Gastroparesis in patients with inactive Crohn's disease: a case series

Background  

Few studies have described patients with foregut dysmotility in inflammatory bowel disease. The aim of this case series was to evaluate clinical characteristics of 5 patients with inflammatory bowel disease and symptoms and signs of upper gut dysmotility.     

Ontario familial colon cancer registry: methods and first-year response rates

The Ontario Familial Colon Cancer Registry (OFCCR) is a novel registry that collects family history information, epidemiologic data, blood samples and tumour specimens from a population-based sample of colorectal cancer patients and their families. Families are classified as either high familial risk, intermediate familial/other risk or low (sporadic) risk for colorectal cancer. Obtaining high response rates in genetic family studies is especially challenging because of both the time commitment required and issues of confidentiality. The first-year response rate was 61%, resulting in 1,395 participating probands. In an attempt to assess potential response bias, we compared participants with non-participants. The age and sex of participants did not differ from non-participating probands; however, cases in rural areas were somewhat more likely to participate. To date, 57% of 1,587 relatives participated; females were more likely to participate, and relatives of low familial risk were least likely to participate. The OFCCR is an excellent resource that will facilitate the study of genetic and environmental factors associated with colorectal cancer.     

Diverging associations of an intended early invasive strategy compared with actual revascularization, and outcome in patients with non-ST-segment elevation acute coronary syndrome: the problem of treatment selection bias

AIMS: In several observational studies, revascularization is associated with substantial reduction in mortality in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine early angiography would lead to a reduction in mortality. We investigated the association between actual in-hospital revascularization and long-term outcome in patients with nSTE-ACS included in the ICTUS trial. METHODS AND RESULTS: The study population of the present analysis consists of ICTUS participants who were discharged alive after initial hospitalization. The ICTUS trial was a randomized, controlled trial in which 1200 patients were randomized to an early invasive or selective invasive strategy. The endpoints were death from hospital discharge until 4 year follow-up and death or spontaneous myocardial infarction (MI) until 3 years. Among 1189 patients discharged alive, 691 (58%) underwent revascularization during initial hospitalization. In multivariable Cox regression analyses, in-hospital revascularization was independently associated with a reduction in 4 year mortality and 3 year event rate of death or spontaneous MI: hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.37-0.96] and 0.46 (95% CI 0.31-0.68). However, when intention-to-treat analysis was performed, no differences in cumulative event rates were observed between the early invasive and selective invasive strategies: HR 1.10 (95% CI 0.70-1.74) for death and 1.27 (95% CI 0.88-1.85) for death or spontaneous MI. CONCLUSION: The ICTUS trial did not show that an early invasive strategy resulted in a better outcome than a selective invasive strategy in patients with nSTE-ACS. However, similar to retrospective analyses from observational studies, actual revascularization was associated with lower mortality and fewer MI. Whether an early invasive strategy leads to a better outcome than a selective invasive strategy cannot be inferred from the observation that revascularized patients have a better prognosis in non-randomized studies.     

Cyclin D1 protein analysis in the diagnosis of mantle cell lymphoma

Mantle cell lymphoma (MCL) is a clinicopathologic entity that is difficult to diagnose on histopathologic criteria. Approximately 50% to 70% of MCL contain a t(11;14)(q13;q32) translocation involving the cyclin D1 gene. Irrespective of this rearrangement, almost all MCL show overexpression of the cyclin D1 gene at the mRNA level. Other B-cell non-Hodgkin's lymphomas (NHL) do not show this rearrangement or overexpression of cyclin D1. We developed an immunohistochemical assay to detect overexpression of the cyclin D1 protein on conventional formalin-fixed, paraffin-embedded biopsies using the well-defined monoclonal antibody DCS-6. Expression in tumor cells was compared with expression of cyclin D1 in endothelial cells and fibroblasts. An exclusively nuclear staining pattern was observed. Moreover, expression was directly compared with the expression observed by immunoblot analysis with the same antibody, as well as with mRNA expression and with the occurrence of genomic rearrangements within the BCL-1 locus. Of 13 MCL that were analyzed by immunohistochemistry and immunoblot, 12 showed overexpression with both techniques, whereas no overexpression was observed in 39 other NHL. Of 13 additional MCL studied either by immunohistochemistry or immunoblot, 11 also showed overexpression. Two lymphomas morphologically indistinguishable from MCL but with an aberrant immunophenotype (CD5 negative, CD10 positive) both lacked overexpression of cyclin D1. These results underscore the significance of overexpression of the cyclin D1 protein as a specific marker for MCL. Detection of cyclin D1 overexpression on formalin-fixed, paraffin- embedded tissues using the DCS-6 monoclonal antibody can be applied for routine diagnostic purposes.     

Bone marrow transplantation for patients with Philadelphia chromosome- positive acute lymphoblastic leukemia

We report the treatment outcome of allogeneic bone marrow transplantation in ten patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Six patients are alive and well for 6 to 30 months (median 19 months) after transplantation. Four patients died with transplant related complications. In view of the poor prognosis associated with this disease, marrow ablation followed by allogeneic or syngeneic marrow grafting may be the preferred treatment modality if a suitable marrow donor is available.     

Role of Toll‐like receptor 9 signaling on activation of nasal polyp–derived fibroblasts and its association with nasal polypogenesis

Background

Nasal polyposis is characterized by persistent inflammation and remodeling in sinonasal mucosa. Toll‐like receptor 9 (TLR9) is a DNA receptor of the innate immune system that plays a pivotal role in fibrosis and inflammatory responses. The aim of this study is to explore the expression, activity, and potential pathogenic role of TLR9 signaling in tissue remodeling in nasal polyp–derived fibroblasts (NPDFs).

Methods

Fibrotic and inflammatory responses elicited by type A CpG oligonucleotides were examined in the NPDFs by a combination of real‐time quantitative polymerase chain reaction, Western blot analysis, enzyme‐linked immunosorbent assay, and immunofluorescence staining. For these experiments, the NPDFs were stimulated with different TLR9 agonists (CpG A and B) and blocked with inhibitors (MyD88 inhibitor and chloroquine).

Results

TLR9 expression was significantly higher in nasal polyposis (NP) tissues compared to control or chronic rhinosinusitis (CRS) mucosa. In the NPDFs, TLR9 showed intracellular localization and expression of TLR9 was increased after treatment with CpG A. CpG A increased production of α‐smooth muscle actin (α‐SMA), fibronectin, and matrix metalloproteinases (MMPs) (MMP1, MMP2, and MMP9) in the NPDFs, while MyD88 inhibitor and chloroquine, which are known to block the TLR9 signaling pathway, inhibited their production. CpG A also produced type I interferons (IFN‐α and IFN‐β), which were inhibited by MyD88 inhibitor.

Conclusion

Our data indicates that CpG A–induced fibroblast activation and cytokine production were mediated via TLR9 stimulation in NPDFs. Disrupting this process with an inhibitor targeting TLR9 or its downstream signaling pathways could represent a novel approach to CRS with NP (CRSwNP) therapy.

     

Letter to the editor in response to the article of Dekkers and Søballe (Activities and impairments in the early stage of rehabilitation after Colles' fracture; Vol. 26, No. 11, June 3, 2004)

Aim.?To study psychological well-being (health-related quality of life) in a population of adults 20 years and over with hearing impairment (HI) and its relation to audiological factors, consequences of the HI, sense of humour, and use of communication strategies.

Subjects and methods.?Consecutive adults (n = 343) at the outpatient Unit of Audiology of a Norwegian university hospital answered the Psychological General Well-being inventory (PGWB), Hearing Disability and Handicap Scale (HDHS), Sense of Humour Questionnaire-6 (SHQ-6), and Communication Strategies Scale (CSS) in relation to an audiological examination and medical consultation.

Results.?Mean PGWB index for the whole sample was 81.4 (SD 14.3) and females reported a significantly lower psychological well-being. In multiple linear regression analyses well-being was negatively associated with high levels of activity limitation and participation restriction. PGWB index was positively associated with high sense of humour, but was neither explained by audiological factors nor use of communication strategies.

Conclusions.?Psychological well-being was associated with the outcome of a standard HI assessment of activity limitation and participation restriction, but not with degree of HI and use of communication strategies.     

Transmission of hepatitis G virus in patients with angioedema treated with steam-heated plasma concentrates of C1 inhibitor

BACKGROUND: Hepatitis G virus (HGV) is a blood-borne flavivirus that may cause acute and chronic transfusion-transmitted infections. Patients with complement component 1 (C1) inhibitor (C1-INH) deficiency may acquire blood-borne infections through infusion of plasma concentrates. STUDY DESIGN AND METHODS: Serum samples from 84 patients with C1-INH deficiency (19 who received unmodified C1-INH concentrates, 23 who received steam-heated concentrates, and 42 untreated patients) were tested for HGV RNA and hepatitis C virus (HCV) RNA by a nested polymerase chain reaction (PCR). The samples were also tested for antibodies to the E2 envelope protein of HGV (anti-HGV) and to HCV with enzyme-linked immunosorbent assays. RESULTS: Nine (11%) patients had serum HGV RNA; that is, 7 (17%) of 42 patients previously treated with C1-INH concentrates and 2 of 42 previously untreated patients. HGV RNA was as common in the 19 patients treated with unmodified concentrates as in the 23 given steam-heated concentrates (16 vs. 17%, p = 0.60). Anti-HGV was more common among the recipients of unmodified concentrates than among those given steam-heated concentrates (26 vs. 0%, p = 0.014). HCV RNA was more frequently detected in treated patients than in untreated patients (33 vs. 7%, p = 0.005) and in the 19 recipients of unmodified concentrates than in the 23 treated with steam-heated concentrates (58 vs. 16%, p = 0.003). Only one HGV RNA- seropositive patient had elevated serum aminotransferase activity, compared to 11 with HCV RNA. CONCLUSION: HGV was transmitted by both unmodified and steam-heated concentrates, but it caused persistent viremia in a minority of the cases and was rarely associated with liver disease.     

Visual Assessment of Brain Magnetic Resonance Imaging Detects Injury to Cognitive Regulatory Sites in Patients With Heart Failure

BackgroundHeart failure (HF) patients exhibit depression and executive function impairments that contribute to HF mortality. Using specialized magnetic resonance imaging (MRI) analysis procedures, brain changes appear in areas regulating these functions (mammillary bodies, hippocampi, and frontal cortex). However, specialized MRI procedures are not part of standard clinical assessment for HF (which is usually a visual evaluation), and it is unclear whether visual MRI examination can detect changes in these structures.Methods and ResultsUsing brain MRI, we visually examined the mammillary bodies and frontal cortex for global and hippocampi for global and regional tissue changes in 17 HF and 50 control subjects. Significantly global changes emerged in the right mammillary body (HF 1.18 ± 1.13 vs control 0.52 ± 0.74; P = .024), right hippocampus (HF 1.53 ± 0.94 vs control 0.80 ± 0.86; P = .005), and left frontal cortex (HF 1.76 ± 1.03 vs control 1.24 ± 0.77; P = .034). Comparison of the visual method with specialized MRI techniques corroborates right hippocampal and left frontal cortical, but not mammillary body, tissue changes.ConclusionsVisual examination of brain MRI can detect damage in HF in areas regulating depression and executive function, including the right hippocampus and left frontal cortex. Visual MRI assessment in HF may facilitate evaluation of injury to these structures and the assessment of the impact of potential treatments for this damage.     

Serial immunoreactive erythropoietin levels in autologous blood donors

The variations in plasma erythropoietin (EPO) concentration during preoperative deposit of autologous blood were studied in 12 patients (8 men, 4 women). Four donations were scheduled at weekly intervals. A predonation hemoglobin concentration of 11 g per dL (110 g/L) was required. Hemoglobin concentration decreased from 14.3 +/- 1.1 g per dL (143 +/- 11 g/L) (mean +/- SD) before the first donation to 11.7 +/- 0.7 g per dL (117 +/- 7 g/L) on Day 22 (p less than or equal to 0.0001). Reticulocyte counts increased from a median of 31,800 (range, 4900-95,000) per microL (median, 32 x 10(9)/L [range, 5-95 x 10(9)/L]) to 93,800 (16,800-194,900) per microL (median, 94 x 10(9)/L [range, 17-195 x 10(9)/L]) on Day 28 (p less than or equal to 0.01). Plasma EPO concentration was 17.8 +/- 5.1 mU per mL prior to the first donation and displayed a small and transient peak after each donation. A sustained elevation followed each peak. Although plasma EPO concentration differed significantly from the baseline value after the first donation, only the peak concentrations after the second (35.5 +/- 15.5 mU/mL), third (38.0 +/- 14.5 mU/mL), and fourth (36.1 +/- 11.0 mU/mL) donations exceeded the normal range. The moderate, biphasic increase in plasma EPO concentration and the moderate increase in erythropoiesis suggest two strategies in autologous blood donation that should be investigated with respect to efficiency and safety: 1) more aggressive donation schemes, which reduce donation intervals and/or the minimum hemoglobin concentration and 2) the administration of recombinant human EPO.