This is a report of an infant with 3-hydroxy-3-methylglutaryl-CoA-lyase deficiency. During infancy vomiting and feeding difficulties had been found repeatedly. Nutrition consisted in a mixture of one third of milk diluted with two thirds of water. Shortly before admission a change to whole milk had taken place. The one year old girl was admitted to the hospital because of vomiting and diarrhoea. Liver was enlarged and consciousness reduced. There was acidosis, hypoglycemia and an elevation of the transaminases. The typical pattern of organic acids in urine and dicarboxylic aciduria was pathognomonic. The diagnosis was proved by a deficiency of 3-hydroxy-3-methylglutaryl-CoA-lyase in fibroblasts. A protein and fat restricted diet, but also carnitine supplement was introduced. With the exception of severe hypoglycemia seizures on one morning the more than 2 1/2 year old girl is developed normally. It is of importance for future to avoid hypoglycemia after fasting, infections diseases or stress. The possible impairment of pancreatic function even in a normal clinical condition with normal values of transaminases is especially pointed out.

Amino Acid Metabolism, Inborn Errors↗

PubMedDate not supplied

[The intermediate form of maple syrup disease].

A severely retarded and tetraspastic child died at the age of four years upon a respiratory infection with acidosis, disturbances of serum electrolytes and lactic aciduria. Brain autopsy showed a spongy degeneration and led to suspect an inborn error of amino-acid metabolism. These findings corresponded with the results of computer-tomography and were supported by post mortem amino-acid analysis. An intermediate variant of leucinosis was detected in an younger sister at the age of five months after cerebral convulsions and opisthotonic posture. The activity of the branched chain ketoacid decarboxylase in fibroblasts was reduced to 3-4% of normal. A protein restricted diet allowed a nearly normal cerebral development and improvement of computer-tomographic results. The similarity of clinical and biochemical data in both children indicate that a maple syrup urine disease was most likely the underlying disease in the older sister. Later performed electron-microscopical examinations of the older sister indicate that spongy degeneration of the central nervous system in leucinoisis is caused by a spongy myelinopathy, which is different from the alterations found in Canavan's disease, what could be pointed out for the first time.

Amino Acids, Branched-Chain↗

PubMedDate not supplied

Increase in circulating insulin induced by atrial natriuretic peptide in normal humans.

To search for possible metabolic interactions of alpha-human-atrial natriuretic peptide (alpha hANP), we evaluated in 20 normal subjects blood levels of alpha hANP, glucose, insulin, cortisol, electrolytes, catecholamines, free fatty acids, carnitine and amino acids, blood pressure (BP), and heart rate before, during, and after a 45-min infusion of synthetic alpha hANP. Group A [n = 10] was studied on liberal and Group B on three consecutive sodium (Na) intakes of 17, 140, and 310 mM/day. Plasma alpha hANP was slightly but not significantly higher following 5 days on "normal" or high than on low Na+ intakes. alpha hANP infused at 0.1 microgram/kg/min produced on all Na+ intakes comparable percentage increases in plasma insulin (+34 to 63%, p less than 0.001), norepinephrine (+76 to 155%, p less than 0.001) and heart rate (p less than 0.001), and a similar fall in diastolic BP (p less than 0.001). Plasma glucose tended to be decreased slightly and cortisol was reduced; epinephrine, dopamine, and potassium levels were not significantly modified. As evaluated in group A, serum free fatty acids were increased (p less than 0.01), plasma free carnitine levels were reduced (p less than 0.001), and amino acids were not consistently altered. These findings indicate that in normal humans alpha hANP may, on various sodium intakes, modulate insulin secretion and/or metabolism and elicit a possibly baroreflex-mediated sympathetic activation and lipolysis.

Adult↗

PubMedDate not supplied

Serum lipoproteins during treatment with the antihypertensive agent indapamide.

Considering the documented, potentially undesirable influence of various thiazide-type or loop diuretics on serum lipoproteins, we prospectively investigated in 69 men (mean age +/- SEM, 32 +/- 1 years) the metabolic effects of the new diuretic-antihypertensive compound indapamide. Compared to placebo, indapamide (2.5 mg/day) given for 6 to 8 weeks lowered (p less than 0.02 to less than 0.001) blood pressure (supine values from 148/98 +/- 3/2 to 137/93 +/- 3/2) in 29 men with mild to moderate essential hypertension, but not in 40 healthy men. In both groups, significant (p less than 0.05 to less than 0.001) decreases in body weight (-0.8 kg) and plasma potassium (-0.6 mmol/L), and increases in plasma uric acid (+20%), renin activity (+200%), and aldosterone documented good compliance. There were no significant changes in total cholesterol (in all subjects, from 208 +/- 6 to 213 +/- 6 mg/dl), low- or very low-density lipoprotein (VLDL) cholesterol (127 +/- 6 to 129 +/- 6 and 21 +/- 1 to 21 +/- 2 respectively), high-density lipoprotein cholesterol (50 +/- 1 to 51 +/- 1 mg/dl), total triglycerides (Tg) (108 +/- 5 to 112 +/- 6 mg/dl), VLDL-Tg, apoproteins A1 and A2, plasma glucose, epinephrine, norepinephrine, sodium, calcium, magnesium, and creatinine; apoprotein B (84 +/- 2 to 88 +/- 3 mg/dl) and plasma insulin after glucose loading dose tended to be increased minimally. The absence of distinct lipoprotein alterations after short-term indapamide treatment may be of clinical and epidemiological interest.

Adult↗

PubMedDate not supplied

Evaluation of an intrathecal immune response in amyotrophic lateral sclerosis patients implanted with encapsulated genetically engineered xenogeneic cells.

A phase I/II clinical trial has been performed in 12 amyotrophic lateral sclerosis (ALS) patients to evaluate the safety and tolerability of intrathecal implants of encapsulated genetically engineered baby hamster kidney (BHK) cells releasing human ciliary neurotrophic factor (CNTF). These patients have been assessed for a possible intrathecal or systemic immune response against the implanted xenogeneic cells. Hundreds of pg CNTF/ml could be detected for several weeks in the cerebrospinal fluid (CSF) of 9 out of 12 patients, in 2 patients up to 20 weeks after capsule implantation. Slightly elevated leukocyte counts were observed in 6 patients. Clear evidence for a delayed humoral immune response was found in the CSF of only 3 patients out of 12 (patients #4, #6, and #10). Characterization of the antigen(s) recognized by the antibodies present in these CSF samples allowed to identify bovine fetuin as the main antigenic component. The defined medium used for maintaining the capsules in vitro before implantation contains bovine fetuin. Fetuin may therefore still be adsorbed to the surface of the cells and/or the polymer membrane, or be present in the medium surrounding the encapsulated cells at the time of implantation. Because of the insufficient availability of CSF samples, as well as the relatively poor sensitivity of the assays used, a weak humoral immune response against components of the implanted cells themselves cannot be excluded. However, the present study demonstrates that encapsulated xenogeneic cells implanted intrathecally can survive for up to 20 weeks in the absence of immunosuppression and that neither CNTF nor the presence of antibodies against bovine fetuin elicit any adverse side effects in the implanted patients.

Adult↗

PubMedDate not supplied

Processing of artificial peptide-DNA-conjugates by the mitochondrial intermediate peptidase (MIP).

Import of DNA from the cytoplasm into the mitochondrial matrix is an obligatory step for an in organello site-directed mutagenesis or gene therapy approach on mitochondrial DNA diseases. In this context, we have developed an artificial DNA translocation vector that is composed of the mitochondrial signal peptide of the ornithine transcarbamylase (OTC) and a DNA moiety. While this vector is capable of directing attached passenger molecules to the mitochondrial matrix, the recognition of this artificial molecule by the endogenous mitochondrial signal peptide processing machinery as well as the cleavage of the peptide plays a pivotal role in the release of the attached DNA. To study the proteolytic processing of the artificial vector, various signal peptide-DNA-conjugates were treated with purified mitochondrial intermediate peptidase. When the leader peptide is directly linked to the DNA moiety without an intervening spacer, MIP processing is prevented. Cleavage of the peptide can be restored, however, when the first ten amino acid residues of the mature part of OTC are appended at the carboxy-terminal end of the signal peptide. Our results show that artificial peptide-DNA-conjugates are recognized by the mitochondrial proteolytic machinery, and therefore an interference of the peptide with the DNA function can be excluded.

Amino Acid Sequence↗

PubMedDate not supplied

History of drug metabolism: the first half of the 20th century.

Explore the source record for details and available documents.

Acetates↗

PubMedDate not supplied

Long-term outcome of urea cycle disorders.

Evaluation of long-term outcome of patients with urea cycle diseases (UCD) is needed for medical decisions and counselling. Own data comparing outcome of UCD patients with the old treatment limited to protein restriction (i.e. close to the natural history) with that of patients on the modern conservative treatment have shown that gains in survival occur at the cost of more mentally retarded surviving patients. We discuss the possible bias in long-term outcome studies of those rare inheritable disorders where non-predictable environmental factors leading to catabolic crises have a crucial impact on prognosis. A combination of peak or initial ammonia value combined with the duration of coma is discussed as a criterion for prognosis of handicap. The neglect of dietary compensation of branched chain amino acid deficiency worsened by phenylbutyrate treatment in some published protocols could well be an additional cause of the non satisfactory long-term results of conservative treatment which--in our view--mainly aim at bridging optimally the period of late neonatal presentation until liver transplantation in patients with CPS and OTC deficiency (except for mild forms).

Age Factors↗

PubMedDate not supplied

Automated analysis with computerized information transfer in a university hospital.

The organization of a central clinical chemistry laboratory of a university hospital, which in 1992 analyzed 880,000 results, is presented. Automation with midsize selective analyzers, which run in parallel and are able to do positive sample identification on the primary bar-coded tubes, in connection with a laboratory computer system and a central hospital computer allowed for reliable and timely obtainment of results. The output of the results is made on laser printers in the medical wards, thus alleviating the pneumatic sample transport systems. Assessment of the turnaround time show that it can be kept below one hour. Such a setup without sorting out emergency demands allows a simplified sample flow. Thus, there is no need for a laboratory to make "stat" requests.

Autoanalysis↗