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Biomedical subjects

R A Grossman

Publications and source records attributed to R A Grossman.

At least 19 recordsLinked to original sources
PubMed1992

A recent decrease in the time to development of monomorphous and polymorphous posttransplant lymphoproliferative disorder.

We have noted a decrease in the time to development of posttransplant lymphoproliferative disorder (PTLD) over the last two and one-half years in our multiorgan transplant program. From February 1965 until December 1990, 1622 transplants were performed including 1489 kidneys (KTxp), 87 livers (LTxp), and 46 pancreata. Between February 1965 and July 1988 (group 1), there were 1260 transplants performed and nine cases of either monomorphous PTLD (M-PTLD, n = 8) or polymorphous PTLD (P-PTLD, n = 1) were diagnosed. The mean time to development of PTLD was 163 +/- 128 weeks, all after KTxp. Five of these nine patients received haploidentical living-related grafts. All patients had presented with advanced disease, none had transplant nephrectomy, and all died of their disease. Between July 1988 and December 1990 (group 2), 362 transplants were performed, and four cases of M-PTLD and three cases of P-PTLD were recognized. Of the seven cases of PTLD in group 2, six developed within 90 days posttransplant (early PTLD). The mean time to development of PTLD was 11 +/- 16 weeks. This was significantly earlier than group 1 (P less than .01). Four of the five cases after KTxp had a 1 or 2 DR-matched donor. Five of these seven patients had serological evidence of recent Epstein-Barr Virus infection, and four of these five had received OKT3 and then developed early PTLD. In group 2, three patients are alive 7-15 months after KTxp nephrectomy, the remaining four have died. We hypothesize that risk factors for the development of PTLD may include heavy immunosuppression, including the use of OKT3, good DR matching, and active EBV infection. Treatment should include graft removal, if applicable, and reduction or cessation of immuno-suppression.

Herpesvirus 4, Human↗
PubMed1992

Normocalcemia thirteen years after successful parathyroid allografting in a recipient of a renal transplant.

Two months after receiving a cadaveric renal allograft, a 36-year-old woman received a parathyroid allograft from a living unrelated donor, who was haploidentical to the renal donor. Her preoperative 24-hour urinary excretion of calcium was 0.18 gm/24 hrs, and after operation it decreased to 0.004 gm/24 hrs, (normal, less than 0.20 gm/24 hrs). The C-terminal parathyroid hormone level increased from 155 pg/ml (normal, 275 to 675 pg/ml) to 327 pg/ml after operation. The N-terminal parathyroid hormone level in her grafted arm has varied between 2.5 to 10 times the level in her nongrafted arm. Thirteen years later, both allografts are functioning normally. To our knowledge, this is the longest functioning parathyroid allograft.

Calcium↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1979

Relapse of pneumonia caused by cytomegalovirus in two recipients of renal transplants.

Two cases of relapse of pneumonia caused by cytomegalovirus (CMV) in recipients of renal transplants were studied. Between episodes of pneumonia, both patients recovered completely as judged by X-ray clearing and by resolution of fever and respiratory symptoms. CMV was isolated during each episode of pneumonia from lung tissue, pleural fluid, or buffy coat cultures. Serologic studies revealed a rise in titer of antibody, confirming recent infection with CMV during the first epidose of pneumonia in each patient. Intranuclear inclusions consistent with CMV infection were detected in each of the three episodes where lung tissue was obtained. Special stains and cultures for Pneumocystis carinii, fungi, Nocardia, and mycobacteria yielded negative results. The renal allograft continued to function in both patients after they recovered from the first bout of pneumonia, and the relapse was temporally related to reinstitution of aggressive immunosuppressive therapy. The relapse of pneumonia emphasizes the need for caution when immunosuppressive therapy is reinstituted after recovery from serious CMV infection.

Adolescent↗
PubMed1979

Lethal post-transplantation calcinosis.

The case studies of four patients with post-transplantation calcinosis are presented. Three of the four patients died of inanition and sepsis secondary to infection of extensive soft tissue ulcers and diffuse cutaneous vascular calcification with gangrene. The fourth patient survived following removal of all four parathyroid glands and autografting of approximately one-half of one gland. Common to the patients was secondary hyperparathyroidism, elevated mean serum calcium levels after transplantation, and radiographic evidence of small and medium vessel calcification. No other differences could be found between these patients and other patients with post-transplantation hyperparathyroidism without calcinosis. In the face of apparently minor complaints of lower extremity discomfort, elevated parathyroid hormone levels (PTH) and positive xerography may indicate subtotal parathyroidectomy regardless of the serum calcium level.

Adult↗
PubMed1979

Live cytomegalovirus vaccination of renal transplant candidates. A preliminary trial.

Significant morbidity and mortality are associated with primary cytomegalovirus infections in renal-transplant recipients. In the hope that immunity to cytomegalovirus could safely be established before transplantation, we vaccinated 12 seronegative renal-transplant candidates with the Towne 125 strain of live human cytomegalovirus. Before transplantation, there were no significant reactions except for erythema and induration at the site of inoculation. All vaccinees seroconverted, and the three patients tested acquired a cytomegalovirus-specific cellular immune response. Ten vaccinees underwent transplantation: Nine have completed at least 3 months of follow-up, and eight retain functioning allografts up to 1 year later. Although cytomegalovirus was isolated from six patients after transplantation, the restriction endonuclease patterns of the viral DNA of four of these isolates differed significantly from those of the vaccine strain. Therefore, it appears that the vaccine strain did not become latent in the host, at least in a form that could be reactivated.

Cytomegalovirus↗
PubMed1977

Association of graft survival with host response to hepatitis B infection in patients with kidney transplants.

We studied the relation of host response to hepatitis B infection before transplantation with survival of kidney grafts in 79 patients receiving 87 transplants. Antibody to hepatitis B surface antigen (anti-HBs) signaled early graft rejection (median survival congruent to two months), whereas hepatitis B surface antigen (HBsAg) signaled delayed rejection (greater than 22 months). Patients with neither HBsAg nor anti-HBs had graft survival times (median congruent to 16 months) similar to the HBsAg carriers but significantly longer than the anti-HBs-positive patients (p less than 0.01). Similar results were observed when patients who received HLA-identical kidneys or had anti-HLA antibodies before transplantation were excluded. The highest probability of graft rejection was in patients with anti-HBs who received kidneys from male donors. The probability that such grafts would survive for four months was less than 20 per cent. HLA-nonidentical kidneys transplanted into patients with anti-HBs have a poor prognosis, whereas such grafts in HBsAg carriers have as good a prognosis as grafts in uninfected recipients.

Antibodies, Viral↗
PubMed1977

Effects of the injectable contraceptive depot medroxyprogesterone acetate in Thai women with liver fluke infestation: results after six months.

The effect of the three-monthly injectable contraceptive depot medroxyprogesterone acetate (DMPA) on liver and lipid function was assessed in Thai women with liver fluke (Opisthorchis viverrini) infestation, DMPA administration being started in the immediate postpartum period. Immediate postpartum IUD and sterilization acceptors with fluke infestation were recruited as a comparison (control) group for the fluke-positiv DMPA acceptors. Comparable groups of fluke-negative acceptors were recruited in an area of Thailand free of liver fluke transmission. Results are presented for the first 6 follow-up months for 170 DMPA and 177 control fluke-positive subjects and for 153 DMPA and 150 control fluke-negative subjects. Small and similar increases occurred in each of the four groups for alanine amino transferase, isocitrate dehydrogenase, and total bilirubin levels while aspartate amino transferase levels changed less in the DMPA groups than in their respective control groups. None of the subjects in either DMPA group had clearly abnormal results in these tests at 6 months. Alkaline phosphatase, cholesterol, and triglycerides levels were markedly lower in each group at 6 months than in the puerperal specimens. There was a greater decrease in triglycerides levels in both DMPA groups than in their respective control groups. However, the decrease in the alkaline phosphatase and cholesterol levels was greater only in the fluke-positive DMPA group than in the fluke-positive control group. None of these biochemical results were related to differences in age, parity, or lactation status between the groups. The results indicate that DMPA did not cause any early deleterious effects in the metabolic factors studied in women with liver fluke infestation.

Adolescent↗