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Biomedical subjects

G Weiss

Publications and source records attributed to G Weiss.

At least 127 records · Page 7Linked to original sources
PubMed1998

[Manufacture and in vitro characterization of a new fluid theophylline sustained-release form. Sachets with microcapsules for administration in a drinkable sustained-release suspension].

The administration of currently available theophylline (CAS 58-55-9) sustained release preparations with high drug doses (hard capsules, tablets) presents difficulties for certain patient groups as children and elderly, due to the large geometry of these dosage forms. Therefore, a suspension for easy administration based on the novel Liquitard technology was developed using theophylline microcapsules. This paper describes the manufacturing procedure of the new dosage form and its in vitro release characteristics as a function of various parameters. During manufacturing, the suspension-forming excipients are first granulated and then filled into sachets together with the microcapsules. The sustained release suspension is prepared by the patient himself immediately before administration. The in vitro release of theophylline from the dosage form is neither affected by the suspension-forming excipients nor by the drug amount. This allows for the manufacture of sachets with different drug strength maintaining the same qualitative composition. Furthermore, the in vitro release is independent of pH, osmolality, agitation and of the addition of surfactants and native bile to the dissolution medium. The new dosage form thus meets the current EC-guidelines for oral sustained release dosage forms. The in vitro limits of the dissolution testing were verified on the basis of the bioequivalence of the batches at the upper and lower specification limits.

Anti-Asthmatic Agents↗
PubMed1998

[Pharmacokinetics of a new fluid theophylline sustained-release drug form. Microcapsules in a sachet].

A new sustained release theophylline (CAS 58-55-9) formulation was especially designed for the elderly and children. Microcapsules of theophylline, administered as a suspension in water, proved to be a suitable dosage form for a clientele with impaired or difficult deglutition. Pharmacokinetic characteristics of 2 batches at the lower (T1) and upper (T2) in vitro dissolution specification range of this new formulation and a pellet formulation (R) as a comparator were evaluated in an open, randomised, 3-way, multiple dose, crossover study with an asymmetric dosage regimen of 400 mg and 200 mg theophylline. Smooth and safe plasma concentrations with a high and long-lasting plateau were achieved with this new formulation. Plateau times which are independent of the asymmetric dosage regimen ranged from 16.4 h (T1) to 13.8 h (T2) and could therefore cover sufficient time of the dosage interval. Maximum plasma levels of 9.6 micrograms/ml and 10.0 micrograms/ml were attained 6.6 and 6.1 h after dosing of T1 and T2, coinciding perfectly with the time of the critical morning dip at 2-6 a.m. With a nocturnal excess of 15.5% (T1) and 17.9% (T2), this circadian-tailored asymmetric dosage regimen proved to take into account the chronopathology of asthma and the chronopharmacokinetics of theophylline sustained release preparations. Bioequivalence of all 3 formulations compared with each other with regard to rate (Cmax ss) and extent (AUCss) of absorption could be established for the 2 batches at the upper and lower in vitro specification range and for both batches of the new formulation compared to the reference. All in all, the safety and efficacy of this new liquid sustained release theophylline preparation could be established. Furthermore, in vitro specifications were justified according to current EC guidelines.

Aged↗
PubMed1998

Modulation of iron metabolism in monocytic THP-1 cells and cultured human monocytes by the acute-phase protein alpha1-antitrypsin.

The reticuloendothelial (RE) system plays an important role in the changes in iron metabolism associated with the anemia of chronic disease (ACD). We previously reported that the acute-phase protein alpha1-antitrypsin (alpha1-AT) reduced growth and proliferation in cells of the erythroid cell system by interfering with transferrin (Tf)-mediated iron uptake. The regulation of iron metabolism in cells of the RE system is distinctly different from that in other cell systems; moreover, monocytes and macrophages play an essential part in the regulation of the production and clearance of alpha1-AT. In the present study we examined the effect of alpha1-AT on cells of the monocyte-macrophage lineage. Alpha1-AT completely inhibited the binding of Tf to its receptor (TfR) on THP-1 human myelomonocytic cells and cultured human monocytes. Results of equilibrium saturation and kinetic studies indicated that this inhibition was competitive. No other acute-phase protein demonstrated the same inhibitory potency. Furthermore, alpha1-AT almost completely prevented internalization of the Tf-TfR complex in a dose-dependent manner. Interestingly, and in sharp contrast to the results of our studies with erythroid cells, this inhibition did not reduce the growth and proliferation of THP-1 cells. Furthermore, alpha1-AT significantly increased the concentration of intracellular ferritin in THP-1 cells and monocytes, whereas the number of TfR remained unchanged. Because alpha1-AT showed no enhancing effect on ferritin transcription and translation, we believe that an as-yet unidentified posttranslational mechanism may be responsible for this phenomenon. In addition, our results indicate that the increase in ferritin concentration caused by alpha1-AT is mediated independently of iron supply, as has previously been shown for several proinflammatory cytokines. These data provide further evidence that alpha1-AT is a mediator of the alterations in iron metabolism characteristic of ACD.

Cell Division↗
PubMed1998

A Phase I and pharmacological study of the glutamine antagonist acivicin with the amino acid solution aminosyn in patients with advanced solid malignancies.

Acivicin is a glutamine analogue antimetabolite that inhibits several glutamate-dependent synthetic enzymes. Previous studies of this agent administered on a 72-h continuous i.v. infusion schedule every 3 weeks demonstrated a high rate of severe, albeit reversible, central nervous system (CNS) toxicity at the 30 mg/m2/day dose level. Animal studies have shown that the CNS toxicity of acivicin can be prevented by a concomitant infusion of amino acids postulated to block drug uptake in the CNS by a saturable transport system that is common to endogenous amino acids. This study evaluated the feasibility of escalating acivicin doses in cancer patients by administering acivicin with a concomitant 96-h i.v. infusion of a mixture of 16 amino acids (Aminosyn, 10%). Twenty-three patients with advanced malignancies were treated with acivicin on a 72-h continuous infusion schedule at doses ranging from 25 to 60 mg/m2/day every 3 weeks. Reversible, dose-limiting CNS toxicity, characterized by lethargy, confusion, and decreased mental status, occurred in the two patients enrolled at the 60 mg/m2/day dose level, precluding further dose escalation. The maximum tolerated dose (MTD) and recommended dose for additional evaluation of acivicin on this schedule is 50 mg/m2/day. Other toxicities observed were dose-related neutropenia that was grade 4 in four patients (four courses), complicated with fever in three of those patients, and grade 3-4 thrombocytopenia in three patients (three courses). Pharmacokinetics studies performed in 15 patients revealed that the acivicin plasma Css increased from 0.44 microg/ml (range, 0.28-0.59 microg/ml) at the 25 mg/m2/day to 1.06 microg/ml (0.64-1.5 microg/ml) at the 50 mg/m2/dose level. Acivicin Css at the MTD was not significantly higher than previously reported values with single-agent acivicin on the same schedule of administration at the MTD of 25 mg/m2/day dose level (0.60 microg/ml; range, 0.43-0.81 microg/ml). Neurotoxicity did not correlate with acivicin Css, but relationships between exposure to acivicin and the occurrence of both neutropenia and thrombocytopenia were well described by a sigmoidal Emax model. This trial demonstrated that concomitant infusions of amino acid can prevent acivicin-induced CNS toxicity, which allows the dose of acivicin to be escalated 2-fold above previously tolerable doses; however, this effect did not translate in a significant increment in acivicin Css.

Adult↗
PubMed1998

[Bronchoscopically controlled percutaneous puncture tracheotomy].

With extending duration of translaryngeal intubation the rate of lesions in the oral cavity, pharynx and trachea caused by the orotracheal tube increase. To prevent these complications ventilated patients receive early tracheostomy. PDT is an alternative procedure to the conventional, surgically performed tracheostomy. We performed 60 dilatational tracheostomies using the Ciaglia percutaneous tracheostomy set (W. Cook-Critical Care, Bjaeverskov). Complication rate was 17% due to minor bleeding (n = 7), subcutaneous emphysema (n = 2) and fracture of one tracheal cartilage ring (n = 1). This rate is equivalent to that of surgical procedure. Advantage of PDT is that it can be performed by intensive care doctors without a specific surgical background. Further follow up after removal of the tracheal cannula was uneventful. Tracheal stenosis requiring intervention are rare. The remaining scar after PDT is significantly smaller than after conventional tracheostomy.

Adult↗
PubMed1998

[Indications for urgent carotid reconstruction].

Diagnostic methods and indications for carotid surgery must be coordinated with the individual carotid-related stroke risk. The indication for urgent carotid reconstruction within a few days after the initial event should always be evaluated when a clinical and/or morphological unstable and therefore risky carotid lesion is present and the 30-day stroke risk without surgery is > 5%. Patients with high-grade symptomatic carotid stenoses fulfill these criteria as do patients with recurrent carotid-related TIA, patients with hemipheric TIA, patients with symptomatic carotid stenosis and contralateral carotid occlusion and patients after a non-disabling carotid-related stroke. The clinical significance of sonographic carotid plaque criteria and intracranial emboli detected by TCD must be further evaluated in prospective studies.

Carotid Stenosis↗
PubMed1997

Mechanism of suppression of macrophage nitric oxide release by IL-13: influence of the macrophage population.

IL-13 is a cytokine produced by T lymphocytes, mast cells, basophils, and certain B cell lines that up-regulates or inhibits various macrophage functions. In the present study we analyzed the mechanisms of suppression of nitric oxide (NO) release by IL-13 in the macrophage cell line J774A.1 and in thioglycolate-elicited mouse peritoneal macrophages. In both cell types efficient reduction (>80%) of NO production required treatment of the macrophages with IL-13 for at least 7 h before stimulation with IFN-gamma and LPS. In J774A.1 cells, increasing concentrations of IFN-gamma partially antagonized the suppression mediated by IL-13, whereas in peritoneal macrophages, the inhibitory effect of IL-13 was largely independent of the concentrations of IFN-gamma and LPS. In J774A.1 cells, IL-13 strongly reduced both the mRNA and protein levels of inducible nitric oxide synthase (iNOS, NOS-2), as determined by Northern blot analysis and immunoprecipitation. In peritoneal macrophages, in contrast, IL-13 decreased iNOS protein and enzyme activities after 8 to 48 h of stimulation, without altering the expression of iNOS mRNA. Pulse labeling with [35S]methionine revealed that IL-13 caused a 4.7-fold reduction of the de novo synthesis of iNOS protein in these cells. These data demonstrate for the first time that IL-13 is capable of regulating iNOS at both the mRNA and translational levels and underline the important influence of the macrophage population when studying mechanisms of cytokine functions.

Animals↗
PubMed1997

A coalescent approach to the polymerase chain reaction.

A versatile algorithm is developed to model PCR on a computer. The method is based on a modification of the coalescent process and provides a general framework to analyse data from PCR. It allows for incorporation of the dynamics of the replication process as described in terms of the number of starting template molecules and cycle-dependent PCR efficiency. The simulation method generates, as a first step, the genealogy of a set of sequences sampled from a final PCR product. In a second step a mutation process is superimposed and the resulting data set is analysed. The efficiency of our algorithm enables us to get reliable approximations of various sample distributions. We demonstrate the relevance of our method with two applications: maximum likelihood estimation of the error rate in PCR and a test of homogeneity of the template.

Algorithms↗
PubMed1997

Modulation of transferrin receptor expression by dexrazoxane (ICRF-187) via activation of iron regulatory protein.

Dexrazoxane (ICRF-187) has recently been demonstrated to reduce cardiac toxicity induced by chemotherapy with anthracyclines, although the reason for this phenomenon has remained obscure thus far. In order to investigate whether ICRF-187 might exert its effects by modulating iron metabolism, we studied the drug's potential to influence the maintenance of iron homeostasis in two human cell lines. We demonstrate that ICRF-187 enhanced the binding affinity of iron regulatory protein (IRP), the central regulatory factor for posttranscriptional iron regulation, to RNA stem loop structures, called iron responsive elements (IRE), in THP-1 myelomonocytic as well as K562 erythroleukemic cells. Increased IRE/IRP interaction was paralleled by an elevation of transferrin receptor (trf-rec) mRNA levels which, according to the well-established mechanism of posttranscriptional iron regulation, was likely due to stabilisation of trf-rec mRNA by IRP. Subsequently, ICRF-187 treatment of cells increased trf-rec surface expression and enhanced cellular iron uptake. All these events, i.e. IRP activation, stabilisation of trf-rec mRNA and increased surface expression of the protein in response to ICRF-187, follow a dose-response relationship. Increased cellular uptake and sequestration of iron in response to ICRF-187 may contribute to the protective activity of ICRF-187 by reducing the iron-anthracycline complex and iron-catalysed generation of hydroxyl radicals via the Haber-Weiss reaction.

Antineoplastic Agents↗
PubMed1997

Regulation of cellular iron metabolism by erythropoietin: activation of iron-regulatory protein and upregulation of transferrin receptor expression in erythroid cells.

Erythropoietin (Epo) is the central regulator of red blood cell production and acts primarily by inducing proliferation and differentiation of erythroid progenitor cells. Because a sufficient supply of iron is a prerequisite for erythroid proliferation and hemoglobin synthesis, we have investigated whether Epo can regulate cellular iron metabolism. We present here a novel biologic function of Epo, namely as a potential modulator of cellular iron homeostasis. We show that, in human (K562) and murine erythroleukemic cells (MEL), Epo enhances the binding affinity of iron-regulatory protein (IRP)-1, the central regulator of cellular iron metabolism, to specific RNA stem-loop structures, known as iron-responsive elements (IREs). Activation of IRP-1 by Epo is associated with a marked increase in transferrin receptor (trf-rec) mRNA levels in K562 and MEL, enhanced cell surface expression of trf-recs, and increased uptake of iron into cells. These findings are in agreement with the well-established mechanism whereby high-affinity binding of IRPs to IREs stabilizes trf-rec mRNA by protecting it from degradation by a specific RNase. The effects of Epo on IRE-binding of IRPs were not observed in human myelomonocytic cells (THP-1), which indicates that this response to Epo is not a general mechanism observed in all cells but is likely to be erythroid-specific. Our results provide evidence for a direct functional connection between Epo biology and iron metabolism by which Epo increases iron uptake into erythroid progenitor cells via posttranscriptional induction of trf-rec expression. Our data suggest that sequential administration of Epo and iron might improve the response to Epo therapy in some anemias.

Animals↗
PubMed1997

Pathways for the regulation of macrophage iron metabolism by the anti-inflammatory cytokines IL-4 and IL-13.

Macrophage effector functions are influenced by their iron status and by shifts in the balance between type 1 Th1 and Th2 cells. To elucidate the influence of the Th2 cytokines IL-4 and IL-13 on macrophage iron metabolism, we investigated activated primary mouse macrophages and the murine macrophage cell line J774. Stimulation of J774 cells and primary macrophages with IFN-gamma/LPS activates the RNA binding affinities of iron regulatory protein-1 (IRP-1) and IRP-2 for iron-responsive elements, leading to translational repression of the iron storage protein ferritin. Activation of IRP-1 and IRP-2 is caused by increased formation of nitric oxide (NO) via stimulation of the inducible NO synthase by IFN-gamma/LPS. Treatment of macrophages with IL-4 and/or IL-13 before stimulation with IFN-gamma/LPS suppresses NO formation and IRP activation, with concomitantly enhanced ferritin synthesis despite a small reduction in ferritin heavy chain mRNA levels. The mRNA levels for the membrane receptor for iron uptake, transferrin receptor (TfR), decrease following stimulation with IFN-gamma/LPS, although IRP-mediated stabilization of the TfR mRNA would have been expected. This as yet unidentified proximal inhibitory signal by IFN-gamma/LPS is antagonized by IL-4 and/or IL-13, which leads to increased TfR mRNA expression in an IRP-independent manner. Thus, IL-4 and IL-13 regulate the iron metabolism of activated macrophages by at least two different pathways: first, by opposing NO-mediated IRP activation, thereby increasing ferritin translation; and second, by an IRP-independent augmentation of TfR mRNA expression. We suggest that IL-4 and IL-13 may enhance iron uptake and storage in activated macrophages and thereby contribute to down-regulation of macrophage effector functions.

Animals↗
PubMed1997

Unidirectional upregulation of the synthesis of the major iron proteins, transferrin-receptor and ferritin, in HepG2 cells by the acute-phase protein alpha1-antitrypsin.

BACKGROUND/AIMS: We have previously shown that the hepatic acute-phase protein alpha1-antitrypsin (alpha1-AT) is an important mediator of changes in iron metabolism in the course of anaemia of chronic disease. Alpha1-AT profoundly reduces growth of erythroid cells by interfering with transferrin-mediated iron uptake. In the present work we investigate the effects of alpha1-AT on hepatic iron metabolism, as the liver plays a central role in body iron metabolism and in metabolic changes during acute-phase response. METHODS: The human hepatoma cell line Hep G2 was cultured in RPMI 1640+10% FCS. The effect of alpha1-AT on transferrin-receptor binding was investigated in equilibrium binding assays with 125I-transferrin. Expression of transferrin receptor was determined by saturation experiments and intracellular ferritin was measured in cell lysates after incubating cells either alone or with alpha1-AT. To determine iron regulatory protein binding activity to iron responsive elements we used gel retardation assays and Northern blot analysis was carried out to investigate transferrin receptor and ferritin mRNA expression. RESULTS: Alpha1-AT completely prevented transferrin from binding to its receptor and internalization of the transferrin-transferrin receptor complex on HepG2. In addition, alpha1-AT caused a distinct increase in iron regulatory protein binding activity to iron responsive elements, which is characteristic of iron deprivation. Normally, the synthesis of transferrin receptor and ferritin is regulated bidirectionally, but alpha1-AT promoted a unidirectional regulation. Alpha1-AT increased the synthesis of both transferrin receptor and ferritin and, moreover, increased cellular amounts of transferrin receptor mRNA and ferritin H-chain mRNA. CONCLUSIONS: The effect of alpha1-AT on transferrin receptor synthesis appears to be mediated via activation of iron responsive element binding affinity of iron regulatory protein leading to an increased stability of transferrin receptor mRNA. Changes in ferritin, however, may be related to a transcriptionally mediated, iron-independent pathway which overrides the influence of activated iron regulatory protein. These specific changes in iron metabolism are the very ones seen in the course of anaemia of chronic disease. Our results emphasize the central role of alpha1-AT as a mediator of altered iron metabolism, characteristic of anaemia of chronic disease, not only with respect to erythroid cells but also with respect to liver cells.

Cell Division↗
PubMed1997

Phase I study of daily times five topotecan and single injection of cisplatin in patients with previously untreated non-small-cell lung carcinoma.

BACKGROUND: The objectives were to determine the dose-limiting toxicity of topotecan in combination with cisplatin, to describe the principal toxicities, and to define the maximally-tolerated doses of the drugs in previously untreated patients with advanced non-small-cell lung carcinoma. PATIENTS AND METHODS: The study was designed to evaluate escalated doses of topotecan (starting at 0.75 mg/m2/day) as a 30-minute infusion daily for five consecutive days with a fixed clinically-relevant dose of 75 mg/m2 cisplatin given on day 1, every three weeks. RESULTS: Fifteen chemotherapy-naive patients entered the study and 14 were evaluable for toxicity. All 11 patients treated at the first topotecan/cisplatin dose level of 0.75/75 mg/m2, experienced at least one episode of grade 4 neutropenia. For six patients, absolute neutrophil counts were below 500/ml for more than five days, and two of them developed a grade 4 thrombocytopenia. At the next higher topotecan/cisplatin dose level (1.0/75 mg/m2), grade 4 neutropenia lasting longer than five days occurred in all three evaluable patients, including one patient who expired due to a severe neutropenia associated with sepsis. Non-hematologic toxicities, predominantly nausea and vomiting, were mild to moderate in severity and manageable. Four patients had partial responses (30.7%; 95% confidence interval (9%-61%) of relatively short duration. CONCLUSION: Both severe neutropenia and thrombocytopenia precluded dose escalation of topotecan and cisplatin administered on this schedule. In previously untreated patients, the first topotecan/cisplatin dose level (0.75/75 mg/m2), was associated with intolerable myelosuppression, and, therefore, the dose levels evaluated in this study cannot be recommended for subsequent phase II investigations. The high toxicity of this schedule and the recent understanding of the pharmacokinetic interaction between those drugs may encourage the investigation of the alternate sequence of cisplatin after TPT in phase II studies.

Aged↗
PubMed1997

Modulatory potential of iron chelation therapy on nitric oxide formation in cerebral malaria.

To determine whether iron chelation modulates nitric oxide (NO) formation and cell-mediated immune effector function in children with cerebral malaria, serum concentrations were measured of the stable end products of NO, nitrite and nitrate (NO2-/NO3-), interleukin (IL)-4, -6, and -10, and neopterin in 39 Zambian children enrolled in a placebo-controlled trial of desferrioxamine B and quinine therapy. Mean concentrations of NO2-/NO3- increased significantly over 3 days in children receiving desferrioxamine plus quinine but not in those given placebo and quinine. Neopterin levels declined significantly with placebo but not with desferrioxamine. IL-4 levels increased progressively in the placebo group and ultimately decreased in the desferrioxamine group, but the trends were not statistically significant. IL-6 and IL-10 levels were elevated initially and decreased significantly in both groups over 3 days. These data are consistent with the hypothesis that iron chelation therapy in children with cerebral malaria strengthens Th1-mediated immune effector function involving increased production of NO.

Biopterins↗
PubMed1997

Uterus didelphis with obstructed hemivagina and ipsilateral renal agenesis: ultrasound and magnetic resonance imaging diagnosis.

The association of uterus with unilateral imperforate hemivagina and ipsilateral renal agenesis is extremely rare. We present a case of a 13-year-old virginal patient in whom a combination of intravenous pyelogram and ultrasound was comparable to magnetic resonance imaging in permitting an accurate preoperative diagnosis thus allowing for early and appropriate surgical intervention and possible preservation of fertility.

Adolescent↗
PubMed1997

Patterns of hepatitis C viremia in patients receiving hemodialysis.

OBJECTIVES: Chronic hepatitis C virus (HCV) infection is common in patients who receive hemodialysis (HD). The aim of this study was to determine the natural history of hepatitis C viremia and the clinical utility of quantitation and genotyping of HCV in this population of patients. METHODS: Consecutive sera from two groups of HD patients who were HCV RNA positive, a group of 33 patients treated with interferon alfa (5 MU, three times a week for 4 months) and a group of 31 untreated patients, were analyzed by qualitative polymerase chain reaction, quantitative polymerase chain reaction, and a line probe assay for genotyping. RESULTS: Serum HCV RNA was detected continuously in 20 of 31 untreated patients (65%), and 11 patients (35%) showed a fluctuating pattern of viremia with virus-free intervals of up to 4 wk. Twenty-five of 33 patients (76%) treated with interferon alfa became HCV RNA negative during therapy; eight of these 25 patients had a breakthrough, which was transient in seven patients and persistent in one. Of the remaining 24 end-of-treatment responders, 17 relapsed after completion of therapy, and seven (21%) had a sustained response with undetectable serum HCV RNA for 1 yr of follow-up. Initial serum HCV RNA levels in HD patients were generally low (median, 1 x 10(5) genome eq/ml). Sustained responders had significantly lower median levels of viremia (4 x 10(4) eq/ml) than relapsers and nonresponders (9 x 10(4) and 1.8 x 10(5) eq/ml, respectively). Genotyping revealed a predominance of genotype 1a (33%) and 1b (48%). CONCLUSIONS: This study documents that fluctuating hepatitis C viremia with periods of undetectable HCV RNA is common and that low viral load predicts a sustained response to interferon therapy in HD patients. Diagnosis of chronic hepatitis C and monitoring of interferon therapy in HD patients should include initial HCV RNA quantitation and repeated qualitative measurements of HCV RNA.

Adult↗
PubMed1997

[Cellular and humoral functions in acute pancreatitis].

Infectious complications are the leading cause of death in acute pancreatitis. Individual factors of immune defence could be of significance, whether or not a patient develops a severe course with infectious complications. In a prospective 5-year trial including 72 patients, we investigated 29 cellular and humoral markers of the body's defence system for their potential to indicate the severity and course of acute pancreatitis. Complement factors C3 and C4 as well as immunoglobulins IgG, IgM and IgA were normal, in general. Measurable levels of IL-1 alpha, IL-1 beta, IL-2 and sIL-2R could be detected only occasionally. Values of alpha 1-AT, TNF-alpha, TNF alpha-Rp75, neopterin, sICAM-1, IL-8, IL-1RA and sIL-6R did not correlate with a severe course. Due to the high magnitude of increase, CRP, IL-6 and granulocyte elastase were the best indicators of the inflammatory process. Delayed-type hypersensitivity response was the only early predictor of a severe course. It was superior over other cellular markers such as monocyte count or CD4+/CD8+ ratio. In vitro function of polymorphonuclear granulocytes (PMN) was not adequate to the severity of the disease already during the first week of illness. During further course, PMN motility and capacities to produce reactive oxygen species even worsened. The compromized PMN function could explain the frequent development of infectious complications in patients suffering from severe pancreatitis. These results should encourage new concepts of infection prophylaxis using stimulants of cellular defence.

Acute Disease↗