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Biomedical subjects

W R Bell

Publications and source records attributed to W R Bell.

At least 19 recordsLinked to original sources
PubMed1995

Laboratory monitoring of thrombolytic therapy.

The concept and strategy of thrombolytic therapy are absolutely correct. The obstructing intraluminal thrombus is in urgent need of resolution to permit reestablishment of blood flow. As investigative efforts in this area continue, more effective and more rapidly acting thrombolytic agents will be forthcoming. The thrombolytic agents available today are excellent and can definitely be used safely. However, a modicum of common sense must be employed in initiating their use. There must be frequent contact with the patient receiving such important and needed therapy. It is foolish for those individuals either not familiar with or not educated to utilize thrombolytic agents to make broad sweeping statements that such agents, whose efficacy has been demonstrated, should not be employed in the treatment of thrombosis. Such an attitude is an example of how not to proceed to further improvement in health care. To be content to remain in the past will never permit entrance into the future.

Drug Monitoring↗
PubMed1994

Characteristics of zinc binding to human red blood cell membranes.

The objective of the present study was to standardize the analysis of zinc binding on human red blood cell (RBC) membranes in 20 normal adults. The displacement studies revealed that at the maximal stable zinc concentration tested (600 microM), 57% (mean) of the bound 65Zn was displaced and to displace half maximal 65Zn, the stable zinc concentration was 300 microM. Scatchard plots revealed two classes of binding sites for zinc on RBC membranes: one with higher affinity, Kd = 1.20 x 10(-5) M (site I), and the other with lower affinity, Kd = 2.77 x 10(-4) M (site II). Binding sites occupancy was 97% means and 58.5% means for sites I and II, respectively. The displacement was affected by temperature, membrane protein concentration, freezing, thawing, and dialysis. Other metal cations, including Co++, Fe++, and Mn++, had very little effect on 65Zn displacement, in contrast copper displaced 65Zn from its binding sites on RBC membranes. Zinc binding to RBC membranes was rapid and readily reversible in a dynamic equilibrium with its binding sites. It is anticipated that this method will be applicable to studies of a wide variety of diseases specifically related to zinc metabolism in humans as well as in animals.

Adult↗
PubMed1994

Thrombolytic therapy. Agents, indications, and laboratory monitoring.

The patient must be educated to seek medical attention promptly when this malady strikes, and the physician must likewise be taught to institute this therapy as soon as the patient is seen. Less than 6 years ago, it was strongly expressed that there was no rationale for attempting to restore blood flow in the coronary arteries in the setting of myocardial infarction. It was believed that once the diagnosis of myocardial infarction was made, it was too late to relieve myocardial fibers and avert myocyte necrosis. If this thinking and advice of "the damage has already occurred" and "it is too late" prevailed, it would not be known today that treatment of myocardial infarction with thrombolytic therapy within 6 hours of onset of symptoms significantly reduces mortality in comparison with optimal medical treatment (including heparin) without thrombolytic therapy. The concept of thrombolytic therapy is correct. Persistent investigative work in this area will result in better thrombolytic agents and greater dexterity in their use. The thrombolytic agents available today are good, and they can be used safely. To state that agents that have been established to be capable of thrombus resolution should not be used in the treatment of thrombosis is a true example of how not to proceed toward improvement. To be content to remain in the past will not permit entrance into the future.

Embolism↗
PubMed1992

A unique circulating inhibitor with specificity for coagulation factor X.

An 84-year-old woman presented with extensive cutaneous and gastrointestinal bleeding. Initial laboratory studies revealed a prolonged prothrombin time and activated partial thromboplastin time. Further investigations revealed a circulating anticoagulant with specificity for factor X. The patient's hemorrhage resolved with supportive measures only. Approximately 11 months after presentation, the inhibitor disappeared.

Aged↗
PubMed1992

Breath ethane: a specific indicator of free-radical-mediated lipid peroxidation following reperfusion of the ischemic liver.

A major component of the organ injury mediated by toxic oxidants, such as seen following reperfusion of the ischemic liver, is due to the peroxidation of polyunsaturated fatty acids, especially of cell membranes. We utilized the measurement of exhaled breath ethane, a metabolic product unique to oxidant-mediated lipid peroxidation, as a noninvasive indicator of this process in swine liver subjected to warm ischemia/reperfusion. Under rigorously controlled anesthesia conditions, pig livers were subjected to 2 h of warm total ischemia, followed by reperfusion in situ. Expired air was collected and its ethane content quantitated by a novel gas chromatographic technique. The time course of breath ethane generation correlated closely with the appearance of hepatocellular injury as measured by impairment of Factor VII generation and other measures of liver integrity. Moreover, the administration of the specific superoxide free radical scavenger, superoxide dismutase (SOD), significantly attenuated both the elaboration of ethane and the hepatocellular injury. These findings not only provide confirmation of the previously reported link between hepatocellular injury by free radicals generated at reperfusion, but also establish the use of expired breath ethane analysis as a sensitive, specific, and noninvasive indicator of the injury process in real time.

Alanine Transaminase↗
PubMed1992

Existence of multiple peaks in plasma ethinyl estradiol and norethindrone after oral administration of a contraceptive pill.

Previous measurements of plasma ethinyl estradiol (EE2) and norethindrone (NE) over 24 h after oral administration of a contraceptive pill have demonstrated a single steroid peak occurring 1-2 h after pill ingestion, with a gradual decline over the next 22 h. In the present study plasma concentrations of EE2 and NE were measured 0, 0.5, 0.75, 1, 2, 4, 12, and 24 h after oral ingestion of a contraceptive pill containing 35 micrograms EE2 and 1 mg NE at 0, 3, 6, and 9 months of use in 58 normal healthy women. Contrary to previous reports, analysis of the 464 steroid curves (58 subjects x 4 time periods x 2 steroids) revealed the presence of multiple hormone peaks. Two peaks of EE2 were identified in 44.8% of women during the first pill cycle and in 75.9%, 55.2%, and 67.2% of women after 3, 6, and 9 months of pill use. Two hormone peaks of NE were observed in 29.3% of women during the first cycle and in 36.2%, 50%, and 44.8% at 3, 6, and 9 months, respectively. Existence of these multiple peaks at the frequency observed has not previously been reported. Further quantification of the frequency and magnitude of these peaks could be helpful in explaining differences in biological responses associated with pill use.

Adult↗
PubMed1992

Intra-arterial urokinase for treatment of retrograde thrombosis following resection of an arteriovenous malformation. Case report.

Retrograde thrombosis of feeding arteries is a potentially catastrophic complication occasionally reported following resection of arteriovenous malformations (AVM's). No successful therapy for this condition, which causes postoperative stroke, has previously been reported. A case of retrograde thrombosis of the left middle cerebral artery immediately following resection of a parietal AVM is reported in a patient with a retained intra-arterial catheter from preoperative embolization. The administration of urokinase within 4 hours of surgery resulted in dramatic clinical and angiographic improvement without hemorrhagic complications. While urokinase is considered highly experimental in this setting, this case demonstrates that thrombolytic agents should be viewed as therapeutic options worthy of further investigation.

Adult↗
PubMed1991

Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients.

BACKGROUND AND METHODS: Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, central nervous system abnormalities, and renal dysfunction. In early reports the mortality approached 100 percent. A treatment protocol was introduced in 1979 for patients admitted to Johns Hopkins Hospital with the diagnosis of TTP-HUS. Treatment regimens included 200 mg of prednisone a day, for patients with minimal symptoms and no central nervous system symptoms, and prednisone plus plasma exchange, for patients with rapid clinical deterioration who did not improve after 48 hours of prednisone alone and for patients presenting with central nervous system symptoms and rapidly declining hematocrit values and platelet counts. RESULTS: A total of 108 patients were treated, and 91 percent survived. Prednisone alone was judged to be effective in 30 patients with mild TTP-HUS (two relapses and two deaths). Plasma exchange plus prednisone was given to 78 patients with complicated TTP-HUS, resulting in 67 relapses and 8 deaths. Relapses occurred in 22 of 36 patients given maintenance plasma infusions. Neither splenectomy nor treatment with aspirin and dipyridamole was effective in those with a poor response to plasma exchange. None of the 71 patients tested had positive cultures for O157:H7 Escherichia coli. Nine percent of the patients were pregnant, and none gave birth to infants with TTP-HUS. CONCLUSIONS: Effective treatment with 91 percent survival is available for patients with TTP-HUS.

Adolescent↗
PubMed1991

Obstetric complications in a patient with Bernard-Soulier syndrome.

We describe the obstetric complications and management of a patient with Bernard-Soulier syndrome. Severe bleeding at the time of delivery and delayed postpartum hemorrhage were prominent features of her pregnancies. Further complicating this woman's pregnancies was the development of antibodies to platelet glycoprotein IB/IX, leading to neonatal alloimmune thrombocytopenia.

Adult↗
PubMed1991

Oral contraceptives and antithrombin III: variations by dosage and ABO blood group.

A randomized clinical trial of oral contraceptives evaluated 67 women on a regimen of 50 micrograms ethinyl estradiol and 1.0 mg norethindrone, 61 women on a regimen of 35 micrograms ethinyl estradiol and 1.0 mg norethindrone, and 64 women on a regimen of 35 micrograms ethinyl estradiol and 0.5 mg norethindrone. ABO blood group type was determined in all women. At baseline and at 3, 6, and 9 months, plasma antithrombin III levels, by both an immunologic and an activity method, and selected plasma levels of the contraceptive steroids were measured. Antithrombin III levels for all oral contraceptive groups combined decreased from baseline by 19.7% and 28.8% for the immunologic and activity methods, respectively. Analysis of interrelationships among antithrombin III by activity method, oral contraceptive type, and ABO blood group showed larger declines in antithrombin III for type O women using the highest estrogen dose preparation (31.6%) and for non-type O women using the lowest progestin dose preparation (38.9%). Plasma levels of contraceptive steroids also were related to changes in the most extreme levels of antithrombin III.

ABO Blood-Group System↗
PubMed1991

Aspirin in the prevention of thrombosis.

More than a decade has passed since the introduction of the concept that inhibition of platelet function may be helpful in preventing the initiation of thrombus formation. Aspirin has been recognized as inhibiting normal platelet function and the mechanism has been clearly delineated. Legions of patients have been studied to answer the question of whether aspirin is efficacious in the primary prevention of acute myocardial infarction. At the present time, however, a solid, clear answer is not available and firm recommendations cannot be made. A large number of studies evaluating aspirin and other antiplatelet agents in the prevention or delay of recurrent myocardial infarction (secondary prevention) have been completed and those studies reporting a favorable beneficial effect are in the minority. In these secondary prevention studies reporting success, the doses of aspirin employed were large enough to inhibit both the cyclo-oxygenase system and thromboxane A2 production as well as the synthesis of prostacyclin. Thus, in these studies if aspirin is effective in reducing adverse cardiovascular events, its efficacy is being mediated by an unknown mechanism. If the reader of the few studies that report positive results is convinced of the benefit of aspirin, it must be emphasized that thoughtful, cautious patient selection based upon the individual's cardiovascular risk profile must be exercised. Individual variation may exist with respect to aspirin's beneficial effect. It must be absolutely recognized that aspirin or any antiplatelet agent does not in any way substitute for the removal or treatment of coexisting risk factors such as tobacco, obesity, hypercholesterolemia, hyperlipidemia, hypertension, and metabolic disease. In contrast to aspirin, control of the above risk factors has been established as beneficial. Aspirin is not free of undesirable side-effects; fatalities secondary to hemorrhage have been reported, and these must be known in detail and understood by both physician and patient before this agent is prescribed in the prophylactic treatment of cardiovascular disease.

Aspirin↗
PubMed1991

Assessment of fibrin(ogen) degradation products in preeclampsia using immunoblot, enzyme-linked immunosorbent assay, and latex-based agglutination.

Plasma and serum from pregnant women with preeclampsia (N = 35) and normotensive pregnant (N = 71) and nonpregnant (N = 10) controls were screened for fibrin(ogen) degradation products (fibrinogen and cross-linked fibrin degradation products, and fibrin polymers) using three different assay systems (immunoblot, enzyme-linked immunosorbent assay [ELISA], and latex-bead agglutination assay). All tests showed statistically significant differences (P less than .05) between the preeclamptic patients and the other two groups (pregnant and nonpregnant women). The ELISA assay for total fibrin(ogen) degradation products was the most sensitive test, but was less specific than D-dimer latex. Eleven of the 35 preeclamptic women developed HELLP syndrome (hemolysis, elevated liver enzyme, and low platelet counts). Positive tests were as common in the 11 preeclamptic women who developed the syndrome as in the 24 who did not. These results suggest that fibrinolytic disorders are secondary pathophysiologic events in the course of preeclampsia, but further studies with a larger number of patients are needed.

Adolescent↗
PubMed1990

Fibrinogen Baltimore I: polymerization defect associated with a gamma 292Gly----Val (GGC----GTC) mutation.

Fibrinogen Baltimore I is one of the very first congenital abnormal fibrinogens reported over several decades ago; however, the molecular defect of this dysfibrinogen has eluded identification. In fact, several reports misidentified the functional defect of Baltimore I, which has impaired fibrin monomer polymerization. Reversed-phase high-performance liquid chromatography analysis of lysyl endopeptidase digest of the purified Baltimore I gamma-chain showed an abnormal peptide not found in the co-existing normal gamma-chain of this heterozygote. Amino acid sequencing of this peptide indicated that gamma-chain Gly292 is replaced by valine. This observation was confirmed, and the genetic defect was determined by direct nucleotide sequencing of a polymerase chain reaction product containing codon gamma 292, which is mutated: GGC----GTC. The molecular defect of Fibrinogen Baltimore I lies in a region of the gamma-chain required for fibrin polymerization, suggesting that the integrity of gamma Gly292 is critical for fibrin assembly.

Adult↗
PubMed1990

Polymerization defect of fibrinogen Baltimore III due to a gamma Asn308----Ile mutation.

Fibrinogen Baltimore III, a congenital abnormal fibrinogen with impaired fibrin monomer polymerization, displays a normal gamma-chain and a gamma-variant that has an apparently lower relative molecular weight (mol wt) than normal on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Reverse phase high-performance liquid chromatography (HPLC) analysis of the lysyl endopeptidase digest of the purified gamma-chains of fibrinogen Baltimore III revealed the presence of a peptide that is not found in the digest of the normal fibrinogen gamma-chain. Amino acid sequence analysis of this peptide indicated that the gamma-chain residue 308, asparagine, is replaced by isoleucine. Concanavalin A bound both normal and variant gamma-chains of fibrinogen Baltimore III, indicating that the carbohydrate moiety is not altered and is not responsible for the increase in electrophoretic mobility of the Baltimore III gamma-chain. This study suggests that the integrity of gamma Asn308 is critical for fibrin monomer polymerization, since alteration to either a basic (fibrinogen Kyoto I, Asn----Lys) or hydrophobic (Asn----Ile) residue results in significantly delayed polymerization of fibrinogen to fibrin.

Amino Acid Sequence↗
PubMed1990

Acute management of intracranial hemorrhage in patients receiving thrombolytic therapy: case reports.

Intracranial hemorrhage is an uncommon complication of antithrombotic therapy. We present two patients who suffered life-threatening intracranial bleeding as a complication of thrombolytic/anticoagulant treatment. Early diagnosis and treatment appear to be crucial factors for survival. We suggest an approach to perioperative management for intracranial hemorrhage resulting from antithrombotic therapy.

Aged↗
PubMed1990

Fibrinolytic agents in the treatment of thrombotic disorders.

The oncology patient is often at increased risk of bleeding when thrombolytics are administered. Fortunately, the factors placing the patient at risk are easily identified and include intracranial disease, vascular defects produced by surgery, instrumentation or tumor invasion, underlying coagulopathy, and severe thrombocytopenia. Unfortunately, new clot-specific agents have not eliminated the problem of undesirable bleeding; in fact, they may cause more bleeding by more efficiently dissolving both pathological thrombi and hemostatic plugs. The development of a means of delivering thrombolytics solely to the target clot is desirable and should be performed when possible. Despite the need for caution, thrombolytics are remarkably effective in treating both venous and arterial thrombi, and it is a disservice to the patient not to carefully consider their use.

Arterial Occlusive Diseases↗
PubMed1989

Fibrinogen Baltimore IV: congenital dysfibrinogenemia with a gamma 275 (Arg----Cys) substitution.

The major functional characteristics of fibrinogen Baltimore IV include delayed fibrin monomer polymerization which is not corrected by the addition of calcium, inhibition of normal plasma coagulation upon mixing, and a biphasic polymerization profile in which the abnormal fibrin monomers appear to polymerize at about 2% of the normal rate (Ebert & Bell, Thromb. Res. 38:121-128, 1985). We now report the detection of an abnormal peptide in a comparative peptide map from a cyanogen bromide digest of fibrinogen Baltimore IV. The sequence of this peptide corresponds to the fibrinogen sequence gamma 265-310, except that Arg275 is replaced by Cys. Amino acid analyses of carboxymethylated peptides from control vs. fibrinogen Baltimore IV confirmed the sequencing data. Both the propositus and his affected daughter were heterozygous for the trait.

Amino Acid Sequence↗