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Biomedical subjects

A Teubner

Publications and source records attributed to A Teubner.

15 recordsLinked to original sources

Review article: intestinal failure.

Intestinal failure is a specific disease entity resulting from intestinal resection or disease-associated malabsorption and characterized by the inability to maintain protein-energy, fluid, electrolyte or micronutrient balance. We performed a MEDLINE search (1966-2006) to identify relevant articles, using keywords intestinal failure, parenteral or enteral nutrition, intestinal fistula and short bowel syndrome. Causes of intestinal failure are varied, with self-limiting or 'Type 1' intestinal failure occurring relatively commonly following abdominal surgery, necessitating short-term fluid or nutritional support. The rarer, 'Type 2' intestinal failure, is associated with septic, metabolic and complex nutritional complications, usually following surgical resection in patients with Crohn's or mesenteric vascular disease. A multidisciplinary approach to the management of patients with Type 2 intestinal failure is crucial: resolution of sepsis is required before adequate nutritional repletion can be achieved, and it is important to optimize nutritional status, not only through enteral or parenteral supplementation, but also by addressing complications of short bowel syndrome, before considering definitive surgical reconstruction. A structured approach to the management of Type 2 intestinal failure should reduce the likelihood of these complex patients developing 'Type 3' intestinal failure, which is characterized by the need for long-term parenteral nutrition.

Humans↗

[Hepatitis C, hemochromatosis and porphyria cutanea tarda].

Porphyria cutanea tarda (PCT) is characterized by decreased activity of the enzyme uroporphyrinogen decarboxylase (URO-D) and the accumulation of uro- and heptaporphyrins in the liver. Apart from increased alcohol exposure and certain drugs, PCT is associated with antibodies to the hepatitis C virus (HCV), with its prevalence increasing from Northern (8-10%) to Southern Europe (71 to 91%). Chronic HCV-infection is thus considered to be a major trigger for PCT and PCT is said to be an important extrahepatic manifestation of HCV-infection in predisposed individuals. Iron overload is common in PCT. Iron is an inhibitory co-factor of URO-D activity in hepatocytes. Accordingly, in support of the critical role of iron, the clinical efficacy of iron removal is coupled to an improvement of hepatic URO-D activities. Up to two thirds of Saxon patients with PCT carry the classical hemochromatosis (HFE) mutations (C282Y and/or H63D). HFE genotyping can help to further classify patients with PCT and associated hemochromatosis. Simple or compound heterozygosity of HFE mutations does not affect the therapeutic response to chloroquine in PCT. Since Patients carrying homozygous mutations (C282Y/C282Y) with hemochromatosis and PCT do not respond to chloroquine, phlebotomy should be first-line treatment to remove toxic iron.

Hemochromatosis↗

Proximal loop jejunostomy is a useful adjunct in the management of multiple intestinal suture lines in the septic abdomen.

BACKGROUND: Bowel repair in the septic abdomen can be problematic. This study investigated the use of a proximal loop jejunostomy to protect injured or fistulated bowel that had been returned to the abdomen after repair and/or anastomosis. METHODS: Ten patients who underwent laparotomy for intra-abdominal sepsis and/or fistulation, followed by distal enteric repair and/or anastomosis and construction of a proximal defunctioning loop jejunostomy, were studied retrospectively. Seven patients had 21 intestinal suture lines returned to the peritoneal cavity in the presence of intra-abdominal sepsis (14 anastomoses, two enterotomy closures and five serotomy repairs). Two patients had a difficult relaparotomy for pelvic abscess (two distal anastomoses, one enterotomy closure and three serotomy repairs). The final patient had pelvic sepsis and radiation enteritis; the distal anastomosis was defunctioned by a loop jejunostomy. RESULTS: The median distance from the duodenojejunal flexure to the loop stoma was 80 (range 30-170) cm. All jejunostomies were closed via a local approach, a median of 11 (range 9-18) months after formation. There was no significant postoperative morbidity and no postoperative death. At a median follow-up of 7 (range 0.5-56) months eight patients had no requirement for nutritional support. CONCLUSION: Use of a loop jejunostomy to protect suture lines in the septic abdomen justifies consideration of this procedure in selected patients.

Abdomen↗

Efficient and fast targeted production of murine models based on ENU mutagenesis.

Mice with targeted genetic alterations are the most effective tools for deciphering organismal gene function. We generated an ENU-based parallel C3HeB/FeJ sperm and DNA archive characterized by a high probability to identify allelic variants of target genes as well as high efficiencies in allele retrieval and model revitalization. Our archive size of over 17,000 samples contains approximately 340,000 independent alleles (20 functional mutations per individual sample). Based on an estimated number of approximately 30,000 mouse genes, the parallel sperm/DNA archive should permit the identification and recovery of ten or more alleles per average target gene which translates to a calculated 99% success rate in the discovery of five allelic variants for any given average gene. The low rate of unrelated ENU-induced passenger mutations has no practical impact on the analysis of the allele-specific phenotype at the G3 generation because of dilution and free segregation of such unrelated passenger mutations. To date 39 mouse models representing 33 different genes have been recovered from our archive using in vitro fertilization techniques. The generation time for a murine model heterozygous for a mutation in a gene of interest is less than 2 months, i.e., three to four times faster compared with current embryonic stem-cell-based technologies. We conclude that ENU-based targeted mutagenesis is a powerful tool for the fast and high-throughput production of murine gene-specific models for biomedical research.

Alleles↗

Fistuloclysis can successfully replace parenteral feeding in the nutritional support of patients with enterocutaneous fistula.

BACKGROUND: Use of total parenteral nutrition (TPN) in patients with acute intestinal failure due to enteric fistulation might be avoided if a simpler means of nutritional support was available. The aim of this study was to determine whether feeding via an intestinal fistula (fistuloclysis) would obviate the need for TPN. METHODS: Fistuloclysis was attempted in 12 patients with jejunocutaneous or ileocutaneous fistulas with mucocutaneous continuity. Feeding was achieved by inserting a gastrostomy feeding tube into the intestine distal to the fistula. Infusion of enteral feed was increased in a stepwise manner, without reinfusion of chyme, until predicted nutritional requirements could be met by a combination of fistuloclysis and regular diet, following which TPN was withdrawn. Energy requirements and nutritional status were assessed before starting fistuloclysis and at the time of reconstructive surgery. RESULTS: Fistuloclysis replaced TPN entirely in 11 of 12 patients. Nutritional status was maintained for a median of 155 (range 19-422) days until reconstructive surgery could be safely undertaken in nine patients. Two patients who did not undergo surgery remained nutritionally stable over at least 9 months. TPN had to be recommenced in one patient. There were no complications associated with fistuloclysis. CONCLUSION: Fistuloclysis appears to provide effective nutritional support in selected patients with enterocutaneous fistula.

Adult↗

Kinetic evidence for a readily exchangeable nucleotide at the terminal subunit of the barbed ends of actin filaments.

The time course of actin depolymerization was quantitatively analyzed to obtain insight into the reactions occurring during actin disassembly. Polymeric actin was diluted, and subsequently the time course of depolymerization was measured. In the presence of 0.5 mM ATP, 100 mM KCl, and 1 mM MgCl2, continuous depolymerization was observed both when the filaments were carefully diluted and when the filaments were fragmented to produce short filaments. The rates of the reactions that are known to occur during depolymerization, such as dissociation and association of ADP- and ATP-actin molecules and exchange of nucleotides bound to monomeric actin, were determined by independent experiments. When the determined rate parameters were used to calculate the time course of depolymerization, consistently in the simulations fast depolymerization of ADP-actin was followed by slower polymerization of ATP-actin that was formed from ADP-actin by nucleotide exchange. The lack of fast depolymerization and subsequent slower polymerization in the experiments suggests that our present conception about actin disassembly requires modification. Good agreement of calculated time courses with the experimentally determined continuous depolymerization was achieved if ADP bound to the terminal subunit of barbed filament ends was assumed to be readily exchangeable for ATP. Fast nucleotide exchange at terminal subunits may contribute to the stability of barbed filament ends and to their role as polymerizing ends in living cells.

Actin Depolymerizing Factors↗

Derivation of insertin.

Insertin is an actin-binding protein that has been isolated from chicken gizzard smooth muscle that has been shown to be highly homologous to amino acids 962-1292 of tensin [Weigt et al., 1992]. Because of the high homology, we investigated the question whether the mRNAs of insertin and of tensin are derived from the same gene by alternative splicing, whether insertin and tensin are encoded by two different genes, or whether insertin is a proteolytic fragment of tensin. In a Northern blot analysis, mRNA from chicken gizzard was hybridized with oligonucleotides specific for tensin and for the insertin domain of tensin. The tensin-specific oligonucleotide hybridized only with the previously reported 8- and 10-kbp RNAs. However, the insertin domain-specific oligonucleotide hybridized with a 1.2 and a 1.6 kbp RNA in addition to the 8 and 10 kbp RNA. The 1.2- and 1.6-kbp RNA occurred in small amounts, as compared with the 8- and 10-kbp RNA. Southern blot analysis of DNA cleaved by the restriction endonucleases BamH1 and HindIII demonstrated that only one gene for the insertin and tensin exists. Insertin isolated from chicken gizzard smooth muscle was investigated by mass spectrometry. The N-termini of three isolated peptides were found to begin at adjacent amino acids and were likely to be formed from tensin by proteolysis. The results suggest that, for insertin, an mRNA exists that is derived from one gene common for insertin and tensin. However, the insertin-specific mRNA contributes relatively little to expression of insertin domains in cells. Insertin preparations from chicken gizzard contain mainly insertin domains formed from tensin by proteolysis.

Amino Acid Sequence↗

[Clinical picture, diagnosis and therapy of acromegaly patients in Eastern and Western Germany].

Acromegaly, a chronic disease characterized by an excessive secretion of growth hormone (GH), is not commonly diagnosed timely enough. Therefore, investigations have been conducted through standardized questionnaires concerning the path to diagnosis, clinical data, therapy, and the patient care of 46 acromegalic patients. The acquired information has been compared in the former Eastern and Western German states. The mean duration of disease before diagnosis was estimated to be 6.1 +/- 5.3 years in the area surrounding Erlangen and 9.3 +/- 7.3 years in the Leipzig and Dresden areas. Despite current trends, a significant difference could not be established regarding the age in which the first symptoms are noted, time of diagnosis, and the delay between the two points in time General practitioners have diagnosed about 35 percent of the occurrences of acromegaly, 15 percent of the cases were accidentally found and about as many were discovered in hospitals. 11 percent of the occurrences were diagnosed by neurologists and another 11 percent by internists. The remaining cases were established by eye specialists. ENT departments, orthopedic specialists or gynaecologists. The most frequent symptoms are increased acral growth, coarse facial features and excessive sweating. For 91 percent of the acromegaly patients, surgery was voted as the therapy of choice. Acromegalic patients have learned the most about their disease through personal contact with doctors, especially endocrine specialists. Many patients are not informed enough about the possible complications of their disease. Through gathered data, it has been concluded that in Eastern and Western Germany the disease has not been identified soon enough. Interdisciplinary teamwork among doctors is a basis for early diagnosis, as well as better patient awareness and education.

Acromegaly↗

The rate of annealing of actin tropomyosin filaments depends strongly on the length of the filaments.

Actin tropomyosin filaments were sheared to produce short filaments. Following incubation for 0 to 10000 s annealing of the filaments was assayed by determination of the rate of polymerization of monomeric actin onto the filament ends. The rate of decrease of the concentration of filament ends was found to be proportional to its fourth power. In contrast, the rate of end-to-end association of actin filaments in the absence of tropomyosin was proportional to the square of the concentration of filament ends. The strong dependence on the filament length of the rate of annealing of actin tropomyosin filaments was interpreted by the model of Hill (Biophys. J., 44, 285-288 (1983)) who pointed out that the rate constant of end-to-end association of long rod-like filaments is expected to depend on the length of the filaments for sterical conditions.

Actins↗

Distribution of gelsolin in mouse ovary.

The distribution of gelsolin, a calcium-dependent actin-modulating protein, and the expression of the corresponding gene, have been characterized with respect to morphogenetic processes in mouse ovary. Substantial amounts of gelsolin have been detected in the ovary and uterus of the mouse by immunoblot analysis. The similar relative ratio of mRNA of alpha-smooth muscle actin (alpha-SM actin) and gelsolin in the two organs suggests that expression of these two genes is coordinated at the transcriptional level. Immunofluorescence has demonstrated gelsolin predominantly in three types of cells in the ovary: (1) cells of the theca externa and stroma, (2) endothelial cells lining blood vessels, and (3) cells of the superficial epithelium of ovary. In the smooth-muscle-like cells of the theca externa, gelsolin appears tightly associated with the microfilamentous cytoskeleton, which is also rich in alpha-SM actin. The presence of gelsolin in myoid cells suggests that this protein, possibly by modulation of the activity of the actomyosin ATPase, plays a critical role in contractile and morphogenetic processes, e.g., during growth and maturation of the follicle or during ovulation. In cells of the endothelium, intracellular gelsolin is associated with the F-actin cytoskeleton around the nucleus. The circumferential belt lining the lateral cell membranes in cells of the superficial epithelium at the ovarian surface is also rich in gelsolin. Our observations indicate that the function of gelsolin as a calcium- and phospholipid-dependent modulator of actin assemblies is pivotal for the regulation of the dynamic alterations of the actin cytoskeleton in the superficial epithelium when cells become attenuated and retract their microvilli during growth of the follicle.

Actins↗