Splenic Vein Thrombosis Following Pancreas Transplantation: Identification of Factors That Support Conservative Management.

Prophylaxis for graft portal/splenic venous thrombosis following pancreas transplant varies between institutions. Similarly, treatment of venous thrombosis ranges from early re-exploration to conservative management with anticoagulation. We wished to determine the prevalence of graft splenic vein (SV) thrombosis, as well as the clinical significance of non-occlusive thrombus observed on routine imaging. Records of 112 pancreas transplant recipients over a 5-year period at a single center were reviewed. Venous thrombosis was defined as absence of flow or presence of thrombus identified in any part of the graft SV on ultrasound. Thirty patients (27%) had some degree of thrombus or absence of flow in the SV on postoperative ultrasound. There were 5 graft losses in this group. Four were due to venous thrombosis, and occurred within 20 days of transplant. All patients with non-occlusive partial SV thrombus but normal arterial signal on Doppler ultrasound were successfully treated with IV heparin followed by warfarin for 3-6 months, and remained insulin independent. Findings of arterial signal abnormalities, such as absence or reversal of diastolic flow within the graft, require urgent operative intervention since this finding can be associated with more extensive thrombus that may lead to graft loss.

Pancreas-After-Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for Restoring Durable Insulin Independence.

Islet transplantation offers a minimally invasive approach for ß cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. We describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure with long-term follow-up of pancreatic graft survival and renal function. Despite highly variable panel reactive antibody levels prior to pancreas transplant (mean 27 ± 35%), all seven patients achieved stable and durable insulin independence with a mean follow-up of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet, prepancreas levels (mean 8.1 ± 1.5%) to postpancreas levels (mean 5.3 ± 0.1%; p = 0.0022). Three patients experienced acute rejection episodes that were successfully managed with thymoglobulin and methylprednisolone, and none of these preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas-after-islet transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure.

Failure to achieve normal metabolic response in non-obese diabetic mice and streptozotocin-induced diabetic mice after transplantation of primary murine hepatocytes electroporated with the human proinsulin gene (p3MTChins).

BACKGROUND: A recent study by Chen et al described a therapy for diabetes that involved electroporation of primary hepatocytes with human proinsulin cDNA, p3MTChins. Intrahepatic transplantation of treated hepatocytes into streptozotocin (STZ) murine and porcine models led to euglycemia, weight maintenance, and normal insulin production. We tested the repeatability of their basic experiments and transplantation technique and expanded the study to include an autoimmune model. METHODS: Hepatocytes were isolated from B6 mice, electroporated with p3MTChins, and glucose-challenged or were injected into hepatic or spleen parenchyma of STZ-diabetic B6 and non-obese diabetic mice. Outcomes included survival, serum glucose levels, insulin, and c-peptide release. Untransfected primary hepatocytes and mice transplanted with these cells served as controls. RESULTS: p3MTChins-hepatocytes secreted insulin during glucose challenge, but glucose levels did not change with increasing glucose concentrations. Direct hepatic injection led to high mortality rates. Mice that underwent intrasplenic injection survived for >50 days (control = 4 days) and had a mild but stable improvement in hyperglycemia. C-peptide in both mouse models was detectable but eventually declined to baseline in the non-obese diabetic mice. CONCLUSIONS: Hepatocytes can be transfected with p3MTChins to produce human insulin but may lack the proper glucose-sensing or complex storage and secretion capabilities that allow for a finely tuned dynamic insulin response. Treatment is subtherapeutic, and p3MTChins-hepatocyte function may not endure in an autoimmune model. Without successful preliminary findings, cell therapy involving electroporation of p3MTChins does not appear to be practical as a therapy for diabetes and may not be a strategy to pursue at this time.

Case report of intestinal tuberculosis 6 years after simultaneous pancreas and kidney transplant.

Tuberculosis (TB) is often difficult to diagnose in immunocompromised patients and occurs 20 to 74 times more frequently in recipients of solid organ transplants than in the general population. We present the case of a 40-year-old female immigrant from Mexico previously treated for latent TB who underwent a simultaneous pancreas and kidney transplant. She experienced 3 episodes of rejection and then presented with 4 months of nonspecific abdominal pain. She was ultimately diagnosed with disseminated TB presenting with intestinal perforation and pulmonary involvement. This case illustrates the need for clinicians to maintain a high index of suspicion for TB in transplant recipients, especially those previously treated for TB or rejection.

Interactive management of transboundary waters on the external European Union border.

The paper addresses issues specific to planning of water protection measures in transboundary water basins located on the external European Union border. The case study of the Lake Peipsi/Chudskoe, a large transboundary lake shared by Estonia and Russia, is used to demonstrate issues of management of transboundary waters on the Eastern European fringe. The author emphasizes the importance of managing transboundary water basins located on the EU external borders interactively, i.e., through regular communication and consultation among water experts, decision-makers and stakeholders involved in managing waters on transboundary, national and subbasin levels, and discusses difficulties in, and opportunities for, the interactive management of transboundary waters on the EU external borders.

Geometrical optics model of Mie resonances

The geometrical optics model of Mie resonances is presented. The ray path geometry is given and the resonance condition is discussed with special emphasis on the phase shift that the rays undergo at the surface of the dielectric sphere. On the basis of this model, approximate expressions for the positions of first-order resonances are given. Formulas for the cavity mode spacing are rederived in a simple manner. It is shown that the resonance linewidth can be calculated regarding the cavity losses. Formulas for the mode density of Mie resonances are given that account for the different width of resonances and thus may be adapted to specific experimental situations.

A 1-year pharmacokinetic investigation of a novel oral contraceptive containing drospirenone in healthy female volunteers.

Drospirenone is a novel synthetic progestogen with a pharmacological profile similar to that of natural progesterone. It has been developed in combination with ethinylestradiol for use as an oral contraceptive (EE/DRSP, Yasmin, Schering AG, Berlin, Germany). The pharmacokinetic characteristics of drospirenone and ethinylestradiol have been assessed in healthy female volunteers over a 1-year period. During each of the 13 treatment cycles, volunteers received the combined active ingredients for 21 days, followed by a 7-day, tablet-free interval. The concentrations of the serum proteins, sex hormone binding globulin (SHBG) and corticoid binding globulin (CBG), were determined at intervals after the cessation of treatment (day 21) at the end of cycles 1, 6, 9 and 13. Drospirenone and ethinylestradiol were found to be absorbed rapidly and to reach a peak concentration in serum 1.5-2.0 h after dosing. Serum concentrations ofdrospirenone declined, with mean terminal half-lives of 30.8-32.5 h. Accumulation of both drospirenone and ethinylestradiol was observed within a treatment cycle, with a mean accumulation ratio of 3.0 for drospirenone and 2.1 for ethinylestradiol. In addition, serum drospirenone concentrations increased between treatment cycles 1 and 6, but remained steady thereafter, as reflected in the AUC values determined at the end of treatment cycles 1, 6, 9 and 13. Serum SHBG and CBG concentrations declined in a biphasic manner after cessation of treatment at the end of cycle 13, and physiological steady-state concentrations were reached within 4-6 weeks. In conclusion, drospirenone was absorbed at a similar rate as other synthetic progestogens contained in various oral contraceptives, as indicated by similar tmax values. The terminal half-life of drospirenone was intermediate between those of 19-nortestosterone derivatives like desogestrel, levonorgestrel or gestodene and C21-progestogens like cyproterone acetate. Both active ingredients of the new contraceptive EE/DRSP showed accumulation within a treatment cycle, which is also the case with other synthetic progestogen/ethinylestradiol combinations. Similar to other oral contraceptives, a reversible induction of serum SHBG and CBG concentrations was observed under EE/DRSP treatment.

Extracardiac contributions to chest pain perception in patients 6 months after acute myocardial infarction.

OBJECTIVES: The amount of perceived anginal pain in patients after infarction deserves the attention of the physician. This study sought to identify the modulating influence of extracardiac factors on persistent angina pectoris after myocardial infarction. METHODS AND RESULTS: A total of 552 male survivors of acute myocardial infarction (age 29 to 65 years, median 54 years) were followed for a period of 6 months; the affective state was assessed immediately after the acute event. The prognostic importance of postinfarction depression on chest pain perception was evaluated 6 months after the cardiac event in 376 patients. After the 6-month follow-up period, 199 (53%) of the patients with myocardial infarction had angina pectoris. Somatic risk factors and electrocardiographic data at initial testing did not contribute to the risk of having chest pain. However, patients with high levels of depression at initial testing had an almost 3-fold risk of having angina pectoris 6 months after the index event. Older age, lower social class status, and preinfarction angina were also significantly related to angina pectoris at the end of the study. Patients who were pain free before the index infarction reported significantly more symptoms of chest pain at the study end point (P

Controlled modification of the expansion order as a tool in mie computations.

In the framework of Mie theory the involved electromagnetic fields are expanded in an infinite series of multipoles. In numerical computations the summation has to be terminated after a finite number of terms (the expansion order N), which unavoidably produces errors. On the other hand, it is known that the contributions of terms of order l with x

Resonance shift of obliquely illuminated dielectric cylinders: geometrical-optics estimates.

Some characteristics of resonant states in obliquely illuminated cylinders are derived from a geometrical-optics point of view. A formula for the resonance shift that is due to tilted illumination is derived and predictions are compared with data from the literature.

Pharmacokinetics of the liver-specific contrast agent Gd-EOB-DTPA in relation to contrast-enhanced liver imaging in humans.

This study was performed to evaluate the effect of dose on the pharmacokinetics and efficacy of the gadolinium-based contrast medium gadoxetic acid, disodium, [gadolinium (4S)-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6, 9-triazaundecandioic acid-disodium salt] (Gd-EOB-DTPA) as a liver-specific hepatobiliary contrast medium for computed tomography. Pharmacokinetics in serum and the pattern of elimination were investigated in 18 healthy volunteers up to 6 days after a 10-minute infusion of 0.2 mmol, 0.35 mmol, and 0.5 mmol of gadolinium per kilogram of body weight. Pharmacokinetic behavior was compared with the compute tomographic attenuation data in the liver parenchyma after the same doses in patients. Urinary and fecal excretion accounted for approximately equal portions of the administered dose. The degree of renal elimination increased with increasing doses, whereas renal clearance and half-life from urine data were not affected by dose. Dose-normalized area under the concentration-time curve was significantly increased with increasing doses indicating saturation in liver uptake for the highest dose. This finding was in agreement with the measured net increase in liver attenuation by computed tomography. Hepatic disposition revealed slight saturation phenomena for the highest dose (0.5 mmol gadolinium/kg). Nevertheless, this dose resulted in sufficient uptake by human liver, allowing for computed tomographic imaging.

Investigation of coated droplets in an optical trap: Raman-scattering, elastic-light-scattering, and evaporation characteristics.

Single optically levitated microparticles were investigated by Raman spectroscopy. The particles were composed of di-octyl-phthalate (DOP) and glycerol; these substances are not mixable and form a two-phase droplet. Measurements of the Raman spectrum confirm the formation of droplets containing both chemical species. The spectra show strong input and output structural resonances as expected. If the particle is in resonance, the field inside the particle is enhanced, and most of the inelastically scattered light is emitted from molecules close to the droplet rim. If the particle does not fulfill the resonance condition, the contribution of an individual molecule to the Raman scattering does not depend strongly on the radial position of this molecule. On this basis, the radial distribution of the two components inside the evaporating droplet was determined by time-dependent measurements of the Raman spectrum. Furthermore, elastic-light scattering and the evaporation characteristics of the particles were investigated.

Post-infarction depression and incomplete recovery 6 months after acute myocardial infarction.

Patients who suffer from post-infarction depression are a high risk group with an increased mortality risk. The reasons for this are not known although it may be because such patients cannot cope with the chronic condition of cardiac disease. We designed a profile of clinical and behavioural outcome measurements representing recovery after myocardial infarction. 552 male survivors of acute myocardial infarction (29-65 years; mean = 53) were grouped at study entry according to their depression status. 377 patients were reassessed after 6 months and were divided into the following subgroups: 50 (13.3%) patients had severe depression; 85 (22.5%) moderate depression and 242 (64.2%) low degrees of depression in the initial study. There were no substantial differences in baseline characteristics between the index group and the drop-out group. The unadjusted relative risk for follow-up angina pectoris among patients with depression (severe versus low) was 3.12 (95% CI 1.58 to 6.16) and was 5.55 (CI 2.87 to 10.71) for emotional instability. The relative risk for maintenance of smoking habits was 2.63 (CI 1.23 to 5.60) and was for work resumption 0.39 (CI 0.18 to 0.88). There was no association between depression and the occurrence of late potentials. After adjustment for univariate variables (age, social class, recurrent infarction, helplessness) only small and nonsignificant changes in the relative risks were found. However the inverse association of depression and work resumption was lost after adjustment. The investigation revealed that persistent postinfarction depression is an independent and important source of subsequent morbidity and long-acting reduced quality of life. Depression has adverse effects on illness behaviour and pain perception.

Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison.

OBJECTIVES: To compare the prevalence of asthma and allergic disorders among children in Munich, western Germany, and Leipzig, eastern Germany, where environmental exposure, particularly air concentrations of sulphur dioxide and particulate matter, and living conditions have differed over the past 45 years. DESIGN: Prevalence surveys among school-children aged 9-11 years in Leipzig and Munich. Self completion of written questionnaire by the children's parents and lung function measurements. SUBJECTS: 1051 children in Leipzig and 5030 in Munich. SETTING: Primary schools. MAIN OUTCOME MEASURES: Reported lifetime prevalence of asthma and allergic disorders, and bronchial hyperresponsiveness assessed by cold air inhalation challenge. RESULTS: The lifetime prevalence of asthma diagnosed by a doctor was 7.3% (72) in Leipzig and 9.3% (435) in Munich; prevalence of wheezing were 20% (191) and 17% (786) respectively. The prevalence of diagnosed bronchitis was higher in Leipzig than Munich (30.9% (303) v 15.9% (739); p < 0.01). A significant drop in forced expiratory volume (> 9%) after cold air challenge was measured in 6.4% (57) of children in Leipzig and in 7.7% (345) of those in Munich. Hay fever (2.4% (24) v 8.6% (410); p < 0.01) and typical symptoms of rhinitis (16.6% (171) v 19.7% (961); p < 0.05) were reported less often in Leipzig than in Munich. CONCLUSIONS: No significant differences were seen in the lifetime prevalence of asthma, wheezing, and bronchial hyperresponsiveness between children in Leipzig and Munich. The lifetime prevalence of bronchitis was higher in Leipzig than in Munich. The lower prevalence rates of allergic disorders in Leipzig could point toward aetiological factors that are associated with Western lifestyle and living conditions.

Profiles of Super Senior Tennis Players.

These upper middle-class senior citizens play tennis to stay healthy and to enjoy life, but their experience doesn't necessarily apply to the rest of society.