H. von der Hardt

Necrotising enterocolitis: is there a relationship to specific pathogens?

Abstract Outbreaks of necrotising enterocolitis (NEC) have often been related to specific pathogens such as Enterobacteriaceae. This relationship, however, remains uncertain because of the retrospective nature of the studies addressing this issue. We performed a prospective study to investigate whether there is indeed an association between NEC and specific pathogens. Between April 1993 and March 1997, stools of neonates of <36 weeks admitted to our neonatal unit were investigated for bacteria in weekly intervals. Clinical and bacteriological data from each infant who developed NEC were compared with those from two control infants matched for gestational age and date of admission. Eighteen infants developed 19 episodes of NEC (clinical signs + air in portal vein); 8 of these had laparotomy; two died. Occurences of NEC were homogeneously distributed over the 4- year study period. The only significant differences in the clinical course prior to NEC were a more severe stage of respiratory distress syndrome [median 2 (0–4) vs. 0 (0–3), P < 0.05] and a higher proportion of infants who had only been formula fed (63 vs. 32%, P < 0.05) in the cases. Within the last week prior to NEC, potentially pathogenic bacteria were identified in stools of all cases and 79% of controls (P < 0.05). However, there was no significant difference in the occurrence of specific pathogens or groups of pathogens in cases compared with controls. Conclusion Although gut colonisation with potential pathogens appeared to be a prerequisite for the development of NEC, there were no specific bacteria associated with this disease if data from infants with NEC were compared with those from time- and gestational age-matched controls.

LONG-TERM FOLLOW UP OF CHANGES IN FEV1 AND TREATMENT INTENSITY DURING PSEUDOMONAS AERUGINOSA COLONISATION IN PATIENTS WITH CYSTIC FIBROSIS

BACKGROUND Colonisation with Pseudomonas aeruginosa (PA) is a striking feature of lung involvement in cystic fibrosis. To identify the clinical consequences of the different steps of colonisation with PA under a defined therapeutic regime (no prophylactic antibiotic treatment as long as patients had no severe pulmonary disease), their influence on pulmonary function and on therapeutic intensity was examined. METHODS Forty patients with cystic fibrosis were followed from first detection of PA (PA1), chronic PA colonisation (PAc), first mucoid PA detection (PAm), to chronic mucoid PA colonisation (PAcm). Percentage predicted forced expiratory volume in one second (FEV1), the number of intravenous antibiotic treatment courses, and the percentage of patients on inhaled antibiotics were followed retrospectively and longitudinally in relation to the different steps of PA colonisation. The annual changes in FEV1 and therapeutic intensity in the two years preceding each step were compared with the two years following each step. Changes in FEV1 were related to therapeutic intensity. RESULTS The mean (SD) annual changes in FEV1 (% predicted) worsened significantly only with the transition to the mucoid stages (PAm: 4.6 (13.2) versus –4.3 (8.1); PAcm: 7.3 (12.0) versus –4.8 (7.4)) with a mean difference (95% CI) between before and after the transition of 8.9 (2.6 to 15.2) for PAm and 12.1 (6.4 to 17.6) for PAcm. With non-mucoid PA stages the therapeutic intensity increased in the year of transition and with mucoid PA stages it increased in the years following transition. Therapeutic intensity was unrelated to changes in FEV1. CONCLUSION With the treatment regime used an accelerated decrease in FEV1 was successfully prevented in the non-mucoid stages but not in the mucoid stages of PA colonisation.

DNA concentration and length in sputum of patients with cystic fibrosis during inhalation with recombinant human DNase.

BACKGROUND--The clinical benefit of the administration of aerosolised recombinant human DNase (rhDNase) on pulmonary function in patients with cystic fibrosis has already been demonstrated but the biochemical action of rhDNase on DNA in bronchial secretions in vivo has not yet been investigated. METHODS--Sputum was collected from 135 patients with cystic fibrosis before and during treatment with aerosolised rhDNase and examined to ascertain DNA concentration and length by colorimetric assay and densitometry of gel separated DNA. RESULTS--Treatment with rhDNase reduced the concentration and the size of extracellular DNA in the sputum. The median interquartile range of DNA length decreased from 0.5-2.6 kbp before treatment to 0.3-1.0 kbp during treatment. CONCLUSIONS--rhDNase was delivered to the secretions and was enzymatically active in vivo.

Buccal Adherence of Pseudomonas aeruginosa in Patients with Cystic Fibrosis under Long-Term Therapy with Azithromycin

AbstractBackground: The oropharyngeal barrier is an innate host defence mechanism to prevent bacterial lung infection. A compromised barrier function is observed in patients with cystic fibrosis (CF) who are chronically infected with Pseudomonas aeruginosa. Macrolides are assumed to modify host defence. We investigated the oropharyngeal barrier function in CF patients treated with azithromycin (AZM). Patients and Methods: In a prospective study, eleven chronically infected children with CF were treated with long-term low-dose AZM. The oropharyngeal barrier function was assessed by adherence of P. aeruginosa (strain PACF 12-1) to buccal epithelial cells of the patients before and after therapy. Results: The mean (standard deviation, SD) buccal adherence before therapy was markedly high with 8.0 (4.8) bacteria/cell. Following therapy with AZM adherence decreased in all patients by 70% or 5.6 to 2.4 (1.1) bacteria/cell (p = 0.007), representing close to normal levels (1.2 ± 0.6). Conclusion: Long-term low-dose AZM therapy may improve the compromised oropharyngeal barrier function in patients with CF, opening new perspectives for early treatment of P. aeruginosa infection in CF.

Die Chirurgie der erworbenen laryngotrachealen Stenosen im Kindesalter. Erfahrungen und Ergebnisse von 1988 bis 1998 Teil I: Die Laryngotracheale Rekonstruktion

ZusammenfassungSubglottische, laryngotracheale Stenosen stellen die schwerste Form eines Intubationsschadens dar, der auch bei Kindern in zunehmender Häufigkeit als Folge intensivmedizinischer Behandlung mit Langzeitbeatmung beobachtet wird. Da über 90% der betroffenen Kinder tracheotomiert werden müssen, ist ihre körperliche, sprachliche und psycho-soziale Entwicklung hochgradig beeinträchtigt. Die Tracheotomie bei Kleinkindern muß als potentiell lebensbedrohlicher Zustand angesehen werden, so daß die operative Beseitigung der laryngotrachealen Stenose und des Tracheostomas zum frühestmöglichen Zeitpunkt anzustreben ist. Während der vergangenen 10 Jahre betreuten wir 46 Kinder mit laryngotrachealen Problemen, von denen 18 Kinder unter einer schweren laryngotrachealen Stenose litten. 10 Kinder – 3 mit einer Stenose Grad II, 7 mit einer Stenose Grad III – wurden nach der von Cotton angegebenen Methode, der laryngotrachealen Rekonstruktion mit vorderem Rippenknorpeltransplantat, operiert. Bei einem Kind mit zusätzlicher posteriorer Glottisstenose wurde eine Laminotomie mit dorsaler und anteriorer Knorpelimplantation durchgeführt. Abweichend von der Originalmethode, wurden die von uns operierten Kinder postoperativ mit einem Montgomery-T-Tube versorgt. Nach durchschnittlich 10 Monaten konnte der Stent entfernt werden. Sämtliche Kinder sind voll rehabilitiert, ihr Stoma ist verschlossen; 4 der Kinder wurden bereits vorher alio loco erfolglos nach einer anderen Technik operiert; 2 Kinder erwiesen sich auch bei uns zunächst als Therapieversager, konnten aber mit einem 2., gleichartigen Eingriff – der für eins der Kinder die 4. Operation bedeutete – erfolgreich behandelt werden. Die Gründe für die von uns gewählte Modifikation, das operative Vorgehen, sowie postoperative Verhaltensregeln mit Aufzeichnung drohender Komplikationen werden dargestellt.SummarySubglottic laryngotracheal stenosis represents the most severe intubation injury and is increasingly encountered in children due to long-term ventilation during intensive care treatment. Since more than 90% of these children have tracheostomies their physical, psychosocial and speech development can be greatly impaired. A tracheostomy in infants can also be a potentially life-threatening condition, making necessary resolution of the laryngotracheal stenosis and removal of the tracheostoma as soon as possible. During the past 10 years, we have treated 46 children with laryngotracheal problems, including 18 children with severe laryngotracheal stenosis. Ten children (3 with grade II stenosis and 7 with grade III stenosis) were treated by laryngotracheal reconstruction using an anterior rib cartilage graft as described by Cotton. One child with posterior glottic stenosis required a posterior laminotomy with a second rib cartilage graft. Differing from the original method, we stabilized the enlarged endotracheal lumen postoperatively with a Montgomery t-tube. This was kept in place for 10 months on average (shortest period, 6 months; longest period, 12 months). All 10 children could be decannulated, and the tracheostoma closed. Three of the children were operated in other institutions and had a different technique prior to our intervention. Two of our operations failed initially. However, both patients were treated successfully by a second intervention (which was the fourth operation for one of the patients). The reasons for our modification, the operative technique and tips for postoperative management, as well as possible pitfalls and complications, are discussed.

Die Chirurgie der erworbenen laryngotrachealen Stenosen im Kindesalter. Erfahrungen und Ergebnisse von 1988–1998 Teil II: Die cricotracheale Resektion

ZusammenfassungKinder mit schweren, erworbenen subglottischen laryngotrachealen Stenosen sind zu 90% tracheotomiert und daher in ihrer körperlichen und sprachlichen Entwicklung beeinträchtigt. Zusätzlich sind mit einer Trachealkanüle versorgte Kinder, insbesondere Kleinkinder, gefährdet, so daß die chirurgische Beseitigung der Stenose dringend geboten ist. Wir haben innerhalb der vergangenen 10 Jahre 18 Kinder mit einer schweren subglottischen laryngotrachealen Stenose operiert; 10 Kinder, über die kürzlich berichtet wurde, konnten mit der modifizierten Cotton-Technik erfolgreich dekanüliert werden. Über 8 Kinder (Alter 7 Monate bis 15 Jahre, 4mal Stenose II. Grades, 3mal Stenose III. Grades, einmal Stenose IV. Grades), die wir mit cricotrachealer Resektion (CTR) und thyrotrachealer Anastomose operierten, wird in der vorliegenden Arbeit berichtet. 3 Kinder waren anderenorts bereits tracheotomiert. Da die Stomata zu weit kaudal lagen, konnten sie nicht in die Resektion einbezogen werden. Alle 8 Kinder konnten inzwischen dekanüliert werden und sind beschwerdefrei: Die 5 nicht tracheotomierten Kinder konnten problemlos am 5. postoperativen Tag extubiert werden. Die zuvor tracheotomierten Kinder konnten erst nach endotrachealer Schienung (2mal nach zusätzlicher Trachealplastik mit Rippenknorpel bei suprastomaler Tracheomalazie) dekanüliert werden. Bei keinem der Kinder trat eine Recurrensparese auf. Die Stimme bei allen Kindern ist unbeeinträchtigt. Die CTR, über die bei kindlichen laryngotrachealen Stenosen mit dieser Arbeit in der Literatur zum 3. Mal berichtet wird, ist eine sehr effektive, einzeitige, komplikationsarme Operationsmethode, deren Resultate für Atmung und Stimme günstiger sind, als mit der Erweiterungsplastik nach Cotton.SummaryApproximately 90% of infants and children with severe acquired laryngotracheal stenoses are tracheotomy dependent and therefore impaired in their physical and speech developments. In addition, tracheotomized infants can be endangered by the cannula due to the possible crusting of secretions or its dislocation. Thus, early repair of a stenosis is mandatory. Within the last 10 years, we successfully operated on 18 children with severe laryngotracheal stenoses. Ten children were treated with a modified Cotton technique. This paper reports our results of cricotracheal resection performed in 8 children since 1994 (age distribution: 7 months through age 15 years). Four children had Cotton grade II stenoses, three had grade III stenoses and one grade IV stenoses. In 3 patients a tracheotomy had been performed at another institution. Since their tracheostomas were too far caudal, they could not be included in the primary resection. All 8 children have been successfully decannulated. Five children without tracheotomies could be extubated uneventfully on the 5th postoperative day. All three primarily tracheotomized children needed further endotracheal stenting with T-tubes because of stomal and suprastomal collapse. Two of these latter children additionally required a tracheoplasty with rib cartilage grafts in order to stabilize the suprastomal trachea prior to decannulation. No patient experienced injuries to the recurrent laryngeal nerves or insufficiencies of the anastomosis. All children’s voices were not impaired. This is the third report in literature of cricotracheal resections in infants and children, indicating that this effective, one-stage procedure is superior to laryngotracheal reconstruction with rib cartilage.

Atypical spondyloarthritis in children: proposed diagnostic criteria

Clinical and laboratory findings in 26 children with atypical spondyloarthritis were compared with those of 76 children with juvenile rheumatoid arthritis. The sensitivity, specificity, predictive value, and efficiency for diagnosis were calculated. The following findings (major criteria) were much more common in atypical spondyloarthritis than in juvenile rheumatoid arthritis: (1) spondyloarthritis within the family; (2) enthesopathy; (3) arthritis of digital joints; (4) sacro-iliitis; (5) presence of HLA-B27; (6) frequent recurrence of arthritis and arthalgia. Six additional findings (minor criteria) were significantly more common in atypical spondyloarthritis (SA): (1) disease onset after the age of 10 years; (2) male sex; (3) involvement of the lower extremities; (4) acute iridocyclitis or conjunctivitis; (5) arthritis of the hip joints; (6) manifestation following a history of enteritis. In the presence of 4 major criteria or 3 major and 3 minor criteria, the diagnosis of an atypical SA was established with a sensitivity of 84.6%, a specificity of 100%, and an efficiency of 96.1%.

Generation and Metabolism of Leukotrienes in Granulocytes of Patients with Cystic Fibrosis

We studied the generation and metabolism of lipoxygenase products in peripheral granulocytes from children suffering from cystic fibrosis (CF). Peripheral granulocytes were stimulated at different times (days) before and during anti-infectious treatment with the Ca ionophore (7.5 microM, 5 and 20 min), opsonized zymosan (2 mg) and arachidonic acid (50 microM); the amount of lipoxygenase products in the cell supernatants was determined by high performance liquid chromatography. Granulocytes from patients with CF, compared to an age-matched control group, showed an increased omega-oxidation of the synthesized leukotriene (LTB4) into 20-OH- and 20-COOH-LTB4 after stimulation with the Ca ionophore (ratio of LTB4 versus omega-oxidated products in patients with CF: 0.77 +/- 0.07, mean +/- SEM, n = 11; control group: 1.07 +/- 0.1, n = 11, p less than 0.01) whereas the combined amounts of LTB4 and its omega-oxidated products did not differ significantly. A comparable profile was observed with opsonized zymosan. Stimulation of the cells with the Ca ionophore combined with arachidonic acid led to a significantly increased formation of lipoxygenase products in the patient group, whereas only a slight enhancement was observed in the control group. During the 14-day anti-infectious treatment a normalization of the altered pattern was observed. 12-Hydroxyeicosatetraenoic acid (12-HETE) production from platelets within the granulocyte fraction was significantly depressed in the CF group compared to the controls (38.5 +/- 12.5 versus 339 +/- 93 ng/5 +/- 10(6) cells, p less than 0.005). Within the CF group a strong correlation between the release of LTB4 and its metabolites, the production of 12-HETE and clinical (e.g. pO2, FEV1) and laboratory findings (e.g. IgE and IgG levels, C-reactive protein) was established. Our data suggest that the inflammatory process in patients with CF is associated with an alteration of the lipoxygenase pathway of granulocytes which correlates with the clinical signs of inflammation.

Mukoviszidose Auch eine Erkrankung des Erwachsenenalters

Zum ThemaDie Mukoviszidose gehört zu den monogenetischen Erbkrankheiten mit autosomal-rezessivem Erbgang, hat eine vergleichsweise hohe Inzidenz von 1:2500 Neugeborene, besonders in der kaukasischen Bevölkerung, und zeichnet sich durch eine Vielfalt von Symptomen aus. Diese haben ihre gemeinsame Ursache in einer mehr oder weniger ausgeprägten Dysfunktion der Chloridkanäle sezernierender Epithelien mit der Folge von eingedicktem und viskösem Sekret. In den vergangen 10 Jahren seit der Identifizierung des CFTR-Gens (Cystic Fibrosis Transmembrane Conductance Regulatory) sind nicht weniger als 800 verschiedene Genmutanten entdeckt worden.Die klinische Symptomatik ist vor allem durch den betroffenen Respirations- und Gastrointestinaltrakt geprägt, des weiteren sind als Folge der Mukoviszidose ca. 95% erkrankter Männer und ca. 20% erkrankter Frauen infertil.War früher die Lebenserwartung auf das Kindesalter begrenzt und vor kurzem noch auf ca. 20–21 Jahre, geht man heute davon aus, daß bei optimaler Betreuung ca. 80% der Betroffenen die Chance haben, das 45. Lebensjahr zu erreichen. Somit wird die ursprüngliche Kinderkrankheit zur einer Erkrankung des Erwachsenenalters. Über Ätiologie, Pathogenese, Diagnostik, Klinik und Therapie wird an dieser Stelle ein Überblick gegeben. Ausdrücklich sei auf mehrere Internet-Adressen, über die man Kontakt zu entsprechenden Betreuungszentren aufnehmen sowie den letzten Stand der Mutationen finden kann, hingewiesen.

Erwachsene mit Mukoviszidose

ZusammenfassungWie bei kaum einem anderen Krankheitsbild konnte bei der Mukoviszidose (CF) durch medizinische Fortschritte und eine in den Lebensalltag der Betroffenen integrierte Dauertherapie eine beachtliche Verbesserung der Lebenszeit erreicht werden. Die einst als tödliche Krankheit des Kindesalters bekannte CF ist längst in der Erwachsenenmedizin angekommen: Seit 2009 sind Erwachsene mit CF im deutschen CF-Register erstmals in der Mehrheit. Die Schattenseite sind einerseits Spätkomplikationen (zum Beispiel Diabetes, Osteoporose), die man früher wegen des frühen Versterbens der Patienten wenig kannte. Zunehmend bedeutsam werden schädliche Auswirkungen der inzwischen über Jahrzehnte reichenden Therapien. Diese Therapiefolgen müssen ebenso wie die kontinuierlich gestiegene Therapiebelastung der Patienten und ihrer Angehörigen zukünftig sorgfältiger gegen den erhofften Behandlungsgewinn abgewogen werden. Dass nicht das reine Überleben, sondern das subjektiv lohnende Leben Ziel der medizinischen Bemühungen sein muss, hat in der CF-Medizin eine lange Tradition. Hier stellt die spektakuläre Verbesserung der Überlebenszeit eine enorme psychosoziale Herausforderung dar. Die verfügbaren Daten sprechen dafür, dass die Mehrzahl der Betroffenen trotz progredient schlechterer Gesundheit um jeden Zentimeter Normalität ringt.AbstractCystic fibrosis (CF) is one example of serious disorders for which medical progress and the integration of chronic treatment into the patients’ daily routines have led to markedly better longevity. Formerly known as a ‘killer disease’ of childhood, CF is now considered a disorder with childhood onset, but is well known in adult medicine. Since 2009, for the first time CF adults have made up the majority of patients in the German CF registry. The drawbacks of improved longevity are long-term complications (e.g., CFRD, osteoporosis) that were rarely seen before. In particular, unwanted effects of treatments that today are performed for decades rather than years are becoming pressing problems. Unwanted effects as well as the ever-increasing treatment burden must be carefully weighed against the expected benefits of treatment. However, CF medicine has always been aware that it is not just about longevity, but that prolonged life has to have meaning. Therefore, the marked increase in longevity is also a psychosocial challenge. So far, empirical data suggest that the majority of people with CF courageously struggle for a normal life.