Morphological segmentation of FIB-SEM data of highly porous media.

Nanoporous materials play an important role in modern batteries as well as fuel cells. The materials microstructure needs to be analyzed as it determines the electrochemical properties. However, the microstructure is too fine to be resolved by microcomputed tomography. The method of choice to analyze the microstructure is focused ion beam nanotomography (FIB-SEM). However, the reconstruction of the porous 3D microstructure from FIB-SEM image data in general has been an unsolved problem so far. In this paper, we present a new method using morphological operations. First, features are extracted from the data. Subsequently, these features are combined to an initial segmentation, that is then refined by a constrained watershed transformation. We evaluate our method with synthetic data, generated by a simulation of the FIB-SEM imaging process. We compare the ground truth in the simulated data to the segmentation result. The new method is found to produce a much smaller error than existing techniques.

Enteric-coated mycophenolate sodium reduces gastrointestinal symptoms in renal transplant patients.

A main cause for gastrointestinal (GI) complications in graft recipients is the routinely administered inosine monophosphate dehydrogenase inhibitor mycophenolic acid (MPA). MPA is available in two formulations, the prodrug mycophenolate mofetil (MMF) and the enteric-coated sodium salt (EC-MPS). Clinical results point to a better GI tolerability of EC-MPS as compared to MMF. We performed an open surveillance study in 397 organ graft recipients to investigate the clinical tolerability of EC-MPS in renal graft recipients who were converted from MMF to EC-MPS (maintenance) or who received EC-MPS as a new component of their immunsuppressive regimen (de novo). Physicians recorded GI symptoms (nausea, emesis, anorexia, diarrhea, abdominal cramps) at the start of EC-MPS treatment (visit 1) and at the next two visits in the clinic (visits 2 and 3); general tolerability (very good/good/moderate/poor) was assessed at visit 2 and 3. Two hundred seventy-five patients were on maintenance treatment with MMF and were converted to equimolar doses of EC-MPS, and 122 patients received EC-MPS de novo. The mean time since transplantation was 4.2 +/- 4.4 years. Median time until visit 2 was 28 days and until visit 3, 65 days. In 63.0% of patients, tolerability was rated as very good at visit 2 and in 64.7% at visit 3. Most patients who had suffered from GI complications during preceding MMF treatment reported improvement or total disappearance of their symptoms after conversion to EC-MPS. In conclusion, EC-MPS is a useful means to reduce GI complications in MPA-treated patients.

Regulated and constitutive expression of anti-inflammatory cytokines by nontransforming herpesvirus saimiri vectors.

Herpesviral saimiri-(HVS) mediated expression of bovine growth hormone was one of the first applications of an episomal viral vector for gene therapy. Meanwhile, the long-term persistence of HVS vectors has been confirmed in a broad spectrum of infectable target cells in vitro and in vivo. Regulated gene expression is useful for many applications of gene therapy. Therefore, we inserted the Mifepristone-antiprogestin-inducible expression system (GeneSwitchtrade mark) into HVS viral vectors to regulate the combined expression of anti-inflammatory cytokines, IL-10 and IL-1RA. Constitutive CMV-promoter/enhancer-driven and Mifepristone-inducible cytokine expression was compared in the viral context in transduced primary human fibroblasts and rheumatoid arthritis (RA) fibroblast-like cells (RASF). Long-term persistence of vector genomes was shown for both construct types. Constitutive expression was efficient and more rapid in onset than in the inducible system, in which the selective induction of interleukin expression along with low background levels was obtained by Mifepristone concentrations that were more than 1000-fold below those required for endogenous Progesterone antagonism. Furthermore, transgene expression corresponded to vector doses. Global patterns of cytokine secretion were not significantly changed due to viral transduction, indicating a rather inert behavior of the viral vector itself. In an attempt to emulate the inflammatory cytokine-enriched environment in rheumatoid arthritic joints, the function of the vectors could be demonstrated in vitro by the successful blockade of IL-1beta-stimulated matrix-metalloproteinase (MMP)-3 expression from RASF cells. Evaluation of this system in future studies, in suitable long-term SCID models of RA or in non-human primate models, will exploit the possible in vivo benefits of nontransforming HVS vectors in gene therapy.

Free and total bupivacaine plasma concentrations after continuous epidural anaesthesia in infants and children.

We measured free and total venous bupivacaine plasma concentrations in fourteen infants and children aged 6 days (2800 g) to 9 years (27 kg) undergoing epidural anaesthesia. An initial bolus of 0.5 ml.kg-1 bupivacaine 0.25% was followed by a continuous infusion administered one h after bolus over a period of seven h (first hour 0.25 ml.kg-1.h-1 0.25%; then reduced to 0.125%). Although total bupivacaine plasma concentrations were within acceptable limits (< 1.5 micrograms.ml-1), four of the seven infants showed adverse reactions. Maximum plasma concentrations of free bupivacaine were significantly higher in infants (P < 0.05) than in older children. We conclude that toxicity may be underestimated when only measuring total bupivacaine concentrations. In young infants the bupivacaine dose administered for continuous epidural anaesthesia should be further lowered below recommended concentrations and the patients closely observed for possible adverse reactions.

Recurrent liver failure with severe rhabdomyolysis after liver transplantation for carbon tetrachloride intoxication.

Acute liver failure due to intoxication is a rare indication for liver transplantation which a usually has a good prognosis. We herein report the case of a young male, who underwent orthotopic liver transplantation for acute liver failure due to carbon tetrachloride intoxication. Apart from hepatic and renal failure, the patient also developed severe rhabdomyolysis, which has not thus far been described as a toxic effect of this chemical agent. Despite forced hyperventilation, which is known to be the most effective means of eliminating the specifically lipophylic agent, as well as excessive plasma exchange following intravenous administration of fat emulsions, liver failure recurred when blood carbon tetrachloride concentrations were already at non-toxic levels. Retransplantation of the liver together with a kidney was only temporarily successful, since the patient died due to aspergillus sepsis. Based on this experience, we would recommend that whenever possible in patients with carbon tetrachloride intoxication, liver transplant should be delayed until most of the toxic agent has been eliminated in order to prevent fatal graft damage.

Effect of chemical anoxia on protein kinase C and Na+, K+-ATPase in hepatocytes of goldfish (Carassius auratus) and rainbow trout (Oncorhynchus mykiss)

Protein kinase C (PKC) and Na+/K+-ATPase in hepatocytes from the anoxia-tolerant goldfish (Carassius auratus) and the anoxia-intolerant rainbow trout (Oncorhynchus mykiss) were studied to determine their role in the anoxic response of these cells. PKC and Na+/K+-ATPase activities were measured for up to 90 min in the absence (normoxia) and presence (chemical anoxia) of 2 mmol l-1 sodium cyanide. PKC activity of normoxic cells from both species remained constant for the entire experimental period. Addition of cyanide had no effect on PKC activity of trout cells, which was maintained at 25 % of maximal PKC activity. In goldfish hepatocytes, PKC activity remained constant at 56 % of maximal PKC activity for 30 min but fell to 27 % after 90 min of anoxic exposure. ATPase activity was measured in hepatocytes exposed to 100 nmol l-1 phorbol-12,13-dibutyrate (PdBu), a treatment which enhanced PKC activity to its maximum level. In trout cells, there was no significant change in Na+/K+-ATPase activity whereas in goldfish hepatocytes a significant increase to about 150 % of the respective controls was observed. On the basis of the experimental evidence that in hepatocytes of goldfish (1) PKC and Na+/K+-ATPase activities decreased in parallel during chemical anoxia and (2) a stimulation of PKC activity by PdBu increased Na+/K+-ATPase activity, we postulate that PKC activity in goldfish, but not in trout, may be implicated in the Na+/K+-ATPase inhibition observed under anoxia.

Cardiac troponin T release in multiply injured patients.

Cardiac troponin T (cTnT), a new marker of myocardial tissue damage, was investigated in 32 consecutive multiply injured patients. cTnT, creatine kinase (CK) and CK isoenzyme MB (CK-MB) mass concentrations were measured immediately after admission, 12 and 24 h later and daily thereafter for 4 days. We found a moderate increase in cTnT in 22 patients (72 per cent; peaks: 0.6-5.1 micrograms/l). In only four of these 22 patients did the CK-MB mass/CK index indicate myocardial injury. ST-T alterations and arrhythmias did not occur significantly more frequently in patients with increased cTnT plasma concentrations or positive CK-MB mass/CK index. We found a moderate increase in cTnT in 72 per cent of all patients with multiple injuries, but we found no association between an increase in cTnT and the occurrence of electrocardiographic changes and arrhythmias.

[Intraoperative calorimetry in aortic bifurcation reconstruction]. / Intraoperative Kalorimetrie bei Aortengabelrekonstruktion.

Oxygen uptake (VO2) and carbon dioxide elimination (VCO2) can be measured with an indirect calorimeter, this method is well established in routine monitoring of ICU patients to evaluate metabolic state as a reflection of stress. In various experimental studies it was demonstrated that anaesthetics can influence whole-body metabolism. The purpose of this study was to examine whether indirect calorimetry can be used intraoperatively during routine anaesthesia and whether presumable changes in metabolism can be detected immediately. Abdominal aortic cross-clamping changes circulation, nutritional supply of the lower extremities and thus VO2 and VCO2. We therefore used this operation for our study. METHOD. Eleven patients, mean age 64 years, undergoing reconstruction of the aortic bifurcation, were studied. After premedication with piritramid and atropine, total intravenous anaesthesia (TIVA) was performed with fentanyl and midazolam after an induction with thiopental. Patients were ventilated with a Servo-Ventilator 900 D and a constant FiO2 of 0.5, without N2O. Routine monitoring consisted of ECG, pulsoximetry, CVP and continuous AP. VO2 and VCO2 were measured with a Deltatrac (Datex), and data were registered every minute. For statistical evaluation we used a Wilcoxon-Ranksum test for matched pairs, p < 0.05 was considered significant. Data from specific time (5 min after intubation, 5 min before clamping; 5, 10 and 15 min after clamping, before declamping and 5 and 10 min after declamping and at the end of surgery) were calculated. In addition to absolute values, we compared the measured VO2 and VCO2 to baseline (5 min before clamping = MP2). RESULTS. Mean operating time was 139 min +/- 37; aortic cross-clamping time for the first extremity was 38 min and 55 min for the second. As expected, there was a significant decrease in VO2 (90% of baseline) and VCO2 (75% of baseline) during aortic cross-clamping. After declamping VO2 again rose to 110% of baseline, or to 103% for the second limb. VCO2 increased to only 90% and 82%, respectively. At the end of surgery VO2 reached baseline, whereas VCO2 remains at 83%. The respiratory quotient VCO2: VO2 was markedly reduced from 0.95 +/- 0.156 to 0.73 +/- 0.06 during surgery. The Deltatrac showed every change in VO2 without delay; changes in VCO2 seem to occur somewhat retarded. DISCUSSION. Aortic cross-clamping leads to a marked decrease in VO2 and VCO2 reflecting the temporary reduction in whole-body metabolism. Declamping results in a compensatory rise, especially in VO2. VCO2 seems to increase less after declamping, perhaps due to the CO2 pool of the organism or to a change in metabolism from carbohydrate to mainly fat oxidation. The results of this study demonstrate that indirect calorimetry can easily be performed during anaesthesia and surgery. Preconditions are a non-rebreathing system without airleak, constant FiO2 < 0.6 and no use of nitrous oxide.

[Lipid infusion in multiple trauma intensive care patients in the early phase of treatment]. / Fettinfusion bei polytraumatisierten Intensivpatienten in der Frühphase der Behandlung.

OBJECTIVES: To study the metabolic effects of a high-dose fat infusion application in the early phase of total parenteral nutrition (TPN) after major trauma. DESIGN: Prospective study in male patients after major trauma. SETTING: Intensive care unit of the University Clinic. PATIENTS: 21 male, mechanically ventilated patients after major trauma. INTERVENTIONS: Infusion of Elolipid 20% (Fa. Leopold, Graz, Austria), starting on the 3rd day after ICU admission (0.075 g/kg body weight/h) in 8 h. The dose was increased on the 5th day (0.125 g/kg BW/h) and on the 7th day (0.15 g/kg BW/h). RESULTS: There was a pathologic rise in serum triglycerides on days 3, 5 and 7 during the infusion period. A serious diabetic metabolic state was shown on the 3rd day. No significant changes in urea production rate could be demonstrated after the high-dose fat infusion. CONCLUSIONS: The reason for the decreased fat elimination in patients after major trauma after high-dose fat infusion (8 h) remains unclear (fat clearance or fat oxidation failure). Therefore the fat infusion should be started after normalization of the blood glucose level. Thus the fat infusion should be given continuously over 24 h to avoid serious metabolic complications.

Cardiac troponin T: a new marker of myocardial tissue damage in bypass surgery.

The purpose of this study was to evaluate cardiac troponin T (TnT) in the diagnosis of minor perioperative myocardial tissue damage and small myocardial infarctions during aortocoronary bypass surgery. In 15 patients without enzymatic or electrocardiographic signs of perioperative myocardial ischemia (group 1, uncomplicated bypass surgery), TnT did not exceed 3.55 micrograms/L. In 3 patients with perioperative non-Q-wave infarctions (group 2), TnT was significantly higher than in group 1 patients. In all 3 patients, TnT peak concentrations exceeded 3.5 micrograms/L. Thirteen patients (group 3, borderline cases) showed either signs of perioperative myocardial ischemia by creatine kinase isoenzyme MB (CKMB) activity levels (CKMB > 20 U/L on the first postoperative day, 3 patients) or by electrocardiography (new ST-T segment alterations, 10 patients). TnT concentrations were comparable to group 1 patients and indicated uncomplicated bypass surgery in all 3 patients with solely elevated CKMB activities. On the other hand, TnT concentrations in 3 patients with electrocardiographic signs of perioperative myocardial ischemia were significantly higher than in uncomplicated patients (group 1) with peak values exceeding 3.5 micrograms/L. Thus, TnT indicated perioperative non-Q-wave infarctions not detected by CKMB activity in these 3 patients. These results are in accordance with findings in nonsurgical patients. They suggest a higher sensitivity and specificity of cardiac TnT compared to CKMB activity in the diagnosis of small perioperative myocardial infarctions after bypass surgery.

[The effect of various donor factors on primary and long-term function of the transplanted kidney]. / Einfluss verschiedener Spender-Faktoren auf die Primär- und Langzeitfunktion der transplantierten Niere.

Various factors such as cause of brain death, duration of intensive care, single or multiple organ procurement, renal function, heart rate, mean arterial blood pressure, requirement of catecholamines and metabolic derangement were investigated in 86 consecutive organ donors with respect to the possible influence on initial graft function in 86 kidney recipients. Donor conditioning and perioperative recipient management were standardized. Donors of kidneys with initial graft function (group I) showed a significantly higher incidence (80%) of brain death as a consequence of an isolated cerebral incident than donors of kidneys without initial graft function (group II), whereas the incidence of polytrauma (including cerebral) was much higher in donors of group II kidneys (42.9%). The donor requirement of catecholamines was higher in group II donors and the frequency of multiple organ donors was also higher in this group. Five-year graft survival was 80% for group I kidneys but only 62% for group II kidneys. The other factors had no influence on initial graft function. These data demonstrate that multiple injuries and multiple organ procurement have a negative impact on the initial function of the transplanted kidney, possibly due to prolonged ischemic insult.

Atrial natriuretic peptide (ANP), aldosterone, angiotensin II and renin in the 'low T3 syndrome' in organ donors.

The present prospective study was conducted in order to investigate the effect of an acute decrease in serum T3 levels on ANP, aldosterone, angiotensin II, renin and ADH. All patients showed a pathologic TRH stimulation test prior to organ harvesting. Our patients developed secondary T3 hypothyroidism of different severity dependent on intensive care unit (ICU) stay. T3 values in group 1 (ICU stay > or = 77 h) were smaller than 70 ng/dl, those of group 2 (ICU stay < or = 53 h) were greater than 70 ng/dl. In both groups a severe elevation of plasma renin activity was measured, with almost high-normal values for ANP in group 1 and slightly elevated values in group 2 [not significant (n.s.)]. Results demonstrate that, contrary to patients who are not critically ill, brain-dead patients develop a dissociation of the renin-angiotensin-aldosterone mechanism. No statistical significant difference was found between the groups in serum levels of ADH and aldosterone. This endocrine dissociation, however, seems to have no clinical significance with regard to organ function after transplantation in kidney recipients.

[Theodor Kocher and the beginnings of radiology in Switzerland]. / Theodor Kocher und die Anfänge der Radiologie in der Schweiz.

Already in January 1896, Kocher ordered his first clinical radiography. It was executed by Aimé Forster, professor of physics at the University ob Berne. Together, Forster and Kocher elaborated the plans for the Röntgen Institute of the Inselspital, which opened on January 1st, 1898.

Endocrine abnormalities in severe traumatic brain injury--a cue to prognosis in severe craniocerebral trauma?

Patients with severe craniocerebral trauma (sCCT) display metabolic and endocrine changes. The question is raised whether hormonal patterns give cues to the prognosis of outcome or not. In 21 patients the function of the adrenocortical, gonadal, thyroid and human growth hormone (hGH)-insulin system was assessed. LH, FSH, TSH, prolactin and hGH were stimulated. 3 groups of patients were formed. Group I: patients in acute phase with a Glasgow Coma Score (GCS) more than 6 (group Ia) and less than 6 (group Ib). Group II: patients in transition to traumatic apallic syndrome (TAS). Group III: patients with full-blown or resolving TAS. The values of group Ia comprised low T3, T4 and testosterone, elevated insulin, normal hGH. Group Ib had hypothyroid T3 and T4 and an attenuated response of LH, TSH, prolactin and hGH to stimulation. Group III: there was seen an endocrine normalisation with elevated T4 and TBG and an altered response of hGH and prolactin to stimulation. Endocrine abnormalities were not helpful in predicting which course, either to better or to worse, a given patient would follow.