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Biomedical subjects

W W Pfaff

Publications and source records attributed to W W Pfaff.

At least 37 records · Page 2Linked to original sources
PubMed1989

Renal transplantation: a 20-year experience at the University of Florida.

Substantial gains have been made in both patient and graft survival during 20 years of transplanting kidneys at the University of Florida. The number of transplant recipients yearly has increased from six in 1966 to more than 100 in 1986. The use of immunosuppression reflects our evolving understanding of transplant immunology, with current morbidity and mortality rates considerably improved over those of the early years. This paper summarizes our transplantation experience over the past two decades.

Adolescent↗
PubMed1989

Incidental and purposeful random donor blood transfusion. Sensitization and transplantation.

We conducted a prospective study to gauge the frequency and degree of sensitization by transfusion and/or pregnancy in 797 candidates for first renal transplants. Sensitization was proportional to the number of blood transfusions. Multiple transfusions or a history of pregnancy without transfusions had similar effects on sensitization. The combination of transfusion and prior pregnancy resulted in sensitization of 1/3 of the candidates. Patients who were not sensitized and were accepted for 1-haplotype living-related donor grafts or first-cadaver donor grafts were transfused to receive a total of 5 units of packed red blood cells. Parous patients had an undue rate of antibody formation and alternate means of selecting and managing parous women are described. Nonparous candidates had a low rate of sensitization (8%) that did not prove an impediment to obtaining a transplant. Only 2% of prospective LRD graft recipients developed antibody against their intended donor. Transplant patients were generally managed with azathioprine and prednisone. One-haplotype LRD graft survival of protocol patients was 93.7% one year posttransplant, and 82.1% at 5 years. One-year CD graft survival was 77%. There was no reduction in graft survival when the interval between transfusion and transplantation exceeded one year. Random donor transfusion is effective in improving renal graft survival. Some recent multiinstitutional reports indicate a reduction or absence of the transfusion effect with current immunosuppression. Discarding blood transfusion as a preparation for transplantation may be ill-advised pending a prospective study.

Blood Transfusion↗
PubMed1989

Posttransplant antidonor antibodies and graft rejection. Evaluation by two-color flow cytometry.

The posttransplant production of antibodies against cryopreserved donor cells was studied in 50 consecutive cadaveric kidney graft recipients and in 23 additional patients selected for acute rejection. Serum was obtained twice weekly during the first 3 weeks posttransplant and then monthly for 6 months. IgM and IgG anti-T cell Abs were measured by 2-color flow cytometry. Results were analyzed in conjunction with the patients' demographics, previous sensitization, HLA-matching, posttransplant blood transfusions, incidence of delayed function, rejection episodes, and biopsy results. Antidonor antibodies, predominantly IgG, were detected in 19/48 (40%) of the patients proximate to the time of rejection. In contrast, antibodies were seen in only 2/22 (9%) of nonrejecting patients, and these antibodies were exclusively IgM. Younger patients were more likely to have antibody-mediated rejections. Cytotoxic antibody reactivity against panel cells developed or increased posttransplant in some patients, but it did not correlate with rejection. Previous sensitization and posttransplant transfusions favored the development of posttransplant panel reactivity but not of antidonor antibodies. Most rejections, including those associated with antidonor antibodies, were reversed by antirejection therapy. We conclude that antidonor antibodies are involved in a significant proportion of rejection episodes and that the damage induced does not necessarily culminate with loss of the graft.

Adult↗
PubMed1989

Prevention of transfusion-induced broad sensitization in renal transplant candidates.

Blood transfusions can induce broadly reactive anti-HLA cytotoxic antibodies, particularly in patients who have had previous transplants or pregnancies. To evaluate if HLA-matched transfusions were less immunogenic, renal transplant candidates at high risk of becoming sensitized were transfused with blood from partially or totally HLA-matched donors. The study was performed in multiparous patients who in addition had low level antilymphocyte antibodies detected by flow cytometry. Only 1/24 patients (4.2%) developed cytotoxic antibodies. Crossover studies were possible in 3 patients. In 2 patients the HLA-matched transfusions did not elicit a response, but the patients produced cytotoxic antibodies of broad reactivity when they were subsequently transfused with random donor blood. The third patient developed cytotoxic antibodies after transfusions mismatched for only one HLA-A,B antigen. Subsequent transfusions mismatched for a different antigen did not, in contrast, result in sensitization. These results demonstrate that HLA-matched transfusions, unlike regular and leukocyte-free transfusions evaluated in previous studies, can prevent sensitization in patients with a high probability of becoming untransplantable if transfused with random donor blood.

Antibodies↗
PubMed1989

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↗
PubMed1988

Clinically resectable adenocarcinoma of the rectum treated with preoperative irradiation and surgery.

Seventy-four patients with clinically resectable adenocarcinoma of the rectum were treated with preoperative irradiation and surgery at the University of Florida between August 1975 and February 1982. All patients have been followed for at least five years. Between 1975 and 1978, 29 patients received 3500 cGy; thereafter the dose was increased to 4000 to 5000 cGy for the remaining 45 patients. All patients were treated at 180 cGy per fraction. Following preoperative irradiation, 65 of 74 patients (88 percent) underwent complete resection of their lesions. Compared with a series of historical controls treated with surgery alone, the local recurrence rate at five years was 5 of 65 (7.7 percent) vs. 39 of 135 (29 percent) (P = .001), and the five-year absolute survival was 43 of 65 (66 percent) vs. 51 of 135 (38 percent) (P less than .001). The local recurrence rate was 13 percent for patients receiving 3500 cGy and 5 percent for doses of 4000 to 5000 cGy. There was no apparent increased incidence in postoperative complications in the preoperatively irradiated patients.

Actuarial Analysis↗
PubMed1988

Loss of corticomedullary demarcation on magnetic resonance imaging: an index of biopsy-proven acute renal transplant dysfunction.

A prospective study of 19 cadaveric renal allograft recipients with suspected graft rejection was undertaken to compare the histological findings of the renal transplant biopsy with the results of magnetic resonance imaging (MRI). All 19 patients underwent a biopsy of the transplant allograft. Biopsy results included acute cellular rejection, acute vascular rejection, chronic vascular rejection (CVR), and acute tubular necrosis (ATN). Recipients of cadaveric renal allografts with normal function served as controls. The control showed distinct corticomedullary demarcation (CMD) on T1-weighted imaging. In contrast, CMD was absent or diminished in all the patients with suspected allograft rejection. Unfortunately, the loss of CMD did not correlate with a specific biopsy diagnosis. Patients with biopsy evidence of acute and chronic rejection or ATN demonstrated loss of CMD with similar image patterns. In conclusion, MRI is capable of detecting renal allograft dysfunction, but does not permit the determination of a specific cause.

Adult↗
PubMed1988

Evaluation of antibody synthesis in broadly sensitized patients.

This study was conducted to evaluate the rate of lymphocyte antibody synthesis in broadly sensitized patients. Antibody synthesis was estimated utilizing two approaches. In one, the time required by the antibodies to reach half their original values was determined by quantitating their levels by flow cytometry over periods of several months. In the other approach we measured the rate at which antibodies rose after inducing an artificial reduction by means of plasma exchanges. Patients not previously transplanted and not transfused during the study period showed low antibody synthesis and decreasing panel reactivity. In most previously transplanted patients panel reactivity did not change during the observation period. However, some patients displayed low antibody synthesis activity whereas others produced antibodies at a high rate. Extensive studies in one patient demonstrated active antibody synthesis even though he had not been transfused for more than two years. The results suggest that while frequent plasma exchanges can reduce antibody concentrations, concomitant use of immunosuppression may be needed only in patients shown to be actively producing antibodies.

Antibody Formation↗
PubMed1988

Late results of renal transplantation.

A total of 315 (64%) of 491 primary cadaver and living-related donor transplants performed from 1975 through 1984 were still functioning at 24 months. These selected patients were examined further to assess the impact of several risk factors on late graft and patient survival. Black recipients, patients with underlying diabetes mellitus or hypertension, patients with poor renal function at 24 months, and recipients of cadaver grafts had significantly poorer long-term graft survival. Age greater than or equal to 40, diabetes or hypertension, poor 24-month function, and cadaver donor transplantation were associated with poorer long-term patient survival. Considerable improvement in graft survival at 24 months was seen in 1980-1984 compared with the earlier period, coincident with our adoption of routine pretransplant random donor blood transfusion. In contrast, long-term graft survival in patients with functioning graft at two years did not improve significantly over the same period. Although living-related donor transplants showed greater graft and patient survival than cadaver donor grafts by univariate analysis, no such advantage was demonstrated by multivariate analysis.

Actuarial Analysis↗
PubMed1988

Organ sharing for good HLA-A,B, and DR matching improves cadaver renal graft survival in SEOPF: retrospective and prospective studies considering delayed graft function, race, center effects, cyclosporine, and other factors.

1. HLA matching is associated significantly with factors including CsA use, ALS use, recipient race, prior graft loss, presensitization, preservation time and most strongly, with organ sharing. However, HLA match is not directly associated with delayed graft function. 2. By univariate and multivariate analyses, good HLA matching provides significant benefits in graft survival regardless of CsA use, organ source or other potentially confounding factors. 3. HLA-A,B, and DR matching have independent and essentially equivalent benefits on graft survival in CsA-treated patients, whereas HLA-A,B matching has a greater benefit in non-CsA-treated patients. 4. Organ sharing, per se, provides no direct detrimental effect on graft survival by univariate or multivariate analysis. 5. By multivariate and univariate analyses, shared/well-matched kidneys provide significantly better graft survival than local/poorly matched kidneys. 6. Delayed graft function is associated in a complex relationship with organ sharing, prior graft failure, presensitization, and CsA use. 7. The increased rate of delayed graft function associated with organ sharing is overcome by the benefit of good HLA matching. 8. Since April 1986, purposeful organ sharing at SEOPF centers for good HLA matching has been associated with improved graft survival, especially in patients at high risk due to presensitization or prior graft failure.

Actuarial Analysis↗
PubMed1988

Aseptic bone necrosis after renal transplantation.

Osteonecrosis is a common complication of renal transplantation and is an obstacle to rehabilitation. While prednisone has long been implicated as causative, the sporadic nature of aseptic necrosis (ASN) is poorly understood. Four hundred forty-four patients received kidney transplants (TX) between January 1978 and December 1984. Fifty-two patients (16%) have developed ASN. This retrospective study was developed in an attempt to define potential etiologic factors. Age, sex, donor, source, primary renal disease, duration of dialysis, and pre-TX parathyroidectomy did not correlate with ASN. Prednisone administration and duration of use prior to transplantation was equally common in ASN and control patients. Black recipients had a twofold frequency of ASN, although this association did not quite reach significance (p = 0.07). Pretransplant x-ray evidence of either osteopenia or renal osteodystrophy was significant (p less than 0.01) and apparent in 23 of 52 patients (44%). ASN was associated with a history of early acute rejection (p less than 0.02), higher final serum creatinine (p = 0.07), and greater mean prednisone (p less than 0.0001). The mean linear trend of daily prednisone dose was also significant (p less than 0.03). This study suggests that ASN is three times more likely to occur if radiographic evidence is apparent before TX. Rejection and higher daily steroid dosage correlate with a greater incidence of ASN, and blacks appear to be at greater risk.

Adolescent↗
PubMed1987

Initially unresectable rectal adenocarcinoma treated with preoperative irradiation and surgery.

This is an analysis of 23 patients with clinically and/or surgically unresectable adenocarcinoma of the rectum on initial evaluation who were treated with preoperative irradiation and surgery between March 1970 and April 1981. All patients have had follow-up for at least 5 years. Five patients (22%) had exploratory laparotomy and diverting colostomy before irradiation. All patients were irradiated with megavoltage equipment to the pelvis at 180 rad/fraction, continuous-course technique. Total doses ranged from 3500 to 6000 rad with a mean of 4800 rad and a median of 5000 rad. All patients had surgery 2-11 weeks (mean: 4.9 weeks; median: 4 weeks) after radiation therapy. Twelve patients (52%) had lesions that were incompletely resected because of positive margins (7 patients), distant metastasis (1 patient), or both (4 patients). All of these patients died of cancer within 5 years of treatment. Eleven patients had an apparent complete excision of their rectal cancer; six patients (55%) subsequently had a local recurrence. The 5-year absolute survival rate for patients who had complete resection was 18% (2 of 11 patients). The 5-year absolute and determinate survival rates for the entire study were 9% (2 of 23 patients) and 9% (2 of 22 patients), respectively. One patient (in the incomplete resection group) died after operation secondary to sepsis and diffuse intravascular coagulation.

Acute Disease↗