Fluoride metabolism in patients with chronic renal failure.

Studies of fluoride metabolism were carried out in patients with chronic renal failure by determining fluoride balances for several weeks. The fluoride intake was due to the analyzed fluoride content of the diet and of the drinking water. The effect of aluminum hydroxide on fluoride metabolism was investigated because this antacid is commonly used therapeutically for these patients. Studies have shown that urinary fluoride excretion in patients with chronic renal failure was significantly lower than that in patients with normal renal function, resulting in a signicantly higher retention of fluoride. Although the fecal fluoride excretion in patients with chronic renal failure was slightly but significantly increased, this change did not compensate for the decrease of the urinary fluoride excretion. The intake of aluminum hydroxide resulted in a significant increase of fecal fluoride excretion and in a significant decrease of net absorption and retention of fluoride in patients with chronic renal failure.

Blood eosinophilia in patients undergoing maintenance peritoneal dialysis.

To determine the prevalence of blood eosinophilia in patients receiving maintenance peritoneal dialysis, routine peripheral WBC counts of 49 such patients were reviewed. In 29 patients, blood eosinophilia was noted. Elevations in blood eosinophil counts tended to be mild and episodic. They were often associated with concomitant elevation of peritoneal fluid eosinophil counts. Possible predisposing factors included recent peritoneal catheter insertion and antibiotic therapy for peritonitis.

Peritoneal fluid eosinophilia in patients undergoing maintenance peritoneal dialysis.

In ten patients undergoing maintenance peritoneal dialysis, large numbers of eosinophils were found in the peritoneal fluid. A few of the affected patients complained of episodic abdominal pains, but there was no correlation between abdominal symptoms and the number of peritoneal fluid eosinophils. Microorganisms failed to grow on cultures of the peritoneal fluids, and results of tests for endotoxin were negative. The cause of eosinophilia could not be determined. Peritoneal fluid eosinophil counts were noted to be elevated soon after catheter insertion and initiation of peritoneal dialysis. In some patients, peritoneal fluid eosinophil counts spontaneously returned to normal despite continued peritoneal dialysis.

Sclerotic thickening of the peritoneal membrane in maintenance peritoneal dialysis patients.

Five patients receiving maintenance peritoneal dialysis (duration, three months to four years) required surgical exploration of the abdomen for various reasons. Four had a prior history of bacterial peritonitis, and four of aseptic peritonitis. At laparotomy, the peritoneal membrane was found to be markedly thickened and sclerotic in all patients, and loops of bowel were bound together in a dense, opaque casing. On microscopic examination, an increase in fibroconnective tissue in the peritoneum was observed.

Subxiphoid pericardiostomy for hemodialysis-associated pericardial effusion.

Sixteen patients receiving maintenance hemodialysis in whom moderate-to-large pericardial effusions developed were treated with short-term drainage via a large-bore tube implanted into the pericardial sac. Drainage tubes were implanted using a subxiphoid approach (subxiphoid pericardiostomy) while the patient was under local anesthesia. In seven patients, triamcinolone hexacetonide was instilled into the pericardial sac through the drainage tube at regular intervals. In all patients, a drainage period of two to four days, with or without instillation of nonabsorbable steroids, was associated with resolution of the pericardial effusion. Only one recurrence of effusion was demonstrable over a follow-up period extending from three months to eight years (median, 4.2 years). Complications of subxiphoid pericardiostomy were minor (incisional hernia, wound infection, and small pneumothorax) and easily treatable. Our results suggest that short-term drainage via a surgically implanted drainage tube is an effective and safe treatment of moderate-to-large hemodialysis-associated pericardial effusion.

Residual complement activity after incubation with myelin isolated from both the central and peripheral nervous tissues.

The relative ability of isolated central and peripheral nervous system myelin to interact with the complement system of plasma proteins was studied. The myelin used was a highly pure form, devoid of contamination by any subcellular organelles or membranes. Residual complement activity was a linear function of increasing quantities of myelin from 10 to 40 micrograms of myelin protein. Central and peripheral nervous system myelin showed identical residual complement activity at various temperatures above 7 degrees C and also after various time periods of incubation. The results show that central and peripheral nervous system myelin show equal ability to interact with complement, in spite of their different origin and differences in morphology and protein composition.

Methods for assessing nutritional status of patients with renal failure.

Since wasting and malnutrition are common problems in patients with renal failure, it is important to develop techniques for the longitudinal assessment of nutritional status. This paper reviews available methods for assessing the nutritional status; their possible limitations when applied to uremic patients are discussed. If carefully done, dietary intake can be estimated by recall interviews augmented with dietary diaries. Also, in a stable patient with chronic renal failure, the serum urea nitrogen (N)/creatinine ratio and the rate of urea N appearance reflect dietary protein intake. A comparison of N intake and urea N appearance will give an estimate of N balance. Anthropometric parameters such as the relationship between height and weight, thickness of subcutaneous skinfolds, and midarm muscle circumference are simple methods for evaluating body composition. Other methods for assessing body composition, such as densitometry and total body potassium, may not be readily applicable in patients with renal failure. More traditional biochemical estimates of nutritional status such as serum protein, albumin, transferrin, and selected serum complement determinations show that abnormalities are common among uremic patients. Certain anthropometric and biochemical measurements of nutritional status are abnormal in chronically uremic patients who appear to be particularly robust; thus, factors other than altered nutritional intake may lead to abnormal parameters in such patients. Serial monitoring of selected nutritional parameters in the same individual may improve the sensitivity of these measurements to detect changes. Standards for measuring nutritional status are needed for patients with renal failure so that realistic goals can be established optimal body nutriture.

Protein kinase C modulates the release of [3H]5-hydroxytryptamine in the spinal cord of the rat: the role of L-type voltage-dependent calcium channels.

The present studies examined the relationship between protein kinase C (PKC) and L-type voltage-dependent calcium channels in modulating the release of neurotransmitter from K(+)-depolarized rat spinal cord synaptosomes. Activators of PKC, such as phorbol 12-myristate 13-acetate (PMA), mezerein and oleoyl acetylglycerol produced a concentration-dependent potentiation of K(+)-induced release of [3H]5-hydroxytryptamine ([3H]5-HT). Enhanced release was dependent on the concentration of both Ca2+ and K+ in the superfusion medium. Calcium-independent release of [3H]5-HT or release induced by the Ca2+ ionophore were unaffected by PKC activators. Calcium-dependent release of [3H]5-HT, evoked by K+, was enhanced under similar conditions by the L-type Ca2+ channel agonists Bay K 8644 and (+)-SDZ 202-791. Nimodipine, an L-type Ca2+ channel antagonist, while having no independent effect on K(+)-induced release of [3H]5-HT, abolished the potentiative effects of Bay K 8644 and PMA. Similarly, the PKC inhibitors, polymyxin B and staurosporine, blocked effects of both PMA and Bay K 8644 on K(+)-stimulated release of [3H]5-HT. Neither PMA nor Bay K 8644 altered the uptake of [3H]5-HT. These results suggest that PKC-dependent mechanisms utilize calcium influx, via the L-type calcium channel, to modulate release of neurotransmitter and indicate a possible functional link between PKC and L-type voltage-dependent calcium channels in the spinal cord.

Alterations in alpha-adrenergic and muscarinic cholinergic receptor binding in rat brain following nonionizing radiation.

Microwave radiation produces hyperthermia. The mammalian thermoregulatory system defends against changes in temperature by mobilizing diverse control mechanisms. Neurotransmitters play a major role in eliciting thermoregulatory responses. The involvement of adrenergic and muscarinic cholinergic receptors was investigated in radiation-induced hyperthermia. Rats were subjected to radiation at 700 MHz frequency and 15 mW/cm2 power density and the body temperature was raised by 2.5 degrees C. Of six brain regions investigated only the hypothalamus showed significant changes in receptor states, confirming its pivotal role in thermoregulation. Adrenergic receptors, studied by [3H]clonidine binding, showed a 36% decrease in binding following radiation after a 2.5 degrees C increase in body temperature, suggesting a mechanism to facilitate norepinephrine release. Norepinephrine may be speculated to maintain thermal homeostasis by activating heat dissipation. Muscarinic cholinergic receptors, studied by [3H]quinuclidinyl benzilate binding, showed a 65% increase in binding at the onset of radiation. This may be attributed to the release of acetylcholine in the hypothalamus in response to heat cumulation. The continued elevated binding during the period of cooling after radiation was shut off may suggest the existence of an extra-hypothalamic heat-loss pathway.

Surgery, nutritional support, and survival in patients with end-stage renal disease.

In 216 patients with end-stage renal disease (ESRD) undergoing 406 major operations, surgery was elective in 143 cases (mortality, 1.4%) and nonelective in 263 (mortality, 11.1%). Of 82 patients who received 105 pretransplant operations to prevent posttransplant complications, eg, gastrointestinal hemorrhage, urinary tract sepsis, and azathioprine intolerance, surgical mortality was 1.9%, with 80 patients becoming active candidates for transplantation. Sepsis requiring surgical care occurred in 54 patients, in 36 of these in the posttransplant period. Parenteral and enteral hyperalimentation was used as a therapeutic adjunct in 40 of these patients. Overall mortality in those with septic complications was 35.2%, 22.5% in the nutritional support group and 71.4% in the group not receiving hyperalimentation. Improved survival rates can be achieved for surgical emergencies in ESRD, particularly in the posttransplant immunosuppressed patient, if both definitive surgical intervention and nutritional support are actively applied.

Penile calcification in maintenance hemodialysis patients.

Penile calcification was detected in 6 of 32 patients (19%) with end-stage renal disease (ESRD) using soft tissue x-ray techniques. Having been maintained on hemodialysis for a minimum of one year, all the affected patients showed clinical evidence of secondary hyperparathyroidism and calcification in the blood vessels of some other tissues. All had erectile impotence, while in 1 patient gangrene of the penis developed. Penile calcification is probably more common in ESRD patients than realized and should be looked for as a possible cause of impotence in male patients treated with maintenance hemodialysis.

Transdermal clonidine for hypertensive patients.

Seventeen moderately hypertensive patients, whose blood pressure was previously controlled with hydrochlorothiazide and oral clonidine (blood pressure 129 +/- 8/85 +/- 5 mmHg during therapy), were treated with a transdermal system involving application of one or more clonidine-containing patches (3 mg per patch) to the skin once a week. The patients continued to take 50 mg of oral hydrochlorothiazide daily. By four to eight weeks, 15 of 17 patients using the transdermal system had achieved baseline blood pressure levels (130 +/- 10/84 +/- 6 mmHg, NS). During the maintenance phase of transdermal therapy, plasma clonidine levels measured four hours (0.78 +/- 0.43 ng/ml), four days (0.89 +/- 0.48 ng/ml), and seven days (0.78 +/- 0.41 ng/ml) after patch application did not differ significantly from one another or from trough plasma clonidine levels (0.86 +/- 0.54 ng/ml) measured during oral clonidine therapy. The results suggest that, in moderately hypertensive patients, blood pressure can be controlled with a once-weekly application of clonidine-containing skin patches as effectively as with oral clonidine.

Modulation of [3H]serotonin release by dihydropyridines in spinal cord synaptosomes.

The release of [3H]monoamines from preloaded synaptosomes from spinal cord is K(+)-dependent and can be modulated by L-type Ca2+ channel agonists such as the 1,4-dihydropyridine (1,4-DHP), Bay K 8644. Whereas the basal release of [3H]monoamines was not altered by Bay K 8644, K(+)-stimulated release of [3H]norepinephrine was enhanced 35% and [3H]serotonin 50%. Modulation of release by Bay K 8644 was dependent on the K+ concentration in the medium, being present only at submaximal depolarization with 15 mM K+. Enhanced release in the presence of Bay K 8644 was concentration-dependent and Ca2(+)-dependent. Ca2(+)-independent release induced by fenfluramine was not enhanced by Bay K 8644. Both nimodipine and nitrendipine, 1,4-DHP antagonists, produced a concentration-dependent block of the Bay K 8644-induced monoamine release and had no independent effect on basal or K(+)-stimulated release. omega-Conotoxin GVIA (omega-CgTx) produced a concentration dependent decrease of K(+)-stimulated serotonin release, which antagonized the stimulatory effect of low concentrations of Bay K 8644. However, omega-CgTx did not alter the enhancement of K(+)-stimulated release at higher concentrations of Bay K 8644. The data from the present work establish the conditions for modulation of K(+)-evoked monoamine release in spinal cord by 1,4-DHP agonists and suggest a role for the L-type voltage dependent Ca2+ channel in this process.

The effect of kappa agonist U50-488H on [3H]nimodipine receptor binding in rat brain regions.

The effects of a kappa opiate agonist have been evaluated on [3H]nimodipine binding to dihydropyridine receptors for 'L'-type Ca2+ channels in rat brain regions. Administration of U50-488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1,-pyrolidinyl-cyclohexyl benzeneacetamide) produced a 28% decrease in Bmax in cortex and a 23% decrease in cerebellum. No changes were seen in the affinity (Kd) for [3H]nimodipine binding sites. Slight changes in hippocampal and striatal binding capacities were observed with no changes seen in hypothalamus and brainstem. The kappa antagonist MR2266 effectively reversed in vivo all changes in [3H]nimodipine binding without producing any effect alone. These studies suggest that kappa opiate receptors may be directly coupled to L-type calcium channels as evidenced by [3H]nimodipine binding studies and may account for the findings that kappa opiate agonists inhibit neurotransmitter release by allosterically interfering with the Ca2+ channel protein in brain membranes.

Fluoxetine-induced inhibition of synaptosomal [3H]5-HT release: possible Ca(2+)-channel inhibition.

Fluoxetine, a selective 5-HT uptake inhibitor, inhibited 15 mM K(+)-induced [3H]5-HT release from rat spinal cord and cortical synaptosomes at concentrations greater than 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K+ used to depolarize the synaptosomes and the concentration of external Ca2+. Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [3H]5-HT release induced by the Ca(2+)-ionophore A 23187 or Ca(2+)-independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K(+)-induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca2+ channels and Ca2+ entry. Whereas fluoxetine and paroxetine inhibited binding of [3H]nitrendipine to the dihydropyridine-sensitive L-type Ca2+ channel, the less selective uptake inhibitors did not alter binding. The dihydropyridine antagonist nimodipine partially blocked fluoxetine-induced inhibition of release. Moreover enhanced K(+)-stimulated release due to the dihydropyridine agonist Bay K 8644 was reversed by fluoxetine. Fluoxetine also inhibited the K(+)-induced increase in intracellular free Ca2+ in fura-2 loaded synaptosomes. These data are consistent with the suggestion that fluoxetine inhibits K(+)-induced [3H]5-HT release by antagonizing voltage-dependent Ca2+ entry into nerve terminals.

Paecilomyces peritonitis: case report and review of the literature.

While filamentous fungi are a rare cause of peritonitis in peritoneal dialysis patients, there is increasing recognition of Paecilomyces species as pathogens in such patients. We herein report a case of fungal peritonitis secondary to the filamentous Paecilomyces variotii species. The patient had a long and ultimately fatal course of illness despite catheter removal, discontinuation of peritoneal dialysis, recurrent intraabdominal abscess drainage, and prolonged courses of antifungal therapy. Our experience with this case and a review of the literature suggests that infection with this fungus can cause substantial morbidity and is probably best treated with prompt catheter removal, aggressive antifungal therapy and vigilant observation for complications.

Use of a phosphorus-enriched hemodialysate to prevent hypophosphatemia in a patient with renal failure-related pericarditis.

We describe a patient who suffered from renal failure-associated pericarditis and underwent daily 3.5-hour hemodialysis treatments for 17 days. The initially elevated serum phosphorus level gradually fell to below normal on days 11 and 12 as a result of the intensive dialytic therapy. Phosphorus was added to the "base concentrate" of a dual-concentrate, bicarbonate-based dialysate delivery system on days 13 to 17. Because of this phosphorus-enrichment, we were able to maintain the patient's serum phosphorus levels within normal limits in spite of continued daily dialysis treatments.

Amantadine hydrochloride pharmacokinetics in patients with impaired renal function.

To study the disposition of amantadine hydrochloride in patients with impaired renal function, 100 mg was administered orally to 13 patients with creatinine clearances ranging from 48 to 10 ml/min/1.73 m2 body surface area. Six adults with normal renal function served as controls. Plasma half-life averaged 68.5 +/- 9.5 SEM hours in the renal patients (range: 27 to 144), versus 12.6 +/- 1.7 hours in controls. Plasma half-life correlated significantly with serum creatinine (r = 0.8476, P less than 0.001) and serum urea nitrogen levels (r = 0.8791, P less than o.001). Similarly, plasma elimination constant correlated with creatinine clearance/1.73 m2 body surface area (r = 09201, P less than 0.001). Renal amantadine clearance also correlated with creatinine clearance/1.73 m2 body surface area (r = 0.8217, P less than 0.001). However, renal amantadine clearance regularly exceeded creatinine clearance, suggesting that tubular secretion plays a role in the elimination of this drug. Amantadine excretion is decreased in patients with impaired renal function. The amount by which dosage must be reduced can be estimated based on creatinine clearance.

Extreme hyperglycemia in dialysis patients.

In 12 diabetic patients who were being treated with maintenance hemodialysis or maintenance peritoneal dialysis, coma and other neurologic deficits did not occur in spite of extremely elevated serum glucose levels. The mean serum values of these patients were: glucose 1,174 +/- 248 (SD) mg/100 ml, sodium 125 +/- 5 mEq/l, calculated total osmolality 342 +/- 13 mOsm/kg water and calculated effective osmolality (without urea) 316 +/- 13 mOsm/kg water. It is suggested that the absence of osmotic diuresis and the lack of substantial osmotic ultrafiltration prevented the development of hypernatremia and marked hyperosmolality. The osmolar effect of glucose alone at these serum concentrations apparently was not sufficient to induce neurologic impairment.

Treatment of refractory hemodialysis ascites with maintenance peritoneal dialysis.

In 5 patients who were receiving maintenance hemodialysis, ascites developed that was refractory to treatment by ultrafiltration during hemodialysis. Use of sequential isolated ultrafiltration and hemodialysis therapy either precipitated side effects or else required prolongation of total treatment time which the patients declined to accept. In 4 of the patients, ascites was believed to be primarily responsible for severe, progressive cachexia. Maintenance peritoneal dialysis was instituted in all patients, and abdominal fluid was removed gradually, over a period of 2 to 3 days. Ascites resolved promptly in each case. Three patients noted a dramatic improvement in appetite after relief of abdominal distension. Follow-up periods ranged from 6 to 4 1/2 years. Our results suggest that maintenance peritoneal dialysis can successfully control hemodialysis ascites.