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Biomedical subjects

E Sturm

Publications and source records attributed to E Sturm.

At least 19 recordsLinked to original sources
PubMed2004

[Two sisters with progressive familial intrahepatic cholestasis].

A few months after birth two sisters aged 5 and 9 years had developed cholestasis and abnormal liver functions with symptoms including itching and jaundice. The younger sister also developed rickets and clotting disorders. On clinical, biochemical and immunohistopathological grounds the diagnosis of 'progressive familial intrahepatic cholestasis (PFIC) type 2' was made. Medical treatment was not succesfull in reducing symptoms. An ileocolonic bypass in the younger child was not effective. Subsequently, both patients underwent partial external biliary diversion (PEBD). Except for a period of intermittent itching in the younger child, both patients remained free of symptoms 2 years after PEBD. In cases where an early diagnosis is made, PEBD could delay or even prevent the necessity of liver transplantation.

Age Factors↗
PubMed2003

Risk indicators for falls in institutionalized frail elderly.

The aim of this study was to identify individual predisposing risk indicators for falls in a sample of institutionalized frail elderly in southern Germany. The design was a prospective observational study with a 1-year follow-up (October 1998-September 1999). The study population included 472 long-term-care residents whose mean age was 84 years; 77% were female. Risk indicators for accidental falls were analyzed by using logistic regression. Residents were found to have an incidence density rate of falls of 2,558 per 1,000 resident-years. Multiple logistic regression analysis revealed short-term memory loss, transfer assistance, urinary incontinence, positive fall history, and use of trunk restraints as predictors of falls. In a further logistic regression analysis, depressive symptoms, transfer assistance, urinary incontinence, and positive fall history were associated with frequent falls. Using these risk indicators as a screening procedure to identify fallers would be easy to administer and could be accomplished by nursing staff. Study results encourage specifically addressing urinary incontinence, cognitive impairment, use of restraints, depression, and transfer difficulties as modifiable predisposing risk factors for falls. Fall history represents an important nonmodifiable marker to identify residents at high risk.

Accidental Falls↗
PubMed2003

Genetic cholestasis.

Explore the source record for details and available documents.

Cholagogues and Choleretics↗
PubMed2003

[Abilities and restrictions of nursing home residents. Evaluation with the Minimum Data Set of the Resident Assessment Instrument].

UNLABELLED: The main objective of the study was to examine the prevalence of problems and resources of an unselected cohort of nursing home residents. The sample includes residents (n=769) of an urban area in Southern Germany. The assessment definitions were used according to the Minimum Data Set of the Resident Assessment Instruments (Version 2.0). RESULTS: The mean age was 84.2 years, 608 of the residents were female. Dementia (446) and stroke (185) were the most common main diagnosis. Syndrome prevalences are reported for depressive symptoms (323), mobility impairments (608), urinary incontinence (461), decubitus (54), use of restraints (54), disruptive behavior (185), psychopharmacy (377), severe visual impairment (123) and severe hearing impairment (123).

Age Factors↗
PubMed2003

Elevated heels and adaptation to new shoes in frail elderly women.

Footwear is supposed to have influence on postural control and is a potential aspect to address in the prevention of falls in the elderly. This study aimed to show whether measurements of static balance and gait are different with habitual shoes compared to new special senior shoes with different heel height and whether these results change after adaptation. In a randomized controlled intervention study, 26 subjects (median age 87 years) were recruited from two nursing homes and one facility of assisted living. Measurements of static balance and gait were performed with habitual shoes and two types of new special senior shoes differing in heel height. Measurements were repeated after five weeks. There was no difference in static balance and gait with habitual shoes compared to either of the new footwear offered. Results of performance with higher heels were not different compared to lower heels. No further effect of adaptation after wearing a new shoe over five weeks could be demonstrated. With respect to static and dynamic balance, there seems to be a wide range of acceptable footwear as long as the heel height is below a critical value. A standardized shoe can be used in the assessment of balance because the effect of adaptation can be neglected.

Accidental Falls↗
PubMed2002

Extracorporal albumin dialysis (MARS) improves cholestasis and normalizes low apo A-I levels in a patient with benign recurrent intrahepatic cholestasis (BRIC).

The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile salt levels, therapy-resistant extreme pruritus and peculiar biochemical abnormalities including low apolipoprotein apo A-I. Previously, symptomatic improvement has been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS). We hypothesized that MARS improves cholestasis, induces changes in the bile salt profile and normalizes apo A-I serum levels in BRIC. A 17-year-old-female patient with BRIC experienced an episode of cholestasis lasting for more than 6 months with extreme pruritus and diarrhoea not responding to standard therapy. During a period of five days the patient was treated 3 x 8 h with MARS. The procedures were well tolerated and resulted in reduction of plasma bile salts by 58%. The plasma bile salt profile changed into a more hydrophilic composition after MARS. Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a subjective scale. These effects lasted 4 months until a relapse occurred. Low plasma apo A-I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures were well tolerated. Fatigue was noted as the only transient side-effect. In conclusion, MARS may induce a long-term symptomatic improvement and decrease of cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of MARS in patients with BRIC are needed.

Adolescent↗
PubMed2001

The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood.

BACKGROUND & AIMS: We have specified the features of progressive familial intrahepatic cholestasis type 3 and investigated in 31 patients whether a defect of the multidrug resistance 3 gene (MDR3) underlies this phenotype. METHODS: MDR3 sequencing, liver MDR3 immunohistochemistry, and biliary phospholipid dosage were performed. RESULTS: Liver histology showed a pattern of biliary cirrhosis with patency of the biliary tree. Age at presentation ranged from the neonatal period to early adulthood. Sequence analysis revealed 16 different mutations in 17 patients. Mutations were identified on both alleles in 12 patients and only on 1 allele in 5. Four mutations lead to a frame shift, 2 are nonsense, and 10 are missense. An additional missense mutation probably representing a polymorphism was found in 5 patients. MDR3 mutations were associated with abnormal MDR3 canalicular staining and a low proportion of biliary phospholipids. Gallstones or episodes of cholestasis of pregnancy were found in patients or parents. Children with missense mutations had a less severe disease and more often a beneficial effect of ursodeoxycholic acid therapy. CONCLUSIONS: At least one third of the patients with a progressive familial intrahepatic cholestasis type 3 phenotype have a proven defect of MDR3. This gene defect should also be considered in adult liver diseases.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp.

BACKGROUND AND AIMS: Hepatic bile acid homeostasis is regulated by negative feedback inhibition of genes involved in the uptake and synthesis of bile acids. Bile acids down-regulate the rate-limiting gene for bile acid synthesis, cholesterol 7alpha-hydroxylase (cyp7a), via bile acid receptor (fxr) activation of an inhibitory nuclear receptor, shp. We hypothesized that shp would also mediate negative feedback regulation of ntcp, the principal hepatic bile acid transporter. METHODS: Primary rat hepatocytes or transfected HepG2 and Cos cells were treated with retinoids with or without bile acids, and effects on bile acid transport and ntcp and shp gene expression and promoter activity were determined. Gel shift assays were performed using synthetic fxr, rxr, and rar proteins. RESULTS: Bile acid treatment of primary rat hepatocytes prevented retinoid activation of ntcp gene expression and function; this corresponded temporally with shp gene activation. Bile acid-mediated down-regulation occurred via fxr-dependent suppression of the ntcp RXR:RAR response element. Moreover, cotransfected shp directly inhibited retinoid activation of the ntcp promoter. CONCLUSIONS: These studies show negative feedback regulation of ntcp by bile acid-activated fxr via induction of shp. This novel regulatory pathway provides a means for coordinated down-regulation of bile acid import and synthesis, thereby protecting the hepatocyte from bile acid-mediated damage in cholestatic conditions.

Animals↗
PubMed2000

Hex expression suggests a role in the development and function of organs derived from foregut endoderm.

Hex is a divergent homeobox gene expressed as early as E4.5 in the mouse and in a pattern that suggests a role in anterior-posterior patterning. Later in embryogenesis, Hex is expressed in the developing thyroid, lung, and liver. We now show Hex expression during thymus, gallbladder, and pancreas development and in the adult thyroid, lung, and liver. At E10.0, Hex is expressed in the 3rd pharyngeal pouch, from which the thymus originates, the endodermal cells of liver that are invading the septum transversum, the thyroid, the dorsal pancreatic bud, and gallbladder primoridum. At E13.5, expression is maintained at high levels in the thyroid, liver, epithelial cells lining the pancreatic and extrahepatic biliary ducts and is present in both the epithelial and mesenchymal cells of the lung. Expression in the thymus at this age is less than in the other organs. In the E16.5 embryo, expression persists in the thyroid, pancreatic, and bile duct epithelium, lung, and liver, with thymic expression dropping to barely detectable levels. By E18.5, expression in the thyroid and bile ducts remains high, whereas lung expression is markedly decreased. At this age, expression in the pancreas and thymus is no longer present. Finally, we show the cell types in the adult thyroid, lung, and liver that express Hex in the mature animal. Our results provide more detail on the potential role of Hex in the development of several organs derived from foregut endoderm and in the maintenance of function of several of these organs in the mature animal.

Animals↗
PubMed2000

Endotoxin-stimulated macrophages decrease bile acid uptake in WIF-B cells, a rat hepatoma hybrid cell line.

Endotoxemia leads to cytokine-mediated alterations of the hepatocellular sodium-taurocholate-cotransporting polypeptide (ntcp). We hypothesized that stimulated macrophages are essential transducers for down-regulating hepatocellular bile salt uptake in response to endotoxin (lipopolysaccharide [LPS]) exposure. Using an in vitro model, we exposed mouse macrophages (IC-21 cell line) to LPS for 24 hours. Concentrations of cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 increased 10.6-fold, 12.5-fold, and 444-fold, respectively, in LPS-conditioned IC-21 medium (CM) versus unconditioned IC-21 medium (UM). WIF-B rat hepatoma hybrid cells were incubated with either CM or UM or treated directly with medium containing recombinant TNF-alpha, IL-1beta, and IL-6. [(3)H]Taurocholate ([(3)H]TC) uptake decreased in WIF-B cells exposed to either TNF-alpha (54% of control), IL-1beta (78%), IL-6 (55%) as single additives, or in triple combination (TCC) (43%). A virtually identical decrease was observed after exposing WIF-B cells to CM (52%, P <.001). LPS had no direct effect on [(3)H]TC uptake. CM treatment did not decrease L-alanine transport in WIF-B cells. Blocking antibodies against TNF-alpha, IL-1beta, and IL-6 restored the diminished [(3)H]TC uptake in cells exposed to TCC and CM to 87% and 107% of controls, respectively. Northern blotting revealed that ntcp messenger RNA (mRNA) expression was significantly reduced in WIF-B cells after exposure to CM, and in primary rat hepatocytes exposed to CM or TNF-alpha (68%, 14%, and 29% of control, respectively). We conclude that macrophages and their ability to secrete the cytokines TNF-alpha, IL-1beta, and IL-6 may be essential in mediating the endotoxin-induced cholestatic effect of decreased hepatocellular bile salt uptake.

Animals↗
PubMed1999

Hepatic regulation of platelet-activating factor acetylhydrolase and lecithin:cholesterol acyltransferase biliary and plasma output in rats exposed to bacterial lipopolysaccharide.

Normal rat bile contains secretory platelet-activating factor acetylhydrolase (PAF-AH), the enzyme capable of hydrolyzing the inflammatory mediator platelet-activating factor (PAF), and phospholipids containing oxidized truncated fatty acids. Because lecithin:cholesterol acyltransferase (LCAT) possesses intrinsic PAF-AH-like activity, it also may represent a potential anti-inflammatory enzyme. The behavior of PAF-AH and LCAT in hepatobiliary inflammatory responses in vivo has not been characterized. We therefore investigated the biliary and plasma secretion and pharmacological characteristics of these enzymes in rats subjected to intraportal bacterial endotoxin exposure (lipopolysaccharide [LPS], Escherichia coli, 055:B5). Portal vein LPS infusion (1 mg/kg, bolus) resulted in a maximal 4- to 5-fold increase in bile PAF-AH-specific activity with a gradual decline to baseline by 18 hours. Biliary PAF-AH hydrolyzed also the truncated sn-2-succinoyl and sn-2-glutaroyl analogs of PAF, indicating a broader activity of PAF-AH in bile toward byproducts of glycerophospholipid peroxidation. Plasma PAF-AH activity was not altered 5 hours after LPS injection compared with saline injection, but it was significantly elevated 18 hours after endotoxin exposure. The levels of LCAT in bile were low and declined to nearly undetectable values by 5 hours after cannulation in both control and LPS-exposed rats. Plasma LCAT activity was significantly increased after 5 hours and decreased 18 hours after LPS injection. In summary, hepatic exposure to endotoxin results in a rapid increase in biliary secretion of PAF-AH followed by elevation of LCAT and PAF-AH levels in plasma. We propose that biliary secretion of PAF-AH may be involved in the hepatic response to endotoxic insult by counteracting potential inflammatory damage in the biliary tree and gastrointestinal tract, whereas plasma increases in LCAT and PAF-AH may promote elimination of excess PAF and oxidized phospholipids in the circulation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

Liver transplantation in children: long-term outcome and quality of life.

UNLABELLED: Liver transplantation has become a standard therapy in acute and chronic liver failure. Since 1968, 2554 paediatric patients receiving a liver transplant have been registered in the European Liver Transplant Registry (ELTR). Compared with 22,600 total transplants registered in the ELTR over the same period of time this means that about 10% of all liver transplants performed in Europe concern paediatric recipients, aged from 0 to 15 years. The indications in the paediatric population differ significantly from those of adult patients: More than 50% of patients suffer from cholestatic disorders, followed by hepatic based metabolic disorders, acute liver failure, non-cholestatic cirrhosis and liver tumours. The results of liver transplantation in paediatric patients have improved remarkably since the early 1980s. In 1997 a survival rate of 80% is almost the international standard. This improvement is due to the use of better immunosuppressive agents such as cyclosporin A and tacrolimus, followed by improvement in surgical techniques and finally by improvement in intensive care, better diagnostic tools for viral, bacterial and fungal infections and corresponding appropriate therapies. Quality of life as a measure of transplant results has not been sufficiently studied. The majority of paediatric liver transplant recipients has a good quality of life; only 10% suffer from significant morbidity. The impact of pretransplant damage to other organs such as brain, kidneys, bone and lungs and the influence of immunosuppression on somatic growth, neurological development, infection and metabolic balance are subjects of increasing concern. CONCLUSION: The results available today show convincing evidence that liver transplantation is a therapeutic option in otherwise fatal hepatic disorders. Much effort, however, has to be made in order to achieve further improvements by increasing our knowledge of the pathophysiology of both pre- and posttransplant conditions.

Adolescent↗
PubMed1998

Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis.

Class III multidrug resistance (MDR) P-glycoproteins (P-gp), mdr2 in mice and MDR3 in man, mediate the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte. Mice with a disrupted mdr2 gene completely lack biliary phospholipid excretion and develop progressive liver disease, characterized histologically by portal inflammation, proliferation of the bile duct epithelium, and fibrosis. This disease phenotype is very similar to a subtype of progressive familial intrahepatic cholestasis, hallmarked by a high serum gamma-glutamyltransferase (gamma-GT) activity. We report immunohistochemistry for MDR3 P-gp, reverse transcription-coupled PCR sequence analysis, and genomic DNA analysis of MDR3 from two progressive familial intrahepatic cholestasis patients with high serum gamma-GT. Canalicular staining for MDR3 P-gp was negative in liver tissue of both patients. Reverse transcription-coupled PCR sequencing of the first patient's sequence demonstrated a homozygous 7-bp deletion, starting at codon 132, which results in a frameshift and introduces a stop codon 29 codons downstream. The second patient is homozygous for a nonsense mutation in codon 957 (C --> T) that introduces a stop codon (TGA). Our results demonstrate that mutations in the human MDR3 gene lead to progressive familial intrahepatic cholestasis with high serum gamma-GT. The histopathological picture in these patients is very similar to that in the corresponding mdr2(-/-) mouse, in which mdr2 P-gp deficiency induces complete absence of phospholipid in bile.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1998

Synthesis and structural characterization of human-identical lung surfactant SP-C protein.

An efficient synthesis for human-identical lung surfactant protein SP-C is described with a semi-automated solid phase synthesizer using Fmoc chemistry. Double coupling and acetic anhydride capping procedures were employed for synthetic cycles within the highly hydrophobic C-terminal domain of SP-C. Isolation of the protein was performed by mild cleavage and deprotection conditions and subsequent HPLC purification yielding a highly homogeneous protein as established by sequence determination, electrospray, plasma desorption and MALDI mass spectrometry. A general method has been employed for the preparation of Cys-palmitoylated protein by using temporary Cys(tButhio) protection, in situ deprotection with beta-mercaptoethanol and selective palmitoylation of resin-bound SP-C. The mild synthesis and isolation conditions provide SP-C with a high alpha-helical content, comparable to that of the natural SP-C, as assessed by CD spectra. Furthermore, first biophysical data indicate a surfactant activity comparable to that of the natural protein.

Amino Acid Sequence↗
PubMed1998

Depressed plasma platelet-activating factor acetylhydrolase in patients presenting with acute myocardial infarction.

Cell membrane phospholipids, including platelet-activating factor (PAF), participate in the pathogenesis of acute myocardial infarction (AMI). The plasma level of PAF acetylhydrolase (AH) was determined in 18 patients at presentation with AMI before thrombolysis, and the administration of adjunctive therapy, and compared with 13 healthy controls. Plasma levels of PAF-AH were significantly lower in the AMI patients (23.15 +/- 1.75 nmol/min/ml) than in the controls (30.43 +/- 2.13 nmol/min/ml; p = 0.027). Considering normal plasma levels of PAF and lyso-PAF, and lack of evidence that anti-PAF antibodies are really beneficial in myocardial ischemia-reperfusion, it is reasonable to speculate that an inability of systemic PAF to 'turn on' PAF-AH enzymatic activity could contribute substantially to the observed events. Decreased PAF-AH activity in AMI patients may represent not a consequence, but rather, a risk factor for the development of acute coronary syndromes.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

One year of experience with extended application and modified techniques of split liver transplantation.

As organ donation rates decreased in Europe, the authors started a systematic approach of liver splitting in their center in 1994. During this 1-year experience, 73 cadaveric liver transplantations were performed in 66 patients. Sixteen of these transplantations were the result of split-liver transplantation (21.9% of grafts, 24.2% of patients). Patient and graft survival rates at 3 months were 81.2% and 75%, compared with 89.1% and 76.9 % for whole organs. Two modified techniques were developed, based on the technique of living related liver procurement, and applied in 10 cases. With these new techniques, patient and graft survival rates were 90% and 90%. This systematic approach allowed the total number of transplantations in our program to be maintained, despite the decrease in organ availability.

Graft Survival↗