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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

Beneficial effect of low-dose systemic retinoid in combination with topical tretinoin for the treatment and prophylaxis of premalignant and malignant skin lesions in renal transplant recipients.

Renal transplant recipients experience a greatly increased frequency of neoplastic skin lesions, including aggressive squamous cell carcinomas. Recent reports suggest that high doses of systemic retinoids may exert a chemotherapeutic and chemoprophylactic effect. Similarly, topical retinoid, especially tretinoin, has also been shown to be anti-tumoragenic in various settings. Because of the serious toxicity of high-dose systemic retinoid, a protocol was developed that combined topical tretinoin with low-dose etretinate (10 mg daily) for the treatment of frequently occurring dysplastic skin lesions in renal transplant recipients. Seven patients elected to receive combined tretinoin and etretinate therapy, and 4 were treated with tretinoin alone. Clinical evaluations were performed monthly. By 3 months of therapy, 9 of 11 patients exhibited at least a 25% decrease in the number of neoplastic growths. After 6 months, 6 of 8 evaluable patients, including 2 of 3 individuals receiving tretinoin alone, exhibited at least a 50% decrease. Three of 4 patients on the combined regimen and 2 of 3 receiving tretinoin alone for at least 9 months, exhibited a significant decrease in the rate of development of new squamous cell cancers. At the start of treatment, epidermal specimens were almost completely devoid of Langerhans cells (CD1+ cells). Their density increased greatly and in proportion to the duration of therapy. Long term topical tretinoin with or without low-dose oral etretinate seems to be an effective regimen to suppress the development of new tumors and to reduce the numbers of existing lesions in renal transplant recipients.

Administration, Topical

Women cannot discriminate between different paracervical block techniques applied to opposite sides of the cervix.

The purpose of this study was to determine whether women can discriminate better from less effective paracervical block techniques applied to opposite sides of the cervix. If this discrimination could be made, it would be possible to compare different techniques and thus improve the quality of paracervical anesthesia. Two milliliters of local anesthetic was applied to one side and 6 ml to the other side of volunteers' cervices before cervical dilation. Statistical examination was by sequential analysis. The study was stopped after 47 subjects had entered, when sequential analysis found that there was no significant difference in women's perception of pain. Nine women reported more pain on the side with more anesthesia and eight reported more pain on the side with less anesthesia. Because the amount of anesthesia did not make a difference, the null hypothesis (that women cannot discriminate between different anesthetic techniques) was accepted. Women are not able to discriminate different doses of local anesthetic when applied to opposite sides of the cervix.

Abortion, Induced

Nurse-physician collaboration and decision outcomes in transplant ambulatory care settings.

OBJECTIVE: This study examined the nature of nurse-physician collaborative practice as reflected in problems presented by transplant patients in telephone contacts with clinical nurse specialists (CNSs). DESIGN: Exploratory descriptive study. SAMPLE/SETTING: The sample consisted of 202 renal and renal-pancreas transplant recipients who telephoned nurses at the outpatient clinic of a tertiary care medical center. METHODS: Over a period of 6 weeks, using a data collection form, nurse specialists recorded the types and frequencies of problems described by transplant patients via telephone interaction and categorized the outcomes of decisions. RESULTS: Of the 437 calls, averaging 2.16 calls per patient, problems were classified as general questions (46%), medication related (32%), and clinical signs and symptoms (22%) such as fever, rejection, colds, and urinary tract infections. Decision outcomes (n = 354) categorized as independent or collaborative for problem resolution were: CNS only (80%), MD only (11%), and collaborative (9%). CONCLUSIONS: Resolution of 80% of patients' problems presented in telephone interactions shows that advanced practice nurses play a pivotal role in the delivery of care to outpatient transplant recipients. Independent decision making on the part of the nurse occurs within the context of ongoing collaboration and communication with physician colleagues.

Adolescent

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

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

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