Protection from the nephrotoxicity of contrast dye.

Previous studies have reported a 4%-50% incidence of acute renal failure (ARF) following the use of radiocontrast media in patients with preexisting chronic renal insufficiency. In these studies, ARF was defined as a rise of the serum creatinine of at least 1 mg/dl above baseline. Using the same criteria, we studied 214 patients undergoing various intravascular radiocontrast media procedures. Patients were infused with a specially prepared cocktail solution (NSMF) containing 1000 ml half-normal saline, 12.5 g of mannitol (M), I ampule NaHCO3, and 200 mg of furosemide (F) at 100 ml/h from one hour prior to two hours after the procedure. Urinary output was replaced with normal saline for at least 6 h after the procedure. Seven percent of the patients developed acute renal insufficiency. Only 3% of the patients had a rise in serum creatinine greater than 2 mg/dl. No patient required dialysis therapy after the procedure. There was one unrelated death caused by acute myocardial infarction postangioplasty. Risk factors for development of ARF despite cocktail administration included the presence of diabetes mellitus and angiotensin converting enzyme (ACE) inhibitor therapy. We concluded that the properly administered NSMF solution protects against radiocontrast dye induced renal failure. In select patients with chronic renal insufficiency, consideration should be given to withholding ACE inhibitor therapy for 24-48 h prior to administration of intravenous radiocontrast dye. A large controlled trial will be required to establish whether the NSMF solution offers benefit beyond that of saline hydration alone.

Foscarnet alters antidiuretic hormone-mediated transport.

Therapy with foscarnet is associated with acute renal failure. Prior studies have emphasized foscarnet's proximal tubular toxicity, but there have been isolated reports of foscarnet-induced nephrogenic diabetes insipidus. As a phosphate analog, foscarnet is a competitive inhibitor of NaPO4 cotransport. However, foscarnet's effect on antidiuretic hormone (ADH)-induced transport has not been previously investigated. We studied foscarnet's modulation of transport in the toad urinary bladder. Foscarnet at 10 microM to 10 mM did not alter basal water or urea flux. Urea transport induced by a maximal dose of ADH (24 mIU/ml) was inhibited by 0.1 to 5.0 mM foscarnet. In tissues challenged with 0.5 to 1.0 mIU of ADH per ml, 1.0 to 10 mM foscarnet increased water flow but did not alter urea flux. Foscarnet also increased water flow induced by 1.0 to 10 microM forskolin. In tissues pretreated with 10 microM naproxen, foscarnet did not alter water flow induced by 0.5 to 1.0 mIU of ADH per ml or forskolin. These results indicate that foscarnet stimulates water flow induced by 0.5 to 1.0 mIU of ADH per ml at a site proximal to that of the generation of cyclic AMP and inhibits urea flux induced by a maximal dose of ADH at a separate site. In humans, foscarnet nephrotoxicity is likely not limited to the proximal nephron, but extends to the collecting duct. Patients receiving foscarnet should be closely monitored for disorders of urinary concentration.

Dialysis-related amyloidosis manifested as masses in the buttocks.

A 40-year-old man had enlarging painful gluteal masses that developed after 17 years of hemodialysis. Pathologic examination revealed extensive deposition of beta 2-microglobulin amyloid. A bladder biopsy done during evaluation for possible transplantation also showed amyloid deposits. This constellation of findings has not been reported in a patient with beta 2-microglobulin amyloidosis. Patients with dialysis-related amyloidosis should be carefully assessed for systemic involvement. Renal transplantation may prevent further amyloid deposition and provide relief of pain.

The use of fluconazole in the management of Candida peritonitis in patients on peritoneal dialysis.

In patients receiving peritoneal dialysis, fungal peritonitis is generally impossible to eradicate with previously available therapy in the absence of catheter removal. Corbella et al. described a patient with fungal peritonitis treated with fluconazole without catheter removal. We studied this drug's effectiveness in the treatment of 5 patients with peritonitis secondary to Candida species. Patients received a loading dose of 200-400 mg fluconazole, followed by 50-200 mg fluconazole daily. Patients improved initially after therapy with fluconazole. Abdominal pain and fever abated, dialysis returns cleared, cell counts decreased, and, in four cases, cultures were sterilized. Dialysate fluconazole levels were adequate. However, despite maintenance of fluconazole therapy, all patients had recurrent peritonitis within 1 month. Complete cure did not occur unless the Tenckhoff catheter was removed. When the catheter was removed, tip cultures grew pure Candida species, and microscopic examination of catheter sections revealed abundant yeast. Although there may be continued isolated reports of successful eradication of fungal peritonitis without catheter removal, we conclude that in the vast majority of cases catheter removal is required.

Comparative effect of metals on antidiuretic hormone induced transport in toad bladder: specificity of mercuric inhibition of water channels.

We previously reported that HgCl2 inhibits water and urea flux in tissues fixed with glutaraldehyde after antidiuretic hormone (ADH) stimulation and suggested that the ADH-induced water channel may share characteristics of the red blood cell and proximal tubule water transport pathway. To determine the specificity of mercury's action, we examined the effect of numerous other metals. In tissues fixed after ADH stimulation, water flow and urea and sucrose permeabilities are maintained from mucosal bath pH 2.5 through pH 12. Several metals including Ba, Co, Fe, Sr and Zn did not alter flux. Al, Cd, La, Li, Pb and U inhibited urea permeability but not water flow. At pH 2.8, Cu inhibited water flow by 30% and urea permeability by 50%. At pH 4.9-7.4, Cu inhibited urea permeability but not water flow. At pH less than or equal to 3.0, Pt inhibited flow in ADH-pretreated tissues. The inhibitory effect was not present at pH greater than 3.0. At pH less than 3.0, Au inhibited flow by 90% in tissues fixed after pretreatment with ADH but increased the permeability of tissues fixed in the absence of ADH. Ag inhibited flow by 70% but also increased sucrose, urea, and basal permeabilities. This suggests that Ag and Au disrupt epithelial integrity. These results indicate that at physiologic pH, the ADH-induced water channel is specifically blocked by Hg but not by other metals. This specificity may reflect the presence of a large number of sulfhydryl groups in the water channel.

Volunteer participation in feeding residents: training and supervision in a long-term care facility.

The increasing number of residents in long-term care facilities who require full and partial assistance during meals has created a need for volunteer support to enhance the quality of life for residents. The correlation between dependence in eating and the existence of swallowing disorders and the risk of aspiration in persons with swallowing disorders suggests that training must be given to volunteers who feed residents. A formalized program for volunteer training and supervision was implemented at Coler Memorial Hospital, a long-term care facility. The program's development and benefits are outlined. Implementation of this program resulted in better training of volunteers, increased socialization, communication, and safety for patients during meals.

Coagulation and fibrinolytic responses to exercise and cold exposure.

This study examined the effect of acute cold exposure on coagulation (PTT) and fibrinolysis (ELT), and the effect of cooling on subsequent exercise-induced coagulation and fibrinolytic responses. Ten male volunteers were tested at 5 degrees C and 28 degrees C on alternate days. Each subject began by sitting quietly for 60 min. Each then exercised on a cycle ergometer at 50 W for 5 min followed by 150 W for 10 min. Venous blood samples were taken before rest, after rest, and after exercise for each temperature on each of the two days. PTT, ELT, and hematocrit (HCT) were determined at each interval. Rectal temperature (Tre) and mean skin temperature (Tsk) were assessed at 15-min intervals throughout. Tsk was stable under neutral conditions but declined rapidly in the cold environment. Tre response was more complex but was significantly different for one contrast only (CE less than NE). ELT was shortened to 74, 62, and 44% while HCT increased to 107, 107, and 111% of pretest values for CR, NE, and CE, respectively. No significant change was noted for PTT. It is concluded that acute cold exposure as well as exercise stress results in an increase in ELT activity of blood; simultaneous enhancement of the coagulation status of the blood in response to stress is not inextricably linked to an elevation of fibrinolytic activity, a result that questions the importance of the Hageman factor dependent pathway between coagulation and fibrinolysis.

The role of inhibin in adult male rats: the effect of inhibin deficiency and androgen antagonism on serum and pituitary gonadotrophins.

We examined the ability of inhibin-F contained in porcine follicular fluid (pFF) to regulate serum gonadotrophins in male rats made deficient in endogenous inhibin and unable to respond to normal endogenous androgen levels. Efferent duct ligation (EDL) effected endogenous inhibin deficiency and the anti-androgen flutamide (F) (13.4 mg/dose, sc once per day) raised the set point for androgen control of the hypothalamus to a level intermediate between the intact and castrate serum gonadotrophin levels. EDL, F and EDL + F caused serum FSH levels to rise and administration of pFF (2 ml per day) suppressed the elevated serum FSH levels of these experimental models to intact animal levels. Though EDL had no effect on serum LH, F increased the serum LH levels and EDL plus F increased them further. Treatment with pFF suppressed the serum LH to intact levels. EDL rats had slightly increased serum androgen (6 ng/ml) but F and EDL + F treated rats had very greatly increased serum androgen concentrations (22 and 32 ng/ml, respectively) which treatment with pFF suppressed to intact levels. Pituitary FSH was increased by EDL and LH was increased by F. In both cases, the increased pituitary gonadotrophins were suppressed by treatment with pFF. We conclude that inhibin regulates synthesis and secretion of FSH and secretion of LH.

The contribution of gonadostatin (inhibin-F) to the control of gonadotropin secretion in a simulated estrous cycle in steroid-treated ovariectomized rats.

We have examined the contribution of gonadostatin to the control of gonadotropin secretion throughout the rat estrous cycle. The estrous cycle was simulated in rats ovariectomized on diestrus-1, designated day 1 (D-1) by use of low or high level estradiol and progesterone Silastic implants. The steroid implant regimen simulated the major changes of these hormones in the blood during the course of the estrous cycle. Injections of porcine follicular fluid (pFF) were superimposed on this steroid regimen. Four treatment combinations of steroid and pFF or their controls were tested: 1) steroid implants only, 2) pFF only at a constant dose level, 3) steroid implants and pFF injections at a constant dose level, and 4) steroid implants and pFF injections with reduced levels on simulated proestrus. In group 1 both basal and surge release of LH were similar to those in the intact rat, but both basal and surge release of FSH were significantly elevated above levels observed in the intact rat for the respective periods. In group 2 FSH was suppressed to diestrous levels throughout the course of the experiment, with no surge occurring on D-3. Serum LH levels were slightly elevated above diestrous levels (50-150 ng/ml) with no surge. In group 3 serum levels of both gonadotropins were suppressed to diestrous levels on D-1 and D-2, and a steroid-induced, pFF-attenuated surge occurred on the afternoon of D-3. Group 4 had, with a minor variation, proestrous-like FSH and LH surges on D-3 and basal (diestrous) gonadotropin levels during simulated D-1, D-2, and early proestrus. This study supports previous evidence for estradiol and progesterone control of LH secretion and elaborates the control of FSH secretion. The role of gonadostatin and steroids is demonstrated in the negative feedback regulation of FSH secretion.

The dissociation and separation of bovine adenohypophysial cells.

Bovine adenhypophysial tissue was dissociated by sequential enzymatic incubation in a continuous flow system. Dispersed cells separated into discrete fractions after centrifugation in isopycnic bovine serum albumin gradients. The dispersed and separated cells were prepared for microscopic identification and differential counts by centrifugal cytology. Radioimmunoassays for LH, FSH, TSH, and Prl were used to corroborate the differential counts and determine the homogeneity of the fractions. The thyrotrophs banded at an average density (rho) of 1.0417, the FSH-secretory cells at rho = 1.0597, the LH-secretory cells at rho = 1.0458, and the Prl-secretory cells at rho = 1.0126. A 7-16 fold enrichment of different cell populations was possible. In bovine hypophyses each hormone appears to be formed by specific cells: the average TSH concentrations of the thyrotrophs were 5.1 pg/cell for LH- and FSH concentration were 4.7 and 4.9 pg/cell for LH- and FSH-secreting cells, respectively. The average Prl concentration was 4.9 pg/cell for Prl-secreting cells.