Arthroskopische subakromiale Dekompression

Objective

Coracoacromial ligament release to widen the subacromial space, resection of the anterior undersurface of the acromion and, if needed, caudal exophytes at the acromioclavicular joint.

Indications

All types of outlet impingement after 3 months of conservative treatment.

Contraindications

Impingement syndrome with instability/muscular imbalance, massive rotator cuff tear, unstable os acromionale, posterior–superior impingement, joint infection, freezing phase of a secondary frozen shoulder.

Surgical technique

Lateral decubitus position with traction device for the arm. Diagnostic arthroscopy of the glenohumeral joint via standard portals. With arthroscope moved to the subacromial space, bursectomy, electrosurgical release of coracoacromial ligament, resection of acromial hook through standard posterior portal.

Postoperative management

Physiotherapy or self-exercises on postoperative day 1, pain-adapted analgesia to avoid shoulder stiffness.

Results

Several studies present positive long-term results compared to conservative treatment (and open acromioplasty) for partial rotator cuff tears and for elderly patients. With a 20-year follow-up, successful results have been achieved for all patients with isolated impingement syndrome.

     

Conditional destabilization of the TPLATE complex impairs endocytic internalization

In plants, endocytosis is essential for many developmental and physiological processes, including regulation of growth and development, hormone perception, nutrient uptake, and defense against pathogens. Our toolbox to modulate this process is, however, rather limited. Here, we report a conditional tool to impair endocytosis. We generated a partially functional TPLATE allele by substituting the most conserved domain of the TPLATE subunit of the endocytic TPLATE complex (TPC). This substitution destabilizes TPC and dampens the efficiency of endocytosis. Short-term heat treatment increases TPC destabilization and reversibly delocalizes TPLATE from the plasma membrane to aggregates in the cytoplasm. This blocks FM uptake and causes accumulation of various known endocytic cargoes at the plasma membrane. Short-term heat treatment therefore transforms the partially functional TPLATE allele into an effective conditional tool to impair endocytosis. Next to their role in endocytosis, several TPC subunits are also implicated in actin-regulated autophagosomal degradation. Inactivating TPC via the WDX mutation, however, does not impair autophagy, thus enabling specific and reversible modulation of endocytosis in planta.

Endocytosis is an evolutionarily conserved eukaryotic pathway by which extracellular material and plasma membrane (PM) components are internalized via vesicles (1, 2). Clathrin-mediated endocytosis (CME), relying on the scaffolding protein clathrin, is the most prominent and the most studied endocytic pathway (3–5). As clathrin does not interact directly with the PM, nor does it recognize cargoes, adaptor proteins are required to act as essential links between the clathrin coat and the PM (6). In plant cells, material selected for CME is recognized by two adaptor complexes, the adaptor complex 2 (AP-2) and the TPLATE complex (TPC) (7–9). In contrast to TPC, single subunit mutants of AP-2 are viable (7, 8, 10–13) and AP-2 recruitment and dynamics appear to rely on TPC function (8, 14).TPC represents an ancestral adaptor complex, which is however absent in present-day metazoans and yeasts. It was experimentally identified as an octameric complex in Arabidopsis and as a hexametric complex in Dictyostelium (8, 15). Plants, however, are the only eukaryotic supergroup identified so far where TPC is essential for life (8, 15), as knockout or severe knockdown of single subunits of TPC in Arabidopsis leads to pollen or seedling lethality, respectively (8, 13). Two TPC subunits, AtEH1/Pan1 and AtEH2/Pan1, were not associated with the other TPC core components when the complex was forced into the cytoplasm by truncating the TML subunit and did not copurify with the other TSET components in Dictyostelium. This indicates that they may be auxiliary components to the core TPC (8, 15). These AtEH/Pan1 proteins were recently identified as important players in actin-regulated autophagy in plants. AtEH/Pan1 proteins recruit several components of the endocytic machinery to the autophagosomes, and are degraded together with them under stress conditions (16). However, whether this pathway serves to degrade specific cargoes or to regulate the endocytic machinery itself (17), and whether the whole TPC is required for this degradation pathway, remains unclear.Genetic and chemical tools to manipulate endocytosis have been extensively investigated via interfering with the functions of endocytic players, such as clathrin (18–22), adaptor proteins (7, 10–12, 14, 23–25), and dynamin-related proteins (26–30). The chemical inhibitors originally used to affect CME in plants have recently been described to possess undesirable side effects (31) or to affect proteins that are not only specific for endocytosis: for example, clathrin itself, as it is also involved in TGN trafficking (19, 22). The same is true for several genetic tools currently available to affect CME in plants (18, 21, 22, 30). Manipulation of TPC, functioning exclusively at the PM, represents a very good candidate to affect CME more specifically. So far however, there are no chemical tools to target TPC functions or dominant-negative mutants available. Inducible silencing works, but causes seedling lethality and takes several days to become effective (8). The only tools to manipulate TPC function in viable plants consist of knock-down mutants with very mild reduction of expression and consequently similar mild effects on CME (8, 14, 16, 32).     

Identification of psychopathological course trajectories in schizophrenia

Course trajectory analyses have been performed primarily for treatment response in acute episodes of schizophrenic disorders. As yet, corresponding data for the long-term course are lacking. Within a multicenter prospective observational study, 268 patients with schizophrenia were assessed at discharge from hospital and followed up after 6, 12, 18, and 24 months. A latent class growth analysis was performed on the scores from the Positive and Negative Syndrome Scale (PANSS). A two-class conditional latent class model showed the best data fit (Entropy: 0.924). The model divided the sample into a group with amelioration in all PANSS subscales (60%) and a group with stable positive/negative and deteriorating general psychopathology symptoms (40%). Global functioning (GAF score), gender, age, living situation and involuntary admission predicted course trajectory class membership. The model was predictive of significant differences between the two groups in health care service costs and quality of life. The results underline the heterogeneous course of the illness, which ranged from amelioration to deterioration over a 2-year period. Statistical models such as trajectory analysis could help to identify more homogenous subtypes in schizophrenia.     

Growth studies in Jena,Germany: Historical background and secular changes in stature and weight in children 7–14 years

Anthropological investigations have been performed on Jena school children since 1880. The report summarizes the background of the surveys and then considers secular changes in stature and body weight since 1880. The stature of Jena school children shows a major increase over 105 years, ranging from 9.7% to 12.8% in girls and from 9.4% to 14.6% in boys. Changes in estimated growth rates are evident, especially in the preschool ages. Corresponding secular increases in weight between 1880 and 1985 range from 20.7% to 50.4%. Data during and after times of war suggest that females appear to react to changing living conditions more quickly than boys. On the other hand, the smaller variation in the stature of girls suggests more homogeneous and perhaps better buffered growth in girls. Estimated semiannual increments in stature and weight between 1880 and 1985 indicate an increase in the intensity of growth during school age in both sexes and acceleration of the pubertal growth spurt, especially in boys. The average decrease in weight in both sexes between 1932 and 1944 should be emphasized. This is the result of the poor nutritional conditions during the Second World War. Girls show a greater reduction in mean values than boys. © 1996 Wiley-Liss, Inc.     

Invasive Breast Carcinoma with Neuroendocrine Differentiation: A Single-Center Analysis of Clinical Features and Prognosis

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases. Key words: neuroendocrine neoplasia of the breast, invasive breast cancer with neuroendocrine differentiation, neuroendocrine breast cancer, neuroendocrine markers, somatostatin receptor 2A     

HDAC and MAPK/ERK Inhibitors Cooperate To Reduce Viability and Stemness in Medulloblastoma

Journal of Molecular Neuroscience - Medulloblastoma (MB), which originates from embryonic neural stem cells (NSCs) or neural precursors in the developing cerebellum, is the most common malignant...     

A single infusion of the bisphosphonate AHPrBP (APD) as treatment of Paget's disease of bone

PURPOSE: Disabling pain, skeletal deformity, or risk of joint involvement characterize Paget's disease of bone. Because the disease often affects the elderly, for whom compliance is a problem, we investigated therapy with a single intravenous infusion of amino-hydroxypropylidene bisphosphonate (AHPrBP, previously APD). PATIENTS and METHODS: Eleven patients with mild but symptomatic Paget's disease and one patient with very severe disease were treated with AHPrBP administered as a single intravenous infusion of 60 mg over 24 hours. Follow-up with clinical and biochemical evaluations was performed over six months for all patients, and over one year for seven patients. RESULTS: Clinical improvement and normalization of biochemical parameters were observed in all patients except one with extremely severe disease. On average, plasma alkaline phosphatase activity fell progressively and significantly from 256 +/- 29 U/liter (mean +/- SEM) to 97 +/- 6 U/liter after six months, and to 102 +/- 11 U/liter after one year (normal: less than 120 U/liter). Urinary excretion of hydroxyproline decreased within seven days to normal (from 4.3 +/- 0.5 mumol/liter of glomerular filtrate [lGF] to 1.7 +/- 0.2 mumol/lGF; normal: 2.2 mumol/lGF). Thereafter, it remained within the normal range until one year (1.8 +/- 0.2 mumol/lGF after six months and 1.9 +/- 0.3 mumol/lGF after one year). Side effects were negligible. Two patients noted only a transient increase in body temperature. When bone scintigraphy was repeated after six months, it revealed a marked decrease of the activity of the disease. CONCLUSION: Due to the important and sustained inhibition of bone resorption induced by AHPrBP, a single infusion of 60 mg of the bisphosphonate leads to a rapid decline in activity and a long-standing remission of moderate Paget's disease, without significant side effects.