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Biomedical subjects

C A Sullivan

Publications and source records attributed to C A Sullivan.

At least 37 records · Page 2Linked to original sources

The recurrence risk of the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) in subsequent gestations.

OBJECTIVE: Although it is an important clinical issue, accurate prediction of recurrence risk for the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) has been problematic because of limited patient experience. This study was undertaken to determine the likelihood that this form of severe preeclampsia-eclampsia or any other hypertensive disorder would occur in a subsequent pregnancy. STUDY DESIGN: An extensive retrospective analysis of medical records and patient follow-up regarding subsequent pregnancy outcome were undertaken for the 481 patients with HELLP syndrome managed at this tertiary medical center between Jan. 1, 1980, and Oct. 30, 1991. The Mississippi three-class system was used to define severity of disease on the basis of the lowest observed perinatal platelet count (class 1 < or = 50,000/microliters, class 2 > 50,000/microliters to < or = 100,000/microliters, and class 3 > 100,000/microliters to < or = 150,000/microliters). RESULTS: Subsequent gestations (n = 195) occurred in 122 of 481 patients. Evaluable data were available for analysis in 161 of 195 possible pregnancies. Seventy-eight (48%) pregnancies were complicated by some type of hypertensive disorder, 44 (27%) of which had class 1, 2, or 3 HELLP syndrome. Non-HELLP preeclampsia-eclampsia was detected in 25 subsequent gestations (15%). Thus the total frequency of preeclampsia was 69 in 161 (43%). If the data for class 3 HELLP are completely excluded from the analysis, 81 subsequent evaluable and viable gestations were identified, 19 pregnancies with preeclampsia-eclampsia (23%) and 15 patients with HELLP syndrome (19%), for a total recurrence rate of 42%. Subsequent HELLP gestations were frequently delivered abdominally (64%) on average 2 weeks later than the index pregnancy (32.6 +/- 5.0 weeks versus 34.7 +/- 5.3 weeks). Delivery at < 32 weeks conferred a high risk (61%) for a similar preterm delivery in a subsequent gestation. CONCLUSION: The risk of recurrence of the HELLP syndrome in our population is 19% to 27%. When data from all pregnancies with all forms of preeclampsia are considered, the risk of recurrence for any type of preeclampsia-eclampsia is 42% to 43%. A previous preterm delivery is a very high risk factor for recurrence of prematurity with preeclampsia-eclampsia.

Adolescent↗

Assessment of the haemolytic activity of 2-butoxyethanol and its major metabolite, butoxyacetic acid, in various mammals including humans.

2-Butoxyethanol (BE) is a glycol ether produced in volumes exceeding 335 million pounds/year for industrial and domestic uses. BE causes acute haemolytic anaemia in rats and some other mammals. While BE is inactive in vitro, 2-butoxyacetic acid (BAA) is a potent haemolytic agent in vivo and in vitro. This finding suggests that metabolic activation of BE to BAA is required for haemolysis of erythrocytes to occur in vivo. Haemolysis of red blood cells (RBC) by BAA is preceded by swelling (increased mean cell volume [MCV] and haematocrit [HCT]). In an attempt to assess the potential risk to humans exposed to BE, studies were designed to determine the in vitro effect of BAA on RBCs from 10 mammalian species including humans. Blood samples from each mammalian species (n = 3-5) were incubated with BAA at a final concentration of 0 (vehicle), 1 or 2 mM and kept at 37 degrees C in a gently shaking water bath. Complete blood counts (CBCs) were measured at 0, 1, 2 and 4 h, BAA caused a time- and concentration-dependent increase in MCV and HCT of blood from rats, mice and hamsters (rodents), rabbits (lagomorphs), and baboons (primates). In contrast, blood from pigs (artiodactyls), dogs and cats (carnivores), guinea pigs (rodents/marsupials), and humans (primates), was minimally affected by BAA. These results were confirmed in guinea pigs and rats in vivo. Gavage administration of BE (250 mg kg-1) to rats resulted in increased MCV and HCT followed by haemolysis (decreased RBCs). Identical treatment with BE resulted in no significant change in these parameters in guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic↗

Control of proximal gastric bleeding: combined laparoscopic and endoscopic approach.

Dieulafoy's lesion (exulceratio simplex) of the proximal gastric corpus is a more frequent cause of massive upper gastrointestinal hemorrhage than previously appreciated. Recent management has focused on interventional endoscopic and radiologic techniques, but these have been plagued by high rebleeding rates. The traditional surgical approach of suture control of the bleeding or wedge resection is effective but entails significant morbidity and mortality. This article describes endoscopically guided laparoscopic ligation of the feeding vessels in a patient with massive hemorrhage from a Dieulafoy's ulcer.

Aged↗

A prospective randomized study comparing surgical and percutaneous removal of intraaortic balloon pump.

This prospective randomized study of 50 patients compares the prevalence of complications between surgical and percutaneous methods of removal of intraaortic balloons. All patients who had percutaneous placement of a 9.5F intraaortic balloon during a 6-month period were eligible for the study. Patients were excluded if the intraaortic balloon was placed surgically, if a coagulopathy was present, or if acute leg ischemia developed at any time after insertion. After informed consent, 25 patients were randomized to each method of removal. Two complications occurred in the surgical group, including a wound infection and a lymph fistula. In one patient in the percutaneous group, a false aneurysm of the femoral artery developed. There was no significant difference between the mean of 59 minutes for percutaneous removal and 47 minutes for operative removal of the balloon (p = 0.74). The percutaneous method is therefore more cost-effective, because it does not require the use of operating room personnel or equipment necessary for surgical removal. The results of this study indicate that the majority of percutaneously placed intraaortic balloons may be safely removed percutaneously. Surgical removal of 9.5F intraaortic balloons is recommended for patients with bleeding diatheses, hemorrhagic or ischemic complications, or for those in whom the intraaortic balloon was inserted with a surgical procedure.

Aged↗

Clinical management of the symptomatic but unruptured abdominal aortic aneurysm.

Pain or tenderness of an abdominal aortic aneurysm is widely believed to signify acute expansion and imminent rupture. To assess the potential benefit of emergency operation for the group of patients with an acutely expanding aneurysm, the clinical course of 19 patients with a symptomatic but unruptured expanding abdominal aortic aneurysm was compared with 117 patients undergoing elective abdominal aortic aneurysm resection, and 69 patients having operation for a ruptured abdominal aortic aneurysm. Postoperative morbidity was high in the patients with an expanding abdominal aortic aneurysm, and included a 21% incidence of myocardial infarction, a 10% incidence of stroke, a 37% risk of ventilatory failure, and a 31% incidence of acute renal failure, which was not statistically different from the results in patients having ruptured abdominal aortic aneurysm resection. Patients undergoing elective abdominal aortic aneurysm resection had only an 8% risk of myocardial infarction, and only a 2% risk of stroke, ventilatory failure, or renal failure. The mortality rate for expanding abdominal aortic aneurysm resection was 26% compared to 35% for ruptured abdominal aortic aneurysm (p = 0.31). Both emergency operations had a mortality rate more than five times greater than the 5.1% after elective procedures (p = 0.008). Our findings emphasize the need for early and aggressive treatment of abdominal aortic aneurysm in the elective setting, even in the patient at high risk, and suggest that the preoperative assessment and modification of risk factors is important to prevent the cardiac, cerebrovascular, pulmonary, and renal complications seen accompanying an emergency operation of this magnitude.

Acute Kidney Injury↗

The expression and purification of human rhinovirus protease 3C.

Human rhinovirus type 14 protease 3C was expressed as a soluble and active protein in Escherichia coli. The protease was purified by a cationic-exchange step followed by gel filtration on a TSK 3000 column. The final yield of purified protease was in the range 0.5-1.0 mg/l culture grown to A550 = 1.0. Sequence analysis revealed that greater than 90% of the N-terminal residues were methionine. The enzyme activity of the purified protease was measured by cleavage of a synthetic peptide representing a predicted Gln/Gly viral polyprotein cleavage site. A mutant protease (Cys146----Ser) was produced and purified in the same way. The yield of mutant protease 3C was approximately 150 micrograms/l from a culture grown to A550 = 1.0. This mutant protease 3C did not cleave the synthetic peptide substrate.

3C Viral Proteases↗

The isolation and characterisation of human atrial natriuretic factor produced as a fusion protein in Escherichia coli.

Human atrial natriuretic factor [ANF(1-28)] has been isolated from a fusion protein produced in Escherichia coli. ANF(1-28) was linked to a naturally occurring E. coli protein, chloramphenicol acetyltransferase, via unique cleavage sequences susceptible to either human thrombin digestion, or the chemical action of 2-(2-nitrophenylsulphenyl)-3-methyl-3'-bromoindolenine (BNPS-skatole). The linker sequences were Gly-Val-Arg-Gly-Pro-Arg and Trp respectively. The liberated ANF was purified by reversed-phase HPLC. Optimised cleavage conditions released 5-10% (by mass) of the maximal yield of ANF(1-28) from the fusion protein with the thrombin-susceptible linker, whilst a 2-5% (by mass) yield was observed from the fusion protein with the tryptophan linker after BNPS-skatole treatment. The purified cleavage products were biologically active and shown to comprise intact ANF(1-28). Fast-atom-bombardment mass spectrometry confirmed [MH]+ of 3079 m/z, consistent with ANF(1-28).

Acetyltransferases↗

The establishment of polarity by hippocampal neurons in culture.

By the end of the first week in culture, hippocampal neurons have established a single axon and several dendrites. These 2 classes of processes differ in their morphology, in their molecular composition, and in their synaptic polarity (Bartlett and Banker, 1984a, b; Caceres et al., 1984). We examined the events during the first week in culture that lead to the establishment of this characteristic form. Hippocampal cells were obtained from 18 d fetal rats, plated onto polylysine-treated coverslips, and maintained in a serum-free medium. The development of individual cells was followed by sequential photography at daily intervals until both axons and dendrites had been established; identification of the processes was confirmed by immunostaining for MAP2, a dendritic marker. Time-lapse video recording was used to follow the early stages of process formation. Hippocampal neurons acquired their characteristic form by a stereotyped sequence of developmental events. The cells first established several, apparently identical, short processes. After several hours, one of the short processes began to grow very rapidly; it became the axon. The remaining processes began to elongate a few days later and grew at a much slower rate. They became the cell's dendrites. Neurons that arose following mitosis in culture underwent this same sequence of developmental events. In a few instances, 2 processes from a cell exhibited the rapid growth typical of axons, but only one maintained this growth; the other retracted and became a dendrite. Axons branched primarily by the formation of collaterals, not by bifurcation of growth cones. As judged by light microscopy, processes are not specified as axons or dendrites when they arise. The first manifestation of neuronal polarity is the acquisition of axonal characteristics by one of the initial processes; subsequently the remaining processes become dendrites.

Animals↗

Epidermoid cyst of the spleen successfully treated by marsupialization.

Nonparasitic splenic cysts, although rare, should be considered in the differential diagnosis of persistent vague upper abdominal pain in children and young adults. These cysts, which are less common than traumatic pseudocysts, include hemangiomas, dermoids, lymphangiomas, and, as in the present case, epidermoid variants. Ultrasound is diagnostic. The pathogenesis of these lesions remains obscure. While some continue to advocate splenectomy as definitive treatment, an operation with splenic salvage should be possible, even in centrally located lesions.

Adolescent↗

Platelet aggregation and the pharmacology of local anaesthetics.

Local anaesthetics significantly inhibit platelet aggregation and prolong the lag period of collagen-induced aggregation, but only at toxic concentrations. This appears to be due to stabilization of the platelet membrane. While the phenomenon is not clinically significant, the platelet may serve as a readily available, easily harvested, renewable human cellular model for studying the pharmacology of local anaesthetics.

Adenosine Diphosphate↗

A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa.

To define better the role of the fibrinogen receptor in platelet physiology and to characterize it biochemically, a murine monoclonal antibody that completely blocks the binding of fibrinogen to the platelet surface was produced by the hybridoma technique with the aid of a functional screening assay. Purified F(ab')2 fragments and/or intact antibody completely blocked aggregation induced by ADP, thrombin, or epinephrine and the binding of radiolabeled fibrinogen to platelets induced by ADP. The antibody did not block agglutination of formaldehyde-fixed platelets by ristocetin or shape change induced by either ADP or thrombin. ADP- and epinephrine-induced release of ATP was completely inhibited by the antibody, but inhibition of release induced by collagen and thrombin was dose dependent and partial. The antibody also dramatically inhibited platelet retention in glass-bead columns, platelet adhesion to glass, and clot retraction. Thus, the antibody induced a thrombasthenic-like state. Immunofluorescent studies confirmed the specificity of the antibody for normal platelets and megakaryocytes and suggested that there is a marked decrease in detectable antigen in thrombasthenic platelets. Radiolabeled antibody bound to an average of approximately 40,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets of a patient with thrombasthenia. The antibody immunoprecipitated both glycoproteins IIb and IIIa, and both glycoproteins bound to an affinity column of the antibody. These studies indicate that there is probably a single anatomic site that is crucial to the binding of all fibrinogen molecules and that this site is most likely on the glycoprotein IIb/IIIa complex. It also suggests that the thrombasthenic phenotype can be completely accounted for on the basis of the inhibition of fibrinogen binding to platelets.

Animals↗

Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor.

A murine monoclonal antibody directed at or near a platelet membrane receptor for the von Willebrand factor was produced by the hybridoma technique. Purified F(ab')2 fragments and/or intact antibody completely blocked the agglutination of platelets induced by both ristocetin and bovine von Willebrand factor and the binding of von Willebrand factor antigen to platelets. The antibody also decreased platelet retention, prevented the reduction in platelet electrophoretic mobility caused by bovine von Willebrand factor, and decreased the serum prothrombin time. Radiolabeled F(ab')2 fragments bound to or approximately 2.5 X 10(4) sites on normal platelets with high affinity (KD or approximately 1.5 X 10(-8) M); there was no binding to platelets from 2 patients with the Bernard-Soulier syndrome. Immunoprecipitation and affinity chromatography studies indicated that the antibody binds to glycoprotein lb at a site contained on the externally oriented portion of the GPIb alpha chain (glycocalicin). An unidentified mol wt or approximately 20,000 molecule labeled by periodate/NaB3H4 coprecipitated and copurified with GPIb.

Antibodies, Monoclonal↗