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Biomedical subjects

M E Carr

Publications and source records attributed to M E Carr.

At least 73 records · Page 4Linked to original sources
PubMed1987

The impact of delayed fibrinopeptide-A release on fibrin structure. Studies of an abnormal fibrinogen.

The impact of delayed fibrinopeptide-A release on polymerization and structure of fibrin gels was studied utilizing a heterozygously transmitted variant fibrinogen. An arginine to histidine substitution at position 16 of the alpha chain of the abnormal fibrinogen delayed release of an abnormal fibrinopeptide-A (A) by thrombin and completely blocked release of A by reptilase. When clotted with thrombin, patient fibrin formed more slowly than normal fibrin, but clottability was normal and gel fiber mass/length ratios were decreased less than 10%. Gels formed with reptilase clotted slowly, demonstrated reduced clottability, but had normal fiber mass/length ratios. Reptilase clotted the normal but not the variant component of the patient fibrinogen. Thrombin-induced cleavage of fibrinopeptide-B prior to A occurred in these experiments, but polymerization of this species beyond trimers has been reported to be minimal under the conditions used. With time, A is removed by thrombin resulting in the slow production of normal fibrin monomer from the abnormal component. These monomers subsequently polymerize. The minimal change in gel fiber size caused by slow A release implies that fibrin fiber size is primarily a function of ionic environment and not of the sequence of peptide release.

Arginine↗
PubMed1987

Platelet factor 4 enhances fibrin fiber polymerization.

In order to further examine the role of platelet secretory products on fibrin assembly, we have examined the effects of purified platelet factor 4 (PF4) on fibrin formation in vitro. The kinetics of fibrin formation and the structural properties of the resulting fibrin gel are strongly affected by PF4. In the presence of 7.6 ng/mL PF4, the fibrin fiber mass-length ratio increases from 3.5 X 10(12) daltons/cm. These results emphasize the importance of the local microenvironment in clot structure and its subsequent fate at the site of vascular injury.

Fibrin↗
PubMed1987

Spontaneous antithrombin in a patient with benign paraprotein.

A 66-year-old man with peptic ulcer disease developed a paraprotein that resulted in a spontaneously prolonged prothrombin time, activated partial thromboplastin time, and thrombin clotting time. Although the reptilase time was normal, the thrombin clotting time failed to correct with the addition of normal plasma, calcium, or protamine sulfate. The patient's purified fibrinogen was normal, but his serum contained an IgG that inhibited the clotting of normal plasma and purified fibrinogen in the presence of thrombin. In contrast to previously described paraproteins, this patient's IgG appeared to inhibit the activity of thrombin per se rather than to interfere with fibrinogen cleavage or fibrin polymerization. Although immunoprecipitation between thrombin and the paraprotein could not be demonstrated, the patient's purified IgG, in the presence of thrombin, decreased the thrombin activity on a chromogenic substrate. Further, increasing concentrations of thrombin overcame the inhibitory effect of the patient's paraprotein. Thus, the patient's paraprotein appeared to possess antithrombin activity.

Aged↗
PubMed1987

Trimethoprim-sulfamethoxazole in cyst fluid from autosomal dominant polycystic kidneys.

Cyst infection in patients with autosomal-dominant polycystic kidney disease (ADPKD) is often refractory to therapy, in part because of the limited entry of commonly used antibiotics into cyst fluid. To study the efficacy of trimethoprim-sulfamethoxazole in cyst infection, cyst fluid was obtained by percutaneous aspiration or at surgery from eight patients with ADPKD receiving trimethoprim-sulfamethoxazole. Cysts were categorized as nongradient or gradient by cyst-fluid sodium concentration. Trimethoprim-sulfamethoxazole concentrations within cysts were determined and cyst fluid inhibitory and bactericidal titers were assessed in vitro against Escherichia coli, Proteus mirabilis and Streptococcus fecalis. The mean cyst fluid trimethoprim and sulfamethoxazole concentrations were 15.2 micrograms/ml and 42.5 micrograms/ml, respectively. Preferential accumulation of trimethoprim was observed in gradient cysts, exceeding serum levels more than eightfold. Sulfamethoxazole penetrated cysts to a lesser extent, with concentrations ranging from 10 to 70 percent of the serum level. Cyst fluid sampled prior to trimethoprim-sulfamethoxazole administration (control) demonstrated no antibacterial activity, while cyst fluid inhibitory and bactericidal titers following antibiotic administration were 1:32 or greater in most instances. These studies indicate that trimethoprim-sulfamethoxazole is likely to be efficacious in the treatment of cyst infection in polycystic kidneys.

Adult↗
PubMed1987

Bowel ischemia and infarction. Chronic and acute causes of abdominal pain.

Bowel ischemia and infarction are diseases primarily of, but not confined to, the elderly. Insidiously developing bowel ischemia may mimic more common gastrointestinal disturbances, such as peptic ulcer disease or malignancy, and go undiagnosed for long periods. Bowel infarction is a catastrophic event: Mortality rates approach 90%. Chronic intestinal ischemia may precede infarction, or infarction may occur with no warning. Laboratory and radiologic studies have minimal value in diagnosis of these disorders. A high index of suspicion must be maintained in patients complaining of abdominal pain if these diagnoses are to be made promptly.

Abdomen↗
PubMed1987

Fibrin has larger pores when formed in the presence of erythrocytes.

Due to difficulties caused by the presence of hemoglobin-containing erythrocytes, the structures of whole blood clots have not been reported. A perfusion technique described herein allowed the study of plasma and blood clots. Gel fiber diameter, fiber mass-to-length ratio, and average pore diameter were calculated from measurements of solvent flow through gels. When perfused with saline, intact erythrocytes washed from clots of whole blood. Subsequent perfusion with water resulted in rapid hemolyzing of remaining erythrocytes and flushing of hemoglobin from the network. The minimal impact of erythrocytes on fibrin fiber structure was indicated by similar fiber mass-to-length ratios, 7.4 vs. 9.3 X 10(13) Da/cm, for plasma and blood clots, respectively. Pore sizes were larger in gels formed in the presence of erythrocytes, increasing from 3.3 X 10(-4) cm for plasma gels to 5.1 X 10(-4) for gels containing 20% erythrocytes. The washing of red cells from clots confirmed calculated clot pore sizes (approximately 5 microns) and was testimony to the size of the spaces within the gel. Egress of cells and macromolecules to the site of injury during wound healing may be a function of the size of these spaces. The demonstrated applicability of this technique should allow study of this question.

Blood Coagulation↗
PubMed1987

Turbidimetric evaluation of the impact of albumin on the structure of thrombin-mediated fibrin gelation.

Recent studies have reported an interaction of albumin with polymerizing fibrin, resulting in a narrowing of gel fibers. It has been postulated that albumin interacts with the E domain resulting in delayed and thus altered polymerization. Utilizing turbidity techniques, the impact of human albumin on gels of human fibrin, clotted with human thrombin, was studied. The addition of albumin, at concentrations from 3 to 30 microM, to 1 mg/ml fibrin gels produced less than a 10% change in either the kinetics of turbidity increase or the subsequent fiber mass-length ratio. For a given calcium concentration, saturation of albumin's calcium-binding capacity by prior dialysis ablated even these small effects. Given these findings, it seems unlikely that albumin imposes a physiologically significant influence on fibrin polymerization. Structural changes secondary to albumin-mediated enhancement of factor XIII activity remain a possibility.

Calcium↗
PubMed1987

Influence of factor XIII and fibronectin on fiber size and density in thrombin-induced fibrin gels.

The possible role of fibronectin as a molecular anchor for fibrin to ground substance, the ability of factor XIII to cross-link fibronectin to fibrin, and the demonstrated differences between purified fibrin and fibrin formed in plasma prompted this study of the effect of both proteins on fibrin assembly and structure. The influences of activated factor XIII (FXIIIa) and fibronectin were studied by use of turbidity techniques. Fibronectin over a concentration range of 0 to 800 micrograms/ml produced no change in either the mass-length ratio or density of fibrin fibers in 1 mg/ml fibrin gels. FXIIIa at concentrations as high as 6.5 mumol/L, although not altering fiber mass-length ratio, caused a 30% increase in fiber density. Gels formed in the presence of fibronectin plus FXIIIa demonstrated increasing fiber mass-length ratios and increasing fiber density with increasing fibronectin concentration. Mass-length ratios for gels formed in the presence of 3.24 mumol/L FXIIIa increased from 3.25 to 5.20 x 10(13) daltons/cm as the fibronectin concentration increased from 0 to 800 micrograms/ml. Fiber density increased from 13.6 to 19.1 x 10(22) daltons/cm3 over the same fibronectin range. These results imply that FXIIIa-induced structural changes such as increased elastic modulus may be mediated in part by increased fiber density. Fibronectin alone has virtually no impact on fibrin assembly, but in the presence of FXIIIa becomes incorporated into fibrin and results in increased fiber size and density.

Chemical Phenomena↗
PubMed1986

Influence of Ca2+ on the structure of reptilase-derived and thrombin-derived fibrin gels.

The effects of Ca2+ ion on the structure of thrombin-derived and reptilase-derived fibrin gels formed at various ionic strengths were studied turbidimetrically. For both enzymes clotting times were shorter, final gel turbidities were higher and fibre mass/length ratios were increased as the ionic strength was lowered. The addition of 5 mM-Ca2+ augmented each of these effects for any given ionic strength. In the thrombin system, Ca2+ increased the final gel turbidity from 0.04 to 0.26 A632.8 at ionic strength 0.15. Under identical conditions in the reptilase system, the final gel turbidity increased from 0.03 A632.8 in the absence of Ca2+ to 0.345 A632.8 in the presence of 5 mM-Ca2+. In the thrombin system, fibre mass/length ratios increased from 0.4 X 10(12) to 6.9 X 10(12) Da/cm in the absence of Ca2+, and from 4.4 X 10(12) to 7.9 X 10(12) Da/cm in the presence of Ca2+, as the ionic strengths were decreased from 0.15 to 0.08 and to 0.11 respectively. In the reptilase system, the mass/length ratios increased from 0.9 X 10(12) to 5.8 X 10(12) Da/cm in the absence of Ca2+, and from 4.8 X 10(12) to 8.7 X 10(12) Da/cm in the presence of Ca2+, as the ionic strengths were decreased from 0.15 to 0.08 and to 0.10 respectively. At ionic strengths below 0.10, the presence of 5 mM-Ca2+ caused precipitation and macroscopic aggregation of fibrinogen upon the addition of either enzyme. In the presence of 5 mM-Ca2+, the fibres composing thrombin-induced and reptilase-induced gels were virtually identical.

Batroxobin↗
PubMed1986

Hyperfibrinogenemia as a cause of prolonged thrombin clotting time.

Recognized causes of a prolonged thrombin clotting time (TCT) include a decreased plasma fibrinogen level, dysfibrinogenemia, paraproteinemia, heparin contamination, elevated levels of fibrin degradation products, and liver failure. We have frequently seen patients with an isolated prolonged TCT in the absence of any of these conditions and without obvious clinical impact. During a previous evaluation of hyperfibrinogenemia, we noted a surprisingly high incidence of prolonged TCT, prompting this evaluation of hyperfibrinogenemia as a possible cause. In our prospective study nine patients had a TCT more than 3 seconds longer than a matched control subject's TCT, with simultaneously normal prothrombin and activated partial thromboplastin times. Eight patients had fibrinogen levels more than 100 mg/dl above the control level (range 383 to 1,223 mg/dl). Only one patient's prolonged TCT could be explained on the basis of elevated levels of fibrin degradation products. In vitro studies in both a purified fibrinogen system and in plasma confirmed a delay in TCT with increasing initial fibrinogen concentrations. Kinetic measurements demonstrated a slowing of the normal initial increase in turbidity seen upon the addition of thrombin. Possible explanations include binding of thrombin to fibrin, or interference with fibrin assembly by excess fibrinogen. Regardless of the kinetic explanation, isolated prolongations of TCT due to hyperfibrinogenemia appear to be of minimal clinical significance.

Adult↗
PubMed1986

Effect of hydroxyethyl starch on the structure of thrombin- and reptilase-induced fibrin gels.

The effect of hydroxyethyl starch (HES), a complex polysaccharide colloid plasma expander, on the structure of fibrin gels was studied turbidimetrically. HES at concentrations as low as 2.5 mg/ml shortened the lag phase of turbidity increase and caused increased fibrin fiber mass/length ratios in both purified fibrin and plasma systems. For purified fibrin gels clotted with thrombin the mass/length ratio increased in a linear fashion from 2.6 to 6.1 X 10(12) daltons/cm as HES increased from 0 to 15 mg/ml. Fiber mass/length ratios for purified fibrin gels clotted with reptilase increased from 1.1 to 6.4 X 10(12) daltons/cm over the same HES concentration range. The addition of 5 mmol/L calcium to either system produced additional increases in fiber size. In 1:10 dilutions of plasma, HES shortened the lag phase, enhanced the rate of turbidity increase, and increased the final gel turbidity. The fiber mass/length ratio for plasma gels clotted with thrombin increased from 0.3 to 1.7 X 10(12) daltons/cm as HES increased from 0 to 20 mg/ml. For plasma gels clotted with reptilase, the fiber mass/length ratio increased from 1.5 to 2.4 X 10(12) daltons/cm over the same HES concentration range. The effects of HES are comparable to those of dextran at concentrations less than 5 mg/ml and can be explained on the basis of HES-enhanced lateral association of fibrin fibers during polymerization.

Batroxobin↗
PubMed1986

Granulocyte lysosomal cationic protein alters fibrin assembly: a possible mechanism for granulocyte control of clot structure.

The effect of highly positively charged molecules on the assembly and structure of thrombin-induced fibrin gels was studied with turbidity techniques. Lysosomal cationic proteins (LCP) extracted from rabbit heterophils produced enhanced lateral association of fibrin fibers. A crude extract of LCP had little effect on kinetics but produced an increase in the final fiber mass/length ratios. A purified fraction, LCP-5, of the crude extract enhanced both the initial rate of increase and final turbidity of fibrin gels. Mass/length ratios obtained for fibrin fibers as a function of LCP-5 concentration varied from 4.3 X 10(12) in the absence of LCP-5 to 7.8 X 10(12) daltons/cm at 1 microgram LCP-5/ml. Similar studies were conducted with protamine as the perturbant of fibrin assembly. Mass/length ratios were increased from 5.7 X 10(12) daltons/cm with no protamine to 8.5 X 10(12) daltons/cm at 100 micrograms protamine per milliliter. High concentrations of both LCP and protamine precipitated fibrinogen. This phenomenon may imply a mechanism by which the blood cellular components may modulate clot structure through the release of highly charged molecules such as LCP-5.

Animals↗
PubMed1985

Nasal packing with porcine fatty tissue for epistaxis complicated by qualitative platelet disorders.

Medications and renal failure are common causes of qualitative platelet disorders. Epistaxis occurring in these settings may be unresponsive to conventional therapy. Two patients with epistaxis and platelet dysfunction are presented who were successfully treated with porcine nasal packing. The technique, previously shown effective in thrombocytopenic patients, is inexpensive, simple, and effective. The procedure is described and its possible modes of action are discussed. The pathogenesis of platelet disorders induced by uremia and aspirin are also briefly discussed.

Adipose Tissue↗