bluuebunny/crossref_metadata_2025 huggingface dataset:
Networks and epidemic models
Authors: Keeling Matt J , Eames Ken T.D
Published: June 2005

Networks and the epidemiology of directly transmitted infectious diseases are fundamentally linked. The foundations of epidemiology and early epidemiological models were based on population wide random-mixing, but in practice each individual has a finite set of contacts to whom they can pass infection; the ensemble of all such contacts forms a ‘mixing network’. Knowledge of the structure of the network allows models to compute the epidemic dynamics at the population scale from the individual-level behaviour of infections. Therefore, characteristics of mixing networks—and how these deviate from the random-mixing norm—have become important applied concerns that may enhance the understanding and prediction of epidemic patterns and intervention measures.

Here, we review the basis of epidemiological theory (based on random-mixing models) and network theory (based on work from the social sciences and graph theory). We then describe a variety of methods that allow the mixing network, or an approximation to the network, to be ascertained. It is often the case that time and resources limit our ability to accurately find all connections within a network, and hence a generic understanding of the relationship between network structure and disease dynamics is needed. Therefore, we review some of the variety of idealized network types and approximation techniques that have been utilized to elucidate this link. Finally, we look to the future to suggest how the two fields of network theory and epidemiological modelling can deliver an improved understanding of disease dynamics and better public health through effective disease control.
Population pharmacokinetics of imatinib mesylate in patients with chronic‐phase chronic myeloid leukaemia: results of a phase III study
Authors: Schmidli H. , Peng B. , Riviere G‐J. , Capdeville R. , Hensley M. , Gathmann I. , Bolton A. E. , Racine‐Poon A.
Published: June 2005

Aims

This study was designed to investigate the biochemical and physiological covariates or comedications that affect the pharmacokinetics of imatinib mesylate in patients with chronic‐phase chronic myeloid leukaemia (CP CML).

Methods

Pharmacokinetic data were analyzed in 371 patients receiving 400 mg imatinib once daily during a phase III trial of imatinib vs interferon‐alfa plus cytarabine for the treatment of newly diagnosed CP CML. Covariates included age, weight, sex, ethnicity, haemoglobin (Hb) concentration, white blood cell (WBC) count, liver function, and creatinine concentration. Blood samples for imatinib analysis were taken on treatment days 1 and 29. Nonlinear mixed effects modelling was used for the population pharmacokinetic analysis.

Results

Population mean estimates (95% confidence interval) at day 1 for apparent clearance (CL) and apparent volume of distribution (V) of imatinib were 14 (13‐15) l h−1 and 252  (237‐267)  l,  respectively.  Modelling  suggested  that  CL  decreased  by  4  (3‐5) l h−1 from day 1 to day 29, whereas V remained unchanged. Interindividual variability in CL and V was 32% and 31%, respectively. Weight, Hb, and WBC count demonstrated small effects on CL and V. Doubling body weight or Hb or halving the WBC count was associated with a 12%, 86% and 8% increase in CL, respectively, and a 32%, 60% and 5% increase in V, respectively. Comedications showed no clear effects on imatinib CL.

Conclusions

Population covariates and coadministered drugs minimally affected imatinib pharmacokinetics in newly diagnosed CP CML patients.
Deep vein thrombosis and pulmonary embolism reported in the Prescription Event Monitoring Study of Yasmin®
Authors: Pearce Hilary M. , Layton Deborah , Wilton Lynda V. , Shakir Saad A. W.
Published: June 2005

Aim

To evaluate cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) reported in a prescription event monitoring study of Yasmin®, an oral contraceptive.

Methods

Reports of DVT/PE and events suggestive of DVT/PE were followed up by questionnaire.

Results

Thirteen cases (DVT five; PE eight), each with possible risk factor(s), were identified in 15 645 females using Yasmin®. Applying complete case analysis, the crude incidence rate was 13.7 cases per 10 000 woman‐years (95% confidence interval 7.3, 23.4).

Conclusions

Yasmin is associated with venous thromboembolism. An incidence rate has been calculated, but this may be subject to bias and should be interpreted with caution.
Enantioselective disposition of lansoprazole in relation to CYP2C19 genotypes in the presence of fluvoxamine
Authors: Miura Masatomo , Tada Hitoshi , Yasui‐Furukori Norio , Uno Tsukasa , Sugawara Kazunobu , Tateishi Tomonori , Suzuki Toshio
Published: June 2005

Aims

Lansoprazole is affected by polymorphism of CYP2C19. The aim of this study was to examine the effects of fluvoxamine, a CYP2C19 inhibitor, on the pharmacokinetics of each lansoprazole enantiomer among three different CYP2C19 genotype groups.

Methods

Eighteen healthy subjects, of whom six each were homozygous extensive metabolizers (homEMs), heterozygous extensive metabolizers (hetEMs), or poor metabolizers (PMs) for CYP2C19, participated in the study. Each subject received either placebo or fluvoxamine, 25 mg twice daily for 6 days, then a single oral dose of 60 mg of racemic lansoprazole. The plasma concentrations of lansoprazole enantiomers and lansoprazole sulphone were subsequently measured for 24 h post lansoprazole administration using liquid chromatography.

Results

In the homEMs and hetEMs, fluvoxamine significantly increased the AUC(0, ∞) and Cmax and prolonged the elimination half‐life of both (R)‐ and (S)‐lansoprazole, whereas in the PMs, the only statistically significant effect of fluvoxamine was on the AUC(0, ∞) for (R)‐lansoprazole. The mean fluvoxamine‐mediated percent increase in the AUC(0, ∞) of (R)‐lansoprazole in the homEMs compared with the PMs was significant (P = 0.0117); however, Cmax did not differ among the three CYP2C19 genotypes. On the other hand, fluvoxamine induced a significant percent increase in both the AUC(0, ∞) and Cmax for (S)‐lansoprazole in the homEMs compared with the hetEMs (P = 0.0007 and P = 0.0125, respectively) as well as compared with the PMs (P < 0.0001 for each parameter). The mean R : S ratio for AUC(0, ∞) of lansoprazole in the homEMs was significantly different between the placebo and the fluvoxamine treatment groups (12.7 (9.1, 16.8) vs 6.4 (5.4, 7.4), respectively, P < 0.0001), though not in the PMs (5.5 (4.3, 6.7) vs 5.9 (5.3, 6.5), respectively).

Conclusions

The magnitude of the contribution of CYP2C19 to the metabolism of (S)‐lansoprazole is much greater compared with that of the (R)‐enantiomer. In extensive metabolizers, hepatic CYP2C19 plays an important role in the absorption and elimination of lansoprazole, particularly the (S)‐enantiomer.
Efficacy of ACE‐inhibitor therapy on renal disease in glycogen storage disease type 1: a multicentre retrospective study
Authors: Melis D. , Parenti G. , Gatti R. , Casa R. Della , Parini R. , Riva E. , Burlina A. B. , Vici C. Dionisi , Di Rocco M. , Furlan F. , Torcoletti M. , Papadia F. , Donati A. , Benigno V. , Andria G.
Published: June 2005

Background  The efficacy of ACE‐inhibitors in decreasing microalbuminuria and proteinuria has been reported in a few patients with glycogen storage disease type 1 (GSD1); however, no case‐control study has ever been published.

Aim  The aim of the current study was to evaluate the efficacy of ACE‐inhibitors in reducing glomerular hyperfiltration, microalbuminuria and proteinuria, and in delaying the progression of renal damage.

Patients and methods  Ninety‐five patients (median age at the time of the study: 14·5 years) were enrolled from nine Italian referral centres for metabolic diseases. A retrospective study of a 10‐year follow‐up was conducted in order to compare the evolution of these parameters in treated patients with those who were not treated with ACE‐inhibitors.

Results  A significant and progressive decrease of glomerular filtration rate was observed in treated patients vs. those who were not treated with ACE‐inhibitors (P < 0·05). No difference was observed for microalbuminuria and proteinuria between the two groups of patients. Moreover, the ACE‐inhibitors significantly delayed the progression from glomerular hyperfiltration to microalbuminuria, but not that from microalbuminuria to proteinuria.

Conclusions  The results of the present study underline the importance of a strict follow‐up of renal function in GSD1 patients. The detection of glomerular hyperfiltration suggests precocious initiation of ACE‐inhibitor treatment to delay the progression of renal damage. A randomized prospective study is needed to establish for certain the real effectiveness of this treatment in GSD1 patients.
Long‐term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas
Authors: Biswas M. , Smith J. , Jadon D. , McEwan P. , Rees D. A. , Evans L. M. , Scanlon M. F. , Davies J. S.
Published: June 2005

Objective  Reports suggest that up to 70% of patients with microprolactinomas treated with dopamine agonist therapy may achieve long‐term normoprolactinaemic remission following drug withdrawal. Yet, there is no consensus on the duration of therapy nor is therapeutic interruption universally practised. We have assessed remission rates in a large cohort of treatment‐naive subjects with microprolactinomas. Subjects received dopamine agonist (DA) therapy with either cabergoline or bromocriptine for a period of 2 to 3 years in the majority of cases, followed by a trial of treatment withdrawal.

Design  Retrospective analysis of clinic records of 89 patients (mean age 32·7 ± 8·4 years, 84 women and 5 men) who had received either cabergoline (n = 67) (0·5–3 mg weekly) or bromocriptine (n = 22) (2·5–10 mg daily) for a mean duration of 3·1 years.

Results  Following withdrawal of therapy, 57 subjects developed recurrence (64%) and the mean time to recurrence was 9·6 months (range 1–44 months), while 32 subjects (36%) remained in remission beyond 1 year (mean 3·6 years, range 1–7 years). There was no difference in remission rates between subjects treated with cabergoline (n = 21) and bromocriptine (n = 11), but a direct relationship between pretreatment prolactin concentration and risk of recurrent symptomatic hyperprolactinaemia was observed. No subjects developed clinical features to suggest tumour expansion following therapeutic discontinuation.

Conclusions  This study confirms that abrupt withdrawal of chronic dopamine agonist therapy, following 2 to 3 years of treatment is safe and associated with long‐term remission in 30–40% of subjects with microprolactinomas. This therapeutic strategy is convenient and applicable in clinical practice.
Postoperative treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists decreases tumour remnant growth
Authors: Greenman Y. , Tordjman K. , Osher E. , Veshchev I. , Shenkerman G. , Reider‐Groswasser I. I. , Segev Y. , Ouaknine G. , Stern N.
Published: June 2005

Objective  There is no consensus as to the optimal postoperative treatment of patients with clinically nonfunctioning pituitary adenomas (NFPA) in whom total tumour removal has not been achieved. In this study we assessed whether dopamine agonist (DA) treatment can prevent postoperative remnant enlargement in NFPA.

Design and methods  Thirty‐three patients (25 men/8 women; mean age, 61·7 ± 11·2 years; mean follow‐up, 40·6 ± 4·8 months) were treated with DA, and their outcome was compared to that of 47 untreated patients (33 men/14 women; mean age, 59 ± 2 years; mean follow‐up, 42·9 ± 4·2 months).

Results  Tumour mass decreased or remained stable in 18/20 patients in whom DA treatment was initiated upon detection of residual tumour on postoperative MRI (group I). In 13 subjects (group II), DA therapy was started when tumour remnant growth became evident during the course of routine follow‐up. Tumour growth stabilized or decreased in 8/13 (61·5%) of these patients. In contrast, tumour size remained stable in only 38·3% (18/47) of the untreated subjects (P < 0·0001 for comparisons among the three groups) and increased in the remaining 29 patients. Tumour enlargement free mean survival time was 103·7 ± 8·8 months (CI 86·3–121) for group I, 43·9 ± 9·6 months (CI 25·2–62·8) for group II and 36·7 ± 3·8 (CI 29·2–44·2) for the control group (P = 0·0017). Treatment vs. control hazard ratio for tumour enlargement was 0·135 for group I (P = 0·007, 95% CI 0·032–0·577) and 0·892 for group II (P = 0·817; 95% CI 0·34–2·34).

Conclusions  Dopamine agonist therapy is associated with a decreased prevalence of residual tumour enlargement in patients with nonfunctioning pituitary adenomas, particularly when treatment is instituted before tumour remnant growth is detected.
Characterization of antipituitary antibodies targeting pituitary hormone‐secreting cells in idiopathic growth hormone deficiency and autoimmune endocrine diseases
Authors: De Bellis Annamaria , Bizzarro Antonio , Perrino Silvia , Coronella Concetta , Conte Marisa , Pasquali Daniela , Sinisi Antonio Agostino , Betterle Corrado , Bellastella Antonio
Published: June 2005

Objective  In order to investigate whether somatotrophs are the target of antipituitary antibodies (APA) in adult patients with growth hormone deficiency (GHD), we studied the sera of 37 APA positive patients.

Patients  Patients were grouped as follows: nine patients with APA at high titre (> 1 : 8) affected by apparently idiopathic GHD; four of them (group 1a) with isolated GHD diagnosed during childhood and five with GHD diagnosed during adulthood associated with autoimmune endocrine diseases (group 1b), and 28 patients with autoimmune endocrine diseases without pituitary impairment, previously found positive for APA at low titre (1 : 8, group 2).

Measurements  APA were evaluated by a four‐layer double indirect immunofluorescence technique.

Results  In group 1a patients, APA immunostained exclusively GH‐producing cells. In group 1b patients, APA were directed not only to GH‐ but also to other pituitary hormone‐producing cells. In group 2 patients, APA were directed selectively to PRL‐producing cells and rarely to some GH‐producing cells.

Conclusions  In the present study, we demonstrated that GH‐secreting cells are the target of the autoimmune reaction in autoimmune GHD and that the immunostaining of only the somatotrophs is typical of isolated GHD. In contrast, the finding of diffuse staining of APA indicates the need to search for other autoimmune diseases. Finally, the presence of APA at low titre directed against PRL‐secreting cells in patients with autoimmune endocrine diseases in the absence of pituitary impairment, seems to be only a nonspecific marker of pituitary autoimmunity. A longitudinal study would be useful to clarify the relationship between the different pituitary cell involvement and the natural history of pituitary dysfunction in autoimmune hypophysitis.
Correlation between genotype, phenotype and sex of rearing in 111 patients with partial androgen insensitivity syndrome
Authors: Deeb A. , Mason C. , Lee Y. S. , Hughes I. A.
Published: June 2005

Objective  Partial androgen insensitivity syndrome (PAIS) is a heterogeneous group of intersex disorders characterized by a typical perineoscrotal hypospadias/micropenis phenotype, and a normal androgen‐producing testis. Various mutations in the androgen receptor (AR) are known to cause PAIS. Phenotypic expression is widely variable and there are no agreed guidelines to determine the sex of rearing in individuals with borderline masculinization. We aimed to quantitatively assess the external genital phenotype in relation to AR genotype and sex of rearing and identify criteria that differentiate mutation positive (ARmt) from mutation negative (ARwt) PAIS patients.

Patients and design  Cases with a diagnosis of PAIS were identified from the Cambridge Intersex Database. An external masculinization score (EMS) was used to quantify the degree of undermasculinization. Family history of AIS and details of the sex of rearing were recorded. Androgen binding was analysed in fibroblasts obtained from genital skin biopsies and mutational analysis of the AR was performed on genomic DNA extracted from peripheral blood. EMS and sex of rearing were compared in cases with similar mutations reported on the McGill International Database.

Results  Two hundred and sixty‐three patients with PAIS were identified. Androgen receptor gene sequencing was performed in 111 patients. Twenty‐seven (24%) had mutations. Family history of AIS was present in 61 and 21% of ARmt and ARwt patients, respectively. The median EMS was 3 in both groups. The majority of ARmt patients had abnormal binding and there was a tendency to a higher median testosterone rise on hCG stimulation in ARmt (9·3 nmol/l) compared with ARwt patients (6·9 nmol/l). All patients with EMS of 4 or more were raised as male but there was an overlap of sex of rearing in patients with an EMS less than 4. A wide variation of EMS in relation to genotype and sex of rearing was observed.

Conclusion  The phenotype in PAIS is extremely variable and is rarely predicted by the AR genotype. Apart from the family history, there are no specific criteria to differentiate ARwt from ARmt. Sex of rearing is not entirely dependent on the EMS. Cultural issues, other modifying genes and response to androgen trials might be influencing factors. Collaborative studies with uniform protocols are needed to investigate infants with PAIS. Documenting phenotype, surgical procedures and outcome criteria are necessary to enable decision‐making on the sex of rearing in patients with a lower range EMS.
Gender differences in the relation of insulin‐like growth factor binding protein‐1 to cardiovascular risk factors: a population‐based study
Authors: Undén Anna‐Lena , Elofsson Stig , Brismar Kerstin
Published: June 2005

Objective  A possible involvement of insulin‐like growth factor‐I (IGF‐I) and its binding protein IGFBP‐1 in the pathogenesis of cardiovascular disorder has been suggested. However, few publications have addressed the gender differences in cardiovascular risk factors in relation to the IGF/IGFBP system. The aim of the present study was to study gender differences in the relationship between fasting serum levels of IGFBP‐1 and cardiovascular risk factors in a normal population of men and women.

Design  Cross‐sectional study.

Patients  A normal population of 273 men and women aged 20–74 years.

Measurements  A medical examination was performed and blood drawn in the morning after subjects had been fasting overnight. Before the examination, they were asked to fill out a questionnaire concerning lifestyle and psychosocial factors.

Results  Fasting IGFBP‐1 was lower in men than in women and was positively correlated to age in men but not in women. The men had in general a more disadvantageous cardiovascular risk profile than women, with several indicators of the metabolic syndrome: higher blood pressure and higher serum levels of total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL‐C), plasma‐glucose and insulin, as well as lower IGFBP‐1. Women had lower physical activity, lower consumption of alcohol, and lower values on indicators of psychosocial and mental health but had a healthier diet. Our findings indicate that low circulating levels of IGFBP‐1 are associated with the well‐known risk factors of cardiovascular disease; however, the association showed a different pattern for men and women. In men we found a negative association with body mass index (BMI), insulin resistance and diastolic blood pressure, and a positive association with SHBG, cortisol and testosterone. For women low IGFBP‐1 appears in negative associations with BMI, waist–hip ratio (WHR), insulin resistance and testosterone, and in positive associations with SHBG and cortisol. Significant gender differences in the correlation with IGFBP‐1 are seen for testosterone, cortisol, SHBG, WHR and oestradiol. For HDL‐C and diastolic blood pressure the gender difference in correlation was at the limit of significance (P < 0·10).

Conclusion  Low circulating levels of IGFBP‐1 are associated with the well‐known risk factors of cardiovascular disease; however, the association showed a different pattern for men and women. The most marked gender differences in the correlation with IGFBP‐1 are seen for testosterone, cortisol, SHBG, WHR, oestradiol, HDL‐C and diastolic blood pressure. Our study emphasizes the importance of separate analyses for men and women. The results presented are a step towards gaining a better understanding of the gender differences in cardiovascular disease and in the regulation of IGFBP‐1, though further prospective studies are needed.
Assessment of quality of life in patients with uncontrolled vs. controlled acromegaly using the Acromegaly Quality of Life Questionnaire (AcroQoL)
Authors: Trepp Roman , Everts Regula , Stettler Christoph , Fischli Stefan , Allemann Sabine , Webb Susan M. , Christ Emanuel R.
Published: June 2005

Objective Acromegaly is a chronic disease with an important impact on quality of life. An acromegaly disease‐generated quality of life questionnaire (AcroQoL) has recently been developed. We aimed to confirm reliability, construct validity and disease‐specificity of the AcroQoL questionnaire. Second, we investigated the effect of remission status on health‐related quality of life (HRQoL) in patients with acromegaly.

Design and patients Using a prospective, cross‐sectional design, 33 patients with treated acromegaly and 22 patients with treated hormone‐inactive pituitary adenoma under stable replacement therapy completed the German version of the AcroQoL questionnaire.

Measurements and results Cronbach's alpha analysis showed high reliability of the total score and the different scales and subscales in patients with acromegaly (alpha ranging from 0·83 to 0·93, item‐total correlation 0·41–0·84). Patients with hormone‐inactive pituitary adenoma showed lower reliability (alpha ranging from 0·17 to 0·75). Exploratory factor analysis in patients with acromegaly suggested a two‐factorial solution with item distribution largely matching the scaling of the original Spanish questionnaire. Multiple regression analysis revealed significantly lower results of the total score and the different scales and subscales (indicating worse HRQoL) in patients with persistent acromegalic activity compared to patients with acromegaly in remission or discordant remission status. Consistently, IGF‐I was an independent negative predictor of the different scores of the questionnaire.

Conclusions The AcroQoL questionnaire represents a reliable, construct valid and disease‐specific tool for assessing health‐related quality of life in patients with acromegaly. Patients with biochemically uncontrolled acromegaly showed significantly lower HRQoL than patients with acromegaly in remission or discordant remission status.
Rapid turnover of GATA‐2 via ubiquitin‐proteasome protein degradation pathway
Authors: Minegishi Naoko , Suzuki Norio , Kawatani Yukie , Shimizu Ritsuko , Yamamoto Masayuki
Published: June 2005

Transcription factor GATA‐2 is expressed in a number of tissues, including hematopoietic stem and progenitor cells, and is crucial for the proliferation and survival of hematopoietic cells. To further characterize the function of GATA‐2, we examined the cellular turnover mechanism of GATA‐2. In P815 cells, the half‐life of endogenous GATA‐2 was found to be as short as 30 min after cycloheximide treatment. This short half‐life was reproducible in other hematopoietic and neuroblastoma cell lines with moderate variation. We also found that ultraviolet (UV)‐C irradiation markedly represses the GATA‐2 protein level by facilitating the degradation process. Since treatment of the cells with the proteasome inhibitor MG132 or clasto‐Lactacystin substantially abrogated the effects of cycloheximide and UV‐C irradiation and increased the expression level of both endogenous and transfected GATA‐2, the degradation of GATA‐2 seems to occur through the proteasome pathway. Structure‐function analyses with the GAL4‐DNA binding domain (GBD)‐GATA‐2 fusion protein and GATA‐2 deletion mutants suggested that the protein degradation regulatory elements of GATA‐2 reside in three regions, two of which overlap with the transactivation domain. We also detected poly ubiquitinated forms of GATA‐2. Taken together, these results demonstrate that GATA‐2 is turned over rapidly through the ubiquitin‐proteasome pathway.
Multiple roles of Rbx1 in the VBC‐Cul2 ubiquitin ligase complex
Authors: Megumi Yuzuru , Miyauchi Yasuhiro , Sakurai Hitomi , Nobeyama Hiroyuki , Lorick Kevin , Nakamura Eijiro , Chiba Tomoki , Tanaka Keiji , Weissman Allan M. , Kirisako Takayoshi , Ogawa Osamu , Iwai Kazuhiro
Published: June 2005

The importance of the ubiquitin system largely depends on ubiquitin ligases, E3s, as they determine the specificity of the system. Rbx1/ROC1/Hrt1, a RING finger protein, functions as an important component of the cullin‐containing SCF and VBC‐Cul2 ligases. Modification of cullins by NEDD8 (NEDDylation), has been shown to be essential for the E3 activity of both SCF and VBC‐Cul2, and it was suggested that Rbx1 acts as the E3 for cullin NEDDylation. RING finger is composed of eight cysteine and histidine residues that bind to zinc ions. Rbx1 is a highly evolutionarily conserved protein; however, the eighth coordination residue in its RING finger is aspartate (D97) rather than cysteine. Substitution of D97 with each of the other 19 amino acids demonstrates that aspartate is superior to cysteine in cullin NEDDylation. Interestingly, however, different D97 mutants demonstrate different activities towards 6 cullins tested. Importantly, we were able to discriminate between the NEDDylating activity of Rbx1 and its involvement in the ubiquitylation reaction within the context of VBC‐Cul2. Moreover, while Rbx1 is not involved in governing the stability of SCF, Rbx1 mutants destabilize VBC‐Cul2. Taken together, these results indicate that various mechanisms regulate both the activities and the stability of cullin‐based ligases.
Cell‐type specific utilization of multiple negative feedback loops generates developmental constancy
Authors: Iwanami Masaki , Hiromi Yasushi , Okabe Masataka
Published: June 2005

Signaling pathways generally contain multiple negative regulators that are induced by the signal they repress, constructing negative feedback loops. Although such negative regulators are often expressed in a tissue‐ or cell‐type specific manner during development, little is known about the significance of their differential expression patterns and possible interactions. We show the role and interplay of two cell‐type specific negative feedback loops during specification of photoreceptor neurons in the Drosophila compound eye, a process that occurs via epidermal growth factor (EGF)‐mediated sequential induction through the activation of the Ras/MAPK signaling pathway. Inducing cells secreting EGF express a negative regulator Sprouty (SPRY) that lowers Ras/MAPK signaling activity, and as a consequence reduces the signal‐dependent expression of a secreted EGF inhibitor, Argos (AOS). Induced cells in turn express an orphan nuclear receptor Seven‐up (SVP), which represses SPRY expression thereby allowing expression and secretion of AOS, preventing further induction. When this intricate system fails, as in spry mutants, sequential induction is no longer constant and the number of photoreceptor neurons becomes variable. Thus, cell‐type specific utilization of multiple negative feedback loops not only confers developmental robustness through functional redundancy, but is a key component in generating consistent patterning.
A decreased level of FtsZ is responsible for inviability of RNase E‐deficient cells
Authors: Takada Ayako , Nagai Kazuo , Wachi Masaaki
Published: June 2005

The endoribonuclease RNase E, encoded by the essential gene rne, plays a major role in cellular RNA metabolism, i.e. maturation of functional RNAs such as rRNA and tRNA, degradation of many mRNAs and processing of the ftsZ mRNA which encodes the essential cell division protein FtsZ. RNase E function is somehow regulated by the RNA binding protein Hfq. We found that temperature‐sensitive colony formation of a rne‐1 mutant was partially suppressed by introduction of a hfq::cat mutation. Neither accumulation of rRNA and tRNAPhe precursors nor incomplete processing of ftsZ mRNA in the rne‐1 mutant was rescued by the hfq::cat mutation. However, the amount of FtsZ protein that was decreased in the rne‐1 mutant was recovered up to a level similar to that of wild‐type cells by the hfq::cat mutation. Overproduction of Hfq inhibited cell division because of decreased expression of FtsZ. Artificial expression of the FtsZ protein from a plasmid‐borne ftsZ gene partially suppressed the temperature‐sensitivity of the rne‐1 mutant. These results suggest that the decreased level of FtsZ is, at least in part, responsible for the inviability of RNase E‐deficient cells.
Pressure ulcer risk factors in patients undergoing surgery
Authors: Lindgren Margareta , Unosson Mitra , Krantz Ann‐Margret , Ek Anna‐Christina
Published: June 2005

Aim.  This paper reports a study to identify risk factors associated with pressure ulcer development among a mixed group of adult patients undergoing surgery.

Background.  Few studies have been carried out with patients undergoing surgery to assess the risk of pressure ulcer development, and so there is a little knowledge of the risk factors for this group. However, studies among non‐surgical patients have shown that nutritional predictors such as low serum albumin level and low body mass index (BMI) are of great importance. An additional predictive factor may be low blood pressure. It is important to study these predictors further among patients undergoing surgery, using techniques such as multiple regression techniques, designed to identify the most important predictors for pressure ulcer development.

Methods.  A prospective comparative study was carried out in 1996–1998 with 286 adult patients undergoing surgical treatment. The data were collected from patient records by Registered Nurses preoperatively, for seven days postoperatively and thereafter once a week for up to 12 weeks. Perioperative data were also collected. The Risk Assessment Pressure Sore Scale was used, and data were collected on general physical condition, activity, mobility, moisture, food intake, fluid intake, sensory perception, friction and shear, body temperature and serum albumin.

Results.  Forty‐one (14·3%) patients developed pressure ulcers during the observation period. The most common type was non‐blanchable erythema. Those who developed pressure ulcers were significantly older, weighed less, and had a lower BMI and serum albumin. More women than men developed pressure ulcers. Risk factors identified in multiple stepwise regression analyses were female gender, American Society of Anaesthesiologists (ASA) status or New York Heart Association (NYHA) status and food‐intake.

Conclusion.  Special attention, with regard to risk of pressure ulcer development, should be paid to patients undergoing surgery who have low ASA or NYHA scores, low food intake and/or are women.
Impact of tele‐advice on community nurses’ knowledge of venous leg ulcer care
Authors: Ameen Jamal , Coll Anne Marie , Peters Melanie
Published: June 2005

Aim.  This paper reports a study assessing the impact of the provision of expert tele‐advice to community nurses in enhancing their knowledge of leg ulcer care.

Background.  Community nurses have traditionally been responsible for the care of patients with leg ulcers. However, access to expert medical and nursing advice has been restricted to the local hospital environment. The introduction of e‐health and telemedicine have created opportunities to provide online and immediate access to wound care expertise from centres of excellence to primary health care staff in managing patients’ wounds in their own home.

Method.  A stratified randomized controlled trial was used to examine community nurses’ knowledge before and after the provision of expert tele‐advice. A knowledge measurement tool comprised of 40 multiple‐choice questions was adopted, with correct responses identified by a panel of wound care experts. The questions covered the three themes of dressings, management and physiology, with different levels of difficulty categorized as easy, medium or difficult. The tool was administered before and after the intervention (12 weeks) to both the experimental and control groups.

Results.  Statistically significant improvements were observed only for the experimental group in the areas of dressings and management, as well as in the medium level questions. No statistically significant improvement was seen for the easy questions, as there was little room for improvement because of preintervention high scores. For the difficult questions, it was thought that more time would be needed for a more positive outcome.

Conclusions.  The results suggest that tele‐advice can be of great benefit to community nurses in enhancing their knowledge in the practice of leg ulcer care. This will have significant implications for more efficient use of human resources and cost effectiveness in wound care.
Diabetes in children and adolescents from ethnic minorities: barriers to education, treatment and good metabolic control
Authors: Povlsen Lene , Olsen Birthe , Ladelund Steen
Published: June 2005

Aim.  This paper reports an investigation to establish whether metabolic control is different in children and adolescents from ethnic minorities with type 1 diabetes compared with young Danish patients, and to learn about factors affecting their opportunities to achieve good metabolic control.

Background.  The prevalence of diabetes in children and adolescents from ethnic minorities in Denmark is increasing. Having a different ethnic background has frequently been described as a risk factor for poor metabolic control, but whether the risk is represented by the ethnicity and immigration itself or in combination with other factors is unclear.

Methods.  The study included data (gender, age, diabetes duration HbA1c, number of incidents of severe hypoglycaemia and ketoacidosis) from a national register including 919 Danish and 58 children and adolescents from ethnic minorities, questionnaires to all 20 Danish paediatric diabetes centres and questionnaires to 38 families of other ethnic backgrounds completed by professional interpreters. The study was conducted in 2001–2002.

Results.  HbA1c was significantly higher in children and adolescents from ethnic minorities (mean 9·05 ± 1·4%) compared with Danish patients (mean 8·62 ± 1·3%; P = 0·018). There was no significant difference in HbA1c among the different ethnic groups, nor in the prevalence of severe hypoglycaemia or ketoacidosis. Patients from different ethnic minorities were unevenly distributed throughout the country, and generally the centres provided limited specialized knowledge and support. The questionnaires completed by the parents revealed limited schooling, lack of professional education and a major need for interpreters; these characteristics were especially prevalent among the mothers.

Conclusions.  Young patients from ethnic minorities have significantly poorer metabolic control compared with Danish patients, and patients with an immigrant background are seen as a vulnerable group with different needs and probably fewer chances of achieving good control. Special education for health care professionals as well as projects to improve methods, quality and knowledge should be encouraged in order to provide tailored support to members of individual ethnic groups. We recommend that the use of professional interpreters should become the gold standard in health care provision to all immigrant families.
Quality of life, disability and handicap in patients with toxic oil syndrome
Authors: Martín‐Arribas Ma Concepción , De Andrés Copa Pilar , De La Paz Manuel Posada
Published: June 2005

Aim.  This paper reports an investigation of the quality of life of patients most severely affected by toxic oil syndrome and the association between quality of life and disability variables, handicaps and depression.

Background.  In 1981, an epidemic occurred in Central and Northwestern Spain. The illness, now called toxic oil syndrome (TOS), appeared to be caused by consumption of oil mixtures containing rapeseed oil denatured with aniline and affected over 20,000 individuals. Today, it is classified as a chronic disease that has resulted in a large number of sequelae.

Method.  From the 1031 people classified with permanent disability, a random sample of 292 individuals was selected. A structured interview was carried out to investigate the clinical aspects. The Nottingham Health Profile Questionnaire was used to assess quality of life. To study the relationship between quality of life and disability, handicap and depression, a univariate analysis was carried out. The chi‐square test was used for inter‐group comparisons. A P‐value of 0·05 was adopted as the limit for inclusion of a variable in the multivariate analysis. Multivariate analysis was undertaken using logistic regression.

Results.  Two hundred and fourteen patients were interviewed (79% response rate). Mean age was 59·3 (sd: 12·7) years. Quality of life mean score was 52·8 (sd: 22·6). The variables associated with poorer quality of life perception were depression [odds ratio (OR) = 9·66, confidence interval (CI) = 3·71–25·15], role‐related disabilities (occupation role: OR = 2·82 CI = 1·28–6·22) and mobility (bending/picking up: OR = 4·74, CI = 2·31–9·72), as well as economic problems (OR = 1·62, CI = 1·07–2·46).

Conclusion.  The quality of life of those most severely affected by TOS is poor. Their health profile is characterized by depression and important functional and psycho‐social disabilities that limit daily living activities and social roles, and are related to self‐perceptions of poor quality of life.
An evolutionary concept analysis of caring
Authors: Brilowski Gail A. , Cecilia Wendler M.
Published: June 2005

Aim.  The aim of this paper is to identify the core, enduring attributes of nursing caring in order to increase understanding of the concept and to identify its implications for research and practice.

Background.  Caring is considered a core concept in nursing as a practice discipline. During the past 20 years, research into nurse caring has been evolving, but the concept of caring remains ambiguous.

Methods.  Using a rigorous evolutionary method of concept analysis, the concept caring was examined for its significance, use and application as it has unfolded over time, between 1988 and 2002. After applying inclusion and exclusion criteria and a sampling method, a total of 61 articles was included in the final analysis.

Results.  Defining attributes, antecedents, and consequences of caring were identified. Core attributes included relationship, action, attitude, acceptance and variability.

Conclusion.  Identification of the core attributes of concepts, including caring, allows nurses to determine appropriate research questions, develop theory and identify practice priorities at a time of increasing demands and constrained resources.
HIV/AIDS and the workplace: perceptions of nurses in a public hospital in South Africa
Authors: Smit Ria
Published: June 2005

Aim.  The purpose of this article is to report a study of the perceptions and experiences of nurses caring for people living with HIV/AIDS in the public health sector in South Africa.

Background.  The number of people living with HIV/AIDS in South Africa has escalated at an alarming rate. Many people being hospitalized are HIV positive, and hence nurses are in more regular and prolonged contact with people suffering from HIV/AIDS than is the case in other working environments. Although studies focusing on nurses’ experiences of caring for patients with HIV/AIDS have been done in numerous countries, little is known about nurses’ views in Africa, and South Africa in particular. To ensure quality care for patients with HIV/AIDS, it is important to understand nurses’ experiences of nursing HIV‐positive patients and how they may influence their attitudes towards these patients.

Method.  A qualitative approach was used, the primary method of data collection being in‐depth interviews. These interviews were conducted with 35 nurses at a public hospital in the Gauteng province of South Africa in 2002–2003.

Findings.  Seven themes were identified: helplessness, emotional stress and fatigue, fear, anger and frustration, occupational‐related concerns, empathy, and self‐fulfilment.

Conclusions.  Increased understanding of the stresses and rewards experienced by these nurses can contribute to policy development in this area. It is also important to provide appropriate preregistration and continuing education and support for nurses working in this field, and to ensure that the working environment is adequate in terms of resources.
Depressive symptoms in long‐term care residents in Taiwan
Authors: Lin Li‐Chan , Wang Tyng‐Guey , Chen Miao‐Yen , Wu Shiao‐Chi , Portwood Michael J.
Published: June 2005

Aim.  This paper reports a study to investigate the prevalence of and risk factors for depressive symptoms in elders in long‐term care facilities in Taiwan.

Background.  Depression has been identified as a major health concern and is very common among frail elders in Western nursing homes. It is under‐diagnosed, and may be associated with eating difficulties and subsequent malnutrition, functional ability and sociodemographic factors. There have been no previous studies of these issues in Taiwan.

Methods.  Residents of 18 long‐term care facilities were recruited. Those able to communicate in the Mandarin or Taiwanese dialect, resided in long‐term care facilities including skilled nursing facilities and intermediate care facilities, and who scored three or above on the Short Portable Mental Status Questionnaire were selected. Data were collected using the Geriatric Depression Scale, Barthel Index and Masticatory Index, and age, duration of institutionalization, and level of impaired swallowing were also measured.

Results.  The number of participants identified as depressed was 267 (52·05%). There was no significant difference noted relating to age, gender, duration of institutionalization, type of institution, mental status and masticatory ability between the depressed and non‐depressed groups, but significant differences of functional status and impaired swallowing between the two groups were found. However, functional status, impaired swallowing, and type of institution were three independent factors associated with depressive symptoms after controlling for all other factors.

Conclusions.  Future studies on the detection of symptoms of depression should use a validated observational measure to overcome under‐reporting of symptoms by the frailest residents.
Nurses’ and midwives’ assertive behaviour in the workplace
Authors: Timmins Fiona , McCabe Catherine
Published: June 2005

Aim.  This paper reports a study describing the assertive behaviour of a group of professional nurses and midwives and exploring potential barriers and facilitators to the use of assertiveness skills in the workplace.

Background.  As nurses and midwives move away from traditional roles, it is increasingly being recognized that they need to behave in an assertive manner. Much literature supports the use of assertive behaviour in clinical practice. Although specific individual assertive behaviours and skills have been examined in many settings, little empirical evidence exists about the frequency and use of assertiveness skills by nurses and midwives in the workplace. While there is evidence on barriers to the use of assertive skills, there is little information about factors that may facilitate their use.

Method.  A survey design was adopted, using a 44‐item questionnaire to collect data from a 2·5% random sample of nurses/midwives registered with the National Nursing Board of Ireland. The data were collected in 2003.

Results.  While respondents frequently complimented their colleagues and often allowed them to express opinions, they were less accomplished at expressing their own opinions or making requests. Assertive behaviours were used more frequently with nursing/midwifery colleagues than with management/medical colleagues. Most used assertiveness skills with other grades of staff in their own profession. Responsibility to patients/clients emerged as a supporting factor for using assertive behaviour. Managers, the work atmosphere and fear were viewed as obstacles.

Conclusion.  Nurses and midwives needs to learn how to behave assertively, and this should be included in both pre‐ and post‐registration education programmes. As use of assertiveness skills was reported to be least frequent with nurse/midwife managers, local policies and guidelines may be needed to encourage clinical practitioners to act autonomously and as client advocates.
The social construction of ‘reproductive vulnerability’ in family planning clinics
Authors: Hayter Mark
Published: June 2005

Aim.  The aim of this paper is to report a study exploring the discursive construction of contraceptive use within nurse consultations with women in family planning clinics.

Background.  This paper takes as its starting point the lack of a contraceptive ‘strand’ to the literature on the discursive construction of the female body generally, and the female reproductive system specifically, within health care practice. The literature in this field concentrates on pregnancy, menstruation and menopause, and the manner in which contraceptive use is discursively constructed is under‐explored. Furthermore, the literature on nurse–women consultations in family planning clinics is also limited, with the current literature concentrating on assessing clinical skills rather than discourse.

Methods.  Using a grounded theory methodology to explore how nurses educate women about contraception in family planning clinic, 49 consultations were audio‐taped in two large family planning clinics in the United Kingdom (UK).

Findings.  Open coding and subsequent axial coding resulted in the emergence of three elements of contraceptive education. One concerned reproductive anatomy, another reproductive physiology and a third education about contraceptive functioning. These three axial codes were formed into a core category: ‘body education/reproductive vulnerability’. Within the consultation, nurses linked the ‘vulnerable’ reproductive system with the requirement for contraceptive ‘protection’. This approach seems linked to ensuring women's future contraceptive use.

Conclusion.  The discourse employed by nurses differs from the body discourse aimed at menopause and menstruation. These areas of women's health were constructed as disintegrating, malfunctioning and failing, whereas reproductive vulnerability suggests a fully functioning, active system, in need of restraint. However, this discourse still constructs the female body as fundamentally weak and unstable, requiring contraception to protect it and prevent transgression.