bluuebunny/crossref_metadata_2025 huggingface dataset:
Antidiabetic Potentiality of the Aqueous‐Methanolic Extract of Seed of Swietenia mahagoni (L.) Jacq. in Streptozotocin‐Induced Diabetic Male Albino Rat: A Correlative and Evidence‐Based Approach with Antioxidative and Antihyperlipidemic Activities
Authors: De Debasis , Chatterjee Kausik , Ali Kazi Monjur , Bera Tushar Kanti , Ghosh Debidas
Published: September 2010

Antidiabetic, antioxidative, and antihyperlipidemic activities of aqueous‐methanolic (2 : 3) extract of Swietenia mahagoni (L.) Jacq. (family Meliaceae) seed studied in streptozotocin‐induced diabetic rats. Feeding with seed extract (25 mg 0.25 mL distilled water−1100 gm b.w.−1rat−1 day−1) for 21 days to diabetic rat lowered the blood glucose level as well as the glycogen level in liver. Moreover, activities of antioxidant enzymes like catalase, peroxidase, and levels of the products of free radicals like conjugated diene and thiobarbituric acid reactive substances in liver, kidney, and skeletal muscles were corrected towards the control after this extract treatment in this model. Furthermore, the seed extract corrected the levels of serum urea, uric acid, creatinine, cholesterol, triglyceride, and lipoproteins towards the control level in this experimental diabetic model. The results indicated the potentiality of the extract of S. mahagoni seed for the correction of diabetes and its related complications like oxidative stress and hyperlipidemia. The extract may be a good candidate for developing a safety, tolerable, and promising neutraceutical treatment for the management of diabetes.
Continuous Production of Lipase‐Catalyzed Biodiesel in a Packed‐Bed Reactor: Optimization and Enzyme Reuse Study
Authors: Chen Hsiao-Ching , Ju Hen-Yi , Wu Tsung-Ta , Liu Yung-Chuan , Lee Chih-Chen , Chang Cheng , Chung Yi-Lin , Shieh Chwen-Jen
Published: September 2010

An optimal continuous production of biodiesel by methanolysis of soybean oil in a packed‐bed reactor was developed using immobilized lipase (Novozym 435) as a catalyst in a tert‐butanol solvent system. Response surface methodology (RSM) and Box‐Behnken design were employed to evaluate the effects of reaction temperature, flow rate, and substrate molar ratio on the molar conversion of biodiesel. The results showed that flow rate and temperature have significant effects on the percentage of molar conversion. On the basis of ridge max analysis, the optimum conditions were as follows: flow rate 0.1 mL/min, temperature 52.1∘C, and substrate molar ratio 1 : 4. The predicted and experimental values of molar conversion were 83.31 ± 2.07% and 82.81 ± .98%, respectively. Furthermore, the continuous process over 30 days showed no appreciable decrease in the molar conversion. The paper demonstrates the applicability of using immobilized lipase and a packed‐bed reactor for continuous biodiesel synthesis.
A Grounded Theory Study of Homeopathic Practitioners′ Perceptions and Experiences of the Homeopathic Consultation
Authors: Eyles Caroline , Leydon Geraldine M. , Lewith George T. , Brien Sarah
Published: September 2010

Research into the homeopathic consultation has largely focused on patients’ experiences, although the practitioner is a crucial component of the therapeutic context and may have an important part in optimizing health outcomes. Therefore the aim of this qualitative research was to gain an in‐depth understanding of homeopathic practitioners’ perceptions and experiences of the consultation. Medical and non‐medical homeopaths were sampled from the registers of the Faculty and Society of Homeopaths. Two phases of data collection were employed. Phase 1 used in depth face‐to‐face interviews enabling the development of an initial model of the homeopathic consultation. Phase 2 involved observations of homeopathic consultations and practitioner reflective diaries in order to confirm, refute, or enlarge the model. Using the constant comparative method of grounded theory five main categories emerged, exploring the journey, finding the level, responding therapeutically, understanding self, and connecting, forming a model entitled “a theoretical model of a UK classical homeopathic consultation” which describes how homeopaths view and enact the consultation process. This study suggests that the process of identifying and prescribing the remedy is embedded in the consultation, highlighting the interconnectedness of the whole homeopathic consultation and aspects of the consultation that are unique and specific to homeopathy.
Thirteenth AACR Special Conference on Cancer Epigenetics
Authors: Ross Jason P. , Molloy Peter L.
Published: September 2010

The 13th American Association of Cancer Research (AACR) Special Conference on Cancer Epigenetics was held in San Juan, Puerto Rico, on January 20–23, 2010. This event heralded insights arising from the large sequencing efforts within the NIH Epigenetics Roadmap Project and the Cancer Genome Atlas Project, as well as important new discoveries in the basic biology of epigenetics and results of epigenetic drug clinical trials. A summary of the recent findings is presented here, with particular emphasis on the major themes of the conference. Cancer Res; 70(19); 7372–8. ©2010 AACR.
Trigeminal and Spinal Dorsal Horn (Dis)continuity and Avian Evolution
Authors: Wild J. Martin , Krützfeldt Nils O.E. , Altshuler Douglas L.
Published: September 2010

The organization of the dorsal horn in the avian spinal cord differs in different species. For instance, in pigeons and doves, cranes, cuckoos, songbirds, ratites and tinamous, the dorsal horn is organized in laminar fashion, such that laminae II and III are sandwiched between lamina I dorsally and lamina IV ventrally, as they are in mammals and other nonavian amniotes. In most other avian species, including chickens, however, the organization of the dorsal horn is not strictly laminar, in that the structures homologous to laminae II and III lie side by side rather than in dorsoventral order. Because spinal and trigeminal dorsal horns are generally thought to be continuous, the question arises as to the organization of the trigeminal dorsal horn in these species. We examined this question in chickens, first by defining II and III of trigeminal and spinal dorsal horns using calcium-binding protein immunohistochemistry, and second by determining the caudal extent of the projections of the three branches of the trigeminal nerve using injections of cholera toxin B chain. It was found (1) that the trigeminal dorsal horn and the spinal dorsal horn of the first 2 cervical segments are organized in laminar fashion, but further caudally, II and III in the spinal dorsal horn gradually come to be arranged side by side and (2) that the descending trigeminal tract terminates no further caudal than the 3rd spinal segment. Therefore, unlike spinal nerves, trigeminal nerve branches do not project to II and III, once these cease to be organized in laminar fashion. These findings imply some kind or organizational discontinuity of trigeminal and spinal dorsal horns in the chicken and perhaps in other species with a side-by-side arrangement of II and III. It has also been suggested that the condition in which the spinal dorsal horn structures homologous to laminae II and II lie side by side may define a novel clade of birds. This suggestion was reexamined within the context of a modern phylogenetic framework based on 32 kb of nuclear DNA, and using a parsimony reconstruction of dorsal horn character states. The original suggestion of a novel clade was not supported. Instead, it appears that the side-by-side condition evolved very early in the radiation of Aves and that independent reversion to a laminar dorsal horn condition has evolved at least 4–5 times.
Alpha-Crystallin Promotes Rat Retinal Neurite Growth on Myelin Substrates in vitro
Authors: Wang Yan Hua , Wang Dong Wu , Wu Nan , Wang Yi , Yin Zheng Qin
Published: September 2010

Background: Myelin-associated molecules are major impediments to axon regeneration after optic nerve injury. Intravitreal injection of α-crystallin can protect axons from optic nerve degeneration after crushing in rats. Objectives: Our purpose was to investigate whether α-crystallin could counteract the inhibitory effect of myelin and promote neurite growth. Methods: Newborn rat retinal neurons were cultured on myelin-coated dishes with DMEM containing α-crystallin (10–4 g/l) or bovine serum albumin. The density of neurons with neurites and the length of the longest neurite of the cells were analyzed on days 1, 3 and 5. Results: Cultures containing α-crystallin had significantly higher neurite-containing cell densities, and the neurites were significantly longer compared with cultures containing bovine serum albumin. These findings indicated that α-crystallin could counteract the effect of myelin inhibitory factors and stimulate neurite growth.
On the Origin and Evolution of the Tripartite Brain
Authors: Hirth Frank
Published: September 2010

The many different nervous systems found in bilaterally symmetric animals may indicate that the tripartite brain appeared several times during the course of bilaterian evolution. However, comparative developmental genetic evidence in arthropods, annelids, urochordates, and vertebrates suggests that the development of a tripartite brain is orchestrated by conserved molecular mechanisms. Similarities in the underlying genetic programs do not necessarily reflect a common origin of structures. Nevertheless, 3 lines of evidence support a monophyletic origin of the tripartite brain and possibly also an elongated central nervous system (CNS): structural homology, character identity networks, and the functional equivalence of character identity genes. Monophyly of the brain also implies that the brain was secondarily reduced and lost multiple times during the course of evolution, leading to extant brainless bilaterians. The likelihood of secondary loss can be estimated by metazoan divergence times and through reconstructed cases such as limb loss in tetrapods or eye loss in fish. When scaled to molecular clock dates, monophyly of the tripartite brain indicates that existing brainless Bilateria had several hundred million years’ time for the secondary modification and eventual loss of a primitive/ancestral brain and CNS. To corroborate this conjecture, ancestral character identity genes of living brainless Bilateria can be tested for their potential to substitute Drosophila or Mus homologs in tripartite brain development.
Capsule and Balloon Endoscopy: When Are They Really Needed in Patients with Inflammatory Bowel Diseases?
Authors: Herfarth Hans H. , Long Millie D.
Published: September 2010

The evaluation of the small bowel in patients with suspected or established IBD is generally performed by radiologic techniques. Capsule endoscopy and balloon enteroscopy may offer additional advantages in the evaluation of small bowel inflammation in patients with suspected small bowel involvement but negative prior radiologic evaluation. This review summarizes the current clinical status of capsule and balloon enteroscopy in patients with suspected or established IBD.
Epstein-Barr Virus, Lymphoma Risk and the Potential Role of HIV Infection in IBD Patients Undergoing Immunosuppression
Authors: Weinstock David M.
Published: September 2010

For decades, lymphoma has been considered a dreaded and untoward complication of autoimmune disorders, including inflammatory bowel disease (IBD). Yet until recently, the data linking inflammatory bowel disease with an increased risk for lymphoma has been equivocal. With the publication of the CESAME trial in 2009, a greater understanding of lymphoma risk has begun to emerge. In this Falk Symposium paper, I discuss the available data from studies that interrogated the relationship between lymphoma and IBD, thiopurines and TNFα-directed agents. While recent data has clarified some aspects of lymphoma epidemiology in patients with IBD, causality and the mechanisms that underlie it remain very poorly understood.
How Rapidly Should Remission Be Achieved?
Authors: Isaacs Kim L.
Published: September 2010

The major goal of therapy in inflammatory bowel disease is to induce remission. Remission has multiple definitions – clinical remission, where the patient’s symptoms have remitted, and endoscopic remission, in which there has been complete mucosal healing. Mucosal healing is a harder endpoint of remission but may be more difficult to achieve. In clinical trials we are forced to use activity indices such as the Crohn’s disease activity index that may not completely reflect the endoscopic and histologic state of the bowel. Ideally we would like to see remission as quickly as possible to improve patient quality of life. The time to remission varies between different therapeutic approaches. Steroids tend to have a rapid clinical effect with remission seen in some patients as early as two weeks. In early anti-TNF trials, a single dose of infliximab lead to 27% remission at two weeks compared to 4% of placebo patients. Adalimumab and certolizumab have similar reports of early induction of remission. Mesalamine in Crohn’s disease has inconsistent and delayed remission rates, whereas in ulcerative colitis, response and remission rates are more consistent in the three-week time frame. Azathioprine and 6-mercaptopurine have delayed onset of action but may induce remission as early as six weeks if dosing is optimized. In this presentation induction of clinical remission and mucosal healing in Crohn’s disease and ulcerative colitis will be discussed. The impact of early remission on disease course will also be reviewed.
Importance of Ferritin for Optimizing Anemia Therapy in Chronic Kidney Disease
Authors: Nakanishi Takeshi , Kuragano Takahiro , Nanami Masayoshi , Otaki Yoshinaga , Nonoguchi Hiroshi , Hasuike Yukiko
Published: September 2010

The clinical significance of serum ferritin in monitoring the iron status of patients on maintenance hemodialysis (MHD) has become suspected. In this review, we reassess the interpretation of high serum ferritin values in such patients, with the goal of treating their anemia in a safe way. From the observations that (1) H-ferritin gene transcription is predominantly active in inflammatory conditions, whereas L-ferritin is induced only after exposure to very high iron concentrations and is preferentially secreted to plasma from hepatocytes; (2) the expression of both types of ferritin proteins are exclusively dependent on intracellular free iron, which is often sequestered by LPS or cytokines in several cell types, and (3) splenic iron is depleted and serum ferritin does not increase in the combined conditions of both inflammation and iron deficiency, it is deduced that elevated serum ferritin levels are caused by the accumulation of intracellular iron, especially reticuloendothelial cells or macrophages, hepatocytes, and other cells, while cytokines or inflammation might modulate the relative ratio of ferritin to body iron storage. Therefore, high levels of serum ferritin in patients on MHD can be used to indicate iron deposition in most cells, including vascular and immunocompetent cells, and is still a reliable indicator of the need to withhold iron administration.
Leukoaraiosis Predicts Poor Outcome after Spontaneous Supratentorial Intracerebral Hemorrhage
Authors: Won Yu Sam , Chung Pil-Wook , Kim Yong Bum , Moon Heui-Soo , Suh Bum-Chun , Lee Yong Taek , Park Kwang-Yeol
Published: September 2010

Background and Aims: Leukoaraiosis (LA) is associated with aging and vascular risk factors, and is a risk factor of intracerebral hemorrhage (ICH) after treatment with warfarin or thrombolytic treatment for ischemic stroke. In this study, we sought to examine whether LA is a predictor of outcome after spontaneous ICH. Methods: We retrospectively analyzed 238 consecutive patients with spontaneous supratentorial ICH identified by a database search. Patients were divided into two groups according to neurological outcome at 90 days: patients with good outcomes (Glasgow Outcome Scale ≧4) and patients with poor outcomes. Demographic features, ICH characteristics, and LA severity as assessed by van Swieten score on brain CT were compared between the two groups. Results: Overall, 105 (44.1%) of the patients analyzed had poor outcomes. In univariate analysis, LA severity, ICH volume on initial brain CT, initial Glasgow Coma Scale (GCS), presence of intraventricular hemorrhage (IVH), old age, surgical treatment, and higher admission serum glucose level were associated with poor outcome. Multiple logistic regression analysis showed that severity of LA, initial GCS score, hematoma volume, presence of IVH, and surgical treatment were independent predictors of poor outcome. Conclusion: LA is an independent predictor of poor neurological outcome in patients with spontaneous supratentorial ICH.
The Dialectics of Chauvinism: Minority Nationalities and Territorial Sovereignty in Mao Zedong’s New Democracy
Authors: Howland Douglas
Published: September 2010

This article examines Mao Zedong’s theory of new democracy in order to explicate the relationship between minority nationalities and sovereignty within the state system of the People’s Republic of China. It argues that the position of minority nationalities in China has been overdetermined by territorial sovereignty in the identification of the Chinese peoples, with the result that minority nationalities are fixed within China because of the imperialist framework of the contemporary international order. Chinese government policy remains bound by a contradiction between imperialism and socialism, a dialectic that has created and determines the dialectics of chauvinism— that contradiction between the Han majority and the minority nationalities.
Further Remarks on Stochastic Damage Evolution of Brittle Solids Under Dynamic Tensile Loading
Authors: Mastilovic S.
Published: September 2010

This article illuminates some general features and provides elementary interpretations of the deformation, damage, and failure of brittle solids characterized by very low fracture energy. The dynamic response of these materials is determined to a large extent by stochastic and random factors. The investigation emphasis is on the moderate-to-extremely high rate range (10 s-1, 1 × 109 s-1), explored under practically identical in-plane stress conditions. The statistical approach is based on repeated particle dynamics simulations for different physical realizations of micromechanical disorder of a 2D brittle discrete system. The proposed strategy is computationally intensive, which necessitates simplicity of the laws governing the interparticular interaction. Based on the simulation results, an expression is proposed to model the mean tensile strength dependence on the strain rate. The linearity of the rate dependence of the stress-peak macroscopic response parameters is observed and discussed.
Facilitative interaction between angiotensin II and oxidised LDL in cultured human coronary artery endothelial cells
Authors: Mehta Jawahar L , Dayuan Li
Published: September 2010

Background Several studies have shown that angiotensin II (Ang II) and oxidised low-density lipoprotein (ox-LDL) are critical factors in atherosclerosis. In this study, we examined the molecular basis of mutually facilitative interactions between Ang II and ox-LDL in human coronary artery endothelial cells (HCAECs).

Methods and results We observed that incubation of cultured HCAECs with Ang II (10-12 to 10-6 M) for 24 hours caused a concentration-dependent increase in the expression of mRNA and protein of a specialised receptor for ox-LDL (LOX-1). These effects of Ang II were completely blocked by pretreatment of HCAECs with candesartan (10-6 M), a specific AT1-receptor blocker, but not by PD 123319 (10-6 M), a specific AT2-receptor blocker. On the other hand, incubation of HCAECs with ox-LDL (10 and 40 µg/ml) for 24 hours progressively upregulated AT1-, but not AT 2-, receptor mRNA and protein. Pretreatment of cells with the anti-oxidant alpha-tocopherol (1—5 x 10-6 M) inhibited the upregulation of AT1-receptor expression induced by ox-LDL (p<0.05). To determine the significance of expression of AT1-receptors and LOX-1, we measured cell injury in response to Ang II and ox-LDL. Incubation of cells with both ox-LDL and Ang II synergistically increased cell injury, measured as cell viability and LDH release, compared with either ox-LDL or Ang II alone (both p<0.05). Alpha-tocopherol, as well as candesartan, attenuated cell injury in response to Ang II and ox-LDL (both p<0.05).

Conclusions These observations show that Ang II upregulates a novel endothelial receptor for ox-LDL (LOX-1) gene expression and ox-LDL in turn upregulates Ang II AT 1receptor gene expression. This interaction between Ang II and ox-LDL further augments cell injury in HCAECs. These findings provide basis for the use of AT1-receptor blockers and anti-oxidants in designing therapy for atherosclerosis and myocardial ischaemia.
Prevention of atherosclerosis by specific AT1-receptor blockade with candesartan cilexetil
Authors: Papademetriou Vasilios , Mammillot Philippe , Redman Robert , Notargiacomo Aldo , Narayan Puneet , Lakshman Raj
Published: September 2010

Several studies indicate that blockade of the renin-angiotensin-aldosterone system (RAAS) can prevent atherosclerosis and vascular events, but the precise mechanisms involved are still unclear. In this study, we investigated the effect of the AT 1-receptor blocker, candesartan, in the prevention of atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits and also the effect of AT1-receptor blockade in the uptake of oxidised LDL by macrophage cell cultures. In the first set of experiments, 12 WHHL rabbits were randomly assigned to three groups: placebo, atenolol 5 mg/kg daily or candesartan 2 mg/kg daily for six months. Compared with controls and atenolol-treated rabbits, candesartan treatment resulted in a significant 50—60% reduction of atherosclerotic plaque formation and a 66% reduction in cholesterol accumulation in the thoracic aorta.

Studies in macrophage cultures indicated that candesartan prevented uptake of oxidised LDL-(oxLDL)-cholesterol by cultured macrophages. Candesartan inhibited the uptake of oxLDL in a dose-dependent manner, reaching a maximum inhibition of 70% at concentrations of 5.6 µg/ml. Further studies in other animal models and well-designed trials in humans are warranted to further explore the role of AT1-receptor blockade in the prevention of atherosclerosis.
Candesartan prevents L-NAME-induced cardio-renal injury in spontaneously hypertensive rats beyond hypotensive effects
Authors: Casellas Daniel , Herizi Abderraouf , Artuso Annie , Mimran Albert , Jover Bernard
Published: September 2010

Our goal was to assess the cardiovascular and renal protection afforded by angiotensin II type 1-receptor blockade against NG-nitro-L-arginine methyl ester (L-NAME)-exacerbated hypertension in young spontaneously hypertensive rats (SHR), in comparison with the antihypertensive drug, hydralazine. Male SHR were assigned to four groups (n=8 per group): no treatment (controls); L-NAME-treated group (20 mg/kg/day, 10 days, orally); co-treatment with L-NAME and hydralazine (15 mg/kg/day, by gavage); co-treatment with L-NAME and candesartan cilexetil (10 mg/kg/day, by gavage), i.e. at a dose that inhibited acute pressor responses to 5—20 ng angiotensin II. One animal died in the L-NAME group, and tail-cuff systolic blood pressure (SBP) increased significantly compared with controls to 201±5 mmHg. Albumin excretion increased 235-fold in L-NAME-treated rats. Heart weight index averaged 3.5±0.1 and 3.8±0.1 mg/g body weight (p<0.05) in control and L-NAME rats, respectively, indicating moderate cardiac hypertrophy induced by L-NAME. Preglomerular vascular lesions affected 63±6% of interlobular arteries and 10±2% of afferent arterioles (vs. 8±3 and 0.8±0.4% in controls, respectively). Hydralazine and candesartan cilexetil treatment similarly reduced SBP to 153±7, and 165±6 mmHg, respectively. However, candesartan provided more protection, in terms of no significant change in albuminuria (vs. 25-fold increase with hydralazine), regression of cardiac hypertrophy, frequency of vascular lesions and histological indices of renal injury maintained within control values. In conclusion, candesartan cilexetil prevented L-NAME-exacerbated hypertension and associated cardio-renal injury in young SHR, the beneficial effects exceeding those of hydralazine.
Persistent effect of treatment with candesartan cilexetil on blood pressure in spontaneously hypertensive rats
Authors: Skov Karin , Mogensen Susie , Mulvany Michael J
Published: September 2010

We have investigated whether the angiotensin II type-1 (AT1) receptor antagonist, candesartan cilexetil, has a persistent effect on blood pressure even after withdrawal of treatment, as has been shown consistently for angiotensin-converting enzyme inhibitors (ACE-1). Spontaneously hypertensive rats (SHR) were divided into four groups (n=16 per group) and treated with candesartan cilexetil (high-dose: 5 mg/kg/day; middle-dose: 1 mg/kg/day; low-dose: 0.5 mg/kg/day) or control from age four weeks to 20 weeks. Normotensive Wistar-Kyoto rats (WKY) were also investigated. The drug was given in the drinking water, the concentration adjusted for water consumption and rat weight. Blood pressure (BP) was measured regularly by the indirect tail-cuff method during the treatment period and after treatment, from age 20 weeks to 32 weeks.

At age 20 weeks, candesartan treatment had caused a slight reduction in body weight, an increase in water consumption and a reduction in heart rate. During treatment, candesartan caused a dose-dependent reduction in BP. After withdrawal of treatment, BP increased but remained lower than that of untreated control SHR for the medium- and high-dose groups throughout the follow-up period, the reduction being 8—11% at the end of follow-up. At age 32 weeks, there was no significant difference between the three candesartan-treated groups.

We conclude that treatment with the AT1-receptor antagonist candesartan has a modest persistent effect on BP after withdrawal of treatment.
Use of angiotensin II receptor blockers alone and in combination with other drugs: a large clinical experience trial
Authors: Weir Matthew R , Wang Rebecca Y
Published: September 2010

Angiotensin II (Ang II) receptor blockers are the newest class of antihypertensive drugs to be developed. No large-scale clinical trials have been performed to evaluate their efficacy alone, or in combination with other drugs. A large-scale, eight week, open-label, non-placebo-controlled, single-arm trial evaluated the efficacy, tolerability and dose-response of candesartan cilexetil, 16—32 mg once-daily, either as monotherapy or as part of combination therapy, in a diverse hypertensive population in actual practice settings. 6465 patients with high blood pressure, of whom 52% were female and 16% African American, with a mean age of 58 years, were included. 5446 patients had essential hypertension and 1014 patients had isolated systolic hypertension. In order to be included in this study, patients had either untreated or uncontrolled hypertension (systolic blood pressure (SBP) 140—179 mmHg and/or diastolic blood pressure (DBP) 90—109 mmHg inclusive at baseline), despite a variety of other antihypertensive drugs. Of the 5156 patients with essential hypertension and at least one post baseline efficacy measurement, the mean pretreatment blood pressure (BP) was 156/97 mmHg. Candesartan cilexetil monotherapy reduced mean SBP/DBP by 18.0/12.2 mmHg. Similarly, in the 964 patients with isolated systolic hypertension and at least one post baseline efficacy measurement, candesartan cilexetil monotherapy reduced SBP/DBP from 158/81 by 16.5/4.5 mmHg. Candesartan cilexetil was similarly effective when employed as add-on therapy. When added to baseline antihypertensive medication in 51% of the patients with essential hypertension not achieving BP control, additional reduction in BP was achieved regardless of the background therapy, including diuretics (17.8/11.7 mmHg) calcium antagonists (16.6/11.2 mmHg), beta-blockers (16.5/10.4 mmHg), angiotensin-converting enzyme inhibitors (ACE-I) (15.3/10.0 mmHg), and alpha blockers (16.4/10.4 mmHg). Likewise, when candesartan cilexetil was used as add-on therapy in patients with isolated systolic hypertension, there was a consistent further reduction of mean SBP/DBP, regardless of the background therapy. Moreover, these monotherapeutic or add-on efficacy benefits were seen regardless of age (<65 or >65 years), gender, or race. Despite the open-label design of the study which enhances efficacy owing to the placebo effect, the Ang II receptor blocker, candesartan cilexetil either alone, or as an add-on therapy, is highly effective for assisting in the control of systolic and diastolic hypertension.
Interim report: Review of evidence of the health impact of famine in Ethiopia
Authors: Taye A. , Haile Mariam D. , Murray V.
Published: September 2010

Historical accounts of famines in Ethiopia go as far back as the 9th century, however, evidence on its impact on health only started to emerge from the 15th century onwards. Unfortunately, famine has been endemic in Ethiopia in the last few decades. The 1973 famine is reported to have claimed over 300,000 lives. In 1985 approximately 10 million people were reported to be starving, with approximately 300,000 already dead and about 1,000 dying daily. In the following years, droughts leading to food shortage have had local and national adverse health effects, in particular in 1999/2000. This paper describes the initial findings of a literature review of evidence on the health impact of droughts leading to famine in Ethiopia and highlights gaps in knowledge. The key finding, thus far, is the marked paucity of health impact data. This review also highlights the fact that adverse health impacts of famines are probably complex and long lasting. Interpretation of any health impact data is difficult as there are few baseline data to compare. Health effects also impact livelihoods. Livelihood disruption following famine does not just affect one generation but also subsequent generations. Surveillance systems are needed so that records of the health impacts of a drought that leads to famine can inform action. With climate change bringing increased likelihood of drought and famine in some parts of the world, the findings of this review could be beneficial not just for Ethiopia but also elsewhere.
Impact of An Evidence Based Prenatal Care Model on Patient Outcomes
Authors: Lewallen Lynne Porter , Jarrett-Pulliam Cindy , Dixon Kelly Herger
Published: September 2010

Health care providers face many challenges when providing prenatal care. This article reports on a program called Prenatal Care: the Beginning of a Lifetime (PCBL), to implement standardized prenatal care in central North Carolina. The purpose of this pilot study was to determine if there were differences in patient outcomes between a control group and 3 groups (A, B, and C) of increasing levels of intervention in standardized prenatal care. A total of 150 patients were enrolled and followed through delivery. There were no significant differences between the groups in cigarette smoking status, weight gain, genetic screening, sexually transmitted infection screening, diabetes screening, domestic violence assessment, 17P candidacy assessment, gestational age at delivery, or infant birth weight. However, a significant difference was found in depression screening. An association between intervention group membership and likelihood of being screened for depression was found in each trimester. As the level of intervention increased, the number of participants screened for depression increased significantly.
Exploring the Role of Body Mass Index on Balance Reactions and Gait in Overweight Sedentary Middle-aged Adults
Authors: Southard Veronica , Dave Arti , Douris Peter
Published: September 2010

Background/Purpose: Being overweight is defined as having a body mass index greater than 25. Reduced postural control has been implicated in the presence of increased body mass index. The purpose of this study was to assess the effects of body mass index on postural stability in healthy sedentary middle-aged adults. Based on body mass index, subjects were divided into 2 groups (25.00-27.49 and 27.50-29.99) to assess for differences in postural control. Methods: Twenty healthy sedentary subjects between 40 and 64 years (13 women and 7 men) with a mean age of 52.45 years were recruited by convenience. After determination of body mass index, postural control was assessed on all subjects using the Activities Specific Balance Confidence Scale, Berg Balance Scale, Timed Up and Go Test, gait speed measurement, and Biodex Stability Index testing. Results: The Timed Up and Go Test duration was increased in these subjects when compared with normative data. Gait speed was also reduced in those subjects in the fifth and sixth decades when compared with established norms. Biodex SD balance system scores demonstrated reduced postural stability. A 2-tailed t test revealed no significant difference between body mass index ranges of 25.0 to 27.5 and 27.6 to 29.99. Conclusion: There may be increased risk for falls with increases in body mass short of obesity thresholds of body mass index 30% for this sedentary middle-aged adult population. Future studies, with larger groups of subjects, that address postural stability and body mass index are necessary. Although these subjects are younger, falls screening measures may prove beneficial as a prevention strategy for sedentary overweight middle-aged adults.
Efficient differentiation of human pluripotent stem cells into functional CD34+ progenitor cells by combined modulation of the MEK/ERK and BMP4 signaling pathways
Authors: Park Sang-Wook , Jun Koh Young , Jeon Jongwook , Cho Yun-Hee , Jang Mi-Jin , Kang Yujung , Kim Min-Jeong , Choi Chulhee , Sook Cho Yee , Chung Hyung-Min , Young Koh Gou , Han Yong-Mahn
Published: September 2010

Differentiation of human pluripotent stem cells (hPSCs) into functional cell types is a crucial step in cell therapy. In the present study, we demonstrate that functional CD34+ progenitor cells can be efficiently produced from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) by combined modulation of 2 signaling pathways. A higher proportion of CD34+ cells (∼ 20%) could be derived from hPSCs by inhibition of mitogen-activated protein kinase (MAPK) extracellular signal-regulated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling and activation of bone morphogenic protein-4 (BMP4) signaling. hPSC-derived CD34+ progenitor cells further developed to endothelial and smooth muscle cells with functionality. Moreover, they contributed directly to neovasculogenesis in ischemic mouse hind limbs, thereby resulting in improved blood perfusion and limb salvage. Our results suggest that combined modulation of signaling pathways may be an efficient means of differentiating hPSCs into functional CD34+ progenitor cells.
Three novel beta-galactosidase gene mutations in Han Chinese patients with GM1 gangliosidosis are correlated with disease severity
Authors: Yang Chi-Fan , Wu Jer-Yuarn , Tsai Fuu-Jen
Published: September 2010

Background

GM1 gangliosidosis (GM1) is an autosomal recessive lysosomal storage disease caused by deficiency of acid beta-galactosidase (GLB1; EC3.2.1.23). Here, we identify three novel mutations in the GLB1 gene from two Han Chinese patients with GM1 that appear correlated with clinical phenotype.

Methods

One of the two Han Chinese patients with GM1 presented with the juvenile form, and the other with the infantile form with cardiac involvement. Sequencing of the entire GLB1 gene revealed three novel mutations (p.H102 D, p.G494V, c.495_497delTCT), which were absent in 94 normal controls. Transient expression of cDNA encoding these variants was performed in COS-1 cells to evaluate β-galactosidase activities.

Results

The first case (patient 1) with the juvenile form contained two missense mutations, p.H102 D and p.A301V. Patient 2 diagnosed with the infantile form of the disease with cardiac involvement was compound heterozygous for p.G494V and c.495_497delTCT mutations. All mutant beta-galactosidases exhibited significantly reduced activity (12%, 0%, 0%, and 0% for p.H102 D, p.A301V, p.G494V, and c.495_497delTCT), compared with the wild-type beta-galactosidase cDNA clone. The mutations identified in patient 2 with cardiomyopathy were localized in the GLB1 gene region common to both lysosomal beta-galactosidase and elastin binding protein (EBP), and caused a deletion in the elastin-binding domain of EBP.

Conclusions

All four mutations identified in Han Chinese patients induce significant suppression of β-galactosidase activity, correlating with severity of disease and presence of cardiomyopathy.
Clinical significance of Polycomb gene expression in brain tumors
Authors: Crea Francesco , Hurt Elaine M , Farrar William L
Published: September 2010

Polycomb group (PcG) proteins are crucial for neural cancer stem cell (NCSC) self-renewal. However, the relative expression levels of PcG genes in different subtypes of brain tumors, their prognostic role and their effects on cellular pathways have not been investigated. For this purpose, we queried the Oncomine database and found that 4 PcG genes (EZH2, RBBP7, SUZ12, YY1) are specifically expressed in brain tumors. EZH2 expression increases with tumor grade in adult and pediatric brain tumors, and is a poor prognostic factor. In glioblastoma, EZH2 inhibits differentiation, and activates cancer-, cell cycle- and cellular movement-related genes. In keeping with previously published data, our results suggest that EZH2 is both a prognostic factor and a promising therapy target in brain tumors.
Disability in people clinically at high risk of psychosis
Authors: Velthorst Eva , Nieman Dorien H. , Linszen Don , Becker Hiske , de Haan Lieuwe , Dingemans Peter M. , Birchwood Max , Patterson Paul , Salokangas Raimo K. R. , Heinimaa Markus , Heinz Andreas , Juckel Georg , von Reventlow Heinrich Graf , French Paul , Stevens Helen , Schultze-Lutter Frauke , Klosterkötter Joachim , Ruhrmann Stephan
Published: September 2010

Background

Decline in social functioning occurs in individuals who later develop psychosis.

Aims

To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition.

Method

Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS–II).

Results

At baseline, the transition group displayed significantly greater difficulties in making new friends (z =−3.40, P = 0.001), maintaining a friendship (z =−3.00, P = 0.003), dealing with people they do not know (z =−2.28, P = 0.023) and joining community activities (z =−2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (β = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238–2.550).

Conclusions

Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.
Factors influencing the decision to use hanging as a method of suicide: qualitative study
Authors: Biddle Lucy , Donovan Jenny , Owen-Smith Amanda , Potokar John , Longson Damien , Hawton Keith , Kapur Nav , Gunnell David
Published: September 2010

Background

Hanging is the most frequently used method of suicide in the UK and has high case fatality (>70%).

Aims

To explore factors influencing the decision to use hanging.

Method

Semi-structured qualitative interviews with 12 men and 10 women who had survived a near-fatal suicide attempt. Eight respondents had attempted hanging. Data were analysed thematically and with constant comparison.

Results

Hanging was adopted or contemplated for two main reasons: the anticipated nature of a death from hanging; and accessibility. Those favouring hanging anticipated a certain, rapid and painless death with little awareness of dying and believed it was a ‘clean’ method that would not damage the body or leave harrowing images for others. Materials for hanging were easily accessed and respondents considered it ‘simple’ to perform without the need for planning or technical knowledge. Hanging was thus seen as the ‘quickest’ and ‘easiest’ method with few barriers to completion and sometimes adopted despite not being a first choice. Respondents who rejected hanging recognised it could be slow, painful and ‘messy’, and thought technical knowledge was needed for implementation.

Conclusions

Prevention strategies should focus on countering perceptions of hanging as a clean, painless and rapid method that is easily implemented. However, care is needed in the delivery of such messages as some individuals could gain information that might facilitate fatal implementation. Detailed research needs to focus on developing and evaluating interventions that can manage this tension.
Alternative futures for the DSM revision process: iterationv.paradigm shift
Authors: Kendler Kenneth S. , First Michael B.
Published: September 2010

Two major approaches can be used for the up-coming revisions of DSM–V and ICD–10: an ‘iterative model’ in which incremental changes are made or a ‘paradigm shift model’ in which the existing approach is jettisoned in favour of a new nosological model. We explore each of these two approaches and conclude that although they both have strengths and limitations, our field is not currently ready for a paradigm shift.
Treatment with antipsychotics and the risk of diabetes in clinical practice
Authors: Kessing Lars Vedel , Thomsen Anders Frøkjær , Mogensen Ulla Brasch , Andersen Per Kragh
Published: September 2010

Background

Treatment with antipsychotics seems to increase the risk of developing diabetes but the association is poorly characterised in clinical practice.

Aims

To investigate and characterise the incidence of diabetes for people treated with antipsychotic medication in clinical practice.

Method

The study used the linkage of registers of all prescribed antipsychotics, antidiabetics and diagnoses of diabetes in Denmark during a period from 1996 to 2005 and identified all people treated with antipsychotics in Denmark and a random sample of about 30% of the total Danish population.

Results

In total, 345 937 patients who purchased antipsychotics and 1 426 488 unexposed individuals were included in the study. Among the total population, 50 379 individuals subsequently developed incident diabetes. Compared with unexposed individuals, treatment with first- (rate ratio, RR = 1.53, 95% CI 1.49–1.56) as well as second-generation (RR = 1.32, 95% CI 1.22–1.42) antipsychotics was associated with increased risk of subsequent incident diabetes. The rate of incident diabetes varied substantially between individual second-generation antipsychotic drugs (olanzapine, risperidone clozapine compared with unexposed individuals: low to moderate rate ratio between 1.17 and 1.57; ziprasidone and sertindol: two or more times increased rate ratio; amisulpride, quetiapine and aripiprazole: no significantly increased rate ratio). For both first- and second-generation antipsychotics, the incidence of diabetes increased with the number of prescriptions. Additionally, the incidence of diabetes increased with the number of combined antipsychotic drugs.

Conclusions

In clinical practice, treatment with first- and second-generation antipsychotics is associated with an increased risk of developing incident diabetes with large differences between individual drugs. The risk increases with the duration of treatment and with polypharmacy of antipsychotic drugs.
Cyclic variations in demand for out-of-hours services in child and adolescent psychiatry: implications for service planning
Authors: Hillen Thomas , Szaniecki Eduardo
Published: September 2010

Aims and method

We examined peaks and troughs in demand for out-of-hours consultations and assessments in child and adolescent psychiatry and whether these have implications for service development. All out-of-hours referrals in three teaching hospitals providing services to a large and diverse inner-city population were prospectively registered from 1 January 2002 to 31 December 2005.

Results

In total, 323 individuals under 18 years were referred; 21.6 (95% CI 19.3-24.0) per 100 000 general population per year. Bedside assessments were required in 37%, the remainder were dealt with by telephone. The work took more than 4 h for 22%; 46% of individuals presenting were aged 16-18 years. Significant diurnal variation was observed with a peak in referrals between 17.00 h and 00.59 h. More referrals were made when daytime liaison services were closed (odds ratio (OR) = 2.46, 95% CI 1.15-1.87), after referral pathways had been clarified (OR = 2.33, 95% CI 1.92-3.23) and during spring (OR = 1.50, 95% CI 1.14-1.98). Other factors analysed showed no association with referral activity.

Clinical implications

Cyclic variations in the demand for out-of-hours services in child and adolescent psychiatry should be considered for service planning. Although paediatric psychiatric emergencies are relatively rare, they can take up considerable clinician time.
Written information on bipolar affective disorder: the patients' perspective
Authors: White Daniel C. , Schelten Sofia Laureano , Kelly Brendan D. , Casey Patricia
Published: September 2010

Aims and method

The mental health information available to people with bipolar affective disorder is variable in quality. We conducted a qualitative survey in an urban out-patient department to elicit the opinions of people with bipolar affective disorder on the written information provided by three health information providers.

Results

Participants' responses were generally positive for each leaflet. The two leaflets rated highest by participants used quality assurance tools. However, 20-30% had difficulty understanding the leaflets. Medical jargon and verbosity were common criticisms.

Clinical implications

Professional bodies such as the Royal College of Psychiatrists play an important role in providing patients with written information. Quality assurance standards should be used in the production of patient information. A tool measuring individuals' appraisal of information may ensure information is appropriate to their requirements.
Assessing the security needs of patients in medium secure psychiatric care in Northern Ireland
Authors: McClean Rowan James
Published: September 2010

Aims and method

To determine the security needs of patients in medium secure services in Northern Ireland and to identify those requiring long-term secure care. Patients were rated on the Security Needs Assessment Profile.

Results

Fifteen patients (45%) could be managed in conditions of low security. Twelve patients (36%) require over 5 years' further treatment in secure care. Particular security needs include relational nursing skills, restricted access to alcohol and drugs, and robust physical security.

Clinical implications

This study should be replicated across the UK to determine whether forensic services are responding to patients' needs. Pathways out of medium security need to be better developed, with regional expansion of low secure services.
Involuntary treatment in the community: role of community treatment orders
Authors: Woolley Sarah
Published: September 2010

Although community treatment orders (CTOs) have been used internationally since the 1980s, they were only introduced into England and Wales in 2007 by amendments to the 1983 Mental Health Act. Aimed to replace the common use of extended Section 17 leave to enforce community treatment, CTOs are believed to offer patients more protection owing to stringent criteria for their use. Literature reviews, however, do not demonstrate any evidence favouring the use of CTOs and in this age of evidence-based medicine it is questionable whether psychiatrists will change from a familiar practice to an unproven one.