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Biomedical subjects

W K Vaughn

Publications and source records attributed to W K Vaughn.

At least 127 records · Page 7Linked to original sources

Continuing neonatal morbidity in infants of women with class A diabetes.

Despite having implemented rigorous glucose control for women with gestational diabetes early in the third trimester, we found excessive morbidity among the neonates of these women. To accurately assess the risk of newborn complications, we did a five-year review (1977 to 1981) of infants of class A diabetic mothers to determine the incidence and scope of morbidity in these infants. Fifty-one infants of class A mothers were identified (group 1) and randomly matched with 102 infants of nondiabetic mothers (group 2). The distribution of morbidity between the two groups was as follows: hypoglycemia 9/51 (18%) vs 0/102 (P less than .001); birth injuries 4/51 (8%) vs 1/102 (2%) (P less than .05); pulmonary edema 3/51 (6%) vs 0/102 (P less than .05); respiratory distress 4/51 (8%) vs 7/102 (7%) (NS); macrosomia 18/51 (35%) vs 23/102 (23%) (NS); and hyperbilirubinemia 3/51 (6%) vs 8/102 (8%) (NS). There were two fetal deaths and three infants with major congenital anomalies among the diabetic pregnancies compared to none from the nondiabetic pregnancies. Compared to insulin-dependent diabetes, class A diabetes is accompanied by relatively mild metabolic disturbances in the mother. On the other hand, the infant of a mother with class A diabetes appears to be at risk for serious and life-threatening complications, both before and after birth. These results raise the question of whether earlier identification, subsequent meticulous diabetic management, and altered timing of delivery might reduce the complications experienced by these infants.

Abnormalities, Multiple↗

The association of pretransplant native nephrectomy with decreased renal allograft rejection.

Analysis of 2808 first and 823 second or subsequent cadaveric renal allograft recipients transplanted between June 1977 and July 1982 as part of the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to determine the influence of pretransplant bilateral native nephrectomy (BNN) on graft and patient outcome. A highly significant increase in overall graft survival was associated with BNN in first transplant recipients (P less than 0.003) but not in regrafted patients. However, no increased graft survival was seen in patients receiving BNN at the time of the transplant operation. Interestingly, the improvement in graft survival associated with BNN appeared to be the result of a significant decrease in the incidence of graft loss caused by rejection--and especially accelerated acute rejection (P less than 0.007). Comparing actuarial graft survival for first graft recipients that had BNN prior to transplantation (n = 434) with those who had no nephrectomy (n = 2240) showed differences of 62% +/- 3 vs. 52% +/- 1 and 46% +/- 3 vs. 38% +/- 2 at one and three years, respectively. Analysis of first graft survival stratified for other factors known to influence outcome showed that the beneficial influence of BNN was independent of transfusion status or the number of transfusions given, use of antilymphocyte serum, pretransplant splenectomy, HLA match, or time on dialysis. The most striking increase in graft survival associated with BNN was seen in patients with evidence of presensitization as manifested by a positive panel reactive antibody (PRA) and in patients having delayed function (ATN) posttransplantation. The beneficial association of BNN was also found to be independent of the primary cause of renal failure or the specific indication leading to nephrectomy. These results suggest that patients receiving native bilateral nephrectomy prior to transplantation have a reduced incidence of graft loss from rejection by some as yet unexplained mechanism.

Adult↗

The timing of pretransplant transfusions and renal allograft survival.

Analysis of over 3000 cadaveric renal allograft recipients transplanted between June 1977 and June 1982 as part of the South-Eastern Organ Procurement Foundation Prospective Study was performed to determine the influence of timing of blood transfusions (BT) on patient and graft survival. Four mutually exclusive BT groups were identified for 2480 first-transplant and 655 regrafted patients studied: group 1 (n = 348, 29, respectively) received no BT; group 2 (n = 256, 29, respectively) received perioperative BT only (i.e., at the time of, or within 10 days of transplant); group 3 (n = 972, 287, respectively) received preoperative BT only (i.e., 10 or more days pretransplant); group 4 (n = 904, 310, respectively) received both preoperative and perioperative BT. For first graft recipients, actuarial graft survival for group 2 was significantly greater (P less than 0.035) than group 1 (49% vs. 41% at one year; 35% vs. 25% at 4 years), but to a lesser degree than groups 3 or 4, which were equivalent (58% at one year and 38% at 4 years). For regrafted patients, actuarial graft survival was again significantly greater (P less than 0.03) for group 2 patients, as compared with group 1 (59% vs. 29% at one year), and group 3 and 4 patients were not significantly different from each other (45% and 48% at one year, respectively) or from group 2. Interestingly, for regrafted patients who were presensitized at the time of transplant, those in group 4 (n = 94) had significantly better graft survival than group 3 (n = 111) at all time points examined (54% vs. 47% at one year, 46% vs. 22% at 3 years). In all comparisons, increases in graft survival were associated with decreased graft loss resulting from rejection, and no significant differences in patient survival were seen between any of these groups. These findings indicate that: (1) perioperative transfusions alone may have benefit in decreasing allograft rejection; (2) perioperative transfusions provide no apparent risk for patients who have already received pretransplant transfusions; and, (3) sensitized regrafted patients who receive pretransplant transfusions may gain an additional benefit from perioperative transfusions.

Adult↗

The influence of pretransplant transfusions, using different blood products, on patient sensitization and renal allograft survival.

An analysis of data collected during the South Eastern Organ Procurement Foundation (SEOPF) Prospective Study from 1977-1982 was performed to identify the relative effects of different blood products on patient sensitization and graft survival in cadaveric donor renal transplant recipients. More than 2700 primary and 800 regrafted patients from 40 transplant centers were included in this study. A significant increase in actuarial graft survival was seen in primary recipients who had pretransplant transfusions with only frozen blood (P less than 0.003), washed blood (P less than 0.0005), packed blood (P less than 0.0001), or any combination of blood products (P less than 0.002) as compared with those who received no transfusions. No blood product was found to provide a significantly greater increase in graft survival than any other blood product. Likewise, regrafted patients had significant and equivalent increases in graft survival associated with each type of blood product examined. The increased graft survival associated with each blood product was the result of decreased graft rejection, and not apparently related to other differences among patients receiving different types of blood. Furthermore, the type of blood used in pretransplant transfusions did not significantly influence the degree of patient sensitization for first-graft recipients, although regrafted recipients who received packed blood or a combination of blood products showed a slightly greater degree of sensitization than those who received only frozen or washed blood. First-graft recipients given packed or mixed blood had a small, statistically insignificant increase of hepatitis B virus (HBV) antigenemia, compared with those receiving frozen, washed, or no blood. Regrafted patients given any type of transfusion had a 3-4-fold increased incidence of HBV antigenemia as compared with nontransfused patients, but this difference also was statistically not significant. These findings suggest that the benefits of increased graft survival and the risks of sensitization or HBV infection associated with pretransplant transfusions are not significantly affected by the type of blood used.

Adult↗

Cadaver renal transplantation ignoring peak-reactive sera in patients with markedly decreasing pretransplant sensitization.

A review of more than 3000 cadaver donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to identify patients who received a transplant following a significant decrease in pretransplant sensitization as measured by the percentage of panel-reactive antibody (PRA). Such patients were identified as having had a most reactive (historical peak sera) PRA level at least 40 percentage points higher than their last sample tested prior to transplant (current sera). Additional data were obtained on 157 of these patients, who also had no history of pretransplant immunosuppression and had a negative pretransplant crossmatch with current sera. Data included the dates of pretransplant sera samples, the specific techniques used for each serum sample that was crossmatched or screened for PRA, and the serological results. The population studied included 17 of 87 first-transplant recipients and 17 of 70 regrafted recipients whose pretransplant crossmatches with peak sera were positive or not done. These subgroups showed no decrease in graft or patient survival compared with cohorts (70/87 first-transplant recipients and 53/70 regrafted recipients) for whom peak sera crossmatching was performed with negative results. Additional stratification for the techniques used in crossmatching and screening, as well as the interval between peak and current PRA levels, showed no significant associations with eventual graft or patient outcome. These results suggest that crossmatch testing using peak sera may not be important in predicting eventual graft or patient outcome for patients with a marked decrease in PRA prior to transplantation and a negative crossmatch with current sera.

Adult↗

Influence of changes in pretransplant sensitization on patient and graft survival in cadaver renal transplantation.

Analysis of 2778 primary and 606 regrafted cadaveric donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to determine the influence of changes in presensitization on graft and patient outcome. Four mutually exclusive groups of patients were identified based on the relative difference in the percentage of panel-reactive antibody (PRA) from highest ever (peak) to most recent (current) pretransplant levels as follows: group 1 (unsensitized): peak = current PRA = 0; group 2 (rising or stable PRA): (peak = current PRA) greater than 0; group 3 (small decrease): (peak - current PRA) = 1-40%;) and group 4 (large decrease): (peak - current PRA) greater than 40%. First-transplant recipients in group 4 had significantly higher mortality when compared with groups 1-3 (P less than 0.002). This decrease in patient survival was evident at 6 months (81% +/- 4 vs 91% +/- 1) and persisted to three years (68% +/- 8 vs 78% +/- 2), and it was associated with a significant (P less than 0.037) increase in death from infectious causes. This finding was even more striking when only transfused recipients were considered: at three years the difference in patient survival was 63% +/- 11 vs. 77% +/- 2. In addition, transfused patients with a decrease in pretransplant PRA of greater than 40% had significantly lower overall graft survival (P less than 0.02) and a higher incidence of irreversible graft rejection (50% +/- 8 vs 33% +/- 1 at two years). For regrafted recipients, there were no differences in patient survival among groups, but those in group 4 had significantly lower graft survival (P less than 0.0033) than groups 1-3. These findings suggest that a substantial decrease in PRA prior to transplant does not necessarily indicate a decrease in potential donor alloreactivity, and in first-graft recipients it may reflect an increased susceptibility to life-threatening infections following transplantation.

Adult↗

The effect of HLA-A, -B matching on cadaver renal allograft rejection comparing public and private specificities.

Data collected prospectively on 3811 cadaver renal transplants performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation (SEOPF) were analyzed to determine whether donor-recipient compatibility based on public rather than private HLA-A,-B specificities influenced the beneficial effect of HLA matching on outcome. HLA compatibility was calculated considering match and mismatch based on common private or various public (crossreactive group, [CREG]) specificities. Donor-recipient compatibility using certain CREG assignments provided an equivalent means of stratifying graft outcome by the degree of HLA-A,-B match or mismatch, and other CREGs assignments did not. Multivariate Cox regression analysis of donor-recipient compatibility based on certain public antigens showed as high an association (P less than 10(-5) between good matching and decreased graft rejection as did matching for private antigens alone. Patient stratification by HLA match provided a stronger association with graft outcome than by HLA mismatch, irrespective of whether private or public antigens were considered. The likelihood of finding a better match was significantly increased using CREG assignments, and patients with at least one matched private antigen had equivalent or better graft survival when additional public antigens were matched. These findings indicate that with conventional immunosuppressive therapy: (1) matching of private or public HLA-A,-B antigens plays a highly significant role in decreasing renal allograft rejection; (2) matching based on certain public antigens can provide the same or a better association with outcome as private antigens; and (3) the association (crossreactivity) of various HLA specificities can be defined on a functional basis in terms of graft survival.

Cadaver↗

The detrimental effects of delayed graft function in cadaver donor renal transplantation.

Data collected prospectively on over 3800 cadaveric renal transplants performed between June 1977 and July 1982 by the 41 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of delayed graft function (DGF) on patient and graft outcome. Approximately 35% of first graft recipients and 47% of regrafted patients were found to have DGF, as determined by the necessity for dialysis at one week posttransplant. First-graft recipients with DGF tended to include more black recipients, patients with higher peak levels of panel reactive antibody (PRA), less use of antilymphocyte serum (ALS) posttransplant, slightly longer organ preservation times and the more frequent use of organs by ice alone. Multivariate (Cox) regression analysis considering DGF simultaneously with ten other potentially confounding variables showed a highly significant association between DGF and overall graft loss from all causes (P less than 10(-5], irreversible graft rejection (P less than 0.001) as well as patient death (P = 0.012). The differences in graft survival between first graft recipients with DGF (n = 961) versus those without DGF (n = 1769) at one and four years posttransplant were 46% +/- 2 vs. 60% +/- 1 and 28% +/- 3 vs. 40% +/- 2, respectively. The detrimental effect of DGF was highly significant irrespective of the source of donor organs or the type of preservation used. For first transplant recipients who recovered good graft function by one month following DGF (n = 564), there was a significant decrease in eventual graft survival, as compared with patients who had graft function at one month but no prior history of DGF (n = 1407; P = 0.008). However, patients with history of DGF who had good graft function at six months (n = 361) showed no significant difference in longer-term graft survival when compared with similar patients with good graft function at six months but no history of DGF (n = 912). Interestingly, first transplant recipients with DGF were found to have significantly better graft survival if they had received bilateral native nephrectomy at least one month prior to transplantation. These results indicate that delayed graft function following cadaver donor renal transplantation provides a significant risk for eventual graft and patients survival that is principally manifested during the first six months posttransplant. In addition, patients who recover graft function following DGF appear to also remain at higher risk for early graft loss, while pretransplant bilateral native nephrectomy may afford some protection against the detrimental effects of DGF.

Female↗

The effect of type of delivery on neonatal outcome in singleton infants of birth weight of 1,000 g or less.

To evaluate the relationship between management of delivery and neonatal outcome in singleton neonates with birth weights between 501 and 1,000 g, a retrospective analysis was performed. In the 54-month period ending June 30, 1981, a total of 109 singleton neonates were born at Vanderbilt University Hospital, Nashville, Tenn, with birth weights between 501 and 1,000 g, 31 weighing 501 through 750 g, and 78 weighing 751 through 1,000 g. The overall neonatal survival rate was 60%, 39% in the group weighing 501 through 750 g and 69% in the group weighing 751 through 1,000 g. In terms of morbidity and mortality, there was no difference between neonates delivered by cesarean section compared with those delivered vaginally. The only significant factor found relating to neonatal mortality was the occurrence of labor. In the 17 newborns delivered without occurrence of labor, the frequency of neonatal death was significantly decreased, although this difference may be caused by differing risk factors in the infants delivered without occurrence of labor. When labor was present and the fetus had a cephalic presentation, cesarean section was not found to be superior to vaginal delivery in terms of neonatal morbidity or mortality for neonates of 1,000 g or less.

Cesarean Section↗

Pneumococcal vaccine in normal children. Primary and secondary vaccination.

A pneumococcal polysaccharide vaccine containing 50 micrograms of each of 14 pneumococcal types was administered to 79 children 2 to 5 years of age. In earlier studies, 52 of these children had received pneumococcal vaccine; 27 had received a placebo. Local reactions were significantly greater in the reimmunized group. Antibody response to the vaccine was similar in both groups. Mean fold rises to most vaccine components were at least twofold. The response to specific pneumococcal types was unrelated to the frequency with which each type causes illness. Response to type 6 continued to be poor for children up to age 5 years. A vaccine with improved immunogenicity must be developed before widespread use in normal children is advocated. However, the 14-valent pneumococcal polysaccharide vaccine currently available is moderately immunogenic in children by age 2 years and should be given to patients with increased risk of pneumococcal illness at that time.

Age Factors↗

Why do secondary cadaver renal transplants succeed? Results of the South-Eastern Organ Procurement Foundation prospective study, 1977-1982.

We report the selective and therapeutic factors affecting multiple kidney transplant success from a prospective multicenter study of the South-Eastern Organ Procurement Foundation. From June 1977 to March 1982, 3,215 cadaver kidney transplants were performed at 39 institutions. There were 2,535 first, 564 second, 103 third and 13 fourth grafts. The actuarial graft survival rates at 1 and 2 years were 52 plus or minus 1 and 45 plus or minus 1 per cent, respectively, for first grafts, 44 plus or minus 2 and 40 plus or minus 3 per cent for second grafts, and 42 plus or minus 5 and 31 plus or minus 6 per cent for third grafts. Graft survival rates were significantly lower for second and third than for first transplants (p less than 0.003). There was no difference in patient survival rates. The data were analyzed to determine which selective and therapeutic variables governed success of primary and secondary grafts. Pre-transplant blood transfusions were associated with a significant increase in graft survival rates in primary (p less than 0.00005) and secondary transplants (p less than 0.01), and did not affect patient survival rates. The administration of antilymphocyte serum also improved graft survival rates significantly in primary (p less than 0.00005) and secondary grafts (p less than 0.00002), without alteration of patient survival rates. HLA compatibility improved primary graft survival rates (p less than or equal to 0.022) but this did not reach statistical significance in secondary graft survival rates. Second transplant graft survival rates were best when the primary graft functioned for more than 12 months (Breslow p less than or equal to 0.02) but were not related to the reason for loss of the first graft. Pre-transplant bilateral nephrectomy improved graft survival rates significantly but this phenomenon was linked to other treatment factors. No beneficial effect on graft survival rate could be shown after pre-transplant splenectomy in patients with primary or secondary grafts and this procedure was associated with reduced patient survival rates in both groups.

Adolescent↗

Transplantation for polycystic kidney disease.

During the 4-year period from June 1977 to May 1981, a total of 108 patients with polycystic kidney disease and 2440 nonpolycystic patients received cadaver renal allografts in the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study. There were no significant differences between the groups with and without polycystic disease in terms of recipient blood group, history of splenectomy, or preformed antibody status. As a group, transplanted polycystic patients underwent native nephrectomy more often, had a better HLA match, received less antilymphocyte serum (ALS), and were slightly older than nonpolycystic patients. Although proportionately fewer polycystic patients received pretransplant transfusions than nonpolycystic patients (P = .002), transfusion was associated with a significant increase in graft survival in the polycystic group (P less than .05), as well as in the nonpolycystic group (P less than .0001). Gene frequency analysis showed no HLA-A, or -B antigen linkage with polycystic disease. No significant differences existed between the polycystic and nonpolycystic groups in terms of overall graft and patient survival. However, transplanted polycystic patients died more frequently from bacterial sepsis (P less than .05), especially from gram-positive organisms (P = .01). Pretransplant bilateral nephrectomy did not affect the incidence of sepsis. However, following graft failure, patients with bilateral native nephrectomy had a greater incidence of severe anemia (50% versus 39%) and death (58% versus 25%; P less than .05) than those with unilateral nephrectomy or no nephrectomy. Treatment with ALS did not significantly improve graft survival in those with polycystic disease. A strong positive correlation was found between patient death and treatment with ALS only in the polycystic group (P less than .01). These findings indicate that the use of pretransplant bilateral native nephrectomy and posttransplant ALS should be judicious in the polycystic patient because they may be associated with increased morbidity and mortality.

Adolescent↗

Assessment of prognostic factors and projection of outcomes in renal transplantation.

Analysis of data on renal transplantation collected in two large multicenter observational studies resulted in the concordant identification of five factors that correlated highly and at a substantial level of statistical significance with the outcome of unrelated cadaveric donor transplantation (i.e., they were associated with differences in one-year graft survivals of 0.07-0.21 and P values less than 0.05). These factors were: blood transfusions prior to the transplant, race of the recipient (white or black), prior failure in transplantation, level of sensitization to lymphocyte alloantigens, and diabetes as the cause of end-stage renal failure. Multivariate analysis with a mathematical survival model confirmed the importance and independence of these prognostic factors. Matching of HLA antigens appeared to be beneficial in both studies, but failed to attain high statistical significance in one. Systematic differences in the use of pretransplant splenectomy and, probably, in the nature of the antilymphocyte serum or globulin led to discordance in assessment of the importance of these factors in the two studies. Although advanced age (greater than 45 years) of the recipient was associated with reduced graft survival in both studies, analysis by means of the model failed to detect a significant correlation between the recipient's age and the outcome in one of the studies because the relation was not monotonic. In an illustration of their utility in the detailed assessment of performance, the prognostic factors were found to substantially account for the markedly superior results at one center and partly for lower graft survivals at another. These prognostic factors may be used to predict probable outcomes for populations and for individual patients subjected to particular arrays of conditioning strategies.

Analysis of Variance↗

Exacerbation of vasotonic angina pectoris by propranolol.

Using a double-blind protocol, we investigated the use of propranolol in patients with coronary artery spasm as assessed by subjective and objective variables. Both low-dose (40 mg every 6 hours) and high-dose (160 mg every 6 hours) propranolol were administered. At both doses, the duration of angina attacks was significantly prolonged but the frequency was not. We conclude that propranolol at doses up to 160 mg every 6 hours as single therapy is frequently detrimental in angina pectoris due to coronary artery spasm and should not be used as the sole treatment of this disorder.

Aged↗

Method of preservation is not a determinant of graft outcome in kidneys transplanted by Southeastern Organ Procurement Foundation Institutions.

We report the observation that the major sources of variation in cadaver renal allograft survival rates are not related to the technique of donor organ preservation but are related solely to other factors including pretransplant blood transfusion of the recipient, antilymphocyte serum (ALS) treatment of the recipient, and high HLA match. In contrast to prior studies which used univariate methods to analyze similar data, our analysis shows that it is imperative that comparisons of different methods of cadaver preservation must include adjustments for the effects of pretransplant blood transfusions, antilymphocyte serum, and HLA match.

Antilymphocyte Serum↗

Comparison of radionuclide and contrast ventriculography for detection and quantitation of regions of myocardial ischemia in dogs.

Radionuclide and contrast ventriculography were evaluated for their ability to estimate myocardial ischemia. In 14 closed-chest, sedated dogs, a small and larger region of ischemia were produced by inflating balloon occluders on the left anterior descending coronary artery. The systemic arterial pressure, atrial-paced heart rate, global ejection fraction by radionuclide and contrast ventriculography, regional wall-motion abnormalities (as the percentage of abnormally contracting segments), and regional myocardial blood flow (using the microsphere technique) were measured during an initial control period, two separate ischemic periods, and a final control period. The regional ischemic weights based on myocardial blood flow ranged from 0 to 38.5 g and were grouped as zero, small (range 0 to less than 10 g, mean 3.40 g), and large regions of ischemia (greater than 10 g, mean 24.8 g). Regional wall-motion abnormalities were sensitive qualitative indicators of ischemia. Receiver operating characteristic analysis showed that both ventriculographic methods were highly sensitive, specific, and accurate for detecting regional ischemia. Contrast ventriculography was slightly superior for detecting small regions less than 4 g, but the methods were equal for regions greater than 4 g. The arterial pressure and heart rate were unchanged during ischemia. For small regions of ischemia, the global ejection fraction did not fall using either the contrast or radionuclide technique, but it fell significantly when large regions were produced. There was a quantitative relationship between the percentage of abnormally contracting segments and the grams of myocardial ischemia (for radionuclide ventriculography, r = 0.65, P = 0.003, and for contrast ventriculography, r = 0.75, P less than 0.001), but for many small regions of ischemia, wall-motion changes were greater than anticipated, suggesting hypofunction of the continguous normal tissue. This study demonstrated that both radionuclide and contrast ventriculography were quite sensitive and specific for detecting measured amounts of regional ischemia. The functional changes resulting from ischemia are quantitatively related to the extent of regional ischemia, small areas resulting in regional wall motion abnormalities, and large areas producing both reduced global ejection fraction and wall motion changes.

Animals↗