bluuebunny/crossref_metadata_2025 huggingface dataset:
The process of teacher education for inclusion: the Maltese experience
Authors: Bartolo Paul A.
Published: August 2010

This paper discusses major challenges for the development of teacher education for inclusion through an analysis of relevant recent experience in Malta. Inclusion in society and in education has been explicitly on the Maltese national agenda for the past two decades. The Faculty of Education of the University of Malta has been one of the main actors of the inclusion initiative and has also taken a European initiative through the recent co‐ordination of a seven‐country, 3‐year European Union Comenius project on preparing teachers for responding to student diversity. This paper is based mostly on the reflective experience of the author at the Faculty of Education over the past several years. A brief picture of the Maltese education system is followed by a description of the challenges that have been encountered in the promotion of inclusion. These include the development of a rights‐based approach to the education of persons with disability and the widening of its application to all minority or disadvantaged groups, and the impact of political and social contexts on the development of inclusive schools. These developments are then related to intertwined initiatives for teacher education for diversity that were further influenced by the leadership of deans and heads of the department in the faculty of education. Finally, four current issues are highlighted, namely: the strategic balance between the education of specialist educators and that of all teachers for diversity, and between specific and infusion models for such education, and, finally, the pedagogic balance between the academic and experiential learning about inclusion, and between the theory and practice of inclusive teaching.
Key challenges for Latvian teachers in mainstream schools: a basis for preparing teachers for inclusion
Authors: Nimante Dita , Tubele Sarmite
Published: August 2010

This paper analyses current research in Latvia to identify key issues related to inclusive education, special education and social pedagogy. A review of Latvian literature since 2004 was undertaken to determine what is known about special and inclusive education, how it is reflected in various research papers and how it related to the current situation in schools. Key findings suggest that teachers need to be better informed about the potential of inclusion. They need to be prepared to teach children with diverse educational needs in a changing educational landscape. Teacher education for inclusion is identified as a 21st‐century priority in Latvia.
The influence of a fast ramp rate on peak cardiopulmonary parameters during arm crank ergometry
Authors: Castro Renata R. T. , Pedrosa Sabrina , Chabalgoity Fernanda , Sousa Eduardo B. , Nobrega Antonio C. L.
Published: August 2010

The influence of a very fast ramp rate on cardiopulmonary variables at ventilatory threshold and peak exercise during a maximal arm crank exercise test has not been extensively studied. Considering that short arm crank tests could be sufficient to achieve maximal oxygen consumption (VO2), it would be of practical interest to explore this possibility. Thus, this study aimed to analyse the influence of a fast ramp rate (20 W min−1) on the cardiopulmonary responses of healthy individuals during a maximal arm crank ergometry test. Seventeen healthy individuals performed maximal cardiopulmonary exercise tests (Ultima CardiO2; Medical Graphics Corporation, St Louis, USA) in arm ergometer (Angio, LODE, Groningen, The Netherlands) following two protocols in random order: fast protocol (increment: 2 w/6 s) and slow protocol (increment: 1 w/6 s). The fast protocol was repeated 60–90 days after the 1st test to evaluate protocol reproducibility. Both protocols elicited the same peak VO2 (fast: 23·51 ± 6·00 versus slow: 23·28 ± 7·77 ml kg−1 min−1; P = 0·12) but peak power load in the fast ramp protocol was higher than the one in the slow ramp protocol (119 ± 43 versus. 102 ± 39 W, P < 0·001). There was no other difference in ventilatory threshold and peak exercise variables when 1st and 2nd fast protocols were compared. Fast protocol seems to be useful when healthy young individuals perform arm cardiopulmonary exercise test. The usefulness of this protocol in other populations remains to be evaluated.
Peak cardiac power output in healthy, trained men
Authors: Schlader Zachary J. , Mündel Toby , Barnes Matthew J. , Hodges Lynette D.
Published: August 2010

Previous investigations into peak cardiac power output (CPO peak) have been limited to clinical populations and healthy, but non‐athletic adults, and normative data on trained individuals would allow a greater understanding of this parameter. Therefore, we recruited eight healthy, well‐trained male cyclists. Peak oxygen consumption ( peak) was assessed using an incremental ergometer test, and following a 40‐min recovery period, peak cardiac output (T peak) was measured during a constant load test that elicited peak (±5%) using the Defares CO2 rebreathing technique. CPO peak was calculated as described by Cooke et al. (1998). Mean (±SD) values during the constant load test were: peak, 4·94 ± 0·41 l min−1; T peak, 36·5 ± 3·7 l min−1; mean arterial pressure, 123 ± 8 mmHg and CPO peak, 9·9 ± 1·0 W. These results demonstrate CPO peak in a well‐trained population to be approximately twice those observed in healthy, but non‐athletic adults. The current data provide useful information regarding the upper limits and possible ‘trainability’ of cardiac pumping capacity for sedentary and clinically compromised individuals.
Epidermal growth factor receptor as a therapeutic target in veterinary oncology
Authors: Bergkvist G. T. , Yool D. A.
Published: August 2010

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that stimulates cell proliferation and survival and becomes dysregulated in a range of solid tumours in man. It is recognized as a key oncogenic driver and has become a favoured therapeutic target and a prognostic and predictive marker of cancer in man. In animals, EGFR dysregulation is emerging as a potential factor in the development of a number of naturally occurring tumours including mammary, lung, glial and epithelial cancers. Comparative analyses suggest that these diseases share many features with equivalent diseases in man and EGFR may have value as a prognostic or a biological marker of animal disease. There is still little direct evidence that EGFR is a critical oncogenic driver in naturally occurring animal disease and there are no veterinary trials of EGFR‐targeted therapy. These will be critical steps in establishing a role for EGFR in veterinary oncology.
PROFESSIONAL STOCK‐TAKING
Authors: MAXTON JOHN P.
Published: August 2010

When the subject of this paper was chosen, it was intended to open a discussion at the Summer Conference at Oxford. For that purpose, a great deal could have been left to be raised in discussion, points clarified, and possible misunderstandings removed. It is a subject clearly more suitable for the atmosphere of intimate discussion than for that of emphatic presentation. The Conference was cancelled, but the writer was asked to make the paper available for publication– without its anticipated discussion. As a result, the liberty has been taken of extending its length far beyond the legitimate limits of a Conference paper in order that the points which could otherwise have been left to oral discussion might be more fully amplified in the initial presentation.
Knemometry in Children with Atopic Dermatitis Treated with Topical Glucocorticoids
Authors: Heuck Carsten , Ternowitz Thomas , Herlin Troels , Wolthers Ole D.
Published: August 2010

Abstract: Recently the knemometer, a lower leg length measuring device, has been introduced for sensitive assessment of systemic activity of exogeneous glucocorticoids in children. The aim of this study was to assess by means of knemometry whether the topical glucocorticoid budesonide affects short‐term growth in children with atopic dermatitis. Fourteen children 5 to 12 years old were studied in an open longitudinal trial with three periods of 2 weeks duration. In periods 1 (run‐in) and 3 (run‐out), the children were treated with emollient. In period 2, budesonide cream 0.025% was followed by emollient twice daily to all of the body except the face. Eczema was evaluated according to a score based on extent and activity. Knemometry was performed twice weekly. Compared to the run‐in and run‐out periods the mean growth rate during budesonide treatment was reduced by 0.11 mm/wk (p > .05) and 0.40 mm/wk (p < .05), respectively. The mean growth rate during run‐out was increased by 0.29 mm/wk as compared to run‐in (p < .05). Compared to run‐in the mean severity indices during budesonide treatment and runout were reduced by 1.55 (p < .05) and 1.55 points (p <.05), respectively. The concomittant variations in lower leg growth rate and disease activity suggest that short‐term treatment with topical glucocorticoids may provide a better growth potential during the weeks after withdrawal of the treatment. Whether this is due to improved disease control needs further study. Being a noninvasive method, knemometry may be useful for comparing different topical glucocorticoids and administration regimens in children in whom vasoconstrictor assays are difficult.
A New Variant of Trichothiodystrophy with Recurrent Infections, Failure to Thrive, and Death
Authors: Petrin James H. , Meckler Kenneth A. , Sybert Virginia P.
Published: August 2010

Abstract: Two brothers demonstrated a severe variant of trichothiodystrophy. Both had brittle hair, developmental delay with severe failure to thrive, recurrent infections, cataracts, and angioendotheliomas of the liver at autopsy. The elder died at 12 weeks, the younger at 6 months. The younger had the typical appearance of banded hair on polarizing microscopy and a low cystine content measured by ion exchange chromatography. The history, clinical findings, and basic defects of trichothiodystrophy are discussed.
Petechial Gloves and Socks Syndrome Caused by Parvovirus B19
Authors: Saulsbury Frank T.
Published: August 2010

Abstract: This report describes a 14‐year‐old boy with petechial gloves and socks syndrome associated with acute parvovirus B19 infection. This represents only the second child reported with this distinctive exanthem.
Adams‐Oliver Syndrome with Unusual Central Nervous System Alterations
Authors: Romaní Jorge , Puig Lluís , Aznar Gemma , Demestre Xavier , Altirriba Orenci , Alomar Agustin
Published: August 2010

Abstract: The association of aplasia cutis congenita of the scalp with distal malformations of the limbs is known as Adams‐Oliver syndrome. Other reported associations include palatine or auricular malformations, cardiovascular alterations, and spina bifida. Multiple hereditary patterns have been described for this condition, and sporadic cases have also been reported. We report an infant with Adams‐Oliver syndrome associated with intracranial calcifications in whom no evidence of intrauterine infection could be demonstrated.
Childhood Vitiligo Successfully Treated with Bath PUVA
Authors: Mai David W. , Omohundro Craig , Dijkstra Jacob W. E. , Bailin Philip L.
Published: August 2010

Abstract: A significant proportion of vitiligo patients are children. Systemic PUVA therapy, the most consistently effective and practical therapy for this disease, has not been recommended in pediatric patients because of concerns regarding potential long‐term side effects. We report a 9‐year‐old Caucasian girl with progressive vitiligo who was successfully treated with bath PUVA. This form of PUVA therapy may provide a wider margin of safety, in that less exposure to ultraviolet A (UVA) radiation is required and systemic absorption of psoralen is minimal.
Coexistence of Incontinentia Pigmenti and Neonatal Herpes Simplex Virus Infection
Authors: Stitt W. Zoe D. , Scott Glynis A. , Caserta Mary , Goldsmith Lowell A.
Published: August 2010

Abstract: We present a female infant with classic clinical and histologic features of stage I incontinentia pigmenti with coexistent neonatal herpes simplex virus infection. The diagnosis of a heritable cutaneous condition does not exclude the possibility of a coexistent infection and, given the similar clinical presentation of neonatal vesicular eruptions, accurate diagnoses may require skin biopsy and culture.
Median Raphe Cysts of the Penis: A Report of Five Cases
Authors: Nagore Eduardo , Sánchez‐Motilla Jose M. , Febrer M. Isabel , Aliaga Adolfo
Published: August 2010

Abstract: Cysts of the median raphe are embryologic developmental anomalies of the male genitalia. Although generally present since birth, these lesions tend to manifest in adult life. Histologically the cysts are characterized by a pseudostratified epithelium in the middle dermis. The early age at consultation is a common characteristic in four of the five patients reported herein and is probably due to the growing concern among the general population about skin problems.
Itraconazole Pulse Therapy for Tinea Capitis: A Novel Treatment Schedule
Authors: Gupta Aditya K. , Adam Paul , De Doncker Piet
Published: August 2010

Abstract: Itraconazole 5 mg/kg/day given as pulse therapy, each of 1 week duration, for 1 to 3 pulses appears to be an effective and safe method of treating tinea capitis. The number of pulses of therapy may depend upon several factors, including the severity of disease and area of involvement. Controlled studies are needed to determine the number of pulses of itraconazole required to treat tinea capitis.
Tinea Capitis: Fluconazole in Trichophyton tonsurans Infection
Authors: Mercurio Mary Gail , Silverman Robert A. , Elewski Boni E.
Published: August 2010

Abstract: Tinea capitis is the most common dermatophyte infection in children. Trichophyton tonsurans is the most common etiologic agent in the United States, and for more than four decades the standard therapy has been griseofulvin. The availability of newer, and often more effective, antifungal drugs creates the opportunity for choice and the ability to optimally tailor treatment for a particular patient. Fluconazole is an azole antifungal drug available in a pleasant, well‐tolerated, liquid formulation ideal for the pediatric population. It has a good safety profile and is approved in the United States for use in children, although not for tinea capitis. We present five patients with tinea capitis successfully treated with fluconazole.
Eruptive Collagenomas of the Skin: A Case History
Authors: Downs A. M. R. , Lear J. T. , Condon C. A. , Porter H. , Kennedy C. T. C.
Published: August 2010

Abstract: We present a case of eruptive collagenomas of the skin in a young girl. The typical clinical features and histology of this rare condition are described. The differential diagnosis and other types of cutaneous collagenomas are briefly discussed. A biopsy is required to confirm the excessive mature collagen which predominates in these lesions.
Perianal Striated Muscle Hamartoma Associated with Hemangioma
Authors: Scrivener Y. , Petiau P. , Rodier‐Bruant C. , Cribier B. , Heid E. , Grosshans E.
Published: August 2010

Abstract: Striated muscle hamartoma is a rare entity which was described only recently. It is a congenital malformation characterized by the presence of striated, mature muscle fibers in the reticular dermis and hypodermis. We describe a striated muscle hamartoma of the perianal region in a female infant associated with an hemangioma in the same area that regressed completely. Including the present patient, only 14 cases of striated muscle hamartomas have been reported, but this association with an hemangioma is unique. The lesion was polypoid and histopathologic examination showed numerous striated muscle fibers located within the dermis.
Cutaneous Bronchogenic Cyst: Delineation of a Poorly Recognized Lesion
Authors: Zvulunov A. , Amichai B. , Grunwald M. H. , Avinoach I. , Halevy S.
Published: August 2010

Abstract: Bronchogenic cyst is a benign congenital developmental abnormality of the embryonic foregut. The most common extrapulmonary location of these lesions is the mediastinum. Over 50 cases of cutaneous bronchogenic cyst were reported in the English literature. Nevertheless, it is poorly recognized by clinicians and is sometimes confused with branchial cyst. In almost all cases the diagnosis is established by histopathologic examination. We report an unusual clinical presentation of bronchogenic cyst in a 4‐year‐old girl and review the literature. This lesion is four times more common in males than in females. The most common location is the suprasternal notch, followed by the presternal area, neck, and scapula. The characteristic histologic findings are a ciliated pseudostratified epithelial lining with the presence of smooth muscle cells, goblet cells and, less frequently, cartilage. Our review of the clinical and histologic features of all reported cases further delineates this entity and may facilitate its clinical diagnosis. Bronchogenic cyst should be included in the differential diagnosis of congenital cystic and nodular skin lesions on the upper chest, upper back, and neck.
Folliculitis Ulerythematosa Reticulata (Atrophoderma Vermiculata): Early Detection of a Case with Unilateral Lesions
Authors: Nico Marcello Menta S. , Valente Neusa Y. Sakai , Sotto Mirian N.
Published: August 2010

Abstract: A 5‐year‐old girl had a unilateral rash on her right cheek. Histologic investigations showed aberrant pilosebaceous units and elastotic material in the papillary dermis. Unilateral folliculitis ulerythematosa reticulata (a variant of keratosis pilaris atrophicans) is strikingly rare, and its very early clinical and microscopic changes are demonstrated in this case report.
Congenital Melanosis and Hypertrichosis in a Bilateral Distribution
Authors: Ferreira Maria João , Bajanca Rui , Fiadeiro Teresa
Published: August 2010

Abstract: We report a 4‐year‐old Caucasian girl with congenital skin lesions consisting of hyperpigmented macules that were bilateral and roughly symmetrical, covered with terminal hair and located on the scapular regions, shoulders, and arms. A cutaneous biopsy specimen showed the histologic pattern of Becker nevus. We discuss the classification of this case in the context of the published literature.
Hemorrhagic Bullous Lesions in Henoch‐Schönlein Purpura
Authors: Saulsbury Frank T.
Published: August 2010

Abstract:This report describes two children with Henoch‐Schönlein purpura (HSP) associated with hemorrhagic bullous lesions. This unusual cutaneous manifestation of HSP may be a source of diagnostic confusion, but it does not appear to have prognostic implications.
Pebbling of the Skin: A Marker of Hunter's Syndrome
Authors: Thappa Devinder M. , Singh Ajit , Jaisankar Telanseri J. , Rao Ramachandra , Ratnakar Chaganti
Published: August 2010

Abstract: A 9‐year‐old boy, the third child of nonconsanguinous parents, presented with asymptomatic, solid, raised skin lesions over the upper back. They first appeared at the age of 4 years. Gradually similar lesions appeared over the chest, neck, arms, and thighs. On examination, he had firm, hypopigmented to skin‐colored papules and nodules which coalesced to form ridges in a reticular pattern (pebbling of the skin) and were arranged bilaterally and symmetrically over the scapulae, pectoral region of the chest, and lateral aspects of the arms and thighs. They resembled sulci and gyri of the brain. He had normal intelligence, short stature, coarse facial features, thick lips, a large tongue, clear corneas, a protuberant abdomen with hepatosplenomegaly, and broad hands with clawlike contractures of the distal interphalangeal joints. Investigations revealed cardiomegaly and proximal tapering of metacarpal bones. Although peripheral blood smear and urine spot test for mucopolysaccharides were negative, histopathology of a representative skin lesion was compatible with the diagnosis of Hunter's syndrome. The case is reported for its rarity and the typical skin lesions, the recognition of which may be helpful in diagnosis and genetic counseling.
Hermansky‐Pudlak Syndrome: A Case Report and Discussion
Authors: Vanhooteghem O. , Courtens W. , Andre J. , Sass U. , Song M.
Published: August 2010

Abstract: Hermansky‐Pudlak syndrome is a rare, inherited, autosomal recessive disease. Diagnosis is based on a triad of signs: oculocutaneous albinism, a hemorrhagic tendency due to a platelet disorder, and an accumulation of lipopigments in different organs, particularly the medullary macrophages. We describe a child with the characteristic findings of this syndrome, which often goes unrecognized because of the discrete nature of the cutaneous and hemorrhagic manifestations. This diagnosis is important because of the risk not only of hemorrhage but also of granulomatous colitis and long‐term pulmonary fibrosis.
A Case of Herpetic Whitlow Associated with Erythema Multiforme
Authors: de Ocariz María del Mar Sáez , Vega‐Memije Ma. Elisa , Muñoz‐Hink Heidi
Published: August 2010

Abstract: We report a 6‐month‐old girl with erythema multiforme minor occurring during the course of a herpetic whitlow. Erythema multiforme minor is unusual in infants, and in this population herpes simplex virus has not been reported as a significant etiologic factor. The clinical coexistence of erythema multiforme minor and the herpetic lesion is also atypical. To our knowledge, this is the first report of erythema multiforme minor associated with a concomitant HSV infection in an infant.
PHARMACOLOGY AND THERAPEUTICS: Onychomycosis in Children: Prevalence and Management
Authors: Gupta Aditya K. , Chang Patricia , Del Rosso James Q. , Adam Paul , Hofstader Sophie L. R.
Published: August 2010

Abstract: Onychomycosis in children is often accompanied by tinea pedis and a family history of onychomycosis. The prevalence of onychomycosis in children is substantially lower than that of adults; therefore it is important to confirm the clinical diagnosis. The most common presentation of onychomycosis is the distal and lateral subungual type. The organism most commonly isolated in North America is Trichophyton rubrum. Oral antifungal therapy is required, especially when the onychomycosis is of moderate to severe intensity, with nail matrix involvement. The new oral antifungal agents itraconazole, terbinafine, and fluconazole are being increasingly used for the treatment of onychomycosis. Review of the literature suggests that these agents are effective and safe in managing onychomycosis in children. The short duration of therapy required with these drugs should help improve compliance. The data suggest that the new oral antifungal agents have a role in the treatment of onychomycosis in children. Further experience will help us better position these drugs when evaluating the management of onychomycosis in children.
The Clinical Profile of Children in India with Pigmentary Anomalies along the Lines of Blaschko and Central Nervous System Manifestations
Authors: Pinheiro Anita , Mathew M.C. , Thomas Maya , Jacob Mary , Srivastava Vivi M , Cherian Rekha , Raju Renu , George Renu
Published: August 2010

Abstract:  The aim of this study was to describe the clinical profile of children with congenital pigmentary anomalies along Blaschko lines and the associated manifestations in the central nervous system. Twenty‐six children aged 12 years or less (14 boys and 12 girls), with hypopigmentation and hyperpigmentation along Blaschko lines and central nervous system manifestations were included during the period June 2001 to December 2003. Detailed physical, cutaneous, and systemic examinations were carried out. Relevant investigations included histopathology, karyotyping, electroencephalogram, computerized tomography scans, and magnetic resonance imaging of the brain whenever possible. Twenty children had hyperpigmentation along the lines of Blaschko, four had hypopigmentation, and two had a combination of the two. Eight children had diffuse involvement. Of these, two each had hypomelanosis of Ito, incontinentia pigmenti and linear and whorled nevoid hypermelanosis. The remaining 20 patients could not be categorized as any of the described entities. The majority (92.3%) of patients manifested skin and central nervous system disorders before the age of 2 years. Hyperpigmentation along Blaschko lines was significantly higher in patients with central nervous system manifestations (p = 0.01). Developmental delay was the most frequent central nervous system presentation. Multiple systems were affected, including the eyes. Histology was useful to distinguish incontinentia pigmenti from other types of nevoid hyperpigmentation.
Ramsay Hunt Syndrome in a 3‐Month‐Old Infant
Authors: Balatsouras Dimitrios G. , Rallis Efstathios , Homsioglou Elias , Fiska Alice , Korres Stavros G.
Published: August 2010

Abstract:  Ramsay Hunt syndrome is a disorder characterized by herpetic eruptions on the auricle, facial paralysis, and vestibulocochlear dysfunction, and is attributed to varicella zoster virus infection in the geniculate ganglion. Although it is a common cause of acute peripheral facial paralysis, children are not usually affected. We describe Ramsay Hunt syndrome in a 3‐month‐old infant who was referred because of a 2‐day‐old appearance of herpetic blisters on the right auricle and along the distribution of the right facial nerve. His mother had been infected with chickenpox during the second trimester of pregnancy. The infant presented with right facial palsy and was anxious, but had no fever. Otoscopy revealed herpetic eruptions in the right ear canal. Otoacoustic emissions were absent in the right ear and auditory brainstem responses confirmed moderate sensorineural hearing loss. Appropriate treatment resulted in slight improvement after the first week and complete recovery within 4 months. Infection with varicella zoster virus was proved by a significant increase in the serum anti‐varicella zoster virus antibody titer during the convalescent phase of the disease.
Pigmentary Changes and Atopic Dermatitis in a Patient with Seckel Syndrome
Authors: Brackeen Amy , Babb‐Tarbox Michelle , Smith Jennifer
Published: August 2010

Abstract:  Seckel syndrome is a very rare form of primordial dwarfism characterized by antenatal and postnatal growth delay, proportionate extreme short stature, a prominent beak‐like nose, hypoplasia of the malar area, small chin, microcephaly, deformed ears lacking lobules, skeletal malformations, mental retardation, and developmental delay. This syndrome has been described with associated disorders of orthopedic, neurologic, hematologic, cardiac, and ocular systems; however, only a few reports mention dermatologic involvement. We describe a 5‐year‐old girl with classic Seckel syndrome who presented with moderately severe atopic dermatitis and diffuse hypopigmented macules and papules.
Heterochromia of the Scalp Hair Following Blaschko Lines
Authors: Iorizzo Matilde , Piraccini Bianca Maria , Tosti Antonella
Published: August 2010

Abstract:  Heterochromia of the scalp hair is characterized by the presence of tufts of hair of a color that differs from the general hair color. It is considered a disorder of pigmentation when the tufts are asymmetrically distributed. We report four patients with isolated congenital tufts of heterochromia in the scalp hair following the Blaschko lines of the head.
Tacrolimus Ointment is Effective for Psoriasis on the Face and Intertriginous Areas in Pediatric Patients
Authors: Brune Adriana , Miller Drew W. , Lin Peggy , Cotrim‐Russi Daniela , Paller Amy S.
Published: August 2010

Abstract:  Children with psoriasis often have involvement of the face and intertriginous areas. While corticosteroids have been the mainstay of treatment for plaque‐type psoriasis, the face and intertriginous areas are more sensitive to local effects of topical steroid use such as cutaneous atrophy. Topical tacrolimus has shown promise in adult patients as an alternative antiinflammatory without the cutaneous side effects of steroids. Eleven patients between 6 and 15 years of age with facial or inverse psoriasis were evaluated in a 6‐month, single‐center, open‐label trial. Clinical evaluations were made at baseline and days 30, 90, and 180. Severity was assessed using the physician's global assessment of improvement relative to baseline, a 6‐point rating scale for signs of disease (erythema, infiltration, desquamation), and an overall severity score. Within the first 30 days of treatment, every patient had cleared or achieved excellent improvement with the use of tacrolimus ointment. Statistically significant improvement was achieved in each sign of disease and the overall severity score. The only adverse event reported in 6 months of observation was significant pruritus in one patient. We therefore conclude that tacrolimus ointment is an effective treatment for psoriasis on the face or intertriginous areas in children.
Response to IL‐1‐Receptor Antagonist in a Child with Familial Cold Autoinflammatory Syndrome
Authors: O'Connell Susan M. , O'Regan Grainne M. , Bolger Turlough , Hoffman Hal. M. , Cant Andrew , Irvine Alan D. , Watson Rosemarie M.
Published: August 2010

Abstract:  Familial cold auto‐inflammatory syndrome, Muckle–Wells syndrome and chronic infantile neurologic, cutaneous, articular syndrome are related disorders associated with mutations in the CIAS1 gene. They appear to represent a continuum of one disease characterized by IL‐1‐mediated inflammation. Until recently, these conditions have been difficult to treat; however, with the advent of IL‐1‐receptor antagonist therapy, many reports of successful treatment of patients with these autoinflammatory diseases have emerged in the past 2 years. We describe an 8‐year‐old girl, diagnosed with Familial cold auto‐inflammatory syndrome, confirmed by presence of a novel CIAS1 mutation, who was refractory to symptomatic treatment. As frequent attacks of urticaria and associated arthralgia had a debilitating effect on the child's lifestyle, a trial of IL‐1‐receptor antagonist (anakinra) was instituted. Dramatic sustained clinical improvement was evident within days and serum amyloid and C‐reactive protein levels normalized within a month. Although several authors have reported successful use of this agent in children with chronic infantile neurologic, cutaneous, articular syndrome, we believe ours is the first report of successful treatment with anakinra in a young child with familial cold auto‐inflammatory syndrome.
AHC‐52, a Dihydropyridine Compound with Chloride Current Blocking and Cardioprotective Activities
Authors: Tanaka Hikaru , Shigenobu Koki
Published: August 2010

AHC‐52 is a dihydropyridine compound known to reverse multidrug resistance through inhibition of the P‐glycoprotein. In whole‐cell voltage‐clamped cardiomyocytes, AHC‐52 had no effect on L‐type calcium current but inhibited cAMP‐activated chloride current. In an ischemia‐reperfusion model with coronary‐perfused right ventricular tissue, AHC‐52 markedly enhanced the recovery of contractile force on reperfusion without any negative inotropic effect during normal perfusion and experimental ischemia, which is similar to the effects of chloride blockers such as 9‐anthracenecarboxylic acid (9AC) and 4‐acetamido‐4′isothiocyanostilbene‐2,2 disulfonic acid (SITS). Thus, AHC‐52 appears to be an interesting prototype of cardioprotective drugs acting through mechanisms related to modification of anion homeostasis.
A Review on Telmisartan: A Novel, Long‐Acting Angiotensin II‐Receptor Antagonist
Authors: Wienen Wolfgang , Entzeroth Michael , van Meel Jacobus C. A. , Stangier Joachim , Busch Ulrich , Ebner Thomas , Schmid Jochen , Lehmann Horst , Matzek Kandace , Kempthorne‐Rawson Joan , Gladigau Volker , Hauel Norbert H.
Published: August 2010

Telmisartan is a potent, long‐lasting, nonpeptide antagonist of the angiotensin II type‐1 (AT1) receptor that is indicated for the treatment of essential hypertension. It selectively and insurmountably inhibits stimulation of the AT1receptor by angiotensin II without affecting other receptor systems involved in cardiovascular regulation. Very high lipophilicity, a unique feature of telmisartan, coupled with a high volume of distribution, indicate that the compound offers the clinically important advantage of good tissue penetration. Telmisartan is not a prodrug and has a longer terminal elimination half‐life than other commercially available sartans (∼24 h), making it suitable for once‐daily dosing. The compound is not metabolized by cytochrome P450 isoenzymes and has a low risk for P450‐based drug interactions. In animal models, telmisartan exhibits pronounced cardio‐and renoprotective effects in animals with severe, essential hypertension. In clinical studies, telmisartan shows comparable antihypertensive activity to members of other major antihypertensive classes, such as ACE inhibitors, beta blockers and calcium antagonists. These trials have confirmed the placebo‐like safety and tolerability of telmisartan in hypertensive patients. Based on these data, telmisartan offers advantages over other sartans and represents an important new treatment option for hypertension.
Multilateral in Vivo and in Vitro Protective Effects of the Novel Heat Shock Protein Coinducer, Bimoclomol: Results of Preclinical Studies
Authors: Nánási P. P. , Jednákovits A.
Published: August 2010

Bimoclomol, the recently developed non‐toxic heat shock protein (HSP) coinducer, was shown to display multilateral protective activities against various forms of stress or injuries at the level of the cell, tissue or organism. The compound enhanced the transcription, translation and expression of the 70 kD heat shock protein (HSP‐70) in myogenic and HeLa cell lines exposed to heat stress, and increased cell survival on exposure to otherwise lethal thermal injury. Bimoclomol increased contractility of the working mammalian heart, this effect was associated with the increased intracellular calcium transients due to increased probability of opening of ryanodine receptors in the sarcoplasmic reticulum (SR). In healthy tissues these cardiac effects were evident only at relatively high concentrations of the drug, while in the ischemic myocardium bimoclomol exerted significant cardioprotective and antiarrhythmic effects at submicromolar concentrations. It decreased ischemia‐induced reduction of contractility and of cardiac output, and dramatically decreased the elevation of the ST‐segment during ischemia as well as the occurrence of ventricular fibrillation upon reperfusion.

Bimoclomol was also active in various pathological animal models subjected to acute or chronic stress. In the spontaneously hypertensive rats chronic pretreatment with bimoclomol restored sensitivity of aortic rings to acetylcholine; this effect was accompanied by accumulation of HSP‐70 in the tissues. Bimoclomol pretreatment significantly diminished the consequences of vascular disorders associated with diabetes mellitus. Diabetic neuropathy, retinopathy, and nephropathy were prevented or diminished, while wound healing was enhanced by bimoclomol. Enhancement of wound healing by bimoclomol was observed after thermal injury as well as following ultraviolet (UV) irradiation. In addition to the beneficial effects on peripheral angiopathies, bimoclomol antagonized the increase in permeability of blood‐brain barrier induced by subarachnoid hemorrhage or arachidonic acid.

A general and very important feature of the above effects of bimoclomol was that the drug failed to cause alterations under physiological conditions (except the enhanced calcium release from cardiac sarcoplasmic reticulum). Bimoclomol was effective only under conditions of stress. Consistent with its HSP‐coinducer property, bimoclomol alone had very little effect on HSP production. Its protective activity became apparent only in the presence of cell damage. Currently, bimoclomol reached the end of the Phase II clinical trial in a group of 410 patients with diabetic complications. Results of this trial will answer the question, whether a compound with promising in vitro and in vivo preclinical findings will produce the anticipated beneficial effects in humans. In the event of a positive outcome of this trial, the indications for bimoclomol will be substantially extended.
Pranidipine, a 1,4‐Dihydropyridine Calcium Channel Blocker that Enhances Nitric Oxide‐Induced Vascular Relaxation
Authors: Mori Toyoki , Takase Hiromichi , Toide Kiyotaka , Hirano Takahiro , Kambe Toshimi , Nakayama Natsuki , Schwartz Arnold
Published: August 2010

Pranidipine, a long acting 1,4‐dihydropyridine calcium channel blocker, prolongs nitric oxide (NO)‐mediated relaxation of rat aorta; it prolongs acetylcholine‐induced relaxation in presence of endothelium as well as nitroglycerin‐induced relaxation in absence of endothelium. In rat aorta the effect of pranidipine on NO‐mediated relaxation is cyclic guanosine monophosphate (cGMP)‐independent, but in guinea pig carotid artery the same effect of pranidipine is cGMP‐dependent. It has been reported that in co‐cultured human endothelial and smooth muscle cells pranidipine, at a higher concentration (10−6M), enhances vasorelaxant effect of NO by blocking NO decomposition. The enhancement of NO action by pranidipine differs from the direct NO‐releasing action of other 1,4‐dihydropyridines. It is expected that enhancement of NO‐induced vasodilatation will lead to a venodilator action in vivo and less peripheral edema. The target organ protective effects of pranidipine are also reviewed in this article.
Fondaparinux, a Synthetic Pentasaccharide: The First in a New Class of Antithrombotic Agents — The Selective Factor Xa Inhibitors
Authors: Bauer Kenneth A. , Hawkins David W. , Peters Paul C. , Petitou Maurice , Herbert Jean‐Marc , van Boeckel Constant A. A. , Meuleman Dirk G.
Published: August 2010

Despite currently available antithrombotic therapies, venous thromboembolism (VTE) remains a major cause of morbidity and mortality. Fondaparinux sodium (pentasaccharide), the first in a new class of antithrombotic agents developed for the prevention and treatment of VTE, inhibits thrombin generation by selectively inhibiting factor Xa. Fondaparinux exhibits complete bioavailability by the subcutaneous route and is rapidly absorbed, reaching its maximum concentration approximately 2 h post dosing. It has a terminal half‐life of 13 to 21 h, permitting once‐daily dosing. Fondaparinux's reproducible linear pharmacokinetic profile exhibits minimal intrasubject and intersubject variability, suggesting that individual dose adjustments will not be required for the vast majority of the population and that there will be no need for routine hemostatic monitoring. At therapeutic concentrations (<2 mg/L), fondaparinux exhibits >94% binding to its target protein, antithrombin. Within this same concentration range there is no specific binding by fondaparinux to plasma proteins commonly involved in drug binding, indicating a low potential for drug‐drug interactions by protein displacement. Unlike antithrombotic agents prepared from animal extracts (heparins), fondaparinux is chemically synthesized; this leads to batch‐to‐batch consistency and the absence of potential risk of contamination problems. In recently completed phase III clinical trials in VTE prevention in major orthopedic surgery, fondaparinux showed significant superiority over the low‐molecular‐weight heparin enoxaparin, providing an overall >50% (P < 0.001) reduction in VTE risk without increasing clinically important bleeding. Additional clinical data support its potential benefits in other venous and arterial thrombotic disorders. In view of these collective findings, fondaparinux is expected to play a major role in the prevention and treatment of venous and arterial thrombotic disease.
Efonidipine Hydrochloride: A Dual Blocker of L‐ and T‐Type Ca2+ Channels
Authors: Tanaka Hikaru , Shigenobu Koki
Published: August 2010

T‐type Ca2+ channels have properties different from those of the L‐type and are involved in cardiac pacemaking and regulation of blood flow, but not in myocardial contraction. Efonidipine is an antihypertensive and antianginal drug with dihydropyridine structure that was recently found to block both L‐ and T‐type Ca2+ channels. In isolated myocardial and vascular preparations, efonidipine has potent negative chronotropic and vasodilator effects but only a weak negative inotropic effect. In experimental animals and patients, reduction of blood pressure by the drug was accompanied by no or minimum reflex tachycardia leading to improvement of myocardial oxygen balance and maintenance of cardiac output. Efonidipine increased glomerular filtration rate without increasing intraglomerular pressure. By relaxing both the afferent and efferent arterioles, efonidipine markedly reduced proteinuria. Thus, efonidipine, an L‐ and T‐type dual Ca2+ channel blocker, appears to have an ideal profile as an antihypertensive and antianginal drug with organ‐protective effects in the heart and kidney.
Sitosterolemia
Authors: Salen Gerald , Patel Shailesh , Batta A. K.
Published: August 2010

Sitosterolemia was first described 28 years ago in two sisters. They had tendon xanthomas, normal plasma cholesterol levels, and elevated plant sterol levels. The high plant sterol levels were shown to be due to the increased absorption and delayed removal of plant sterols from the body. The increased absorption of plant sterols does not affect cholesterol absorption in these patients. However, cholesterol biosynthesis pathway is downregulated and turnover rates are reduced. Bile acid binding resins and ileal bypass surgery are effective treatments for sitosterolemic patients, whereas statins are ineffective. Sitosterolemia is inherited as a recessive trait. Recent studies have shown that mutations in ABCG5 and ABCG8 genes contribute to sitosterolemia. Most likely, ABCG5 and ABCG8 proteins function as obligate heterodimers and play a role in the absorption of plant sterol or control their rate of absorption.
Update on Fenofibrate
Authors: Guay David R. P.
Published: August 2010

Fenofibrate is a fibric acid derivative that has been marketed since the mid‐1970's (1998 in the United States). Its active metabolite, fenofibric acid, is responsible for the primary pharmacodynamic effects of the drug: reductions in total plasma cholesterol, lowdensity lipoprotein cholesterol, triglycerides, and very low‐density lipoprotein concentrations and increases in high‐density lipoprotein cholesterol and apolipoproteins AI and AII concentrations. These effects are mediated by activation of peroxisome proliferator‐activated receptor‐α (PPARα). The drug has broad spectrum utility, with documented efficacy in Fredrickson types IIa, IIb, III, IV, and V hyperlipidemias. Fenofibrate is well tolerated, with digestive and musculoskeletal side effects similar to those of other fibrates. Results of the initial cardiovascular morbidity/mortality outcomes study with fenofibrate (known as DAIS [Diabetes Atherosclerosis Intervention Study]) were encouraging vis‐à‐vis slowing of atherosclerotic progression in the coronary vasculature of type II diabetics. The results of other ongoing outcome trials are eagerly awaited. These results will help to establish the overall place of fenofibrate in the hypolipidemic armamentarium.
Rosuvastatin: A Highly Effective New HMG‐CoA Reductase Inhibitor
Authors: Olsson Anders G. , McTaggart Fergus , Raza Ali
Published: August 2010

Rosuvastatin, a new statin, has been shown to possess a number of advantageous pharmacological properties, including enhanced HMG‐CoA reductase binding characteristics, relative hydrophilicity, and selective uptake into/activity in hepatic cells. Cytochrome P450 (CYP) metabolism of rosuvastatin appears to be minimal and is principally mediated by the 2C9 enzyme, with little involvement of 3A4; this finding is consistent with the absence of clinically significant pharmacokinetic drug‐drug interactions between rosuvastatin and other drugs known to inhibit CYP enzymes. Dose‐ranging studies in hypercholesterolemic patients demonstrated dose‐dependent effects in reducing low‐density lipoprotein cholesterol (LDL‐C) (up to 63%), total cholesterol, and apolipoprotein (apo) B across a 1‐ to 40‐mg dose range and a significant 8.4% additional reduction in LDL‐C, compared with atorvastatin, across the dose ranges of the two agents. Rosuvastatin has also been shown to be highly effective in reducing LDL‐C, increasing high‐density lipo‐protein cholesterol (HDL‐C), and producing favorable modifications of other elements of the atherogenic lipid profile in a wide range of dyslipidemic patients. In patients with mild to moderate hypercholesterolemia, rosuvastatin has been shown to produce large decreases in LDL‐C at starting doses, thus reducing the need for subsequent dose titration, and to allow greater percentages of patients to attain lipid goals, compared with available statins. The substantial LDL‐C reductions and improvements in other lipid measures with rosuvastatin treatment should facilitate achievement of lipid goals and reduce the requirement for combination therapy in patients with severe hypercholesterolemia. In addition, rosuvastatin's effects in reducing triglycerides, triglyceride‐containing lipoproteins, non‐HDL‐C, and LDL‐C and increasing HDL‐C in patients with mixed dyslipidemia or elevated triglycerides should be of considerable value in enabling achievement of LDL‐C and non‐HDL‐C goals in the numerous patients with combined dyslipidemias or metabolic syndrome who require lipid‐lowering therapy. Rosuvastatin is well tolerated alone, and in combination with fenofibrate, extended‐release niacin, and cholestyramine, and has a safety profile similar to that of currently marketed statins. A large, long‐term clinical trials program is under way to investigate the effects of rosuvastatin on atherosclerosis and cardiovascular morbidity and mortality.
Pioglitazone: Cardiovascular Effects in Prediabetic Patients
Authors: Mizushige Katsufumi , Tsuji Teppei , Noma Takahisa
Published: August 2010

Pioglitazone is the second thiazolidine derivative used clinically in the type 2 diabetes mellitus (DM). In the prediabetic stage, hyperinsulinemia or insulin resistance has been suggested to be closely associated with the oxidative stress. The first thiazolidine derivative used to treat DM, troglitazone, is chemically related to α‐tocopherol, a known anti‐oxidant. Troglitazone prevents tissue damage, but has been reported to produce hepatotoxicity. Pioglitazone strongly increases insulin sensitivity, improves glucose and lipid metabolism and showed no evidence of hepatotoxicity. The mechanism of the antidiabetic action of pioglitazone involves activation of insulin receptors and /or high affinity for peroxisome proliferator‐activated receptor γ (PPARγ). Hydroxylation of the phenyl and pyridine rings in the chemical structure of pioglitazone may facilitate the scavenging of hydro‐xyl radicals. The direct antioxidant effect of pioglitazone may contribute to its effect on insulin resistance. The hypoglycemic and hypolipidemic effects of pioglitazone are likely to reduce the expression of TNFα. The reduction in the oxidative stress may lead to the suppression of TGFβ and of collagen accumulation. A decrease in collagen content is likely to improve left ventricular diastolic function and distensibility of the aortic wall. Reduction in the oxidative stress may prevent the proliferation of vascular smooth muscle cells and contribute to the decrease in the aortic wall stiffness.