Karl Reiter

Self-reported muscle pain in adolescents with migraine and tension-type headache

Aim: To identify possible associations between muscular pain and headache in adolescents in a large population-based sample. Methods: Grammar school students were invited to fill in a questionnaire on headache and associated lifestyle factors. Headache was classified according to the German version of the International Classification of Headache Disorders (2nd edition). Muscular pain was assessed via denoting affected areas in schematic drawings of a body and via provoked muscular pain on controlled movements of head, neck and shoulder regions. Results: Prevalence of any headache within the previous 6 months exceeded 80%. In all subjects muscular pain or pain on movement was most prominent in the neck and shoulder region, ranging from 9% to 27% in the non-headache population to up to 63% for individuals with migraine or mixed migraine and tension-type headache (TTH). Frequency of muscular pain increased significantly with growing chronicity of TTH. Interpretation: A strong association between muscle pain in the neck/shoulder region and headache was observed, pointing to the importance of muscular pain for headache in adolescents. Also, in this age group muscular pain appears to be of particular importance in chronic TTH and – unexpectedly – in migraine, which is the most important new finding in our study.

Therapeutic lung lavages in children and adults

BackgroundPulmonary alveolar proteinosis (PAP) is a rare disease, characterized by excessive intra-alveolar accumulation of surfactant lipids and proteins. Therapeutic whole lung lavages are currently the principle therapeutic option in adults. Not much is known on the kinetics of the wash out process, especially in children.MethodsIn 4 pediatric and 6 adult PAP patients 45 therapeutic half lung lavages were investigated retrospectively. Total protein, protein concentration and, in one child with a surfactant protein C mutation, aberrant pro-SP-C protein, were determined during wash out.ResultsThe removal of protein from the lungs followed an exponential decline and averaged for adult patients 2 – 20 g and <0.5 to 6 g for pediatric patients. The average protein concentration of consecutive portions was the same in all patient groups, however was elevated in pediatric patients when expressed per body weight. The amount of an aberrant pro-SP-C protein, which was present in one patient with a SP-C mutation, constantly decreased with ongoing lavage. Measuring the optical density of the lavage fluid obtained allowed to monitor the wash out process during the lavages at the bedside and to determine the termination of the lavage procedure at normal protein concentration.ConclusionFollowing therapeutic half lung lavages by biochemical variables may help to estimate the degree of alveolar filling with proteinaceous material and to improve the efficiency of the wash out, especially in children.

Pro/con clinical debate: Is high-volume hemofiltration beneficial in the treatment of septic shock?

Although there have been exciting advances in the management of sepsis and septic shock, mortality still remains high. Recent data suggest that high-volume hemofiltration (HVHF) may play a role in these patients. In contrast to the usual rate of hemofiltration, HVHF is felt to be better able to remove the inflammatory mediators associated with sepsis and septic shock. Such an approach is currently incapable of selectively removing specific mediators. This may be a problem when one considers that several mediators may in fact be beneficial. When determining whether HVHF should be instituted in a patient with septic shock, one need remember that its role is far from clear and its usefulness remains the subject of much debate. Although early data is encouraging, it is clear that additional data is required before HVHF becomes standard management. The authors of this pro/con debate, which is based on a clinical scenario, first describe their own position and then respond to their opponents position.

Risk Factors for Morbidity and Mortality in Pediatric Home Mechanical Ventilation

Background: Home mechanical ventilation (HMV) is increasingly used in children with chronic respiratory insufficiency, but data on incidence and type of adverse events are limited. Setting: Pediatric HMV program at a tertiary university hospital. Methods: The authors retrospectively analyzed the type and incidence of severe emergencies in a mixed pediatric HMV program. Results: In all, 295 patient-years of HMV in 54 patients could be analyzed. A total of 26 patients had neuromuscular disease. In 16 patients, mechanical ventilation was initiated at <1 year of age. A total of 45 children were ventilated via tracheostomy and 9 by nasal mask. This study identified 68 severe emergencies (0.2 per patient-year) leading to 4 deaths. Respiratory causes were found in 48 cases (including 15 tracheostomy-related and 3 ventilator failures). Only age, but not underlying diagnosis or mode of ventilation, correlated with incidence of emergencies. Conclusions: Pediatric HMV including all age and diagnostic groups shows a low incidence of emergencies.

Long-term follow-up and treatment of congenital alveolar proteinosis

BackgroundClinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to mutations in the GM-CSF receptor are not well known.Case presentationA 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child.ConclusionsThe long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.

Whole‐lung lavage in infants and children with pulmonary alveolar proteinosis

Background:  Pulmonary alveolar proteinosis (PAP) is a rare alveolar filling syndrome where the mainstay of treatment is therapeutic whole‐lung lavage (WLL). WLL techniques used in adults have to be modified for children because of their small‐diameter airways.

In vitro removal of therapeutic drugs with a novel adsorbent system

Background/Aim: Substances in the middle molecular weight range have been shown to play a significant pathogenetic role in as diverse disorders as end-stage renal disease and multiple organ failure. To overcome the limitations in the amount removed by hemofilters, new sorbents with a high biocompatibility are actively being developed. Furthermore, biocompatible sorbents by their nonspecific adsorptive behavior could have great impact on detoxification treatment in exogenous intoxications. We performed an in vitro evaluation of a newly developed highly biocompatible sorbent cartridge (Betasorb®), examining its adsorptive capacity concerning therapeutic drugs. Methods: Uremic blood spiked with a range of therapeutic drugs was recirculated for 2 h in an in vitro hemoperfusion circuit containing a Betasorb device for hemoperfusion. The drug concentrations before and after the passage of the cartridge were measured, and the total amount removed was calculated. Results: The sorbent showed effective removal of glycopeptide antibiotics, digoxin, theophylline, phenobarbital, phenytoin, carbamazepine, and valproic acid. Moderate removal could be demonstrated for tacrolimus and cyclosporine A; aminoglycosides were removed to a small extent only. Conclusions: Betasorb hemoperfusion shows a potent adsorptive capacity concerning therapeutic drugs (except aminoglycosides) and could be of major value in the treatment of intoxications. On the other hand, drug monitoring and possible adjustments are necessary during Betasorb hemoperfusion to maintain the therapeutic ranges of the drugs in blood.

Polyomaviruses KI and WU in children with respiratory tract infection

The polyomaviruses KI (KIPyV) and WU (WUPyV) have recently been discovered in specimens from patients with respiratory tract infections. To analyze the frequency and clinical impact in a cohort of pediatric patients in a German University Children’s Hospital. Nasopharyngeal aspirates or bronchoalveolar lavage specimens of 229 children with acute respiratory tract infection were screened for KIPyV and WUPyV using polymerase chain reaction-based methods. KIPyV was detected in 2 (0.9%) and WUPyV in 1 (0.4%) patients, without co-infections with other respiratory viruses but with co-detection of CMV, EBV and HHV 6 in one immunocompromised patient. Only a very small proportion (1.3%) of positive samples for KIPyV and WUPyV was documented in this study; the clinical relevance of these viruses remains unclear and requires further evaluation.

Characterization of CSF2RA mutation related juvenile pulmonary alveolar proteinosis.

BackgroundJuvenile pulmonary alveolar proteinosis (PAP) due to CSF2RA mutations is a rare disorder with only a few cases described worldwide.MethodsWe identified nine children with severe diffuse interstitial lung disease due to CSF2RA mutations. Clinical course, diagnostic findings and treatment were evaluated and correlated to the genotype. Functional impairment of the intracellular JAK/pStat5 signaling pathway was assessed using flow-cytometry of peripheral mononuclear cells (PBMC) and granulocytes.ResultsWe identified six individuals with homozygous missense/nonsense/frameshift mutations and three individuals homozygous for a deletion of the complete CSF2RA gene locus. Overall, four novel mutations (c.1125 + 1G > A, duplication exon 8, deletion exons 2–13, Xp22.3/Yp11.3) were found. Reduced STAT5 phosphorylation in PBMC and granulocytes was seen in all cases examined (n = 6). Pulmonary symptoms varied from respiratory distress to clinically silent. Early disease onset was associated with a more severe clinical phenotype (p = 0.0092). No association was seen between severity of phenotype at presentation and future clinical course or extent of genetic damage. The clinical course was favorable in all subjects undergoing whole lung lavage (WLL) treatment.ConclusionsOur cohort broadens the spectrum of knowledge about the clinical variability and genotype-phenotype correlations of juvenile PAP, and illustrates the favorable outcome of WLL treatment in severely affected patients.

High Volume Hemofiltration in Sepsis

Continuous renal replacement therapy (CRRT) in the ICU is a common treatment in acute renal failure (ARF). CRRT is mainly conceived as merely supportive and as a replacement of the lost kidney function. On the other hand, evidence accumulating over the last years demonstrates that many soluble mediators of the systemic inflammatory (and anti-inflammatory) response syndrome can be removed by CRRT. This has led to the suggestion that CRRT could play a major role in sepsis therapy as immunomodulatory treatment and not only as a blood purification technique. In this perspective, whereas animals studies yielded encouraging results, early clinical trials only showed minor clinical benefits, mainly dealing with hemodynamic improvements. The question of treatment dose has appropriately been raised which still has to be defined and it represents a matter of controversy. A large-scale clinical trial has clarified issues on treatment dose in ARF, but a sufficiently powered study on hemofiltration dose in sepsis is still lacking. In this article we will review the rationale for application of CRRT in treatment of the septic syndrome with specific focus on the use of high ultrafiltration rates (i.e. high-volume hemofiltration: HVHF). We will integrate the discussion into the most recent hypothesis proposed to explain some of the clinical results obtained with high efficiency non-selective removal of mediators of sepsis. Further, we will describe the necessary technical requirements for HVHF and the most recent machine development concurring with these.