The development of skilled walking in the rat

The rat is an altricial species and consequently undergoes considerable postnatal development. Careful analysis of the emergence and disappearance of motor behaviours is essential to gain insight into the temporal pattern of maturation of motor system structures. This study presents a qualitative analysis of the developmental progression of skilled movement in the rat by using a skilled walking task. A new rung bridge task was used to expose rat pups to a novel environment in order to reveal their potential capabilities. Ten rat pups were filmed daily from postnatal day 7 through postnatal day 30 as they explored the rung bridge task. Discrete changes in skilled and non-skilled walking in fore- and hind-limbs were evaluated by scoring seven categories and 24 subcategories of motor behaviour, including limb flexion and extension, coordination, posture, sensorimotor responses, distal control, and tail use in rat pups. Frame-by-frame analysis of ambulatory movement revealed six distinct stages of locomotor development. The most significant transformation to mature gait patterns was found between postnatal days 15 and 19, and maturation of all motor behaviour was completed by postnatal day 27. The findings are discussed in relation to the maturation of underlying structures and their relevance to studies of brain damage.     

Antimicrobial therapy of febrile complications after high-dose chemo-/radiotherapy and autologous hematopoietic stem cell transplantation--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

Infectious complications occur in 60-100% of patients following high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT), and are commonly caused by Gram-negative aerobic bacteria (such as Pseudomonas aeruginosa and enterobacteriacea e) and Gram-positive cocci (such as enterococci, streptococci and staphylococci), which should be covered by empiric first-line antibiotic therapy. Less frequently, infections are caused by fungi and anaerobic bacteria, and initial therapy does not necessarily have to cover coagulase-negative staphylococci, oxacillin-resistant S. aureus (MRSA), anaerobic bacteria and fungi. Patients who already receive antibiotics and develop pulmonary infiltrates should immediately be treated with systemic antifungals. Patients with fever and diarrhea or other signs and symptoms of gastrointestinal or perianal infection should be treated with antibiotics covering anaerobic bacteria and enterococci. Clinically stable patients with skin infections or central venous catheter-related infections can be treated with standard empiric antibiotic therapy including a beta-lactam active against Pseudomonas aeruginosa with or without an aminoglycoside, and should only receive glycopeptides if they do not respond to first-line therapy within 72 hours, become clinically unstable, have severe mucositis, or when resistance against the empiric antibiotics is demonstrated. Recombinant hematopoietic growth factors should not be added routinely but may be considered in life-threatening situations such as invasive pulmonary mycoses or sepsis.     

C5a stimulates production of plasminogen activator inhibitor-1 in human mast cells and basophils

We have recently shown that resting human mast cells (MCs) produce tissue-type plasminogen activator (t-PA) without simultaneously expressing plasminogen activator inhibitor 1 (PAI-1). In the present study we have identified the anaphylatoxin rhC5a as a potent inducer of PAI-1 expression in human MCs and basophils. In primary human skin MCs and primary blood basophils, exposure to rhC5a was followed by an increase from undetectable to significant levels of PAI-1. In addition, rhC5a induced a concentration- and time-dependent increase in PAI-1 antigen in the MC line HMC-1 and the basophil cell line KU-812 and increased the expression of PAI-1 mRNA in HMC-1. In conditioned media of HMC-1 treated with rhC5a, active PAI-1 could be detected. A simultaneous loss of t-PA activity in conditioned media from the same cells indicated that rhC5a-induced PAI-1 was capable of inhibiting the enzymatic activity of coproduced t-PA. Correspondingly, the levels of t-PA-PAI-1 complexes increased in rhC5a-treated cells. When HMC-1 cells were incubated with pertussis toxin or anti-C5a receptor antibodies, the effect of rhC5a on PAI-1 production was completely abolished. Treatment of C5a with plasmin resulted in loss of its ability to induce PAI-1 production in MCs. Considering the suggested role for MCs and components of the complement system in the development of cardiovascular diseases, we hypothesize that MCs, by producing t-PA in a resting state and by expressing PAI-1 when activated by C5a, might participate in the modulation of the balance between proteases and protease inhibitors regulating tissue injury and repair in such disease processes.     

Pulmonary dysfunction in non-cirrhotic patients with chronic viral hepatitis

Background: Hepatopulmonary syndrome (HPS), defined as hypoxemia and functional intrapulmonary right-to-left shunts in the presence of chronic liver disease, is a frequent complication of end-stage liver disease. The aim of this study was to determine the extent of pulmonary dysfunction and the prevalence of HPS in non-cirrhotic patients with chronic viral hepatitis. Methods: Lung function tests were carried out in 178 patients with chronic viral hepatitis (mean age 43.2 years, 95 smokers). To demonstrate intrapulmonary shunting, contrast echocardiography was performed in all patients with hypoxemia (paO(2)<70 mmHg) or a reduced diffusion capacity (DLCO<70% predicted). Results: The median results of lung function parameters (FVC, FEV(1), FEV(1)/FVC, TLC, DLCO, and blood gas analysis) were normal. Despite normal lung function, hypoxemia and/or DLCO reduction were observed in 17 of 178 patients (9.6%). A correlation with inflammatory activity, extent of fibrosis, or etiology was not found. Intrapulmonary shunting was observed in three of 17 patients. Two of these patients fulfilled the diagnostic criteria of HPS. Conclusions: Impaired gas exchange is a common finding even in non-cirrhotic patients with chronic viral hepatitis. HPS, however, was present in 1.1% of patients with chronic viral hepatitis and is thus not restricted to patients with liver cirrhosis, portal hypertension, or acute liver failure.     

Acetylcholine receptor ɛ-subunit deletion causes muscle weakness and atrophy in juvenile and adult mice

In mammalian muscle a postnatal switch in functional properties of neuromuscular transmission occurs when miniature end plate currents become shorter and the conductance and Ca²⁺ permeability of end plate channels increases. These changes are due to replacement during early neonatal development of the γ-subunit of the fetal acetylcholine receptor (AChR) by the -subunit. The long-term functional consequences of this switch for neuromuscular transmission and motor behavior of the animal remained elusive. We report that deletion of the -subunit gene caused in homozygous mutant mice the persistence of γ-subunit gene expression in juvenile and adult animals. Neuromuscular transmission in these animals is based on fetal type AChRs present in the end plate at reduced density. Impaired neuromuscular transmission, progressive muscle weakness, and atrophy caused premature death 2 to 3 months after birth. The results demonstrate that postnatal incorporation into the end plate of -subunit containing AChRs is essential for normal development of skeletal muscle.     

Activation of BDNF- and VEGF-mediated Neuroprotection by Treadmill Exercise Training in Experimental Stroke

Metabolic Brain Disease - Early treatment of ischemic stroke is one of the most effective ways to reduce brains’ cell death and promote functional recovery. This study was designed to examine...     

Idiopathic bone marrow dysplasia of unknown significance (IDUS): definition, pathogenesis, follow up, and prognosis

Minimal diagnostic criteria for myelodysplastic syndromes (MDS) include constant cytopenia recorded for at least 6 months, dysplasia, and exclusion of other causes of cytopenia and dysplasia. However, there are patients with dysplastic bone marrow features with or without a karyotype, who have only mild if any cytopenia. This condition has been termed idiopathic dysplasia of unknown significance (IDUS). Out of a series of 1,363 patients with suspected MDS or mild cytopenia seen between 1997 and 2010, we have identified 10 patients with IDUS, and analyzed their clinical course and outcome as well as features potentially involved in disease-evolution. Follow-up ranged between 2 and 13 years. Progression to an overt myeloid neoplasm was observed in 4 patients: two progressed to frank MDS, one to chronic myelomonocytic leukemia, and one to a myelodysplastic/myeloproliferative neoplasm exhibiting 5q-and JAK2 V617F. Consecutive studies revealed that most IDUS patients have an adequate production of erythropoietin (EPO) and sufficient numbers of EPO-responsive erythroid progenitors, features rarely seen in MDS. The erythropoiesis-promoting JAK2 mutation V617F was only detectable in one case. We hypothesize that the dysplastic clone in IDUS cannot manifest as frank MDS because i) the clone retains responsiveness against EPO, and ii) an adequate EPO-production counteracts anemia. Evolution of IDUS to low risk MDS may thus depend on the biological properties of the clone as well as patient-related factors such as EPO production. The latter often decreases with age and may thus explain why MDS often manifests in the elderly.     

Airway management and anesthesia in neonates, infants and children during endolaryngotracheal surgery

BACKGROUND: Endolaryngotracheal surgery in neonates, infants and children poses a big challenge for both anesthesiologist and surgeon. The narrowness of the airways and the great variability of the pathological lesions necessitate close collaboration between the surgical and the anesthesia team to provide optimal operating conditions and ensure adequate ventilation and oxygenation. METHODS: Sixty-two anesthetic records of endolaryngotracheal surgical procedures in neonates, infants and children with ASA physical status 1-3 were analyzed retrospectively. Anesthesia was administered as total intravenous anesthesia; propofol supplemented with remifentanil. Ventilation was performed as supraglottic, superimposed high-frequency jet ventilation via jet laryngoscope with integrated jet nozzles. RESULTS: Age was 58.93 (SD 35.40) months, range 3 weeks to 14 years; body weight 17.83 (SD 8.79) kg, range 2.4-50 kg. The capillary pCO(2) 5 min after the start of the surgical procedure (n = 62) was 40.01 (SD 7.71) mmHg and after 20 min (n = 24) 41.77 (SD 7.12) mmHg. No hypoxemia (oxygen saturation <90%) developed. All patients were hemodynamically stable during jet ventilation. Barotrauma or gas insufflation in the stomach did not occur. No perioperative tracheostomy was necessary. Laryngospasm occurred in one child during emergence from anesthesia. Four infants received postoperative conventional respirator therapy in the ICU overnight. CONCLUSIONS: Supraglottic superimposed high-/low-frequency jet ventilation via jet laryngoscopes with integrated jet nozzles is a minimally invasive ventilation technique for neonates, infants and children in endolaryngotracheal surgery, which allows an unimpaired operating field for the surgeon especially in LASER surgery.