Frühe Gefäßveränderungen bei adipösen Kindern

ZusammenfassungHintergrund   Die Adipositas führt über die Ausprägung atherogener Risikofaktoren (RF) zu einem deutlich erhöhten kardiovaskulären Risiko. Mittels hoch auflösender Sonographie lassen sich frühzeitig Gefäßveränderungen im Sinne einer eingeschränkten Endothelfunktion (FMD) und einer erhöhten Intima-Media-Dicke (IMT) der A. carotis nachweisen. Es wurde geprüft, ob bei adipösen Kindern bereits erste Gefäßveränderungen vorliegen und welchen Einfluss das kardiovaskuläre Risikoprofil auf den Gefäßstatus hat.Methode   Untersucht wurden 54 adipöse (Body-Mass-Index, BMI>97. Perzentile) und 55 normalgewichtige Kinder im Alter zwischen 8 und 16 Jahren hinsichtlich eines erweiterten RF-Profils und sonographisch nachweisbarer Gefäßveränderungen (FMD, IMT).Ergebnisse   Die Adipositasgruppe zeigte eine hochsignifikant verminderte FMD (4,96±2,8%, p=0,001) und vermehrte IMT (0,55±0,12 mm, p<0,001) im Vergleich zur Kontrollgruppe (FMD=10,2±3,1%, IMT=0,43±0,06 mm). Zusätzlich konnten viele signifikant erhöhte RF bei adipösen Kindern nachgewiesen werden. In einer multivariaten Analyse erwiesen sich ein BMI >30 kg/m², ein Körperfettgehalt >30%, das Vorliegen einer arteriellen Hypertonie, Insulinspiegel >10 pmol/l, Fibrinogen >3,5 g/l, Triglyzeride >1,2 mmol/l und eine reduzierte körperliche Fitness als unabhängige RF für das Auftreten früher Gefäßveränderungen.Diskussion   Bereits bei adipösen Kindern und Jugendlichen lassen sich neben einem pathologischen atherogenen Risikoprofil frühe Gefäßveränderungen feststellen. Das Ausmaß der Adipositas, ein arterieller Hypertonus, eine verminderte körperliche Fitness sowie erhöhte Serumspiegel für Insulin, Triglyzeride und Fibrinogen bestimmen dabei das Risiko für die frühe Entwicklung der Atherosklerose. Die beschriebenen Parameter und Gefäßuntersuchungen scheinen geeignete Marker für eine Risikoabschätzung und ein Therapiemonitoring bei adipösen Kindern zu sein.Die Studie wurde durch das Forschungsförderungsprogramm der Universität Rostock (FORUN2004) unterstützt     

Cutaneous larva migrans in northern Germany

We report a 14-month-old female infant with typical cutaneous larva migrans, but without a history of travelling outside Germany. Cutaneous larva migrans is most commonly observed in and imported from tropical countries. Only a few cases have been described in northern Europe. This report serves as a reminder that under certain circumstances acquisition of this “tropical” parasite is possible even in non-tropical countries.     

Regulation of immunomodulatory functions by granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in vivo

 The present study was designed to investigate in vivo immunomodulatory properties of hematopoietic growth factors. The influence on the activation of cytokine synthesis and on the expression of surface antigens associated with cellular activation of G-CSF or GM-CSF was investigated in cancer patients receiving these factors. One single dose of growth factor was administered to patients with bladder cancer (G-CSF group) or small cell lung cancer (GM-CSF group) before chemotherapy. After cytoreductive chemotherapy patients received supportive therapy with G-CSF or GM-CSF. Peripheral blood mononuclear cells and plasma samples were obtained for flow cytometry, Northern blot analysis, and assessment of cytokine protein levels after single-dose as well as after continous cytokine administration. Our results demonstrate differences in the induction of biological activities by GM-CSF and G-CSF in vivo which correlate well with in vitro findings. Among mature hematopoietic cells the effect of G-CSF is restricted to the granulocyte lineage. With GM-CSF moderate but unequivocal modulation of monocyte function was observed. On peripheral blood monocytes expression of MHC class-II molecules and CD44 was markedly stimulated. After one single dose of GM-CSF, plasma levels of sCD25 and IL-1RA were significantly induced (p<0.0001, p=0.032, respectively) and a trend to increased IL-8 levels was observed. The changes in plasma proteins were not correlated with shifts of mRNA expression for IL-8 and IL-1RA. T-cell activation was not observed with either cytokine. These results suggest that immunomodulatory features are differentially regulated by G-CSF and GM-CSF. The clinical relevance of a selective use of both hematopoietic growth factors in various disease settings remains to be determined. Received: 20 March 1996 / Accepted: 19 July 1996     

Allergische Kontaktekzeme bei Kindern

The incidence of contact allergy increases with age. This is due to increasing allergen exposure combined with maturation of the immune system. By the age of school enrolment responsiveness to contact allergens is the same as in adults. Since the 1980s, patch testing has become more common in children. It should be performed with standardized methodology. The most common contact allergens in children are nickel sulphate, cobalt chloride, thimerosal, neomycin, benzoyl peroxide, gentamicin, mercury compounds, fragrances and herbal allergens (composites), bufexamac, propylene glycol and turpentine. Preventive measures such as the use of fragrance- and preservative-free products and minimization of contact with potent allergens such as nickel should be considered especially in atopic children.     

Lactobacillus paracasei endocarditis in an 18-yeard-old patient with trisomy 21, atrioventricular septal defect and Eisenmenger complex: therapeutic problems

Endocarditis caused by lactobacilli is very rare and so far has been rarely published in adults with cardiac valve diseases especially after dental manipulations. Because of diagnostic and therapeutical problems we hereby report on one case of a female adolescent with Down's syndrome who did not undergo surgical correction of atrioventricular septal defect because of early development of Eisenmenger's syndrome. The onset was subacut and the diagnostic procedures were considerably delayed. Risk factors for the development of endocarditis in this case were preceding antibiotic treatments which increased the risk of selective growth of the causative germs as well as the tricuspidal valve incompetence with simultaneous pulmonary hypertension. The antimicrobial treatment was difficult due to resistance to antibiotic drugs generally applied in such cases and the restricted bacteriological diagnostic methods. Finally we had successfully administered chloramphenicol. The course was complicated by cerebral embolic events. FACIT: Lactobacillus species are facultative pathogenic which should be consideration in cases of subacute endocarditis in children and adolescents with ventricular septal defects and valve diseases. The determination of minimal bactericidal concentration of antibiotic agents and time-kill studies of combined antibiotics are recommended. For initial therapy we recommend high dose penicillin combined with an aminoglycoside. In cases of resistance chloramphenicol should be taken into account as second choice antibiotic drug. The duration of antibiotic therapy should at least over six weeks. In cases of risk systemic embolization is suspected therapy with low dose acetylsalicyclic acid or cardiosurgery should be assumed as therapeutic options.     

Improvement of early vascular changes and cardiovascular risk factors in obese children after a six-month exercise program.

OBJECTIVES: The present study aimed to assess the effect of a 6-month exercise program in obese children on flow-mediated vasodilation (FMD) carotid intima-media thickness (IMT) and cardiovascular risk factors (RF). BACKGROUND: Childhood obesity contributes to adult obesity and subsequent cardiovascular disease. Physical inactivity is a major RF for obesity, endothelial dysfunction, and elevated carotid IMT, culminating in early atherosclerotic disease. METHODS: Sixty-seven obese subjects (age 14.7 +/- 2.2 years) were randomly assigned to 6 months' exercise or non-exercise protocol. We examined the influence of exercises (1 h, 3 times/week) on FMD, IMT, and cardiovascular risk profile. RESULTS: Compared with lean control subjects, obese children demonstrated at baseline significantly impaired FMD (4.09 +/- 1.76% vs. 10.65 +/- 1.95%, p < 0.001), increased IMT (0.48 +/- 0.08 mm vs. 0.37 +/- 0.05 mm, p < 0.001), and a number of obesity-related cardiovascular RF. Significant improvements were observed in the exercise group for IMT (0.44 +/- 0.08 mm, p = 0.012, -6.3%) and FMD (7.71 +/- 2.53%, p < 0.001, +127%). This improvement correlated with reduced RF, such as body mass index standard deviation scores, body fat mass, waist/hip ratio, ambulatory systolic blood pressure, fasting insulin, triglycerides, low-density lipoprotein/high-density lipoprotein ratio, and low-degree inflammation (C-reactive protein, fibrinogen). CONCLUSIONS: The present study documented increased IMT, impaired endothelial function, and various elevated cardiovascular RF in young obese subjects. Regular exercise over 6 months restores endothelial function and improves carotid IMT associated with an improved cardiovascular risk profile in obese children.     

Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen.

In a few patients with chronic sarcoidosis, prolonged, unacceptably high doses of corticosteroids are required to achieve symptomatic relief. In these cases, a corticosteroid-sparing drug might be administered to allow long-term treatment without the adverse effects of corticosteroids. This study examines azathioprine as a prednisolone-sparing treatment. In an open study, the course of 11 patients with chronic sarcoidosis was analysed. In an induction phase, 2 mg azathioprine x kg body weight (BW)(-1) x day(-1) in combination with 0.6-0.8 mg prednisolone x kg BW(-1) x day(-1) were administered with prednisolone being reduced to 0.1 mg x kg BW(-1) x day(-1) within 2-3 months. This was followed by a 21-22-month maintenance phase with 2 mg azathioprine x kg BW(-1) x day(-1) and 0.1 mg prednisolone x kg BW(-1) day(-1). Clinical parameters and immunological findings of bronchoalveolar lavage (BAL) were analysed. All patients had significant symptomatic relief and improvements or resolutions of physiological, serological and radiographic findings without suffering from serious adverse effects. Nine of 11 patients completed therapy after 19-26 months, and 2/11 patients terminated therapy after 8 and 12 months, respectively. Eight patients had remissions lasting 4-73 months. Three relapses occurred after 8, 18, and 22 months. During the induction phase, BAL cell composition changed and their activity in terms of cytokine release was suppressed. This preliminary study suggests that azathioprine may be effective as a corticosteroid-sparing agent in long-term therapy of sarcoidosis, but a much larger study is necessary to give the definitive answer.     

Cutis marmorata telangiectatica congenita: a prospective study of 27 cases and review of the literature with proposal of diagnostic criteria

Background.  Cutis marmorata telangiectatica congenita (CMTC) is a congenital vascular anomaly of unknown aetiology. About 300 cases have been reported in the literature. The rate of associated anomalies varies between 20% and 70%.
Methods.  We report a series of 27 children with CMTC, 18 of whom were followed-up prospectively for a median of 22 months (range 2 months–5.3 years).
Results.  Both genders were equally affected (13 male/14 female). The legs were involved in 20 cases (74%), the arms in 10 (37%), the face in 4 (15%) and the trunk in 18 (67%). There were 20 (74%) patients who presented with involvement of both trunk and limbs, a further 20 patients had lesions affecting the limb on only one side of the body, and 7 children (26%) had bilateral lesions; 1 child had generalized CMTC lesions. The involved areas covered a mean of 18% of body surface area (range 3–90). Associated anomalies were found in 15 patients (56%), with some exhibiting more than one. There was body asymmetry (hypertropy or hypotrophy of the affected limb) in nine patients (33%), seven patients had a variety of other malformations (congenital glaucoma, syndactyly, lipoma, macrocephaly, renal hypoplasia, Kartagener's syndrome), and other vascular lesions were present in four patients (15%). There was no correlation between the extent of skin lesions and likelihood of associated anomalies. On follow-up, fading of skin lesions was noted in 67% of our patients.
Conclusion.  Body asymmetry is the most common anomaly associated with CMTC; other associations might be pure chance. In order to separate CMTC from other vascular malformations, notably Klippel–Trénaunay syndrome, we suggest diagnostic criteria for their differentiation.     

Neurobiology of substance-related addiction: findings of neuroimaging

Neuroimaging provides insight into the main biological mechanisms underlying drug and alcohol dependence. Cardinal symptoms of drug dependence are the development of tolerance against drug effects, withdrawal symptoms, drug craving, reduced control over drug intake and harmful consequences of drug consumption. Brain imaging studies support the hypothesis that tolerance development can be understood as a neuroadaptive mechanism to ensure homeostasis during chronic drug intake. When drug consumption is suddenly interrupted during detoxification, the loss of homeostasis can manifest as a withdrawal syndrome. While tolerance development reduces the effects of chronic drug intake, sensitization is a neuroadaptive process that increases the effects of a drug dose. Brain imaging studies indicate that sensitisation and drug craving are associated with neuroadaptive processes in the brain reward system. Harmful consequences of drug intake include neurotoxic effects on the central nervous system. Besides discussing brain imaging studies on the neurobiological correlates of drug dependence, this review also presents studies on vulnerability factors that predispose individuals to excessive drug intake.