Loa loa macrofilariasis in the eyelid: case report of the first periocular subcutaneous manifestation in Germany

Purpose We report a case of periocular subcutaneous macrofilariasis as an initial sign of a systemic Loa loa infection.Methods Thorough history, eye examination and surgical intervention. Parasitological and serological analysis.Results A periocular adult Loa loa worm was extracted from the left upper eyelid in an African student living in Germany after presenting to our department with intermittent attacks of painful lid swelling. Four weeks later he presented with Calabar swellings in his arms without serological evidence of microfilaria and was treated with diethylcarbamazine.Conclusion Due to increasing migration of populations to Europe rare manifestations of ocular loiasis are becoming more common. Intermittent painful eyelid swelling in patients who visited or have lived in Africa should always raise the suspicion of systemic loiasis.     

Characterization of normal and infarcted rat myocardium using a combination of small-animal PET and clinical MRI.

The combination of small-animal PET and MRI data provides quantitative in vivo insights into cardiac pathophysiology, integrating information on biology and morphology. We sought to determine the feasibility of PET and MRI for the quantification of ischemic injury in the rat model. METHODS: Fourteen healthy male Wistar rats were studied with 18F-FDG PET and cine MRI. Myocardial viability was determined in a transmural myocardial infarction model in 12 additional rats, using 18F-FDG PET and delayed-enhancement MRI with gadolinium-diethylenetriaminepentaacetic acid. All PET was acquired with a dedicated small-animal PET system. MRI was performed on a 1.5-T clinical tomograph with a dedicated small-animal electrocardiographic triggering device and a small surface coil. RESULTS: In normal rats, 18F-FDG uptake was homogeneous throughout the left ventricle. The lowest mean uptake of the 18F-FDG was found in the apical regions (79% +/- 6.0% of maximum) and the highest uptake was in the anterior wall (93% +/- 4.3 % of maximum). Myocardial infarct size as determined by histology correlated well with defects of glucose metabolism obtained with 18F-FDG PET (r = 0.89) and also with delayed-enhancement MRI (r = 0.91). Left ventricular ejection fraction in normal rats measured by cine MRI was 57% +/- 5.4% and decreased to 38% +/- 12.9% (P < 0.001) in the myocardial infarction model. CONCLUSION: Integrating information from small-animal PET and clinical MRI instrumentation allows for the quantitative assessment of cardiac function and infarct size in the rat model. The MRI measurements of scar can be complemented by metabolic imaging, addressing the extent and severity of ischemic injury and providing endpoints for therapeutic interventions.     

Fixation instability and oculomotor abnormalities in Friedreich's ataxia

Eye movements were studied in 13 patients with Friedreich's ataxia and correlated with MRI findings to investigate whether oculomotor abnormalities can be traced to cerebellar disturbances in this disease. One of the most prominent eye signs was fixation instability (square-wave jerks, SWJ.). Besides SWJ the patients showed various combinations of cerebellar, vestibular and brain-stem oculomotor signs. Our patients did not comprise a homogeneous group with regard to their oculomotor findings. There was no correlation between the severity of any of the so-called cerebellar oculomotor disturbances and the number of SWJ. We tried to correlate the extent of oculomotor disturbances with floccular atrophy and atrophy of the dorsal vermis on MRI in seven of the patients. None of the oculomotor features (including SWJ) correlated with flocculus or dorsal vermis size. Furthermore, floccular and vermal measurements on MRI were normal. Accordingly, we think it unlikely that the oculomotor disturbances, including SWJ, are attributable to cerebellar pathology per se.     

Kreatinverluste und Kreatinaufnahme durch isolierte Herzen bei Durchströmung mit kreatinhaltigen Lösungen

Zusammenfassung Mit Krebs-Ringerlösung durchströmte Rattenherzen geben um so weniger Kreatin an die Durchströmungsflüssigkeit ab, je schonender sie präpariert wurden.Nach Zugabe von 3 mg bzw. 5 mg Kreatin zu 100 ml Durchstrom nahmen die meisten Herzen innerhalb von 30 min 400 bzw. 830 Kreatin/g Trockengewicht auf. Weitere Steigerung des Kreatinangebotes verbesserte die Kreatinaufnahme nicht, ebensowenig wie Zugabe von Glucose. Enthielt der Durchstrom Insulin, so wurde die Kreatinaufnahme signifikant erhöht.Die Mehrzahl der mit Kreatin durchströmten Herzen nahm aus der Krebs-Ringerlösung Phosphat auf.Kalium wurde von einigen Herzen abgegeben, von anderen aufgenommen. Die Kaliumaufnahme aus dem Durchstrom war bei geschädigten Herzen am größten. Zusammenhänge zwischen dem Verhalten von Kalium einerseits und Kreatin oder Phosphat andererseits wurden in den Versuchen an isolierten Herzen nicht erkennbar.

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Summary Rat hearts perfused with Krebs' Ringer solution, yielded creatine in the perfusion fluid; the more carefully the hearts were dissected, the smaller was the yield.When creatine was added to the perfusion fluid in concentrations of 3 or 5 mg-%, the hearts took up creatine in most cases to the extent of 400g or 830µg respectively, per g dry weight. A further increase in the creatine concentration did not improve the creatine uptake, nor did an addition of glucose to the perfusion fluid. When the latter contained insulin, the creatine uptake was significantly increased.The majority of the creatine-perfused hearts took up phosphate from the Krebs' Ringer solution.During perfusion some of the hearts yielded potassium, others took up potassium. The potassium uptake was greatest with hearts which had been damaged during the dissection. No connection could be observed in the experiments with isolated hearts between the behaviour of potassium on the one hand, and that of creatine or phosphate on the other.

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Ausgeführt mit Unterstützung des Landes Nordrhein-Westfalen (Landesamt für Forschung).

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Herrn Prof. Dr.E. Lehnartz zum 65. Geburtstag.     

Avoiding deceptive imprinting of the immune response to HIV-1 infection in vaccine development

Lymphocyte clonal restriction is caused by priming the immune system with an antigen and has been referred to infectious disease study as "original antigenic sin" (OAS), described first for influenza by Francis. OAS is a dominant feature of a normal immune response. Benefits of OAS come from the initial contact with the pathogen, which induces immunological memory. Memory is achieved by priming B and T cells of an immunologically na?ve host, and confers protection against infection with the antigen-related pathogen. Thus, a restricted antibody response to viral or parasite antigens is not per se pathogenic. However, the interplay between a "locked-in" immune response and the high genetic variation of the pathogenic agent can result in a deception of the immune system. In the following, clonal restriction of the immune response to HIV is described by giving examples of restricted anti-HIV antibody formation in maternally infected children. Clonal restriction results in host resistance of infected individuals to emerging HIV variants and quasispecies. The problems of classical approaches of vaccine design in AIDS and the lack of protection in vaccinated patients is reviewed.     

Management of lower urinary tract fibroepithelial polyps in children

IntroductionFibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date.ObjectiveThe aim of this study was to address the experience of FEP management in children.Study designA retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed.ResultsA total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1–48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1–10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1–34) months.DiscussionThe main limitation of our study is the retrospective design, although it is the largest one for this pathology.ConclusionThis series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences.Level of EvidenceLevel V.     

Channelrhodopsin-2–XXL,a powerful optogenetic tool for low-light applications

Channelrhodopsin-2 (ChR2) has provided a breakthrough for the optogenetic control of neuronal activity. In adult Drosophila melanogaster, however, its applications are severely constrained. This limitation in a powerful model system has curtailed unfolding the full potential of ChR2 for behavioral neuroscience. Here, we describe the D156C mutant, termed ChR2-XXL (extra high expression and long open state), which displays increased expression, improved subcellular localization, elevated retinal affinity, an extended open-state lifetime, and photocurrent amplitudes greatly exceeding those of all heretofore published ChR variants. As a result, neuronal activity could be efficiently evoked with ambient light and even without retinal supplementation. We validated the benefits of the variant in intact flies by eliciting simple and complex behaviors. We demonstrate efficient and prolonged photostimulation of monosynaptic transmission at the neuromuscular junction and reliable activation of a gustatory reflex pathway. Innate male courtship was triggered in male and female flies, and olfactory memories were written through light-induced associative training.Identifying causal relationships between neuronal activity and animal behavior is a fundamental goal of neuroscience. Crucially, this task requires testing whether defined neuronal populations are sufficient for eliciting behavioral modules. The development of light-gated ion channels that can be genetically targeted to specific cells has provided a unique solution to this challenge. In pioneering work, such optogenetic effectors or actuators were originally used as multicomponent approaches (1–3). The introduction of Channelrhodopsin-1 (ChR1) (4) and especially ChR2 as a light-sensitive cation channel (5) dramatically advanced the field by providing an efficient and straightforward single-component strategy for stimulating neuronal activity (6, 7).Besides cell-specific targeting of appropriate effector elements, precise neuronal control by optogenetics demands efficient light delivery to the neurons of interest. For behavioral studies, photostimulation is ideally accomplished in intact, freely moving organisms and accompanied by functional readouts. The combination of a rich, well-characterized behavioral repertoire and elegant molecular genetics has contributed to Drosophila’s strong impact on behavioral neurogenetics (8, 9). However, low light transmission through the pigmented cuticle presupposes high light intensities for using ChR2 in flies. This obstacle greatly complicates the experimental setup for freely moving animals, and the required light energies can cause heat damage when stimulation is applied over extended time periods. Moreover, limited cellular availability of all-trans-retinal (hereafter retinal for short) demands adding high retinal concentrations as a dietary supplement. If optical access to target cells is not provided by a translucent body wall (e.g., as in nematodes, zebrafish, and Drosophila larvae), an alternative solution is the implantation of an optical fiber directly into the brain. Although this approach has been used successfully in mammals (10), such an invasive procedure is infeasible for the study of intact small organisms.Due to these restrictions in Drosophila, ChR2 has not reached the popularity attained in other organisms, and instead the field has turned mainly to thermogenetic neuronal stimulation (11–13). As with all techniques, there are also drawbacks to using temperature as a stimulus, such as undesired background activity and a multitude of temperature-sensitive cellular processes and behavioral responses. Photo-liberation of caged ATP, combined with genetic targeting of ATP-gated ion channels, has been introduced as a different optogenetic technique in Drosophila (3, 14). However, its applications are constrained by invasive, time-consuming procedures for injection of caged ATP and a limited experimental time window.Here, we introduce improved ChR2 variants as an alternative approach to address these shortcomings in Drosophila. Compared with wild-type ChR2 (ChR2-wt), expression of these mutants in target cells led to strongly enhanced photocurrents. We provide the first report, to our knowledge, of ChR2-T159C (15, 16) in flies and describe a ChR2 variant, ChR2-XXL (extra high expression and long open state), that is characterized by an extended open-state lifetime, elevated cellular expression, enhanced axonal localization, and reduced dependence on retinal addition. As a consequence, this mutant does not require dietary retinal supplementation to depolarize cells, evoke synaptic transmission, and activate neuronal networks at very low irradiance. These features enabled behavioral photostimulation in freely moving flies using diffuse low-intensity light.