Sildenafil in pediatric pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.KEY WORDS: Child, phosphodiesterase (PDE)-5 inhibitor, Pulmonary hypertension therapy     

Gonadal hormone levels and platelet tryptophan and serotonin concentrations in perimenopausal women with or without depressive symptoms

Introduction: The etiology of depressive symptoms associated with the transition to menopause is still unknown; hormonal changes, serotonergic system or insomnia, could be a trigger to depressive symptomatology. The aim of the present study was to evaluate gonadal hormonal levels, platelet serotonin concentrations and platelet tryptophan concentrations in a group of depressed perimenopausal women and their healthy counterparts.

Methods: A total of 63 perimenopausal women between 45 and 55 years old were evaluated; of these, 44 were depressed patients, and 19 were perimenopausal women without depression. The instruments that were applied included the Center for Epidemiologic Studies Depression Scale (CES-D), the Hamilton Depression Rating Scale (HDRS) and the Green Climacteric Scale (GCS); gonadal hormone levels and platelet tryptophan and serotonin concentrations were measured in all participants. Differences in hormonal levels and tryptophan and serotonin concentrations were evaluated with respect to specific symptoms, such as insomnia, hot flashes, nervousness, depressed mood and loss of interest.

Results: No differences between groups were observed with respect to hormonal levels and tryptophan and serotonin concentrations; mean sleep hours and insomnia were significantly correlated with platelet tryptophan concentrations.

Conclusions: In this sample, all symptoms of depression could not be explained by platelet tryptophan and serotonin concentrations and hormonal levels; differences were observed only when we evaluated insomnia and hot flashes.     

Growth of the human septal cartilage: cell density and colony formation of septal chondrocytes

Human chondrocytes from 24 patients (5 to 52 years) with septal deviation were isolated in different areas of the septal cartilage. Cell density was counted, and the chondrocytes were grown in an assay system for determining the number of chondrocytes capable of proliferating. High cell density and excellent proliferative capacity were found in the anterior free end of the septal cartilage in all age groups. The central area showed the highest growth index in childhood, and increasing cell density from childhood to puberty. Generally the growth index decreased with age in all septal areas. The results help to explain some clinical observations: increasing septal cartilage even in adults, growth of nasal tip in adults, regenerative potential of septal cartilage after injuries or surgery, importance of the central area for septal growth and surgery.     

Heme arginate improves reperfusion patterns after ischemia: a randomized, placebo-controlled trial in healthy male subjects

Background

Heme arginate can induce heme oxygenase-1 to protect tissue against ischemia-reperfusion injury. Blood oxygen level dependent (BOLD) functional magnetic resonance imaging measures changes in tissue oxygenation with a high spatial and temporal resolution. BOLD imaging was applied to test the effect of heme arginate on experimental ischemia reperfusion injury in the calf muscles.

Methods

A two period, controlled, observer blinded, crossover trial was performed in 12 healthy male subjects. Heme arginate (1 mg/kg body weight) or placebo were infused 24 h prior to a 20 min leg ischemia induced by a thigh cuff. 3 Tesla BOLD-imaging of the calf was performed and signal time courses from soleus, gastrocnemius and tibialis anterior muscle were available from 11 participants for technical reasons.

Results

Peak reactive hyperemia signal of the musculature was significantly increased and occurred earlier after heme arginate compared to placebo (106.2±0.6% at 175±16s vs. 104.5±0.6% at 221±19s; p = 0.025 for peak reperfusion and p = 0.012 for time to peak).

Conclusions

A single high dose of heme arginate improves reperfusion patterns during ischemia reperfusion injury in humans. BOLD sensitive, functional MRI is applicable for the assessment of experimental ischemia reperfusion injury in skeletal muscle.

Trial registration

ClinicalTrials: {"type":"clinical-trial","attrs":{"text":"NCT01461512","term_id":"NCT01461512"}}NCT01461512EudraCT: 2008-006967-35     

Kopfschmerz durch Liquordrucksteigerung

Increased cerebrospinal fluid (CSF) pressure is often accompanied by headache. The term idiopathic intracranial hypertension (pseudotumor cerebri) describes an increase in CSF pressure without a space-occupying intracranial lesion or hydrocephalus. After headaches, visual field defects are the second most common feature. Therapeutic measures include both drugs and surgical procedures. In high-pressure hydrocephalus, the volume of the CSF is increased, resulting either from increased production or reduced absorption. If an acquired or congenital obstruction of the ventricular system can be demonstrated, the term non-communicating hydrocephalus is used. In contrast, the CSF passage is blocked outside the ventricles in communicating hydrocephalus. Symptoms include diffuse headache worsening in the morning and with the Valsalva-like maneuver. Treatment is guided by etiology whenever possible; otherwise, drainage of CSF by ventriculostomy or shunt is necessary.     

Verschiedenartige Kopfschmerzformen des Kapitels?4 der Internationalen Kopfschmerzklassifikation

Chapter 4 of the International Classification of Headaches contains a group of clinically very heterogeneous primary headache forms. Little is known about the pathogenesis of these headache types and therapy is usually based on isolated case reports and uncontrolled studies. The forms include primary stabbing headache, primary cough headache, primary exertional headache, primary headache associated with sexual activity, hypnic headache, primary thunderclap headache, hemicrania continua and the new daily persistent headache. Some of these headache forms may be of a symptomatic nature and require careful examination, imaging and further tests. Primary and secondary headache forms must be carefully distinguished.     

Aging and reproduction in social insects--a mini-review

Perennial social insects are characterized by the extraordinarily long lifespan of their reproductive females, which may be tens or hundreds of times larger than that of non-social insects of similar body size and also greatly surpasses that of conspecific non-reproductives. Evolutionary theories of aging explain this phenomenon from the low extrinsic mortality queens experience once they have successfully established their colony. The aim of our review is to summarize recent findings on the ultimate and proximate causes of increased queen longevity in social insects, in particular ants and honey bees. While progress is being made in elucidating the interrelations between the vitellogenin, juvenile hormone, fecundity, and senescence, we feel that the explanation for the comparatively short lifespan of queens in multi-queen societies is as yet not satisfactory and needs further attention, both concerning its proximate and ultimate basis.     

Differential expression of genes encoding tight junction proteins in colorectal cancer: frequent dysregulation of claudin-1, -8 and -12

Background and aims As integral membrane proteins, claudins form tight junctions together with occludin. Several claudins were shown to be up-regulated in various cancer types. We performed an expression analysis of genes encoding tight junction proteins to display differential gene expression on RNA and protein level and to identify and validate potential targets for colorectal cancer (CRC) therapy. Patients and methods Amplified and biotinylated cRNA from 30 microdissected CRC specimen and corresponding normal tissues was hybridized to Affymetrix U133set GeneChips. Quantification of differential protein expression of claudin-1, -8 and -12 between normal and corresponding tumour tissues was performed by Western blot analyses. Paraffin-embedded CRC tissue samples, colon cancer cell lines and normal tissue microarray were analysed for protein expression of claudin-1 by immunohistochemistry (IHC). Results Claudin-1 (CLDN1) and -12 (CLDN12) are frequently overexpressed in CRC, whereas claudin-8 (CLDN8) shows down-regulation in tumour tissue on RNA level. Quantification of proteins confirmed the overexpression of claudin-1 in tumour tissues, whereas changes of claudin-8 and -12 were not significantly detectable on protein level. IHC confirmed the markedly elevated expression level of claudin-1 in the majority of CRC, showing membranous and intracellular vesicular staining. Conclusions Differential expression of genes encoding claudins in CRC suggests that these tight junction proteins may be associated to and involved in tumorigenesis. CLDN1 is frequently up-regulated in large proportion of CRC and may represent potential target molecule for blocking studies in CRC.     

Sturzprävention bei Menschen mit Demenzerkrankungen

Elderly persons suffering dementia are at increased risk for falls. Because of this, an investigation of the state of the science and the state of the art in fall prevention in patients suffering dementia has been made. A systematic literature review showed lack of documentation of effective interventions in preventing falls in persons with cognitive impairment. This was the reason for studying which measures nurses undertake in the field of long-term-care. Focus-group interviews with experienced geriatric nurses were undertaken. Nurses assume that there are specific risk factors in this patient group which have to be taken into account. Cognitive deficits are causing an increased fall risk in a specific manner. Geriatric nurses have ideas about how to adapt interventions for persons with dementia. They also assume that interventions primarily addressing cognitive disorders may also reduce the risk of falling. The interventions mentioned by the interviewed experts have not yet been examined concerning their effectiveness, therefore, fall prevention for people with dementia has to be further differentiated and systemized on a scientific basis.