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Biomedical subjects

R W Anderson

Publications and source records attributed to R W Anderson.

At least 127 records · Page 7Linked to original sources

Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatibility complex antigens on infected cells.

Cytotoxic T lymphocytes (CTL) generated in C57BL/6 (H-2b) mice in response to infection with the serologically distinct herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) were cross-reactive against target cells infected with either serotype. However, HSV-2-infected cells were shown to be much less susceptible to CTL-mediated lysis, and analysis through the use of HSV-1 X HSV-2 intertypic recombinants mapped the reduced susceptibility to a region contained within 0.82 to 1.00 map units of the HSV-2 genome. The study reported here was undertaken to determine the possible reasons for the reduced susceptibility of HSV-2-infected cells to lysis by CTL. Competition for the specific lysis of labeled HSV-1-infected cells by either HSV-1- or HSV-2-infected, unlabeled inhibitor cells and frequency analysis of the CTL precursor able to recognize HSV-1- and HSV-2-infected cells suggested that the reduced susceptibility of HSV-2-infected cells to lysis could be explained, at least in part, by reduced levels of target cell recognition. A determination of the surface expression of the critical elements involved in target cell recognition by CTL following infection with HSV-1 or HSV-2 revealed that all the major HSV-specific glycoprotein species were expressed. Infection with both HSV-1 and HSV-2 caused a reduction in the expression of the class I H-2 antigens. However, this reduction was much greater following infection with HSV-2. This suggested that one important factor contributing to reduced lysis of HSV-2-infected cells may be the altered or reduced expression of the class I H-2 self-antigens.

Animals↗

Percutaneous catheter balloons: failure to deflate.

Three examples of permanently inflated transluminal catheter balloons are presented. Two of these occurred during attempted percutaneous transluminal angioplasty. Nonsurgical solutions, which were successful in each case, are described. Percutaneous puncture with a needle or a larger diameter coaxial catheter under fluoroscopic guidance may be useful when this complication occurs during attempted balloon angioplasty or embolization with proximal balloon occlusion in large vessels.

Aged↗

Electrophysiological effects of transient aortic occlusion in intact canine heart.

This study utilized sonomicrometers transmural multipolar electrodes and cardiac electrical stimulation techniques to examine the effect on myocardial electrophysiological characteristics of altering ventricular systolic mechanical properties by transient aortic occlusion. Nine anesthetized open-chest dogs were atrially paced, and timed extrastimuli were inserted during alternate drive-train sequences at right or left ventricular (RV, LV) epicardial sites to measure ventricular effective refractory period (ERP). Sonomicrometer measurements of LV systolic mechanical parameters and both RV and LV electrophysiological findings were determined prior to and during periods of transient aortic occlusion. Aortic occlusion was applied just prior to the last beat of each eight-beat atrial drive train and released immediately following the programmed ventricular extrastimulus. Aortic occlusion increased LV systolic pressure (+42 +/- 26.6 mmHg, P less than 0.01) and diminished segmental stroke shortening (0.100 +/- 0.059 mm, P less than 0.02), shortening fraction (0.086 +/- 0.048, P less than 0.001), mean velocity of stroke shortening (0.444 +/- 0.186 mm/s, P less than 0.001), and stroke work (P less than 0.001). LV epicardial and endocardial ERP were prolonged as a result of aortic occlusion (5 +/- 7.2 and 6 +/- 6.5 ms, respectively, P less than 0.05), whereas RV ERP was unchanged. Latency of premature beats at equivalent coupling intervals was unaltered. ERP prolongation correlated most strongly with reductions of segmental stroke shortening (r = 0.928, P less than 0.001), shortening fraction (r = 0.901, P less than 0.001), and mean shortening velocity (r = 0.819, P less than 0.01). Thus transient aortic occlusion prolonged LV refractoriness, and electrophysiological changes closely paralleled the severity of systolic mechanical disturbance.

Animals↗

Effects of global ischemia on the diastolic properties of the left ventricle in the conscious dog.

The alterations in regional diastolic mechanics that occur during regional myocardial ischemia (creep and increased myocardial stiffness) may be the result of interactions between the ischemic and surrounding nonischemic myocardium rather than the direct result of ischemia. Thus similar changes may not occur when the entire left ventricle is ischemic. Thus similar changes may not occur when the entire left ventricle is ischemic. To investigate this proposition, left ventricular diastolic mechanics were studied in seven chronically instrumented conscious dogs during global left ventricular ischemia. The anterior-posterior, septal-free wall, and base-apex axes of the left ventricle were measured with ultrasonic dimension transducers. Left and right ventricular pressures were measured with micromanometers. Myocardial blood flows were measured with left atrial injections of 15 microns radioactive microspheres. Global left ventricular ischemia was induced by hydraulic constriction of the left main coronary artery, which resulted in a 54% decrease in mean left ventricular subendocardial blood flow. Left ventricular volume, midwall circumference, and midwall circumferential stress were calculated from ellipsoidal shell theory. To construct pressure-strain and stress-strain relationships from diastolic data collected during vena caval occlusions, all measured and calculated dimensions were normalized to Lagrangian strains (fractional extension from unstressed dimension). During ischemia, creep (elongation of unstressed dimension) occurred in each of the three left ventricular axes. The mean unstressed dimension of the anterior-posterior axis increased from 5.39 +/- 0.53 to 5.85 +/- 0.50 cm ( p less than or equal to .05); the septal-free wall unstressed dimension increased from 5.11 +/- 0.53 to 5.72 +/- 0.80 cm (p less than or equal to .05); and the base-apex unstressed dimension increased from 7.04 +/- 0.61 to 7.25 +/- 0.65 cm (p less than or equal to .05). The relationship between diastolic midwall circumferential stress and strain shifted upward and to the left with ischemia, indicating that an increase in intrinsic myocardial stiffness had occurred. As a result of these mechanical alterations, there was a decrease in left ventricular chamber compliance that was manifested by a leftward shift of the diastolic pressure-volume strain relationship. Neither systolic bulging nor dysynchronous systolic shortening occurred in any of the three left ventricular spatial axes during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Successful treatment of mediastinal germ cell/endodermal sinus tumors.

Three patients with endodermal sinus tumor of the mediastinum and two with endodermal sinus tumor mixed with other histologies were treated with CEBA (cisplatin, etoposide, bleomycin, and doxorubicin [Adriamycin]) and by cytoreductive surgery. Three patients treated with CEBA followed by surgery achieved a complete remission and remain free of disease at 36+, 35+, and 28+ months, respectively, from diagnosis. Two patients were treated initially with vinblastine, bleomycin, cisplatin, and surgery, and neither achieved a complete remission. Both then received CEBA, and one achieved a complete remission (duration 47 + months). Bone marrow toxicity from CEBA was severe, abrupt, and cumulative. All patients experienced neutropenic fever, anemia, and thrombocytopenia requiring platelet transfusions. The CEBA followed by vigorous cytoreductive surgery is effective treatment for germ cell tumors of the medastinum containing endodermal sinus tumor elements.

Adolescent↗

Permeability of four disposable protective-clothing materials to seven antineoplastic drugs.

The permeability of four types of protective-clothing material to seven injectable antineoplastic drugs was studied. The protective materials tested were Saranex-laminated Tyvek, polyethylene-coated Tyvek, nonporous Tyvek, and Kaycel. Circles 6 cm in diameter were cut from a single garment of each material and exposed to each drug. Permeation of cisplatin, etoposide, mitomycin, cyclophosphamide, carmustine, and thiotepa was assessed by the Salmonella mutagenicity test after four hours of exposure. Doxorubicin permeation was assessed qualitatively over an eight-hour exposure period using a coloration assay. Saranex-laminated Tyvek was not permeable under the test conditions. Polyethylene-coated Tyvek was slightly permeable to thiotepa and carmustine. Nonporous Tyvek was permeable to all seven drugs, and the Kaycel garment was permeable to all of the drugs except etoposide. In no instance did permeation exceed 3.3% of the applied drug dose. Saranex-laminated Tyvek was the most protective of the barrier garments, followed closely in effectiveness by the polyethylene-coated Tyvek. Clothing made from these two Tyvek composites would allow less air flow and, therefore, would be less comfortable to wear for extended periods. Garments made of nonporous Tyvek or Kaycel would be more comfortable, but their use should be accompanied by an awareness of their potential permeability to certain antineoplastic drugs.

Antineoplastic Agents↗

Global left ventricular contractility in three models of hypertrophy evaluated with Emax.

Using the load independent contractility index, end-systolic pressure-volume ratio (Emax), contractility of the hypertrophied left ventricle (LV) from three different models was evaluated in conscious, resting dogs. The experimental animals included 12 dogs with perinephritic hypertension (HYP) (aortic diastolic pressure 130 +/- 5 mm Hg), 12 dogs who underwent aortic banding (AOB) at 6 to 8 weeks of age (resting aortic gradient 110 +/- 15 mm Hg), and 12 dogs with chronic fluid overload from aortocaval fistula (ACF). These were compared with 12 normal dogs (CTL). LV dimension and pressure were measured with ultrasonic tranducers and micromanometers. All three models resulted in hypertrophy with significant (P less than 0.01) increase in LV weight-to-body weight ratio (6.3 +/- 0.4, 8.4 +/- 0.5, 6.3 +/- 0.4, respectively, vs 4.4 +/- 0.1 g/kg). Cardiac output (6908 +/- 740 vs 2424 +/- 276 ml/min) and end-diastolic volume (118 +/- 11 vs 50 +/- 4 ml) were significantly (P less than 0.01) increased in AOB (18 +/- 1 vs 9 +/- 2 mm Hg). dp/dtmax was not significantly different among all groups. Emax (CTL = 5.3 +/- 0.4 mm Hg/ml) was not significantly changed in HYP (9.5 +/- 2.1) but was significantly (P less than 0.01) increased in AOB (14.1 +/- 2.6), and significantly (P less than 0.01) depressed in ACF (2.4 +/- .03). Thus, LV hypertrophy from systemic hypertension (HYP) or proximal aortic hypertension (AOB) is, at least initially, associated with preservation of contractility and normal hemodynamic performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Early mechanical function in the heterotopic heart transplant.

The characteristics of left ventricular (LV) function in the nonimmunosuppressed heterotopic heart transplant (TX) with less than 3 hr of cold preservation, were studied in 12 awake chronically instrumented dogs prior to TX (control), 1-12 hr post TX (P1), 12-24 hr post TX (P2), and 24-48 hr post TX (P3). Micromanometers measured LV transmural pressure and ultrasonic transducers measured ventricular dimension in order to allow calculations of myocardial mechanical properties. Immediately after transplant (P1) there was significant (P less than 0.05) depression noted in both diastolic function and systolic function (peak LV pressure, 137 +/- 5 vs 80 +/- 10 mm Hg; dp/dtmax, 2642 +/- 170 vs 1038 +/- 98 mm Hg/sec; maximum velocity of minor axis shortening, 4.46 +/- 0.50 vs 2.41 +/- 0.56; and Emax, 6.5 +/- 1.2 vs 2.0 +/- 1.4 mm Hg/ml). However, the contractility reserve (studied in six dogs) as estimated by postextrasystolic potentiation ratio was maintained (1.41 +/- 0.07 vs 1.37 +/- 0.15), suggesting reversibility of the depressed function. Over the next 2 days the diastolic function and the systolic function (at P3: 109 +/- 6 mm Hg, 1842 +/- 450 mm Hg/sec, 5.54 +/- 0.77 cm/sec, and 4.5 +/- 1.3 mm Hg/ml, respectively) gradually improved toward control. Microscopic examination of the autopsied hearts did not show significant evidence of rejection. Thus, the early depression of function in the heart TX appeared to be the result of ischemia from preservation and surgical trauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Atrial flutter, atrial fibrillation, and other primary atrial tachycardias.

Traditional classifications of atrial tachycardias include not only rhythm disturbances arising primarily within the atria, but also dysrhythmias in which it is now recognized that participation of both atrial and non-atrial tissue is required. We prefer to consider those arrhythmias in which the atria are the principal site of electrophysiologic disturbance as "primary" atrial tachyarrhythmias. The mechanisms, diagnosis, and treatment of these "primary" atrial tachycardias are the subject of this article.

Anti-Arrhythmia Agents↗

Infection of normal human thymic epithelial cells by Epstein-Barr virus (EBV) following implantation of EBV receptors.

Normal human thymic epithelial cells cannot be infected and transformed by Epstein-Barr virus (EBV). Measurements using fluorescein-labelled EBV and cytofluorograph revealed that the cells do not have receptors for the virus. Following transplantation of functional EBV receptors onto epithelial cell membranes, however, the cells were infected with EBV and expressed EBV-determined nuclear antigen (EBNA). No EBV associated antigens characteristic of the lytic cycle of the virus were detected. This method of in vitro infection by transforming viruses such as EBV may provide ways of deriving functioning thymic epithelial cell lines.

Antigens, Viral↗

Cardiac operations in patients with functioning renal allografts.

The Transplant Service at the University of Minnesota Hospitals has performed over 2,000 kidney transplants. Fourteen of these patients have developed cardiac conditions necessitating surgical intervention at intervals of 9 to 144 months (mean 67 months) following their transplantation. These individuals had a mean age of 42 years, and five (36%) were diabetic. All patients had functioning renal allografts with preoperative serum creatinine levels ranging from 1.0 to 1.8 mg/100 ml (mean 1.4 mg/100 ml). Ten patients underwent aorta-coronary saphenous vein bypass grafting. One patient underwent bypass grafting and concomitant left ventricular aneurysmectomy. Native valvular endocarditis developed in two patients. One had tricuspid valve debridement for fungal endocarditis and the other had aortic valve replacement for bacterial endocarditis. The final patient had calcific aortic stenosis and coronary artery disease necessitating aortic valve replacement and coronary bypass. Two patients (14%) died perioperatively. One was a young woman with juvenile-onset diabetes and preinfarction angina who died suddenly several days after the operation; at autopsy, she was found to have an occluded graft to the right coronary artery and extensive infarction. The other was a 54-year-old woman with calcific aortic stenosis, coronary artery disease, and unstable angina who died perioperatively of uncontrollable arrhythmias. Autopsy suggested that she may have had an unsuspected infarction 1 to 2 days before the operation. The remaining 12 patients had uneventful postoperative courses and returned to Class I functional status from a cardiac standpoint. There has been one late death (7%), 45 months after successful coronary artery bypass grafting, as a result of complications attendant to a perforated gastric ulcer. The remaining 11 patients are alive and well at intervals of 8 to 93 months (mean 31 months) after operation. Postoperative serum creatinine levels at hospital discharge averaged 1.6 mg/100 ml, not significantly changed from preoperative levels. Cardiac operations can be performed safely in patients with functioning renal allografts. Patient survival is acceptable and preservation of renal function has been uniformly successful in surviving patients.

Adult↗

Permeability of latex and polyvinyl chloride gloves to 20 antineoplastic drugs.

Permeability of latex and polyvinyl chloride (PVC) gloves to 20 injectable antineoplastic drugs was studied. Four types of gloves were evaluated: latex surgical gloves, latex examination gloves, and PVC gloves in two thicknesses. Each glove material was exposed to each drug for 90 minutes, and permeation was tested using a mutagenicity assay. Individual fingertips of thin PVC gloves and latex surgical gloves were tested for permeability at five time points (2-30 minutes) using a doxorubicin coloration assay. All drugs permeated the thin PVC gloves. Latex surgical gloves were definitely permeable to two drugs (carmustine and thiotepa) and exhibited borderline permeability to mechlorethamine hydrochloride. The thick PVC gloves were definitely permeable to four drugs (carmustine, thiotepa, mechlorethamine hydrochloride, and daunorubicin hydrochloride) and exhibited borderline permeability to two drugs (doxorubicin and mercaptopurine). The latex examination gloves were permeable to carmustine, thiotepa, mechlorethamine hydrochloride, and cyclophosphamide. Doxorubicin permeation of individual fingertips of thin PVC gloves varied in time and amount. Doxorubicin did not permeate the latex surgical glove material, but testing with thiotepa showed that individual fingertips of this material also varied in permeability. Glove thickness was a major determinant of permeability; latex surgical gloves were the least permeable and thin PVC gloves the most permeable to the antineoplastic drugs tested. Within individual gloves and glove types, time and amount of permeation were not uniform.

Antineoplastic Agents↗

Left ventricular adaptation to volume overload from large aortocaval fistula.

The manner in which the left ventricle responds to an acute volume overload has not been well defined. Left ventricular performance was studied in six chronically instrumented resting awake dogs in the control state and serially after creation of a large abdominal aortocaval shunt. Ultrasonic transducers measured minor and major axis diameters and equatorial wall thickness. Left ventricular pressure was obtained with micromanometers. Cardiac contractility was evaluated by the load-independent contractility index, EMAXsc (slope of the normalized end-systolic equatorial midwall circumferential stress-equatorial midwall circumference relationship). By 1 week postshunt, the dog had clinical signs of congestive heart failure (ascites, dyspnea, limb edema); although systolic aortic pressure remained stable, heart rate, end-diastolic volume, pulse pressure (systolic minus diastolic pressure), cardiac output, minute work and dp/dtmax were significantly increased. At 1 week the calculated left ventricular mass was increased by 10.1% +/- 4.0% above control. EMAXsc was significantly increased immediately after shunting but returned to control at 1 day and was less than control at 1 week. Thus adaptation of the left ventricle to acute volume overload is characterized by use of inotropic, chronotropic, and Starling reserves. However, chronic volume overload is characterized by decreased inotropic state and an apparent increase in hemodynamic performance (dp/dtmax, cardiac output, minute work), which appears to be maintained by an increase in cardiac mass and by chronotropic and Starling reserves.

Adaptation, Physiological↗

Permeability of latex and polyvinyl chloride gloves to carmustine.

Permeability of latex and polyvinyl chloride gloves to the antineoplastic agent carmustine was studied. The latex gloves were of two types: sterile surgical gloves and disposable utility gloves. Polyvinyl chloride gloves of two thicknesses (0.20 mm and 0.35 mm) were tested. Both single and double thicknesses of each material were exposed to carmustine 3.33 mg/ml in a 10% aqueous solution of ethanol, and to the solvent alone, for 5-90 minutes. Permeation of carmustine was tested using a mutagenicity assay and a chemical assay. A time-dependent increase in carmustine permeation was observed for all types of materials (both double and single thicknesses). Mean amounts of carmustine permeating single gloves at 90 minutes ranged from 53 to 86 micrograms for the mutagenicity assay and 49 to 78 micrograms for the chemical assay. Double thicknesses of glove material (especially of the thicker polyvinyl chloride) reduced the amount of drug permeation. These latex and polyvinyl chloride glove materials offer only limited protection against contact exposure to carmustine. Latex surgical gloves may be slightly less permeable than the other types tested.

Carmustine↗

Surgical resection for isolated cardiac metastases.

We performed what we believe to be the second successful resection of metastatic liposarcoma to the heart using cardiopulmonary bypass. Analysis of ten previous resections of cardiac metastases from a variety of tumors from distant primary sites revealed survivals from four months to two years. When patients can tolerate a major operative procedure, resection of solitary cardiac metastases can be successful if the primary tumor is well controlled. Patients with sarcomas and with long disease-free intervals should strongly be considered for aggressive surgical therapy. Computed tomographic scans of the chest were useful in the diagnosis and accurate delineation of the extent of tumor.

Aged↗

Cardiac arrest in young, ostensibly healthy patients: clinical, hemodynamic, and electrophysiologic findings.

This study examines the clinical, hemodynamic, and electrophysiologic findings in a unique group of 11 young (aged 15 months to 29 years) survivors of a cardiac arrest. All patients were previously in good health, and cardiac arrest was the initial manifestation of cardiac disease in all. Overt clinical and hemodynamic abnormalities were not as common as previously reported, and in some instances apparent cardiac abnormalities failed to provide a link to cardiac arrest. No patient had congenital heart disease or hypertrophic cardiomyopathy. However, during multicatheter electrophysiologic study, sustained tachyarrhythmia was reproducibly initiated in 8 of 11 patients (73%). Young, ostensibly healthy patients who survive cardiac arrest form a diverse group. Diligent programmed intracardiac electrical stimulation may demonstrate life-threatening tachycardias in these patients. Treatment to prevent recurrence of cardiac arrest is difficult in this group of patients. However, the ability to initiate tachycardia in the electrophysiologic laboratory may be useful in the management of these patients.

Adolescent↗