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Biomedical subjects

B Schwahn

Publications and source records attributed to B Schwahn.

16 recordsLinked to original sources
PubMed2006

Acute neuronopathic Gaucher disease complicated by fatal gastrointestinal bleeding.

Gaucher disease, a rare lysosomal storage disease caused by deficiency of glucocerebrosidase, may present with gastrointestinal bleeding. We report about an 11-month-old boy suffering from acute neuronopathic Gaucher disease who died after massive gastrointestinal bleeding. A gastric ulcer was found as the sole bleeding source. The gastric mucosa showed marked infiltration with Gaucher cells, in particular around the ulcer. Alterations of the gastrointestinal mucosa offer a new explanation for gastrointestinal bleedings in this disease.

Fatal Outcome↗
PubMed2005

Diagnosis of MSUD by newborn screening allows early intervention without extraneous detoxification.

Maple syrup urine disease (MSUD) is a genetic metabolic disorder resulting from the defective activity of branched-chain 2-ketoacid dehydrogenase complex. Due to the metabolic block, high concentrations of the branched-chain amino acids (BCAA) leucine, valine, isoleucine, and allo-isoleucine as well as their corresponding branched-chain 2-keto acids accumulate in patients on a BCAA-unrestricted diet or during episodes with increased protein catabolism. Early diagnosis and management are essential to prevent permanent brain damage. Newborn screening by tandem MS allows for detection of elevated BCAA concentrations in blood in patients with classical MSUD before they show severe encephalopathic symptoms. Here, we report that newborn screening by expanded tandem MS enables for reversing the intoxication in newborns with MSUD within 24-48 h without any need for extraneous detoxification and thus decreasing the risk of brain damage during a particularly vulnerable period.

Amino Acids, Branched-Chain↗
PubMed2005

Severe hyperhomocysteinaemia and 5-oxoprolinuria secondary to antiproliferative and antimicrobial drug treatment.

A hitherto healthy 7-year-old girl underwent antiproliferative and antibiotic treatment owing to the diagnosis of T-cell lymphoma and concomitant bacterial infection. She developed an encephalopathic crisis associated with metabolic acidosis, hyponatraemia and severe hyperhomocysteinaemia and 5-oxoprolinuria. Laboratory tests normalized completely after recovery. Primary defects in glutathione metabolism could be excluded.

Acidosis↗
PubMed2004

Dysmyelination in the brain of adolescents and young adults with maple syrup urine disease.

Maple syrup urine disease (MSUD) is associated with increased branched-chain amino acids (BCAA), their keto acids (BCKA), and acute or chronic encephalopathy. Aim of treatment is to reduce BCAA and BCKA to prevent or minimize brain dysfunction. We investigated 14 juvenile and adult patients with MSUD by means of cerebral magnetic resonance imaging (MRI) and correlated MRI changes to biochemical control measured as median plasma BCAA concentrations over 6-36 months prior to investigation. Abnormalities consisted of an increased signal in the white matter on T2-weighted images which is compatible with a disturbed water content of the white matter and dysmyelination. Areas affected most commonly were mesencephalon, brain stem, thalamus and globus pallidus; supratentorial lesions seem to be restricted to severe cases. No patient with white matter changes had acute neurological/encephalopathic symptoms indicating that the severity of dysmyelination does not correlate to acute neurotoxicity.

Adolescent↗
PubMed2001

Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia.

This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or liver disease. Abnormal elevations of their plasma S-adenosylmethionine (AdoMet) concentrations proved they do not have deficient activity of methionine adenosyltransferase I/III. A variety of studies provided evidence that the elevations of methionine and AdoMet are not caused by defects in the methionine transamination pathway, deficient activity of methionine adenosyltransferase II, a mutation in methylenetetrahydrofolate reductase rendering this activity resistant to inhibition by AdoMet, or deficient activity of guanidinoacetate methyltransferase. Plasma sarcosine (N-methylglycine) is elevated, together with elevated plasma AdoMet in normal subjects following oral methionine loads and in association with increased plasma levels of both methionine and AdoMet in cystathionine beta-synthase-deficient individuals. However, plasma sarcosine is not elevated in these siblings. The latter result provides evidence they are deficient in activity of glycine N-methyltransferase (GNMT). The only clinical abnormalities in these siblings are mild hepatomegaly and chronic elevation of serum transaminases not attributable to conventional causes of liver disease. A possible causative connection between GNMT deficiency and these hepatitis-like manifestations is discussed. Further studies are required to evaluate whether dietary methionine restriction will be useful in this situation.

Alanine Transaminase↗
PubMed2001

Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences.

5,10-Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism by channeling one-carbon units between nucleotide synthesis and methylation reactions. Severe enzyme deficiency leads to hyperhomocysteinemia and homocystinuria, with altered folate distribution and a phenotype that is characterized by damage to the nervous and vascular systems. Two frequent polymorphisms in the human MTHFR gene confer moderate functional impairment of MTHFR activity for homozygous mutant individuals. The C to T change at nucleotide position 677, whose functional consequences are dependent on folate status, has been extensively studied for its clinical consequences. A second polymorphism, an A to C change at nucleotide position 1298, is not as well characterized. Still equivocal are associations between MTHFR polymorphisms and vascular arteriosclerotic or thrombotic disease. Neural tube defects and pregnancy complications appear to be linked to impaired MTHFR function. Colonic cancer and acute leukemia, however, appear to be less frequent in individuals homozygous for the 677T polymorphism.MTHFR polymorphisms influence the homocysteine-lowering effect of folates and could modify the pharmacodynamics of antifolates and many other drugs whose metabolism, biochemical effects, or target structures require methylation reactions. However, only preliminary evidence exists for gene-drug interactions. This review summarizes the biochemical basis and clinical evidence for interactions between MTHFR polymorphisms and several disease entities, as well as potential interactions with drug therapies. Future investigations of MTHFR in disease should consider the influence of other variants of functionally-related genes as well as the medication regimen of the patients. Animal models for genetic deficiencies in folate metabolism will likely play a greater role in our understanding of folate-dependent disorders.

Female↗
PubMed1999

Craniomandibular disorders--comparative investigations with clinical examination and electronic axiography.

An essential problem in the diagnosis of craniomandibular disorders is still the evaluation of the type and severity of the TMJ diseases. For a differential classification of TMJ diseases, we developed an electronic axiography system which facilitates a recording of lower jaw movements. It works 3-dimensionally and relates to the joints. The measuring system, which was internationally patented, is based on a linear resistive foil for the sagittal plane and an inductive gauge for the horizontal plane. The aim of this pilot study was to evaluate the usefulness of our electronic axiography system in obtaining a differential diagnosis of craniomandibular disorders. We examined 30 patients (60 joints) with complaints in the TMJ area (pain and TMJ sounds). Clinical examinations yielded only uncertain indications of TMJ disease. With the help of electronic axiography we could differentiate the TMJ diseases into microtrauma and macrotrauma. Both forms may show a loss of function and an audible TMJ clicking. 23 joints had a macrotrauma (disk displacement with reduction, 20 times; disk displacement without reduction, 3 times). In 8 joints, a microtrauma was found. 3 joints showed a subluxation. In 4 uncertain cases, the diagnosis was confirmed with the help of magnetic resonance imaging (MRI). All patients with a diagnosed arthrogenic disorder received adequate treatment with reposition splints. Our initial results show that 3-dimensional electronic axiography can be a good aid in further characterization of craniomandibular disorders and permits an effective therapy.

Female↗
PubMed1998

Decreased trabecular bone mineral density in patients with phenylketonuria measured by peripheral quantitative computed tomography.

The bone mineral density (BMD) of 14 children, adolescents, and adults with phenylketonuria (PKU) on dietary treatment (age 5-28 y; 6F, 8M) was investigated using peripheral quantitative computed tomography (pQCT) of the distal radius. BMD of total (TBMD) and spongy bone (SBMD) were compared to those of healthy gender-, age-, weight- and height-matched controls. We found a significant decrease of SBMD in patients with PKU while TBMD was only slightly decreased, reaching no statistical significance. These results indicate minor changes of BMD in patients with PKU under treatment, which are more accentuated in the trabecular bone compartment. One additional patient who was untreated until the pQCT investigation at the age of 10 y also showed markedly decreased SBMD and TBMD.

Adolescent↗
PubMed1998

Diurnal changes in plasma amino acids in maple syrup urine disease.

Protein turnover is a cyclic process with a net loss of protein in the (catabolic) fasted state and a net gain in the (anabolic) fed state. In maple syrup urine disease (MSUD) the early block of degradation of the branched-chain amino acids (BCAA) brings about the opportunity for evaluation of the diurnal variation in net protein anabolism and catabolism by studying cyclic changes in the plasma concentrations of BCAA. The alterations in plasma BCAA in a 3-y-old boy with classical MSUD were studied in the fed and fasted state over a period of 19 months. For each amino acid a total of 34 data pairs was calculated. The plasma concentrations of the BCAA leucine, valine and isoleucine were constantly higher in the fasted than in the fed state. Plasma concentrations of alloisoleucine, being a non-protein amino acid, did not participate in cyclic changes. In contrast, the essential amino acid pair tyrosine and phenylalanine increased after meals. The fasting concentration of alanine increased after feeding, while glycine did not change significantly. Healthy subjects show a decrease in all amino acids in the fasted (mild catabolic) state and an increase in the fed state. These findings in MSUD suggest a net decrease in non-BCAA as result of a greater rate of amino acid oxidation rate than of protein breakdown and a net entry of BCAA into plasma in the fasted state due to the specific metabolic block. Such changes in amino acid plasma pools have to be taken into account during monitoring of treatment and especially when in vivo leucine oxidation is assessed.

Amino Acids↗
PubMed1992

Distribution of osteonectin mRNA and protein during human embryonic and fetal development.

We investigated the temporal and spatial distribution of osteonectin during human embryonic and fetal development, using in situ hybridization and immunohistochemistry. Osteonectin gene expression was generally found in cells exhibiting high rates of matrix production/proliferation. In mineralized tissue, a strong signal was obtained in osteoblasts, odontoblasts, and chondrocytes of the upper hypertrophic and proliferative zones. Chondrocytes of the mineralized zone showed no expression throughout the different stages of development. Strong osteonectin expression was found in odontoblasts of developing teeth. In addition, osteonectin mRNA and protein were detected in several non-mineralized tissues: steroid-producing cells of the adrenal gland and the gonads, kidney (glomeruli), lung (bronchi), skin, megacaryocytes, and large vessels. Histochemistry confirmed the results and detected extracellular osteonectin in bone and in the zone of mineralized cartilage only. The localization of osteonectin in bone, cartilage, and teeth is consistent with a role in the initiation of mineralization. However, the organ-specific distribution in non-mineralized tissues suggests an important multifunction role of this protein during human development.

Abortion, Spontaneous↗
PubMed1992

Strategic planning as used by chief executive officers.

In summary, the interviews obtained from this study suggest that CEO's in a variety of industries are attempting to "fit" their strategic planning process to their perceived environmental conditions. Indeed, management thinkers believe the biggest challenge in strategic planning will be turning CEO's into true strategic thinkers. The most successful companies, ultimately, will make strategic planning a high priority and involve all levels of management in the process. Planning becomes the unifying force that directs company actions. Hospital CEO's are obviously becoming more aware of this point as they strive to include all relevant parties (boards, physicians, etc.) in the process. Further, they seem to view planning in the classical sense, that is, as a dynamic, ever-evolving cyclical process more so than their general industry and academic contemporaries. Those hospitals that do develop strategic planning and strategic management have a definite advantage over competitors. Priorities are set and objectives are validated. This, in turn, improves productivity and creates the necessary framework for controlled growth. In addition, planning promotes teamwork and heightens motivation, bringing managers and employees together not only to meet but to exceed company goals.

Arizona↗
PubMed1990

Propensity of health administration faculty to publish in scholarly research journals.

Health administration faculty are interested in publishing activities in academic research journals. Perceived institutional quality and faculty professional advancement are strongly influenced by faculty's propensity to publish articles in scholarly journals. A five-year review of 10 of the health administration field's research-oriented journals showed that between 1983 and 1988 publication activity was heavily concentrated among four to seven institutions. These institutions also tended to publish in a greater breadth of journals selected by our criteria.

Faculty↗
PubMedDate not supplied

Propionic acidemia revisited: a workshop report.

Propionic acidemia (PA) is one of the most frequent organic acidurias, but information on the outcome of individuals with PA is rather limited. We present data of 49 patients with PA, which were gathered from 18 metabolic centers throughout Central Europe on the occasion of an international workshop. All patients were identified by selective metabolic screening, and 86% of them were classified as having early-onset PA owing to their presentation with clinical symptoms within the first 90 days of life. Mortality rate was one third, and details of symptoms and treatment of the surviving patients are discussed. The great variation of phenotypic expression of the disease and different therapeutic strategies (especially in regard to the degree of protein restriction) used at the various institutions involved in this study imply the need for a registry of PA patients and for a multicenter prospective treatment study.

Amino Acid Metabolism, Inborn Errors↗