Primary small intestine tumour as the cause of gastrointestinal tract occlusion

The following paper presents the case of a 40-year-old patient staying in our Clinic between 2 March 2010 and 12 March 2010 due to the symptoms of permeable occlusion of gastrointestinal tract. This is a patient with a several weeks' history of non-specific abdominal pain, vomiting and significant weight loss (ca 20 kg). Until recently he has not suffered from any serious illnesses. In the performed abdominal ultrasound, gastroscopy and colonoscopy no pathology was affirmed. CT scan with intravenous and oral contrast showed significantly widened intestinal loops with residual liquid matter in the stomach, duodenum and a part of the jejunum without any distinguishing pathological mass, and also single mesenteric lymph nodes and para-aortic nodes enlarged to the size of 12 mm. The patient was qualified for laparatomy. During the surgery, a 4-cm tumour of the jejunum, concentrically narrowing intestinal lumen was found. Segmental resection of the small intestine was performed with side to side anastomosis with the use of a linear stapler. Currently the general condition of the patient is good, without any ailments, and the patient is undergoing systemic treatment.     

Association between cerebral microbleeds and hypertension in the Swedish general population “Good Aging in Skåne” study

Cerebral microbleeds (CMB) on MRI are frequent in healthy aging individuals but precede ischemic and hemorrhagic stroke and dementia. Different etiologies have been suggested for nonlobar CMB, which have a stronger connection to hypertension (HT) than do lobar CMB. This study aimed to investigate the prevalence of CMB and the association between nonlobar/lobar CMB and different blood pressure (BP) and HT treatment conditions in a longitudinal, population‐based cohort of the Good Aging in Skåne (GÅS) study. White matter hyperintensities (WMH), CMB, atrophies, and infarctions were identified with brain 3T MRI, and BP parameters were examined in 344 randomly selected subjects between 70 and 87 years old. CMB were observed in 26% of the whole cohort, increasing from 19% of subjects in their 70s to 30% of those over 80 years of age. Of these subjects, 38% had multiple CMB, and 59% had a lobar localization. CMB were associated with severe confluent WMH (odds ratio = 7.02; 2.16‐18.84). Increasing age, being male, and having HT, impaired cognition, or a history of angina pectoris were associated with CMB. Both lobar and nonlobar CMB were associated with HT. Nonlobar CMB were particularly associated with increased BP, pulse pressure, controlled HT, and uncontrolled HT. After controlling for sex and HT, age was no longer a risk factor for CMB In conclusion, sex and HT are the major risk factors for CMB, especially nonlobar CMB, which suggests stricter implementation of recommended guidelines for HT treatment in the elderly.     

Microarray-based survey of CpG islands identifies concurrent hyper- and hypomethylation patterns in tissues derived from patients with breast cancer

Maintenance of CpG island methylation in the genome is crucial for cellular homeostasis and this balance is disrupted in cancer. Our rationale was to compare the methylation of CpG islands in tissues (tumor, healthy breast and blood) from patients with breast cancer. We studied 72 genes in 103 samples using microarray hybridization and bisulfite sequencing. We observed tumor specific hyper- or hypomethylation of five genes; COL9A1, MT1A, MT1J, HOXA5 and FLJ45983. A general drop of methylation in COL9A1 was apparent in tumors, when compared with blood and healthy breast tissue. Furthermore, one tumor displayed a complete loss of methylation of all five genes, suggesting overall impairment of methylation. The downstream, evolutionary conserved island of HOXA5 showed hypomethylation in 18 tumors and complete methylation in others. This CpG island also displayed a semimethylated state in the majority of normal breast samples, when compared to complete methylation in blood. Distinct methylation patterns were further seen in MT1J and MT1A, belonging to the metallothionein gene family. The CpG islands of these genes are spaced by 2 kb, which shows selective methylation of two structurally and functionally related genes. The promoters of FLJ45983 and MT1A were methylated above 25% in 18 primary and metastatic tumors. Concurrently, there was also >10% methylation of healthy breast tissue in 11 and 5 samples, respectively. This suggests that the methylation process for the latter two genes takes place already in normal breast cells. Our results also point to a considerable heterogeneity of epigenetic disturbance in breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.     

Generalized five-dimensional dynamic and spectral factor analysis

We have generalized the spectral factor analysis and the factor analysis of dynamic sequences (FADS) in SPECT imaging to a five-dimensional general factor analysis model (5D-GFA), where the five dimensions are the three spatial dimensions, photon energy, and time. The generalized model yields a significant advantage in terms of the ratio of the number of equations to that of unknowns in the factor analysis problem in dynamic SPECT studies. We solved the 5D model using a least-squares approach. In addition to the traditional non-negativity constraints, we constrained the solution using a priori knowledge of both time and energy, assuming that primary factors (spectra) are Gaussian-shaped with full-width at half-maximum equal to gamma camera energy resolution. 5D-GFA was validated in a simultaneous pre-/post-synaptic dual isotope dynamic phantom study where 99mTc and 123I activities were used to model early Parkinson disease studies. 5D-GFA was also applied to simultaneous perfusion/dopamine transporter (DAT) dynamic SPECT in rhesus monkeys. In the striatal phantom, 5D-GFA yielded significantly more accurate and precise estimates of both primary 99mTc (bias=6.4 % +/- 4.3 %) and 1231 (-1.7% +/- 6.9%) time activity curves (TAC) compared to conventional FADS (biases = 15.5% +/- 10.6% in 99mTc and 8.3% +/- 12.7% in 123I, p < 0.05). Our technique was also validated in two primate dynamic dual isotope perfusion/DAT transporter studies. Biases of 99mTc-HMPAO and 123I-DAT activity estimates with respect to estimates obtained in the presence of only one radionuclide (sequential imaging) were significantly lower with 5D-GFA (9.4% +/- 4.3% for 99mTc-HMPAO and 8.7% +/-4.1% for 123I-DAT) compared to biases greater than 15% for volumes of interest (VOI) over the reconstructed volumes (p < 0.05). 5D-GFA is a novel and promising approach in dynamic SPECT imaging that can also be used in other modalities. It allows accurate and precise dynamic analysis while compensating for Compton scatter and cross-talk.     

Does morphology of carotid plaque depend on patient's oxidative stress?

Objectives

This study explored the relationship between oxidative stress biomarkers and stability of carotid plaque. We decided to analyze the broad range of parameters describing oxidative stress in patients with carotid stenosis.

Design and methods

124 consecutive patients undergoing carotid endarterectomy were enrolled in the study group. The control group consisted of 49 patients without symptoms of atherosclerosis. The stability of carotid plaques was assessed using GSM (gray-scale median) scoring system and the study group was divided into three subgroups according to echogenicity of the plaque. The following parameters of oxidative stress/DNA damage were analyzed: i) urinary excretion of the products of oxidative DNA damage repair; ii) the background level of 8-oxo-7,8-dihydro-2′-deoxyguanosine in leukocytes' DNA and in atherosclerotic plaques; and iii) the concentrations of antioxidant vitamins, uric acid and C-reactive protein in plasma.

Results

Oxidative stress (described by redox status) was higher in the patient group than in the control group. There is a correlation between oxidative stress of the patients and stability of the plaque, echolucent plaques (GSM < 25) being associated with the highest antioxidant level and lowest excretion of DNA repair markers.

Conclusions

The plaque formation/morphology may depend on local environment and is independent of oxidative stress/inflammation observed on the level of the whole body.     

Popliteal artery thrombosis secondary to a tibial osteochondroma

Popliteal artery thrombosis may present as a complication of an osteochondroma located in the vicinity of the knee joint. This is a case report of a 26-year-old man with symptoms of the right lower extremity ischaemia without a previous history of vascular disease or trauma. Plain radiography, magnetic resonance angiography and Doppler ultrasonography documented the presence of an osteochondrous structure of the proximal tibial metaphysis, which displaced and compressed the popliteal artery, causing its occlusion due to intraluminal thrombosis..The patient was operated and histopathological examination confirmed the diagnosis of osteochondroma.     

Simultaneous single-molecule measurements of phage T7 replisome composition and function reveal the mechanism of polymerase exchange

A complete understanding of the molecular mechanisms underlying the functioning of large, multiprotein complexes requires experimental tools capable of simultaneously visualizing molecular architecture and enzymatic activity in real time. We developed a novel single-molecule assay that combines the flow-stretching of individual DNA molecules to measure the activity of the DNA-replication machinery with the visualization of fluorescently labeled DNA polymerases at the replication fork. By correlating polymerase stoichiometry with DNA synthesis of T7 bacteriophage replisomes, we are able to quantitatively describe the mechanism of polymerase exchange. We find that even at relatively modest polymerase concentration (∼2 nM), soluble polymerases are recruited to an actively synthesizing replisome, dramatically increasing local polymerase concentration. These excess polymerases remain passively associated with the replisome through electrostatic interactions with the T7 helicase for ∼50 s until a stochastic and transient dissociation of the synthesizing polymerase from the primer-template allows for a polymerase exchange event to occur.