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Biomedical subjects

J R Stewart

Publications and source records attributed to J R Stewart.

At least 127 records · Page 7Linked to original sources
PubMed1985

Transhiatal (blunt) esophagectomy for malignant and benign esophageal disease: clinical experience and technique.

"Blunt" transhiatal esophagectomy was performed in 23 selected patients. Nineteen had squamous carcinoma of the esophagus (upper third, 1; middle third, 12; distal third, 6), and 2 had adenocarcinoma of the distal esophagus. The other 2 patients had severe lye strictures. Resection with reconstruction was performed in one stage. Esophagogastric continuity was restored using the stomach in the posterior mediastinal position in 20 patients and in the substernal position in 2. The colon in the posterior mediastinal position was used in 1 patient with a lye stricture. Transmural tumor extension or cervical or celiac nodal metastases or both were present in 18 of 21 patients with carcinoma. There was 1 hospital death due to pericardial tamponade. Morbidity included a transient cervical anastomotic leak in 3 patients, one temporary and three permanent unilateral recurrent laryngeal nerve palsies, one intraoperative splenic injury, and severe hemorrhage requiring sternotomy for control in 1 patient. Pulmonary complications occurred in 4 patients: aspiration pneumonia (1) and moderate atelectasis (3). Three patients have died (11, 12, and 17 months postoperatively) in the group with cancer, with follow-up time of 3 to 30 months (mean, 15 months). Transhiatal blunt esophagectomy is a safe and effective procedure in many patients with either esophageal cancer or extensive, benign esophageal strictures.

Adenocarcinoma↗
PubMed1985

Sequelae of left ventricular electrical endocardial ablation.

The endomyocardial residual effects of left ventricular endocardial electrical ablation utilizing unipolar and bipolar electrode catheters were studied in 15 dogs. Histopathologic techniques specific for contraction band necrosis revealed that the mean maximal depth and breadth of necrosis was 0.63 +/- 0.44 and 1.23 +/- 0.82 cm, respectively. The dimensions of necrosis were significantly increased when utilizing larger energy discharges, especially through unipolar electrodes. Four dogs died during the procedure, three from ventricular fibrillation and one from asystole, and two died suddenly within the succeeding 24 hours. Endocardial thrombi were noted at necropsy in two dogs. In conclusion, transcatheter endocardial electrical ablation may destroy a sufficient mass of myocardium to interrupt arrhythmogenic conduction tissue, especially when larger currents are delivered through unipolar electrodes. However, serious ventricular arrhythmias and endocardial thrombi should be anticipated.

Animals↗
PubMed1985

Prevention of free radical-induced myocardial reperfusion injury with allopurinol.

Growing evidence supports the concept that oxygen free radicals are an important cause of myocardial ischemic and reperfusion injury. This study was designed to determine if toxic oxygen metabolites may exacerbate ischemic injury upon reoxygenation. Left ventricular function was studied in a group of seven dogs receiving intermittent, 4 degrees C, hyperosmolar, hyperkalemic (KCI 25 mEq/L) saline cardioplegic solution. This group was compared to a group (n = 7) receiving a hyperkalemic (KCI 25 mEq/L) cardioplegic solution designed to scavenge superoxide anion and hydroxyl radical: superoxide dismutase (3,000 U/ml) and mannitol (325 mOsm/L). A third group of five animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours and hyperkalemic saline cardioplegic solution. After 60 minutes of ischemia (10 degrees to 15 degrees C) and 45 minutes of reperfusion, left ventricular mechanical function was better in the groups receiving free radical scavengers and allopurinol pretreatment than in the group receiving only hyperkalemic saline cardioplegic solution. Free radical scavengers preserved myocardial function in this model of hypothermic global ischemia and reperfusion. Our data support the concept that injury occurs primarily during reperfusion with the generation of oxygen free radicals via the hypoxanthine-xanthine oxidase reaction. Allopurinol has potential clinical application in the prevention of reperfusion injury.

Allopurinol↗
PubMed1985

Thoracentesis.

Use of the Intracath technique for thoracentesis has been described previously. However, the addition of side holes to the catheter and water seal drainage have improved the safety and facility of thoracentesis allowing complete evacuation of the pleural space. This method has proved safe and useful for thoracentesis and occasional chemical pleurodesis in our clinical applications over the past six years.

Catheters, Indwelling↗
PubMed1985

The influence of infarction site and size on the ventricular response to coronary thrombolysis.

To test the hypothesis that myocardial infarction (MI) size rather than location determines the ventricular response to reperfusion, we studied 69 patients receiving intracoronary streptokinase within five hours of chest pain onset who displayed sustained reperfusion at 8.4 +/- 3.4 (SD) days. Twenty reperfusion failures served as controls. There were 31 patients with anterior MIs, 18 of which were estimated to be large based on an ejection fraction (EF) at reperfusion of less than 50%; 14 of 38 patients with inferior MIs also had large MIs. The EF increased at follow-up by 6.4% +/- 2.6% in patients with large anterior MIs and by 8.2% +/- 2.5% in those with large inferior MIs; in contrast, it increased by only 1.8% +/- 2.6% in patients with small anterior MIs and significantly decreased by 5.8% +/- 1.9% in patients with small inferior MIs. Six controls with large MIs (four anterior) displayed no change in EF; in 14 with small MIs (ten inferior), it fell slightly. There were no significant group differences in the number of diseased vessels, residual stenosis, or collaterals. It is concluded that MI size, not site, largely determines the ventricular functional response to early reperfusion; thus, patients with inferior MIs cannot be disqualified on this basis alone for thrombolytic therapy.

Coronary Disease↗
PubMed1984

Hyperthermia in the treatment of cancer. Perspectives on its promise and its problems.

The potential for the use of hyperthermia in the treatment of cancer is based on a strong and compelling biologic rationale. In the laboratory it has been shown in quantitative assays both in vitro and in vivo that (1) hyperthermia is cytotoxic to tumor cells as a function of time at temperatures above 42 degrees C; (2) cytotoxicity is relatively high for radioresistant S-phase cells and for cells that are nutritionally deprived and acidotic, conditions one might expect in regions of tumors containing large numbers of radioresistant hypoxic cells; and (3) heat is a radiosensitizer and a chemosensitizer. Clinical study is hampered by less than optimal physical heating methods and the need for invasive thermometry. Ultrasonic and electromagnetic approaches each have limitations and advantages. In spite of technical limitations, efficacy has been shown for superficial tumor sites treated by local hyperthermia and Phase I studies are underway investigating the more complicated problem of deep regional hyperthermia. Although whole body hyperthermia has the attractive capability of treating metastatic as well as more localized cancer, it is toxic therapy and its role in treatment remains undefined. Research advances in equipment design and treatment optimization are needed; however, there are studies underway utilizing existing methods and rationale which should further clarify the potential clinical usefulness of regional hyperthermia in combined modality approaches to cancer therapy.

Animals↗
PubMed1984

Proteins of the kidney microvillar membrane. Biosynthesis of endopeptidase-24.11, dipeptidylpeptidase IV and aminopeptidases N and A in pig kidney slices.

An organ culture employing slices of renal-cortex tissue from piglets of the Yucatan strain was used to study the biogenesis of four microvillar peptidases: endopeptidase-24.11 (EC 3.4.24.11), dipeptidyl peptidase IV (EC 3.4.14.5), aminopeptidase N (EC 3.4.11.2) and aminopeptidase A (EC 3.4.11.7). The viability of the culture system was confirmed by the preservation of ultrastructural integrity and by an unchanged uptake of [3H]alanine into cells during the period of the experiments. After labelling with [35S]methionine, treatment with Mg2+ yielded two fractions, one containing microvilli and another, the Mg2+ pellet, containing intracellular and basolateral membranes. The labelled forms of the peptidases, isolated by immunoprecipitation, were analysed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and fluorography. The Mg2+ pellet contained the earliest detectable forms of the enzymes. In each case, a polypeptide of lower Mr than the mature form and sensitive to treatment with endo-beta-N-acetylglucosaminidase H was the first form to be detected. These high-mannose forms were followed, about 30 min after the pulse, by a complex glycosylated form of higher Mr. Only the latter form was observed in microvilli and then only after 90 min of the chase period. A quantitative study of dipeptidyl peptidase IV showed that the forms observed in the Mg2+ pellet were precursors of those in the microvillar fraction. No labelled forms were observed in the cytosol. All four peptidases were thus synthesized within membrane compartments and glycosylated in two steps before assembly in microvilli.

Aminopeptidases↗
PubMed1984

Proteins of the kidney microvillar membrane. Effects of monensin, vinblastine, swainsonine and glucosamine on the processing and assembly of endopeptidase-24.11 and dipeptidyl peptidase IV in pig kidney slices.

The effects of various inhibitors were studied on the biogenesis of endopeptidase-24.11 (EC 3.4.24.11) and dipeptidyl peptidase IV (EC 3.4.14.5) in slices of renal cortex, from piglets of the Yucatan strain, maintained in organ culture. These microvillar peptidases were synthesized within membrane compartments and underwent glycosylation to yield high-mannose and complex forms [the preceding paper, Stewart & Kenny (1984) Biochem. J. 224, 549-558]. Monensin caused very gross ultrastructural changes in the proximal-tubular cells, resulting from distension of the Golgi sacs. It blocked the processing of the high-mannose to the complex glycosylated forms of the peptidases and prevented their assembly in the microvillar membrane. Swainsonine, an inhibitor of alpha-mannosidase II, generated new 'hybrid' forms of the proteins, intermediate in Mr between the high-mannose and the complex forms, but did not prevent assembly of the hybrid forms in microvilli. Vinblastine, an agent that affects microtubules, delayed, but did not abolish, either the processing or the transport to microvilli. Glucosamine interfered with the initial glycosylation reactions and generated heterogeneous sets of partially glycosylated polypeptides of lower Mr than the high-mannose forms. These results are discussed in relation to the site and mechanism of glycosylation and the involvement of the Golgi complex and microtubules in the biogenesis of these membrane peptidases.

Alkaloids↗
PubMed1984

Deglycosylation by trifluoromethanesulphonic acid of endopeptidase-24.11 purified from pig kidney and intestine.

Endopeptidase-24.11, an integral microvillar membrane enzyme, exists in differently glycosylated forms when purified from pig kidney and intestine [Fulcher, Chaplin & Kenny (1983) Biochem. J. 215, 317-323]. When these glycoproteins, and another form of the kidney enzyme prepared from the Yucatan dwarf strain of piglet, were treated, under controlled conditions, with trifluoromethanesulphonic acid, the proteins were freed of carbohydrate and all had the same apparent subunit Mr (77 000) even though the untreated forms varied from Mr 89 000 to Mr 95 000.

Amino Acids↗
PubMed1984

A proposal for the clinical use of flecainide.

Effective antiarrhythmic therapy requires a carefully considered approach, including an understanding of the arrhythmia, the underlying cardiac disease and the drug's pharmacokinetics. Flecainide is a new antiarrhythmic drug that may soon be released for general use. Flecainide demonstrates unsurpassed efficacy in chronic ventricular arrhythmias in stable patients and may become a first-choice drug because of its ease of administration, efficacy and favorable tolerance. Twice-daily dosing with 100 to 200 mg usually provides effective therapy. Clinical experience suggests flecainide to be indicated in the treatment of uniform and multiform ventricular premature complexes, coupled ventricular premature complexes, and episodes of nonsustained ventricular tachycardia. A lower response rate is observed in preventing induction of sustained ventricular tachycardia, and these patients should be carefully selected. Flecainide is promising in the treatment of supraventricular tachycardias using atrioventricular nodal or extranodal reentrant pathways, although this use is still investigational in the United States. The drug's use for arrhythmias during acute myocardial infarction requires further study. Flecainide possesses modest negative inotropic potential. Proarrhythmic or other adverse reactions have occurred primarily in settings of high drug level, poor ventricular function or refractory, malignant arrhythmias, suggesting caution in these groups.

Anti-Arrhythmia Agents↗
PubMed1984

Procidentia in identical twins. Report of cases and analysis of treatment options.

Within a six-week interval, adult identical twin brothers presented with third-degree complete rectal prolapse. Since no other predisposing factors were evident, contribution of an inherited predisposition is implied. Evaluation of alternatives supports use of presacral rectal mobilization with subtotal anterior resection and reanastamosis of sigmoid colon and rectum as the curative procedure.

Colon, Sigmoid↗
PubMed1984

The effect of electrode position on atrial sensing for physiologically responsive cardiac pacemakers.

Fully automatic pacing systems rely on accurate identification of spontaneous atrial signals for physiologically responsive pacing. These signals must be discriminated from far-field ventricular activity, which might otherwise be sensed in the atrium. To amplify on the previously reported superiority of bipolar signals and high-impedance circuitry for atrial sensing, we studied the effects of various intraatrial electrode positions on the atrial and ventricular contribution to electrograms recorded in this chamber. Compared with other intraatrial endocardial sites, right atrial signals were greatest in amplitude and slew rate in the appendage (RAA), averaging 3.3 +/- 0.41 mV and 1.15 +/- 0.16 V/sec (mean +/- SEM), respectively. These values were substantially higher than in the low atrium (p less than 0.001 and 0.0005 for amplitude and slew rate, respectively) and the high lateral atrium (p less than 0.05 for slew rate). Appendage atrial electrograms also had significantly higher amplitude and slew rate than far-field R waves recorded here (p less than 0.0001 for both). Additionally, the greatest difference in spectral content between atrial and far-field ventricular signals was also observed in the RAA. Thus, parameters in the domain of both time and frequency identified the RAA as the superior location for atrial sensing. Except for phrenic nerve problems with pacing, the HRA also appears to be a suitable electrode location for sensing. These considerations are germane in light of a growing number of atrial active and passive fixation leads now being employed for physiologic pacing.

Cardiac Pacing, Artificial↗
PubMed1984

Electron arc therapy: clinical experience with chest wall irradiation.

In order to overcome the technical problems commonly encountered in fixed field photon and electron beam chest wall irradiation, we have treated the chest wall in 22 breast cancer patients with a moving electron beam that rotates about the patient's thorax. This paper discusses the clinical results of chest wall treatment by electron arc therapy. Twenty-one patients were treated following mastectomy, 16 electively because of high risk for local failure, and 5 because of local recurrence. One patient with advanced local-regional disease was treated primarily. During a median follow-up period of 24 months there has been one chest failure in one of the patients treated for local recurrence. No major complications were observed in skin, lung, soft tissue or esophagus, even in the 7 patients recently or concomitantly treated with multiagent cytotoxic chemotherapy. In 3 patients, small areas of telangiectasia developed in the region of abutment of the electron arc field to a photon field used to irradiate the supraclavicular nodal area. We conclude that the technique as applied to these patients is safe and efficacious. In certain clinical settings it has advantage over standard, fixed field approaches to treat the chest wall.

Breast Neoplasms↗