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Biomedical subjects

W W Pfaff

Publications and source records attributed to W W Pfaff.

At least 19 recordsLinked to original sources
PubMed1995

Hypomagnesemia in renal transplant patients: improvement over time and association with hypertension and cyclosporine levels.

Hypomagenesemia is frequently encountered early after kidney transplantation, especially in patients receiving cyclosporine (CsA). However, there have been no studies addressing the natural history of this disorder in adult transplant recipients. We conducted this investigation to study the change in the prevalence of hypomagnesemia over time in renal transplant patients as well as to determine the factors associated with this change. Three patient groups were studied: 24 CsA-treated patients followed longitudinally at 1, 3 and 6 months post-transplant (Group 1a, 1b, 1c); 33 CsA-treated patients at least 2 years post-transplant (Group 2; mean follow-up 55 +/- 25 months); and 31 non-CsA-treated patients at least 2 years post-transplant (Group 3; mean follow-up 132 +/- 57 months). The following parameters were monitored: serum and urine magnesium levels; serum potassium; creatinine clearance; fractional excretion of magnesium; and trough CsA levels. In group 1 patients, longitudinal follow-up showed a significant linear trend for improvement in the serum magnesium over time (1.6 +/- 0.3, 1.7 +/- 0.2, 1.8 +/- 0.2 mg/dl; p = 0.0015) as well as a decline in the whole blood CsA level (316 +/- 103, 251 +/- 82, 194 +/- 67 ng/ml; p = 0.0015) at 1, 3 and 6 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Increased antibody responsiveness to blood transfusions in pediatric patients.

Heightened immune responsiveness has been proposed as one of the reasons underlying suboptimal renal transplant results in very young children or African American recipients. Because multiple factors influence graft outcome, it has been difficult to provide experimental evidence to confirm or refute this suggestion. In the present study we measured IgG antibodies with confirmed HLA specificity produced in response to blood transfusions. The patients evaluated were renal transplant candidates who had not had previous pregnancies or transplants. The overall incidence of HLA sensitization was 12%. Age was the most influential factor in sensitization: patients < 20 years old were 4-5 times as likely to produce anti-HLA antibodies than patients > 20 (P = 0.0018). Female patients were also high responders. However, this was explained by the higher proportion of children among nulliparous female patients rather than by differences in gender. In contrast, the antibody response of black and white recipients was similar. The antibody levels in most patients were low and decreased significantly with time. We conclude that the immunoregulatory influences in patients < 20 years old favor the production of anti-HLA antibodies in response to blood transfusions, a fact that may explain some clinical observations in pediatric transplant recipients.

Adolescent↗
PubMed1994

A preliminary report of diltiazem and ketoconazole. Their cyclosporine-sparing effect and impact on transplant outcome.

A prospective randomized trial was conducted to compare the effect of diltiazem (DILT) with ketoconazole (KETO) on sparing of cyclosporine dose and renal transplant outcome. Renal allograft recipients 18 years old and older were eligible for the study. Triple immunosuppression (TRIPLE) including prednisone, azathioprine, and CsA was administered to all patients. The maintenance CsA dose varied by study group. Patients were randomized to receive one of three treatment strategies: group 1-TRIPLE (CsA 8 mg/kg/day); group 2--TRIPLE (CsA 6 mg/kg/day) + DILT (60 mg b.i.d.); group 3--TRIPLE (CsA 3 mg/kg/day) + KETO (200 mg/day). Modification of the DILT dose was allowed as needed to effect blood pressure control in group 2 patients. Mean 1-month CsA dose reductions were 30% and 60% of controls in group 2 and 3, respectively. A continued effect over time was observed in patients administered KETO but not DILT. At 1 year patients taking KETO required an average of 77% less CsA than the average dose necessary to effect similar parent CsA blood levels when no enzyme inhibitor was used. The use of KETO and DILT for 1 year allowed for 53% and 14% reductions in CsA cost, respectively. These savings include the cost of the KETO or DILT. Serum creatinines, mean arterial pressure (MAP), and incidence of liver function abnormalities were similar throughout treatment groups. The rate of rejection, time to rejection onset, and survival (GS/PS) were not different among the groups. Fungal infections were fewer in patients treated with KETO (12%) than in controls (16%) and patients randomized to DILT (19%). KETO failed to prevent Aspergillus infection in one individual. The investigation failed to identify any harmful result of treating renal allograft recipients with either DILT or KETO for the purpose of reducing CsA expense.

Adult↗
PubMed1994

The crossmatch in renal transplantation. Evaluation of flow cytometry as a replacement for standard cytotoxicity.

Flow cytometry (FC) is increasingly being used as a crossmatch procedure in addition to the standard complement-dependent cytotoxicity (CDC) test. In fact, FC offers a number of advantages over CDC and has the potential to become the primary crossmatch technique for cadaveric donor renal transplantation. We evaluated this possibility in 230 patients crossmatched by both CDC and FC. The results showed that when the T cell crossmatch was negative by FC it was always negative by CDC, and that when the T cell results were positive by CDC (IgM antibodies excluded) they were also positive by FC. As expected, a number of tests were T cell-positive by FC but negative by CDC. A T cell CDC crossmatch was more likely to be positive when FC was positive for both T and B cells and when FC results were quantitatively higher. However, FC was unable to consistently predict a positive, dithiothreitol-resistant B cell CDC crossmatch. A policy to transplant patients with negative FC results (70% of the patients evaluated) and not to transplant sensitized patients with FC+ T cell results (10%) would allow us to make a final decision with only FC in 80% of the cases. Actual graft survival was similar for nonsensitized first-transplant candidates with positive (83%) or all patients with negative (86%) FC results. We conclude that FC is sufficient to make a final decision in most cases. Wider utilization will require improvements in the ability of FC to measure B cell antibodies and to quantitate antibodies to T cells.

B-Lymphocytes↗
PubMed1994

Duplicate publication.

Explore the source record for details and available documents.

Duplicate Publications as Topic↗
PubMed1994

Increased incidence of rejection in patients with delayed graft function.

Because of the difficulties in diagnosing rejection in patients with delayed graft function, such patients were routinely biopsied 7-10 days after kidney transplantation. We found histologic evidence of rejection in 48% of the cases during the lst month posttransplant, a proportion that was significantly higher than in patients with immediate graft function. Furthermore, the 2-year graft survival in patients with delayed graft function and rejection, but not in those without rejection, was significantly lower than in patients with immediate function. The results suggest that there is an association between delayed graft function and rejection and that rejection is the component responsible for the decreased graft survival previously reported for patients with delayed graft function.

Adult↗
PubMed1993

Non-A, non-B hepatitis and elevated serum aminotransferases in renal transplant patients. Correlation with hepatitis C infection.

One hundred renal transplant recipients were studied for antibodies to hepatitis C virus (HCV), and to HCV RNA in serum by reverse transcription+nested polymerase chain reaction (RT-PCR). Presence of antibody to HCV confirmed by recombinant immunoblot assay II was considered evidence of HCV infection, and detection of HCV RNA by RT-PCR was considered evidence for active viremia. On pretransplant sera, 18 patients were RT-PCR positive and an additional 3 had antibody evidence of HCV infection. At 1-year follow-up, all of these patients were RT-PCR positive and an additional 7 patients became RT-PCR positive. Clinical diagnosis of non-A, non-B hepatitis underestimated the prevalence of HCV infection (5/28 cases, 18%). Serum alanine aminotransferase (ALT) elevations were neither sensitive nor specific. An isolated pretransplant ALT elevation predicted a 52% chance of being RT-PCR positive for HCV. An ALT elevation greater than 2 months after transplant predicted a 45% chance of HCV positivity; however, 18% of patients who never had any ALT abnormality were also HCV positive. Sixty-eight patients had an early postoperative rise in ALT, but there was no correlation with HCV status. After an average follow-up of over 4 years, 3/28 HCV-positive patients developed cirrhosis. HCV infection in the renal transplant population is common and underdiagnosed by clinical and biochemical parameters. HCV appears not to cause aggressive liver disease in the early posttransplant period, but longer follow-up is needed to define the natural history of HCV in the renal transplant population.

Adult↗
PubMed1992

Does preoperative radiation therapy enhance the probability of local control and survival in high-risk distal rectal cancer?

One hundred forty-eight patients were treated with preoperative radiation therapy and surgery for resectable rectal adenocarcinoma at the University of Florida between 1975 and 1986. All patients had at least 5 years' follow-up; no patient was lost to follow-up. Three treatment protocols were used over the study period: 1975 to 1978, 3500 cGy in 20 fractions; 1979 to 1983, 4000 to 5000 cGy at 180 cGy per fraction; and 1984 to 1986, 3000 cGy in 10 fractions. The change was made to 3000 cGy in 10 fractions to reduce the inconvenience and expense associated with preoperative radiation therapy without sacrificing any improvement in local control or complication rates. There were no significant differences in the rates of local control, absolute survival, cause-specific survival, or complications between the three preoperative radiation therapy protocols. The results were compared for the 132 patients who underwent complete resection after preoperative radiation therapy and a series of 135 patients who underwent a complete resection alone for adenocarcinoma of the rectum at the University of Florida between 1959 and 1976. The results at 5 years, calculated by the product-limit method, for preoperative radiation therapy and surgery compared with surgery alone, respectively, were as follows: for local recurrence-free survival, 96% and 67%; for absolute survival, 66% and 40%; and for cause-specific survival, 77% and 50%. All of these differences are significant (p = 0.0001 or less). A subset of 56 patients with locally advanced lesions, based on tethering or circumferential involvement of the rectal lumen, treated with preoperative radiation therapy and surgery were compared with patients treated with surgery alone for stage B2 and C cancers. There was a significant improvement in local control and survival rates in the group irradiated before operation. There was no apparent increase in the incidence of postoperative complications in the patients irradiated before operation.

Adenocarcinoma↗
PubMed1992

Hyperacute and acute kidney graft rejection due to antibodies against B cells.

Because of the perception of its uncertain clinical significance, the B cell crossmatch is not universally performed before renal transplantation. Even though sporadic cases of hyperacute rejection associated with B cell antibodies have been reported, doubts remain in light of other studies suggesting no effect on graft survival. This report describes 4 cases of graft rejection (3 hyperacute and 1 acute) that occurred in patients with anti-B-cell antibodies specific against donor HLA-DR or DQ antigens. Absence of anti-donor class I antibodies was confirmed in all cases by 2-color flow cytometry. Strong evidence for an antibody-mediated mechanism was found in one patient with anti-class I and anti-class II antibodies in serum transplanted with a class II mismatched kidney. In this case, only anti-class II antibodies were recovered in the eluate of the nephrectomy specimen. These four cases were compiled from three different institutions over a four-year period, which confirms the infrequent occurrence of these events. While anti-class II antibodies may not always be detrimental for graft survival, these results also confirm that they have the potential to cause hyperacute or acute graft loss. We conclude that the information provided by the B cell crossmatch should be available at the time that a decision to proceed with a renal transplant is made.

Adult↗
PubMed1992

Immunosuppression without prophylactic antilymphocyte preparations.

1. Triple-drug immunosuppression following third party transfusion can result in graft survival equal to protocols that employ prophylactic antilymphocyte preparations. 2. T1/2 was statistically improved in cadaveric and living-related donor grafts in the CsA era. 3. Patients 65 years and older had an excessive death rate. Younger groups were admixed. Extreme youth was not a risk factor. 4. Black recipients had excessive late graft loss. 5. Diabetic recipients had only a slight decline in graft and patient survival rates. 6. First and multiple graft recipients had similar transplant survival rates. 7. Delayed graft function remains costly in this immunosuppressive scheme.

Academic Medical Centers↗
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↗