Role of gonadotropins in malignant progression of sex cord stromal tumors produced by sequential auto- and isogenic transplantation of ovarian tissue in ovariectomized rats

Purpose: In this study the effect of continuous stimulation of gonadotropins on sex cord stromal tumors in the rat was examined. Methods: Sex cord stromal tumors were induced by transplantation of ovaries under the splenic capsule of ovariectomized rats. Beginning 180 days after transplantation, these tumors were taken out and cut into several pieces, which were then retransplanted (by isotransplantation) under the splenic capsule of 80 either intact or ovariectomized rats. Results: Most of the tumor grafts grew up to a median size of 0.7 cm in ovariectomized rats. However, some of the tumors recovered from recipient rats that were retransplanted with donor tumors differed significantly from the others. Characterized by a high mitotic rate, nuclear atypia, size (up to 3.8 cm) as well as growth in intact animals, these tumors were defined as malignant. They could be kept in culture and always led to the development of metastases after retransplantation into other rats. Conclusion: Benign sex cord stromal tumors can show malignant growth after transplantation. This study for the first time demonstrates that gonadotropins are involved in the induction of ovarian malignancies. Received: 15 December 2000 / Accepted: 15 February 2001     

Über das Bronchuskarzinoid

Zusammenfassung Mittels der modifizierten Imprägnationsmethode nachBodian gelang es, argyrophile Körnchen in den epithelialen Zellen zweier Bronchuskarzinoide darzustellen, in einem der Fälle auch in hämatogenen Fernmetastasen. Man kann in diesem Befund eine weitere Analogie zwischen den Bronchus- und Darmkarzinoiden erblicken, denen die Bronchuskarzinoide auch sonst in Struktur (s. Abb. 3a und b) und klinischem Verhalten weitgehend entsprechen. Die Bezeichnung Karzinoid ist also treffender als die Bezeichnung Bronchialadenom, eventuell unter Beifügung vom karzinoiden Typ. Anhangseeise wird eine Übersicht über die in der Literatur mitgeteilten Fälle von Bronchuskarzinoiden gegeben.Mit 5 Textabbildungen     

Non-linear adaptive controllers for an over-actuated pneumatic MR-compatible stepper

Pneumatics is one of the few actuation principles that can be used in an MR environment, since it can produce high forces without affecting imaging quality. However, pneumatic control is challenging, due to the air high compliance and cylinders non-linearities. Furthermore, the system’s properties may change for each subject. Here, we present novel control strategies that adapt to the subject’s individual anatomy and needs while performing accurate periodic gait-like movements with an MRI compatible pneumatically driven robot. In subject-passive mode, an iterative learning controller (ILC) was implemented to reduce the system’s periodic disturbances. To allow the subjects to intend the task by themselves, a zero-force controller minimized the interaction forces between subject and robot. To assist patients who may be too weak, an assist-as-needed controller that adapts the assistance based on online measurement of the subject’s performance was designed. The controllers were experimentally tested. The ILC successfully learned to reduce the variability and tracking errors. The zero-force controller allowed subjects to step in a transparent environment. The assist-as-needed controller adapted the assistance based on individual needs, while still challenged the subjects to perform the task. The presented controllers can provide accurate pneumatic control in MR environments to allow assessments of brain activation.     

Augmented Renal Clearance Implies a Need for Increased Amoxicillin-Clavulanic Acid Dosing in Critically Ill Children

There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [{"type":"clinical-trial","attrs":{"text":"NCT02456974","term_id":"NCT02456974"}}NCT02456974].)     

Droplet formation and scaling in dense suspensions

When a dense suspension is squeezed from a nozzle, droplet detachment can occur similar to that of pure liquids. While in pure liquids the process of droplet detachment is well characterized through self-similar profiles and known scaling laws, we show here the simple presence of particles causes suspensions to break up in a new fashion. Using high-speed imaging, we find that detachment of a suspension drop is described by a power law; specifically we find the neck minimum radius, r(m), scales like near breakup at time τ = 0. We demonstrate data collapse in a variety of particle/liquid combinations, packing fractions, solvent viscosities, and initial conditions. We argue that this scaling is a consequence of particles deforming the neck surface, thereby creating a pressure that is balanced by inertia, and show how it emerges from topological constraints that relate particle configurations with macroscopic Gaussian curvature. This new type of scaling, uniquely enforced by geometry and regulated by the particles, displays memory of its initial conditions, fails to be self-similar, and has implications for the pressure given at generic suspension interfaces.     

Plasmacytic differentiation in MALT lymphomas following treatment with rituximab

Mucosa-associated lymphoid tissue (MALT) lymphomas are B cell neoplasms which commonly affect the gastrointestinal (GI) tract. Gastrointestinal MALT lymphomas rarely show plasmacytic differentiation (PCD), and limited data on the potential influence of the anti-CD20 antibody rituximab (R) on PCD exist in the current literature. We have retrospectively analyzed patients with GI MALT lymphomas treated with R-containing regimens because restaging is routinely performed by repeated biopsies with pathohistological response assessment. Twenty-one patients with GI MALT lymphoma were identified to have undergone R-containing therapy. In 19 patients, the lymphoma originated in the stomach, while the colon was the primarily affected organ in two cases. Four patients received R monotherapy and 17 combinations of R with various chemotherapeutic agents. Only two patients with gastric MALT lymphoma had PCD before initiation of therapy. In 7 of 19 patients (37%) without PCD at diagnosis, restaging revealed PCD after or while on treatment with R-containing regimens. Out of these seven patients, only one patient had a complete response as opposed to 10/12 without PCD. These data suggest that R or R-containing treatment regimens may not optimally eradicate the plasma cell component and thus lead to PCD in patients with GI MALT lymphoma. In view of this, rebiopsy and histological re-assessment appear mandatory in patients failing/relapsing after R-containing regimens.