Health literacy and the provision of information to women with breast cancer.

AIMS: Health literacy and functional health literacy are important for patients with cancer, as key information regarding treatment complications and clinical trials is often imparted using written educational material. This study measured the health literacy and functional health literacy levels in a population of women with breast cancer and compared these with the level of written information provided. MATERIALS AND METHODS: A cross-sectional survey of women with stage I-III breast cancer attending an outpatient clinic was conducted. Health literacy levels were assessed using the Rapid Estimate of Adult Literacy in Medicine (REALM) score and functional health literacy was assessed using three validated screening questions. Patient education materials were assessed using the Simple Measure of Gobbledygook (SMOG) and Flesch Reading Ease (FRE) systems. RESULTS: One hundred and twenty-seven women were recruited. For patients, the mean REALM score was 64.3 (≥US 9th grade/reading age 14 years). The mean SMOG score of patient education materials was 80.5 (reading age 17 years). The mean FRE score of patient education materials was 55.7 (reading age 15-17 years). All patient information sheets assessed were written at ≥8th grade (reading age 13 years) and as a result up to 9% of patients would be unable to read them. Nineteen per cent of the population had inadequate functional health literacy. CONCLUSIONS: Health literacy levels were high in the population studied. However, the reading level of written patient information was also high, meaning that up to 9% of patients would be unable to read the information provided. Functional health literacy levels were lower, with 19% of patients having inadequate ability. This means that although most patients are able to read the information sheets provided, there is a larger proportion that would be unable to understand and act upon this information. Patient education materials should be written at an appropriate level and different modalities of communication should be used to ensure adequate comprehension.

Immunolocalisation of adenosine A(1) receptors in the rat kidney.

The location of adenosine A(1) receptors in the rat kidney was investigated using immunolabelling with antibodies raised to a 15-amino-acid sequence near the C-terminus of the receptor (antibody I) and to a 14-amino-acid sequence in the second extracellular loop (antibody II). In the cortex, antibody I bound to adenosine A(1) receptors in mesangial cells and afferent arterioles, whilst antibody II bound to receptors in proximal convoluted tubules. In the medulla, both antibodies bound to receptors in collecting ducts and the papillary surface epithelium. These observations provide support for the diverse functional roles previously proposed for the adenosine A(1) receptor in the kidney. The labelling of distinct but different structures in the cortex by antibodies raised to different amino acid sequences on the A(1) receptor protein suggests that differing forms of the receptor are present in this region of the kidney.

Subcutaneous administration of recombinant glycosylated interleukin 6 in patients with cancer: pharmacokinetics, pharmacodynamics and immunomodulatory effects.

This is the first report of the serum profile of a glycosylated recombinant form of human IL-6 (rhIL-6) administered subcutaneously (1-10 microg/kg/day) in a phase I/II trial as a thrombopoietic agent in patients with advanced cancer. The pharmacodynamic effects of IL-6 were also examined. Detailed pharmacokinetic measurements were made in four patients. Peak concentrations at 5-8 h and a median t0.5 of ca. 5 h were similar to those previously reported for non-glycosylated IL-6. However, higher peak concentrations and apparent differences in effective dose levels to those previously reported with the non-glycosylated form were seen. Indications of an apparent attenuation in circulating IL-6 concentrations with continuing injections were seen in eight of 10 patients examined but anti-IL-6 antibody generation was seen in only two patients. Soluble interleukin 6 receptor concentrations generally decreased. No major changes in T cell subsets were seen but expression of CD25 and CD54 by T lymphocytes significantly increased, accompanied by marked increases in soluble CD25 (sIL-2R) and CD54 (sICAM-1). No consistent change in B cells, monocytes or NK cells were seen. No evidence for induction of TNF-alpha was found. This study demonstrates similar biological effects of glycosylated rhIL-6 to those reported for the non-glycosylated form but illustrates several apparent differences which are discussed further.

Differential expression of renal adenosine A(1) receptors induced by acute renal failure.

The distribution of renal adenosine A(1) receptors was investigated in rats with glycerol- or mercuric chloride (HgCl(2))-induced acute renal failure. Receptors were localised by autoradiography using [(3)H]8-cyclopentyl-1,3-dipropylxanthine ([(3)H]DPCPX), a selective A(1) adenosine receptor antagonist. In saline-injected control animals, significant labelling with [(3)H]DPCPX was detected in glomeruli, the inner stripe of outer medulla, and the inner medulla. Sixteen hours following induction of glycerol-induced acute renal failure (ARF), a 34% increase in labelling in glomeruli was noted compared to saline-injected controls, and by 48 hr, glomerular labelling had increased by 200%. In addition, 48 hr following glycerol injection, significant labelling was now detected in the cortical labyrinth and medullary rays whilst, in the inner medulla, labelling had decreased by 34%. By contrast to glycerol-induced ARF, the only significant change noted 48 hr following induction of HgCl(2)-induced ARF was a 39% decrease in labelling in the inner medulla. It is concluded that glycerol-induced ARF results in differential expression of renal adenosine A(1) receptors with increased expression in the cortex and reduced expression in the inner medulla. Increased density of A(1) receptors in glomeruli may account, at least in part, for the increased renal vasoconstrictor response to adenosine and depressed glomerular filtration rate noted previously in this type of acute renal failure.

Regulation of renal adenosine A(1) receptors: effect of dietary sodium chloride.

The influence of dietary NaCl on the regulation of renal adenosine A(1) receptors was investigated in the rat. Renal membranes from rats fed on a diet low (0.04%) in NaCl showed a 46% increase in B(max) for the binding of [3H]-1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX), a selective adenosine A(1) receptor antagonist, compared to membranes from rats fed on a normal diet (0.4% NaCl). Conversely, a high NaCl diet (4.0%) resulted in a 37% decrease in B(max). Levels of renal adenosine A(1) receptor mRNA were 65% lower in rats on a high salt diet. Autoradiographic studies showed that, for the inner medullary collecting ducts, a low NaCl diet resulted in a 30% increase in [3H]DPCPX binding with a 39% decrease noted in rats maintained on a high salt diet. The results indicate that changes in adenosine A(1) receptor density may represent a novel mechanism whereby the kidneys adapt to changes in salt load.

The ecotoxicity and the biodegradability of lactic acid, alkyl lactate esters and lactate salts.

The ecotoxicity of lactic acid, its alkyl esters and selected metal salts was studied experimentally with the micro alga Selenastrum capricornutum, the crustacean Daphnia magna and the fish species Brachydanio rerio and Pimephales promelas. In addition, the biodegradation of lactate esters was also studied. The aim of the study was to provide predicted environmental data for additional alkyl homologues and metal salts. The ecotoxicity data are evaluated by means of Structure Activity Relations (SAR), using literature data on a non-polar narcotic mechanism of toxicity as a baseline for comparison. Lactate salts were evaluated by comparison to the toxicity of the metal ion. For the fish and D. magna, it was evident that methyl, ethyl, propyl and to a lesser extent butyl lactate were slightly more toxic in comparison to baseline non-polar narcotic toxicity data. The toxicity tests carried out with lactate-salts demonstrated clearly that the toxicity in standard tests is only determined by the associated cation and not by the lactate part. Lactic acid and its alkyl esters were degraded for more than 60% in the ready biodegradability tests and from the data presented, it is evident that the majority of alkyl lactates are readily biodegradable. The results presented in this study indicate that alkyl lactate esters show some differences in their ecotoxicity when compared to non polar narcotic compounds in but that these differences are generally small. When aquatic toxicity is considered together with their rapid tendency to biodegrade, it is concluded that lactate esters show generally favourable environmental characteristics.

Adenosine receptor mRNA levels during postnatal renal maturation in the rat.

Adenosine may affect the pattern of intrarenal blood flow during renal development. It provides an angiogenic stimulus for the growth of new blood vessels and may be involved in compensatory renal growth. It is therefore of interest to investigate the expression of adenosine receptor genes during postnatal renal development. In the present study this was carried out by measuring adenosine receptor mRNA levels in rats aged between 2 and 60 days. The order of abundance of adenosine receptor mRNA levels in 60-day-old rats was A2A > A2B > or = A1 > A3. A1 receptor mRNA levels showed only small changes with increasing age although, by contrast, A3 receptor mRNA increased markedly with age with levels at 60 days twenty-fold greater than at 2 days. A2A receptor mRNA levels declined during renal maturation with transcript numbers four- to fivefold that at 12-18 days compared with numbers at 60 days. By contrast to the A2A receptor, there were no significant changes in the renal levels of A2B receptor mRNA during kidney maturation. During postnatal renal maturation, the levels of mRNA for A2A and A3 adenosine receptor subtypes undergo marked changes which may be related to functional maturation, morphological development, or both.

Renal adenosine A1 receptor binding characteristics and mRNA levels during the development of acute renal failure in the rat.

1. The binding characteristics and mRNA levels for renal adenosine A1 receptors were investigated in normal rats and rats with acute renal failure (ARF) induced by either glycerol or HgCl2. 2. Saturation isotherms determined from the binding of [3H]-1,3-dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), a selective adenosine A1 antagonist, to renal membranes of untreated rats gave values of 0.62 nM for the equilibrium dissociation constant (Kd) and 19.9 fmol mg-1 protein for the density of binding sites (Bmax). No saturable binding was observed with [3H]-2-(p-(carboxylethyl)-phenylethylamino)-5'-N-ethylcar box amido adenosine ([3H]-CGS 21680), a selective adenosine A2a agonist. 3. By contrast to time-matched controls, renal membranes obtained from rats 16 and 48 h following the induction of ARF with glycerol, showed statistically significant increases (2-4 fold) in both Bmax and Kd for the binding of [3H]-DPCPX. No significant changes in the binding characteristics of [3H]-DPCPX were noted with membranes from rats 48 h following the production of ARF with HgCl2. 4. Adenosine A1 receptor mRNA levels were significantly elevated 0.5, 16 and 48 h following induction of ARF with glycerol, whilst no change was noted in mRNA levels for beta-actin at the same time points. No statistically significant changes in adenosine A1 receptor or beta-actin mRNA levels were noted 48 h after the induction of ARF with HgCl2. 5. This study indicates that glycerol-induced ARF in the rat is associated with an increase in renal adenosine A1 receptor density which appears to result from increased transcription of the gene for this receptor. An increase in adenosine A1 receptor density in renal resistance vessels may explain, at least in part, the enhanced renal vasoconstrictor response to adenosine in glycerol-induced ARF that was noted in a previous study.

Treatment of metastatic renal cell carcinoma with subcutaneous interleukin 2: evidence for non-renal clearance of cytokines.

The circulating cytokine concentrations following administration of subcutaneous recombinant interleukin 2 (IL-2) in combination with interferon alpha and 5-fluorouracil used to treat advanced renal cancer were studied. One patient was anephric and on dialysis, and seven had normal biochemical renal function, although five had undergone single nephrectomy. The pharmacokinetics of IL-2 and changes in IL-6 and tumour necrosis factor (TNF)-alpha were essentially similar in all patients including the anephric patient, irrespective of the periods of dialysis, although at some time points, IL-2 concentrations were slightly higher in the anephric patient than in the others. These results show that for subcutaneous administration of low-dose IL-2, renal clearance of IL-2 is not important. This contrasts with high-dose, intravenous IL-2 where blood concentrations are higher and renal clearance seems to occur, perhaps because of saturation of the non-renal mechanisms of clearance. The subcutaneous route is certainly preferred if IL-2 is used in anephric patients and in those with impaired renal function, and it may be generally preferred for most purposes.

Drug binding sites on chicken albumin: a comparison to human albumin.

Mammalian albumins have two main structurally selective ligand binding sites. Site I binds drugs such as azapropazone, phenylbutazone and warfarin; whereas benzodiazepines, some dansyl amino acids, such as dansylsarcosine, and short chain fatty acids like octanoic acid interact with site II. However, it is not known if non-mammalian albumins have similar binding loci. In this study, drug binding sites on chicken albumin were investigated using site selective fluorescent probes (warfarin and dansylsarcosine) and p-nitrophenyl acetate (NPA); the hydrolysis of which is selectively inhibited by site II ligands. Azapropazone and phenylbutazone decreased the binding of warfarin and dansylsarcosine to a similar extent. Diazepam and octanoic acid also inhibited binding of the two fluorescent probes in a non-selective manner. However, the fluorescence intensity of the warfarin-chicken albumin complex decreased when the pH was increased from 6.0-9.0; but by contrast, the fluorescence of bound dansylsarcosine remained unchanged. Furthermore, the hydrolysis of NPA was selectively inhibited by dansylsarcosine, diazepam and octanoic acid (ligands selective for site II on mammalian albumins), but not by site I selective ligands such as azapropazone and warfarin. Overall, the results suggest that chicken albumin, like mammalian albumins, has discrete binding sites for warfarin and dansylsarcosine.

Binding of sulphamethazine to pig plasma proteins and albumin.

The interaction of sulphamethazine (SMZ) with pig plasma proteins and albumin was studied by ultrafiltration and equilibrium dialysis. Binding to pig plasma proteins was monophasic (affinity approximately 9.0 mol/L x 10(3)) and the main binding protein was albumin. At 37 degrees C and pH 7.4, the affinity of SMZ for albumin was about 8.0 mol/L x 10(3) and the number of binding sites was estimated as 1.4. Increasing the temperature from 4 to 45 degrees C resulted in a seven-fold decrease in affinity, and increasing pH from 6.0 to 8.0 enhanced affinity for pig albumin ten-fold. The free energy of binding (-delta G) and enthalpy change (-delta H) were around 5.5 and 5.1 Kcal/mol, respectively. The total entropy change (delta S) was small and positive, around 2 cal/mol/degree K. Studies with the fluorescent probes warfarin and dansylsarcosine, suggest that these bind to separate sites on porcine albumin. SMZ displaced both probes and inhibited the deacetylation of p-nitrophenyl acetate by pig albumin. We conclude that: (1) binding of SMZ to pig plasma proteins and albumin is weak; (2) the interaction with albumin is exothermic and enthalpy driven, and (3) pig albumin, like other mammalian albumins, appears to possess discrete binding sites for warfarin and dansylsarcosine. SMZ interacts with both these loci.

Amelioration of cisplatin nephrotoxicity with glycine: dose dependency in rats.

The effects of glycine (0.1-1.0 g kg-1, i.v.) on the acute changes in renal haemodynamics and nephrotoxicity produced by cisplatin (6.0 mg kg-1, i.v.) were investigated in the rat. Cisplatin produced decreases of 50% in the clearance of [3H] inulin (CIN) and renal blood flow (RBF), 110 min following its injection. Glycine at a dose of 0.1 g kg-1 produced no attenuation of the cisplatin-induced decrease in CIN or RBF. Furthermore, this dose of glycine provided no significant protection of renal function over a 7-day period following cisplatin injection. By contrast, glycine at a dose of either 0.5 or 1.0 g kg-1 markedly attenuated cisplatin-induced falls in CIN and RBF, with the highest dose completely preventing any falls in these indices during the course of the experiment. Treatment with these higher doses of glycine produced prominent protection from the nephrotoxic actions of cisplatin, as evidenced by improvements in a range of indices of renal function which included plasma urea and creatinine concentrations, urine output, sodium excretion, CIN and the clearance of [14C] p-aminohippurate. The results of experiments with an intermediate dose of 0.25 g kg-1 glycine revealed some degree of amelioration of acute renal haemodynamic effects of cisplatin, particularly with regard to CIN; whilst in the nephrotoxicity study, 0.25 g kg-1 glycine produced a modest but significant reduction in cisplatin-induced acute renal dysfunction. The results have revealed a clear association between the acute renal haemodynamic effects produced by glycine in cisplatin-injected rats with the longer-term renal protective effects of glycine in cisplatin nephrotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Renal haemodynamic responses to adenosine in acute renal failure.

Renal vascular reactivity was studied in rats with acute renal failure (ARF) to investigate whether changes in sensitivity to the renal haemodynamic effects of adenosine can explain why adenosine plays a significant role in some but not all forms of ARF. Experiments involved rats with glycerol-induced ARF in which adenosine antagonists have been shown previously to have beneficial effects and rats with HgCl2-induced ARF which was not ameliorated by treatment with the selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.1 mg/kg). Close renal arterial injections of adenosine (0.1-10 micrograms) or noradrenaline (0.003-0.1 microgram) produced falls in renal blood flow in rats with HgCl2-induced ARF which were not statistically different from controls. Adenosine evoked falls in renal blood flow in rats with glycerol-induced ARF which were significantly greater 16 and 48 h, but not 30 min after glycerol injection. The enhanced responsiveness to adenosine's renal constrictor effects was most pronounced 48 h following glycerol injection when, for example, a dose of 10 micrograms produced a fall of 60 +/- (SEM) 5% (n = 8) in renal blood flow in comparison to a fall of 27 +/- 5% (n = 8) in controls. By contrast to the renal vascular response to adenosine, the falls in renal blood flow induced by noradrenaline in rats 48 h following glycerol injection were not statistically different from the decreases in renal blood flow recorded in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of arginine on cisplatin-induced acute renal failure in the rat.

The effect of arginine on the nephrotoxicity produced by cisplatin (6.0 mg/kg i.v.) was investigated in the rat. Intravenous administration of L-arginine at doses of 0.26-2.63 g/kg at the time of cisplatin injection produced significant protection of renal function as evidenced by reductions in plasma urea and creatinine concentrations, decreased polyuria and increases in the plasma clearance of [3H]inulin and [14C]-p aminohippurate. Administration of D-arginine (2.63 g/kg i.v.) also significantly ameliorated the renal dysfunction induced by cisplatin although this protective effect was not as great as produced by the same dose of L-arginine. D-arginine, by contrast to its L-isomer, is reported to have little or no effect on renal haemodynamics. Consequently, the results of this study indicate that the protective effect of L-arginine in cisplatin nephrotoxicity involves both haemodynamic and nonhaemodynamic components.

Diuretic effect of NG-nitro-L-arginine methyl ester in the rat.

Intravenous infusion of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, L-NAME (10 micrograms kg-1 min-1), to anaesthetized rats produced a diuresis and natriuresis. By contrast, infusion of the same dose of NG-nitro-D-arginine methyl ester had no effect on either urine output or sodium excretion. The effects of L-NAME were first evident 120 min after the start of infusion and by 170 min a fivefold increase in urine volume and sodium excretion was recorded. L-NAME also produced a transient fall in inulin clearance and a persistent decline in renal blood flow. These renal effects of L-NAME were associated with a gradual elevation of mean arterial blood pressure, although this only attained statistical significance, in comparison with saline-infused animals, 170 min after the start of infusion. The findings indicate the diuresis and natriuresis evoked by L-NAME in the rat is a result of a direct tubular action together with a pressure diuresis.

The protective effect of glycine in cisplatin nephrotoxicity: inhibition with NG-nitro-L-arginine methyl ester.

The effect of glycine on the acute changes in renal haemodynamics and nephrotoxicity produced by cisplatin was investigated in the rat. Cisplatin (6.0 mg kg-1, i.v.) injection in anaesthetized rats produced, over a period of 2 h, falls of approximately 50% in renal blood flow (RBF) and the clearance of [3H]inulin (CLIN), effects which were prevented by co-administration of glycine (1.0 g kg-1). Infusion of the nitric oxide (NO) synthase-inhibitor NG-nitro-L-arginine methyl ester, L-NAME (10 micrograms min-1 kg-1, i.v.), abolished glycine's ability to maintain RBF in cisplatin-injected rats whilst partially inhibiting the ability of glycine to preserve CLIN. Treatment of cisplatin-injected rats with glycine (1.0 g kg-1, i.v.) significantly ameliorated the nephrotoxic effects of cisplatin (6.0 mg kg-1) as judged by improvements in a range of indices of renal function which included plasma urea and creatinine concentrations, urine output, sodium excretion, CLIN and the clearance of [14C]p-aminohippurate. Administration of L-NAME (1.0 mg kg-1, i.v.) to rats which received cisplatin and glycine significantly inhibited the reno-protective effect of glycine. However, L-NAME administration to rats which were treated only with cisplatin did not result in any potentiation of cisplatin nephrotoxicity. The findings of this study suggest that glycine can block the acute falls in RBF and CIN produced by cisplatin by a mechanism which involves the production of NO. Furthermore, the results indicate that these renal haemodynamic actions of glycine are responsible, at least in part, for the ability of this amino acid to ameliorate cisplatin nephrotoxicity.

Absorption of N4-D-glucopyranosylsulphamethazine by rat everted intestinal sacs.

Absorption of the N4-D-glucose conjugate of sulphamethazine (glucose-SMZ, 0.5 mM) by isolated everted sacs of the rat small intestine was studied at 37 degrees and pH 6.6. Phlorizin (0.5-2.0 mM) significantly reduced (P < 0.05) both mucosal and serosal transfer of glucose-SMZ and inhibition of mucosal transfer appeared to be concentration-dependent. Phloretin (0.5 mM) and removal of Na+ from the incubation medium also diminished absorption of glucose-SMZ. Furthermore, D-glucose (0.5 and 5.0 mM) inhibited mucosal and serosal transfer of the glycoside. The results suggest the D-glucose/Na+ cotransporter mediates absorption of glucose-SMZ from the small intestine of the rat. Thus, glucose-SMZ might be bioavailable from ingested tissues in which it is present.

Effect of the selective A1 adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine on acute renal dysfunction induced by Escherichia coli endotoxin in rats.

The effect of the selective A1 adenosine antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), on Escherichia coli endotoxin-induced acute renal dysfunction was determined in anaesthetized rats. Bolus administration of endotoxin at doses of either 1 or 20 mg kg-1 evoked decreases in inulin clearance, renal blood flow, urine flow and excretion of sodium, potassium and chloride. The changes in renal function produced by 20 mg kg-1 endotoxin were more severe than those noted with 1 mg kg-1 toxin and, by contrast to this lower dose, renal function showed no signs of recovery. Intravenous administration of CPX (0.1 mg kg-1) elicited a statistically significant, although modest, attenuation of the decline in inulin clearance, renal blood flow, urine output and electrolyte excretion induced by 20 mg kg-1 endotoxin. By contrast, treatment with 0.1 mg kg-1 CPX resulted in statistically significant protection against the falls in excretory function evoked by 1 mg kg-1 endotoxin but not against the reductions in renal blood flow and inulin clearance produced by the lower dose of toxin. These results suggest that adenosine may play a role, albeit not a major one, in the pathophysiology of endotoxaemic acute renal failure.

The diuretic action of 8-cyclopentyl-1,3-dipropylxanthine, a selective A1 adenosine receptor antagonist.

1. The diuretic effect of the selective A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), was investigated in anaesthetized rats. 2. CPX (0.1 mg kg-1, i.v.) produced significant increases in urine flow, and the excretion rate and fractional excretion of both sodium and chloride. By contrast, CPX administration did not result in any significant change in the excretion of potassium. 3. The diuretic effect of CPX was accompanied by a transient increase in inulin clearance although p-amino-hippurate clearance was unaffected, indicating the CPX induced a temporary elevation of glomerular filtration rate but no change in renal blood flow. 4. The fractional excretion of lithium (a marker of delivery of fluid out of the proximal tubule) was also significantly increased by CPX. However, other measures of tubular function derived from lithium clearance indicated that there were no changes in the handling of sodium or water in the distal regions of the nephron. 5. CPX did not significantly alter the relationship between either free water reabsorption or free water clearance and the distal delivery of sodium, which suggests that CPX does not affect the renal concentration/dilution mechanism. 6. The results of this study show that the diuresis and increased excretion of sodium and chloride induced by CPX (0.1 mg kg-1) in the rat, occurs with only transient elevation in glomerular filtration rate and no change in renal blood flow. The primary reason for the diuresis appears to be inhibition of sodium reabsorption in the proximal tubule. Furthermore, the results provide evidence that production and release of endogenous adenosine modifies renal excretory function via stimulation of the A1 receptor subtype.