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Biomedical subjects

W K Vaughn

Publications and source records attributed to W K Vaughn.

At least 19 recordsLinked to original sources

Factors affecting the waiting time of cadaveric kidney transplant candidates in the United States.

UNLABELLED: OBJECTIVE--To evaluate the relative impact of various factors that could account for differences in waiting time of cadaveric kidney transplant candidates (eg, black and sensitized patients). DESIGN: --A cohort study using multivariate analyses to identify associations between 36 patient, donor, and center factors with waiting time for all US cadaveric kidney transplant candidates listed between October 1, 1987, and June 30, 1990. SETTING--All US kidney transplant centers. PATIENTS--The study included 23,468 cadaveric renal transplant candidates on active waiting status. RESULTS--The patient characteristics most significantly associated with increased waiting time (adjusted for all other variables) were immunologic and included presensitization to HLA antigens, O or B blood type, candidacy for a repeat transplantation, and expression of rare HLA-A or HLA-B antigen phenotypes. Nonimmunologic factors also affected waiting times, which were significantly shorter for patients younger than 15 years vs those aged 15 through 44 years (8.4 vs 12.9 months, respectively; P less than .0001), for those listed at multiple centers vs one center (7.0 vs 13.3 months, respectively; P less than .0001), or for white vs black patients (11.9 vs 15.4 months, respectively; P less than .0001). Local transplant center characteristics associated with a significantly shorter waiting time included a small number of transplantation candidates, a high (greater than 35 per million population) local kidney organ recovery rate, and an approved variance from the Organ Procurement and Transplantation Network allocation algorithm. CONCLUSIONS--The time renal transplant candidates must wait for kidney transplantation is influenced by several factors in addition to those expected due to immunologic reasons of donor incompatibility, the algorithms used for organ distribution, or the effectiveness of local kidney recovery. The impact of these factors should be considered as the current US system for allocating scarce donor organs for kidney transplantation is modified.

Black or African American

The use of "marginal" donors for organ transplantation. The influence of donor age on outcome.

The influence of donor age on outcome was studied in the recipients of 12,131 cadaveric renal allografts, 3026 heart allografts, and 2913 liver allografts with followup information in the UNOS data base for transplants performed between 10/1/87 and 12/31/89. For recipients of kidney transplants, donors of ages 6-15 had significantly better 1-year graft survival than donors of ages 56-65, but the difference was only 7.0%. Donors of age greater than 65 actually did better than donors ages 56-65, but donors less than or equal to 5 were less satisfactory. Kidneys from older donors survived as well as kidneys from younger donors in patients with repeat transplants, diabetes, black race, age over 45, O HLA or 5 and 6 HLA matches, delayed graft function, shared kidneys and PRA greater than 50. For kidney recipients, multifactorial analysis by Cox regression showed that donor age was less important than the use of ALG, donor race, diabetes or peak PRA in ages 16-45, delayed function, repeat transplant, and HLA match. Recipients of heart transplants from donors ages 45-55 had 1-year graft survival that was 8.4% less than recipients of hearts from donors age 16-45. However, 32.7% of heart patients died during the first 12 months after listing without benefit of a transplant. Liver transplant recipients of donor ages 16-45 had 10.8% better 1-year graft survival than recipients of donors greater than 45, but a greater percentage of older donors were transplanted to high risk and older recipients. Tragically, 24.3% of patients listed for liver transplantation died within 12 months without a transplant. This analysis shows that satisfactory graft survival can be achieved using older donors and that age in itself should not be a barrier to organ donation, providing that organ function is normal and that specific disease of the organ is absent.

Adolescent

Effect of diabetes mellitus on mouse pre-implantation embryo development.

Fifteen spontaneously diabetic, non-obese mice (NOD strain), 17 non-diabetic NOD mice (in which diabetes had not yet developed) and 9 diabetic NOD mice were treated with insulin. All animals were superovulated with 5 iu of pregnant mares' serum gonadotrophin followed 48 h later by 5 iu human chorionic gonadotrophin (hCG) and mated overnight with NOD males of proven fertility. To assess in-vitro and early in-vivo development, 23 NOD mice were killed 72 h after hCG treatment. Embryos were recovered from oviduct flushings and cultured in Ham's F-10 medium with 0.1% bovine serum albumin at 37 degrees C in an atmosphere of 5% O2, 5% CO2, and 90% N2. Development was assessed at intervals of 24 h for 72 h. Compared with embryos from non-diabetic NOD mice (n = 81), embryos from diabetic NOD mice (n = 68) demonstrated marked impairment in growth assessed by distribution of developmental stages at each observation period (24, 48, 72 h, all P less than 0.001) and by overall rates of progression of developmental stages (P less than 0.01). In diabetic NOD mice treated with insulin, embryo development (n = 7) was not significantly different from that of embryos from non-diabetic NOD mice (n = 81), but was significantly faster than in embryos from diabetic NOD mice not treated with insulin (n = 68) (P less than 0.001, for all periods, overall rate P less than 0.01). To assess late in-vivo growth, 18 NOD mice were killed 120 h after hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Algorithm for the national allocation of hearts and heart-lungs.

The algorithm used for the equitable allocation of hearts and heart-lungs to potential recipients in the United States is presented. A brief history of the development of the algorithm is followed by discussion of the input criteria and implementation. The current computer system is discussed with emphasis on access by organ procurement personnel.

Algorithms

Manifestation of diabetes mellitus on mouse follicular and pre-embryo development: effect of hyperglycemia per se.

Animal models of diabetes mellitus during pregnancy have repeatedly suggested that maternal hyperglycemia was teratogenic during organogenesis, and thus may contribute to diabetic teratogenesis. However, little attention has been focused on the effects of hyperglycemia on pre-organogenic development. In this report, we examine the effect of hyperglycemia (950 mg glucose/dL) on the development of mouse pre-embryos in vitro. B6C3F1 mice were superovulated with 5 U pregnant mare serum gonadotropin (PMSG) followed by 5 U human chorionic gonadotropin (hCG) 48 hours later. Two cell pre-embryos were recovered 48 hours later, pooled together, and randomly assigned to different treatment groups. Cultures were performed in HAM's F-10 media (Gibco, Long Island, NY) with 0.1% bovine serum albumin (BSA; Sigma, St. Louis, MO) BSA at 37 degrees C in an atmosphere of 5% CO2, 5% O2, and 90% N2 with 15 to 30 embryos per milliliter of culture fluid. Cultures were viewed daily at 24, 48, and 72 hours after culturing, with recording of the development. Compared with control pre-embryos (n = 216), embryos cultured in elevated glucose levels (950 mg/dL) (n = 226) demonstrated marked growth retardation as assessed both by (1) distribution of developmental stages at each observation point (24 hours, P less than .001; 48 hours, P less than .006; 72 hours, P less than .001); and (2) a difference in the average rank sums indicating a delay in maturation (P less than .005). In a second protocol group, pre-embryos were cultured in an equivalent amount of L-glucose; no impairment in development compared with controls was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Organs for transplantation: analysis of 27,000 cadaveric donor organs.

Organs from brain-dead cadaveric donors have been increasingly used for saving lives and preserving health. During the 5 calendar years 1984 through 1988, specific organ recovery patterns were reported for 10,488 donors of 27,833 vascular organs. Transplantation of 18,277 kidneys, 3425 hearts, 2957 livers, and 411 pancreatic grafts (as well as smaller numbers of lung, intestine, heart-lung, and multivisceral grafts) represented an organ utilization rate exceeding 90%. Organ sharing was common and had a beneficial effect overall. Renal allografts from multiorgan donors showed better early function and long-term survival. A steady decrease in organ wastage has been accompanied by a substantial increase in numbers of cadaveric multiorgan donors. The resource of life-saving cadaveric organs is effectively and widely dispersed, allowing increasingly common treatment of end-stage organ failure by transplantation.

Age Factors

Living-donor renal transplantation in SEOPF. The impact of histocompatibility, transfusions, and cyclosporine on outcome.

The impact of haplotype match (HM), pretransplant transfusions, and cyclosporine use were examined for living-donor renal transplants performed among 49 centers in the South-Eastern Organ Procurement Foundation (SEOPF) from November 1983 to June 1988 with follow-up through March 1989. During this period, 750 2-HM, 1246 1-HM, and 120 0-HM living-donor transplants were performed at 46, 47, and 27 centers, respectively. Demographic comparisons of the HM categories demonstrated the greatest use of cyclosporine and donor-specific transfusions in the 0-HM group, and the greatest use of random blood transfusions (RBT) or no blood transfusions (NBT) in the 2-HM group. By univariate and multivariate (Cox regression) analyses, actuarial graft survival was significantly associated with haplotype match, although excellent 3-year graft survival was seen for 0-HM as well as 1-HM and 2-HM first transplant recipients: 74 +/- 5%, 80 +/- 2%, and 85 +/- 2%, respectively. Comparisons were also made among patients receiving DST +/- CsA, RBT +/- CsA, and NBT +/- CsA for each HM group by univariate and multivariate analyses. For 0-HM recipients, DST + CsA was most frequently used and associated with the best long-term survival (86 +/- 5% at 3 years) by univariate analysis. For 1-HM recipients, there were no apparent differences in graft survival between DST and RBT groups +/- CsA by univariate analysis, but the absence of transfusion (NBT +/- CsA) was associated with the poorest 3-year survival (79 +/- 4%). This was confirmed by multivariate analysis, where DST (P less than 0.06) and RBT (P less than 0.02) were each significantly associated with graft survival, and provided relative benefits (vs. NBT) of 0.56 and 0.44, respectively; CsA use was not significantly associated with outcome or a significant benefit. For 2-HM recipients, the poorest results were seen with DST + CsA (78 +/- 6% at 3 years) by univariate analysis; multivariate analysis suggested no benefit with DST or RBT, and an increased risk of graft loss with CsA. These results indicate that the use of pretransplant transfusions and CsA therapy may have differential benefits depending upon HM in living-donor renal transplantation.

Adolescent

Beneficial effect of cyclosporine on renal transplantation. A multicenter long-term study.

Data were collected prospectively on 8581 cadaveric renal transplants performed by institutions of the South-Eastern Organ Procurement Foundation (SEOPF) during the period November 1, 1983 through December 31, 1987. Cyclosporine was the initial then always used immunosuppressant for 5742 of these patients while 1050 never received cyclosporine. The drug was started late in the course of 481 transplants and stopped early in 378 cases. This allowed for 7651 transplants to be analyzed regarding these four categories of cyclosporine use or non-use. Actuarial graft survival for the cyclosporine "ALWAYS" group was 75% at one year, 68% at two years, 62% at three years, and 59% at four years compared with 55%, 49%, 45%, and 43%, respectively for the cyclosporine "NEVER" group (P less than 0.0001). Inclusion of the 930 cases that could not be categorized regarding cyclosporine use or for which actuarial data was not complete allowed all 8581 transplants to be analyzed by multivariate methods. This analysis disclosed significant effects on graft survival due to delayed graft function, prior transplant, recipient race, HLA match, level of PRA, and cyclosporine use. Organ sharing had no effect on graft outcome. While cyclosporine improves outcome in renal transplantation, the importance of other biologic factors affecting graft survival is not diminished by its use.

Cadaver

Liver transplantation in the United States: 1988 to 1989.

Orthotopic liver transplantation was performed more often in 1989 than in 1988. This procedure was performed at 57 institutions in 1988 and at 64 in 1989. Among the 53 institutions in which OLTX was performed in both years, the tendency was to increase volume. Volume in 1988 was not an indicator for volume increase or decrease in the next year. For example, about 60% of the centers which performed 5-9 OLTXs in 1988 had a greater volume in 1989. This was similar to the percentage among centers which performed 30-49 OLTXs in 1988. Only centers which performed at least 100 OLTXs in 1988 increased in volume uniformly (3 centers). There was about a 25% increase in the number of OLTX recipients, and the characteristics of the recipient population changed. In 1989, as compared to 1988, there was a larger proportion of recipients over age 40 with a concomitant proportionate decrease in pediatric recipients. Indications for OLTX were also different. In 1988, biliary atresia and primary biliary cirrhosis were the major diagnoses for which OLTX was performed. In 1989, however, alcoholic cirrhosis was the most prevalent diagnosis among OLTX recipients, accounting for more than 1 of every 7 procedures. We also found that the distribution of UNOS description changed. Significantly more recipients were classified in the best functional group, and significantly more recipients were on life support in 1989 compared to 1988. Whether this reflects a change in the actual functional status of recipients, or change in the management of these patients, is a topic for further research.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of streptozotocin- and alloxan-induced diabetes mellitus on mouse follicular and early embryo development.

Mice were made diabetic by intraperitoneal injection of streptozotocin or alloxan. Germinal vesicle breakdown in the ovarian follicles at 8 h after hCG in control animals (57%) was significantly greater than in streptozotocin-(24%) and alloxan-(42%) diabetic animals (P less than 0.001). This delay in oocyte maturation was reversible by in-vivo insulin administration to diabetic mice. A developmental delay was also found for embryos recovered from diabetic mice. This developmental delay extended into the 72 h in-vitro cultures. Compared to control embryos, those from alloxan- and streptozotocin-treated mice demonstrated marked impairment in development as assessed by (1) distribution of developmental cell stages at each observation period and (2) rates of development which increasingly diverged at each observation period. In diabetic mice treated with insulin in vivo, the percentage of 2-cell embryos recovered increased. Furthermore, in streptozotocin- and alloxan-animals treated with insulin, the rate of in-vitro development of embryos, as well as their developmental stage distribution improved. We therefore suggest that uncontrolled diabetes mellitus, as well as contributing to the development of congenital malformations, may deleteriously affect reproductive performance both before fertilization and at the very earliest gestational stages.

Alloxan

Pitt-UNOS Liver Transplant Registry.

The Pitt-UNOS Liver Transplant Registry maintains a computerized database of all orthotopic liver transplantations (OLTX) performed in the United States since October 1, 1987. Recipient data, which are collected at the time of transplantation and at specified follow-up time periods, are reported to the Registry directly, while donor data are transmitted through UNOS Central. During the first year of registration (October 1, 1987 through September 30, 1988), 1,561 liver transplantations were performed on 1,377 patients; 146 patients received 2 livers and another 19 patients received 3 livers. There were 29 multiorgan transplants, including 18 liver/kidney, 7 liver/pancreas, 1 liver/small bowel, 2 liver/kidney/heart, and 1 liver/kidney/pancreas. Among the 52 centers reporting at least 1 liver transplant during this time period, 34 (65%) performed less than 20 procedures and only 7 (13%) performed at least 50 transplantations. Sixty-three percent of the donors were male; 63% were less than 25 years of age and in 72% the cause of death was motor vehicle accidents, gunshot wounds, or cerebrovascular accidents. Recipients were older than donors, 37% above age 45. About 25% of the recipients required intensive care or life support. The majority suffered from cirrhosis of cholestatic, autoimmune, viral, alcoholic, or unspecified etiology. The 6-month cumulative survival following OLTX was 76%, and the 6-month retransplant-free survival rate was 69%. Survival rates at 1 year were 72% and 64%, respectively. Factors associated with patient survival were diagnosis of liver disease and work (UNOS) status. Patients with fulminant liver failure or malignancies had the poorest survival, and patients with cholestatic cirrhosis or other cirrhosis had the best.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The impact of purposeful sharing by HLA matching in the South Eastern Organ Procurement Foundation (SEOPF).

A voluntary system was created to foster early sharing of well-matched organs between like-minded renal transplantation programs. In the two historic periods 1982-85 and 1985-86, sharing programs (Category I & II) and nonsharing programs (Category III) had similar graft survival. In the study period 1986-88, graft survival improved in Category I and II programs and was unchanged in Category III programs. Highly sensitized recipients in sharing programs had an incremental gain of 15.0%, patients receiving multiple grafts 12.6%. Grafts derived from local donors and transplants in less sensitized patients also were improved but for less obvious reasons. The implementation of this study was followed by a slight decrement in delayed graft function. It is our conclusion that early graft sharing can result in improved overall early graft survival.

Graft Survival

The effect of the incubation temperature on the cleavage rate of mouse embryos in vitro.

We have studied the effect of an elevated incubation temperature on the in vitro cleavage rate of one- and two-cell mouse embryos. Two-cell embryos demonstrated a significantly higher rate of cleavage when incubated at 39 degrees C as compared to 37 or 41 degrees C. When recovered at the one-cell stage, the difference in cleavage rate between the groups incubated at 37 and 39 degrees C did not reach significance. While the morphology of the embryos incubated at 37 degrees C did not differ from that of the embryos incubated at 39 degrees C in either group, a significantly higher rate of degeneration was noted in the group of two-cell embryos incubated at 41 degrees C. These findings may apply to the human in vitro fertilization and embryo transfer system (IVF-ET), where the existing "lag" between embryo and endometrium could be narrowed if embryo cleavage rates could be accelerated. Further documentation of the normality of these "advanced" embryos is required.

Animals

Impact of recurrent otitis media on middle ear function, hearing, and language.

Whether recurrent otitis media in infants and young children is followed by delayed language development was addressed by following 210 normal subjects longitudinally through the first 2 years of life with pneumatic otoscopy and tympanometry performed at every physician encounter. Otitis accounted for 26% of the medical visits. One hundred fifty-six of these children had speech and hearing evaluation at 2 years of age. Thirty percent of the children with recurrent otitis media had a mild or moderate hearing loss. However, after multiple speech and language tests, we could not identify a delay in language acquisition in the otitis-prone children. At 3 to 4 years old, 36 children, including nine with a hearing loss at 2 years of age, were retested; all nine had normal hearing. Recurrent otitis media induced a temporary decrease in hearing sensitivity demonstrable at 2 years of age, which appeared to resolve as the children matured and which was not associated with delay in language acquisition.

Child, Preschool

Antagonists for acute oral cadmium chloride intoxication.

An examination has been carried out on the relative efficacy of a number of chelating agents when acting as antagonists for oral cadmium chloride intoxication in mice. The compounds were administered orally after the oral administration of cadmium chloride at 1 mmol/kg. Of the compounds examined, several were useful in terms of enhancing survival, but by far the most effective in both enhancing survival and leaving minimal residual levels of cadmium in the liver and the kidney, was meso-2,3-dimercaptosuccinic acid (DMSA). Several polyaminocarboxylic acids also enhanced survival. The most effective of these in reducing liver and kidney levels of cadmium were diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetic acid (CDTA), and triethylenetetraminehexaacetic acid (TTHA). D-Penicillamine (DPA) was found to promote survival but also led to kidney cadmium levels higher than those found in the controls. Sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) was as effective in promoting survival as DMSA but left levels of cadmium in the kidney and liver that were approximately four times greater than those found with DMSA.

Administration, Oral