Characterization of small nodules by automatic segmentation of X-ray computed tomography images

OBJECTIVE: To characterize the ability of an automatic lung nodule segmentation algorithm to measure small nodule dimensions and growth rates. METHODS: A phantom of 20 sets of 6 balls each (11 different nylon balls and 9 acrylic balls) of 1 to 9.5 mm in diameter, in foam, was imaged using x-ray computed tomography with slice thicknesses of 5, 2.5, and 1.25 mm, pitches of 3 and 6, and standard and lung resolution. Measurements consisted of volume and maximum in-plane cross-sectional areas and their derived maximum and effective diameters. Growth rates were simulated using pairs of groups of balls. RESULTS: Volume measurements overestimate volume, more so for thicker slices. For the largest balls, the error is 60% for 5-mm slices and 20% for 1.25-mm slices. Effective diameter calculated from volume better approximates actual diameter. For area measurements, errors are 0% to 5% for the largest balls, and the effective and actual diameters are closely matched. CONCLUSIONS: Below 5 mm in diameter, changes in volume should reach 100% for reliable indication of growth. Above 6 mm, the threshold for detecting change is on the order of 25% growth. Even under ideal conditions, results indicate the need for caution when making a diagnosis of malignancy on the basis of volume change.     

The role of the polio virus receptor and the herpesvirus entry mediator B genes for the development of MS

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS). Although the cause of MS is still uncertain, it is well accepted that both genetic and environmental factors are important for the development of disease. In this study, we focused on the Polio Virus Receptor (PVR) and Herpesvirus entry mediator B (HVEB) receptor genes, which are located on chromosome 19q13, a region previously linked to MS. Both receptors are expressed in the brain and immune system and play an important role for inter-cellular adhesion and entry of neurotropic viruses to the brain. We identified four new polymorphisms in the PVR gene, which were located in the promoter region and three different exons. All exonic polymorphisms altered the amino acid sequence of the receptor. No new polymorphisms were found in the HVEB gene, but we confirmed a previously identified intronic polymorphism. We analyzed the frequency of the polymorphisms by RFLP analysis in sporadic MS patients, MS families, and healthy controls and determined the surface expression of HVEB and PVR on peripheral blood monocytes. We did not find differences in the frequency of the polymorphisms or surface expression between MS patients and controls. Overall, our findings do not support a role of HVEB and PVR genes in the development of MS.     

Evaluation of the German Type D Scale (DS14) and prevalence of the Type D personality pattern in cardiological and psychosomatic patients and healthy subjects

The Type D personality pattern, consisting of negative affectivity and social inhibition, has been shown by Denollet et al. to predict adverse prognosis in patients with coronary heart disease. For measuring the Type D characteristics, Denollet has devised the 14 item Type D scale (DS14). In the present study, this instrument was translated into German. The validity, reliability and adequacy of the German DS14 were then tested in 2421 persons, including cardiological and psychosomatic patients as well as healthy factory workers. The results document sound psychometric properties of the scale. Cronbach's alpha was 0.87 for the negative affectivity subscale and 0.86 for social inhibition. The two-factor structure of the original instrument could be clearly replicated. The prevalence rates of the Type D pattern were lowest in cardiological patients (25 %) and highest in psychosomatic patients (62 %). The prevalence in this German sample of cardiology patients was also lower than the one observed in healthy factory workers (32.5 %) and in CHD samples reported in the literature. These group differences could not be accounted for by differences in age and sex distribution. In conclusion, the DS14 is a valid and reliable instrument that can be used for an economic evaluation of the Type D characteristics in patients and healthy persons. The possible meaningfulness of the low Type D prevalence in cardiac patients and the prognostic relevance of this pattern require further study.     

Extensive exercise is not harmful in amyotrophic lateral sclerosis

Whether physical activity increases risk or promotes progression of motor neurone degeneration in amyotrophic lateral sclerosis (ALS) is still debated. Current pathophysiological hypotheses include excitotoxicity, oxidative stress and increased calcium loads as causes of selective degeneration of vulnerable motor neurones. Vigorous exercise might amplify these factors by increasing firing rates at motor neurones. To test this hypothesis, we constrained a transgenic mouse model of ALS overexpressing the mutant human form of the Cu/Zn superoxide dismutase-1 (SOD-1) to a lifetime exercise on motor-driven running wheels for 10 h daily (active group, n = 12). Onset and progression of disease were assessed by grip strength, stride length and tight rope test. Data were compared with SOD-1 mice placed in running wheels set to slow speed (sedentary group, n = 13). Untreated SOD-1 mice were an additional control group (n = 12). We found no differences in disease onset, which was determined by a change-point analysis using an iterative fitting of segmented linear regression models, or in disease progression. However, the running group showed a non-significant 6-day improvement in survival (133.7 +/- 3.2 days) compared with the sedentary group (127.2 +/- 3.2 days) and a 4-day improvement compared with the control group (129.1 +/- 2.5 days). We demonstrate that a lifetime of vigorous exercise does not promote onset or progression of motor degeneration in SOD-1-mediated ALS. Moreover, the results suggest that the level of excitatory input and calcium turnover at motor neurones, both of which should be increased by running activity, do not interfere with the pathophysiology of SOD-1-mediated ALS.     

Benefit and risk of heparin for maintaining peripheral venous catheters in neonates: a placebo-controlled trial

OBJECTIVES: Heparin addition to infusion fluids is used to prolong catheter patency in newborns. Heparin may also induce adverse effects such as bleeding complications and immune-mediated heparin-induced thrombocytopenia (HIT). One objective was peripheral venous catheter patency with heparinization of continuous infusions (0.5 IU/mL). Secondary objectives were incidences of bleeding, clinically manifest HIT, HIT antibodies, and catheter-related complications. STUDY DESIGN: Inclusion criteria were anticipated need for intravenous peripheral infusion (>or=5 days for HIT-related endpoints) and postnatal age <28 days at study entry. Exclusion criteria were bodyweight <1000 g, congenital malformation, need for therapeutic anticoagulation or mechanical ventilation, and severe bleeding. HIT antibodies were assessed by enzyme-linked immunosorbent assay. RESULTS: A total of 145 infants received heparin, and 151 infants received saline. Patient characteristics, number of additional drugs, duration of treatment, and location and size of catheters did not differ. Patency of catheters was 7.4 hours longer in the heparin group (33.8 hours vs 26.4 hours, P<.0001), but the total numbers of catheters did not differ (565 vs 692, P=.3). No infant developed HIT antibodies. Incidences of bleeding complications and thrombocytopenia were comparable between groups. CONCLUSIONS: Balancing the benefits against the risks of heparin addition and the rare complication of HIT, we will not use 0.5 IU/mL heparin addition to parenteral fluids.     

Shortening of telomeres: Evidence for replicative senescence of T cells derived from patients with Wegener's granulomatosis

BACKGROUND: Replicative senescence describes the fact that somatic cells undergo a finite and predictable number of cell divisions before entering an irreversible state of growth arrest. Progressive shortening of the telomeres, a consequence of cell division, is a reliable indicator of replicative senescence. METHOD: We analyzed telomere length of DNA derived from T cells of patients suffering from Wegener's granulomatosis by Southern blotting. Moreover, expression of CD28, another marker for replicative senescence, was tested by cytofluorometry. RESULTS: In patients with disease for more than 5 years, short telomeres were detected in addition to telomeres of normal length, indicating replicative senescence of discrete T-cell clones. Reduced expression of CD28 was noted, particularly on CD8-positive T cells, derived from patients with disease for more than 5 years and short telomeres. CONCLUSION: Our data provide evidence that a portion of T cells had undergone replicative senescence, which in turn indicates clonal expansion of T cells as consequence of activation.     

Successful human islet isolation utilizing recombinant collagenase

The enzymatic dissociation of acinar tissue by collagenase is a substantial step in the isolation of pancreatic islets. Although essential collagenase components have been purified, the variability in the activity of different batches limits long-term reproducibility of isolation success. The utilization of purified recombinant proteases would solve this problem. In the present study, pancreases from multiorgan donors were dissociated by means of digestion-filtration using either Liberase HI (n = 51) or a recombinant collagenase blend (n = 25). No significant differences were found regarding islet yield before and after purification, the percent of exocrine-attached islets, and final purity. However, the ratio between islet equivalents and islet numbers indicated a lesser fragmentation in islets isolated with recombinant collagenase (P < 0.01). In contrast, viability was slightly higher in islets isolated with Liberase (92.3 +/- 0.8 vs. 85.6 +/- 2.9%; P < 0.05). Insulin release during static glucose incubation was not different between experimental groups. Islet transplantation into diabetic nude mice resulted in sustained normoglycemia in either group until the graft was removed. These results demonstrated that viable human islets can be isolated using recombinant collagenase. Final optimization of this enzyme blend would offer continuous reproducibility of isolation success.