Reinhart Willers

Correlation of viral load of respiratory pathogens and co-infections with disease severity in children hospitalized for lower respiratory tract infection.

Abstract Background The clinical significance of viral load and co-infections in children with respiratory infections is not clear. Objective To evaluate the correlation of viral load as well as viral and bacterial co-infections with disease severity in hospitalized children with lower respiratory tract infections (LRTIs). Study design This is a prospective study conducted in children admitted for LRTIs for two seasons. To determine viral and bacterial load of respiratory pathogens we performed multiplex real-time polymerase chain reaction and semiquantitative bacterial cultures on nasopharyngeal aspirates (NPA). Results During the study period 244 (60%) children were hospitalized for LRTI with acute virus-induced wheezing and 160 (40%) for radiologic confirmed pneumonia. In the first NPA, viruses were identified in 315 (78%) of the 404 samples and bacteria in 198 (63.3%) of 311 samples. The viral load significantly decreased between the first and second NPA sample in most single and viral co-infections, except rhinovirus and human bocavirus infections. Viral load was inversely related to CRP in RSV infections, whereas a positive correlation was observed in adenovirus infections. Duration of hospitalization was significantly longer in RSV single infections compared to rhinovirus single infections whereas in the latter, leucocytosis and use of systemic steroids was more common. In RSV viral co-infections the presence of fever, leucocytosis, and the use of antibiotics was significantly more frequent. Positive cultures of Haemophilus influenzae dominated in RSV and rhinovirus single infections and Moraxella catarrhalis in RSV viral co-infections. Conclusions Specific viral single and co-infections as well as viral load contribute to disease severity in children with LRTIs.

p53 protein expression and prognosis in squamous cell carcinoma of the esophagus.

Background. The p53 gene product is known to regulate cell growth and proliferation. Whereas the wild‐type p53 protein suppresses cell growth, the mutated p53 protein acts as an oncogene. Mutations in the p53 gene usually result in p53 protein stabilization and accumulation; so that the gene product can be detected by immunohistochemistry. Recently, the immunohistochemical detection of the p53 protein was associated with prognosis in breast, colorectal, and other types of cancer. However, its prognostic role in esophageal cancer remains to be elucidated.

Basaloid squamous cell carcinoma of the esophagus

Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract.

Self-assessments of patients via Tablet PC in routine patient care: comparison with standardised paper questionnaires

Objective: We evaluated the feasibility of electronic data capture of self-administered patient questionnaires using a Tablet PC for integration in routine patient management; we also compared these data with results received from corresponding paper–pencil versions. Methods: Standardised patient questionnaires (FFbH/HAQ, BASDAI, SF-36) were implemented in our documentation software. 153 outpatients (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis) completed sets of questionnaires as paper–pencil and electronic versions using a Tablet PC. The quality and validity of data obtained using a Tablet PC and the capability of disabled patients to handle it were assigned; patients’ experiences, preferences and computer/internet use were also assessed. Results: Scores obtained by direct data entry on the Tablet PC did not differ from the scores obtained by the paper–pencil questionnaires in the complete group and disease subgroups. No major difficulties using the Tablet PC occurred. 62.1% preferred remote data entry in the future. Seven (4.6%) patients felt uncomfortable with the Tablet PC due to their rheumatic disease. Conclusions: Self-administered questionnaires via Tablet PC are a facile and capable option in patients with rheumatic diseases to monitor disease activity, efficacy and safety assessments continuously. Tablet PC applications offers directly available data for clinical decision-making improves quality of care by effective patient monitoring, and contributes to patients’ empowerment.

Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

Abstract.Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021).

Prognostic relevance of Tiam1 protein expression in prostate carcinomas

The Rac-specific guanine nucleotide exchange factor, Tiam1, plays a major role in oncogenicity, tumour invasion and metastasis but its usefulness as a prognostic marker in human cancer has not been tested yet. In the present study, Tiam1 expression was analysed in benign secretory epithelium, pre-neoplastic high-grade prostatic intraepithelium neoplasia (HG-PIN) and prostate carcinomas of 60 R0-resected radical prostatectomy specimens by semiquantitative immunohistochemistry. Tiam1 proved significantly overexpressed in both HG-PIN (P<0.001) and prostate carcinomas (P<0.001) when compared to benign secretory epithelium. Strong Tiam1 overexpression (i.e. ⩾3.5-fold) in prostate carcinomas relative to the respective benign prostatic epithelium was statistically significantly associated with disease recurrence (P=0.016), the presence of lymph vessel invasion (P=0.031) and high Gleason scores (GS) (i.e. ⩾7) (P=0.044). Univariate analysis showed a statistically significant association of strong Tiam1 overexpression with decreased disease-free survival (DFS) (P=0.03). This prognostic effect of strong Tiam1 overexpression remained significant in multivariate analysis including preoperative prostate-specific antigen levels, pT stage, and GS (relative risk= 3.75, 95% confidence interval=1.06–13.16; P=0.04). Together, our data suggest that strong Tiam1 overexpression relative to the corresponding benign epithelial cells is a new and independent predictor of decreased DFS for patients with prostate cancer.

The use of different buffers during continuous hemofiltration in critically ill patients with acute renal failure

Objective: To determine the impact of different hemofiltration (HF) replacement fluids on the acid-base status and cardiovascular hemodynamics in patients with acute renal failure (ARF) and continuous veno-venous hemofiltration (CVVH).¶Design: Prospective, cohort study.¶Setting: Intensive Care Unit of the Heinrich Heine University Hospital, Düsseldorf, Germany.¶Subject and methods: One hundred and thirty-two critically ill patients with acute renal failure and continuous veno-venous HF were studied. Fifty-two patients were subjected to lactate-based (group 1), and 32 to acetate-based hemofiltration (group 2)while 48 (group 3) were treated with bicarbonate-based buffer hemofiltration fluid. Fifty-seven had a septic, and 75 a cardiovascular, origin of the ARF. Creatinine, blood urea nitrogen (BUN), serum bicarbonate, arterial pH, lactate and Apache II scores were noted daily.¶Main results: The mean CVVH duration was 9.8 ± 8.1 days, mortality was 65 %. No difference was present between the groups under investigation with regard to the main clinical parameters. Lactate- and bicarbonate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Serum bicarbonate values at 48 h after the initiation of CVVH treatment were 25.7 ± 3.8 mmol/l (p < 0.001) in group 1, 20.6 ± 3.1 mmol/l in group 2 and 23.3 ± 3.9 mmol/l (p < 0.001) in group 3. While a lack of increase in serum bicarbonate and arterial pH was correlated to poor prognosis in lactate- and bicarbonate-based hemofiltration, no such observation was made in acetate-based hemofiltration. Cardiovascular hemodynamics were superior in patients treated with lactate- and bicarbonate-based buffer solution as compared to those treated with acetate-based buffer solution.¶Conclusions: The degree of correction of acidosis during hemofiltration was determined by patient outcome in patients treated with lactate- and bicarbonate-based buffer solutions, but not in patients receiving acetate-buffered solution. Bicarbonate and lactate-based buffer solutions were found to be superior to acetate-based replacement fluid.

Association between NAD(P)H: Quinone oxidoreductase 1 (NQ01) inactivating C609T polymorphism and adenocarcinoma of the upper gastrointestinal tract

NQO1 is an antioxidant enzyme, important in the detoxification of environmental carcinogens. A single nucleotide polymorphism (C→T) at position 609 of the NQO1 cDNA has been associated with susceptibility to tumours induced by chemical carcinogens. In our case‐control study, we determined the prevalence of the C609T NQO1 polymorphism by PCR‐RFLP analysis in Caucasian patients with oesophageal adenocarcinoma (OAC; n=61), cardiac adenocarcinoma (CAC; n=120) or gastric adenocarcinoma (GAC; n=203) vs. a control group that consisted of 252 healthy blood donors. Additionally, NQO1 mRNA expression and NQO1 protein expression were determined by RT‐PCR and immunohistochemistry in a subset of cases. The NQO1 C609T genotype distribution was significantly different among controls (C/C, 73.4%; C/T, 25.0%; T/T, 1.6%) as compared to OAC patients (C/C, 49.2%; C/T, 47.5%; T/T, 3.3%; p=0.0004), CAC patients (C/C, 55.8%; C/T, 40.0%; T/T, 4.2%; p=0.0005) and with GAC patients (C/C, 65.5%; C/T; 30.6%, T/T; 3.9%; p=0.0377). The 609T allele overall frequency was 0.141 in controls, 0.270 in OAC patients, 0.241 in CAC patients and 0.192 in GAC patients. Individuals carrying 1 or 2 609T alleles had a 2.85‐fold higher risk (95% CI: 1.61–5.07; p=0.0003) for the development of OAC and a 2.18‐fold higher risk (95% CI: 1.38–3.44; p=0.0007) for the development of CAC than wild‐type gene homozygotes. Immunohistochemical analysis showed NQO1 protein expression in 133 carcinomas, whereas 17 carcinomas were negative. Negativity for NQO1 protein expression correlated strongly with the NQO1 genotype being present in 3.9% of cases with C/C, 13.9% of cases with C/T and 62.5% of cases with T/T genotype (p<0.001). In contrast, NQO1 mRNA expression was detectable irrespective of underlying genotype. In conclusion, determination of the NQO1 genotype may gain importance as a stratification marker in future prevention trials for adenocarcinoma of upper gastrointestinal tract.

Prognostic value of histopathologic parameters of esophageal squamous cell carcinoma

Background. The grading of squamous cell carcinoma (SCC) of the esophagus as proposed by the World Health Organization (WHO) has not yet proved to be prognostically significant. Therefore, the prognostic impact of various histologic parameters was investigated and compared with that of the WHO grading.

bcl-2 expression and prognosis in squamous-cell carcinomas of the esophagus

The bcl‐2 proto‐oncogene is a known inhibitor of apoptosis and may be an important regulator of tumor growth. In the present study, bcl‐2‐protein expression was investigated by immunohistochemistry and correlated with prognosis in a series of 150 potentially curatively resected squamous‐cell carcinomas of the esophagus. For comparison bcl‐2‐protein expression was analyzed in normal esophageal mucosa, severe squamous dysplasias and carcinomas in situ. bcl‐2 immunoreactivity was found in 48 out of 150 invasive squamous‐cell carcinomas; the remaining carcinomas were completely negative. bcl‐2‐protein expression was found more frequently among poorly differentiated than among well‐differentiated tumors (p < 0.0001). No correlation was found between bcl‐2‐protein expression and the parameters tumor size, depth of invasion and nodal status. Moreover bcl‐2‐protein expression had no significant influence on overall survival. Whereas in normal mucosa bcl‐2 immunoreactivity was restricted to the basal‐cell layer, in 9 out of 15 severe squamous dysplasias and in 7 out of 14 carcinomas in situ bcl‐2 staining was detected in all epithelial layers. Thus bcl‐2‐protein is frequently expressed in invasive squamous‐cell carcinomas of the esophagus and in precursor lesions of esophageal cancer but has no significant impact on the outcome of esophageal cancer.