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Biomedical subjects

K Ullrich

Publications and source records attributed to K Ullrich.

At least 91 records · Page 5Linked to original sources
PubMed1994

Assessment of tubular reabsorption of sodium, glucose, phosphate and amino acids based on spot urine samples.

Reference values for tubular transport of sodium, phosphate, glucose and amino acids are generally based on inulin or creatinine short-term clearances, which are difficult to obtain in children. Hence, quantitative assessment of tubular transport capacities is rarely performed. For a simplified procedure, reference values for fractional sodium excretion, phosphate reabsorption related to glomerular filtration rate, percent glucose and percent amino acid reabsorption were established in 62 children from spot urine and simultaneously obtained blood samples. Sodium excretion, and glucose and amino acid reabsorption were significantly lower in infants than children, whereas phosphate reabsorption decreased during the first year of life. Results using the proposed protocol and those obtained from timed urine specimens correlated well; the phenomenon of renal adaptation during childhood could equally well be demonstrated. Renal tubular dysfunction can be diagnosed without timed urine specimens.

Absorption↗
PubMed1994

White matter abnormalities in phenylketonuria: results of magnetic resonance measurements.

In adolescents and adults with PKU, blood phenylalanine levels above 10 mg/dl are generally associated with white matter changes in MRI. The grade of these changes is correlated to most recent blood phenylalanine levels. Based on studies using T2 relaxometry the MRI changes seem to be the consequence of a reversible dysmyelination. The clinical relevance of these white matter changes remains unclear as the extent of MRI alterations did not correlate with IQ, neurological and electrophysiological deficits of the patients. The intracerebral phenylalanine concentration as measured by protonspectroscopy amounts to about 50% of blood phenylalanine concentrations. Preliminary data indicate that brain phenylalanine levels remain constant if blood concentrations exceed 20 mg/dl. This might be of clinical relevance for the treatment of adolescent and adult PKU patients.

Brain Chemistry↗
PubMed1993

[Phenylketonuria--change in therapeutic strategies. Study of intellectual development and dietary compliance of young phenylketonuria patients].

Recent results of research appear to show that over the past few years, clearly more restrictive dietary recommendations have become accepted in the treatment of phenylketonuria (PKU). A lifelong diet low in phenylalanine is the goal, since poor dietary discipline can lead to an appreciable decrease in the level of intelligence and, in rare cases, to severe neurological deficits. Furthermore, neuropsychological symptoms as sequelae of current high serum phenylalanine levels also occur. In the present study, the question as to the development of intelligence and compliance with diet was investigated. The results underscore the need for continuing adherence to a diet on the one hand, and for continuous psychosocial support on the other.

Adolescent↗
PubMed1993

Excitotoxicity, energy metabolism and neurodegeneration.

There is increasing evidence that the neurotoxic effects of excitatory amino acids and their analogues are part of the pathogenesis of neuronal degeneration in acute and chronic neurological disease. Recent studies indicate that activation of excitatory amino acid receptors is also induced in the mechanism of neuronal damage induced by impairment of cellular energy metabolism. This article briefly summarizes the evidence for the presence of such a mechanism and discusses metabolic diseases in which excitatory amino acids alone or in combination with energy deficiency could play a pathogenetic role. In these and other metabolic diseases, antagonists to excitatory amino acid receptors may offer a therapeutic opportunity; however, there are potential limits that may prevent chronic use.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Effective renal plasma flow in patients with glycogen storage disease type I.

To evaluate effective renal plasma flow (ERPF) we performed renal scintigraphies with 99mTc-Mercaptoacetyl-triglycine (MAG3) in nine patients with glycogen storage disease I (GSD I) (age: 16 +/- 7 years). Two patients presented with proteinuria, none showed hyperaminoaciduria, disturbed tubular reabsorption of phosphate or hypertension. 99mTc-MAG3 clearance values were elevated in eight out of nine patients (865 +/- 233 ml/min/1.73 m2 body surface area) and exceeded the age-dependent mean values by 21%-145%. ERPF values in patients with poor metabolic control were higher than in patients with long-term good metabolic control (988 +/- 186 vs. 619 +/- 55 ml/min/1.73 m2; P < 0.05). We conclude that enhanced ERPF is a common finding in GSD I patients, which precedes clinically overt nephropathy. Renal scintigraphy with 99mTc MAG3 is a suitable method for the early detection and monitoring of kidney dysfunction in GSD I.

Adolescent↗
PubMed1993

White matter abnormalities in patients with treated hyperphenylalaninaemia: magnetic resonance relaxometry and proton spectroscopy findings.

In order to further clarify the pathogenesis and clinical significance of MRI white matter abnormalities in treated hyperphenylalaninaemia (HPA), ten patients (seven type I HPA, two type II and one type III) underwent T2 relaxometry (n = 8) and/or 1H spectroscopy (n = 7) in addition to conventional MR spin-echo imaging at 1.5 T. Two patients with severe MRI abnormalities had repeat examinations during and after a 6- to 8-month period of strict diet control. The clinical evaluation included a detailed neurological examination. In nine out of ten patients visual evoked potentials (VEP) were obtained parallel to the MR examination. MR imaging demonstrated typical symmetrical areas of prolonged T2 relaxation time predominantly in the posterior periventricular white matter in all but one of type I and II patients. There was no consistent relationship between MRI findings and time of diagnosis/initiation of therapy, IQ or visual evoked potential changes. MRI abnormalities tended to be more severe in patients with poor dietary control and high current plasma phenylalanine levels, whereas a normal MRI was found only in patients with plasma phenylalanine levels continuously below 0.36 mmol/l. There was marked regression of MRI abnormalities already after 3 months of strict diet control. T2 relaxometry showed a bi-exponential behaviour of T2 in the affected white matter, with a slow component of about 200-450 ms, indicating an increase in free (extracellular) water. 1H spectroscopy revealed no signs of severe neuronal damage. We conclude, that the observed white matter changes in treated HPA probably represent reversible structural myelin changes rather than permanent demyelination.

Adolescent↗
PubMed1993

Glucose-6-phosphate: a key compound in glycogenosis I and favism leading to hyper- or hypolipidaemia.

The glycogen storage disorders (GSD)-I, -III, -VI and -VIII are associated with hypertriglyceridaemia or mixed hyperlipidaemia which poses the question whether these patients have an increased risk for atherosclerosis. The atherogenicity of triglycerides has remained controversial, while increased plasma cholesterol levels are generally accepted as a significant risk factor for coronary heart disease. However, clinical data show that one has to differentiate between metabolic conditions where triglycerides are atherogenic and those which are not significantly related to early onset of atherosclerosis but may cause other disorders such as pancreatitis. Among the disorders of carbohydrate metabolism patients with diabetes mellitus frequently have enhanced plasma triglycerides associated with a higher risk for coronary heart disease, while patients with certain types of glycogen storage disease have high triglyceride levels but do not seem to have an enhanced risk for atherosclerosis. Here we have compared the biochemical abnormalities and the atherogenic risk of three different disorders of glucose metabolism including GSD-I (glucose-6-phosphatase deficiency), favism (glucose-6-phosphate dehydrogenase deficiency), and diabetes mellitus which are related to either hyper- or hypolipidaemia. The available data indicate that glucose-6-phosphate (Glc-6-P) is a central molecule in cellular glucose metabolism which critically influences pentose phosphate cycle activity and, via NADPH2-generation, regulates glutathione peroxidase activity for radical detoxification and also cholesterol and triglyceride synthesis. Radical detoxification is a major protective factor for cell membrane integrity and together with an appropriate renewal of membrane lipids may protect against the development of atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1993

Transmural redistribution of myocardial blood flow during isoflurane anesthesia and its effects on regional myocardial function in a canine model of fixed coronary stenosis.

BACKGROUND: The effects of isoflurane on the transmural distribution of myocardial blood flow distal to an acute critical coronary stenosis and the relationship between the changes in regional blood flow and function were studied to determine whether isoflurane can produce a transmural "steal" phenomenon and to assess the role of this phenomenon in producing changes in regional myocardial function. METHODS: After production of acute critical coronary stenosis under baseline chloralose and fentanyl anesthesia, the animals were exposed to increasing end-tidal concentrations of isoflurane (0.7%, 1.4%, and 2.1%) without control of the hemodynamic parameters. At 2.1% isoflurane, the blood pressure then was restored to the baseline level by administration of phenylephrine. Changes in the following parameters were assessed: global contractility (measured by changes in pressure with time), regional myocardial function (assessed by systolic wall thickening and measured by sonomicrometers), transmural distribution of myocardial perfusion (measured by the radioactive microsphere method), and regional oxygen consumption and extraction. RESULTS: Distal to the critical stenosis, a transmural redistribution of myocardial blood flow (endocardial-epicardial ratio < 1) occurred with all concentrations of isoflurane. With higher concentrations (1.4% and 2.1%), a significant decrease in subendocardial blood flow occurred only in the presence of hemodynamic changes and was restored by phenylephrine. In this area, changes in regional myocardial function correlated most strongly with changes in subendocardial perfusion (y = -0.17 + 1.70x -0.58x2, r2 = 0.90). In the stenotic region, oxygen extraction remained stable, but oxygen consumption decreased in parallel with reductions in regional myocardial function. In the normal region, oxygen consumption did not change, but oxygen extraction decreased with increasing isoflurane concentrations. CONCLUSIONS: These results show that isoflurane is a coronary vasodilator able to induce a transmural redistribution of myocardial blood flow distal to an acute critical coronary stenosis. A true transmural steal, however, was not produced reliably in the absence of hemodynamic changes, suggesting that isoflurane either is only a moderate vasodilator, or that the decrease in subendocardial blood flow is offset by the negative inotropic action of the drug. When regional myocardial dysfunction distal to a severe coronary stenosis occurs, this correlates with decreasing subendocardial blood flow during isoflurane anesthesia, suggesting ischemia as the cause.

Anesthesia, Inhalation↗
PubMed1993

A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.

The genetic defect leading to cholesteryl ester storage disease (CESD) has been determined in a 12-yr-old patient. Lysosomal acid lipase (LAL) activity in cultured skin fibroblasts was reduced to approximately 9% of control fibroblasts. Plasma cholesterol (255 mg/dl) and LDL-cholesterol (215 mg/dl) were elevated whereas HDL-cholesterol was reduced (19 mg/dl). Triglycerides were moderately elevated (141 mg/dl). There were no clinical abnormalities with the exception of hepatosplenomegaly. Both parents have reduced LAL activity in white blood cells. PCR analysis of the LAL mRNA from the propositus revealed a single slightly smaller mRNA species in skin fibroblasts as well as in leukocytes. The mother of the patient and his older brother had two mRNA species: one of normal size and one of the same size as the propositus. The father has a LAL mRNA of normal size only. Sequence analysis of a PCR-amplified cDNA fragment showed a 72-bp in-frame deletion resulting in the loss of the codons for amino acids 254-277. Analysis of genomic DNA revealed that the 72 bp represent an exon, indicating that the deletion in the mRNA is caused by defective splicing. Sequence analysis of the patient's genomic DNA revealed a G-->A substitution in the last nucleotide of the 72-bp exon in one of his alleles. The mutant allele was shown to cosegregate with the truncated mRNA in the pedigree, providing further evidence that the G-->A substitution causes aberrant splicing and exon skipping. No normal-sized mRNA is detectable in the propositus even though he is not homozygous for the splice site mutation. This can be only accounted for by assuming that he is a compound heterozygote with a null allele inherited from his father. In summary, the data presented provide evidence that deletion of the codons for amino acids 254-277 in the LAL mRNA in combination with a null allele cause the clinical expression of CESD in our patient.

Adolescent↗
PubMed1993

[Phenylketonuria: illness experience and coping mechanisms].

If patients with PKU follow a strict diet low in phenylalanine from soon after birth their intellectual and psychomotor development will be within the normal range. Recent studies have shown that it is necessary to continue the burdensome diet throughout one's life. This is in contrast to past practice and puts additional emphasis on psychosocial aspects of PKU. In the present retrospective study we investigated how adolescent patients and their relatives' experience and cope with this chronic disease.

Adaptation, Psychological↗
PubMed1993

[Treatment of phenylketonuria: wish and reality].

A diet strictly low in phenylalanine from soon after birth on can protect patients with phenylketonuria against intellectual and psychomotor retardation. Our study tries to answer the questions how the patients and their relations cope with the diet, and weather they reach the serum-phenylalanine-limits recommended by the German Association of Pediatric Metabolic Diseases in 1990.

Adaptation, Psychological↗
PubMed1993

[Ifosfamide-induced nephrotoxicity].

BACKGROUND: A number of acquired De-Toni-Debre-Fanconi-Syndromes have been reported after cytostatic treatment with Ifosfamide. For the majority of these patients prognosis of renal function was poor. In our study we evaluated the frequency of subclinical tubulopathies, the influence of the cumulative Ifosfamide dose and other risk factors and the prognosis of once established tubular dysfunction. METHODS: 79 patients after polychemotherapy regimens employing Ifosfamide (n = 39), Ifosfamide plus Cisplatinum (n = 35) or Cisplatinum (n = 5) were examined at least 3 months after completion of therapy. Beside the creatinine-clearance we evaluated glomerular and tubular function by measurement of transferrin, immunoglobuline G, Alpha-1-microglobuline and N-Acetyl-beta-D-Glucosamidaseexcretion and by tubular reabsorption of phosphate and aminoacids. RESULTS: Renal hyperaminoaciduria was found most often, and there was no linear correlation between the cumulative Ifosfamide-dose and phosphate reabsorption. A reduced glomerular filtration rate and glomerular proteinuria were found in about 10.5% of patients. Approximately half of the patients had tubular dysfunction. Impairment of phosphate reabsorption once established did not normalize in the majority of patients. Cisplatinum was found to worsen the Ifosfamide-induced tubulopathy. CONCLUSION: Our results indicate subclinical tubulopathy after Ifosfamide in a high proportion of patients. This Ifosfamide induced nephrotoxicity is worsened by Cisplatinum and seems to be irreversible for the majority of patients. To describe and to prevent Ifosfamide-induced nephrotoxicity, further studies should focus on: 1. the identification of the risk-groups/patients and additional risk factors, 2. the estimation of the prognosis of once established renal damage, 3. the clarification of the pathomechanism.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Psychological and social findings in adolescents with phenylketonuria.

In a retrospective study, 34 early treated, normally intelligent adolescents with phenylketonuria (PKU) and their parents were tested with several psychometric personality inventories and self-developed questionaires concerning their psychosocial situation and their disease- and diet-specific knowledge. Results show that the patients are characterized by less autonomy, a more negative evaluation of their scholastic ability, less achievement motivation, low frustration tolerance, more negative self description, less extraversion and impulsiveness, a feeling of not being quite healthy, more grave and a higher level of dependency from their families. The patients saw their whole social situation as being distinctly restricted. Their knowledge concerning disease and diet was alarmingly poor and the majority had great difficulties in managing the diet satisfactorily without parental help. Up to the age of 15 years the serum phenylalanine levels were persistently above the desired range.

Adolescent↗
PubMed1992

Disturbance of GABA metabolism in pyridoxine-dependent seizures.

In an infant with typical pyridoxine-dependent seizures, CSF GABA level, was determined before treatment with pyridoxine. Before onset of treatment, level of GABA in CSF was highly lowered (16 pmol/ml), pyridoxine level in serum was within normal range. Immediately after application of 80 mg pyridoxine fits stopped and the EEG was without seizure activity. The data substantiate previous findings in brain tissue from a patient with pyridoxine-dependent seizures. They are proof of a disturbed GABA metabolism in pyridoxine dependent seizures.

Brain↗
PubMed1992

Neurological outcome in 22 treated adolescents with hyperphenylalaninemia. A clinical and electrophysiological study.

We examined clinically and electrophysiologically 22 adolescents suffering from hyperphenylalaninemia. Three of 16 treated patients showed slight impairment of proprioception; their examination was otherwise unremarkable. Subclinical deficits were present in the central motor and sensory pathway. In addition, we had evidence of a minor sensory neuropathy: 32% of the 22 patients had subclinical deficits in the visual system. However, in contrast to earlier reports we saw no relation to the degree of metabolic control. Our results suggest that treated adolescent patients with hyperphenylalaninemia show neurological dysfunction that may be related to morphological, as well as pharmacological changes.

Adolescent↗
PubMed1992

[Maternal phenylketonuria. Problems in detecting and risk educating identified females].

Maternal PKU is an embryo-fetopathy caused by elevated plasmaphenylalanine levels in pregnant women with hyperphenylalaninemia and phenylketonuira. Leading symptoms are microcephaly, mental retardatioin and congenital malformations, especially congenital heart disease. Maternal PKU becomes more important since early treated and normally developed girls with PKU are reaching their reproductive age in increasing numbers. There is a lack of adequate knowledge about the dangers of maternal PKU in at-risk women. Only 43% of these women in the Federal Republic of Germany are located by now and can be informed and instructed. Ways and conditions of tracking are described.

Adolescent↗