Alexander P. Reske

Lack of correlation for sodium iodide symporter mRNA and protein expression and analysis of sodium iodide symporter promoter methylation in benign cold thyroid nodules.

Cold thyroid nodules (CTNs) are characterized by a reduced iodide uptake in comparison to normal thyroid tissue. The sodium iodide symporter (NIS) is the first step in thyroid hormone synthesis and mediates the active iodide transport in the thyroid cells suggesting that decreased iodide uptake could be a result of changes in NIS expression or molecular defects in the NIS gene. In contrast to previous studies, an intraindividual comparison of NIS mRNA expression in CTNs and their corresponding surrounding tissue was performed using direct detection of NIS mRNA. A significant reduction in NIS mRNA expression was detected in 86% of the 14 investigated CTNs. We hypothesized that human sodium iodide symporter (hNIS) transcriptional failure could be caused by primary molecular NIS gene defects and/or methylation of DNA in the NIS promoter. However, no mutation in the NIS cDNA nor in the NIS promoter region upstream up to-443 bp from the ATG start codon was detected. Therefore, primary molecular NIS gene defects were excluded. However, in 50% of CTNs with reduced NIS mRNA expression, the promoter region was hypermethylated. NIS mRNA expression in these hypermethylated CTNs only reached a maximum of 30% of the corresponding surrounding tissue. Hence, methylation of CpG islands in the NIS promotor could be a regulatory mechanism of NIS transcription in CTNs. Immunoblot revealed absent hNIS protein expression in the total cell membrane fraction in 45% of investigated nodules. In the majority of the remaining CTNs NIS protein expression was decreased in the nodule tissue compared to the corresponding surrounding tissue. For investigating protein expression immunhistochemistry has two advantages. First, the whole nodule area can be investigated, and second, NIS expression can be detected in areas where an immunoblot of a cell membrane fraction is negative. Interestingly, immunhistochemistry revealed higher NIS expression in 50% of CTNs compared to their corresponding surrounding tissues and NIS staining was predominantly intracellular. These data demonstrate that NIS protein expression does not reflect NIS mRNA expression. Therefore, factors that affect targeting of NIS to the plasma membrane are likely to be affected.

Ras mutations are rare in solitary cold and toxic thyroid nodules

OBJECTIVE Activation of ras proto‐oncogenes as a result of point mutations is detectable in a significant percentage of most types of tumour. Similar to neoplasms of other organs, mutations of all three ras genes can be found in thyroid tumours. H‐, K‐ and N‐ras mutations have been detected in up to 20% of follicular adenomas and adenomatous nodules which were not functionally characterized. This raises the question as to whether ras mutations are specific for hypofunctional nodules and TSH receptor mutations for hyperfunctioning nodules.

Bedside Estimation of Nonaerated Lung Tissue Using Blood Gas Analysis

Objectives:Studies correlating the arterial partial pressure of oxygen to the fraction of nonaerated lung assessed by CT shunt yielded inconsistent results. We systematically analyzed this relationship and scrutinized key methodological factors that may compromise it. We hypothesized that both physiological shunt and the ratio between PaO2 and the fraction of inspired oxygen enable estimation of CT shunt at the bedside. Design:Prospective observational clinical and laboratory animal investigations. Setting:ICUs (University Hospital Leipzig, Germany) and Experimental Pulmonology Laboratory (University of São Paulo, Brazil). Patients, Subjects and Interventions:Whole-lung CT and arterial blood gases were acquired simultaneously in 77 patients mechanically ventilated with pure oxygen. A subgroup of 28 patients was submitted to different Fio2. We also studied 19 patients who underwent repeat CT. Furthermore we studied ten pigs with acute lung injury at multiple airway pressures, as well as a theoretical model relating PaO2 and physiological shunt. We logarithmically transformed the PaO2/Fio2 to change this nonlinear relationship into a linear regression problem. Measurements and Main Results:We observed strong linear correlations between Riley’s approximation of physiological shunt and CT shunt (R2 = 0.84) and between logarithmically transformed PaO2/Fio2 and CT shunt (R2 = 0.86), allowing us to construct a look-up table with prediction intervals. Strong linear correlations were also demonstrated within-patients (R2 = 0.95). Correlations were significantly improved by the following methodological issues: measurement of PaO2/Fio2 during pure oxygen ventilation, use of logarithmically transformed PaO2/Fio2 instead of the “raw” PaO2/Fio2, quantification of nonaerated lung as percentage of total lung mass and definition of nonaerated lung by the [–200 to +100] Hounsfield Units interval, which includes shunting units within less opacified lung regions. Conclusion:During pure oxygen ventilation, logarithmically transformed PaO2/Fio2 allows estimation of CT shunt and its changes in patients during systemic inflammation. Relevant intrapulmonary shunting seems to occur in lung regions with CT numbers between [–200 and +100] Hounsfield Units.

Extrapolation in the analysis of lung aeration by computed tomography: a validation study

IntroductionComputed tomography (CT) is considered the gold standard for quantification of global or regional lung aeration and lung mass. Quantitative CT, however, involves the exposure to ionizing radiation and requires manual image processing. We recently evaluated an extrapolation method which calculates quantitative CT parameters characterizing the entire lung from only 10 reference CT-slices thereby reducing radiation exposure and analysis time. We hypothesized that this extrapolation method could be further validated using CT-data from pigs and sheep, which have a different thoracic anatomy.MethodsWe quantified volume and mass of the total lung and differently aerated lung compartments in 168 ovine and 55 porcine whole-lung CTs covering lung conditions from normal to gross deaeration. Extrapolated volume and mass parameters were compared to the respective values obtained by whole-lung analysis. We also tested the accuracy of extrapolation for all possible numbers of CT slices between 15 and 5. Bias and limits of agreement (LOA) were analyzed by the Bland-Altman method.ResultsFor extrapolation from 10 reference slices, bias (LOA) for the total lung volume and mass of sheep were 18.4 (-57.2 to 94.0) ml and 4.2 (-21.8 to 30.2) grams, respectively. The corresponding bias (LOA) values for pigs were 5.1 (-55.2 to 65.3) ml and 1.6 (-32.9 to 36.2) grams, respectively. All bias values for differently aerated lung compartments were below 1% of the total lung volume or mass and the LOA never exceeded ± 2.5%. Bias values diverged from zero and the LOA became considerably wider when less than 10 reference slices were used.ConclusionsThe extrapolation method appears robust against variations in thoracic anatomy, which further supports its accuracy and potential usefulness for clinical and experimental application of quantitative CT.

Early recovery from post-traumatic acute respiratory distress syndrome.

Background  To present and discuss the rationale and possible benefits of timely alveolar recruitment in early post‐traumatic acute respiratory distress syndrome.

Pharyngeal wall injury during videolaryngoscopy-assisted intubation.

709 March 2013 A 77-YR-OLD woman was admitted to our intensive care unit after uncomplicated on-pump coronary artery bypass grafting. The anesthesiologist reported that direct laryngoscopy was impossible. Use of a videolaryngoscope (GlideScope; Verathon Medical, IJsselstein, Netherlands) improved the laryngeal visibility. After repeated attempts, a standard endotracheal tube with an inner diameter of 7.5 mm was successfully inserted using the recommended Rigid Stylet (Verathon Medical, IJsselstein, Netherlands). Slight intraoral bleeding after intubation was explained by nasogastric tube placement under dual antiplatelet and heparin therapy. No further problems were reported on admission. During preparation for extubation, large oral and pharyngeal blood clots had to be removed, and an atypical tube position was noted. The tube perforated the palatoglossal arch and the right tonsil, as indicated by the arrow in the figure. Conventional extubation was considered too dangerous because of recent intubation problems and potential rebleeding from the perforation. The consultant otolaryngologist cut through the tissue-band, released the tube, and closed the mucosal wound surgically. The patient was eventually extubated without complications on the first postoperative day. There are several reports on pharyngeal injuries after intubation using videolaryngoscopy. Mechanisms of injury include a blind-spot in the oropharynx, where the videolaryngoscope can hide the tube during advancement and concentration may be focused on the videolaryngoscopy monitor before the stylet-reinforced tube becomes visible on the screen.1–3 Therefore tube advancement should be directly visualized from the mouth until the tube has entered the hypopharynx, and thorough oral and pharyngeal inspection for airway trauma should be considered after difficult airway management.

Computed tomographic assessment of lung weights in trauma patients with early posttraumatic lung dysfunction

IntroductionQuantitative computed tomography (qCT)-based assessment of total lung weight (Mlung) has the potential to differentiate atelectasis from consolidation and could thus provide valuable information for managing trauma patients fulfilling commonly used criteria for acute lung injury (ALI). We hypothesized that qCT would identify atelectasis as a frequent mimic of early posttraumatic ALI.MethodsIn this prospective observational study, Mlung was calculated by qCT in 78 mechanically ventilated trauma patients fulfilling the ALI criteria at admission. A reference interval for Mlung was derived from 74 trauma patients with morphologically and functionally normal lungs (reference). Results are given as medians with interquartile ranges.ResultsThe ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen was 560 (506 to 616) mmHg in reference patients and 169 (95 to 240) mmHg in ALI patients. The median reference Mlung value was 885 (771 to 973) g, and the reference interval for Mlung was 584 to 1164 g, which matched that of previous reports. Despite the significantly greater median Mlung value (1088 (862 to 1,342) g) in the ALI group, 46 (59%) ALI patients had Mlung values within the reference interval and thus most likely had atelectasis. In only 17 patients (22%), Mlung was increased to the range previously reported for ALI patients and compatible with lung consolidation. Statistically significant differences between atelectasis and consolidation patients were found for age, Lung Injury Score, Glasgow Coma Scale score, total lung volume, mass of the nonaerated lung compartment, ventilator-free days and intensive care unit-free days.ConclusionsAtelectasis is a frequent cause of early posttraumatic lung dysfunction. Differentiation between atelectasis and consolidation from other causes of lung damage by using qCT may help to identify patients who could benefit from management strategies such as damage control surgery and lung-protective mechanical ventilation that focus on the prevention of pulmonary complications.

Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs.

Background Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. Methods Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). Results Mtotal was 768 (715–884) g in sheep and 543 (503–583) g in pigs. Atelectasis was 26 (16–47) % in sheep and 18 (13–23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106–414) mmHg in sheep and 480 (437–514) mmHg in pigs. Shunt was 39 (29–51) % in sheep and 15 (11–20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. Discussion and Conclusion In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis.

Circulatory Arrest due to Retrograde Embolization of a Transapically Implanted Aortic Valve Prosthesis with Subsequent Inversion and Left Ventricular Outflow Occlusion.

An 82-year-old man required aortic valve replacement because of aortic stenosis. A transapical approach was chosen to reduce surgical mortality. Initially, echocardiography and fluoroscopy confirmed correct valve positioning. Shortly thereafter, progressive paravalvular leakage, embolization of the valve prosthesis into the ventricle, and subsequent inversion of the prosthesis with complete left ventricular outflow occlusion were observed by echocardiography. Left ventricular outflow occlusion resulted in immediate circulatory arrest. We immediately converted to on-pump surgical aortic valve replacement. Cardiac output was restored once the valve was replaced. The patient fully recovered. This case report highlights the importance of periprocedural transesophageal echocardiography, which instantly detected the malpositioned valve and guided emergency management of this severe complication.

[Case report: sepsis and multi organ dysfunction syndrome in a patient returning from holiday on the Canary Islands: a difficult diagnosis].

UNLABELLED A forty-five year old male tourist suffers a febrile illness, delirium and severe abdominal pain on the fifth day of his holiday trip to the Canary Islands (Spain). After hospitalization he presents a surgical abdomen which requires emergency laparotomy however without detectable pathology. Progressing critical illness and septic shock leads to multiple organ failure, but focus identification is not possible. Well after return to Germany diagnostic uncertainty persists due to recurrent fever and possible travel-associated infections. Finally, besides a simple pararectal abscess, manifestation of acute intermittent porphyria is diagnosed. CONCLUSION Clinicians should consider acute intermittent porphyria as a rare cause of a surgical abdomen. Its clinical presentation include abdominal pain, life-threatening neurovisceral, neurological and psychiatric symptoms, hypertension, tachycardia, hyponatriemia and reddish urine.