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Biomedical subjects

M E Carr

Publications and source records attributed to M E Carr.

At least 55 records · Page 3Linked to original sources
PubMed1991

Effects of poloxamer 188 on the assembly, structure and dissolution of fibrin clots.

Poloxamer 188, N.F. (RheothRx), a nonionic block copolymer composed of 2 hydrophilic polyoxyethylene chains connected by a hydrophobic polyoxypropylene chain, normalizes the viscosity of whole blood high in soluble fibrin(ogen) complexes. Normalization may be via a poloxamer 188-induced decrease in fibrin(ogen)-red cell interaction. Our study examined the influences of poloxamer 188 on fibrin assembly and structure. Studies were performed in both purified and plasma systems with a poloxamer 188 concentration range of 0.1-20 mg/ml and specific clotting conditions (fibrinogen 1 mg/ml, thrombin 1 NIH u/ml, pH 7.4 [Tris 0.05 M], ionic strength 0.15 and calcium 5 mM). Fibrin assembly was accelerated in the presence of poloxamer 188. As poloxamer 188 concentration was increased from 0 to 8 mg/ml in plasma: a) the lag phase prior to initial turbidity rise decreased from 25 to less than 5 s; b) the final gel optical density (OD) increased from 0.65 to 1.28 and c) fiber size (mass/length ratio [mu]) increased from 4.3 to 12.6 x 10(13) daltons/cm. Similar results were seen in the purified system with a poloxamer 188 concentration range of 0-8 mg/ml. OD increased from 0.26 to 0.51, and mu increased from 2.3 to 5.3 x 10(13) daltons/cm. Above 8 mg/ml, precipitation of fibrinogen was noted in this system. Since large fibrin fibers tend to be degraded more rapidly, possible poloxamer mediated enhancement of r-tPA-mediated clot lysis was investigated. With r-tPA (70 lu/ml) present at the time of clotting, clot lysis in the presence of ploxamer 188 (8 mg/ml) was 50% complete at 1,600 s compared to 2,540 s for the control. Thus, poloxamer 188-induced alterations in fibrin structure and fibrin-cell interactions may explain some of this agent's interesting hemorrheologic and antithrombotic properties.

Blood Coagulation↗
PubMed1991

Measurement of platelet-mediated force development during plasma clot formation.

We have developed an instrument that measures force development during clot retraction. Clots are formed between an aluminum plate and cup. The plate is coupled to a strain gauge transducer. Force generated by platelets is transmitted to the upper plate and the resulting voltage change is recorded. Calibration using standard weights allows conversion of the voltage signal to dynes/cm2. Study parameters include lag phase prior to force development, maximum rate of force development (MRFD), and maximum force generated (MFG). When controlled for platelet count, ionic strength (0.15), pH (7.4), calcium concentration (10mM), thrombin concentration (1.5 u/ml), temperature, and gap distance (1 mm), measurements are reproducible. Control of each variable is critical since clot retraction depends on platelet function and fibrin structure. At 37 degrees C and 26 x 10(3) platelets/microL, the lag phase was 300 seconds, the MRFD was 0.69 dynes/(cm2 sec), and the force at 1000 seconds (MFG) was 2450 dynes. At 7.5 x 10(4) platelets/microL, the lag phase was 160 seconds, the MRFD was 1.06 dyne/(cm2 sec), and the MFG was 4400 dynes. Decreasing the sample temperature from 37 degrees C to 27 degrees C (75 x 10(3) platelets/microL) increases the lag phase from 170 to 300 seconds, decreases MRFD from 1.06 to 0.66 dynes/(cm2 sec), and decreases the MFG at 1000 seconds from 4,400 to 2,800 dynes. At 15 degrees C, retraction is totally inhibited. This instrument provides a simple way to quantify the impact of altered fibrin structure and platelet function on clot retraction. Measurement of force development during clot retraction may offer a new approach to the study of qualitative platelet dysfunction.

Blood Platelets↗
PubMed1991

Force monitoring of clot retraction during DDAVP therapy for the qualitative platelet disorder of uraemia: report of a case.

The qualitative platelet disorder of uraemia results in decreased primary haemostatic capacity which can result in significant blood loss during invasive procedures. Treatments of the disorder tend to be empirical and include measures such as aggressive dialysis, conjugated oestrogens, and use of DDAVP. Improvement in platelet function is typically monitored by repeated bleeding times. The variability of the bleeding time is an all too recognized limitation of its usefulness. We report here the case of a 35-year old male with end stage renal disease who presented with intractable bleeding secondary to peptic ulcer disease and haemorrhagic gastritis. Platelet function tests including bleeding time, platelet aggregation studies, and clot retraction measurements were monitored before and after intravenous administration of DDAVP (0.3 microgram/kg). The bleeding time which had been 8 min before DDAVP did not change. Platelet aggregation studies revealed improved aggregation by both collagen and adenosine diphosphate. Clot retraction forces were dramatically enhanced after DDAVP. Pre-DDAVP clots containing 72 x 10(9) platelets per 1 and 1 g fibrinogen per 1 produced 90 dynes/cm2 of force at 800 s post-thrombin addition. Identical clots formed with blood drawn 2 h post-DDAVP produced 750 dynes/cm2. The DDAVP dose was repeated after 8 h with obvious slowing of blood loss. The marked effect of DDAVP on clot retraction may allow monitoring of DDAVP therapy utilizing this technique.

Adenosine Diphosphate↗
PubMed1991

Differential effects of divalent cations on fibrin structure.

Calcium, a divalent cation, serves as a cofactor for several reactions of the haemostatic cascade and causes concentration-dependent enhancement of fibrin fibre size and fibrin structure. We have evaluated the ability of magnesium and zinc to influence fibrin assembly and structure. 20 mM magnesium shortened the lag phase prior to turbidity development and increased the fibre mass/length ratio (0.28 to 1.23 x 10(13) Da/cm) in a purified fibrin-thrombin system. In plasma clotted with thrombin, 20 mM magnesium increased fibre mass/length ratios from 0.60 to 1.65 x 10(13) Da/cm. Fibrinopeptide B release was not required for expression of magnesium's effect since lag phase shortening and increased fibre mass/length ratios occurred when clotting was initiated with batroxobin. In all cases, magnesium effects were similar to effects seen with calcium. In the purified system, zinc exerted effects at concentrations as low as 5 microM. At 10 microM, zinc shortened the period prior to turbidity rise from 15.3 to 2.3 s. The final fibre size increased from 0.30 to 1.16 x 10(13) Da/cm over the same concentration range. Zinc caused similar alterations in gels clotted with batroxobin. The lag phase shortened from 38.3 to 15.3 s, and the fibre mass/length ratio increased from 0.49 to 1.47 x 10(13) Da/cm as zinc concentration increased from 0 to 10 microM. The addition of zinc to citrated plasma at concentrations as high as 100 microM had no appreciable impact on fibrin assembly or structure. To avoid possible effects of citrate, zinc was added to fresh non-anticoagulated plasma. At concentrations as high as 100 microM, zinc had no effect on thrombin-induced clot formation or structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1990

Calculation of plasma fibrin fiber mass-length ratios utilizing platelet aggregometers.

We report a technique for measuring plasma gel fiber size utilizing optical platelet aggregometers. Three aggregometers were used to measure gelation kinetics and final gel turbidity: Sienco Model DP247E, Bio-Data Model PAP-2A, and Chrono-log Model 500-VS aggregometer. Each aggregometer was calibrated using dilutions of latex microspheres. Optical densities of microsphere solutions were measured at 626, 670 and 945 nm. Calibration curves were plots of aggregometer readings versus absorbance. Gels of various fiber size were prepared by varying thrombin concentrations and ionic strength. Fiber mass-length ratios were calculated from the wavelength dependence of gel turbidity. Gel optical densities at 640 nm and 945 nm were shown to be linear functions of fiber mass-length ratio. Aggregometer study gels were formed directly in aggregometer cuvettes. Gel formation kinetics were easily measured in the Sienco and Chrono-log instruments. Gelation kinetics in the Bio-Data instrument did not allow measurement of maximum turbidity. The latter value could be measured, however, once gelation was complete. Final aggregometer readings were made one hour after thrombin addition, and were converted to absorbance values using calibration curves. Absorbencies were then converted to mass-length ratios using the optical density versus mass-length ratio plots. Fiber mass-length ratios measured with aggregometers were in good agreement with those measured spectrophotometrically. This technique may allow routine quantification of plasma clot structure utilizing equipment ordinarily available in clinical laboratories.

Fibrin↗
PubMed1990

The prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis in victims of sexual assault.

The prevalence of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in 232 sexual assault victims who presented for examinations between August 1, 1987, and July 31, 1988, was determined. Results are reported for cervical, rectal, and oropharyngeal NG cultures and for cervical and rectal CT smears. Results from a one-week follow-up are also reported. Cervical test results from the initial sexual assault examination were compared with cervical tests on 399 randomly selected female emergency department patients who presented for other gynecological conditions or lower abdominal pain. The victims of sexual assault had ten of 210 positive cervical NG cultures (4.76%), and 13 of 213 positive cervical CT smears (6.1%) at the first visit. These prevalence rates were not significantly different (P = .3058). There were none of 28 positive rectal NG cultures (0%) and one of 22 positive rectal CT smears (4.34%) (P = .451). None of the 43 oral NG cultures was positive. Seventy-three victims returned for follow-up examination. No follow-up cervical, rectal, or oral NG cultures were positive. However, one of 53 follow-up cervical smears for CT was positive, but this was not significantly different than for cervical NG (P = .461). Sexually assaulted patients had ten of 210 (4.76%) cervical NG cultures positive, and nonassaulted patients showed 53 of 393 positives (13.4%) (P less than .001). Assaulted patients had 13 of 213 (6.1%) cervical CT smears positive, and nonassaulted patients showed 33 of 352 (9.3%) positives (P = .11).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Enhancement of red cell washout from blood clots by alteration of gel pore size and red cell flexibility.

Plasma clots formed in the presence of erythrocytes have pores large enough to allow significant perfusion induced washout of red cells. Erythrocyte washout is a function of gel pore size and erythrocyte flexibility. This study evaluated the possibility of increasing cell washout by enhancing gel pore size and/or erythrocyte flexibility. Addition of increasing concentrations of Dextran 40 resulted in gels composed of large fibers with large intervening pores. Gel fiber mass-to-length ratios increased from 2.6 to 8.1 x 10(13) Da/cm as Dextran 40 concentration increased from 0 to 12 mg/ml. Over the same dextran concentration range, perfusion measurements revealed an increase in gel pore diameter from 1.4 to 3.5 x 10(-4) cm and an increase in erythrocyte washout from 8.2 to 30.4% during a 1.5 gel volume exchange. Pentoxifylline was added to blood to enhance erythrocyte flexibility. Whereas turbidity measurements indicated minimal direct impact of pentoxifylline (50 micrograms/ml) on fibrin assembly or structure, perfusion measurements indicated an increase in erythrocyte washout from 8.1 to 13.4% after a 1.5 gel volume exchange. Efforts to evaluate pentoxifylline effects at higher concentrations were hampered by decreased adhesion of the gel to the sides of the perfusion chamber. These results indicate that it may be possible to enhance erythrocyte washout and thereby increase diffusion and perfusion of materials through in situ clots.

Blood Coagulation↗
PubMed1989

Effect of glycosaminoglycans on thrombin- and atroxin-induced fibrin assembly and structure.

This study was performed to quantitate the impact of several glycosaminoglycans (GAG) on fibrin assembly and structure. Gel formation was monitored as the increase in optical density at 633 nm subsequent to thrombin (2 NIH u/ml) or atroxin (0.10 mg/ml) addition to solutions of buffered fibrinogen (1 mg/ml) or plasma. Gel absorbance was measured as a function of wavelength (400 to 800 nm) and gel fiber diameter and mass/length ratio (mu) were calculated. Chondroitin sulfate A (CSA) shortened the lag phase, enhanced the maximal rate of turbidity increase, and increased the final gel turbidity of fibrin gels formed by thrombin or atroxin. CSA (16 mg/ml) increased fiber mu from 1.3 to 3.1 x 10(13) dalton/cm and fiber radius from 6.0 to 8.6 x 10(-6) cm in thrombin-induced gels. Mu increased from 0.7 to 2.7 x 10(13) dalton/cm and fiber radius from 4 to 7.8 x 10(-6) cm for atroxin-induced gels. Above 16 mg/ml, CSA caused fibrinogen precipitation in purified solutions but not in plasma. CSA inhibited thrombin-induced plasma clotting of plasma but effects in atroxin-mediated plasma gels paralleled those seen in purified solutions. Chondroitin sulfate B (CSB)-induced changes in fibrin were similar but slightly less dramatic than those seen with CSA. Mu increased from 0.9 to 2.0 x 10(13) dalton/cm for atroxin-induced fibrin gels and from 0.8 to 2.3 x 10(13) dalton/cm for atroxin-induced gels. Low molecular weight heparin (Mr = 5100) slowed fibrin assembly and reduced fiber size by 50% in thrombin-induced gels. Changes in mu of atroxin-induced gels were much less pronounced (less than 20%).(ABSTRACT TRUNCATED AT 250 WORDS)

Batroxobin↗
PubMed1989

Methylene blue enhances lateral association of fibrin resulting in rapid gelation and thick fiber formation.

Methylene blue (MB) has been suggested as a therapeutic alternative for heparin reversal in patients sensitive to protamine. We investigated the impact of MB on the assembly and structure of thrombin induced fibrin and plasma gels. MB (1,600 micrograms/ml) reduced the thrombin clotting time (TCT) of plasma by 30% and of purified fibrinogen by 46%. Above 1,600 micrograms/ml, TCTs were prolonged due to MB mediated fibrinogen precipitation. The presence of 5 mM CaCl2 masked the effect of MB in both purified and plasma systems and lowered the threshold for MB-induced purified fibrinogen precipitation to 800 micrograms/ml. MB shortened the lag phase prior to thrombin-induced turbidity increase, and enhanced final gel turbidity. The fibrin fiber mass/length ratio increased from 5.2 to 13.1 X 10(13) dalton/cm in purified fibrin gels and from 3.2 to 10.4 X 10(13) dalton/cm in plasma gels as the MB concentration increased from 0 to 200 micrograms/ml. Due to the photooxidant effect of MB on fibrinogen, rapid time-dependent loss of fibrinogen clottability was obvious at low MB concentrations (50 to 400 micrograms/ml). At high MB concentrations, intense MB light absorption partially protected fibrinogen within the sample. Accurate measurements could only be made, however, when MB was added just prior to thrombin and the assays were performed in the dark. While erythrocytes may reduce the impact of MB photooxidation in whole blood, plasma samples must be shielded from light if reproducible results are to be obtained.

Fibrin↗
PubMed1989

Effect of homo poly(L-amino acids) on fibrin assembly: role of charge and molecular weight.

Positively charged molecules such as protamine, leukocyte cationic protein, and the carboxyl terminus of platelet factor 4 have been shown to increase fibrin fiber thickness. Synthetic homo poly(L-amino acids) were used to explore the role of charge and molecular weight of cationic molecules on fibrin assembly. The effects of poly(L-lysine) (PLL), poly(L-glutamic acid) (PLG), poly(L-aspartic acid) (PLA), poly(L-histidine) (PLH), and poly(L-arginine) (PLArg) on the assembly and structure of fibrin gels were studied by using light-scattering techniques. At a PLG (Mr 60,000) concentration of 80 micrograms/mL and a PLA (Mr 20,000) concentration of 64 microgram/mL, neither of these negatively charged polymers produced a detectable change in either fibrin assembly kinetics or final structure. Positively charged PLArg (16 micrograms/mL) caused a 30% increase in fibrin fiber mass/length ratio without calcium. In contrast, PLH (16 micrograms/mL), also positively charged, had no effect in the absence of CaCl2 but produced a 40% increase in fiber mass/length ratio with 5 mM CaCl2. At concentrations as low as 1 microgram/mL, positively charged PLL increased the initial fibrin assembly kinetics and led to larger fiber mass/length ratio. The impact on fibrin mass/length ratio was equivalent for three different molecular weight preparations of PLL (Mr 25,000, 90,000, and 240,000). The lack of a molecular weight effect on fiber thickness and the low polymer concentrations required to produce the perturbation argue against an excluded volume effect as the mechanism by which lateral fiber growth is augmented. Mechanisms by which poly(L-amino acids) may perturb fibrin assembly are discussed.

Fibrin↗
PubMed1989

Calcium destabilizes and causes conformational changes in hyaluronic acid.

The physical properties of proteoglycans found in the extracellular matrix influence the behavior of resident macromolecules, micro-ions, and cells. The forces stabilizing structured regions of hyaluronic acid (HA), a major component of extracellular matrix, were measured. The free energy of stability associated with structured regions within human HA was determined by potentiometric titration. A plot of free energy versus temperature demonstrated that the secondary structure was most stable at 25 degrees C and was destabilized at temperatures near 50 degrees C. In the presence of 5 mM CaCl2, the free energy of stability of the structured regions was reduced by 30 cal/mole. Classical light scattering and viscosity measurements confirmed the impact of calcium on HA. CaCl2 (5 mM) reduced the radius of gyration of HA. Above concentrations of 3 mM calcium, the viscosity of 0.1% HA solutions was reduced sharply. The ability of cells to secrete calcium, combined with the exquisite sensitivity of HA to calcium, may permit cell-mediated modification of the extracellular matrix and thus may facilitate cell motility.

Calcium↗
PubMed1989

Extramedullary blast crisis and hemolytic anemia in a patient with t(3p+;4q-) and rapidly evolving myelogenous leukemia.

We have reported the case of a patient with a rapidly evolving myelogenous leukemia associated with hemolytic anemia, extramedullary evolution, and an isolated translocation of the long arm of chromosome 4 to the short arm of chromosome 3. The hemolytic process was primarily extravascular and was not associated with pyruvate kinase or glucose-6-phosphate dehydrogenase deficiency. Although blasts were absent from the peripheral smear and represented less than 10% of the bone marrow myeloid precursors, multiple organs including the heart, liver, lungs, and spleen were infiltrated with blasts at autopsy.

Anemia, Hemolytic↗
PubMed1989

Lupus anticoagulant and cerebrovascular accident in a patient with neurofibromatosis.

This report describes the case of a young woman with biopsy-proven neurofibromatosis and a history of recurrent fetal wastage who had sudden onset of slurred speech and left-sided weakness. CT scan and MRI revealed multiple cerebral infarcts. Laboratory evaluation revealed lupus anticoagulant and high levels of anticardiolipin antibody. This case illustrates the thrombotic tendencies seen in patients with lupus anticoagulant and anticardiolipin antibody, and is the first reported case of LA in association with neurofibromatosis.

Abortion, Spontaneous↗
PubMed1989

Catheter embolization from implanted venous access devices: case reports.

Two cases of catheter embolization from implanted venous access devices are reported and the available literature is reviewed. The catheter from an implanted venous access device migrated into the right heart after slippage of the O-ring, which attaches the catheter to the infusion port. The distal 6 cm of an infusion port catheter embolized to the right heart after spontaneous fracture of the catheter at the point where it passed between the clavicle and first rib. Both catheters were removed percutaneously without complication. Risk factors for embolization were apparent on x-ray films with evidence of O-ring slippage in 1 case an obvious kinking of the catheter in the other. Symptoms of embolization included chest discomfort, right upper quadrant pain, and nausea. In 1 case, an extra heart sound, initially thought to be an S3, disappeared when the catheter was removed.

Adult↗
PubMed1988

Fibrin formed in plasma is composed of fibers more massive than those formed from purified fibrinogen.

Reports of altered fibrin resulting from interactions with plasma proteins and cellular release products have raised the possibility that plasma fibrin may differ from purified fibrin. To investigate this possibility, the structures of thrombin-induced gels formed from platelet poor plasma and from purified fibrinogen were compared using turbidity and gel perfusion techniques. Plasma gels formed more slowly and were composed of fibers two to four times more massive than gels formed from purified fibrinogen. Increasing calcium concentration, decreasing ionic strength, decreasing thrombin concentration, or increasing fibrinogen concentration resulted in increasing fiber size. Addition of excess thrombin accelerated plasma gel formation and decreased gel fiber size, but did not totally eliminate the structural differences between the two systems. Thus, antithrombin activity, while possibly contributory, is not solely responsible for the altered gel structure. Penetration of plasma gels by fibrinolytic agents, egress to areas of injury by inflammatory cells, and gel removal by plasmin are processes at least partially dependent on gel fiber and pore size.

Chemical Phenomena↗
PubMed1988

Fluid phase coagulation events have minimal impact on plasma fibrin structure.

Reports of altered fibrin structure in clots formed from factor VIII-deficient plasma have raised the possibility that plasma clots mediated by activation of the fluid phase coagulation system might differ from clots formed by the direct addition of thrombin to plasma. In this study, turbidity measurements were used to compare the assembly and structure of clots formed from platelet-poor plasma by either the addition of thrombin or the exposure of recalcified plasma to glass. When clotted by recalcification, the lag phase before initial increase in turbidity was 10 to 25 times longer than when clotted by the addition of thrombin. Decreasing the ionic strength or increasing the calcium concentration shortened the lag phase. At high calcium concentrations (greater than 25 mM) polymerization was delayed and precipitation was noted. pH had a minimal impact over the range of 7.0 to 7.4. Fibrin fiber mass-length ratios for plasma gels formed by activation of the intrinsic cascade were virtually identical to those in gels formed by the direct addition of thrombin. These studies indicate that fluid phase coagulation events before the production of thrombin have a minimal impact on plasma fibrin structure.

Blood Coagulation↗
PubMed1988

Ciprofloxacin activity in cyst fluid from polycystic kidneys.

Renal cyst infection in patients with polycystic kidney disease (PKD) is often unresponsive to standard antimicrobial therapy, in part because of the failure of most antibiotics to adequately penetrate cyst fluid. Ciprofloxacin, a new quinolone antibiotic, possesses in vitro activity against most pathogens likely to be encountered in renal cyst infection. To study the potential usefulness of ciprofloxacin for the treatment of cyst infection, fluid from 70 cysts was obtained from seven patients with polycystic kidney disease who were receiving the drug. Cysts were categorized as nongradient or gradient by the sodium concentration in the fluid. The ciprofloxacin concentration within cysts was measured, and the cyst fluid bactericidal activity against likely cyst fluid pathogens was determined. The mean (+/- standard error) ciprofloxacin concentration was 12.7 +/- 2.9 micrograms/ml. Preferential accumulation of ciprofloxacin occurred in gradient cysts; these levels exceeded levels in serum by more than fourfold. Cyst fluid bactericidal activity titers were uniformly high against Escherichia coli and Proteus mirabilis, while less activity was observed against Streptococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis.

Adult↗