M. A. Überall

A Comparative Efficacy Trial in Germany in Infants Who Received Either the Lederle/Takeda Acellular Pertussis Component DTP (DTaP) Vaccine, the Lederle Whole-Cell Component DTP Vaccine, or DT Vaccine

Background. The goal of the trial was to determine the efficacy of a multicomponent acellular pertussis vaccine against Bordetella illnesses in comparison with a whole-cell product and DT. Design. In a randomized, double-blind fashion, 2- to 4-month-old infants received 4 doses of either DTP or DTaP vaccine at 3, 4.5, 6, and 15 to 18 months of age. The controls received 3 doses (3, 4.5, 15 to 18 months of age) of DT vaccine. The DTP vaccine was Lederle adsorbed vaccine (licensed in the United States) and DTaP was Lederle/Takeda adsorbed vaccine. Follow-up for vaccine efficacy started 2 weeks after the third dose (DTP/DTaP) and at the same age (6.5 months) in DT recipients. Reactogenicity of all doses of all three vaccines was documented by standardized parent diary cards. In addition, all subjects were monitored for respiratory illnesses and serious adverse events by biweekly phone calls. Results. From May 1991 to January 1993, a total of 10 271 infants were enrolled: 8532 received either DTP or DTaP and 1739 received DT. Specific efficacy against B pertussisinfections with cough ≥7 days duration was 83% (95% confidence interval [CI]: 76–88) and 72% (95% CI: 62–79) for DTP and DTaP, respectively; results for DTP and DTaP based on ≥21 days of cough with either paroxysms, whoop or posttussive vomiting (PWV) were 93% (95% CI: 89–96) and 83% (95% CI: 76–88), respectively. For DTaP vaccine, efficacy was higher after the fourth dose as compared with its efficacy after the third dose (78% vs 62% for cough ≥7 days and 85% vs 76% for cough ≥21 days with PWV). For DTP vaccine, efficacy was less varied after the third and fourth dose (78% vs 85% for cough ≥7 days and 93% vs 93% for cough ≥21 days with PWV). In contrast with DTP, the DTaP vaccine had some efficacy against B parapertussisinfection (point estimate for cough ≥7 days: 31% [95% CI: −10–56]). All vaccines were generally well-tolerated. However, side reactions were significantly less after DTaP compared with DTP. Conclusions. Like other multicomponent acellular pertussis vaccines, the Lederle/Takeda DTaP vaccine demonstrated good efficacy against mild and typical pertussis due to B pertussisinfections. Interestingly, it also may have some efficacy againstB parapertussis. Based on the results of this trial, the vaccine was licensed in the United States in December 1996 for all 5 doses of the currently recommended immunization schedule in this country.

Clinical characteristics of illness caused by Bordetella parapertussis compared with illness caused by Bordetella pertussis

In conjunction with a pertussis vaccine efficacy trial in Germany, nasopharyngeal specimens were collected from May, 1992, to March, 1993, from patients with cough illnesses. Clinical data were obtained by initial and follow-up questionnaires. Bordetella parapertussis was isolated from 38 patients (mean age, 3.5 years; 68% girls). Clinical characteristics in these cases were compared with those of 76 patients (matched by age and sex) with illness caused by Bordetella pertussis during the same period. Findings were: (B. pertussis/B. parapertussis): cough > 4 weeks 57%/37% (P = 0.06); whoop 80%/59% (P = 0.07); whoop > 2 weeks 26%/18% (P = 0.05); paroxysms 90%/83% (P = 0.5); body temperature > or = 38 degrees C 9%/0% (P = 0.17); vomiting 47%/42% (P = 0.69); and mean leukocyte and lymphocyte counts 12,500/mm3 and 7600/mm3 (P < 0.0001) and 7800/mm3 and 3500/mm3 (P < 0.0001), respectively. Illness caused by B. parapertussis was typical of pertussis but less severe than that caused by B. pertussis. In contrast with B. pertussis infection, lymphocytosis is not a characteristic of B. parapertussis infection. This is most likely a result of the lack of production of lymphocytosis-promoting factor toxin by B. parapertussis.

Intravenous valproate in pediatric epilepsy patients with refractory status epilepticus.

Since its first clinical use in France in 1963, valproic acid (VPA) has rapidly established itself worldwide as one of the major antiepileptic drugs, with a broad efficacy for treatment of both generalized and partial seizures in children and adults.1 In October 1996, an IV VPA formulation was approved in Germany for the short-term supplementation of an established oral VPA treatment in patients with epilepsy, when oral-to-parenteral substitution becomes necessary.2 However, IV VPA also offers the opportunity to treat epileptic emergency situations such as prolonged or serial seizures, or even patients with status epilepticus (SE). We report on 41 children with therapy-resistant SE treated with IV VPA. The clinical details of our patients are listed in the table. All children had SE that was refractory to commonly recommended IV antiepileptic drugs (i.e., benzodiazepine compounds, phenytoin, and barbiturates). Whereas 22 of these children received antiepileptic long-term therapy that started before this SE event, SE was the initial presentation of an …

Polymerase chain reaction identification of Bordetella pertussis infections in vaccinees and family members in a pertussis vaccine efficacy trial in Germany.

The polymerase chain reaction (PCR) was recently added to conventional culture and serology for the diagnosis of Bordetella pertussis infection in a large vaccine efficacy trial in Germany. In vaccinees or family members who had illnesses with cough, two nasopharyngeal swabs (calcium alginate for culture and Dacron for PCR) were taken and initial and follow-up clinical data were obtained. PCR was done using oligonucleotide primers PTp1 and PTp2 which amplify a 191-base pair DNA fragment of pertussis toxin operon. From December, 1993, to May, 1994, 555 pairs of swabs were processed; 28 grew B. pertussis and 9 grew B. parapertussis. Twenty

Therapie idiopathischer Kopfschmerzen im Kindesalter

ZusammenfassungNach den Richtlinien der Evidence-Based Medicine sind die spezifischen kontrollierten Studien für die Behandlung idiopathischer Kopfschmerzen im Kindesalter analysiert und in Therapieempfehlungen zusammengefasst worden. Mit der höchsten Evidenz werden für die Behandlung akuter Migräneattacken oder Kopfschmerzen vom Spannungstyp Ibuprofen (10 mg/kg KG) und Paracetamol (15 mg/kg KG) empfohlen, im Ersatzfall kann Sumatriptan intranasal (10–20 mg) eingesetzt werden. Für die medikamentöse Prophylaxe der Migräne werden Betablocker (Propranolol oder Metoprolol), Flunarizin und Valproat empfohlen. Flunarizin ist auch prophylaktisches Mittel der 1. Wahl bei migräneähnlichen Syndromen. Für andere Kopfschmerzarten liegen keine kontrollierten Studien für das Kindesalter vor. In der nichtmedikamentösen Prophylaxe von Kopfschmerzen im Kindesalter werden mit höchster Evidenz Entspannungsverfahren (progressive Muskelrelaxation), Biofeedbackenverfahren und kindgerechte Trainingsprogramme empfohlen.AbstractAccording to the principles of evidence-based medicine, the controlled studies on the treatment of idiopathic headache in childhood have been analysed and compiled to treatment recommendations. For the acute treatment of migraine attacks or tension-type headache, ibuprofen (10 mg per kg body weight) or acetaminophen (15 mg per kg body weight) are recommended with highest evidence, intranasal sumatriptan (10 to 20 mg) can be given as second choice. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, and valproic acid are recommended. Flunarizine is the drug of first choice in the treatment of migraine-related disorders. No controlled studies are available for the treatment of further headache types. First line methods for the non-drug treatment of headache in childhood are relaxation therapies, biofeedback, and specific training schedules.According to the principles of evidence-based medicine, the controlled studies on the treatment of idiopathic headache in childhood have been analysed and compiled to treatment recommendations. For the acute treatment of migraine attacks or tension-type headache, ibuprofen (10 mg per kg body weight) or acetaminophen (15 mg per kg body weight) are recommended with highest evidence, intranasal sumatriptan (10 to 20 mg) can be given as second choice. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, and valproic acid are recommended. Flunarizine is the drug of first choice in the treatment of migraine-related disorders. No controlled studies are available for the treatment of further headache types. First line methods for the non-drug treatment of headache in childhood are relaxation therapies, biofeedback, and specific training schedules.

Effectiveness of lamotrigine in children with paroxysmal kinesigenic choreoathetosis.

Paroxysmal kinesigenic choreoathetosis (PKC) is a rare movement disorder, characterized by recurrent, brief involuntary dystonic attacks that are provoked by sudden movements. Pathophysiology is uncertain, but a channelopathy is discussed. Treatment recommendations favour antiepileptic drugs (AEDs) acting on voltage‐gated neuronal ion channels. This report summarizes the history of three children (6, 8, and 10 years of age) with idiopathic PKC successfully treated with low doses of lamotrigine, an AED acting primarily via neuronal voltage‐sensitive sodium channels.

Therapie idiopathischer Kopfschmerzen im Kindesalter Empfehlungen der Deutschen Migräne- und Kopfschmerzgesellschaft (DMKG)

ZusammenfassungHintergrund. Nach den Richtlinien der Evidence-based medicine sind die spezifischen kontrollierten Studien für die Behandlung von idiopathischen Kopfschmerzen im Kindesalter analysiert und in Therapieempfehlungen zusammengefasst worden. Therapieempfehlungen. Mit der höchsten Evidenz werden für die Behandlung akuter Migräneattacken oder Kopfschmerzen vom Spannungstyp Ibuprofen (10 mg/kg KG) und Parazetamol (15 mg/kg KG) empfohlen, im Ersatzfall kann nur bei Migräneattacken Sumatriptan intranasal (10–20 mg) eingesetzt werden. Prophylaxe. Für die medikamentöse Prophylaxe der Migräne werden β-Blocker (Propranolol oder Metoprolol), Flunarizin und Valproat empfohlen. Flunarizin ist auch prophylaktisches Mittel der ersten Wahl bei migräneähnlichen Syndromen. Für andere Kopfschmerzarten liegen keine kontrollierten Studien für das Kindesalter vor. In der nicht-medikamentösen Prophylaxe von Kopfschmerzen im Kindesalter werden mit höchster Evidenz Entspannungsverfahren (progressive Muskelrelaxation), Biofeedbackenverfahren und kindgerechte Trainingsprogramme empfohlen.AbstractBackground. According to the principles of evidence-based medicine, the controlled studies on the treatment of idiopathic headache in childhood have been analysed and compiled to treatment recommendations. Treatment. For the acute treatment of migraine attacks or tension-type headache, ibuprofen (10 mg per kg body weight) or acetaminophen (15 mg per kg body weight) are recommended with highest evidence, intranasal sumatriptan (10 to 20 mg) can be given as second choice in migraine attacks. Prophylaxis. For the prophylaxis of migraine, β-Blockers (propranolol and metoprolol), flunarizine, and valproic acid are recommended. Flunarizine is the drug of first choice in the treatment of migraine-related disorders. No controlled studies are available for the treatment of further headache types. Frist line methods for the non-drug treatment of headache in childhood are relaxation therapies, biofeedback, and specific training schedules.

[Treatment of idiopathic headache in childhood - recommendations of the German Migraine and Headache Society (DMKG)].

ZusammenfassungNach den Richtlinien der Evidence-Based Medicine sind die spezifischen kontrollierten Studien für die Behandlung idiopathischer Kopfschmerzen im Kindesalter analysiert und in Therapieempfehlungen zusammengefasst worden. Mit der höchsten Evidenz werden für die Behandlung akuter Migräneattacken oder Kopfschmerzen vom Spannungstyp Ibuprofen (10 mg/kg KG) und Paracetamol (15 mg/kg KG) empfohlen, im Ersatzfall kann Sumatriptan intranasal (10–20 mg) eingesetzt werden. Für die medikamentöse Prophylaxe der Migräne werden Betablocker (Propranolol oder Metoprolol), Flunarizin und Valproat empfohlen. Flunarizin ist auch prophylaktisches Mittel der 1. Wahl bei migräneähnlichen Syndromen. Für andere Kopfschmerzarten liegen keine kontrollierten Studien für das Kindesalter vor. In der nichtmedikamentösen Prophylaxe von Kopfschmerzen im Kindesalter werden mit höchster Evidenz Entspannungsverfahren (progressive Muskelrelaxation), Biofeedbackenverfahren und kindgerechte Trainingsprogramme empfohlen.AbstractAccording to the principles of evidence-based medicine, the controlled studies on the treatment of idiopathic headache in childhood have been analysed and compiled to treatment recommendations. For the acute treatment of migraine attacks or tension-type headache, ibuprofen (10 mg per kg body weight) or acetaminophen (15 mg per kg body weight) are recommended with highest evidence, intranasal sumatriptan (10 to 20 mg) can be given as second choice. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, and valproic acid are recommended. Flunarizine is the drug of first choice in the treatment of migraine-related disorders. No controlled studies are available for the treatment of further headache types. First line methods for the non-drug treatment of headache in childhood are relaxation therapies, biofeedback, and specific training schedules.According to the principles of evidence-based medicine, the controlled studies on the treatment of idiopathic headache in childhood have been analysed and compiled to treatment recommendations. For the acute treatment of migraine attacks or tension-type headache, ibuprofen (10 mg per kg body weight) or acetaminophen (15 mg per kg body weight) are recommended with highest evidence, intranasal sumatriptan (10 to 20 mg) can be given as second choice. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, and valproic acid are recommended. Flunarizine is the drug of first choice in the treatment of migraine-related disorders. No controlled studies are available for the treatment of further headache types. First line methods for the non-drug treatment of headache in childhood are relaxation therapies, biofeedback, and specific training schedules.

Inzidenz und Symptomatik von hospitalisierten Gastroenteritiden in einer Kohorte von 10.271 Säuglingen und Kleinkindern

ZusammenfassungFragestellung: Eine prospektive Pertussisimpfstudie mit engmaschiger Überwachung des gesamten Kollektivs erlaubte uns, erstmals das Risiko von Säuglingen und Kleinkindern, wegen einer Gastroenteritis hospitalisiert zu werden, in einer umfangreichen Kohorte zu bestimmen. Methode: Die Kohorte aus 10.271 gesunden Kindern wurde, beginnend im Alter von 2–4 Monaten, über einen mittleren Zeitraum von 2,5 Jahren beobachtet (Gesamtbeobachtungsdauer 25.284 Jahre). Dabei wurden u.a. alle Krankenhausbehandlungen erfaßt. Ergebnisse: Bei 173 Kindern (1,7%) registrierten wir insgesamt 179 Gastroenteritisepisoden, die stationär behandelt wurden. Dies entspricht einer mittleren Inzidenz von 7,1/1000 Beobachtungsjahren mit einem Maximum von 11,2/1000 im 7. bis 12. Lebensmonat und einer Abnahme mit steigendem Lebensalter. Die beiden am häufigsten nachgewiesenen Erreger waren Rotaviren (34%) und Salmonellen (20%). Rotavirus-Infektionen traten gehäuft in der kalten Jahreszeit auf, die höchste Inzidenz lag bei Säuglingen im 7. bis 12. Lebensmonat. Die Symptomatik war geprägt von Enteritis (90%), Erbrechen (85%) und Zeichen der Dehydratation (58%). Demgegenüber trat der Großteil aller Salmonellosen in den Monaten Juli-September auf, mit einem Altersgipfel im 19. bis 24. Lebensmonat, charakterisiert durch Enteritis (92%), hohes Fieber (56%, >39°C) und erhöhte Werte des C-reaktiven Proteins (68%). Bei 5% bzw. 12% der wegen Rotavirus- bzw. Salmonelleninfektionen hospitalisierten Kinder war ein Fieberkrampf Anlaß für die Klinikeinweisung. Schlußfolgerung: Gastroenteritiden führen bei primär gesunden Kindern in den ersten Lebensjahren häufig zu Krankenhausbehandlungen. Rotaviren und Salmonellen sind dabei die prädominierenden Erreger.SummaryObjective: A pertussis vaccine efficacy trial included a prospective follow up of all hospitalizations involved. This allowed us to calculate the rates of hospitalization due to acute gastroenteritis in a large cohort of infants and children in Germany. Methods: 10271 healthy children were enrolled at the age of 2–4 months and followed up for a mean of 2.5 years. All hospitalizations during follow-up of the study were registered and letters of discharge from hospital in children with gastroenteritis were evaluated for the present analysis. Results: A total of 179 episodes of hospitalization due to a gastroenteritis were reported in 173 children (total observation years 25284). The mean calculated incidence was 7.1/1000 observation years, with a maximum of 11.2/1000 years in 7–12 month old children. Rotavirus and Salmonella spp. were the most frequently identified agents. Rotavirus infections were most prevalent during the cold season and the maximum incidence was between 7 and 12 months of age. Characteristic symptoms of rotavirus infections were diarrhea (90%), vomiting (85%) and signs of dehydration (58%). In contrast most Salmonella infections occurred between July and September with a peak between 19 and 24 months of age. Salmonella infections were characterized by enteritis (92%), high fever (56% >39°C) and significantly increased values for the c-reactive protein (68%). In this study rotavirus and Salmonella infections leading to hospitalization were associated with febrile seizures in 5% and 12% of cases, respectively. Conclusion: Gastroenteritis frequently leads to hospitalization in previously healthy infants and young children. Rotavirus and Salmonella spp. are the predominant causative agents.

Biadrenales Phäochromozytom bei einem Jungen

ZusammenfassungWir berichten über einen 8 Jahre alten Jungen, bei dem 6 Monate nach einem unklaren zerebralen Krampfanfall aufgrund der augenärztlichen Symptomatik (Skotom, Fundus hypertonicus Grad IV) ein arterieller Hochdruck diagnostiziert wurde. Die weiteren Untersuchungen ergaben ein isoliertes Phäochromozytom der linken Nebenniere. Der Tumor wurde durch eine Adrenalektomie entfernt, und der Junge war im weiteren Verlauf beschwerdefrei. 3 Jahre später wurde er mit der gleichen klinischen Symptomatik wie bei der Erstdiagnose stationär aufgenommen. Jetzt wurde ein Phäochromozytom in der rechten Nebenniere diagnostiziert. Der Tumor wurde erneut mittels Adrenalektomie entfernt. Andere Tumoren konnten bislang bei dem Jungen nicht gefunden werden. Die Familienanamnese für Phäochromozytome war negativ. Die molekulargenetische Diagnostik ergab eine Mutation im Von-Hippel-Lindau-Gen. Diskussion: Auch bei einem isolierten biadrenalen Phäochromozytom muß eine Phakomatose molekulargenetisch ausgeschlossen werden. In unserem Fall wurde die Diagnose eines Von-Hippel-Lindau-Syndroms gestellt.SummaryWe report on a 8 year old boy in whom ophthalmological signs (scotoma, fundus hypertonicus stage IV) and an elevated blood pressure lead to the diagnosis of an isolated pheochromocytoma of the left adrenal. 6 months before, a cerebral convolsion was interpreted as a benign convulsion caused by infection. The boy was cured by adrenalectomy. However, 3 years after the initial diagnosis, he showed again typical clinical signs of a pheochromocytoma which was finally confirmed by laboratory tests and computertomography. The right adrenal was removed. Family history was negative. By molecular analysis, an association with von Hippel-Lindau disease was found. Discussion: Our case emphasizes the necessity to exclude a phacomatosis in all cases of pheochromocytoma.