Double burst monitoring during surgical degrees of neuromuscular blockade: A comparison with train-of-four

With double burst stimulation (DBS) it is possible to monitor more profound degrees of neuromuscular blockade than with train-of-four stimulation (TOF). It may therefore be indicated to change between DBS and TOF stimulation during moderate to profound degrees of neuromuscular blockade. Consequently, the aim of the study was to evaluate and compare the twitch height of the first twitch (D1) in DBS and the twitch height of the first twitch (T1) in TOF stimulation during moderate to profound degrees of neuromuscular blockade. Thirty-three patients scheduled for gynaecological laparotomy under general anaesthesia were studied. Mechanomyography was used for neuromuscular monitoring. The T1 twitch height before atracurium was administered served as the control twitch height (T1 control). T1 control was considered as 100%. A constant degree of neuromuscular blockade was maintained at a T1 twitch height at a point between 4 and 11% of T1 control, using a continuous infusion of atracurium. Sequences of 16 DBS and 16 TOF stimulations were given. Two different DBS patterns were examined: DBS_3,350/50, (3 stimuli at 50 Hz followed 0.75 sec later by 3 stimuli at 50 Hz), and DBS_3,380/40, (3 stimuli at 80 Hz followed 0.75 sec later by 3 stimuli at 40 Hz). The data were analysed by the method described by Bland and Altman (1). The D1 repeatability coefficients of 1.72% for DBS_3,350/50 and 1.20% for DBS_3,380/40 were significantly greater than the repeatability coefficient of 1.02% for T1 (p<0.05). The D1 bias of 16.7% for DBS_3,350/50 was significantly less than the D1 bias of 25.7% for DBS_3,380/40 (p<0.05). The limits of agreement between D1 and T1 were 0.1 to 33.3% for DBS_3,350/50 and 2.9 to 48.5% for DBS_3,380/40. In conclusion: The repeatability of responses to DBS and TOF stimulations during moderate to profound degrees of neuromuscular blockade where only one twitch is consistently present is satisfactory. The responses to DBS were greater than responses to TOF as indicated by a positive bias of DBS. The limits of agreement between DBS and TOF responses were so wide that they cannot be used interchangeably.     

Central retinal artery occlusion as a first sign of atrial fibrillation: A 3‐year retrospective single‐center analysis

BackgroundCentral retinal artery occlusion ((C)RAO) is known to be associated with stroke and/or atrial fibrillation (AF). Nevertheless, patients often present at the ophthalmologist initially and it is unknown how many of these receive an adequate cardiological/neurological work‐up (CWU/NWU), including a 24 h‐Holter‐ECG.HypothesisHypothesis of this study was that patients with (C)RAO do not undergo CWU on regular basis and that new‐onset AF is more often detected in patients with CWU.Methods and resultsWe performed a retrospective analysis of n = 292 consecutive patients who presented at an ophthalmology department with the diagnosis of (C)RAO during a 3‐year period. After excluding patients with known AF, meeting exclusion criteria, inability to comply with the protocol, missed land phoneline, or death during follow‐up a total of 174 patients were enrolled; mean follow‐up was 20 ± 12 months. The CHA₂DS₂‐VASc score of the cohort was 5.3 ± 1.4. Our analysis revealed that only 50.6% of patients received a CWU including a single Holter‐ECG after the index‐event. In 12.6% cases new‐onset AF was diagnosed, while the rate was higher in patients with CWU compared to patients without CWU (18.2 vs. 7.0%; p = 0.26). Evaluation of oral anticoagulation (OAC) therapy showed that only 66% of patients with AF were treated according to guidelines.ConclusionOnly half of patients with (C)RAO underwent CWU. Despite minimal monitoring, rate of new diagnosed AF was high. Our results confirm that (C)RAO identifies a high‐risk population for AF. These results illustrate the importance to implement standardized CWU in (C)RAO patients presenting at the ophthalmologist.     

Local and systemic delivery of a stable aspirin-triggered lipoxin prevents neutrophil recruitment in vivo

Aspirin (ASA) triggers a switch in the biosynthesis of lipid mediators, inhibiting prostanoid production and initiating 15-epi-lipoxin generation through the acetylation of cyclooxygenase II. These aspirin-triggered lipoxins (ATL) may mediate some of ASA's beneficial actions and therefore are of interest in the search for novel antiinflammatories that could manifest fewer unwanted side effects. Here, we report that design modifications to native ATL structure prolong its biostability in vivo. In mouse whole blood, ATL analogs protected at carbon 15 [15(R/S)-methyl-lipoxin A4 (ATLa1)] and the omega end [15-epi-16-(para-fluoro)-phenoxy-LXA4 (ATLa2)] were recoverable to approximately 90 and 100% at 3 hr, respectively, compared with a approximately 40% loss of native lipoxin A4. ATLa2 retains bioactivity and, at levels as low as approximately 24 nmol/mouse, potently inhibited tumor necrosis factor-alpha-induced leukocyte recruitment into the dorsal air pouch. Inhibition was evident by either local intra-air pouch delivery (approximately 77% inhibition) or systemic delivery by intravenous injection (approximately 85% inhibition) and proved more potent than local delivery of ASA. Rank order for inhibiting polymorphonuclear leukocyte infiltration was: ATLa2 (10 micrograms, i.v.) approximately ATLa2 (10 micrograms, local) approximately dexamethasone (10 micrograms, local) >ASA (1.0 mg, local). Applied topically to mouse ear skin, ATLa2 also inhibited polymorphonuclear leukocyte infiltration induced by leukotriene B4 (approximately 78% inhibition) or phorbol ester (approximately 49% inhibition), which initiates endogenous chemokine production. These results indicate that this fluorinated analog of natural aspirin-triggered lipoxin A4 is bioavailable by either local or systemic delivery routes and is a more potent and precise inhibitor of neutrophil accumulation than is ASA.     

Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals

Aspirin (ASA) is unique among current therapies because it acetylates cyclooxygenase (COX)-2 enabling the biosynthesis of R-containing precursors of endogenous antiinflammatory mediators. Here, we report that lipidomic analysis of exudates obtained in the resolution phase from mice treated with ASA and docosahexaenoic acid (DHA) (C22:6) produce a novel family of bioactive 17R-hydroxy-containing di- and tri-hydroxy-docosanoids termed resolvins. Murine brain treated with aspirin produced endogenous 17R-hydroxydocosahexaenoic acid as did human microglial cells. Human COX-2 converted DHA to 13-hydroxy-DHA that switched with ASA to 17R-HDHA that also proved a major route in hypoxic endothelial cells. Human neutrophils transformed COX-2-ASA-derived 17R-hydroxy-DHA into two sets of novel di- and trihydroxy products; one initiated via oxygenation at carbon 7 and the other at carbon 4. These compounds inhibited (IC(50) approximately 50 pM) microglial cell cytokine expression and in vivo dermal inflammation and peritonitis at ng doses, reducing 40-80% leukocytic exudates. These results indicate that exudates, vascular, leukocytes and neural cells treated with aspirin convert DHA to novel 17R-hydroxy series of docosanoids that are potent regulators. These biosynthetic pathways utilize omega-3 DHA and EPA during multicellular events in resolution to produce a family of protective compounds, i.e., resolvins, that enhance proresolution status.     

Fluorescence in situ hybridization investigation of cutaneous lesions in acute promyelocytic leukemia.

Cutaneous manifestations of acute promyelocytic leukemia are rare but well documented. Skin biopsies of leukemia can be difficult to confirm using morphology alone, and paraffin section immunophenotyping is not specific in separating acute promyelocytic leukemia from other acute myeloid leukemias involving the skin or inflammatory conditions, such as Sweet's syndrome and all-trans retinoic acid-associated genital ulcers, which may mimic leukemia cutis. Fluorescence in situ hybridization has been shown to be a fast and effective method of detecting the PML/RARA fusion gene characteristic of acute promyelocytic leukemia in fresh blood and bone marrow samples. Fluorescence in situ hybridization has also been demonstrated to be effective in detecting other chromosomal rearrangements in paraffin-embedded tissue. This retrospective study of cutaneous lesions from four patients with acute promyelocytic leukemia evaluates the utility of performing fluorescence in situ hybridization to confirm the presence of cutaneous manifestations of acute promyelocytic leukemia in formalin-fixed, paraffin-embedded skin biopsies. All patients had previous bone marrow findings of acute promyelocytic leukemia with characteristic morphology, immunophenotype, and cytogenetic studies, which detailed the presence of the t(15;17)(q22;q12) rearrangement. Two skin biopsies showed an infiltrate of blastic cells involving the dermis in a diffuse pattern and one biopsy had a perivascular/periadnexal pattern. The fourth case, involving the scrotum, showed a predominant neutrophilic infiltrate diffusely involving the dermis and epidermis with a subset of blastic cells. Nuclei were extracted from core biopsies of the formalin-fixed paraffin-embedded tissue and fluorescence in situ hybridization was performed using a dual color, dual fusion PML / RARA probe. All cases showed evidence of the t(15;17) rearrangement, with 90, 79, 51 and 16% positive signal patterns, each well above background limits. Fluorescence in situ hybridization appears to be a robust technique to detect cutaneous manifestations of acute promyelocytic leukemia in formalin-fixed paraffin-embedded skin biopsies.     

Evaluation of two chromogenic agar media for recovery and identification of Staphylococcus aureus small-colony variants

To identify the most rapid and reliable technique for recovery and identification of Staphylococcus aureus small-colony variants (SCVs), the colonial appearance of 106 isolates representing SCVs and the normal phenotype were evaluated on two newly described chromogenic agar media. Although almost all of the SCVs grew on the chromogenic agar media, they did not exhibit a change of color. In comparison with conventional media, S. aureus ID agar (SAID; bioMerieux, La Balme Les Grottes, France) showed the most reliable results, with 49 of 53 SCVs tested growing either as an SCV colony or with a normal phenotype after only 24 h of incubation. Growth of SCVs was often not detected before 72 h of incubation on some of the media tested. In conclusion, the most accurate and rapid method to detect both the species S. aureus and the SCV phenotype is to inoculate specimens onto both Columbia blood agar and SAID.     

Inter-laboratory validation of PCR-based detection of Mycobacterium tuberculosis in formalin-fixed, paraffin-embedded tissues

The present study is based on the initiative for quality assurance in pathology of the German Society of Pathology and the Professional Association of German Pathologists. Four panel laboratories with experience and expertise in polymerase chain reaction (PCR) detection of Mycobacterium tuberculosis were selected to establish the prerequisites for continuous external laboratory trials, in particular, by providing pre-tested specimens and evaluation criteria for participating institutes. In the first step, the four panel laboratories performed an internal trial to test their own reliability and reproducibility. Paraffin sections and DNA preparations from 34 tissues (25 clinical specimens and 9 controls) totalling to 66 samples were evaluated by each panel institute according to their own protocols. The methodologies differed and are described in detail. Despite these differences, a high degree of inter-laboratory reliability was achieved. In this report, we summarise our results including the correlation with the histology and provide recommendations for applying PCR-based methodology for the detection of mycobacterial DNA in surgical specimens. Supplementary data are available online at (rubric Forschung). Pre-tested specimens are now available for the external trial and can be ordered from the steering institute via Oligene (). All molecular pathology laboratories are invited to participate in this quality assurance initiative.