Semiquantitative analysis of ultrasonic cerebral perfusion imaging

The bolus kinetic in ultrasonic cerebral perfusion imaging is the most favored data acquisition and processing technique. However, there has not yet been convincing evidence for the potential to (semi-) quantitatively describe perfusion. Aim of this study was to determine the intraindividual range of relevant perfusion parameters to describe individual physiological cutoff scores. In 20 healthy volunteers, cerebral perfusion was evaluated using the bilateral approach with phase inversion harmonic imaging and the bolus kinetic. Relevant parameters (time-to-peak intensity, TPI; peak width, PW) were derived in 14 regions-of-interest in both hemispheres. The median and quartile deviation (QD) of these values were individually calculated. Within the 20 individuals, the mean QD of TPI was 0.68 s, and there was no case in which any TPI exceeded the mean more than 2 s. With PW, the mean QD was 1.2 s, and the mean was not exceeded by more than 6 s. Intraindividual perfusion parameters, especially TPI, show a considerable small range. Thus, the bolus kinetic derives reliable semiquantitative information once intraindividual comparison can be accomplished. We therefore propose that bilateral examination with the unaffected hemisphere as referential region should be performed in acute stroke. Future studies have to evaluate the potential of this approach of discriminating ischemia and hypoperfusion in the affected hemisphere.     

Polymorphisms in human connexin40 gene promoter are associated with increased risk of hypertension in men

OBJECTIVE: Gap junctions, formed by connexins (Cx), are important in the regulation of vascular tone. Previously, we reported two closely linked polymorphisms (-44G --> A and +71A --> G) within regulatory regions of the gene for Cx40, a major connexin in the vascular wall and the kidney. In the present study, we examined the hypothesis that these polymorphic variants are associated with hypertension and that they interact with blood pressure in healthy individuals. METHODS: Cx40 genotypes were determined in 191 subjects with essential hypertension, 198 normotensive individuals, and a healthy control population (178 twin pairs, 108 monozygotic, 70 dizygotic). RESULTS: We found a significant contribution of the minor Cx40 allele or genotype (-44AA/+71GG) to the risk of hypertension in men (P = 0.013 or P = 0.035; odds ratio, 1.87 or 2.10, respectively), but not in women. Moreover, in the healthy control population a significant effect of Cx40 genotype and sex on systolic blood pressure was found (P < 0.05 and P < 0.0001, respectively). Women carrying the minor Cx40 genotype had significantly higher systolic blood pressure compared with non-carriers (P < 0.05). In men, systolic blood pressure in carriers of the minor Cx40 genotype was not significantly different from the other two genotypes, possibly because of the small number of men in this group. However, men carrying the -44GA/+71AG genotype had higher standing systolic blood pressure compared with the more common Cx40 genotype (-44GG; P = 0.033). CONCLUSION: These findings suggest that the Cx40 polymorphisms may form a genetic susceptibility factor for essential hypertension in men.     

Overexpression of cyclooxygenase-2 in human prostate carcinoma and prostatic intraepithelial neoplasia-association with increased expression of Polo-like kinase-1

BACKGROUND: Cyclooxygenases (COX) as well as Polo-like kinases (PLK) are involved in proliferation and cell cycle regulation and have been suggested for preventive and therapeutic approaches in prostate carcinoma. METHODS: In this study, we studied expression and prognostic impact of COX-2 in invasive prostate carcinoma, prostatic intraepithelial neoplasia (PIN), atrophic glands, and normal prostatic glands, and investigated the association between COX-2 and PLK-1. RESULTS: We observed a positivity for COX-2 in 72.1% of PIN and in 44.7% of prostate carcinomas with an overexpression of COX-2 in prostate cancer and PIN compared to benign prostatic tissue (P < 0.0005). Furthermore, we observed a strong correlation between expression of PLK-1 and COX-2 (P < 0.0005). CONCLUSIONS: To our knowledge, this is the first report of a correlation between COX-2 and PLK-1 in a malignant tumor. COX-2 and PLK-1 may be interesting targets for new molecular therapies in prostate cancer.     

Evaluation of two 3D virtual computer reconstructions for comparison of cleft lip and palate to normal fetal microanatomy

Cleft lip and palate reconstructive surgery requires thorough knowledge of normal and pathological labial, palatal, and velopharyngeal anatomy. This study compared two software algorithms and their 3D virtual anatomical reconstruction because exact 3D micromorphological reconstruction may improve learning, reveal spatial relationships, and provide data for mathematical modeling. Transverse and frontal serial sections of the midface of 18 fetal specimens (11th to 32nd gestational week) were used for two manual segmentation approaches. The first manual segmentation approach used bitmap images and either Windows-based or Mac-based SURFdriver commercial software that allowed manual contour matching, surface generation with average slice thickness, 3D triangulation, and real-time interactive virtual 3D reconstruction viewing. The second manual segmentation approach used tagged image format and platform-independent prototypical SeViSe software developed by one of the authors (F.W.). Distended or compressed structures were dynamically transformed. Registration was automatic but allowed manual correction, such as individual section thickness, surface generation, and interactive virtual 3D real-time viewing. SURFdriver permitted intuitive segmentation, easy manual offset correction, and the reconstruction showed complex spatial relationships in real time. However, frequent software crashes and erroneous landmarks appearing "out of the blue," requiring manual correction, were tedious. Individual section thickness, defined smoothing, and unlimited structure number could not be integrated. The reconstruction remained underdimensioned and not sufficiently accurate for this study's reconstruction problem. SeViSe permitted unlimited structure number, late addition of extra sections, and quantified smoothing and individual slice thickness; however, SeViSe required more elaborate work-up compared to SURFdriver, yet detailed and exact 3D reconstructions were created.     

Co-expression of MET and CD47 is a novel prognosticator for survival of luminal-type breast cancer patients

Although luminal-type primary breast cancer can be efficiently treated, development of metastatic disease remains a significant clinical problem. We have previously shown that luminal-type circulating tumor cells (CTCs) co-expressing the tyrosine-kinase MET and CD47, a ligand involved in cancer cell evasion from macrophage scavenging, are able to initiate metastasis in xenografts. Here, we investigated the clinical relevance of MET-CD47 co-expression in 255 hormone receptor positive breast tumors by immunohistochemistry and found a 10.3-year mean overall-survival difference between MET-CD47 double-positive and double-negative patients (p<0.001). MET-CD47 co-expression defined a novel independent prognosticator for overall-survival by multivariate analysis (Cox proportional hazards model: HR: 4.1, p<0.002) and CD47 expression alone or in combination with MET was strongly associated with lymph node metastasis. Furthermore, flow cytometric analysis of metastatic patient blood revealed consistent presence of MET⁺CD47⁺ CTCs (range 0.8 – 33.3% of CTCs) and their frequency was associated with increased metastatic spread. Finally, primary uncultured CTCs with high MET⁺CD47⁺ content showed an enhanced capacity to initiate metastasis in mice. Detection and targeting of MET and CD47 may thus provide a rational basis for risk stratification and treatment of patients with luminal-type breast cancer.     

Noncompaction myocardium in association with type Ib glycogen storage disease

Noncompaction myocardium is a rare disorder assumed to occur as an arrest of the compaction process during the normal development of the heart. Left ventricular noncompaction has been reported to be associated with a variety of cardiac and extracardiac, especially neuromuscular abnormalities. Moreover, it has been suggested that metabolic alterations could be responsible for the noncompaction. However, no association of noncompaction myocardium with type Ib glycogen storage disease (GSD) has been reported so far. Type Ib GSD is due to a defect of a transmembrane protein which results, similar to type Ia GSD, in hypoglycemia, a markedly enlarged liver and, additionally, in neutropenia, recurrent infections, and inflammatory bowel disease. Until now, no muscular or cardiac involvement has been described in type Ib GSD patients. The present case represents the first report of a noncompaction myocardium in a child with type Ib GSD who died of sudden clinical deterioration at the age of four.     

Training increases concordance in classifying pulmonary adenocarcinomas according to the novel IASLC/ATS/ERS classification

The International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) proposed a classification for lung adenocarcinomas (ADC) based on the predominant growth pattern. This classification has been shown to have prognostic and maybe even predictive impact. However, until now, the reproducibility of this classification has not been sufficiently demonstrated. Digital images of 40 selected ADC cases were shown twice to members of the Pulmonary Pathology Working Group of the German Society of Pathology. Each time a teledialogue-based survey on the classification was performed. Between the voting procedures, salient features of the novel classification were presented and discussed in detail by its members. The mean percentages of consensual votes per pattern ranged between 59.6 and 75?%, with lepidic and solid being the pattern with the most discordant and concordant votes, respectively. The other patterns ranged in between (papillary 65.8?%; acinar 67.8?%; micropapillary 74.2?%). The extent of disagreement decreased after the educational session. This decrease, however, was heterogeneous for the different patterns with acinar being the pattern with the strongest improvement. The overall number of abstentions decreased significantly after the educational session (p?相似文献   

The cholinergic blockade of both thermally and non-thermally induced human eccrine sweating

Thermally induced eccrine sweating is cholinergically mediated, but other neurotransmitters have been postulated for psychological (emotional) sweating. However, we hypothesized that such sweating is not noradrenergically driven in passively heated, resting humans. To test this, nine supine subjects were exposed to non-thermal stimuli (palmar pain, mental arithmetic and static exercise) known to evoke sweating. Trials consisted of the following four sequential phases: thermoneutral rest; passive heating to elevate (by ~1.0°C) and clamp mean body temperature and steady-state sweating (perfusion garment and footbath); an atropine sulphate infusion (0.04 mg kg(-1)) with thermal clamping sustained; and following clamp removal. Sudomotor responses from glabrous (hairless) and non-glabrous skin surfaces were measured simultaneously (precursor and discharged sweating). When thermoneutral, these non-thermal stimuli elicited significant sweating only from the palm (P < 0.05). Passive heating induced steady-state sweating ranging from 0.20 ± 0.04 (volar hand) to 1.40 ± 0.14 mg cm(-2) min(-1) (forehead), with each non-thermal stimulus provoking greater secretion (P < 0.05). Atropine suppressed thermal sweating, and it also eliminated the sudomotor responses to these non-thermal stimuli when body temperatures were prevented from rising (P > 0.05). However, when the thermal clamp was removed, core and skin temperatures became further elevated and sweating was restored (P < 0.05), indicating that the blockade had been overcome, presumably through elevated receptor competition. These observations establish the dependence of both thermal and non-thermal eccrine sweating from glabrous and non-glabrous surfaces on acetylcholine release, and challenge theories concerning the psychological modulation of sweating. Furthermore, no evidence existed for the significant participation of non-cholinergic neurotransmitters during any of these stimulations.