bluuebunny/crossref_metadata_2025 huggingface dataset:
Levels of IL‐6 and soluble IL‐6 receptor are increased in HIV patients with a history of immune restoration disease after HAART
Authors: Stone SF , Price P , Keane NM , Murray RJ , French MA
Published: March 2003

Objectives We have previously described immune restoration diseases (IRD) associated with asymptomatic opportunistic infections presenting in immunodeficient HIV patients responding to highly active antiretroviral therapy (HAART). Here we address the question of whether patients with a history of IRD exhibit persistent immune activation, shown by elevated levels of interleukin‐(IL)‐6 and soluble IL‐6 receptor (sIL‐6R).

Methods Peripheral blood mononuclear cells (PBMCs) and plasma were collected from HIV patients with nadir CD4 T cell counts of < 80/µL and who had achieved immune reconstitution after HAART with (n=14) or without (n=15) experiencing IRD, severely immunodeficient (SID) patients with < 80 CD4 T cells/µL (n=8) and HIV seronegative controls (n=15). PBMC production and plasma levels of IL‐6, sIL‐6R and interferon (IFN)‐γ (PBMC only) were measured by enzyme linked immunosorbent assay (ELISA). Intracellular flow cytometry was used to determine the predominant cellular source of IL‐6 in HIV patients and controls.

Results Unstimulated PBMC from IRD patients produced significantly higher amounts of IL‐6 and sIL‐6R than non‐IRD patients and HIV seronegative controls. The sIL‐6R concentration was also significantly higher in supernatants from mitogen‐stimulated PBMC from IRD patients compared to non‐IRD patients. The production of IFN‐γ did not differ between IRD and non‐IRD patients. IRD patients had significantly higher plasma levels of IL‐6 compared to non‐IRD patients, SID patients and controls. Monocytes were the predominant source of IL‐6 in both HIV patients and controls.

Conclusions Patients with a history of IRD after HAART have elevated levels of IL‐6 and sIL‐6R.
The myrosinase‐glucosinolate system in the interaction between Leptosphaeria maculans and Brassica napus
Authors: Andreasson Erik , Wretblad Sofia , Granér Georg , Wu Xiaoming , Zhang Jiaming , Dixelius Christina , Rask Lars , Meijer Johan
Published: March 2003

summary

Leptosphaeria maculans causes blackleg disease, and resistance to this fungal pathogen is an important trait in the breeding of oilseed rape. A better comprehension of the role of the myrosinase‐glucosinolate system in this context is of great value. The present study is the first to address effects on multiple components of this complex system, including concentrations of individual glucosinolates, product formation, myrosinase isoform distribution and activity, and levels of myrosinase binding proteins during the infection process. One resistant B. napus cultivar (Maluka) and one susceptible cultivar (Westar) were compared in the investigation. Our results show that the two cultivars had the same histological distribution, isoform expression, and activity of the myrosinase enzymes. The glucosinolate levels were also similar, with the exception of glucobrassicin and neoglucobrassicin, which were significantly lower in the resistant cultivar at 11 days post‐infection. Growth of the fungus on the plant tissues did not alter glucosinolate levels, suggesting that L. maculans does not degrade these compounds. When the plants were starved of sulphur, and thereby depleted of glucosinolates, no increased susceptibility was observed. Hence, we suggest that the myrosinase‐glucosinolate system does not determine the outcome of the interaction between B. napus and L. maculans.
Core promoter for initiation of Cucumber mosaic virus subgenomic RNA4A
Authors: Sivakumaran K. , Chen M.‐H. , Roossinck M. J. , Kao C. C.
Published: March 2003

summary

The core subgenomic promoter for the initiation of Cucumber mosaic virus (CMV) RNA4A was characterized in vitro using a template‐dependent RNA synthesis assay and variants of the core promoter RNAs. The minimal sequence required for specific initiation from the cytidylate (T1) used in vivo consists of 31‐nucleotides (nt) 3′ of T1 and a 13 nt template sequence. This 44 nt RNA was found to provide three elements that contribute to efficient initiation of RNA4A synthesis by the CMV replicase: a stem‐loop secondary structure 3′ of T1, a template sequence that is rich in adenylates and uridylates, and T1 in an unbase‐paired sequence.
Developing information literacy: a key to evidence‐based nursing
Authors: Shorten A. , Wallace . C. , Crookes P. A.
Published: March 2003

This report describes the evaluation of a curriculum‐integrated programme designed to help students develop an awareness of the nursing literature, the skills to locate and retrieve it, and skills required in its evaluation; in other words ‘information literacy’. Positive changes in student performance on objective measures of information‐literacy skills were revealed as well as a significant increase in the levels of confidence of the student in performing those skills. Students who had undertaken the information‐literacy programme (‘programme’ students) performed better on a range of objective measures of information literacy, as well as reporting higher levels of confidence in these skills, than students who had not participated in the programme (‘non‐programme’ students). Evaluation of this programme provides evidence of the potential usefulness of a curriculum‐integrated approach for the development of information‐literacy skills within nursing education. With these underlying skills, students will be better equipped to consolidate and extend their key information‐literacy skills to include research appreciation and application. These are vital for effective lifelong learning and a prerequisite to evidence‐based practice.
Culturally competent care: emphasis on understanding the people of Afghanistan, Afghanistan Americans, and Islamic culture and religion
Authors: Giger J. Newman , Davidhizar R.
Published: March 2003

Since the attacks in New York and Washington, DC, in September 2001, increased racial and religious animosity has left Arabs, other Middle Easterners, Muslims, and those who bear physical resemblance to members of these groups, fearful. This article provides information about the people of Afghanistan, Afghanistan Americans, and Islamic culture and religion, which can greatly assist the nurse who is confronted with persons from diverse cultures during the provision of care. The Giger & Davidhizar Transcultural Assessment Model was first published in the International Nursing Review in 1990. This model is now used worldwide and provides an assessment model to assist in understanding cultural phenomena and individuals from different cultures.
Nietzsche for nurses: caring for the Übermensch
Authors: Drummond John S.
Published: March 2003

Abstract We hear much these days of lifelong learning and higher levels of nursing practice. We have even been introduced to the concept of the supernurse. This paper seeks to contribute an ethico‐political dimension to the largely performative uses of these terms in contemporary nursing politics. This is done by exploring the promise of certain elements of Nietzsche's philosophy for nursing. Certain major Nietzschean themes are outlined in the context of modernity followed by their exploration in a nursing context. These themes come principally from Thus Spake Zarathustra, and include not only that of Übermensch (Superman), but also the related ideas of eternal recurrence, nihilism, and the last Man. It is argued that the conditions in which nurses now learn and practice have become increasingly instrumentalized and technorational to the extent that they are in danger of effecting a nihilism in what becomes a culture of perpetual obligation to those who would seek to measure our performance. It is against this background that Nietzsche's idea of the Übermensch is explored as a figure for self‐overcoming the professional subjectivity that may be constructed in the face of these conditions. However, it will be seen that this raises certain issues which beg the question of the productive value of Nietzsche's philosophy in this particular context. At this point, in the last part of the paper, by considering the tensive relation between the discourse practices of present‐day managerialism and nursing ethics, it is argued that it is these very problems that present the Übermensch as a tensive but potentially productive figure for nursing and nurse education in its broadest sense.
Building the science of health promotion practice from a human science perspective
Authors: Northrup Deborah Thoun , Purkis Mary Ellen
Published: March 2003

AbstractWhile health promotion is widely acknowledged as a practice field where multidisciplinary teamwork is important, within nursing's discipline‐specific literature, a strong argument can be discerned regarding the profession's belief that it has a clear and unique role to play in that field. Yet rarely is this unique role, how it arises, and specifically how its effects are to be demarcated, attended to within the discipline‐specific literature. Two philosophical perspectives on science are presented and we demonstrate the extent to which these two perspectives influence nursing scholarship, including nursing practice within the field of health promotion. We then go on to argue that, for nurses to sustain their claim to a unique and important contribution within health promotion, clear articulation of the philosophical premises underpinning practice methodologies is warranted. Specifically we argue the importance of such clarity within the context of an analysis of the discourse of multidisciplinary practice as a strategy for avoiding confronting the ways in which bio‐medical authority has already significantly demarcated how health promotion practice can proceed.
Nursing responsibility and conditions of practice: are we justified in holding nurses responsible for their behaviour in situations of patient care?
Authors: Pask Elizabeth J.
Published: March 2003

Abstract This paper analyses a situation where a patient's suffering provoked feelings of compassion in a student nurse, and distress at her patient's circumstances. The reported behaviour of qualified nurses within the situation suggests that they lacked compassion, had inadequate knowledge, and that they failed to understand their patient's plight. An account of the situation is followed by an exploration of the nature of moral agency, and understanding in nursing. Nurses' capacity for moral imagination is shown to be of crucial importance to the care that patients receive. The extent of nurses' responsibility for their behaviour is considered, and in particular, the extent of nurses' responsibility during times when they experience strain. Argument leads to the conclusion that we are justified in holding nurses responsible for their behaviour in situations of patient care, although we must not judge a nurse's behaviour too hastily. Attention is drawn to the need for a moral climate to sustain those nurses who struggle to give good patient care, despite the strain that is ever present within today's world of health care.
The person of the voice: narrative identities in informed consent
Authors: McCormack Brendan
Published: March 2003

Abstract This paper explores the dominant rational approach to informed consent and challenges the appropriateness of this approach to ethical decision‐making with people with dementia. In dementia care a dominant assumption exists that people are not autonomous because of their inability to make decisions and exercise freedom of choice. The rational understanding of autonomy being the capacity to exercise freedom of choice means that health and social care professionals feel justified in making decisions on behalf of the person with dementia. If a person cannot consent to an intervention then a proxy is used to make the decision. This paper argues that such an approach reinforces the mind‐body dualism that dominates health and social care discourse. Whilst acknowledging the place of proxy decision‐making, it is argued that there is a need to hear the voice of the person with dementia that goes beyond rational understandings of what is heard and that does not reinforce separation of the mind and body. An understanding of the person through their ‘narrative identity’ is proposed and illustrated through a case example. Drawing on the philosophy of Ricoeur it is argued that an individual's narrative identity can be developed and used to underpin informed consent decisions. Using a case example it is argued that paying attention to an individual's narrative identity provides a way of respecting the autonomy of the individual with dementia in a way that is consistent with their overall life plan.
Pieces of time
Authors: Young Valerie
Published: March 2003

Abstract Drawing on research data from a recent project, this paper reveals how cultural, organizational, professional and personal dimensions of time affect nurses’ availability to care and patients’ experiences of being cared for. Here, I will philosophize these dimensions of time through both the philosophical stance of the research methodology used in the study – phenomenological hermeneutics – and by engaging in philosophical theory that explores and challenges nurse and patient talk during interview. Patients’ experiences of time tend to be embodied, whereas nurses choose between a disembodied structure of linear clock time or an embodied more spiritual experienced sense of time. To capture differences and their significance to caring, this paper first explores the way cursive time shapes and controls caring encounters. Following this, research data will be explored to demonstrate how an expanded notion of time as both cursive and circular enables nurses to sense patients’ illness patterns and to move with the ebb and flow of patients’ life/illness experiences. Next, the moment or the act of caring is explored as a presence, as a moral stance or presencing of the nurse for the patient. Finally, the notion of timelessness or what Kristéva calls ‘monumental time’ is explored in the context of the nurse/patient giving and gifting relationship, particularly their giving/gifting of voice and words to each other. Sensual, cultural and historical appreciation of these time dimensions is invited through the use of visual imagery. Exposure of the limitations, locations and dislocations of language reveals the therapeutic power of silence, quiet and stillness. Consequently, poetry will be used to expand the visual imagery and engage the reader in the silence from which words emerge, and the silence that lives between and within words, the silence of timelessness. O O’Donohue says ‘When we forget or neglect this silence we empty our world of its secret and subtle presences’.
Stratum Corneum Barrier Integrity Controls Skin Homeostasis
Authors: Smith Walter
Published: March 2003

The stratum corneum water barrier controls structural and functional properties of both the epidermis and the dermis. Treatments which chronically disrupt the stratum corneum water barrier can induce changes similar to those seen with ’anti‐aging’ treatments such as (‐Hydroxy acids (AHAs) and Retin A™.

Barrier disruption via daily tape stripping increases epidermal and dermal thickness, superficial and integral skin firmness, and improves skin surface texture. Modest or transitory disruption did not produce such effects. Similar results were observed with topical application of AHAs, retinoids or mild irritants after about 4‐6 weeks provided such treatments resulted in prolonged elevation in TEWL (trans‐epidermal water loss). Treatments that did not chronically elevate TEWL could also produce positive cosmetic effects, but such effects were in general restricted to the skin surface or epidermis. Irritation, which was observed with some treatments, was not solely responsible for the positive effects observed.
Derivatization Procedure and HPLC Determination of 2‐Ethoxyethanol in Cosmetic Samples
Authors: Mariani E. , Villa C. , Neuhoff C. , Dorato S.
Published: March 2003

Ethylene glycol monoethyl ether or 2‐ethoxyethanol finds a wide industrial application as a solvent for lacquers, inks, dyes, household products and as a surfactant. It is also found in cosmetics such as nail products, face cleansers, liquid soaps, oral care products, hair colours and fixatives. The potential hazard to human health of 2‐ethoxyethanol following inhalation and dermal exposure has been recently reviewed and the European Cosmetic, Toiletry and Perfumery Association (COLIPA) has issued recommendations suggesting its non‐use as a cosmetic ingredient. Therefore a simple and fast monitoring method is necessary for routine control to identify and quantify 2‐ethoxyethanol in raw materials and finished cosmetics. We have developed a sensitive and selective method to determine 2‐ethoxyethanol in complex matrices by precolumn derivatization with 1‐naphthyl isocyanate and RP‐HPLC analysis. Four laboratory‐made cosmetic formulations (a nail lacquer remover, a baby oil, a skin lotion and an emollient O/W emulsion) containing three known amounts of 2‐ethoxyethanol (0.1%, 2.0%, 5.0%) have been studied. The obtained results show that this chromatographic procedure provides a good estimate of the true concentration of 2‐ethoxyethanol in complex matrices and it is reliable for routine analyses in quality control.
Removal and prevention of dental plaque with d‐tagatose
Authors: Lu Y. , Levin G. V.
Published: March 2003

Synopsis

Dental plaque develops when early bacterial colonizers adhere to the acquired pellicle (saliva‐derived proteinous coating on the tooth surface) followed by adhesion of late interspecies colonizers to form this type of biofilm (coaggregation). In developing a d‐tagatose‐based toothpaste, we examined 15 oral isolates, including both early colonizers (Streptococcus and Actinomyces) and late colonizers (Fusobacterium, Porphyromonas, Prevotella, Veillonella, Capnocytophaga, and Actinobacillus), and tested them for their ability to coaggregate with each other. We then tested the ability of d‐tagatose to reverse any such coaggregations. Coaggregation was examined visually and scored by using a system ranging from 0, for no visible coaggregation to 4, for maximum coaggregation. d‐Tagatose, at a concentration of less than 750 mm, completely reversed the coaggregation of 17 (60%) of 28 strongly coaggregating pairs (coaggregation score = 2 or higher) tested. In contrast, d‐sorbitol had little reversal effect. d‐Tagatose‐sensitive coaggregations were d‐galactose‐reversible as well. d‐Tagatose acted on both early and late colonizers; both groups, especially the late colonizers, were frequently involved in periodontal diseases. Thus, d‐tagatose has the potential for preventing and removing plaque development and for altering the subgingival microbiota. These effective qualities offer conservative control of gingival and periodontal disease.
Insulin resistance and associated metabolic abnormalities in muscle: effects of exercise
Authors: Pérez‐Martin A. , Raynaud E. , Mercier J.
Published: March 2003

Skeletal muscle is a major site of insulin resistance. In addition to glucose transport, oxidative disposal and storage defects, insulin resistant muscle exhibit many other metabolic abnormalities. After a brief review of insulin resistance determinants, we will focus on muscular abnormalities in obesity and type 2 diabetes. Glucose and lipid metabolism defects will be analysed and their interactions discussed. Exercise can improve many of these muscular abnormalities and the mechanisms underlying exercise‐induced benefits have been clarified during the past decades. Therefore, exercise training has proved to be useful in the management of insulin resistant states, i.e. mainly obesity, especially in its truncal distribution, and type 2 diabetes. However, exercise prescription remains poorly codified, and results on glycaemic control are sometimes conflicting. In the last part of this review, we will emphazise the pathophysiological basis for an individualized exercise prescription in insulin resistant subjects.
Self‐help in the long‐term treatment of obesity
Authors: Latner J. D.
Published: March 2003

Despite the short‐term success of professional behavioural techniques for obesity, weight losses are typically regained following treatment. The long‐term maintenance of treatment effects will probably require ongoing, continuing care. Continuing care may be economically feasible when administered through self‐help treatment modalities. Self‐help confers a number of psychological benefits, such as self‐reliance and an increased sense of empowerment. The effectiveness and cost‐effectiveness of various modalities of self‐help are reviewed, including purely self‐prompted help, self‐administered manuals, computer‐assisted therapy, professionally assisted correspondence courses, and non‐profit and commercial self‐help groups. Stepped‐care models suggest using a combination of these approaches when appropriate. However, logistical difficulties present themselves in stepped‐care approaches with obesity, such as the complicating effects of severity and comorbidity on stepped‐care status. Self‐help groups are a promising venue for the provision of continuing care and as an adjunct to more intensive, specialty therapies.
ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION
Authors: Bensinger William I. , Storb Rainer
Published: March 2003

Granulocyte colony stimulating factor (G‐CSF)‐mobilized peripheral blood stem cells (PBSC) are now widely used instead of bone marrow for autologous transplantation due to earlier hematopoietic recovery after transplant. The low toxicity of G‐CSF has prompted phase I and II studies to evaluate PBSC for allogeneic transplantation; these studies have demonstrated that engraftment of neutrophils, red blood cells and platelets is faster with peripheral blood cells compared to marrow. In randomized studies comparing mobilized PBSC and marrow for allogeneic transplantation, most trials have confirmed significantly earlier engraftment with PBSC and similar risks of acute graft‐vs.‐host disease (GVHD). In some trials, an increase of 10–15% in grade II–IV GVHD has been noted with PBSC. All studies showed a trend towards more chronic GVHD with PBSC. Some randomized studies have shown improved survival and disease‐free survival with the use of PBSC due to lowered transplant‐related mortality and fewer relapses in recipients of PBSC as a result of improved immune reconstitution and a graft‐vs.‐leukemia (GVL) effect. This survival benefit is most apparent in patients with more advanced hematologic malignancies, but further studies are needed to define the relative benefits of PBSC for patients with less advanced disease. The GVL effect of PBSC is currently being exploited with the use of non‐ablative allografts.
VON WILLEBRAND FACTORANDVON WILLEBRAND DISEASE
Authors: Budde Ulrich , Schneppenheim Reinhard
Published: March 2003

von Willebrand disease (vWD) is caused by quantitative and/or qualitative defects of the von Willebrand factor (vWF), a multimeric high molecular weight glycoprotein. Typically, it affects the primary hemostatic system, which results in a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (i) by initiating platelet adhesion to the injured vessel wall under conditions of high shear forces, and (ii) by its carrier function for factor VIII in plasma. Accumulating knowledge of the different clinical phenotypes and the pathophysiological basis of the disease translated into a classification that differentiated between quantitative and qualitative defects by means of quantitative and functional parameters, and by analyzing the electrophoretic pattern of vWF multimers. The advent of molecular techniques provided the opportunity for conducting genotype‐phenotype studies which have recently helped, not only to elucidate or confirm important functions of vWF and its steps in post‐translational processing, but also many disease causing defects. Acquired von Willebrand syndrome (avWS) has gained more attention during the recent years. An international registry was published and recommendation by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis in 2000. It concluded that avWS, although not a frequent disease, is nevertheless probably underdiagnosed. This should be addressed in future prospective studies. The aim of treatment is the correction of the impaired hemostatic system of the patient, ideally including the defects of both primary and secondary hemostasis. Desmopressin is the treatment of choice in about 70% of patients, mostly with type 1, while the others merit treatment with concentrates containing vWF.
CMV sinusitis as the initial manifestation of AIDS
Authors: Jütte A. , Fätkenheuer G. , Hell K. , Salzberger B.
Published: March 2003

Summary Cytomegalovirus (CMV) disease is a typical late‐stage complication of AIDS. Only six cases of CMV sinusitis have been reported in the literature. This is the first case of CMV sinusitis leading to the diagnosis of HIV and CMV retinitis. Diseases of the sinonasal tract may represent an initial manifestation of HIV or AIDS.
Combined therapy with saquinavir, ritonavir and stavudine in moderately to severely immunosuppressed HIV‐infected protease inhibitor‐naive patients
Authors: Battegay M , Vernazza Pl , Bernasconi E , Flepp M , Sendi P , Erb P , Malinverni R , Jaccard C , Morgenthaler S , Bedoucha V , Hirschel B ,   for the Swiss HIV Cohort Study
Published: March 2003

1

Basel Centre for HIV Research, Outpatient Department of Internal Medicine, University Hospital Basel,

2

Department of Internal Medicine, Cantonal Hospital St Gallen,

3

Department of Internal Medicine, Regional Hospital Lugano,

4

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich,

5

Basel Centre for HIV Research, Institute for Medical Microbiology, University Basel,

6

Division of Infectious Diseases, University Hospital Bern,

7

Division of Infectious Diseases, University Hospital Lausanne,

8

Roche Pharma AG, Reinach, and

9

Division of Infectious Diseases, University Hospital Geneva, Switzerland

Objective  To assess the short‐term and long‐term effect of a combination of saquinavir, ritonavir and stavudine in moderately to severely immunosuppressed protease inhibitor‐naive patients.

Design  Prospective open‐label multicentre study.

Patients and Methods  A total of 64 protease inhibitor‐naive and stavudine‐naive HIV‐infected patients with a CD4 count of < 250 cells/μL and > 10 000 HIV‐1 RNA copies/mL received saquinavir hard‐gelatin capsules, ritonavir and stavudine. Full (drop in viraemia of > 2 log10 and/or < 500 copies/mL) and partial responders (drop to between 500 and 5000 viraemia copies/mL) at week 9 (end of phase I) entered the second phase (additional 12‐month period).

Results  Fifty‐six patients completed phase I, 45 (70%) full responders and nine (14%) partial responders by intent‐to‐treat analysis. Thirty‐nine patients completed phase II, 33 (52%) full responders and two (3%) partial responders. Six patients had < 50 HIV‐1 RNA copies/mL at week 9, and 20 (31%) patients at month 12 of phase II. Mean CD4 cell counts increased significantly in the 56 patients from 89 to 184 cells/μL after 9 weeks and from 100 to 292 cells/μL in the 39 patients treated for another 12 months. Higher baseline viraemia and lower baseline CD4 cell counts were not associated with an unfavourable virological response at week 9 and month 12 of phase II. HIV DNA in peripheral blood monocytes decreased substantially (− 1.5 log10) but was detectable in all except one patient at the end of phase II.

Conclusion  In protease‐ and stavudine‐naive HIV‐infected patients with moderate to severe immunosuppression, saquinavir in combination with ritonavir and stavudine caused a substantial long‐term decrease in plasma viral load in approximately half the participants and a substantial increase in CD4 cell counts.
Switch studies: a review
Authors: Murphy RL , Smith WJ
Published: March 2003

Many physicians and patients wish to switch from successful protease inhibitor (PI)‐based regimens to alternative regimens, usually composed of a nonnucleoside reverse transcriptase inhibitor (NNRTI) or abacavir plus two nucleoside reverse transcriptase inhibitors (NRTIs). This reflects a desire to avoid or reverse the metabolic changes observed during long‐term PI‐based antiretroviral therapy; to alleviate PI‐associated adverse effects; and to improve adherence by simplifying the regimen. Data from a number of randomized and cohort PI switch studies are reviewed.

Overall, the results of these studies are mixed, perhaps because of limitations in study design, patient number and duration of follow‐up. In most studies, the frequency of virological failure is reduced by switching to a NNRTI regimen. Switching to an abacavir‐based regimen is associated with two‐fold higher risk of virological failure if mutations in the reverse transcriptase gene pre‐exist. Improvements in metabolic and lipid abnormalities have not been uniform but favourable lipid changes have been reported, particularly after switching to nevirapine. Resolution of lipodystrophy symptoms has not been demonstrated objectively, perhaps because of insufficient follow‐up and/or the role of NRTIs in this syndrome.
The relationship between ritonavir plasma trough concentration and virological and immunological response in HIV‐infected children
Authors: Gatti G , Pontali E , Boni S , De Pascalis CR , Bassetti M , Bassetti D
Published: March 2003

Background

We studied a number of factors, including ritonavir plasma levels, and their capability of predicting response to therapy with ritonavir (RTV).

Methods

Eleven HIV‐positive children, nucleoside reverse transcriptase inhibitor (NRTI)‐experienced, protease inhibitor (PI) naive, receiving RTV in combination with two NRTIs were enrolled in the study. Demographic parameters were: median age (range) 10 (2–13) years, weight 26 (10–38) kg, body surface area (BSA) 0.93 (0.47–1.21) m2. Baseline values of CD4, percent CD4 and viral load were 137 (2–1390) cells/µL, 9.5 (0.4–32.4)%, and 5.15 (4.30–6.18) log10 copies/mL, respectively. The dose of RTV was 318 (266–409) mg/m2 twice daily. Peak (3.5 h after administration) and trough (predose) plasma concentrations of RTV were determined on one occasion at steady‐state after a morning dose. Virological response to treatment was quantified as the difference between the baseline value of viral load and the value observed at 6 months of therapy (Δ6).

Results

The relationship between Δ6 and demographic parameters (age, weight, BSA, and baseline CD4, percent CD4, and viral load) and plasma concentrations of RTV was studied by linear regression. Median (range) Δ6 was 0.88 (0.77–2.62) log10 copies/mL. Peak and trough of RTV were 14.9 (3.2–31.4) and 5.0 (0.1–15.6) mg/L, respectively. Trough concentration of RTV was the best predictor of Δ6, although the relationship between these two variables was not statistically significant (r = 0.56, P= 0.075).

Conclusion

Our observation of a trend for a greater decrease in viral load in patients with higher trough concentration of RTV warrants further pharmacodynamic studies of PI in paediatric patients.
Naively changing HAART
Authors: Mandalia S , Parmar D , Fisher M , Pozniak A , Tang A , Youle M , Gazzard B , Beck EJ ,   on behalf of the NPMS‐HHC Steering Group
Published: March 2003

Background

Few UK studies have systematically investigated which antiretroviral therapy (ART) combinations HIV‐infected people are commenced on, when they start and reasons for stopping or changing their regimens.

Objective

To describe when HIV‐infected ART‐naive patients started first‐, second‐ or third‐line triple ART, classes of drugs prescribed and whether stopping ART was associated with virological, immunological or clinical indicators of treatment failure.

Design

A multicentre prospective open cohort study, employing the National Prospective Monitoring System on the use, cost and outcome of HIV service provision in UK hospitals‐HIV Health‐economics Collaboration (NPMS‐HHC).

Setting

Five hundred and eighty‐five ART‐naive patients seen in one London and two non‐London HIV clinics between 1 January 1998 and 31 December 1999.

Results

Of 4044 HIV‐infected individuals seen, 585 (15%) were ART naive. Median time interval (interquartile range, IQR) between HIV diagnosis and starting triple ART was 800 (63–2094) days. Median CD4 count when first diagnosed with HIV infection was 278 (IQR 127–481) cells/µL which dropped to 190 (IQR 86–297) cells/µL when starting triple ART. Of these 585 patients, 162 started second‐line and 46 third‐line ART during the study period. Of those patients who stopped ART, 51% did not have evidence of virological, immunological or clinical indicators of therapy failure.

Conclusions

Reasons for the delay between diagnosis of HIV infection and starting ART are varied. The large proportion of individuals who stopped ART for reasons other than virological, immunological or clinical indicators of therapy failure, are most likely due to drug‐associated toxicity. Both of these findings need to be elucidated in greater detail through prospective studies.
Assessing limiting factors to the acceptance of antiretroviral therapy in a large cohort of injecting drug users
Authors: Clarke S , Delamere S , McCullough L , Hopkins S , Bergin C , Mulcahy F
Published: March 2003

Objective

A comprehensive questionnaire was designed to assess the knowledge and understanding of injecting drug users (IDUs) regarding their HIV disease, and to determine any factors that may increase the acceptance of antiretroviral therapy (ART) by this group.

Results

Twenty percent of the total IDU cohort attending the GUIDE (GenitoUrinary Medicine and Infectious Diseases) clinic participated in the study. Fifty‐two percent had been homeless in the past 5 years and 84% are unemployed. Seventy‐two percent of patients did not complete second level education and 10% were illiterate. Fifty‐one percent had siblings or parents with a history of injection drug misuse, and 25% had at least one sibling also HIV positive. Forty‐seven percent started using drugs before the age of 13 years, and the most common initial drug was heroin (44%). Ninety‐five percent had attended for methadone maintenance therapy (MMT), with 39% currently attending for daily therapy. The majority of patients were unable to simply explain or interpret CD4 cell counts (54%) and ‘viral loads’ (65%). Fifty‐seven percent of patients were receiving highly active antiretroviral therapy (HAART). There was a statistically significant association between patients receiving HAART and both attendance at a primary care physician for methadone maintenance therapy (P = 0.005), and weekly take‐outs of methadone (P = 0.005). There was also an association between adherence to HAART and attendance at a methadone maintenance clinic (P = 0.04).

Conclusions

This study highlights the chaotic lifestyle and complex social background of the IDU. Such factors were not, however, associated with acceptance of HAART. The primary factor associated with both the acceptance of and adherence to HAART was regular and stable attendance for methadone therapy.
Findings from the first national clinical audit of treatment for people with HIV
Authors: Curtis H , Sabin CA , Johnson MA ,   the British HIV Association Clinical Audit Committee
Published: March 2003

Objectives

We reviewed the impact of and assessed adherence to British HIV Association (BHIVA) guidelines in routine clinical practice. Feedback has been provided to clinical centres to facilitate any necessary change.

Methods

We used a questionnaire to gauge clinicians' views on the guidelines and availability of antiretroviral therapy (ART) drugs and specialized tests. A case note review of 2044 patients was conducted to assess adherence to guideline recommendations plus patterns of use of HIV resistance testing.

Results

Most clinicians (74.1%) report that BHIVA guidelines have influenced care at their centres. A significant minority report problems with access to specialized tests. Most patients who started ART did so at CD4 counts lower than guidelines recommend but in most cases this reflected the CD4 count at diagnosis of HIV. Of patients on ART, an overwhelming majority (97.6%) were receiving three or more drugs. Of those on three or more drugs, 58.9% had latest viral load (VL) below 50 HIV‐1 RNA copies/mL and a further 18.1% below 500 copies/mL. Only 19.3% of patients had been tested for HIV resistance, of whom more than half showed resistance to more than one class of drugs.

Conclusions

This clinical audit provides encouraging evidence of the quality of care offered to people with diagnosed HIV in the UK. However late diagnosis means most people start ART at a more advanced stage than guidelines recommend.
One‐year treatment of chronic urticaria with mizolastine: efficacy and safety
Authors: Lorette G , Giannetti A , Pereira Rs , Leynadier F , Murrieta‐Aguttes M ,   the URTOL study group
Published: March 2003

Aim To assess the long‐term safety and efficacy of the H1‐receptor antagonist mizolastine in the symptomatic treatment of chronic urticaria (CU).

Background Mizolastine is a novel second generation antihistamine with additional anti‐inflammatory properties which has been shown to be effective in this condition as well as in allergic rhinitis. As the drug is used for chronic treatment, a detailed study of its efficacy and safety over a prolonged period was warranted.

Methods This open label multicentre trial recruited 211 patients suffering from CU (67% female; mean age 40 ± 13 years), with ≥ 1 episode/week if untreated. After a 7‐day placebo run‐in period, patients received mizolastine (10 or 15 mg) for 12 months. Efficacy was assessed by the patient using daily diary cards and overall condition evaluation at study visits. Clinicians also assessed the same parameters at each visit, and gave a global assessment at study termination. Safety was assessed by monitoring adverse events and laboratory parameters. Cardiac safety was monitored every 4 months using 12‐lead ECGs, with particular attention to QT intervals.

Results The trial was completed by 127 patients. Mizolastine reduced overall discomfort from the second week of therapy, and reduced itching and the number and size of wheals, as assessed by the patients. The clinician’s assessment of the proportion of patients with > 10 wheals decreased from 42% to 28% after 2 months. Clinical assessment also indicated that itch intensity and angioedema were improved by mizolastine, and the improvement was sustained throughout the trial. The investigators estimated that 70% of patients benefited from therapy. There were no drug‐related serious adverse events during the study. The cardiac repolarization assessed according to the QTc intervals was not modified during prolonged administration.

Conclusion Mizolastine improves CU symptoms, and these improvements are sustained over 12 months with no loss of drug sensitivity. No specific side‐effects are associated with its long‐term use in the current study.
Patient attitudes to topical antipsoriatic treatment with calcipotriol and dithranol
Authors: Poyner Tf , Menday Ap , Williams Zv
Published: March 2003

Objective Assessment of patient preference for antipsoriatic treatment with calcipotriol ointment or short‐contact dithranol cream.

Methods Two hundred and fifty‐eight psoriatic patients treated with calcipotriol (n = 138) or dithranol (n = 120) for up to 3 months, assessed the acceptability of treatment, overall satisfaction with treatment, their treatment preference using the ‘willingness to pay’ principle and selected their treatment of choice.

Results Overall satisfaction with calcipotriol was significantly better (72.7%, dithranol 60.3%; odds ratio 1.75, 95% CI 1.03, 2.99: P = 0.04). Patients considered calcipotriol a more acceptable treatment than dithranol in its appearance, smell, non‐irritancy, method and ease of application and lack of staining. Dithranol was considered less sticky than calcipotriol. Patients were ‘willing to pay’ a mean of £12.16 monthly for calcipotriol and £10.66 monthly for dithranol. ‘Willingness to pay’ did not correlate well with overall treatment satisfaction and was not correlated with household income. Calcipotriol was the preferred treatment of choice (calcipotriol 63%, dithranol 24%).

Conclusion Patients with psoriasis prefer treatment with calcipotriol ointment over short‐contact dithranol cream.
Polypoid clear cell acanthoma: case report
Authors: Inalöz Hs , Patel G , Knight Ag
Published: March 2003

Clear cell acanthoma of Degos is a rare benign tumour of epidermal origin with distinct histological features. Clinically, clear cell acanthoma is characterized by a ‘stuck on’ appearance of a nodule or dome‐shaped plaque that usually occurs on the legs of middle‐aged or elderly persons. We observed an unusual case of polypoid clear cell acanthoma on the right thigh of a 58‐year‐old male.
Atypical familial Papillon–Lefèvre syndrome
Authors: Inalöz H Serhat , Harman M , Akdeniz S , Inalöz SS , Isik A Gulden
Published: March 2003

The Papillon–Lefèvre syndrome is a rare autosomal recessive disorder. Consanguinity seems a notable prerequisite. Papillon–Lefèvre syndrome manifests in the first 6 months of life with rapidly progressive periodontitis and severe alveolar bone destruction leading to early loss of both the deciduous and permanent teeth in association with palmo‐plantar hyperkeratosis. We present two unusual cases of familial Papillon–Lefèvre syndrome, one of whom has only late onset of mild skin lesions and the other has severe skin lesions and relatively mild periodontal disease. A number of other cases recently described have also had atypical features.
Examination of mycosis fungoides for the presence of Epstein–Barr virus and human herpesvirus‐6 by polymerase chain reaction
Authors: Erkek E , Sahin S , Atakan N , Kocagöz T , Olut AI , Gököz A
Published: March 2003

Background

The aetiology of cutaneous T‐cell lymphoma (CTCL) remains unknown despite numerous investigations. In recent years, retroviruses and human herpesviruses have been implicated to play a causal part in CTCL.

Objective

The aim of this study was to elucidate the possible aetiopathogenetic role of human herpesviruses (HHV) in mycosis fungoides (MF).

Methods

Polymerase chain reaction was used to study formalin‐fixed, paraffin‐embedded lesional skin biopsies from 92 subjects with MF to evidence possible presence of Epstein–Barr virus (EBV) and HHV‐6.

Results

Biopsy specimens from nine subjects (9.8%) evidenced EBV DNA, whereas all except one of the subjects (1.1%) lacked HHV‐6 DNA.

Conclusions

Although these findings do not support a primary aetiological role for EBV and HHV‐6 in classical CTCL, the possibility remains that both viruses, particularly EBV, may act as potential cofactors in the development of CTCL.
Five cases of livedo‐like dermatitis (Nicolau’s syndrome) due to bismuth salts and various other non‐steroidal anti‐inflammatory drugs
Authors: Corazza M , Capozzi O , Virgili A
Published: March 2003

The authors report five cases of Nicolau’s syndrome observed over a period of about 25 years. The disease had occurred after intramuscular injections of different drugs (bismuth, diclofenac and ibuprofen). In all the described cases the clinical aspect was characterized by a livedoid pattern followed by a slow necrotizing evolution with scar formation; in some cases surgical debridement and plastic reconstructive surgery were performed. In the past Nicolau’s syndrome was described after intramuscular injections of bismuth salts for the treatment of syphilis; now, although still rare, it is described after injections of various aqueous drug solutions. The pathogenesis of Nicolau’s dermatitis appears to be more complex than the previous hypothesized embolism caused by oleous drugs.
Treatment of chronic radiation ulcers with recombinant platelet‐derived growth factor and a hydrophilic copolymer membrane
Authors: Wollina U , Liebold K , Konrad H
Published: March 2003

We report on a 59‐year‐old woman suffering from cutaneous T‐cell lymphoma of the mycosis fungoides type, who developed chronic ulcerating radiation dermatitis after total body electron beam irradiation with a cumulative dose of 36 Gy. The painful and easily bleeding ulcers could be markedly improved using a combined approach with topical platelet‐derived growth factor gel and hydrophilic copolymer membranes.
Successful treatment of postoperative pyoderma gangrenosum with cyclosporin
Authors: Schöfer H , Baur S
Published: March 2003

Postoperative pyoderma gangrenosum (PPG), also known as postoperative progressive gangrene of Cullen, is a rare and rapidly evolving complication of surgical procedures. Since the first description by Cullen in 1924 (Surg Gynecol Obstet 1924; 38: 579–582) various case reports have been published. Even in typical cases PPG is often misdiagnosed and therefore wrongly treated; the unknown aetiology makes treatment difficult. The therapies used for pyoderma gangrenosum include systemic corticosteroids, azathioprine, dapsone, mercaptopurine, sulphasalazine, sulphapyridine, thalidomide, cyclophosphamide, clofazimine, isotretinoin, immunoglobulins and cyclosporin. We report on two patients with PPG following breast surgery who were successfully treated with low‐dose cyclosporin (2.5–5 mg/kg per day).
Malignant eccrine poroma in an unusual location1
Authors: Sahin Mt , Türel A , Gündüz K , Kandiloglu Ar , Öztürkcan S
Published: March 2003

Malignant eccrine poroma is a rare skin appendage tumour, originating from the intraepidermal and upper dermal eccrine ducts. The tumour either arises spontaneously or develops in a long‐standing eccrine poroma, generally in elderly people over 60. Clinically, it tends to be a localized lesion, which manifests itself as a nodule or ulcerated tumour, favouring extremities. We report an 83‐year‐old female with an enlarging and bleeding tumour on her lumbosacral region. This lesion first appeared as a small pigmented papule and progressed to an erythematous patch with central papular portion and some peripheral pigmentation. Histopathology revealed malignant eccrine poroma. Also, immunohistochemically, diffuse and intense p53 staining was observed. Regular pigment pattern, brown globules and black dots were seen in dermoscopic examination. After performing a wide excision, 20 months of follow‐up revealed no recurrence or metastasis of the tumour. This case represents an unusually located malignant eccrine poroma with some pigmentation.
Cutaneous infection due to Scedosporium apiospermum in an immunosuppressed patient
Authors: Chaveiro MA , Vieira R , Cardoso J , Afonso A
Published: March 2003

Scedosporium apiospermum, the anamorphic form of Pseudallescheria boydii, is a filamentous fungus with low inherent virulence. Increasing numbers of cases of this infection have been reported probably related to the rising number of immunosuppressed persons. Apart from mycetoma, cutaneous and subcutaneous infection is rarely encountered in clinical practice.

We describe a case of cutaneous infection caused by Scedosporium apiospermum in a subject with rheumatoid arthritis and diabetes mellitus who was submitted to long‐term therapy with cyclosporin and corticosteroids. Histopathologic examination of a skin biopsy showed a granulomatous infiltrate with hyaline septate hyphae. Culture of two skin biopsies taken at two different observations of the woman, 3 weeks apart, allowed isolation of Scedosporium apiospermum. Therapy with itraconazole, 400 mg/day, for 3 months was effective in curing the infection.