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Biomedical subjects

J F Moran

Publications and source records attributed to J F Moran.

At least 19 recordsLinked to original sources

A randomized trial of the low-molecular-weight heparin certoparin to prevent restenosis following coronary angioplasty.

OBJECTIVES: The objectives of this study were to evaluate the effectiveness and safety of the low-molecular-weight heparin (LMWH) certoparin in preventing restenosis following balloon coronary angioplasty. BACKGROUND: Restenosis following coronary angioplasty continues to limit the long-term efficacy of this procedure. Animal studies have indicated a potential role for LMWH in reducing restenosis by limiting smooth muscle proliferation. METHODS: This study tested the effects of certoparin, self-administered for 3 months, in reducing restenosis following balloon coronary angioplasty. One hundred and eighteen patients with 158 lesions treated with angioplasty were enrolled in this randomized, placebo-controlled trial. One hundred and two patients completed the study. The endpoint was relative loss measured with quantitative coronary angiography. RESULTS: The relative loss for placebo was 0.19 +/- 0.23 compared to 0.14 +/- 0.21 for LMWH (p = NS). The minimum lumen diameter (MLD) was 1.47 +/- 0.66 for placebo and 1.40 +/- 0.57 for the LMWH (p = NS). There was a reduction (31% for LMWH; 49% for placebo PSDP) in the percent of patients having binary restenosis (MLD < 50% of reference diameter). At the end of the study 77% of the placebo patients and 76% of the LMWH group were asymptomatic (p = NS). There was a low rate of bleeding complications and these were minor. Bone density scans showed that there was no significant occurrence of osteoporosis with 3 months of LMWH. CONCLUSIONS: Administration of certoparin for 3 months is safe, but appears ineffective in reducing post-PTCA restenosis.

Adult↗

Myocardial revascularization in the elderly using beating heart coronary artery bypass surgery.

BACKGROUND: Beating heart or "off-pump" coronary artery bypass (OP-CAB) has become an accepted method of myocardial revascularization by reducing the perioperative morbidity related to cardiopulmonary bypass (CPB). However, the efficacy of OP-CAB has not been well established in the elderly patient population. METHODS: OP-CABs were performed in 53 patients aged 75 years and older, at Pitt County Memorial Hospital from January 1996 to October 1999, either through a median sternotomy or an anterior thoracotomy. These results were compared with 220 patients who underwent standard coronary artery bypass graft (CABG) operation using CPB during the same time period. RESULTS: Mean patient age for both groups was 79+/-0.5 years and preoperative risk factors were similar. There were no differences in postoperative myocardial infarction, atrial fibrillation, bleeding, neurologic complications, or renal failure. There were no deaths after OP-CAB, compared with the 7.6% operative mortality rate after CABG (p<0.05). The OP-CAB group had a significantly shorter postoperative length of stay (4.4+/-0.4 days vs. 8.4+/-0.6 days) and lower transfusion requirements (0.4+/-0.1 units packed red blood cells vs 1.9+/-0.2 units packed red blood cells) than the CABG group. CONCLUSIONS: Our data demonstrate that OP-CAB is a safe and efficacious method of myocardial revascularization in the elderly, and may actually be preferential in these patients when applicable.

Aged↗

Glutathione and homoglutathione synthetases of legume nodules. Cloning, expression, and subcellular localization.

The thiol tripeptides glutathione (GSH) and homoglutathione (hGSH) are very abundant in legume root nodules and their synthesis is catalyzed by the enzymes gamma-glutamylcysteine synthetase (gammaECS), GSH synthetase (GSHS), and hGSH synthetase (hGSHS). As an essential step to elucidate the role of thiols in N(2) fixation we have isolated cDNAs encoding the three enzymes and have quantified the transcripts in nodules. Assay of enzyme activities in highly purified nodule organelles revealed that gammaECS is localized in the plastids, hGSHS in the cytosol, and GSHS in the cytosol and mitochondria. These results are consistent with sequence analyses. Subcellular fractionation of nodules also showed that bacteroids contain high thiol concentrations and high specific gammaECS and GSHS activities. Results emphasize the role of nodule plastids in antioxidant protection and in control of thiol synthesis, and suggest that plastids may be important in the stress response of nodules. Overall, our results provide further evidence that thiol synthesis is critical for nodule functioning.

Amino Acid Sequence↗

Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia.

PURPOSE: The complications of heparin-induced thrombocytopenia include thrombosis and death. The purpose of the study was to determine whether early heparin cessation can prevent these outcomes. SUBJECTS AND METHODS: We performed a retrospective analysis of consecutive patients with heparin-induced thrombocytopenia diagnosed by platelet aggregometry. Demographic, clinical, and laboratory findings were compared in patients by whether heparin treatment was stopped early (< or = 48 hours) or late (>48 hours) after the onset of thrombocytopenia, as well as between patients with and without thrombosis. Thrombocytopenia was defined as a 50% decline in baseline platelet counts or an absolute platelet count < 100,000/mm3. RESULTS: Of the 113 patients, 38% developed thrombosis and 27% died. One-half of patients had thrombosis diagnosed >24 hours after heparin cessation. No difference in thrombosis or mortality was found in the 40 patients with early heparin cessation [mean (+/-SD) time of cessation 0.7 +/- 0.6 days] compared with the 73 patients with late heparin cessation (5 +/- 3 days). Thrombosis >24 hours after heparin cessation occurred in 61% of the patients in the early group and in 40% of the late group (P = 0.17). In a multivariate analysis, only a lower nadir of the platelet count (percent of baseline) was associated with thrombosis. Neither thrombosis nor the time to heparin cessation were associated with mortality. CONCLUSIONS: Early heparin cessation was not effective in reducing morbid events in patients with heparin-induced thrombocytopenia. Treatment strategies other than heparin cessation alone should be considered in patients with this condition.

Adult↗

Stress-induced legume root nodule senescence. Physiological, biochemical, and structural alterations.

Nitrate-fed and dark-stressed bean (Phaseolus vulgaris) and pea (Pisum sativum) plants were used to study nodule senescence. In bean, 1 d of nitrate treatment caused a partially reversible decline in nitrogenase activity and an increase in O(2) diffusion resistance, but minimal changes in carbon metabolites, antioxidants, and other biochemical parameters, indicating that the initial decrease in nitrogenase activity was due to O(2) limitation. In pea, 1 d of dark treatment led to a 96% decline in nitrogenase activity and sucrose, indicating sugar deprivation as the primary cause of activity loss. In later stages of senescence (4 d of nitrate or 2-4 d of dark treatment), nodules showed accumulation of oxidized proteins and general ultrastructural deterioration. The major thiol tripeptides of untreated nodules were homoglutathione (72%) in bean and glutathione (89%) in pea. These predominant thiols declined by approximately 93% after 4 d of nitrate or dark treatment, but the loss of thiol content can be only ascribed in part to limited synthesis by gamma-glutamylcysteinyl, homoglutathione, and glutathione synthetases. Ascorbate peroxidase was immunolocalized primarily in the infected and parenchyma (inner cortex) nodule cells, with large decreases in senescent tissue. Ferritin was almost undetectable in untreated bean nodules, but accumulated in the plastids and amyloplasts of uninfected interstitial and parenchyma cells following 2 or 4 d of nitrate treatment, probably as a response to oxidative stress.

Antioxidants↗

Glutathione and homoglutathione synthesis in legume root nodules.

High-performance liquid chromatography (HPLC) with fluorescence detection was used to study thiol metabolism in legume nodules. Glutathione (GSH) was the major non-protein thiol in all indeterminate nodules examined, as well as in the determinate nodules of cowpea (Vigna unguiculata), whereas homoglutathione (hGSH) predominated in soybean (Glycine max), bean (Phaseolus vulgaris), and mungbean (Vigna radiata) nodules. All nodules had greater thiol concentrations than the leaves and roots of the same plants because of active thiol synthesis in nodule tissue. The correlation between thiol tripeptides and the activities of glutathione synthetase (GSHS) and homoglutathione synthetase (hGSHS) in the nodules of eight legumes, and the contrasting thiol contents and activities in alfalfa (Medicago sativa) leaves (98% hGSH, 100% hGSHS) and nodules (72% GSH, 80% GSHS) indicated that the distribution of GSH and hGSH is determined by specific synthetases. Thiol contents and synthesis decreased with both natural and induced nodule senescence, and were also reduced in the senescent zone of indeterminate nodules. Thiols and GSHS were especially abundant in the meristematic and infected zones of pea (Pisum sativum) nodules. Thiols and gamma-glutamylcysteinyl synthetase were also more abundant in the infected zone of bean nodules, but hGSHS was predominant in the cortex. Isolation of full-length cDNA sequences coding for gamma-glutamylcysteinyl synthetase from legume nodules revealed that they are highly homologous to those from other higher plants.

Amino Acid Sequence↗

A community hospital-based congestive heart failure program: impact on length of stay, admission and readmission rates, and cost.

OBJECTIVE: To do an analysis of patients with a primary diagnosis of congestive heart failure at discharge before (n = 407) and after (n = 347) the implementation of a comprehensive inpatient and outpatient congestive heart failure program consistent with the guidelines of the Agency for Health Care Policy and Research. STUDY DESIGN: A retrospective analysis of the impact of the congestive heart failure program on length of stay, admission and readmission rates, and costs to both patient and provider. The program, which used a multidisciplinary team approach, included an intensive education program focusing on diet, compliance, and symptom recognition, as well as the use of outpatient infusions. It also incorporated aggressive pharmacologic treatment for patients with advanced congestive heart failure. RESULTS: Our analysis revealed significant decreases in length of stay, admission and readmission rates, and costs to the patient and provider (P < or = .05). The mean cost per admission decreased 17% ($1118), and a substantial 77% ($718,468) net reduction in nonreimbursed (lost) hospital revenue was noted. CONCLUSION: A multidisciplinary, comprehensive congestive heart failure program can improve patient care in a community-hospital setting while significantly reducing costs to both the patient and the institution.

Cardiology Service, Hospital↗

Minimally invasive mitral valve repair using transthoracic aortic occlusion.

This report describes a minimally invasive mitral valve repair done through a limited (6-cm) thoracic incision. The patient was supported by peripheral extracorporeal perfusion with cardiac arrest established using a new transthoracic aortic cross-clamp and antegrade blood cardioplegia. The patient was discharged on postoperative day 3 with minimal pain. This less invasive approach to mitral valve surgery may offer combined advantages to patients by increasing comfort, expediting recovery, and decreasing surgical costs by using modified traditional methods compared with specialized intraaortic occlusive balloons.

Cardiac Surgical Procedures↗

Video-assisted minimally invasive mitral valve surgery.

OBJECTIVE: This study was done to determine the potential benefits of minimally invasive mitral surgery performed with intraoperative video assistance. METHODS: From May 1996 until March 1997, a minithoracotomy and video assistance were used in 31 consecutive patients undergoing mitral repair (n = 20) and replacement (n = 11). Their ages ranged from 18 to 77 years (59 +/- 2.6 years; mean +/- standard error of the mean). Ejection fractions were 35% to 62% (55% +/- 1.5%). Operations were done with either antegrade/retrograde (n = 10) or antegrade (n = 19) cold blood cardioplegia and a new transthoracic crossclamp or with ventricular fibrillation (n = 2). Peripheral arterial cannulation (n = 28) and pump-assisted right atrial drainage (n = 26) were used most often. RESULTS: No hospital deaths occurred, but the 30-day mortality was 3.2%. Complications included deep venous thrombosis and a phrenic nerve palsy in one patient each. No patient had a stroke or required reoperation for bleeding. Postoperative echocardiography showed excellent valve function in all but one patient. Cardiopulmonary bypass and arrest times averaged 183 +/- 7.2 and 136 +/- 5.5 minutes, respectively. Compared with 100 patients having conventional mitral valve operations, these patients had significantly shorter hospitalization times (8.6 +/- 0.5 vs 5.1 +/- 0.9 days, p = 0.05). Moreover, 81% of the later cohort were discharged between day 3 and 5 (3.6 +/- 0.2 days). Hospital charges (decreases 27%, p = 0.05) and costs (decreases 34%, p < 0.05) were less than in conventional operations. Patient follow-up suggested minimal perioperative pain and rapid recovery. CONCLUSIONS: Early results suggest that video-assisted minimally invasive mitral operations can be done safely. These methods may benefit patients through less morbidity, earlier discharge, and lower cost.

Cardiopulmonary Bypass↗

Complexes of iron with phenolic compounds from soybean nodules and other legume tissues: prooxidant and antioxidant properties.

The low-molecular-mass fraction of the soybean nodule cytosol contains Fe capable of catalyzing free radical production through Fenton chemistry. A large portion of the pool of catalytic Fe, measured as bleomycin-detectable Fe, was characterized as complexes of Fe with phenolic compounds of three classes: phenolic acids, cinnamic acids, and flavonoids. Many of these compounds, along with other phenolics present in legume tissues, were used for a systematic structure-activity relationship study. All phenolics tested were able to chelate Fe, as judged from their inhibitory effect on site-specific deoxyribose degradation (minus EDTA assay). However, only those having catechol, pyrogallol, or 3-hydroxy-4-carbonyl groupings were potent chelators and reductants of Fe3+ at pH 5.5. The same phenolics promoted oxidative damage to DNA (bleomycin assay) and to deoxyribose (plus EDTA assay), but inhibited linolenic acid peroxidation by chelating and reducing Fe3+ and by neutralizing lipid radicals. Also, phenolics having a pyrogallol nucleus attenuated the free radical-mediated inactivation of glutamine synthetase, which was used as a model system, by chelating Fe2+. It is reasoned that under the microaerobic (10-20 nM O2) and acidic (pH 5.5-6.4) conditions prevailing in nodules, phenolics are likely to act primarily as antioxidants, decreasing oxidative damage to biomolecules.

Antioxidants↗

Molecular cloning of the cowpea leghemoglobin II gene and expression of its cDNA in Escherichia coli. Purification and characterization of the recombinant protein.

Cowpea (Vigna unguiculata) nodules contain three leghemoglobins (LbI, LbII, and LbIII) that are encoded by at least two genes. We have cloned and sequenced the gene that encodes for LbII (lbII), the most abundant Lb in cowpea nodules, using total DNA as the template for PCR. Primers were designed using the sequence of the soybean lbc gene. The lbII gene is 679 bp in length and codes for a predicted protein of 145 amino acids. Using sequences of the cowpea lbII gene for the synthesis of primers and total nodule RNA as the template, we cloned a cDNA for LbII into a constitutive expression vector (pEMBL19+) and then expressed it in Escherichia coli. Recombinant LbII (rLbII) and native LbII (nLbII) from cowpea nodules were purified to homogeneity using standard techniques. Properties of rLbII were compared with nLbII by partially sequencing the proteins and by sodium dodecyl sulfate- and isoelectric focusing polyacrylamide gel electrophoresis, western-blot analysis using anti-soybean Lba antibodies, tryptic and chymotryptic mapping, and spectrophotometric techniques. The data showed that the structural and spectral characteristics of rLbII and nLbII were similar. The rLbII was reversibly oxygenated/deoxygenated, showing that it is a functional hemoglobin.

Amino Acid Sequence↗

Rice hemoglobins. Gene cloning, analysis, and O2-binding kinetics of a recombinant protein synthesized in Escherichia coli.

Although nonsymbiotic hemoglobins (Hbs) are found in different tissues of dicots and monocots, very little is known about hb genes in monocots and the function of Hbs in nonsymbiotic tissues. We report the cloning and analysis of two rice (Oryza sativa L.) hb genes, hb1 and hb2, that code for plant Hbs. Rice hb1 and hb2 genes contain four exons and three introns, as with all of the known plant hb genes. At least three copies of the hb gene were detected in rice DNA, and analysis of gene expression shows that hb1 and hb2 are expressed in leaves but only hb1 is expressed in roots. A cDNA for rice Hb1 was expressed in Escherichia coli, and the recombinant Hb (rHb1) shows an unusually high affinity for O2 because of a very low dissociation constant. The absorbance spectra of the ferric and deoxyferrous rHb1 indicate that, in contrast to symbiotic Hbs, a distal ligand is coordinated to the ligand-binding site. Mutation of the distal His demonstrates that this residue coordinates the heme Fe of ferric and deoxyferrous rHb1 and stabilizes O2 in oxy-rHb1. The biochemical properties of rice rHb1 suggest that this protein probably does not function to facilitate the diffusion of O2.

Amino Acid Sequence↗

Transhiatal versus transthoracic esophagectomy for adenocarcinoma of the distal esophagus and cardia.

BACKGROUND: Transhiatal esophagectomy is a popular method of resection because of its reported lower morbidity and mortality and similar survival rates compared to transthoracic esophagectomy. A review of recent experience with these two procedures for resection of distal esophageal and cardia adenocarcinoma is reported. METHODS: From 1988 to 1994, 48 patients with adenocarcinoma of the distal esophagus and gastric cardia were resected with intent to cure, 32 by transhiatal esophagectomy (group 1) and 16 by transthoracic esophagectomy (group II). The two groups were comparable in terms of patient demographics, preoperative risk factors, tumor stage, tumor differentiation, and involvement of resection margins (all not significant [NS]). RESULTS: There was no significant difference in median intensive care unit stay, median hospital stay, incidence of postoperative anastomotic leak, and stricture. Respiratory complications were higher in group I (41% versus 6%, P = 0.01). Hospital mortality was not significantly different for the two groups (group I 3.1% versus group II 0%, NS). Actuarial 5-year survival rates (Kaplan-Meier) were 12% for group I and 39% for group II (NS). CONCLUSIONS: These results suggest that when compared with transhiatal esophagectomy, the transthoracic approach is at least as safe, has comparable complication and survival rates, and remains an acceptable procedure for resection of adenocarcinomas of the distal esophagus and gastric cardia.

Adenocarcinoma↗

Significance of electrocardiographic ST elevation during coronary artery bypass surgery.

The aim of this study was to determine the significance of new electrocardiographic (ECG) ST elevation during coronary artery bypass surgery. Multilead ECGs were recorded intraoperatively approximately every 3 min on 105 patients. Cases of new ST elevation were divided into ischemic and those considered to be due to nonischemic causes such as cooling during cardiopulmonary bypass (CPB), defibrillation, new cardiac conduction abnormalities, and pericarditis. The myocardial fraction of creatine kinase (CK-MB) > or = 25 IU/L was considered to be indicative of myocardial injury. Both patients who had ischemic ST elevation prior to CPB and all seven patients who had ST elevation in temporal association with the administration of protamine had peak CK-MB > or = 25 IU/L. One patient with peak CK-MB > or = 25 IU/L did not have ST elevation and was considered to have injury during CPB. Two of these ten patients had Q wave myocardial infarctions (MIs). For the detection of patients with peak CK-MB > or = 25 IU/L, the sensitivity of ischemic ST elevation was 90% and the specificity was 100%. A history of MI prior to surgery and a history of Type I diabetes were associated with peak CK-MB > or = 25 IU/L (P < 0.05).

Aged↗

Infective aortic endocarditis after percutaneous balloon aortic valvuloplasty.

Infective aortic endocarditis developed in an elderly patient after a percutaneous balloon aortic valvuloplasty. The transesophageal echocardiogram demonstrated a perivalvular abscess. The patient underwent surgical replacement of the infected valve, but later succumbed to renal failure. The development of infective aortic endocarditis should be recognized as a potentially fatal complication of percutaneous balloon aortic valvuloplasty. The important measures in preventing bacteremia during percutaneous balloon aortic valvuloplasty and the appropriate role of operation are discussed.

Aged↗

Pulmonary mucinous cystic tumor. Case report with review of the literature.

Mucinous cystic tumors of the lung are exceedingly rare. We describe the case of a 59-year-old white man with a left upper lobe mass documented on chest radiographs 11 years before thoracotomy. Grossly, the lobectomy specimen contained a 4.5 x 4.5 x 4.0 cm cystic gelatinous mass with complete occlusion of the anterior segmental bronchus by mucinous material. Although microscopically this pulmonary mucinous cystic tumor contained a focus of marked glandular atypia consistent with adenocarcinoma, the patient has remained free of recurrence or metastasis during 5 years of close postoperative follow-up. Pulmonary mucinous cystic tumors appear to have a remarkably favorable prognosis and should be distinguished from other common lung neoplasms.

Cysts↗

The clinical significance of exercise-induced bundle branch block.

Exercise-induced bundle branch block is an uncommon electrocardiographic entity said to be associated with coronary heart disease. Thirty-seven patients were studied to determine if exercise hemodynamics and stress/rest thallium scans could identify those patients with coronary heart disease. Eighteen patients of the study group also had coronary angiography. Group I (n = 17) with normal thallium scans and group II (n = 20) with abnormal thallium scans had significantly different maximal heart rate, maximal blood pressure, and double product in exercise as well as duration of exercise. Clinical evaluation of the patient study group permitted a division of the patients into two subgroups: group A, atypical chest pain or abnormal exercise electrocardiogram (n = 12), and group B, definite or probable angina (n = 25). Group B patients had significantly more abnormal thallium scans (17/25) than group A patients (3/12) (p less than 0.04). When compared to coronary angiography, stress/rest thallium scans had a predictive accuracy of 85% for coronary heart disease. While exercise-induced ST-segment depression and R wave amplitude increases are not specific in exercise-induced bundle branch block, exercise hemodynamics and stress/rest thallium scans can help diagnose patients with coronary heart disease. These test findings added to a clinical evaluation permit a more accurate stratification of the patients and indicate which patients need further study.

Bundle-Branch Block↗

Electrophysiological testing and nonsustained ventricular tachycardia. Use and limitations in patients with coronary artery disease and impaired ventricular function.

Electrophysiological testing was performed in 100 consecutive patients with spontaneous asymptomatic nonsustained ventricular tachycardia, chronic coronary artery disease, and ejection fraction of less than 40%. Fifty-seven patients without inducible sustained ventricular arrhythmias were discharged on no antiarrhythmic therapy. Sustained monomorphic ventricular tachycardia was induced in 37 patients, and polymorphic ventricular tachycardia or ventricular fibrillation was induced in six patients. Of the 43 patients with inducible sustained ventricular arrhythmias, three had spontaneous cardiac arrest during serial drug testing and were excluded from further analysis. Twenty patients were discharged on drug therapy, resulting in suppression of inducible sustained ventricular arrhythmias. The remaining 20 patients with persistently inducible sustained arrhythmias were discharged on drug therapy, resulting in maximal rate slowing of the induced tachycardia. During a mean follow-up of 16.7 months, there were 10 recurrent cardiac arrests or sudden deaths. The 1- and 2-year actuarial incidence of these events was 2% and 6%, respectively, in patients without inducible sustained ventricular arrhythmias; 0% and 11%, respectively, in patients in whom inducible arrhythmias were suppressed; and 34% and 50%, respectively, in patients with persistently inducible sustained ventricular arrhythmias. Multivariate Cox analysis identified only the persistence of inducible sustained ventricular arrhythmias as a significant independent predictor of sudden death or recurrent sustained arrhythmias (p less than 0.001; relative risk, 3.5; 95% confidence intervals, 2.1-4.9). In this population, therapeutic intervention to prevent sudden death is unnecessary in patients without inducible sustained ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗