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S Dikman

Publications and source records attributed to S Dikman.

32 records · Page 2Linked to original sources

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↗

Differential binding of folates by rat renal cortex brush border and basolateral membrane preparations.

The binding of radioactive 5-methyltetrahydrofolate and folic acid was found to be greater in brush border than in basolateral membrane preparations of rat renal cortex. This appeared to be due to an increased amount of a specific folate binding protein in the brush border membrane preparations as compared to those of the basolateral membrane. The binding was saturable and inhibited by nonradioactive folic acid and, therefore, a specific, rather than nonspecific process. The Km's for folic acid binding in brush border and basolateral membrane preparations were similar and involved a single high-affinity binding site. In contrast, methotrexate was found to bind equally well to both brush border and basolateral membrane preparations. Moreover, folic acid binding was not inhibited by an equimolar amount of methotrexate. A folate binding protein could be extracted from either membrane preparation with 1% Triton X-100 and, to a lesser extent, with 0.6 M NaCl. These different extraction procedures resulted in different apparent molecular weights for folate binding protein (greater than 160,000 for Triton X-100-extracted samples and 40,000 for NaCl-extracted samples). The membrane preparation pellets remaining after NaCl extraction were able to rebind tritiated folic acid and also the 40,000-Da folate binding protein. On the other hand, membrane preparations extracted with Triton X-100 lost the ability to bind folic acid or the 40,000-Da folate binding protein. These differences in molecular weight and rebinding capacity may be explained by the existence of a receptor for folate binding protein which was extracted by Triton X-100, but not by NaCl. The greater concentration of folate binding protein in the renal tubule cell brush border membrane preparations as compared to those from basolateral membranes ascribes, for the first time, a functional role for folate binding protein in the renal reabsorption of folates which is required to prevent loss of folate in the urine and perhaps in the membrane transport of folates in general.

Animals↗

Epidermoid cyst of testicle. Ultrasonographic characteristics.

Epidermoid cyst is a benign lesion of the testis which represents approximately 1 per cent of all testicular tumors. We describe a case in which preoperative ultrasound of the testis suggested a benign testicular lesion, thus permitting testis-sparing surgery. The proper management of this lesion remains a source of urologic controversy, and we review the rationales for both radical orchiectomy and simple excision.

Adult↗

True histiocytic lymphoma of the thymus. Report of a case and a study of the distribution of histiocytic cells in the fetal and adult thymus.

The thymus was the site of a true histiocytic lymphoma. Immunohistochemical demonstration of lysozyme and alpha-1-antitrypsin in the tumor cells indicated the histiocytic nature of the tumor. Five fetal and five adult thymus glands were studied for the presence and distribution of true histiocytic cells. Histiocytes were demonstrated predominantly in the connective tissue septa and constituted approximately 2% of cells in these thymuses. Histiocytes are therefore a normal constituent of the thymus, which may become the primary site of true histiocytic lymphoma.

Adult↗

Cutaneous vasculitis complicating coeliac disease.

A 38 year old female, with chronic uncontrolled coeliac disease, presented with the rare complication of cutaneous leucocytoclastic vasculitis. Detailed study failed to identify any cause for the vasculitis, other than the underlying coeliac disease. Haematuria and proteinuria with mesangial nephritis were also demonstrated on renal biopsy with electron microscopic study. It is speculated that exogenous or endogenous antigens permeated the abnormal small bowel mucosa leading to formation of circulating immune complexes. Subsequent tissue deposition of these complexes then resulted in vasculitis and nephritis. The skin lesions cleared completely after treatment with a strict gluten free diet.

Adult↗

Cisplatin nephrotoxicity in rats: defect in papillary hypertonicity.

We examined the effects of cisplatin (5 mg/kg BW) on renal function in rats. Three days after administration of cisplatin whole kidney clearance of inulin fell and 24-h urine volume increased. Maximal urine osmolality and papillary solute content were reduced. Superficial nephron glomerular filtration rate measured along the proximal tubule, where no leak of inulin could be demonstrated, was reduced in cisplatin-treated animals. Differences between superficial nephron glomerular filtration rate determined in proximal and distal tubules were greater in cisplatin-treated rats than in control rats. Neither a change in fluid or sodium movement along superficial nephrons nor a reduced early distal tubule transepithelial sodium gradient explain the polyuria. Urea was reabsorbed from, not added to, the loop fluid in cisplatin-treated animals. Morphologic changes were evident in the S3 segment of the proximal tubule in cisplatin-treated animals but the glomeruli were normal. Polyuria occurred despite diminished glomerular filtration rate in cisplatin nephrotoxicity. The diminished concentration of salt and urea in the papilla as a result of abnormal function of the collecting duct or pars recta portion of the proximal tubule contributed to the defect in concentrating ability.

Acute Kidney Injury↗

Course of gentamicin nephrotoxicity.

Metabolic balance and morphologic studies were performed on rats receiving gentamicin 100 mg/kg/day for a period of 8--10 days and during the recovery period. Daily urine flow rate increased with the administration of gentamiccin and remained elevated up to 20 days following the discontinuation of gentamicin, although BUN and plasma creatinine were virtually normal 10 days after the discontinuation of gentamicin. During the development of renal failure means daily electrolyte excretion remained normal. During the recovery period, however, sodium and potassium excretion exceeded control values while chloride and net acid excretion remained normal. Proteinuria developed during the administration of gentamicin and returned to normal 6--10 days after the discontinuation of gentamicin. Ten days of netilmicin administration (150 mg/kg/day) resulted in only mild tubular degeneration and no azotemia.

Animals↗

The correlation of sequential changes in the distribution of pulmonary blood flow in hemorrhagic shock with the histopathologic anatomy.

Histopathologic changes were described and correlated with hemodynamic changes in a series of farm-reared dogs by a preparation and a protocol which were shown to simulate closely physiologic events in clinical hemorrhagic shock; neither anesthesia nor thoracotomy was used and flush solutions for catheters were strictly limited; a series of sham-treated controls was used for comparison. Five different isotopes were used to label microspheres to measure blood flow sequentially at the tissue level at various stages of the shock protocol. At death, multiple tissue sections were taken relative to six parallel segments of the lung arranged according to dependency so that correlations of structure and function might be related to the influence of gravity. The degrees of severity of atelectasis, hemorrhage, edema, congestion, inflammation, and hyperaeration were evaluated by rating scales. Tissues from the most dependent areas had a higher incidence and greater severity of histologic lesions. Tissues with mild histologic rating tended to have lower percentages of flow after hemorrhage, but normal or increased flow after reinfusion. The severely damaged tissue received greater than average flow throughout. Tissues with severe atelectasis paralleled the course of those with a high over-all severe pathologic rating. Tissues with severe inflammation had less blood flow in the control period, increased flow in Stages B1 and B2 and a subsequent return to control values. Those with severe edema had reduced flow in Stages B2 and B3, but high flows after reinfusion.

Animals↗

Renal biopsy: why and when.

The purpose of this paper is to emphasize the importance of information obtained by renal biopsy in the diagnosis, prognosis, and therapy of patients with renal disease. Because controversy persists regarding the value of renal biopsy as an aid in determining prognosis and in choosing appropriate therapy, there has been some reluctance to use it early after the onset of obvious signs, symptoms, and laboratory findings indicative of renal disease with or without involvement of other organs. Although all such patients may not benefit from the information provided by a proper biopsy, we will illustrate some of the characteristic histologic details found in specific circumstances in our experience where the biopsy has been particularly helpful in reaching a diagnosis, in assessing prognosis, and in choosing therapy.

Adult↗