Congenital myopathy with focal loss of cross striations: a case report with morphologic and immunohistochemical study.

A case of an unusual congenital myopathy is reported. The boy presented at birth with generalized muscular hypotonia and dysmorphic features. Muscle biopsy at the age of 10 years revealed focal areas with decreased ATPase activity and variable oxidative enzyme activity. There was only one type II fiber in the whole section. 22.5% of fibers had central nuclei, sometimes with radial arrangement of the intermyofibrillary network. Focal lesions displayed strong desmin and weak vimentin immunoreactivity. On electron microscopic examination normal sarcomeres were focally disrupted and mitochondria were absent from these areas; the normal structure was replaced by numerous fragments of sarcoplasmic reticulum, filamentous material, scattered glycogen particles, and the Z-line was replaced by irregular longitudinal streaks of electron-dense fibrillar material. We classify this case as a congenital myopathy with focal loss of cross striations.

Lead and cadmium in breast milk. Higher levels in urban vs rural mothers during the first 3 months of lactation.

Breast milk from 10 women each from the city of Hamburg and from a rural area was analyzed by atomic absorption spectrometry for contamination with lead and cadmium. Samples were examined at regular intervals for 3 months after birth. On day 5 a diurnal profile was analyzed; on the other days milk was taken before and after the morning feed. Daily permissible intake (DPI) for lead is 5 micrograms/kg/day for children; the DPI for cadmium has as yet been determined only for adults as 400-500 micrograms/week, equivalent to about 1 microgram/kg/day (WHO 1972). For breast milk as the main source of nutrition in infants, this study shows values of 9.1 +/- 2.5 (SD) microgram/l for lead in the rural population, with a tendency to decrease towards the end of lactation. Urban mothers had 13.3 +/- 5.5 (SD) microgram/l, with a tendency to increase. This difference was significant only on day 45. Mean cadmium content in rural mothers was 17.3 +/- 4.9 micrograms/l, with much higher values in the colostrum and a decrease after 15 days. Urban mothers had 24.6 +/- 7.3 micrograms/l, again with high colostrum values and a subsequent decrease. These latter values are not significantly different. Calculated daily intake according to these values is presented, based on 840 ml breast milk for a 5.5 kg infant per day. Rural infants ingested 0.9-1.3 micrograms/kg/day of lead, and in the city 1.5-2.3 micrograms/kg/day. Cadmium intake in rural infants amounted from 1.2-1.8 micrograms/kg/day; in Hamburg it was 1.6-2.2 micrograms/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

[Traumatic pancreatitis with peripheral osteolysis suggesting child abuse]. / Traumatische Pankreatitis mit peripheren Osteolysen als Hinweis auf Kindesmisshandlung.

In a nine year old girl pancreatitis was suspected after roentgenologic demonstration of osteolytic lesions in the short bones of her hands and feet. Similar to the 18 cases found in the literature she had upper abdominal trauma in her history, and as in 6 other cases there was a history of child abuse and battering. There was complete remission of the lesions following operation of the pancreatic pseudocyst. In this disease pseudocysts develop very often, they were found in 12 of the 18 cases reported. There is no valid explanation of the pathogenetic mechanism leading to osteolytic lesions. Intracapillary coagulation might contribute to the development of necrotic areas in the bone. It is concluded that especially in patients with only slight upper abdominal pain roentgenologic examination of part of the skeleton might be helpful in establishing the diagnosis.

Neuronal ceroidlipofuscinosis: CCT findings in fourteen patients.

CCT was performed in 14 children/adolescents with juvenile ceroid lipofuscinosis (JNCL) at different stages of the disease. CCT was normal in 7 patients; mildly abnormal in 3, clearly abnormal in another 3 and severely abnormal in 1 patient. Characteristic findings were symmetrical enlargement of subarachnoid spaces and of the lateral and third ventricles. White matter showed no changes in density. In later stages also the fourth ventricle was enlarged and cerebellar atrophy was seen. CCT findings were not closely correlated with onset and/or severity of the neurological abnormalities. CCT findings were positively correlated with age of the patients: CCT was usually normal if patients were less than 10 years old, and usually abnormal if patients were more than 14 years old.

[Phenobarbital in febrile convulsions of children (author's transl)]. / Phenobarbital bei Fieberkrämpfen im Kindesalter.

Phenobarbital (Luminal) was given to 41 children (aged 11 months to 4 1/2 years) with uncomplicated febrile convulsions. The drug was administered orally or intramuscularly at an initial dose of 10 mg/kg or 15 mg/kg, respectively. Twelve hours later and then every 24 hours until the fever had subsided the dosage was 5 mg/kg orally or intramuscularly. The effective serum phenobarbital level of 15 micrograms/ml was reached with an oral dose of 10 and 15 mg/kg after 25 hours or 90 minutes, respectively, with an intramuscular injection at the same dose after 12 hours and 40 minutes, respectively. These results indicate that the initial dose of phenobarbital in the prevention of further febrile convulsions in children should be 15 mg/kg intramuscularly. Treatment can then be continued orally with 5 mg/kg.

Treatment of childhood epilepsy with dipropylacetic acid (DPA).

Dipropylacetate (DPA) was used in the treatment of different types of epilepsy in 112 children aged 1--20 years, with a mean age of 9.2 years, for a period of 19.8 months, ranging from 1 to 49 months. Of this group, 64 children were therapy-resistant to other antiepileptic medications prior to the introduction of DPA; 31 were treated for the first time with an antiepileptic drug, which was DPA; 44 were treated with DPA alone; and 68 had one or more additional antiepileptic medication. The following results were found while DPA was administered in a relatively high dosage with a mean of 48 mg/kg body weight/day and ranging from 7 to 125 mg/kg/day. 1. Statistically, the results are significantly better in primary generalized epilepsy than in partial or in secondary generalized epilepsy. 2. Ninety-two percent of 51 patients who had absences were treated successfully. The same applies to 87% of 30 patients with primary generalized grand mal with spike wave, to all four patients who had impulsive petit mal, and to 47% of the 15 patients who had centrencephalic myoclonic-astatic petit mal. 3. Positive effect of DPA in partial epilepsy and secondary generalized epilepsy was seen only if the EEG pattern was 'centrencephalic' besides focal changes. During therapy with DPA, five patients with pure focal EEG showed an increase in seizure frequency, which demonstrated complete therapeutic failure. 4. Centrencephalic seizure activity (irregular spike wave, 3/s spike wave, and more than 3.5/s spike wave) were treated successfully (P less than 0.001). Focal changes or focal sharp wave with tendency to spread or generalization were treated unsucessfully.

[Myoclonic-astatic seizures (Lennox syndrome) in the course of juvenile neuronal ceroid-lipofuscinosis (M. Batten-Spielmeyer-Vogt) (author's transl)]. / Myoklonisch-astatische Anfälle (Lennox-Syndrom) im Verlauf der juvenilen neuronalen Ceroidlipofuscinose (M. Batten-Spielmeyer-Vogt).

EEG findings and the course of epileptic seizures in two patients with neuronal ceroid lipofuscinosis (Batten Spielmeyer Vogt syndrome) are presented. Both patients, during the course of disease, developed therapy resistant epileptic reactions with myoclonicastatic seizures. These seizures in connection with diffuse encephalopathy and EEG pattern with 2.5 to 3.5/sec slow-spike-wave meet the criteria of the Lennox syndrome. Pathogenetic questions regarding possible additional genetic predisposition for epileptic seizures are discussed. Since therapeutic effect of different medications is uncertain hormonal therapy may be considered.

[Organic acids including alpha-keto acids. Their importance and gaschromatographic-mass spectrometric analysis in serum and urine of infants]. / Die organischen Säuren einschliesslich der alpha-Ketosäuren.

Alpha-ketoacids are of some importance as intermediary metabolic products of aminoacids. Analysis of alpha-ketoacids has been difficult due to their ketogroups. A newly applied method is described by which these ketogroups are transformed to oximes. Linearity, massspectrometric verification, stability, sensitivity, and extractability allow the application to physiologic fluids: 1. when challenged with oral 1-leucine, children with maple syrup urine disease show an increase in all three branched-chain alpha-ketoacids; 2. apparently branched-chain alpha-ketoacids play a major role in the pathogenesis of the so-called ketotic hypoglycemia; 3. infants, newborns, and prematures have higher serum concentrations and higher urinary excretion of organic acids including the alpha-ketoacids than oder children; 4. even when humanized milk is fed there appears to be a higher metabolic load in newborns and prematures than under human milk; 5. tyrosine and its organic acids pHPPA, pHPLA, and pHPAA are significantly increased in newborns and prematures when humanized milk versus real human milk is fed. These are further reasons, among many others, to prefer human milk in infant feeding over all artificial products.

Homocysteine and cysteine loads in patients with homocystinuria due to cystathionine synthase deficiency: effects of vitamin B-6.

The metabolic response of patients with homocystinuria due to cystabhionine synthase deficiency to oral loads of homocysteine indicates: that even severely affected patients with homocystinuria have pools of cystine in their tissues; that control of sulfur amino acid metabolism favors increased concentrations of methionine rather than homocystine in the plasma; and that even patients who apparently are not B-6-responsive respond differently to the loads of homocysteine when challenged during B-6-treatment compared with their response before B-6 treatment. Loading tests with homocysteine indicate that B-6 treatment be of some benefit even in individuals who do not have an obvious biochemical response to such therapy.

Intoxication with primidone: continuous monitoring of serum primidone and its metabolites during forced diuresis.

An 18 year old girl is reported, who ingested 15 g of primidone (Liskantin), 330 mg/kg, to commit suicide. Continuous monitoring of the serum levels of primidone, PEMA, and phenobarbital revealed increased elimination of primidone by forced diuresis (6000 ml/24 hours). It is concluded that forced diuresis inhibits the otherwise mandatory increase in primidone metabolites, PEMA and phenobarbital. It is suggested that even after improvement of the clinical symptoms forced diuresis should be continued for at least 48 hours. In epileptic patients the reinstitution of primidone therapy should be considered only on the third day after accidental ingestion, if the clinical symptoms have improved, and if there is no possibility of immediate determination of primidone serum levels.

Juvenile familial hypertriglyceridemia and growth retardation. Clinical and biochemical observations in three siblings.

Familial hypertriglyceridemia or hyperlipoproteinemia type I was detected in three siblings aged 6, 11, and 14 of an otherwise normal Turkish family of 10 members. Initial values ranged from 1780 to 3750 mg/100 ml triglycerides in the milky white serum; cholesterol was normal. Lipoprotein pattern on agarose and acrylamide gel revealed a heavy band of chylomicrons and missing HDL; post-heparin lipolytic activity was decreased to about 30% of normal. Chylomicronemia could be induced by a fat-rich (50% of total calories) diet, but not by carbohydrates. On a low fat diet (5%) during hospitalization chylomicrons disappeared, and triglycerides decreased to about 450 mg/100 ml. Phenocopies of hypertriglyceridemia could be excluded. All three patients were the only members of the family who were small, below the third percentile. Their bone age was retarded from 18 to 30 months. There was no indication for an endocrine cause of the growth retardation: four different stimulation tests revealed normal growth hormone response, thyroid and adrenal functions were not impaired; sexual development was normal. Increased glucose assimilation was observed during intravenous and oral glucose load. Peak serum insulin response was above normal during stimulation tests. The possible etiologic role of hypertriglyceridemia in this concomitant growth retardation is discussed.

[The treatment of primary generalized epilepsies with dipropyl acetate (DPA)]. / Die Behandlung primär generalisierter Epilepsien mit Dipropylazetat (DPA)

79 patients with primary generalized epilepsies have been treated with DPA in a medium dosage of 51 mg/kg bodyweight/day, range 14 to 125 mg/kg/day, for a medium time of 22 months, range 2 to 49 months. 51 children out of this group had been treated previously and were therapy resistant to other medications. 27 children got DPA for their first medication. 34 patients were treated with DPA as a single drug, 45 were treated in combination with other medications. Therapeutic success was found to be remarkable good in impulsive petit mal (n = 4, all patients without any more seizures), in absences (n = 52, complete success in 84%), and in primary generalized grand mal seizures with spike-waves in the EEG alone or in combination with petit mal (n = 30, 87% success). However, centrencephalic myoclonic-astatic seizures (n = 17, no more seizures in 35%) were influenced significantly less. Side effects were rarely seen, mostly they could be observed in those patients treated with DPA and another medication. Side effects never induced interruption of treatment with DPA.

Methionine adenosyltransferase and transmethylation in fetal and neonatal lung of the human, monkey, and rabbit.

Optimal conditions for the assay of methionine adenosyltransferase in crude extracts of human fetal lung were determined. Maximal activity was obtained with 36 mM ATP, 20 mM L-methionine, 240 mM Mg++, and 160 mM K+. The pH optimum was 6.2--6.4, which is the same as that for adult human lung but lower than that for human liver. In human fetal lung, there was an increase in specific activity of methionine adenosyltransferase with increasing gestational age (r = 0.87; P less than 0.01) up to 25 weels of gestation, after which time no fetal specimens were obtained. The specific activity of 5-methyltetrahydrofolate-homocysteine methyltransferase of human fetal lung was 2.51 +/- 0.88 nmol/mg protein/hr, which was higher (P less than 0.001) than the activity found in newborn lung (0.14 +/- 0.01). Activity of serine hydroxymethyltransferase and of betaine-homocysteine methyltransferase was absent from human fetal lung. Activity of cystathionine synthase was absent from fetal, neonatal, and mature human lung. Activity of cystathionase in fetal and newborn human lung was present only in trace amounts. In rhesus monkey lung, beginning 15 days before term, the activity of methionine adenosyltransferase increased 6-fold to reach a maximum before term (165 days), and during the first weeks of life the activity gradually diminished. 5-Methyltetrahydrofolate-homocysteine methyltransferase activity in fetal (100--145 days) monkey lung was higher (6.57 +/- 0.95 nmol/mg protein/hr) than in newborn lungs (1.91 +/- 0.97) (P less than 0.001). In fetal rabbit lung, the activity of methionine adenosyltransferase decreased 2.5-fold during the last third of pregnancy, whereas a 2-fold increase occurred during the first 48 hr after term birth.