[Schooling, living conditions and study motivation of students partaking in the traditional or reformed course of instruction at the Charité (Hospital)]. / Schulbildung, Lebensumstände und Studienmotive von Studierenden des Regel- und des Reformstudiengangs an der Charité1.

BACKGROUND: There are two different tracks in undergraduate medical education at the Charité, a traditional (TT) one and a reformed one (RT) which was implemented in 1999. We report a survey reflecting on possible differences between students joining the two tracks. METHODS: During the winter term 2001/02 a questionnaire was sent to all 223 newly enrolled medical students. Three groups were distinguished: those following either the traditional or the reformed course (TT or RT), or those who followed the TT, although they had applied for it, because there were not enough vacancies in the RT. PARTICIPANTS: 150 (63% female; average age: 21.5 years) of 223 first year medical students. RESULTS: Applicants for the RT did not differ significantly from those of the other groups with respect to school-leaving grades, their choice of main courses at school an their motivation to study medicine. But they differed in the demands that they placed on their instruction. The wish for a good practical medical training, advancing their individual potential and the ability to select for themselves any instructional priorities were of greater importance for those choosing the RT than those who preferred the TT. More students of the RT than the TT would again have chosen to study medicine and less often stated that they had considered giving up their medical course. CONCLUSION: Students have different expectations concerning medical curricula. The possibility to choose between different ways of studying may help to meet different expectations.

Effect of L-carnitine treatment for valproate-induced hepatotoxicity.

The authors analyzed the association of L-carnitine treatment with hepatic survival in 92 patients with severe, symptomatic, valproate-induced hepatotoxicity. Forty-eight percent of the 42 patients treated with L-carnitine survived, but only 10% of the 50 patients treated solely with aggressive supportive care survived (p < 0.001). Early intervention with IV rather than enteral L-carnitine was associated with the greatest hepatic survival. Specifically, all 10 patients who were diagnosed in <5 days and treated with IV L-carnitine survived. Most patients had features of chronic illness and most children appeared to be malnourished.

Serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen and laminin P1 in Duchenne muscular dystrophy.

The striking proliferation of connective tissue in Duchenne muscular dystrophy is attributed, besides other components of the extracellular matrix, to an increase of endomysial and perimysial type III and type I collagen. We investigated if muscle fibrosis correlates to an increased serum concentration of procollagen I or III. Therefore, we measured the serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen and laminin P1 in 20 boys with progressive muscular dystrophy (16 definite Duchenne muscular dystrophy, 2 suspected of Duchenne muscular dystrophy, 2 Becker muscular dystrophy). In contrast to collagen I and III the expression of laminin in the basement membrane is known to be normal in Duchenne muscular dystrophy. There was no significant alteration of serum concentration of procollagen III N-peptide, procollagen I C-peptide and laminin P1 in boys with Duchenne muscular dystrophy. Measuring these parameters is not useful for investigating the extent of muscle fibrosis or for monitoring the effect of therapeutic trials such as steroid treatment.

Severe transitory encephalopathy with reversible lesions of the claustrum.

Reversible bilateral lesions of the claustrum and external capsule in a 12-year-old girl suffering from a severe, transitory encephalopathy are reported. After a prodromal stage of feeling uncomfortable a sudden onset of status epilepticus occurred, followed by recurrent complex partial and myoclonic seizures for 3 weeks, with psychotic symptoms and temporary loss of vision, speech and hearing. After treatment with phenytoin the patient became free of seizures and recovered completely without neurological deficit. The initial cranial CT was normal; however, cranial MRI 7 days later showed bilateral selective lesions of the claustrum and external capsule, which disappeared completely 5 weeks later. The aetiology of these lesions remains obscure; repeated cerebrospinal fluid and blood tests were negative for herpes simplex virus and other infectious agents. The clinical and radiological improvement were concomitant. This may indicate a functional disturbance of the claustrum grey matter, rather than lesions of the white matter of the external and extreme capsules.

Risk factors for latex allergy in patients with spina bifida.

OBJECTIVE AND METHODS: In order to study risk factors for latex allergy in patients with spina bifida, we investigated 165 patients with spina bifida (mean age 9 years). Besides answering a questionnaire, patients underwent skin-prick testing and determination of specific serum IgE to latex as well as a screening test for specific IgE to environmental allergens. A total of 80 patients (49%) were sensitized to latex according to the presence of specific IgE to latex. RESULTS: Skin-prick tests (SPT) with high ammonia latex milk were performed in 81 of our patients with spina bifida and were positive in 36 patients (46%). Concordance of SPT with specific IgE in serum was good. Nineteen out of 165 patients suffered from a clinically relevant latex allergy: five patients had a history of systemic reactions to latex (e.g. severe bronchospasm, anaphylactic reactions), mostly during surgery. Fourteen patients reported clinical symptoms while inflating a balloon; all these 19 patients were sensitized to latex. Number of operations ranged from one to 26 (mean 5 operations). Concentration of specific IgE to latex in serum correlated well with increasing numbers of operations. Some 32/76 patients (41%) with spina bifida who were sensitized to latex showed an atopic disposition, while 21 out of 81 latex-negative patients (26%) were atopic. Of 300 consecutive sera (mean age of patients 9 years) sent to our laboratory for routine determination of specific IgE, 144 (48%) were positive in terms of specific IgE to environmental allergens, of which 247144 (17%) were sensitized to latex. CONCLUSIONS: From our data we conclude that in order to minimize risk of severe systemic clinical reactions, all patients with spina bifida should be screened for their individual risk of latex allergy to plan preventive measures before operations. Main risk factors for latex allergy seem to be: more than five operations, atopic predisposition, history of clinical symptoms while inflating a balloon, and a sensitization with a CAP-class of > or = 4.

Clinical, radiological and histological findings in desmoplastic infantile ganglioglioma.

The clinical course and radiological and histological findings in a 30-month-old boy suffering from desmoplastic infantile ganglioglioma are reported. The child's development was normal until a series of complex partial seizures occurred at the age of 7 months. Cranial computed tomography and magnetic resonance imaging revealed a cystic mass with intensive ring-shaped contrast enhancement in the right temporal fossa without shift of intracranial structures. Histologically, the firm, grayish tumor showed an enormous amount of connective tissue, cystic areas, and some mitoses. Glial and neuronal cell lines were identified by immunocytochemical methods. Eighteen months after surgery the boy had developed well without any neurological dysfunction; no radiation or chemotherapy was given. For the first time a synopsis of radiological findings in this rare brain tumor is correlated with the results of multiple histological and immunocytochemical studies. Despite some malignant characteristics, the prognosis of this dysontogenetic brain tumor is good.

Cranial ultrasound findings in aspartoacylase deficiency (Canavan disease).

Canavan disease (CD) is a rare leukodystrophy which is lethal in infancy or early childhood. The underlying biochemical abnormality in CD is a hereditary deficiency of N-aspartoacylase transmitted in an autosomal recessive fashion. We report on the ultrasound (US), CT, and MRI findings of three unrelated boys with biochemically confirmed CD. At 6 and 9 months of age, two CD patients with rapid neurological deterioration showed markedly enhanced acoustic attenuation of the white matter with the exception of the corpus callosum, giving the appearance of a reversed pattern of echogenicity of cortical gray and subcortical white matter. While gyri and sulci had an almost normal US appearance, the periventricular gray matter featured prominently with increased echogenicity. In contrast another CD patient with a more protracted course had ventricular enlargement when examined by US at 5 and 9 months but no alteration in white matter echogenicity. MRI showed impaired myelinization in all three patients with Canavan disease.

Variable course of Canavan disease in two boys with early infantile aspartoacylase deficiency.

This is a report of two patients with Canavan disease from the Federal Republic of Germany. One is a severely retarded, macrocephalic boy, who had the characteristic laboratory findings of Canavan disease and progressive leucodystrophy on neuro-imaging. The other is retarded, with signs of a cerebral movement disorder showing no deterioration during the first 15 months. The significance of aspartoacylase deficiency in Canavan disease for differential diagnosis, genetic counselling and prenatal diagnosis of leucodystrophy is discussed.

MR-imaging findings in children with Sturge-Weber syndrome.

Intracranial extent and distribution of leptomeningeal angiomatosis, visualized by magnetic resonance imaging (MRI) with Gadolinium-DTPA (Gd-DTPA) enhancement, is demonstrated in four children with Sturge-Weber syndrome (SWS). Aged 7, 9, 11 and 19 months, they presented with cutaneous, neurologic and ocular symptoms at the time of MRI examination. Angiomatous alteration of the skull, atypically located and congested intracerebral and basal veins as well as intracerebral changes secondary to the leptomeningeal angiomatosis are demonstrated with T2 weighted images. Gd-DTPA enhanced T1 weighted images exhibit clearly the regional distribution of angiomatosis in the skull, meninges and within the brain. Before calcifications in children with SWS are detectable by CT, MRI is the method of choice to detect intracranial involvement. Enhancement with Gd-DTPA improves the diagnostic value of MRI, before neurological symptoms appear. Follow-up studies with Gd-DTPA enhanced MRI can be applied to recognize thrombotic changes of leptomeningeal angiomatosis as well as subsequent intracerebral impairment.

[Vitamin K deficiency with erythromycin. Observation of a boy treated with valproate]. / Vitamin K-Mangel unter Erythromycin. Beobachtung bei einem mit Valproat behandelten Jungen.

A nine year old boy had been treated with valproic acid during one and a half years because of a grand mal epilepsy. Under an additional medication with erythromycin succinate syrup this patient developed a deficiency of prothrombin-complex, which was reversible immediately after oral intake of vitamin K. In this case it is assumed that the simultaneous application of both valproic acid and erythromycin succinate seems to suppress the vitamin K producing intestinal tract bacteria, which has not been reported in the literature so far.

Syndrome of the posterior and anterior root in a late isolated CNS relapse of c-ALL. Case report.

A 15 year-old girl who had c-ALL diagnosed in 1982 was presented in our clinic suffering from an ascended flaccid paresis and dysaesthesia of both legs. These are typical symptoms of polyradiculitis of the nerve roots L2-S2. A lumbal puncture revealed a pleocytosis with lymphoblasts which were up to 40% CD10 (cluster of differentiation) up to 70% CD19 and TdT (terminal transferase) positive. The diagnosis of late isolated CNS relapse was made. It is assumed that local residual infiltrations of leukemic cells into the nerve roots L2-S2 got into cell cycle and caused these rare CNS leukemia symptoms. Therefore the value of a craniospinal irradiation to prevent a CNS and systemic relapse is discussed.

Fatal liver failure in 16 children with valproate therapy.

The data of 16 children who died while receiving valproate (VPA) therapy in West Germany were analyzed. Five were normally developed, 5 were receiving VPA-monotherapy, and only 2 patients were aged less than 3 years. The first clinical symptoms of impending hepatotoxicity usually included nausea, vomiting, and apathy; pathologic laboratory tests reflected liver failure. Liver histology revealed microvesicular steatosis, cell necrosis, and bile duct proliferation of varying degree. An abnormal metabolite, 4-ene-VPA, was detected in all examined patients (six of six) and persisted after drug withdrawal. The pathogenesis of fatal liver failure during VPA treatment remains unknown. World-wide, approximately 100 fatalities have been reported in relation to VPA treatment. More than 90% were aged less than 20 years, 95% developed their first symptoms within the first 6 months of treatment, and 16 were treated with VPA alone. Since it is difficult precisely to define a group at risk for fatalities with VPA, careful clinical and laboratory monitoring with a special focus on vomiting and apathy, liver enzymes, and coagulation tests seem mandatory during the first 6 months after introduction of VPA. Taking into account the considerable number of fatalities during VPA treatment, the indication for its use requires careful reevaluation.

Long-term development of intelligence (IQ) and EEG in 34 children with phenylketonuria treated early.

In 34 children with phenylketonuria (PKU) treated early the prognostic value of the age on institution of the diet (within the first 3 months of life) and of the quality of dietary treatment was determined in two different ways: 1) following intelligence closely (IQ) and (2) evaluating the EEG development up to their 12th (n = 34) and 15th (n = 18) years of life as appropriate. In general, IQ scores were found to be normal from the 4th-15th years of life. In our group of patients there was no effect on the IQ of the timing of diet onset. Children with "strict" dietary control showed a significantly higher IQ than those with "loose" control. One hundred and fifty-four EEGs (10/20 system, awake with eyes closed) were recorded at intervals of 2 years and conventionally evaluated. The development of alpha-activity was found to be normal. Beta-activity was enhanced. Abnormal EEG findings like general slowing and generalized paroxysmal activity (GPA) with or without spikes were more frequent in children with PKU than in controls, with the exception of focal abnormalities. EEG abnormalities increased with advancing age independently of IQ development and showed no relation to either the age at the onset nor the quality of dietary treatment.

[Fatal hepatic failure in a normally developed 5-year-old boy caused by VPA monotherapy]. / Tödliches Leberversagen bei einem altersgemäss entwickelten fünf Jahre alten Jungen unter VPA-Monotherapie.

A five-year-old, normally developed boy who had been healthy except for an absence epilepsy prior to valproate (VPA) treatment died 16 weeks after the introduction of VPA-monotherapy due to liver failure and intractable bleeding disorder. This case emphasizes that the restriction of VPA-therapy to children of more than two years of age, on monotherapy, and without evidence of other diseases or retardation does not exclude fatal complications. Until today world-wide about 100 patients have died during VPA-treatment.

Changes in the EEG background activity of children with acute lymphoblastic leukemia during cytotoxic therapy.

Thirteen children with acute lymphoblastic leukemia (ALL) were investigated before and during cytotoxic therapy. EEG findings were correlated with the clinical course and the therapy protocol and compared with normal data obtained from 295 healthy children. Frequency analysis of the background activity of the EEG revealed an initial slowing of the background activity prior to therapy and further slowing each time a combination of vincristine (VCR), daunorubicin (DAU) or adriblastine (ADR), prednisone (PRED), and L-asparaginase (L-ASP) was administered. The slowing of the background activity correlated only with the administration of these drugs. DAU, ADR, and PRED are not known to influence the EEG; therefore, VCR and L-ASP remain the primary candidates responsible for the central nervous system alteration.

Muscle adenylate kinase in Duchenne muscular dystrophy.

On the basis of electrophoretic and enzyme inhibition studies it was postulated that an aberrant adenylate kinase occurs in muscle and serum of patients with Duchenne muscular dystrophy (Schirmer, R.H. and Thuma, E. (1972) Biochim. Biophys. Acta 268, 92-97; Hamada, M. et al. (1981) Biochim. Biophys. Acta 660, 227-237; Hamada et al. (1985) J. Biol. Chem. 260, 11595-11602). On the basis of the following results we conclude that Duchenne muscular dystrophy patients do not possess an unusual adenylate kinase isoenzyme. In muscle biopsies from five Duchenne patients, the electrophoretic mobility of adenylate kinase and the inhibition of the enzyme by P1, P5-di(adenosine-5')pentaphosphate (Ap5A) was normal. Because of the high SH-group content of the extracts from Duchenne muscle, high concentrations of Ellman's reagent were needed to inhibit adenylate kinase activity in these samples. In Duchenne plasma the adenylate kinase activity was elevated. Like in muscle specimens, the DTNB inhibition curves were shifted to higher reagent concentrations; this was due to a high SH-group content of Duchenne plasma when compared with normal plasma. With respect to inhibition by Ap5A and electrophoretic mobility, Duchenne adenylate kinase in Duchenne plasma behaved like normal muscle adenylate kinase in normal plasma. It was noted that normal muscle adenylate kinase changes its electrophoretic behaviour when mixed with normal or Duchenne plasma. This finding had been considered previously as evidence for the presence of an aberrant adenylate kinase in Duchenne plasma.

Spectral analysis of the EEG in children during the introduction of antiepileptic therapy with valproic acid.

The EEGs of 16 newly diagnosed children with primary generalized epilepsy were examined before and during up to 3 years of antiepileptic therapy with valproic acid. Spectral analysis was performed and parameters of the relative power within the conventional frequency bands were compared with norm data. Before treatment no significant differences of the background activity between epileptic children and healthy controls were found. While treatment was able to reduce seizures and spike-wave activity, EEG parameters did not change systematically. There was no relation between valproate serum levels and parameters of the background activity.