Distinct Aβ pathology in the olfactory bulb and olfactory deficits in a mouse model of Aβ and α‐syn co‐pathology

Several degenerative brain disorders such as Alzheimer''s disease (AD), Parkinson''s disease (PD) and Dementia with Lewy bodies (DLB) are characterized by the simultaneous appearance of amyloid‐β (Aβ) and α‐synuclein (α‐syn) pathologies and symptoms that are similar, making it difficult to differentiate between these diseases. Until now, an accurate diagnosis can only be made by postmortem analysis. Furthermore, the role of α‐syn in Aβ aggregation and the arising characteristic olfactory impairments observed during the progression of these diseases is still not well understood. Therefore, we assessed Aβ load in olfactory bulbs of APP‐transgenic mice expressing APP695 ^KM670/671NL and PSEN1 ^L166P under the control of the neuron‐specific Thy‐1 promoter (referred to here as APPPS1) and APPPS1 mice co‐expressing SNCA ^A30P (referred to here as APPPS1 × [A30P]aSYN). Furthermore, the olfactory capacity of these mice was evaluated in the buried food and olfactory avoidance test. Our results demonstrate an age‐dependent increase in Aβ load in the olfactory bulb of APP‐transgenic mice that go along with exacerbated olfactory performance. Our study provides clear evidence that the presence of α‐syn significantly diminished the endogenous and seed‐induced Aβ deposits and significantly ameliorated olfactory dysfunction in APPPS1 × [A30P]aSYN mice.     

Acute arterial occlusion of the extremities. Rate of success following simple embolectomy and following combined procedures

Acute arterial obstruction of the extremities represents the most common emergency in vascular surgery. Diagnosis is based on the typical history and clinical symptoms. Emboli in vessels without atherosclerotic changes can be removed by simple embolectomy. In atherosclerotic arteries or in cases of acute thrombotic occlusion preoperative angiography is recommended in order to perform extensive reconstructive procedures. 400 arterial reconstructions for acute obstruction of the extremities were analysed. 46 operations were done in the upper extremities. In the majority of the cases simple embolectomy was successful. Limb salvage was 100% although one embolectomy and one bypass procedure failed to restore full revascularization. Complication and mortality rate was low. 354 lower limbs were operated. 274 extremities could be saved (77.4%). Among 80 poor results 48 major amputations had to be done (13.5%). Perioperative mortality was 12.4%. Death was mainly attributed to myocardial infarction.     

Contribution of diffusion‐weighted imaging to dynamic contrast‐enhanced MRI in the characterization of papillary breast lesions

Papillary lesions have a broad spectrum of appearances on magnetic resonance imaging (MRI ). The purpose of this study was to evaluate whether apparent diffusion coefficient (ADC ) values of papillary lesions can be used to characterize lesion as benign or malignant. This retrospective study included 29 papillary lesions. Diagnostic values of dynamic contrast‐enhanced MRI (DCE‐MRI), DWI ‐ADC , and DCE ‐MRI plus DWI ‐ADC were separately calculated. The malignant papillary lesions (0.744×10^?3 mm²/s) exhibited significantly lower mean ADC values than the benign lesions (1.339×10^?3 mm²/s). Addition of DWI to standard DCE ‐MRI provided 100% sensitivity. We hypothesized that this combination may prevent unnecessary excisional biopsies.     

Shall We Inject Superficial or Deep to the Plantar Fascia? An Ultrasound Study of the Treatment of Chronic Plantar Fasciitis

We compared the effectiveness of ultrasound (US)-guided corticosteroid, injected superficial or deep to the fascia, in patients with plantar fasciitis. Thirty patients (24 females [75%] and 6 males [25%]) with unilateral chronic plantar fasciitis were divided into 2 groups according to the corticosteroid injection site: superficial (n = 15) or deep (n = 15) to the plantar fascia. Patient heel pain was measured using a Likert pain scale and the Foot Ankle Outcome Scale (FAOS) for foot disability, evaluated at baseline and repeated in the first and sixth weeks. The plantar fascia and heel pad thicknesses were assessed on US scans at baseline and the sixth week. The groups were similar in age, gender, and body mass index (p > .05 for all). Compared with the baseline values, the Likert pain scale (p < .001 for all) and FAOS subscale (p < .01 for all) scores had improved at the first and sixth week follow-up visits in both groups. Although the plantar fascia thickness had decreased significantly in both groups at the sixth week (p < .001 for both), the heel pad thickness remained unchanged (p > .05 for both). The difference in the FAOS subscales (pain, p = .002; activities of daily living, p = .003; sports/recreational activities, p = .008; quality of life, p = .009) and plantar fascia thickness (p = .049) showed better improvement in the deep than in the superficial injection group. US-guided corticosteroid injections are safe and effective in the short-term therapeutic outcome of chronic plantar fasciitis. Additionally, injection of corticosteroid deep to the fascia might result in greater reduction in plantar fascia thickness, pain, and disability and improved foot-related quality of life.     

Effects of ischemic liver preconditioning on hepatic ischemia/reperfusion injury in the rat

To minimize bleeding during major liver resections or liver transplantation, surgical measures have been adopted that induce ischemia-reperfusion injury (I/R) which may significantly contribute to morbidity and mortality of partial liver resections. Several methods have sought to minimize I/R hepatic lesions. The present project assessed the protective role of ischemic preconditioning (IPC) in rat livers. The IPC was accomplished by clamping the hepatic pedicle for 5 minutes, followed by a 5-minute reperfusion (R) period before a 2-hour ischemia. Thereafter, reperfusions of 1, 3, and 24 hours were compared among IPC and control groups without IPC. Liver biopsy and blood samples were measured for mitochondrial respiratory control ratio (RCR), serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT). IPC protected liver mitochondrial function. Serum aminotransferase levels were significantly lower among animals undergoing IPC compared with groups without IPC. Thus, we verified the effects of IPC for hepatocellular protection against I/R lesions.     

Staginglaparoskopie in der Onkologie

The availability of more treatment options for gastrointestinal cancer requires precise and reliable pretherapeutic staging. Despite impressive technical progress in modern imaging procedures, this high level of staging quality is not yet warranted in all instances. Visual exploration of the abdominal cavity in extended diagnostic laparoscopy (EDL), including surgical dissection of areas which are primarily inaccessible, biopsy retrieval, and laparoscopic ultrasound, is superior in the diagnostic workup of early peritoneal carcinomatosis and (small) liver metastases. It is helpful to evaluate lymph node infliction and local resectability. In esophageal carcinoma, pretherapeutic EDL is valuable in case of advanced adenocarcinoma of the distal esophagus (AEG I according to Siewert), whereas the incidence of abdominal tumor manifestations in squamous cell carcinoma is too low to perform staging laparoscopy. In advanced gastric cancer, EDL yields relevant additional information in up to 20% of cases. If a multimodal therapeutic strategy is considered, EDL should be obligatory at least in prospective therapeutic studies. In carcinoma of the pancreas, EDL is in general not recommended by the majority of centers. Selective use (in particular in advanced cancer with a high probability of local irresectability) is gaining importance. In hepatobiliary malignancy including colorectal metastases, the high yield of additional information by EDL was confirmed in recent studies.     

German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors

Introduction

Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable (“low risk”) papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages.

Methods

The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization.

Results

The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases.

Conclusion

These evidence-based recommendations for surgical therapy reflect various “treatment corridors” that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.     

Contrasting effects of recombinant human granulocyte-macrophage colony- stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.     

The arsenic-based cure of acute promyelocytic leukemia promotes cytoplasmic sequestration of PML and PML/RARA through inhibition of PML body recycling

Arsenic in the form of arsenic trioxide (ATO) is used as a therapeutic drug for treatment of acute promyelocytic leukemia (APL). The mechanism by which this agent cures this disease was previously shown to involve direct interactions between ATO and the promyelocytic leukemia protein (PML), as well as accelerated degradation of the APL-associated fusion oncoprotein PML/retinoic acid receptor α (RARA). Here we investigated the fate of PML-generated nuclear structures called PML bodies in ATO-treated cells. We found that ATO inhibits formation of progeny PML bodies while it stabilizes cytoplasmic precursor compartments, referred to as cytoplasmic assemblies of PML and nucleoporins (CyPNs), after cell division. This block in PML body recycling is readily detected at pharmacologic relevant ATO concentrations (0.02-0.5μM) that do not cause detectable cell-cycle defects, and it does not require modification of PML by SUMOylation. In addition, PML and PML/RARA carrying mutations previously identified in ATO-resistant APL patients are impeded in their ability to become sequestered within CyPNs. Thus, ATO may inhibit nuclear activities of PML and PML/RARA in postmitotic cells through CyPN-dependent cytoplasmic sequestration.