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Biomedical subjects

M Heinzelmann

Publications and source records attributed to M Heinzelmann.

At least 37 records · Page 2Linked to original sources
PubMed1998

Modulation of lipopolysaccharide-induced monocyte activation by heparin-binding protein and fucoidan.

Activated polymorphonuclear leukocytes release heparin-binding protein (HBP; also known as CAP37 or azurocidin) from azurophilic granules. HBP is a strong chemoattractant for monocytes that also prolongs monocyte survival and potentiates endotoxin (lipopolysaccharide [LPS])-induced production of tumor necrosis factor alpha (TNF-alpha). We investigated the binding of fluorescein isothiocyanate-conjugated HBP to human monocytes in the presence of EDTA and the polysaccharide fucoidan. EDTA, which chelates divalent cations, has been widely used to study the role of divalent cations in receptor-ligand interactions or enzyme activity. Fucoidan has been used to inhibit the binding of various ligands to scavenger receptors or selectins. Scavenger receptors are multiligand receptors that mediate endocytosis of proteases, protease-inhibitor complexes, lipoproteins, and LPS-lipid A. Fucoidan also interferes with leukocyte rolling by binding to L-selectins (expressed on leukocytes) and P-selectins (expressed on platelets and endothelium). We demonstrate that the binding of the neutrophil-derived protein HBP to monocytes is inhibited in the presence of EDTA and fucoidan. In addition, fucoidan and EDTA abrogate the enhancing effect of HBP on LPS-induced TNF-alpha production. These data provide supporting evidence that HBP binds to a receptor expressed on monocytes. This receptor is dependent on divalent cations and is possibly related to the scavenger receptor. Furthermore, we demonstrate that fucoidan, by itself, stimulates TNF-alpha release from isolated monocytes in a CD14-independent fashion. This is an important finding for the interpretation of results from studies that use fucoidan to "block" either scavenger receptors or L- or P-selectins.

Antimicrobial Cationic Peptides↗
PubMed1997

Bacterial cell wall products increase monocyte HLA-DR and ICAM-1 without affecting lymphocyte CD18 expression.

Bacterial cell wall products such as lipopolysaccharide (LPS) and muramyl dipeptide (MDP) have the capacity to enhance immune responses to antigens. The expression of surface class II major histocompatibility antigens and the costimulatory receptors CD18 and CD54/ICAM-1 (intercellular adhesion molecule) was used to evaluate the comparative influence of these immunostimulators. On monocytes, both LPS and MDP increased the expression of human leukocyte antigen (HLA)-DR (maximal at 6 hr), CD18 (maximal at 1-3 hr), and ICAM-1 (maximal at 18-24 hr for LPS and 12 hr for MDP) without increasing the production of superoxide. MDP-induced ICAM-1 expression on monocytes returned to baseline values after 12 hr. On lymphocytes, only LPS increased ICAM-1 (after 18 hr) without affecting CD18, and a differential analysis demonstrated a generalized ICAM-1 upregulation in lymphocyte subsets after 18 hr: the most pronounced effect was measured in natural killer cells, followed by CD8(+) T cells, B cells, and CD4(+) T cells. MDP did not alter ICAM-1 or CD18 expression on lymphocytes. These similar but smaller effects of MDP may, in part, explain the lesser toxicity of MDP when compared to LPS.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

Inflammatory response after abdominal trauma, infection, or intestinal obstruction measured by oxygen radical production in peritoneal fluid.

BACKGROUND: Reactive oxygen intermediates (ROI) have been implicated in many pathophysiological processes of inflammatory tissue damage and tissue repair. In the present study we compared the production of ROI in three different types of tissue damage in surgical patients. METHODS: Peritoneal fluid specimens were harvested during the initial operation and postoperatively from 25 surgical patients with abdominal trauma, intraabdominal infection, and intestinal obstruction. The optical density at 412 nm, representing the peroxidation of hemoglobin, was measured to assess intraperitoneal ROI production. Patients were categorized into 3 groups: (A) infected patients with good outcome, (B) patients after trauma or obstruction with good outcome, and (C) patients with poor outcome due to persistent or secondary infection and multiple organ failure. Analysis of variance (ANOVA) and paired t test were used for statistical analysis. RESULTS: Overall, the ROI production decreased significantly at days 2 and 3 compared with day 0 and 1 (P = 0.0013). No initial differences of intraoperative ROI concentrations were found among the three groups; however, patients with a poor outcome showed increased ROI values after 4 to 5 days (P = 0.038) when compared with the good outcome group. CONCLUSIONS: We have demonstrated that intraperitoneal ROI production (1) can be measured in patients with intraabdominal tissue damage, (2) is not different between patients with intraabdominal infections, abdominal trauma, or intestinal obstruction, and (3) correlates with the clinical picture and the presence of an inflammatory intraabdominal focus or tissue damage.

Abdominal Abscess↗
PubMed1997

The pulmonary inflammatory response to experimental fecal peritonitis: relative roles of tumor necrosis factor-alpha and endotoxin.

The roles of endotoxin (LPS) and tumor necrosis factor-alpha (TNF-alpha) in the causation of organ injury during sepsis are unclear. To study LPS and TNF-alpha in the genesis of lung inflammation after cecal ligation and puncture (CLP), we used endotoxin-resistant (C3H/HeJ) and endotoxin-sensitive mice (C3H/HeOuJ). We examined lung neutrophil sequestration, interleukin 1 (IL-1)beta mRNA expression, IL-1 beta protein expression, and injury. We also determined the expression of two C-X-C chemokine mRNAs, macrophage inflammatory protein-2 (MIP-2) and KC, in the lung to determine whether in vivo, endotoxin, or TNF-alpha are significant modulators of MIP-2 and KC mRNA expression. After CLP, increased neutrophils sequestrated in the lungs of both strains of mice and coincided with an increase in expression of IL-1 beta, MIP-2 and KC mRNAs, and IL-1 beta protein. Lung and serum TNF-alpha were significantly increased in the C3H/HeOuJ strain but not in the C3H/HeJ strain. Histologic studies of the lung revealed similar injury in both strains. Our results suggest that bacterial factors other than endotoxin cause lung neutrophil sequestration and injury after CLP and, further, that TNF-alpha production is not a prerequisite. Our findings also suggest a potential role for local pulmonary chemokine production in the control of neutrophil sequestration after CLP.

Animals↗
PubMed1997

Haemodynamic effects of pneumoperitoneum in elderly patients with an increased cardiac risk.

We studied the haemodynamic changes induced by pneumoperitoneum (PP) in elderly patients with increased cardiac risk (ASA class III; n = 10; age 72.3 +/- 8.8 years, mean +/- SD, P < 0.05; group 2) and compared the results with patients at normal risk (ASA class I, II; n = 12; age 55.6 +/- 11.8 years; group 1). Thermodilution measurements were performed after induction of general anaesthesia (T1), after onset of PP (T2, intraabdominal pressure 14 mmHg) and after additional 15 degrees head-up tilt (T3). In both groups PP, as compared with T1, induced a significant increase in mean arterial pressure (MAP, mmHg, group 1: 77 +/- 14 to 96 +/- 18, P < 0.05/group 2: 75 +/- 10 to 102 +/- 18, P < 0.01), mean pulmonary artery pressure (MPAP, mmHg: 15 +/- 5 to 22 +/- 4, P < 0.01/18 +/- 3 to 25 +/- 5, P < 0.01), central venous pressure (CVP, mmHg: 7 +/- 2 to 15 +/- 3, P < 0.01/7 +/- 2 to 12 +/- 2, P < 0.01), pulmonary capillary wedge pressure (PCWP, mmHg: 9 +/- 4 to 16.3, P < 0.01/8 +/- 2 to 15 +/- 6, P < 0.01) and in systemic vascular resistance (SVR, dynes s cm-5: 1415 +/- 375 to 1873 +/- 412, P < 0.01/ 1502 +/- 360 to 2067 +/- 647, P < 0.01). Cardiac index (CI, L min-1 m-2: 2.3 +/- 0.3 to 1.9 +/- 0.3, P < 0.05/2.2 +/- 0.4 to 2.2 +/- 0.5 P = 0.76) and oxygen delivery index (DO2I, mL min-1 m-2: 388 +/- 54 to 324 +/- 61, P < 0.05/358 +/- 69 to 353 +/- 82, P = 0.77) decreased in group 1 but not in group 2. Heart rate, stroke Index, pulmonary vascular resistance, arteriovenous oxygen content difference and oxygen consumption index were unchanged. After head-up tilt MAP (mmHg, 92 +/- 15, P < 0.05/ 101 +/- 17, P < 0.01), MPAP (mmHg, 20 +/- 3, P < 0.01/22 +/- 4, P < 0.05), CVP (mmHg, 12 +/- 2, P < 0.01/10 +/- 2, P < 0.01) and PCWP (mmHg, 12 +/- 3, P < 0.05/12 +/- 5, P < 0.05) remained elevated compared with T1 in both groups, SVR (dynes s cm-5, 1575 +/- 372, P = 0.13/1793 +/- 528, P < 0.01) in group 2 only. No complications occurred. The results indicate that PP is associated with significant but relatively benign haemodynamic changes. Anaesthesia for laparoscopic cholecystectomy may be performed safely also in elderly ASA class III patients with increased cardiac risk. An adequate haemodynamic monitoring is recommended.

Aged↗
PubMed1997

Inhibition of neutrophil migration at the site of infection increases remote organ neutrophil sequestration and injury.

Up-regulation of the leukocyte beta 2 integrin, CD18, is a key event in neutrophil-endothelial adhesion and neutrophil-mediated organ injury. Inhibition of CD18 with monoclonal antibodies reduces lung and liver neutrophil sequestration in animal models of Gram-negative bacteremia or endotoxemia. However, with a persistent septic challenge, interference with host leukocyte phagocytic defense could adversely affect outcome. To assess the effects of inhibiting CD18 on organ neutrophil responses, bacteremia, and organ injury after fecal peritonitis, mice underwent cecal ligation and puncture (CLP). At the time of CLP and 12 h later, mice received intravenous anti-CD18 antibody or control IgG. At 3, 6, and 18 h after CLP, lung and liver tissue neutrophil content were measured by myeloperoxidase (MPO) assay, peritoneal cells and blood leukocytes were differentially counted, blood was cultured, and serum aspartate aminotransferase was measured. There was a significant reduction in peritoneal neutrophil migration and an increase in blood neutrophils after anti-CD18 treatment compared with results from treatment with the control antibody. In the anti-CD18-treated group, liver MPO was increased fivefold at 6 and 18 h, while lung MPO was increased two-fold at 18 h when compared with the control antibody-treated group. The anti-CD18-treated group also had an increase in bacteria cultured from the blood at 6 and 18 h and an increase in serum aminotransferase at 18 h. Our data demonstrate that peritoneal neutrophil migration in response to an endogenous fecal challenge is CD18-dependent, and that this mechanism forms a vital part of host defense. Inhibition of CD18 increased neutrophil sequestration in the liver and lung and increased liver injury. This study demonstrates a paradoxical increase in organ neutrophil sequestration using a leukocyte anti-adhesion therapy during sepsis and suggests that anti-adhesion therapies targeted towards neutrophil may worsen outcome if given during an ongoing, localized infection.

Animals↗
PubMed1997

Phagocytosis and oxidative-burst response of planktonic Staphylococcus epidermidis RP62A and its non-slime-producing variant in human neutrophils.

The ability of bacterial organisms to produce an extracellular polysaccharide matrix known as slime has been associated with increased virulence and delayed infections in various prosthetic implants. Within a biofilm, this slime may protect the embedded bacteria from host defense mechanisms, especially phagocytosis by polymorphonuclear leukocytes. To determine whether planktonic Staphylococcus epidermidis is protected in a similar way, a novel flow cytometric assay was performed, measuring ingestion and adherence during phagocytosis and the production of superoxide during oxidative burst. Hydrophobicity was determined by hydrophobic interaction chromatography. Slime-producing S. epidermidis RP62A and its phenotypic variant, non-slime-producing RP62A-NA, were compared. The results showed increased phagocytosis of RP62A at 2, 5, 10, and 30 min; increased adherence of RP62A at 30 s and 30 min; and increased superoxide production of RP62A after 2 min. Decreased hydrophobicity of RP62A over RP62A-NA was correlated with a hydrophilic slime coat. The data argue that the host aggressively combats slime-producing S. epidermidis. This biological phenomenon is potentially important during bacteremia to prevent further adhesion, accumulation, and the genesis of a bacterial biofilm on implants or tissue surfaces.

Animals↗
PubMed1996

Outcome after acute extradural haematoma, influence of additional injuries and neurological complications in the ICU.

The purpose of this study was to evaluate the influence of additional, extracranial injuries and subsequent neurological complications in the intensive care unit on the functional outcome after head injury with extradural haematoma. The retrospective analysis included 139 adult patients with acute extradural haematomas admitted to the intensive care unit. Fifty-seven patients (41 per cent) were multiply injured (Injury Severity Score (ISS) = 36.5), and 82 (59 per cent) had a single head injury (ISS = 24.9). Fifty-four patients (39 per cent) developed neurological complications such as intracranial pressure (ICP) increase alone (N = 16), intracranial bleeding, ischaemic brain lesions or epileptic seizures with an associated ICP increase (N = 24) or without (N = 14). Overall, 77 per cent of the patients had a functional outcome (Glasgow outcome score 4 or 5); 46 per cent had a good recovery, 31 per cent were moderately disabled, 10 per cent were severely disabled, 4 per cent were persistently vegetative, and 9 per cent died. Differences were found between (1) patients with and without complications, (2) patients with extradural haematomas and patients with additional intracranial lesions, and (3) patients with a 'severe' Glasgow Coma Score (GCS) of 3-8 and patients with a GCS of 9-15. The presence of additional intracerebral injuries, and not extracerebral injuries, as well as the management of elevated ICP determines the final outcome in patients with extradural haematomas.

Adult↗
PubMed1996

Constituent analysis may permit improved diagnosis of intra-abdominal abscess.

BACKGROUND: Intra-abdominal abscesses (IAA) often fail to resolve with intravenous antibiotics alone and frequently require drainage. Diagnosis of IAA in postoperative patients with other likely sources of infection is very difficult. PATIENTS AND METHODS: In order to characterize IAA and identify parameters that might facilitate diagnosis, we prospectively examined peripheral blood and pus of 15 consecutive patients with IAA and compared them to samples from 34 consecutive patients with soft-tissue abscesses (STA). RESULTS: Serum interleukin (IL)-10 was elevated in IAA patients, while abnormally detectable serum IL-4 was demonstrated in the pus of both IAA and STA patients. IL-10 in IAA pus was more than 11-fold higher than in STA, whereas IL-4 in pus was similar in both types of abscesses. Both IL-4 and IL-10 were 4- to 10-fold higher in IAA and STA pus than in corresponding patient serum. Serum lysozyme was, however, significantly elevated in all abscess patients. CONCLUSIONS: The presence of IL-4 and IL-10 may indicate a T-helper 2 lymphocyte response in the etiology of abscess formation and persistence, although precise determination of T-helper 1-related cytokines is needed to verify this. Serum lysozyme and IL-10 may be reliable and relatively inexpensive diagnostic aids.

Abdominal Abscess↗
PubMed1996

CD14 expression in injured patients correlates with outcome.

OBJECTIVE: The authors determined the correlation between monocyte CD14 expression and outcome in severely injured patients. SUMMARY BACKGROUND DATA: Human leukocyte antigen-DR (HLA-DR) expression CD14 positive monocytes correlates with the development of major infection and subsequent death in severely injured patients. Recent studies show that CD14 is not only a marker for mature monocytes, but also is an important endotoxin/lipopolysaccharide receptor. METHODS: Flow cytometry data obtained by dual staining techniques (CD14 and HLA-DR) of monocytes in 213 severely injured patients were analyzed over a 30-day period. Outcome criteria included survival and the development of both major and minor infections. RESULTS: The percentage of cells expressing CD14 (%CD14) correlated with clinical outcome, reaching significance (p < 0.05) between noninfected survivors (n = 74) and nonsurvivors (n = 21) at days 3, 7, 11, 17, 24, and 30. At days 3, 7, and 17, the %CD14 also was different between noninfected and infected survivors. After 7 days, differences were only seen between survivors and nonsurvivors (p < 0.05). The mean fluorescence intensity (MC CD14) in monocytes of all patients was significantly reduced at day 3 compared with day 1 and remained low for 30 days (p < 0.05). The nonsurvivor group had consistently low MC CD14 values, which were significant at day 5 (p < 0.05). CONCLUSIONS: In addition to HLA-DR expression, CD14 expression on monocytes is an indicator of clinical outcome after injury and could represent a more precise target for treatment.

Adolescent↗
PubMed1996

[Admission documentation of multiple trauma patients using the Zurich Trauma Protocol--initial experiences].

A new protocol to document multiply injured patients in presented. It consists of 23 pages and is indexed on the right side. The pages are structured according to the Abbreviated Injury Scale (AIS): head/neck, face, thorax, abdomen, extremities/pelvis and integument. Different checklists on the right side of each page help to enter data efficiently; schemes and templates on the left side provide further support to visualize and classify the injuries. Summaries for diagnosis, therapies and for further investigations provide a standardized overview of the patient. The experiences of 22 residents were analyzed after one year of the protocol use. The trauma protocol was shown to be easy to learn, it was well accepted, and it increased the exchange of information between the emergency room and the intensive care unit. However, some residents considered this data entry to more laborious compared with the traditional medical record system. The trauma protocol was designed for prospective data acquisition of intensive care patients; it provides also a uniform structure for retrospective analysis and is therefore a helpful tool to increase quality control and quality assurance.

Abbreviated Injury Scale↗
PubMed1996

Sepsis and septic complications in the surgical patient: who is at risk?

The estimation of patients who are at risk for infection, sepsis, and organ dysfunction/failure is crucial not only for inclusion in treatment algorithms but also for entry into appropriate clinical trials of prophylaxis and therapy. Patients on the surgical service who have sustained major trauma or who have undergone transplantation are clearly at the greatest risk. Other immunosuppressed patients at risk for sepsis include those receiving myelosuppressive chemotherapy, those with overwhelming malignancy, and those who suffer from cirrhosis, diabetes mellitus, and severe malnutrition. We have focused on the trauma patient, in whom infection and organ failure are the leading causes of late death, major morbidity, and prolonged hospital stay. Over a 10 yr period, we have surveyed a number of host defense parameters that pertain to an adequate immune response and found a suppressed response shortly after injury in many. All were anergic to a standard skin test panel, and the duration of anergy varied with the clinical course of infection. Immunoglobulin levels were low after major injury as well as specific antibodies to both Gram-positive and Gram-negative organisms. The ability of serum from the trauma patient to opsonize heat-killed bacteria was markedly depressed 24 h after injury in those patients who subsequently died of infection. Class II major histocompatibility antigen expression on peripheral blood monocytes correlated closely with clinical outcome and led to the development of an Outcome Predictive Score. This score can identify patients within hours of hospitalization who are at risk of subsequently developing overt clinical infection and sepsis. Intervention then can be applied to such at-risk populations prior to the onset of sepsis and to evaluate the efficacy of prophylaxis. Patients in whom prophylaxis fails could be eligible for trials of therapeutic intervention as well.

Cytokines↗
PubMed1995

Is laparoscopic appendectomy the new 'gold standard'?

OBJECTIVES: To determine the efficacy of laparoscopic appendectomy compared with open appendectomy in patients with acute appendicitis and to compare the morbidity between the two groups. DESIGN: Prospective sampling of 102 patients who underwent diagnostic laparoscopy and laparoscopic appendectomy for acute appendicitis and retrospective hospital chart review of 204 patients who underwent open appendectomy for acute appendicitis. RESULTS: The mean +/- SD duration of surgery was 83 +/- 29 minutes in the laparoscopic group and 64 +/- 30 minutes in the open appendectomy group (P < .001). Hospital stay was shorter in the laparoscopic group (P < .04). There was no difference in the complication rate between the patients who underwent laparoscopic appendectomy (13%) and the patients who underwent open appendectomy (11%). The occurrence of postoperative ileus was correlated with the duration of operation (P < .01) but not with laparoscopic appendectomy. CONCLUSIONS: The results confirm that laparoscopic appendectomy had a longer time of surgery, a shorter hospital stay, and no difference in complications. Further investigation will likely establish that laparoscopic appendectomy can be considered the "gold standard."

Acute Disease↗
PubMed1995

Laparoscopic treatment of biliary and gastric outlet obstruction.

To avoid laparotomy in patients with biliary or gastric outlet obstruction in inoperable carcinoma of the pancreas, we evaluated the feasibility of double-bypass operation in 20 pigs. In model A (n = 10), biliary bypass was a Roux-en-Y loop for cholecystojejunostomy after choledochal clip occlusion. In model B (n = 10) an additional Roux-en-Y loop was attached to the stomach after transection of the duodenum. Model A showed functioning biliary bypass with patent and leak-free anastomoses at necropsy on day 28. In model B, four pigs were sacrificed earlier, but nine had normal functioning double bypass (two intussusceptions of the ileum, one bleeding ulcer at the gastroenterostomy, one necrotic Roux-en-Y-loop). Based on the presented bypass function, we are encouraged to perform laparoscopic biliary and gastroenteral bypass in humans to treat malignant jaundice and gastric outlet obstruction.

Anastomosis, Roux-en-Y↗
PubMed1995

[Determination of serum lead levels following shotgun injury].

Lead concentration of pellets is over 95%. Four patients who had sustained shotgun injury with retained shotgun bullets in the body are described. In 3 of 4 patients the blood level of lead was increased, as well as the concentration of Delta-ALA in the urine. In all four patients symptoms due to lead intoxication were absent. Usually the surgical goal is limited to a proper debridement of large wounds in the soft tissue. Therefore it is mandatory to assess the lead level in the blood and the concentration of Delta-ALA in the urine. Thus asymptomatic lead intoxication can be recognized and treated.

Adult↗
PubMed1995

[Chylothorax after blunt thoracic trauma].

The diagnosis of chylothorax following blunt chest trauma is rare, only few cases have been reported. We describe three patients with chylothorax following blunt chest trauma. Conservative treatment consists of drainage, in severe cases mechanical ventilation with PEEP and total parenteral nutrition. In case of persisting and/or increasing chylus production, thoracotomy and ligation of the thoracic duct may be required. In all of our patients thoracostomy was the definite therapeutic modality, no thoracotomy was necessary.

Adult↗
PubMed1995

[Quality control in peripheral vascular surgery].

Indications and modalities of quality control in infrainguinal bypass surgery are reviewed and discussed. A concept and an armamentarium for its practical use are presented. The majority of graft occlusions occur during the first postoperative year. Most failures in the first month are due to technical errors. Many of these can be detected by intraoperative completion control, and immediately repaired. This contributes to improved graft patency rates. In the further course, myo-intimal hyperplasia accounts for most graft stenoses and occlusions. If stenoses are detected and dilated before occlusion occurs, long-term patency is but little impaired. Conversely, patency rates are clearly inferior in grafts following thrombectomy or thrombolysis. Therefore, identification of failing grafts and avoidance of failure are the objectives of surveillance. We have followed routinely a surveillance program since 1991. During surgery, grafts were controlled by completion angiography. Arterial pressures were measured and the ankle-brachial index calculated postoperatively and 1, 3, 6 and 12 months after surgery. In addition, a number of grafts were followed by duplex sonography. Data were stored in an electronic data base featuring several interactive functions. E.g., ankle-brachial and duplex-sonography indices were calculated and rated automatically according to current criteria. Secondary patency after 18 months was 86 per cent in suprageniculate femoro-popliteal bypass grafts, 84 per cent in infrageniculate and 65 per cent in crural (n = 19/23/27).

Blood Vessel Prosthesis↗