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Biomedical subjects

C Hammer

Publications and source records attributed to C Hammer.

At least 19 recordsLinked to original sources
PubMed2006

Fluorescent microspheres reveal different regional blood flow in hyperacutely rejected nontransgenic and hDAF pig hearts.

Classic features of hyperacute rejection show differential severity in the inner compared to the outer myocardium. In the present study, regional blood flow (RBF) measured by fluorescent microspheres served as a marker of the extent of hyperacute rejection. Using a working heart model, hearts of nontransgenic and hDAF transgenic pigs were perfused with human blood. Additionally, hDAF transgenic pig hearts were perfused with human blood containing GAS914 or the GPIIb/IIIa inhibitor tirofiban. Injections of fluorescent microspheres into the donor heart were performed in situ and during perfusion. Reference arterial blood samples were collected from the inferior aorta and the afterload line. Perfusion was terminated before hyperacutely rejected hearts failed to pump against the afterload column. RBF was determined in tissue samples of standardized areas of the left atrium and ventricle. Each specimen was divided into subepicardial and subendocardial tissue samples. Fluorescence intensity was measured using an automated luminescence spectrometer. At the end of perfusion with human blood, hyperacutely rejected nontransgenic pig hearts showed a higher RBF in the subendocardium. In hDAF-transgenic pig hearts perfused with unmodified human blood the subendocardial/subepicardial blood flow ratio changed in favor of the subepicardium. This ratio was not further improved by GAS914. In contrast, tirofiban was able to assimilate subepicardial and subendocardial blood flow. In conclusion, RBF of hyperacutely rejected pig hearts was inhomogeneous. Inhibition of complement activation improved the reduced subepicardial RBF, but depletion of antibodies had no positive effect. The ability of tirofiban to further increase subepicardial RBF affirms thrombosis of subepicardial veins as the defining characteristic of hyperacute rejection.

Acute Disease↗
PubMed2005

Influence of polyclonal ATGs on expression of adhesion molecules: an experimental study.

BACKGROUND: The aim of our study was to assess the influence of polyclonal antithymocyte globulins (ATGs) on the expression of adhesion molecules on lymphocytes, neutrophils, and thrombocytes by means of flow cytometry. ATGs are employed in various regimens for solid organ transplantation. Immunosuppression with ATGs may influence the expression of adhesion molecules on thrombocytes, lymphocytes, and neutrophils due to nonspecific antibodies directed against myeloid and nonmyeloid cells. MATERIAL AND METHODS: Depletion, activation, and expression of adhesion molecules on thrombocytes (CD41, CD42, CD62p and CD107a), neutrophils, and lymphocytes (CD11, CD18, CD62L) were studied in vitro in whole blood of healthy volunteers by means of flow cytometry after incubation with different dosages of three ATGs. RESULTS: Our data showed no ATG-mediated cytotoxic activity against platelets. ATGs were able, however, to induce activation of platelets through increased expression of P-selectin and hLAMP-1. ATGs also influenced the expression of adhesion molecules on lymphocytes and neutrophils by reducing the expression of CD62L. Furthermore, the effects of ATG on CD11/CD18 were dependent on the dosage and type of ATG. CONCLUSION: Polyclonal ATGs induced expression of adhesion molecules and activation of unstimulated thrombocytes as well as reduced the expression of adhesion molecules on lymphocytes and neutrophils. Increased adhesion of thrombocytes may be responsible for the undesirable side effects observed in clinical practice such as thrombocytopenia. However, reduction in the expression of adhesion molecules on lymphocytes and neutrophils may decrease the effects of ischemia/reperfusion injury.

Antigens, CD↗
PubMed2004

Impact of small variations of ischemia time after polyclonal antithymocyte globulins in a nonhuman primate model of ischemia-reperfusion injury.

Ischemia-reperfusion injury leads to increased leukocyte adherence enhancing acute cellular rejection, causing microvascular dysfunction and tissue damage. The length of the ischemic time is important in clinical transplantation. Polyclonal antithymocyte globulins (pATGs) induce T-cell depletion and functional impairment of nondepleted lymphocytes. In this study cynomolgus monkeys were used to evaluate the impact of three different pATGs on the microcirculation, on leukocyte behavior and infiltration, as well as on tissue damage after two different periods of ischemia (60 and 150 minutes). pATGs were administered 30 minutes before ex vivo reperfusion. Using intravital fluorescence microscopy, the postreperfusion microcirculation was visualized in vivo. Morphologic analyses were performed on biopsies obtained after the experiments. Significant differences were observed between the two periods of ischemia in both the ATG-treated and control groups. Minimizing ischemia time, even in short intervals, improves the outcome of ischemia-reperfusion injury by reducing leukocyte adherence to the antigen-presenting endothelial cells, improving the microcirculation, and reducing tissue damage.

Animals↗
PubMed2004

Hormonal counterregulation during severe hypoglycaemia under everyday conditions in patients with type 1 and insulin-treated type 2 diabetes mellitus.

AIM: To determine the counterregulatory hormonal responses to severe hypoglycaemia (SH) in type 1 versus insulin-treated type 2 diabetic patients under everyday conditions. METHODS: Counterregulatory hormones were determined in 28 consecutive type 1 and thirteen insulin-treated type 2 diabetic patients (age 54 +/- 18 vs. 75 +/- 13 yrs; diabetes duration 27 +/- 16 vs. 21 +/- 6 yrs) with SH requiring emergency treatment. Blood samples were taken prior to and after effective treatment of SH. SH was defined as an event with neuroglycopenic presentation requiring external intervention by administration of intravenous glucose or oral carbohydrates. 68 % (19/28) of type 1 diabetic patients but none of those with type 2 diabetes had reduced awareness of hypoglycaemia. RESULTS: Plasma glucose levels were 30 +/- 14 prior to and 179 +/- 82 mg/dl after treatment of SH; the time between the two measurements was 54 +/- 26 minutes. With the exception of higher levels of human growth hormone in type 1 patients - which were attributed to younger age - the other counterregulatory responses to SH showed no significant differences in type 1 vs. type 2 diabetic patients. In both groups glucagon responses were virtually absent while moderate catecholamine responses could be demonstrated. Treatment with beta-blockers did not affect hormonal counterregulation in type 1 diabetic patients. CONCLUSIONS: In patients approaching the insulin-deficient end of the spectrum of type 2 diabetes the hormonal responses to SH are comparable to those in patients with longstanding type 1 diabetes. Thus, in advanced type 2 diabetes the risk of developing SH may be similar to that in individuals with type 1 diabetes.

Adolescent↗
PubMed2004

Xenotransplantation--will it bring the solution to organ shortage?

Xenotransplantation, the transplantation of organs, tissues and cells from animals, preferably pig-to-man, might be considered to become the transplantation of the future. Organs from domestic animals are available in unlimited numbers for xenogeneic transplantation and could swiftly solve the problem of organ shortages. Domestic animals of about the same size as human beings would be ideal organ sources. By selective breeding the anatomical and some physiological characteristics of these animals could be at least partly adapted to match the human body. However, the immunological mechanisms and the antigenicity of cells and their surface structures will remain obstinately unaltered. The only hope is that wide-reaching transgenic manipulation of animals, will soon achieve great changes in immunological and physiological circumstances.

Animals↗
PubMed2003

Hormonal counterregulation and consecutive glimepiride serum concentrations during severe hypoglycaemia associated with glimepiride therapy.

OBJECTIVE: To examine the release of counterregulatory hormones and consecutive glimepiride serum concentrations during severe hypoglycaemia (SH) associated with glimepiride therapy. METHODS: In nine type-2 diabetic patients [age 81+/-9 (65-93) years; diabetes duration 9+/-4 (3-15) years; initial blood glucose 33+/-16 (10-54) mg/dl (1.8+/-0.9 mmol/l); HbA1c 7.2+/-1.1 (5.6-8.7)%; creatinine clearance 49+/-33 (15-107) ml/min] who experienced SH associated with glimepiride therapy with neuroglucopenic presentation, insulin, C-peptide, glucagon, epinephrine, norepinephrine, cortisol, adenocorticotrophic hormone (ACTH), human growth hormone (HGH) and pancreatic polypeptide (PP) were determined in blood samples taken at 4-h intervals prior to and during treatment with glucose i.v. Serum from the same samples was screened for sulphonylurea-type oral antidiabetics. Glimepiride concentrations were determined by a validated atmospheric pressure chemical ionization liquid chromatographic-mass spectrometry (APCI-LC-MS) assay. RESULTS: Once treatment had begun, normoglycaemia was maintained; most glimepiride levels were below the limit of detection (LOD <0.01 mg/l) and further sulphonylureas could be excluded. The secretion of glucagon and epinephrine as counterregulatory hormonal responses was unaffected. In addition, protracted marked increases of cortisol and norepinephrine levels were demonstrated. Protracted stimulation of insulin and C-peptide occurred in a period of up to 24 h after SH. No significant protracted responses were observed for ACTH, HGH or PP. CONCLUSION: In SH associated with glimepiride therapy, no correlation between glimepiride serum concentrations and the protracted stimulation of insulin and C-peptide was observed. The secretion of glucagon and epinephrine as counterregulatory hormonal responses was unaffected. Protracted increased release of cortisol might be a medium-term indicator of glimepiride-associated SH.

Aged↗
PubMed2003

Direct assessment and distribution of regional portal blood flow in the pig by means of fluorescent microspheres.

Measurement of regional organ blood flow by means of fluorescent microspheres (FM) is an accepted method. However, determination of regional portal blood flow (RPBF) cannot be performed by microspheres owing to the entrapment of the spheres in the upstream capillary bed of the splanchnic organs. We hypothesized that an adequate experimental setting would enable us to measure RPBF by means of FM and to analyze its distribution within the pig liver. A mixing chamber for the injection of FM was developed, and its capability to distribute FM homogeneously in the blood was evaluated in vitro. The chamber was implanted into the portal vein of six anesthetized pigs (23.5 +/- 2.9 kg body wt). Three consecutive, simultaneous injections of FM of two different colors into the chamber were performed. Reference portal blood samples were collected by means of a Harvard pump. At the end of the experiment, the liver was explanted and fixed in formalin before dissection. FM were isolated from the tissue samples by an automated process, and fluorescence intensity was determined. Comparison of 5,458 single RPBF values, determined by simultaneously injected FM, revealed good agreement (bias 2.5%, precision 12.7%) and high correlation (r = 0.97, r2 = 0,95, slope = 1.04, intercept = 0.05). Median RPBF was 1.07 +/- 0.78 ml x min(-1) x g(-1). Allocation of the blood flow values to the anatomic regions of the liver revealed a significantly higher RPBF (P = 0.01) in the liver tissue located close to the diaphragm compared with the rest of the organ and a significantly lower RPBF (P = 0.01) in the left liver lobe compared with the median and right lobes. The results show that the model presented makes it possible to measure RPBF by means of FM reliably and that RPBF is distributed heterogeneously in the porcine liver.

Animals↗
PubMed2003

Characteristics and time course of severe glimepiride- versus glibenclamide-induced hypoglycaemia.

OBJECTIVE: To compare the clinical characteristics and time course of severe hypoglycaemia (SH) on glimepiride and the reference drug glibenclamide. METHODS: SH was defined as a symptomatic event requiring administration of i.v. glucose or of glucagon. Four hundred doctors working in acute care hospitals were randomly selected from the membership directory of the German Diabetes Association and sent a standardised questionnaire about sulphonylurea-induced SH that occurred between June 2001 and August 2002. Detailed data on history, medication, laboratory parameters, treatment and time course of the SH were analysed. RESULTS: Altogether, 93 episodes of SH were registered, 37 on glimepiride and 56 on glibenclamide. The characteristics of the glimepiride- versus glibenclamide-induced SH were as follows: initial blood glucose 1.9+/-0.66 mmol/l versus 1.8+/-0.89 mmol/l, P=0.17; age 77+/-11.2 years versus 78+/-9.6 years, P=0.35; HbA1c 5.4+/-0.7% versus 5.2+/-0.9%, P=0.18; creatinine clearance 38+/-23 ml/min versus 54+/-32 ml/min, P=0.005; co-medication 6.2.+/-3 versus 3.6+/-3 preparations, P< 0.0001. Even very low doses of glimepiride (0.5 mg) and glibenclamide (0.88 mg) were associated with SH. Prolonged hypoglycaemia requiring more than 12 h i.v. glucose administration occurred in 8 of 37 of the glimepiride-treated subjects and 5 of 56 of those on glibenclamide. Prolonged hypoglycaemia necessitated infusion of 308+/-256 g (104-862 g) i.v. glucose over 43+/-16 h (24-64 h) in glimepiride-treated patients compared with 168+/-98 g (66-300 g) over 33+/-28 h (14-80 h) in glibenclamide-treated patients. Impaired renal function was present in 11 of 13 of all patients with prolonged hypoglycaemia and impaired liver function in 1 of 13. CONCLUSION: In glimepiride- and glibenclamide-treated individuals with SH, no essential differences in the clinical characteristics or time course were shown; prolonged courses also occurred on glimepiride. Even in patients with only mild renal failure both preparations should be used with caution.

Adult↗
PubMed2003

Xenotransplantation: the good, the bad, and the ugly or how far are we to clinical application?

On the way to successful clinical XTP many obstacles have to be overcome, and new difficulties might still arise. For clinical XTP all "players of the concert" have to harmonize. It is not enough if one molecule is recognized by its receptor. A chain is only as strong as its weakest link; this is also true for xenogeneic immunology, physiology, and pharmacology. The phylogeneic distance between man and pig comprises 180 million years. This tremendous distance has to be bridged by new and still unknown methods to outwit evolution.

Animals↗
PubMed2003

Morphological assessment of reperfusion injury in a concordant xenogeneic primate model.

Ischemia and consecutive reperfusion injury of the graft cannot be avoided in organ transplantation. One principal characteristic of this process is the temporary and permanent adherence of leukocytes to endothelial cells of the graft as well as damage of the associated tissue. Polyclonal antithymocyte globulins (ATGs) are used to prevent acute rejection after transplantation and to overcome graft vs. host disease. ATGs induce apoptosis and complement-mediated cell death in peripheral T-lymphocytes having the potential to inhibit leukocyte adhesion by direct binding to adhesion molecules. The aim of the present study was to analyse in a non-human primate model (cynomolgus monkeys) morphological changes within the microvasculature and the different cell-subpopulations upon ischemia/reperfusion after immunosuppressive treatment. Our results show a decrease of the tissue damage and WBC infiltration in muscular structures as well as a lower number of mononuclear cells in peripheral blood in the ATG-treated group compared to a non-treated control group. We may conclude that pATGs have a beneficial effect on the early mechanisms of ischemia/reperfusion injury.

Animals↗
PubMed2003

Induction of immunosuppression with polyclonal antithymocyte globulins: an overview.

The induction of immunological tolerance to solid organ allograft is currently a subject of major investigation due to the morbidity and mortality related to immunosuppressive therapy. Immunosuppression induction by recipient treatment may allow to tailoring the timing and dosage of standard therapy not only reducing adverse reactions but also improving the graft outcome. Depletion of recipient T cells with polyclonal antithymocyte globulins is one of the methods nowadays investigated both in experimental and clinical procedures, demonstrating a better outcome of organ engraftment. Our intention is to give an overview of the literature about the mechanisms of action of polyclonal ATGs, the status of induction treatment in clinical and experimental transplantation as well as of the possible pathophysiological relationships with acquired tolerance, delayed graft failure and ischemia-reperfusion injury.

Animals↗
PubMed2002

Use of RNA arbitrarily primed PCR to identify genomic alterations in the digestive gland of the freshwater bivalve Unio tumidus at a contaminated site.

The technique of RNA arbitrarily primed polymerase chain reaction (RAP-PCR) was developed to detect DNA damage and variations in gene expression in response to exposure to toxic compounds. This approach was tested on the freshwater bivalve Unio tumidus to explore the ability of RAP-PCR to detect effects induced by river sediment contaminated with polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyls (PCBs), and metals. In a first step the primer concentration was optimized to obtain reproducible amplifications of both high- and low-molecular-weight products. Optimized conditions allowed us to detect variations corresponding to the loss of PCR products in some animals exposed at the contaminated site compared with the control. Our results for the RAP-PCR approach performed on separate animals in field studies showed that interindividual variations could correspond to DNA damage and/or variations in gene expression.

Animals↗
PubMed2002

Xenotransplantation for liver therapy or: Can porcine hepatocytes generate physiological functions sufficient for a human patient in ALF?

Detailed knowledge about physiology, biochemistry and function is required before artificial liver devices using porcine hepatocytes may be used successfully. Improvement of cell culture conditions and tissue engineering may permit the generation of human hepatocytes as substitutes for grafts in a transplantation setting. The physiological functions of xenografts have to be compatible with those of the recipient. However, first observations indicate that most physiological interaction in widely divergent species combinations such as pig and man are considerably different. This may be crucial for the selection of a suitable organ, tissue or cell for a clinical set-up. These differences vary from organ to organ and cell to cell. Only very conservative molecules, like for example insulin or calcitonin function properly in both species, while others such as complement, albumin and erythropoietin do not fulfill their task properly or not at all.

Animals↗
PubMed2001

Chronic persistent knee pain after repeated diagnostic arthroscopy: osteoid osteoma, a primarily overlooked diagnosis in a young woman.

We report a case of osteoid osteoma of the distal femur in an adolescent female patient that was primarily overlooked and led to repeated diagnostic arthroscopy of the knee. A thorough history and physical examination of the joint as well as adequate roentgenographic studies could have spared this patient two unnecessary arthroscopies and indicated the correct therapy.

Adolescent↗
PubMed2001

Evaluation of a system for the perfusion of isolated, rodent organs.

Perfusion of isolated organs is a common experimental approach. However, the surfaces of the perfusion system might alter the components of the blood and thereby negatively affect organ function. The aim of this study was to minimize the influence of the perfusion system on the blood components and to evaluate the system. Pressure and flow in the perfusion system consisting of a roller-pump, reservoir, oxygenator, hemo-filter and bubble-trap with a total tubing length of 4.5 m are controlled by a computer software (DASYLAB, Datalog, Moenchengladbach, Germany) via a transducer connected to the system. The organ to be perfused is positioned under a microscope (Orthoplan, Leica, Bensheim, Germany), allowing the investigation of microcirculatory parameters. The images raised are recorded on video tapes. To evaluate the system it was perfused with human blood (Hct 28 to 30%) for 90 min. Heparin (n = 6) or citrate (n = 6) served as anti-coagulants. The disappearance of cells from the blood was determined at time points 0, 1, 5, 10, 15, 20, 30, 45, 60, 75 and 90 min by means of a cell counter (AC T8, Coulter Beckmann, Krefeld, Germany). Cell activation was assessed by analysis of the expression of L- and P-selectin and CD11b. The activation of the complement system was examined by measuring the serum levels of the complement factors C3c and C4. There was no significant loss or activation of the blood cells at any of the above given time points. The serum levels of the complement factors remained within the physiological range and showed no changes throughout the whole experiments. Thus, the perfusion system does not have a negative influence on the blood and its individual components, and is therefore a reliable tool for perfusion experiments.

Acute Disease↗