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Biomedical subjects

R A Grossman

Publications and source records attributed to R A Grossman.

At least 37 records · Page 2Linked to original sources

Changes in causes of death after renal transplantation, 1966 to 1987.

This descriptive study was undertaken to examine survival and changes in cause of death after renal transplantation. One fourth (259) of the 1,022 patients who received a renal transplant between 1966 and 1987 at the University of Pennsylvania had died by January 1, 1988. Causes of death for 246 (96%) of the deceased patients were analyzed. Despite an increase in age and number of comorbid diseases before transplantation, posttransplant survival increased significantly over the study period. All-cause mortality rates at 1, 2, and 5 years decreased significantly. Infectious disease cumulative mortality rates at 1, 2, and 5 years also decreased between 1966 and 1985. No trend in the 1-, 2-, or 5-year cardiovascular disease cumulative mortality rates was detected. The decline in the rate of deaths due to infection led to a decrease in the proportion of infection-related deaths and an associated increase in the proportion of cardiovascular disease-related deaths. The reduction in mortality over the past 2 decades is associated with the simultaneous improvement in immunosuppression and treatment of infectious diseases.

Cause of Death↗

Adrenal suppression and steroid supplementation in renal transplant recipients.

The use of increased dosages of glucocorticoids during periods of physiologic stress in allograft recipients represents a clinical dilemma in that the short-term exogenous therapy required may significantly impair wound healing and immunocompetence. To investigate whether "stress steroids" are actually necessary, a prospective study was conducted in 40 renal allograft recipients admitted with significant physiologic stress. Stress categories included sepsis, metabolic abnormalities, and surgery. These patients received only their baseline prednisone immunosuppression (5-10 mg/day) and no supraphysiologic or stress doses of glucocorticoids. The clinical course of the patients revealed no evidence of adrenal insufficiency. There was no mortality, increase in hospital stay, or eosinophilia. Five episodes of hyponatremia and seven instances of hypotension were attributed to primary disease processes and responded promptly to specific treatment without steroid supplementation. Biochemical evaluation during stress revealed suppression of ACTH levels in 74.5% of episodes, elevation of urinary free cortisol levels in 79.1% of episodes, and elevation of isolated serum cortisol levels in 55.9% of episodes. This suggested that these patients had physiologically adequate adrenal function. The cosyntropin stimulation test overestimated the incidence and degree of clinically significant adrenal dysfunction (63% of patients) and was not a useful indication of a requirement for additional glucocorticoids. We conclude that functional adrenal suppression is uncommon in renal allograft recipients receiving baseline prednisone immunosuppression (5-10 mg/day) and that the demands of physiologic stress are met by a combination of endogenous adrenal function plus exogenous, baseline, immunosuppressive doses of glucocorticoids. Supra-physiologic or high doses of so-called "stress steroids" are not required. The cosyntropin stimulation test has significant clinical limitations and did not serve to alter clinical care.

Adrenal Glands↗

Renal transplantation despite a positive antiglobulin crossmatch with and without prophylactic OKT3.

The antiglobulin crossmatch (AGXM) is a sensitive technique employed by many transplant centers to enhance detection of preformed antibody to donor antigens that may cause hyperacute rejection. However, positive AGXM may detect irrelevant or very low titers of anti-HLA antibody precluding transplantation in suitable recipients. To investigate the significance of a positive AGXM, cadaveric renal transplantation was carried out despite a weakly positive AGXM (defined as cell killing above background but not greater than 20%) in 48 recipients. In an initial group (n = 10), maintained on triple therapy (cyclosporine, azathioprine, and prednisone), accelerated acute rejection occurred in 4 recipients and 3 grafts were lost. A subsequent group (n = 38) was treated with a prophylactic course of OKT3 then triple therapy. There were no episodes of accelerated acute rejection (P less than 0.01) although clinical hyperacute rejection claimed one graft and the incidence of delayed graft function was high (75%). The prophylactic OKT3 group had a reduced incidence of acute rejection (0.5 versus 1.0) per recipient and the onset of first episodes was delayed (mean onset: 13 versus 35 days after transplantation). One year actuarial primary graft survival was 88% in the prophylactic OKT3 group as compared with only 50% in the initial group. The outcome in the positive AGXM group was similar to a concurrent group (n = 32) with a negative AGXM and immediate graft function. On the other hand, the subset of positive AGXM regraft recipients treated with prophylactic OKT3 fared poorly, with a 36% (4/11) incidence of primary nonfunction. In summary, a positive AGXM, as defined in this report, is not a contraindication to primary renal transplantation--in fact, the use of the AGXM will identify recipients that would benefit from prophylactic OKT3.

Adult↗

Effects of basolateral ouabain, amphotericin B, cyanide and potassium on amiloride noise during voltage clamp of Rana pipiens skin support sodium-amiloride competition.

In a previous study, the amiloride-induced corner frequency (fc) was found to decrease as apical sodium was increased. This effect was small or absent when the basolateral surface was exposed to high potassium. It has been suggested that the apical sodium effect may be indirect, due either to increased intracellular [Na+] which repelled amiloride or to an increased potential at the apical surface which reduced amiloride affinity. High basolateral K+ might then suppress the sodium effect either by preventing intracellular [Na+] from increasing or by allowing a better clamp of the apical membrane potential by reducing basolateral membrane resistance and potential. We checked the effects of basolateral [K+], of cyanide and of ouabain at concentrations known to increase intracellular [Na+]. We found only negligible effects on fc. In addition, amphotericin B added to the basolateral bathing solution either in 115 mM Na+ or in 120 mM K+ had no significant effect on fc. We found that relatively wide variation in clamp potential under all conditions, even with active transport severely inhibited, left fc virtually constant. Since the amiloride kinetics were independent of clamp potential, we were able to measure paracellular and transcellular conductances separately by examining the voltage dependence of clamp current (linear) and amiloride noise power (quadratic). This made possible estimation of channel density and single-channel current.

Amiloride↗

Prophylaxis of serious cytomegalovirus infection in renal transplant candidates using live human cytomegalovirus vaccine. Interim results of a randomized controlled trial.

We report the interim results of a randomized, double-blind, placebo-controlled, clinical trial of prophylactic, live, attenuated cytomegalovirus (CMV) vaccination (Towne strain of CMV) of renal transplant candidates (RTCs). One hundred seventy-two RTCs were treated and subsequently underwent transplantation and followed up for at least one year and up to five years after transplantation. Eighty-eight RTCs received vaccine, and 84 received placebo. Results were analyzed according to the prevaccination serologic status (anti-CMV antibody titer) of the recipient (R- or R+) and the donor (D- or D+). The overall incidence of CMV disease was highest in the R-D+ group and almost absent in the R-D- group. There was no difference in the incidence of CMV infection or disease between vaccinated and respective placebo control recipients in either the R-D+, R+D+, R+D-, or R-D- groups. In contrast, the severity of CMV disease was significantly decreased in R-D+ vaccinees vs R-D+ placebo-treated recipients. Moreover, in the R-D+ group, one- and five-year cadaver renal allograft actuarial survival rates were 73% and 62%, respectively, for CMV vaccinees vs 40% and 25%, respectively, for control placebo patients. We conclude that seronegative cadaver RTCs may benefit from vaccination with live, attenuated, Towne strain CMV vaccine before transplantation.

Adult↗

A survey of prescribing habits for high-estrogen oral contraceptives.

A simple survey was made of health-care providers to determine their attitudes toward oral contraceptives containing more than 50 mcg of estrogen. It was found that about two-thirds of respondents prescribe this group of medication, although few do so regularly. Their use seemed correlated with providers 40 years of age or older. Even members of an association of professionals interested in contraception frequently used these pills. Although this group of contraceptives is being phased out, it is felt that professionals should have ceased their use long ago.

Adult↗

Recurrent sickle cell nephropathy in a transplanted kidney.

Of patients who developed end-stage renal disease secondary to sickle cell anemia (SCA), some have undergone renal transplantation with reasonable success. We recently cared for a patient with SCA and a functioning, transplanted kidney who experienced a permanent decline in renal function three and one-half years following transplant. The evaluation of his renal dysfunction revealed multiple features to support recurrence of sickle cell nephropathy as the cause for the deterioration.

Adult↗

Percutaneous transluminal angioplasty. The procedure of choice in the hypertensive renal allograft recipient with renal artery stenosis.

A retrospective review of 547 renal transplants performed over a six-year period revealed allograft renovascular hypertension secondary to RTAS in 39 (7.1%) patients. Percutaneous transluminal angioplasty (PTA) resulted in immediate cure or improvement in 76% of the patients, increasing to 83% in patients with functioning kidneys at a mean follow-up period of 30 months (1-72 months). The renal artery stenosis (RTAS) was equally distributed between living-related and cadaver kidney recipients and did not appear to be more prevalent in end-to-end or end-to-side anastomoses. The blood pressures fell from pre-PTA levels of 167 +/- 22 mmHg systolic to 141 +/- 23.7 post-PTA and 102 +/- 11 mmHg diastolic pre-PTA to 88 +/- 12 mmHg post-PTA (P less than 0.01). Of 25 cured or improved patients, 24 are on significantly less hypertensive medication. Two patients died of causes unrelated to the PTA and only one patient lost a kidney because of the procedure. Compared with operation, PTA is a safer and more effective procedure for the initial treatment of RTAS.

Adult↗

Autoerythrocyte sensitization worsened by a copper-containing IUD.

Autoerythrocyte sensitization (Gardner-Diamond syndrome) causes painful ecchymoses, and usually occurs in young women. It is rare and of unknown etiology. The young woman in this report probably had the condition beginning at age 14, but the diagnosis was not made until age 19, shortly after a copper-containing intrauterine device (IUD) exacerbated her condition. The ecchymoses disappeared when the IUD was removed, but recurred when replaced. A non-copper IUD caused no ecchymoses. Taping a copper penny to the skin caused a similar rash. It seems that in this woman, the Gardner-Diamond syndrome was markedly worsened by exposure to copper.

Adult↗

Adverse effect of splenectomy on the survival of patients with more than one kidney transplant.

Risk factors associated with death were identified in a cohort of patients who received 2 or more kidney transplants. Data on 19 variables were collected by chart review on 774 patients who received allografts between 1973 and 1980 at any one of 3 hospitals in Philadelphia. 124 of the patients received two or more transplants and were followed for a minimum of 1.5 years. Modified life table analyses of single variables indicated that 7 factors--splenectomy, donor source, age, transplant hospital, number of HLA mismatches, donor sex, and survival time of the prior graft--were significantly related to patient survival. Using all 19 variables, the proportional hazards model was fit to the data. The characteristics most related to survival were splenectomy (P less than .001), donor source (P = .0022), and age (P = .0015). The other 4 factors that were significant on univariate analysis were not significant in this multivariate analysis. The relative risk of death was 5.5 for patients who had had a splenectomy compared with those who had not had a splenectomy. Patients who had received more than one transplant were compared with patients who had received only one transplant, and a subset of recipients of primary transplants who returned to dialysis after primary graft failure. Survival of patients who had received one transplant was approximately the same as that of the retransplanted population. When the proportional hazards model was fit to the populations that received one transplant and compared with the model for the retransplanted group, only age and donor source were common to all three models. The effect of splenectomy on survival was significant for the total population of primary transplant recipients but had no effect on the survival of the subset of recipients whose kidney grafts had failed and were returned to hemodialysis. Infection accounted for 45% of the deaths among splenectomized, retransplanted patients. A higher percentage of septic deaths occurred in patients whose grafts were functioning at the time of death when compared with patients who had returned to dialysis after secondary graft failure. Although retransplantation alone is not associated with an increased mortality, retransplantation in splenectomized patients carries a high risk of death.

Adult↗

Treatment of lymphocele in renal allograft recipients.

Retroperitoneal lymphoceles developed in 12 renal allograft recipients during the last nine years. The interval between transplantation and the development of symptoms averaged seven months. The specific syndrome suggesting the presence of a lymphocele included lower abdominal swelling, weight gain, and, occasionally, fever without an obvious source of infection. Although these symptoms mimicked allograft rejection, diagnosis was easily made by ultrasound and intravenous pyelogram. Surgical marsupialization of the lymphocele with drainage into the peritoneal cavity proved to be an effective treatment.

Adult↗

The role of pretransplant immunity in protection from cytomegalovirus disease following renal transplantation.

To determine the extent to which pretransplant immunity resulting from natural infection protects against cytomegalovirus (CMV) disease, we analyzed CMV serology on 153 kidney donor and recipient pairs and followed transplant patients to determine incidence and severity of CMV disease. The overall incidence of CMV disease was 22%. Significant differences occurred in CMV disease incidence and severity, depending on the immune status of the kidney donor and recipient. Among recipients of kidneys from seropositive donors, immunity offered significant protection from CMV disease, reducing its incidence from 61% in nonimmune to 24% in immune patients (P less than 0.01). Pretransplant immune patients also had fever CMV-related complications. Among recipients of kidneys from seronegative donors, pretransplant immunity conferred a significant risk of CMV disease; immune patients had a 20% incidence of CMV disease compared with 2% in nonimmune patients (P less than 0.02). Disease was generally mild in all patients receiving kidneys from CMV infection had a 3-fold higher incidence of CMV disease than patients with reactivation infection (P less than 0.01). The incidence of CMV disease was similar in immune patients, whether they received a kidney from a seropositive or a seronegative donor. However, an important observation was that disease was significantly more severe in immune patients receiving a kidney from a seropositive donor (P less than 0.05). This indicates that if kidneys from seropositive donors are selected for use only in seropositive recipients, this places the immune patient at a higher risk for severe CMV disease. We conclude that pretransplant immunity offers a significant advantage to patients receiving kidneys from seropositive donors.

Adolescent↗

Effects of diuretics on plasma volume in pregnancies with long-term hypertension.

The purpose of this randomized, prospective study was to investigate the effects of diuretics on plasma volume findings and perinatal outcome in pregnancies complicated by mild long-term hypertension. Twenty patients were in their first trimester and were receiving diuretics at time of entry to the study: Ten patients were allowed to continue their diuretic medication throughout pregnancy (diuretic group), whereas for the other 10 patients, diuretics were discontinued immediately. Plasma volume was serially measured throughout pregnancy with the use of the Evans blue dye-dilution technique. Initial plasma volume was similar in the two groups. However, in the diuretic group, subsequent plasma volume findings at various stages of gestation were markedly reduced when compared to respective plasma volume findings in the other group. In addition, plasma volume expansion was minimal in the diuretic group (mean increase of 18%), whereas it was normal in the other group (mean increase of 52%). Two patients in the diuretic group and one patient in the other group required other antihypertensive medication. There was no difference in perinatal outcome between the two groups. These results suggest that in hypertensive pregnancies, diuretics prevent normal plasma volume expansion without influencing perinatal outcome.

Adult↗