bluuebunny/crossref_metadata_2025 huggingface dataset:
MAP kinases in the mammalian circadian system – key regulators of clock function
Authors: Coogan Andrew N. , Piggins Hugh D.
Published: July 2004

Over the past 7 years, there has been spectacular progress in our understanding of the molecular basis of the circadian pacemaker in many species, from yeast to mammals. However, the biochemical signalling mechanisms that underpin synchronization of the clock to environmental cues are still poorly understood. Recently, attention has been focused on the role of mitogen‐activated protein (MAP) kinase in biological timekeeping. It has been proposed that signal transduction via the MAP kinase cascades allows environmental information to be assimilated intracellularly within the circadian clock to produce changes in the phasing of clock gene expression, which, in turn, underlies clock‐controlled phase‐resetting of biological rhythms. This review examines the evidence for MAP kinase, particularly extracellular regulated kinases 1/2, involvement in the circadian clock and looks at the putative upstream regulators and downstream substrates of this signalling system.
The genetics of pollinosis
Authors: Arakawa H. , Morikawa A.
Published: July 2004

Japanese cedar pollinosis is an allergic disease characterized by sneezing and itchy and watery eyes in persons with a specific immunoglobulin (Ig)E antibody to this allergen. Since 1960, the prevalence of Japanese cedar pollinosis has greatly increased in Japan. Both environmental and host factors contribute strongly to the pathogenesis of allergic disorders such as allergic rhinitis. The best‐established risk factor for nasal allergy is family history of allergy, especially nasal allergy. Susceptibility genes are genes in which only a few mutational changes may lead to sensitivity to certain diseases. Japanese cedar or orchard grass pollinosis may be diseases of this type, related to the haplotype of human leukocyte antigen. Recent studies of susceptibility genes of allergic diseases have focused on the IgE receptor gene, which is closely related to the pathogenesis of allergic diseases, interleukin (IL)‐4, IL‐4 receptor and interferon genes, which are concerned with the Th2‐ and Th1‐immune responses. However, these susceptibility genes exhibit different behaviours in different ethnic populations and their contribution to conferring disease is not yet established. In addition, allergic rhinitis, especially pollinosis, may be strongly influenced by environmental factors.
Allergic rhinitis in children: environmental factors
Authors: Okamoto Y. , Sakurai D. , Horiguchi S.
Published: July 2004

Increasing numbers of patients with allergic rhinitis are being noted on a global scale. Over 90% of Japanese patients with perennial allergic rhinitis show allergic reaction to the mite antigen and major pollen allergens such as Japanese cedar and Japanese cypress, which are carried long distances (> 100 km) by wind and hence can produce substantial harmful effects even in metropolitan areas. This situation is distinct from that in the West, where the most common anemophilous allergen, ragweed, travels much shorter distances of up to only several hundred metres. Environmental factors such as increased antigen, air pollution, diet, intestinal microflora, decreased incidence of infections, smoking, breastfeeding and vaccination may play important roles in the development and manifestation of allergic rhinitis in genetically predisposed subjects. In particular, in newborn infants, who carry the Th2 predominant state, environmental factors may greatly affect the development of balanced production of Th1 and Th2 cytokines. However, the contribution of any environmental factor to the postnatal development of allergic rhinitis has not been sufficiently determined. A better understanding of the processes involved may lead directly to better treatment or cure of allergic rhinitis.
The role of allergic rhinitis in upper respiratory tract inflammatory diseases
Authors: Kurono Y. , Matsune S. , Sun D. , Suzuki M. , Mogi G.
Published: July 2004

The number of patients with allergic rhinitis (AR) is increasing. Furthermore, patients with otitis media with effusion (OME) and chronic sinusitis (CS) are frequently complicated with AR. These findings suggest that AR has an impact on the pathogenesis of both OME and CS. The direct and indirect influence of AR on OME and CS was investigated by clinical and experimental studies to clarify the mechanism by which type I allergic reaction is associated with OME and CS. Clinical findings of patients with OME or CS complicated with AR were analysed and compared with those of nonallergic subjects. Samples such as sinus effusions and middle ear effusions (MEE) were collected from the patients and infiltration of inflammatory cells and concentrations of inflammatory cytokines determined. In addition, previous reports discussing the relationship between AR and OME or CS are reviewed. Eosinophil infiltration and oedema were remarkable in paranasal sinus mucosa of patients with CS complicated with AR, suggesting the presence of type I allergic reaction in sinus mucosa. However, there was little evidence of eosinophils in sinus effusions. Endotoxin was frequently detected in sinus effusions of patients with CS having AR as well as suppurative CS. Hypoxia was also considered an important factor inducing sinus pathology. Eosinophils and IgE antibodies in MEE were not increased in OME patients with AR. Anti‐allergic medicine was effective in OME patients complicated with AR and improvement of nasal symptoms significantly correlated with that of ear symptoms. AR might be directly and indirectly associated with the pathogenesis of OME and CS.
Treatment options for children with allergic rhinitis
Authors: Masuyama K.
Published: July 2004

Allergen avoidance, pharmacotherapy, immunotherapy and surgical procedures are indicated for the treatment of allergic rhinitis (AR) in children. Antihistamines are the usual pharmacotherapeutic option; however, second‐generation antihistamines are of limited availability in Japan. Immunotherapy is the only strategy that can offer remission or cure of paediatric AR.
Prevalence of Japanese cedar pollinosis in children aged under 15 years throughout Japan
Authors: Okubo K. , Gotoh M. , Okuda M.
Published: July 2004

The prevalence of childhood allergic rhinitis is increasing steadily in Japan. Affected children are sensitized mainly by house dust mites; however, the prevalence of Japanese cedar pollinosis (JCP) in children is also on the rise. To ascertain the prevalence and current status of JCP in Japanese children, a retrospective analysis of a nationwide cross‐sectional random sampling study was conducted. The survey, conducted shortly after the peak pollen season, was performed by self‐evaluation questionnaire in 2001. Data from children aged under 15 years were collected and analysed. In these subjects, the response rate was 75.1%. The prevalence of JCP was 10.2% in children. Rhinorrhoea was the severest symptom reported; 19.5% had severe or moderate interference with daily activities and consulted physicians. Few children used prescribed drugs and some took measures to avoid contact with allergens.
Allergic rhinitis in children: association with asthma
Authors: Shimojo N. , Suzuki S. , Tomiita M. , Inoue Y. , Nakano K. , Kohno Y.
Published: July 2004

The incidence of allergic rhinitis in paediatric bronchial asthma patients was about 80% according to a questionnaire survey. Watery nasal discharge and nose rubbing were common symptoms of paediatric allergic rhinitis, while nasal congestion and sneezing increased with age. Although there were slight differences depending on the age of patients, one‐third to nearly half were believed to have nasal symptoms and asthma attacks. The first wheezing episode preceded nasal symptoms in the majority of patients, but onset of allergic rhinitis occurred > 1 year before asthma in a little over 10%. The age of onset of allergic rhinitis was 1 year in these patients, which was clearly earlier than that observed in patients who first developed asthma (4 years). Furthermore, the incidence of cedar pollinosis was higher in patients who developed allergic rhinitis first than in those who developed asthma first, suggesting that asthma patients who develop allergic rhinitis first exhibit pronounced nasal hypersensitivity. Allergic inflammatory cells are present in the nasal mucosa of asthma patients who do not exhibit distinct allergic rhinitis symptoms, so nasal sensitization does not necessarily lead to allergic rhinitis symptoms, suggesting the existence of some other factor that induces nasal hypersensitivity. On nasal smear, the appearance of mast cells preceded a positive radioallergosorbent test (RAST), and the appearance of eosinophils and basophils was consistent with the degree of sensitization. Anti‐allergic agents appear efficacious in patients' mast cells positive on nasal smear cytology with negative house dust mite RAST, suggesting that nasal smear cytology may be useful when beginning medication.
Bullying: Recent Developments
Authors: Smith Peter K.
Published: July 2004

As part of the increasing human rights agenda of the last century, the individual right not to be bullied or harassed in school has gathered considerable academic, social and political attention. This article reviews recent developments in this area, including: the definition and scope of bullying behaviours; roles in bullying; methods of study; correlates of bully and victim status; coping strategies, and peer support against bullying; the outcomes of large‐scale intervention studies; and suggestions for future action.
The Global Absence of Child and Adolescent Mental Health Policy
Authors: Shatkin Jess P. , Belfer Myron L.
Published: July 2004

Background:  Few policies designed specifically to support child and adolescent mental health exist worldwide. The absence of policy is a barrier to the development of coherent systems of mental healthcare for children and adolescents.

Method:  This study collected data on existing policies from international databases, WHO headquarters in Geneva, Switzerland, and in consultation with experts in child and adolescent psychiatry from around the world. A set of criteria for ranking the adequacy of these policies was developed.

Results:  Though no single country was found to have a mental health policy strictly pertaining to children and adolescents alone, 35 countries (corresponding to 18% of countries worldwide) were found to have identifiable mental health policies, which may have some beneficial impact on children and adolescents. Though little has been achieved worldwide in this area, there has been a significant degree of movement towards policy development in the past 10 years. The policies identified vary greatly in terms of their provisions for delivering services, initiating research, training professionals, and educating the public.

Conclusions:  The development of mental health policies is feasible and would substantially aid in the expansion of service systems, the institutionalisation of culturally relevant data gathering, and the facilitation of funding.
A Home and School Support Project for Children Excluded from Primary and First Year Secondary School
Authors: Panayiotopoulos Christos , Kerfoot Michael
Published: July 2004

Background:  In the last 10 years the problem of exclusion has reached a crisis point. Research suggests that exclusion is a complex phenomenon that needs involvement from all the involved services such as Health, Education and Social Services.

Method:  One hundred and twenty‐four pupils, aged 4–12 years who, through school and social exclusion, were at risk of developing more serious mental health difficulties, were randomly allocated to standard care (n = 62) or standard care plus the new intervention (n = 62).

Results:  There were no significant differences in the primary outcomes between the two groups at either of the outcome assessments. However, the intervention group with non‐compliance cases removed from the analysis did significantly better ( p < . 014, 95%CI −12.8 to −1.4).

Conclusions:  The Home and School Support project managed to reduce the number of excluded days and the appearance of mental health symptoms for pupils who engaged fully with the intervention. The project also highlights the importance of multi‐agency involvement at a very early stage.
Coping Strategies Employed by Adolescents with Gambling Problems
Authors: Gupta Rina , Derevensky Jeffrey , Marget Nancy
Published: July 2004

Background:  This study explored the relationship between coping styles, gambling behaviours and substance use amongst adolescents.

Method:  Five hundred and eighty‐seven students, aged 12 to 17, volunteered to participate and completed all scales. Participants completed a gambling screen (DSM‐IV‐J), coping scale (CISS), and a questionnaire developed to assess types and patterns of gambling behaviours (GAQ).

Results:  The results suggest that those youths who gamble excessively exhibit coping styles that are more emotion based, avoidant, and distraction‐oriented.

Conclusions:  The results suggest a need to teach high‐risk youth more effective active coping strategies in order to minimise their potential for engaging in addictive behaviours. Such efforts should form a substantial part of school‐based prevention initiatives.
Need for Child Mental Health Consultation and Paediatricians’ Perception of these Services: A Survey in the West Midlands
Authors: Slowik Michael , Noronha Sandra
Published: July 2004

Background:  High rates of psychopathology have been noted in children presenting to GP surgeries and paediatricians. However, paediatricians do not always recognise this and when they do the Child and Adolescent Mental Health Service (CAMHS) is often unable to meet their consultation needs.

Method:  This postal survey looked at paediatricians’ perception of the need for child psychiatry consultation in the West Midlands.

Results:  The survey confirmed that paediatricians see a significant proportion of children with mental health problems and the findings showed that their need for child psychiatry consultation was not being adequately met. Lack of access to CAMHS was a significant issue.

Conclusions:  This has implications not only for further development of consultation services within CAMHS but also for improving training in child psychiatry for paediatricians in a more formalised way.
The Classification of Soiling and Encopresis and a Possible Treatment Protocol
Authors: Murphy Shona , Carney Terri
Published: July 2004

Background:  It is proposed that the classification of paediatric bowel elimination disorders is central to their effective treatment.

Method:  By separating the terms soiling and encopresis and clearly defining the aetiologies behind both, a treatment pathway begins to emerge.

Results:  The theoretical model described suggests that encopresis may require only psychological management, whereas soiling (caused by constipation) is more complex, and although it needs medical management, it may or may not require psychological input.

Conclusions:  By using such a functional classification to define a treatment protocol, the roles of both medical and psychological services could be more clearly understood from the outset.
School‐Based Open Access Parenting Programmes: Factors Relating to Uptake
Authors: Rooke Oliver , Thompson Margaret , Day Crispin
Published: July 2004

Background:  Many parents of children with conduct problems do not seek professional help.

Method:  A new questionnaire examining the beliefs about the problem behaviour, together with the Strengths and Difficulties Questionnaire, was administered to all parents of five reception year classes. They were then invited to attend school based group parent training.

Results:  Attendance was associated with the beliefs that there was potential for change and the child's behaviour adversely affecting the parent, but not with the child's behaviour adversely affecting the child.

Conclusions:  These findings may be of use when devising promotion for parent training.
Induction of oral immune regulation towards liver‐extracted proteins for treatment of chronic HBV and HCV hepatitis: results of a phase I clinical trial
Authors: Israeli Eran , Safadi Rifaat , Melhem Alaa , Pappo Orit , Shibolet Oren , Klein Athalia , Hemed Nilla , Thalenfeld Barbara , Engelhardt Dean , Rabbani Elazar , Ilan Yaron
Published: July 2004

Abstract:  Background: Anti‐viral immunity can be modulated via oral feeding of viral proteins. Hepatitis B and C viral (HBV, HCV)‐associated hepatocellular injury is mediated by a defective host anti‐viral immune response.

Aims: To determine the effect of oral administration of a mixture of liver‐extracted proteins with HBV/HCV proteins, on viral load, liver injury, and the anti‐viral T‐cell response of chronic HBV/HCV patients.

Methods: Fourteen patients with chronic HBV and 15 patients with chronic HCV were treated orally with hepatocyte‐extracted proteins and HBV or HCV viral proteins for 24 weeks, and followed for an additional 26 weeks. Patients were monitored for HBV‐DNA or HCV‐RNA levels, liver enzymes and liver histology. Viral‐directed T‐cell immunity was assessed by IFNγ and IL10 ELISPOT, viral‐specific T‐cell proliferation, cytotoxicity, and cytokines assays, and followed for peripheral natural killer T‐cell (NKT) number.

Results: In both chronic HBV and HCV patients, oral administration of a mixture of selected liver‐extracted proteins and viral proteins induced a favorable increase in viral‐specific T‐cell proliferation, and IFNγ‐secreting clones, along with a significant decrease in the anti‐viral IL10‐secreting T‐cell clones. However, the effects of modulation of the anti‐viral immunity differed between the HBV and HCV patients. In both groups, no major adverse events were noted. In chronic HBV patients, a significant decrease in viral load was observed in 5/14 (35.7%) of patients. HB surface antigen/HB nucleocapsid antigen scores on liver biopsy improved in 46.1% and 50%, respectively, and the histological necroinflammatory score improved in 4/13 (30.7%). Forty percent of the patients with elevated liver enzymes showed a favorable biochemical response. In contrast, an improvement in the histological necroinflammatory score was observed in only 2/12 (17%) of the chronic HCV patients. No significant decrease in HCV RNA was noted in any of these patients.

Conclusions: Immune regulation of the anti‐HBV/HCV immune response via oral administration of a mixture of liver‐extracted and viral proteins significantly altered the viral‐specific immunity. This effect was associated with clinical and virological improvements in chronic HBV patients.
Lowering of Oxidative Stress in Hemodialysis Patients by Dialysate Cleaning: in Relation to Arteriosclerosis
Authors: Oka Yoshinari , Miyazaki Masashi , Takatsu Shigeko , Kunitomo Kei‐ichi , Kokumai Yoshiaki , Matsuda Hiroaki , Maruyama Masanobu
Published: July 2004

Abstract:  The objective of this study was to investigate changes in oxidative stress associated with the cleaning of the dialysate. Thirty‐six dialysis patients were studied. Changes in soluble CD‐14 (sCD‐14), malondialdehyde‐low‐density lipoprotein (MDA‐LDL), and oxidized‐LDL (Ox‐LDL) were monitored for 1 year before and 1 year after dialysate cleaning. The mean endotoxin (ET) level in the dialysate had previously been confirmed to decrease from 39.0 EU/L to an undetectable level after the cleaning. The mean levels of sCD‐14, MDA‐LDL, and Ox‐LDL decreased significantly after the cleaning (sCD‐14, P < 0.0001; MDA‐LDL, P < 0.001; Ox‐LDL, P < 0.001). One year after the cleaning, six cases still showed high levels of MDA‐LDL and Ox‐LDL. Cardiovascular events occurred in four of those six cases within 2.8 years after the cleaning. These four patients suffered from strong oxidative stress during dialysis, even after the cleaning. We therefore concluded that high levels of MDA‐LDL and Ox‐LDL are improved in dialysis patients by cleaning of the dialysate. These results indicate that even a dialysate containing 50 EU/L or less ET may stimulate monocytes and cause oxidative stress. They also suggest that even low levels of ET may aggravate arteriosclerosis in dialysis patients. Thus, in order to prevent cardiovascular events in dialysis patients, it is necessary to purify the dialysate.
Comparison of the Effects of Angiotensin Receptor Antagonist, Angiotensin Converting Enzyme Inhibitor, and their Combination on Regression of Left Ventricular Hypertrophy of Diabetes Type 2 Patients on Recent Onset Hemodialysis Therapy
Authors: Suzuki Hiromichi , Kanno Yoshihiko , Kaneko Keiko , Kaneko Masaharu , Kotaki Syuhei , Mimura Taku , Takane Hiroshi
Published: July 2004

Abstract:  Left ventricular hypertrophy (LVH) is frequently found at the initiation of dialysis therapy of diabetic and hypertensive patients, and is highly predictive of future cardiac morbidity and mortality. In patients with hypertension and LVH, both an angiotensin converting enzyme (ACE) inhibitor and an angiotensin type 1 receptor (AT1) antagonist regress LVH. However, it remains controversial whether dual blockade of the renin–angiotensin system will regress LVH in these patients using a combination of ACE inhibitor and AT1 antagonist. Thirty‐three type II diabetic patients with end‐stage renal disease who had just entered into hemodialysis therapy and were diagnosed as having LVH evaluated by echocardiography were selected from three dialysis units staffed by the faculty of Saitama Medical School, Saitama, Japan between 1999 and 2001. The study was carried out for 1 year. All patients were assigned randomly to three groups with equal number: group I, an ACE inhibitor, enalapril 10 mg daily; group II, an AT1 antagonist, losartan 100 mg daily; group III, combination of enalapril 10 mg and losartan 100 mg daily. All antihypertensive drugs were given 30 min after the cessation of dialysis therapy. LVH was evaluated by echocardiography before the start of administration of drugs, at 6 months and 12 months after the start of drug therapy. Systolic blood pressure levels less than 140 mmHg were the target for the three groups. Using repeated measures analysis of variance, applied to those with four echocardiograms, there were progressive decreases over time in left ventricular mass index, posterior wall thickness and interventricular septum thickness. There were no significant differences in regression of LVH as well as blood pressure control between enalapril and losartan groups; however, dual blockade induced an additional 28% reduction in left ventricular mass index compared with any type of monotherapy. Both ACE inhibitors and AT1 antagonists benefit the regression of LVH in diabetic patients who start dialysis therapy. Moreover, combination therapy with ACE inhibitors and AT1 antagonists would provide more beneficial effects on LVH in these patients than monotherapy.
Autosomal Recessive Hypercholesterolemia in Three Sisters with Phenotypic Homozygous Familial Hypercholesterolemia: Diagnostic and Therapeutic Procedures
Authors: Thomas Hans‐Peter , Vogt Anja , Wilund Kenneth R. , Schliesser Clemens , Steinhagen‐Thiessen Elisabeth , Kassner Ursula
Published: July 2004

Abstract:  Familial hypercholesterolemia is an autosomal‐dominant inherited disorder caused by mutations in the low‐density lipoprotein (LDL) receptor gene. The homozygous form is characterized by high‐serum LDL cholesterol concentrations, xanthoma formation and premature atherosclerosis. Recently, another molecular defect that also results in severely elevated LDL cholesterol levels was identified: autosomal recessive hypercholesterolemia. This inherited disorder is caused by a mutation in a putative LDL receptor adaptor protein. In our lipid clinic, three sisters with phenotypic homozygous hypercholesterolemia were recently diagnosed as having autosomal recessive hypercholesterolemia. They presented in 1990 with massive tuberous xanthomas at the knees, thighs, elbows and buttocks. LDL receptor and apolipoprotein B gene defects were excluded through mutation analysis. From 1992 onward they underwent LDL‐apheresis on a weekly basis. To date the clinical outcome is very satisfying with no evidence of coronary heart disease or aortic valve lesions  and  almost  complete  regression  of  xanthomatosis.
Measurement of Translymphatic Fluid Absorption Using Technetium‐99m Human Serum Albumin Diethylenetriamine Pentaacetic Acid in Continuous Ambulatory Peritoneal Dialysis Patients
Authors: Terawaki Hiroyuki , Nakayama Masaaki , Seto Kazuhiko , Yoshimura Kazunobu , Hasegawa Toshio
Published: July 2004

Abstract:  We have established a new method of measuring translymphatic fluid absorption (TLA) using technetium‐99m (99mTc) human serum albumin diethylenetriamine pentaacetic acid (99mTc‐HSAD) that can be used commonly in clinical practice. This new method was applied in 13 continuous ambulatory peritoneal dialysis patients (11 males and two females) who had various peritoneal permeability and capacities for peritoneal transport of water. 99mTc‐HSAD 740MBq was injected in 2 L of peritoneal dialysis fluid with 2.5% glucose, mixed well, and administered intraperitoneally. The fluid was drained extraperitoneally after 4 h and TLA was determined by the in vivo loss of 99mTc‐HSAD. TLA was 1.41 ± 1.11 mL/min (mean ± SD; range, 0.27–3.69 mL/min). The estimated reduction rate by TLA in trans‐peritoneally removed fluid ranged from 14.2 to 84.4%, indicating that TLA could have an extremely significant negative effect in some cases on total drainage volume. The present study, using new tracer 99mTc‐HSAD, could confirm a large individual difference in TLA, indicating TLA as an important contributing factor for fluid‐removal failure in continuous ambulatory peritoneal dialysis  patients.
Increased Serum Osteoprotegerin Level in Older and Diabetic Hemodialysis Patients
Authors: Doi Shigehiro , Yorioka Noriaki , Masaki Takao , Ito Takafumi , Shigemoto Kenichiro , Harada Satoru
Published: July 2004

Abstract:  Osteoprotegerin is a circulating osteoclastogenesis inhibitory factor and serum osteoprotegerin levels are elevated in hemodialysis patients. This study investigated whether osteoprotegerin levels correlated with various clinical parameters in hemodialysis patients. The subjects were 45 men and 37 women aged from 27 to 94 years (mean = 60.4 ± 13.9 years), and the duration of dialysis was 9–277 months (mean = 89.5 ± 64.7 months). Serum osteoprotegerin levels were measured by enzyme‐linked immunosorbent assay. Data were analyzed by stepwise multiple regression analysis. The mean osteoprotegerin level of the hemodialysis patients was 303 ± 210 pg/mL, which was higher than in age‐matched healthy controls. Osteoprotegerin levels increased with age, a longer duration of dialysis, and the presence of diabetes. Skeletal resistance to parathyroid hormone might be increased by aging, a long dialysis period, and diabetes, perhaps explaining why adynamic bone disease is more common in older or diabetic patients.
Thyroid Storm‐induced Multiple Organ Failure Relieved Quickly by Plasma Exchange Therapy
Authors: Kokuho Toshiharu , Kuji Tadashi , Yasuda Gen , Umemura Satoshi
Published: July 2004

Abstract:  We report a 54‐year‐old female patient in whom thyroid storm was improved dramatically by plasma exchange. The patient presented with tachycardia, high fever and pulmonary congestion, in addition to left hemiparalysis and dysarthria. Serum thyroid hormone concentrations were markedly increased and computed tomography showed a fresh cerebral infarct, suggesting that she had thyroid storm precipitated by cerebral infarction. As there was no remarkable improvement even after 24 h of conventional therapy, plasma exchange was carried out using fresh frozen plasma. Consequently, her critical condition improved quickly. The half‐life of thyroid hormones is so long that quick improvement is not always achieved even by sufficient doses of antithyroid drugs. Thus, plasma exchange in combination with conventional therapy appears to be effective in relieving the life‐threatening state in our patient with thyroid storm precipitated by acute cerebral infarction.
Clinical Usefulness of a New Hepatitis C Virus RNA Extraction Method Using Specific Capture Probe and Magnetic Particle in Hemodialysis Patients
Authors: Tanaka Motoko , Fujiyama Shigetoshi , Tanaka Motohiko , Itoh Kazuko , Matsushita Kazunori , Matsushita Kazutaka , Matsuyama Kazuhiro , Kakuda Hirokazu , Tomita Kimio
Published: July 2004

Abstract:  Hemodialysis patients are a high‐risk group for hepatitis C virus (HCV) infection. Assessment of HCV infection using HCV‐RNA assay among dialysis patients is important for the issue of safety and environmental protection. However, polymerase chain reaction (PCR)‐based methods are unsuitable for analyzing samples from dialysis patients because the conventional centrifugal extraction method fails to eliminate heparin, a potent inhibitor of PCR. In this study, we evaluated the usefulness of a HCV‐RNA extraction method using probes and magnetic particles for hemodialysis patients in comparison with the centrifugal method. The study population consisted of 17 HCV antibody‐positive patients undergoing hemodialysis. These 17 patients consisted of 12 HCV carrier patients and five patients with past HCV infection. One hundred and two samples from these patients were measured using the centrifugal and magnetic methods. Moreover, we prepared five standards that included theoretically 5 KIU/mL of HCV. One was made from non‐HD patient's serum and the other four were from hemodialysis patients’ serum. These standards were measured using the two methods. False‐negative results were not observed with the magnetic method, but were observed in five out of 102 samples with the centrifugal method. Studies using standard samples revealed that accurate HCV‐RNA measurement is achieved using the magnetic method. In conclusion, the present study showed that this magnetic extraction method is a highly reproducible and reliable assay to obtain correct information about the presence of the infective virus itself in the hemodialysis setting. Precise identification of HCV‐RNA using this specific method is considered to be useful in preventing HCV infection in hemodialysis units.
Efficacy and Safety of DALI‐LDL‐Apheresis in Two Patients Treated with the Angiotensin II‐Receptor 1 Antagonist Losartan
Authors: Bosch Thomas , Wendler Thorsten
Published: July 2004

Abstract:  Direct adsorption of lipids (DALI) is the first low‐density lipoprotein (LDL)‐apheresis technique capable of adsorbing LDL and lipoprotein (a) directly from whole blood. The adsorber consists of negatively charged polyacrylate ligands linked to a Eupergit matrix. Negatively charged ligands give rise to activation of bradykinin, which is rapidly degraded by the angiotensin converting enzyme (ACE). Thus, angiotensin converting enzyme inhibitors are contraindicated in DALI‐LDL‐apheresis. This is the first paper to describe the efficacy and safety of DALI‐LDL‐apheresis in patients treated with 50 mg of the angiotensin II‐receptor 1 antagonist (ARA) losartan. Two hypercholesterolemic patients were treated for 79 patient months with weekly or biweekly DALI sessions (N = 221 sessions). Approximately 1.4 patient blood volumes were treated per session. Acute reductions of LDL‐cholesterol (63%) and lipoprotein (a) (62%) exceeded 60% and laboratory safety parameters remained in the apheresis typical range. Mean bradykinin plasma levels peaked in the efferent line post‐adsorber at 1000 mL of treated blood volume; 467 fmol/mL (N = 6 sessions) in the ARA‐treated patients and 671 fmol/mL (N = 9 sessions) in a control group of three DALI patients without ARA medication (P = 0.69, n.s.). Clinically, the DALI sessions for the ARA‐treated patients were completely uneventful and blood pressure was not significantly different in the two groups. In summary, according to this retrospective pilot study, DALI‐LDL‐apheresis was shown for the first time to be safe and effective in patients on ARA medication.
Kidney Disease Quality of Life of Japanese Dialysis Patients Who Desire Administration of Sildenafil and the Treatment of Erectile Dysfunction Using Sildenafil
Authors: Hyodo Toru , Ishida Hironori , Masui Noriaki , Taira Takayasu , Yamamoto Sumiko , Oka Michiyo , Uchida Toyoaki , Endo Tadao , Sakai Tadasu , Yoshida Kazunari , Baba Shiro
Published: July 2004

Abstract:  Erectile dysfunction (ED) is common among patients on dialysis therapy. In the present study, we attempted administration of sildenafil to Japanese patients undergoing dialysis. In order to diagnose ED before prescribing sildenafil, we assessed the hemodialysis patients who desired sildenafil by using the five items version of the International Index of Erectile Function (IIEF‐5). In addition, the characteristics of the quality of life in Japanese hemodialysis patients who desired sildenafil were assessed using the kidney disease quality of life (KDQOL). To all 37 male subjects (mean age of 53.8 ± 10.4 years) attending the Outpatient Hemodialysis Unit at Atsugi Clinic (Atsugi City, Japan), it was explained by their primary doctor that the treatment of ED with sildenafil was possible. As a result, 10 patients (27.0%) desired the treatment. For eight patients, ED was diagnosed by IIEF‐5 prior to prescription of sildenafil. The mean IIEF‐5 scores were 6.13 ± 4.67 points. Sildenafil was prescribed to five patients (three diabetic, two non‐diabetic) and sexual function was improved in three cases. The main adverse effect was found to be ventricular arrhythmia in one case. As for KDQOL, the group desiring sildenafil showed significantly high values in Dialysis Staff Encouragement and Patient Satisfaction. Among the other nine dialysis patients (five diabetic, four non‐diabetic; mean age of 58.1 ± 8.9 years) who visited the ED department of Ishida Hospital (Asahikawa City, Japan), sildenafil was effective for all non‐diabetic patients (100%) and for only one diabetic patient (20%). Among all 14 patients at Atsugi Clinic and Ishida Hospital, sildenafil efficacy rates were 83.3% for non‐diabetic patients and 37.5% for diabetic patients. Non‐diabetic patients without the side‐effects were all responders for the sildenafil treatment. The patients who relied on the dialysis staff and were more satisfied with the general treatment in the dialysis institute desired the administration of sildenafil under the present circumstances wherein the dialysis population had few experiences of sildenafil treatment. Diabetic status is thought to be a negative factor for the response of sildenafil treatment in dialysis patients.
Effect of Post‐transplant Double Filtration Plasmapheresis on Recurrent Focal and Segmental Glomerulosclerosis in Renal Transplant Recipients
Authors: Otsubo Shigeru , Tanabe Kazunari , Shinmura Hiroaki , Ishikawa Nobuo , Tokumoto Tadahiko , Hattori Motoshi , Ito Katsumi , Nitta Kosaku , Akiba Takashi , Nihei Hiroshi , Toma Hiroshi
Published: July 2004

Abstract:  In the present study, we reviewed the effect of post‐transplant double filtration plasmapheresis (DFPP) on recurrent focal segmental glomerulosclerosis (FSGS) in the transplanted kidney allograft. Sixteen patients with post‐transplant recurrent FSGS were enrolled in this study. Out of 16 patients with recurrent FSGS after transplantation, five did not receive DFPP and lost their grafts, while 11 did receive DFPP and four of these patients lost their grafts. Seven patients were able to maintain normal renal function for an average observation period of 57.1 ± 40.7 months (range 7–125 months). In five patients who had a significant reduction in urinary protein after DFPP, the urinary protein level decreased from 26.60 ± 23.05 g/day (range 3.34–62.6 g/day) to 2.95 ± 3.42 g/day (range 0.02–8.64 g/day) and renal function was maintained. The beneficial effects of DFPP on graft outcome were more likely to occur if the patients experienced a marked drop in urinary excretion. Thus, post‐transplant DFPP appears to be effective for reducing urinary protein levels and improving long‐term graft survival. With the small numbers in this trial, however, none of the findings were statistically significant. We recommend the use of post‐transplant DFPP to prevent  the  progression  of recurrent FSGS.
Immunoadsorption in Lupus Myocarditis
Authors: Griveas Ioannis , Sourgounis Aggelos , Visvardis Georgios , Zarifis Ioannis , Kyriklidou Parthena , Sakellariou Georgios
Published: July 2004

Abstract:  Reduction of pathological autoantibodies may be useful in the treatment of systemic lupus erythematosus (SLE). On the other hand clinically manifested myocarditis in SLE, though uncommon, may be life‐threatening and its pathogenesis has been ascribed to autoimmunity. The aim of this study is to present a rare case of a patient with severe lupus myocarditis, where immunoadsorption (IA) was evaluated as rescue therapy. A case of SLE with initial manifestation of myocarditis is reported in a 29‐year‐old male who presented with arthritis, fever, lymphadenopathy, joint swelling and morning stiffness. Laboratory evaluation revealed increased antinuclear antibody (ANA), slightly decreased complement and positive anticoagulant panel. From the above clinical and laboratory features, criteria of SLE seemed applicable. During his hospitalization, the patient developed pericardial effusion and cardiogenic shock. Although pericardiotomy was performed and was treated with immunosuppressive agents, plasmapheresis and supported with current medications, his clinical condition remained critical with an ejection fraction of 20%. At this point it was decided to receive IA onto staphylococcal protein A. After 6 sessions with IA and concomitant immunosupppression, the patient responded well, his condition improved and was dismissed with an ejection fraction of 50%. Fulminant lupus myocarditis is a severe and rare situation lacking a satisfying specific therapy available today. In our presented case, IA in addition to immunosuppressive therapy was beneficial. Considering the benefits of our case and the current knowledge, it might be useful to clarify the open question in scale pilot studies.
Polymyxin B‐immobilized Fiber Hemoperfusion after Emergency Surgery in Patients with Chronic Renal Failure
Authors: Tojimbara Tamotsu , Sato Sumihiko , Nakajima Ichiro , Fuchinoue Shohei , Akiba Takashi , Teraoka Satoshi
Published: July 2004

Abstract:  The purpose of this study was to evaluate the effect of direct hemoperfusion using a Polymyxin B (PMX) immobilized fiber column in septic patients with chronic renal failure after emergency surgery. Twenty‐four renal failure patients, including 19 dialysis patients, with sepsis or septic shock were treated with direct hemoperfusion after emergency surgery. The 24 consecutive patients included nine with necrotic enterocolitis, six with colonic perforation due to diverticulitis, three with ruptured suture after colectomy, one with duodenal perforation, four with blood access infection, and one with an infected abdominal aortic aneurysm. The acute physiology and chronic health evaluation II score ranged from 13 to 26 (19 ± 3). After completion of the first and the second hemoperfusion, mean blood pressure was significantly elevated from 69 ± 12 mm Hg to 89 ± 15 mm Hg and from 78 ± 14 mm Hg to 95 ± 13 mm Hg, respectively (P < 0.01). In addition, the catecholamine dosage needed to maintain the circulation could be decreased markedly after the treatment. The blood concentration of endotoxin in patients with Gram‐negative sepsis, before and after the treatment, significantly decreased from 36 ± 19 pg/mL to 19 ± 19 pg/mL (P < 0.05). PMX was effective in patients with Gram‐positive sepsis as well as Gram‐negative sepsis. The 28‐day mortality rate in patients who had emergency abdominal surgery was 10% (2/20), whereas that in patients with dialysis access infection was 50% (2/4). There was a significant difference in the Sequential Organ Failure Assessment (SOFA) score of all patients before and after treatment using PMX (9.2 ± 3.3 vs. 7.5 ± 3.5, P < 0.05). Furthermore, the SOFA score of survivors decreased significantly after PMX treatment (8.4 ± 3.5 vs. 6.7 ± 2.6, P < 0.01). Our results suggest that the early application of PMX may prevent multiple organ failure and improve survival in patients with chronic renal failure and sepsis/septic shock after emergency abdominal surgery, regardless of the type of pathogenic bacteria involved.
Clinical Evaluation of PMX‐DHP for Hypercytokinemia Caused by Septic Multiple Organ Failure
Authors: Ikeda Toshiaki , Ikeda Kazumi , Nagura Masatoshi , Taniuchi Hitoshi , Matsushita Mikiko , Kiuchi Shintarou , Kuroki Yuichi , Suzuki Kaori , Matsuno Naoto
Published: July 2004

Abstract:  Endotoxin‐adsorbing fibers have been applied to treat septic shock patients. The limitations of endotoxin hemoadsorption therapy (PMX‐DHP) and the optimal time to start PMX‐DHP were examined in patients with septic multiple organ failure with hypercytokinemia (interleukin‐6 = 1000 pg/mL). Subjects were separated into those who survived more than 28 days after the start of PMX‐DHP therapy (S group) and those who did not (N‐S group). Severity of symptoms and background factors, blood biochemical parameters, hemodynamic parameters, PaO2/FiO2, pathogens, endotoxin, cytokines, and vascular endothelial cell function‐related markers were examined before and after PMX‐DHP. Number of days from onset of shock (or symptom development) to PMX‐DHP initiation was longer in the N‐S group than in the S group. These results suggest that PMX‐DHP could save more lives in patients with septic multiple organ failure with IL‐6 = 1000 pg/mL when applied early after the onset of shock.
Efficacy and Tolerability of Oral Zolmitriptan in Menstrually Associated Migraine: A Randomized, Prospective, Parallel‐Group, Double‐blind, Placebo‐Controlled Study
Authors: Loder Elizabeth , Silberstein Stephen D. , Abu‐Shakra Susan , Mueller Loretta , Smith Timothy
Published: July 2004

Background.—Approximately 60% of female migraineurs report experiencing migraine in association with menstruation, while 7% to 25% experience attacks almost exclusively with menstruation.

Objective.—To examine the efficacy and tolerability of oral zolmitriptan in the acute treatment of menstrually associated migraine. In this study, menstrually associated migraine was defined as migraine that consistently occurred from 72 hours before to 5 days after onset of menses.

Methods.—Participants were women with regular menstrual cycles, aged 18 to 55 years, who had experienced migraine with at least two thirds of prior menstrual cycles. Subjects were randomized to treat one attack per menstrual cycle for 3 months with either zolmitriptan or placebo. Treatment was intensity based: mild migraines were treated with half of a 2.5‐mg zolmitriptan tablet, moderate migraines were treated with zolmitriptan 2.5 mg, and severe migraines were treated with 5 mg (two 2.5‐mg tablets) of zolmitriptan, or placebo.

Results.—Of the 579 women enrolled in the study, 260 were treated with zolmitriptan and 251 were assigned placebo. Twelve hundred thirty‐two attacks were treated, and a 2‐hour headache response was achieved in 48% of zolmitriptan‐treated attacks as compared with 27% of placebo‐assigned attacks (P < .0001). Zolmitriptan was superior to placebo in achieving a headache response as early as 30 minutes (18% versus 14%, P= .03) and at 1 hour (33% versus 23%, P < .001). Drug‐related adverse events were reported in 16% of subjects receiving zolmitriptan and 9% of subjects receiving placebo.

Conclusion.—Oral zolmitriptan exhibits efficacy and good tolerability in the treatment of menstrually associated migraine. Improvement over placebo was observed as early as 30 minutes following treatment.
Consecutive Transcranial Magnetic Stimulation: Phosphene Thresholds in Migraineurs and Controls
Authors: Young William B. , Oshinsky Michael L. , Shechter Aaron L. , Gebeline‐Myers Cheryl , Bradley Kathleen C. , Wassermann Eric M.
Published: July 2004

Objective.—To characterize the temporal course of transcranial magnetic stimulation‐induced phosphene thresholds in subjects with migraine and in controls.

Methods.—Eleven subjects with migraine with aura, 10 subjects with migraine without aura, 9 subjects with menstrual migraine, and 15 controls (no history of migraine and without migraine during the study) were studied. Subjects were not on preventive medication. Transcranial magnetic stimulation was performed, and a phosphene threshold was measured 3 times a week over 3 weeks in a manner timed to incorporate the menstrual period in females. A headache calendar was kept during the study.

Results.—Mean transcranial magnetic stimulation thresholds were lower for each migraine group compared with controls (P < .001) for each comparison. There was a trend for lower thresholds among subjects with migraine with aura compared with subjects with migraine without aura (P < .10), but not subjects with menstrual migraine. There was consistent lowering of thresholds from the first to the last stimulation in all migraine groups and in the controls. Maximum and minimum thresholds did not predict headache occurrence, nor did the occurrence of headache predict an ensuing maximum or minimum phosphene threshold.

Conclusions.—Transcranial magnetic stimulation thresholds are lower in subjects with migraine compared with controls. The reported phosphene threshold is lowered with repeated measurement. Neither high nor low phosphene thresholds predict a subsequent headache, nor do migraines predict a subsequent high or low threshold.