PubMed Health⌕ Search

Biomedical subjects

M Schipper

Publications and source records attributed to M Schipper.

12 recordsLinked to original sources

A prediction rule for elderly primary-care patients with lower respiratory tract infections.

Prognostic scores for lower respiratory tract infections (LRTI) have been mainly derived in a hospital setting. The current authors have developed and validated a prediction rule for the prognosis of acute LRTI in elderly primary-care patients. Data including demographics, medication use, healthcare use and comorbid conditions from 3,166 episodes of patients aged > or =65 yrs visiting the general practitioner (GP) with LRTI were collected. Multiple logistic regression analysis was used to construct a predictive model. The main outcome measure was 30-day hospitalisation or death. The Second Dutch Survey of GPs was used for validation. The following were independent predictors of 30-day hospitalisation or death: increasing age; previous hospitalisation; heart failure; diabetes; use of oral glucocorticoids; previous use of antibiotics; a diagnosis of pneumonia; and exacerbation of chronic obstructive pulmonary disease. A prediction rule based on these variables showed that the outcome increased directly with increasing scores: 3, 10 and 31% for scores of <2 points, 3-6 and > or =7 points, respectively. Corresponding figures for the validation cohort were 3, 11 and 26%, respectively. This simple prediction rule can help the primary-care physician to differentiate between high- and low-risk patients. As a possible consequence, low-risk patients may be suitable for home treatment, whereas high-risk patients might be monitored more closely in a homecare or hospital setting. Future studies should assess whether information on signs and symptoms can further improve this prediction rule.

Aged↗

Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study.

BACKGROUND: Infection with human papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN). Variability in host immunogenetic background is important in determining the overall cellular immune response to HPV infections. OBJECTIVE: To determine whether the HLA-DQ or HLA-DR genes, or others in their vicinity, are associated with cervical cancer. METHODS: Markers covering the entire HLA region were genotyped in a large sample of CIN and cervical cancer patients and in controls (311 CIN, 695 cervical cancer, 115 family controls, and 586 unrelated controls). RESULTS: Two markers were associated with susceptibility to cervical neoplasia, G511525 and MICA. G511525, close to the region containing the HLA-DQ and HLA-DR genes, was most strongly associated, showing a decrease in frequency of allele 221 from 6.7% to 3.3% in patients with squamous cell cancer (SCC). An association was found for MICA (allele 184) with SCC (odds ratio (OR) = 1.31 (95% confidence interval, 1.13 to 1.53); homozygotes, OR = 1.48 (1.06 to 2.06)). No associations were observed with adenocarcinoma or CIN. CONCLUSIONS: There is an association of the region containing the HLA-DQ and HLA-DR genes with the risk of developing squamous cell carcinoma. An increased risk was observed for carriers of allele 184 at the MICA locus, in particular for homozygotes, suggesting a recessive effect.

Adenocarcinoma↗

Glomerular immunoglobulin deposits induce glomerular inflammation in pregnant but not in non-pregnant rats.

PROBLEM: Does an inflammatory stimulus evoke a more intense inflammatory response in pregnant rats as compared with non-pregnant rats? METHOD OF STUDY: Non-pregnant rats were injected with antibodies against the glomerular basement membrane (GBM), 14 days before pregnancy, to induce a subclinical glomerulonephritis. Part of the rats were rendered pregnant, the others remained non-pregnant throughout the experiment. Two experiments were performed: in experiment 1, pregnant and non-pregnant rats were killed at various intervals after the injection with antibody and parameters characteristic of a glomerular inflammation were evaluated using immunohistology on cryostat kidney sections and liver sections. In experiment 2, 24-hr urinary protein excretion was measured at various days after the injection in pregnant and non-pregnant rats. RESULTS: Experiment 1 revealed that a significant glomerular inflammation, as characterized by increased numbers of monocytes and LFA-1 positive cells per glomerulus, was only observed in pregnant rats with glomerulonephritis. Experiment 2 revealed that only pregnant rats with glomerulonephritis showed increased urinary protein excretion. CONCLUSION: The fact that glomerular inflammation coincides with proteinuria only in pregnant rats with glomerulonephritis, may suggest that these phenomena are causally related and promoted by the pregnant condition.

Animals↗

[Sequential analysis in clinical and epidemiological research].

In clinical trials and epidemiological studies, interim analyses are usually performed for ethical or economical reasons, although efficiency aspects can also be a reason. The analysis is referred to as group-sequential analysis or continuous-sequential analysis, dependent on the number of interim analyses performed. Repeated testing of cumulative data requires an adjustment to the significance level or type I error alpha of a statistical test. On average a (group-)sequential analysis of a clinical or epidemiological study requires less patients than the analysis of a fixed-sample study.

Clinical Trials as Topic↗

Follow-up of perfusion defects in pulmonary perfusion scanning after pulmonary embolism: are we too careless?

Persisting perfusion defects may still be found in pulmonary perfusion scintigraphy months or years after pulmonary embolism. The aim of this study was to investigate the rate of persisting perfusion defects and the pattern of scintigraphic follow-up of patients after pulmonary embolism. Only those patients were included into our study who received pulmonary perfusion scintigraphy between 1991 and 1999, and who had perfusion defects including at least one whole segment. These perfusion defects were considered as persisting perfusion defects if unchanged over at least 1 year. From 3640 patients examined, 451 (12.4%) had perfusion defects meeting the criteria of this study. Of those, 129 (28.6%) received a scintigraphic follow-up. In 62 patients (48.1%), a reperfusion of the defects was found. In 38 patients (29.5%), the defects persisted within a follow-up period of up to 12 weeks. However, no pulmonary perfusion scintigraphy was performed thereafter. Out of the 129 patients receiving a scintigraphic follow-up, only 29 (22.5%) had a follow-up over more than 1 year, 19 of those had persisting perfusion defects. It is concluded that our data show an inadequate scintigraphic follow-up of patients with pulmonary embolism which may lead to unnecessary anticoagulant treatment if persisting perfusion defects are misinterpreted as fresh pulmonary embolism. In many cases, there was no further follow-up even if reperfusion of the defects was lacking in early follow-up.

Adult↗

Ductus venosus studies in fetuses at high risk for chromosomal or heart abnormalities: relationship with nuchal translucency measurement and fetal outcome.

OBJECTIVE: To investigate, in a high-risk group of fetuses, the role of ductus venosus Doppler velocimetry as a prognostic factor, in addition to nuchal translucency measurement, for predicting chromosomal anomalies and, where the karyotype was normal, for predicting fetal outcome. METHODS: Nuchal translucency was measured and ductus venosus pulsatility index and late diastolic flow (a-wave) were recorded in 186 fetuses at a median gestational age of 12.6 weeks (range, 10-17). Fetal karyotype, the presence of structural anomalies, pregnancy outcome, neonatal examination at birth and postnatal follow up were the outcome values. RESULTS: Nuchal translucency measurement was increased in 112 fetuses. The outcome of pregnancy was normal in 130 fetuses. Fifty-six fetuses had an adverse outcome (46 chromosomal anomalies, three intrauterine deaths, six structural anomalies and one developmental disorder). The sensitivity of an abnormal ductus venosus pulsatility index or of absent or reversed flow during the a-wave was 65% for chromosomal anomalies and 68% for an adverse outcome. The specificity was 79%. There was a significant correlation between nuchal translucency and ductus venosus pulsatility index. In chromosomally normal fetuses with an enlarged nuchal translucency an abnormal ductus venosus flow was associated with a nearly nine-fold increase in adverse outcome (odds ratio 11.7). CONCLUSION: Ductus venosus Doppler velocimetry can be used in addition to nuchal translucency measurement as a predictor of chromosomal anomalies. However, as the ductus venosus blood flow pattern is correlated with nuchal translucency measurement it cannot be used as an independent variable to reduce the indication for fetal karyotyping. Ductus venosus Doppler velocimetry may have a role in the counseling of parents in the case of an enlarged nuchal translucency and normal karyotype by identifying those fetuses in need of an intensive follow up due to an increased risk of adverse outcome.

Adult↗

Distinct promoters induce APOBEC-1 expression in rat liver and intestine.

The expression of apolipoprotein (apo) B can be modulated by mRNA editing, a unique posttranscriptional base change in the apo B mRNA. Apo B-48, the translation product of edited apo B mRNA, is not a precursor of the atherogenic low density lipoproteins and lipoprotein(a). In humans and various other mammals, the apo B mRNA is edited in the intestine but not in the liver, which exclusively secretes apo B-100-containing lipoproteins as precursors for low density lipoprotein formation. In species such as the rat, mouse, dog, and horse, apo B mRNA is also edited in the liver, resulting in low plasma levels of low density lipoprotein. Editing of the apo B mRNA is mediated by the apo B mRNA-editing enzyme complex, of which the catalytic subunit APOBEC-1 is not expressed in the liver of species without hepatic editing. To understand the molecular basis for liver-specific expression of APOBEC-1 and the editing of hepatic apo B mRNA, the expression pattern and genomic organization of the rat APOBEC-1 gene have been characterized. The rat APOBEC-1 gene contains 6 exons and 2 promoters with distinct activities. The expression of APOBEC-1 in the rat liver is the result of a promoter located upstream, with tissue-specific exon use and alternate splicing within the 5'-untranslated region of APOBEC-1 mRNA encoded by exon 2. In addition to the liver, this promoter also induces APOBEC-1 expression in the spleen, lung, kidney, heart, and skeletal muscle. The promoter located downstream belongs to a new class of TATA-less promoters and is responsible for the abundant expression of APOBEC-1 in the intestine. Mapping of the transcriptional start sites and deletion analysis of the promoter regions by using luciferase as the reporter gene have defined the regulatory elements of both promoters. The downstream, intestine-specific promoter contains a negative regulatory element between -1100 and -500, which appears to restrict its activity to the intestine. The upstream, liver-specific promoter of the rat APOBEC-1 gene induces APOBEC-1 expression and editing of apo B mRNA in human hepatoma HuH-7 and Hep G2 cells. Understanding the molecular basis for the liver-specific expression of APOBEC-1 in the rat promises new strategies to induce APOBEC-1 expression in the human liver for the reduction of atherogenic lipoprotein levels by hepatic apo B mRNA editing.

APOBEC-1 Deaminase↗

Implausibility of an aetiological association between cytomegalovirus and Kaposi's sarcoma shown by four techniques.

The presence of cytomegalovirus (CMV) was analysed in either lymph node or skin and lung tissue necropsy specimens affected by Kaposi's sarcoma, from 10 patients who had died of AIDS. The different detection techniques used were: (i) immunohistochemical demonstration of CMV immediate early antigen (IEA); (ii) in situ hybridisation with a biotinylated CMV DNA probe; (iii) Southern blot hybridisation of DNA extracted from sequential tissue sections; and (iv) polymerase chain reaction (PCR) with CMV specific primers on the DNA samples. The results of these analyses were compared with the postmortem data on CMV obtained by infectious particle assays and histological examination, especially of adrenal glands of the same patients. The results of the various detection methods correlated very well, yielding a combined score of six of 10 patients positive for CMV; there did not seem to be any association between the presence of CMV and the occurrence of Kaposi's sarcoma in our patients.

Antigens, Viral↗

Detection of Campylobacter pylori in stomach tissue by DNA in situ hybridisation.

A non-radioactive DNA in situ hybridisation (DISH) protocol was developed. It requires the use of biotinylated Campylobacter pylori DNA as the probe to detect C pylori DNA in routinely embedded stomach biopsy specimens. In sequential tissue samples from a 58 year old woman with recurrent chronic active gastritis the C pylori probe hybridised with bacteria whenever they were histologically visible. When no bacteria were visible histologically, hybridisation was negative with one exception. In a single biopsy specimen without visible C pylori, hybridisation occurred with the surface of the antrum epithelium, while control hybridisation with a heterologous probe remained negative. From a parallel biopsy specimen taken at the same time the C pylori culture was positive. It is concluded that DISH, although more laborious than routine staining techniques, may be more sensitive in that it detects bacteria very easily, even when sections are not counterstained or when they are present in low numbers, and that bacteria which do hybridise are unequivocally identified as C pylori and not Campylobacter-like organisms.

Campylobacter↗

Lymphadenopathy in HIV infection: histological classification and staging.

The histological alterations seen in HIV-related lymphadenopathy have been described with different terms by different authors. In order to facilitate comparisons of results from various laboratories, a group of pathologists of the European Lymphoma Study Group (later the European Association for Haematopathology) have proposed a histological classification for the evaluation of HIV related lymphadenopathy. Most observers agree that the morphological and immunohistochemical alterations in the follicles (germinal centres) are the most conspicuous and earliest changes seen. The follicular alterations were therefore used as the basis for the proposed classification. In addition, some features occasionally seen were also included, i.e. angioimmunoblastic hyperplasia, multicentric Castleman-like lesions, and vascular lesions, especially pretumorous and tumorous stages of Kaposi's sarcoma. The proposed classification was used by the members of the group of a collection of lymph nodes compiled from the various centres. The classification was shown to be reproducible and to have clinical relevance in staging of the patients. The prognostic relevance as to the survival of the patients has to be further substantiated by follow-up studies. The proposed classification offers a common terminology for the alterations previously described by different terms by various authors.

AIDS-Related Complex↗

Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease.

Infection with oncogenic types of human papillomavirus (HPV) is the main causal factor of cervical cancer and its precursor lesion (cervical intraepithelial neoplasia [CIN]). Cellular immunity may be critical in the elimination of HPV-harboring cells. Interleukin-10, a T-helper type 2 cytokine, has a suppressive effect on cell-mediated immunity. Resistance to apoptosis through the Fas pathway might enable many cancers to escape the immune system. We examined in a large study population whether three polymorphisms in the IL-10 gene and a polymorphism at position -670 of the Fas promotor affect susceptibility for cervical cancer or its precursor. In addition, it was studied whether these polymorphisms were causal and not merely associated by typing microsatellite markers in the region surrounding both genes. A total of 311 CIN, 695 cervical cancer patients, and 115 family-based and 586 unrelated controls were analyzed. Association analysis revealed an increased CIN (II-III) (OR 1.44 [1.06-1.97]) and squamous cell carcinoma of the cervix (OR 1.35 [1.04-1.75]) for individuals heterozygous for the A-allele of the IL-10-592 polymorphism. In contrast to previous findings, no association was found for the IL-10-1082 polymorphism. While an increased risk for adenocarcinoma (AC) in heterozygotes (OR 1.59 [1.02-2.48]) was observed. Our study shows a possible role for the IL-10 gene in CIN and squamous cell cervical cancer susceptibility in the Caucasian population; simultaneously, there might be a role for the Fas gene in the development of AC of the cervix. Further investigations with a higher density of markers are necessary to find the causal mutation.

Adenocarcinoma↗