Search PubMed⌕ Search

Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 163 records · Page 9Linked to original sources
PubMed1997

Duodenal secretion and fecal excretion of pancreatic elastase-1 in healthy humans and patients with chronic pancreatitis.

Fecal elastase-1 is a candidate for a sensitive noninvasive test detecting chronic pancreatitis. This prospective study enrolled 10 healthy male controls and 23 patients referred for tube testing of pancreatic function. It was designed (a) to correlate duodenal outputs and fecal concentrations of elastase-1 with duodenal outputs of amylase, lipase, trypsin, and chymotrypsin in the fed state (duodenal perfusion of a mixed liquid meal at 2.5 kcal/min for 150 min), (b) to compare the diagnostic accuracy of fecal elastase-1 and fecal chymotrypsin, and (c) to characterize the cyclical pattern of postprandial pancreatic secretion in healthy subjects and patients with chronic pancreatitis. Based on their enzyme responses to duodenal meal perfusion and imaging procedures, 12 patients were classified as having normal pancreatic function and 11 patients as having chronic pancreatitis. Duodenal enzyme outputs of elastase-1 were markedly lowered in chronic pancreatitis (p < 0.0001) and correlated well with the outputs of the other four enzymes (r > 0.71, p < 0.00001). Fecal concentrations of elastase-1 were also clearly reduced in chronic pancreatitis (p < 0.0001). Fecal chymotrypsin was less strongly associated with duodenal enzyme outputs (r = 0.33 to r = 0.587), whereas fecal elastase-1 correlated more precisely with the duodenal outputs of all five enzymes (r = 0.637 to r = 0.830, p < 0.00001). Sensitivity and specificity in the detection of chronic pancreatitis amounted to 0.64 and 0.95 for fecal elastase-1 and 0.27 and 0.95 for fecal chymotrypsin, respectively. In the postprandial state, peaks of enzyme secretion occurred at a frequency of about 1 peak/150 min. The amplitude but not the frequency of secretory peaks was markedly reduced in chronic pancreatitis (p < 0.01). We conclude that fecal elastase-1 clearly exceeds the sensitivity of fecal chymotrypsin in the diagnosis of chronic pancreatitis but does not reliably detect all cases with mild to moderate disease. The pattern of postprandial pancreatic secretion is cyclical, even with minimal secretory outputs in chronic pancreatitis.

Adult↗
PubMed1997

National rates and regional differences in sensitization to allergens of the standard series. Population-adjusted frequencies of sensitization (PAFS) in 40,000 patients from a multicenter study (IVDK).

Sensitization rates to contact allergens vary between centers and are influenced by sex and age. Eliminating the latter 2 factors by standardization of data by age and sex, the present analysis addresses possible differences between centers remaining after elimination of these confounders, and analyzes other factors which might influence rates, e.g., the MOAHL index. Overall standardized rates were well within the range reported in previous studies and may be regarded as representing the rates of the "patch test population" in Central Europe (e.g., nickel sulfate 12.9%, fragrance mix 10.5%, balsam of Peru 7.3%, thimerosal 5.6%). For this analysis, data of those departments which contributed more than 2000 patients, or of those with extreme proportions concerning sex, age and occupational cases were selected. Patients from these 10 departments differed considerably with regard to the items of the MOAHL index and with regard to standardized rates. The items of the MOAHL index proved to be suitable for describing different patch test populations and for explaining some differences between centers. Only 'atopic dermatitis' seems to have little influence on (standardized) rates. Face dermatitis is not yet represented in the MOAHL index, but should be included, together with age > 40 years, in an extended index (acronym: MOAHLFA). Regional allergen exposure (with striking differences between East Germany, West Germany and, to a lesser extent, Austria) seems to have a great influence on the sensitization pattern observed in a department. In addition, sociological factors may influence sensitization rates, which is exemplified by high rates of nickel allergy in a socially defined subgroup. Future studies should focus on these factors, as well as on factors concerning patch test practices and quality control.

Adult↗
PubMed1997

Negative protein 1, which is required for function of the chicken lysozyme gene silencer in conjunction with hormone receptors, is identical to the multivalent zinc finger repressor CTCF.

The transcriptional repressor negative protein 1 (NeP1) binds specifically to the F1 element of the chicken lysozyme gene silencer and mediates synergistic repression by v-ERBA, thyroid hormone receptor, or retinoic acid receptor. Another protein, CCCTC-binding factor (CTCF), specifically binds to 50-bp-long sequences that contain repetitive CCCTC elements in the vicinity of vertebrate c-myc genes. Previously cloned chicken, mouse, and human CTCF cDNAs encode a highly conserved 11-Zn-finger protein. Here, NeP1 was purified and DNA bases critical for NeP1-F1 interaction were determined. NeP1 is found to bind a 50-bp stretch of nucleotides without any obvious sequence similarity to known CTCF binding sequences. Despite this remarkable difference, these two proteins are identical. They have the same molecular weight, and NeP1 contains peptide sequences which are identical to sequences in CTCF. Moreover, NeP1 and CTCF specifically recognize each other's binding DNA sequence and induce identical conformational alterations in the F1 DNA. Therefore, we propose to replace the name NeP1 with CTCF. To analyze the puzzling sequence divergence in CTCF binding sites, we studied the DNA binding of 12 CTCF deletions with serially truncated Zn fingers. While fingers 4 to 11 are indispensable for CTCF binding to the human c-myc P2 promoter site A, a completely different combination of fingers, namely, 1 to 8 or 5 to 11, was sufficient to bind the lysozyme silencer site F1. Thus, CTCF is a true multivalent factor with multiple repressive functions and multiple sequence specificities.

Animals↗
PubMed1997

Pathways of Fos expression in locus ceruleus, dorsal vagal complex, and PVN in response to intestinal lipid.

Exogenous cholecystokinin (CCK) injected peripherally mimics effects of lipid entering the intestine on food intake and gastric motility via vagal afferents and induces c-fos expression in the locus ceruleus complex (LCC), nucleus of the solitary tract (NTS), area postrema (AP), and paraventricular nucleus (PVN). However, the role of peripheral endogenous CCK in induction of c-fos expression in the brain at ingestion of nutrients is controversial. In awake rats, intraduodenal lipid infusion markedly increased Fos protein-like immunoreactivity (FLI) in these brain nuclei. Perivagal capsaicin pretreatment reduced the increase of FLI in the LCC, NTS, and PVN by 66-86% and in the AP by 46%. The CCK-A receptor antagonist MK-329 (0.1 mg/kg i.p.) diminished the FLI increase in LC, NTS, AP, and PVN by 39-100%; the CCK-B receptor antagonist L-365,260 reduced the increased FLI in the AP by 54%. After capsaicin pretreatment, both CCK antagonists had additional inhibitory effects only on FLI in the AP. These findings suggest that entry of lipid into the intestine activates c-fos in the LCC, NTS, and PVN predominantly via CCK-A receptors on vagal afferents and in the AP via vagal and nonvagal pathways, as well as CCK-B and CCK-A receptors.

Animals↗
PubMed1997

Small bowel lengthening by mechanical distraction.

To evaluate whether the small bowel can be distracted by mechanical stress in analogy to limb lengthening by osteodistraction, a gut-lengthening apparatus was designed. This distractor was placed at the antimesenterical side of a defined jejunum segment in rabbits. Distraction was performed by 1 mm lengthening of the distractor once daily using extracorporal screws. An effective gut lengthening was achieved of 9.9 +/- 0.5 mm (approximately 100%) within 3 weeks. Treated animals gained weight and remained in good general condition. Fasting plasma levels of cholecystokinin, neurotensin, glucagon-like peptide-1, gastric inhibitory polypeptide, and insulin remained unaffected. Postoperative factor XIII levels were significantly diminished and gastrin was elevated during gut distraction. DNA and protein concentrations in the mucosa of the distracted gut segments corresponded to controls. Mucosal lactase and saccharase activities were reduced. In the distracted bowel segments total tunica muscularis thickness was more than doubled due to muscle cell hypertrophy. In distracted segments villous width was increased. Detection of proliferating mucosal crypt cells utilizing BrdUrd labeling revealed no effects. In conclusion, small gut lengthening by mechanical distraction is possible without major changes in gut morphology. This technique may hint a novel experimental approach for the treatment of short bowel syndrome.

Animals↗
PubMed1997

Differential effects of subcutaneous GLP-1 on gastric emptying, antroduodenal motility, and pancreatic function in men.

In this study of eight healthy male volunteers, we investigated the effects of graded doses of subcutaneous glucagon like peptide-1(7-36)amide (GLP-1) on: 1) the gastric emptying pattern of a mixed liquid meal (300 kcal); 2) pancreatic enzyme secretion; 3) antroduodenal motility; and 4) the glycemic response as well as releases of insulin, C-peptide, and glucagon. GLP-1, 0.125 nmol/kg, or 0.25 nmol/kg, or placebo was injected subcutaneously 5 min before meal ingestion. Subcutaneous GLP-1 dose-dependently prolonged the lag period (i.e., the time to reach maximal velocity of gastric emptying) by 46.2% (low dose) and 93.7% (high dose) (p < .05) but left unaltered maximal emptying velocity, total emptying time, and exponential emptying rate. With and without GLP-1, a fed motor pattern was induced by the meal and was terminated by an antral phase III when 98% of the meal had emptied. In parallel to the prolonged lag period, GLP-1 dose-dependently inhibited antral and duodenal motility and coordinated antroduodenal contractions by > 50% (low dose) and > 70% (high dose) (p < .05). GLP-1 initially reduced and thereafter transiently stimulated pancreatic enzyme secretion. This pattern correlated with the prolonged lag period and mirrored the delayed gastric emptying. GLP-1 retarded and diminished the postprandial glucose peak and reduced the total plasma glucose response by 46.6% (low dose) and by 59.4% (high dose) (p < .05). Both doses of GLP-1 delayed the postprandial insulin peak, enhanced total insulin release, and diminished postprandial responses of glucagon and pancreatic polypeptide. The duration of the lag period strongly correlated with the timing of postprandial glucose and insulin peaks (p < .001). The initial delay of gastric emptying, the enhancement of postprandial insulin release, and the inhibition of postprandial glucagon release were independent determinants (p < .01-.05) of the postprandial glucose response after subcutaneous administration of GLP-1.

Adult↗
PubMed1997

[Improving the human iodine supply by iodination of swine feed].

Germany and several other countries are areas of severe iodine deficiency. In addition to iodized salt additional strategies to fight iodine deficiency exist. A promising possibility is the supplementation of feed with iodine, in order to increase its content in food of animal origin. In a feeding experiment 24 male castrated and female piglets of the cross breed Deutsche Landrasse x Pietrain were fed a high iodine supplemented diet. At a body weight of 100 kg the animals were slaughtered and the effect of the iodine supplementation on iodine content in the organs was studied. Animals receiving 30 mg iodine/kg feed showed significantly higher iodine contents in muscle, heart, kidney, liver, serum, fat and in the thyroidea than animals receiving no iodine supplementation. The iodine content in muscle and organs increased by a factor three to seven. Concerning meat quality and other slaughter parameters there was no difference between the two groups. This demonstrates that this strategy is in addition to iodized salt a possibility to reduce iodine deficiency.

Abattoirs↗
PubMed1996

Microinfusion of corticotropin-releasing factor into the locus coeruleus/subcoeruleus nuclei inhibits gastric acid secretion via spinal pathways in the rat.

Brain corticotropin-releasing factor (CRF) is involved in stress-related alterations of gastric acid secretion. CRF in the locus coeruleus has been shown to induce anxiogenic behavioral responses and to mimic stress-induced alterations of colonic motor function. Whether the locus coeruleus/subcoeruleus nucleus (LC/SC) is a site of action for CRF to alter gastric acid secretion was investigated in urethane-anesthetized gastric fistula rats. In sham-operated animals, CRF (126-420 pmol) microinfused bilaterally into the LC/SC induced a dose-dependent inhibition of pentagastrin (PG)-stimulated gastric acid secretion of 60-81% within the first hour after microinjection. At the 420 pmol dose, this inhibitory effect of CRF into the LC/SC lasted throughout the whole observation period of 120 min. After bilateral vagotomy, basal and PG-stimulated gastric acid secretion at microinjection of vehicle was reduced. Nevertheless, microinfusion of 420 pmol CRF into the LC/SC still inhibited significantly gastric acid secretion by 62.1%. In contrast, in spinal cord transected animals bilateral microinfusion of 420 pmol CRF into the LC/SC did not reduce PG-stimulated gastric acid secretion. These data indicate that CRF acts in the LC/SC to induce a long lasting inhibition of peripherally stimulated gastric acid secretion via spinal pathways. These findings suggest a possible role of the LC/SC in the regulation of gastric secretion and of endogenous CRF at these sites in the stress-related inhibition of gastric acid secretion by affecting autonomic nervous system activity.

Animals↗
PubMed1996

DNA bending by the silencer protein NeP1 is modulated by TR and RXR.

NeP1 binds to the F1 silencer element of the chicken lysozyme gene and, in the presence of TR, v-ERBA or RAR, synergistically represses transcriptional activity. This repression involves a silencing mechanism acting independently of the relative promoter position. Here we show that NeP1 alone can induce a significant directed bend on DNA. The chicken homologue of human NeP1, CTCF, shows identical binding and bending properties. In contrast, the isolated DNA binding domain of CTCF efficiently binds DNA, but fails to confer bending. Similarly, the TR-RXR hetero- or homodimer, binding adjacent to NeP1 at the F2 sequence, do not show significant DNA bending. The binding of the T3 ligand to TR changes neither the magnitude nor the direction of the NeP1 induced bend. However, when all factors are bound simultaneously as a quaternary complex, the TR-RXR heterodimer changes the location of the bend center, the flexure angle and the bending direction.

Animals↗
PubMed1996

Improved outcome in adult B-cell acute lymphoblastic leukemia.

A total of 68 adult patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated in three consecutive adult multicenter ALL studies. The diagnosis of B-ALL was confirmed by L3 morphology and/or by surface immunoglobulin (Slg) expression with > 25% blast cell infiltration in the bone marrow (BM). They were characterized by male predominance (78%) and a median age of 34 years (15 to 65 y) with only 9% adolescents (15 to 20 y), but 28% elderly patients (50 to 65 y). The patients received either a conventional (N = 9) ALL treatment regimen (ALL study 01/81) or protocols adapted from childhood B-ALL with six short, intensive 5-day cycles, alternately A and B. In study B-NHL83 (N = 24) cycle A consisted of fractionated doses of cyclophosphamide 200 mg/m2 for 5 days, intermediate-dose methotrexate (IdM) 500 mg/m2 (24 hours), in addition to cytarabine (AraC), teniposide (VM26) and prednisone. Cycle B was similar except that AraC and VM26 were replaced by doxorubicin. Major changes in study B-NHL86 (N = 35) were replacement of cyclophosphamide by ifosphamide 800 mg/m2 for 5 days, an increase of IdM to high-dose, 1,500 mg/m2 (HdM) and the addition of vincristine. A cytoreductive pretreatment with cyclophosphamide 200 mg/m2, and prednisone 60 mg/m2, each for 5 days was recommended in study B-NHL83 for patients with high white blood cell (WBC) count (> 2,500/m2) or large tumor burden and was obligatory for all patients in study B-NHL86. Central nervous system (CNS) prophylaxis/treatment consisted of intrathecal methotrexate (MTX) therapy, later extended to the triple combination of MTX, AraC, and dexamethasone, and a CNS irradiation (24 Gy) after the second cycle. Compared with the ALL 01/81 study where all the patients died, results obtained with the pediatric protocols B-NHL83 and B-NHL86 were greatly improved. The complete remission (CR) rates increased from 44% to 63% and 74%, the probability of leukemia free survival (LFS) from 0% to 50% and 71% (P = .04), and the overall survival rates from 0% to 49% and 51% (P = .001). Toxicity, mostly hematotoxicity and mucositis, was severe but manageable. In both studies B-NHL83 and B-NHL86, almost all relapses occurred within 1 year. The time to relapse was different for BM, 92 days, and for isolated CNS and combined BM and CNS relapses, 190 days (P = .08). The overall CNS relapses changed from 50% to 57% and 17%, most probably attributable to the high-dose MTX and the triple intrathecal therapy. LFS in studies B-NHL83 and B-NHL86 was significantly influenced by the initial WBC count < or > 50,000/microL, LFS 71% versus 29% (P = .003) and hemoglobin value > or < 8 g/dL, LFS 67% versus 27% (P = .02). Initial CNS involvement had no adverse impact on the outcome. Elderly B-ALL patients (> 50 years) also benefited from this treatment with a CR rate of 56% and a LFS of 56%. It is concluded that this short intensive therapy with six cycles is effective in adult B-ALL. HdM and fractionated higher doses of cyclophosphamide or ifosphamide seem the two major components of treatment.

Adolescent↗
PubMed1996

Gastric emptying and release of incretin hormones after glucose ingestion in humans.

This study investigated in eight healthy male volunteers (a) the gastric emptying pattern of 50 and 100 grams of glucose; (b) its relation to the phase of interdigestive motility (phase I or II) existing when glucose was ingested; and (c) the interplay between gastric emptying or duodenal perfusion of glucose (1.1 and 2.2 kcal/min; identical total glucose loads as orally given) and release of glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1(7-36)amide (GLP-1), C-peptide, insulin, and plasma glucose. The phase of interdigestive motility existing at the time of glucose ingestion did not affect gastric emptying or any metabolic parameter. Gastric emptying of glucose displayed a power exponential pattern with a short initial lag period. Duodenal delivery of glucose was not constant but exponentially declined over time. Increasing the glucose load reduced the rate of gastric emptying by 27.5% (P < 0.05) but increased the fractional duodenal delivery of glucose. Both glucose loads induced a fed motor pattern which was terminated by an antral phase III when approximately 95% of the meal had emptied. Plasma GLP-1 rose from basal levels of approximately 1 pmol/liter of peaks of 3.2 +/- 0.6 pmol/liter with 50 grams of glucose and of 7.2 +/- 1.6 pmol/liter with 100 grams of glucose. These peaks occurred 20 min after glucose intake irrespective of the load. A duodenal delivery of glucose exceeding 1.4 kcal/min was required to maintain GLP-1 release in contrast to ongoing GIP release with negligibly low emptying of glucose. Oral administration of glucose yielded higher GLP-1 and insulin releases but an equal GIP release compared with the isocaloric duodenal perfusion. We conclude that (a) gastric emptying of glucose displays a power exponential pattern with duodenal delivery exponentially declining over time and (b) a threshold rate of gastric emptying of glucose must be exceeded to release GLP-1, whereas GIP release is not controlled by gastric emptying.

Adult↗
PubMed1996

ICAM-1 expression and low-molecular-weight G-protein activation of human bronchial epithelial cells (A549) infected with RSV.

The airway epithelial cell of the lower respiratory tract is the primary host target cell for respiratory syncytial virus (RSV) infection. To estimate whether infected epithelial cells contribute to the inflammatory host response observed during the acute infection phase we analyzed the cell surface expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on human bronchial epithelial cells (A549) following RSV infection and cytokine priming. The epithelial cells constitutively expressed ICAM-1. The ICAM-1 surface expression was significantly up-regulated up to 72 h post RSV infection. In addition, cytokine priming with tumor necrosis factor alpha (TNF-alpha), interferon-gammma (IFN-gamma), or interleukin-1 alpha/beta (IL-1alpha/beta) induced an enhanced ICAM-1 expression on noninfected as well as on RSV-infected epithelial cells. As early as 24 h post RSV infection and cytokine priming, respectively, the maximum of ICAM-1-expressing cells was observed. In contrast, the maximal ICAM-1 up-regulation per cell was measured 24 h later, e.g., after 48 h of culture. Cytokine priming with IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte colony-stimulating factor (G-CSF) did not lead to a significant increase of ICAM-1 expression either on RSV-infected or on noninfected A549 cells up to 72 h of culture time. Performed signal transduction experiments, e.g. [alpha-32P]GTP-binding blot analysis, revealed that low-molecular-weight GTP-binding proteins possess an enhanced GTP-binding capacity in RSV-infected A549 cells.

Bronchi↗
PubMed1996

Medical treatment of metastasizing carcinoid tumors.

Long-acting somatostatin analogs, such as octreotide, comprise the therapeutic modality of choice for the symptomatic relief of flush and diarrhea in patients with carcinoid syndrome. The sequelae of gastric acid hypersecretion in patients with gastrin-producing duodenal carcinoids (gastrinoma) are perfectly controlled by proton pump inhibitors. Antiproliferative medical strategies to control the growth of metastatic carcinoid tumors include long-acting somatostatin analogs, interferon alpha, and the combination of the two. However, the success rate is less than 50%, and it is questionable whether true tumor regression can be expected. Controlled prospective studies are mandatory to address the question whether interferon or somatostatin analogs or the combination of the two should be used as first-line medical strategies and if hepatic artery embolization in patients with liver metastases should be performed before beginning medical therapy. Chemotherapy, including etoposide and cisplatin, has been shown to be effective only for purely differentiated neuroendocrine carcinomas and not for slowly growing carcinoids.

Carcinoid Tumor↗
PubMed1996

Reactivated fulminant hepatitis B virus replication after bone marrow transplantation: clinical course and possible treatment with ganciclovir.

A female chronic hepatitis B virus carrier (HBV-DNA negative) suffered from simultaneous hepatitis B virus and cytomegalovirus reactivation after in vivo T cell depletion preceding transplantation of an in vitro T cell depleted marrow graft for treatment of acute leukaemia. Interstitial pneumonia developing after bone marrow transplantation was successfully treated with ganciclovir (day 13 until day 46). The initially unnoticed extensive hepatitis B virus replication finally led to clinical hepatitis (day 85) and liver failure (day 96). Liver transplantation was performed, but the patient died from septicaemia. Retrospective analysis of hepatitis B virus DNA revealed that the HBV replication started immediately after T cell depletion and was completely suppressed during ganciclovir administration. Screening for HBV-DNA seems to be mandatory in comparable cases, and antiviral chemotherapy should be seriously considered.

Adult↗
PubMed1996

Gastrointestinal endocrine tumours: medical management.

With the introduction of longer-acting somatostatin analogues symptomatic relief is easy to achieve in patients with functionally active endocrine tumours and will be further facilitated by still longer-acting formulations. The consequences of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome can be prevented by all proton-pump inhibitors currently on the market. Despite the various antiproliferative strategies that have been offered to patients with metastatic disease, available data are controversial and, more importantly, are supported by few prospective and controlled studies. Most experts agree that surgery with curative extirpation of the primary in the absence of metastases and tumour debulking in metastatic disease should be intended wherever possible. Controversy concerns residual disease. According to our view, any further antiproliferative strategy should consider the growth characteristics and biology of a given tumour (Figure 4). In the case of rapid progression, chemotherapy should be offered if tumours originate from the pancreas or reveal an undifferentiated histology. In contrast, chemotherapy should not be offered to patients with well-differentiated non-functional or functional tumours (carcinoid syndrome) arising from the intestine. The same applies for patients with tumours with no or only slow growth within an given observation period of 3-12 months. These patients should be treated only symptomatically. Patients with tumours of slow progression might favourably respond to long-acting somatostatin analogues. We start with octreotide and offer patients not responding to octreotide monotherapy additional IFN alpha. If further tumour progression takes place, hepatic artery embolization is the next step (Figure 5) followed by chemotherapy, the latter in patients with tumours of pancreatic origin only. This strategy recognizes the severity of side-effects of the different therapeutic modalities and starts with octreotide because of its very few side-effects. Other groups start with chemoembolization followed by octreotide, alpha-interferon or its combinations (Ahlman et al, 1996). Ongoing studies will, it is hoped, answer the question of the ideal sequence of therapeutic strategies. Every available patient with metastasised gastrointestinal endocrine tumours should be included in one of the ongoing European multicentre trials.

Antineoplastic Agents↗