Hartog calls this regime of historicity “presentism” and defines it as an invasion of the present into the realms of the past and future. For instance, Hartog notes that the conception of the past as a bygone time has recently been replaced by that of memory, which revitalizes in the present what would hitherto have been considered as dead or obsolete. Memory thus

appears as a “presentist Inhibitors,research,lifescience,medical instrument,” allowing for a “presentist use of the past.” Hartog also points to the importance given recently to the notion of heritage, which makes traces of the past necessary components of current individual and collective identities. As for the extension of the present into the future, the historian notes that our societies conceive of the time to come as a source of uncertainty and anguish. Inhibitors,research,lifescience,medical The future must be prepared now, in the present, in order to prevent potential environmental, political, health, and other catastrophes from occurring. According to Hartog, this is evident in the emergence of the principle of responsibility and the precautionary principle, which

state, respectively, that the living are responsible for handing over to future generations a world in which Inhibitors,research,lifescience,medical life will be decent, and that an action should not be undertaken if it is deemed to have serious potential consequences, notably in the long run. For the French historian, presentism differs significantly from previous temporal orders, namely futurism, eschatologism, Inhibitors,research,lifescience,medical and pastism (mentioned here in reverse chronological order). Futurism, which Hartog dates roughly between the French revolution (1789) and the fall of the Berlin Wall (1989), emphasized the present as a step toward the Inhibitors,research,lifescience,medical future; time was seen as a movement of uninterrupted improvement, with an ever-increasing efficiency of technologies and a continuous economic growth. It was an era marked by the idea

of progress and an orientation toward the future. Before the advent of futurism, eschatologism was the dominant temporal order, according to Hartog. It envisaged time above all as a process of salvation. In his theory, the resurrection of SCR7 mw Christ marks the beginning of the process—being a fixed, past event, it acts as one of the delimitations of time—which needs to be completed, and this supposedly occurs through the second coming of Christ (parousia), or Judgement Day—representing the other delimitation Montelukast Sodium of time. In this regime of historicity, the present acts as an in-between stage; it is simultaneously a time of reminiscence about salvation and a time for the expectation of eternal life. “Past, present and future are articulated on the backdrop of eternity,” as Hartog writes (p 75). Finally, pastism, which the historian dates back to ancient times, conceived of the present as the reverberation of a mythical past.

These individual differences have become apparent in rodent models selectively bred for specific traits. The Lewis and Fischer 344 rats

are rodents with heightened (Fischer 344) or attenuated (Lewis) HPA-axis reactivity, and have been shown to differ in a wide range of HPA-axis-related behavioral and physiological traits (Sternberg et al., 1992). Stohr and colleagues showed that PNS had differential effects in the Lewis and Fischer 344 rats. In Lewis rats, PNS improved acquisition of active avoidance, decreased immobility in the forced swim test, and reduced novelty-induced locomotion, whereas in Fischer 344 rats PNS had no effect in the active avoidance or forced swim test, and increased novelty-induced CX-5461 in vivo locomotion (Stohr et al., 1998). Studies in rats selectively bred for High and Low anxiety traits suggest that PNS has opposite effects in anxious versus non-anxious rats. Rats bred for high anxiety traits became less anxious after PNS, whereas rats bred for low anxiety traits became more anxious (Bosch et al., 2006). In a similar fashion, rats selectively bred for low novelty seeking behavior were reported to show less anxiety than their controls, whereas those rats selectively bred for high novelty seeking behavior were not affected by PNS (Clinton et al., 2008). Taken together these studies

suggest that PNS may have opposite effects dependent on the genetic inhibitors background PI3K Inhibitor Library of the individual. In addition to the differences in anxiety traits or HPA-axis responsivity, the way a stressor is perceived may play an important role in effects of PNS. The stress-coping style of an individual TCL determines the behavioral and physiological response of an organism to stress. Two clear stress-coping phenotypes can be distinguished, the proactive and passive stress-coping styles. Behaviorally, proactive stress-copers are characterized

by active responses to stressors; they will attempt to modulate the environment to reduce the stress (Koolhaas et al., 1999). This proactive stress response is illustrated in rodents during a defensive burying test. In this test proactively coping rats will bury an electrified prod that is placed in their cage with saw dust in order to avoid a shock. In contrast, passive stress-copers respond to stress in a more inhibited manner. In the defensive burying test, passive rodents will sit as far away from the prod as possible to avoid being shocked (de Boer and Koolhaas, 2003). These stress-coping phenotypes are highly correlated with other behavioral responses. Proactive stress-coping individuals tend to show more aggression and impulsivity and are less behaviorally flexible than passive stress-copers (Coppens et al., 2010).

Bupropion

immediaterelease and nefazodone were found to have the lowest rate of sexual dysfunction in a study of more than 6000 individuals on SSRIs, bupropion, mirtazapine, nefazodone, rcboxetine, and venlafaxine.29 Studies comparing SSRIs with mirtazapine are inconclusive, some showing higher rates of sexual dysfunction with SSRIs and others with mirtazpine.30-35 Among the SSRIs, paroxetine has been found to have the highest rates of sexual dysfunction.35 Management of sexual dysfunction, like all side effects, begins with a thorough assessment during the initial Inhibitors,research,lifescience,medical evaluation to establish a baseline, including discussion of whether the patient, is sexually active and the degree of satisfaction with sexual function prior to treatment, and to discuss concerns about possible sexual dysfunction related to anticipated treatment. It is important to reassess sexual function periodically during the course of therapy, and also to recognize Inhibitors,research,lifescience,medical that sexual function may become increasingly Inhibitors,research,lifescience,medical important to patients as their depressive symptoms improve.36 Prior to the introduction of sildenafil and similar agents, many methods and medications were used in an attempt to treat the sexual side effects of antidepressants. These included dose reduction, timing of sexual activity toward the end of a dosing interval,

several days’ drug holiday,37 and antidote therapy with medicine such as psychostimulants38 and dopamine Inhibitors,research,lifescience,medical (DA) agonists such as amantadine, pramipexole and Dexedrine, norepinephrine (NE)/DA Wnt cancer agents such as bupropion, serotonin (5-HT)2 receptor antagonists such as nefazodone, and a2-adrenergic receptor antagonists such as yohimbine.39-40 As sildenafil has proven effective in placebo-controlled trials in the treatment of sexual performance,41 this agent, and related phosphdiesterase V inhibitors have become the mainstay of management, of sexual function. A recent trial42 also demonstrated that sildenafil is effective at. Inhibitors,research,lifescience,medical decreasing adverse sexual effects in women taking SSRIs, including improvement in desire, arousal-sensation, arousal-lubrication,

orgasm, and enjoyment. Nevertheless, many patients do not respond sufficiently well to sildenafil and related agents or other attempted medroxyprogesterone antidotes, and efforts to identify other remedies continue. These include complementary and alternative treatments such as maca root, arginine-containing compounds, and ginkgo biloba. When sexual dysfunction persists despite efforts at dose adjustments and antidote therapy, the principal option is to consider switching to agents with lesser degrees of sexual dysfunction, typically bupropion, or, where available, rcboxetine. Nefazodone is another option, though its use has been limited by risk of rare but. serious hepatotoxicity. Gastrointestinal problems Nausea and stomach upset.

[7]. They demonstrate that tumors could be formed in two different mouse strains (NIH Swiss, C57BL/6) that were co-injected with 12.5 μg each of two plasmids, each containing an activated oncogene (activated human H-ras and c-myc). This

value (Om) is calculated from the estimated size of the plasmid backbone (3186 bp) used in Sheng et al. [7], assuming that the oncogene inserted to the plasmid backbone has 1925 bp. Based on the total construct, the oncogene would account for 37.7% of the construct. If 12.5 μg of the plasmid is required for each oncogene of two oncogenes, as described by Sheng et al. [7], then the total oncogene portion amount to 9.4 μg (25 × 37.7% = Om). This evaluation utilizes research results from Peden et al. [8]. Using HIV as a model, they have found that PS-341 in vitro hcDNA from HIV-infected cells is infectious at 2.5 μg. In our single infective agent safety factor calculations, we make the assumptions: (1) 2.5 μg canine hcDNA is assumed to have an infectivity similar to hcDNA containing a HIV provirus; (2) the viral RAD001 genome size is 7000 bp [10], which represents a smaller retrovirus genome than HIV genome of 10,000 bp; (3) a diploid canine genome size is 4.82 × 109 as there is usually a single copy of provirus per cell [8]. To facilitate introduction of our model, we will focus on the assessment of oncogenicity. The same method,

once fully developed, can be directly applied to the infectivity risk evaluation. For the rest of the paper, we use Φ, Ω and however c to denote the host cell genome, oncogene DNA sequence residing in the host genome and phosphate ester bond between two nucleotides, respectively. We further express Φ and Ω as equation(2) Φ=B1cB2c…cBM, Ω=BlcBl+1c…cBl+m−1,Φ=B1cB2c…cBM, Ω=BlcBl+1c…cBl+m−1,where M and m represent haploid size of host genome and oncogene size, respectively, and l ≥ 1, m > 1 and l + m − 1 < M. We refer the bond c's within Ω as c1, c2 … cm−1. Define Xi as random variables that can take value either

0 or 1, with P[Xi = 1] = P[ci is disrupted by the enzyme] = 1 − P[Xi = 0] = p. The probability p represents the cutting efficiency of the enzyme. It is reasonable to assume that all Xi are independent. Therefore these m − 1 variables Xi are independently identically Modulators distributed (i.i.d.) according to a Bernoulli distribution [11]. After the host cell genome Φ is enzymatically digested, for the oncogene Ω to remain intact, none of the bonds c’s within the oncogene should be cut by the enzyme. That is equation(3) X1=X2…=Xm−1=0.X1=X2…=Xm−1=0. Thus the probability for Ω not to be disrupted is equation(4) Pr[X1=X2…=Xm−1=0]=(1−p)m−1. Now assume that the host cell genome Φ contains I0 oncogenes of size mi. equation(5) Ωi=BlicBli+1c…cBli+mi−1, 1≤i≤I0Ωi=BlicBli+1c…cBli+mi−1, 1≤i≤I0 By (4), the probability for Ωi to be uncut by enzyme is given by equation(6) pi=(1−p)mi−1.pi=(1−p)mi−1.

Dai et al. combined targeted delivery with antineoplastic and antiangiogenic agent delivery in PEGylated liposomes [255]. Coloading of the antiangiogenic agent combretastin A-4 in the lipid bilayer and the anticancer drug doxorubicin in the aqueous core of PEGylated liposomes resulted in increased therapeutic activity. Hu et al. also combined liposomal #BYL719 keyword# delivery of the antineoplastic and antiangiogenic agent, honokiol with irradiation for maximal therapeutic efficacy [256]. They hypothesized that this protocol would combine the destruction of

tumor cells by irradiation with inhibition of irradiation-induced neoangiogenesis by honokiol [257]. The combination of PEGylated honokiol-loaded and radiotherapy showed increased survival of Lewis lung carcinoma-bearing

mice compared to radiotherapy or honokiol liposomes alone, resulting in decreased angiogenesis Inhibitors,research,lifescience,medical in vivo. Maitani et al. also combined an antineoplastic drug (irinotecan) and an antiangiogenic agent (sunitinib) [258]. The drug combination had more therapeutic efficacy against pheochromocytoma neuroendocrine tumors in vivo when they were administered as sunitinib liposomes plus irinotecan liposomes or as coloaded liposomes than the combination of the free drugs, with higher drug accumulation as liposomes Inhibitors,research,lifescience,medical than as free drug. In a similar fashion, folate-targeted doxorubicin-loaded liposomes coloaded with a bifunctional peptide capable of vascular disruption and antitumor activity were more effective against KB human nasopharyngeal carcinoma in vivo than untargeted coloaded liposomes than either monotherapy

Inhibitors,research,lifescience,medical [259]. RGD-targeted liposomes coloaded with doxorubicin and the vascular disrupting drug combrestatin A-4 increased Inhibitors,research,lifescience,medical tumor regression of B16F10 melanoma compared to untargeted coloaded liposomes or targeted liposomes with either drug [260]. Zucker and coworkers have optimized the simultaneous loading of vincristine and topotecan into PEGylated liposomes (LipoViTo liposomes) and provided the reader with the methods needed to characterize a liposomal drug combination [261]. Use of LipoViTo increased 100-fold PAK6 the drug distribution to tumors compared to free drug and led to superior therapeutic efficacy over a free drug combination or liposomes with a single drug. PEGylated liposomes containing both vincristine and quercetin allowed reduced blood clearance of both drugs in mice, increased the therapeutic activity over a combination of free drugs and decreased side-toxicity [262]. Celator Pharmaceuticals Inc. (Princeton, NJ) developed a liposomal formulation of cytarabine: daunorubicin (CPX-351, 5:1 molar ratio) [24, 263, 264].

As can be seen in Figure 1,22 people with schizophrenia have a mean level of performance that is 2.0 SD below that of healthy people (70 vs 100). However, half of the healthy population is performing within 2 SD of the mean of people with schizophrenia, and 35% of the people with schizophrenia perform within #signaling pathway randurls[1|1|,|CHEM1|]# 2.0 SD of the mean of the healthy

population. While a score of 115 would be much more rare for someone with schizophrenia than a healthy individual, a score of 85 would be at the 67th percentile for someone with schizophrenia and at the 17th for the healthy population; both of these are clearly within not outlying scores. Figure 1. Normative data compared with Inhibitors,research,lifescience,medical a schizophrenia sample on the RBANS neuropsychological

test. RBANS, Repeatable Battery for Assessments of Neuropsychological Status An additional intriguing result of the Zakzanis et al analyses is that many of the tests that are often described as capturing fundamental characteristics of illnesses Inhibitors,research,lifescience,medical such as schizophrenia fare relatively poorly when evaluated with differential diagnostic standards. For instance, the Wisconsin Card Sorting test/23 a multidimensional test of executive functioning, is associated with 40% overlap Inhibitors,research,lifescience,medical between the performance of patients and healthy controls. In schizophrenia, in fact, the top five discriminators, all associated with 20% or less overlap, are in the domains of verbal and visuospatial memory. In the domain of chronic multiple sclerosis only 1 test Inhibitors,research,lifescience,medical is associated with less than 25% overlap between healthy individuals and MS patients, while many of the tests are associated with about 50% overlap between MS patients and healthy controls. These tests would provide essentially no data useful for differential diagnosis. There are some areas where there a number of excellent differential diagnostic candidates. In the domain of AD there are

15 different tests, all Inhibitors,research,lifescience,medical of memory, that are associated with less than 5% overlap between healthy controls and AD samples. Similarly, the difference between schizophrenia patients and AD patients on delayed recall memory was found to be similar to differences between healthy controls and AD patients. Assessment of functional potential and the course of degenerative conditions One of the more robust correlations in research in mental health is the association between ADAMTS5 cognitive performance and achievements in everyday functioning. This relationship has been appreciated for over 30 years and has been replicated across multiple neuropsychiatric conditions. Table II shows multiple examples of exactly this type of relationship. There are also several additional important points about these findings. These findings tend to be most robust for global aspects of cognitive performance, as indexed by performance on composite measures.

7 Recognizing the wide range of patients with DM, recent guidelines now stress the need to personalize DM management goals and treatments.8 In the face of the “diabetes tsunami”9 the gap between knowledge derived from basic scientific and clinical research, including

newly recognized molecular mechanisms and updated medical management guidelines and their use at the bedside or point of care by practitioners, is growing. Developing strategies and tools to bridge this knowledge and implementation gap is increasingly urgent as medically Inhibitors,research,lifescience,medical relevant and novel scientific discoveries can now be applied to assess risk factors at the genomic level for chronic diseases like cancer and DM, as well as the sensitivity to and efficacy of drug therapy using tools Inhibitors,research,lifescience,medical like bioinformatics and pharmacogenomics. These fields, together with the evolving areas of genomics, proteomics, and metabolomics, constitute the premise and promise of personalized medicine. Evidence-based medicine seeks to narrow the gap between clinical research and practice by explicitly and systematically

focusing the attention of clinicians on the most up-to-date evidence from epidemiologic and clinical trial studies. Specifically, evidence-based medicine promotes the judicious use of meta-analyses of randomized controlled trials and other scientifically derived knowledge for clinical Inhibitors,research,lifescience,medical decision-making. However, an inherent weakness of the meta-analytical focus is that individuals vary greatly in regard to their manifestations of disease, buy PLX4032 symptoms, Inhibitors,research,lifescience,medical co-morbidities, genetic predisposition, and variance in molecular sensitivity to drugs, which cannot be reflected in guidelines derived from meta-analyses of the general patient population. According to the US President’s Council of Advisors on Science and Technology,10 personalized medicine refers to the tailoring Inhibitors,research,lifescience,medical of medical treatment to the individual characteristics

of each patient; […] the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not.10 Given the large health and economic impact of DM, there is understandable interest in using Tolmetin personalized medicine strategies to identify those individuals who are most at risk of developing DM and its various complications, and who are most likely to benefit from a specific management strategy, in order to apply proven measures to delay or prevent their progression to DM and its subsequent complications.11,12 In this review we will provide an introduction to the principal personalized medicine tools and strategies, and provide examples of how they may be applied to diabetes, in particular to type 2 DM (DM2).

4–0.7 indicating that the drug release was by non-Fickian diffusion. Thus the drug release from the microcapsule formulations was by diffusion of the drug from the polymeric matrix followed by erosion of the polymer. Thus mechanism of drug release from all the microcapsule formulations was by polymer erosion and diffusion of

the drug from the channels formed on the coatings. The dissolution parameters were given in Table 3. SEM analysis was performed for some of the microcapsules prepared by solvent evaporation method. The microcapsules formulated were observed to be in fragments find more indicating brittle nature of Eudragit S 100 and the particle size was found to be spherical and uniform. The SEM photographs were shown in Fig. 2. DSC thermographic peak for losartan potassium was observed at temperature 274.8 °C. The DSC thermographic peak for losartan potassium in formulation F-5 was found at 274.8 °C as small peak. The results revealed that there were no major interactions between the drug and the polymers during coating process. Formulation F-5 at 274.8 °C gave a broad endothermic peak. The DSC endothermic peaks were shown in Figs. 3 and 4. The FTIR spectra of losartan potassium exhibited principle peaks at wave numbers of 3197.48 cm−1 (O–H Stretching), 2956.14 cm−1 (C–H

Stretching), 1577.61 cm−1 (C N Stretching), 1459.60 cm−1 why (C C Stretching) and 763.61 cm−1 (C–Cl Stretching). The spectra of optimized microcapsules F-5 exhibited all the principle peaks present in the losartan potassium pure drug. Thus there were no appearance http://www.selleckchem.com/products/LBH-589.html or disappearance of any characteristics peaks which shows that there is no chemical interaction between the drug and the polymer used. The IR spectra of drug and formulation F-5 were shown in Figs. 5 and 6. The concept of formulating microcapsules containing losartan potassium offers a suitable,

practical approach to achieve a prolonged therapeutic effect by continuously releasing the medication over an extended period of time. Thus the microcapsules of losartan potassium were successfully prepared by solvent evaporation method using the different concentration of polymer Eudragit S100. All authors have none to declare. The authors express their inhibitors gratitude to Life line pharmaceuticals limited, Vijayawada, Andhra Pradesh, India, for providing gift samples. The authors are thankful to the management of Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Guntur, for providing the facilities to carry out the research work. “
“In 1961, Sekiguchi and Obi1 first proposed the utilization of solid dispersions to increase the dissolution and oral absorption of poorly water-soluble drugs, it was first used by Mayersohn and Gibaldi (1966).

8 While CT is relatively forgiving due to the ability of the tomographic method to discriminate line-of-sight background, planar angiography is much more susceptible

and often necessitates tens of milliliters per injection, with 20 to 50 injections not uncommonly used in many procedures.9 A consequence of this large concentration of iodinated molecules in the contrast agent formulation Inhibitors,research,lifescience,medical is high osmolality, leading to local irritation, burning sensation, and, in extreme cases, membrane rupture and hemolysis at the injection site.10 11 Second, and most surprisingly, there has been very little attention paid to the pharmacokinetics of contrast agents. Indeed, the initial direction of scanners — towards rapid scanning to overcome the very rapid clearance of injected contrast Inhibitors,research,lifescience,medical agents —has had a “self-fulfilling” effect, whereby contrast agents have always been designed to have rapid clearance. This rapid clearance occurs invariably via the renal route, and the high osmolality (and viscosity)

of the agents leads to acute renal toxcity.12 Indeed, as much as 5% to 10% of the general population, and 25% to 40% of the renally susceptible population, suffers from contrast-induced nephropathy (CIN) after a contrast-CT study.13 14 Ironically, it is this susceptible population that most needs the CT study in the first place. Third, the rapid clearance kinetics (t1/2 Inhibitors,research,lifescience,medical ~ 5 minutes) necessitates a bolus injection and careful timing of the scan to correctly trace the bolus at the moment of entry into the anatomy of interest. This can be challenging, particularly for left-heart-based imaging, since the Inhibitors,research,lifescience,medical intravenous bolus undergoes significant dissipation and dispersion in the pulmonary vasculature prior to collection in, and ejection from, the left ventricle. Thus, at most imaging sites, a “bolus tracking” scan is implemented, which continuously scans a sentinel section immediately upstream of the anatomical region of interest, triggering the scan upon arrival of contrast Inhibitors,research,lifescience,medical in the sentinel.15 However, the bolus tracking scan results in continuous

exposure to X-rays and dramatically increases however the total X-ray dose in such procedures. Indeed, in the pediatric population, where sensitivity to X-ray dose is particularly high and scan doses have been progressively reduced, the bolus tracking contribution to the total dose can be as high as 30% to 40%.16 In spite of all these limitations, however, CT imaging has experienced nothing but continuous growth over the last decade and remains the most widespread imaging technique after ultrasound. The shortcomings of conventional contrast agent kinetics have also been turned into powerful strengths by the clever use of NVP-BKM120 chemical structure delayed-phase imaging. Taking advantage of the rapid renal clearance of contrast agents, arteriography has become the main forte of contrast-enhanced CT.

The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. The cumulative dose, median duration, and number of MLN8237 cycles of Cmab at the onset of hypomagnesaemia were 1400 mg/m2 (900-1650), 6 days (29-42), and 5 cycles (4)-(6), respectively. Among the six patients with hypomagnesaemia, five were treated with 1 mEq/mL of magnesium sulfate. Table 1 Characteristics of six patients

who were treated with oxaliplatin-fluoropyrimidine Inhibitors,research,lifescience,medical combination therapy for metastatic colorectal cancer followed by a combination of Cmab-irinotecan as a secondary treatment All patients experienced mFOLFOX6 regimen-induced peripheral neuropathy at the beginning of Cmab therapy, with grade 1 neuropathy in five patients and grade 2 neuropathy in one patient. After Cmab administration, PSN worsened in all six patients, and three patients progressed to grade 3. Among the three patients

with grade 3 PSN, two required a dose reduction and one had to discontinue treatment. Inhibitors,research,lifescience,medical The cumulative dose, median duration, and the number of cycles of Cmab at the time of PSN exacerbation were 2150 mg/m2 (1150-3150), 59.5 days (29-105), and 8 cycles (4)-(12), respectively. Five of the six patients (83%) developed Inhibitors,research,lifescience,medical hypomagnesaemia prior to PSN progression. Among these five patients, one had hypokalemia but none had abnormal calcium and potassium levels. One patient (17%) whose PSN was exacerbated before the onset of hypomagnesaemia had normal calcium and potassium levels. Discussion In the MOSAIC study, 90% of the neurotoxic effects occurred during active L-OHP therapy and the incidence decreased over time after discontinuation. Up to 70% and 80% improvement was Inhibitors,research,lifescience,medical noted after one and two years of discontinuation, respectively, which means that 20-30% did not even have improvement (1). Although precise mechanisms underlying

the development of PSN have not been fully clarified, PSN has been attributed to the accumulation of platinum in the dorsal root ganglion based on the results from animal experiments (8). Gamelin et al. suggested that a possible mechanism may Inhibitors,research,lifescience,medical be the effect of oxalate, a one of the breakdown products Montelukast Sodium of L-OHP, on neuronal sodium channels (11). Based on this hypothesis, chelation of oxalate can be a possible candidate for improvement of PSN. For this reason, L-OHP therapy is proactively supplemented with calcium and magnesium for chelation of oxalate. Therefore, administering hypomagnesaemia-inducing Cmab to patients who have been treated with L-OHP over a long period is thought to aggravate PSN by depleting magnesium that is necessary to chelate the breakdown the products of accumulated L-OHP. Furthermore, long-term Cmab therapy has been reported to inf luence not only magnesium levels but also the levels of calcium, potassium, and other electrolytes (9),(14)-(16). These results suggest that hypomagnesaemia may not be the only causative etiology.