Time-gated fluorescence spectroscopy improves endoscopic detection of low-grade dysplasia in ulcerative colitis

Dysplasia in ulcerative colitis is frequently missed with 4-quadrant biopsies. An experimental setup recording delayed fluorescence spectra simultaneously with white light endoscopy was recently developed.

Reproducibility and validity of video screen measurements of gait in children with spastic cerebral palsy

PURPOSE: To determine the reproducibility and validity of video screen measurement (VSM) of sagittal plane joint angles during gait. METHODS: 17 children with spastic cerebral palsy walked on a 10m walkway. Videos were recorded and 3d-instrumented gait analysis was performed. Two investigators measured six sagittal joint/segment angles (shank, ankle, knee, hip, pelvis, and trunk) using a custom-made software package. The intra- and interrater reproducibility were expressed by the intraclass correlation coefficient (ICC), standard error of measurements (SEM) and smallest detectable difference (SDD). The agreement between VSM and 3d joint angles was illustrated by Bland-Altman plots and limits of agreement (LoA). RESULTS: Regarding the intrarater reproducibility of VSM, the ICC ranged from 0.99 (shank) to 0.58 (trunk), the SEM from 0.81 degrees (shank) to 5.97 degrees (trunk) and the SDD from 1.80 degrees (shank) to 16.55 degrees (trunk). Regarding the interrater reproducibility, the ICC ranged from 0.99 (shank) to 0.48 (trunk), the SEM from 0.70 degrees (shank) to 6.78 degrees (trunk) and the SDD from 1.95 degrees (shank) to 18.8 degrees (trunk). The LoA between VSM and 3d data ranged from 0.4+/-13.4 degrees (knee extension stance) to 12.0+/-14.6 degrees (ankle dorsiflexion swing). CONCLUSION: When performed by the same observer, VSM mostly allows the detection of relevant changes after an intervention. However, VSM angles differ from 3d-IGA and do not reflect the real sagittal joint position, probably due to the additional movements in the other planes.

Preoperative MRI findings and functional outcome after selective dorsal rhizotomy in children with bilateral spasticity

PURPOSE: To identify MRI characteristics that may predict the functional effect of selective dorsal rhizotomy (SDR) in children with bilateral spastic paresis. METHODS: We performed SDR in a group of 36 patients. The gross motor functioning measure-66 (GMFM-66) was applied before and after SDR. Available cerebral MRIs were retrospectively classified into three diagnostic groups: periventricular leucomalacia (PVL; n = 10), hydrocephalus (n = 2), and normal (n = 6). In patients with PVL, we scored the severity of the MR abnormalities. We compared the changes in the GMFM-66 after SDR in the diagnostic groups. In patients with PVL, we correlated the severity of the MR abnormalities with the changes in the GMFM-66. RESULTS: The mean follow-up period was 5 years and 4 months (range, 1 year and 1 month to 9 years). The best improvement in gross motor function was observed in patients with normal MRI, and the slightest improvement was observed in patients with hydrocephalus. The severity of the PVL did correlate with the GMFM-66 score before SDR but not with the functional effect of SDR. CONCLUSION: We conclude that with respect to gross motor skills, the improvements after SDR are good in patients with no MRI abnormalities. In the patients with hydrocephalus, the improvements after SDR were insignificant. In patients with PVL, the improvements were intermediate and did not correlate with the degree of PVL.

The updated European Consensus 2009 on the use of Botulinum toxin for children with cerebral palsy

An interdisciplinary European group of clinical experts in the field of movement disorders and experienced Botulinum toxin users has updated the consensus for the use of Botulinum toxin in the treatment of children with cerebral palsy (CP). A problem-orientated approach was used focussing on both published and practice-based evidence. In part I of the consensus the authors have tabulated the supporting evidence to produce a concise but comprehensive information base, pooling data and experience from 36 institutions in 9 European countries which involves more than 10,000 patients and over 45,000 treatment sessions during a period of more than 280 treatment years. In part II of the consensus the Gross Motor Function Measure (GMFM) and Gross Motor Function Classification System (GMFCS) based Motor Development Curves have been expanded to provide a graphical framework on how to treat the motor disorders in children with CP. This graph is named "CP(Graph) Treatment Modalities - Gross Motor Function" and is intended to facilitate communication between parents, therapists and medical doctors concerning (1) achievable motor function, (2) realistic goal-setting and (3) treatment perspectives for children with CP. The updated European consensus 2009 summarises the current understanding regarding an integrated, multidisciplinary treatment approach using Botulinum toxin for the treatment of children with CP.

PET/CT-guided biopsies of metabolically active bone lesions: applications and clinical impact

In a minority of cases a definite diagnosis and stage grouping in cancer patients is not possible based on the imaging information of PET/CT. We report our experience with percutaneous PET/CT-guided bone biopsies to histologically verify the aetiology of hypermetabolic bone lesions.

Cost and mortality prediction using polymerase chain reaction pathogen detection in sepsis: evidence from three observational trials

Delays in adequate antimicrobial treatment contribute to high cost and mortality in sepsis. Polymerase chain reaction (PCR) assays are used alongside conventional cultures to accelerate the identification of microorganisms. We analyze the impact on medical outcomes and healthcare costs if improved adequacy of antimicrobial therapy is achieved by providing immediate coverage after positive PCR reports.

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), after slipped capital femoral epiphysis

OBJECTIVE: The aim of this study was to assess the glycosaminoglycan (GAG) content in hip joint cartilage in mature hips with a history of slipped capital femoral epiphysis (SCFE) using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). METHODS: 28 young-adult subjects (32 hips) with a mean age of 23.8+/-4.0 years (range: 18.1-30.5 years) who were treated for mild or moderate SCFE in adolescence were included into the study. Hip function and clinical symptoms were evaluated with the Harris hip score (HHS) system at the time of MRI. Plain radiographic evaluation included Tonnis grading, measurement of the minimal joint space width (JSW) and alpha-angle measurement. The alpha-angle values were used to classify three sub-groups: group 1=subjects with normal femoral head-neck offset (alpha-angle <50 degrees ), group 2=subjects with mild offset decrease (alpha-angle 50 degrees -60 degrees ), and group 3=subjects with severe offset decrease (alpha-angle >60 degrees ). RESULTS: There was statistically significant difference noted for the T1(Gd) values, lateral and central, between group 1 and group 3 (p-values=0.038 and 0.041). The T1(Gd) values measured within the lateral portion were slightly lower compared with the T1(Gd) values measured within the central portion that was at a statistically significance level (p-value <0.001). HHS, Tonnis grades and JSW revealed no statistically significant difference. CONCLUSION: By using dGEMRIC in the mid-term follow-up of SCFE we were able to reveal degenerative changes even in the absence of joint space narrowing that seem to be related to the degree of offset pathology. The dGEMRIC technique may be a potential diagnostic modality in the follow-up evaluation of SCFE.

[The role of PET imaging in patients with lymphoma]

Positron-Emission-Tomography (PET) has emerged as a diagnostic gold standard for most tumor entities during the last 20 years, especially for patients suffering from malignant lymphoma. The development and distribution of machines allowing for hybrid imaging, i.e. the simultaneous acquisition of PET and CT datasets, and the possibility to assess even small pathologic findings with fused PET/CT image visualization, once more significantly improved the diagnostic accuracy of PET. Based on an excellent sensitivity the metabolic imaging with PET or PET/CT allows for a reliable overall assessment of patients with malignant lymphoma before therapy, for the early identification of non-responders during therapy, and for the diagnosis of relapse after therapy.

Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial

Combined-modality treatment consisting of four to six cycles of chemotherapy followed by involved-field radiotherapy (IFRT) is the standard of care for patients with early unfavorable Hodgkin's lymphoma (HL). It is unclear whether treatment results can be improved with more intensive chemotherapy and which radiation dose needs to be applied.

The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer

Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management.

Posttraumatic stress disorder and dyslipidemia: previous research and novel findings from patients with PTSD caused by myocardial infarction

Based on a brief systematic review suggesting dyslipidemia in posttraumatic stress disorder (PTSD), we studied, for the first time, levels of blood lipids in patients with a DSM-IV diagnosis of PTSD caused by myocardial infarction (MI).

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.

Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema

Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.

Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression

Uromodulin (UMOD) mutations are responsible for three autosomal dominant tubulo-interstitial nephropathies including medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Symptoms include renal salt wasting, hyperuricemia, gout, hypertension and end-stage renal disease. MCKD is part of the 'nephronophthisis-MCKD complex', a group of cystic kidney diseases. Both disorders have an indistinguishable histology and renal cysts are observed in either. For most genes mutated in cystic kidney disease, their proteins are expressed in the primary cilia/basal body complex. We identified seven novel UMOD mutations and were interested if UMOD protein was expressed in the primary renal cilia of human renal biopsies and if mutant UMOD would show a different expression pattern compared with that seen in control individuals. We demonstrate that UMOD is expressed in the primary cilia of renal tubules, using immunofluorescent studies in human kidney biopsy samples. The number of UMOD-positive primary cilia in UMOD patients is significantly decreased when compared with control samples. Additional immunofluorescence studies confirm ciliary expression of UMOD in cell culture. Ciliary expression of UMOD is also confirmed by electron microscopy. UMOD localization at the mitotic spindle poles and colocalization with other ciliary proteins such as nephrocystin-1 and kinesin family member 3A is demonstrated. Our data add UMOD to the group of proteins expressed in primary cilia, where mutations of the gene lead to cystic kidney disease.