Timing of adjunctive therapy in the treatment of depression: a chart review.

INTRODUCTION: The objective of this study was to examine the evolution of antidepressant switch and adjunctive therapy. METHODS: This chart review was conducted at 6 primary psychiatric clinics or hospitals, in Tokyo, Japan. A chart review of longitudinal prescriptions was conducted regarding 633 outpatients with major depressive disorder for up to 2 years after their first visit. Patients who had already received antidepressants prior to the visit were excluded. RESULTS: 22.6% (N=143) of the patients completed or continued the outpatient treatment over the 2 years while 27 (4.3%), 23 (3.6%), and 439 (69.4%) patients discontinued it due to hospitalization, referral to another clinic, and loss to follow-up, respectively. A total of 597 episodes of antidepressant treatment were identified. Among them, 482 episodes (80.7%) were associated with the suggested dose ranges while antidepressant drugs were under-dosed in 19.3% (N=115) of the episodes. 50 patients (7.9%) received adjunctive therapy; it was employed after a median of only one antidepressant had been tried. CONCLUSION: Psychiatrists may be hasty in prescribing an adjunctive therapy in the treatment of depression.

Proton-exchange mechanism of specific Cs+ adsorption via lattice defect sites of Prussian blue filled with coordination and crystallization water molecules.

We have revealed the fundamental mechanism of specific Cs(+) adsorption into Prussian blue (PB) in order to develop high-performance PB-based Cs(+) adsorbents in the wake of the Fukushima nuclear accident. We compared two types of PB nanoparticles with formulae of Fe(III)4[Fe(II)(CN)6]3·xH2O (x = 10-15) (PB-1) and (NH4)0.70Fe(III)1.10[Fe(II)(CN)6]·1.7H2O (PB-2) with respect to the Cs(+) adsorption ability. The synthesised PB-1, by a common stoichiometric aqueous reaction between 4Fe(3+) and 3[Fe(II)(CN)6](4-), showed much more efficient Cs(+) adsorption ability than did the commercially available PB-2. A high value of the number of waters of crystallization, x, of PB-1 was caused by a lot of defect sites (vacant sites) of [Fe(II)(CN)6](4-) moieties that were filled with coordination and crystallization water molecules. Hydrated Cs(+) ions were preferably adsorbed via the hydrophilic defect sites and accompanied by proton-elimination from the coordination water. The low number of hydrophilic sites of PB-2 was responsible for its insufficient Cs(+) adsorption ability.

A scatter-compensated crystal interference factor in component-based normalization for high-resolution whole-body PET.

On a positron emission tomography (PET) scanner consisting of block detectors, coincidence responses to scattered radiation may differ from those to true depending on the crystal pair position within a coincidence block pair. Furthermore, these differences are considered to vary according to the radial position of the coincidence block pair. These conditions create ringing artifacts in the reconstructed image due to the lack of scatter compensation in detector normalization. In component-based normalization, a scatter-compensated crystal interference factor is therefore required in addition to the scatter-compensated block profile and intrinsic crystal efficiencies. In this study, we propose a scatter-compensated component-based normalization scheme using an annulus phantom, which provides true and scattered radiations over a large transaxial field of view, and evaluates the quality of three different-sized phantom images with whole-body PET. The results showed that the proposed normalization method significantly reduces the ringing artifacts in reconstructed images with different scattered/true fractions. The proposed algorithm, which introduced the scatter-compensated crystal interference factor, worked well under different scattered/true ratio conditions and was considered to be a robust, practical normalization method in high-resolution whole-body PET.

Dose-response to a jelly preparation of calcium polystyrene sulfonate in patients with hyperkalemia--changes in serum potassium levels with or without a RAAS inhibitor.

AIMS: In this study, dose-response of the serum potassium-lowering effect of a calcium polystyrene sulfonate (PS) preparation was investigated. Changes in the serum potassium level were also examined with or without application of a RAAS inhibitor, which is said to increase the serum potassium level. SUBJECTS AND METHODS: 23 patients diagnosed to have hyperkalemia associated with chronic renal failure were enrolled in this study. The study drug, a PS-Ca jelly preparation (Argamate jelly), was started at a daily dose of 1 preparation (5 g as PS-Ca), and the dose was increased by 1 preparation every month to finally reach 3 preparations per day. Blood samples were collected once a month and serum levels of creatinine and electrolytes were measured. RESULTS: PS-Ca jelly decreased serum potassium levels in a dose-dependent manner. Decreases were 0.67 mEq/l at 5 g of PS-Ca/day, 1.06 mEq/l at 10 g/d, and 1.33 mEq/l at 15 g/d. Irrespective of the use of the RAAS inhibitor, serum potassium levels decreased significantly in a dose-dependent manner. Furthermore, no major change in serum creatinine levels occurred in subjects in which the RAAS inhibitor was used, although in subjects in which the RAAS inhibitor was not used, serum creatinine level tended to gradually increase. CONCLUSION: Serum potassium levels were reduced in a dose-dependent manner by administration of 5-15 g/d of PS-Ca, and it appeared that together with control of serum potassium levels, renal function should be maintained by continuous administration of RAAS inhibitor.

2'-,5'-Oligoadenylate synthetase response ratio predicting virological response to PEG-interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C.

OBJECTIVE: Although all the mechanisms of elimination of hepatitis C virus (HCV) by Interferon (IFN) have not been fully elucidated, the 2'-5'-oligoadenylate (2-5A) system is one of the mechanisms of the antiviral effect of IFN. Consequently, the measurement of 2'-5'-oligoadenylate synthetase (2-5AS) activity could be useful for the evaluation of IFN treatment. This retrospective study was aimed at assessing whether 2-5AS activity functions as a clinical marker of virological response to PEG-interferon-alpha2b (PEG-IFN) plus ribavirin therapy of chronic hepatitis C. METHODS: The 32 patients included in this study had high viral loads of serum HCV-RNA of genotype 1b with chronic hepatitis C. All the patients received a regimen of PEG-IFN plus ribavirin for 48 weeks, and were then divided into two groups: one group (effective group) with undetectable serum HCV-RNA levels at 24 weeks (n = 22) of therapy, the other group (ineffective group) with persistent presence of HCV-RNA in serum at 24 weeks (n = 10). The 2-5AS activity in serum was measured 2, 8 and 12 weeks before initial administration. RESULTS: The 2-5AS response ratio (measured value/measured value of baseline 2-5AS) at 2, 8 and 12 weeks after the administration in the effective group was significantly higher than that in the ineffective group. CONCLUSIONS: These results suggest that the ratio of 2-5AS is closely related to the antiviral effect, and that the measurement of 2-5AS response ratio may be a useful clinical parameter of virological response to PEG-IFN plus ribavirin therapy of chronic hepatitis C.

Molecular cloning and heterologous expression of an alpha-adrenergic-like octopamine receptor from the silkworm Bombyx mori.

A cDNA encoding an octopamine (OA) receptor (BmOAR1) was isolated from the nerve tissue of silkworm (Bombyx mori) larvae. Comparison of amino acid sequences showed that BmOAR1 is highly identical to OA receptors isolated from Periplaneta americana (Pa oa(1)), Apis mellifera (AmOA1), and Drosophila melanogaster (OAMB or DmOA1A). BmOAR1 was stably expressed in HEK-293 cells. OA above 1 microM led to an increase in intracellular cyclic AMP concentration ([cAMP](i)). The synthetic OA-receptor agonist demethylchlordimeform also elevated [cAMP](i) to the same maximal level (approximately 5-fold over the basal level) as that induced by OA. However, other biogenic amines, tyramine and dopamine, and chlordimeform were without effects. The [cAMP](i) level raised by OA was lowered by antagonists; the rank order of antagonist activity was chlorpromazine > mianserin = yohimbine. Cyproheptadine and metoclopramide had little effect. OA above 100 nM induced a transient or sustained increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), depending on the concentration of OA. Sequence homology and functional analysis data indicate that BmOAR1 is an alpha-adrenergic-like OA receptor of B. mori.

Interferon-beta induction/interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C.

Treatment of chronic hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin improves the rate of eradication of the virus by less than 20% in patients with genotype 1b and a high viral load. In this study we assessed whether IFN-beta induction/IFN-alpha2b plus ribavirin enhances the efficacy of the therapy in patients with chronic hepatitis C. The efficacy of IFN-beta induction/IFN-alpha2b plus ribavirin therapy (group A, n=7) was compared with that of IFN-alpha2b plus ribavirin (group B, n=7) in 14 patients with high levels of HCV-RNA (> 100 K/U/ml). No significant differences were observed in the clearance of HCV-RNA between the two groups (A and B, respectively) 2 weeks after the start of the treatment (0% and 14.3%), at the end of the treatment (71.4% and 100%) and 6 months after the end of the treatment (28.6% and 14.3%). Recovery was complete in 28.6% and 14.3%, transient in 42.9% and 85.7% and absent in 28.6% and 0% in groups A and B, respectively. Early log changes in the viral load from the baseline after 2 weeks of treatment were 2.41 +/- 0.91 and 2.77 +/- 0.20 in groups A and B, respectively, with no significant difference between the two groups. In the present study, we were not able to demonstrate that IFN-beta induction/IFN-alpha2b plus ribavirin therapy was superior to IFN-alpha2b plus ribavirin therapy in patients with genotype 1b and high viral loads.

Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis.

BACKGROUND: Anorexia may be associated with decreased plasma levels of branched-chain amino acids (BCAA). In malnourished elderly haemodialysis (HD) patients, oral BCAA supplementation may improve anorexia, resulting in improved nutritional status. METHODS: Among 44 elderly (age >70 years) patients on chronic HD, 28 patients with low plasma albumin concentration (<3.5 g/dl) were classified as the malnourished group; they also suffered from anorexia. The other 16 patients did not complain of anorexia and were classified as the well-nourished group. We performed a 12-month, placebo-controlled, double-blind study on the malnourished group. Fourteen patients each received daily oral BCAA supplementation (12 g/day) or a placebo in random order in a crossover trial for 6 months. Body fat percentage, lean body mass, plasma albumin concentration, dietary protein and caloric intakes, and plasma amino acid profiles were monitored. RESULTS: Lower plasma levels of BCAA and lower protein and caloric intakes were found in the malnourished group as compared to the well-nourished group. In BCAA-treated malnourished patients, anorexia and poor oral protein and caloric intakes improved within a month concomitant with the improvement in plasma BCAA levels over the values in well-nourished patients. After 6 months of BCAA supplementation, anthropometric indices showed a statistically significant increase and mean plasma albumin concentration increased from 3.31 g/dl to 3.93 g/dl. After exchanging BCAA for a placebo, spontaneous oral food intake decreased, but the favourable nutritional status persisted for the next 6 months. In 14 patients initially treated with a placebo, no significant changes in nutritional parameters were observed during the first 6 months. However, positive results were obtained by BCAA supplementation during the subsequent 6 months, and mean plasma albumin concentration increased from 3.27 g/dl to 3.81 g/dl. CONCLUSIONS: Normalization of low plasma levels of BCAA by oral supplementation can reduce anorexia and significantly improve overall nutritional status in elderly malnourished HD patients.

Vitamin C inhibits corpus gastritis in Helicobacter pylori-infected patients during acid-suppressive therapy.

BACKGROUND: Previous studies have shown that gastric acid suppression worsens corpus gastritis in Helicobacter pylori (H. pylori)-positive patients. We evaluated the effect of acid-suppressive therapy and vitamin C on H. pylori-associated gastritis. METHODS: Forty patients with reflux esophagitis were divided into three groups by the status of H. pylori and therapy: group A (n=15), H. pylori (+) and omeprazole 20 mg; group B (n=15), H. pylori (+) and omeprazole 20 mg + vitamin C 1200 mg; and group C (n=10), H. pylori (-) and omeprazole 20 mg. In all three groups, the mucosal interleukin (IL)-8 contents, H. pylori colonization density, neutrophil infiltration in the corpus, and serum gastrin were evaluated at entry and 2 weeks after starting therapy; in group B, serum vitamin C levels were also measured. RESULTS: In group A, the IL-8 contents and the degree of neutrophil infiltration during therapy exceeded those at entry, whereas in groups B and C, these values did not change significantly with treatment. Helicobacter pylori colonization density during therapy was similar to that at entry in all three groups. The serum gastrin (in all groups) and vitamin C levels (in group B) during therapy exceeded those at entry. CONCLUSIONS: Potent acid suppression worsens H. pylori-associated corpus gastritis, although such worsening gastritis may be inhibited by vitamin C.

[Effectiveness of a new toothbrush with irrigation and suctioning capabilities (ty e-Brush) for removing supragingival plaque].

Patients with dysphagia typically have poor oral health. Because of improper swallowing, they cannot easily and safely clean their mouths. As a solution for such a problem, a manual toothbrush with both irrigation and suctioning functions has been developed, called the "e-Brush". The purpose of this study was to evaluate the cleaning effectiveness of the new e-Brush (9 mm and 11 mm in bristle length) for removing supragingival plaque, compared with a conventional toothbrush, GUM # 211 by Butler. In this study, 12 subjects (12 female of average age 20.6) were selected, and plaque control record (PCR) and scrubbing method were used. The following results were obtained: 1. Significant differences (p < 0.05) were recognized between e-Brush/9 mm (55.54 +/- 18.27%) and the others (e-Brush/11 mm: 30.88 +/- 8.14%, GUM # 211: 35.42 +/- 9.32%). 2. Bristles 9 mm in length were more effective than 11 mm bristles (p < 0.05). 3. Irrigation/suctioning function is more effective than the conventional tooth-brushing method. 4. The irrigation function of e-Brush was meritorious in making almost all users comfortable. These results suggest that this new oral hygiene device, "e-Brush/9 mm", is effective for improving oral care management for patients with dysphagia.

Cytotoxicity of cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)]-platinum (II) suspended in Lipiodol in a newly established cisplatin-resistant rat hepatoma cell line.

The cytotoxic activity of cis-[((1R,2R)-1,2-cyclohexanediamine-N, N')bis(myristato)]platinum (II) (SM-11355) was evaluated in a cisplatin (CDDP)-resistant tumor cell line, and compared with that of CDDP. H4-II-E / CDDP with acquired resistance to CDDP was established by continuous exposure of a rat hepatic tumor line, H4-II-E, to increasing concentrations of CDDP over 12 months. Compared with the parental cell line, this cell line exhibited an 8.8-fold increase in resistance to CDDP and was not cross-resistant to 1,2-diaminocyclohexane platinum (II) dichloride (DPC). There were no differences in sensitivity to six non-platinum antitumor drugs between H4-II-E and H4-II-E / CDDP, which suggests that H4-II-E / CDDP is not multidrug-resistant. Intracellular platinum accumulation and the formation of a platinum-DNA adduct following CDDP exposure were significantly reduced in H4-II-E / CDDP compared to the parental cell line. The acquired CDDP resistance in H4-II-E / CDDP appeared to be predominantly due to reduced CDDP uptake. H4-II-E / CDDP was also resistant to CDDP suspended in Lipiodol (CDDP / Lipiodol), but was not cross-resistant to SM-11355 suspended in Lipiodol (SM-11355 / Lipiodol). Also, there were no differences in intracellular platinum accumulation or the formation of platinum-DNA adducts after SM-11355 / Lipiodol exposure between H4-II-E and H4-II-E / CDDP. These results suggest that acquired CDDP resistance in H4-II-E / CDDP does not influence the cytotoxic activity of SM-11355 / Lipiodol.

Pharmacokinetic interactions between HIV-1 protease inhibitors in rats: study on combinations of two kinds of HIV-1 protease inhibitors.

The drug interactions between four human immune deficiency virus (HIV-1) protease inhibitors have been characterized by in-vitro metabolic studies using rat liver microsomal fractions and in-vivo oral administration. In this study, a new HPLC analytical method developed by us was used for the simultaneous determination of saquinavir and nelfinavir in rat plasma and microsomes. The metabolic clearance rates (Vmax/Km) of saquinavir, nelfinavir, and indinavir were 170.9 +/- 10.9, 126.1 +/- 4-4, and 73.0 +/- 2.0 microL min(-1) (mg protein)(-1), respectively. Ritonavir was the strongest inhibitor with inhibition constants (Ki) of 1.64 microM for saquinavir, 0.95 microM for indinavir, and 1.01 microM for nelfinavir. Nelfinavir was the second strongest inhibitor with Ki's of 2.35 microM for saquinavir and 2.14 microM for indinavir. Indinavir was the third strongest inhibitor with Ki's of 2.76 microM for nelfinavir and 3.55 microM for saquinavir. Saquinavir was the weakest inhibitor for the other three HIV- 1 protease inhibitors. After oral co-administration in combination with another HIV-1 protease inhibitor, the AUCs of saquinavir, indinavir, and nelfinavir were significantly increased compared with mono-treatment. The AUCs of saquinavir were increased about 10.1-, 3.1- and 45.9-fold in the presence of indinavir, nelfinavir and ritonavir, respectively. The AUCs of indinavir were increased about 6.8-, 5.9- and 9.4-fold in the presence of nelfinavir, saquinavir and ritonavir, respectively. The AUCs of nelfinavir were increased about 2.2-, 6.6- and 8.5-fold in the presence of indinavir, saquinavir and ritonavir, respectively. The in-vivo effects observed after co-administration of two kinds of HIV-1 protease inhibitor were not always expected from in-vitro data, suggesting the presence of other interaction processes besides metabolism in the liver. These results provide useful information for the treatment of AIDS patients receiving combination therapy with two HIV-1 protease inhibitors.

Effect of acid-suppressive therapy on Helicobacter pylori production of interleukin-8 in the gastric mucosa.

BACKGROUND: Recent studies have shown that acid-suppressive therapy increases the severity of Helicobacter pylori- associated gastritis in the corpus. PURPOSE: To evaluate interleukin (IL)-8 production in the gastric corpus mucosa before and during acid-suppressive therapy in H pylori-infected patients. PATIENTS AND METHODS: Ten patients with reflux esophagitis (five H pylori-positive and five H pylori-negative) were treated with omeprazole 20 mg. Serum gastrin concentrations, H pylori colonization density and mucosal IL-8 levels in the corpus were investigated at entry and two weeks after starting therapy. IL-8 levels were measured by ELISA. The organism density was determined, and scored according to area occupied by the bacterial colonies. The presence of H pylori was assessed by rapid urease testing and histological finding of gastric biopsy specimens. RESULTS: In H pylori-positive patients, concentrations of IL-8 during therapy significantly exceeded those before therapy (36.2+/-6. 8 versus 18.3+/-3.8 pg/mg protein; P<0.05) without altering H pylori density. In H pylori-negative patients, IL-8 levels were similar before and during therapy (6.1+/-2.7 versus 6.3+/-3.0 pg/mg protein). Concentrations of gastrin during therapy were significantly higher than those before therapy in all patients. CONCLUSIONS: The results suggest that acid suppression increases mucosal IL-8 levels in H pylori-infected patients with reflux esophagitis.

The contribution of residual renal function to overall nutritional status in chronic haemodialysis patients.

BACKGROUND: The benefits of residual renal function (RRF) in peritoneal dialysis patients have been described frequently. However, previous reports have shown that RRF diminished faster in haemodialysis (HD) patients than in peritoneal dialysis patients, and in most of the studies in HD patients, RRF was ignored. In this study, the RRF in chronic HD patients was studied to assess its impact on patients' nutritional status. METHODS: In 41 chronic HD patients with at least a 2-year history of HD treatment, RRF was determined by a urine collection for 7 consecutive days. Nutritional parameters, such as percentage body fat, fat-free mass index, serum albumin concentration and normalized protein catabolic rate, were also measured. RESULTS: In all 41 patients, mean weekly total Kt/V urea was 4.88 and renal Kt/V urea was 0.65. RRF was well correlated with serum albumin concentration, but dialysis Kt/V urea was not. One year after the start of this study, RRF and nutritional indices were re-examined and patients were classified into two groups: with RRF, preserved residual renal diuresis over 200 ml/day (mean, 720 ml; range, 230-1640 ml), N=23; and without RRF, persistent anuria (mean, 51 ml; range, 0-190 ml), N=18. At the start of this study, the mean serum albumin concentration and mean normalized protein catabolic rate in patients with RRF were 3.84 g/dl and 1.16 g/kg/day, respectively, which were significantly higher than those in patients without RRF (P=0.02 and P=0.0002, respectively), despite total (renal+dialysis) Kt/V urea being equal in both groups. During the 1-year study period, there was no significant change in total Kt/V urea in either group. Mean serum albumin concentration increased to 4.05 g/dl in patients with RRF, but did not change significantly (from 3.66 to 3.62 g/dl) in patients without RRF. The same trend was observed in all other parameters. CONCLUSION: Over half of our HD patients had sufficient RRF. RRF itself may have a beneficial effect on nutritional parameters, and it is important to determine RRF over time, even in chronic HD patients.

Elimination of iomeprol in patients undergoing continuous ambulatory peritoneal dialysis.

OBJECTIVE: To examine the elimination of iomeprol, its safety in clinical use, and its peritoneal permeability in continuous ambulatory peritoneal dialysis (CAPD) patients with variable degrees of residual renal function (RRF). DESIGN: A nonrandomized comparison study. SETTING: Hospitalized patients in CAPD unit of Chikuho and University Hospitals. PARTICIPANTS: Fourteen patients treated by CAPD and 6 by hemodialysis (HD). INTERVENTIONS: Total dialysate, blood, and 24-hour urine collections were obtained for 4 consecutive days after the administration of iomeprol. A peritoneal equilibration test was performed just before and after the administration of iomeprol. MEASUREMENTS: Iomeprol (iodine) concentration was measured. Residual renal function was estimated as the mean of renal creatinine and urea clearances. Dialysate-to-plasma ratios (D/P) of creatinine and iomeprol were also determined. RESULTS: In all CAPD patients, plasma iomeprol clearance was markedly slow, with a biological half-life (T1/2) of over 32 hours. However, no patients suffered from any adverse effects, and over 80% of plasma iomeprol was eliminated during the 4-hour HD. The plasma iomeprol elimination rate was significantly higher from 4 hours after the iomeprol administration in CAPD patients with RRF [mean estimated creatinine clearance (CCr) 3.8 mL/min, n = 7] compared to the remaining patients (mean estimated CCr 0.6 mL/min, n = 7); however, T1/2 in patients with RRF was over 24 hours. D/P creatinine was significantly correlated with D/P iomeprol, and peritoneal iomeprol permeability may depend on an individual's peritoneal solute transport properties. CONCLUSIONS: A prolonged elimination rate of iomeprol was documented in our CAPD patients both with and without RRF. A HD procedure or intensive peritoneal dialysis just after the use of iomeprol may be advisable to promptly remove circulating iomeprol.

Imidapril, an angiotensin-converting enzyme inhibitor, inhibits thrombosis via reduction in aortic plasminogen activator inhibitor type-1 levels in spontaneously hypertensive rats.

It is known that angiotensin II (Ang II) exerts an antifibrinolytic effect by stimulating synthesis of plasminogen activator inhibitor type-1 (PAI-1), a specific inhibitor of tissue plasminogen activator (t-PA). The aim of this study was to compare the antithrombotic potency of imidapril, an angiotensin-converting enzyme (ACE) inhibitor, and candesartan, an angiotensin II type 1 (AT1) receptor antagonist, in a model of arterial thrombosis in spontaneously hypertensive rats (SHRs). Oral treatment with 5 mg/kg imidapril 1 h before induction of thrombosis resulted in a significant reduction in thrombus weight, whereas candesartan did not affect thrombus weight under the same treatment conditions. Candesartan lowered blood pressure to the same degree as in the imidapril-treated rats. Imidapril not only reduce the serum and aortic ACE activities, but also reduced aortic PAI-1 protein levels, while candesartan had no effect on theses. These results suggest that imidapril, but not the AT1 receptor antagonist, candesartan, enhances fibrinolysis via a reduction of aortic PAI-1 levels by inhibiting ACE and prevents thrombus formation in SHRs.

Pharmacokinetics of bisoprolol and its effect on dialysis refractory hypertension.

The efficacy, safety, and pharmacokinetics of bisoprolol were investigated following oral administration once daily for 12 weeks in hyperreninemic patients with dialysis-refractory hypertension. Mean blood pressure rapidly fell from 132 to 112 mmHg in the 5.0-mg/day (n = 6) and from 142 to 128 mmHg in the 2.5-mg/day patients (n = 5), which were accompanied by a fall in plasma renin activity. On nondialysis days, Cmax and T1/2 were significantly higher in patients than in healthy control subjects. However, Cmax in the 2.5-mg/day patients was almost equal to that in healthy control subjects receiving 5.0 mg/day of bisoprolol. Plasma bisoprolol was dialyzable. During the course of the study, dialysis hypotension and bradycardia occurred in two patients receiving 5.0 mg/day of bisoprolol. In conclusion, a daily dose of 2.5 mg bisoprolol seems to be an adequate and relatively effective dose in our patients with dialysis-refractory hypertension.

Prolonged use of intradialysis parenteral nutrition in elderly malnourished chronic haemodialysis patients.

BACKGROUND: The treatment of malnutrition, frequently present in elderly dialysis patients, is important to promote better quality of life and rehabilitation. The aim of this study was to assess the impact of prolonged use of intradialysis parenteral nutrition (IDPN) as a strategy for malnutrition in elderly haemodialysis patients. METHODS: Twenty-eight elderly patients (non-diabetic, age over 70) on chronic haemodialysis for at least 2 years were evaluated. Ten consenting patients were treated with IDPN containing glucose, essential amino acids, and lipid emulsion during the course of regularly scheduled dialysis treatments for approximately 1 year. Nutritional evaluation using seven parameters (anthropometric measurements such as body mass index, triceps skinfold thickness, mid-arm circumference, mid-arm muscle circumference, and albumin, transferrin, and total lymphocyte count) was performed at various intervals on patients with IDPN and 18 patients without IDPN. The plasma amino-acid profile and dietary protein calorie intake were also determined. RESULTS: In patients receiving IDPN, significant increases in serum albumin and transferrin concentrations and total lymphocyte count in peripheral blood smears paralleled increases in protein-calorie intake beginning after 3 months of treatment and remained favourable throughout the study period. Anthropometric data started to improve significantly after 6 months of treatment. Patients without IDPN had gradual decreases in all parameters during the study period. A significant increase in essential amino acids and a significant decrease in 3-methyl-histidine were observed in patients with IDPN and a further decrease in essential amino acids was observed in patients without IDPN. CONCLUSION: Prolonged use of IDPN prevents muscle protein catabolism and promotes body protein and fat accumulation. IDPN appears to be effective in malnourished elderly haemodialysis patients.