bluuebunny/crossref_metadata_2025 huggingface dataset:
Tuberculosis control in resource‐poor countries: have we reached the limits of the universal paradigm?
Authors: Lienhardt Christian , Ogden Jessica Ann
Published: July 2004

The aim of TB control is to break the cycle of transmission by treating TB cases as early and efficiently as possible. In its efforts to promote a model of worldwide TB control, WHO defined specific targets and launched the ‘Directly Observed Therapy, Short‐course’ (DOTS) strategy as the main tool to reach them. However, the diversity of patients’ attitudes towards the disease and the extreme variability of access to care, especially in resource‐poor countries, are amongst the many factors of social context that profoundly affect the ability of control programmes to implement this policy effectively. There are multiple reports of TB control programmes using various types of intervention to promote adherence and enhance case‐holding, but most of these interventions depend on external funding, which bring into question their long‐term sustainability. In this paper, we address the problems related to operational variabilities in the implementation of the DOTS strategy in resource‐poor countries and question the appropriateness of a universal paradigm for global TB control. This analysis is of particular importance as programmers consider using this model in the delivery of anti‐retroviral therapies for the treatment of HIV in resource‐limited settings.
Placebo‐controlled evaluation of direct electrical current administration for palmoplantar hyperhidrosis
Authors: Karakoc Yunus , Aydemir Ertugrul H. , Kalkan M. Tunaya
Published: July 2004

Background  Direct electrical current (d.c.) administration based on tap water iontophoresis has been used as a therapeutic option for palmoplantar hyperhidrosis. The placebo effect of this technique has not been investigated adequately.

Aim  To investigate whether d.c. administration has a possible placebo effect in the treatment of palmoplantar hyperhidrosis.

Methods  As a placebo, low alternating electrical current (a.c.; 9–12 mA, 10–15 V, and 8–10 Hz) was applied to the palms of 15 patients with idiopathic palmoplantar hyperhidrosis. The placebo effect was evaluated by inspection and sweat intensity measurements performed before and after placebo application. Patients then received d.c. treatment (18–22 mA, 40–60 V) according to the same procedure as applied for placebo. The final sweat intensity measurements of the patients were performed 1 week after the last session of d.c. treatment. Sweat intensities measured before and after placebo and at the end of d.c. treatment were analyzed statistically by paired t‐test.

Results  The initial sweat intensity measurements of the palms, before placebo application, were 3.12 ± 0.39 g/h on the right side and 3.17 ± 0.28 g/h on the left side. The second sweat intensity measurements, 1 week after the last session of placebo, were 3.08 ± 0.46 g/h on the right side and 3.16 ± 0.21 g/h on the left side. There were no significant differences between the initial and second sets of sweat intensity measurements of the hands (P > 0.05 for both sides). The final sweat intensity measurements, 1 week after the last session of d.c. treatment, were 0.38 ± 0.06 g/h on the right side and 0.39 ± 0.07 g/h on the left side.

Conclusions  Statistical evaluation of sweat intensity measurements and inspections revealed that d.c. administration had no placebo effect in the treatment of palmoplantar hyperhidrosis.
Onychomycosis in central India: a clinicoetiologic correlation
Authors: Garg Amit , Venkatesh Vimala , Singh Mastan , Pathak Kushal P. , Kaushal Gyan P. , Agrawal Surendra K.
Published: July 2004

Background  Onychomycosis is mainly caused by dermatophytes, but yeasts and nondermatophyte molds have also been implicated, giving rise to diverse clinical presentations. The etiological agents of the disease may show geographic variation. The aim of the present study was to isolate the causative pathogens and to determine the various clinical patterns of onychomycosis in central India.

Methods  The study population comprised 90 patients with onychomycosis. Nail samples were collected for direct microscopic examination and culture. Clinical patterns were noted and correlated with causative pathogens.

Results  The male : female ratio was 3:1 and the mean age was 29.40 ± 13.61 years. Fingernails were involved in 60%, toenails in 26.67% and both fingernails and toenails in 13.34% of the 90 patients. The clinical types noted were distolateral subungual onychomycosis (64.44%), total dystrophic onychomycosis (17.78%), proximal subungual onychomycosis with paronychia (12.2%), proximal subungual onychomycosis without paronychia (4.44%) and superficial white onychomycosis (1.11%). Dermatophytes were the most common pathogens isolated, being found in 24 patients (26.36%) [Tricophyton rubrum (23.07%), Tricophyton verrucosum (2.22%) and Epidermophyton floccosum (1.11%)], followed by Candida albicans, which was found in 22 patients (24.27%). Thirty‐six (39.58%) nondermatophyte molds were isolated from 29 patients. Of these 29 cases, six were associated with Tricophyton rubrum, which was considered the primary pathogen.

Conclusions  Distolateral subungual onychomycosis was the most common clinical presentation; however, total dystrophic onychomycosis and proximal subungual onychomycosis were not uncommon in this part of India. Tricophyton rubrum and Candida albicans were the major pathogens. The clinicoetiologic correlation revealed that a single pathogen could give rise to more than one clinical type.
Plasma reactive oxygen species activity and antioxidant potential levels in rosacea patients: correlation with seropositivity to Helicobacter pylori
Authors: Baz Kiymet , Cimen M. Y. Burak , Kokturk Aysin , Aslan Gonul , Ikizoglu Guliz , Demirseren D. Deniz , Kanik Arzu , Atik Ugur
Published: July 2004

Background  Recent studies have suggested that there might be an etiologic role for Helicobacter pylori (HP) in rosacea. HP is a Gram‐negative bacterium that colonizes the gastric mucosa, increases the generation of reactive oxygen species (ROS), and decreases plasma antioxidants such as ascorbic acid.

Aim  To investigate plasma ROS activities and antioxidant status, and their relationship with HP infection, in rosacea patients.

Methods  Twenty‐nine rosacea patients and 20 age‐ and sex‐matched healthy controls were examined for specific immunoglobulin G (IgG) and IgM against HP, plasma malondialdehyde (MDA), and antioxidant potential (AOP) levels.

Results  Compared with controls, the seropositivity of HP for IgM was significantly higher (P = 0.03) and the seropositivity of HP for IgG was significantly lower (P = 0.0001) in patients with rosacea. Plasma MDA levels were higher (P = 0.0001) and AOP levels were lower (P = 0.019) in patients than in controls, regardless of the severity of the disease. Plasma MDA and AOP levels were not affected by the seropositivity of HP for IgM and/or IgG in either group.

Conclusion  Our results suggest that rosacea is an oxidative stress condition, as reflected by the increased ROS activity and decreased AOP, regardless of HP infection.
Systemic sarcoidosis presenting with alopecia of the scalp
Authors: Cho Hang Rae , Shah Arpana , Hadi Suhail
Published: July 2004

A 39‐year‐old African‐American woman was referred to the department of dermatology, Mount Sinal Hospital, New York for evaluation of a skin lesion on her scalp which had been present for 3 years and had recently changed in appearance. On examination, she was found to have erythematous plaques with hair loss extending from the frontal hairline on the right side in a “C‐shaped” distribution, terminating behind the left ear. Two years later the lesion had rapidly extended to the vertex of the scalp and left temporal area (Fig. 1). There was a 10 cm × 12 cm area of alopecia at the vertex with slight erythema, but there was no evidence of scarring, inflammation or nodularity of the scalp (Fig. 2). A skin biopsy taken from the forehead revealed granulomatous dermatitis showing noncaseating granuloma with negative acid fast bacilli (AFBC) and ammonical‐silverstain for fungus (GMS) (Fig. 3).

Erythematous plaque with hair loss on the left temporal area

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Nonscarring alopecia at the vertex with slight erythema

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Noncaseating granuloma consisting of lymphocytes, histiocytes, plasma cells and multinucleated giant cells (hematoxylin and eosin staining; magnification ×100)

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She complained of chronic nasal congestion for 8 months. Nasal cavity examination and laryngeal endoscopy showed multiple nodules on the nasal septum and vocal cord. At that time, a presumptive diagnosis of sarcoidal nodule of the nasal septum and vocal cord was made and corticosteroids were administered orally.

A chest X‐ray demonstrated prominence of the right peritracheal and perihilar regions consistent with sarcoid. A 67 Gallium scan disclosed increased uptake in the lung and perihilar lymph nodes.

A skull X‐ray showed soft tissue density of the skull, probably indicating a subcutaneous sarcoidal nodule. Computed tomography (CT) scanning of her brain and skull base showed a soft tissue mass along the outer table of the calvarium within the frontal region.

Six years ago, she experienced visual changes: blurred vision, tearing, floaters on both eyes and a 1 cm × 1 cm subcutaneous, painful, firm mass on the lateral side of her left upper eyelid. A skin biopsy was performed in another hospital and revealed noncaseating granuloma.

A diagnosis of sarcoidosis involving the central nervous system, lacrimal gland, nasal septum, vocal cord, lung and scalp was made, and the patient was treated with 20 mg of methylprednisone on alternate days with intralesional triamcinolone injection for skin lesions. During the follow‐up period, nasal, laryngeal, pulmonary, ocular and cutaneous lesions were slightly improved and magnetic resonance imaging (MRI) scanning will be carried out for further evaluation of the brain lesion.
Cutaneous larva migrans (creeping eruption) in an urban slum in Brazil
Authors: Heukelbach Jörg , Wilcke Thomas , Feldmeier Hermann
Published: July 2004

Background Cutaneous larva migrans (CLM) is caused by the penetration of larvae of animal hookworms into the skin. Knowledge about this ectoparasitosis is mainly based on the examination of travelers or other expatriates. Population‐based studies in an endemic area have never been performed.

Methods A representative population sample of an urban slum in a Brazilian city was examined for the presence of CLM and asked about symptoms associated with the ectoparasitosis.

Results In total, 3.1% (95% confidence interval, 2.2–4.3%) of the 1185 inhabitants examined presented CLM. Forty‐three per cent had more than one larval track (range, 1–17). The prevalence rate in males was 4.2% vs. 2.3% in females. CLM occurred at similar prevalence rates in all age groups. All patients complained of moderate or severe itching. In three cases (8.1%), superinfection was present. Most lesions were located on the trunk, legs, and arms. Not a single lesion was located on the feet.

Conclusions This population‐based study showed that CLM is endemic in this deprived community. The number of lesions and their topographic localization are in contrast with those obtained in previous reports based on the examination of individuals or groups affected in small outbreaks. We conclude that the clinico‐epidemiologic pattern of CLM in a deprived community is different from that observed in travelers.
Granulomatous cheilitis resulting from a tuberculide
Authors: Kavala Mukaddes , Südoğan Sibel , Can Burçe , Sarıgül Şükran
Published: July 2004

Granulomatous cheilitis (GC) is a chronic granulomatous inflammation of the lips of unknown etiology. The possible relationship with tuberculosis has been described although most of the studies excluded infectious agents as potential causes of the granulomatous response.

To our knowledge only one case of granulomatous cheilitis resulting from a tuberculide has been reported in the literature but accompanying internal involvement has not been previously described.

We report a case of GC resulting from a tuberculide. Investigations showed pulmonary involvement compatible with tuberculosis and improvement following antituberculous chemotherapy for 3 months.
Pigmented purpuric dermatoses: An overview
Authors: Sardana Kabir , Sarkar Rashmi , Sehgal Virendra N.
Published: July 2004

Pigmented purpuric dermatoses are a spectrum of disorders characterized by a distinct purpuric rash, mainly localized to the lower limbs, which are morphologically dissimilar but histopathologically indistinguishable. Their etiology remains obscure. They are rather resistant to treatment. Although diagnosed quite straightforwardly, the disease entity remains an enigma and a therapeutic challenge. The current narration discusses the outline of the epidemiology, etiopathogenesis, clinical features, histopathology and management of these disorders. The current review, hopefully, may once again rekindle interest in the entity, for it has been sparingly reported or discussed for the benefit of under‐ and/or postgraduates and those in practice, including family physicians.
Association of p53 arginine polymorphism with skin cancer
Authors: De Oliveira Walmar Roncalli P. , Rady Peter L. , Grady James , Hughes Thomas K. , Neto Cyro F. , Rivitti Evandro A. , Tyring Stephen K.
Published: July 2004

Background  The presence of arginine at codon 72 in p53 protein is proposed to be a genetic risk factor in human papillomavirus (HPV)‐related carcinogenesis.

Objective  To study the prevalence of p53 polymorphism at codon 72 in skin biopsies of epidermodysplasia verruciformis (EV) patients compared to DNA samples from healthy individuals.

Patients and methods  DNA samples extracted from normal skin and tumor biopsies of 22 Brazilian patients with EV and blood samples from 27 healthy Brazilian individuals were studied for p53 codon 72 polymorphisms using restriction fragment length polymorphism (RFLP) analysis.

Results  All EV patients with the malignant form of EV were homozygous for arginine (Arg/Arg) at codon 72 of the p53 gene, in contrast to none with the benign form (P < 0.0001).

Conclusions  p53 arginine polymorphism is likely to be associated with the development of skin malignancies in EV patients from Brazil.
Tangential excision of nevocellular nevus on the face
Authors: Pereira Carlos Augusto Zanardini , Alchorne Alice de Oliveira de Avelar
Published: July 2004

Background  Tangential excision (shaving) is an effective surgical technique for the excision of nevocellular nevi on the trunk, limbs, and scalp. There are few studies on the application of this technique to lesions on the face.

Aims  To demonstrate the technique of tangential excision for the removal of nevocellular nevi on the face and to evaluate the cosmetic results, recurrence index, and possible complications.

Methods  Two hundred and fifteen patients with multiple nevocellular nevi on different aesthetic units of the face (total of 225 lesions) were selected. All the lesions were removed by tangential excision. The patients returned for postsurgical evaluation at 30, 60, and 90 days.

Results  The results were evaluated in relation to the skin type, sex, age, and histologic type of the lesions. An excellent result was achieved in 90.7%, good in 8.4% and poor in 0.9%, with a low index of complications. For comparison, the face was divided into seven aesthetic units.

Conclusion  Tangential excision is an alternative surgical technique for the treatment of nevi. It is simple, fast, and efficient, has low risks and low cost for the patient, and yields excellent results when used for cosmetic purposes.
N95 acne
Authors: Tan Kian Teo , Greaves Malcolm W.
Published: July 2004

Two women, aged 27 and 45 years, presented to the Dermatology Outpatient Clinic with acne vulgaris. Both had nodular acne in a similar distribution over the cheeks, chin, and perioral areas (Fig. 1). Each had a history of acne vulgaris as a teenager. Both were healthcare assistants working in the Singapore General Hospital throughout the severe acute respiratory syndrome (SARS) crisis, had worn N95 masks continuously for about 3 months whilst on the wards, and had suffered an outbreak of acne of the skin occluded by the mask. They were treated with topical retinoid and systemic antimicrobials, and both responded well.

Twenty‐seven‐year‐old woman with acne papules and nodules on the face over the area occluded by the N95 mask

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Determinants of outcome in the pathways through care for children hearing voices
Authors: Escher Sandra , Morris Mervyn , Buiks Alex , Delespaul Philippe , Van Os Jim , Romme Marius
Published: July 2004

Auditory hallucination, or hearing voices, is generally associated with psychopathology. In psychiatry it is inter‐preted as a symptom of an illness, with no connection to the individual's life history. Voice hallucinations in childhood occur in a variety of contexts and have variable long‐term outcomes. Little is known about the course of the experience. In this study, 80 children and youngsters hearing voices were interviewed on four occasions over a period of three years about the content of the voices and their overall experience of voices, focusing on the determinants for a promising outcome in the pathways through care. The results indicate that the need for care in the context of the experience of voices is associated not only with high levels of problem behaviour and associated negative symptoms of psychosis, but also, independently, with an appraisal of the voices in terms of anxiety, depression, dissociation and frequency of occurrence. In 60 per cent of the participants the voices disappeared during the three‐year research period. The relationship between the disappearance of voices and the course of mental health treatment is, however, ambiguous.
Cytokine‐regulated accumulation of eosinophils in inflammatory disease
Authors: Lampinen M. , Carlson M. , Håkansson L. D. , Venge P.
Published: July 2004

The role of cytokines in the accumulation of eosinophil granulocytes in inflamed tissue has been studied extensively during recent years, and these molecules have been found to participate throughout the whole process of eosinophil recruitment. Haematopoietic cytokines such as IL‐3, IL‐5 and GM‐CSF stimulate the proliferation and differentiation of eosinophils in the bone marrow, and the release of mature eosinophils from the bone marrow into the blood is probably promoted by IL‐5. Priming of eosinophils in the blood following, for example, allergen challenge is performed mainly by IL‐3, IL‐5 and GM‐CSF. An important step in the extravasation of eosinophils is their adhesion to the vascular endothelium. Adhesion molecules are upregulated by, e.g. IL‐1, IL‐4, TNF‐α and IFN‐γ and the same cytokines may also increase the affinity of adhesion molecules both on eosinophils and endothelial cells. Finally, a number of cytokines have been shown to act as eosinophil chemotactic factors, attracting the cells to the inflammatory focus in the tissue. Some of the most important eosinophil chemoattractant cytokines are IL‐5, IL‐8, RANTES, eotaxin, eotaxin‐2, eotaxin‐3, MCP‐3, MCP‐4 and TNF‐α. Th2 cells, mast cells and epithelial cells are important sources of proinflammatory cytokines, but in recent years, the eosinophils have also been recognized as cytokine‐producing and thereby immunoregulatory cells. The aim of this paper is to review the role of cytokines in the process of eosinophil recruitment in asthma, allergy and ulcerative colitis.
Unproven diagnostic procedures in IgE‐mediated allergic diseases
Authors: Niggemann B. , Grüber C.
Published: July 2004

A considerable body of literature on therapeutic aspects of complementary and alternative medicine has been published in recent years, but little is known on diagnostic procedures. This short review lists complementary and alternative diagnostic procedures for the diagnosis of allergic diseases and presents an assessment of their usefulness for the daily practice. The review of the literature revealed that neither the determination of specific immunoglobulin G‐antibodies in serum, the hair‐analysis, the cytotoxic test, kinesiology, iridology, or electrodermal testing represent useful tests for the daily practice. To date, no complementary or alternative diagnostic procedure can be recommended as a meaningful element in the diagnostic work‐up of allergic diseases. This is especially true for food allergy: properly performed oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals. Ineffective diagnostic approaches may be costly for the consumer and delay appropriate therapy.
Effect of inhalation aspirin challenge on exhaled nitric oxide in patients with aspirin‐inducible asthma
Authors: Rolla G. , Di Emanuele A. , Dutto L. , Marsico P. , Nebiolo F. , Corradi F. , Brussino L. , Bucca C.
Published: July 2004

Background:  A complex relationship between arachidonic acid metabolites and nitric oxide (NO) synthesis has been reported in asthma. The effects of inhaled aspirin on fractional exhaled NO (FENO) in patients with aspirin‐tolerant (ATA) and aspirin‐inducible (AIA) asthma compared with normal controls have been investigated.

Methods:  The FENO was measured baseline, after saline and lysine‐aspirin (L‐ASA) bronchial challenge in 10 patients with ATA and in 10 patients with AIA [mean (PD20FEV1 L‐ASA): 14.7 ± 12.7 mg], who had comparable age and baseline FEV1. Ten healthy subjects served as controls. Sputum eosinophils were counted after saline and after L‐ASA challenge in the two groups of asthmatics.

Results:  Asthmatic patients had baseline FENO significantly higher than controls (29.7 ± 6.8 vs 9.8 ± 2.05 p.p.b. respectively, P < 0.0001). No difference was observed in methacholine PD20FEV1 and baseline FENO between ATA and AIA patients. After L‐ASA inhalation, FENO increased significantly only in patients with AIA, reaching the peak value 4 h after bronchoconstriction (from 31.1 ± 6 to 43 ± 4.8 p.p.b., P < 0.001), while no change was observed in patients with ATA and in controls. Sputum eosinophils increased significantly after L‐ASA inhalation only in patients with AIA (from 8.1 ± 2.7 to 11.1 ± 2.8%, P < 0.005) and there was a significant relationship between the increase in sputum eosinophils and the increase in FENO after ASA challenge.

Conclusion:  Exhaled NO may indicate eosinophilic airway inflammation during ASA exposure in patients with ASA inducible asthma.
Lower prevalence of reported asthma in adolescents with symptoms of rhinitis that received neonatal BCG
Authors: da Cunha S. S. , Cruz A. A. , Dourado I. , Barreto M. L. , Ferreira L. D. A. , Rodrigues L. C.
Published: July 2004

Background:  BCG is a vaccine used against tuberculosis and leprosy and is an immunostimulant that primes TH1 lymphocytes to produce cytokines that antagonize atopy both in animal models and in man. Considering that atopy is the main risk factor for asthma, one can hypothesize that vaccination inducing TH1 responses, such as BCG, can be protective against asthma.

Methods:  Objective: To estimate the association between neonatal BCG vaccination and prevalence of asthma among adolescents. Study design: Cross‐sectional study with schoolchildren aged 12–16 years. The presence of a scar compatible with BCG was used as a surrogate of neonatal vaccination. A self administered structured questionnaire was prepared based on that used by the International Study of Asthma and Allergies in Childhood. The prevalence of asthma was categorized according to the report of lifetime wheeze, lifetime asthma, lifetime asthma among those referring allergy and among those referring allergy and sneezing.

Results:  Neonatal BCG vaccination was not associated with the overall prevalence of reported wheezing or asthma. However, in the subgroup reporting current allergy and sneezing, neonatal BCG was associated with a 37% reduction of prevalence of lifetime asthma.

Conclusions:  In the population we surveyed, neonatal BCG scar was associated with a reduction in the risk of asthma only in individuals with a past history suggestive of allergic rhinitis.
Association study of polymorphisms within interleukin‐18 in juvenile idiopathic arthritis and bronchial asthma
Authors: Heinzmann A. , Gerhold K. , Ganter K. , Kurz T. , Schuchmann L. , Keitzer R. , Berner R. , Deichmann K. A.
Published: July 2004

Background:  Interleukin‐18 (IL‐18) plays an important role in the regulation of TH1 as well as TH2 immunologic responses and thus in the development of chronic inflammatory diseases. Positive association studies of polymorphisms in IL‐18 with different diseases have underlined the involvement of IL‐18 in the pathogenetics processes. Our interest was to test polymorphisms of IL‐18 for association with a typical TH1‐mediated disease – juvenile idiopathic arthritis – and the TH2‐mediated disease bronchial asthma in Caucasian children.

Methods:  We genotyped five polymorphisms that were in association with chronic inflammatory diseases (−607C, −137C, 113G, 127T, and −133G). This was performed by restriction fragment length polymorphism in populations of asthmatic children, control individuals, and children with antinuclear antibodies (ANA)‐positive juvenile idiopathic arthritis. Statistical analysis was performed by the Armitage trend test; haplotypes were calculated by the Arlequine program.

Results:  No significant association was found between any single nucleotide polymorphism or any haplotype and bronchial asthma or ANA‐positive juvenile idiopathic arthritis.

Conclusion:  We conclude that the effect of IL‐18 in the immunologic context of diseases like bronchial asthma or juvenile arthritis might be too complex to be reflected in a simple one‐way association study. Furthermore, the polymorphisms under investigation might be nonfunctional.
Rye flour induces a stronger early bronchial response than wheat flour in occupational asthma
Authors: Bensefa L. , Villette C. , Tabka F. , Causse‐Sounillac E. , Fabriès J. F. , Choudat D.
Published: July 2004

Background:  Our aims were to compare the doses of wheat and rye flour that induce early bronchial responses in occupationally exposed asthmatic subjects and to assess the effects of the dose of inhaled flour, the duration of exposure and the dose rate.

Methods:  Ten patients underwent tests with lactose, wheat flour and rye flour. We compared the decrease in forced expiratory volume in 1 s (FEV1) observed during the challenge with flour and with lactose. We also calculated the amount of flour that was instantaneously active.

Results:  Seven subjects had significantly decreased FEV1 values following exposure to wheat and rye flour and two subjects only did so for rye flour. The provocative dose (PD, dose required to reduce FEV1 by 15%) of rye was lower than that of wheat flour (geometric mean; PD15 rye: 95 μg; wheat: 368 μg). The calculated doses of rye and wheat flour were better correlated with the change in FEV1 than were the cumulative doses.

Conclusion:  The bronchial response was greater with rye than with wheat flour. The response was related to the dose of allergen inhaled and to the dose rate.
Response to clozapine of rapid cycling versus non‐cycling patients with a history of mania
Authors: Suppes Trisha , Erkan Ozcan M , Carmody Thomas
Published: July 2004

Objective:  Rapid cycling (RC) bipolar disorder (BD) patients often do not respond fully to mood‐stabilizers. Atypical antipsychotics including clozapine may be good candidates as an alternative mood‐stabilizer for these patients.

Methods:  Twenty‐eight treatment‐resistant patients with either Bipolar Disorder Type I (n = 20), or Schizoaffective Disorder Bipolar Type (n = 8) received clozapine add‐on therapy. Patients were followed for up to 1 year. Patients were seen monthly and assessed on a number of symptom domains.

Results:  Fifteen of 28 patients met RC criteria. Differences between groups was non‐significant for reported age of onset, age at study entry, past history of treatment or hospitalization, or diagnosis. However, significantly more women were RC. More than 80% of patients in either group showed at least some improvement over the 1‐year study. Random regression analyses found the non‐rapid cycling (NRC) group experienced significantly greater improvement than RC patients (p < 0.0001).

Conclusions:  Clozapine is more effective in NRC patients with a history of mania in comparison to patients with a recent history of RC.
Perception of facial expressions of emotion in bipolar disorder
Authors: Venn Helen R , Gray John M , Montagne Barbara , Murray Lindsey K , Michael Burt D , Frigerio Elisa , Perrett David I , Young Allan H
Published: July 2004

Objectives:  Some studies have reported deficits in the perception of facial expressions among depressed individuals compared with healthy controls, while others have reported negative biases in expression perception. We examined whether altered perception of emotion reflects an underlying trait‐like effect in affective disorder by examining facial expression perception in euthymic bipolar patients.

Methods:  Sensitivity to six different facial expressions, as well as accuracy of emotion recognition, was examined among 17 euthymic bipolar patients and 17 healthy controls using an interactive computer program.

Results:  No differences were found between euthymic bipolar patients and controls in terms of sensitivity to any particular emotion. Although initial analysis of the data suggested impairment in the recognition of fear among the patients, identification of this emotion was not relatively impaired compared with that of the other emotions.

Conclusions:  The study did not find any conclusive evidence for trait‐like deficits in the perception of facially conveyed emotions in bipolar disorder. Altered perception of facial expressions that has been found to accompany depressed mood may instead reflect mood‐congruent biases.
Neurocognitive function in unaffected first‐degree relatives of patients with bipolar disorder: a preliminary report
Authors: Nicol Ferrier I , Chowdhury Rumana , Thompson Jill Maria , Watson Stuart , Young Allan H
Published: July 2004

Objective:  Patients with remitted bipolar disorder (BD) have persistent impairments in neuropsychological function, particularly in the domains of executive control and declarative memory [Br J Psychiatry 180 (2002) 293]. If these were the phenotypic expression of genetic vulnerability to BD, then healthy subjects with a genetic predisposition to BD would be expected to display the same deficits. This study, therefore, examined neuropsychological function in healthy first‐degree relatives of patients with BD.

Method:  A cross‐sectional design was employed to compare the performance of 17 unaffected first‐degree relatives of BD patients and 17 demographically matched controls on a range of neuropsychological tests.

Results:  Relatives were significantly impaired on Backward Digit Span, Spatial Span and on tasks of visuospatial declarative memory in comparison with controls. Psychomotor performance and verbal declarative memory were intact, as were non‐working memory aspects of executive performance.

Conclusion:  The selective deficits in executive control and declarative memory exhibited by relatives in this study have previously been reported in euthymic BD patients suggesting they may be useful endophenotypic markers of genetic vulnerability to BD.
Pediatric bipolar disorder: phenomenology and course of illness
Authors: Faedda Gianni L , Baldessarini Ross J , Glovinsky Ira P , Austin Nancy B
Published: July 2004

Background:  Specific features and diagnostic boundaries of childhood bipolar disorder (BD) remain controversial, and its differentiation from other disorders challenging, owing to high comorbidity with other common childhood disorders, and frequent lack of an episodic course typical of adult BD.

Methods:  We repeatedly examined children meeting DSM‐IV criteria for BD (excluding episode‐duration requirements) and analyzed their clinical records to evaluate age‐at‐onset, family history, symptoms, course, and comorbidity.

Results:  Of 82 juveniles (aged 10.6 ± 3.6 years) diagnosed with BD, 90% had a family history of mood or substance‐use disorders, but only 10% of patients had been diagnosed with BD. In 74%, psychopathology was recognized before age 3, usually as mood and sleep disturbances, hyperactivity, aggression, and anxiety. At onset, dysphoric‐manic and mixed presentations were most common (48%), euphoric mania less (35%), and depression least (17%). Subtype diagnoses were: BP‐I (52%) > BP‐II (40%) > cyclothymia (7%). DSM episode‐duration criteria were met in 52% of cases, and frequent shifts of mood and energy were common.

Limitations:  Partly retrospective study of clinically diagnosed referred outpatients without a comparison group.

Conclusions:  Pediatric BD is often mis‐ or undiagnosed, although it often manifests with mood lability and sleep disturbances early in life. DSM BD criteria inconsistent with clinical findings require revision for pediatric application.
Community‐based care for youths with early and very‐early onset bipolar I disorder
Authors: Jerrell Jeanette M , Shugart Margaret A
Published: July 2004

Objective:  Phenomenological and treatment differences between children and adolescents with bipolar I disorder in a public mental health system were examined.

Method:  A systematic medical record review was performed on a sample of 83 patients, focusing on documented DSM IV symptoms of mania or depression, attention deficit hyperactivity disorder, conduct disorder, schizophrenia, and post‐traumatic stress disorder. Cross‐tabulation and logistic regression analyses were performed comparing the presence/absence of symptoms for each disorder and treatments provided for children and adolescents.

Results:  Prepubertal patients were significantly more likely to be male, easily distracted, inattentive, detached from others, hyper‐vigilant, prescribed stimulant medication, and to meet the diagnostic criteria for attention‐deficit/hyperactivity disorder or Conduct Disorder than adolescents.

Conclusions:  Consistent with the published literature, phenomenological differences between children and adolescents are present and being recognized for differential diagnosis and treatment by community practitioners. More attention to documenting some cardinal symptoms of mania, the persistence of bipolar symptoms, and the nature of cycling for those with mixed states is needed.
Bioinformatics of the glycoside hydrolase family 57 and identification of catalytic residues in amylopullulanase from Thermococcus hydrothermalis
Authors: Zona Richard , Chang‐Pi‐Hin Florent , O'Donohue Michael J. , Janeček Štefan
Published: July 2004

Fifty‐nine amino acid sequences belonging to family 57 (GH‐57) of the glycoside hydrolases were collected using the CAZy server, Pfam database and blast tools. Owing to the sequence heterogeneity of the GH‐57 members, sequence alignments were performed using mainly manual methods. Likewise, five conserved regions were identified, which are postulated to be GH‐57 consensus motifs. In the 659 amino acid‐long 4‐α‐glucanotransferase from Thermococcus litoralis, these motifs correspond to 13_HQP (region I), 76_GQLEIV (region II), 120_WLTERV (region III), 212_HDDGEKFGVW (region IV), and 350_AQCNDAYWH (region V). The third and fourth conserved regions contain the catalytic nucleophile and the proton donor, respectively. Based on our sequence alignment, residues Glu291 and Asp394 were proposed as the nucleophile and proton donor, respectively, in a GH‐57 amylopullulanase from Thermococcus hydrothermalis. To validate this prediction, site‐directed mutagenesis was performed. The results of this work reveal that both residues are critical for the pullulanolytic and amylolytic activities of the amylopullulanase. Therefore, these data support the prediction and strongly suggest that the bifunctionality of the amylopullulanase is determined by a single catalytic centre. Despite this positive validation, our alignment also reveals that certain GH‐57 members do not possess the Glu and Asp corresponding to the predicted GH‐57 catalytic residues. However, the sequences concerned by this anomaly encode putative proteins for which no biochemical or enzymatic data are yet available. Finally, the evolutionary trees generated for GH‐57 reveal that the entire family can be divided into several subfamilies that may reflect the different enzyme specificities.
How mammalian transcriptional repressors work
Authors: Thiel Gerald , Lietz Michael , Hohl Mathias
Published: July 2004

Research on the regulation of transcription in mammals initially focused on the mechanism of transcriptional activation and ‘positive control’ of gene regulation. In contrast, transcriptional repression and ‘negative control’ of gene transcription was viewed rather as part of the ‘prokaryotic book of biology’. However, results obtained in recent years have shown convincingly that transcriptional repression mediated by repressor proteins is a common regulatory mechanism in mammals and may play a key role in many biological processes. In particular, the fact that human diseases, such as Rett and ICF syndromes as well as some human forms of cancer, are connected with the activities of human repressor proteins indicates that transcriptional repression and gene silencing is essential for maintenance of the cellular integrity of a multicellular organism. The wide range of diseases caused by aberration in transcriptional repression sheds light on the importance of understanding how mammalian transcriptional repressor proteins work.
The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks
Authors: Holzhütter Hermann‐Georg
Published: July 2004

Cellular functions are ultimately linked to metabolic fluxes brought about by thousands of chemical reactions and transport processes. The synthesis of the underlying enzymes and membrane transporters causes the cell a certain ‘effort’ of energy and external resources. Considering that those cells should have had a selection advantage during natural evolution that enabled them to fulfil vital functions (such as growth, defence against toxic compounds, repair of DNA alterations, etc.) with minimal effort, one may postulate the principle of flux minimization, as follows: given the available external substrates and given a set of functionally important ‘target’ fluxes required to accomplish a specific pattern of cellular functions, the stationary metabolic fluxes have to become a minimum. To convert this principle into a mathematical method enabling the prediction of stationary metabolic fluxes, the total flux in the network is measured by a weighted linear combination of all individual fluxes whereby the thermodynamic equilibrium constants are used as weighting factors, i.e. the more the thermodynamic equilibrium lies on the right‐hand side of the reaction, the larger the weighting factor for the backward reaction. A linear programming technique is applied to minimize the total flux at fixed values of the target fluxes and under the constraint of flux balance (= steady‐state conditions) with respect to all metabolites. The theoretical concept is applied to two metabolic schemes: the energy and redox metabolism of erythrocytes, and the central metabolism of Methylobacterium extorquens AM1. The flux rates predicted by the flux‐minimization method exhibit significant correlations with flux rates obtained by either kinetic modelling or direct experimental determination. Larger deviations occur for segments of the network composed of redundant branches where the flux‐minimization method always attributes the total flux to the thermodynamically most favourable branch. Nevertheless, compared with existing methods of structural modelling, the principle of flux minimization appears to be a promising theoretical approach to assess stationary flux rates in metabolic systems in cases where a detailed kinetic model is not yet available.
Two functionally redundant isoforms of Drosophila melanogaster eukaryotic initiation factor 4B are involved in cap‐dependent translation, cell survival, and proliferation
Authors: Hernández Greco , Vázquez‐Pianzola Paula , Zurbriggen Andreas , Altmann Michael , Sierra José M. , Rivera‐Pomar Rolando
Published: July 2004

Eukaryotic initiation factor (eIF) 4B is part of the protein complex involved in the recognition and binding of mRNA to the ribosome. DrosophilaeIF4B is a single‐copy gene that encodes two isoforms, termed eIF4B‐L (52.2 kDa) and eIF4B‐S (44.2 kDa), generated as a result of the alternative recognition of two polyadeynlation signals during transcription termination and subsequent alternative splicing of the two pre‐mRNAs. Both eIF4B mRNAs and proteins are expressed during the entire embryogenesis and life cycle. The proteins are cytoplasmic with polarized distribution. The two isoforms bind RNA with the same affinity. eIF4B‐L and eIF4B‐S preferentially enhance cap‐dependent over IRES‐dependent translation initiation in a Drosophila cell‐free translation system. RNA interference experiments suggest that eIF4B is required for cell survival, although only a modest reduction in rate of protein synthesis is observed. Overexpression of eIF4B in Drosophila cells in culture and in developing eye imaginal discs promotes cell proliferation.
A new rice zinc‐finger protein binds to the O2S box of the α‐amylase gene promoter
Authors: Peng Rihe , Yao Quanhong , Xiong Aisheng , Fan Huiqin , Li Xian , Peng Youliang , Cheng Zong‐Ming , Li Yi
Published: July 2004

A putative transcription factor, named RAMY, that binds to the 20‐bp O2S sequences of the regulatory region of the Amy2 gene promoter has been identified using the yeast one‐hybrid system from a rice library. The full length RAMY cDNA clone encodes a 218‐amino acid protein and is homologous to the late embryogenesis‐abundant protein (LEA5). In vitro mutagenesis and electrophoretic mobility shift assays confirmed that RAMY can bind with O2S specifically through an unusual zinc finger with a CXCX4CX2H consensus sequence. Low levels of RAMY mRNAs were detected in rice leaves and roots by Northern blot hybridization. The plant hormone gibberellin (GA) induces expression of both RAMY and Amy2 genes, as performed by Northern blot hybridization, but the increase in RAMY mRNA level occurs prior to that of the Amy2 mRNA level in the GA‐treated aleurone tissues. These data suggest that RAMY may act as a trans‐acting protein and is probably involved in the GA‐induced expression of the rice α‐amylase gene.
Solution structure of 2′,5′ d(G4C4)
Authors: Premraj Bernard J. , Raja Swaminathan , Bhavesh Neel S. , Shi Ke , Hosur Ramakrishna V. , Sundaralingam Muttaiya , Yathindra Narayanarao
Published: July 2004

The NMR structure of 2′,5′ d(GGGGCCCC) was determined to gain insights into the structural differences between 2′,5′‐ and 3′,5′‐linked DNA duplexes that may be relevant in elucidating nature's choice of sugar‐phosphate links to encode genetic information. The oligomer assumes a duplex with extended nucleotide repeats formed out of mostly N‐type sugar puckers. With the exception of the 5′‐terminal guanine that assumes the syn glycosyl conformation, all other bases prefer the anti glycosyl conformation. Base pairs in the duplex exhibit slide (−1.96 Å) and intermediate values for X‐displacement (−3.23 Å), as in ADNA, while their inclination to the helical axis is not prominent. Major and minor grooves display features intermediate to A and BDNA. The duplex structure of iso d(GGGGCCCC) may therefore be best characterized as a hybrid of A and BDNA. Importantly, the results confirm that even 3′ deoxy 2′,5′ DNA supports duplex formation only in the presence of distinct slide (≥−1.6 Å) and X‐displacement (≥−2.5 Å) for base pairs, and hence does not favor an ideal BDNA topology characterized by their near‐zero values. Such restrictions on base pair movements in 2′,5′ DNA, which are clearly absent in 3′,5′ DNA, are expected to impose constraints on its ability for deformability of the kind observed in DNA during its compaction and interaction with proteins. It is therefore conceivable that selection pressure relating to the optimization of topological features might have been a factor in the rejection of 2′,5′ links in preference to 3′,5′ links.
Factor XII binding to endothelial cells depends on caveolae
Authors: Schousboe Inger , Thomsen Peter , Van Deurs Bo
Published: July 2004

It is now generally accepted that factor XII (FXII) binds to cellular surfaces in the vascular system. One of the suggested receptors of this binding is the glycosylphosphatidylinositol‐anchored urokinase‐like plasminogen activator (u‐PAR) harbored in caveolae/lipid rafts. However, binding of FXII to human umbilical vein endothelial cells (HUVEC) has never been shown to be localized to these specialized membrane structures. Using microscopical techniques, we here report that FXII binds to specific patches of the HUVEC plasma membrane with a high density of caveolae. Further investigations of FXII binding to caveolae were performed by sucrose density‐gradient centrifugations. This showed that the majority of FXII, chemically cross‐linked to HUVEC, could be identified in the same fractions of the gradient as caveolin‐1, a marker of caveolae, while the majority of u‐PAR was identified in noncaveolae lipid rafts. Accordingly, cholesterol‐depleted cells were found to bind significantly reduced amounts of FXII. These observations, combined with the presence of a minority of u‐PAR in caveolae concomitant with FXII binding, indicate that FXII binding to u‐PAR may be secondary and depends upon the structural elements within caveolae. Thus, FXII binding to HUVEC depends on intact caveolae on the cellular surface.
Properties of two multifunctional plant fatty acid acetylenase/desaturase enzymes
Authors: Carlsson Anders S. , Thomaeus Stefan , Hamberg Mats , Stymne Sten
Published: July 2004

The properties of the Δ6 desaturase/acetylenase from the moss Ceratodon purpureus and the Δ12 acetylenase from the dicot Crepis alpina were studied by expressing the encoding genes in Arabidopsis thaliana and Saccharomyces cerevisiae. The acetylenase from C. alpinaΔ12 desaturated both oleate and linoleate with about equal efficiency. The desaturation of oleate gave rise to 9(Z),12(E)‐ and 9(Z),12(Z)‐octadecadienoates in a ratio of approximately 3 : 1. Experiments using stereospecifically deuterated oleates showed that the pro‐R hydrogen atoms were removed from C‐12 and C‐13 in the introduction of the 12(Z) double bond, whereas the pro‐R and pro‐S hydrogen atoms were removed from these carbons during the formation of the 12(E) double bond. The results suggested that the Δ12 acetylenase could accommodate oleate having either a cisoid or transoid conformation of the C12‐C13 single bond, and that these conformers served as precursors of the 12(Z) and 12(E) double bonds, respectively. However, only the 9(Z),12(Z)‐octadecadienoate isomer could be further desaturated to 9(Z)‐octadecen‐12‐ynoate (crepenynate) by the enzyme. The evolutionarily closely related Δ12 epoxygenase from Crepis palaestina had only weak desaturase activity but could also produce 9(Z),12(E)‐octadecadienoate from oleate. The Δ6 acetylenase/desaturase from C. purpureus, on the other hand, produced only the 6(Z) isomers using C16 and C18 acyl groups possessing a Δ9 double bond as substrates. The Δ6 double bond was efficiently further converted to an acetylenic bond by a second round of desaturation but only if the acyl substrate had a Δ12 double bond and that this was in the Z configuration.