The brain's specialized systems for aesthetic and perceptual judgment.

We recorded brain activity when 21 subjects judged the beauty (aesthetic or affective judgment) and brightness (perceptual or cognitive judgment) of simultaneously presented paintings. Aesthetic judgments engaged medial and lateral subdivisions of the orbitofrontal cortex as well as subcortical stations associated with affective motor planning (globus pallidus, putamen-claustrum, amygdala, and cerebellar vermis), whereas the motor, premotor and supplementary motor areas, as well as the anterior insula and the dorsolateral prefrontal cortex, were engaged by both kinds of judgment. The results lead us to conclude: (i) that there is a functional specialization for judgment, with aesthetic judgments engaging distinct systems, in addition to those that they share with perceptual judgments; (ii) that the systems engaged by affective judgments are those in which activity correlates with polar experiences (e.g. love-hate, beauty-ugliness, and attraction-repulsion); and (iii) that there is also a functional specialization in the motor pathways, with aesthetic judgments engaging motor systems not engaged by perceptual judgments, in addition to those engaged by both kinds of judgment.

Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity.

AIMS/HYPOTHESIS: The role of the intestine in the pathogenesis of metabolic diseases is gaining much attention. We therefore sought to validate, using an animal model, the use of positron emission tomography (PET) in the estimation of intestinal glucose uptake (GU), and thereafter to test whether intestinal insulin-stimulated GU is altered in morbidly obese compared with healthy human participants. METHODS: In the validation study, pigs were imaged using [(18)F]fluorodeoxyglucose ([(18)F]FDG) and the image-derived data were compared with corresponding ex vivo measurements in tissue samples and with arterial-venous differences in glucose and [(18)F]FDG levels. In the clinical study, GU was measured in different regions of the intestine in lean (n = 8) and morbidly obese (n = 8) humans at baseline and during euglycaemic hyperinsulinaemia. RESULTS: PET- and ex vivo-derived intestinal values were strongly correlated and most of the fluorine-18-derived radioactivity was accumulated in the mucosal layer of the gut wall. In the gut wall of pigs, insulin promoted GU as determined by PET, the arterial-venous balance or autoradiography. In lean human participants, insulin increased GU from the circulation in the duodenum (from 1.3 ± 0.6 to 3.1 ± 1.1 µmol [100 g](-1) min(-1), p < 0.05) and in the jejunum (from 1.1 ± 0.7 to 3.0 ± 1.5 µmol [100 g](-1) min(-1), p < 0.05). Obese participants failed to show any increase in insulin-stimulated GU compared with fasting values (NS). CONCLUSIONS/INTERPRETATION: Intestinal GU can be quantified in vivo by [(18)F]FDG PET. Intestinal insulin resistance occurs in obesity before the deterioration of systemic glucose tolerance.

Neural damage associated with atopic diathesis: a nationwide survey in Japan.

BACKGROUND: We previously reported the occurrence of myelitis in patients with atopic disorders (atopic myelitis [AM]). To uncover the spectrum of neural damage associated with atopy, we conducted a cross-sectional nationwide survey of AM and atopy-related peripheral neuritis (APN), including Churg-Strauss syndrome (CSS), in individuals with atopic diathesis. METHOD: Cases with AM diagnosed between 1996 and 2006 and cases with APN between 2000 and 2006 were collected from all over Japan. Detailed data on 109 patients with AM and 133 patients with APN were collated. RESULTS: Patients with APN showed a preponderance of women, higher age at onset, and greater eosinophil counts than patients with AM. Patients with AM most commonly showed cervical cord involvement, whereas patients with APN preferentially exhibited mononeuritis multiplex predominantly affecting the lower limbs. Among patients with AM, motor weakness and muscle atrophy were significantly more frequent in those with bronchial asthma than in those with other atopic disorders. Patients with APN who met the criteria for CSS showed a higher age at onset, higher frequencies of systemic organ involvement, and greater disability than those who did not. Abnormalities suggesting peripheral nervous system involvement were seen in 25.7% of patients with AM, whereas 18.8% of patients with APN had abnormalities indicating CNS involvement. Multiple logistic regression analyses revealed that atopic dermatitis increased the risk of myelitis, whereas high age at onset and bronchial asthma decreased that risk. CONCLUSIONS: Atopy-related neural inflammation multifocally affects CNS and peripheral nervous system tissues. Both preceding atopic disorders and age seem to influence the distribution of neural damage.

Extensive vasogenic edema of anti-aquaporin-4 antibody-related brain lesions.

OBJECTIVE: Using neuroimaging, we analyzed the nature of extensive brain lesions in five anti-aquaporin-4 (AQP4) antibody-positive patients with neuromyelitis optica spectrum disorders. RESULTS: Extensive brain lesions involved white matter in three, and basal ganglia and corpus callosum in one each. Four patients showed high diffusivity on apparent diffusion coefficient maps and three demonstrated increased choline/creatine ratios and decreased N-acetyl-aspartate/creatine ratios on (1)H-magnetic resonance spectroscopy. These findings suggested that the lesions were vasogenic edema associated with inflammation. Unusual brain symptoms associated with such lesions included recurrent limbic encephalitis, parkinsonism, and coma. CONCLUSION: Anti-AQP4 antibody is considered to be associated with the neuroimaging appearances of vasogenic edema.

Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese.

BACKGROUND: Antibodies to aquaporin-4 (AQP4) are found in a fraction of Japanese opticospinal multiple sclerosis (OSMS) patients. However, it remains unknown whether anti-AQP4 antibody-positive and negative OSMS patients possess an identical disease. OBJECTIVE: The objective of the current study was to clarify immunological differences between the two groups of patients. METHODS: We studied the serum antibody titers against AQP4 in 191 patients with idiopathic central nervous system demyelinating diseases and clarified their relationships with immunological parameters. RESULTS: Anti-AQP4 antibody positivity rate was higher in patients with OSMS (21/58, 36.2%), idiopathic recurrent myelitis (4/17, 23.5%), and recurrent optic neuritis (7/26, 26.9%), than in conventional MS (CMS) patients (6/90, 6.7%) and patients with other diseases (0/87). Anti-AQP4 antibody titer was significantly higher in patients with SS-A/B antibodies than in those without them. Anti-AQP4 antibody-negative OSMS patients showed significantly higher CD4(+)IFN-gamma(+)IL-4(-)T cell percentages and intracellular IFN-gamma/IL-4 ratios than anti-AQP4 antibody-positive patients, anti-AQP4 antibody-negative CMS patients, and healthy controls, and CD4(+)IFN-gamma(+)IL-4(-)T cell percentages were negatively correlated with anti-AQP4 antibody titers. CONCLUSION: Anti-AQP4 antibody-positive patients are immunologically distinct from anti-AQP4 antibody-negative OSMS patients owing to a Th2 shift in the former group in comparison to a Th1 shift in the latter.

Increase of CD4+TNF{alpha}+IL-2-T cells in cerebrospinal fluid of multiple sclerosis patients.

Intracellular production of TNFalpha and IL-2 after stimulation with phorbol myristate/ionomycin was flowcytometrically measured in CD4(+) T cells from peripheral blood (PB) and cerebrospinal fluid (CSF) of 29 patients with multiple sclerosis (MS), and 16 with other inflammatory and 41 with other non-inflammatory neurological diseases. In CSF, the percentages of CD4(+)TNFalpha(+)IL-2(-)T cells were significantly higher in patients with MS than either of the controls, whereas no difference was found in CD4(+)TNFalpha(+)IL-2(+)T or CD4(+)TNFalpha(-)IL-2(+)T cells. The increase was more pronounced at relapse than in remission. No significant change was detected in PB. These findings suggested that CD4(+)TNFalpha(+)IL-2(-)T cells are intrathecally upregulated in MS.

Neural processes of attentional inhibition of return traced with magnetoencephalography.

Inhibition of return (IOR) is a phenomenon that involves reaction times (RTs) to a spatially cued target that are longer than RTs to an uncued target when the interval between the cue and target is prolonged. Although numerous studies have examined IOR, no consensus has yet been reached regarding the neural mechanisms responsible for it. We used magnetoencephalography (MEG) and measured the human neural responses underlying the time course of IOR, applying a typical spatial cueing paradigm. The cue-target interval was 600+/-200 ms. Three experimental conditions were employed. Cued; the cue and target were presented at the same location. Uncued; the two stimuli were presented at opposite locations. Neutral; the cue stimulus was presented bilaterally. We found differences in the amplitudes of signals in the postero-temporal and bilateral temporal areas, and peak latencies in a central area between the cued and uncued conditions. These signals were localized to the extrastriate cortex, bilateral temporal-parietal junction (TPJ), and primary motor cortex, respectively. Bilateral TPJ activities are related to the identification of salient events in the sensory environment both within and independent of the current behavioral context and may play an important role in IOR in addition to extrastriate and the primary motor cortex.

Inhibitors of platelet lipoxygenase from Ponkan fruit.

An activity-guided separation for inhibitors of rat platelet 12-lipoxygenase led to the isolation of two compounds, 4-O-feruloyl-5-O-caffeoylquinic acid (IC50; 5.5 microM) and methyl 4-O-feruloyl-5-O-caffeoylquinate (IC50; 1.9 microM) from the peel of Ponkan fruit (Citrus reticulata). The complete structure of each phenolic ester was determined by NMR spectroscopy [1H and 13C NMR spectra, 1H-1H correlation spectroscopy (COSY), 1H-detected heteronuclear multiple quantum coherence (HMQC), and heteronuclear multiple bond connectivity (HMBC) spectroscopies] and other spectral methods.

The effect of breath termination criterion on breathing patterns and the work of breathing during pressure support ventilation.

UNLABELLED: With pressure support ventilation (PSV), each PSV breath is flow-cycled, and the breath termination criterion (TC) is usually nonadjustable. When TC does not match the interaction between the patient's inspiratory-expiratory efforts to the opening and closing of the inspiratory and expiratory valves, patient-ventilator asynchrony may occur, and the work of breathing (WOB) may increase. Therefore, we studied the effect of TC on breathing patterns and WOB during PSV in eight patients with acute respiratory distress syndrome or acute lung injury. We studied five levels of TC during PSV-1%, 5%, 20%, 35%, and 45% of the peak inspiratory flow. With increasing levels of TC, the tidal volume decreased and respiratory frequency increased, along with a decrease in duty cycle. WOB markedly increased with increasing levels of TC from 0.31 +/- 0.12 J/L with TC 1% to 0.51 +/- 0.11 J/L with TC 45%. Premature termination with double breathing occurred in one patient with TC 35% and four patients with TC 45%. Delayed termination with a duty cycle of >0.5 occurred in two patients with TC 1%. In conclusion, the proper adjustment of TC improves patient-ventilator synchrony and decreases WOB during PSV. IMPLICATIONS: Although termination criterion (TC) is usually nonadjustable, it influences the effectiveness of pressure support ventilation for mechanical ventilation. The proper adjustment of TC is crucial to improve patient-ventilator synchrony and decrease work of breathing. TC 5% of the peak inspiratory flow may be the optimal value for patients with acute respiratory distress syndrome or acute lung injury.

Estimating pulmonary capillary wedge pressures using Doppler variables of early diastolic left ventricular inflow.

The present study was performed to determine whether a multilineal regression model based on the early diastolic transmitral flow peak velocity (E) and the propagation velocity of early diastolic inflow (PV) could estimate the pulmonary capillary wedge pressure (PCWP). PCWP and Doppler variables were simultaneously recorded in 30 patients. PCWP was estimated by multilinear regression analysis using E and PV. The predictive accuracy of the equation obtained from the analysis was tested prospectively in a separate group of 65 patients divided into 3 groups: left ventricular (LV) systolic dysfunction (Group A), LV hypertrophy (Group B), and preserved systolic function without hypertrophy (Group C). The initial results obtained in groups B and C, respectively, were: r=0.77; r=0.81. These results indicate that a multilinear regression model based on E and PV is a noninvasive method of accurately estimating PCWP in a variety of cardiac disease states.

[A patient with restless legs syndrome/periodic limb movement successfully treated by wearing a lumbar corset].

We report a 77-year-old woman with restless legs syndrome(RLS) and periodic limb movement(PLM). From 62 years of age, she was awakened by tingling and involuntary movement in her legs during sleep. There symptoms disappeared when she stood up and walked. She was treated with clonazepam (2.5 mg/day) and valproate (400 mg/day) at 77 years of age, and the symptoms clearly ameliorated. However, she developed mild truncal ataxia and was referred to our hospital. On admission, neurological examination revealed Babinski and Chaddock signs bilaterally with depressed tendon reflexes in the lower limbs, mild truncal ataxia and horizontal gaze nystagmus. She did not present with involuntary movement of the legs while taking the anti-epileptic drugs. Cessation of these drugs alleviated the truncal ataxia and nystagmus, but reexacerbated abnormal sensation with involuntary movement in her legs during sleep. The involuntary movements in her legs were slower than myoclonus and resembled a Babinski reflex (duration about 1 second), and they appeared periodically (around every 30 seconds) in I-II sleep stages. Neither brain MRI nor EEG detected any abnormality. Cervical MRI revealed focal compression of the spinal cord by osteophytes at C5-C6 (more severe on the left side). Motor evoked potentials with transcranial magnetic stimulation revealed a mild delay in the central conduction time (CCT), which was more prolonged on the left side. She was thus diagnosed as having RLS/PLM with involvement of the bilateral pyramidal tracts. Although nerve conduction studies did not detect any abnormality in the peripheral nerves, RLS/PLM of the left leg was induced by electric stimulation of the left tibial nerve. Because she did not want medication any more, we treated her with a lumbar corset, hoping that wearing a lumbar corset might induce contraction of the truncal muscles that would mimic standing and walking or might produce additional sensory input that would induce a 'sensory trick'. Consequently, her abnormal sensation and involuntary movement during sleep as well as the stimulation of the tibial nerve disappeared. Wearing a lumbar corset may inhibit the excitability of the spinal cord that generates RLS/PLM, though the level of sensory input by the corset was higher than the input level of abnormal sensation in her legs. A lumbar corset may be a useful alternative choice for patients with RLS/PLM, who cannot tolerate either anti-epileptic or dopaminergic drugs.

[Chirality of natural products: hyoscyamine and scopolamine].

Monthly changes of the content-ratio between S-(-)- and R-(+)-hyoscyamine as well as those between S-(-)- and R-(+)-scopolamine in the leaves of Datura metel L. cultivated in the field, were quantitatively analyzed by the use of HPLC with a chiral adsorbent. It was found that S-(-)-isomer was predominant for hyoscyamine and the ratio of R-(+)-isomer gradually increased during the growth, whereas in the case of scopolamine, S-(-)-isomer was the sole one found throughout the cultivation period. The 1H-NMR study in the CD3OD solution has suggested that S-(-)-hyoscyamine (1) and S-(-)-scopolamine (2) take a "face-to-face" conformation between their tropane skeletons and the benzene rings of the tropic acid moieties. In the presence of an equimolar NaOD in the CD3OD solution, the racemization at C-2' of 1 and 2 proceeded more rapidly than the hydrolysis at the tropic acid ester bond, presumably due to the steric hindrance caused by their "face-to-face" conformations. In the D2O and H2O solutions, on the other hand, the racemization and the hydrolysis of 1 proceeded smoothly, while those of 2 did not occur. It has been supposed that these individual reaction manners are ascribable in considerable extent to the different basicity of N atom in each tropane skeleton of 1 and 2 and to stronger intramolecular hydrogen bond occurring between the carbonyl oxygen at C-1' and the hydroxyl group at C-3' in the tropic acid moiety of 1.

[Usefulness of nitrendipine and its effects on quality of life and brain blood flow in elderly hypertensive patients].

There are many reports on the efficacy of Ca-antagonists for treatment of elderly essential hypertension. In particular, many studies have noted the beneficial effects of antihypertensive therapy on the quality of life (QOL). Nevertheless, there are no reports on antihypertensive therapy regarding the relationship between brain blood flow (BBF) and QOL. Therefore, we examined the efficacy of nitrendipine, a Ca-antagonist, on the brain blood flow and QOL, and its side effects in elderly essential hypertensive patients. The subjects were 17 (males: 4, females: 13) patients with untreated hypertension of WHO stage I or II, aged 70 years or older. The mean dose of nitrendipine was 9.4 +/- 0.4 mg daily. Before and 6 months after treatment, we examined blood pressure (BP), heart rate (HR), echocardiography (left ventricular mass index [LVMI], % fractional shortening [% FS]), plasma noradrenaline (Nad), plasma renin activity (PRA), BBF using the IMP-ARG method with BBF scintigraphy, and QOL was examined with a questionnaire. Two patients were excluded from this study because 1 had no decrease in BP, and another was moved to a different hospital. BP significantly decreased from 178/93 to 137/77 mmHg, but HR was not changed after treatment. BBF significantly increased from 37.0 +/- 4.9 to 41.0 +/- 4.9 ml/dl/min, but % FS, Nad, and PRA did not significantly change. The degree of QOL was improved by 4.2 +/- 1.2 points and there was a significant positive correlation between the changes of BBF and of QOL (r = 0.66, p = 0.04). However, moderate pharmacotherapy for BP seems to be necessary because there were 2 patients whose BBF decreased accompanied by excessive drop in BP after treatment. In conclusion, it is possible to safely use nitrendipine for elderly essential hypertensive patients. Nitrendipine has beneficial effects on BBF, and it was suggested that the increase of BBF is one of the most important factors in improvement of QOL.

Hydroxyprolylserine derivatives JBP923 and JBP485 exhibit the antihepatitis activities after gastrointestinal absorption in rats.

It has been a desire to develop orally effective therapeutic agents that restore the liver function in chronic injury. Here we demonstrated that trans-4-L-hydroxyprolyl-L-serine (JBP923) and cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485), which was previously isolated from hydrolysate of human placenta, exhibit potent antihepatitis activity after their oral administration. The increase in bilirubin concentration and activities of liver cytosolic enzymes in serum caused by alpha-naphthylisothiocyanate intoxication in rats were significantly countered both after i.v. and oral administration of these dipeptides, whereas glycyrrhizin, which has been used in the treatment of chronic hepatitis, is active only after its i.v. administration. Antihepatitis activity of dipeptides results, at least partially, from their direct effect on hepatocytes because glutamic-oxaloacetic transaminase and lactate dehydrogenase activities in the medium of hepatotoxin-exposed primary cultured hepatocytes were reduced by these compounds. When comparing the plasma concentration-time profile of JBP923 after its i.v., oral, and portal vein injection, it is suggested that JBP923 is almost completely absorbed from gastrointestinal lumen, and hepatic first-pass removal is minor. JBP923 inhibited the proton-dependent transport of glycylsarcosine in brush-border membrane vesicles, suggesting that peptide transport system(s) may recognize JBP923. Thus, these dipeptides are potent antihepatitis reagents that are still active after oral administration and may be useful for clinical applications.

Cytokines and T-cell responses in superantigen-related glomerulonephritis following methicillin-resistant Staphylococcus aureus infection.

BACKGROUND: We have previously reported that 10 patients who developed glomerulonephritis (GN) in association with methicillin-resistant Staphylococcus aureus (MRSA) infection showed a marked increase in DR+CD4+ and DR+CD8+ subsets of T cells and in T cells expressing several T-cell receptor (TCR) V beta+cells, perhaps representing V beta-specific T-cell activation by MRSA-derived superantigens (Kidney Int 1995; 47: 207-216). In this study we examine cytokine levels, T-lymphocyte subsets, natural killer NK cells, memory T cells, and the expression of IL-2 receptors in order to better understand the role of bacterial superantigens and cytokines in the pathogenesis of MRSA-associated GN. METHODS: Twenty-two patients with MRSA infection who later developed GN caused by staphylococcal enterotoxin were evaluated immunologically in comparison with patients whose MRSA infection was not followed by GN (non-GN group) and normal individuals. RESULTS: Among peripheral lymphocytes, the frequency of T cells expressing several TCR V betas, especially V beta 5-family TCR, was higher in the GN group than in both the non-GN group and the normal healthy control group. GN patients also showed increased serum levels of several cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-2, IL-6, IL-8, and IL-10, which have been implicated in the onset of nephritis. Memory cells, and IL-2 receptors also were elevated in the GN group. CONCLUSION: These results suggest that T cells activated by MRSA-derived staphylococcal enterotoxins and subsequent production of cytokines may play an important role in the pathogenesis of MRSA-associated GN.

Prevalence of Japanese dialysis patients with an A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene.

BACKGROUND: A high prevalence of an A-to-G mutation at nucleotide 3243 of the mitochondrial genome in patients with diabetes mellitus (DM) and/or deafness has been reported previously. We investigated the prevalence of this mutation in Japanese dialysis patients with associated DM and/or deafness. METHODS: We studied 106 dialysis patients with DM, 26 with DM and deafness, and 26 with deafness alone, using peripheral leucocytes to detect an A-to-G transition at nucleotide 3243 of the mitochondrial gene. RESULTS: We identified this transition in 1 of 26 patients with DM and deafness. None of the 106 DM or 26 dialysis patients with deafness but no DM was positive for this mutation. A 42-year-old male patient on continuous ambulatory peritoneal dialysis (CAPD) who carried this mutation had a 20-year history of sensory hearing loss as well as hypertrophic cardiomyopathy. CONCLUSION: We found that a mitochondrial gene mutation at nucleotide 3243 was present in one dialysis patient with NIDDM and deafness. The prevalence of this mutation was found to be below 1% in diabetic end-stage renal disease patients in Japan.

[Unexpected difficult intubation caused by a laryngeal web].

We report a case of unexpected difficult intubation in an adult caused by a laryngeal web. A 43-year-old woman with uterine myoma was scheduled for abdominal hysterectomy. After induction of anesthesia, the vocal cords were seen clearly under laryngoscopy. Although intubation was attempted several times, a 6.5 mm internal diameter tracheal tube could not be passed below the level of the vocal cords because of resistance, and we used a laryngeal mask during anesthesia. Next morning after the operation, she developed dyspnea. Bronchoscopy revealed a very narrow airway below the level of vocal cords caused by a laryngeal web. Tracheostomy was performed. Two weeks later, tracheostomy was closed without any sequela.

[A case of nephrotic syndrome associated with myasthenia gravis and malignant thymoma].

A 26-year-old woman who presented facial and lower leg edema associated with massive proteinuria was admitted to our hospital in February 1992. Nine months before this admission, she exhibited myasthenia gravis and malignant thymoma, and underwent total thymectomy. On admission, there was no symptom of myasthenia gravis. She was diagnosed as having nephrotic syndrome and the first renal biopsy was performed. The histological findings showed membranous nephropathy. Immunofluorescent microscopy revealed that IgG and C3 were stained in a granular pattern in the periphery, and subepithelial deposits were observed in the basement membrane of the glomerulus by electron microscopy. With the administration of prednisolone, proteinuria disappeared and the nephrotic syndrome remitted. She was admitted again in January 1993 due to proteinuria and lower leg edema following cystitis. The findings of the second renal biopsy were unremarkable. She was administered cyclosporin A to improve the nephrotic syndrome and to reduce the side effects of prednisolone. The proteinuria disappeared again and this effect was dependent on the dose of cyclosporin A. Since the first administration, no symptoms of myasthenia gravis or malignant thymoma have been observed. The relationships among myasthenia gravis, malignant thymoma and nephrotic syndrome were examined. Although the first renal biopsy findings showed membranous nephropathy, from the therapeutic responses of both prednisolone and cyclosporin A, the main course of proteinuria in this case may have been due to minimal change nephrotic syndrome. We consider this case of nephrotic syndrome to be important considering its etiology and the relationship between the histological findings and its clinical course.

Effect of histamine H2-receptor antagonist on the phosphorus-binding abilities of calcium carbonate and calcium lactate in hemodialysis patients.

The effect of histamine H2-receptor antagonist (famotidine) on the phosphorus-binding abilities of calcium carbonate and calcium lactate were examined in 13 chronic hemodialysis patients. In seven patients receiving calcium carbonate, famotidine (20 mg/d) was given because of gastroduodenal disorders, and calcium carbonate was replaced with calcium lactate as a phosphorus binder after 4 wk of treatment with famotidine. With the 4-wk administration of famotidine accompanied by calcium carbonate, the serum phosphorus level increased from 6.3+/-0.9 to 7.1+/-0.5 mg/dl (P<0.05). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly when compared to that before substitution (6.3+/-0.2 and 6.0+/-0.9 mg/dl after 4 and 8 wk of substitution, respectively), despite continued administration of famotidine. Serum calcium, creatinine, alkaline phosphatase, high sensitive parathyroid hormone, blood urea nitrogen, arterial blood pH, and bicarbonate were not significantly altered during the trial period. In six control patients treated with calcium carbonate alone, there were no statistical changes in serum calcium and phosphorus levels after substitution of calcium lactate for calcium carbonate. These results suggest that famotidine significantly affects the phosphorus-binding ability of calcium carbonate, but not that of calcium lactate. A careful observation of changes in the serum phosphorus level should be required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphorus binder in such hemodialysis patients.