Biomedical subjects

Wim C J Hop

Publications and source records attributed to Wim C J Hop.

At least 37 records · Page 2Linked to original sources

PubMed2005

Bronchial challenge, assessed with forced expiratory manoeuvres and airway impedance.

OBJECTIVE: The Methacholine concentration at which a 20% decrease of the forced expiratory volume in 1s (PC20_FEV1) or a 40% increase in airway resistance (PC40_Rrs6) occur are accepted indicators for airway hyperresponsiveness. We hypothesised that the level of detection of bronchial hyperresponsiveness will differ between the two methods. METHODS: The response to Methacholine was assessed by forced oscillation technique (FOT) and spirometry in 20 stable hyperresponsive asthmatics. The effects of repeated lung function measurements on respiratory muscle fatigue were measured from maximal inspiratory mouth pressure (MIP). After each dose, patients scored their perception of dyspnoea on a BORG scale. Differences in patient's burden were measured by comparing the BORG-score at PC40_Rrs6 (BORG-PC40_Rrs6) and at PC20_FEV1 (BORG-PC20_FEV1). Reproducibility was also evaluated. RESULTS: The PC20_FEV1-values were 2.2 (0.4) doubling dose higher as compared to the PC40_Rrs6 (P<0.001). The mean BORG-score at PC40_Rrs6 was 1.7 points lower as compared to the BORG-score at PC20_FEV1 (P<0.001). The difference (mean(sd)) between the PC20_FEV1 of measurement 1 and 2 was -0.1 (1.4) doubling dose, and -0.3 (2.7) doubling dose for PC40_Rrs6. The MIP after Methacholine provocation was 1.0(0.2) kPa lower as compared to the MIP before the challenge test (P<0.001), suggesting respiratory muscle fatigue. CONCLUSION: Measuring PC40_Rrs6 shortens the challenge test and lowers the concentrations of bronchoconstrictor agents as compared to measurements of PC20_FEV1. The FOT-method was less strenuous for patients. In spite of the fact that the reproducibility is two-fold worse than measuring PC20_FEV1, it still remains quite acceptable at a mean of 0.3 doubling dose. The respiratory muscle strength was deteriorated after the challenge test.

Adult↗

PubMed2005

Strain-specific in vitro cytokine production profiles do not predict rat liver allograft survival.

The aim of this study was to assess whether differences in cytokine production between inbred rat strains could explain differences in liver allograft survival. Splenocytes from five different strains were cultured with Concanavalin A to determine in vitro cytokine production profiles. Strain-specific TNF-alpha, IFN-gamma, IL-6 and IL-10 responses in naive animals were not associated with survival after rat liver transplantation. To investigate whether in vitro cytokine responses changed during the allogeneic inflammatory response, Brown Norway livers were transplanted to Lewis and Pivold Virol Glaxo recipients. During the early postoperative phase IL-6 and IL-10 (Th2-like) responses were significantly up-regulated in Lewis recipients, whereas Th2-like responses were not increased in Pivold Virol Glaxo. Our results do not support the generally held view that differential in vitro cytokine responses are related to liver allograft survival but suggest that cytokine responses are affected by the allogeneic inflammatory response after liver allografting.

Acute Disease↗

PubMed2005

High-resolution array comparative genomic hybridization of chromosome arm 8q: evaluation of genetic progression markers for prostate cancer.

Copy number increase of 8q has previously been shown to be associated with a poor clinical outcome and tumor recurrence in patients with prostate cancer. In this study, a detailed genomic analysis of 8q was performed of archival primary and metastatic prostatic adenocarcinomas (n = 22), and prostate cancer xenografts (n = 9), and cell lines (n = 3). We performed array comparative genomic hybridization (aCGH) using a whole chromosome arm contig array consisting of 702 8q-specific BAC clones. Five regions of frequent copy number increase were identified, i.e. at chromosome bands 8q21.13 (81-82 Mb), 8q22.1 (94-96 Mb), 8q22.2-3 (101-103 Mb), 8q24.13 (124-126 Mb), and 8q24.21 (127-129 Mb), the most distal region containing the MYC oncogene. MYC and 13 genes of the other four regions with putative relevance to cancer were selected. Two additional genes were derived from high-level amplifications detected by 8q aCGH analysis of prostate cancer xenograft PC339. Quantitative RT-PCR of these 16 genes was performed in a series of 26 prostate specimens, including normal tissue (n = 5), fresh-frozen adenocarcinoma (n = 7), cancer xenograft (n = 9), and cancer cell line material (n = 2). Three of the 16 genes were significantly overexpressed in cancer compared with that in normal prostate tissue, i.e. PDP, located at 8q22.1 (95 Mb), PABPC1 located at 8q22.3 (102 Mb), and KIAA0196 located at 8q24.13 (126 Mb). These genes can be considered putative progression markers for prostate cancer.

Adenocarcinoma↗

PubMed2005

Can a single-shot black-blood T2-weighted spin-echo echo-planar imaging sequence with sensitivity encoding replace the respiratory-triggered turbo spin-echo sequence for the liver? An optimization and feasibility study.

PURPOSE: To optimize and assess the feasibility of a single-shot black-blood T2-weighted spin-echo echo-planar imaging (SSBB-EPI) sequence for MRI of the liver using sensitivity encoding (SENSE), and compare the results with those obtained with a T2-weighted turbo spin-echo (TSE) sequence. MATERIALS AND METHODS: Six volunteers and 16 patients were scanned at 1.5T (Philips Intera). In the volunteer study, we optimized the SSBB-EPI sequence by interactively changing the parameters (i.e., the resolution, echo time (TE), diffusion weighting with low b-values, and polarity of the phase-encoding gradient) with regard to distortion, suppression of the blood signal, and sensitivity to motion. The influence of each change was assessed. The optimized SSBB-EPI sequence was applied in patients (N = 16). A number of items, including the overall image quality (on a scale of 1-5), were used for graded evaluation. In addition, the signal-to-noise ratio (SNR) of the liver was calculated. Statistical analysis was carried out with the use of Wilcoxon's signed rank test for comparison of the SSBB-EPI and TSE sequences, with P = 0.05 considered the limit for significance. RESULTS: The SSBB-EPI sequence was improved by the following steps: 1) less frequency points than phase-encoding steps, 2) a b-factor of 20, and 3) a reversed polarity of the phase-encoding gradient. In patients, the mean overall image quality score for the optimized SSBB-EPI (3.5 (range: 1-4)) and TSE (3.6 (range: 3-4)), and the SNR of the liver on SSBB-EPI (mean +/- SD = 7.6 +/- 4.0) and TSE (8.9 +/- 4.6) were not significantly different (P > .05). CONCLUSION: Optimized SSBB-EPI with SENSE proved to be feasible in patients, and the overall image quality and SNR of the liver were comparable to those achieved with the standard respiratory-triggered T2-weighted TSE sequence.

Adenoma, Liver Cell↗

PubMed2005

Cytokine gene polymorphisms and acute liver graft rejection: a meta-analysis.

In the field of liver transplantation, 7 reports have been published investigating the association between polymorphisms in cytokine genes and the occurrence of acute rejection in liver graft recipients. However, most of the individual studies lack the statistical power to detect a small-to-moderate effect of cytokine gene polymorphisms on the acute rejection rate. To overcome this problem, we performed a quantitative meta-analysis of 7 gene-association studies that were comparable with regard to definition of acute rejection and the type of immunosuppression used. In the overall analysis, the interleukin (IL)-10 polymorphism at position -1082 was identified as a genetic risk factor for acute liver graft rejection; liver transplant recipients carrying the IL-10 -1082.A allele displayed a lower rejection rate (common odds ratio [OR], .6; 95% confidence interval [CI], .4-.9). For the tumor necrosis factor (TNF)-A -308 polymorphism, a common OR could not be calculated due to significant heterogeneity of ORs between the studies (mean OR, 1.4; 95% CI, .8-2.6). No associations were found between acute liver graft rejection and single nucleotide polymorphisms in the IL-6 (position -174) and transforming growth factor (TGF)-beta1 (positions +869 and +915) genes. In conclusion, results from this meta-analysis suggest a role for the IL-10 -1082 polymorphism in human liver graft rejection.

Acute Disease↗

PubMed2005

Cell biological evaluation of liver cell carcinoma, dysplasia and adenoma by tissue micro-array analysis.

The clinical and morphological definition of hepatocellular carcinoma (HCC), dysplasia and adenoma suffers from a lack of biological understanding. This is especially important in the histomorphological diagnosis of nodular liver lesions in needle biopsies. Therefore, we constructed a liver tissue micro-array (TMA) and evaluated 48 HCCs, 46 dysplasias, 8 adenomas, 20 cirrhotic specimens and 28 normal liver samples derived from 68 patients. Protein (over)expression by tumor suppressor genes p16, p53 and Rb1 was assessed by immunohistochemistry, the proliferative capacity was examined by immunostaining of Ki67. Further, DNA ploidy status (hyperdiploidy) was measured by fluorescent in situ hybridization (FISH) with a chromosome 1-specific repetitive DNA probe. An abnormal chromosome 1 number, i.e. the percentage of hyperdiploid cells, was 11.0, 13.7, 16.1, 23.7 and 31.3 for normal liver samples, adenomas, cirrhosis, dysplasias and HCCs, respectively. A significant difference was found for HCC versus cirrhosis (P = 0.024) or adenoma (P = 0.033), a trend (borderline significance) was seen for dysplasia versus cirrhosis (P = 0.094). Immunohistochemical protein localisation of p53 and Rb1, as well as Ki67 indicating proliferation, was clearly higher in HCC than in cirrhosis or dysplasia (all P < 0.001). Proliferation was also higher in HCC than in adenoma (P = 0.025), whereas a trend (borderline significance) was observed for Rb1 overexpression (P = 0.063). These data suggest that in the liver cell dysplasia-carcinoma pathway, changes in ploidy are followed by increased proliferation and cell biological perturbations involving p53 and Rb1. Adenomas can be distinguished from carcinomas, but not from dysplasias, based on ploidy and proliferation characteristics.

Adenoma, Liver Cell↗

PubMed2005

Hereditary breast cancer growth rates and its impact on screening policy.

Imaging is often performed yearly for the surveillance of BRCA1/2 mutation carriers and women at high familial breast cancer risk. Growth of cancers in carriers may be faster as these tumours are predominantly high grade. Quantitative data on tumour growth rates in these 2 groups are lacking. Here, we have examined 80 high-risk women under surveillance for tumour size at diagnosis and preceding examinations at mammography and/or MRI. Tumour volume doubling time (DT) was assessed in 30 cancers in BRCA1/2 mutation carriers and 25 non-carriers. Impact of age and menopausal status were also evaluated. Mean DT of all invasive cancers was shorter in carriers (45 days CI: 26-73) than non-carriers (84 days CI: 58-131) (P = 0.048). Mean age at diagnosis was lower in carriers (40 years) than non-carriers (45 years) (P = 0.007). At multivariable analysis only age (P = 0.03), not risk-group (P = 0.26) nor menopause (P = 0.58) correlated significantly with DT. The mean growth rate slowed down to half in each successive 10 years-older group. In conclusion, age at detection indicated the growth rates of hereditary and familial breast cancers. It is recommended that the screening frequency should be adjusted according to a woman's age and a high-sensitive biannual test may be appropriate before the age of 40 years.

Adult↗

PubMed2005

Intrinsic abnormalities of lymphocyte counts in children with down syndrome.

OBJECTIVE: Down syndrome (DS) is associated with an increased frequency of infections, hematologic malignancies, and autoimmune diseases, suggesting that immunodeficiency is an integral part of DS that contributes significantly to the observed increased morbidity and mortality. We determined the absolute counts of the main lymphocyte populations in a large group of DS children to gain further insight into this immunodeficiency. STUDY DESIGN: In a large group of children with DS (n = 96), the absolute numbers of the main lymphocyte subpopulations were determined with 3-color immunophenotyping using the lysed whole-blood method. The results were compared with previously published data in healthy children without DS. RESULTS: In healthy children with DS, the primary expansion of T and B lymphocytes seen in healthy children without DS in the first years of life was severely abrogated. The T- lymphocyte subpopulation counts gradually reached more normal levels with time, whereas the B- lymphocyte population remained severely decreased, with 88% of values falling below the 10th percentile and 61% below the 5th percentile of normal. CONCLUSIONS: The diminished expansion of T and B lymphocytes strongly suggests that a disturbance in the adaptive immune system is intrinsically present in DS and is not a reflection of precocious aging. Thymic alterations have been described in DS that could explain the decreased numbers of T lymphocytes, but not the striking B lymphocytopenia, seen in these children.

Adolescent↗

PubMed2005

No association between tumor necrosis factor-alpha production and gene polymorphisms among inbred rat strains.

Differences in spontaneous allograft acceptance after liver transplantation among inbred rat strains might be explained by variation in the local production of TNF-alpha as a potent mediator of the inflammatory response. In this study, we hypothesize that nucleotide differences in the rat Tnf gene influence TNF-alpha protein expression. As such, polymorphisms in the Tnf gene may also provide a possible explanation for differences in survival of allogeneic liver grafts among inbred rat strains. We therefore investigated the capacity of mononuclear cells to produce TNF-alpha in response to a mitogenic stimulus and the Tnf locus was sequenced in six different inbred rat strains. Among the six strains (AUG, BN, DA, LEW, PVG and WF), 44 nucleotide differences including 36 single nucleotide polymorphisms (SNPs), five simple sequence length polymorphisms, two deletions and one insertion, were found in the Tnf gene. Although, the inbred rat strains differed significantly in mean levels of maximum TNF-alpha production (P = 0.001), no associations were found with nucleotide differences within the Tnf gene. In conclusion, our results indicate that differential in vitro TNF-alpha responses among inbred rat strains are not associated with nucleotide differences within non-coding regulatory regions of the rat TNF-alpha gene. Without an established relationship between polymorphisms and expression of the TNF-alpha gene, it is preliminary to address a possible association of Tnf gene polymorphisms with rat liver allograft survival.

Animals↗

PubMed2005

Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial.

BACKGROUND: The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable. The multicentre COLOR (COlon cancer Laparoscopic or Open Resection) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon. METHODS: 627 patients were randomly assigned to laparoscopic surgery and 621 patients to open surgery. The primary endpoint was cancer-free survival 3 years after surgery. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, metastasis, overall survival, and blood loss during surgery. Analysis was by intention to treat. Here, clinical characteristics, operative findings, and postoperative outcome are reported. FINDINGS: Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection (median 100 mL [range 0-2700] vs 175 mL [0-2000], p<0.0001), although laparoscopic surgery lasted 30 min longer than did open surgery (p<0.0001). Conversion to open surgery was needed for 91 (17%) patients undergoing the laparoscopic procedure. Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups. Laparoscopic colectomy was associated with earlier recovery of bowel function (p<0.0001), need for fewer analgesics, and with a shorter hospital stay (p<0.0001) compared with open colectomy. Morbidity and mortality 28 days after colectomy did not differ between groups. INTERPRETATION: Laparoscopic surgery can be used for safe and radical resection of cancer in the right, left, and sigmoid colon.

Adult↗

PubMed2005

The incidence of adenocarcinoma and squamous cell carcinoma of the esophagus: Barrett's esophagus makes a difference.

BACKGROUND: Adenocarcinoma limited to the esophagus (ACE) arises in Barrett's esophagus (BE). The incidence of ACE is therefore restricted to this BE subpopulation, whose size is unknown and which is for 95% unidentified. AIMS: To determine the age- and gender-specific incidence rates of ACE, limited to the BE subpopulation, within a defined geographical area and to compare them with those of squamous cell carcinoma of the esophagus (SCC), which can affect the entire population. METHODS: The age- and gender-specific incidence rates for ACE and adenocarcinoma of the cardia (AGC) were calculated after an expert panel classified 87% of all cases of adenocarcinoma of the esophagus reported to the Danish Cancer Registry over a 6-yr period as ACE or AGC. RESULTS: The age-specific incidence rates of ACE for males rose from 0.09/10(5) (30-34 yr) to 14.14/10(5) (80-84 yr), falling to 7.2/10(5) (85+ yr), for females from 0.19/10(5) (45-49 yr) to 2.79/10(5) (80-84 yr), falling to 2.43/10(5) (85+ yr) and yielding a gender ratio of 5.9:1; AGC demonstrated a similar pattern and a gender ratio of 4.26:1. However, the incidence rates of SCC continued rising after the age of 80 yr, with a gender ratio of 2.46:1. CONCLUSIONS: The continuing rise in the SCC incidence rates in the elderly demonstrated that the unexpected decline and fall in the incidence rates of ACE over the age of 80 yr did not result from underdiagnosis but were most probably caused by a declining prevalence rate of BE, restricting the elderly BE subpopulation at risk of developing ACE.

Adenocarcinoma↗

PubMed2005

A randomized, placebo-controlled GH trial in very preterm infants who were at risk for bronchopulmonary dysplasia and were treated with dexamethasone.

Very preterm infants who develop bronchopulmonary dysplasia are often treated with dexamethasone (DEXA) to wean them from the ventilator. As DEXA has growth-suppressive and catabolic effects, which might have long-term consequences on growth and organ development, we investigated whether high-dose GH treatment could overcome these effects. In a randomized, double-blind, placebo-controlled trial, 30 ventilated very low birth weight infants were assigned to receive either GH or placebo treatment after start of DEXA. DEXA was given for 24 d (starting dose 0.5 mg . kg(-1) . d(-1), tapering off every third day). Simultaneously, high-dose GH (0.3 mg . kg(-1) . d(-1)) or placebo was administered during 6 wk. During high-dose DEXA treatment (dose 0.5-0.3 mg . kg(-1) . d(-1)), no gain in head circumference, weight, crown-heel length, and knee-heel length occurred in the GH and placebo groups. Growth during the 6-wk study period was not different between the GH and the placebo groups. Two patients in the placebo group died, but the number and the severity of adverse effects was not statistically different between the GH and placebo groups. In conclusion, high-dose GH treatment did not improve growth in DEXA-treated very preterm infants and thus cannot be recommended to prevent growth failure in these infants. During high-dose DEXA, a complete growth arrest occurred, including stunting of head growth. Growth in head circumference and weight with lower dose DEXA was comparable to growth after discontinuation of DEXA.

Anti-Inflammatory Agents↗

PubMed2004

Salbutamol pMDI gives less protection to methacholine induced airway obstruction than salbutamol via spacer or DPI.

BACKGROUND: Inhalation device and inhalation technique influence the deposition of drug in the lung. This study evaluated the efficacy of salbutamol as a bronchoprotective agent administered via Diskus, Turbuhaler, pMDI or pMDI + Volumatic against methacholine-induced bronchoconstriction. METHODS: Twenty stable asthmatics participated in this open randomised comparison of the protective effects of 200 microg salbutamol, administered via the various inhalation devices on methacholine-induced airway obstruction, with respect to pulmonary function and dyspnoea sensation. The inhalation technique was controlled by measuring the peak inspiratory flow (and actuation time, in the case of pMDI and Volumatic) through the device, during inhalation. RESULTS: Inhalation of salbutamol increased the provocative dose of methacholine by 1.2 doubling doses (dd) for pMDI, 1.9 dd for Diskus, 2.3 dd for Turbuhaler and 2.5 dd for Volumatic. Salbutamol via pMDI provided less protection from methacholine-induced airway obstruction than did salbutamol administered via Diskus, Turbuhaler or Volumatic (P<0.05). The inadequate pMDI use of 70% of our patients might contribute to a lower deposition of drug in the central airways, resulting in the lower protective effect. However, the PC20_FEV1 of the adequate- and inadequate pMDI users showed no significant difference. CONCLUSION: Salbutamol administered via pMDI gave less protection from methacholine-induced bronchoconstriction than did salbutamol via Diskus, Turbuhaler or Volumatic. This study suggests that the pMDI may be less suitable for protecting a patient against bronchoconstriction due to airway hyperresponsiveness.

Administration, Inhalation↗

PubMed2004

Efficacy of fluticasone propionate on lung function and symptoms in wheezy infants.

The role of inhaled corticosteroids in the treatment of recurrent or persistent wheeze in infancy remains unclear. We evaluated the effect of 3 months of treatment with inhaled fluticasone propionate, 200 microg daily (FP200), on lung function and symptom scores in wheezy infants. Moreover, we evaluated whether infants with atopy and/or eczema respond better to FP200 as compared with non-atopic infants. Forced expiratory flow (Vmax(FRC)) was measured at baseline and after treatment. Sixty-five infants were randomized to receive FP200 or placebo, and 62 infants (mean age, 11.3 months) completed the study. Mean Vmax(FRC), expressed as a Z score, was significantly below normal at baseline and after treatment in both groups. The change from baseline of Vmax(FRC) was not different between the two treatment arms. After 6 weeks of treatment, and not after 13 weeks, the FP200 group had a significantly higher percentage of symptom-free days and a significant reduction in mean daily cough score compared with placebo. Separate analysis of treatment effect in infants with atopy or eczema showed no effect modification. We conclude that in wheezy infants, after 3 months of treatment with fluticasone, there was no improvement in lung function and no reduction in respiratory symptoms compared with placebo.

Administration, Inhalation↗

PubMed2004

Pulmonary disease assessment in cystic fibrosis: comparison of CT scoring systems and value of bronchial and arterial dimension measurements.

PURPOSE: To retrospectively compare thin-section computed tomographic (CT) scores obtained with five scoring systems for assessment of pulmonary disease in children with cystic fibrosis and to determine additional value of bronchial and arterial dimension measurements. MATERIALS AND METHODS: Scores obtained with five thin-section CT scoring systems were compared. A score of 0 indicated the absence of abnormalities; a higher score meant that more structural abnormalities were seen. Three observers assigned scores and then reassigned scores after intervals varying from 1-2 weeks to 1-2 months at review of thin-section CT scans obtained in 25 children with cystic fibrosis. Interobserver and intraobserver reliability was calculated with intraclass correlation coefficients. Quantitative measurements of bronchial and arterial dimensions were obtained. Thin-section CT scores were correlated (Spearman correlation) with bronchial and arterial dimensions and with results of pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV(1)). RESULTS: Scores with all five scoring systems were reproducible, with intraclass correlation coefficients of 0.74 and higher (P <.05), and showed significant correlations with FEV(1) (R = -0.73 to -0.69, P <.01). Ratio of bronchial diameter to accompanying pulmonary arterial diameter was correlated with thin-section CT scores but not with FEV(1). Ratio of bronchial wall thickness to accompanying pulmonary arterial diameter was not correlated with thin-section CT scores or PFT results. CONCLUSION: Thin-section CT scores were reproducible and were correlated with PFT results. Measurements of bronchial dimensions were not significantly related to scores or PFT results.

Adolescent↗

PubMed2004

Transjugular intrahepatic portosystemic shunts: long-term patency and clinical results in a patient cohort observed for 3-9 years.

PURPOSE: To retrospectively assess the outcome of transjugular intrahepatic portosystemic shunt (TIPS) placement in a nonselected group of consecutive patients. MATERIALS AND METHODS: TIPS placement was attempted in 82 patients. Patients were followed up for at least 3 years according to a standard protocol that included repeated shunt evaluations. Fifty-four patients underwent TIPS placement for variceal bleeding, 24 for refractory ascites, and four for other indications. Recurrent bleeding, effect on ascites, long-term patency, development of encephalopathy, and survival and complication rates were evaluated with Kaplan-Meier survival analysis and Cox multivariate analysis. RESULTS: TIPS placement was successful in 75 patients (91%). Mean follow-up lasted 29.4 months. Primary patency was 22% and 12%, primary-assisted patency was 67% and 46%, and secondary patency was 91% and 91% at 1- and 5-year follow-up, respectively. Nonalcoholic liver disease (P =.007) and increasing platelet counts (P =.006) independently predicted development of shunt insufficiency. The 1- and 5-year rates of recurrent variceal bleeding were 21% and 27%, respectively. In the majority of patients with refractory ascites, a beneficial effect of TIPS placement was observed. The risk for encephalopathy was 25% at 1-month follow-up and 52% at 3-year follow-up. The risk for chronic or severe intermittent encephalopathy was 15% at 1-year follow-up and 20% at 3-year follow-up. Serum creatinine levels (P =.001) and age (P =.02) were independent risk factors. Overall survival rate was 61%, 49%, and 42% at 1-, 3-, and 5-year follow-up, respectively. Age (P =.03), serum albumin level (P =.02), and serum creatinine level (P <.001) were independently related to mortality. CONCLUSION: The risk for definitive loss of shunt function was 17% at 5-year follow-up, indicating that surveillance with shunt revision-when indicated-results in excellent long-term TIPS patency. TIPS placement effectively protects against recurrent bleeding.

Adult↗

PubMed2004

Intrahepatic CD8 T-lymphocytes and HBV core expression in relation to response to antiviral therapy for chronic hepatitis B patients.

Recognition of HBV-infected hepatocytes by CD8 T-lymphocytes is important for viral clearance. Expression of hepatitis B core antigen (HBcAg) in HBV-infected hepatocytes can trigger this antiviral T-cell response. The intrahepatic CD8 T-lymphocytes and HBcAg expression were investigated in relation to response to antiviral therapy. Forty chronic HBeAg-positive patients treated with either lamivudine (n = 20) or interferon-alpha (n = 20) were investigated. Ten patients from each treatment group exhibited a response. Liver biopsies were carried out before and after therapy. CD8 T-lymphocytes and HBcAg expression were detected by immunohistochemistry. The number of pretreatment intrahepatic CD8 T-lymphocytes was significantly higher in responders (P = 0.008). In responders baseline nuclear HBcAg expression tended to be lower (P = 0.09). Cytoplasmic expression was not significantly different between responders and non-responders (P = 0.46). The number of CD8 T-lymphocytes correlated with cytoplasmic HBcAg (r(s) = 0.31; P = 0.04); CD8 T-lymphocytes were situated in clusters of hepatocytes with cytoplasmic HBcAg. Longitudinal analysis showed a significant reduction of CD8 T-lymphocytes after treatment in responders (P < 0.001). Multivariate analysis revealed pretreatment CD8 T-lymphocytes and age as independent prognostic factors for response (n = 40). The number of pretreatment CD8 T-lymphocytes was the only independent prognostic indicator for response to interferon-alpha (P = 0.03); it was of borderline significance for lamivudine therapy (P = 0.06). It is concluded that the number of pretreatment intrahepatic CD8 T-lymphocytes is an important predictor of response to HBV therapy with either interferon-alpha or lamivudine. Response to therapy led to a significant reduction of intrahepatic CD8 T-lymphocytes. Co-localisation of CD8 T-lymphocytes and HBcAg-positive hepatocytes suggests antiviral activity predominantly at the site of maximum HBV replication.

Adolescent↗

PubMed2004

The effect of cumulative energy and protein deficiency on anthropometric parameters in a pediatric ICU population.

BACKGROUND AND AIMS: Nutritional support is essential in the care of critically ill children since inadequate feeding increases morbidity and negatively affects growth. We aimed to compare cumulative energy and protein intakes with recommended dietary intakes (RDA) and examine relationships between accumulated balances and anthropometric parameters. METHODS: Prospective, observational study. Total daily energy and protein intakes were determined during a maximum of 14 days in 261 children admitted to our multidisciplinary tertiary pediatric ICU. Actual intakes were subtracted from RDA and cumulative balances were calculated. Relations between cumulative balances, various clinical factors and changes in anthropometry (weight, arm and calf circumference) were analyzed using regression analysis. RESULTS: At 14 days after admission children showed significant cumulative nutritional deficits compared to RDA. These deficits were on average 27, 20, 12 kcal/kg and 0.6, 0.3, and 0.2 g protein/kg per day for preterm neonates (n = 103), term neonates (n = 91) and older children (n = 67), respectively. Age at admission, length of ICU-stay and days on mechanical ventilation were negatively related to cumulative balances. Cumulative energy and protein deficits were associated with declines in SD-scores for weight and arm circumference. CONCLUSIONS: Children admitted to the ICU accumulate substantial energy and protein deficits when compared to RDA. These deficits are related to decreases in anthropometric parameters.

Adolescent↗