bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the impact of information about treatment‐related risks in patients receiving blood‐derived or recombinant medications
Authors: Magli‐Barioz D. , Ounnoughène N. , Paugy P. , Quarrè M.‐C. , Vassilief D. , Lopez I. , Goudemand J. , Negrier C. , Assogba U. , Driss F. , A.‐Dumont M. , Molho P.
Published: September 2004

Summary.  The aims of the study were to evaluate the impact of a written information about treatment related risks in patient receiving blood derived or recombinant medications. Haemophiliac patients and patients with constitutional or acquired immune deficiencies are concerned by this treatment and these information. Our objectives are to evaluate the efficacy of the written information, the knowledge of the patients about these medications and the psychological, emotional impact if these information. The study is based on questionnaires which specified how the patient treat bleeding episodes, their knowledge about viral safety of blood products, the patient's perception of his or her health status and relationship with the physician. Psychological and emotional status are evaluated with the Hospital Anxiety and Depression Scale. The results show the difficulty to inform patients: if the information generate only limited anxiety in patients with haemophilia or immune deficiencies, we observe that the delivery of a written information got a mediocre effect on overall knowledge. We think that this information must be appropriate for patients and be communicated orally within the patient–physician relationship.
Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin‐free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A1
Authors: Tarantino M. D. , Collins P. W. , Hay C. R. M. , Shapiro A.D. , Gruppo R. A. , Berntorp E. , Bray G. L. , Tonetta S. A. , Schroth P. C. , Retzios A. D. , Rogy S. S. , Sensel M. G. , Ewenstein B. M. ,   the RAHF‐PFM Clinical Study Group
Published: September 2004

Summary.  The efficacy and safety of an advanced category recombinant antihaemophilic factor produced by a plasma‐ and albumin‐free method (rAHF‐PFM) was studied in 111 previously treated subjects with haemophilia A. The study comprised a randomized, double‐blinded, crossover pharmacokinetic comparison of rAHF‐PFM and RECOMBINATE rAHF (R‐FVIII); prophylaxis (three to four times per week with 25–40 IU kg−1 rAHF‐PFM) for at least 75 exposure days; and treatment of episodic haemorrhagic events. Median age was 18 years, 96% of subjects had baseline factor VIII <1%, and 108 received study drug. Bioequivalence, based on area under the plasma concentration vs. time curve and adjusted in vivo recovery, was demonstrated for rAHF‐PFM and R‐FVIII. Mean (±SD) half‐life for rAHF‐PFM was 12.0 ± 4.3 h. Among 510 bleeding events, 473 (93%) were managed with one or two infusions of rAHF‐PFM and 439 (86%) had efficacy ratings of excellent or good. Subjects who were less adherent to the prophylactic regimen had a higher bleeding rate (9.9 episodes subject−1 year−1) than subjects who were more adherent (4.4 episodes subject−1 year−1; P < 0.03). One subject developed a low titre, non‐persistent inhibitor (2.0 BU) after 26 exposure days. These data demonstrate that rAHF‐PFM is bioequivalent to R‐FVIII, and suggest that rAHF‐PFM is efficacious and safe, without increased immunogenicity, for the treatment of haemophilia A.
The rare coagulation disorders – review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation
Authors: Bolton‐Maggs P. H. B. , Perry D. J. , Chalmers E. A. , Parapia L. A. , Wilde J. T. , Williams M. D. , Collins P. W. , Kitchen S. , Dolan G. , Mumford A. D.
Published: September 2004

Summary.  The rare coagulation disorders are heritable abnormalities of haemostasis that may present significant difficulties in diagnosis and management. This review summarizes the current literature for disorders of fibrinogen, and deficiencies of prothrombin, factor V, FV + VIII, FVII, FX, the combined vitamin K‐dependent factors, FXI and FXIII. Based on both collective clinical experience and the literature, guidelines for management of bleeding complications are suggested with specific advice for surgery, spontaneous bleeding, management of pregnancy and the neonate. We have chosen to include a section on Ehlers‐Danlos Syndrome because haematologists may be consulted about bleeding manifestations in such patients.
Clinical manifestations and management of labor and delivery in women with factor IX deficiency*
Authors: Yang M. Y. , Ragni M. V.
Published: September 2004

Summary.  Haemophilia is uncommon in females and little is known about the clinical manifestations and postpartum management of women with this disorder. Clinical characteristics of postpartum bleeding were evaluated in women with factor IX deficiency (FIX:C < 0.20 U mL−1), including two with haemophilia B and three carriers of haemophilia B, undergoing labour and delivery. Data were collected prospectively during routine outpatient comprehensive haemophilia care at the haemophilia Center of Western Pennsylvania and during inpatient management. Four of five women experienced postpartum bleeding, during six of 16 deliveries: the median haemoglobin was 10.7 g% and two required blood transfusion. Postpartum bleeding was significantly more common among those receiving fewer than 4 days of FIX replacement: six of 13 (46.1%) receiving fewer three or fewer days bled vs. none of three (0%) receiving six or more days treatment [P < 01 (Wilcoxon)]. Postpartum bleeding was not related to the route of delivery (P = 0.525), vaginal vs. Caesarean, nor the FIX level (P = 0.371; FIX > 0.05 U mL−1 vs. ≤0.05 U mL−1). Compared with females with von Willebrand disease or FXI deficiency, females with FIX deficiency were more likely to experience postpartum bleeding (P = 0.008) and anaemia (P = 0.045); and they were less likely to experience menorrhagia (P = 0.065), but the latter did not reach significance. Postpartum bleeding is common in women with haemophilia B or carriers of haemophilia B, and treatment with factor replacement for at least 4 days of postpartum may prevent bleeding following delivery in such women.
Novel missense mutation in the coagulation factor IX catalytic domain associated with severe haemophilia B – Factor IXDelhi
Authors: Mahajan A. , Sharma A. , Chavali S. , Kabra M. , Chowdhury M. R. , Srinivasan N. , Bharadwaj D.
Published: September 2004

Summary.  Factor IX is a vitamin K‐dependent serine protease, which exists as a zymogen in the blood. On activation to factor IXa, by factor XIa or tissue factor–factor VIIa complex, it forms tenase complex with factor VIIIa, in the presence of Ca2+. This tenase complex enzymatically converts factor X to factor Xa, thereby bringing about the coagulation cascade. Mutations in factor IX gene have been shown to cause haemophilia B, which is inherited as an X‐linked recessive disorder. Herein we report a novel missense mutation at the nucleotide position 30829‐T > A in the exon 8 of factor IX gene. This transversion leads to the substitution of histidine 236 to glutamine. This resulting abnormal protein has been named factor IXDelhi. Molecular modelling was performed to predict the molecular pathology of this mutation. We predict that this change in the catalytic domain may affect the surface loop that accommodates Ca2+, thereby leading to severe bleeding disorder.
Severe factor X deficiency in pregnancy: case report and review of the literature
Authors: Romagnolo C. , Burati S. , Ciaffoni S. , Fattori E. , Franchi M. , Zanon E. , Girolami A.
Published: September 2004

Summary.  Isolate factor X deficiency is an extremely rare clotting factor disorder inherited in autosomal recessive fashion and pregnancy in a homozygous patient is frequently complicated by recurrent miscarriage, uterine bleeding and premature labour. Eleven pregnancies in seven patients affected by FX deficiency have been reported in the literature. Two additional pregnancies have been reported in a FX variant (FX Friuli). We present a new case of successful at term pregnancy in a homozygous patient.
Functional consequences of haemophilia in adults: the development of the Haemophilia Activities List
Authors: van Genderen F. R. , van Meeteren N. L. U. , van der Bom J. G. , Heijnen L. , de Kleijn P. , van den Berg H. M. , Helders P. J. M.
Published: September 2004

Summary.  Several instruments can be used to evaluate the functional status of patients with haemophilia, but none of these instruments is specific for haemophilia. We developed a haemophilia‐specific self‐assessment questionnaire to evaluate and monitor a patient's perceived functional health status: the Haemophilia Activities List (HAL). In three separate but interlinked substudies, the questionnaire was constructed and tested for face, expert, and convergent validity, as well as internal consistency and patient‐evaluated relevance. Items for the questionnaire were collected by interviewing 162 patients, using the McMaster‐Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR). The items were combined to generate the first version of the questionnaire [HAL(1)]. This version was evaluated and commented on by two focus groups (patients and caregivers), and then the questionnaire was adapted on the basis of these comments, forming the final version, HAL(2). This version was then validated in a pilot study with 50 consecutive patients using the Dutch Arthritis Impact Measurements Scales 2 (Dutch‐AIMS2) and the Impact on Participation and Autonomy (IPA) questionnaires. The HAL(2) showed good convergent validity (Pearson correlation 0.80–0.91; P < 0.01), and the internal consistency was good for six of the eight domains (Cronbach's α 0.83–0.95). Patients considered the content of the HAL to be more relevant to their situation than the content of the other questionnaires (P < 0.01). Three major factors (upper extremity function, lower extremity function, key activities/major problem activities) were identified by factor analysis. The questionnaire seems to be a useful tool to identify problematic activities as part of the functional health status of patients with haemophilia. The construct validity, test–retest reliability, and responsiveness of the HAL will be established in the future.
Yttrium synoviorthesis of the elbow joints in persons with haemophilia
Authors: Heim M. , Tiktinsky R. , Amit Y. , Martinowitz U.
Published: September 2004

Summary.  Yttrium has been used as the material of choice for synoviorthesis in our centre since 1984. An audit was carried out to determine the long‐term results of this modality for treating elbow joints. An unacceptably high percentage of patients lost range‐of‐movements in the articulation treated. Good results were achieved with respect to a reduction in the bleeding incidences. It is suggested that another isotope be utilized and that other centres carry out an audit and publish their data.
An examination of senior nursing roles: challenges for the NHS
Authors: Williams Angela , McGee Paula , Bates Lindsay
Published: September 2004

• Wellhouse NHS Trust moved its inpatient services to the new Barnet General Hospital in 1997 and merged with Chase Farm Hospital NHS Trust in 1999.

• To assist with the trust's management of resulting changes in care provision, a short project was conducted to examine the nursing services provided by ward managers (20) and senior nurses (27), that is nurses who undertake specialist/advanced nursing practice.

• The project also aimed to present the views of the stakeholders (66) with regard to nursing in the trust and nurse‐led services. The project involved two stages of data collection – focus groups and postal questionnaires.

• The project provided a great deal of information about the nursing service within the trust: a profile of the senior nurses, roles and responsibilities, skills and competencies, training and development, and support needs for their roles.

• The findings considered a number of issues: (i) employment – diversity of grading for posts; (ii) work roles – conflicts in role composition; (iii) stakeholders – perspectives of stakeholders on nursing.

• It is anticipated that the findings are not unique to the one trust and that they will contribute to the development of new clinical career pathways for senior nurses within the trust.
Mothers’ expressed emotion towards children with and without intellectual disabilities
Authors: Beck A. , Daley D. , Hastings R. P. , Stevenson J.
Published: September 2004

Objectives  To identify factors associated with maternal expressed emotion (EE) towards their child with intellectual disability (ID).

Design and method  A total of 33 mothers who had a child with ID and at least one child without disabilities between the ages of 4 and 14 years participated in the study. Mothers completed self‐assessment questionnaires which addressed their sense of parenting competence, beliefs about child‐rearing practices, and their reports of behavioural and emotional problems of their child with ID. Telephone interviews were conducted to assess maternal EE towards the child with ID and towards a sibling using the Five Minute Speech Sample (FMSS; Magana et al. 1986), and also to assess the adaptive behaviour of the child with ID using the Vineland Adaptive Behaviour Scale (VABS; Sparrow et al. 1984).

Results  Mothers with high EE towards their child with ID were more satisfied with their parenting ability, and their children had more behaviour problems. Analysis of differential maternal parenting, through comparisons of EE towards their two children, showed that mothers were more negative towards their child with ID for all domains of the FMSS except dissatisfaction.

Conclusions  A small number of factors associated with maternal EE towards children with ID were identified. Differences in maternal EE towards their child with ID and their other child suggest that EE is child‐driven rather than a general maternal characteristic. Implications of the data for future research are discussed.
Prevention of unintentional injury to people with intellectual disability: a review of the evidence
Authors: Sherrard J. , Ozanne‐Smith J. , Staines C.
Published: September 2004

Background Recent research evidence shows that people with intellectual disability (ID) have double the unintentional injury risk of the general population and the risk is further increased in the presence of psychopathology and epilepsy. The pattern of injury and the circumstances surrounding an injury event in those with ID have some similarity with that of young children in the general population. Interventions to prevent injuries are an important health priority in this vulnerable population. This paper reviews evidence from injury prevention studies for people with ID and also considers the relevance of general population injury interventions for this population.

Method Information regarding injury prevention in both ID and general populations was identified using online systems and consultation with research and public health organizations.

Results Few published studies were identified addressing the issue of injury prevention for those with ID. Possible injury prevention strategies appropriate for the major causes of injury in the ID population were identified from the general population literature. While many environmental injury prevention strategies for young children in the general population are applicable to the population with ID, some may require design modification to ensure effectiveness. Other promising approaches include improved information for parents/carers, primary care physician counselling, and home visits by well‐informed and motivated professionals. There may be injury prevention benefit from improved management of psychopathology and epilepsy.

Conclusions The issue of injury prevention for those with ID has not been addressed to the extent that the magnitude of the problem requires. Injury prevention programmes trialling a variety of evidence‐based approaches and strategies are needed to protect the quality of life for the ID population and their families.
Cross‐cultural working in community learning disabilities services: clinical issues, dilemmas and tensions
Authors: Summers S. J. , Jones J.
Published: September 2004

Background  People with learning disabilities from minority ethnic communities face many layers of disadvantage. Providing services that are culturally appropriate and sensitive can be difficult.

Method  Through the use of clinical examples the issues, tensions and dilemmas raised for a community learning disabilities team in attempting to provide culturally sensitive services in an increasingly multicultural environment are discussed. Ways in which good practice can be more closely achieved are debated.

Conclusions  Conflicts between the principal service values of individuality, choice, promotion of mental health and normalization, whilst also respecting the beliefs and values of other religions and cultures, can raise tensions and dilemmas for learning disabilities services. The importance of sensitive and appropriate service configuration, sharing of good practice, and good staff training are emphasized.
Cutaneous manifestations associated with antiphospholipid antibodies
Authors: Diógenes Maria José Nogueira , Diógenes Pedro Coelho N. , De Morais Carneiro Raquel Maia , Neto Carlos C. Ribeiro , Duarte Fernando B. , Holanda Rosangela R. A.
Published: September 2004

Background  Primary Antiphospholipid Antibody Syndrome (PAAS) is characterized by detection of antiphospholipid antibodies associated with venous or arterial thrombosis and/or miscarriages by patients with no other associated disease such as systemic lupus erythematosus (SLE). Primary Antiphospholipid Antibody Syndrome has many clinical manifestations of which dermatological ones are probably the most common. The purpose of this study was to determine the frequency of each cutaneous lesion, describing clinical features essential for diagnosis, in patients with Antiphospholipid Antibody Syndrome (AAS) attending Walter Cantídio University Hospital.

Methods  Sixty patients with clinical findings suggestive of AAS were screened, and submitted for clinical and laboratory evaluations including lupus anticoagulant (KCT), anticardiolipin antibodies (IgG and IgM: ELISA), routine laboratory tests and screening tests for possible associated conditions.

Results  Twenty‐five cases of primary and 14 cases of secondary AAS were diagnosed by clinical and laboratory evidences. Persistent elevated antiphospholipid antibodies without history of thromboembolic events or miscarriages were demonstrated in 21 patients. Forty percent of the patients with AAS had a cutaneous feature as the major complaint. These were dermographism (15), acrocyanosis (13), urticaria (9), diffuse alopecia (9), livedo reticularis (seven), Raynaud's phenomenon (three), purpura (two), ulcers and necrosis (four), nodules (four), pterygium ungueum (one) and subungual hemorrhage (one).

Conclusions  Dermatological complaints are very frequent in patients with AAS and may be the first clue to the syndrome. Therefore a careful history and detailed physical examination are essential to diagnose AAS. All dermatologists should investigate the possibility of AAS when facing cutaneous findings related to venous or arterial thrombosis or microthrombosis.
Alpha‐1‐antitrypsin deficiency associated with panniculitis treated with plasma exchange therapy
Authors: De Oliveira Priscila , Paz‐Melgar Libania , Takahashi Maria Denise F. , Nico Marcello Menta S. , Rivitti Evandro A. , Mendrone Alfredo , Tatsui Nelson H.
Published: September 2004

Background  Alpha‐1‐antitrypsin is the principal serum protease inhibitor. In addition to the well‐recognized association with early‐onset emphysema and cirrhosis, alpha‐1‐antitrypsin deficiency may be associated with panniculitis. The treatment of this type of panniculitis presents a significant challenge. Previous attempts using immunosuppressive, anti‐inflammatory, and cytotoxic drugs have shown variable results.

Aim  To report a case of alpha‐1‐antitrypsin deficiency‐associated panniculitis treated with plasma exchange therapy.

Methods  A 23‐year‐old patient developed painful red nodules on her thighs and buttocks with spontaneous ulceration and discharge of oily fluid. A skin biopsy specimen showed septal and lobular panniculitis. The serum alpha‐1‐antitrypsin level was 22 mg/dL. She was treated with plasma exchange therapy.

Results  Treatment of this patient with plasma exchange therapy led to the control of the cutaneous lesions.

Conclusions  Plasma exchange therapy represents an alternative treatment which restores serum and tissue alpha‐1‐antitrypsin levels. This method is proposed because of its clinical benefits and greater availability.
Awareness of, knowledge of and attitudes to nonmelanoma skin cancer (NMSC) and actinic keratosis (AK) among physicians
Authors: Halpern Allan C. , Hanson Laura J.
Published: September 2004

Background  Nonmelanoma skin cancer (NMSC) is the most common type of cancer that affects the Caucasian population. Approximately 80% of NMSCs are basal cell carcinoma (BCC) and 20% are squamous cell carcinoma (SCC). Actinic keratosis (AK) is a precancerous lesion that may develop into SCC.

Methods  A market research survey was conducted in which dermatologists and primary care physicians (PCPs) were randomly selected from seven countries (USA, Australia, UK, Italy, France, Germany and Spain). Their knowledge of nonmelanoma skin cancer and their current clinical practice were assessed.

Results  In total, 2100 physicians took part in the survey. They had practised medicine for between 1 and 30 years and saw at least 30 patients in a typical week. The majority of dermatologists (97%) were familiar with BCC and AK, and treated each condition with a minimum of referrals. PCPs were more familiar with BCC (90%) than with AK (74%). Of the PCPs that were aware of BCC, only 31% treated the condition, and of those aware of AK, 40% treated the condition. Surgery was the most common choice of treatment for BCC. The most popular treatment choice for AK lesions was cryotherapy. Eighty to 100% of physicians reported that they discussed skin cancer prevention with their patients. A much lower number of physicians (ranging from 5 to 37%) provided educational material to patients. Overall, PCPs in the two countries that have a high incidence of NMSC (USA and Australia) were more familiar with BCC and AK and more likely to treat each condition than PCPs in Europe. All physicians rated BCC as a more serious condition than AK. Facial lesions were considered more serious than lesions on the head or trunk for both conditions.

Conclusions  As the burden of disease and the number of patients seeking treatment for NMSC increase, dermatologists are well placed to lead educational initiatives for PCPs and provide educational material for patients. This would increase awareness of AK and BCC and could improve early diagnosis.
Penile self‐injections: an unusual act
Authors: Al‐Mutairi Nawaf , Sharma Ashok K. , Zaki Amr , Nour‐Eldin Osama , Joshi Arun
Published: September 2004

A 42‐year‐old healthy Thai male presented with a 1‐week history of painful swelling of the penis following self‐injection of two tablets of vitamin A dissolved in 10 mL of tap water with an unsterilized syringe, in order to achieve a more prolonged erection for sexual intercourse, on a friend's advice. He injected himself all around the penile shaft “just under the skin.” Eight hours after injection, the penis started to become progressively swollen and painful, but it was a further 2 days before he presented to our clinic. He denied a history of any urinary obstructive or irritative symptoms. There was no history of genital ulceration or urethral discharge or any similar acts of self‐injection in the past.

Physical examination revealed a markedly edematous, erythematous, and tender penis with multiple yellowish pus discharge points and small superficial ulcerations all around the shaft. The scrotum also showed mild edema and tenderness. There was tender bilateral inguinal lymphadenopathy. The patient was febrile (temperature, 39 °C) and was admitted. Complete blood count revealed a raised white blood cell count of 19.1 × 109/L. Urinalysis was normal. Ultrasonography of the genitalia revealed soft tissue thickening and multiple small collections of pus in the subcutaneous penile tissue; the corpora cavernosa and corpus spongiosum were normal. The patient declined urethrography.

Cultures of blood and urine were sterile. Pus culture revealed Staphylococcus aureus. Microscopic examination of the discharge did not show any granular material. A biopsy was deferred at this stage considering the pyogenic nature of the patient's presentation. Parenteral antimicrobials, including ceftazidime, gentamicin, and metronidazole, were started. The patient's temperature rapidly fell to normal and, over a period of 10 days, the pus discharge points and pain and swelling of the penis resolved (Fig. 1) and the inguinal lymphadenopathy subsided. The patient was discharged with advice for regular follow‐up for any late sequelae. The patient refused to undergo psychiatric evaluation and counseling.

Edema and induration of the penis after 10 days of therapy. Resolving superficial erosions are also seen

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Case of disseminated Langerhans’ cell histiocytosis presenting with sclerosing cholangitis
Authors: Doganci Tumay , Sayli Tulin , Gulderen Ferda , Erden Esra , Sencer Huriye
Published: September 2004

Langerhans’ cell histiocytosis is an uncommon disorder of childhood with a wide clinical spectrum. Although liver involvement is common in the disseminated form, presentation with hepatic disfunction is unusual. We describe an 18‐month‐old girl who presented with intrahepatic cholestasis. The patient was shown to have Langerhans’ cell histiocytosis with sclerosing cholangitis by liver biopsy and skin biopsy showing S‐100, CD1a positivity, and Birbeck granules by electron microscopy.
Epidemiology of Kaposi's sarcoma in patients with acquired immunodeficiency syndrome in São Paulo, Brazil
Authors: Yoshioka Márcia Cristina Naomi , Alchorne Mauricio Mota de Avelar , Porro Adriana Maria , Tomimori‐Yamashita Jane
Published: September 2004

Background  Kaposi's sarcoma (KS) is the most frequent neoplasm in patients with acquired immunodeficiency syndrome (AIDS). Although many studies on KS epidemiology have been performed in other countries, few have been carried out in Brazil despite the high incidence of AIDS.

Methods  One hundred and seven KS patients seen in São Paulo, Brazil, between August 1995 and November 1998 were studied. The patients were followed for 1 year with assessment of the immunologic status, improvement of the lesions, treatment, and causes of death at the end of this period.

Results  KS occurred mainly in men (94.4%) with a mean age of 37 years, and 25.2% of these patients were found to be human immunodeficiency virus (HIV) seropositive through KS. HIV was acquired mainly through homosexual contact. The patients presented an average of 15.9 KS lesions at the first visit and the mean duration of KS lesions before the first visit was 15.5 months. The clinical presentation was predominantly papules and plaques, and 33.6% presented with mucosal and/or visceral disease. KS affected mainly the lower limbs. The mean time since the diagnosis of HIV infection was 42.4 months. The CD4+ cell count was lower than 200 cell/mm3 in 60.8% of patients, but patients with a complete response showed an improvement in immune status after 1 year. Patients who did not show progression received a protease inhibitor as part of highly active antiretroviral therapy (HAART). Patients treated exclusively with HAART presented a complete response (61.6%), partial response (23%) or progression (15.4%) of KS.

Conclusions  An improvement in immune status and the use of HAART were the most important prognostic features.
Cutaneous hyalohyphomycosis caused by Paecilomyces lilacinus: report of three cases and review of the literature
Authors: Hall Virginia C. , Goyal Sanjiva , Davis Mark D. P. , Walsh John S.
Published: September 2004

Cutaneous infection with Paecilomyces lilacinus is encountered worldwide, with most infections occurring either iatrogenically or in immunocompromised hosts. We report three cases of cutaneous hyalohyphomycosis caused by P. lilacinus, one of which occurred in an immunocompetent individual. In addition, we review the 17 cases previously reported in the literature. Although this infection can be difficult to treat, most cases are not fatal. Most cases responded well to systemic azole antifungal agents, either alone or in association with surgical excision of the lesion. Paecilomyces species are saprophytic fungi found in soil and decaying organic matter. Infection in humans is rare, but when it occurs treatment is often difficult. We report three cases of cutaneous hyalohyphomycosis caused by P. lilacinus and review the 17 previously reported cases in which the clinical history and response to therapy were described.
Combined basal cell carcinoma and Langerhans cell histiocytosis of the scrotum in a patient with occupational exposure to coal tar and dust
Authors: Izikson Leonid , Vanderpool John , Brodsky Gilbert , Mihm Martin C. , Zembowicz Artur
Published: September 2004

The patient was a 77‐year‐old male former smoker, with history of several basal cell carcinomas (BCCs) in sun‐protected areas around the waistline, who presented with another small ulceration on the anterior right upper scrotum near the base of the penis. BCC was suspected clinically and the lesion was treated with cryosurgery. The tumor recurred, became raised, and began to bleed. On examination, it was found to be a 3 cm × 4 cm, raised, light and dark gray variegated lesion with fissures, crusted bloody scale, and necrosis. There were no other penile, testicular, or scrotal lesions or masses. There was no regional lymphadenopathy. An excisional biopsy was performed. It showed nodular BCC surrounded by a cellular proliferation of round histiocytic cells with convoluted, lobulated and reniform nuclei and abundant cytoplasm (Fig. 1). The histiocytic proliferation was associated with numerous eosinophils. Histological features and immunohistochemical phenotype, including expression of CD1a and S‐100 antigens by histiocytic cells, were all consistent with Langerhans cell histiocytosis. As expected, BCC expressed keratin.

(a) Low magnification (×40) view of the scrotal tumor showing nodular basal cell carcinoma surrounded by a cellular zone of Langerhans cell proliferation. (b) Langerhans cells showed typical irregular reiniform nuclei with convoluted outlines and were associated with eosinophilic infiltrate (×400). In immunohistochemical studies, they expressed (c) S‐100 and (d) CD1A antigens (both ×400)

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The patient had no history of exposure to ionizing radiation, chemotherapy, immunosuppressive medications, prior lymphoma or other malignancy. However, he spent 4 years on a ship loading coal into the furnace of a steam engine, during which he slept in adjacent quarters that were covered with coal dust. Additionally, he had a several‐year history of occupational skin exposure to machine oil, oil refinery waste, sulfur waste, hydraulic fluid, and asbestos. He also reported a history of nude sunbathing. His current medical problems include pleural asbestosis, poorly controlled type II diabetes, and congestive heart failure. His past dermatologic history includes intertrigo, onychomycosis, and an unknown skin lesion removed from the face 40 years ago. Recent clinical follow‐up and imaging studies, including chest X‐ray and bone scan, showed no evidence of visceral lesions, lytic bone lesions, or other signs of systemic involvement by Langerhans cell histiocytosis. The scrotal lesion was re‐excised and the patient remains disease‐free more than 1 year after the diagnosis.
The CD63 basophil activation test in Hymenoptera venom allergy: a prospective study
Authors: Sturm G. J. , Böhm E. , Trummer M. , Weiglhofer I. , Heinemann A. , Aberer W.
Published: September 2004

Background:  The basophil activation test (BAT), which relies on flow cytometric quantitation of the allergen‐induced up‐regulation of the granule‐associated marker CD63 in peripheral blood basophils, has been suggested to be a useful approach in detecting responsiveness to allergens. The purpose of this study was to establish the usefulness of the BAT with regard to the clinical history and current diagnostic tools in Hymenoptera venom allergy using a prospective study design.

Methods:  Fifty‐seven consecutive patients allergic to Hymenoptera venom as defined by a systemic reaction after an insect sting, and 30 age‐ and sex‐matched control subjects with a negative history were included. The degree and nature of sensitization was confirmed by skin testing, specific immunoglobulin E (IgE), serum tryptase levels and BAT. In the nonallergic control group only analysis of specific IgE and BAT were performed. Correlation of BAT, skin test and specific IgE, respectively, with the clinical history in the allergic group was termed as sensitivity and in the control group as specificity.

Results:  Twenty one of 23 (91.3%) bee venom allergic patients and 29 of 34 (85.3%) patients allergic to wasp and hornet venom tested positive in BAT. The overall sensitivity of BAT, specific IgE and skin tests were 87.7, 91.2 and 93.0%, respectively. The overall specificities were 86.7% for BAT and 66.7% for specific IgE. No correlation between the severity of clinical symptoms and the magnitude of basophil activation was observed.

Conclusion:  The BAT seems to be an appropriate method to identify patients allergic to bee or wasp venom with a comparable sensitivity to standard diagnostic regimens. The higher specificity of BAT as compared with specific IgE makes this test a useful tool in the diagnosis of Hymenoptera venom allergy.
Bronchial hyperresponsiveness in children with atopic rhinitis: a 7‐year follow‐up
Authors: Cibella F. , Cuttitta G. , La Grutta S. , Hopps M. R. , Passalacqua G. , Pajno G. B. , Bonsignore G.
Published: September 2004

Background:  A high prevalence of bronchial hyperresponsiveness (BHR) was found in atopic subjects with rhinitis. Those subjects may be at higher risk for developing bronchial asthma. We evaluated, in a 7‐year follow‐up, BHR and atopy in a homogeneous population of nonasthmatic children with allergic rhinitis (AR), and their role in asthma development.

Methods:  Twenty‐eight children (6–15 years) with AR were studied. At enrollment (T0), skin tests, total serum IgE assay, peak expiratory flow (PEF) monitoring and methacholine (Mch) bronchial challenge were performed. BHR was computed as the Mch dose causing a 20% forced expiratory volume (FEV)1 fall (PD20FEV1) and as dose–response slope (DRS). Subjects were reassessed after 7 years (T1) using the same criteria.

Results:  At T0, 13 children (46%), showing a PD20FEV1 <1526 μg of Mch, had BHR (Mch+), although PEF variability (PEFv) was within normal limits. None of the children with negative methacholine test developed bronchial asthma after 7 years. Of the 13 Mch+, only two reported asthma symptoms after 7 years. No significant change was seen in the other parameters of atopy considered.

Conclusion:  Children with allergic rhinitis present a high prevalence of BHR. Nevertheless, their PEFv is normal and the rate of asthma development low.
Allergen stimulates bone marrow CD34+ cells to release IL‐5 in vitro; a mechanism involved in eosinophilic inflammation?
Authors: Johansson A.‐K. , Sjöstrand M. , Tomaki M. , Samulesson A.‐M. , Lötvall J.
Published: September 2004

The specific mechanisms that alter bone marrow (BM) eosinophilopoiesis in allergen‐induced inflammation are poorly understood. The aims of this study were to evaluate (a) whether the number of BM CD34+ cells is altered due to allergen sensitization and exposure in vivo and (b) whether BM CD34+ cells produce and release interleukin (IL)‐5, IL‐3 and granulocyte macrophage‐colony stimulating factor (GM‐CSF) after stimulation in vitro. A mouse model of ovalbumin (OVA)‐induced airway inflammation was used. Bone marrow CD34+ cells were cultured in vitro and the cytokine release was measured by enzyme‐linked immunosorbent assay. The IL‐5‐production from CD34+ cells was confirmed by immunocytochemistry. Airway allergen exposure increased the number of BM CD34+ cells (P = 0.01). Bone marrow CD34+ cells produced IL‐5 when stimulated with the allergen OVA in vitro, but not IL‐3 or GM‐CSF. Nonspecific stimulus with calcium ionophore and phorbol‐myristate‐acetate of BM CD34+ cells caused release of IL‐5, IL‐3 and GM‐CSF. The induced release of IL‐5 was increased in alum‐injected vs naive mice (P = 0.02), but was not affected by allergen sensitization and exposure. The release of IL‐3 and GM‐CSF was increased after allergen sensitization and exposure (P < 0.02). In conclusion, allergen can stimulate BM CD34+ cells to produce IL‐5 protein. It is likely that the CD34+ cells have autocrine functions and thereby regulate the early stages of BM eosinophilopoiesis induced by airway allergen exposure. Alum, a commonly used adjuvant, enhances the release of IL‐5 and may thereby enhance eosinophilopoiesis.
Cat allergen peptide immunotherapy reduces CD4+ T cell responses to cat allergen but does not alter suppression by CD4+ CD25+ T cells: a double‐blind placebo‐controlled study
Authors: Smith T. R. F. , Alexander C. , Kay A. B. , Larché M. , Robinson D. S.
Published: September 2004

Background:  We have previously described both modification of allergen immunotherapy using peptide fragments, and reduced regulation of allergen stimulated T cells by CD4+ CD25+ T cells from allergic donors when compared with nonallergic controls. It has been suggested that allergen immunotherapy induces regulatory T cell activity: we hypothesized that allergen peptide immunotherapy might increase suppressive activity of CD4+ CD25+ T cells.

Objective:  To examine cat allergen‐stimulated CD4 T cell responses and their suppression by CD4+ CD25+ T cells before and after cat allergen peptide immunotherapy in a double‐blind placebo‐controlled study.

Methods:  Peripheral blood was obtained and stored before and after peptide immunotherapy or placebo treatment. CD4+ and CD4+ CD25+ were then isolated by immunomagnetic beads and cultured with allergen in vitro.

Results:  Comparing cells from blood taken before with that after peptide immunotherapy there was a significant reduction in both proliferation and IL‐13 production by allergen‐stimulated CD4+ T cells, whereas no change was seen after placebo. CD4+ CD25+ T cells suppressed both proliferation and IL‐13 production by CD4+ CD25− T cells before and after therapy but peptide therapy was not associated with any change in suppressive activity of these cells.

Conclusion:  Allergen peptide immunotherapy alters T cell response to allergen through mechanisms other than changes in CD4+ CD25+ T cell suppression.
Human mast cells express receptors for IL‐3, IL‐5 and GM‐CSF; a partial map of receptors on human mast cells cultured in vitro
Authors: Dahl C. , Hoffmann H. J. , Saito H. , Schiøtz P. O.
Published: September 2004

Background:  Mast cells have long been recognized as the principal cell type that initiates the inflammatory response characteristic of acute allergic type 1 reactions. Our goal has been to further characterize maturation of progenitors to mast cells.

Methods:  Mast cells were cultured from human cord blood derived CD133+ progenitors. Mast cell function was tested using histamine release. During differentiation mast cells surface marker expression was monitored by flow cytometry.

Results:  CD133+ progenitors expressed the early haematopoietic and myeloid lineage markers CD34, CD117, CD13 and CD33. Mature mast cells expressed CD117, CD13 and CD33, and expression of the high affinity immunoglobulin E recpetor FcɛRI increased during culture. Cytokine receptors interleukin (IL)‐5R, IL‐3R, granulocyte‐macrophage‐colony stimulating factor (GM‐CSF)R and IL‐18R were expressed at high levels during maturation. Chemokine receptors CXCR4 and CXCR2 were highly expressed on both newly purified CD133+ cells and mature cells.

Conclusion:  Human mast cells can be cultured from a CD34+/CD117+/CD13+/CD33+ progenitor cell population in cord blood that is tryptase and chymase negative. Developing and mature mast cells express a wide range of chemokine and cytokine receptors. We found high levels of expression of CD123, IL‐5R and GM‐CSF receptors, also found on eosinophils and basophils, and high levels of expression of the receptor for the inflammatory cytokine IL‐18.
Glucocorticoid receptors in human airways
Authors: Pujols L. , Mullol J. , Torrego A. , Picado C.
Published: September 2004

Inhaled and intranasal glucocorticoids are the most common and effective drugs for controlling symptoms and airway inflammation in respiratory diseases such as asthma, allergic rhinitis, and nasal polyposis. The last few years have seen a growing understanding of the mechanisms of glucocorticoid action and, in particular, the receptor that mediates glucocorticoid actions, the glucocorticoid receptor (GR). In this revision we present an update on the GR gene, the expression and regulation of its gene products, namely GRα and GRβ, as well as their alterations in pathological states. GRα is responsible for the induction and repression of target genes, it is expressed in virtually all human cells and tissues, and its expression is known to be downregulated by glucocorticoids. GRβ has been found to act as a dominant negative inhibitor of GRα‐mediated transactivation in in vitro studies with transfected cells, but it does not appear to have a significant inhibitory effect on GRα‐mediated transrepression. In addition, for most tissues the expression of GRβ, at least at the mRNA level, is extremely low compared with that of GRα. Some pro‐inflammatory cytokines appear to upregulate the expression of GRβ, and increased GRβ expression has been reported in diseases associated with glucocorticoid resistance or insensitivity, such as bronchial asthma, nasal polyposis, and ulcerative colitis. However, the possible role of GRβ in modulating glucocorticoid sensitivity and/or resistance in vivo has been highly debated and it is not yet clear.
Troponin T‐values provide long‐term prognosis in elderly patients undergoing non‐cardiac surgery
Authors: Oscarsson A. , Eintrei C. , Anskär S. , Engdahl O. , Fagerström L. , Blomqvist P. , Fredriksson M. , Swahn E.
Published: September 2004

Background:  The aim of this study was to evaluate the significance of elevated postoperative Troponin T (TnT) levels in an elderly population undergoing non‐cardiac surgery.

Methods:  Five hundred and forty‐six consecutive patients aged 70 years or older undergoing non‐cardiac surgery of >30‐min duration were enrolled in this prospective, observational study. A postoperative TnT measurement was obtained on the 5th to 7th postoperative day. Troponin T values greater than 0.02 ng ml−1 were considered positive. Patients were followed over a 1‐year period, and mortality and non‐fatal cardiac events (acute myocardial infarction and coronary interventions) were recorded.

Results:  Troponin T concentrations greater than 0.02 ng ml−1 were detected in 53 of the study subjects (9.7%). Eleven per cent of the patients with elevated TnT had electrocardiographic or clinical signs of myocardial ischemia. One year after surgery, 17 (32%) of the patients with abnormal TnT concentrations had died. In a multivariate Cox regression analysis adjusting for baseline and perioperative data, a TnT value >0.02 ng ml−1 was an independent correlate of the mortality adjusted hazard ratio (HR): 14.9 (95% CI 3.7–60.3). Other independent predictors of death were tachycardia (HR, 14.9 95% CI 3.45–64.8), ASA 4 (HR, 8.1 95% CI 1.3–50.0), reoperation (HR, 6.4 95% CI 1.1–36.9), and use of diuretics (HR, 4.2 95% CI 1.3–13.8).

Conclusion:  We conclude that elevated TnT levels in the postoperative period confer a 15‐fold increase in mortality during the first year after surgery. Our findings also provide evidence that silent myocardial ischemia is common in an elderly population. Routine perioperative surveillance for TnT might therefore be of use in detecting patients at an increased risk of mortality during the first postoperative year.
Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy
Authors: Hiller A. , Silvanto M. , Savolainen S. , Tarkkila P.
Published: September 2004

Background:  Diclofenac and paracetamol have different mechanisms and sites of action. Therefore, we tested if their combination is more effective for analgesia after tonsillectomy than either drug alone with respect to rescue analgesic consumption and visual analog scale values.

Methods:  The analgesic effects of intravenously administered propacetamol (injectable pro‐drug of paracetamol) and diclofenac or a combination on postoperative pain were compared in 71 adult elective tonsillectomy patients in a randomized, double‐blind study. After induction of anesthesia the patients received monotherapy with 2 g propacetamol (n = 25) or 75 mg diclofenac (n = 25), or a combined treatment with 2 g propacetamol and 75 mg diclofenac (n = 21) in physiologic saline as an infusion. Postoperatively the propacetamol dosage was repeated twice and diclofenac once on the ward. Oxycodone (0.03 mg kg−1) was used as a rescue analgesic by patient‐controlled analgesia.

Results:  On average the patients needed oxycodone 15.3, 13.2 and 10.6 times in the propacetamol, diclofenac and combination groups, respectively (NS). A verbal rating scale and a visual analog scale were employed for assessing post‐tonsillectomy pain, nausea and patient satisfaction in all groups. No statistically significant differences were found between the groups. Twelve of the 25 (48%) patients having received propacetamol complained of pain at the cannulation site.

Conclusion:  Combined treatment with propacetamol and diclofenac with the dosages used provided clinically only a minor advantage over monotherapy with propacetamol or diclofenac with respect to postoperative analgesia or the incidence of side‐effects in adult tonsillectomy patients.
Supplemental remifentanil during coronary artery bypass grafting is followed by a transient postoperative cardiac depression
Authors: Pleym H. , Stenseth R. , Wiseth R. , Karevold A. , Dale O.
Published: September 2004

Background:  The pharmacokinetic properties of the short‐acting µ opioid receptor‐agonist remifentanil makes it possible to give cardiac surgical patients a deep intraoperative anesthesia without experiencing postoperative respiratory depression and a prolonged stay in the intensive care unit (ICU). However, previous investigations have shown that patients who received remifentanil required additional analgesia during the early postoperative period as compared to patients who received fentanyl. The aim of the present study therefore was to investigate the effects of supplementing remifentanil to a standard fentanyl‐based anesthesia in coronary artery bypass grafting (CABG).

Methods:  The study was prospective, randomized, double‐blind, and placebo‐controlled. Twenty male patients aged 55–70 years were included. All patients received a standard fentanyl and isoflurane‐based anesthesia. In addition, the patients were randomized to receive either remifentanil 0.5 µg kg−1 min−1 or placebo during surgery. Hemodynamic recordings and measurements of blood glucose and plasma adrenaline and noradrenaline were performed intra‐ and postoperatively.

Results:  Remifentanil reduced the hemodynamic and metabolic response to surgical stress compared to the standard fentanyl‐based anesthetic regimen. However, the patients in the remifentanil group had a lower cardiac output (CO), left ventricular stroke work index (LVSWI), and mixed venous oxygen saturation (SvO2), and a higher central venous pressure (CVP) than the patients in the placebo group during the early postoperative phase, indicating a postoperative cardiac depression in the remifentanil group.

Conclusion:  In CABG, remifentanil reduces the hemodynamic and metabolic responses during surgery but seems to give a cardiac depression in the early postoperative phase.