Search PubMed⌕ Search

Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 181 records · Page 10Linked to original sources
PubMed1998

Efficacy of interferon dose and prediction of response in chronic hepatitis C: Benelux study in 336 patients.

BACKGROUND/AIMS: In an attempt to improve the limited efficacy of treatment of chronic hepatitis C with interferon-alpha 3 MU tiw, we studied the effects of double-dose therapy followed by downward titration, and analyzed the pre- and pertreatment factors associated with response or non-response. METHODS: Three hundred and fifty-four consecutive patients in 19 centers were randomized to interferon-alpha 3 MU tiw for 6 months or 6 MU tiw for 8 weeks followed by down-titration (3,1 MU tiw) till alanine aminotransferase remained normal and plasma HCV RNA was repeatedly undetectable. The primary outcome measure was sustained alanine aminotransferase and HCV RNA response 6 months after treatment. RESULTS: Three hundred and thirty-six patients received treatment. The sustained response rate for patients receiving 3 MU tiw for 6 months was 14% (9-21%,) and for patients receiving double dose tiw for 8 weeks and thereafter titrated therapy 15% (10-21%) (p=0.8). Pretreatment factors associated with a sustained alanine aminotransferase plus HCV RNA response were the absence of cirrhosis, presence of genotype 2 or 3, a low viral load and, in addition, a low alanine aminotransferase/aspartate aminotransferase ratio; a model was developed to allow estimation of the chance of response for the individual patient. The most powerful predictor of sustained response, however, was plasma HCV RNA at week 4; a positive test virtually precluded a sustained response (1.7%, 0.4-5.0%). If week 4 HCV RNA was not detectable, the chance of a sustained response was 21% (12-34%) for genotype 1 versus 40% (28-54%) for the others (p=0.02). Six MU tiw led to a significantly higher week 4 HCV RNA response (47% not detectable) than 3 MU (37%) (p=0.02). During down-titration this difference in viral on-treatment response was lost. CONCLUSIONS: In the treatment of hepatitis C, an early HCV RNA response is a prerequisite for long-term efficacy. Doubling the initial interferon dose increases this early response, but subsequent downward titration negates this effect, especially in genotype 1.

Adult↗
PubMed1998

Sexual networks: the integration of social and genetic data.

New methods for studying sexual networks are presented, drawing upon routine procedures followed in genitourinary medicine clinics in the UK for tracing partners and identifying strains of infection. The routine social procedures were developed to incorporate a structured interview. The routine microbiological diagnosis of gonorrhoea was augmented by phenotyping and the development of new genetic techniques for the fine discrimination of gonococcal strains (opa-typing). Selected results from a study in Sheffield, UK show that each method has limitations, when conducted separately, but these are minimised when the methods are combined. Moreover, the use of simple and routine methods of data collection resolve issues of scale and sample that have beset other network studies, as they provide a means of covering a larger and defined population. Popular concepts about these methods are discussed in the conclusion. The integrated approach employed in our research raises questions both about social methods, 'of people who lie, particularly when they talk about sex', and about microbiological methods, 'of genes that tell the truth' and bypass what people say and think altogether. We argue that these stereotypes are misleading insofar as they suggest that genetic techniques can substitute for the social, and we suggest that even the finest discrimination of organisms at the genetic level will never obviate the need for their interpretation in the light of social data.

Adult↗
PubMed1998

Non-invasive temperature mapping using MRI: comparison of two methods based on chemical shift and T1-relaxation.

PURPOSE: To implement and evaluate the accuracy of non-invasive temperature mapping using MRI methods based on the chemical shift (CS) and T1 relaxation in media of various heterogeneity during focal (laser) and external thermal energy deposition. MATERIALS AND METHODS: All measurements were performed on a 1.5 T superconducting clinical scanner using the temperature dependence of the water proton chemical shift and the T1 relaxation time. Homogeneous gel and heterogeneous muscle phantoms were heated focally with a fiberoptic laser probe and externally of varying degree ex vivo by water circulating in a temperature range of 20-50 degrees C. Magnetic resonance imaging data were compared to simultaneously recorded fiberoptic temperature readings. RESULTS: Both methods provided accurate results in homogeneous media (turkey) with better accuracy for the chemical shift method (CS:+/-1.5 degrees C, T1:+/-2.0 degrees C). In gel, the accuracy with the CS method was +/-0.6 degrees C. The accuracy decreased in heterogeneous media containing fat (T1:+/-3.5 degrees C, CS: +5 degrees C). In focal heating of turkey muscle, the accuracy was within 1.5 degrees C with the T1 method. CONCLUSION: Temperature monitoring with the chemical shift provides better results in homogeneous media containing no fat. In fat tissue, the temperature calculation proved to be difficult.

Animals↗
PubMed1998

Oxygen-induced MR signal changes in murine tumors.

Breathing of 100% oxygen was used to challenge vascular autoregulation in 14 mice with either osteosarcomas (n = 6) or mammary carcinomas (n = 8). Reproducible and statistically significant signal intensity changes of -29 +/- 6% to +35 +/- 3% were observed on heavily T2*-weighted images in the tumors during the oxygen challenge. No significant changes were observed in muscle. For the mammary carcinomas a higher percentage of tumor voxels showed significant signal-intensity decrease (31 +/- 8%) compared to the percentage of voxels showing a signal-intensity increase (22 +/- 3%). In contrast, for the osteosarcomas, a higher percentage of tumor voxels showed signal-intensity increase (52 +/- 9%) compared to the percentage of voxels showing signal-intensity decrease (27 +/- 9%). The regional distribution of these signal intensity changes did not correlate with the signal pattern on T1-, T2-,and T2*-weighted and Gd-DTPA enhanced images acquired without breathing 100% oxygen. Most likely, the signal intensity changes represented the inability of the tumor's neovascularization for autoregulation during the oxygen challenge, particularly in hypoxic regions. Although further investigation is needed, the findings that malignant tumor tissue showed signal intensity changes, whereas normal muscle tissue did not, suggests that this technique may prove useful in distinguishing benign from malignant tissue.

Adenocarcinoma↗
PubMed1998

Epidemiological study of p53 tumor suppressor gene mutations in patients from Luxembourg and the German Saar region with an advanced colorectal cancer using PCR-SSCP analysis.

Mutations in the p53 tumor suppressor gene are usually associated with an advanced development of colorectal cancer characterized by the transition from the adenoma to the carcinoma stage. We used the polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) analysis to screen for the presence of mutations in the p53 gene of patients from Luxembourg and the German Saar region with colorectal cancers at various developmental stages. While we detected no mutations in 16 colic polypi at an early to intermediate stage (adenoma), we revealed seven (13.7%) non-silent point mutations (transitions) in exons 5 to 9 of the p53 gene in 51 colorectal tumors at a late stage (carcinoma). In addition to confirming previous observations, these results show that PCR-SSCP analysis can provide both a sensitive and rapid method for the genetic determination of the histopathological stage of colorectal samples.

Adult↗
PubMed1998

Growth inhibition of newly established human glioma cell lines by leukemia inhibitory factor.

We have established three new cell lines deriving from malignant human gliomas. The cell lines were described in terms of both morphology and growth characteristics. Most cells in all three cell lines expressed the neuroepithelial marker protein GFAP. In terms of growth characteristics, the cells showed only slight differences. The cell lines showed no expression of the neural form of the c-src gene, pp60c-srcN, but did express the ubiquitous form, pp60c-src. The established glioma cell lines were also examined for expression of members of the neuropoietic cytokine family, CNTF and LIF, and their respective receptor components CNTFRalpha, LIFRbeta and gp130. With the exception of CNTFRalpha both the ligands and their receptor components were expressed in similar amounts in all three cell lines. The presence of ligand and receptor prompted us to study the effects of exogenously supplied factors on the growth of the glioma cell lines. Whereas LIF induced a high c-fos expression, only low c-fos induction was observed upon CNTF treatment. Accordingly, CNTF did not have any noticeable effects on glioma cell growth in culture, while LIF mediated an inhibiting effect on the growth of the three glioma cell lines in culture.

Aneuploidy↗
PubMed1998

Psychiatric co-morbidity, suicidal behaviour and suicidal ideation in alcoholics seeking treatment.

AIMS: To estimate the impact of co-morbid disorders for suicidal ideas in alcohol-dependent subjects seeking treatment. DESIGN: Life-time psychiatric co-morbidity and previous suicidal behaviours were assessed retrospectively after detoxification (t1). In addition, suicidal behaviours were assessed 12 months after discharge (t2). SETTING: An inpatient detoxification treatment unit. PARTICIPANTS: Two hundred and fifty dependent inpatients were studied after detoxification. One hundred and forty-nine of them participated in the follow-up face-to-face interviews. MEASUREMENTS: Using two extended standardized interviews (CIDI and IPDE) psychiatric co-morbidity (DSM-III-R, Axes I and II) was assessed at t1; suicide attempts were reported at t1 and t2, and suicidal ideas were assessed at t2. FINDINGS: A history of suicide attempts was reported by 29.2% at t1, and suicidal ideas by 14.1% and suicide attempts by 5.4% at the follow-up (t2). One female patient committed suicide within 6 months of discharge from hospital. The following co-morbidity patterns were associated with the greatest risk for suicidal ideas. Anxiety and depressive disorders, Axes I and 11 disorders, and a history of suicide attempt (for suicidal ideas at (t2). CONCLUSION. Our results underline the importance of psychiatric co-morbidity for the suicidal risk in alcohol-dependent patients, while alcoholism itself appears to be only a moderate risk factor.

Adult↗
PubMed1998

Approaches and issues in defining asthma and associated phenotypes map to chromosome susceptibility areas in large Minnesota families. The Collaborative Study for the Genetics of Asthma (CSGA).

Evidence for linkage of asthma and its associated phenotypes with susceptibility genes on chromosome 12 has been demonstrated in one group of Minnesota families. The evidence is strong in affected sib pairs and weakens in analysis of the large pedigrees. A second group of families provided little evidence for such linkage. A discrepancy has been demonstrated in different families. This may be due to several factors, including genetic heterogeneity and gene-gene, or gene-environmental interaction effects as well as the statistical power of the sample population used.

Adolescent↗
PubMed1998

Neutralization of primary and T-cell line adapted isolates of human immunodeficiency virus type 1: role of V3-specific antibodies.

The role of the third variable domain (V3) of gp120 in the neutralization of primary and T-cell line adapted (TCLA) strains of human immunodeficiency virus type 1 (HIV-1) by serum from HIV-1-infected individuals was investigated. A primary virus isolate, M2424/4, when adapted to H9 cells, was more sensitive to neutralization on MT2 cells than the same stock passaged in PBMC. Neutralization of the PBMC-passaged stock by V3-specific MAbs was abrogated by addition of V3 (MN) peptide. However, exogenous V3 (MN) peptide failed to reduce the neutralization of this isolate on PBMC, or MT2 cells, by high titre anti-HIV-1 polyclonal human sera in contrast to the extensive reduction of neutralization by the same sera on MT2 cells using the prototype MN strain (4- to > or = 24-fold) and the TCLA M2424/H9 isolate (2- to 8-fold). These results indicate that the neutralization of primary virus isolates by serum from HIV-1-infected individuals is not significantly mediated by V3-specific antibodies.

Adaptation, Biological↗
PubMed1998

Large-scale sequencing of two regions in human chromosome 7q22: analysis of 650 kb of genomic sequence around the EPO and CUTL1 loci reveals 17 genes.

We have sequenced and annotated two genomic regions located in the Giemsa negative band q22 of human chromosome 7. The first region defined by the erythropoietin (EPO) locus is 228 kb in length and contains 13 genes. Whereas 3 genes (GNB2, EPO, PCOLCE) were known previously on the mRNA level, we have been able to identify 10 novel genes using a newly developed automatic annotation tool RUMMAGE-DP, which comprises >26 different programs mainly for exon prediction, homology searches, and compositional and repeat analysis. For precise annotation we have also resequenced ESTs identified to the region and assembled them to build large cDNAs. In addition, we have investigated the differential splicing of genes. Using these tools we annotated 4 of the 10 genes as a zonadhesin, a transferrin homolog, a nucleoporin-like gene, and an actin gene. Two genes showed weak similarity to an insulin-like receptor and a neuronal protein with a leucine-rich amino-terminal domain. Four predicted genes (CDS1-CDS4) CDS that have been confirmed on the mRNA level showed no similarity to known proteins and a potential function could not be assigned. The second region in 7q22 defined by the CUTL1 (CCAAT displacement protein and its splice variant) locus is 416 kb in length and contains three known genes, including PMSL12, APS, CUTL1, and a novel gene (CDS5). The CUTL1 locus, consisting of two splice variants (CDP and CASP), occupies >300 kb. Based on the G, C profile an isochore switch can be defined between the CUTL1 gene and the APS and PMSL12 genes.

Alternative Splicing↗
PubMed1998

Comparison of culture- and non-culture-based methods for quantification of viral load and resistance to antiretroviral drugs in patients given zidovudine monotherapy.

Virological assays for human immunodeficiency virus type 1 load and drug resistance can broadly be divided into culture-based and molecular biology-based methods. Culture-based methods give a direct measure of infectious virus load and phenotypic drug resistance, whereas molecular biology-based methods are indirect, assaying nucleic acid levels to determine virus load and point mutations associated with drug resistance. We have compared culture-based and non-culture-based methods for patients enrolled in a placebo-controlled trial of zidovudine (the Concorde Trial). Virus loads were assayed by culture of peripheral blood mononuclear cells (PBMCs) or quantitative PCR, and drug resistance was assayed in culture or in a quantitative, PCR-based point mutation assay. The rates of detection of viremia and drug resistance were higher by PCR than by culture for this population of subjects. Comparison of the virus loads by the two measures showed a good correlation for virus loads in PBMCs but a poor correlation for virus loads in plasma. The latter result probably reflected the inaccuracies of culture in assaying plasma with the low infectious virus titers seen in the study population. The concordance of phenotypic and genotypic drug resistance methods was high, with all phenotypically resistant isolates having at least one resistance-associated mutation and with no mutations being found in a drug-sensitive isolate. Genomic resistance scores (weighted sums of levels of resistance mutations) showed good correlations with the levels of phenotypic resistance, and both resistance measures were observed to increase as the duration of exposure to drug increased. Overall, non-culture-based methods were shown to correlate well with culture-based methods and offer a low-cost, high-throughput alternative. However, culture-based methods remain the final arbiters of infectious virus load and phenotypic drug resistance and are unlikely to be superseded entirely.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Are iodinated contrast agents detrimental in acute cerebral ischemia? An experimental study in rats.

PURPOSE: To study the effects of iothalamate sodium and two dosages of iopromide in acute cerebral ischemia on infarction volume, neurologic performance, and mortality in a rat model of middle cerebral artery occlusion. MATERIALS AND METHODS: Sixty-four rats underwent endovascular occlusion of the middle cerebral artery. Four hours later, 16 animals received iothalamate sodium (588 mg iodine per kilogram); 16, iopromide as a single bolus (518 mg iodine per kilogram); and 16, iopromide as a double bolus (1,036 mg iodine per kilogram). Sixteen animals received equivolumetric saline (control group). Neurologic score and body weight were recorded every 8 hours. Twenty-four hours after occlusion, all animals were killed; brains were stained to assess the infarction size. RESULTS: Single and double doses of iopromide did not affect infarction volume or neurologic performance. Iothalamate caused an increase in infarction volume and worsening of the neurologic score (p < .05). Mortality rate was 25% in the iothalamate group, 12% in the control group, and 6% in the iopromide groups. CONCLUSION: Bolus injection of the nonionic iopromide does not statistically significantly affect infarction volume or cerebral ischemia symptoms. Nonionic rather than ionic contrast agents should be preferred during acute cerebral ischemia.

Acute Disease↗
PubMed1998

Selective intra-arterial fibrinolysis of acute central retinal artery occlusion.

BACKGROUND AND PURPOSE: Occlusion of the central retinal artery (CRAO) causes a sudden decrease of monocular vision. Because early restoration of blood flow may improve outcome, we attempted to treat CRAO with selective intra-arterial fibrinolysis. METHODS: Intra-arterial fibrinolysis was performed within 6 hours after symptom onset in 17 patients with thromboembolic CRAO. Symptoms were painless, acute and severe decrease of vision. Urokinase (100 000 to 900 000 IU) was given through a microcatheter into the ophthalmic artery over 10 to 90 minutes. For comparison, the history and visual outcome of 15 control patients who did not receive fibrinolytics were evaluated. In both groups some of the patients underwent paracentesis and/or received carboanhydrase inhibitors. RESULTS: Patients who underwent fibrinolysis fared better than control patients (P=0.01). Three patients (17.6%) recovered completely after fibrinolysis and regained visual acuity of 20/20 (n=2) to 25/20 (n=1). Two additional patients (11.8%) showed a marked improvement to a visual acuity of 20/30. In 6 patients (35. 3%) vision improved slightly. They were able to count fingers, detect hand movements, or perceive light. In 6 patients (35.3%), fibrinolytic treatment was without effect. Among control patients, 1 patient (6.7%) showed partial, 4 patients (26.7%) minimal, and 10 (66.7%) no improvement of vision. CONCLUSIONS: A complete or marked improvement of visual acuity was achieved in one third of intra-arterial fibrinolysis patients but in none of the control patients. Intra-arterial fibrinolysis seems to have the potential to "lighten" the spontaneously poor outcome of CRAO.

Acute Disease↗
PubMed1998

An unusual case of Hughes-Stovin syndrome.

In 1959 HUGHES and STOVIN described a syndrome consisting of multiple pulmonary aneurysms and peripheral venous thrombosis. Since that time several cases of the Hughes-Stovin syndrome have been published. We present the case of a 25 yr old man who, in addition to the classical symptoms, had multiple aneurysms of the bronchial arteries, which were the cause of severe haemoptysis. An aneurysm of the left hepatic artery was also detected. To our knowledge this is the first description of aneurysms of the bronchial arteries in Hughes-Stovin syndrome. Bleeding was successfully treated by double embolization of bronchial arteries via transfemoral catheter.

Adult↗
PubMed1998

Sexual histories, partnerships and networks associated with the transmission of gonorrhoea.

We aimed to describe and compare sexual links among people with gonorrhoea, by studying patients in 2 UK departments of genitourinary medicine. Interviews were completed for 510 and 235 cases in London and Sheffield respectively. There was a greater proportion of cases in men, homosexual men, non-white and non-British people and fewer female sex workers in London. Total networks of 1738 people in London and 570 people in Sheffield were described. Large linked heterosexual networks identified in Sheffield were associated with local contact, including men with higher numbers of sexual partners. Condom use for vaginal sex was reported for 11% of heterosexual partnerships in Sheffield, and 27% in London, with little difference between regular and casual partners. It was more difficult to define networks in London due to a high proportion of relatively anonymous contacts. These difficulties suggest that research and interventions may profitably focus upon venues for meeting partners as well as partner notification.

Adolescent↗
PubMed1998

[Kinematics of the healthy and arthritic hip joint during walking. A study of 136 subjects].

PURPOSE OF THE STUDY: The study aimed to analyze the spatiotemporal parameters and 3-dimensional pelvic and hip kinematic components during gait in two groups: patients with a primitive osteoarthritis of the hip and control normal subjects. MATERIAL: The study included 51 patients, ranged from 42 to 81 years, and 86 normal subjects. METHOD: Gait analysis was performed using the optoelectronic system VICON with 5 cameras in free-speed conditions. Functional grading of the patients was assessed by Lequesne's score. Thickness of the hip cartilage was measured on pelvis AP radiograph. A preliminary study was performed to measure reliability of the data on 11 patients. RESULTS: At the initial stage of osteoarthritis, speed, cadence, stride length and hip flexion-extension motion appeared as very close to normal data. After this initial stage, there was a statistical relationship between these parameters and arthritis functional grading. Pelvis rotation around the vertical axis did not change according to severity of functional grading. The mean value of this component of pelvis motion was 10 degrees in the pathological group, whereas it was 8 degrees in the female normal group, and 7 degrees in the male group. There were no significant relationship between radiographical thickness of hip cartilage and functional grading of patients or gait parameters. DISCUSSION: This study demonstrates that spatiotemporal gait parameters and kinematic data appear as quantitative index which could be used in future studies. It also shows that pelvic rotation is greater in pathological group than in normal subjects, even in the extreme beginning of the hip osteoarthritis. This particularity can be explained as a very early consequence of the arthritis or, in the opposite, as risk factor.

Adult↗