The utilization of Tc-99m-TBI as a myocardial perfusion agent in exercise studies: Comparison with Tl-201 thallous chloride and examination of its biodistribution in humans

Twenty-four patients were studied with both ²⁰¹Tl-thallous chloride and ^99mTc-TBI scintigraphy following exercise. Comparison of the two agents in detecting segmental myocardial ischemia and scar was made in 18 patients with evidence of coronary artery disease on ²⁰¹Tl-thallous chloride scintigraphy. Agreement between the two studies was observed in 77% (125 of 162) of left ventricular segments, suggesting that ^99mTc-TBI can be used as a myocardial perfusion agent. Limitations were related to early high background activity from lungs and liver. The high lung activity and early myocardial redistribution within the 1st hour contributed to the failure of ^99mTc-TBI to detect 16 segmental defects seen in the immediate post-exercise thallous chloride scan. Persistently high liver activity additionally affected accurate interpretation in the left ventricular segments close to the diaphargm. Improvement in the accuracy of ^99mTc-TBI stress studies might be achieved with tomographic imaging to reduce the problem of background activity or by the development of ^99mTc-labeled isonitrile analogues with rapid lung and liver clearance.     

Fully automated localization of the human primary somatosensory cortex in one minute by functional magnetic resonance imaging

A clinical functional magnetic resonance imaging (fMRI) protocol based on a fully automated tactile stimulation was optimized in 10 right-handed volunteers at 1.5 T for minimum scan time, high BOLD-signals and robust localization of the primary somatosensory cortex (S1) by systematically varying the applied block design. All volunteers had six different fMRI measurements of 5 stimulation/baseline cycles each with equal block duration that was changed between the measurements from 6 to 30 s. Data sets of 4, 3 and 2 cycles were generated post hoc resulting in a total of 240 data sets that were evaluated individually for BOLD-signal intensity (dS%), correlation to the hemodynamic reference function (r) and Euclidean coordinates (x, y, z). The protocol with 5 cycles, a block duration of 6 s and a total scan time of 66 s provided the best BOLD-signal characteristics (dS% = 1.15, r = 0.78). Compared to the mean scan time of other clinical fMRI protocols (174 s) a reduction of 62% was achieved.     

Formation and differentiation of the avian sclerotome

The avian sclerotome forms by epitheliomesenchymal transition of the ventral half-somite. Sclerotome development is characterized by a craniocaudal polarization, resegmentation, and axial identity. Its formation is controlled by signals from the notochord, the neural tube, the lateral plate mesoderm, and the myotome. These signals and crosstalk between somite cells lead to the separation of various subdomains, such as the central and ventral sclerotomes that express Pax1 under the control of Sonic hedgehog and Noggin, and the dorsal and lateral sclerotome that do not express Pax1 and are controlled by Bmp-4. Further subdomains that give rise to specific derivatives are the syndetome, neurotome, meningotome, and arthrotome. The molecular control of subdomain formation and cell type specification is discussed.     

Novel approaches to primary snoring

Snoring is a widespread disorder, mostly affecting middle-aged men. Snoring is not harmful in itself, but may lead to social impairment. Therefore, snorers often seek for medical advice and effective treatment. Sleep studies are mandatory especially when surgical procedures are intended. Due to the lack of reliable objective snoring analysis, the evaluation by the bed partners is the most relevant criteria in estimating treatment success. Body weight and behaviour patterns are crucial in the treatment of snoring. Furthermore, oral appliances and other implements may be beneficial. Various kinds of surgical procedures are available, soft palate techniques being the most widespread. Minimally invasive procedures are safe and effective in the majority of patients. Temperature controlled radiofrequency tissue ablation offers much potential in the treatment of primary snoring. Furthermore, a system is currently being developed which is supposed to stabilise the soft palate with the help of implants.     

Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity

OBJECTIVE: The autosomal-dominant form of the hyperimmunoglobulin E syndrome (AD-HIES) has been described as a multisystem disorder including immune, skeletal, and dental abnormalities. Variants of AD-HIES are known but not well defined. METHODS: We evaluated 13 human immunodeficiency virus-seronegative patients from six consanguineous families with an autosomal-recessive form of hyperimmunoglobulin E syndrome (AR-HIES) and 68 of their relatives. RESULTS: Persons affected with AR-HIES presented with the classical immunologic findings of hyperimmunoglobulin E syndrome, including recurrent staphylococcal infections of the skin and respiratory tract, eczema, elevated serum immunoglobulin E, and hypereosinophilia. In addition, severe recurrent fungal and viral infections with molluscum contagiosum, herpes zoster, and herpes simplex were noted. Autoimmunity was seen in two patients. Central nervous system sequelae, including hemiplegia, ischemic infarction, and subarachnoid hemorrhages, were common and contributed to high mortality. Notably, patients with AR-HIES did not have skeletal or dental abnormalities and did not develop pneumatoceles, as seen in AD-HIES. In lymphocyte proliferation assays, patients' cells responded poorly to mitogens and failed to proliferate in response to antigens, despite the presence of normal numbers of lymphocyte subpopulations. CONCLUSION: The autosomal-recessive form of hyperimmunoglobulin E syndrome is a primary immunodeficiency with elevated immunoglobulin E, eosinophilia, vasculitis, autoimmunity, central nervous system symptoms, and high mortality. AR-HIES lacks several of the key findings of AD-HIES and therefore represents a different, previously unrecognized disease entity.     

Serum and bile markers for cholangiocarcinoma

Surgery remains the only curative treatment option for cholangiocarcinoma (CC). Currently, both early identification of CC in affected individuals at high risk and accurate diagnosis of unexplained biliary strictures are problematic. However, growing insights into biochemical and molecular mechanisms underlying biliary carcinogenesis have suggested serum and bile markers for the diagnosis of CC. These tools include tumor antigens or products (e.g., carbohydrate antigen [CA] 19-9), cytokines (e.g., interleukin-6), metabolic products (e.g., lactate), proteases (e.g., trypsinogen-2), regulatory peptides (e.g., pancreatic polypeptide), and (epi-)genetic lesions (e.g., K- ras and p53 mutations, p16 (INK4a) or p14 (ARF) promoter hypermethylation). In this article we discuss these new potential tumor markers for the diagnosis of CC.     

High expression of focal adhesion kinase (p125FAK) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome

IntroductionFocal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis. In breast carcinoma, FAK overexpression has been linked to cancer progression but the prognostic relevance remains unknown. In particular, with regard to lymph node-negative breast cancer it is important to identify high-risk patients who would benefit from further adjuvant therapy.MethodsWe analyzed 162 node-negative breast cancer cases to determine the prognostic relevance of FAK expression, and we investigated the relationship of FAK with major associated signaling pathways (HER2, Src, Akt and extracellular regulated kinases) by immunohistochemistry and western blot analysis.ResultsElevated FAK expression did not predict patient outcome, in contrast to tumor grading (P = 0.005), Akt activation (P = 0.0383) and estrogen receptor status (P = 0.0033). Significant positive correlations were observed between elevated FAK expression and HER2 overexpression (P = 0.001), as well as phospho-Src Tyr-215 (P = 0.021) and phospho-Akt (P < 0.001), but not with phospho-ERK1/2 (P = 0.108). Western blot analysis showed a significant correlation of FAK Tyr-861 activation and HER2 overexpression (P = 0.01).ConclusionsImmunohistochemical detection of FAK expression is of no prognostic significance in node-negative breast cancer but provides evidence that HER2 is involved in tumor malignancy and metastatic ability of breast cancer through a novel signaling pathway participating FAK and Src.     

The natural course of atopic dermatitis from birth to age 7 years and the association with asthma

BACKGROUND: Atopic dermatitis (AD) is considered to be one of the first manifestations in the atopic march. However, few prospective studies on AD and its association with childhood asthma exist. OBJECTIVE: The aim of this study was to prospectively investigate the natural course of AD to determine factors influencing its prognosis and to analyze the relationship of AD with childhood asthma. METHODS: The Multicenter Allergy Study, a German birth cohort, followed 1314 children from birth to age 7 years. Physical examinations, parental interviews on atopic symptoms and diagnoses, and determination of specific IgE levels were performed regularly. RESULTS: The cumulative prevalence of AD in the first 2 years of life was 21.5%. Of these children with early AD, 43.2% were in complete remission by age 3 years, 38.3% had an intermittent pattern of disease, and 18.7% had symptoms of AD every year. Severity (adjusted cumulative odds ratio, 5.86; 95% CI, 3.04-11.29) and atopic sensitization (adjusted cumulative odds ratio, 2.76; 95% CI, 1.29-5.91) were major determinants of prognosis. Early wheeze and a specific sensitization pattern were significant predictors for wheezing at school age, irrespective of AD. Early AD without these cofactors constituted no increased risk of subsequent wheeze (adjusted odds ratio, 1.11; 95% CI, 0.56-2.20) or bronchial hyperreactivity. CONCLUSION: AD is a common condition in infancy but disappears around age 3 years in a significant proportion of children. The prognosis is mostly determined by the severity and the presence of atopic sensitization. Early AD is associated with asthma at school age, but in many of these asthmatic children, wheezing manifests before or with the onset of AD. Children with AD and wheeze have a marked loss in lung function, suggesting a distinct phenotype rather than a progressive development from AD to asthma.