Giant Diffusion of Nanomechanical Rotors in a Tilted Washboard Potential.

We present an experimental realization of a biased optical periodic potential in the low friction limit. The noise-induced bistability between locked (torsional) and running (spinning) states in the rotational motion of a nanodumbbell is driven by an elliptically polarized light beam tilting the angular potential. By varying the gas pressure around the point of maximum intermittency, the rotational effective diffusion coefficient increases by more than 3 orders of magnitude over free-space diffusion. These experimental results are in agreement with a simple two-state model that is derived from the Langevin equation through using timescale separation. Our work provides a new experimental platform to study the weak thermal noise limit for diffusion in this system.

Modified ante situm liver resection without use of cold perfusion nor veno-venous bypass for treatment of hepatic lesions infiltrating the hepatocaval confluence.

PURPOSE: Treatment of malignancies invading the hepatic veins/inferior vena cava is a surgical challenge. An ante situm technique allows luxation of the liver in front of the situs to perform tumor resection. Usually, cold perfusion and veno-venous bypass are applied. Our experience with modified ante situm resection relying only on total vascular occlusion is reported. METHODS: Retrospective analysis on an almost 15-year experience with ante situm resection without application of cold perfusion or veno-venous bypass RESULTS: The ante situm technique was applied on eight patients. Five individuals were treated due to intrahepatic cholangiocellular cancer and one case each for mixed cholangio-/hepatocellular carcinoma, colorectal liver metastasis, and pheochromocytoma. Trisectorectomy (n = 4), left hemihepatectomy, right hepatectomy, atypical resection, or mesohepatectomy (each n = 1) were performed, combined with dissection of suprahepatic/retrohepatic vena cava/hepatic veins. Venous reconstruction was achieved by reimplantation of hepatic veins with/without vascular replacement using allogeneic donor veins or PTFE grafts. Median total vascular occlusion of the liver was 23 min. Severe morbidity occurred in three patients (Dindo-Clavien > 3A). R0 status was achieved in six cases with a median overall survival of 33.5 months. CONCLUSIONS: Ante situm liver resection can be applied without cold perfusion nor veno-venous bypass with acceptable morbidity and mortality. However, this procedure remains challenging even for the experienced hepato-pancreato-biliary surgeon.

RNase 7 downregulates TH2 cytokine production by activated human T cells.

BACKGROUND: The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity, immunoregulatory functions have been published for several AMPs. In this study, we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T cells. METHODS: Isolated human CD3+T cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T cells and in polarized TH2 cells using skin-derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay. RESULTS: Treatment of activated human CD4+T cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T cells with RNase 7. CONCLUSION: Our data indicate that RNase 7 has immunomodulatory functions on TH2 cells and decreases the production of TH2 cytokines in the skin.

A case of successful renal transplantation for hydatid disease after surgical treatment of disseminated cysts.

Hydatid disease is a systemic disorder affecting especially the liver and lungs. Although it is not endemic in Europe, it can be seen sporadically, particularly because of travel and immigration. Severe, multiple organ involvement is quite rare. A 39-year-old Kurdish male patient presented with the previous diagnosis of hydatid disease and disseminated cysts in the liver, lung, and left kidney, leading to renal failure and the need for hemodialysis. Following multiple operations, complete eradication of infectious cysts was achieved, and kidney transplantation was performed. After 4 years of follow-up, the patient is in good condition, especially with normal renal function and no sign of recurrent hydatid disease.

The impact of abdominal complications on the outcome after thoracic transplantation--a single center experience.

BACKGROUND: Abdominal complications after thoracic transplantation (Tx) are potentially associated with an increased risk of mortality. We recently reported about the severe outcome after bowel perforation in patients following lung transplantation (LuTx). The aim of the present study was to likewise identify the risk factors with an impact on patient survival following heart transplantation (HTx). METHODS: A retrospective analysis for the frequency and outcome of abdominal interventions following HTx was performed in 342 patients, and these data thereafter compared to a re-evaluated pool of 1,074 patients following LuTx. All patients were transplanted at Hanover Medical School, Germany, between January 2000 and October 2011. RESULTS: The incidence for abdominal surgery was comparable between patients following HTx (n = 33; 9.6 %) and LuTx (n = 90; 8.4 %). Elective operations were more frequently performed in patients after HTx (8.5 vs. 5.1 %). In contrast, the incidence of emergency interventions was higher after LuTx (5.3 %) than that following HTx (2.3 %). Herewith associated was the mortality observed in these transplant recipients (15.3 and 9.9 % for LuTx and HTx, respectively). Leading diagnosis for emergency surgery was bowel perforation (n = 18, regarding all cases). In 11 of these patients, perforation occurred within the first 6 months after Tx and eight of them died in the course of this complication (one patient after HTx and seven patients after LuTx). CONCLUSIONS: Abdominal complications after HTx are less frequently than after LuTx but equally correlate with a high mortality rate. In finding or even reasonable suspicion of an acute abdomen after thoracic Tx, a broad practice for extended diagnostics and a low barrier for an early explorative laparotomy thus are recommended.

Extended surgery for advanced pancreatic endocrine tumours.

BACKGROUND: Pancreatic endocrine tumours are often diagnosed at an advanced stage with hepatic metastasis. This study investigated whether extended resections for advanced malignant pancreatic endocrine tumours influenced disease-free and disease-specific survival. METHODS: Patients who had curative resection of pancreatic endocrine tumours were analysed retrospectively for disease-free and disease-specific survival, with a focus on the role of extended surgical resection. RESULTS: Forty-one patients were included in the analysis, 13 of whom underwent extended surgical resection in addition to pancreatic resection. This included partial liver resection in nine patients, portal vein resection in three, partial gastric resection in five and liver transplantation in three patients. There were no deaths in hospital or within 30 days. Median follow-up was 40 (range 2-239) months. Thirty-five, 24 and 13 patients survived more than 1, 3 and 5 years respectively. Patients who underwent extended resection had similar disease-specific survival to those who had pancreatic resection alone (hazard ratio (HR) 1·50, 95 per cent confidence interval (c.i.) 0·35 to 6·35; P = 0·581) but with a higher frequency of complications (odds ratio (OR) 4·28, 95 per cent c.i. 1·04 to 17·62; P = 0·044). Among patients with liver metastases, the mortality rate was higher in those in whom liver resection was not possible than in patients who had liver resection (HR 9·24, 1·00 to 85·18; P = 0·049). Patients who had liver resection had similar disease-specific survival to those without liver metastases (HR 0·84, 0·09 to 7·57; P = 0·877). CONCLUSION: Extended surgical resection for locally advanced and metastatic pancreatic endocrine tumours is feasible with encouraging disease-specific survival.

Prediction of fetal lung immaturity using gestational age, patient characteristics and fetal lung maturity tests: a probabilistic approach.

OBJECTIVES: The lecithin/sphingomyelin (L/S) ratio and the lamellar body count (LBC) can be used to predict respiratory distress syndrome (RDS). DESIGN: We performed a retrospective cohort study among consecutive women who underwent amniotic fluid sampling for the assessment of fetal lung maturity. Logistic regression was used to construct models for the prediction of RDS in three gestational age categories, with models based on clinical characteristics only, clinical characteristics and the LBC, and on clinical characteristics and L/S ratio. RESULTS: When amniotic fluid was collected <30 weeks, the specificity of the LBC was 30% and the sensitivity 100%. Addition of the L/S ratio increased the specifity to 60%, for a sensitivity of 100%. When amniocentesis was performed between 30 and 33 weeks, addition of the L/S ratio only marginally improved the performance of the LBC. CONCLUSIONS: At a gestational age <30 weeks, the L/S ratio has additional value over the LBC. Above 30 weeks of gestation, single use of the LBC seems sufficient.

Positional cloning of a gene for nematode resistance in sugar beet.

The Hs1(pro-1) locus confers resistance to the beet cyst nematode (Heterodera schachtii Schmidt), a major pest in the cultivation of sugar beet (Beta vulgaris L.). The Hs1(pro-1) gene was cloned with the use of genome-specific satellite markers and chromosomal break-point analysis. Expression of the corresponding complementary DNA in a susceptible sugar beet conferred resistance to infection with the beet cyst nematode. The native Hs1(pro-1) gene, expressed in roots, encodes a 282-amino acid protein with imperfect leucine-rich repeats and a putative membrane-spanning segment, features similar to those of disease resistance genes previously cloned from higher plants.

Tocolytic effectiveness of nifedipine versus ritodrine and follow-up of newborns: a randomised controlled trial.

BACKGROUND: Several studies have demonstrated the superior tocolytic effectiveness of nifedipine over ritodrine. Only 1 trial conducted a long-term follow-up of newborns and found no difference in psychosocial and motor functioning. In a randomised, multicentre trial, we compared the tocolytic effectiveness of nifedipine and ritodrine and included a long-term follow-up of the newborns after 2 years of age. METHODS: Patients with imminent preterm labour were randomised and received either nifedipine or ritodrine. Side-effects, tocolytic effectiveness and neonatal outcome were studied. Development of the children was studied after the age of 2 years by a parental questionnaire. RESULTS: Ninety-three patients were included. Birth was postponed for an average of 4.3 weeks in the ritodrine group and 5.0 weeks in the nifedipine group (p=0.4). Patients who received ritodrine experienced significantly more side-effects compared to patients who received nifedipine (29 versus 4%, p<0.05). No significant differences were found in either group for average birth weight, Apgar scores after 1 min, neonatal intensive care unit (NICU) admission and neonatal complications. Parental questionnaires after 2 years had a response rate of 70%. Two-thirds of the children had developed normally in both groups. In both groups, only a few children were severely retarded (n=4). No significant differences in development were found between the 2 groups. CONCLUSIONS: Both nifedipine and ritodrine proved effective tocolytic drugs, however ritodrine caused significantly more maternal side-effects. Neonatal outcome and long-term development after 2 years of age were not significantly different. We favour nifedipine over ritodrine as a tocolytic drug.

Use of the liver maximum function capacity test (LiMAx) for the management of liver resection in cirrhosis - A case of hypopharyngeal cancer liver metastasis.

INTRODUCTION: The presence of liver cirrhosis goes along with a higher chance for the need of liver resection. As established laboratory parameters often underestimate the degree of cirrhosis this is associated with an increased risk for postoperative liver failure due to the preoperatively impaired liver function. Known liver function tests are unlikely to be performed in daily use because of high cost or expenditure of time. Liver maximum function capacity test (LiMAx) provides a novel tool for measurement of liver function and references for the safety of liver resection. PRESENTATION OF CASE: A 63-year old patient presented at our hospital with a large, solitary liver metastasis from hypopharyngeal cancer in segments VII/VIII with infiltration of the diaphragm. Liver resection was unsuccessful in a peripheral hospital 10 months before due to considerable macroscopic liver cirrhosis (CHILD B). Upon presentation conventional laboratory parameters revealed sufficient liver function. LiMAx was performed and showed regular liver function (354µg/kg/h; at norm >315µg/kg/h). Consequently, atypical liver resection (R0) was performed resulting in a postoperative LiMAx value of 281µg/h/kg (>150µg/kg/h). The patient was discharged from hospital 37days after surgery without any signs of postoperative liver failure. CONCLUSION: The LiMAx-test enables determination of liver function at a so far unavailable level (metabolism via cytochrome P450 1A2) and hence might provide crucial additional diagnostic information to allow for safe liver resection even in cirrhotic patients.

Behavioural and emotional problems in very preterm and very low birthweight infants at age 5 years.

BACKGROUND: Children born very preterm (VP; <32 weeks' gestation) or with very low birth weight (VLBW, <1500 g; hereafter called VP/VLBW) are at risk for behavioural and emotional problems during school age and adolescence. At school entrance these problems may hamper academic functioning, but evidence on their occurrence at this age in VP/VLBW children is lacking. AIM: To provide information on academic functioning of VP/VLBW children and to examine the association of behavioural and emotional problems with other developmental problems assessed by paediatricians. DESIGN, SETTING AND PARTICIPANTS: A cohort of 431 VP/VLBW children aged 5 years (response rate 76.1%) was compared with two large national samples of children of the same age (n = 6007, response rate 86.9%). OUTCOME MEASURES: Behavioural and emotional problems measured by the Child Behavior Checklist (CBCL), and paediatrician assessment of other developmental domains among VP/VLBW children. RESULTS: The prevalence rate of a CBCL total problems score in the clinical range was higher among VP/VLBW children than among children of the same age from the general population (13.2% v 8.7%, odds ratio 1.60 (95% confidence interval 1.18 to 2.17)). Mean differences were largest for social and attention problems. Moreover, they were larger in children with paediatrician-diagnosed developmental problems at 5 years, and somewhat larger in children with severe perinatal problems. CONCLUSION: At school entrance, VP/VLBW children are more likely to have behavioural and emotional problems that are detrimental for academic functioning. Targeted and timely help is needed to support them and their parents in overcoming these problems and in enabling them to be socially successful.

Intraoperative Conversion to ALPPS in a Case of Intrahepatic Cholangiocarcinoma.

Background. Surgical resection remains the best treatment option for intrahepatic cholangiocarcinoma (ICC). Two-stage liver resection combining in situ liver transection with portal vein ligation (ALPPS) has been described as a promising method to increase the resectability of liver tumors also in the case of ICC. Presentation of Case. A 46-year-old male patient presented with an ICC-typical lesion in the right liver. The indication for primary liver resection was set and planed as a right hepatectomy. In contrast to the preoperative CT-scan, the known lesion showed further progression in a macroscopically steatotic liver. Therefore, the decision was made to perform an ALPPS-procedure to avoid an insufficient future liver remnant (FLR). The patient showed an uneventful postoperative course after the first and second step of the ALPPS-procedure, with sufficient increase of the FLR. Unfortunately, already 2.5 months after resection the patient had developed new tumor lesions found by the follow-up CT-scan. Discussion. The presented case demonstrates that an intraoperative conversion to an ALPPS-procedure is safely applicable when the FLR surprisingly seems to be insufficient. Conclusion. ALPPS should also be considered a treatment option in well-selected patients with ICC. However, the experience concerning the outcome of ALPPS in case of ICC remains fairly small.

Comparison of prophylaxis and rescue treatment with Curosurf in neonates less than 30 weeks' gestation: a randomized trial.

OBJECTIVE: The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management. STUDY DESIGN: Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPO2) (kPa) and fraction of inspired oxygen (FIO2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an FIO2 > or = 0.6. RESULTS: At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPO2/FIO2 ratios (mean +/- SD: 39.7 +/- 15.3 vs 28.1 +/- 18.1; P < .001) and less severe RDS by radiological scoring (chi 2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of FIO2 > 0.40 than the rescue-eligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality. CONCLUSIONS: Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age < 28 weeks or birth weight < 1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteroids. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria.

Endothelial cell activation is associated with cerebral white matter lesions in patients with cerebrovascular disease.

Cerebral MRI scanning frequently shows white matter lesions in elderly people. They are related to cognitive impairment and may result in dementia. Although vascular risk factors are associated with the presence of white matter lesions, the exact pathogenesis remains unclear. Animal studies have indicated involvement of endothelial cells in the pathogenesis of white matter lesions and possibly dementia. We investigated the relation between endothelial cell activation and white matter lesions in individuals with cerebrovascular disease. In 29 patients with an acute stroke (n = 11) or TIAs associated with a symptomatic internal carotid artery stenosis (n = 18), markers of endothelial cell activation such as intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, and sP-selectin were measured by means of ELISA. All individuals underwent 1.5-T MRI scanning. White matter lesions were rated for the periventricular and the subcortical region separately. Individuals with severe periventricular white matter lesions had higher levels of sP-selectin (245.5 ng/mL vs. 172.7 ng/mL, p = 0.01) and sVCAM-1 (547.8 ng/mL vs. 454.0 ng/mL, p = 0.04) than those without. This association was only found in individuals with a symptomatic carotid artery stenosis. No such association was found for subcortical white matter lesions. We did not detect any relation between sICAM-1 and sE-selectin and white matter lesions. Endothelial cell activation may play a role in the pathogenesis of white matter lesions, especially in periventricular white matter. Possibly, this activation represents the influence of vascular factors on the cerebral endothelium as a prelude to increasingly severe small vessel disease.

Guidance after twin and singleton neonatal death.

A study was made to determine whether parents whose newborn twin (n = 72) had died differed from bereaved singleton parents (n = 70) concerning their satisfaction with professional guidance and care. Most parents felt supported by hospital staff, but the twin parents had fewer avenues of available support, especially after their baby's death. The twin parents' situation requires special attention because they have specific needs that are not always addressed by the current range of available support services.

Neonatal form of nemaline myopathy, muscle immaturity, and a microvascular injury.

An infant with a neonatal form of nemaline myopathy showed ultrastructural features of muscle immaturity. Immaturity was characterized by an abnormal presence of myotubes, as well as cells in clusters within a common basement membrane and a great number of satellite cells adhering to very small muscle fibers. In addition, degenerative changes and a severe microvascular lesion were observed. The pathologic findings in the muscle of this patient were those of neonatal nemaline myopathy complicating severe microvascular injury, possibly induced by an unknown toxic agent.

Circadian rhythms in preterm infants: a preliminary study.

A method has been developed for long-term continuous recordings of several physiological variables in humans, including body movements, core temperature, heart rate and respiratory rate. This method enabled us to study circadian rhythms of body temperature and rest-activity in preterm infants. In 5 out of 9 infants (recorded at 28-34 weeks conceptional age) circadian rhythms were found in body temperature. We conclude that circadian rhythmicity is present during the early neonatal period in certain physiological variables (body temperature) but not in others (rest-activity).

Intraventricular haemorrhage in utero. A case-report and review of the literature.

Intraventricular haemorrhages (IVH) are the most commonly occurring intracranial haemorrhages in neonates, especially in preterm infants. The origin of IVHs is located in the germinal matrix. The cause of an IVH is a combination of intravascular, vascular and extravascular factors. The diagnosis is made by ultrasound. Knowledge on the causes of antenatal haemorrhages lags far behind knowledge on the causes of postnatal haemorrhages. In cases of haemodynamic changes in utero, ultrasound could be useful to examine the foetal brain. The presence of an intracranial haemorrhage in utero greatly influences the prognosis of the infant.

A randomized comparison of nifedipine and ritodrine for suppression of preterm labor.

OBJECTIVES: To compare the efficacy and safety of nifedipine and ritodrine in preventing preterm labor, and to evaluate maternal side effects and neonatal outcome. STUDY DESIGN: Non-blind, randomized controlled trial RESULTS: A randomized trial of 102 pregnant women with gestational ages under 34 weeks, including 24 with twin pregnancies and 45 on betasympathicomimetic drugs, who had regular uterine contractions with either observed cervical changes or preterm rupture of membranes. After stratification women were randomly assigned to receive either ritodrine intravenously or nifedipine orally. Fifty-five women were randomized to the nifedipine group and 47 to the ritodrine group. As expected, both groups were comparable in terms of several entry variables, including mean gestational age, ruptured membranes, treatment with tocolytic drugs, cervical examination, contraction frequency, age, and twin gestation. Delivery of women in the nifedipine group was delayed for 48 h, 7 days, and until 34 weeks gestation in 33 (60%), 26 (47%) and 21(38%) cases, respectively, compared with 31 (66%), 21(45%) and 11(23%) women in the ritodrine group (no significant difference). Maternal side effects were significantly less common in the nifedipine group than in the ritodrine group, however after 7 days of therapy there was no difference between the two groups. Neonatal outcome was similar in the two groups, with four neonatal deaths in the nifedipine and five in the ritodrine group. CONCLUSIONS: Nifedipine seems to be as effective as ritodrine in the treatment of preterm labor and is associated with less frequent side effects.