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Biomedical subjects

D Graf

Publications and source records attributed to D Graf.

At least 55 records · Page 3Linked to original sources

Homograft valve durability: host or donor influence?

Antibiotic sterilized valves have been shown to function longer than those chemically sterilized; however, the reason remains obscure. Current hypotheses cite either retention of donor fibroblasts capable of repairing the grafted valve, or host fibroblast ingrowth into and onto the leaflet ground substance. A cryopreserved aortic homograft from a male donor was explanted from a female recipient after 10 months, and subjected to immunocytochemistry, tissue culture, and karyotyping. The leaflet bases exhibited normal morphology with an intact endothelium. The distal one-third of the leaflets was devoid of fibroblasts from the leaflet bases showed them to be of host origin. This homograft seems to have been implanted with an intact ground substance which allowed for host cell repopulation of the inner one-third of the leaflets. Perhaps donor cell viability in itself is not as important to durability as is preservation of the leaflet ground substance, but rather the presence of viable cells may be an index of the structural integrity of the collagen and elastic matrix.

Adult↗

Hospital death on a cardiac surgical service: negative influence of changing practice patterns.

From January 1982 through December 1985, 3,772 patients underwent a cardiac surgical procedure for coronary or acquired heart disease. Operative mortality increased from 4% in 1982 to 7% in 1985 (p less than 0.001 by chi 2 analysis). There was an increase over time of patients older than 70 years (p less than 0.001). Female patients increased from 31% in 1982 to 35% in 1985 (p less than 0.001). The percentage of patients having isolated coronary artery bypass grafting decreased from 69% in 1983 to 60% in 1985 (p less than 0.001), and hospital mortality after this procedure increased (p = 0.058). Patients requiring more complex procedures including multiple-valve operations or combined valve replacement or repair plus bypass grafting increased from 1982 through 1985 (p = 0.005). Reoperations for multiple-valve procedures or combined valve repair or replacement plus coronary artery bypass grafting also increased (p = 0.02), particularly for patients more than 70 years of age (p less than 0.001). Changing practice patterns have had a negative impact on surgical results. This evolution in cardiac surgical practice has important implications related to peer review and quality-assurance screening, diagnosis-related group reimbursement, and reporting of surgical outcomes to governmental agencies.

Adult↗

Mechanical testing of cryopreserved aortic allografts. Comparison with xenografts and fresh tissue.

Reports indicate that cryopreserved aortic valve allografts have a better long-term survivability than other bioprostheses, such as the porcine xenograft. Unlike xenografts, allograft valves do not require treatment with glutaraldehyde and may therefore retain much of their original mechanical function. The effects of cryopreservation on the mechanical integrity of collagen fibers and mucopolysaccharides, however, are still largely unknown. We therefore compared the mechanical behavior of cryopreserved allograft leaflet material to that of fresh tissue and xenografts by measuring their bending stiffness (nine strips of tissue) and their uniaxial tensile stress/strain and stress/relaxation behavior (six strips of each tissue type). The bending tests showed no significant difference between the pliability of cryopreserved allografts and fresh pig aortic valve tissue, but the xenograft material was significantly stiffer than both (p less than 0.001). The mean circumferential tensile elastic moduli of the allografts, fresh tissue, and xenografts at a stress of 300 kPa were 9.1 +/- 5.4 MPa, 13.0 +/- 1.7 MPa, and 12.5 +/- 3.0 MPa, respectively, and were not significantly different from each other. We also found that the transition from a low to a high modulus on the stress/strain curves, a measure of extensibility, occurs at 23%, 22%, and 12% strain for the three materials. There was no significant difference between the allograft and the fresh tissues, but the xenograft material was less extensible than the other two (p less than 0.001). The xenograft tissue also had significantly lower rates of stress relaxation than the other two materials (p less than 0.005). Thus no detectable differences were found between the mechanical behavior of the cryopreserved allograft aortic leaflets and fresh tissue, whereas the xenograft material was less extensible and less capable of relaxing than both the allograft and fresh tissue. The ability of allografts valves to respond to tensile and flexural stresses in a manner similar to that of the natural aortic valve may therefore contribute to their good in vivo survivability.

Aorta↗

Pulmonary artery balloon counterpulsation for right ventricular failure after right ventriculotomy in the swine.

To assess the efficacy of intrapulmonary balloon counterpulsation in the management of right ventricular failure after right ventriculotomy, we undertook an experimental study in a swine model. To mimic the clinical settings more closely, (1) we left the automatic control of the heart intact (2) did not use cardiopulmonary bypass to support the left side of the heart, and (3) induced right ventricular failure by means of a generous surgical incision (50% to 70% of the anterior wall) of the right ventricle. The criteria set for right ventricular failure were (1) 50% increase in right ventricular end-diastolic pressure, (2) 30% decrease in mean arterial pressure, and (3) 30% decrease in cardiac output. Right ventricular failure was attained in all animals studied: A 230% increase in right ventricular end-diastolic pressure, a 43% decrease in cardiac output, and a 34% decrease in mean arterial pressure were evident after the right ventriculotomy. A specially designed intrapulmonary balloon catheter (Datascope Corp., Oakland, N.J.) was placed into the left pulmonary artery through the right ventricular outflow tract. A Datascope console was used for counterpulsation. Effects of counterpulsation for 40 minutes in a 1:1 mode were assessed after surgical induction of right ventricular failure in 14 swine. Each animal served as its own control. The mean hemodynamic changes are outlined: Right ventricular end-diastolic pressure decreased by 48.9% (p = 0.01). Mean arterial pressure increased by 68.8% (p = 0.01) and cardiac output by 44.2% (p = 0.01). Histologic studies disclosed no morphologic damage to the pulmonary artery or valve in the specimens analyzed. In addition, these results were compared with those in a second group of seven swine in which right ventricular failure was induced by right ventriculotomy and a balloon was placed into the left pulmonary artery but not activated. These results of short-term counterpulsation should be evaluated in a longer term model so as to mimic more closely the clinical setting. If the hemodynamic benefits are duplicated, intrapulmonary balloon counterpulsation should be considered as a simple, effective device when right ventricular failure develops after right ventriculotomy. It effectively improves right ventricular function without damaging the pulmonary artery or valve.

Animals↗

Factors determining in-hospital or late survival after aortic valve replacement.

To ascertain incremental risk factors for in-hospital and late mortality of patients undergoing AVR with the bovine pericardial valve, multiple variables were analyzed in a group of 240 patients undergoing AVR between 1977 and 1983. Follow-up totaled 12,023 patient-months (mean, 52.7 +/- 1.7 patient-months) and was 100 percent complete. Univariate analysis of incremental risk factors for in-hospital mortality identified the following: age over 60 years (p = 0.015); and advanced preoperative NYHA class (p = 0.003). Multivariate analysis of risk factors for in-hospital mortality identified the following: age (p = 0.038); NYHA class (p = 0.018); and year of operation (p = 0.049). Incremental risk factors for late mortality were identified as age (p = 0.003), year of operation (p = 0.003), concomitant procedure (p = 0.047), and valvular lesion (regurgitation) (p = 0.053). Actuarial survival of patients (+/- SE) was 87 +/- 2 percent, 75 +/- 3 percent, and 61 +/- 5 percent at 2, 5, and 8.7 years, respectively. The actuarial survival of patients experiencing valve-related events was 62.6 +/- 10.1 percent at 8.7 years, compared to 55.4 +/- 7 percent for those who did not (p = 0.38).

Actuarial Analysis↗

[A drowning accident of long duration with deep hypothermia and rewarming with extracorporeal circulation. A report of 2 patients].

Two nearly drowned, 2 9/12 and 3 6/12 years old boys with profound hypothermia were admitted to our pediatric intensive care unit with all signs of clinical death. Both patients could be rewarmed and oxygenated by extracorporeal circulation. One of them died 36 hours after the accident with severe brain edema. The second one survived without any defect. Rewarming of cold-water nearly-drowned patients by extra-corporeal circulation seems to be a very effective way of treatment.

Accidents↗

Isolation of four rat creatine kinase genes and identification of multiple potential promoter sequences within the rat brain creatine kinase promoter region.

Rat genes encoding muscle creatine kinase (gene ckm) and brain creatine kinase (gene ckb) have been cloned. The two genes have an identical intron-exon distribution, although introns of the ckb gene are much smaller than those for ckm. The complete nucleotide sequence has been determined for the ckb gene. 5'-Flanking sequences have been compared for both ckm and ckb. The ckb gene has a structurally complex 5'-flanking region with multiple TATA and CAAT sequences suggesting that the gene may contain overlapping promoter elements. Examination of ckb RNA from brain tissue provides no evidence for the existence of more than one set of transcriptional start points. The ckm and ckb genes show little homology in the 5'-flanking regions, although we observed some sequence conservation in the regions immediately surrounding the CAAT and TATA sequences. The rat genome also contains two other creatine kinase-like sequences which may represent processed pseudogenes or mitochondrial creatine kinase.

Amino Acid Sequence↗

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Aged↗

Estrogen and progesterone receptors as prognostic factors in breast cancer.

The relation between estrogen receptors (ER) and/or progesterone receptors (PgR) and some clinical factors such as tumor size, axillary node involvement, histological tumor grade, and disease-free interval (DFI) in 500 patients with operable (TNM stage I-III) breast cancer was studied. ER-positive (ER+) tumors were commoner in older patients, whereas PgR-positive (PgR+) tumors were similarly distributed within the age groups. The concentration of ER+ protein also increased with age in contrast to PgR+ protein concentration. However, receptor status was not associated with menopausal status independently of age. Axillary node involvement influenced neither ER nor PgR status, but there was a statistically significant relation between tumor size and positivity of ER or PgR. There was no association between histologic tumor grade and either steroid receptor phenotype. DFI was longer in patients with ER+ than those with ER- tumors, independently of axillary nodal status. The positivity of PgR in patients with ER+ tumors contributed to an even longer DFI, suggesting that the combination of ER/PgR is a better indicator of DFI than ER or PgR alone.

Adult↗

Pulmonary homograft implantation for ventricular outflow tract reconstruction: early phase results.

The pulmonary valve homograft (PH) has been reported to have potential advantages over the aortic valve homograft, including a larger diameter, a thinner wall, and decreased intrinsic calcification. From January 16, 1986, to July 14, 1987, eight consecutive patients underwent repair of congenital cardiac anomalies using a cryopreserved PH. Patients ranged in age from 18 months to 32 years. Diagnoses included tetralogy of Fallot with pulmonary atresia (3 patients); tetralogy with absent pulmonary valve (1 patient); corrected transposition with pulmonic stenosis (1 patient); transposition of the great arteries, ventricular septal defect, and pulmonic stenosis (2 patients); and double-outlet right ventricle with pulmonic stenosis (1 patient). The PH was implanted orthotopically in the patient with absent pulmonary valve, and in the other 7 it was placed as a valved extracardiac conduit. Two of the tetralogy patients with severe bifurcational pulmonary stenosis and another with nonconfluent pulmonary arteries and origin of the left pulmonary artery from a patent ductus arteriosus had their repairs facilitated using the branching pulmonary arterial portion of the PH. There were no hospital or posthospital deaths. Postrepair right ventricular to left ventricular systolic pressure ratios were a mean of 0.35 at 18 hours postoperatively (range, 0.21-0.61). All patients were studied with Doppler and echocardiography after repair. The mean gradient across the PH was 9 mm Hg (range, 2-27 mm Hg), and no pulmonary valve incompetence was present. One patient (12.5%) required reoperation seven months after repair for conduit revision due to compression by the sternum and is now well.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The Ross operation: the autologous pulmonary valve in the aortic position.

Aortic valve replacement (AVR) with a pulmonary valve autograft (PVA) was first reported by Donald N. Ross (DNR) in 1967. The expectation of this procedure was to avoid degenerative changes seen in other biological tissue valves such as calcification, attenuation, and rupture of the leaflets. Recent reports by the original investigator's group have confirmed the lack of degenerative changes in PVA. To corroborate their conclusions, the fate of 12 patients undergoing AVR with PVA by one of us (LGL) has been ascertained. From March 1969 to June 1971, 12 patients underwent AVR with PVA. The right ventricular outflow tract (RVOT) was reconstructed with an aortic homograft valved conduit. The mean age was 42.7 years (range 21 to 52 years). The mean follow-up for 11 hospital survivors is 12.4 years. Three PVA have been replaced; one following infective endocarditis at 13 years, and two at 15 and 73 months due to technical malalignment. There was no evidence of PVA degeneration during histological examination of these explanted PVAs. Six patients are alive and retain the original PVA at 12 years (55%). This analysis corroborates the conclusions of the DNR report and strongly suggests an immunological mechanism in the process of calcification of other biological tissue valves. The Ross operation is advocated for AVR in young patients as valve durability is of paramount importance especially in this group.

Adult↗

Morbidity following the Ross operation.

Aortic valve replacement (AVR) with a pulmonary valve autograft (PVA) was first reported by Donald N. Ross in 1967. The expectation of this procedure was to avoid degenerative changes seen in other biological tissue valves such as calcification, attenuation, and rupture of the leaflets. Recent reports by the original investigator's group have confirmed the lack of degenerative changes in PVA. To corroborate their conclusions, the fate of 12 patients undergoing AVR with PVA by Dr. Gonzalez-Lavin has been ascertained. From March 1969 to June 1971, 12 patients underwent AVR with PVA. The right ventricular outflow tract (RVOT) was reconstructed with an aortic homograft valved conduit. The mean age was 42.7 years (range 21 to 52 years). The mean follow-up for 11 hospital survivors is 12.4 years. Three PVAs have been replaced; one following infective endocarditis at 13 years, and two at 15 and 73 months due to technical malalignment. There was no evidence of PVA degeneration during histologic examination of these explanted PVA. Six patients are alive and retain the original PVA at 12 years (55%). This analysis corroborates the conclusions of Dr. Ross and strongly suggests an immunological mechanism in the process of calcification of other biological tissue valves. The Ross operation is believed to be the preferred method of AVR in young patients.

Adult↗

Homograft valve preparation and predicting viability at implantation.

An experimental study was performed using C14 proline uptake in order to: (1) assess the effects of current sterilization and storage methods on fibroblast viability, and (2) establish a control tissue that could be used to determine viability of each homograft valve at the time of implantation in the clinical setting. The results were expressed as disintegrations per minute per milligram of tissue (DPM/mg). Swine aortic (AV), pulmonary (PV), and tricuspid leaflets (TV), and adjacent AV and PV arterial wall were procured sterile and subjected to routine sterilization and storage. Thirty samples of AV were analyzed for incorporation of labeled proline at procurement (208 +/- 7 DPM/mg), following 48-hour antibiotic exposure (87 +/- 6 DPM/mg, P less than .0001), and following controlled rate cryopreservation and storage for 12 days at -80 degrees C (78 +/- 8 DPM/mg, P = .42). Proline uptake of the other tissues at the same intervals disclosed that only the TV resulted in the same degree of viability at implantation (AV 78 +/- 8, PV 68 +/- 3, TV 75 +/- 2, P = NS). The homograft valves were obtained under sterile conditions from brain dead, multiorgan donors (homovital). It has been postulated that these valves are sterile and ready for implantation. Of 17 homovital valves cultured at procurement, 9 had positive cultures within 48 hours (53%). We conclude that: (1) the TV can be processed as a control tissue with each homograft and then utilized to predict viability at the time of implantation in the clinical setting; (2) antibiotic exposure is an essential step in the preparation of all homografts, however, modification of the antibiotic solution is necessary.

Carbon Radioisotopes↗

[Perforation of the large intestine by a contrast medium enema with barium].

This is a report about five patients who suffered a perforation of the colon during a barium-sulfate enema. In one case, barium leaked into the intraperitoneal cavity causing a barium peritonitis. In the other four cases, leakage into the retroperitoneal cavity occurred. All patients underwent surgical removal and drainage of the barium-sulfate and subsequently required a colostomy. In two cases a bowel resection was additionally performed. In one case the defect re-sutured. Antibiotic therapy was included in all cases. All patients survived the incident and were discharged between 20 days and four months postoperatively. Publications and personal experience led us to manage intraperitoneal or large retroperitoneal perforations by prompt laparotomy with removal of barium and faeces. A proximal colostomy is also required. In smaller retroperitoneal perforations conservative management is feasible, however, if the patient's condition deteriorates, they should be treated as recommended for an intraperitoneal perforation.

Aged↗

Determining viability of fresh or cryopreserved homograft valves at implantation.

Studies of homograft valves in the past two decades have suggested that "viable" valves, i.e., those maintaining chemical and structural integrity of their leaflet intercellular matrix, have a better long-term function than nonviable valves. The most effective qualitative methods of assessing leaflet viability involve destruction of the valve leaflets; thus, these methods have been limited to random use in selected valves. A study was conducted in swine in an attempt to establish a control tissue which could be tested in place of the homograft leaflets, thereby determining viability levels of every valve clinically implanted and correlating the results with long-term clinical function. Thirty samples each of the aortic and pulmonary artery wall and tricuspid leaflet were compared with aortic and pulmonary leaflets. Utilizing the technique of C14-proline uptake, viability was assessed at procurement, following sterilization, and following cryopreservation and short-term storage. The tricuspid leaflet was found to retain the same level of viability as the aortic and pulmonary leaflets before and after the cryopreservation period. It was concluded that the tricuspid leaflet could be utilized as the control tissue.

Animals↗