Synthetic biology as driver for the biologization of materials sciences.

Materials in nature have fascinating properties that serve as a continuous source of inspiration for materials scientists. Accordingly, bio-mimetic and bio-inspired approaches have yielded remarkable structural and functional materials for a plethora of applications. Despite these advances, many properties of natural materials remain challenging or yet impossible to incorporate into synthetic materials. Natural materials are produced by living cells, which sense and process environmental cues and conditions by means of signaling and genetic programs, thereby controlling the biosynthesis, remodeling, functionalization, or degradation of the natural material. In this context, synthetic biology offers unique opportunities in materials sciences by providing direct access to the rational engineering of how a cell senses and processes environmental information and translates them into the properties and functions of materials. Here, we identify and review two main directions by which synthetic biology can be harnessed to provide new impulses for the biologization of the materials sciences: first, the engineering of cells to produce precursors for the subsequent synthesis of materials. This includes materials that are otherwise produced from petrochemical resources, but also materials where the bio-produced substances contribute unique properties and functions not existing in traditional materials. Second, engineered living materials that are formed or assembled by cells or in which cells contribute specific functions while remaining an integral part of the living composite material. We finally provide a perspective of future scientific directions of this promising area of research and discuss science policy that would be required to support research and development in this field.

Observations on the retina and 'optical fold' of a mesopelagic sabretooth fish, Evermanella balbo.

The 'optical fold' of Evermanella balbo covers the ventro-lateral cornea and is presumed to capture illumination that would otherwise remain undetected by the tubular eye of this mesopelagic teleost. It contains alternating bands of cellular and acellular material, running approximately perpendicular to the lateral surface of the eye. Only parts of this lamellar body lie within the eyelid-like structure. The cellular lamellae are 2-2.5 µm thick centrally and composed of fibroblast-like cells. The extracellular bands (4.5-5 µm thick) contain regular arrays of collagen fibrils, with layers of thin fibrils sandwiching a region of thicker fibrils. The thin fibrils are organised in alternating sheets where fibrils, although all parallel, change their orientation by 90° between each sheet. All thick fibrils are oriented parallel to the lateral surface of the 'optical fold'. In the main retina, small bundles of rod inner/outer segments are separated by the processes of the retinal pigment epithelium (rpe) laterally. Centrally, the length of tightly packed rods increases, but rpe processes no longer divide them into bundles. Medially, rod length increases further, but packing is less dense. The accessory retina is significantly thinner, and less well-developed than the main retina. Ventrally, the rods show no regular arrangement and are not grouped. Dorsally, however, rods are arranged into bundles, separated by melanosome-filled rpe processes. The thickness of the retina increases as it approaches the crystalline lens. It is on this dorsal accessory retina that light traversing the 'optical fold' most likely falls, facilitating the detection of moving objects in the ventro-lateral field of view.

[Image-guided pain therapy. Sympathicolysis]. / Bildgestützte Schmerztherapie. Sympathikolyse.

BACKGROUND: In the autonomic nerve system most sympathetic neurons synapse peripherally in the ganglia of the sympathetic trunk. A reduction in sympathicotonia by partial elimination of these ganglia is a therapeutic approach that has been used for more than 100 years. In the early 1920s the first attempts at percutaneous sympathicolysis (SL) were carried out. Nowadays, minimally invasive image-guided SL has become an integral part of interventional radiology. Established indications for SL are hyperhidrosis, critical limb ischemia and the complex regional pain syndrome. METHODS: The standard imaging guidance modality in SL is computed tomography (CT) which allows the exact placement of the puncture needle in the target area under visualization of the surrounding structures. Ethanol is normally used for chemical lysis, which predominantly eliminates the unmyelinated autonomic axons. In order to visualize the distribution of the ethanol during application, iodine-containing contrast medium is added. RESULTS: The sympathetic nervous system (SNS) controls sweat secretion via the efferent neurons; therefore, effective therapy of idiopathic palmar, axillary and plantar hyperhidrosis can be achieved when SL is performed at the corresponding level of the sympathetic trunk. Furthermore, due to the vasomotor innervation of most blood vessels, by reduction of the sympathicotonus an atony of the smooth muscles and therefore vasodilatation occurs, which is used as a palliative therapeutic option in patients with critical limb ischemia. By elimination of the afferent sensory fibers this also results in pain relief. This principle is also used in the SL therapy of the complex regional pain syndrome. CONCLUSION: After the introduction of CT guidance, major complications have become rare events. In addition to the usual risks of percutaneous interventions there are, however, a number of specific complications, such as syncope caused by irritation of cardiac sympathetic nerves in thoracic SL and ureteral injury in lumbar SL.

Reflecting optics in the diverticular eye of a deep-sea barreleye fish (Rhynchohyalus natalensis).

We describe the bi-directed eyes of a mesopelagic teleost fish, Rhynchohyalus natalensis, that possesses an extensive lateral diverticulum to each tubular eye. Each diverticulum contains a mirror that focuses light from the ventro-lateral visual field. This species can thereby visualize both downwelling sunlight and bioluminescence over a wide field of view. Modelling shows that the mirror is very likely to be capable of producing a bright, well focused image. After Dolichopteryx longipes, this is only the second description of an eye in a vertebrate having both reflective and refractive optics. Although superficially similar, the optics of the diverticular eyes of these two species of fish differ in some important respects. Firstly, the reflective crystals in the D. longipes mirror are derived from a tapetum within the retinal pigment epithelium, whereas in R. natalensis they develop from the choroidal argentea. Secondly, in D. longipes the angle of the reflective crystals varies depending on their position within the mirror, forming a Fresnel-type reflector, but in R. natalensis the crystals are orientated almost parallel to the mirror's surface and image formation is dependent on the gross morphology of the diverticular mirror. Two remarkably different developmental solutions have thus evolved in these two closely related species of opisthoproctid teleosts to extend the restricted visual field of a tubular eye and provide a well-focused image with reflective optics.

Comparison of six different specimen types for Epstein-Barr viral load quantification in peripheral blood of pediatric patients after heart transplantation or after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Epstein-Barr Virus (EBV) a gamma-herpes virus is associated with a spectrum of lymphoid and epithelial malignancies including posttransplant lymphoproliferative disorders (PTLD). EBV-load measurement has been shown to be important for the monitoring of these patients. However, in contrast to the viral quantification of human immunodeficiency virus or human hepatitis C virus, the EBV-load measurement has not been completely standardized as yet. OBJECTIVES: In this study, we compared the EBV DNA levels in whole blood (WB), plasma, peripheral mononuclear cells (PBMC) and B-cells (BC) in children and adolescents after heart transplantations (HTx) and allogeneic hematopoietic stem cell transplantations (HSCT). STUDY DESIGN: In a period of 2 years (from May 2007 to May 2009) we collected 547 samples of 96 cardiac transplant recipients and 248 samples of 37 patients who underwent HSCT. For EBV DNA quantification we used a duplex real-time PCR (ABI Prism 7500, Applied Biosystems). Additionally, EBV-load of PBMC and BC were normalized with respect to endogenous cell DNA. RESULTS: In both patient populations we found no significant difference of test sensitivity for the EBV detection. In PBMC as well as BC, there was a high correlation between the analysis of cells with and without normalization in both populations. Spearman's correlation coefficient ρ between PBMC without and PBMC with normalization was ρ=0.98 (P<0.0001) in patients after HTx and ρ=0.99 (P<0.0001) in patients after HSCT. Correlation between BC with and without normalization was ρ=0.98 (P<0.0001) in patients after HTx and ρ=0.995 (P<0.0001) in patients after HSCT. When comparing the different blood compartments for EBV quantification in both populations, the strongest correlations were found between the EBV DNA levels in WB and PBMC (HTx: ρ=0.93, P<0.0001; HSCT: ρ=0.81, P<0.0001) followed by PBMC and BC (HTx: ρ=0.87, P<0.0001; HSCT: ρ=0.81, P<0.0001) as well as WB and BC (HTx: ρ=0.86, P<0.0001; HSCT: ρ=0.75, P<0.0001). In contrast, the correlation coefficients between plasma and the other blood compartments (WB as well as PBMC or BC) were lower. Six patients developed seven episodes of PTLD (five patients after HTx and one after renal transplantation). Analyzing the different blood compartments, we found that a threshold of WB ≥20,000EBV-copies/ml and plasma ≥1000EBV-copies/ml had the highest sensitivities and specificities (WB: sensitivity 100%, specificity 87% and plasma: sensitivity 88%, specificity 98%). CONCLUSION: Normalization towards an endogenous control does not seem to be necessary for EBV quantification in peripheral blood. The analysis of whole blood correlates well with B-cells and PBMC. Routine screening of EBV DNA in whole blood appeared to be a useful tool supplemented by EBV-load measurement in plasma to discriminate chronic high EBV-load carrier without risk for PTLD from those who are at risk for PTLD. Values in whole blood higher than 20,000EBV-copies/ml WB and plasma values higher than 1000EBV-copies/ml plasma indicated PTLD in our series.

Surgical prosection in a traditional anatomical curriculum-Tübingens' Sectio chirurgica.

Despite the rapid rise of integrated curricula, the teaching of gross anatomy by traditional dissection remains a central element in most medical programs worldwide. However, modern didactic concepts demand the integration of clinical content in preclinical settings. The implementation of interdisciplinary tools often leads to a reduction in teaching of comprehensive anatomy. 'Tübingen's Sectio chirurgica' (TSC) introduces a concept of a teaching activity in which surgical prosection is performed in addition to the traditional dissection course. TSC is designed to integrate clinical and preclinical content in a traditional medical curriculum without affecting the systematic presentation of anatomical content. In the past 2 years, about 10,000 medical students have participated in the use of telemedical transmissions of 'live surgery' in a total of 25 sessions of TSC. Here we describe the organisational plan of TSC and the results of an evaluation which was performed to monitor the influence of TSC on student motivation for surgical disciplines as well as for the learning of anatomical factual content. We demonstrate that additional surgical prosection is a valuable tool in increasing the coherence between preclinical and clinical parts of medical education programs.

An inflammatory myofibroblastic tumor of the stomach as a rare cause of gastric outlet obstruction in an 8-month-old infant.

Inflammatory myofibroblastic tumors (IMT) are a rare entity. Localization in the stomach is extremely seldom and almost exclusively seen in children. Invasive growth of IMT may lead to irresectability or recurrence. In an 8-month-old girl presented with repetitive vomiting for several days. Complete surgical resection of a gastric IMT was possible.

Posaconazole salvage treatment in paediatric patients: a multicentre survey.

While a paediatric dosage has not been defined, posaconazole is occasionally being used in children. We conducted a multicentre retrospective survey and identified 15 patients (median age 10 years [range 3.6-17.5]) who received posaconazole salvage therapy for proven (9 patients) or probable (6 patients) invasive fungal infections. Posaconazole was administered for a median of 32 days (range 4-262) at a median dosage of 21 mg/kg (range 4.8-33.3). None of the patients discontinued therapy due to adverse events, which were mostly mild and observed in 11 patients. Complete or partial responses were observed in 4/7 patients with zygomycosis, 3/4 patients with invasive mould infection, 1/2 patients with invasive aspergillosis and 1/2 patients with chronic disseminated candidiasis. We conclude from the data that posaconazole displays favourable safety and tolerance and may be useful for management of individual paediatric patients with invasive infections.

Sarcoidosis following Cushing's syndrome: A report of two cases and review of the literature.

Cushing's syndrome is characterized by excessive elevation of glucocorticoid concentrations. In rare cases, the treatment of Cushing's syndrome may result in unmasking or aggravation of diseases responsive to glucocorticoid medication. We report two cases of sarcoidosis following Cushing's syndrome. A 43 year-old male developed cutaneous sarcoidosis and mediastinal lymphadenopathy after resection of an ACTH-secreting pituitary microadenoma. A 32 year-old female showed cutaneous sarcoidosis, arthralgia, mediastinal lymphadenopathy and elevation of angiotensin-converting enzyme and interleukin 2-receptor concentrations after traumatic adrenal bleeding, which ceased formerly undiagnosed hypercortisolism caused by an adrenal adenoma. Sarcoidosis seems to be a rare sequel following the treatment of hypercortisolism. Skin affections were present and suggestive for the diagnosis in all reported cases. As some cases are probably missed when skin affections are lacking, a more frequent evaluation of patients after Cushing's syndrome for the possible diagnosis of sarcoidosis might be necessary.

Dysregulated Epstein-Barr virus infection in patients with CIDP.

Ubiquitous viruses have frequently been proposed as a cause or trigger of chronic immune-mediated diseases. Infections are reported to be temporally associated with clinical exacerbations in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We examined immunological parameters of herpesvirus infections in untreated patients with CIDP compared to demographically matched controls. Patients with CIDP were uniformly seropositive for EBV-specific IgG and the disease was associated with a moderately enhanced IgG reactivity to EBV-encoded antigens expressed during both B cell transformation and productive viral replication. Moreover, cellular EBV copy numbers were 3-fold increased in patients with CIDP. In contrast, humoral immune responses to other herpesviruses (HCMV, HSV) as well as virus-specific IgM responses were unchanged in CIDP. These data indicate that host-pathogen interactions during chronic EBV infection are dysregulated in treatment-naïve patients with CIDP.

Long-term engraftment of systemically transplanted, gene-modified bone marrow-derived cells in the adult mouse retina.

AIMS: To provide evidence for a novel route of gene administration to normal and diseased retinas, we performed systemic transplantation of genetically engineered bone marrow-derived cells (BMDCs) to wild-type mice and to mutant mice with retinal degeneration. METHODS: Lethally irradiated recipient mice-C57BL/6 (wild-type), SCA7 (spinocerebellar ataxia type 7) and FVB/N (rd1 mutant)-were transplanted intravenously with 5x106 BMDCs, which were transduced with a retroviral vector to express the enhanced green fluorescent protein (GFP). Chimeras were killed at 1, 3, 8, 11, 12 and 15 months (wild-type) or at 8 and 12 months (mutants) after transplantation. Eyes were enucleated, and the retinas were analysed using immunohistochemistry. RESULTS: In wild-type retinas, BMDCs preferentially engrafted in the inner and outer plexiform layers, the ganglion cell layer and the optic nerve. No BMDCs were found in the photoreceptor layer. BMDCs were more common in the degenerating retinas of the mutant mice. The majority of BMDCs in the retina were identified as microglia based on morphology and immunophenotype. Approximately 8-16% of all CD11b(+) cells in the retina expressed GFP. None of the BMDCs expressed neuronal cell markers. GFP-expressing BMDCs were found to persist for more than 1 year after transplantation. CONCLUSIONS: We demonstrate that gene-modified BMDCs show long-term engraftment and stable expression of GFP from a retrovirus in both wild-type and mutant mouse retinas. Thus, BMDCs may be used as vehicles for gene delivery to the retina.

[Periinterventional prophylactic antibiotics in radiological port catheter implantation]. / Periinterventionelle prophylsktische Antobiotikagabe bei der radiologischen Portkatheterimplantation.

PURPOSE: To evaluate whether catheter-related infections after radiologically placed port catheters can be reduced by single-shot periinterventional antibiosis. MATERIALS AND METHOD: Between January and September 2002, 164 consecutive patients with indication for central venous port catheter implantation were included in the present study. During implantation the interventional radiologist was responsible for deciding whether to administer a prophylactic single-shot antibiosis. The prophylactic antibiosis entailed intravenous administration of ampicillin and sulbactam (3 g Unacid, Pfizer) or 100 mg ciprofloxacine (Ciprobay, Bayer) in the case of an allergy history to penicillins. Catheter-related infection was defined as a local or systemic infection necessitating port catheter extraction. RESULTS: Indication for port catheter implantation was a malignant disease requiring chemotherapy in 158 cases. The port catheter (Chemosite [Tyco Healthcare] [n = 123], low-profile [Arrow International] [n = 35], other port system [n = 6]) was implanted via sonographically guided puncture of the right jugular vein in 139 patients, via the left jugular vein in 24 cases and via the right subclavian vein in one patient. 75 patients received periinterventional prophylactic antibiosis (Unacid [n = 63] Ciprobay [n = 12]) and 89 patients did not receive antibiosis. The prophylactic antibiosis caused a minor allergic reaction in one patient that improved with antihistamic and corticoid medication. A total of 7 ports, 6 without prophylactic antibiosis versus one with periinterventional prophylaxis, were extracted due to infectious complications. CONCLUSION: Single-shot periinterventional prophylactic antibiosis can reduce early and late infectious complications after radiological-interventional placement of central venous port catheters.

[Long-term results after balloon angioplasty of the crural artery]. / Langzeitergebnisse nach Ballonangioplastie kruraler Arterien.

PURPOSE: To evaluate the technical success rate, procedure-related complications, and clinical long-term results for patients who underwent infrapopliteal angioplasty. MATERIALS AND METHODS: We retrospectively evaluated all patients who underwent infrapopliteal angioplasty to treat critical chronic limb ischemia or severe claudication from 1/1997 to 12/1999. We excluded patients with acute (< 2 weeks) limb ischemia. Procedure-related data were prospectively documented in a database and analyzed with a focus on the technical success rate and procedure-related complications. In addition all clinical documents were analyzed, and a follow-up examination was performed or telephone interviews were conducted with patients, relatives and referring doctors for follow-up. The primary end points were the limb salvage rate and patient survival rate. The secondary end points included the complication rate, technical success rate, and walking distance. RESULTS: 112 patients with a mean age of 72 years (41 women, 71 men) underwent crural angioplasty on 121 limbs. Four patients suffered from severe claudication (Rutherford category 3) and all others had critical chronic limb ischemia (category 4 to 6). The complication rate was 2.7 %. The technical success rate was 92 %. The ankle brachial index increased from 0.59 to 0.88. The mean walking distance increased significantly from 52 +/- 66 to 284 +/- 346 meters at the time of follow-up. The limb salvage rate was 83.6 % after one year and 81.1 % after three years. The mean survival rate according to Kaplan-Meier was 79.4 %, 69.2 %, and 54.2 % at 1, 2, and 3 years, respectively. Patients with at least one patent run-off vessel after angioplasty had a significantly better limb salvage rate. Diabetes was not a risk factor for limb salvage. CONCLUSION: Infrapopliteal angioplasty shows a high technical success rate with an acceptable complication rate. The clinical long-term success seems favorable if a least one open run-off vessel was able to be achieved. However, the survival rate was limited by the co-morbidity in this patient group.

[Peripheral arterial obstruction and acute lower limb ischemia]. / Periphere arterielle Verschlusskrankheit und akute Extremitätenischämie.

In this article, current evidence-based treatment recommendations for acute and chronic lower limb ischemia will be presented considering the varied possibilities of endovascular techniques and open surgical vascular strategies. Beside presentation of the different therapeutic possibilities, advantages of the combination of both techniques will be described. Despite the BASIL trial, there are no prospective randomised controlled trials comparing endovascular and open surgical interventions. Different therapeutic rules along the different vascular segments will be discussed for both acute and chronic peripheral arterial disease. Generally it can be stated that aortoiliac revascularization for chronic obstructions is increasingly being carried out by endovascular means or hybrid procedures using a minimally invasive femoral approach, whereas acute occlusions in this vascular segment are still treated with open surgical techniques (Fogarty balloon thrombectomy). In the infrainguinal region, endovascular therapeutic strategies are gaining favor. However, multilevel occlusions and long-segment obstructions in the femoral and popliteal segment are still treated by bypass procedures. Acute ischemia in the infrainguinal segment is increasingly treated with endovascular methods (local thrombolysis and percutaneous thrombectomy).

High seroprevalence of Epstein-Barr virus in children with multiple sclerosis.

We studied seroprevalence and concentrations of Epstein-Barr virus (EBV) antibodies in 147 pediatric patients with multiple sclerosis (MS) and paired controls. The children with MS showed a near-complete seropositivity for EBV antibody against virus capsid antigen (98.6% vs 72.1% in controls, p = 0.001) but did not display serologic evidence for a recent EBV infection. EBV antibody concentrations of pediatric patients with MS were significantly higher vs controls.

[Dysphagia caused by neurogenic deglutition disorders and diffuse idiopathic skeletal hyperostosis (DISH)]. / Dysphagie in Folge einer neurogenen Schluckstörung und einer diffusen idiopathischen Skeletthyperostose (DISH).

BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) may lead to dysphagia caused by osteophytes of the cervical spine. Osteophytes can be resected transorally or transcervically, but operative ablation should not be indicated generously because of the threat of severe complications. PATIENT: A fifty-year-old man with dysphagia and loss of weight of 15 kg in the last three months is presented. He also suffered from a brain damage during infancy which caused grand-mal-seizures. One seizure lead to cardiac arrest which required cardio-pulmonary resuscitation and subsequent tracheostomy. A spheric tumor of the posterior pharyngeal wall could be seen endoscopically, it appeared radiologically as an osteophytic formation of the segments C (3) - C (5). Ossification of the anterior longitudinal ligament was also seen. Diagnosis of DISH was made on the basis of these results. Contrast imaging of the esophagus and videofluoroscopy showed aspiration in terms of neurogenic disorders. The patient received a percutaneous gastrostomy after his case was discussed with neurologic and orthopaedic colleagues, because a causal therapy of the combined disease seemed to be impossible. CONCLUSION: Dysphagia in the presented case was caused by a combination of neurogenic deglutition disorders and oropharyngeal obstruction through osteophytes. Surgical removal of the osteophytes was not indicated because it would have put the patient at a certain risk, but only a part of the underlying problem would have been removed. Symptomatic therapy with a gastrostomy secures normocaloric diet. The patient's weight remained stable and he can follow his habitual daily routine.

[Rare cause of chronic recurrent pulmonary emboli and pulmonary artery hypertension]. / Seltene Ursache chronisch rezidivierender Lungenembolien und pulmonal-arterieller Hypertonie.

HISTORY AND CLINICAL FINDINGS: A 41-year-old man with known Klippel-Trenaunay syndrome was admitted to hospital because of progressive dyspnea on exertion. Examination on admission revealed the typical signs of Klippel-Trenaunay syndrome, predominantly of the left leg. INVESTIGATIONS: D-dimers were significantly increased. Contrast-enhanced computed tomography of the chest revealed multiple small pulmonary arterial emboli in subsegmental arteries on both lungs. Pulmonary arterial digital subtraction angiography revealed extensive peripherally localized perfusion defects. Pulmonary artery pressure measurement demonstrated bilateral pulmonary artery hypertension. Phlebography of the left lower leg showed marked varices in the calf. There was also a persisting sciatic vein. DIAGNOSIS, TREATMENT AND COURSE: The recurrent peripheral pulmonary emboli with pulmonary arterial hypertension was a complication of a Klippel-Trenaunay syndrome. Another rare entity of this syndrome was a persisting sciatic vein. Heparinization was initiated, followed by oral anticoagulation. As the patient had not been anticoagulated before, implantation of an inferior vena cava filter was not deemed appropriate. CONCLUSIONS: Recurrent peripheral pulmonary emboli leading to chronic pulmonary artery hypertension is a rare but typical complication of Klippel-Trenaunay syndrome. Early recognition of this syndrome and any complications as a separate entity, as well as initiation of therapeutic measures, like anticoagulation or early pulmonary thrombendarterectomy for chronic pulmonary artery emboli, are of prognostic importance.

[Contrast media pressure injection using a portal catheter system--results of an in vitro study]. / Kontrastmitteldruckinjektion in Portkathetersysteme -- Ergebnisse einer In-vitro-Studie.

PURPOSE: Are implanted central venous port catheters suitable for contrast media pressure (power) injection in computed tomography? MATERIAL AND METHODS: In an in vitro study 100 ml of contrast medium (Ultravist 370, Schering, Berlin, Deutschland) was injected through 20 different port catheter systems using a power injector (Stellant, Medrad, Inianola, USA) with a pressure limit of 325 PSI. The injection rate was increased from 2 ml/s to 10 ml/s in increments of 2 ml/s. The maximum injection pressure and maximum injection rate were assessed. RESULTS: An injection rate of 2 ml/s was possible in all catheter systems. Injection rates of 4 ml/s in 18 systems, 6 ml/s in 13 systems and 8 ml/s in 6 systems were achieved. With a given pressure limit of 325 PSI an injection rate of 10 ml/s was not possible in any of the port catheter systems. There were no catheter ruptures, catheter disconnections or contrast extravasations noted. CONCLUSION: Power injection of contrast media with a pressure limit of 325 PSI seems to be tolerated by port catheter systems. Most of the evaluated port systems allow flow rates suitable for multislice computed tomography requiring rapid contrast injection.

Successful treatment of solid-pseudopapillary tumor of the pancreas with multiple liver metastases.

The solid-pseudopapillary tumor (SPT) is a very rare pancreatic neoplasm that predominantly affects young females. About 450 cases have been described in the world literature and approximately 20% of the reported patients were children. The occurrence of SPT with distant metastases in children is extremely rare with only two previously reported cases. We now report a 16-year-old Asian girl with a large SPT and synchronous multiple liver metastases who was successfully treated in a 2-step strategy, including initial pylorus-preserving partial duodenopancreatectomy, right hemicolectomy, resection and allografting of the portal vein and secondary resection of 12 liver metastases. The patient is disease free after a follow-up of 18 months after resection of the primary tumor, suggesting that an aggressive surgical treatment might also be justified for metastasized SPT.

The pupillary response of cephalopods.

This paper provides the first detailed description of the time courses of light-evoked pupillary constriction for two species of cephalopods, Sepia officinalis (a cuttlefish) and Eledone cirrhosa (an octopus). The responses are much faster than hitherto reported, full contraction in Sepia taking less than 1 s, indicating it is among the most rapid pupillary responses in the animal kingdom. We also describe the dependence of the degree of pupil constriction on the level of ambient illumination and show considerable variability between animals. Furthermore, both Sepia and Eledone lack a consensual light-evoked pupil response. Pupil dilation following darkness in Sepia is shown to be very variable, often occurring within a second but at other times taking considerably longer. This may be the result of extensive light-independent variations in pupil diameter in low levels of illumination.