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Biomedical subjects

B S Edwards

Publications and source records attributed to B S Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1985

Morphologic changes in the pulmonary arteries after percutaneous balloon angioplasty for pulmonary arterial stenosis.

The pathologic appearance of pulmonary arteries subjected to balloon dilation was studied in four subjects with stenosis of pulmonary arteries. Nine vessels were dilated. Successful dilation in seven vessels was accompanied by intimal disruption and tearing of the media. In one vessel, at the site of a previous surgical procedure, dilation could not be accomplished. Histologically, this vessel was encased by reactive fibrous tissue, which may have precluded successful dilation. In one case, simultaneous rupture of the dilating balloon and the left pulmonary artery occurred. Morphologic examination could not adequately explain the cause of vessel rupture. Among the six vessels successfully dilated and studied 4 to 14 months after the dilation, the postdilation luminal diamter had been maintained. Tears in the intima and media as seen histologically had been filled in by scar tissue. In one artery a dilated segment distal to a residual obstruction revealed marked intimal proliferation.

Angioplasty, Balloon↗
PubMed1985

Low doses of interferon alpha result in more effective clinical natural killer cell activation.

To define critical parameters concerning interferon (IFN) effects upon natural killer (NK) cells in vivo, we gave cancer patients serial weekly intramuscular injections of purified lymphoblastoid IFN in six doses ranging from 10(5) to 3 X 10(7) U. Dose sequences were determined by randomly allocating patients to one of six levels in a latin square ordering scheme. NK cell stimulation, a threefold peak increase above preinjection levels of cytolysis (P = 0.022), occurred in peripheral mononuclear cells (PMC) sampled 24 h postinjection, of 3 X 10(6) U, but was not detectable at any dose in PMC sampled 7 d postinjection. No blunting occurred in NK cell responsiveness to repeated injection of IFN dosages a second time at or several weeks after study completion. At IFN doses of 3 X 10(6), 10(7), and 3 X 10(7) U, a negative correlation existed between the amount of IFN injected and the average extent of NK cell activation (r = -0.423, P less than 0.05). This contrasted with the progressively increasing response of NK cells to in vitro incubation with increasing concentration of up to 3,000 U/ml of IFN. Overnight culturing of PMC sampled before IFN injections resulted in a mean 1.9-fold increase in cytolytic activity (P = 0.0005) and a mean 53% decrease in variance (P = 0.024) between serial preinjection NK cell activity determinations. Cell separation procedures may, therefore, have resulted in NK cell inactivation, from which overnight culturing permitted recovery. We found that maximal NK cell activation at a low IFN dose, decreasing NK cell responsiveness at higher doses, and the need to culture PMC to efficiently detect NK cell boosting may account for disparities in reported effects of IFN on NK cell function.

Cells, Cultured↗
PubMed1985

Pathology of surgically excised mitral valves. One hundred consecutive cases.

In this study, 100 consecutive, surgically excised, mitral valves were examined pathologically. The valves were classified according to primary conditions that resulted in valvular malfunction. Rheumatic mitral valvular diseases (stenosis and/or insufficiency) accounted for 54% of the cases. Myxomatous changes (prolapse) were present in 32 cases. Fifty-nine percent (19 cases) of those cases with myxomatous changes also had chordal rupture. Four of the cases had papillary muscle rupture, and in seven cases, papillary muscle dysfunction occurred. In one case bacterial endocarditis was observed on a previously normal valve. In one case the pathology of valvular. In one case the pathology of valvular changes was indeterminant. Lupus erythematosus was diagnosed in one patient, and mitral valve insufficiency may have resulted as a complication.

Aged↗
PubMed1984

Ventricular septal rupture complicating acute myocardial infarction: identification of simple and complex types in 53 autopsied hearts.

Fifty-three hearts with rupture of the ventricular septum complicating acute myocardial infarction (AMI) were studied. Thirty-three of the hearts were from men (average age 76 years) and 20 were from women (average age 73 years). The study showed 2 types of rupture of the ventricular septum: simple (28 patients) and complex (25 patients). Simple ruptures were direct through-and-through defects. Complex ruptures were associated with serpiginous dissection tracts remote from the primary site of tear of the ventricular septum. Specimens were classified as to the location of the underlying AMI and the level of the septum (apex to base) at which the rupture occurred. Twenty-nine hearts had an inferior AMI and 24 an anterior AMI. Complex ruptures occurred in 20 of the inferior AMIs (69%) and in 5 of the anterior AMIs (21%) (p less than 0.001). Ruptures that involved the inferobasal portion of the septum were much more likely to be complex (94%) than ruptures in all other locations (27%, p less than 0.001). Significant 3-vessel obstructive coronary arterial atherosclerosis was present in 48 hearts. Rupture of a second structure in addition to the ventricular septum was observed in 11 hearts (left ventricular free wall in 9 cases and papillary muscle in 2). The interval from the onset of the AMI to rupture of the septum could be estimated in 22 patients and averaged 4 days (median 2.5 days). Complete heart block reportedly occurred in 6 patients during hospitalization.

Adult↗
PubMed1984

Effects of interferon alpha on the sheep erythrocyte "receptor" of human lymphocytes.

The percentage of peripheral blood lymphocytes (PBLs) which formed rosettes with sheep erythrocytes declined from 62 +/- 2% to 29 +/- 4% (p = 0.001) when PBLs were incubated 18 h at 37 degrees C. In the presence of alpha interferon (IFN-alpha), a dose-dependent increase occurred in the percentage of sheep erythrocyte-binding PBL at the end of incubation compared with PBL incubated without IFN-alpha. Change in the number of sheep erythrocyte "receptors" (SER) probably did not account for the observed modulation of rosetting capacity, since the frequency and density of an SER-associated determinant (T11, as defined by immunofluorescence flow cytometry using the monoclonal antibody OKT11A) was unaffected by incubation with or without IFN-alpha. Treatment of PBL, control or IFN-alpha-treated, with neuraminidase (0.4 u/ml), restored rosetting capacity to levels characteristic of freshly prepared PBL. Neuraminidase did not affect rosetting or T11 expression by freshly prepared PBL, nor did it affect T11 expression on PBL cultured with or without IFN-alpha. We thus postulated that steric interference with SER function by sialic acid residues might result from de novo protein synthesis and glycosylation at the cell surface. Inhibition of either protein glycosylation by tunicamycin or protein synthesis by cycloheximide prevented the incubation-induced depression of rosetting capacity. IFN-alpha may modulate functional expression of SER and other surface receptors by altering cell-surface glycoprotein composition and distribution.

Animals↗
PubMed1984

Comparison of the biologic effects of two recombinant human interferons alpha (rA and rD) in humans.

IFN-alpha (rD) was investigated to determine the relationship between antiviral activity in vitro and the modulation of biologic effects in vivo. Eight patients with malignancy were given 15 and 45 micrograms weekly injections of IFN-alpha (rA) and IFN-alpha (rD). The frequency of side effects was much lower with IFN-alpha (rD) injections. This was objectively documented both in incidence of side effects (20 versus 45, p less than 0.01) and mean maximum temperature (1 degree C lower with IFN-alpha (rD), p less than 0.002). A bovine cell line, MDBK, was used to measure interferon concentrations in the serum. Geometric mean peak titers and time-to-peak titers were similar with the two recombinant interferon preparations. Although IFN-alpha (rD) has relatively less antiviral activity on human cells, its effect on the total granulocyte count, natural killer (NK) cell cytotoxicity, and 2'5'-A activity was comparable to IFN-alpha (rA). Mean NK cell percent specific 51Cr release was enhanced by both interferons (after 15 micrograms doses, mean percent NK cell cytotoxicity IFN-alpha (rD) preinjection, 10.5% +/- 2.3%; post-injection, 27.2% +/- 4.5%; IFN-alpha (rA), preinjection, 14.4% +/- 3.2%, postinjection, 25.1% +/- 5%). Species-specific antiviral activity of an interferon does not necessarily predict other biologic properties following in vivo administration.

2',5'-Oligoadenylate Synthetase↗
PubMed1984

Arterial-esophageal fistulae developing in patients with anomalies of the aortic arch system.

Two cases are presented in which anomalies of the aortic arch system were associated with development of an arterial-esophageal fistula. The fistula resulted in massive upper gastrointestinal hemorrhage and death. In each malformation, part of the anomalous aortic arch system lay against the esophagus and thereby provided the anatomic substrate for an arterial-esophageal fistula. In both cases, nonmassive ("sentinel") hemorrhage occurred prior to the massive fatal hemorrhage. Recognition of the significance of the "sentinel" hemorrhage may allow surgical correction of the problem avoiding uncontrolled massive hemorrhage.

Adult↗
PubMed1984

Effects of diethyldithiocarbamate, an inhibitor of interferon antiviral activity, upon human natural killer cells.

In support of a postulated role of the Cu++-dependent enzyme, superoxide dismutase (SOD), in antiviral effects of interferon (IFN), a close correspondence was previously shown to exist between inactivation of cellular SOD and concomitant blockade of IFN antiviral activity in fibroblasts by the Cu++-chelating agent, diethyldithiocarbamate (DDC). To further define the extent of "anti-IFN" activity, we initiated studies of DDC effects on IFN stimulation in the NK cell system. Unexpectedly, DDC directly inhibited cytotoxicity mediated by unstimulated NK cells. Pronounced inactivation occurred rapidly (less than 30 min), but was spontaneously reversible in the absence of DDC. Neither cell viability nor lymphocyte binding to target cells was detectably affected. Preincubation of DDC with Cu++ or Zn++ failed to neutralize its inhibitory effects nor could function be restored in DDC-pretreated NK cells by subsequent addition of Cu++, Zn++, Mg++, or Ca++. DDC treatment that inactivated NK cells did not detectably alter lymphocyte SOD activity. Thus, inhibition was probably not attributable to chelating properties of DDC. N-ethyl maleimide (NEM) and para-( hydroxymercuri ) benzoic acid ( PMBA ), enzyme inhibitors that preferentially react with sulfhydryl groups, both inactivated NK cells in a time- and dose-dependent manner similar to that of DDC. Preincubation with the sulfhydryl compound, cysteine, neutralized in parallel fashion the capacity of NEM, PMBA , and DDC to inhibit NK cell activity. Thus, a previously unreported reactivity of DDC with sulfhydryl groups appeared to be the basis of inhibition. NK cells incubated 1 hr with IFN and subsequently cultured 17 to 23 hr without IFN were activated to an extent comparable to cells continuously incubated 18 to 24 hr with IFN. Exposure to IFN for 1 hr was therefore sufficient to commit NK cells to acquisition of a fully activated state. Whether preactivated by a 1-hr or 18- to 24-hr IFN treatment, activated NK cells retained the DDC-sensitive phenotype characteristic of fresh unstimulated NK cells. Thus, prolonged IFN treatment did not render NK cells resistant to DDC or preferentially activate a DDC-sensitive NK cell subset. An 18- to 24-hr incubation of DDC-pretreated cells in the continual presence of IFN resulted in the boosting of NK cell activity. However, the 1-hr IFN pulse treatment protocol was consistently ineffective in boosting when IFN was added just after DDC-pretreatment. These results strongly suggested that DDC temporarily rendered NK cells unresponsive to what, under normal circumstances, approximated an optimally potentiating IFN stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1984

American cancer society Phase I trial of naturally produced beta-interferon.

Naturally produced beta-interferon was evaluated following i.m. and i.v. administration to 18 patients with advanced cancer. Fever (mean +/- S.E. = 38.1 degrees +/- 1.7 degrees), enhancement of natural killer cell cytotoxicity, and depression of the white blood cell count occurred following a single i.m. injection in the absence of detectable serum antiviral activity. Fever, rigors, and fatigue were dose-limiting toxicities following daily i.v. administration of 10 million units. Tachyphylaxis, as reported following repetitive administration of alpha-interferons, did not occur. Side effects, depression of the white blood cell count, and enhancement of natural killer cell cytotoxicity were similar when beta-interferon was administered daily as a 10-min bolus or as a 6-hr infusion. However, while natural killer cell cytotoxicity increased progressively over 10 days of bolus injections, it was maximal after the initial 6-hr infusion of beta-interferon. Administration of 10 million units of beta-interferon divided equally between a 10-min bolus injection and a 3-hr infusion was well tolerated and resulted in high initial peak and lower sustained serum interferon levels. Based on pharmacokinetic criteria, this schedule of administration can be recommended for further study in Phase II trials. However, in light of the biological activity of beta-interferon following i.m. administration, the level of beta-interferon in the serum may have limited value as a predictor of antitumor response, toxicity, or biological response modification.

American Cancer Society↗
PubMed1984

Comparative in vivo and in vitro activation of human natural killer cells by two recombinant alpha-interferons differing in antiviral activity.

Natural killer (NK) cell activation by two interferon-alpha subtypes, interferon-alpha A and interferon-alpha D, was examined in vitro and in vivo in eight cancer patients. When assessed in vitro, NK cells in six of eight patients lysed K562 target cells to a greater extent when incubated with interferon-alpha A (1 ng/ml) than with the same concentration of interferon-alpha D. However, when patients were evaluated collectively, no significant difference was detectable in the effectiveness of the two subtypes in enhancing NK cell activity. Patients received the same interferons given as four injections which were randomized with respect to subtype and were separated by intervals of six or more days. NK cell activity was consistently elevated in peripheral mononuclear cells sampled 24 hr but not seven days after injection as compared to peripheral mononuclear cells sampled just prior to each injection (p less than 0.001 for both subtypes). At a given dose level, both interferon subtypes resulted in comparable NK cell activation. However, a negative correlation existed between the amount of interferon administered and the magnitude of enhancement (p less than 0.05). In 16 separate paired determinations, there were eight in which NK cell activity was lower after the second injection of an interferon dose than after the first injection of the same dose (15 or 45 micrograms, irrespective of subtype), and eight in which the alternate pattern occurred. Thus, repeated injection in the same patient of one or the other dose resulted in no consistent changes in the extent of NK cell stimulation. Since the two interferons have a 20-fold difference in specific antiviral activity for human amnion cells and up to an 80-fold difference in human fibroblasts, either different mechanisms are involved in antiviral and NK cell-stimulatory activity, or activities of these two subtypes for cells of different histogenesis vary. Greater NK cell-stimulatory activity therefore occurred at the lowest tested doses, a dose which was less than 10% of previously reported maximally tolerated doses of these interferons.

Cell Line↗
PubMed1983

Correlation between in vitro and systemic effects of native and recombinant interferons-alpha on human natural killer cell cytotoxicity.

The relationship between interferon (IFN) stimulation of natural killer (NK) cell cytotoxicity in vitro and changes in NK cell cytotoxicity resulting from systemic IFN administration was examined in 15 cancer patients in two clinical trials. Ficoll-Hypaque-separated peripheral mononuclear cells (PMC) were incubated 18-20 h with or without IFN on 2 different days prior to therapy initiation to determine in vitro responsiveness to IFN and unstimulated basal levels of NK cell activity, respectively. Three different preparations of IFN-alpha were tested, including native Cantell IFN-alpha and two recombinant DNA-generated species, IFN-r alpha A and IFN-r alpha D. Twenty-four hours after i.m. injection of IFNs, significant NK cell activity enhancement occurred (p = 0.003). The relative extent of cytotoxicity elevation in individual patients resulting from injection significantly correlated (p less than 0.01) with the degree of NK cell activity enhancement induced in vitro by treatment of PMC with the same IFN preparation. These results suggest that patients exhibited individual differences in acute responsiveness to systemic IFN administration, which could be predicted to a certain extent by in vitro testing prior to therapy.

Adolescent↗
PubMed1983

Anomalies of the left atrium and mitral valve: cords, flaps, and duplication of valve.

We studied seven hearts with abnormalities of the atrial septum of the mitral valve. Three had abnormalities of the atrial septum, characterized by a flap or a diaphragm within the left atrium. Another three cases had abnormal cords extending from the atrial septum to the anterior or the posterior mitral leaflets. A seventh case had a duplicated mitral valve. Grossly, the specific conditions among these seven hearts appeared very different: however, we believe that the origin of each anomaly can be explained by one of three developmental aberrations or a combination thereof. Although only one case was associated with severe cardiac disease, such structures may be seen during cardiac imaging or operation.

Adult↗
PubMed1982

Isolated renal artery dissection, presentation, evaluation, management, and pathology.

Isolated nontraumatic renal artery dissection is rare. In this communication, 35 cases are presented; 24 cases (group 1) (22 male, 2 female) were diagnosed angiographically, and 11 (group 2) (10 male, 1 female) were observed at autopsy. In group 1, 23 of the patients were hypertensive when they were first seen, and in 17 of them the hypertension was of recent onset. Additional presenting signs and symptoms included flank pain (10 patients), gross hematuria (5), and headaches (6). Renal function was satisfactory. Renal vein renin levels could be lateralized in 8 of 16 patients. Isotope renograms performed in 18 patients, showed unilateral abnormalities in 7, bilateral abnormalities in 6, and normal results in 5. Angiograms showed that the dissection was unilateral in 18 cases and bilateral in 6 cases. Fibromuscular dysplasia was observed radiographically in 22 cases and was bilateral in 12. In group 1, 13 patients were treated with antihypertensive medication only, and 11 underwent operation. At follow-up (mean 52.0 months), the mean blood pressure were 128/88 mm Hg and 139/89 mm Hg for the medical and surgical groups, respectively. Eleven medical and nine surgical patients continued to require antihypertensive drugs at follow-up. Among the 11 patients in group 2, only 4 were hypertensive. In only one case the dissection may have contributed significantly to the patient's death. These studies indicate that isolated nontraumatic renal artery dissection most commonly occurs in young men with coexistent fibromuscular dysplasia. Hypertension is commonly present and therapy should be directed toward its control. In this study, blood pressure control was effectively accomplished with medical therapy.

Adult↗
PubMed1981

Aortic origin of conus coronary artery. Evidence of postnatal coronary development.

The conus coronary artery has been reported to arise independently from the aorta in approximately 45 per cent of hearts. In this study, 305 necropsy specimens were examined to determine the origin of the conus coronary artery and variations in patterns of origin with respect to age. Three patterns were recognised: 1, in which the conus artery arose from the aorta independently of the right coronary artery; 2, in which the conus artery and the right coronary arose from a common ostium; and 3, in which only the right coronary artery took origin from the right aortic sinus. The relative incidence of the three patterns varied with age. Pattern 1 was recognised in 14 to 24 per cent of specimens from patients under the age of 2 years, whereas in older patients, it occurred in 41 to 63 per cent. These data suggest that aortic origin of the conus arterial ostium may appear in some individuals between 2 and 4 years of age, and they support the concept that some coronary arterial patterns are not fully established at the time of birth.

Adolescent↗
PubMed1981

Effect of imidazole on renal function in unilateral ureteral-obstructed rat kidneys.

Imidazole has been proposed to reverse renal vasoconstriction following unilateral obstruction, presumably through blockade of thromboxane A2 (TXA2) synthesis. We examined this hypothesis in rats subjected to unilateral ureteral obstruction for 24 h by 1) performing renal function studies before and during imidazole infusion, and 2) measuring TXB2 and prostaglandin E2 (PGE2) in urine collected before and during imidazole infusion and the profile of products generated by metabolism of arachidonic acid with renal microsomes in vitro. Imidazole infusion was associated with only a bicarbonaturia in the postobstructed kidney; in contrast, clearance of PAH and inulin, fractional sodium excretion, and bicarbonate excretion were all increased in the contralateral kidney. In the postobstructed and contralateral kidneys, TXB2 excretion was diminished and PGE2 excretion was variable not only following imidazole infusion but after saline infusion as well. The profile of products generated by renal microsomal metabolism of arachidonic acid was similar among obstructed, contralateral, and normal kidneys. These results do not support the proposal that TXA2 is the mediator of renal vasoconstriction following unilateral ureteral obstruction.

Animals↗
PubMed1980

Tumor-immunotherapeutic efficacy of Serratia marcescens polyribosomes.

The ability of polyribosomes, obtained from several bacterial species, to suppress the development of cutaneous SaD2 fibrosarcomas in DBA/2 mice were evaluated. Suppression of tumor appearance depended upon the tumor load at the time of treatment, dose of polyribosomes, and species source of polyribosomes, with Serratia marcescens being superior to Escherichia coli, Streptococcus pneumoniae, Mycobacterium bovis (Pasteur), Mycobacterium smegmatis, and Propionibacterium acnes (formerly Corynebacterium parvum). A single injection of 5 or 50 microgram of Serratia polyribosomes at the tumor site 72 hr after the intradermal administration of 1.5 X 10(3) SaD2 cells resulted in 66 to 95% survival. All untreated animals expired within 50 days. Tumor suppression occurred at both flank and footpad sites. Presensitization with polyribosomes and incorporation of polyribosomes into adjuvant were not required for the tumor-suppressive effect. Treatment of Serratia polyribosomes with RNase or pronase reduced the number of survivors. Endotoxin was not detectable with the Limulus amebocyte lysate assay.

Animals↗
PubMedDate not supplied

Developing a computer program to assist the nursing process: phase I-from systems analysis to an expandable program.

In a three-stage project, a computer program was devised to assist in the nursing process. As Stage I, a definition of nursing was developed upon which a systems model of the nursing process was constructed. In Stage II, the computer program was written to collect patient data and formulate nursing diagnoses related to functions of the skin, mucous membranes, nails, and hair. The program was designed to serve as a model for the development of a more comprehensive program that would include other functional areas, suggest patient objectives and nurse interventions, and help to evaluate nursing care. In Stage III, initial trials were conducted to obtain feedback from nurses. Nurses found the program took too long but agreed that with modification it could help them give better care.

Computers↗