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Novel strategies aiming to increase survival rates in patients with advanced stage mantle cell lymphoma (MCL) and relapsing diffuse large B cell lymphoma (DLBCL) are a clinical need. High dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) has improved progression free (PFS) and overall survival (OS) in MCL and relapsed DLBCL. However the role of CD34+ cell selection before ASCT in MCL and DLBCL is unclear. We retrospectively analyzed the outcome of 62 consecutive patients with advanced stage MCL or relapsed DLBCL undergoing ASCT with (n=31) or without (n=31) prior CD34+ selection. All patients had stage III or IV disease with 47 having DLBCL and 53 MCL. The median duration for neutrophil and platelet recovery was 12 and 16 days in CD34+ selected patients and 11 (P

Die Ernahrung von Schulkindern und Jugendlichen ist ein wichtiges Thema im Rahmen der Gesundheitsforderung in Schulen. Sie spielt in dieser Altersgruppe eine wichtige Rolle fur die spatere Gesundheit und stellt damit einen bedeutenden wirtschaftlichen Faktor im Gesundheitswesen dar. Untersuchungen in den letzten Jahren uber das Ernahrungsverhalten und den Ernahrungszustand bei Schulkindern haben gezeigt, dass deutliche Abweichungen gegenuber den Empfehlungen fur eine optimale Nahrstoffzufuhr bestehen. Die Ernahrung ist z. T. zu arm an Energie und Kohlehydraten, v. a. komplexe, und zu reich an Eiweisen und Fetten, und auch im Bereich von Mineralstoffen und Vitaminen bestehen Unterversorgungen. Die Zunahme der Adipositas als Folge einer zu fettreichen Ernahrung und eines Bewegungsmangels gibt zu Besorgnis Anlass. Anhand von Ernahrungserhebungen bei deutschen, osterreichischen und schweizerischen Schulkindern wird die heutige Ernahrungssituation bezuglich des Ernahrungsverhaltens und des Ernahrungszustands dargestellt. Spezielle Aspekte wie Kalzium- und Eisenversorgung und die Einnahme von Ballaststoffen werden besonders hervorgehoben. Die heutigen neuen gemeinsamen Referenzwerte 2000 fur die Nahrstoffzufuhr der deutschen (D), osterreichischen (A) und schweizerischen (CH) Ernahrungsgesellschaften (D-A-CH) werden vorgestellt und die praktische Umsetzung wird mittels der vom Forschungsinstitut fur Kinderernahrung in Dortmund erarbeiteten optimierten Mischkost beschrieben. 2 Projekte im Rahmen der Gesundheitsforderung in Schulen finden besondere Beachtung: die Aktion “Pausenkiosk” oder “Pausenverpflegung” und das Projekt “Energiemanagement”, das Ernahrung und Bewegung gemeinsam erfasst.

Die Ernahrung der Mutter in Schwangerschaft und Stillzeit hat eine grose praventive Bedeutung fur die Gesundheit des Kinds. Entscheidende Faktoren sind dabei der pragravide Ernahrungsstatus der Mutter, Quantitat und Qualitat der Ernahrung und die Gewichtszunahme wahrend der Schwangerschaft. Mutterliche Krankheiten, die eine diatetische Behandlung notig machen, wie Diabetes oder maternale PKU, konnen die Situation erschweren. Die optimale Ernahrung in der Schwangerschaft umfast v.a. im 2. und 3. Trimenon eine hohere Energiezufuhr (+1,257·106 J/Tag=+300 kcal/Tag) sowie eine Mehreinnahme aller Nahrstoffe, inklusive Mineralstoffe und Vitamine. Von besonderer Bedeutung sind die ω-3-Fettsauren (Fischol), die Mineralien Eisen, Magnesium, Zink und Jod sowie die Vitamine Folsaure, B12 und K. Sowohl Unterernahrung als auch Uberernahrung und Mangel an den aufgefuhrten Nahrstoffen konnen sich beim Kind in verschiedener Weise auswirken: gehaufte Aborte, Fruhgeburt, erniedrigtes Geburtsgewicht, Misbildungen, intrauterine und postnatale Entwicklungsstorungen sowie spezifische Organstorungen. Folsaure: Eine besondere Bedeutung kommt heute der Folsaure zur Pravention von Neu-ralrohrdefekten zu. Zahlreiche Interven-tionsstudien zeigen, das 70–80% der Neu-ralrohrdefekte (NRD) mit einer pra- und postkonzeptionellen Zufuhr von Folsaure vermieden werden konnen. Fur die Pravention der Wiederholung von NRD innerhalb einer Familie (recurrence) werden tagliche Dosen von 4 mg Folsaure empfohlen. Zur primaren Pravention (occurrence) von NRD sollte eine tagliche Dosis von 400 μg Folsaure eingenommen werden, entweder in Form folsaurereicher naturlicher Nahrungsmittel, was allerdings schwierig zu erreichen ist, oder folsaureangereicherter Nahrungsmittel wie Brot und Zerealien oder durch eine Einnahme von Folsaure als Einzel- oder Multivitaminpraparat. Vitamine und Spurenelemente: Auch Jod und Vitamin B12 mussen in der Ernahrung der schwangeren Frau zur Verhutung von Entwicklungsstorungen beim Kind in genugender Menge (Jod 230 μg/Tag/, Vitamin B12 2,2–3,5 μg/Tag) vorhanden sein, ansonsten ist eine tagliche Zufuhr in Form von Vitaminpraparaten notwendig. Schon wahrend der Schwangerschaft bereitet sich die Mutter durch Aufbau von Reserven auf die Stillzeit vor. In dieser Phase ist der Nahrstoff- und Energiebedarf noch etwas hoher (+1,695·106 J=+500 kcal/Tag). Die Zusammensetzung der Muttermilch kann v.a. bei den Fettsauren beeinflust werden. Von den Mineralstoffen lassen sich nur Mangan, Jod und Fluor durch Supplemente in der Muttermilch erhohen, hingegen fast alle Vitamine, z.T. allerdings nur begrenzt (Vitamin C, B1 und Biotin). Von besonderer Bedeutung sind wiederum die ω-3-Fettsauren, Vitamin B12 und Jod. Eiweis: Fremdeiweise in der Muttermilch konnen kindliche Allergien auslosen und so die Mutter zu einer speziellen praventiven Ernahrung veranlassen. Diskussion: Die Ernahrung der Mutter in Schwangerschaft und Stillzeit beinhaltet also viele praventive Aspekte. Vertiefte Kenntnisse daruber sind die Grundlage fur eine gute Beratung und Betreuung sowohl in der geburtshilflichen als auch in der kinderarztlichen Praxis.

Eine Patientin mit juveniler chronischer Arthritis erlitt im Alter von 16 Jahren in kurzem Abstand im Zusammenhang mit der Menstruation 2mal ein toxisches Schocksyndrom. Bei der 2. Episode konnte Mycoplasma hominis im Trachealsekret nachgewiesen werden. Diskussion: Beim toxischen Schocksyndrom ist die Atiologie, das Toxic-shock-Syndrom-Toxin-1, welches als Superantigen die Krankheit auslost, bekannt. Bei der juvenilen chronischen Arthritis wird ein ahnlicher Mechanismus diskutiert. Unser Fallbeispiel last vermuten, das beiden Krankheiten ahnliche immunpathogenetische Prinzipien zugrundeliegen,.

Erbliche Storungen im Galaktosestoffwechsel fuhren zu Galaktosamie. Drei Enzymstorungen sind bekannt: Mangel an Galaktokinase, Galaktose-1-Phosphatu-ridyltransferase (klassische Galaktosamie) und an UDP-Ga-laktose-4-Epimerase (Abb. 41.1). Die Anreicherung von Ga-laktosemetaboliten fuhrt zu Schadigungen vor allem von Leber, Niere, Gehirn, Ovar und Linse. Durch eine galakto-seeingeschrankte Diat konnen akute toxische Erscheinungen vermieden werden, doch zeigen Patienten mit klassischer Galaktosamie trotz Diat neurologische Auffalligkeiten und Ovardysfunktion.

Das Menkes-Syndrom (M-S) ist seit 1962 bekannt [139]. Mit der Entdeckung einer Storung im Kupferstoffwechsel durch Danks 10 Jahre spater nahm das Interesse an diesem Krankheitsbild betrachtlich zu [52]. Viele Einzelbeobachtungen haben seither die abnormen Befunde im Cu-Stoffwechsel bestatigt. Neue biochemische Methoden ermoglichten einen besseren Einblick in die Pathogenese dieser Krankheit und die Entwicklung einer pranatalen Diagnostik.

It is still an important duty for pediatricians to inform parents about infant nutrition. An effort to insure successful breastfeeding in newborns is particularly necessary in order to avoid the introduction of foreign proteins, especially in high risk children. Allergy prevention is thus instigated early on. If necessary, a hypoallergenic milk may be used. Recently, there has been great concern that a high content of dioxine in breast milk exists, higher than in infant formulas. However, no evidence of toxicity has been noticed to date in breast fed children due to dioxine. Therefore, because of the many advantages, breast feeding should still be recommended for the first 4-6 months. In the last few years infant formulas have been adapted to simulate breastmilk by supplementation with taurine, carnitine and nucleotides. Most recently, Omega-3-fatty acids, which are important constituents of membrane phospholipids in the nervous system and the retina, have been added. In infant nutrition there is a trend nowadays toward unconventional forms of nutrition. An exclusive "lactoovo-vegetable" diet is able to meet all the requirements of a growing child. The critical components of a vegetarian diet are iron, calcium, vitamin B12 and vitamin D. These few examples demonstrate how important a nutrition-committee could be in elaborating basic information for the pediatrician, which would be useful in his daily work.

The Dubowitz-syndrome, a rare, autosomal-recessive condition, was seen in a 6-year-old female patient. Verbal, fine motor, and social development were severely retarded. Behavioral disturbances, predominantly hyperactivity were apparent. Short stature of unknown origin became evident during infancy and early childhood. Atopic dermatitis and specific sensitivity to inhalant and nutritive allergens was found. A pattern of minor anomalies included inner epicanthic folds, hypertelorism, flat nasal bridge, globular nasal tip, coarse lips, and retrogenia as well as pes planovalgus, and a sacral dimple.

Gluconeogenesis is the formation of glucose from noncarbohydrate precursors such as lactate, pyruvate, glycerol, and certain amino acids. It is a continuous process important for maintaining glucose homeostasis during fasting.

tyrosine metabolites. 3-(4-Hydro~y[3,5-~H2]phenyI)propionic acid and 3-(4-hydro~y[3,5-~H2]pheny1)lactic acid yielded the rearrangement product 3-(3-hydro~y[2,4-~H2]phenyl)propionic acid. The starting materials as well as the product all contained two deuterium atoms both ortlzo to the hydroxyl group. Therefore the rearrangement reaction must depend on a shift of the side chain. Studies of tyrosine metabolism in vivo were done by dosing normal subjects as well as patients with dideuterated tyrosine [l, 21. One patient with hyperphenylalaninaemia, one with phenylketonuria and another with oligophrenia of unknown genesis were dosed orally with 150 mg ~-[3,5-~Hz]tyrosine/kg, i.e. the tyrosine contained two deuterium atoms in ortlzo positions to the hydroxyl group. Gas chromatography/ mass spectrometry investigations of the urine revealed that the same metabolites were deuteratcd as in normal controls, but in addition [3H]benzoic acid, [2H]hippuric acid and 3-(3-hydro~y[~H]phenyl)hydracrylic acid were found and were excreted in increased concentrations. When neomycin was given for three days to sterilize the intestine partially before the dosing, tyrosine was no longer converted into the three additional compounds mentioned above. No excretion of the ordinary urinary metabolites p-cresol and phenol was found after administration of neomycin. All tyrosine metabolites still contained two deuterium atoms/molecule. This leads to the conclusion that benzoic acid, hippuric acid, 3-(3-hydroxyphenyl)hydracrylic acid, phenol and p-cresol are derived from the degradation of tyrosine or tyrosine metabolites by the intestinal flora. We were therefore interested in studying the metabolic activities of the human intestinal flora by means of tyrosine and its metabolites. In analogy to the above experiments in vivo, we used deuterated compounds for incubation with human faecal contents. From the patients with high concentrations of phenylalanine in the blood only the mentally normal subjects showed the abnormal tyrosine metabolite 3-(3-hydroxyphenyl)hydracrylic acid. Analogous dosing tests with mentally handicapped patients with phenylketonuria did not show this abnormal urinary tyrosine metabolite. Therefore, this new rearrangement reaction was of special interest. The small yield of 3-(3’-hydroxypheny1)hydracrylic acid by dosing tcsts in vivn and the low stability of this aromatic acid made it difficult to study the rearrangement reaction with 3-( 3-hydroxypheny1)hydracrylic acid itself. We therefore looked for the same or an analogous reaction by incubation of tyrosine and tyrosine metabolites with human faecal specimens in vitro.

Menkes' disease is a rare X-linked recessive inherited disorder of copper metabolism characterized by neurodegeneration, peculiar hair, and early death. The symptoms can be attributed to decreased activity of copper-dependent enzymes, but treatment with copper has so far failed to influence the course of the disease. We present the case of an 8.5-year-old boy, whom we treated alternately with intramuscular copper-histidine and oral D-penicillamine and who showed an extraordinary mild form of Menkes' disease. In contrast to his untreated maternal uncle, this patient had normal growth and intellectual development, but showed marked ataxia and slight speech difficulties. We suggest that parenteral copper-histidine supplemented by oral D-penicillamine may be of benefit to early-treated patients with Menkes' disease.

White-cell count and differential blood count, total protein, lactate dehydrogenase activity (E.C. 1.1.1.27) and lactate concentration were determined in 496 CSF samples, obtained by lumbar puncture. Lactate was measured with a new enzymatic test. Reference values were determined for lactate and lactate dehydrogenase (90% limits: 1.2-2.1 mmol/l and 6-26 U/l, respectively). Lactate content proved to be best in the differential diagnosis between acute bacterial and abacterial meningitis: concentrations of 3.5 mmol/ml and above were found exclusively in bacterial meningitis. As for other diseases, markedly increased lactate concentrations were measured only in patients with brain tumour or cerebrovascular disease (up to 9.3 mmol/l). Determination of lactate concentration alone would have led to a misdiagnosis of acute bacterial meningitis in 3% of cases. If the CSF contains 3.5 mmol/l lactate or more and the leucocyte cell count is above 800/microliter, brain tumour or cerebrovascular disease can be practically excluded and the diagnosis of bacterial meningitis made with a high degree of reliability.

Hydantion-5-propionic acid was detected in massive amounts in the urine of two previously described sisters with folic acid nondependent formiminoglutamic aciduria. HPA was identified rigorously, e.g. by gas chromatography-mass spectrometry, and was measured quantitatively by selected ion monitoring (mass fragmentography) using deuterated HPA as internal standard. Before histidine loading, both girls with the postulated formiminotransferase deficiency excreted an amount of HPA more than 50 times greater than the control subjects. After histidine ingestion, HPA excretion was still doubled or tripled. With the exception of the father, the values for the other members of the family also markedly exceeded the normal range and were of the same order of magnitude as in folate deficiency. Measurement of HPA excretion in urine seems to be a valuable supplement or alternative to the enzymatic FIGu test for the detection of general or functional folate deficiency or impaired folate utilization and it will be indispensable for the detection of (as yet unknown) 4-imidazolone-5-propionic acid hydrolase deficiency.

The application in vivo of stable isotopes, e.g. deuterium, for the study of metabolic pathways is demonstrated on the example of the phenylalanine-tyrosine metabolism. A healthy child, a patient with phenylketonuria and a patient with hyper phenylalaninemia were loaded with 200 mg/kg of deuterated phenylalanine. The concentration and deuterium content of the excreted aromatic acids were examined by gas chromatography and gas chromatography/mass spectrometry. Unlike in the healthy child, no deuterium was incorporated into the metabolites of tyrosine by the patients with phenylketonuria and hyperphenylalaninemia. The m-hydroxylation of phenylalanine leading to m-OH-phenylacetic acid was blocked during the loading test in phenylketonuric as well as in hyperphenylalaninemic patients.

Two sisters were detected with normal serum folic acid excreting formiminoglutamic acid (FIGLU) in urine in excessive amounts (582 ± 76 mmoles FIGLU/mole creatinine; about 0.5 g/day). The intelligence quotient of the girls is now 0.83 and 1.13, respectively. FIGLU was isolated from urine by ionexchange chromatography, high-voltage electrophoresis and adsorption chromatography on Porapak Q , and was identified by mass spectrometry of the free acid and of the dimethyl ester hydrochloride, by elemental analysis, chemical degradation, and by enzymatic action (EC 2.1.2.5). Increase in serum folate ( L. casei ) after a single oral dose of folic acid was normal. The urinary FIGLU excretion was not influenced by pharmacological oral doses of folic acid (10 mg/day for 8 days), nor by a load with glycine or serine, but was reduced by a diet low in histidine, and was increased by oral loading with histidine (3 × 198 mg/kg body weight) to about 2900 mmoles/ mole creatinine (about 1.5 g/day). Of the ingested excess histidine, 22% were excreted as FIGLU. Urinary histidine, urocanic acid, formic acid, and aminoimidazole carboxamide remained normal. After a glycine load (0.3 g/kg) serine concentration in serum increased normally. The abnormality is believed to be caused by a folic acid non-dependent deficiency in formimino- l -glutamate :tetrahydrofolate 5-formiminotransferase (EC 2.1.2.5). No liver biopsy was available to measure this enzyme in our subjects. All attempts to measure the enzyme activity in normal human erythrocytes failed. Instead, a significant decrease of hog liver enzyme activity was noted after addition of hemolysate from normal controls. The abnormality differs from the published cases of postulated formiminotransferase deficiency in the 10-fold higher FIGLU excretion after histidine loading, the normal hematological findings, the normal serum folic acid, and the lack of mental retardation in one case. The formation of N , N ′-di-(2-glutaryl)formamidine in concentrated solutions of FIGLU is evidenced by mass spectrometry.

For the understanding and interpretation of hypoglycemia it is important to know the many complex endocrine and metabolic regulations in the homoeostasis of blood glucose. Glucose-absorption, distribution and availability, glycolysis, production and utilization of glycogen as well as gluconeogenesis are important steps of this homoeostasis, and hypoglycemia always reflects a disturbance in it. When blood glucose is low the availability of energy for the brain is decreased if no alternative energy sources like lactate or ketones are provided. Hypoglycemia is more often in the neonatal period than in later childhood. The causes can be divided into different groups according to pathogenetic mechanisms. Within each group again many singular defects are known. Fructose-1,6-diphosphatase deficiency, hereditary fructose intolerance, glycogenosis type I and so called "ketotic hypoglycemia" are given as examples to elucidate special clinical and biochemical aspects of inborn errors of carbohydrate metabolism.

BCG osteitis is a rare complication after vaccination in the newborn. On the basis of various, not yet fully known mechanisms, an increase in the number of cases is nevertheless possible. In the period 1980-1985 the authors recorded 6 instances of BCG osteitis. The clinical findings and diagnostic criteria are described. The incidence, pathogenesis and therapy of the disease are discussed.

On routine smears of blood and bone marrow of four patients with GM1 gangliosidosis type I, eosinophil granulocytes were unusually pale and contained faintly stained, unevenly spaced granules some of which were larger than normal and had abnormal ultrastructural appearance. The anomaly may represent a hitherto overlooked but easily obtainable diagnostic marker.

A 6-month-old boy is described presenting with BCG osteomyelitis of the distal metaphysis of the left femur extending into the epiphysis. Epidemiological, diagnostic and therapeutical problems of BCG osteomyelitis after BCG vaccination in the newborn period are discussed reviewing 89 published records of this late onset complication of BCG vaccination.

In two infants with pneumonia, Coombs test positive hemolytic anemia and hemolytic uremic syndrome (HUS), exposure of the Thomsen cryptantigen, probably due to the action of circulating neuraminidase, was demonstrated. Reaction between the exposed T-antigen and anti-T agglutinin, normally present in human blood, can lead to difficulties in serological testing and during blood transfusion. The place of exchange transfusions using washed RBC or heparinized whole blood in the management of this subgroup of HUS is discussed.

An in vivo determination of the phenylalanine-4-hydroxylase (E. C. 1.14.16.1) activity is described. Subjects were loaded wit deuterated L-phenylalanine-d5 (200 mg/kg), and the deuterated tyrosine and deuterated phenylalanine in plasma was analyzed using mass fragmentography. Six phenylketonurics (PKU), four hyperphenylalaninemics and two healthy controls were investigated. This method allowed a specific differentiation between PKU's, hyperphenylalaninemics and health controls. The remaining enzyme activity in hyperphenylalaninemics and in PKU patients can be estimated with relatively high accuracy. The hyperphenylalaninemic patients showed 7--17% of the phenylalanine-4-hydroxylase activity found in the two control persons. The PKU patients under diet showed approximately 2--3% of the activity found in the control group. In the PKU patients, loaded while showing high phenylalanine blood concentrations, no remaining activity could be measured. The logarithm of phenylalanine-d5 over tyrosine-d4 in plasma 1 h after loading gives the best differentiation. One single plasma sample of approximately 0.5 ml is sufficient.

Carbamyl phosphate synthetase (CPS) catalyses the synthesis of carbamyl-phosphate from ammonia and bicarbonate and is the first step in ureagenesis. The infant described in this report suffered from deficiency of this enzyme. The symptoms started on the 2nd day of life with tachycardia, apathy, irritability and metabolic alcalosis, on the 4th day coma and fits occurred due to hyperammonia (ammonia in the blood max 496 mumol/l, normally up to 150 in newborns). In hepatic tissue no activity of carbamyl phosphate synthetase could be measured (normal range 0.66-2.1 mumol/h/mg protein). Peritoneal dialysis was instituted, but the metabolic crisis could only be overcome by the following therapeutic measures: restriction of protein intake to 1.5 g/kg/d in part as a special aminoacid mixture, in part as breast milk; sufficient caloric supply (600-500 kJ/kg/d); sodium benzoate 350 mg/kg/d: arginine 2 mmol/kg/d respectively citrulline 350 mg/kg/d, and carnitine 150 mg/kg/d. By these procedures the exogenous and endogenous load of ammonia could be minimized. Electroencephalogram and mental development were normal. Acute metabolic crises with hyperammonia during catabolic states (infections) could be treated several times. At the age of 8 months, however, the patient died during such a crisis. This case shows that it is possible to achieve a normal psychomotor development in complete CPS-deficiency by adequate therapy. Catabolic states are difficult to manage.

White-cell count and differential blood count, total protein, lactate dehydrogenase activity (E.C. 1.1.1.27) and lactate concentration were determined in 496 CSF samples, obtained by lumbar puncture. Lactate was measured with a new enzymatic test. Reference values were determined for lactate and lactate dehydrogenase (90% limits: 1.2-2.1 mmol/l and 6-26 U/l, respectively). Lactate content proved to be best in the differential diagnosis between acute bacterial and abacterial meningitis: concentrations of 3.5 mmol/ml and above were found exclusively in bacterial meningitis. As for other diseases, markedly increased lactate concentrations were measured only in patients with brain tumour or cerebrovascular disease (up to 9.3 mmol/l). Determination of lactate concentration alone would have led to a misdiagnosis of acute bacterial meningitis in 3% of cases. If the CSF contains 3.5 mmol/l lactate or more and the leucocyte cell count is above 800/microliter, brain tumour or cerebrovascular disease can be practically excluded and the diagnosis of bacterial meningitis made with a high degree of reliability.

Antipyretic effect, tolerability, and acceptance of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) drops were tested within the scope of an open study including a total of 111 children with fever of various etiology; two investigational centers participated in this study. The initial mean rectal temperature averaged 39.3 degrees C. The dosage of suprofen drops depended upon the patient's body weight and age; the drug was administered up to q.i.d., for 4 days at the longest. Body temperature, pulse rate, and respiratory rate were recorded prior to administration and 1/2, 1, 1 1/2, 2, 3, 4, 5 and 6 h after first administration of the drug. The antipyretic effect of the treatment was appreciated good in 89% of the cases. Reduction in temperature was statistically significant at all rating times after first administration of the drops as compared with the initial values. Adverse drug experiences such as vomiting and loose stools were seen in only 5 cases. The tolerability was considered good in 96% and the acceptance in 94% of the cases.

Hemolytic-uremic syndrome (HUS) accompanied by pneumococcal infections forms a characteristic subgroup of HUS. Pneumococcal neuraminidase splits off neuraminic acid from the glycoproteins present on the surface of red cells, thrombocytes and endothelial cells, and thus exposes the hidden Thomsen cryptantigen (T-Ag). The T-Ag can then react with a complement-fixing antibody of the IgM class which is present in all human plasmas after the age of 6 months. Early diagnosis of T-transformation should be attempted. Highly suggestive hints are: pneumonia, hemolytic anemia, reticulocytopenia, difficulties in ABO typing, a positive direct Coombs test and a positive minor cross-match. The definite diagnosis of T-transformation is established with the aid of anti-T agglutinins from Arachis hypogaea, the common peanut. Two children aged 19 and 22 months with pneumonia, Coombs-positive hemolytic anemia, HUS and exposure of the T-Ag on the red cell membrane are described. In one of them, circulating neuraminidase and circulating pneumococcal antigen of serotype 3 were found. In both children exchange transfusions resulted in elimination of circulating neuraminidase and of T-transformed red cells prone to hemolysis.

A diphtheria epidemic in the eastern part of Switzerland in 1974 and the measures which were taken for its management and eradication are described. In particular it is pointed out that at present diphtheria displays atypical clinical symptoms in Europe, a fact that renders the diagnosis very difficult in many cases. Therefore, it is important to perform a throat swab in every patient with suspected diphtheria; it is also necessary to explicitly require a search for C. diphtheriae. The early recognition and early treatment of diphtheria with penicillin or erythromycin is of the utmost importance in order to avoid neurological and cardiac complications. With regard to the management and eradication of a diphtheria epidemic, the most important measures are rapid antibiotic protection of all contacts and a widespread immunization of the population. Vaccination of adults with a DiTe vaccine containing a reduced amount of Di-toxoid is recommanded.

IN 1966 Davis et al.1 described two girls with chronic eczema, recurrent staphylococcal infections and an abnormal inflammatory response with the formation of "cold" staphylococcal abscesses (Job's syndrome). Buckley et al.2 observed hyperimmunoglobulinemia E in two boys with severe recurrent skin and lung infections, and Clark et al.3 demonstrated depressed chemotaxis of polymorphonuclear leukocytes and hyperimmunoglobulinemia E in a girl with similar clinical manifestations. Subsequently, Hill et al.4 reported hyperimmunoglobulinemia E and defective chemotaxis of polymorphonuclear leukocytes in the two original cases of Job's syndrome. Several other patients with related disorders have recently been described.4 5 6 7 8 9 10 11 12 13 Cell-mediated immunity was abnormal in . . .

Bejar et al. described increased concentrations of valine, leucine and isoleucine in the plasma of 2 patients with cerebral gigantism (Sotos-syndrome). We have recently investigated a group of 14 children with Sotos-syndrome. The data of the plasma amino-acid determinations were compared with those of aged-matched healthy controls, 9 children with benign muscular hypotonia, 10 children with Down's syndrome and finally with those of 13 children with familial tall stature. The mean concentration of serine, glutamic acid, valine, isoleucine, leucine and phenylalanine was lower in the patients with Sotos-syndrome when compared to the healthy control group. However, all patients with benign muscular hypotonia and Down's syndrome showed increased concentrations of proline, glycine, alanine, ornithine and lysine in the plasma whereas the mean values of the children with familial tall stature differed only slightly from those of the controls. The levels of the plasma-aminoacids in patients with Sotos-syndrome were only slightly different from those in patients with muscular hypotonia, but generally lower than in tall children. We conclude that the determination of plasma-aminoacids is of no value in the diagnosis of Sotos-syndrome.

Total urinary biopterin (B), neopterin (Ne) and monapterin (M) were measured in 25 healthy newborns, children and adults, in 49 patients with phenylketonuria (PKU) assumed to be deficient in phenylalanine-4-hydroxylase (PH), in 7 patients with dihydrobiopterin synthetase (DHBS) deficiency and in 4 patients with dihydropteridine reductase (DHPR) deficiency. Excretion of Ne based on creatinine (Ne/C) was 6.6 times higher in healthy newborns than in adults, suggesting a slow maturation of DHBS activity. Newborns excreted more Ne than B and adults more B than Ne (32 and 72% B of the sum of B + Ne, respectively). In all cases, excretion of M was 4-15% of that of Ne. PH deficient patients excreted more B and Ne than healthy controls and again, newborns more than older children. In individual patients, excretion of pterins correlated with phenylalanine (Phe) concentration in plasma; plasma Phe of different patients did not correlate well with excretion of pterins. In PKU variants with deficiency of tetrahydrobiopterin (BH4), extreme pterin patterns were observed: in DHBS- and DHPR-deficient patients, less than 3.5 and more than 81% B were found, respectively. All 30 samples from these patients investigated could be distinguished from those of PH-deficient patients and controls by a two-dimensional plot of % B versus B/C. Thus it seems likely that PKU variants due to BH4 deficiency could be detected early and differentiated by measurement of urinary B, Ne and C. This was exemplified already in one case. - In urine of patients with DHBS deficiency, high concentrations of 3'-hydroxysepiapterin were found in addition to Ne.

Subdural interhemispheric empyema was diagnosed by angiography and computerized tomography (CT) in a 7-year-old boy suffering from acute left hemiparesis. After neurosurgical intervention his condition improved. Peptostreptococcus intermedius was cultured from the empyema. One year after hospitalisation the boy is in good condition. The importance of the CT-scanning for diagnosis and management of brain abscess or empyema is stressed.

Twenty infants and young children with hereditary fructose intolerance (HFI) were admitted to hospital. None was diagnosed at admission. Referals were for vomiting of unknown aetiology (16X), pyloric stenosis or hiatus hernia (5X), toxic condition (3X), and hepatomegaly of unknown origin (5X). Feeding difficulties (20X), vomiting (18X), and failure to thrive (16X) were leading symptoms. The most frequent clinical findings were hepatomegaly (18X), pallor (14X), haemorrhages (13X). Ascites, oliguria, tachypnoea, fever, splenomegaly and rickets were less frequent. Laboratory findings were indicative of disturbed hepatic and renal tubular function and also of disturbed intermediary metabolism (hypokaliaemia, hypophosphataemia). However, hypoglycaemia was found in only 4 out of 15 patients tested. Differential diagnosis after hospital admission centered on metabolic disorders such as glycogenoses, galactosaemia, tyrosinosis, or Wilson's disease. Hepatitis, toxic hepatosis, liver tumour, intrauterine infection and sepsis were also considered. Eleven children had first ingested fructose within the first 6 weeks of life. The diagnosis was usually established only many weeks or months after first fructose intake and appearance of symptoms. This documents how difficult the diagnosis of this disease can be both in practice and in hospital. The course was severe in 11 children and lethal in 4. In only 5 patients was the course mild. The 16 survivors are doing well under fructose-exclusion diet. Irreversible visual impairment after intraocular haemorrhage occurred once. In each case HFI could have been suspected immediately, had a detailed nutritional history been taken. Practising paediatricians should know the composition of commonly used infant formulae. They should never prescribe sugared condensed milk for intractable vomiting prior to excluding HFI. Solution for intravenous infusion containing fructose and sorbitol are life-threatening for undiagnosed HFI patients.

Fructose is a major food constituent in human nutrition. In the form of refined sugar its consumption has steadily increased during recent decades. It has been used widely for clinical purposes as it has been claimed to be of advantage for diabetics, and for parenteral nutrition in adults and children. The latter use has remained controversial as many studies have indicated that for infusion therapy glucose is safest and cheapest1,2. The clinical and metabolic aspects of fructose have been discussed at several symposia3–6.

In 1966 Davis et al.1 reported two girls with chronic eczema and recurrent ‘cold’ staphylococcal infections. The authors suggested that these patients may have a defect in local resistance to staphylococcal infections, related to an abnormality of the mediators of the acute inflammatory response. These and other patients with comparable clinical findings have subsequently been studied by Hill et al.2 who found hyperimmunoglobulinaemia E and impaired chemotaxis of polymorphonuclear leukocytes (PMN) in vitro as the particular immunological features of this clinical syndrome. A substantial number of patients has since been reported with similar clinical and immunological characteristics3–12. The mechanisms leading to granulocyte dysfunction in vitro and the relationship to the recurrent, atypical staphylococcal infections in vivo, however, are not yet understood. There is some evidence that immediate-type hypersensitivity reactions and impaired PMN function in vitro may be related. We have observed in recent years three patients with chronic eczema, recurrent ‘cold’ staphylococcal infections and hyperimmunoglobulinaemia E. One patient has been studied more extensively and the preliminary data obtained suggest that the diminished PMN chemotaxis in vitro is probably not due to an intrinsic cellular defect but results from antigen-induced and IgE mediated hypersensitivity reaction interfering with normal local neutrophil function.