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Biomedical subjects

W O'Brien

Publications and source records attributed to W O'Brien.

At least 19 recordsLinked to original sources
PubMed1995

Pseudoaneurysm complicating knee arthroscopy.

Pseudoaneurysm formation is a rare complication of knee arthroscopy. Cases reported in the literature have involved the popliteal, superior and inferior medial geniculate, and the inferior lateral geniculate arteries. These cases have all been described as presenting within 2 to 3 weeks of the arthroscopic procedure. Described here are two unique cases, the first a delayed presentation and the second involving the recurrent anterior tibial artery.

Adult↗
PubMed1995

Comparison of characteristics of Q beta replicase-amplified assay with competitive PCR assay for Chlamydia trachomatis.

In order to study infections due to Chlamydia trachomatis, we have compared semiquantitative PCR and Q beta replicase-amplified assays for detection of this organism. The PCR assay was directed against the C. trachomatis 16S rRNA gene. Quantitation was accomplished by adding known amounts of a plasmid containing a truncated segment of the 16S rRNA gene target to chlamydia-containing samples and then amplifying with a common primer set. The Q beta replicase assay consisted of reversible target capture of C. trachomatis 16S rRNA, which was followed by amplification of an RNA detector probe in the presence of the enzyme Q beta replicase. In a clinical matrix, the lower limit of detection of both the PCR and Q beta replicase assays was five elementary bodies. The Q beta replicase and PCR assays were quantitative over 10,000- and 1,000-fold ranges of organisms, respectively. Analysis of the effects of endocervical matrix on amplification was accomplished by examining 94 endocervical specimens by each technique. Both assays detected five of six culture-confirmed specimens as well as three culture-negative specimens. PCR inhibitors were detected in 13 specimens. The Q beta replicase assay, in contrast, showed no evidence of sample inhibition. The Q beta replicase and PCR assays should allow quantitative investigation of infections due to C. trachomatis. In addition, because it targets highly labile RNA, the Q beta replicase assay may facilitate investigations into the role of active persisting infection in culture-negative inflammatory conditions.

Base Sequence↗
PubMed1994

Killing of primary CD4+ T cells by non-syncytium-inducing macrophage-tropic human immunodeficiency virus type 1.

Understanding the mechanism by which human immunodeficiency virus type 1 (HIV-1) kills CD4+ T lymphocytes is important to the development of therapeutic and prophylactic strategies. Recent studies have indicated that, in some cases, progression to AIDS is associated with the appearance of syncytium-inducing, T cell line-tropic HIV-1 variants. Nevertheless, approximately 50% of subjects with AIDS harbor only non-syncytium-inducing, macrophage-tropic (NSI-M) variants of HIV-1. In most asymptomatic patients, NSI-M HIV-1 isolates are the predominant virus type found. We report here that cytopathicity of NSI-M HIV-1 for primary CD4+ T lymphocytes can be directly detected in vitro. The extent of CD4+ T-cell killing was not completely correlated with the rate of viral replication, suggesting that other characteristics of HIV-1 contribute to its cytopathicity. Our findings suggest that: (i) direct killing by NSI-M HIV-1 may contribute to CD4+ T-lymphocyte depletion in vivo, and (ii) the determinants of HIV-1 cytopathicity for CD4+ T lymphocytes and cell tropism or syncytia-forming ability are not necessarily tightly linked.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Reduced muscle protein breakdown in septic rats following treatment with interleukin-1 receptor antagonist.

1. The role of interleukin-1 (IL-1) in sepsis-induced muscle proteolysis was assessed by treating septic rats with recombinant IL-1 receptor antagonist (rIL-1ra). 2. In initial experiments, we tested the effectiveness of IL-1ra in preventing muscle proteolysis induced by administration of IL-1. 3. When normal rats were treated with rIL-1 alpha (three intraperitoneal doses of 100 micrograms/kg body weight each over 16 hr), total and myofibrillar muscle protein breakdown rates, measured as release of tyrosine and 3-methylhistidine, respectively, by incubated extensor digitorum longus muscles, were significantly increased. 4. This metabolic response to IL-1 alpha was completely abolished by rIL-1ra, administered as three intraperitoneal doses of 3 mg/kg body weight each over 16 hr. 5. In subsequent experiments, sepsis was induced in rats by cecal ligation and puncture (CLP); non-septic rats were sham-operated. 6. Treatment of septic rats over 16 hr with a total dose of 25 mg/kg body weight of rIL-1ra reduced, but did not normalize, the increased muscle protein breakdown rates seen during sepsis. 7. When the dose of rIL-1ra was more than doubled and given as a constant infusion at a rate of 4.2 mg/kg body weight/hr for 16 hr, the increased rate of muscle proteolysis in septic rats was normalized. 8. The present study offers the first direct evidence that IL-1 is involved in the regulation of muscle proteolysis during sepsis.

Animals↗
PubMed1994

Effect of sepsis on mucosal protein synthesis in different parts of the gastrointestinal tract in rats.

1. In a previous study we found that the protein synthesis rate was increased by 50-60% in the mucosa of the jejunum and ileum during sepsis in rats. It is not known if sepsis affects protein turnover in other parts of the gastrointestinal tract as well. 2. In the present study, the influence of sepsis on mucosal protein synthesis in different parts of the gastrointestinal tract, from the stomach to the rectum, was determined in rats. 3. Sepsis was induced by caecal ligation and puncture; control rats underwent sham-operation. Protein synthesis rate was measured in vivo after administration of a flooding dose of [14C]leucine. 4. Basal mucosal protein synthesis rates were lower in the colon than in the rest of the gastrointestinal tract. Sixteen hours after caecal ligation and puncture, the protein synthesis rates were increased by 40-85% in the mucosa of the small and large intestine and the rectum, whereas in the gastric mucosa, the protein synthesis rate was reduced by approximately 40%. 5. The results suggest that mucosal protein synthesis rates differ in the various regions of the gastrointestinal tract, and that the metabolic response to sepsis is different in the stomach than in the rest of the gastrointestinal tract. The finding of a reduced protein synthesis rate in the gastric mucosa may partly explain the tendency to gastric stress ulcers and bleeding seen clinically in sepsis.

Animals↗
PubMed1994

Structure-function studies of the Na,K-ATPase.

Na,K-ATPase catalyzes the movement of sodium and potassium ions across the cell membrane utilizing ATP as an energy source. This enzyme is present in almost all tissues of higher organisms but is most abundant in the kidney where it is responsible for reabsorbing sodium ions from the glomerular filtrate. The enzyme is composed of two subunits and serves as the receptor for cardiac glycosides. Utilizing an expression/selection system it has been possible to identify several amino acid residues that affect sensitivity to the cardiac glycoside, ouabain. Those identified to date are located in the first transmembrane region and first extracellular region. The fact that amino acid residues within a transmembrane region affect ouabain sensitivity suggests that the drug is partially internalized in the lipid bilayer. In an effort to determine whether any of the amino acid residues which affect ouabain sensitivity interact with the sugar part of cardiac glycosides, ouabain and ouabagenin were tested in terms of their ability to inhibit enzyme containing substitutions at these positions. The two compounds differ in that ouabagenin lacks a sugar moiety. Interestingly, the ratio of I50's for the substituted enzymes remains the same as the wild type, which suggests that the amino acids identified as determinants of ouabain sensitivity to date are not likely to interact with the sugar. Another set of studies focused on cation binding. It has been proposed that cation transport involves negatively charged residues in one or more transmembrane regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Comparison of postoperative wound complications and early cancer recurrence between patients undergoing mastectomy with or without immediate breast reconstruction.

The incidence of postoperative wound complications and early cancer recurrence was studied in 289 patients who had mastectomy alone and in 113 patients who underwent immediate reconstruction following mastectomy. Patients undergoing immediate reconstruction were younger and had less advanced disease than patients who had mastectomy alone. The postoperative hospital stay was 3.8 days and 4.4 days (p < 0.05) in patients with and without reconstruction, respectively. The overall incidence of postoperative complications was similar in the two groups of patients: 31% and 28% in patients with and without reconstruction, respectively. The incidence of postoperative seroma was higher among patients with mastectomy alone (19% versus 3%, p < 0.05), whereas the incidence of other wound complications was similar in the two groups of patients. Prosthesis-specific complications occurred in 17%. Eight prostheses were removed because of complications. During the relatively short follow-up period (approximately 20 months), local recurrence was noted in 16 patients (6%) who had mastectomy alone and in 1 patient (1%) who had immediate reconstruction after mastectomy (p < 0.05). There was no significant difference in the incidence of distant metastases between the two groups of patients. The results suggest that immediate breast reconstruction can be performed following mastectomy for cancer without increased risk for overall postoperative complications, prolonged hospital stay, or local recurrence. However, patients who choose to have immediate reconstruction need to be informed about risks for specific complications associated with the procedure, especially if an implant is used.

Adult↗
PubMed1993

Spinal cord perfusion pressure in dogs after control of proximal aortic hypertension during thoracic aortic cross-clamping with esmolol or sodium nitroprusside.

BACKGROUND: Spinal cord perfusion pressure may be reduced when sodium nitroprusside is used to control proximal aortic hypertension during thoracic aortic clamping. The effect of esmolol infusion on spinal cord perfusion pressure during thoracic aortic clamping is unknown. This study compares spinal cord perfusion pressure following control of proximal hypertension with either sodium nitroprusside or esmolol during thoracic aortic clamping. METHODS: The thoracic aorta was cross-clamped for 30 min in 18 dogs anesthetized with halothane. A control group (n = 6) received no treatment of proximal hypertension during cross-clamping. In two other groups, proximal arterial pressure was controlled (100 mmHg) by infusion of either sodium nitroprusside (n = 6) or esmolol (n = 6). Brachial and femoral arterial pressures, spinal cord perfusion pressure, pulmonary artery occlusion, central venous pressures, and cardiac output were monitored. Neurologic assessment was performed 24 h following surgery. RESULTS: Femoral arterial pressure was lower with nitroprusside (14 +/- 3 mmHg) compared to esmolol (24 +/- 4 mmHg) after 15 min of aortic cross-clamping. Cerebrospinal fluid pressure increased during aortic cross-clamping in the sodium nitroprusside group (from 7 +/- 5 to 16 +/- 6 mmHg) but not in esmolol or control groups. Spinal cord perfusion pressure was lower with nitroprusside at 15 min of aortic cross-clamping (2 +/- 4 mmHg) compared to control (15 +/- 7 mmHg) and esmolol groups (17 +/- 11 mmHg). Esmolol infusion reduced cardiac output and increased ventricular filling pressures compared to control and nitroprusside groups. CONCLUSIONS: Esmolol was associated with greater spinal cord perfusion pressure, but adverse hemodynamic effects, when compared with nitroprusside during thoracic aortic cross-clamping. When only surviving dogs (4 control, 5 esmolol, 6 nitroprusside) are considered, the incidence of neurologic deficit was greater in nitroprusside-treated dogs than in either control or esmolol-treated dogs. No difference in outcome was present when all dogs are considered.

Adrenergic beta-Antagonists↗
PubMed1992

Prevention of anticardiolipin antibody-related pregnancy losses with prednisone and aspirin.

PURPOSE: Prevention and treatment of pregnancy loss associated with the antiphospholipid syndrome (APS) are controversial. Successful pregnancies have been reported with prednisone and low-dose aspirin in patients with lupus anticoagulant and anticardiolipin antibodies (aCL), but failure has also been reported. The purpose of this prospective study was to define the efficacy of such combination therapy in the prevention of pregnancy loss related to aCL. PATIENTS AND METHODS: Consecutive pregnant patients with a minimum of one pregnancy loss and at least two positive aCL determinations more than 3 months apart, and in whom other causes of pregnancy loss were ruled out, were included in the study. aCL concentrations were determined by enzyme-linked immunosorbent assay before and during therapy. Patients received prednisone, at a dosage of 40 mg/d, for 4 weeks. The dose was then tapered down 10 mg every 4 weeks, and then to a maintenance dose of 5 mg/d. They also received aspirin, 81 mg/d, throughout the pregnancy. Babies were evaluated during the pregnancy by measurement of fetal heart rate and ultrasonography, and after the delivery by measurement of weight and Apgar scores, and, in some cases, by arterial gasometry. RESULTS: Eleven patients with a mean (+/- SD) age of 33.2 +/- 5.01 years were included. Prior to therapy, the rate of live-born babies was 15.6% (32 previous fetal losses and 5 live-born babies), and, after therapy, it was 100% (12 pregnancies and 12 live-born babies). There were no significant adverse effects to either mothers or babies. All the patients had positive aCL determinations. Nine patients had positive IgG aCL. The levels of the antibodies decreased during treatment in these nine patients. IgM aCL determinations were positive in nine patients. The levels of this isotype decreased in eight patients (90%) during treatment. CONCLUSIONS: Treatment with prednisone and aspirin appears to be efficacious, safe, and economic in the prevention of pregnancy loss and fetal growth retardation in patients with aCL.

Abortion, Spontaneous↗
PubMed1992

Muscle protein breakdown during endotoxemia in rats and after treatment with interleukin-1 receptor antagonist (IL-1ra).

The purpose of this study was to examine the effect of endotoxemia on muscle protein degradation and to test the hypothesis that muscle proteolysis during endotoxemia is regulated by interleukin-1 (IL-1). Both total and myofibrillar protein breakdown rates in incubated extensor digitorum longus muscles were increased after the subcutaneous injection of 0.1 or 1.0 mg/kg endotoxin in rats. The endotoxin-induced increase in muscle protein breakdown was blunted by IL-1 receptor antagonist, administered intraperitoneally at a total dose of 45 or 105 mg/kg. Results suggest that endotoxemia in rats gives rise to sepsislike changes in muscle protein breakdown. Increased muscle protein breakdown during endotoxemia may be regulated, at least in part, by IL-1.

Animals↗
PubMed1992

The region of the envelope gene of human immunodeficiency virus type 1 responsible for determination of cell tropism.

Different isolates of human immunodeficiency virus type 1 (HIV-1) vary in the cell tropisms they display, i.e., the range of cell types in which they are able to establish a productive infection. Here, we report on the phenotypes of recombinants between two molecularly cloned strains of HIV-1. Our results prove that the envelope glycoprotein gp120 is solely responsible for the difference in cell tropism between the two parental isolates and that no other genes or sequences are involved in determining the cell tropism of these strains. The region of the envelope involved in the determination of cell tropism includes sequences which encode the V3 loop of gp120. Control of cell tropism by this region of the virus env gene is a general phenomenon which applies to many different HIV-1 isolates.

Amino Acid Sequence↗
PubMed1992

Effect of abrupt changes in ventricular loading on repolarization induced by transient aortic occlusion in humans.

We have investigated the influence of ventricular loading on repolarization from beat to beat in the human heart. Sixteen patients undergoing routine coronary artery surgery were studied. Left ventricular epicardial monophasic action potentials and local electrograms were recorded during acute changes in ventricular loading induced by transient aortic occlusion. Monophasic action potential duration shortened (P less than 0.0001) and returned to control values within one or two beats after release (P less than 0.0001). Values at 90% repolarization were 325 +/- 31 ms preocclusion, 311 +/- 29 ms during occlusion, 326 +/- 32 ms postocclusion. The Q-T interval of the local epicardial electrogram shortened during occlusion (P less than 0.001) and returned to control values after release (P greater than 0.0001): 396 +/- 44 ms preocclusion, 379 +/- 41 ms during occlusion, and, 399 +/- 42 ms postocclusion. A significant correlation was obtained between changes in peak systolic pressure and changes in monophasic action potential duration (R = 0.96; P less than 0.0001 at 90% repolarization). A significant correlation was also observed between changes in peak systolic pressure and the Q-T interval of the local electrogram (R = 0.91; P less than 0.0001). This study shows that abrupt changes in ventricular loading from one beat to the next induce significant changes in the timing of ventricular repolarization. These results may well be relevant to the initiation of arrhythmia by a single ventricular ectopic beat, particularly under pathological conditions.

Action Potentials↗
PubMed1992

An interesting case presentation: peripartum meningococcal meningitis.

Meningococcal disease during pregnancy is extremely rare. A single reported case occurred more than 20 years ago in England. We present the case of a young woman who just hours after delivery of her baby developed fulminant meningococcal meningitis with its classic findings. Our experience illustrates the importance of early diagnosis and appropriate therapy of meningococcal disease in the gravid as well as in the nongravid population.

Adult↗
PubMed1991

Alternans of epicardial repolarization as a localized phenomenon in man.

Electrophysiological alternans (beat-to-beat alternation of the configuration of the action potential and/or electrocardiogram) may be important in the causation of ventricular arrhythmias. We recorded monophasic action potentials from the left ventricular epicardium in patients undergoing routine cardiac surgery. We set out to determine: (a) whether a small increase in atrial pacing rate could elicit electrophysiological alternans; (b) whether different phases of the operation influence the incidence and; (c) whether electrical alternans was a localized phenomenon. Thirty-six patients were studied, and alternans of action potential duration was observed in 14 (39%). The difference between alternate long and short action potential durations ranged from 4 to 112 ms. The mean differences during each stage of the protocol were: pacing before bypass 33.3 +/- 22.7 ms (three of 17 patients); pacing after bypass 46.7 +/- 37.8 ms (nine of 36 patients); pacing during transient graft occlusion 28.0 +/- 23.1 ms (five of 17 patients); pacing following release of the grafts 29.6 +/- 30.0 ms (five of 17 patients). None of the patients showed any evidence of alternans in the electrocardiogram or mechanical alternans in radial artery pressure. In seven of the 14 patients showing alternans, recordings were made in closely adjacent (approximately 1 cm) areas showing that alternans could be a localized phenomenon. The findings indicate that electrical alternans was a frequent occurrence in this study (39% of patients) and may be a localized phenomenon.

Action Potentials↗
PubMed1991

Primary leiomyosarcoma of adrenal gland. Case report with immunohistochemical and ultrastructural study.

A primary leiomyosarcoma of the right adrenal gland is reported in a 49-year-old male who presented with progressive flank pain. This is the second case in the English language literature and the first to have documentation of malignant behavior. The tumor measured 11 cm in diameter and showed marked necrosis with prominent mitotic activity (average 15 per 10 high-power fields). Smooth muscle differentiation was apparent ultrastructurally and confirmed by positive immunostaining for muscle-specific and alpha-smooth muscle actin. Bony metastases developed; following palliative treatment with radiation and chemotherapy, the patient is alive with tumor 9 months later. Origin from smooth muscle associated with the central adrenal vein or its tributaries is proposed.

Adrenal Gland Neoplasms↗
PubMed1991

Identification of human immunodeficiency virus envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T-leukemia cells, and macrophages.

Infectious recombinant viruses were constructed from three molecularly cloned human immunodeficiency virus (HIV) strains varying in cell tropism. All recombinants showed a high infectivity titer on phytohemagglutinin-stimulated normal T lymphocytes. However, a 120-bp region of the envelope gene including the area of the V3 hypervariable loop was found to influence infectivity titer on both clone 1022 CD4-positive HeLa cells and CD4-positive CEM leukemia cells. Infectivity for macrophages was more complex. All viruses replicated in macrophages to a low level, but viral sequences both inside and outside the V3 loop region influenced the efficiency of replication. Two experiments showed that the mechanism of restriction of infection of 1022 cells by HIV strain JR-CSF was related to lack of virus entry. First, productive virus infection occurred after transfection of 1022 cells with viral plasmid DNA. Second, the nonpermissive HIV strain JR-CSF could infect 1022 cells when pseudotyped with the envelope of other retroviruses, including human T-cell leukemia virus type I (HTLV-I), HTLV-II, and amphotropic murine leukemia virus. These results demonstrate the possibility that unexpected cell types might be infected with HIV in human patients coinfected with HIV and HTLV-I or HTLV-II.

Amino Acid Sequence↗
PubMed1990

Endoscopic stent configuration and bile flow rates in a variable diameter bile duct model.

Endoscopically placed biliary stents are used in the treatment of biliary strictures and obstruction. Patency of the stent is related to bile flow rate through the stent. The purpose of this study was to examine the influence of stent diameter, configuration, and common duct diameter on bile flow rates. Flow rates were examined in straight and pigtail stents, 7 Fr and 10 Fr, and in a 1 cm and 2.3 cm diameter CBD model. Bile-flow rates were greater in the straight and 10 Fr stents. Bile-duct diameter had no influence on flow rate in pigtail stents. Though flow rates decreased with straight stents in bile ducts of increasing diameter, the absolute flow rates always remained greater in the straight stents when compared to the pigtail stents. We conclude that straight stents, because of greater flow rates, are to be preferred over pigtail stents for the treatment of biliary obstruction in dilated and nondilated systems.

Bile Ducts↗