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Biomedical subjects

G Peer

Publications and source records attributed to G Peer.

At least 19 recordsLinked to original sources
PubMed2006

Elevated platelet vesicular monoamine transporter 2 in former heroin addicts maintained on methadone.

The brain vesicular monoamine transporter (VMAT2) is essential for neuronal monoamine storage and regulation of monoaminergic neurotransmission. We demonstrated previously a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. Opioids induce increase of dopamine release in limbic structures. In the present study we assessed the VMAT2 pharmacodynamic characteristics using high affinity [(3)H]dihydrotetrabenazine (TBZOH) binding to platelets of former male heroin addicts maintained on methadone (n = 12) compared to age-matched healthy controls (n = 13). A significant increase (19%, p < 0.05) in platelet VMAT2 density (Bmax) was observed in the methadone treated patients compared to controls. There was no significant difference in the affinity of [(3)H]TBZOH to its platelet binding site. The increased VMAT2 density may reflect a compensatory attempt to prevent vesicular depletion due to chronic methadone exposure.

Blood Platelets↗
PubMed2003

Epidemiological study of Culicoides hypersensitivity in horses in Israel.

The variations with breed, gender, age and coat colour in the prevalence of Culicoides hypersensitivity were studied in 408 horses on 18 farms in Israel. Data were gathered by means of questionnaires and the diagnoses were confirmed by direct physical examinations. The prevalence of Culicoides hypersensitivity was 28 per cent. The disease was rare on farms more than 800 m above sea level but was more prevalent at lower altitudes. The most important factors affecting the prevalence of Culicoides hypersensitivity were the farm, breed and age, but gender and colour were not significantly correlated with its prevalence.

Altitude↗
PubMed2003

Compound heterozygosity for mutations in the hairless gene causes atrichia with papular lesions.

BACKGROUND: Congenital atrichias represent a complex and heterogeneous group of genodermatoses, which have been shown in several consanguineous families to result from homozygous mutations in the hairless gene (HR). OBJECTIVES: To identify the molecular basis of congenital atrichia in a non-consanguineous family. METHODS: Genetic analysis was carried out in a two-generation family with two children with congenital atrichia and one healthy child. RESULTS: We established a diagnosis of atrichia with papular lesions based on clinical and histopathological data. We identified a heterozygous 11-bp deletion (189-199del) in the two affected children and their mother. In addition, the two affected children and their father were shown to carry a non sense mutation (Q478X), which has previously been described in a Pakistani family. Haplotype analysis revealed that mutation Q478X occurred independently in the two families. CONCLUSIONS: We have identified the first case of compound heterozygosity for mutations in HR as well as the first instance of a recurrent mutation in this gene. These data further expand our understanding of the molecular pathomechanisms underlying congenital atrichias.

Alopecia↗
PubMed2001

Methylene blue, a nitric oxide inhibitor, prevents haemodialysis hypotension.

BACKGROUND: Plasma nitric oxide (NO) levels have been found to be high in haemodialysis (HD) patients, especially in those prone to hypotension in dialysis. The aim of the study was to prevent dialysis hypotension episodes by i.v. administration of methylene blue (MB), an inhibitor of NO activity and/or production. METHODS: MB was given i.v. in 18 stable HD patients with hypotensive episodes during almost every dialysis, in 18 HD patients without hypotension during dialyses, and in five healthy controls. MB was given as a bolus of 1 mg/kg bodyweight followed by a constant infusion of 0.1 mg/kg bodyweight lasting 210 min until the end of the dialysis session and only as a bolus on a non-dialysis day. Systolic and diastolic blood pressures (BP) were measured at 10-min intervals during HD sessions with or without MB and on a non-dialysis day with MB. RESULTS: In hypotension-prone patients, MB completely prevented the hypotension during dialysis and increased both systolic and diastolic BP on non-dialysis days. In normotensive patients, MB increased BP during the first hour of dialysis and for 90 min on the non-dialysis day. The BP in the healthy controls remained unchanged. Plasma and platelet NO(2)+NO(3) (stable metabolites of NO) levels were determined. The NO(2)+NO(3) generation rate in the first post-dialysis day was calculated. The plasma and platelet NO(2)+NO(3) were higher in the hypotensive group than in the normotensive dialysis group. The generation rate of nitrates was higher (P<0.01) in the hypotensive group (1.21+/-0.13 micromol/min and 0.74+/-0.16 after MB) than in the normotensive patients (0.61+/-0.11 micromol/ min and 0.27+/-0.14 after MB). No side-effects were recorded. CONCLUSIONS: MB is an efficient therapy in the prevention of dialysis hypotension.

Adult↗
PubMed2001

Comparison of the responses of global tests of coagulation with molecular markers of neutrophil, endothelial, and hemostatic system perturbation in the baboon model of E. colisepsis--toward a distinction between uncompensated overt DIC and compensated non-overt DIC.

This study correlates changes in neutrophilic activity and endothelial injury with markers of hemostatic activity following the infusion of increasing concentrations of E. coli organisms. It focuses on the hemostatic response as a marker of microvascular injury and uses the response to increasing concentrations of E. coli to refine our definition of disseminated intravascular coagulation (DIC) and distinguish between a compensated (non-overt DIC) and uncompensated (overt DIC) response. We observed that the global coagulation tests reflected activation of the hemostatic system in a dose dependent manner (overt DIC) in the early phases (T+2 to 6 h) of the response to increasing concentrations of E. coli, but that they failed to do so in the late phases (T+ 24 to 48 h). We observed that molecular markers, soluble thrombomodulin and elastase, unlike thrombin/antithrombin and plasmin/antiplasmin complexes, remained elevated out to T+24 to 48 h indicating endothelial injury that persists beyond the initial inflammatory insult in compensated as well as uncompensated DIC.

Animals↗
PubMed2000

The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis.

The influence of the endothelial protein C receptor (EPCR) on the host response to Escherichia coli was studied. Animals were treated with 4 separate protocols for survival studies and analysis of physiologic and biochemical parameters: (1) monoclonal antibody (mAb) that blocks protein C/activated protein C binding to EPCR plus sublethal numbers of E coli (SLEC) (n = 4); (2) mAb to EPCR that does not block binding plus SLEC (n = 3); (3) SLEC alone (n = 4); and (4) blocking mAB alone (n = 1). Those animals receiving blocking mAb to EPCR plus sublethal E coli died 7 to 54 hours after challenge, whereas all animals treated with the other protocols were permanent survivors. Histopathologic studies of tissues from animals receiving blocking mAb plus SLEC removed at postmortem were compared with those animals receiving SLEC alone killed at T+24 hours. The animals receiving the blocking mAb exhibited consumption of fibrinogen, microvascular thrombosis with hemorrhage of both the adrenal and renal cortex, and an intense influx of neutrophils into the adrenal, renal, and hepatic microvasculature, whereas the tissues from animals receiving only sublethal E coli exhibited none of these abnormal histopathologic changes. Compared with the control animals, the animals receiving the blocking mAb exhibited significantly elevated serum glutamic pyruvic transaminase, anion gap, thrombin-antithrombin complex, IL-6, IL-8, and soluble thrombomodulin. The levels of circulating activated protein C varied too widely to allow a clear determination of whether the extent of protein C activation was altered in vivo by blocking protein C binding to EPCR. We conclude that protein C/activated protein C binding to EPCR contributes to the negative regulation of the coagulopathic and inflammatory response to E coli and that EPCR provides an additional critical step in the host defense against E coli. (Blood. 2000;95:1680-1686)

Animals↗
PubMed2000

Luminescence studies of the phagocyte response to endotoxin infusion into normal human subjects: multiple discriminant analysis of luminescence response and correlation with phagocyte morphologic changes and release of elastase.

A blood luminescence system (BLS) was employed to analyze blood phagocyte function in response to infusion of endotoxin (4 ng Escherichia coli lipopolysaccharide (LPS)/kg body weight) into 7 healthy human subjects. The subjects were closely monitored clinically, and extensive chemical, hematological and coagulation measurements were taken during the pretreatment, early (symptomatic, 1-8 h post-LPS), and late (asymptomatic, 12-48 h post-LPS) phases of acute inflammation. BLS assessment included measurement of basal and PMA-stimulated phagocyte oxidase and myeloperoxidase (MPO) activities, and also included measurement of circulating (COR) and PAF-primed maximum (MOR) opsonin receptor-dependent phagocytic activities. Basal oxidase activity peaked at T + 1 h and showed an additional peak at T + 24 h post-LPS. The COR activity also peaked at 1-2 h, but remained elevated through T + 24 h post-LPS, while the basal MPO activity peaked only once at T + 1 h. We concluded that while MPO evidence of phagocyte respiratory activation returned to baseline by T + 4 h, COR evidence of receptor expression (receptor alert) remained elevated through T + 24 h. During this early (0-8 h) period, elastase/alpha 1AT complex concentration peaked at T + 3-4 h and again at T + 8 h. Peak numbers of circulating polarized and vacuolated phagocytes also appeared at T + 3 h and 7 h. We concluded that there was biochemical and morphological evidence of continuing phagocyte activity beyond T + 4 h to T + 8 h, and that this corresponded with the period during which the subjects were symptomatic. In addition, the appearance of a second peak of basal oxidase activity at T + 24 h, multiple discriminant analyses of all the luminescence data, and the sustained elevation of lactate suggested that there was a later second stage (T + 12 h to 48 h) of the human response to endotoxin, during which time the subjects were asymptomatic.

Adult↗
PubMed1999

Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure.

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20-21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100+/-18 pg/ml) and low calcitriol levels (10.6+/-4.3 pg/ml) compared with normal rats [N1: 14+/-2.5 pg/ml (P<0.001) and 18.2+/-4.2 pg/ml (P<0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2+/-5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4+/-8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87+/-17 pg/ml) and low calcitriol levels (9.3+/-1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.

Analysis of Variance↗
PubMed1998

Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and interleukin-6 and -8, but not tumor necrosis factor, responses of the baboon to LD100 Escherichia coli.

Antitissue factor antibody attenuated the coagulopathic and lethal responses to LD100 Escherichia coli, whereas active site inhibited factor Xa inhibited only the coagulopathic response. In this study, we wished to determine: (1) whether active site inhibited factor VIIa blocks the coagulopathic and/or attenuates the lethal effects of LD100 E coli and (2) whether these effects are accompanied by attenuation of the inflammatory cytokine response to LD100 E coli. Eight baboons infused for 2 hours with LD100 E coli also were given five bolus infusions of DEGR VIIa of 280 microg/kg at T = -10 minutes, +2, 4, 6, and 8 hours and observed for changes in vital signs, and the concentrations of hemostatic components (fibrinogen, platelets, fibrin degradation products) and inflammatory mediators (tumor necrosis factor [TNF], interleukin-6 [IL-6], IL-8) at T = 0, 1, 2, 4, 6, and 8 hours. Eight control baboons were also infused with LD100 E coli alone and followed as described above. Four of the eight baboons treated with DEGR VIIa were permanent 7-day survivors versus none in the control group. The mean survival times for the treated and control groups were 116 +/- 22 and 26 +/- 8 hours, respectively. These values differed significantly from each other, (P = .0008). The decrease in platelet and fibrinogen concentrations and the increase in fibrin degradation products observed in the control group were significantly attenuated in the treated group, as was thrombosis of renal glomerular capillaries. Treatment with DEGR VIIa showed no effect on the peak TNF response to LD100 E coli at T = 2 hours (170 +/- 32 v 120 +/- 35 ng/mL). DEGR VIIa, however, did attenuate the IL-6 and IL-8 responses at T = 8 hours (ie, the IL-6 concentrations were 81 +/- 10 for treated and 1,256 +/- 236 for the control groups and the IL-8 concentrations were 28 +/- 3.9 for the treated and 60 +/- 8.2 for the control group). These values for IL-6 and IL-8 differed significantly from each other between the treated and control groups (P = .0001 and .0074, respectively). It should be noted that the initial responses of IL-6 and IL-8 up to T = 4 hours were not attenuated. We concluded that DEGR VIIa treatment attenuates inflammatory, as well as hemostatic system responses to LD100 E coli. We hypothesize that this occurs through interference with the assembly and/or interactions of tissue factor/VIIa complexes.

Animals↗
PubMed1998

Methylene blue prevents pulmonary injury after intestinal ischemia-reperfusion.

OBJECTIVE: To investigate the effect of methylene blue, an inhibitor of oxygen radicals, on lung injury caused by reperfusion of ischemic tissue. METHODS: Intestinal ischemia-reperfusion injury was induced in rats by clamping the superior mesenteric artery for 1 hour. Thereafter, the experimental group was administered 1% methylene blue intraperitoneally and the control group received saline. After 4 hours, pulmonary histopathologic features were assessed, and lung wet-weight to dry-weight ratios and tissue xanthine oxidase were determined. RESULTS: The control group suffered from severe pulmonary parenchymal damage, compared with slight damage in the experimental group. The number of sequestered neutrophils was significantly higher in the control group (319 +/- 60 polymorphonuclear cells per 10 high-power fields) than in the methylene blue-treated group (91 +/- 8 polymorphonuclear cells per 10 high-power fields; p < 0.001). The wet-weight to dry-weight ratio was significantly increased in the saline-treated rats compared with the methylene blue-treated group (6.19 +/- 0.28 vs. 5.07 +/- 0.21; p < 0.001). Xanthine oxidase activity was similar in both groups. CONCLUSION: Methylene blue attenuated lung injury after intestinal ischemia-reperfusion. Inhibition of oxygen free radicals may be the protective mechanism.

Animals↗
PubMed1998

Comparison of a vegetable-based (soya) and an animal-based low-protein diet in predialysis chronic renal failure patients.

There is some experimental evidence to suggest that progression of chronic renal failure (CRF) is slower on diets based on soya protein than on diets based on animal protein. We have compared the effect of a soya-based vegetarian low-protein diet (VPD) and an animal-based low-protein diet (APD) in 15 patients with CRF. 15 patients with CRF (51Cr-EDTA-measured glomerular filtration rate 15-50 ml/min/1.73 m2) were studied. In a randomized crossover trial, the patients were given each diet (each containing 0.75 g protein and 32 kcal per kilogram body weight) for a 6-month period. Nine patients completed the trial, 2 others dropped out because they could not tolerate the VPD, 3 because of unrelated medical complications, and 1 for technical reasons. The caloric intake was higher and the protein, phosphate and essential amino acid intake lower on the VPD than on the APD. The compliance with the suggested caloric intake was better with the VPD than with the APD (97 vs. 88% of recommended intake), as was the compliance with the suggested protein intake (94 vs. 112% of recommended intake) and with the suggested phosphate intake (102 vs. 116%). The mean glomerular filtration rate, as judged by 51Cr-EDTA, was similar after 6 months on each diet and remained unchanged throughout the entire year of the study. The rate of fall of glomerular filtration, as measured by the slope of 1/serum creatinine was slowed by 73% during the 1-year study period as compared with the prestudy period. Nutritional status (as measured by body mass index, midarm circumference, and lean body mass and percent body fat), serum transferrin, cholesterol and albumin, and total lymphocyte count were similar on the two diets. The serum albumin level on both diets, however, was significantly higher on the two diets than during the prediet period. Blood urea nitrogen, urine urea nitrogen, protein catabolic rate, and 24-hour urine creatinine and phosphate were lower on the VPD than on the APD. The 24-hour protein excretion was similar on the two diets. The two low-protein diets resulted in a slowing in the progression of CRF. A VPD is well tolerated in CRF and is associated with lower protein and phosphate intakes and a higher caloric intake than an APD and may, therefore, be used as a safe alternative or partial substitute for the usual APD in CRF.

Adult↗
PubMed1998

Low nitric oxide production in patients with chronic renal failure.

BACKGROUND: Rats with chronic renal failure have a low nitric oxide (NO) production and a diminished NO excretion. The supplementation of L-arginine has an inhibitory effect on the progression of renal insufficiency. METHODS: The present study was designed to determine whether chronic renal failure patients have a low NO production. Plasma and urine nitrate (NO3) and nitrite (NO2), stable metabolites of NO, were measured in 83 consecutive patients with chronic renal failure. The 83 chronic renal failure patients were divided into three groups: group 1, mild renal failure (creatinine clearance >60 ml/min/1.73 m2); group 2, moderate renal failure (creatinine clearance >30 <60 ml/min/1.73 m2), and group 3, severe renal failure (creatinine clearance <30 ml/min/1.73 m2). Thirty-three healthy volunteers served as controls. RESULTS: The daily urinary NO excretion was significantly lower in patients with moderate and severe renal failure as compared with those with mild renal failure and normal controls. The lowest values were found in the severe renal failure group. When the 24-hour urinary NO excretion or NO per milligram creatinine and the NO clearance were correlated with the renal function in all patients as a group, these parameters were directly correlated with the creatinine clearance and inversely correlated with the serum creatinine level. The plasma NO concentration was not different between the three chronic renal failure groups, but higher than in the controls. Plasma NO in renal failure patients was not correlated with the creatinine clearance or serum creatinine levels. CONCLUSIONS: Chronic renal failure is a state of NO deficiency. Treatment strategies to increase NO production (L-arginine supplementation or other NO compounds) may prove to be useful in maintaining the renal function and slow the progression of renal disease.

Aged↗
PubMed1998

[Diagnosis in chronic inflammatory bowel diseases--report of the Austrian Chronic Inflammatory Bowel Disease Study Group].

Diagnostic procedures in inflammatory bowel diseases (IBD) serve to secure the diagnosis and to optimize treatment. Upon initial diagnosis endoscopy up to the terminal ileum is mandatory including multiple step biopsies. When diagnostic guidelines are followed and adequate clinical information is available, IBD will be correctly classified in about 80 to 90% of cases upon first examination. In contrast endoscopic studies are only of limited value in monitoring treatment. The decision if and when to perform endoscopy during exacerbation of disease must be an individual one. When disease activity is evaluated, a distinction must be made between degree of activity as reflected by laboratory parameters and severity of illness as reflected by the clinical presentation with abdominal complaints, fistulas, abscesses, etc. Distinct activity indices are useful in clinical studies to obtain an objective evaluation of activity and severity of disease. At clinical routine visits questions should not only concern the basic illness but also ask for quality of life and psychosocial status. Only a small number of laboratory tests are needed for basic diagnosis and follow-up. A small bowel enteroclysis should always be performed upon primary diagnosis of Crohn's disease and during the course of disease when there is suspicion of small-bowel involvement. Double contrast barium enema should be limited to special indications as incomplete colonoscopy e.g. due to stenosis or suspected fistula. Sonography is the primary investigation when complications are suspected. CT is useful as an adjunct or when the afore mentioned methods do not show clear findings. NMR is the procedure of choice for detection of pararectal fistulas and abscesses. Transrectal endosonography is comparably good but limited to the experience of the investigators and by patient's tolerability.

Biopsy↗
PubMed1997

7E3 F(ab')2, a monoclonal antibody to the platelet GPIIb/IIIa receptor, protects against microangiopathic hemolytic anemia and microvascular thrombotic renal failure in baboons treated with C4b binding protein and a sublethal infusion of Escherichia coli.

We have used our previously described baboon model of infusion of both a sublethal dose of Escherichia coli and C4b binding protein to assess the impact of inhibiting platelet function with the F(ab')2 fragment of the monoclonal antibody 7E3, directed against the platelet glycoprotein (GP)IIb/IIIa receptor, on the characteristic microvascular changes. At a dose of 0.25 to 0.35 mg/kg bolus plus an infusion of 0.25 to 0.35 mg/kg over 6 hours, c7E3 F(ab')2 had only a minimal impact on fibrinogen consumption and delayed but did not prevent, the development of thrombocytopenia. Treatment with 7E3 F(ab')2, however, produced significant protection from the development of microangiopathic hemolysis and renal insufficiency. Histologic examination supported these observations, with treated animals having fewer schistocytes on blood smear and less evidence of ischemic renal changes. Treated animals also had more rapid recovery of peripheral white blood counts, suggesting a possible protective effect of treatment on ischemic damage to the bone marrow. These data indicate that potent inhibition of platelet function via GPIIb/IIIa receptor blockade can decrease ischemic organ damage in this animal model that has features similar to those found in diffuse intravascular coagulation, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura.

Anemia, Hemolytic↗
PubMed1997

The effect of naloxone on basophil histamine release from dialyzed patients.

OBJECTIVE AND DESIGN: Naloxone had been shown to be effective in relieving pruritus of dialyzed patients. In order to determine the mechanism by which this is accomplished, we studied its effect on histamine release from white blood cells taken from this group. SUBJECTS: We compared 12 dialyzed patients (before and after dialysis) and 12 healthy controls. METHODS: The effect of naloxone (5 x 10(-3) M) on histamine release from the subjects' white blood cells was measured following anti-IgE + IL3 and TPA administration. RESULTS: The white blood cells of dialyzed patients had a high degree of histamine release compared to the healthy controls. Neither dialysis nor the patient's plasma affected this release. Naloxone markedly inhibited histamine release from white blood cells when stimulated with anti-IgE + IL3 or with TPA. CONCLUSIONS: We concluded that naloxone may have a beneficial effect in treating dialyzed patients suffering from pruritus, probably by inhibiting histamine release.

Antibodies↗
PubMed1997

Glomerular basement membrane polyanionic sites and nitric oxide in genetically salt-sensitive and resistant hypertensive rats.

Cationic colloid gold, a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanions, including heparan sulfate protoglycan in genetic salt-sensitive (SBH/Y) and resistant (SBN/Y) hypertensive rats, with or without high dietary salt intake. GBM morphology, renal function and nitric oxide, as measured by plasma and urine nitrite (NO2) and nitrate (NO3) were also determined. In the salt-sensitive rats the high-salt dietary intake resulted in severe hypertension, proteinuria and decreased glomerular filtration rate. After 1 month of high-salt intake, the average width of the GBM of salt-sensitive rats was higher by 27% than that of salt-resistant rats. The number of GBM anionic sites (lamina rata externa and interna) was much lower in both salt-sensitive and salt-resistant groups after 1 month of salt loading, 8.04+/-0.36 and 7.8+/-0.25 counts/cm, respectively, compared to the respective values of non-salt-loaded animals, 20.58+/-1.08 counts/cm in the SBH/Y (p < 0.001) and 21+/-1.86 counts/cm in the SBN/Y (p < 0.001). A decreased nitric oxide production was found in the salt-sensitive rats before and after salt loading compared with the salt-resistant group. No correlation was found between the nitric oxide changes and the GBM modifications. It is concluded that high-salt intake may be deleterious to the permselectivity of the GBM. It is suggested that salt restriction in hypertension may have a beneficial effect in preventing GBM permselectivity changes and proteinuria.

Animals↗
PubMed1996

Randomised crossover trial of naltrexone in uraemic pruritus.

BACKGROUND: Most dialysis patients develop pruritus, for which current treatment is unsatisfactory. Endogenous opioids may be involved in this pruritus. We studied the effect of the opioid antagonist naltrexone on the pruritus of haemodialysis patients. METHODS: Naltrexone 50 mg per day by mouth was given to 15 haemodialysis patients with severe resistant pruritus in a randomised, double-blind, placebo-controlled crossover trial. The naltrexone or placebo periods lasted 7 days each with a 7-day washout between the two periods. Pruritus was assessed by the patients on a visual analogue scale from 0 (no pruritus) to 10 (maximum), and mean daily scores were calculated. Plasma histamine and beta-endorphin levels were measured, and spontaneous and stimulated basophil histamine-release were determined. FINDINGS: The median pruritus scores at the end of the naltrexone treatment were 2.1 (interquartile range 1.5-2.15) for the naltrexone-placebo sequence and 1.0 (0.4-1.15) for the placebo-naltrexone sequence. The respective values before naltrexone was given were 9.9 (9.85-9.95) and 9.9 (9.3-10.0). Plasma beta-endorphin levels were normal and remained unchanged during the study. Plasma histamine levels were high (mean 2.32 [SD 0.11] ng/mL, normal < 1.0) and decreased after naltrexone (to 1.8 [0.09], p < 0.01). Basophils from haemodialysis patients stimulated by interleukin-3 plus IgE antibodies released high amounts of histamine. The increase was 78.3 (19.3)% compared with 26.6 (16.3)% for five normal controls (p < 0.01). Incubation of the basophils with naloxone, another opioid antagonist, prevented this effect. INTERPRETATION: Our data suggest short-term efficacy with few side-effects for the amelioration of uraemic pruritus with naltrexone.

Cross-Over Studies↗