Search PubMed⌕ Search

Biomedical subjects

D E Hammerschmidt

Publications and source records attributed to D E Hammerschmidt.

At least 73 records · Page 4Linked to original sources
PubMed1985

Blood-membrane interaction: C3a, an indicator of biocompatibility.

An interest in hemodialysis-related patient symptomatology dating back to the beginnings of maintenance hemodialysis (HD) therapy prompted our investigations to determine the etiology of such discomfort. Since the discovery by Craddock et al (1) of the activation of the alternative complement pathway by hemodialyzer membrane, our efforts toward defining the relationship of symptoms to complement activation have been done in collaboration with the Minnesota group. Results of an earlier blinded study, (2) and continuing investigations of HD membranes provide data which support the contention that complement activation, although not necessarily etiologic in the symptoms related to dialysis, serves as an indicator of membrane compatibility. These newer data reveal C3a rises in vivo and in vitro by a Japanese processed cuprammonium membrane for dialysis to be similar to cuprophane. In vivo C3a elevation using Travenol CA-110 hemodialyzers of cellulose acetate are significantly lower and are similar to earlier results obtained by cellulose acetate of CD manufacture.

Cellulose↗
PubMed1985

Sodium morrhuate stimulates granulocytes and damages erythrocytes and endothelial cells: probable mechanism of an adverse reaction during sclerotherapy.

Stimulated by a patient with dyspnea, thrombocytopenia, and leukopenia after sodium morrhuate sclerotherapy, we studied the effect of this agent on the plasma coagulation and complement systems, the formed elements of the blood, and cultured human endothelial cells. The addition of sodium morrhuate to citrated plasma did not cause clotting or shorten the prothrombin time or partial thromboplastin time. Incubation of a 1:100 dilution of the clinical sodium morrhuate preparation in heparinized plasma led to a modest rise in [C3a]. The addition of the drug (dilutions 1:50 to 1:300) to granulocytes caused prompt aggregation (and, at the higher concentrations, granulocyte cytotoxicity [trypan blue exclusion; lactate dehydrogenase release]), but the same dilutions failed to aggregate platelets. However, 0.05% morrhuate added to washed red blood cells caused a prompt 84.0% (+/- 0.8% SEM) hemolysis, rendering the supernatant buffer a potent platelet aggregant. Not only was this sclerosing agent toxic to granulocytes and red cells, but a 1:1000 dilution of the drug also caused the destruction of 35.5% (+/- 6.6%) of cultured endothelial cells as measured by chromium 51 release. Three other agents in current use (ethanolamine oleate, sodium tetradecyl sulfate, and polidocanol) were studied and found to cause effects qualitatively similar to those of sodium morrhuate. We conclude that these drugs cause phlebosclerosis not primarily through induction of plasma coagulation, but by directly damaging endothelium and red cells, triggering platelets, and aggregating granulocytes at the venous wall endothelium. These effects likely derive from the surfactant properties of sodium morrhuate as well as its high arachidonate content.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1984

Ibuprofen inhibits granulocyte responses to inflammatory mediators. A proposed mechanism for reduction of experimental myocardial infarct size.

The use of nonsteroidal antiinflammatory agents to reduce myocardial infarct size has demonstrated a dichotomy between ibuprofen, which reduces myocardial infarct size, and aspirin, which does not. A feline model of coronary ischemia using ligation of the anterior descending artery demonstrated that intravenous ibuprofen (2.5-20 mg/kg) given immediately and 2 h after ligation significantly decreased (by about 40%) myocardial infarct size. In contrast, aspirin did not diminish infarct size at any achieved dose; in fact, at some doses it tended to increase infarct size. In vitro studies with purified granulocytes demonstrated a similar dichotomy between ibuprofen and aspirin. Ibuprofen inhibits granulocyte aggregation, superoxide production, lysosomal enzyme release, and granulocyte-mediated endothelial cytotoxicity, while aspirin is without effect on these modalities. We propose that ibuprofen's beneficial effect in experimental myocardial ischemia is related to its ability to inhibit activated granulocytes and thus to diminish myocardial cell death in experimental myocardial infarction.

Animals↗
PubMed1984

Protein loss induced by complement activation during peritoneal dialysis.

A variable loss of macromolecules during peritoneal dialysis has been noted in both humans and experimental animals. We investigated the potential role of the complement system for inducing protein loss during peritoneal dialysis, both to shed light on clinical variability of protein loss and to develop a model for quantitatively studying complement-induced microvascular protein leakage. Rats received intra-arterial injections of a fluorescent dye conjugated to rat serum albumin and underwent a 3.5-hr series of 15-min peritoneal dialysis exchanges. After the control exchanges, rats received either intra-arterial zymosan-activated rat serum, saline, unactivated rat serum, or endotoxin; other rats received an intraperitoneal injection of endotoxin, histamine, phenylephrine, or nitroprusside. The drainage volume from each exchange was measured, and the concentrations of labeled albumin, total protein, and urea were determined by spectroscopy. Zymosan-activated rat serum and endotoxin injections (both intraperitoneal and intra-arterial), each of which may activate the alternative pathway of complement, produced a dramatic increase in dialysate protein concentrations. In addition, histamine, which is a vasodilator but which may also be involved as a mediator of the activated complement system and/or endotoxemia, also produced an increase in dialysate protein concentrations. On the other hand, drugs which may alter peritoneal blood flow such as the vasodilator nitroprusside or the vasoconstrictor phenylephrine, did not affect dialysate protein concentrations. These data suggest that activation of the alternative pathway of complement may cause variation in protein loss during peritoneal dialysis and that in some situations, pharmacological control of this system could be an important therapeutic consideration.

Animals↗
PubMed1984

Hemodynamic profile of adverse clinical reactions to Fluosol-DA 20%.

Hemodynamic changes of 2 patients to a 0.5-ml test-dose infusion of Fluosol-DA 20% are presented. The first patient had the following symptoms and signs approximately 2 min after receiving the test dose: normotensive bradycardia of 30 beat/min, a 35% drop in cardiac output, a 50% increase in systemic vascular resistance, and a 100% increase in pulmonary artery systolic and diastolic pressures. The patient complained of shortness of breath and diffuse pressure pain of the chest. All the signs and symptoms gradually resolved without treatment over the following 3 min. The second patient complained of mild, vague chest and abdominal pressure 2 min after the test dose. The only associated hemodynamic change was a slight increase in pulmonary artery systolic pressure. A 74% drop in the neutrophil count returned to the pretest value in 10 min. In contrast to anaphylactic or anaphylactoid-type reactions, these patients did not have urticaria and had an increase in systemic vascular resistance. Their reactions were reminiscent of those occurring during systemic complement activation. The possible mechanisms and prevention of these reactions are discussed.

Adult↗
PubMed1984

Chemotactic and phagocytic responses of human alveolar macrophages to activated complement components.

Human alveolar macrophages (AMs) migrated toward and aggregated to C5a but not toward C5a-deficient serum. Human AMs from cigarette smokers migrated significantly farther than did AMs from nonsmokers. Human AMs phagocytized Escherichia coli opsonized with activated C3. Immunoglobulin G was not required for phagocytosis. Human AMs demonstrate chemotaxis and aggregation to C5a. Further, human AMs can phagocytize bacteria coated with activated C3.

Chemotaxis↗
PubMed1984

Effect of dialyzer reuse on complement activation and neutropenia in hemodialysis.

A prospective study of 10 patients undergoing hemodialysis showed that less neutropenia and complement activation occurred with dialyzer reuse. Neutrophil counts fell 95% +/- 5% (SEM) with first use and 66% +/- 8% and 48% +/- 10% with second and third uses, respectively (p less than 0.05). The production of complement component C5a-desarg, as measured by the bioassay granulocyte aggregation, was decreased by 96% +/- 1% and 93% +/- 2% with second and third uses, respectively (p less than 0.05). We investigated the role of the dialyzer disinfectant formaldehyde in decreased neutropenia. In vitro, formaldehyde inhibited granulocyte aggregation and chemotaxis and the dialyzer membrane's ability to generate granulocyte aggregating activity; however, this occurred only at concentrations higher than those likely to obtain in patients. The ability of dialysis membranes to generate granulocyte aggregating activity in plasma was decreased 55% +/- 5% by their prior sequential preincubation in plasma and then formalin (p less than 0.05) and extensive rinsing, which is similar to the circumstances obtaining with dialyzer reuse. Preincubation of membranes in plasma or formalin alone resulted in no change in the membrane's ability to generate granulocyte aggregating activity. We conclude that the exposure of membranes to both plasma and formalin during dialysis and storage is responsible for the decreased C5a-desarg production with reuse, probably because plasma proteins are fixed to the membrane in such a way that interrupts free interaction between the membrane and plasma complement components.

Agranulocytosis↗
PubMed1984

Amniotic fluid activates complement. A role in amniotic fluid embolism syndrome?

A 30-year-old woman died with massive pulmonary microvascular leukostasis immediately after cesarean hysterectomy. We postulated that this might have resulted from amniotic fluid embolization and, therefore, tested amniotic fluids as activators of granulocytes and the plasma complement system. Normal human amniotic fluid failed to aggregate granulocytes, provoke a respiratory burst, or attract the cells chemotactically. However, amniotic fluid activated complement when incubated with normal plasma. The ability to activate complement resided in lipid-rich particulate material in the fluid, and activation proceeded mainly (but probably not exclusively) via the alternative complement pathway. Amniotic fluids varied widely in their ability to activate complement, with the most potent samples derived from women with distressed pregnancies. Plasma samples from donors also varied widely in their ability to be activated by amniotic fluid, and many of the most activatable plasma samples derived from gravid women. We propose that amniotic fluid embolization can, like "shock lung" syndrome, have a leukostatic early phase, and that complement and granulocyte activation on embolization of amniotic fluid can contribute to the pulmonary collapse characteristic of that syndrome, especially when a potently activating fluid is combined with a potently activatable plasma.

Adult↗
PubMed1984

Quantitative assessment of leukostasis in experimental hypovolemic-traumatic shock.

Using a hypovolemic-traumatic shock model without reinfusion of shed blood, 111In-oxine-labeled granulocytes were injected to quantify pulmonary leukostasis in dogs. Labeling was facilitated by a non-traumatic and rapid technique for granulocyte processing and a commercially available 111In-oxine solution. Lung biopsy material taken before and after shock showed granulocyte-associated radioactivity to be significantly increased 90 min after the onset of shock. This observation established that pulmonary leukostasis in shock models is not caused solely by reinfusion of shed blood, but rather by humoral factors operative during shock, e.g. by complement activation. The described experimental design should also be useful for in vivo tests of drugs which act on granulocyte function and may have a potential place in the management of shock.

Animals↗
PubMed1983

Chronic myelogenous leukemia. Development of blast crisis with both lymphoid and myeloid features.

A 50-year-old man had chronic myelogenous leukemia and entered a blast crisis that was both morphologically and histochemically lymphoid. The blasts contained terminal deoxyribonucleotidyl transferase and expressed lymphoblastic leukemia-associated antigen. He rapidly entered remission with vincristine sulfate and prednisone therapy. Nevertheless, his blasts displayed a marker generally considered unique to myeloid cells: they selectively bound the granulocyte chemotaxin N-formyl-Met-Leu-Phe. In addition, some cells contained granules resembling those of basophils or mast cells. Such mixed myeloid-lymphoid features in chronic myelogenous leukemia blast cells may reflect malignant transformation of a stem cell capable of both myeloid and lymphoid differentiation, or they may reflect the dedifferentiation as a feature of malignant change.

Antigens, Neoplasm↗
PubMed1983

Fatal complement-induced leukostasis after diatrizoate injection. Principles of clinicopathologic diagnosis.

A case of fatal radiographic contrast medium (RCM)-induced pulmonary granulocyte aggregation (leukostasis) showed massive elevation of the postmortem histamine level. Suspicion of this phenomenon in diverse clinical settings permits clinical and pathological documentation via increased plasma levels of C3a and other means. The existence of effective prophylaxis stimulates a search for predictive tests.

Aged↗
PubMed1983

Mechanisms of vascular damage in gout and oxalosis: crystal induced, granulocyte mediated, endothelial injury.

Immune triggered granulocyte (PMN)-endothelial interactions have been implicated in the pathogenesis of vascular diseases. While hyperuricemia and gout are associated with an increased risk of atherogenesis, we studied the modulation by monosodium-urate (MSU) crystals of PMN-endothelial interactions in vitro. The relationship between calcium oxalate (COX) crystals - implicated in the vasculitis of primary oxalosis - and immunologically mediated endothelial injury was also explored. Both MSU- and COX-crystal treated sera stimulate PMN to adhere to and induce significant 51Cr-release from endothelial cells in vitro. Platelets significantly increase crystal-triggered PMN endothelial cell adherence and 51Cr-release. This platelet augmenting effect depends on the release of platelet constituents (e.g. serotonin). Microcrystalline material present in vessel walls, thus may cause C-activation and may trigger PMN and platelets to damage endothelium in vitro and in vivo. These findings may have relevance to the understanding of the accelerated atherogenesis of hyperuricemia and the fulminant vasculitis of oxalosis or ethylene glycol poisoning.

Blood Physiological Phenomena↗
PubMed1983

Hyperacute pulmonary vasculitis in rabbits receiving prolonged infusions of activated complement. A possible model for triggering events in adult respiratory distress syndrome.

We have postulated a role for activated plasma complement and for stimulated granulocytes in the triggering events of the adult respiratory distress syndrome (ARDS). Because brief periods of complement activation have proved to be pale mimics of the clinical syndrome, we extended our earlier models by infusing potently activated plasma complement into rabbits over a prolonged period of time (3 h). The expected leukostasis occurred, but pulmonary dysfunction remained modest. Nonetheless, piecemeal microvascular necrosis did develop, rendering this current model more credible than former models as a mimic of triggering events in ARDS; longer-term follow-up of such animals will be necessary to determine if this is indeed the case. Perhaps of even greater interest, the neutrophilic leukostasis was observed to progress over the 3 h to a predominantly lymphocytic leukostasis, a dramatically more rapid progression than is typical of such immune complex diseases as serum sickness and the Arthus reaction; further studies are in progress to elucidate the mechanism of this lymphostasis.

Acute Disease↗
PubMed1983

Aggregation, chemotaxis, and chemiluminescence of canine granulocytes. Studies utilizing improved cell preparation techniques.

Wishing to extrapolate in vitro observations of granulocyte function and pharmacology made with human cells to animal models of diseases in which we believe granulocyte stimulation to play a major role, we examined techniques for preparation of canine granulocytes and conducted a survey of the function and pharmacology of those cells. Isotonic density gradients of Percoll proved a simple and highly satisfactory method of preparation. Canine granulocytes in most respects paralleled human cells in function and pharmacology, except that canine cells lacked receptors for formylated oligopeptides and resisted them as stimuli; canine plasma contained a heat-labile inhibitor of canine PMN aggregation, oxidative metabolism, and myeloperoxidase release; canine PMNs were not inhibited in aggregation by protease inhibitors such as aprotinin; canine response to ibuprofen and steroids was more variable than that of human cells, and synergy between those agents was less readily demonstrated; heterologous stimulation (canine cells by human C5a or vice versa) led to a different time course and maximum response from those observed in the homologous systems. Canine granulocytes were readily marked with indium-111, and functioned normally in vitro and survived well in vivo after marking. We conclude that the dog is a suitable animal for studying the role of stimulated PMNs in disease, as long as the observed differences are taken into account in experimental design and data interpretation.

Animals↗
PubMed1983

Symptoms and activation of granulocytes and complement with two dialysis membranes.

Complement (C) activation, neutropenia, and mild pulmonary dysfunction attend hemodialysis (HD) with cellophane [for example, cuprophan (Cu)] membranes. While usually asymptomatic, these phenomena may cause distress in patients with cardiopulmonary disease, and "start-up" symptoms of HD might be mediated by C-stimulated granulocytes (PMNs). Cellulose acetate (CA) hemodialysis membranes have been devised and claimed more blood compatible than Cu. In a blinded series of HD patients, pruritus, fatigue, and sense of well-being were each scored statistically more favorably by the patients during HD with CA than during HD with Cu (P less than 0.05). Postulating that less C activation might underlie the benefit, we showed that neutropenia was less severe with CA (nadir 77.6% of initial count, +/- 4 SEM) than with Cu (38.3% +/- 2.9; P less than 0.01). In vitro, incubation of CA membranes with plasma led to less C3 conversion (20% vs. 40%), less PMN aggregating activity (5.9 ZAP units vs. 36.3) and less decrement in CH50 (6.5% vs. 22%) than like incubations of Cu. C activation was also less potent in vivo: During HD plasma C3a rose from a mean 401 ng/ml to a peak 6,325 in patients on Cu dialyzers, but from 426 to only 3,637 in patients on CA devices (P less than 0.05). Time-course studies suggested CA was initially as potent an activator as Cu but rapidly lost ability to activate C, possibly because of saturation of C3b binding sites. As an index of PMN activation, we also assayed plasma lactoferrin and found levels significantly higher during Cu than CA dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylatoxins↗
PubMed1983

Complement activation by trichophyton rubrum.

The role of complement in infections by dermatophytes is unknown. Therefore we evaluated the ability of the dermatophyte Trichophyton rubrum to activate complement in vitro. Aliquots of human plasma that had been incubated with T. rubrum were examined for evidence of complement activation. Following incubation, the total hemolytic complement activity of plasma fell 76%. Further, each T. rubrum incubation led to obvious C3 conversion and generation of polymorphonuclear leukocyte (PMN) aggregating activity. Plasma that had complement activity depleted by heat (56 degrees C x 30 min) or 10 mM EDTA failed to develop C3 conversion or PMN aggregating activity. Complement activation was not affected when the classical complement pathway was selectively blocked by MgEGTA. These studies indicate that T. rubrum can activate the complement system by the alternative pathway. The consequent generation of anaphylatoxins, chemotaxins, and opsonins might be important both in host defense against dermatophytic infections and in the inflammatory reactions mediated by them.

Animals↗