Posterior fossa syndrome in a patient with an ornithine transcarbamylase deficiency.

UNLABELLED: The posterior fossa syndrome (PFS) is a well-known clinical entity and mainly occurs in children. Ornithine transcarbamylase deficiency (OTC) is the most common urea cycle disorder, which occurs in an estimated 1 per 50.000 live births in Japan. Symptoms are mostly due to hyperammonemia and include nausea, vomiting, lethargia and even convulsions and coma. Common neurological symptoms at presentation of a hyperammonemia are a decreased level of consciousness, abnormal motor function or seizures. In this case we describe a girl with late onset OCT deficiency presenting with transient mutism and subsequent dysarthria, ataxia and behavioural changes. This is an exceptional report of a not yet described neurologic syndrome in OTC. SYNOPSIS: Neurologic symptoms in ornithine transcarbamylase deficiency do not only occur during an episode of hyperammonemia and may present as a transient neurologic symptoms compatible with the posterior fossa syndrome.

Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop.

Published data on treatment of fatty acid oxidation defects are scarce. Treatment recommendations have been developed on the basis of observations in 75 patients with long-chain fatty acid oxidation defects from 18 metabolic centres in Central Europe. Recommendations are based on expert practice and are suggested to be the basis for further multicentre prospective studies and the development of approved treatment guidelines. Considering that disease complications and prognosis differ between different disorders of long-chain fatty acid oxidation and also depend on the severity of the underlying enzyme deficiency, treatment recommendations have to be disease-specific and depend on individual disease severity. Disorders of the mitochondrial trifunctional protein are associated with the most severe clinical picture and require a strict fat-reduced and fat-modified (medium-chain triglyceride-supplemented) diet. Many patients still suffer acute life-threatening events or long-term neuropathic symptoms despite adequate treatment, and newborn screening has not significantly changed the prognosis for these severe phenotypes. Very long-chain acyl-CoA dehydrogenase deficiency recognized in neonatal screening, in contrast, frequently has a less severe disease course and dietary restrictions in many patients may be loosened. On the basis of the collected data, recommendations are given with regard to the fat and carbohydrate content of the diet, the maximal length of fasting periods and the use of l-carnitine in long-chain fatty acid oxidation defects.

Management and outcome in 75 individuals with long-chain fatty acid oxidation defects: results from a workshop.

At present, long-chain fatty acid oxidation (FAO) defects are diagnosed in a number of countries by newborn screening using tandem mass spectrometry. In the majority of cases, affected newborns are asymptomatic at time of diagnosis and acute clinical presentations can be avoided by early preventive measures. Because evidence-based studies on management of long-chain FAO defects are lacking, we carried out a retrospective analysis of 75 patients from 18 metabolic centres in Germany, Switzerland, Austria and the Netherlands with special regard to treatment and disease outcome. Dietary treatment is effective in many patients and can prevent acute metabolic derangements and prevent or reverse severe long-term complications such as cardiomyopathy. However, 38% of patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency had intermittent muscle weakness and pain despite adhering to therapy. Seventy-six per cent of patients with disorders of the mitochondrial trifunctional protein (TFP)-complex including long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, had long-term myopathic symptoms. Of these, 21% had irreversible peripheral neuropathy and 43% had retinopathy. The main principle of treatment was a fat-reduced and fat-modified diet. Fat restriction differed among patients with different enzyme defects and was strictest in disorders of the TFP-complex. Patients with a medium-chain fat-based diet received supplementation of essential long-chain fatty acids. l-Carnitine was supplemented in about half of the patients, but in none of the patients with VLCAD deficiency identified by newborn screening. In summary, in this cohort the treatment regimen was adapted to the severity of the underlying enzyme defect and thus differed among the group of long-chain FAO defects.

Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism.

Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because their diet is low in EFAs and LCPUFAs. We have investigated the EFA and LCPUFA status of children with various amino acid metabolism disorders (not PKU) under treatment. Fatty acid profiles of plasma and erythrocyte phospholipids of 33 patients (aged 0-18 years) and 38 matched controls were determined by gas-liquid chromatography. Food-frequency questionnaires were used to assess the mean fatty acid intake. The dietary intake of the EFAs linoleic acid (LA) and alpha-linolenic acid (ALA) was comparable in both groups, while the LCPUFA intake was much lower in patients. This was associated with lower relative concentrations (% of total fatty acids) of n-3 docosahexaenoic acid (DHA) in plasma and erythrocyte phospholipids. Concentrations of arachidonic acid (AA) did not differ. The same was observed for the two EFAs LA and ALA. Thus, as compared to healthy controls, children with amino acid metabolism disorders have a lower intake of LCPUFAs and have lower concentrations of DHA but not of AA in plasma and erythrocyte phospholipids. This suggests that endogenous AA synthesis might guarantee an adequate AA status. The lower DHA status, however, warrants further investigations regarding the impact of DHA supplementation on growth and development of these children.

Retinal dystrophy in long chain 3-hydroxy-acyl-coA dehydrogenase deficiency.

BACKGROUND: Long chain 3-hydroxyacyl-CoA-dehydrogenase (LCHAD) is one of the enzymes involved in the breakdown of fatty acids. A deficiency of this enzyme is associated with life threatening episodes of hypoketotic hypoglycaemia during prolonged fasting. Neuropathy and retinopigmentary changes were mentioned in only a few cases. METHODS: The case histories of two girls, aged 8 and 15 years, with LCHAD deficiency are reported. RESULTS: Both children with LCHAD deficiency exhibited extensive macular pigmentary depositions and a 'salt and pepper' scattering of pigment in their retinas. The patients have decreasing visual acuity. CONCLUSION: The early recognition of LCHAD deficiency can increase the life expectancy in these patients through avoiding catabolism and through appropriate diets. Patients tend to be free of symptoms between attacks, however. Testing for the disorder, therefore, should be included in the diagnostic process for children with retinal dystrophy, in particular when other clinical symptoms are known to have occurred.

Respiratory control determines respiration and nitrogenase activity of Rhizobium leguminosarum bacteroids.

The relationship between the O2 input rate into a suspension of Rhizobium leguminosarum bacteroids, the cellular ATP and ADP pools, and the whole-cell nitrogenase activity during L-malate oxidation has been studied. It was observed that inhibition of nitrogenase by excess O2 coincided with an increase of the cellular ATP/ADP ratio. When under this condition the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) was added, the cellular ATP/ADP ratio was lowered while nitrogenase regained activity. To explain these observations, the effects of nitrogenase activity and CCCP on the O2 consumption rate of R. leguminosarum bacteroids were determined. From 100 to 5 microM O2, a decline in the O2 consumption rate was observed to 50 to 70% of the maximal O2 consumption rate. A determination of the redox state of the cytochromes during an O2 consumption experiment indicated that at O2 concentrations above 5 microM, electron transport to the cytochromes was rate-limiting oxidation and not the reaction of reduced cytochromes with oxygen. The kinetic properties of the respiratory chain were determined from the deoxygenation of oxyglobins. In intact cells the maximal deoxygenation activity was stimulated by nitrogenase activity or CCCP. In isolated cytoplasmic membranes NADH oxidation was inhibited by respiratory control. The dehydrogenase activities of the respiratory chain were rate-limiting oxidation at O2 concentrations (if >300 nM. Below 300 nM the terminal oxidase system followed Michaelis-Menten kinetics (Km of 45 +/- 8 nM). We conclude that (i) respiration in R. leguminosarum bacteroids takes place via a respiratory chain terminating at a high-affinity oxidase system, (ii) the activity of the respiratory chain is inhibited by the proton motive force, and (iii) ATP hydrolysis by nitrogenase can partly relieve the inhibition of respiration by the proton motive force and thus stimulate respiration at nanomolar concentrations of O2.

Ethanol stimulates phospholipid turnover and inositol 1,4,5-trisphosphate production in Chlamydomonas eugametos gametes.

Alcohols induce mating-structure activation in Chlamydomonas eugametos gametes. From the effect of ethanol on the (32)P-labelling of polyphosphoinositides, we conclude that the synthesis of these lipids is stimulated. Biologically inactive concentrations of ethanol (<6%) had no effect on synthesis, but 6-8% ethanol stimulated synthesis for upto 60 min. The (32)P incorporated into polyphosphoinositides and phosphatidic acid during ethanol treatment was readily chased out when 1 mM unlabelled Na3PO4 was added. Using a binding assay for inositol 1,4,5-trisphosphate, we show that the production of this phospholipid constituent is dramatically increased after ethanol treatment. This effect, coupled to a rise in intracellular calcium concentration, could explain gamete activation. The significance of these results in explaining other ethanol-induced phenomena in algae is discussed.

GELANAL, a personal computer-program to compare protein patterns on two-dimensional polyacrylamide gels.

Comparing and analyzing a series of two-dimensional gels by hand is troublesome and subjective. So far a number of systems for automatic analysis have been developed on mainly mainframe computers, using complex algorithms. This paper presents an inexpensive system, based on a simple Pascal program, to compare individual spots on two-dimensional gels using an IBM or compatible personal computer in a qualitative way. The accuracy of the method is demonstrated by comparing two patterns of the same extract from different runs.

Two higher molecular weight forms related to ferritin are synthesizedin vitro by RNA from developing cotyledons and leaves ofPhaseolus vulgaris.

Using RNA from developing cotyledons and leaves of bean two products were synthesizedin vitro, with Mr 31000 and 31500 which are antigenically related to the subunit of phytoferritin (Mr 26500). The relative abundance of the two products is dependent on the type of tissue from which the RNA was derived. Evidence is presented for the assumption that both products are precursors of the phytoferritin subunit. The hypothesis is put forward that different transit sequences direct the phytoferritin subunits to different cell organelles.

The in vitro activity of amoxycillin with clavulanic acid against clinically significant bacteria. A multicentre study.

A multicentre study to evaluate the activity of amoxycillin when combined with clavulanic acid against clinical bacterial isolates was performed in South Africa. Minimum inhibitory concentrations for amoxycillin alone and in combination with clavulanic acid were determined by agar dilution. The majority of amoxycillin-resistant Klebsiella and Escherichia coli strains became sensitive to amoxycillin in the presence of low concentrations of clavulanic acid. Beta-lactamase-producing strains of Staphylococcus aureus showed increased susceptibility to amoxycillin in the presence of clavulanic acid. Minimum bactericidal concentrations indicated that amoxycillin retains bactericidal activity in the presence of clavulanic acid. Enterobacter and Serratia species and Pseudomonas aeruginosa remained amoxycillin-resistant in the presence of clavulanic acid.

Ascaris lumbricoides and allergic asthma: A new perspective.

Infestation of humans with the parasite Ascaris lumbricoides may induce high total serum IgE levels, but the influence of this immunogenic response on allergic asthma has not been defined. In this study, the specific antiparasitic IgE-mediated response as determined by skin-prick testing was related to the incidence of allergic asthma in Ascaris-infested patients. A limited number--17% of the non-allergic controls and 51% of the allergic asthmatics--had a clinically detectable immunogenic response to the parasite. The predicted incidence of asthma was significantly higher than the observed incidence in the subjects in whom the Ascaris skin test was positive. This was not found in subjects in whom the Ascaris skin test was negative. Inhalation of Ascaris antigen induced asthmatic reactions in 7 of 8 patients who were Ascaris-positive on skin testing, but not in the negative controls. The groups of patients who respond immunogenically to parasite infestation need to be defined, as they may be predisposed to allergic diseases such as asthma.

Antibiotic-resistant Serratia marcescens infection in a hospital.

Over a 12-month period, 74 isolates of Serratia marcescens were obtained from various sources at Tygerberg Hospital. The majority of these isolates were from catheterized patients with urinary tract infections, and were non-pigmented and resistant to all antibiotics tested, excepting amikacin and neomycin. All isolates transferred resistance to tobramycin, gentamicin and tetracycline by conjugation to Escherichia coli recipients as separate markers at low frequency. A non-self-transmissible plasmid conferring resistance to kanamycin, ampicillin and gentamicin was mobilized from Serratia species to E. coli, and became fully self-transmissible in subsequent matings.

A multicentre study of the susceptibility of a variety of bacteria to cephalothin, cefamandole, tobramycin and gentamicin.

A multicentre study of antibiotic susceptibility was performed in South Africa. Sensitivity to cephalothin, cefamandole, tobramycin and gentamicin was tested on a variety of aerobic and anaerobic bacteria. Two disc susceptibility techniques were used, i.e. the Kirby-Bauer technique (aerobes) and the broth-disc method (anaerobes); minimum inhibitory concentrations (MICs) were determined according to the International Collaborative Study techniques, and regression lines for individual centres were constructed. Satisfactory lines were obtained for cephalosporins, but, in some centres, problems were experienced with the aminoglycosides. Variations in MICs for Haemophilus influenzae were probably due to an inoculum effect. Accumulative percentage tables of the number of strains inhibited were compiled, and the comparative performance of the antibiotics was assessed.