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Biomedical subjects

J H Walter

Publications and source records attributed to J H Walter.

At least 73 records · Page 4Linked to original sources
PubMed1990

The use of metronidazole in management of methylmalonic and propionic acidaemias.

Gut bacteria have been implicated as an important source of propionate in children with inborn errors of propionate metabolism. We have investigated the value of oral metronidazole (10-20 mg/kg per day) in five children with methylmalonic acidaemia (MMA) and four with propionic acidaemia (PA). Urinary excretion of propionate metabolites fell significantly during the treatment in all subjects, the mean decrease being 41% (range 12-76, P less than 0.01), while mean plasma propionate was reduced from 45.0 mumol/l to 25.1 mumol/l (P less than 0.05). Substantial reduction of the gut bacterial population was confirmed by lactulose breath hydrogen tests and by stool culture, and stool propionate concentration was reduced in most subjects. Clinical improvement was noted in three children. These results suggest that long-term antimicrobial therapy may offer significant clinical benefit to children with inborn errors of propionate metabolism.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

In vivo propionate oxidation as a prognostic indicator in disorders of propionate metabolism.

Biochemical markers such as plasma and urinary metabolite concentrations and in vitro enzyme activity are of limited prognostic value in the most common disorders of propionate metabolism, methylmalonic acidaemia (MMA) and propionic acidaemia (PA). In vivo propionate oxidation was compared with conventional prognostic measures as predictors of clinical severity in seven children with MMA and six with PA. Propionate oxidation was measured using a continuous infusion of [1-13C]propionate and was expressed as the rate of appearance of 13CO2 as a percentage of the propionate infusion rate. Children with MMA (mean oxidation 51.2%, range 17.5-91.6, P less than 0.05) and with PA (mean oxidation 36.3%, range 3.0-91.1, P = NS) oxidised substantially less propionate than controls (mean oxidation 81.9%, range 69.4-101.0, n = 5). Percentage oxidation was a better predictor of the clinical severity score (r = 0.75, P less than 0.01) than was in vitro enzyme activity, plasma propionate or methylmalonate concentration or urinary metabolite excretion. Studies were repeated after an interval of 1-3 weeks in six of the subjects; the percentage oxidation in each subject was virtually unchanged between studies (coefficient of variation 8.6%). These results suggest that in vivo oxidation measurements using [13C]propionate are both reproducible and prognostically useful in disorders of propionate metabolism.

Adolescent↗
PubMed1990

Sources of propionate in inborn errors of propionate metabolism.

Amino acids are widely regarded as the most important sources of propionate in disorders of propionate metabolism. Propionate production was measured in the fasting state by continuous infusion of sodium [1-13C]propionate in three children with methylmalonic acidemia (MMA) and three with propionic acidemia (PA). The contribution of isoleucine, valine, threonine, and methionine catabolism to total propionate production was estimated by extrapolation from the hydroxylation of phenylalanine determined by a continuous-infusion [2H5]phenylalanine technique. The contribution of gut bacterial propionate production was determined by measuring total propionate production before and after treatment with oral metronidazole (10 to 20 mg/kg/d for 1 week). Amino acid catabolism accounted for a mean of 51.7% (range, 24.5% to 66.4%) of total propionate production. The mean decrease in propionate production after metronidazole was 22.2% +/- 8.5 (P less than .02); this percentage is likely to represent the minimum propionate production attributable to gut bacteria. Approximately 30% of total propionate production was unaccounted for, and is likely to arise primarily from odd-chain fatty acid catabolism in the fasting state. These results indicate that sources of propionate other than from protein catabolism are important in disorders of propionate metabolism, and explain the generally disappointing response to dietary protein restriction.

Amino Acids↗
PubMed1990

In vivo enzyme activity in inborn errors of metabolism.

Low-dose continuous infusions of [2H5]phenylalanine, [1-13C]propionate, and [1-13C]leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

Adult↗
PubMed1990

Protein and leucine metabolism in maple syrup urine disease.

Constant infusions of [13C]leucine and [2H5]phenylalanine were used to trace leucine and protein kinetics, respectively, in seven children with maple syrup urine disease (MSUD) and eleven controls matched for age and dietary protein intake. Despite significant elevations of plasma leucine (mean 351 mumol/l, range 224-477) in MSUD subjects, mean whole body protein synthesis [3.78 +/- 0.42 (SD) g.kg-1. 24 h-1] and catabolism (4.07 +/- 0.46) were similar to control values (3.69 +/- 0.50 and 4.09 +/- 0.50, respectively). The relationship between phenylalanine and leucine fluxes was also similar in MSUD subjects (mean phenylalanine-leucine flux ratio 0.35 +/- 0.07) and previously reported adult controls (0.33 +/- 0.02). Leucine oxidation was undetectable in four of the MSUD subjects and very low in the other three (less than 4 mumol.kg-1.h-1; controls 13-20). These results show that persistent elevation in leucine concentration has no effect on protein synthesis. The marked disturbance in leucine metabolism in MSUD did not alter the relationship between rates of catabolism of protein to phenylalanine and leucine, which provides further support for the validity of the use of a single amino acid to trace whole body protein metabolism. The minimal leucine oxidation in MSUD differs from findings in other inborn metabolic errors and indicates that in patients with classical MSUD there is no significant route of leucine disposal other than through protein synthesis.

Child↗
PubMed1990

Anatomical and histologic investigation of the syndesmotic area in the ankle joint.

The syndesmotic area in the ankle joint is analyzed by reviewing the literature and by examining its gross anatomy and histology. Seventy-five ankles were dissected and examined, with an emphasis on the syndesmotic area. The gross anatomical results of this study differ somewhat with those of other authors. The average height, attachments, consistency, color, and shape are reported. In addition to gross examination, four ankles were examined histologically, and the findings are discussed. The results of this study define in detail the anatomy of the syndesmotic area.

Ankle Joint↗
PubMed1989

Measurement of propionate turnover in vivo using sodium [2H5]propionate and sodium [13C]propionate.

The outcome for children with inherited disorders of propionate metabolism is poor. To facilitate development of improved treatment in these conditions, we described techniques for the estimation of the rate of production and removal of propionate in vivo. Propionate turnover was determined in 4 healthy adults using continuous infusions of sodium [2H5]propionate and sodium [13C]propionate. The mean fasting plasma propionate concentration measured by a sensitive technique employing high performance liquid chromatography, following a two-stage extraction procedure and derivatisation with bromophenacyl bromide, was 3.3 mumol/l (SD 0.5). The isotopic enrichment of the bromophenacyl propionate derivative was measured by gas chromatography/mass spectrometry and mean propionate turnover was calculated to be 17.6 mumol/kg per h (SD 5.9). These methods allow rapid (less than 3 h) assessment of propionate turnover in man and are suitable for application in children with inherited disorders of propionate metabolism.

Adult↗
PubMed1989

Contribution of aminoacid catabolism to propionate production in methylmalonic acidaemia.

The rates of propionate production and aminoacid catabolism in 5 children with methylmalonic acidaemia were measured by use of stable isotope techniques. Total propionate production was 55-186 mumol/kg per h, to which the maximum contribution of protein catabolism was 10-35 mumol/kg per h (5-40%). These findings indicate important sources of propionate other than protein catabolism, which may account for the limited efficacy of dietary protein restriction in treatment of methylmalonic acidaemia.

Acyl Coenzyme A↗
PubMed1989

Chronic renal failure in methylmalonic acidaemia.

The renal function of 12 patients with non vitamin B12 responsive methylmalonic acidaemia has been investigated. Eight patients had reduced glomerular filtration rates, but the plasma creatinine concentration was only raised in those with values of less than 40 ml/min per 1.73 m2 surface area. The reduction in glomerular filtration was a function of the age and the severity of the disease. Plasma urate concentrations were increased in four patients but this may be secondary to the renal disease rather than its cause.

Biopsy↗
PubMed1989

Substrate disposal in metabolic disease: a comparison between rates of in vivo propionate oxidation and urinary metabolite excretion in children with methylmalonic acidemia.

The relative importance of endogenous metabolism and urinary metabolite excretion was assessed in vivo in six children with methylmalonic acidemia by examining the kinetics of the immediate precursor to methylmalonate, propionate. Total production and oxidation of propionate were measured by means of a continuous infusion of (1-13C)propionate and were compared with the urinary excretion of propionate metabolites. Propionate oxidation was substantial (mean 48.9 mumol/kg/hr +/- SD 18.0) and, in four children, exceeded urinary metabolite excretion (mean urinary excretion in all subjects 40 mumol/kg/hr +/- 25). The sum of urinary excretion and oxidation rates (88 mumol/kg/hr +/- 29) approximated the total propionate production (93.4 +/- 37.0), suggesting that these routes together constitute the major mechanisms of propionate disposal. These results suggest that propionate oxidation is an important route of disposal in methylmalonic acidemia. Variations in the relative proportions of propionate disposal through oxidation and urinary excretion may be one reason for the often poor correlation between clinical status and urinary metabolite excretion. Measurement of urinary metabolite concentration alone may not always reflect clinical status and responses to treatment accurately.

Humans↗
PubMed1989

[The frequency and pathogenesis of feline infectious peritonitis (FIP)].

Between 1980 and 1987 about 10% of the cats which underwent a post mortem examination at the Institute of Veterinary Pathology of the Freie Universität Berlin were infected with feline infectious peritonitis (FIP). The exudative, granulomatous or mixed form of the FIP are all symptoms of the same disease whose clinical picture is dependent on the state of the cellular immunity. Statistically there is no significant relationship between the form of the FIP and the age of the cats. A breed or a sex disposition is also not apparent. 42 organs and/or tissue samples were taken from a total of 30 cats and were examined both histologically and immunohistochemically. The antigen is located, above all, in the mesothelium and the cells of the mononuclear phagocyte system, whereas the parenchymatous inflammation foci show little evidence of the FIP-virus-antigen. The antigen is, however, also found in the nerve cells. Within the framework of a second viraemia, occurring after infection of the mesothelium (polyserositis), a perivasculitis non purulenta generalisata occurs. Possible excretory organs of the antigen are the respiratory, digestive and urinary tract.

Animals↗
PubMed1987

Inborn errors of the urea cycle.

Inborn errors of the urea cycle are an important cause of hyperammonaemia throughout childhood, and are associated with high morbidity and mortality rates. If they are diagnosed early and treated appropriately, the outcome for affected children is significantly improved.

Amino Acid Metabolism, Inborn Errors↗
PubMed1985

External fixation. Its use in podiatric surgery.

Rigid fixation of osseous fragments with the ability to supply additional compression or distraction at will is achieved only by external fixation. Of course, the treatment of nonunions, infections, fixation of osteotomies, fusion of joints, and lengthening of bone can be accomplished by other satisfactory means with and without fixation. External fixation is only one method of fixation. From this list the practitioner can choose the method of fixation best suited to the contemplated procedure and the one with which the surgeon feels most comfortable. However, a good surgeon will have prepared alternative methods of fixation if, in fact, the first and preferable method of fixation fails. It would be wonderful if our plans became a reality; quite often they do not and this is what one must prepare for. External fixation in many of the cases presented was not the original form of fixation to be used; in a few cases it had not been seriously considered. Fortunately, however, it was considered and allowed a difficult situation to be remedied with relative ease. Although elaboration of the categories in which external fixation was employed has been brief, the numerous presentations lend themselves to further investigation into external fixation.

Adult↗