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Biomedical subjects

J Stein

Publications and source records attributed to J Stein.

At least 145 records · Page 8Linked to original sources
PubMed1999

[Tube feeding in malnutrition].

Malnutrition is known to be very common in geriatric patients. The incidence is ranging from 30 to 60% of all patients. Therefore, indication for nutritional support via nasogastric or percutaneous tubes is frequently given. Since percutaneous endoscopic gastrostomy (PEG) has several advantages over nasogastric tube feeding including reduced risk of tube displacement and blockage, and higher patient acceptance, it has become the method of choice in enteral tube feeding. Complication rates are low provided that guidelines for enteral tube feeding are considered. Early home enteral nutrition contributes to patients quality of life.

Aged↗
PubMed1999

Mediation of differentiating effects of butyrate on the intestinal cell line Caco-2 by transforming growth factor-beta 1.

BACKGROUND: Beside their role as the main energy source in the colonic mucosa, short chain fatty acids were found to act as potent antiproliferative and differentiation agents in various cancer cell lines. It has recently been shown that butyrate also induces TGF-beta 1 mRNA in human keratinocytes, suggesting that TGF-beta 1 may play a role in butyrate induced cell differentiation. AIM OF THE STUDY: The objective of our study was to investigate the possible role of exogenous and endogenous TGF-beta on butyrate induced differentiation of intestinal epithelium. METHODS: Studies were performed in Caco-2 cells, a cell line resembling functionally normal enterocytes. Cells, cultured in standard medium were studied over a 15-day period. Sodium butyrate (5 mM), TGF-beta 1 (2 ng/ml) or butyrate (5 mM) + anti-human TGF-beta 1 antibody (30 micrograms/ml) were added to the medium. At day 4, 8, 11 and 15 total protein content, alkaline phosphatase activity, lactate dehydrogenase activity and transepithelial resistance were measured. RESULTS: Under culture conditions both, butyrate and TGF-beta 1 inhibited growth accompanied by an induction of cell differentiation approved by increased alkaline phosphatase activity and transepithelial resistance. The differentiating effect of butyrate was accompanied by an increased endogenous TGF-beta 1, but not TGF-beta 2 expression in Caco-2 cells. Co-incubation of butyrate with anti-human TGF-beta 1 antibody suppressed at least in part the differentiating effects of butyrate. CONCLUSIONS: Our results directly implicate that the TGF-beta isoform TGF-beta 1 is necessary for butyrate-induced Caco-2 cell differentiation, but other molecular mechanisms may also play a role in the differentiation of this cell line.

Alkaline Phosphatase↗
PubMed1999

Reduction of cell density dependent antigenic properties of intracellular Ca(2+)-regulating membranes by isoflurane in human endothelial cells.

An established cell line of human umbilical vein endothelial cells displays a pronounced shift in the distribution of intracellular Ca(2+)-regulating membranes as the cells grow towards confluence. In sparsely populated cultures a linearly oriented punctate pattern of vesicle-like structures is observed similar to the distribution found in many other eucaryotic cells. As the cell population increases, the membranes condense around the nucleus. In completely confluent cultures when the cells cease to proliferate, the antigen is no longer detectable by immunofluorescence; its absence is confirmed by Western blotting experiments. Double-labeling with antitubulin or phalloidin shows that the distribution of microtubules is not related to the distribution of the Ca(2+)-regulating membranes whereas the actin fibers are superimposable onto the linearly oriented punctate vesicle-like structures. If proliferating cells are treated with the volatile anesthetic isoflurane, the Ca(2+)-regulating membranes can no longer be detected with the antibody; however, in Western blots the antigen is still present. Staining is restored after the removal of isoflurane. Such a temporary disappearance of the immunocytochemical staining might be explained by a transient oxidation and subsequent configuration change of the antigen, rendering the epitope inaccessible to the antibody, since a treatment with low concentrations of NaBH4 of cells exposed to isoflurane restores the access of the antigen to the antibody.

Anesthetics, Inhalation↗
PubMed1999

Patient and physician agreement on abdominal pain severity and need for opioid analgesia.

Whereas controversy surrounds emergency department (ED) analgesia administration to patients with undifferentiated abdominal pain, few studies have addressed the level of patient-physician agreement on abdominal pain severity and need for opioid analgesia. This prospective study was undertaken to assess concordance between emergency physicians and patients on abdominal pain severity. Study subjects were a convenience sample of 30 adults seen in an urban university-affiliated tertiary care ED (annual census 65,000) who had undifferentiated abdominal pain meeting an initial severity threshold of 5 on a 10 cm visual analog scale (VAS) marked by the patient. Patients' and physicians' VAS scores, obtained in blinded fashion at presentation (t0) and at one (t1) and two (t2) hours into the ED stay, were compared with t test (VAS scores) and sign-rank (percent change in VAS scores) analyses. In addition, patients and physicians were asked at each assessment time, in blinded fashion, "Is the pain severe enough to warrant morphine?" The kappa statistic was used to characterize the degree of agreement between physician and patient assessments as to whether opioids were indicated. At t0, t1, and t2, patients' mean VAS scores (7.5, 6.7, and 5.1) were significantly (P < .05) higher than the corresponding physicians' VAS scores (5.3, 4.7, and 3.9). Though VAS scores for physicians started lower than those of patients, the percentage changes in scores from one assessment to the next were similar by Wilcoxon sign-rank testing (P > .50 for time intervals t0 - t1 and t1 - t2). Overall, patients and physicians agreed on the question of whether pain was sufficient to warrant opioids in 71 of 90 (78.9%) assessments; the corresponding kappa statistic of .57 indicated moderate agreement (P < .0001). These results, indicating that patients and physicians usually agree on whether opioids are warranted for abdominal pain, have important implications for further research on ED analgesia in this population.

Abdominal Pain↗
PubMed1999

Borrelia burgdorferi sensu lato in Ixodes ricinus ticks and rodents in a recreational park in south-western Ireland.

Ixodes ricinus ticks infected with Borrelia burgdorferi sensu lato were numerous on the edges of paths and roads in a recreational park in south-western Ireland. The abundance of ticks at different sites was related to the presence of deer, but a negative relationship was shown between tick abundance and tick infection rates. This is thought to be due to the deposition of large numbers of uninfected ticks by deer, which are apparently not good reservoir hosts of B. burgdorferi s.l. Blood meal analysis only detected deer DNA in uninfected nymphs. Reservoir competent rodents, Apodemus sylvaticus and Clethrionomys glareolus, were abundant at all sites and a high proportion of captured specimens were infested with larval ticks. However, very few rodents were infected with B. burgdorferi s.l. and none of the unfed infected nymphs analysed for the identity of their larval blood meal had fed on rodents. The spirochaetes detected in I. ricinus in the study area may be poorly adapted to rodents or are not transmitted readily because of the absence of nymphal infestation. The majority of spirochaetes in these ticks were apparently acquired from non-rodent hosts, such as birds.

Animals↗
PubMed1999

Roles of the C terminus of Armadillo in Wingless signaling in Drosophila.

Drosophila melanogaster Armadillo and its vertebrate homolog beta-catenin play multiple roles during development. Both are components of cell-cell adherens junctions and both transduce Wingless (Wg)/Wnt intercellular signals. The current model for Wingless signaling proposes that Armadillo binds the DNA-binding protein dTCF, forming a bipartite transcription factor that activates Wingless-responsive genes. In this model, Armadillo's C-terminal domain is proposed to serve an essential role as a transcriptional activation domain. In Xenopus, however, overexpression of C-terminally truncated beta-catenin activates Wnt signaling, suggesting that the C-terminal domain might not be essential. We reexamined the function of Armadillo's C terminus in Wingless signaling. We found that C-terminally truncated mutant Armadillo has a deficit in Wg-signaling activity, even when corrected for reduced protein levels. However, we also found that Armadillo proteins lacking all or part of the C terminus retain some signaling ability if overexpressed, and that mutants lacking different portions of the C-terminal domain differ in their level of signaling ability. Finally, we found that the C terminus plays a role in Armadillo protein stability in response to Wingless signal and that the C-terminal domain can physically interact with the Arm repeat region. These data suggest that the C-terminal domain plays a complex role in Wingless signaling and that Armadillo recruits the transcriptional machinery via multiple contact sites, which act in an additive fashion.

Amino Acid Sequence↗
PubMed1999

Diseases of the small intestine.

During the past 10 years considerable progress and increase of knowledge on small intestinal diseases has been achieved. This short review will cover some selected small bowel diseases including coeliac disease, Whipple's disease, rare congenital enteropathies, non-steroidal anti-inflammatory drug enteropathy and autoimmune enteropathy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Superoxide: a major factor for stress protein induction in reoxygenation injury in the intestinal cell line Caco-2.

BACKGROUND/AIMS: Acute intestinal ischemia is followed by cellular destruction and loss of mucosal barrier function. Posthypoxic injury of cellular proteins leads to the synthesis of heat shock proteins. The role of oxygen radicals in this process, however, is not fully established. METHODS: In the present study, using the intestinal cell line Caco-2, we investigated the relationship between the synthesis of the heat shock protein HSP70, detected by Western blot and oxygen radicals as well as lactate dehydrogenase (LDH) release, as measured in photometrical tests. RESULTS: Various periods of hypoxia and 30 min of reoxygenation resulted in an increased generation of superoxide as measured by the tetrazolium base 3-(4, 5-dimethylthiazol-2-yl)2,5-diphenyltetrazoliumbromide. The inhibitor of superoxide dismutase (SOD), diethyldithiocarbamate (DDC) increased and addition of SOD decreased intracellular superoxide levels. HSP70 synthesis was detectable after 2 h of hypoxia. Similar to superoxide production, DDC increased and SOD reduced the HSP70 synthesis. In contrast, the increased LDH release from the cells observed after hypoxia was not significantly altered by DDC and SOD. CONCLUSION: The production of superoxide correlates with HSP70 induction, but not with LDH release. We conclude that hypoxia/reoxygenation induces heat shock protein production, a result of protein damage, by increased superoxide generation, whereas superoxide does not correlate with membrane damage in Caco-2 cells.

Adenosine Triphosphate↗
PubMed1999

Membrane-tethered Drosophila Armadillo cannot transduce Wingless signal on its own.

Drosophila Armadillo and its vertebrate homolog beta-catenin are key effectors of Wingless/Wnt signaling. In the current model, Wingless/Wnt signal stabilizes Armadillo/beta-catenin, which then accumulates in nuclei and binds TCF/LEF family proteins, forming bipartite transcription factors which activate transcription of Wingless/Wnt responsive genes. This model was recently challenged. Overexpression in Xenopus of membrane-tethered beta-catenin or its paralog plakoglobin activates Wnt signaling, suggesting that nuclear localization of Armadillo/beta-catenin is not essential for signaling. Tethered plakoglobin or beta-catenin might signal on their own or might act indirectly by elevating levels of endogenous beta-catenin. We tested these hypotheses in Drosophila by removing endogenous Armadillo. We generated a series of mutant Armadillo proteins with altered intracellular localizations, and expressed these in wild-type and armadillo mutant backgrounds. We found that membrane-tethered Armadillo cannot signal on its own; however it can function in adherens junctions. We also created mutant forms of Armadillo carrying heterologous nuclear localization or nuclear export signals. Although these signals alter the subcellular localization of Arm when overexpressed in Xenopus, in Drosophila they have little effect on localization and only subtle effects on signaling. This supports a model in which Armadillo's nuclear localization is key for signaling, but in which Armadillo intracellular localization is controlled by the availability and affinity of its binding partners.

Animals↗
PubMed1999

Evaluation of institutional cancer registries in Colombia.

The four primary objectives of this descriptive study were to: 1) design a quality-measurement instrument for institutional cancer registries (ICRs), 2) evaluate the existing ICRs in Colombia with the designed instrument, 3) categorize the different registries according to their quality and prioritize efforts that will efficiently promote better registries with the limited resources available, and 4) determine the institution with the greatest likelihood of successfully establishing Colombia's second population-based cancer registry. In 1990 the National Cancer Institute of Colombia developed 13 institution-based cancer registries in different Colombian cities in order to promote the collection of data from a large group of cancer diagnostic and treatment centers. During the first half of 1997, this evaluation reviewed 12 registries; one of the original 13 no longer existed. All of the Colombian institutions (hospitals) that maintain institution-based cancer registries were included in the study. At each institution, a brief survey was administered to the hospital director, the registry coordinator, and the registrar (data manager). Researchers investigated the institutions by looking at six domains that are in standard use internationally. Within each domain, questions were developed and selected through the Delphi method. Each domain and each question were assigned weights through a consensus process. In most cases, two interviewers went to each site to collect the information. The university hospitals in Cali, Pereira, and Medellín had substantially higher scores, reflecting a good level of performance. Four of the 12 institutions had almost no cancer registry work going on. Five of the 12 hospital directors considered that the information provided by the cancer registries influenced their administrative decisions. Three of the registries had patient survival data. Four of the institutions allocated specific resources to operate their cancer registries; in the other 8 hospitals there was no clear budget allocation. Seven of the hospital directors could not identify five or more objectives of a cancer registry. Data management was usually poor and resources insufficient at most of the institutions. In summary, the cancer registry system in Colombia varies greatly from institution to institution. A few of the hospitals do a good job while others have neglected the registries. The high, identical total scores for Pereira and Medellín suggest they would be good locations to establish new population-based cancer registries similar to the existing one in Cali. However, the overall characteristics in Pereira may provide a more appropriate environment for the second registry, with Medellín as an alternative.

Colombia↗
PubMed1999

The methadone-maintained pregnancy.

Methadone treatment during pregnancy offers overwhelming advantages compared with the less acceptable option of medical detoxification or the unacceptably dangerous option of leaving heroin-addicted women dependent on street drugs. General agreement exists that pregnancy offers a unique opportunity to bring women into medical, obstetric, and drug treatment. Methadone maintenance in the setting of comprehensive service provision during pregnancy reduces maternal morbidity and mortality and promotes fetal stability and growth. With an accumulated experience of over 25 years, methadone maintenance has been shown to be an invaluable and often an essential ingredient in bettering the health of women during pregnancy, in improving the outcomes of those pregnancies, and in offering opiate-addicted women a chance to improve both their lives and the lives of their families.

Comprehensive Health Care↗
PubMed1999

[Methotrexate in therapy of gastrointestinal diseases].

This review is not only a comprehensive synopsis of the published data on methotrexate treatment for inflammatory bowel disease and primary biliary cirrhosis but gives also an overview about acting mechanisms, pharmacologic properties and limiting toxicities of low-dose methotrexate. Methotrexate and its polyglutamate analogues are structurally related to folic acid and inhibit many enzymes in the metabolic pathway of folic acid. Long-term low-dose methotrexate treatment (7.5-25 mg) inhibits production of thymidylate, purines, and methionine and leads to intracellulary accumulation of adenosin. These actions lead to inhibition of cellular proliferation, decreased formation of antibodies and reduced productions of inflammatory medicators. Several trials have demonstrated the efficacy of low-dose methotrexate therapy for certain indications as a promising new agent in the treatment of inflammatory bowel disease and primary biliary cirrhosis. However, several serious toxicities potentially limit its use.

Antimetabolites, Antineoplastic↗
PubMed1999

[Gastrointestinal complications of adult patients with cystic fibrosis].

Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population. The primary cellular defect, the reduced expression of the cystic fibrosis transmembrane conductance regulator (CFTR), leading to a chloride secretory defect, is present in all epithelial cells of endodermal and mesodermal origin and has been described in sweat glands, the airway epithelium and the small intestine, the colon and rectum, including the pancreas. In the upper GI-tract the most troublesome complaints and symptoms originating from the esophagus are peptic esophagitis or esophageal varices. In the small intestinal wall, the clinical expression of CF largely depends on the decreased secretion of fluid and chloride ions and the sticky mucous covering the enterocytes. Although CFTR expression in the colon is lower, the large intestine may be the site of several serious complications such as rectal prolapse, distal intestinal obstruction (DIOS), and intussusception. In recent years an increase in colonic strictures after the use of high-dose pancreatic enzymes, has been increasingly reported. CF has also been reported to be increasingly associated with a number of hepatic and/or biliary abnormalities, of which chronic cholestatic liver disease is by far the most relevant. Plugging of intrahepatic bile ducts with inspissated secretions is thought to play a major role in the pathogenesis. It has been estimated that about 15% of cystic fibrosis patients reveal serum liver enzyme abnormalities, but prevalence of liver involvement is likely to be higher. Oral bile acid therapy is promising, but its long-term benefits in terms of survival and prevention of major complications by liver cirrhosis remain to be established. Pancreatic dysfunction in cystic fibrosis (CF) is characterized by an insufficient pancreatic exocrine function. However, 10-15% of CF patients have pancreatic sufficiency and this status is genetically determined by one or two "mild" mutations in the CFTR.

Adult↗
PubMed1999

Setting up a breast cancer family history clinic.

Breast cancer causes around 21,000 deaths per year in the UK, the vast majority of these occurring in women aged over 50 years with no genetic predisposition to the disease. Screening and symptomatic services for these women, although by no means perfect or homogeneous, have gradually improved over the last 10 years and, perhaps as a result of this, together with increased use of adjuvant systemic therapy, mortality in this group has fallen. Despite this reassuring state of affairs, media interest in the disease and patients' perception of their risk of developing breast cancer have risen. Part of this is undoubtedly due to the new scientific developments in cancer genetics and, in particular, identification of the BRCA1 gene in 1994 and BRCA2 gene shortly afterwards. These genes are dominantly inherited with up to 80% penetrance; thus, women (and occasionally men) inherit these genes and have a high lifetime risk of developing breast cancer, usually at a younger age than average and possibly of a more aggressive phenotype. Unaffected family members can now be screened and, if they prove carriers, screening for early detection and prevention strategies such as bilateral prophylactic mastectomy can be offered. Because of the high risk of ovarian cancer in BRCA1 carriers, screening or prophylactic ovariectomy may also be considered.

Adult↗