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Biomedical subjects

D Graf

Publications and source records attributed to D Graf.

At least 37 records · Page 2Linked to original sources
PubMed1993

Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM.

X chromosome-linked immunodeficiency with hyper-IgM (HIGM1, MIM number 308230) is a rare disorder characterized by recurrent bacterial infections, very low or absent IgG, IgA and IgE, and normal to increased IgM and IgD serum levels. HIGM1 has been suggested to result from ineffective T-cell help for B cells. We and others have identified a novel, TNF-related activation protein (TRAP) that is exclusively expressed on the surface of stimulated T cells. TRAP, a type II transmembrane protein of M(r) 33,000, is the physiological ligand for CD40 (refs 5-8). Crosslinking of CD40 on B cells induces, in the presence of lymphokines, immunoglobulin class switching from IgM to IgG, IgA or IgE. Mapping of the TRAP gene to the X-chromosomal location q26.3-q27.1 (ref. 6) suggested a causal relationship to HIGM1, which had previously been assigned to Xq26 (refs 12-14). Here we present evidence that point mutations in the TRAP gene give rise to nonfunctional or defective expression of TRAP on the surface of T cells in patients with HIGM1. The resultant failure of TRAP to interact with CD40 on functionally intact B cells is responsible for the observed immunoglobulin isotype defect in HIGM1.

Antigens, CD↗
PubMed1993

[Solid and cystic pancreatic tumor].

The solid and cystic tumor of the pancreas (also called pancreatic cystic tumor of the pancreas) is a very rare tumor of the pancreas, which we meet mainly in younger women. The tumor was described for the first time in 1981 and since that time there were published more than 150 cases. It is a matter of a potentially malign tumor with low malign characteristics. By radical exstirpation most of the patients can be healed definitely. Long-term controls are yet necessary although recidives are rare (4-7%), but are described up to 10 years after the first treatment. Also singular cases with synchronous metastasis of the liver are mentioned. Except of abdominal volume increase the tumor gives little trouble. The diagnosis is placed with ultrasonography resp. with a computer-tomogram and ensured by needle cytology. The therapy consists in the radical exstirpation with resection of the left pancreas in case of location on the left side, with Whipple operation in case of localisation in the head of the pancreas.

Adult↗
PubMed1992

Cloning of TRAP, a ligand for CD40 on human T cells.

A cDNA clone, designated TRAP (TNF-related activation protein) was isolated from a collection of T cell activation genes. The polypeptide encoded by a mRNA of approx. 2.3 kb is 261 amino acids long with a calculated M(r) of 29.3 kDa. The structural features predict a type II transmembrane protein, but are also compatible with a secreted form. TRAP is highly similar to an identified murine CD40 ligand both at the cDNA (82.8% identity) and the protein (77.4% identity) levels, and related to tumor necrosis factor/lymphotoxin. Expressed in a murine myeloma, TRAP was identified as a ligand for CD40 by binding to a soluble CD40 construct. TRAP mRNA is expressed in a T cell-specific fashion with a maximum at 8 h after stimulation. The TRAP gene is located in the q26.3-q27.1 region of the X chromosome.

Amino Acid Sequence↗
PubMed1992

[Anticardiolipin antibodies in rheumatic autoimmune diseases. Correlation with clinical and laboratory findings].

The prevalence of anticardiolipin antibodies (ACA) was determined using an Elisa method in sera of 60 patients with autoimmune diseases. ACA were correlated with clinical manifestations of the antiphospholipid syndrome and other serological markers of autoimmunity. Sixty three percent of sera had ACA IgG (+) and 50% ACA IgM (+). Nine patients, five of them with systemic lupus erythematosus, had a history of arterial or venous thrombosis and all had positive ACA (IgG (+) in 7 and IgM (+) in 2). In patients with rheumatoid arthritis, no association was found between the presence of ACA and thrombosis. Patients with a history of spontaneous abortion had non significantly higher levels of ACA. There was a significant correlation between ACA levels and rheumatoid factor (ACA IgG r = 0.374, ACA IgM r = 0.676), no other association was found between ACA and other autoantibodies. It is concluded that ACA are found frequently in patients with autoimmune diseases and its clinical significance may be different in patients with lupus than in patients with rheumatoid arthritis or other connective tissue diseases.

Adult↗
PubMed1992

Quality control program of steroid receptor assays: an international study.

Lyophilized calf uterine cytosol standards were prepared for quality control of estrogen receptor (ER) determination, and lyophilized cytosols and tissue powders were used for quality control of progesterone receptor (PR) analysis. Two series of four samples were analyzed either for ER or PR contents, twice within one month, by 7 laboratories in 5 countries. Coefficient of variation (CV) of the between-laboratory averages assayed in a single run of ER-positive (ER+) and PR-positive (PR+) standards varied from 29.6 to 61.8% and from 32.4 to 76.2%, respectively. All laboratories, with the exception of a single value, could recognize samples of low, medium, an high ER level, as well as a negative sample. Most laboratories evaluated properly also the level of PR samples. The average between-laboratory CV values of protein determination in the relevant standards were 23%.

Animals↗
PubMed1991

Actuarial survival and other events following valve surgery in octogenarians: comparison with an age-, sex-, and race-matched population.

From January 1973 to December 1989, 54 patients over 80 years of age underwent an intracardiac repair which included a cardiac valve operation. There were 21 males and 33 females. Mean age at operation was 82 years, range 80-89 years. Fifty-two patients (96%) were in New York Heart Association functional class III or IV preoperatively. Six patients had undergone previous valve surgery (11%). There were eight hospital deaths (14.8%). Risk factors for hospital death included older age at repair (p = 0.008), increased total cardiopulmonary bypass time (p = 0.06), and, possibly, smaller aortic valve prosthesis (p = 0.10). All 46 hospital survivors were followed up at a mean of 28.8 months after hospital discharge. There were 11 late deaths (23.9%), occurring at a mean of 32.3 months postoperatively. Survival analysis indicated that increased age (p = 0.06) and increased pulmonary artery diastolic pressure preoperatively (p less than 0.07) were multivariate risk factors for overall mortality. Actuarial survival at 5 years was 44%, with no difference from survival in an age-, sex-, and race-matched population. We conclude that octogenarians in the modern era have good chance for survival following valvular surgery. As hazards for full anticoagulation were low in this series, if valve repair is not feasible, we presently recommend the use of mechanical valves in the elderly to reduce the requirement for late reoperation due to bioprosthesis degeneration.

Actuarial Analysis↗
PubMed1991

Recurrent bleeding from a hepatic artery aneurysm feeding a large cavernous hemangioma of the liver.

We describe a patient with an aneurysmatic dilatation of the hepatic artery feeding a giant cavernous hemangioma. The 51-years-old man presented with massive gastrointestinal hemorrhage due to chronic rupture of the aneurysm into the pancreatic duct. The patient died 25 days after resection of the aneurysm in liver failure and septic shock. We think that this cavernous hemangioma was responsible for a high blood flow within the hepatic artery for many years. This high blood flow caused the degenerative alterations in the wall of the artery, resulting in aneurysm formation and rupture. This is the first case mentioned in literature with rupture of a hepatic aneurysm generated by high blood flow.

Aneurysm↗
PubMed1991

The pericardial valve in the aortic position ten years later.

To assess the behavior of the pericardial valve at 10 years after implantation, the cases of 240 patients who had undergone aortic valve replacement with the standard Ionescu-Shiley (Shiley, Inc., Irvine, Calif.) bovine pericardial valve between February 1977 and December 1983 were reassessed. Follow-up of the 224 hospital survivors was 99.6% complete. Fifty-seven valve-related events occurred. Fourteen were thrombotic events (1.2%/patient-year), 28 were intrinsic tissue failures (2.4%/patient-year), 13 were cases of prosthetic valve endocarditis (1.1%/patient-year), and 2 were paravalvular leaks (0.17%/patient-year). The linearized rate for death, reoperation, or both resulting from valve-related events was 3.6%/patient-year. Time-related hazard function for the instantaneous risk of death and/or reoperation resulting from valve-related events demonstrated an exponential increase after 80 months. These data, in conjunction with our previous reports on the histologic changes in pericardial collagen and the incidence of calcification (26/28), should be considered regarding new and future generations of pericardial bioprostheses. Although this device provides good hemodynamics and carries a low incidence of thromboembolism, it has a limited durability. New generations of pericardial valves may have improved structural features, but the behavior of glutaraldehyde-fixed, formaldehyde-stored bovine pericardium as currently selected and prepared is unlikely to change.

Adolescent↗
PubMed1990

[Whipple's duodenopancreatectomy].

Patients who underwent Whipple duodenopancreatectomy in the years 1972-1987 were analyzed retrospectively. The study covered indications and early and late results, and our own results were compared with those in the literature. Of 70 patients 36 were men and 34 women, with a mean age of 64 (33-84) years. 36 had carcinoma of the head of the pancreas, 13 carcinoma of the papilla Vateri, 9 carcinoma of choledochus, 4 another carcinoma and 8 a benign disease of the pancreas. 30-day mortality was 10% (7/70): all of these patients had a carcinoma. 29/32 patients with carcinoma of the head of the pancreas had a mean survival of 14.8 (2-59) months. Three patients are still alive. Mean survival in 8/11 patients with carcinoma of the papilla Vateri was 32 (6-122) months, with 3 patients still alive. 7/8 patients with carcinoma of the distal choledochus survived 20 (5-38) months. The 4 patients with another carcinoma died after a mean of 31 (9-75) months. 60 (21-111) months is the mean survival in 3/8 patients with benign disease of the pancreas.

Adult↗
PubMed1990

Late events following repair of aortic coarctation with resection and end-to-end anastomosis: a twenty-five-year experience.

From November 24, 1964 through July 3, 1979, 81 patients underwent coarctation repair with resection and end-to-end anastomosis. Mean age at operation was 13.4 years, with a range of 4 months to 55 years. Thirty-two patients (39%) had associated cardiac defects. There were no hospital deaths. Eighty of the 81 hospital survivors were followed (99%) for a total of 10,780 months postoperatively, at a mean of 134.6 (+/- 7.1) months. There was one late death (1.3%) of a ruptured berry aneurysm at 120 months after repair. Actuarial survival was 100% at 10 years and 92.9 +/- 7% at 20 years. Five patients (6.3%) required late re-repair at a mean of 142.8 months postoperatively, range 85 months to 195 months. Actuarial freedom from reoperation was 97 +/- 2.0% at 5 years and 91.7 +/- 3.6% at 20 years. Earlier age at initial repair (P = 0.002), higher mean transrepair gradient (P = 0.005), and late hypertension (P = 0.08) were associated with re-coarctation. The hazard function for reoperation according to age at initial repair revealed a single early risk phase with a plateau starting at 7 years of age and zero hazard after 10 years of age. We conclude that correction of coarctation of the aorta using resection and end-to-end anastomosis permits a long history of event-free survival and continues to be an excellent method of repair.

Actuarial Analysis↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

[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↗