that category, thus allowing multiple categories per case; but kappa was still higher for images than sections. Classifying DCIS by nuclear grade gave kappa values of 0.36 for sections and 0.49 for images, indicating that intralesional heterogeneity has hitherto been underestimated as a cause of inconsistency in classifying DCIS by this method. More rigorous assessment of the proportions of the different nuclear grades present could lead to an improvement in consistency.

Breast↗

Parity and mammographic breast density in relation to breast cancer risk: indication of interaction.

We examined whether the harmful influence of nulliparity on breast cancer risk could be mediated by high mammographic density. Another possibility is that mammographic density and nulliparity act independently or perhaps synergistically on breast cancer risk. Our study population consisted of 129 cases and 517 controls who had been participants in the Nijmegen breast cancer screening programme for 10 years. Breast density was classified with a fully automated technique on digitized mammograms from the screening examination 10 years before diagnosis. Classification was based on the proportion of the breast that was composed of high density: < 5%, 5-25% or > 25%. Data on parity and potential confounders were obtained using a questionnaire, administered at the same examination. We found that nulliparae with low breast density (< 5%) were not at increased risk compared to parous women with low density: OR 1.1 (95% CI 0.2-5.8). Parous women with < 5% density formed the reference category throughout all analyses. The risks for parous women with 5-25% or > 25% density were 2.7 (95% CI 1.3-5.6) and 3.6 (95% CI 1.7-7.7) fold increased, respectively. However, when both factors were present (nulliparity and > or = 5% density), breast cancer risk was 7.1 times higher (95% CI 3.2-15.9). This could indicate that nulliparity and high breast density might work synergistically and that breast density is not just an explanatory factor in the influence of nulliparity on breast cancer risk. It is hypothesized that high breast density (reflecting fibro-glandular tissue with increased epithelial cell proliferation) is more susceptible to carcinogenic effects in the undifferentiated epithelial breast tissue of nulliparae than in the differentiated tissue of parous women. Since there were few data, no firm conclusions can be drawn. If these findings can be confirmed in a larger study population, however, they may have important implications for the prevention and early detection of breast cancer.

Adult↗

Increased levels of homocysteine in patients with Crohn's disease are related to folate levels.

OBJECTIVES: The risk for thrombotic events is increased in inflammatory bowel disease. The factors responsible for such a risk are poorly defined. Recently, an elevated homocysteine level is emerging as a risk factor for thrombosis. The aim of this study was to determine the levels of homocysteine in a well-characterized population of patients with Crohn's disease and to compare it to controls. METHODS: The levels of homocysteine were determined in 105 well-characterized patients with Crohn's disease and 106 controls. The levels of folate and B12, which are involved in the metabolism of homocysteine were determined as well. Patients were treated with steroid preparations only. RESULTS: Homocysteine levels were significantly elevated in the patient population. Elevated levels were correlated with both low B12 and folate levels, but folate deficiency turned out to be a more important factor. Low B12 levels were in correlation with the involvement of the terminal ileum. No correlation was found between homocysteine levels and either disease activity or involvement of the terminal ileum. CONCLUSIONS: Homocysteine levels are increased in patients with Crohn's disease and this finding is inversely correlated with folate levels. Supplementation of folate to patients with Crohn's disease may be warranted.

Adult↗

Cloning, characterization, controlled overexpression, and inactivation of the major tributyrin esterase gene of Lactococcus lactis.

The gene encoding the major intracellular tributyrin esterase of Lactococcus lactis was cloned using degenerate DNA probes based on 19 known N-terminal amino acid residues of the purified enzyme. The gene, named estA, was sequenced and found to encode a protein of 258 amino acid residues. The transcription start site was mapped 233 nucleotides upstream of the start codon, and a canonical promoter sequence was identified. The deduced amino acid sequence of the estA product contained the typical GXSXG motif found in most lipases and esterases. The protein was overproduced up to 170-fold in L. lactis by use of the nisin-controlled expression system recently developed for lactic acid bacteria. The estA gene was inactivated by chromosomal integration of a temperature-sensitive integration vector. This resulted in the complete loss of esterase activity, which could then be recovered after complementation of the constructed esterase-deficient strain with the wild-type estA gene. This confirms that EstA is the main enzyme responsible for esterase activity in L. lactis. Purified recombinant enzyme showed a preference for short-chain acyl esters, surprisingly also including phospholipids. Medium- and long-acyl-chain lipids were also hydrolyzed, albeit less efficiently. Intermediate characteristics between esterases and lipases make intracellular lactococcal EstA difficult to classify in either of these two groups of esterolytic enzymes. We suggest that, in vivo, EstA could be involved in (phospho)lipid metabolism or cellular detoxification or both, as its sequence showed significant similarity to S-formylglutathione hydrolase (FGH) of Paracoccus denitrificans and human EstD (or FGH), which are part of a universal formaldehyde detoxification pathway.

Amino Acid Sequence↗

Tracking clock-shifted homing pigeons from familiar release sites.

Clock-shifted homing pigeons were tracked from familiar sites 17.1 km and 23.5 km from the home loft in Pisa, Italy, using an on-board route recorder. At the first release site, north of home, the majority of clock-shifted birds had relatively straight tracks comparable with those of control birds. At the second release site, south of home, the clock-shifted birds deflected in the direction predicted for the degree of clock shift, with many birds travelling some distance in the wrong direction before correcting their course. The possible role of large-scale terrain features in homing pigeon navigation is discussed.

Animals↗