Pharmacist Interventions for Adverse Drug Reactions in Palliative Care: A Multicentre Pilot Study.

This study aimed to investigate adverse reactions to medications administered during palliative care and compare the responses of Board-Certified Pharmacists in Palliative Pharmacy (BCPPP) and non-BCPPP professionals. Methods: This multicentre prospective survey included hospital and community pharmacists who are members of the Japanese Society for Pharmaceutical Palliative Care and Sciences. Study participants included patients who experienced new drug reactions during the study period and responded to the requested survey items. The follow-up period for each eligible patient began on the day the pharmacists initiated the intervention and ended at discharge, death, or after one month of intervention. The primary endpoint was the impact of pharmacist intervention on adverse drug reactions. The pharmacists included in the study evaluated the severity of adverse drug reactions to assess the effect of their intervention using an integrated palliative care outcome scale before and after the intervention. Key findings: During the survey period, 79 adverse drug reaction intervention reports from 69 patients were obtained from 54 pharmacists (28 certified and 26 non-certified). The response rate was 1.62% (54/3,343). The management of palliative pharmacotherapy side effects by BCPPP and non-BCPPP significantly improved the patients' activities of daily living (P < 0.001). The BCPPP group intervened for significantly more patients with adverse drug reactions and overall adverse drug reactions than the non-BCPPP group (P < 0.023 and P < 0.013, respectively). Conclusion: BCPPP interventions can improve symptom management.

Good Outcomes in Kidney Transplantation With Deceased Donor With Acute Kidney Injury: Donor's Age and Not Acute Kidney Injury Predicts Graft Function.

BACKGROUND: With the increased demand for kidney transplants and the short supply of organs, it is necessary to have a better strategy to evaluate the available organs, especially from donors with acute kidney injury (AKI), because these organs are often rejected for transplantation. METHODS: We evaluated patients undergoing transplantation with kidneys from deceased donors with AKI. The cases were divided into AKI stages according to the Acute Kidney Injury Network (AKIN) criteria. The outcomes examined were delayed graft function (DGF), creatinine (Cr), and creatinine clearance (CrCl) at 6 months after transplantation. RESULTS: We evaluated 101 patients and included 53 in the final model. There was no statistical difference in the demographic characteristics, comorbidities, and immunosuppression according to each AKIN stage, showing a population of homogeneous transplant recipients. Recipients in AKIN stages I, II, and III, respectively had DGF in 72.7%, 61.9%, and 71.4% of cases; Cr of 1.6 ± 0.5, 1.7 ± 0.7, and 1.6 ± 0.2 mg/dL at 6 months; and CrCl of 60.6 ± 22.4, 52.4 ± 27.4, and 52.03 ± 12.1 mL/min at 6 months. Each additional year in donor age increased the relative risk of DGF by 1.08 (1.0-1.13) (P = .01), and organs from older donors were associated with worse renal function at 6 months. CONCLUSION: Kidney transplantation of organs from deceased donors with AKI showed greater DGF but good outcomes. Donor age was the only characteristic that correlated with outcome.

Uric acid levels predict future blood pressure and new onset hypertension in the general Japanese population.

We tested the hypothesis that uric acid levels predict new-onset hypertension in the Japanese general population. Normotensive individuals who visited our hospital for a yearly health checkup (n=8157, men=61.0% and age=50.7±12.2 years) were enrolled in the present study. After baseline evaluation, participants were followed up for a median of 48.3 months (range 4.9-101.0 months), with the endpoint being the development of hypertension, defined as systolic blood pressure (BP) > or = 140 mm Hg, diastolic BP > or = 90 mm Hg or the use of antihypertensive medication. The impact of uric acid and other cardiovascular risk factors at baseline on future BP and development of hypertension was assessed. During follow-up, 19.0% of women (n=605) and 29.5% of men (n=1469) participants developed hypertension. Incident hypertension was increased across the quartiles for baseline uric acid levels (P<0.0001), and multivariate Cox proportional hazards analysis revealed a significant and independent association between the uric acid level and the onset of hypertension in both men and women participants (P<0.05). Furthermore, uric acid was independently and positively correlated with future BP (P<0.05). Thus, uric acid is an independent predictor of new-onset hypertension in both women and men.

Factors associated with brachial-ankle pulse wave velocity in the general population.

The present study investigated factors that modify or affect arterial stiffness as assessed by brachial-ankle pulse wave velocity (baPWV) in the general population. Subjects had previously participated in a physical checkup program (n=911), and baPWV and urinary albumin and sodium excretion were also measured. Urine albumin was expressed as the ratio of urine albumin to urine creatinine. Individual salt intake was assessed by estimating 24-h urinary salt excretion and expressed as the ratio of estimated salt intake to body weight. The mean blood pressure and baPWV were 127.1±15.2/77.0±9.5 mm Hg and 15.9±3.3 m s(-1), respectively. Univariate analysis demonstrated that baPWV correlated with various factors including age, blood pressure, electrocardiogram voltage (SV(1)+RV(5)), urine albumin and salt intake. Multivariate regression analysis revealed that electrocardiogram voltage (P<0.001), systolic blood pressure (P<0.0001), urine albumin (P<0.001) and salt intake (P<0.001), independently correlated with baPWV after adjustment for other possible factors. Similar results were obtained for participants not taking any medication. These results suggest that the baPWV value is independently associated with individual salt intake and cardiac and renal damage, and could be a useful procedure for identifying individuals with concealed risk of cardiovascular disease.

Parathyroid hormone upregulates BMP-2 mRNA expression through mevalonate kinase and Rho kinase inhibition in osteoblastic MC3T3-E1 cells.

It is well known that parathyroid hormone (PTH) possesses an anabolic effect on bone. However, the mechanisms are not fully elucidated. So far, it is unclear whether or not PTH could stimulate the expression of bone morphogenetic protein-2 (BMP-2), a strong mediator for bone formation. Growing evidence suggests that BMP-2 expression is regulated by the mevalonate pathway and Rho-associated protein kinase (ROK) activity. This study was performed to examine if PTH affects BMP-2 expression and to clarify its involvement of the mevalonate pathway. Osteoblastic MC3T3-E1 cells were treated with human PTH-(1-34) to determine BMP-2 mRNA expression levels by real-time PCR and to measure the ROK activity by the kinase assay. Incubation with 10 (-9)-10 (-8) M of hPTH-(1-34) for 6 h induced significant upregulation of BMP-2 mRNA levels in MC3T3-E1 cells. Short-term treatment of hPTH-(1-34) suppressed Rho kinase activity and mevalonate kinase mRNA levels. PTH-induced BMP-2 mRNA upregulation was selectively reversed by geranylgeranyl pyrophosphate (GGPP) pretreatment, but not by mevalonate pretreatment. These findings suggest that BMP-2 mRNA expression was upregulated by PTH in MC3T3-E1 cells mediated by mevalonate pathway suppression followed by ROK inhibition. We have now demonstrated for the first time that PTH stimulated BMP-2 mRNA expression via the mevalonate pathway and ROK in osteoblastic MC3T3-E1 cells.

Greater fat oxidation with diacylglycerol oil consumption for 14 days compared with triacylglycerol oil consumption in overweight men and women.

BACKGROUND: Several studies have reported increased fat oxidation with diacylglycerol (DAG) oil consumption. However, the effects of long-term DAG oil consumption on energy metabolism remain to be investigated. OBJECTIVE: The objective of this study was to compare the effects of 14 days of either DAG or triacylglycerol (TAG) oil consumption on substrate oxidation, energy expenditure (EE) and dietary fat oxidation. DESIGN: Eight males and six females participated in this randomized, double-blind, crossover feeding study. Each patient consumed the 14-day controlled test diet containing either 10 g day(-1) of DAG or TAG oil for acclimatization before a respiratory chamber measurement, followed by a 2-week washout period between diet treatments. Substrate oxidation and EE were measured in the respiratory chamber at the end of each dietary treatment. The patients consumed test oil as 15% of total caloric intake in the respiratory chamber (mean test oil intake was 36.1+/-6.6 g day(-1)). RESULTS: Twenty-four hour fat oxidation was significantly greater with 14 days of DAG oil consumption compared with TAG oil consumption (78.6+/-19.6 and 72.6+/-14.9 g day(-1), respectively, P<0.05). There were no differences in body weight or body composition between diet treatments. Dietary fat oxidation was determined using the recovery rate of (13)CO(2) in breath, and was significantly enhanced with DAG oil consumption compared with TAG oil consumption, measured over 22 h after ingestion of (13)C-labelled triolein. Resting metabolic rate (RMR) was significantly greater with DAG oil consumption compared with TAG oil consumption (1766+/-337 and 1680+/-316 kcal day(-1), respectively, P<0.05). CONCLUSION: Consumption of DAG oil for 14 days stimulates both fat oxidation and RMR compared with TAG oil consumption, which may explain the greater loss of body weight and body fat with DAG oil consumption that has been observed in weight-loss studies.

Electron microscopic observation of cytoskeletal frame structures and detection of tubulin on the apical region of Cryptosporidium parvum sporozoites.

Cryptosporidium parvum is an intracellular protozoan parasite belonging to the phylum Apicomplexa, and a major cause of waterborne gastroenteritis throughout the world. Invasive zoites of apicomplexan parasites, including C. parvum, are thought to have characteristic organelles on the apical apex; however, compared with other parasites, the cytoskeletal ultrastructure of C. parvum zoites is poorly understood. Thus, in the present study, we ultrastructurally examined C. parvum sporozoites using electron microscopy to clarify the framework of invasive stages. Consequently, at the apical end of sporozoites, 3 apical rings and an electron-dense collar were seen. Two thick central microtubules were seen further inside sporozoites and extended to the posterior region. Using anti-alpha and -beta tubulin antibodies generated from sea urchin and rat brain, both antibodies cross-reacted at the apical region of sporozoites in immunofluorescent morphology. The molecular mass of C. parvum alpha tubulin antigen was 50 kDa by Western blotting and the observed apical cytoskeletal structures were shown to be composed of alpha tubulin by immunoelectron microscopy. These results suggested that C. parvum sporozoites were clearly different in their cytoskeletal structure from those of other apicomplexan parasites.

Coronary artery disease investigated using 99mTc-tetrofosmin myocardial SPECT.

BACKGROUND: Coronary artery disease can be diagnosed from stress and delayed images of myocardial single photon emission computed tomography (SPECT) using technetium-99 m-tetrofosmin (TcTF). However, the negative predictive value of stress SPECT images after a single injection of a low tracer dose remains unknown. Thus, the present study investigates whether normal stress SPECT results predict event-free survival. MATERIALS AND METHODS: We screened 302 consecutive patients who were randomly assigned to two groups for myocardial ischaemia using either stress SPECT with a low dose of TcTF (296 MBq, TcTF group, n = 150) or stress together with rest SPECT using thallium(201) chloride (TlCl, 111 MBq; TlCl group, n = 152) as the tracer. A total of 80 patients with abnormal SPECT findings were excluded and the remaining 222 with normal results (age, 66.5 +/- 0.7 years; TcTF/TlCl, 112/110) were enrolled in the present study and followed up for 401 +/- 9 days, with the endpoint being ischaemic cardiac events. RESULTS: The incidence of cardiac events did not differ between the two groups (0.9% and 0.0% in TcTF and TlCl groups, respectively). The cost and duration of TcTF and TlCl SPECT examinations were about 425 and 603 Euros and 50 and 280 min, respectively. CONCLUSIONS: The negative predictive values of stress SPECT using a low dose of TcTF and of combined stress and rest SPECT using TlCl did not differ and both were clinically acceptable. Thus, stress SPECT using low dose TcTF is useful in screening patients for myocardial ischaemia.

Brain natriuretic peptide detects cardiac abnormalities in mass screening.

BACKGROUND: Plasma brain natriuretic peptide (BNP) is elevated in asymptomatic patients with various cardiac abnormalities. We tested the hypothesis that measuring BNP is useful for detecting asymptomatic patients with cardiac abnormalities who are not identified by conventional health check-up programmes. MATERIALS AND METHODS: From 2001 to 2002, 6189 subjects (women 34.0%; mean age 56.6 years) underwent multiphasic health check-ups in our hospital, of which 4818 without cardiac abnormalities as revealed by the health check-up were enrolled in the present study. Their plasma concentrations of BNP were measured. RESULTS: Plasma concentrations of BNP were higher than the normal reference upper limit of our hospital (21.3 pg mL(-1)) in 925 of the 4818 subjects. Echocardiography was performed in 471 subjects who were randomly selected from the 925 subjects with elevated BNP. Abnormal findings were detected in 174 subjects, comprising valvular heart disease in 83, systolic dysfunction in 10, diastolic dysfunction in 54, left ventricular hypertrophy in 41, left ventricular enlargement in 11, left atrial enlargement in 13 and paroxysmal atrial fibrillation in 3. CONCLUSIONS: Since BNP measurement identifies additional subjects with cardiac abnormalities, it is useful for detecting asymptomatic cardiac abnormalities among apparently healthy subjects, and is suitable for use in high-quality mass screening.

Capacity of ocular infiltrating T helper type 1 cells of patients with non-infectious uveitis to produce chemokines.

BACKGROUND/AIMS: Chemokines are key molecules that initiate leucocyte infiltration to the inflammatory site. The involvement of chemokines in uveitis is well studied, yet the source of this molecule in the inflamed eye is not clearly identified. The possible sources of chemokines are ocular resident cells or the inflammatory cells infiltrated to the eye. Here the authors examined whether ocular infiltrating T cells of uveitis patients do produce chemokines. METHODS: T cell clones (TCCs) were established from ocular infiltrating cells of patients with non-infectious uveitis. TCCs were characterised using flow cytometry. Spontaneous production of chemokines by TCCs was evaluated by ELISA. RESULTS: TCCs from ocular infiltrating cells were revealed to be memory activated Th1 type CD4 positive cells. Those TCCs produced larger amounts of chemokines than TCCs from peripheral blood mononuclear cells of uveitis or healthy donors. CONCLUSIONS: The present data indicate that ocular infiltrating T cells of patients with non-infectious uveitis produce chemokines and recruit further infiltrating lymphoid cells. Such T cells may have roles in the prolonged/chronic state of non-infectious uveitis.

Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): potential neuroprotective role of SOCS proteins.

Suppressors of cytokine signaling (SOCS) are implicated in immunopathogenic mechanisms of autoimmune diseases. We show here that SOCS expression in retina is temporarily correlated with progression of experimental autoimmune uveitis (EAU), an organ-specific autoimmune disease that serves as model of human uveitis. Peak of EAU correlates with highest SOCS genes expression while disease resolution coincides with their down-regulation. Surprisingly, SOCS5 is constitutively expressed in retina. SOCS5 expression increases significantly during EAU and remains elevated even after disease resolution. Our data suggest that cytokine-inducible SOCS members may be involved in negative regulation of inflammatory cytokines activities during EAU, while constitutively expressed SOCS5 may have neuroprotective functions.

Brain natriuretic peptide in the prediction of recurrence of angina pectoris.

BACKGROUND: Circulating levels of brain natriuretic peptide (BNP) provide prognostic information for patients with heart failure, but little is known about its prognostic usefulness in patients with stable angina pectoris. We investigated whether BNP could be used as a marker for the prediction of anginal recurrence after successful treatment. DESIGN: Brain natriuretic peptide levels of 77 patients with stable angina pectoris were measured at enrolment and after confirmation of successful treatment (i.e. no anginal attack for at least 6 months: chronic phase) with percutaneous transluminal coronary angioplasty and/or conventional medication. Then, we prospectively followed them up for 25.9 +/- 1.4 months, with the endpoint being a recurrence of anginal attacks. RESULTS: An anginal attack recurred in seven patients. In patients without recurrence, BNP levels in the chronic phase (21 +/- 12 [median +/- median absolute deviation] pg mL-1) were lower than those measured at enrolment (46 +/- 25 pg mL-1, P < 0.0001), whereas the levels in patients with recurrence increased during the same period (from 36 +/- 16 to 72 +/- 42 pg mL-1, P < 0.05). A univariate analysis revealed that the BNP level measured in the chronic phase was the significant predictor of future anginal recurrence. Analysis of the receiver operating characteristic curve indicated that the cutoff level of BNP in the chronic phase was 68 pg mL-1. The Kaplan-Meier method revealed that the incidence of anginal recurrence was higher in patients with higher (71.4%) than lower levels of BNP (2.9%; P < 0.0001). CONCLUSIONS: Measurement of BNP levels after successful therapy is clinically useful for the prediction of recurrence of anginal attacks in patients with angina pectoris.

Circulating concentrations of cardiac proteins indicate the severity of congestive heart failure.

OBJECTIVE: To test the hypothesis that myocardium specific proteins may be useful markers for evaluating the severity of congestive heart failure. METHODS: Serum concentrations of myosin light chain I (MLC-I), heart fatty acid binding protein (H-FABP), creatine kinase isoenzyme MB (CK-MB), and troponin T (TnT) and plasma concentrations of brain natriuretic peptide (BNP) were determined in 48 patients with acute deterioration of congestive heart failure, both before and after effective treatment. RESULTS: Before treatment, MLC-I (mean (SEM) 3.2 (2.2) microg/l), H-FABP (9.0 (3.5) microg/l), TnT (30 (21) ng/l), and BNP (761 (303) ng/l) were higher than the normal reference range, and concentrations of CK-MB (5.4 (2.9) microg/l) were near normal. Treatment of congestive heart failure with conventional medication significantly decreased the concentrations of MLC-I (1.2 (0.3) microg/l, p < 0.0001), H-FABP (6.0 (2.0) microg/l, p < 0.0001), CK-MB (2.9 (1.5) microg/l, p < 0.0001), TnT (9 (1) ng/l, p < 0.001), and BNP (156 (118) ng/l, p < 0.0001). The decreases in H-FABP and CK-MB concentrations after treatment correlated with the decrease in BNP concentrations (p < 0.05). The absolute concentrations of MLC-I, H-FABP, CK-MB, and TnT correlated positively with those of BNP (p < 0.01). CONCLUSIONS: These findings suggest that MLC-I, H-FABP, CK-MB, and TnT may be used as reliable markers for the evaluation of the severity of congestive heart failure.

Development of myopia as a hazard for workers in pneumatic caissons.

BACKGROUND/AIM: Pneumatic caisson engineering has been developed for large civil engineering constructions. Because of complaints of blurred vision by personnel working in pneumatic caissons, the development of myopia was suspected. The aim of this study was to determine the cause of the blurred vision and the mechanism underlying the changes. METHODS: 12 caisson workers underwent a complete ophthalmological examination after completing up to 11 weeks of work (4 days/week) in a pneumatic caisson. Six months later, nine of the workers were examined again. RESULTS: Nine subjects were myopic at the initial examination, and seven of these were considered to have developed the myopia after starting to work in the pneumatic caisson. Six months after completion of the work, the mean refractive change was significantly towards hyperopia. CONCLUSIONS: The blurred vision in pneumatic caisson workers was in all likelihood due to the development of myopia. The refractive shift towards hyperopia after completion of work in the pneumatic caisson supports this and demonstrates that the changes were temporary. The myopia is similar to the myopia seen in patients treated by hyperbaric oxygen. Careful monitoring of the refraction of caisson workers should be performed for industrial health control.

Role of Ca2+-sensitive protein kinase C in phenylephrine enhancement of Ca2+ sensitivity in rat tail artery.

We investigated the role of protein kinase C (PKC) isoforms on changes in sensitivity of contractile mechanisms to intracellular Ca(2+) (force /[Ca(2+)]i) by phenylephrine (0.1-100 microM) in rat tail arterial helical strips using simultaneous measurements of force and [Ca(2+)]i. Force/[Ca(2+)]Ii induced by phenylephrine was greater than that induced by 80 mM K+. Force/[Ca(2+)]i induced by phenylephrine in physiologic saline solution or low Ca(2+) solution was dependent on the agonist concentration. Removal of Ca(2+) completely abolished the phenylephrine-induced contraction. The PKC inhibitors staurosporine and calphostin C inhibited the increase in force/[Ca(2+)]i induced by phenylephrine to a much greater extent than that induced by 80 mM K+. LY379196, a specific PKCbeta inhibitor, did not inhibit the increase of calcium sensitivity due to phenylephrine. The classic PKC isoforms, alpha, betaI, and II not gamma were demonstrated in the artery by immunohistochemistry. These results suggest that in rat tail arterial smooth muscle, PKCalpha, and not beta or gamma, mediates the increase of changes in sensitivity of contractile mechanisms to intracellular Ca(2+) to high dose of alpha1 receptor stimulation (phenylephrine 100 microM) on nonphysiologic conditions.

Pranidipine, a 1,4-dihydropyridine calcium channel blocker that enhances nitric oxide-induced vascular relaxation.

Pranidipine, a long acting 1,4-dihydropyridine calcium channel blocker, prolongs nitric oxide (NO)-mediated relaxation of rat aorta; it prolongs acetylcholine-induced relaxation in presence of endothelium as well as nitroglycerin-induced relaxation in absence of endothelium. In rat aorta the effect of pranidipine on NO-mediated relaxation is cyclic guanosine monophosphate (cGMP)-independent, but in guinea pig carotid artery the same effect of pranidipine is cGMP-dependent. It has been reported that in co-cultured human endothelial and smooth muscle cells pranidipine, at a higher concentration (10(-6) M), enhances vasorelaxant effect of NO by blocking NO decomposition. The enhancement of NO action by pranidipine differs from the direct NO-releasing action of other 1,4-dihydropyridines. It is expected that enhancement of NO-induced vasodilatation will lead to a venodilator action in vivo and less peripheral edema. The target organ protective effects of pranidipine are also reviewed in this article.

SoI--gel modification of pH electrode glass membranes for sensing anions and metal ions.

To obtain glass membrane electrodes selective for anions and metal ions, pH electrode glass membranes were modified by a sol-gel method using a quaternary ammonium salt and a bis(crown ether). A chloride ion-sensing glass membrane was designed, in which a pH electrode glass membrane was modified chemically by an alkoxysilyl quaternary ammonium chloride. X-ray photoelectron spectroscopy confirmed the chemical bonding of the quaternary ammonium moiety to the starting glass surface, which afforded the first example of glass-based "anion"-sensing membranes. A neutral carrier-type sodium ion-selective glass membrane was also fabricated which encapsulates a bis(12-crown-4) derivative in its sol-gel-derived surface. Both sol-gel-modified anion and metal ion-selective glass electrodes exhibited high sensitivity to their ion activity changes. The present sol-gel modification paves the way for designing glass-based ion sensors with tailor-made ion selectivities toward anions as well as cations.

A non-surgical rat model of foreign body-associated urinary tract infection with Pseudomonas aeruginosa.

This study established a rat model of foreign body-associated urinary tract infection. A spiral polyethylene tube (PT) was placed transurethrally into the bladder without surgical manipulation, followed by transurethral inoculation with Pseudomonas aeruginosa. The persistence of P. aeruginosa in the kidneys and bladder was significantly enhanced by placement of the PT, whereas the bacteria were eliminated rapidly from the urinary tract in the animals without the PT. Scanning electron microscopy revealed a thick biofilm on the surface of the PT from the early stage of infection. Histopathologically, acute pyelonephritis was followed by chronic renal inflammation as well as continuous and sporadic polymorphonuclear leukocyte accumulation and hemorrhage in the pelvis and adjacent tissues, suggesting continuous ascending introduction of the bacteria from the biofilm adhering to the PT. We believe our model simulates the pathophysiology of foreign body-associated urinary tract infection characterized by biofilm formation on the surface of a foreign body.