Fixation stability and macular light sensitivity in patients with diabetic maculopathy: a microperimetric study with a scanning laser ophthalmoscope

BACKGROUND: In patients with diabetic maculopathy, evaluation of visual acuity alone may not represent central retinal function sufficiently. Despite good visual acuity, patients may suffer from visual disturbances like waviness, relative scotoma, loss of fixation and decrease of contrast sensitivity. The aim of the study was to assess localized light sensitivity in the central visual field and to determine fixation stability in patients with diabetic maculopathy with moderate visual loss in comparison to healthy controls. METHODS: Twenty-seven patients (mean age: 54 +/- 15; range 17-81 years) with diabetic maculopathy and 61 controls (mean age: 45 +/- 22; range 18-85 years) were included in the study. Light sensitivity was quantified by presenting stimuli with different light intensity with simultaneous real-time monitoring of the retina (intensity: 0-27.9 dB; size: Goldmann III, wavelength: 633 nm). Eye movements were controlled by semiautomatic fundus tracking. Fixation stability was quantified by measuring the area within 75% of all points of fixation. RESULTS: Fixation stability was significantly decreased in diabetic patients in comparison to controls (43 +/- 22 vs. 31 +/- 16 arc min, p < 0.01). There was a significant difference in macular light sensitivity in diabetic patients compared to controls (19.6 +/- 0.5 dB), both in mean difference (15.6 +/- 1.4 dB) and if affected with macular edema (16.1 +/- 4.5 dB), hard exudates (13.3 +/- 6.7 dB), nonperfusion areas (10.3 +/- 7.9 dB) and laser burns (3.0 +/- 6.1 dB). Temporal parts of the macula were more affected than other parts. No correlation was found between visual acuity and foveal light sensitivity and foveal fixation, respectively. CONCLUSION: Macular light sensitivity decreased progressively with the kind and severity of retinal alteration independent of visual acuity. The assessment of macular light sensitivity and stability of fixation with automatic threshold microperimetry may help to identify patients with diabetic maculopathy and could improve the management of diabetic maculopathy.     

Percutaneous peripheral laser angioplasty with a pulsed Nd-YAG laser and sapphire tips

Percutaneous transluminal laser angioplasty with a pulsed Nd-YAG laser (1064 nm wavelength, 100s pulse duration, up to 0.4 J per pulse, 10 Hz repetition rate) coupled to optical fibres with sapphire tips of 1.8 and 2.2 mm diameter was performed under experimental conditions and then in 30 chronic occlusions of femoral and popliteal arteries in 22 patients.The experimental study in 11 human cadaverous arteries revealed that this laser system was effective in the recanalization of seven femoropopliteal occlusions, but the relative rigidity of the sapphire-tipped contact probe prevented its access to two infrapopliteal vessels. Two perforations occurred after the recanalization of 18 and 15 cm, respectively.Clinically the procedure was successful in 17 out of 25 sessions (68%). The probe formed a primary channel of at least 2.0 mm width which was further dilated by conventional balloon catheter. Ankle/brachial systolic pressure index (ABPI) increased from 0.43±0.13 to 0.79±0.21 after the procedure. In eight cases complications occurred. Two reocclusions were treated by Streptokinase infusion, two procedures were repeated 2 months later, one patient was referred to elective bypass surgery, and three patients were treated conservatively. Six patients were followed-up for more than 6 months. In one patient claudication of 400 m reappeared. ABPI showed a moderate decrease from 0.84±0.20 to 0.69±0.19.These first results are encouraging and it is likely that this method could become an important adjunct to balloon angioplasty.     

Conservation of proteobacterial magnetosome genes and structures in an uncultivated member of the deep-branching Nitrospira phylum

Magnetotactic bacteria (MTB) are a phylogenetically diverse group which uses intracellular membrane-enclosed magnetite crystals called magnetosomes for navigation in their aquatic habitats. Although synthesis of these prokaryotic organelles is of broad interdisciplinary interest, its genetic analysis has been restricted to a few closely related members of the Proteobacteria, in which essential functions required for magnetosome formation are encoded within a large genomic magnetosome island. However, because of the lack of cultivated representatives from other phyla, it is unknown whether the evolutionary origin of magnetotaxis is monophyletic, and it has been questioned whether homologous mechanisms and structures are present in unrelated MTB. Here, we present the analysis of the uncultivated "Candidatus Magnetobacterium bavaricum" from the deep branching Nitrospira phylum by combining micromanipulation and whole genome amplification (WGA) with metagenomics. Target-specific sequences obtained by WGA of cells, which were magnetically collected and individually sorted from sediment samples, were used for PCR screening of metagenomic libraries. This led to the identification of a genomic cluster containing several putative magnetosome genes with homology to those in Proteobacteria. A variety of advanced electron microscopic imaging tools revealed a complex cell envelope and an intricate magnetosome architecture. The presence of magnetosome membranes as well as cytoskeletal magnetosome filaments suggests a similar mechanism of magnetosome formation in "Cand. M. bavaricum" as in Proteobacteria. Altogether, our findings suggest a monophyletic origin of magnetotaxis, and relevant genes were likely transferred horizontally between Proteobacteria and representatives of the Nitrospira phylum.     

Nierenaktinomykose nach Ureterosigmoidostomie

Actinomycosis is a chronic infectious disease caused by a gram-positive anaerobe. The bacterial disease is known to predominantly affect the oropharyngeal mucosa and soft tissues as well as the gastrointestinal tract. However, renal involvement by actinomycosis is exceedingly rare. Thus, renal actinomycosis is usually diagnosed by means of histopathological assessment of nephrectomy specimens because affected patients seek medical care due to (peri-) renal mass lesion clinically mimicking cancer. To best of our knowledge, we present the first case worldwide reporting on a 65-year-old man diagnosed with renal actinomycosis following ureterosigmoidostomy in whom nephrectomy was performed due the clinical suspicion of renal cancer (stage cT4). Subsequently, calculated antibiotic therapeutic regimens were initiated after the diagnosis was suspected by the pathologist. During the entire postsurgical follow-up comprising a total of 6 months, the patient did not experience any local or systemic recurrence. In summary, detailed information concerning the etiology, the clinical symptoms as well as diagnostic and therapeutic options are discussed in our case report.     

Repeated clonal relapses in classical Hodgkin's lymphoma and the occurrence of a clonally unrelated diffuse large B cell non-Hodgkin lymphoma in the same patient

Classical Hodgkin's lymphoma (cHL) and B-cell Non-Hodgkin Lymphoma (B-NHL) occasionally occur in the same patient. However, molecular studies that aim at determining the clonal relationship between both lymphomas are rare. In most instances, the lymphoma components appear to be derived from the same germinal center (GC) B cell precursor. We describe the molecular monitoring of repeated clonal relapses in a patient with cHL in whom diffuse large B cell NHL (DLBCL) developed concurrently. Intriguingly, both lymphomas were clonally unrelated. Thus, the derivation from a shared precursor likely is not a general rule in cHL and DLBCL arising in the same patient.     

Therapy of mRCC beyond mTOR-inhibition in clinical practice: results of a retrospective analysis

Purpose

Renal cell carcinoma (RCC) is the most common renal tumor and accounts for nearly 3 % of adult cancers. In the recent years, seven new targeted agents have been approved changing the treatment in metastatic RCC dramatically. So far, however, it remains unclear which sequence is best for those patients. This study analyzed retrospectively the outcome of patients treated with everolimus after failure of a vascular endothelial growth factor receptor-directed therapy and which therapies were used after everolimus.

Patients and methods

In a retrospective analysis, patients receiving everolimus after failure of first-line VEGFR-directed therapy have been analyzed in regard to response, duration of treatment and subsequent therapies. In total, the data of 81 patients have been analyzed.

Results

The most observed first-line therapy was sunitinib followed by sorafenib. Thirty-two patients received everolimus as second-line therapy, and 49 as third-line therapy. The median duration of treatment with everolimus was 4.5 months. Seventy-seven of eighty-one patients (95 %) received a further therapy after discontinuation of everolimus. The agents administered beyond were sunitinib (28.6 %), sorafenib (28.6 %) and 42.8 % received other therapies. Twenty-seven patients received an additional sequence of therapy (fourth to fifth line). Fifty-eight percentage of patients have still been alive at time of analysis.

Conclusion

The duration of everolimus therapy beyond failure of anti-VEGF-directed therapy and the reported time to progression was in the range of the RECORD-1 trial in daily practice as well. After failure of everolimus, reexposure to tyrosine kinase inhibitors is a common clinical practice and demonstrates a clinical benefit of therapies beyond everolimus.