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Biomedical subjects

D Moel

Publications and source records attributed to D Moel.

11 recordsLinked to original sources
PubMed1987

Cisplatin nephrotoxicity: insights into mechanism.

Cis-dichlorodiammine platinum (II), or cisplatin, is currently among the most widely used agents in the chemotherapy of cancer. The chief limit to its greater efficacy is its nephrotoxicity. Acute and chronic nephrotoxicity of cisplatin occurs in man and animals especially after repeated administration. Morphological damage is restricted to the P3 segment of the proximal tubule. Abnormalities of water and solute reclamation and transglomerular passage of fluid are commonly associated with cisplatin nephrotoxicity. The vulnerability of the kidney to cisplatin may be related to its function as the primary excretory organ for platinum. Platinum binds to multiple cellular organelles and macromolecules, yet the precise mechanism of its cytotoxicity has not been delineated. Because abnormalities in renal function are preceded by a period where gross renal function appears normal, it is an ideal model to study the early physiological and biochemical determinants of metal induced acute renal failure.

Acute Kidney Injury↗
PubMed1987

Pediatric phase I trial of carboplatin: a Childrens Cancer Study Group report.

Carboplatin is one of a series of cisplatin analogs now undergoing clinical investigation. Phase I and II trials in adults demonstrate activity in a number of human cancers and less toxicity than might be expected with the parent compound. This phase I trial was undertaken to establish the maximum tolerated dose and the recommended phase II dose in children treated by a 1-hour iv infusion every 4 weeks. Twenty-nine patients with recurrent or progressive tumor were entered in this study at the Children's Hospital of Los Angeles and Children's Memorial Hospital in Chicago between April 12, 1983, and November 27, 1984. Beginning with a dose of 350 mg/m2 (about 80% of the adult phase II dose), we escalated the dose in groups of patients to 670 mg/m2; dose-limiting myelosuppression was encountered at this dose. Fifty-seven infusions are at least partially evaluable for toxicity. Asymptomatic hypomagnesemia, hypocalcemia, and ototoxicity were observed infrequently, and nausea and vomiting were mild. One patient with a mixed glioma of the posterior fossa achieved a good partial response lasting 9 months. Stable disease for greater than or equal to 6 months was observed in three patients: one each with ependymoma, brain stem glioma, and spinal cord astrocytoma. The recommended pediatric phase II dose is 560 mg/m2 given as a 1-hour iv infusion every 4 weeks.

Adolescent↗
PubMed1986

Cisplatin nephrotoxicity.

Cis-dichlorodiammine platinum (II), or cisplatin, has emerged as a principal chemotherapeutic agent in the treatment of otherwise resistant solid tumors and is currently among the most widely used agents in the chemotherapy of cancer. The chief limit to its greater efficacy is its nephrotoxicity, which has made it necessary both to lower its dosage and actively hydrate patients to reduce it. The vulnerability of the kidney to cisplatin is almost certainly related to its primary role in the excretion of cisplatin. Cisplatin enters renal cells by a process that depends on normal oxygen utilization and is specifically inhibited by organic bases. Greater localization of platinum to the S3 segment of the proximal tubules suggests that the vulnerability of this segment may depend on its specific uptake of the drug. The majority of intracellular platinum is bound to macromolecules, including protein and DNA, yet a significant portion of cell platinum is biotransformed to a nonmutagenic and possibly nontoxic compound. Polyuria and hypomagnesemia, which are commonly associated with cisplatin nephrotoxicity, may be due to defects in deep nephron or collecting duct fluid and solute transport. Low single nephron glomerular filtration rates (SNGFR) during early cisplatinum-induced acute renal failure is accompanied by reduced renal blood flow and transglomerular hydrostatic pressure without elevated intratubular hydrostatic pressure, suggesting preglomerular vasoconstriction as an important determinant of renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Ethylene oxide (ETO) as a possible cause of an allergic reaction during peritoneal dialysis and immunologic detection of ETO from dialysis tubing.

An infant with end-stage renal disease requiring continuous ambulatory peritoneal dialysis (CAPD) had a cutaneous eruption with eosinophilia. This reaction was not associated with any drug administration. An analysis for antibodies against ethylene oxide-human serum albumin (ETO-HSA) was conducted because IgE antibodies have been correlated with allergic reactions during hemodialysis. IgE and IgG antibodies against ETO-HSA were demonstrated in one of two serum samples available. Serologic evidence is presented that ETO may be eluted from the dialysis tubing, react with HSA in the peritoneum, and immunize the dialyzed host. This may be a possible explanation for allergic manifestations in our patient and others undergoing peritoneal dialysis.

Antibodies↗
PubMed1982

Observations on persistently dilated ureter after posterior urethral valve ablation.

The persistent ureteral dilatation frequently seen months or even years after posterior urethral valve ablation, continues to present a dilemma to the urologist. We have classified these dilated ureters into 3 types: (I) unobstructed with either an empty or filling bladder, (II) unobstructed with an empty bladder but obstructed with a filling bladder, and (III) obstructed with either an empty or filling bladder. The majority of ureters with persistent dilatation were found to be of the type II variety where appropriate treatment is not obvious. Classic ureteral tailoring and reimplantation offers little advantage since in such cases a narrower ureter is passed through a new hiatus in an otherwise unchanged bladder. When high renal pelvic pressures are found only with bladder filling, then consideration must be given to not only reconstructing the ureter but also to affecting the dynamics of the bladder and the large urinary output characteristically found in these patients.

Child↗
PubMed1980

Pediatric and adult renal transplants: a comparative study.

In order to compare the results of renal transplantation in pediatric and adult recipients, a retrospective analysis of first transplants done at a single institution over a 6-yr period was carried out. The study included 21 pediatric and 196 adult recipients of cadaveric grafts, and 18 pediatric and 156 adult recipients of living related grafts. Pediatric and adult recipient groups were shown to be similar to each other with respect to donor-recipient HLA antigen matching and to causes of graft failure and patient mortality. Actuarial graft and patient survival data for pediatric recipients was found to be better than for the corresponding adult recipient groups, although the differences were not statistically significant. When clinical results, technical problems, and psychosocial adaptation are considered critically, transplantation is clearly preferable to both hemodialysis and to no treatment for pediatric patients with end stage renal disease (ESRD). There is a considerable discrepancy between the estimated incidence of ESRD in children and the number of children being tranplanted for this disease. Many patients are, therefore, receiving less than optimum treatment. Efforts to correct this discrepancy are in order.

Actuarial Analysis↗
PubMed1978

Growth and glucocorticoids in children with kidney disease.

Glucorticoid therapy inhibits statural growth. Alternate-day therapy causes less growth suppression than does daily therapy, and, in experimental animals and children with asthma, it has been associated with normal growth. Although catch-up growth may occur after cessation of steroid therapy, this is not always the case, especially when therapy has been prolonged. In children treated with steroids for glomerulonephritis or nephrotic syndrome and especially in children after renal transplantation, factors other than steroid therapy may contribute to growth retardation. Steroids may suppress growth by direct action on cell metabolism, by inhibition of growth hormone or somatomedin and/or by effects on calcium and phosphorus metabolism. Present knowledge of mechanisms of action and dose-response relationships is complete, and it is difficult to prescribe therapy which will achieve a predictable therapeutic effect without inhibiting growth.

Animals↗
PubMed1977

Successful renal transplantation in infancy.

This infant's post renal transplantation course, representing apparently the smallest long term survivor, illustrates that neither age nor size are contraindications to successful renal transplantation in infants with end stage renal failure. Additional experience with the transplantation of a single kidney into a 1-yr-old baby weighing 4650 gm with congenital bilateral renal hypoplasia has also been successful with a 3-mo follow-up. Both cases demonstrate that single or double renal transplantation in infants is feasible and should be considered when indicated.

Acute Kidney Injury↗
PubMed1976

Cortisol-dihydrotachysterol antagonism in a patient with hypoparathyroidism and adrenal insufficiency: apparent inhibition of bone resorption.

This report describes a case of chronic mucocutaneous candidiasis with associated hypoparathyroidism and acutely developed adrenocortical insufficiency. The latter was heralded by hypercalcemia. Upon the institution of cortisol therapy, while still under the effects of a vitamin D analog dihydrotachysterol (DHT), the patient exhibited severe hypocalcemia and tetany. Since calcium intake was minimal during this period of presumed corticosteroid-DHT antagonism, it is suggested that the cortisol disturbed calcium homeostasis by in inhibiting bone calcium resorption.

Adrenal Insufficiency↗