Budesonide for the treatment of obstructive eosinophilic jejunitis.

Eosinophilic gastroenteritis is a rare gastrointestinal (GI) disorder of undetermined origin, characterized by infiltration of eosinophils in the GI tract. Different layers of the bowel wall can be involved and the clinical outlook depends on the area affected. Our subject is a male patient in whom the disease involves the muscular layer causing obstructive jejunitis. The diagnosis was made after surgical resection. A relapse was subsequently treated with short-term intravenous steroids followed by oral budesonide for three months. Treatment was effective with no apparent side effects.

[Splenectomy for thrombocytopenic purpura. Retrospective analysis of the postoperative course]. / Splenektomie bei idiopathischer thrombozytopenischer Purpura. Retrospektive Analyse des postoperativen Verlaufs.

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) comprises approximately 8% of all haemorrhagic diseases. Typical findings are a very low platelet count which manifests as petechial bleeding. Therapy consists of medication and removal of the spleen if conservative therapy fails. PATIENTS AND METHODS: Between 1988 and 1999, 47 patients with ITP were splenectomized in our surgical department. We examine the postoperative development of platelet counts and long-term results in 33 of these patients. RESULTS: After splenectomy, more then 75% of our patients had normal platelet counts. In long-term examination, 58% remained in stable condition with normal platelet counts. Retrospectively we tried to identify preoperative clinical features that could predict the long-term outcome of splenectomy in ITP but were unable to find reliable factors. CONCLUSION: Idiopathic thrombocytopenic purpura can be treated by surgical means but should be considered only when conservative treatment has failed. The long-term outcome of splenectomy is not predictable. Reliable predictive factors have to be identified through further research.

[Life threatening complication after transthoracic esophageal resection]. / Lebensbedrohliche Komplikation nach transthorakaler Oesophagusresektion.

Acute inflow stasis of the vena cava superior is an emergency case. Because of the rapidly rising venous pressure, life-threatening complications can arise (e.g. cerebral hemorrhage, hemorrhagic venous infarcts). The main cause of central venous thrombosis is bronchial carcinoma (incidence: 3-5%). Iatrogenic reasons are thrombosis caused by pacemaker electrodes, dialysis catheter, central vein catheters, implanted ports and radiation-induced venous fibrosis. In this case a patient with an esophageal carcinoma was pretreated by a neoadjuvant chemoradiotherapy. The chemotherapy was given through a venous access port, which was implanted earlier. Radiation therapy with a total of 60 Gy followed. After the esophagectomy the patient developed an acute inflow stasis of the vena cava superior.

[Developments in inguinal hernia based on newly introduced intervention techniques in the North Rhine district]. / Entwicklungen bei der Leistenhernie vor dem Hintergrund neu eingeführter Eingriffstechniken im Kammerbereich Nordrhein.

In Germany inguinal hernia surgery has changed over the last decade from conventional repairs without alloplastic material to video-assisted minimal invasive techniques or Lichtenstein repair. Since 1991 every patient undergoing inguinal hernia repair has been documented in the North-Rhine area in a routine quality-surveillance study. A total of 173,923 patients with 192,718 groin hernias (85.26% male and 14.74% female) were operated on. In 1993 the Shouldice repair was performed in 54.2%, the Bassini operation in 26%, the transabdominal laparoscopic TAPP repair in only 3.2% of cases. In 1999 the TAPP repair was performed in 13%, the extraperitoneal video-assisted TEP repair in 14%, Lichtenstein repair in 18.5%, Shouldice repair in 35% and the Bassini operation in only 4.8%. The percentage of operations was 13.4% over the last 10 years. However, there was an increase from 12.8% in 1993 to 14.1% in 1997, and a rate of 13.5% in 1999. The following complications were observed: hematoma/seroma formation in 3.78%, wound infection in 1.15%, testicular edema in 0.37% and scrotal edema in 0.64%. The data document the introduction of three new methods for inguinal hernia repair (TAPP, TEP and Lichtenstein repair). A decrease in operations on recurrences is not observed.

[Tumor necrosis factor-alpha (TNF-alpha) gene polymorphism in surgical intensive care patients with SIRS]. / Tumornekrosefaktor-alpha (TNF-alpha) Gen-Polymorphismus bei chirurgischen Intensivpatienten mit SIRS.

Biallelic polymorphism in the promotor region of the TNF-alpha gene have been associated with variation in TNF-alpha production. We determined the TNFA polymorphism (position--308) and related these data to plasma cytokine levels of TNF alpha, IL6, IL6R and IL8 in patients with SIRS and sepsis. Although there seems to be a different cytokine secretion pattern for both allelic groups (TNFA1 and TNFA2), a clear risk group could not be determined. It still remains unclear whether there is a genetic factor that influences the development of sepsis and multi organ failure.

Granulocyte colony-stimulating factor (G-CSF) serum levels in surgical intensive care patients.

The granulocyte colony-stimulating factor (G-CSF) regulates neutrophil differentiation and function. Serum levels of G-CSF increase during acute infectious processes. The levels of G-CSF were measured in 59 surgical intensive care unit (ICU) patients. In general, G-CSF was only elevated during the first 2 days after admission to the ICU. Higher G-CSF levels were more frequently observed in patients without infectious complications and in patients who survived. Later on, G-CSF levels were below 100 pg/ml in almost all patients studied. The highest G-CSF level (20,000 pg/ml) was observed in one patient with septic shock 36 h after leukopenia. The patient recovered from septic shock and multiple organ failure and was discharged. It is proposed that surgical ICU patients with low or undetectable G-CSF serum levels may benefit from exogenous G-CSF substitution protocols.

Safety of a low-dosage Filgrastim (rhG-CSF) treatment in non-neutropenic surgical intensive care patients with an inflammatory process.

OBJECTIVE: To evaluate the effect and safety of a low dose Filgrastim treatment in surgical intensive care patients. DESIGN: Prospective, clinical study. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: Ten patients with the systemic inflammatory response syndrome (SIRS) and ten patients with sepsis were included in the study. INTERVENTIONS: Filgrastim was given intravenously at 1.0 microgram/kg for 3 days, followed by 0.5 microgram/kg for 4 days. MEASUREMENTS AND RESULTS: Filgrastim treatment increased leukocyte counts and plasma levels of G-CSF. Cytokine levels (IL-6 and IL-8) decreased in the first 3 days of treatment. None of the SIRS patients developed sepsis or multiple organ failure and none of the patients died. In the sepsis group four patients died. No adverse side effects were observed, especially no attenuation of lung injury. CONCLUSIONS: Low-dosage Filgrastim treatment in ICU patients is safe. Whether the observed changes of the inflammatory response can be attributed to Filgrastim has to be clarified in further randomized trials.

Filgrastim (RHG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis.

Over a period of 14 days a longitudinal analysis was performed on the effects of filgrastim (recombinant human granulocyte colony stimulating factor, rhG-CSF) administered to 20 postoperative/posttraumatic patients at risk of or with sepsis. The following parameters were determined: leukocyte counts, serum cytokine levels and the surface expression of functional antigens and adhesion molecules. Filgrastim (1 mu g/kg.day) was infused continuously on the first 3 days and tapered to 0.5 mu g/kg.day on the following 4 days or until discharge from the surgical intensive care unit. During infusion of filgrastim, G-CSF levels increased in 16 out of the 20 patients within 48 h. In these 16 patients, leukocyte counts increased in 15 out of 16 patients. Expression of CD64 was upregulated within 24 h. The expression of CD32 was upregulated in 8 out of 9 patients with an initial expression < 55%. LAM-1 expression was downregulated in all patients revealing an initial expression of LAM-1 > 40%. Soluble ICAM increased in 9 out of 11 patients. IL-8 decreased in all 6 patients presenting initial values of IL-8 > 90 pg/ml. IL-1RA increased in 10 patients. Filgrastim had no effect on the expression of CD14, CD16 and CD34 and on the levels of TNF-alpha and sTNF-R type I (p55). In conclusion, infusion of filgrastim in postoperative/post traumatic patients at risk of and with sepsis resulted in improved generation and function of neutrophils and appeared to counterregulate hyperactivation of proinflammatory processes.

Enhancement of neutrophil function by in vivo filgrastim treatment for prophylaxis of sepsis in surgical intensive care patients.

PURPOSE: To determine the kinetics of leukocyte counts and of oxygen radical production of neutrophils from postoperative/posttraumatic patients with or without infusion of filgrastim (recombinant human granulocyte colony-stimulating factor, rhG-CSF) as prophylaxis against sepsis. METHODS: Twenty postoperative/posttraumatic patients with a Therapeutic Intervention Scoring System (TISS) score greater than 30 were included in this study. In the 10 patients of the study group, filgrastim (1 microgram/kg/d) was infused continuously within the first 3 days and tapered to 0.5 microgram/kg/d on the following 4 days or until discharge from the surgical intensive care unit. Ten patients without administration of filgrastim served as controls. Oxygen radical production of isolated neutrophils of these patients was tested by N-formyl-methionyl-leucyl-phenylalanine (FMLP)- and zymosan-induced chemiluminescence from serial blood samples, taken until the 16th postoperative day. RESULTS: Compared with the first postoperative day, in vitro FMLP-induced neutrophil chemiluminescence was significantly increased during the following 4 postoperative days in the patients with filgrastim infusion; however, only during the first 2 postoperative days in the control group. The increase in the FMLP-induced neutrophil chemiluminescence was significantly greater (P < .05) in the study group than in the control group on the third and on the fourth postoperative day. Tapering of filgrastim by 0.5 microgram/kg/d in the study group resulted in a reduction of FMLP-induced neutrophil oxygen radical production within 48 hours. In contrast, zymosan-induced neutrophil chemiluminescence was not measurably affected in both groups. Leukocyte count of the study group significantly (P < .05) exceeded the leukocyte count of the control group from the third up to the 10th postoperative day. None of the patients treated with filgrastim developed sepsis; however, three patients within the control group did. CONCLUSIONS: Prolonged enhancement of neutrophil count and function induced by rhG-CSF may be useful in the prophylaxis of sepsis in posttraumatic/postoperative patients at high risk of sepsis.

[Follow-up of severely injured patients with scoring systems on the intensive care unit]. / Verlaufsbeobachtung von Schwerstverletzten mittels Scoringsystemen auf der Intensivstation.

A variety of different scoring systems are in current use, with an increasing impact on intensive care treatment. Originally these scoring systems were applied to evaluate objective grading and to estimate survival and mortality. More recently, other potential applications have been investigated. While clinical monitoring and assessment of therapeutic success are the primary goals, scoring systems can be used to define comparable patient collectives and to delineate predefined patient groups for clinical trials. Scoring systems are gaining increasing importance in evaluation of the level of therapeutic intervention and care provided as well as in quality assessment. On the whole, however, accuracy, the probability that outcome will be correctly predicted for an individual patient, is still inadequate. Although desirable, individual patient prediction is therefore not allowed, and therapeutic strategies and therapy evaluation based on scoring systems cannot be implemented, or only in a limited way. For daily use in individual patient evaluation--monitoring, therapy response, prognosis--biochemical monitoring is still of primary importance. Scoring systems have now found a useful application as a supplement, rather than a rival, to clinical patient evaluation.

Instant therapy of acquired agranulocytosis and sepsis by recombinant granulocyte-macrophage colony-stimulating factor in a polytrauma patient.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was given to an intensive-care patient with polytrauma in a life-threatening situation with acquired agranulocytosis and sepsis. Mature granulocytes reappeared in the blood 2 days after initiation of rhGM-CSF therapy; granulocyte precursors peaked at 43% after 5 days. Bone marrow examination performed 7 days after the beginning of rhGM-CSF therapy revealed complete regeneration of granulopoiesis. The functional analysis of these blood leukocytes in vitro showed regular production of reactive oxygen radicals. Clinically, the patient recovered without any serious side effects due to the rhGM-CSF therapy. These results suggest that rhGM-CSF accelerates granulocyte recovery from acquired agranulocytosis with the presence of their functional activity.

Basophil releasability in severely burned patients.

Thermal injury is known to induce dysregulation of the immune system; however, the precise mechanisms have to be clarified. We investigated the histamine release of basophil granulocytes from severely burned patients (n = 12) after stimulation with anti-IgE or the Ca-ionophore A 23187, respectively. The anti-IgE-induced basophil histamine release of all patients was reduced in comparison to healthy donors beginning at day one postburn (p.b.) (5.0 +/- 2.3% vs. 30.5 +/-3.4%), while the Ca-ionophore-induced release was not decreased before day two p.b. Basophils of patients who finally succumbed to their injuries showed poor responsiveness (to zero levels) over the total time. In contrast, the basophil releasability of surviving patients returned to nearly normal levels (fifth to seventh week p.b.). Already in the second week p.b. there was a significant difference in histamine release between survivors and nonsurvivors [e.g., days 6-9 p.b.: 23.7 +/- 4.0 vs. 6.9 +/- 2.7 (p less than 0.005) after Ca-ionophore stimulation]. The altered basophil histamine release was neither due to a diminished dose- or a delayed time-response to the stimuli nor due to differences in the basophil counts or the cellular histamine content. Our data indicate that the decrease of the basophil releasability, which may be secondary to altered signal transduction pathways in severely burned patients correlates with the clinical outcome.

Induction of histamine release from rat mast cells and human basophilic granulocytes by clinical Escherichia coli isolates and relation to hemolysin production and adhesin expression.

We investigated the role of 27 disease-relevant Escherichia coli strains isolated from humans in the induction of histamine release from rat peritoneal mast cells and human basophilic granulocytes. Our data indicated that only the hemolysin-positive (HLY+) bacteria and the hemolysin-positive culture supernatants induced histamine release. For the latter, the hemolysin activity determined the degree of histamine secretion. Incubation of the target cells with washed HLY+ bacteria revealed a different secretory response. For the rat mast cells, histamine release paralleled expression of hemolysin activity, with the exception of strain S98 (O75:K5:H- HLY+), which induced less histamine, although its hemolysin activity was relatively high. No correlation between histamine secretion and hemolysin activity was observed when human basophils were stimulated with the HLY+ bacteria. Large amounts of histamine were still released, even when the hemolysin activity declined to zero. Our results support the potent role of the E. coli hemolysin as a pathogenicity factor in bacterial infection.

Generation of leukotrienes from human polymorphonuclear granulocytes of severely burned patients.

The Ca ionophore A23187-induced leukotriene (LT) release (LTC4, LTB4, 20-OH-LTB4, 20-COOH-LTB4) of human PMN's from severely burned patients (n = 6) was studied by reversed-phase HPLC. The patients' granulocytes demonstrated a decrease (to zero levels) in LT generation postburn. The level of generated LT's resembled that of healthy donors when the patients recovered from their trauma (after day 40 postburn). In contrast, the granulocytes of patients who finally succumbed to their injuries showed poor responsiveness over the total time. An enhanced LTC4 production by granulocytes correlated with an increase in eosinophils within the granulocyte fraction. In addition, the reduced LTB4 production was accompanied by an enhanced LTB4 metabolism to biologically less active products (omega-oxidated metabolites). Thus, the capacity of patients' PMN's to release chemotactic substances was further decreased. The onset of this PMN dysfunction correlated with the onset of invasive microbial growth as determined by the quantitative bacterial analysis of full-thickness biopsy specimens. Our data provide evidence that the altered mediator release of patients' PMN's is closely related to a depressed host defense.

Metabolism of leukotriene B4 by polymorphonuclear granulocytes of severely burned patients.

Leukotriene B4 release from polymorphonuclear granulocytes of severely burned patients was reduced as compared to healthy donor cells. This decrease is due to an enhanced conversion of LTB4 into the 20-hydroxy- and 20-carboxy-metabolites and further to a decreased LTB4-synthesis. In addition, studies on the exogenous LTB4-conversion revealed an unidentified compound which was derived from LTB4. Our data suggest a modulation of the enzymatic activities involved in omega-oxidation of LTB4 (isoenzymes of cytochrome P-450).

Inhibition of histamine release in vitro by a blocking factor from human serum: comparison with the iron binding proteins transferrin and lactoferrin.

Recently, we described the presence of a blocking factor (BF) in rat serum, which inhibited the histamine release from rat mast cells in vivo and in vitro. The blocking activity was demonstrated in human serum as well. Qualitative analysis of the purified preparations demonstrated a major component with an apparent molecular weight of 70,000 daltons. In human serum the blocking factor was identified as transferrin (TF) by serological and biochemical methods. BF (DEAE-peak 1) and the iron binding proteins transferrin and lactoferrin (LF) are shown to inhibit the histamine release in vitro. The dose response curves reveal that inhibition by these proteins is dependent on their degree of iron saturation. Furthermore, unlike lactoferrin, the effects of transferrin and BF (DEAE-peak 1) follow the same pattern. Their mechanism of action remains to be elucidated.