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Careful Monitoring (careful + monitoring)
Selected AbstractsWeight gain in bipolar disorder: pharmacological treatment as a contributing factorACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2008C. Torrent Objective:, The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder. Method:, Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder. Results:, Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight. Conclusion:, Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues. [source] HHV8 a subtype is associated with rapidly evolving classic Kaposi's sarcomaJOURNAL OF MEDICAL VIROLOGY, Issue 12 2008Roberta Mancuso Abstract The link between human herpesvirus 8 (KSHV) and Kaposi's sarcoma (KS) has been proven, but many important aspects including risk factors, genetic predisposition to tumor development, transmission of KSHV, and the pathogenic potential of different genotypes remain to be elucidated. Possible associations between clinical parameters and antibody levels, viral load fluctuations, and viral genotype were analyzed by quantitative real-time PCR, an in-house developed IFA assay, and sequence analysis of ORF K1-VR1 in blood, serum and saliva of 38 subjects with classic KS (cKS). KSHV lytic antibodies were significantly increased in stage IV compared to stage I and II patients (p,=,0.006 and p,=,0.041, respectively). KSHV blood, serum, and saliva viral load was comparable in all stages. The highest viral loads were detected in saliva, and they decreased in stages III,IV compared to stages I,II patients. Higher concentrations of lytic antibodies and higher viral loads were observed in fast progressing cKS patients, in whom KSHV detection from blood was also more frequent. Type A KSHV strain was almost exclusively present in rapid progressors (12/17 cases), while C type was mainly present in slow progressing patients (6/7 cases). Finally, detection of type A KSHV strain associated with higher blood viral loads. KSHV lytic antibody levels and viral load can be used to monitor clinical evolution of cKS. Infection supported by KSHV A subtype is associated with more rapid progressive disease. Careful monitoring and aggressive therapeutic protocols should be considered in patients with KSHV A-supported infection. J. Med. Virol. 80:2153,2160, 2008. © 2008 Wiley-Liss, Inc. [source] Review article: drug hepatotoxicityALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2007C. Y. CHANG SUMMARY Background Drug toxicity is the leading cause of acute liver failure in the United States. Further understanding of hepatotoxicity is becoming increasingly important as more drugs come to market. Aims (i) To provide an update on recent advances in our understanding of hepatotoxicity of select commonly used drug classes. (ii) To assess the safety of these medications in patients with pre-existing liver disease and in the post-liver transplant setting. (iii) To review relevant advances in toxicogenomics which contribute to the current understanding of hepatotoxic drugs. Methods A Medline search was performed to identify relevant literature using search terms including ,drug toxicity, hepatotoxicity, statins, thiazolidinediones, antibiotics, antiretroviral drugs and toxicogenomics'. Results Amoxicillin-clavulanic acid is one of the most frequently implicated causes of drug-induced liver injury worldwide. Statins rarely cause clinically significant liver injury, even in patients with underlying liver disease. Newer thiazolidinediones are not associated with the degree of liver toxicity observed with troglitazone. Careful monitoring for liver toxicity is warranted in patients who are taking antiretrovirals, especially patients who are co-infected with hepatitis B and C. Genetic polymorphisms among enzymes involved in drug metabolism and HLA types may account for some of the differences in individual susceptibility to drug hepatotoxicity. Conclusions Drug-induced hepatotoxicity will remain a problem that carries both clinical and regulatory significance as long as new drugs continue to enter the market. Future results from ongoing multicentre collaborative efforts may help contribute to our current understanding of hepatotoxicity associated with drugs. [source] Prospective evaluation of acute and chronic renal function in children following matched related donor hematopoietic stem cell transplantationPEDIATRIC TRANSPLANTATION, Issue 1 2010Talia Ileri Ileri T, Ertem M, Ozcakar ZB, Ince Unal E, Biyikli Z, Uysal Z, Ekim M, Yalcinkaya F. Prospective evaluation of acute and chronic renal function in children following matched related donor hematopoietic stem cell transplantation. Pediatr Transplantation 2010: 14: 138,144. © 2009 John Wiley & Sons A/S. Abstract:, Acute and chronic renal impairment are important complications after HSCT. A prospective study was conducted to investigate the glomerular renal function in children who received allogeneic HSCT from matched related donors. Non-radiation conditioning regimens were used in all but one patient. CrCl and serial measurements of serum creatinine were evaluated prior to HSCT, within the first 100 days and one yr after. AKI was defined as at least a 1.5-fold rise in pre-HSCT serum creatinine within the first 100 days and classified as grade 1 to 3 according to the new definition criteria proposed by "AKI Network." Fifty-seven patients were enrolled in the study and 24 patients (42%) had AKI. CsA, amphotericin B, and SOS were found as risk factors for AKI. One yr after HSCT five patients (10%) had CKD and none of them required dialysis. None of the parameters were found as a predictor for CKD. We conclude that AKI is an important complication of HSCT. Careful monitoring of renal function, minimizing the use of nephrotoxic medication, prophylaxis, and effective treatment of SOS might be effective preventive measures to decrease the incidence of AKI. [source] Peripheral neuropathy associated with leflunomide: is there a risk patient profile?,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2007Karin Martin pharmD Abstract Purpose (i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms. Method All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses. Results One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range,=,27,81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p,=,0.0006), more often diabetic (30% vs. 2.9%, p,=,0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p,=,0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV). Conclusion Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory. Copyright © 2006 John Wiley & Sons, Ltd. [source] A laboratory and clinical evaluation of single-use instruments for tonsil and adenoid surgeryCLINICAL OTOLARYNGOLOGY, Issue 2 2005A. Tomkinson Objectives:, To compare the quality and consistency of single-use adenotonsillectomy instruments available in the UK with reusable instruments and examine their performance in a clinical setting. Design:, A laboratory assessment of each reusable instrument created a detailed specification for the respective single-use equivalent. A surveillance system monitored the performance of a selected set of specified single-use instruments. Setting:, Single-use instruments were withdrawn shortly after their introduction in 2001. Persisting concerns from the Spongiform Encephalopathy Advisory Committee led to an investigation into the feasibility of continuing to use such instruments. Main outcome measures:, The numbers of instruments from each set judged as unacceptable or as good as the original. The number and cause of instrument failure during clinical surveillance. Results:, Between 40% and 93% of the instruments on each set were as good as the original and between 0% and 40% of the instruments were unacceptable from six sets of steel and one set of polymer instruments. 4151 procedures were monitored between 1 February 2003 and 31 March 2004 using a total of 41 376 instruments. Problems were reported with 335 (0.8%) instruments, 46% attributable to instrument design, 14% to poor design control and 13% to instruments escaping quality control systems. Following correction of the faults, between 1 January 2004 and 31 March 2004 the problem rate fell to 0.4%. Conclusions:, High quality single-use instruments for tonsil and adenoid surgery are available in the UK. Some companies offered inferior instruments not fit for their purpose. The procurement, introduction and subsequent clinical approval of single-use instruments requires a radically different approach to that currently applied to the purchase of reusable surgical equipment. Careful monitoring of their introduction is essential. [source] Medium-chain triglyceride (MCT) ketogenic therapyEPILEPSIA, Issue 2008Yeou-mei Christiana Liu Summary The medium-chain triglyceride diet (MCTD) is a variant of the classic 4:1 ketogenic diet (KD) introduced in 1971 by Huttenlocher as an attempt to improve the palatability of the KD by allowing more carbohydrates yet preserving ketosis. Although initially found to be equally effective as the classic KD, use of the MCTD declined because of frequent gastrointestinal side effects such as cramps, diarrhea, and vomiting. Recently, we have used the MCTD in more than 50 patients. We have found excellent seizure control, similar to the classic KD, and with careful monitoring, we have encountered minimal side effects. The MCTD should remain a viable dietary option for children with refractory epilepsy who have large appetites, can tolerate more calories, or cannot accept the restrictions of the classic KD. [source] Risk factors for severe infection in patients with hairy cell leukemia: a long-term study of 73 patientsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2009Ghandi Damaj Abstract Although the survival of patients with hairy cell leukemia (HCL) has been improved by the therapeutic introduction of interferon , and purine analogs, it is still worsened by complications such as severe infections. In this long-term study, we identified factors influencing patient outcomes in 73 patients with HCL. Median age at diagnosis was 53 yr and the gender ratio (M/F) was 2.3. At the time of HCL diagnosis, 60 patients (82%) were symptomatic and 22 of these had an infection. After a median follow-up of 13 yr, eight patients had died of secondary cancer (n = 2), HCL progression (n = 1) and age-related complications (n = 5). The 10-yr overall survival (OS), progression-free survival and relapse rates were 91 ± 3%, 14 ± 5% and 87 ± 5%, respectively. In multivariate analyses, age >53 yr was the only factor adversely influencing OS and secondary cancer incidence, with adjusted hazard ratio (HR) of 9.30 (95%CI, 1.15,76.6; P = 0.037) and 2.80 (95%CI, 1.05,7.71; P = 0.04), respectively. Eleven patients developed severe infections. Absolute lymphocyte count (<1 × 109/L) at diagnosis was the only factor influencing the occurrence of severe infections, with an adjusted HR of 4.01 (P = 0.007). Strikingly, we did not observe any significant correlation between neutrophil or monocyte counts and the incidence of infection. We confirmed long-term survival in HCL but found a high incidence of infection , even late in the course of the disease. The absolute lymphocyte count at diagnosis is a risk factor for the occurrence of severe infections. In addition to careful monitoring of infections, prompt initiation of anti-HCL treatment should be considered in patients with low lymphocyte counts. [source] Does propofol and alfentanil-induced sedation cause periodic apnoea in chronic renal failure patients?INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2010S. M. Lee Summary Aims:, There is evidence suggesting that the respiratory response to sedation is different in patients with sleep apnoea, which is common in patients with chronic renal failure (CRF). This study examined the respiratory response of sedation with propofol and alfentanil, whose pharmacokinetics are not affected by the renal function, in CRF patients. Methods:, Chronic renal failure patients who underwent arteriovenous-fistular surgery (CRF group) and patients who underwent chemoport insertion (control group) were enrolled in this study. Sedation was induced by infusing propofol 1.5 ,/ml and alfentanil 0.2 ,/kg/min continuously in both groups. In the desaturation study, the respiratory rate and peripheral oxygen saturation in room air were checked. In the apnoea,hypopnoea study, the patient's sedation (Observer's Assessment of Alertness/Sedation) score, apnoea,hypopnoea index (AHI) was recorded using a portable ventilation effort recorder (microMesam) while applying 5 l/min of oxygen through a facial mask. Results:, The desaturation event was more common (21.5/h vs. 2/h, p = 0.001) in the CRF patients. Apnoea and hypopnoea (AHI: 13.0 vs. 1.6, p = 0.012, per cent of patients with an AHI > 5: 53.3% vs. 7.1%, p = 0.014) occurred more frequently in the CRF patients but the sedation score was not different. Conclusion:, Chronic renal failure patients have a higher risk of developing apnoea and hypopnoea during sedation, which highlights the need for careful monitoring and management in these patients. [source] Promoting acute thrombolysis for ischaemic stroke (PRACTISE)INTERNATIONAL JOURNAL OF STROKE, Issue 2 2007Protocol for a cluster randomised controlled trial to assess the effect of implementation strategies on the rate, effects of thrombolysis for acute ischaemic stroke (ISRCTN 20405426) Rationale Thrombolysis with intravenous rtPA is an effective treatment for patients with ischaemic stroke if given within 3 h from onset. Generally, more than 20% of stroke patients arrive in time to be treated with thrombolysis. Nevertheless, in most hospitals, only 1,8% of all stroke patients are actually treated. Interorganisational, intraorganisational, medical and psychological barriers are hampering broad implementation of thrombolysis for acute ischaemic stroke. Aims To evaluate the effect of a high-intensity implementation strategy for intravenous thrombolysis in acute ischaemic stroke, compared with regular implementation; to identify success factors and obstacles for implementation and to assess its cost-effectiveness, taking into account the costs of implementation. Design The PRACTISE study is a national cluster-randomised-controlled trial. Twelve hospitals have been assigned to the regular or high-intensity intervention by random allocation after pair-wise matching. The high-intensity implementation consists of training sessions in conformity with the Breakthrough model, and a tool kit. All patients who are admitted with acute stroke and onset of symptoms not longer than 24 h are registered. Study outcomes The primary outcome measure is treatment with thrombolysis. Secondary outcomes are admission within 4 h after onset of symptoms, death or disability at 3 months, the rate of haemorrhagic complications in patients treated with thrombolysis, and costs of implementation and stroke care in the acute setting. Tertiary outcomes are derived from detailed criteria for the organisational characteristics, such as door-to-needle time and protocol violations. These can be used to monitor the implementation process and study the effectiveness of specific interventions. Discussion This study will provide important information on the effectiveness and cost-effectiveness of actively implementing an established treatment for acute ischaemic stroke. The multifaceted aspect of the intervention will make it difficult to attribute a difference in the primary outcome measure to a specific aspect of the intervention. However, careful monitoring of intermediate parameters as well as monitoring of accomplished SMART tasks can be expected to provide useful insights into the nature and role of factors associated with implementation of thrombolysis for acute ischaemic stroke, and of effective acute interventions in general. [source] Absence of transmission of potentially xenotic viruses in a prospective pig to primate islet xenotransplantation study,JOURNAL OF MEDICAL VIROLOGY, Issue 11 2008Olga Garkavenko Abstract Shortage of human donor organs for transplantation has prompted usage of animals as an alternative donor source. Pigs are the most acceptable candidate animals but issues of xenozoonoses remain. Despite careful monitoring of designated pathogen free pigs there is still a risk that their tissues may carry infectious agents. Thus xenotransplantation requires extensive pre-clinical study on safety of the graft especially for those viruses that are either potentially oncogenic and/or immunosuppressive, or can establish persistent infection. A prospective pig-to-primate islet xenotransplantation study was performed which includes monitoring for potentially xenotic viruses namely porcine endogenous retrovirus (PERV), porcine cytomegalovirus (PCMV), porcine lymphotropic herpesvirus (PLHV), and porcine circovirus (PCV) using both molecular diagnostic,PCR and RT-PCR and serology methods. There was no evidence of pig virus transmission into primate recipients. This preclinical study underlines the information concerning viral safety of islet cell xenograft in pig-to-primate xenotransplantation. J. Med. Virol. 80:2046,2052, 2008. © 2008 Wiley-Liss, Inc. [source] Intra-arterial chemotherapy with mitomycin C in gallbladder cancer: A follow-up studyJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2005Michaela K. Bode MD Abstract Background and Objectives There is only limited and somewhat controversial information available on hepatic artery infusion of cytotoxic agents in gallbladder cancer. We report the results of 5-year follow-up of all gallbladder cancer patients treated with surgery and intra-arterial mitomycin C or mitomycin C alone in our hospital during 15 years. Methods Thirty-five patients with gallbladder cancer were treated with superselective intra-arterial chemotherapy (SIAC) with mitomycin C during 1981,1996. Survival was measured from diagnosis, and all patients were followed up until death or the end of January 2002. Cumulative survival rates and median survival times were calculated for all patients, according to response to treatment and staging. The data are presented as 5-year survival. Results Median survival times after SIAC for all patients, responders, and non-responders were 48, 60+, and 8.5 months, respectively. Overall response rate was 60%. Survival was significantly better for tumors limited to the gallbladder wall, as expected. Drug toxicity occurred in half of the patients, requiring cessation of chemotherapy in 25% of the cases. Conclusions The median survival of gallbladder cancer patients treated with surgery and SIAC seems to be significantly better compared to the previously reported outcome of surgical treatment alone. Drug toxicity limits the use of i.a. chemotherapy and requires careful monitoring for early side-effects. J. Surg. Oncol. 2005;91:102,106. © 2005 Wiley-Liss, Inc. [source] Desmopressin treatment in nocturia; an analysis of risk factors for hyponatremiaNEUROUROLOGY AND URODYNAMICS, Issue 2 2006A. Rembratt Abstract Aims To explore the incidence, severity, time course, and risk factors of clinically significant hyponatremia in desmopressin treatment for nocturia. Methods Data from three multi-center phase III trials were pooled. Hyponatremia was categorised as borderline (134,130 mmol/L) or significant (<130 mmol/L). Risk factors were explored with logistic regression and subgroup analysis performed to explore threshold values for contra-indication. Results In total 632 patients (344 men, 288 women) were analyzed. During dose-titration, serum sodium concentration below normal range was recorded in 95 patients (15%) and 31 patients (4.9%) experienced significant hyponatremia. The risk increased with age, lower serum sodium concentration at baseline, higher basal 24-hr urine volume per bodyweight and weight gain at time of minimum serum sodium concentration. Age was the best single predictor. Elderly patients (,65 years of age) with a baseline serum sodium concentration below normal range were at high risk (75%). Limiting treatment in elderly with normal basal serum sodium concentration to those below 79 years and with a 24-hr urine output below 28 ml/kg would reduce the risk from 8.1% to 3.0% at the cost of 34% fulfilling the contra-indication. Conclusions The majority of nocturia patients tolerate desmopressin treatment without clinically significant hyponatremia. However, the risk increases with increasing age and decreasing baseline serum sodium concentration. Treatment of nocturia in elderly patients with desmopressin should only be undertaken together with careful monitoring of the serum sodium concentration. Patients with a baseline serum sodium concentration below normal range should not be treated. © 2005 Wiley-Liss, Inc. [source] Making Government Accountable: Lessons from a Federal Job Training ProgramPUBLIC ADMINISTRATION REVIEW, Issue 5 2007Pascal Courty This article describes the evolution of a performance measurement system in a government job training program. In this program, a federal agency establishes performance measures and standards for substate agencies. The performance measurement system's evolution is at least partly explained as a process of trial and error characterized by a feedback loop: The federal agency establishes performance measures, the local managers learn how to game them, the federal agency learns about gaming and reformulates the performance measures, possibly leading to new gaming, and so on. The dynamics suggest that implementing a performance measurement system in government is not a one-time challenge but benefits from careful monitoring and perhaps frequent revision. [source] Clinical and Subclinical Endometritis in the Mare: Both Threats to FertilityREPRODUCTION IN DOMESTIC ANIMALS, Issue 2009MM LeBlanc Contents Endometritis, a major cause of mare infertility arising from failure to remove bacteria, spermatozoa and inflammatory exudate post-breeding, is often undiagnosed. Defects in genital anatomy, myometrial contractions, lymphatic drainage, mucociliary clearance, cervical function, plus vascular degeneration and inflamm-ageing underlie susceptibility to endometritis. Diagnosis is made through detecting uterine fluid, vaginitis, vaginal discharge, short inter-oestrous intervals, inflammatory uterine cytology and positive uterine culture. However, these signs may be absent in subclinical cases. Hypersecretion of an irritating, watery, neutrophilic exudate underlies classic, easy-to-detect streptococcal endometritis. In contrast, biofilm production, tenacious exudate and focal infection may characterize subclinical endometritis, commonly caused by Gram-negative organisms, fungi and staphylococci. Signs of subclinical endometritis include excessive oedema post-mating and a white line between endometrial folds on ultrasound. In addition, cultures of uterine biopsy tissue or of small volume uterine lavage are twice as sensitive as guarded swabs in detecting Gram-negative organisms, while uterine cytology is twice as sensitive as culture in detecting endometritis. Uterine biopsy may detect deep inflammatory and degenerative changes, such as disruption of the elastic fibres of uterine vessels (elastosis), while endoscopy reveals focal lesions invisible on ultrasound. Mares with subclinical endometritis require careful monitoring by ultrasound post-breeding. Treatments that may be added to traditional therapies, such as post-breeding uterine lavage, oxytocin and intrauterine antibiotics, include lavage 1-h before mating, carbetocin, cloprostenol, cervical dilators, systemic antibiotics, intrauterine chelators (EDTA,Tris), mucolytics (DMSO, kerosene, N -acetylcysteine), corticosteroids (prednisolone, dexamethasone) and immunomodulators (cell wall extracts of Mycobacterium phlei and Propionibacterium acnes). [source] Enduring love: A grounded formal theory of women's experience of domestic violenceRESEARCH IN NURSING & HEALTH, Issue 4 2001Margaret H. Kearney Abstract Using a grounded formal theory approach, 13 qualitative research reports were analyzed with the goal of synthesizing a middle-range theory of women's responses to violent relationships. The combined sample numbered 282 ethnically and geographically diverse women ages 16,67. Within cultural contexts that normalized relationship violence while promoting idealized romance, these women dealt with the incongruity of violence in their relationships as a basic process of enduring love. In response to shifting definitions of their relationship situations, many women moved through four phases, which began with discounting early violence for the sake of their romantic commitment ("This is what I wanted"), progressed to immobilization and demoralization in the face of increasingly unpredictable violence that was endured by the careful monitoring of partner behavior and the stifling of self ("The more I do, the worse I am"), shifted to a perspective that redefined the situation as unacceptable ("I had enough"), and finally moved out of the relationship and toward a new life ("I was finding me"). Variations in the manifestation and duration of these phases were found to be linked to personal, sociopolitical, and cultural contexts. © 2001 John Wiley & Sons, Inc. Res Nurs Health 24:270,282, 2001 [source] High-resolution diffracting crystals of intrinsically active p38, MAP kinase: a case study for low-throughput approachesACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2007Ron Diskin p38 MAP kinases are central signalling molecules that mediate cellular responses to numerous environmental conditions and signalling molecules. Their proper function is required for many processes, including stress response, apoptosis, differentiation, growth and even learning and memory. Abnormal activity of p38 MAP kinases is associated with the aetiology of many diseases, making understanding their activation mechanisms highly critical. In this respect, mechanistic insights may be derived from structural studies of recently developed intrinsically active p38, mutants. Unlike wild-type p38,, which routinely crystallized, the active mutants caused severe difficulties during the crystallization process. The main hindrance was found to be protein heterogeneity, which was meticulously resolved by genetically modifying the recombinant protein and optimizing the expression and purification protocols. The success in obtaining crystallizable proteins strongly emphasizes that in certain cases, high-throughput techniques (crystallization robots) together with low-throughput approaches, with careful monitoring and analysis of the results, are essential. [source] Mechanism of decrease of oral bioavailability of cyclosporin A during immunotherapy upon coadministration of amphotericin BBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2008Junko Ishizaki Abstract The trough level of blood concentration of cyclosporin A (CyA) in a patient receiving immunotherapy was observed to decrease following coadministration of amphotericin B (AMB). This clinical observation was confirmed experimentally in Wistar rats intravenously given AMB (1.5 or 3.0,mg/kg) or saline (control) for 4 days, followed by CyA (10,mg/kg). The blood concentration of CyA after i.v. or p.o. administration in both AMB groups was significantly decreased compared with the control. The oral bioavailability of CyA after 1.5 or 3.0,mg/kg AMB treatment was decreased to 67% or 46%, respectively, of that of the control group. AMB treatment increased the expression levels of mdr1a and mdr1b mRNAs in the duodenum to about three times the control, and expression of CYP3A2 mRNA in the liver was increased to about twice the control. The P-gp and CYP3A2 proteins were increased significantly. These findings suggest that the oral bioavailability of CyA is reduced as a result of both increased efflux transport via P-glycoprotein in the duodenum and an increased first-pass effect of CYP3A2-mediated hepatic metabolic activity, induced by AMB. It is suggested that careful monitoring of CyA levels is necessary in the event of AMB administration to patients receiving immunotherapy with CyA. Copyright © 2008 John Wiley & Sons, Ltd. [source] Fumaric acid esters in severe psoriasis, including experience of use in combination with other systemic modalitiesBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2004P. Balasubramaniam Summary Background Fumaric acid esters (FAE) are used as a systemic treatment for severe psoriasis in Germany but there has been only very little published experience from the U.K. The potential for use in combination with other systemic drugs has not been explored. Objectives To present data relating to the efficacy of FAE in severe psoriasis and to examine the potential dose-sparing effect and safety issues when FAE are combined with other systemic agents. Methods We retrospectively analysed the records of patients who had received FAE for severe psoriasis either alone (in two cases) or along with other systemic medications (in 10 cases). We reviewed the efficacy of FAE and assessed whether dose reductions were achieved for other systemic drugs. Patients were monitored carefully for possible adverse effects. Results Of 12 patients treated with FAE one discontinued the drug very early, due to flushing, while on a very low dose. The other 11 patients all demonstrated an improvement in psoriasis after starting FAE. Nine patients received FAE in combination with other systemic therapies including ciclosporin, acitretin, hydroxyurea and methotrexate. Seven achieved useful overall reductions in the dose of the other drugs. In two patients severe psoriasis was controlled using FAE alone. The side-effect profile of FAE was similar to that previously reported. There was no evidence of drug interactions. Conclusions FAE appear effective and less toxic than other systemic treatments for psoriasis. FAE were used successfully in combination with other systemic agents and generally enabled the doses of the more hazardous drugs to be reduced. Extremely careful monitoring is required when using FAE in such combined regimens as experience is currently very limited. [source] Managing sexually abused and/or abusing children in substitute careCHILD & FAMILY SOCIAL WORK, Issue 2 2003Elaine Farmer ABSTRACT This paper reports on research on the characteristics, management and therapeutic treatment of sexually abused and/or abusing children in substitute care. Of the 40 sexually abused and/or abusing young people aged 10 or over in the interview sample, two-thirds showed sexual behaviours in the placement studied but one-third did not. The range of sexual behaviours shown by the young people is described. Analysis of the findings shows that four key components of effective management are supervision, adequate sex education, modification of inappropriate sexual behaviour and therapeutic attention to the needs that underlie such behaviour. Supervision includes planning for safe care before placement, preparing other children in the setting, teaching young people how to keep themselves safe when out on their own, and careful monitoring of contact with birth family members. The need for a proactive approach to sex education is stressed. Effective management approaches to masturbation, sexualized behaviour and sexually abusing behaviour are discussed but the processes of denial and minimization of sexual abuse and the development of high thresholds for action when looked after children are abused or at risk are shown to present obstacles to effective care. Finally, the importance of addressing children's deeper needs is emphasized, including the importance of regular review of their need for counselling. At the end of the article two case examples from the study are given. [source] How do you initiate oestrogen therapy in a girl who has not undergone puberty?CLINICAL ENDOCRINOLOGY, Issue 1 2009Peter C. Hindmarsh Summary The physiology of puberty needs to be taken into consideration in the induction of puberty. Puberty is a relatively slow process and replacement therapy should mimic this. Long-term maintenance requires careful monitoring and long-term assessment of risk-benefit. This has not been appreciably defined in the adolescent population. Options for fertility need careful consideration and may depend on the adequacy of pubertal induction in terms of uterine development. A number of regimens are available for pubertal induction but the lack of comparisons makes it difficult to advocate for a particular regimen. There remain a number of areas of uncertainty, and future studies need to consider these issues and whether there are cardiovascular risk factor advantages to certain preparations. The long-term risks of breast and gynaecological malignancy remain uncertain. Long-term cohort studies are required to address these issues. [source] | ||||||||||