A compression transmission device for the evaluation of bonding strength of biocompatible microfluidic and biochip materials and systems.

Bonding of a variety of inorganic and organic polymers as multi-layered structures is one of the main challenges for biochip production even to date, since the chemical nature of these materials often does not allow easy and straight forward bonding and proper sealing. After selection of an appropriate method to bond the chosen materials to form a complex biochip, function and stability of bonding either requires qualitative burst tests or expensive mechanical multi-test stations, that often do not have the right adaptors to clamp biochip slides without destruction. Therefore, we have developed a simple and inexpensive bonding test based on 3D printed transmission elements that translate compressive forces via manual compression, hand press or hydraulic press compression into shear and tensile force. Mechanical stress simulations showed that design of the bonding geometry and size must be considered for bonding tests since the stress distribution thus bonding strength heavily varies with size but also with geometry. We demonstrate the broad applicability of our 3D printed bonding test system by testing the most frequent bonding strategies in combination with the respective most frequently used biochip material in a force-to-failure study. All evaluated materials are biocompatible and used in cell-based biochip devices. This study is evaluating state-of-the-art bonding approaches used for sealing of microfluidic biochips including adhesive bonding, plasma bonding, solvent bonding as well as bonding mediated by amino-silane monolayers or even functional thiol-ene epoxy biochip materials that obviate intermediate adhesive layers.

[Prevalence of carbapenemase-producing bacteria in hospitals in Saxony, Germany]. / Prävalenzerhebung zum Vorkommen von Carbapenemase-Bildnern in sächsischen Kliniken.

The presence of pathogenic bacteria with acquired carbapenem resistance constitutes an increasing problem for infection control and infectious disease management. Prompted by an outbreak of infections with Klebsiella pneumoniae producing the carbapenemase KPC-2 at a hospital in Saxony, the Saxon State Ministry of Social Affairs and Consumer Protection (SMS) initiated a point-prevalence survey for carbapenemase-producing gram-negative bacteria. Wards at 53 hospitals in Saxony, mainly intensive care units, were investigated between October 2012 and February 2013. Stool samples and rectal swabs of 1,037 patients were analyzed for the presence of bacteria with resistance against four major groups of antibiotics (4MRGN). Carbapenemase producers were detected in 3 patients [0.3% CI95 (0.0596; 0.843)] and carbapenem-resistant bacteria without carbapenemases were detected in 9 patients [0.9% CI95 (0.397; 1.64)]. Furthermore, antimicrobial susceptibility testing revealed 166 patients [16.0% CI95 (13.82; 18.38)] with extended-spectrum beta-lactamase (ESBL)-producing bacteria. At the time of investigation, K. pneumoniae producing the carbapenemase KPC-2 was diagnosed in 2 patients at one hospital. Moreover, it is necessary to remain vigilant towards other types of carbapenemase producers, as demonstrated by the finding of a Pseudomonas aeruginosa strain harbouring the carbapenemase VIM-1 in another hospital.

18F-labelled CCR1-receptor antagonist is not suitable for imaging of Alzheimer's disease.

Diagnosis of Alzheimer's disease (AD) with positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) relies on typical alterations of brain glucose metabolism which are, however, not disease specific. Amyloid-ß imaging has not entered clinical routine yet. Post mortem histological specimen of brain tissue from AD patients revealed enhanced expression of the chemotactic cytocine receptor 1 (CCR1). PARTICIPANTS, METHODS: CCR1-antagonist ZK811460 was labeled with fluorine-18 to explore its possible use as specific diagnostic tool in AD. Tracer characterization comprising PET imaging of brain and metabolite analysis was performed in AD patients and controls. RESULTS: Neither qualitative evaluation nor quantitative compartment analysis of PET data did show any enhanced binding of the 18F-labeled CCR1-antagonist in the brain of AD patients or controls. CONCLUSION: 18F-ZK811460 did not fulfill the expectation as diagnostic tracer in PET imaging of AD.

Neoadjuvant chemotherapy affects staging of colorectal liver metastasis--a comparison of PET, CT and intraoperative ultrasound.

PURPOSE: Surgery for colorectal liver metastasis facilitates long-term survival, and neoadjuvant chemotherapy improves resectability but may also alter staging accuracy. The aim of this study was to evaluate the effects of neoadjuvant chemotherapy on the efficacy of positron emission tomography (PET), PET-computed tomography (CT), CT and intraoperative ultrasound (IUS) in the detection of liver metastasis. METHODS: Between January 2007 and January 2010, 34 patients with resectable colorectal liver metastasis were included in this retrospective analysis. Seventeen patients had received neoadjuvant chemotherapy. PET or PET-CT, CT or magnetic resonance imaging (MRI) and IUS were performed in all patients. Sensitivity, specificity, positive predictive value and negative predictive value were analysed. Histopathological examination of the resected specimens served as standard reference. RESULTS: A total of 109 liver segments were resected, of which 50 showed no metastatic involvement (45.9%). For patients without systemic chemotherapy, sensitivities for PET, CT/MRI and IUS were 92%, 64% and 100% respectively as compared with 63%, 65% and 94% for patients after neoadjuvant chemotherapy in a segment-based analysis. For PET, standardised uptake values were decreased by 3.9 in 10 patients after chemotherapy whereas lesion diameters were similar (3.0 vs. 3.2 cm). Additional metastases were detected by IUS in seven patients resulting in a change of operative procedure in 20.6%. CONCLUSION: Staging accuracy of colorectal liver metastasis is influenced by neoadjuvant chemotherapy. For PET, decreased tumour metabolism rather than downsizing may account for a drop in sensitivity after neoadjuvant chemotherapy. IUS is critical to avoid incomplete resections.

Validation of sentinel lymph node dissection in prostate cancer: experience in more than 2,000 patients.

PURPOSE: Sentinel lymph node dissection (SLND) has replaced extended lymphadenectomy for nodal staging in several solid tumours. We present our results of SLND in prostate cancer in regard to detection and false-negative rate. METHODS: In a 2-day protocol about 300 MBq (99m)Tc-nanocolloid are injected into the prostate. Two hours later static scans of the pelvis are performed to get information about the number and location of radioactive lymph nodes. During surgery the radioactive nodes are excised with the help of a gamma probe and sent separately to the pathologist. The histological procedure includes haematoxylin and eosin staining, serial sections and immunohistochemistry. RESULTS: Since 1999, a total of 2,020 men underwent SLND alone or in combination with either standard or extended lymphadenectomy after radical retropubic prostatectomy. Lymph nodes positive for metastases were found in 16.7% of patients. The scintigraphic detection rate was 97.6% and the intraoperative detection rate 98%. For 187 lymph node-positive men who had either standard or extended lymphadenectomy in addition to SLND the false-negative rate could be calculated, resulting in false-negative findings in 11 of 187 patients (6%). CONCLUSION: Our results demonstrate that SLND in prostate cancer is a reliable procedure for nodal staging.

[Impact of nuclear medicine imaging techniques for lymph node surgery]. / Bedeutung der nuklearmedizinischen Bildgebung für die Lymphknotenchirurgie.

Nuclear medicine imaging techniques allow the noninvasive in vivo visualization of cellular and subcellular molecular processes. In the context of lymph node surgery and patient management in uro-oncology, two molecular nuclear imaging techniques deserve special interest: positron emission tomography (PET) for staging, restaging, and follow-up, and preoperative identification and subsequent biopsy of the sentinel lymph node (the first lymph node in the lymphatic drainage system of the tumor). Both methods and their clinical potential are described in this review. Future trends in molecular imaging in uro-oncology are also discussed.

[Influence of the injection technique on the false negative rate of SLNE in multifocal breast cancer]. / Einfluss der Injektionstechnik auf die Falsch-negativ-Rate bei der SLNE des mehrherdigen Mammakarzinoms.

AIM: We investigated the influence of the injection technique on the false negative rate in identifying the sentinel lymph node in multifocal breast cancer. PATIENTS, METHODS: 958 consecutive patients were divided into unifocal and multifocal breast cancer patients. The scintigrafic and intraoperative detection rate as well as the false negatives were calculated in relation to peritumoral or subareolar injection. RESULTS: In all patients the scintigrafic and intraoperative detection rate exceeded 99%, except in patients with multifocal cancer, who were injected peritumorally. In this group the intraoperative detection rate declined to 96%. In patients with unifocal breast cancer the false negative rate was below 5%, independent of the injection technique. Multifocal breast cancer patients showed a significant dependence on the injection technique. The false negative rate was 26.3% in patients with peritumoral injection and 5.6% in those with subareolar injection. CONCLUSION: The results clearly demonstrate that in multifocal breast cancer a reliable detection of a SLN is impossible with the peritumoral injection technique. Subareolar injection seems to be a way to operate on multifocal breast cancer with SLNE, but the number of investigated patients is too low for statistic approval. So, prospective studies should be performed to validate these preliminary results before SLNE becomes routine in multifocal breast cancer.

[Sentinel node dissection in prostate cancer: current status]. / Sentinel-Lymphadenektomie beim Prostatakarzinom - Aktueller Stand.

Sentinel lymph node (SLN) dissection is an excellent staging procedure with high sensitivity (>95%) for detecting positive nodes. When the sentinel node is negative, there is high certainty that other lymph nodes are also negative. Limitations of this technique include the use of hormone therapy over several months and a preceding transurethral resection or suprapubic adenomectomy. When sentinel node dissection is performed in patients with intermediate and high-risk prostate cancer, it should be kept in mind that when the SLN is positive, other lymph nodes can be positive, too. The positive non-SLN can be located outside the SLN region. Therefore, both sentinel and extended lymph node dissection should be used in men with a higher risk of lymph node metastases.

Effect of aged garlic extract on caspase-3 activity, in vitro.

In neurodegeneration, such as Alzheimer's disease (AD), apoptosis results in the loss of valuable neurons. A key mechanism in apoptosis is the activation of caspase-3. Caspase-3 activity first becomes detectable early in apoptosis, continues to increase as cells undergo apoptosis, and rapidly declines in late stages of apoptosis. Its activity is an early marker of cells undergoing apoptosis. Caspase-3 catalyzes the formation of beta-amyloid peptide, a hallmark of AD. The purpose of the study was to determine whether dietary aged garlic extract (AGE), with known antioxidant properties and neuroprotection against Alzheimer's beta-amyloid cytotoxicity, inhibits the caspase-3 activity in vitro. Caspase-3 activity was assayed according to the prescribed protocol and incubated overnight at ambient temperature. We report that AGE inhibits caspase-3 in dose dependent manner. Caspase-8 was not inhibited by AGE. As a caspase-3 inhibitor, AGE may be effective in reducing apoptotic death of neurons since caspase inhibitors have been shown to inhibit neuronal cell death. We propose a scheme for the ameliorative effect of AGE on deleterious effects of beta-amyloid and possibly uncontrolled caspase-3 activity.

[N(2)H(5)](+)(2)[N(4)C-N=N-CN(4)](2-): a new high-nitrogen high-energetic material.

The reaction of [N(2)H(5)](+)(2)[SO(4)](2-) with barium 5,5'-azotetrazolate gave new high-energy-density materials (HEDM) based on the 5,5'-azotetrazolate dianion. The dihydrazinium salt of [N(4)C-N=N-CN(4)](2-) 1, its dihydrate 2, and its dihydrazinate 3 were prepared in high yield. Synthesis in water afforded yellow needles of [N(2)H(5)](2)(+)[N(4)C-N=N-CN(4)](2-).2H(2)O (2): monoclinic, P2/c, a = 8.958(2) A, b = 3.6596(7) A, c = 16.200(3) A, beta = 96.834(3) degrees, V = 527.3(2) A(3), Z = 2; synthesis in anhydrous hydrazine gave yellow [N(2)H(5)](2)(+)[N(4)C-N=N-CN(4)](2-).2N(2)H(4) (3): triclinic, P1, a = 4.6208(6) A, b = 8.585(1) A, c = 9.271(1) A, alpha = 108.486(2) degrees, beta = 95.290(2) degrees, gamma = 102.991(2) degrees, V = 334.51(8) A(3), Z = 1. The compounds were characterized by elemental analysis and vibrational (IR, Raman) and multinuclear NMR spectroscopy ((1)H, (13)C, (14)N, (15)N). The new compounds represent new high-nitrogen HEDMs with one of the highest nitrogen contents reported to date ([N(2)H(5)](+)(2)[N(4)C-N=N-CN(4)](2-) 85.2%; [N(2)H(5)](+)(2)[N(4)C-N=N-CN(4)](2-).2H(2)O 73.3%; [N(2)H(5)](+)(2)[N(4)C-N=N-CN(4)](2-).2N(2)H(4) 85.7%). The standard heat of formation of the solvate-free compound 1 was computed at the MP2(FULL)/6-311+G(d,p) level of theory to be DeltaH degrees (f) = 264 kcal mol(-1), which translates to 1147 kcal kg(-1) and is one of the highest ever reported. The compounds are stable at room temperature, almost insensitive to friction and impact, but detonate violently when the explosion is initiated, e.g., by rapid heating over the decomposition temperature or by using an initiator.

Effect of the cholinesterase inhibiting substance galanthamine on human EEG and visual evoked potentials.

The action of galanthamine (GAL), a cholinesterase inhibiting substance, on resting EEG and on flash visual evoked potentials (VEPs) was tested in 9 healthy subjects. Alpha power was increased significantly in 4 of 8 subjects after the infusion of 10 mg, which provided a median inhibition of 47% of acetylcholinesterase in erythrocytes. Mean alpha frequency and peak alpha frequency decreased significantly in 5 of the 8 subjects by 0.22-0.98 Hz. Alpha power increase and alpha frequency decrease were not accompanied by changes in theta power. The amplitudes of the late components of the flash VEP were increased in 8 of 9 subjects receiving doses of 10-35 mg of GAL, while the early components remained unaffected. Increase of late VEP components was significantly correlated with the strength of cholinesterase inhibition. The synchronizing effect of GAL in these healthy volunteers obviously contrasts with the known desynchronizing effect of physostigmine in animal experiments.

A technique for eliciting muscular reflex responses using position controlled dc motors.

A method for generating fast ramp movements is described. A direct current (dc) motor serves as a drive in position feedback mode. In addition to a regulator and a power amplifier, basically only two relatively simple analog circuits are required. One is a ramp function generator with continuously adjustable parameters. The ramp function can be adjusted to the electromechanic transfer function of the motor. A second circuit comprises an analog position storage and allows the ramp to be started from any resting position.

A method for separation of superimposed electromyographic responses in man.

Superposition of electromyographic potentials occurs when motor nerves are excited at intervals that are shorter than the duration of one single muscular signal. The method introduced here allows the separation of compound responses into their constituents in experiments with two closely spaced stimuli (conditioning stimulus and test stimulus), each of them eliciting a defined electromyographic response. Stimulus generation is controlled by a small laboratory computer which produces paired stimuli or the conditioning stimulus alone in random order. All responses are classified according to the size of the initial part of the response to the conditioning stimulus and averaged. The response to the test stimulus is obtained by a subtraction procedure. The method takes into account the considerable variability of reflex responses in man. It was tested in the analysis of recovery curves of spinal reflexes elicited by short vibratory pulses onto the tendons of relaxed human arm muscles.

[Histamine poisoning following consumption of fried fish]. / Histaminvergiftungen nach Bratfischverzehr.

Cases of food poisoning after consumption of fried fish in marinades are often caused by increased content of histamine. From 1973 to 1988 28 outbreaks in groups of persons with symptoms of histamine poisoning were analysed in the district of Dresden (GDR). The content of histamine most commonly exceeded the tolerance limit of 300 mg/kg fried fish.

[Use of digital technics in the display of electromyography signals]. / Uber die Anwendung digitaler Techniken bei der Darstellung von EMG-Signalen.

The use of digital techniques for the display of electromyographic signals often introduces grave errors in the visualization of the high frequency signal components. The causes for this can be quantitatively deduced from the technical principles of the systems. In the digital storage oscilloscope, the accuracy of reproduction is determined by the sampling rate and the memory capacity. In addition, there may be a considerable loss of quality in the visual display of systems using computer graphics despite accurate signal acquisition. Based on the quantitative analysis recommendations as to the technical equipment and use of digital neurophysiological systems are given.

Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves' disease.

Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were retrospective [corrected] and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P less than 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P = 0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P = 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P = 0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P less than 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P less than 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.

False-positive granulocyte scintigraphy in a patient with acute leukemia.

This study describes a 12-year-old patient who was hospitalized because of arthritislike symptoms. A scintigraphy performed with in vivo labelled granulocytes revealed, in addition to a few foci, an abnormal intravasal persistence of the labelled cells. An acute leukemia was found that was restricted to the bone marrow.

Primidone and essential tremor.

To clarify whether primidone itself, and not only its metabolite phenobarbitone, suppresses essential tremor, the effect of a high single dose of primidone was tested. Of 11 patients, 8 showed a reduction of their tremor by 54%-69% for up to 28 h. The serum concentration of primidone was as expected, whereas those of the metabolites phenyl-ethyl-malonamide and phenobarbitone were very low. The tremor suppression can thus be considered to be an effect of primidone. Three of the 11 patients did not show a reduction of tremor.

Do HLA-DR-typing and measurement of TSH-receptor antibodies help in the prediction of the clinical course of Graves' thyrotoxicosis after antithyroid drug treatment?

In patients with Graves' hyperthyroidism, the relapse rate after antithyroid drug treatment is in the range of about 30-70%. Different attempts have been made to obtain criteria for the prediction of the clinical outcome after drug therapy, especially HLA-DR typing and measurement of TSH receptor antibodies. So far, very conflicting results have been reported. This is not surprising in view of the many genetically controlled and environmental factors that play a role in the pathogenesis of this disease. Moreover, most reports are based on retrospective studies with a relatively small number of patients. Our own data, obtained in a prospective multicenter study, yield strong evidence against the relevance of HLA-DR3 typing (n = 187, sensitivity = 0.38, specificity = 0.67) or measurement of TSH receptor antibodies at the end of therapy (n = 269, sensitivity = 0.49, specificity = 0.72) for the prediction of the clinical course after drug treatment.

[Effect of cefaclor and tobramycin on the phagocytic activity of peritoneal macrophages in mice]. / Einfluss von Cefaclor und Tobramycin auf die Phagozytoseleistung von Peritonealmakrophagen der Maus.

The influence of Cefaclor and of Tobramycin on phagocytosis of sheep erythrocytes by murine peritoneal macrophages was investigated. The antibiotics in various concentrations were either added to the cells directly during the phagocytosis period or injected i.v. into cell donor mice at different times before cell harvest and the cells subsequently assayed for phagocytic activity in vitro. When antibiotic was added during the phagocytosis a dose-dependent inhibition of phagocytosis was observed which, however, became significant only at extremely high concentrations of the antibiotic. In all other experimental set-ups, phagocytosis was not influenced by antibiotics. Restrictive usage of either antibiotic in clinical situation does not appear mandatory on the basis of the reported observations.