Metachronous hepatic resection for liver only pancreatic metastases.

BACKGROUND: The value of liver resection (LR) for metachronous pancreatic ductal adenocarcinoma (PDAC) metastases remains controversial. However, in light of increasing safety of liver resections, surgery might be a valuable option for metastasized PDAC in selected patients. METHODS: We performed a retrospective, multicenter study including patients undergoing hepatectomy for metachronous PDAC liver metastases between 2004 and 2015 to analyze postoperative outcome and overall survival. All patients were operated with curative intent. Patients with oligometastatic metachronous liver metastasis with definitive chemotherapy (n = 8) served as controls. RESULTS: Overall 25 patients in seven centers were included in this study. The median age at the time of LR was 63.8 years (56.9-69.9) and the median number of metastases in the liver was 1 (IQR 1-2). There were eight non-anatomical resections (32%), 15 anatomical minor (60%) and 2 major LR (8%). Postoperative complications occurred in eleven patients (eight Clavien-Dindo grade I complications (32%) and three grade IIIa complications (12%), respectively). The 30-day mortality was 0%. The median length of stay was 8.6 days (IQR 5-11). Median overall survival following LR was 36.8 months compared to 9.2 months in patients with metachronous liver metastasis with chemotherapy (p = 0007). DISCUSSION: Liver resection for metachronous PDAC metastasis is safe and feasible in selected patients. To address general applicability and to find factors for patient selection, larger trials are urgently warranted.

Insulin secretion measured by stimulated C-peptide in long-established Type 1 diabetes in the Diabetes Control and Complications Trial (DCCT)/ Epidemiology of Diabetes Interventions and Complications (EDIC) cohort: a pilot study.

AIMS: To evaluate whether clinically relevant concentrations of stimulated C-peptide in response to a mixed-meal tolerance test can be detected after almost 30 years of diabetes in people included in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. METHODS: Mixed-meal tolerance tests were performed in a sample of 58 people. C-peptide levels were measured using a chemiluminescent immunoassay. This sample size assured a high probability of detecting C-peptide response if the true prevalence was at least 5%, a level that would justify the subsequent assessment of C-peptide in the entire cohort. RESULTS: Of the 58 participants, 17% showed a definite response, defined as one or more post-stimulus concentrations of C-peptide > 0.03 nmol/l, and measurable concentrations were found in all participants. CONCLUSIONS: These results show that a stimulated C-peptide response can be measured in some people with long-term Type 1 diabetes. Further investigation of all participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study will help relate long-term residual C-peptide response to glycaemia over time and provide insight into the relevance of this response in terms of insulin dose, severe hypoglycaemia, retinopathy, nephropathy and macrovascular disease. Establishing the clinical relevance of long-term C-peptide responses is important in understanding the impact that therapy to preserve or improve ß-cell function may have in patients with long-term Type 1 diabetes.

[Obstructive sleep apnoea syndrome as the cause of atypical depression]. / Obstruktives Schlaf-Apnoe-Syndrom als Ursache einer atypischen Depression.

Sleep apnoea is a common disorder presenting with somatic comorbidities and psychiatric symptoms. This case report describes a 43-year-old man with an organic depressive disorder due to obstructive sleep apnoea. Initially, an atypical depressive episode or schizophrenic residual syndrome had been considered likely diagnoses; subsequent polysomnography results, however, suggested obstructive sleep apnoea instead. Upon nasal continuous positive airway pressure (nCPAP), the respiratory distress symptoms improved. The case report highlights the association between sleep disturbances and depressive symptoms. In patients presenting with symptoms of atypical depression and excess body weight sleep apnoea should be considered.

Perception and suppression of thermally induced pain: a fMRI study.

Two neuroimaging studies using functional magnetic resonance imaging (fMRI) and thermally induced pain are presented. Fifteen healthy right-handed subjects were imaged while they had to discern different levels of thermal stimuli in the first study and while they disengaged from the feeling of pain during constant stimulation in the second study. In the first experiment, during painful phasic stimuli, right-sided anterior insular activation as well as bilateral posterior insular activation could be shown regardless of stimulation side, as well as right-sided activation of sensory association areas in the superior parietal lobule. Also, activation of the ipsilateral sensorimotor cortex could be shown. In the second experiment, all subjects succeeded in suppressing the feeling of pain during previously painful levels of stimulation. During the early part of the tonic painful stimulation, bilateral activation of caudate head and dorsolateral prefrontal cortex (DLPFC) as well as insular cortex and dorsal anterior cingulated cortex (dACC) was observed. During the late part of the tonic painful stimulation, anterior insular activation as well as dACC and bilateral prefrontal cortical activation could be shown. Taken together, the activation of PFC and caudate nucleus hints at an important role in the initiation (caudate) and maintenance (PFC) of suppression of the feeling of pain. No ipsilateral sensorimotor activation could be shown in the second experiment. The possible import of unwanted sensorimotor activation due to the simultaneous rating process in the first experiment is discussed.

Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes.

AIMS/HYPOTHESIS: Diabetes results in the upregulation of the production of several components of the inflammatory response in the retina, including inducible nitric oxide synthase (iNOS). The aim of this study was to investigate the role of iNOS in the pathogenesis of the early stages of diabetic retinopathy using iNOS-deficient mice (iNos (-/-)). MATERIALS AND METHODS: iNos (-/-) mice and wild-type (WT; C57BL/6J) mice were made diabetic with streptozotocin or kept as non-diabetic controls. Mice were killed at different time points after the induction of diabetes for assessment of vascular histopathology, cell loss in the ganglion cell layer (GCL), retinal thickness, and biochemical and physiological abnormalities. RESULTS: The concentrations of nitric oxide, nitration of proteins, poly(ADP-ribose) (PAR)-modified proteins, endothelial nitric oxide synthase, prostaglandin E(2), superoxide and leucostasis were significantly (p < 0.05) increased in retinas of WT mice diabetic for 2 months compared with non-diabetic WT mice. All of these abnormalities except PAR-modified proteins in retinas were inhibited (p < 0.05) in diabetic iNos (-/-) mice. The number of acellular capillaries and pericyte ghosts was significantly increased in retinas from WT mice diabetic for 9 months compared with non-diabetic WT controls, these increases being significantly inhibited in diabetic iNos (-/-) mice (p < 0.05 for all). Retinas from WT diabetic mice were significantly thinner than those from their non-diabetic controls, whereas diabetic iNos (-/-) mice were protected from this abnormality. We found no evidence of cell loss in the GCL of diabetic WT or iNos (-/-) mice. Deletion of iNos had no beneficial effect on diabetes-induced abnormalities on the electroretinogram. CONCLUSIONS/INTERPRETATION: We demonstrate that the inflammatory enzyme iNOS plays an important role in the pathogenesis of vascular lesions characteristic of the early stages of diabetic retinopathy in mice.

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.

The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

[Squamous cell carcinoma of the liver. A rare diagnosis in the course of intrahepatic cholangiolithiasis]. / Plattenepithelkarzinom der Leber. Ein seltener Zufallsbefund im Rahmen einer intrahepatischen segmentalen Cholangiolithiasis.

We report the rare case of a squamous cell carcinoma of the liver in a 69-year-old female Asian suffering from cholangitis and a liver abscess due to segmental intrahepatic cholangiolithiasis. The patient was an immigrant who had been living for several years in Austria. After pigtail drainage of an abscess in segment II and III, a bisegmentectomy was performed. Histopathological examination of the specimen showed structures of an invasive squamous cell carcinoma close to the resection margin.For that reason we performed a left lobectomy. Seven years thereafter the patient is well and free of local and distant recurrences. The case is discussed based on a review of the literature.

[18F-fluorodeoxyglucose positron emission tomography in colorectal cancer: value in primary staging and follow-up]. / 18F-Fluorodeoxyglukose-Positronenemissionstomographie beim kolorektalen Karzinom: Wertigkeit in Primärstaging und Follow-up.

Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) is a encouraging imaging technique allowing a highly sensitive whole-body search for malignant foci detected by their increased glucose metabolism compared with benign tissues. Several studies are now available that indicate its added value for diagnosis and staging of colorectal cancer. In all, patient management seems to be changed in 20-30% of patients who undergo Fluorodeoxyglucose positron emission tomography in addition to standard staging procedures. Fluorodeoxyglucose positron emission tomography is also useful in monitoring radiation therapy and chemotherapy. Regarding preoperative staging of primary colorectal cancer the literature is very limited.

Small bowel perforation after extracorporeal shockwave lithotripsy of an ureter stone.

A 60-year-old man was treated by extracorporeal shock wave lithotripsy (ESWL) for an impacted ureter stone. Two days after the procedure he developed an acute abdomen. On laparotomy, a small bowel perforation in the area of an adhesion to the abdominal wall was found. The adherent intestinal segment was located exactly in the range of the ESWL field, so that excluding further reasons the shockwave lithotripsy must be assumed to be causative.

Two enzymes of diacylglyceryl-O-4'-(N,N,N,-trimethyl)homoserine biosynthesis are encoded by btaA and btaB in the purple bacterium Rhodobacter sphaeroides.

Betaine lipids are ether-linked, nonphosphorous glycerolipids that resemble the more commonly known phosphatidylcholine in overall structure. Betaine lipids are abundant in many eukaryotes such as nonseed plants, algae, fungi, and amoeba. Some of these organisms are entirely devoid of phosphatidylcholine and, instead, contain a betaine lipid such as diacylglyceryl-O-4'-(N,N,N,-trimethyl)homoserine. Recently, this lipid also was discovered in the photosynthetic purple bacterium Rhodobacter sphaeroides where it seems to replace phosphatidylcholine under phosphate-limiting growth conditions. This discovery provided the opportunity to study the biosynthesis of betaine lipids in a bacterial model system. Mutants of R. sphaeroides deficient in the biosynthesis of the betaine lipid were isolated, and two genes essential for this process, btaA and btaB, were identified. It is proposed that btaA encodes an S-adenosylmethionine:diacylglycerol 3-amino-3-carboxypropyl transferase and btaB an S-adenosylmethionine-dependent N-methyltransferase. Both enzymatic activities can account for all reactions of betaine lipid head group biosynthesis. Because the equivalent reactions have been proposed for different eukaryotes, it seems likely that orthologs of btaA/btaB may be present in other betaine lipid-containing organisms.

Broadband parallel-fiber optical link for short-distance interconnection with multimode fibers.

In a multimode step-index fiber the propagation angle of a beam is conserved over short distances even if the fiber is bent slightly. This behavior can be exploited for a multiplexed signal transmission by the assignment of different channels to different propagation angles [angle-division multiplexing (ADM)]. Thus parallel transmission can be achieved. Because each channel occupies only a subrange of the fiber's numerical aperture, modal dispersion is reduced compared with single-channel transmission through the same fiber. The transmission properties of an ADM-based transmission line are analyzed for short propagation distances. Passive all-optical setups for multiplexing and demultiplexing operations are proposed. Cross-talk measurements are shown for a transmission with a length of 8 m and 13 multiplexed channels.

Implementation of multilens micro-optical systems with large numerical aperture by stacking of microlenses.

In the field of micro-optics there is a demand for objectives with large numerical aperture (NA). One example is optical storage in which a NA greater than 0.5 is required. For planar microlenses the NA is determined by means of the maximal index difference and the degree of exchange and reaches typical values of 0.13-0.2. Thus stacking is needed to build high NA objectives from planar microlenses. An additional benefit of stacking lenses is the possibility to correct for different types of aberrations. We realized two stacked systems: an array of micro-objectives with a NA of 0.45 from three microlens arrays and a confocal sensor head from four microlens arrays and one pinhole array mask.

Fatty acid ethyl esters, nonoxidative metabolites of ethanol, accelerate the kinetics of activation of the human brain delayed rectifier K+ channel, Kv1.1.

Herein we demonstrate that the major metabolites of ethanol in neural tissues, fatty acid ethyl esters, dramatically accelerate the kinetics of the voltage-induced activation of the human brain delayed rectifier potassium channel, Kv1.1. Specifically, the external application of ethyl oleate (20 microM) to Sf9 cells expressing the recombinant Kv1.1 channel resulted in a decrease in the rise times of the macroscopic current (e.g. from 51.7 +/- 13.1 to 12.8 +/- 3.0 ms at 0 mV for 10-90% rise times) and a 10-mV hyperpolarizing shift (at 0 mV) in the voltage dependence of channel activation. These effects were dose-dependent (half-maximal effect at 7 microM), saturable and specific (i.e. fatty acid methyl esters were without effect). Although application of either ethanol or oleic acid alone did not result in alterations of the activation kinetics, the concomitant application of ethanol and oleic acid reproduced the effects of fatty acid ethyl esters with a temporal course which paralleled the intracellular accumulation of fatty acid ethyl esters in Sf9 cells. Moreover, application of fatty acid ethyl esters (but not ethanol) to rat hippocampal cells in culture produced similar effects on hippocampal delayed rectifier currents. Collectively, these results demonstrate that pathophysiologically relevant concentrations of metabolites of ethanol, fatty acid ethyl esters, modulate the function of a prototypic neuronal ion channel and thus likely contribute to the pathophysiologic sequelae of ethanol abuse in excitable tissues.

Alterations in individual molecular species of human platelet phospholipids during thrombin stimulation: electrospray ionization mass spectrometry-facilitated identification of the boundary conditions for the magnitude and selectivity of thrombin-induced platelet phospholipid hydrolysis.

Although the rapid thrombin-induced release of arachidonic acid in human platelets has been known for over 20 years, the amount of arachidonic acid mass mobilized and the source of the released arachidonic acid has remained a subject of intense controversy. Herein, we exploit the analytic power and sensitivity of electrospray ionization mass spectrometry to identify plasmenylethanolamines as the largest source of arachidonic acid mass released during thrombin stimulation and to demonstrate the presence of multiple novel molecular species of plasmenylethanolamines in human platelets. Specifically, 90 s after thrombin stimulation a total of 60.1 nmol of arachidonic acid-containing phospholipids/10(9) platelets was hydrolyzed which included the loss of 31.8 nmol/10(9) platelets from ethanolamine glycerophospholipids (hydrolysis of plasmenylethanolamines represented 63% of the mass lost from the ethanolamine glycerophospholipid pool) but only 10.9 nmol/10(9) platelets from choline glycerophospholipids. Human platelet phosphatidylserine and phosphatidylinositol pools contained similar amounts of arachidonic acid mass in resting platelets (approximately equal to 20 nmol/10(9) platelets), and each pool contributed 8.7 nmol/10(9) platelets after thrombin stimulation. From these results, a lower boundary for the rate of thrombin-induced arachidonic acid mobilization in human platelets can be set at > 60 nmol/10(9) platelets, thereby identifying specific kinetic characteristics and substrate selectivities of the phospholipase(s) activated during platelet stimulation. Collectively, these results underscore the importance of plasmenylethanolamines as the major storage depot of arachidonic acid in resting platelets and as the major source of arachidonic acid mobilized after thrombin stimulation of human platelets.

Concomitant acceleration of the activation and inactivation kinetics of the human delayed rectifier K+ channel (Kv1.1) by Ca(2+)-independent phospholipase A2.

The electrophysiologic sequelae of arachidonic acid release mediated by the major phospholipase A2 (PLA2) in electrically active tissues (i.e. the 40-kDa Ca(2+)-independent PLA2) were assessed in Sf9 cells expressing the human recombinant delayed rectifier K+ channel Kv1.1. Intracellular administration of Ca(2+)-independent PLA2 increased the rate of activation of the macroscopic current (from tau act = 6.25 +/- 0.76 ms to tau act, PLA2 = 2.78 +/- 0.78 ms at 40 mV) and resulted in channel inactivation (from no observed inactivation to tau inact = 103 +/- 6 ms at 40 mV), which were: 1) dependent on the enrichment of Sf9 cell phospholipids in esterified arachidonic acid; 2) ablated by pretreatment of the PLA2 by the mechanism-based inhibitor (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one; and 3) manifest prior to development of alterations in cellular permeability. The bidirectional effects of Ca(2+)-independent PLA2 were indistinguishable from the effects of exogenously applied arachidonic acid (AA), which specifically and reversibly increased the rates of channel activation (from tau act = 5.73 +/- 0.88 ms to tau act,AA = 1.91 +/- 0.39 ms at 40 mV) and inactivation (from no observed inactivation to tau inact = 76.6 +/- 1.4 ms at 40 mV). These electrophysiologic alterations resulted from the effects of arachidonic acid per se since Sf9 cells did not produce oxygenated eicosanoid metabolites, and neither exogenous administration nor in situ generation of other fatty acids resulted in these effects. Collectively, these results unambiguously demonstrate the role of arachidonic acid per se on Kv1.1 electrophysiologic function and suggest the importance of Ca(2+)-independent PLAs as an enzymic modulator of ion channel function in electrically active tissues.

Evaluation of the Ottawa clinical decision rules for the use of radiography in acute ankle and midfoot injuries in the emergency department: an independent site assessment.

STUDY OBJECTIVE: Decision rules for the use of radiography in acute ankle and midfoot injuries have been developed. Radiographs are indicated if there is tenderness at the posterior edge or tip of either malleolus or at the navicular or base of the fifth metatarsal or there is inability to both weight bear immediately after the injury and ambulate four steps in the emergency department. This study assessed the efficacy of these rules with health care providers who had not been involved in their development. DESIGN: Prospective patient survey by emergency department attending physicians and triage nurses. SETTING: EDs of a university hospital and a community hospital with a combined annual volume of 100,000. PARTICIPANTS: One hundred ten patients older than 16 years who presented with acute blunt ankle and midfoot trauma during the 3 months of summer 1993. RESULTS: Fourteen fractures were diagnosed. When used by ED attending physicians, the decision rules had a sensitivity of 1.0 and specificity of 0.19 in detecting all midfoot and ankle fractures. When used by triage nurses, the sensitivity was 0.9 and specificity was 0.1. The negative predictive values of the decision rules were 1.0 for ED attending physicians and 0.88 for triage nurses. ED attending physicians and triage nurses agreed in 90% of cases regarding the overall decision to obtain radiographs. However, there was only a 47% agreement on all components of the clinical decision rules, with kappa values ranging from 0.60 to 0.76. The accuracies of the predictive rules were similar as applied by the ED attending physicians and the triage nurses (chi 2, P = .23). Application of the Ottawa predictive rules by ED attending physicians would have resulted in a 19% reduction in use of midfoot and ankle radiographs. CONCLUSION: Use of the Ottawa and midfoot clinical decision rules by ED attending physicians of institutions not familiar with the rules' development resulted in 100% sensitivity for all fractures and would have allowed these physicians to safely reduce the number of radiographs ordered by 19%.

Setting home care standards.

Setting standards for home health care is a necessary component to ensuring the delivery of quality care efficiently and effectively. The generic standards established by the American Nurses' Association are reviewed while other resources available when pursuing the development of home health standards are described. The author discusses the concept of developing standards based on cost, quality, and process.

Clarifying roles and expectations in home care.

Home care nurses work in an entirely different environment from where they were trained. This unique situation requires understanding the difference in the nurse's role in the home, and establishing rules that promote a therapeutic environment.

Selecting a home care agency.

Selecting a home care agency must be a collaborative effort on the part of families and the discharging facility. Guidelines for selecting home care providers eases the transition from the acute care facility to home.