bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure in family therapy: a catalogue of engagement mistakes
Authors: Carr Alan
Published: November 2003

Eleven key positions within the social system which evolves around a presenting problem are set out. A catalogue of common mistakes which arise from failing to distinguish between these elements and take account of their significance during the engagement process is presented, along with specific suggestions for avoiding these clinical errors.
Abstracts
Authors: Frude Neil
Published: November 2003

Korner, S. and Brown, G. (1990) Exclusion of children from family psychotherapy: Family therapists' beliefs and practices. Journal of Family Psychology

Scharff, J.S. (1989) Play with young children in family therapy: An extension of the therapist's holding capacity. Journal of Psychotherapy and the Family

Halperin, S. M. (1989) A neglected triangle: Grandmother, mother, and daughter. Contemporary Family Therapy: An International Journal

Wojcik, J.V. and Iverson, E.R. (1989) Therapeutic letters: The power of the printed word. Journal of Strategic and Systemic Therapies

Cassano, D.R. (1989) Multi‐family group therapy in social work practice. Social Work with Groups

Roberts, M., Caesar, L., Perryclear, B. and Phillips, D. (1989) Reflecting team consultations. Journal of Strategic and Systemic Therapies

Warner, M.S. (1989) Empathy and strategy in the family system. Person Centered Review

DeBord, J.B. (1989) Paradoxical interventions: A review of the recent literature. Journal of Counseling and Development

Cole, D.A. and Jordan, A.E. (1989) Assessment of cohesion and adaptability in component family dyads: A question of convergent and discrimimant validity, Journal of Counseling Psychology

Musante, L., Treiber, F.A., Strong, W.B. and Lecy, M. (1990) Individual and cross‐spouse correlations of perceptions of family functioning, blood pressure and dimensions of anger. Journal of Psychosomatic Research
Admissions to neonatal intensive care unit following pregnancies complicated by gestational or type 2 diabetes
Authors: Watson Diana , Rowan Janet , Neale Lee , Battin Malcolm R.
Published: November 2003

Background:  When gestational diabetes mellitus (GDM) is diagnosed in a population with a high prevalence of unrecognised type 2 diabetes mellitus (type 2 DM), the rate of neonatal morbidity is not clear. There is also a paucity of data reporting neonatal outcome in women with recognised type 2 DM.

Aim:  To describe, in a population with a high background prevalence of type 2 DM, neonatal morbidity in infants of women with GDM and type 2 DM admitted to the neonatal intensive care unit (NICU).

Methods:  A 2‐year audit was carried out in a tertiary level obstetric hospital with a multi‐ethnic delivery population. All infants admitted to the NICU whose mothers had GDM or type 2 DM were identified from the hospital database. The records of 136 infants were retrospectively reviewed and data collected on outcome measures including maternal diagnosis, macrosomia, mode of delivery, delivery complications, hypoglycaemia, respiratory distress and congenital anomalies.

Results:  Admission to NICU occurred in 29% of GDM and 40% of type 2 DM pregnancies. Median gestation was 37 weeks (range: 25–41), with 46% delivered preterm. Forty percent of infants were delivered by emergency Caesarean section. Fifty‐one percent of admissions had hypoglycaemia and 40% required support for respiratory distress. Women with type 2 DM diagnosed either prepregnancy or post‐partum were the highest risk group for neonatal morbidity, including congenital anomalies.

Conclusions:  Neonatal morbidity is common in infants of women with type 2 DM and GDM in a population with high prevalence of type 2 DM.
Effects of inter‐row hoeing and fertilizer placement on weed growth and yield of winter wheat
Authors: Melander B , Cirujeda A , Jørgensen M H
Published: November 2003

Inter‐row hoeing is known to control tap‐rooted and erect weed species more effectively in winter wheat than weed harrowing. However, little is known about its effectiveness for use in the spring in winter wheat grown at wide row spacing (240 mm) under the influence of different placement of fertilizer. Two field experiments, one in 1999 and one in 2000, were conducted to study the influence of fertilizer placement, timing of inter‐row hoeing, and driving speed on the weeding effect on different weed species and crop growth. Placement of fertilizer below the soil surface improved crop growth and grain yield in both years compared with placement on the surface, but the more vigorous crop did not give any better suppression of the weeds surviving hoeing. Timing was not important in one experiment, whereas hoeing twice beginning in early April was more effective in the other experiment where weed growth over the winter had been vigorous. Driving speed had no influence on either the weeding effect or the yield, except for one case where increasing speed reduced the control of well‐developed weeds. Compared with unweeded reference treatments, inter‐row hoeing reduced total weed biomass by 60–70% and tap‐rooted and erect weed species in particular by 50–90%. Sowing at 240 mm row spacing yielded less than 120 mm (Danish standard), and inter‐row hoeing for winter wheat needs to be adapted to narrower row spacing to avoid such yield decreases.
Optimization of hydroponic bioassay for herbicide tepraloxydim by using water free from chlorine
Authors: Sandín‐España P , Llanos S , Magrans J O , Alonso‐Prados J L , García‐Baudín J M
Published: November 2003

Initial attempts to develop a hydroponic bioassay test for tepraloxydim failed due to lack of repeatability. Investigation of the fate of tepraloxydim in test media revealed that small residues of chlorine and chloramines present on distilled water cause fast degradation of the herbicide. Half‐life of tepraloxydim in the presence of a chlorine excess was determined to be DT50 < 5 s. Reaction with chloramines was slower (DT50 = 4.5 h). Finally, when this factor was eliminated by using water completely free of chlorine, the main process that took place was the isomerization of the oxime group (E vs. Z). However, the overall degradation was slow (DT50 = 17 days) and the hydroponic bioassay was optimized in the absence of chlorine.
Field assessment of thermal after‐ripening time for dormancy release prediction in Lolium rigidum seeds
Authors: Steadman K J , Bignell G P , Ellery A J
Published: November 2003

Dormancy release was studied in four populations of annual ryegrass (Lolium rigidum) seeds to determine whether loss of dormancy in the field can be predicted from temperature alone or whether seed water content (WC) must also be considered. Freshly matured seeds were after‐ripened at the northern and southern extremes of the Western Australian cereal cropping region and at constant 37°C. Seed WC was allowed to fluctuate with prevailing humidity, but full hydration was avoided by excluding rainfall. Dormancy was measured regularly during after‐ripening by germinating seeds with 12‐hourly light or in darkness. Germination was lower in darkness than in light/dark and dormancy release was slower when germination was tested in darkness. Seeds were consistently drier, and dormancy release was slower, during after‐ripening at 37°C than under field conditions. However, within each population, the rate of dormancy release in the field (north and south) in terms of thermal time was unaffected by after‐ripening site. While low seed WC slowed dormancy release in seeds held at 37°C, dormancy release in seeds after‐ripened under Western Australian field conditions was adequately described by thermal after‐ripening time, without the need to account for changes in WC elicited by fluctuating environmental humidity.
Effect of triclosan on healing following non‐surgical periodontal therapy in smokers
Authors: Kerdvongbundit Varunee , Wikesjö Ulf M. E.
Published: November 2003

Background: Tobacco smoking is an established risk factor for periodontitis, and is associated with periodontal attachment and tooth loss. Clinical studies have indicated that smoking may adversely affect and impede healing following periodontal therapy. Adjunctive antimicrobials, on the other hand, have been shown to enhance the effect of non‐surgical periodontal therapy. The objective of this study was to evaluate the effect of a triclosan/copolymer/fluoride dentifrice on healing following non‐surgical periodontal therapy in smokers.

Methods: Sixty smokers (aged 35–59 years; 23 females) with chronic periodontal disease volunteered to participate in a double‐blind, randomized, controlled, clinical trial. The subjects were randomly assigned to use a triclosan/copolymer/fluoride (30 subjects) or a standard fluoride (30 subjects) dentifrice and received detailed information on proper techniques for self‐performed plaque control. The participants then received non‐surgical periodontal therapy followed by periodontal maintenance care every 6 months over 24 months. Clinical recordings included evaluation of oral hygiene standards, gingival health, and periodontal status.

Results: Subjects using the triclosan/copolymer/fluoride dentifrice exhibited significantly improved oral hygiene conditions, gingival health, and periodontal status compared with those using the standard fluoride dentifrice over the 24‐month maintenance interval.

Conclusions: The results suggest that an oral hygiene regimen including a triclosan/copolymer/fluoride dentifrice may sustain the short‐term effect of non‐surgical periodontal therapy in smokers.
Psychometric properties of the SF‐36 in the early post‐stroke phase
Authors: Hagen Suzanne , Bugge Carol , Alexander Helen
Published: November 2003

Background.  Patients who have had a stroke are a large group in whom long‐term disability is common and therefore impaired general health is likely. The Short Form 36 (SF‐36) is a popular measure of general health that has been used with this patient group, but not all aspects of its psychometric properties have been established for use in this context, and its use in the early post‐stroke phase has been neglected.

Aims.  To examine the reliability, validity and sensitivity to change of the SF‐36 (UK version I) in patients in the early post‐stroke period.

Design.  A prospective, observational study of stroke outcomes was carried out.

Research methods.  From May 1996 to April 1997, patients who had had a stroke were identified by 24 general practices in Scotland and were recruited within 1 month of their stroke, whether in hospital or at home. Outcome measures including the SF‐36 were administered at one, 3 and 6 months after onset.

Results.  The internal consistency of the eight subscales at all three time‐points was good except for 1 month Vitality (α = 0·6824) and 3 month General Health (α = 0·6650), which were borderline in comparison with the criterion value of 0·7. Construct validity was adequate overall, although correlations between Role Physical and General Health and the Barthel Index and Canadian Neurological Scale were lower than hypothesized. Most SF‐36 subscales were sensitive to change between 1 and 3 months post‐stroke, but none detected change between 3 and 6 months.

Conclusions.  There were some practical problems in using the SF‐36 in an acutely unwell stroke population. However, analysis of psychometric properties suggested that most of the subscales were adequately reliable and valid. Sensitivity to change was poorer in the later stages of the study.
On Balancing and Subsumption. A Structural Comparison
Authors: Alexy Robert
Published: November 2003

The formal structure of subsumption may be represented in a deductive scheme, which one might call the “Subsumption Formula.” The author argues that there is an analogous scheme for the formal structure of balancing or weighing, which he terms the “Weight Formula.” In short, subsumption and balancing have comparable schemata, through which the formal structure of a set of premisses, which warrant the inference to a legal result, can be identified. The relation in the two cases between these premisses and the ensuing legal result is, however, different. The Subsumption Formula is represented by a scheme that works according to the rules of logic, the Weight Formula, by a scheme that works according to the rules of arithmetic. In spite of this difference, the two formulae are alike in that judgments, in both cases, remain the basis of the argument.
The Existence and Life of Law
Authors: Urbina Sebastián
Published: November 2003

From a commonsense view we usually accept that the claim “there is a dog in this garden” implies the existence of this dog. If instead of a dog we are dealing with black holes or quarks, our senses do not play the same role. We usually use instruments that mediate between the object and us. What if we move from this, let's say, natural world to the legal normative field? Unlike the task of Legal Dogmatics the task of Physics, for example, is not both descriptive and normative but only descriptive of what there is (or a selected part of it) although they “see” what there is through theories. In any case, Physicists do not try to “optimise” the laws of nature as legal scholars (sharing an internal point of view) do with the legal order.
Toward a New Critical Theory with a Cosmopolitan Intent
Authors: Beck Ulrich
Published: November 2003

In this article I want to outline an argument for a New Critical Theory with a cosmopolitan intent. Its main purpose is to undermine one of the most powerful beliefs of our time concerning society and politics. This belief is the notion that “modern society” and “modern politics” are to be understood as society and politics organized around the nation‐state, equating society with the national imagination of society. There are two aspects to this body of beliefs: what I call the “national perspective” (or “national gaze”) of social actors, and the “methodological nationalism” of scientific observers. The distinction between these two perspectives is important because there is no logical co‐implication between them, only an interconnected genesis and history.
Concurrent total hip and knee replacements in a patient with haemophilia with inhibitors using recombinant factor VIIa by continuous infusion
Authors: Tagariello G. , Bisson R. , Radossi P. , Petris U. , Zanardo G. , De Biasi E. , Risato R. , Polese F. , Davoli P. G.
Published: November 2003

Summary.  The introduction of activated recombinant factor VIIa (rFVIIa) has allowed elective surgery to be safely performed in haemophiliacs with inhibitors. The main problems associated with its use are the short half‐life, necessitating frequent intravenous injections, and its very high cost. Here we describe, for the first time, the performance of total hip and knee replacements in a haemophiliac with inhibitors at the same operation. The amount of rFVIIa concentrate used (8.57 mg) was similar to that normally used for a single joint replacement. The use of continuous infusion allowed for easier administration and further contributed to the reduction in cost as it avoids the peak levels associated with bolus injections.
The dental management of adult patients with haemophilia and other congenital bleeding disorders
Authors: Brewer A. K. , Roebuck E. M. , Donachie M. , Hazard A. , Gordon K. , Fung D. , Clarkson J.
Published: November 2003

Summary.  The management of adult dental patients with congenital bleeding disorders has caused a considerable number of problems to the dental profession [1]. There is a need to simplify the process and identify what can be safely carried out on a ‘shared care’ basis in General Dental Practice or the Community Dental Service. Particular problems are discussed with special reference to those requiring hospital care.

The Scottish Oral Health Group for Medically Compromised Patients has developed this clinical guidance in conjunction with the Scottish Haemophilia Directors. It is important that dental care is easily available for this group of patients, especially those living at some distance from the regional centres. The aim is to simplify planning dental care for this group of patients and remove a number of myths concerning their management [2]. The hospital departments, both medical and dental, must be available for advice and to arrange for treatment that is inappropriate outside a specialist hospital.
Why is primary prophylaxis underutilized in the United States?
Authors: Shapiro A. D.
Published: November 2003

Summary.  A recent article published in Haemophilia reports the results of a survey of treatment center practices in the United States, and specifically the use of prophylaxis as treatment regimen [7] . This article discusses the issues that may contribute to utilization of prophylactic regimens and issues to consider when determining treatment programs for pediatric patients.
Differential effect of dexamethasone on cell death and STAT5 activation during in vitro eosinopoiesis
Authors: Debierre‐Grockiego Françoise , Fuentes Vincent , Prin Lionel , Gouilleux Fabrice , Gouilleux‐Gruart Valérie
Published: November 2003

Summary.  Glucorticoids reduce eosinophilia through a direct effect on eosinophils or indirectly on cells producing cytokines and chemokines. Conflicting data have been previously reported concerning glucocorticoid effects on eosinopoiesis. To elucidate this point, dexamethasone was added during eosinophil differentiation of CD34+ cells. Dexamethasone enhanced proliferation and differentiation through an early effect on immature cells. Dexamethasone inhibited apoptosis during early differentiation, whereas death of mature cells was increased. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor involved in the proliferation, differentiation and survival of haematopoietic cells, which interacts with glucocorticoid receptor. Activation of STAT5 by interleukin‐5 was investigated during eosinophil differentiation. Long isoforms of STAT5 were activated during the entire period in the culture as well as in blood eosinophils, while short isoforms were only activated during early differentiation. Short isoforms were less activated in the presence of dexamethasone. This suggests that dexamethasone could act on proliferation, differentiation and apoptosis during eosinophil differentiation through an association of STAT5 with the glucocorticoid receptor.
Imatinib mesylate (STI571) inhibits multiple myeloma cell proliferation and potentiates the effect of common antimyeloma agents
Authors: Pandiella Atanasio , Carvajal‐Vergara Xonia , Tabera Soraya , Mateo Gema , Gutiérrez Norma , San Miguel Jesús F.
Published: November 2003

Summary.  c‐Kit has been shown to be mutated in several types of tumours, and its activity has been correlated with increased proliferation rates in a subset of multiple myeloma (MM) patients. We have investigated the effect of imatinib mesylate (STI571), an inhibitor of c‐Kit, on MM cells. STI571 inhibited the proliferation of MM cells by arresting cell cycle progression. Western blotting of cell cycle proteins showed that STI571 increased the levels of p21 and p16. MM cells expressed abl, but its level of tyrosine phosphorylation was low and unaffected by treatment with STI571. c‐Kit was also expressed in certain MM cell lines, and its phosphorylation was stimulated by stem cell factor. However, the failure to detect the receptor protein in other MM cell lines in which cell proliferation was inhibited by STI571 suggests that its effect on these c‐Kit‐negative MM cell lines might be caused by the action of the drug on yet unknown targets. STI571 inhibited the proliferation of MM cells resistant to dexamethasone or melphalan and had an additive effect when combined with dexamethasone. Efforts to understand the action of STI571 in MM cells may help to identify these potentially useful targets in the treatment of this and other disorders.
The role of occupational and environmental exposures in the aetiology of acquired severe aplastic anaemia: a case control investigation
Authors: Muir K. R. , Chilvers C. E. D. , Harriss C. , Coulson L. , Grainge M. , Darbyshire P. , Geary C. , Hows J. , Marsh J. , Rutherford T. , Taylor M. , Gordon‐Smith E. C.
Published: November 2003

Summary. Aplastic anaemia is a rare but serious disorder with a high morbidity and mortality rate. The causes of aplastic anaemia are, for the most part, unknown. We report on the hypothesis that aplastic anaemia may be caused by occupational and/or environmental exposures to certain chemicals. The UK Aplastic Anaemia Study was an interview‐based case–control study covering the whole of Great Britain. Those patients diagnosed between 1 July 1993 and 20 October 1997, aged ≤75 years and born and diagnosed in the UK were eligible for the study. Two hundred eligible cases of aplastic anaemia were compared with 387 age‐ and sex‐matched controls. A number of occupational exposures showed increases in risk. In a multivariate model of these exposures the odds ratios (ORs) for solvents/degreasing agents, pesticides and radiation were >2 and statistically significant. Reported chemical treatment of houses within 5 years of diagnosis had a significantly raised risk for adults [OR = 2·51, 95% confidence interval (CI) 1·02–12·01], particularly for woodworm treatment (OR = 5·1, 95% CI 1·5–17·4). This study identified significant risks associated with self‐reported exposure to solvents, radiation and pesticides in the workplace. Self‐reported chemical treatment of houses was also associated with an increased risk of developing aplastic anaemia, in keeping with previous literature.
Exogenous retinoic acid decreases in vivo and in vitro proliferative activity during the early migratory stage of neural crest cells
Authors: Salvarezza S. B. , Rovasio R. A.
Published: November 2003

We have previously demonstrated that directional migration of neural crest cells (NCC) is associated with a high cell density, resulting from an active cell proliferation. It is also known that treatment with retinoic acid (RA) causes a dose‐dependent inhibition of proliferation of some cell types, and that administration of RA during the early stages of embryonic development, induces cranio‐facial abnormal patterns corresponding to NCC derivatives. In view of these findings, it was of interest to determine if exogenous RA is a potential modulator of the mitotic rate of NCC, and to explore the hypothesis of an inhibitory effect exerted by RA on the proliferative behaviour of NCC in vivo and in vitro.

Homogenates of RA‐treated chick embryos showed a low [3H]dT incorporation, indicating a generalized diminution of DNA synthesis. The labelling index (LI=number of labelled cells/total number of cells) revealed that NCC from RA‐treated and control embryos had higher values of [3H]dT incorporation than neural tube cells (P < 0.0001). Autoradiographs of RA‐treated chick embryos showed a significantly lower [3H]dT incorporation in NCC at the prosencephalic and mesencephalic levels, as well as in the neural tube cells at the prosencephalic, mesencephalic and rhombencephalic levels, than in control chick embryos (P < 0.0001). NCC cultures treated with 1 or 10 μm RA had a significantly lower LI than in cultures treated with 0.1 μm RA or control cultures (P < 0.04). In chick embryos, the mitotic index of NCC was 0.026 for RA‐treated and 0.033 for controls, while the duration of the cell cycle was significantly longer in the NCC of RA‐treated embryos (∼ 40 h) than in controls (∼ 25 h). The length of the cell cycle phases of NCC was similar in both experimental conditions, except for G1 phase, which was significantly longer in the RA‐treated group than in controls.

These results show that RA blocks DNA synthesis and lengthens the proliferative behaviour of NCC both in early chick embryos and in vitro, effects that could modify the morphogenetic patterns of NCC distribution through a decreased cell population.
Acromegalic features in growth hormore (GH)‐deficient patients after long‐term GH therapy
Authors: Carvalho Luciani R. , Justamante de Faria Maria Estela , Farah Osorio Maria Geralda , Estefan Vivian , Lima Jorge Alexander Augusto , Arnhold Ivo Jorge Prado , Mendonca Berenice Bilharinho
Published: November 2003

background  Craniofacial, hand, foot and somatic growth depend on normal GH secretion. Acromegalic features have been described in children with GH insensitivity after IGF‐I treatment. We observed patients with acromegalic features such as increase of foot size, nose and jaw enlargement among our cases with GH deficiency, treated with standard recombinant (rh)GH doses. The aim of our study was to analyse the possible factors involved in the development of acromegalic features in these patients.

patients  We evaluated 21 patients, 17 with combined pituitary hormone deficiency and four with isolated GH deficiency treated with rhGH (0·05–0·15 U/kg/day, sc, at night) for 2–12 years who achieved final height. IGF‐I and IGFBP‐3 were measured before and every 6 months during therapy and bone age was evaluated yearly. At the end of therapy, patients’ hand and foot sizes and height were measured and plotted on nomograms for hand according to height and age, and foot size according to height. Lateral radiographs of the face were performed to obtain the linear measurement of the lower jaw length.

results  Foot size was greater than 97th percentile in 8/21 patients and lower jaw length was greater than +2SD in 4/21 patients. Patients were classified in two groups: group 1 (with foot size greater than 97th percentile and/or lower jaw length greater than +2SD) consisted of 11 patients (six females); nine had combined pituitary hormone deficiency (six associated to hypogonadotrophic hypogonadism) and three had isolated GH deficiency; group 2 (with foot size smaller than 97th percentile and lower jaw length less than +2SD) consisted of 10 patients (seven boys); nine had combined pituitary hormone deficiency (six associated to hypogonadotrophic hypogonadism) and one with isolated GH deficiency. During treatment, IGF‐I levels ranged from ≤ 3 to +2SD and IGFBP‐3 levels ranged from −3 to +2SD, in both groups. We observed no statistically significant differences between the two groups regarding chronological age, bone age, height at the beginning and at the end of therapy, pubertal development, duration of rhGH treatment and IGF‐I and IGFBP‐3 levels (P > 0·05). Foot size percentile exceeded final height percentile in 11/21 patients (seven girls).

conclusion  Long‐term rhGH treatment with standard doses might be associated with acromegalic features (increased foot size and lower jaw measurements) in patients with GH deficiency who achieved final height, especially in girls. Neither the clinical nor the hormonal parameters, IGF‐I and IGFBP‐3 levels, were useful to predict the development of these features. Further studies are necessary to analyse the frequency of this side‐effect and how to prevent it.
Genetic analysis of mitochondrial complex II subunits SDHD, SDHB and SDHC in paraganglioma and phaeochromocytoma susceptibility
Authors: Astuti Dewi , Hart‐Holden Niki , Latif Farida , Lalloo Fiona , Black Graeme C. , Lim Caron , Moran Anthony , Grossman Ashley B. , Hodgson Shirley V. , Freemont Anthony , Ramsden Richard , Eng Charis , Evans D. Gareth R. , Maher Eamonn R.
Published: November 2003

background  Germline mutations in three subunits of mitochondrial complex II (SDHB, SDHC and SDHD) may be associated with susceptibility to phaeochromocytoma (PC) and/or head and neck paraganglioma (HNPGL).

methods  To further define the role of SDH subunit mutations in these disorders, we analysed a series of 22 probands with PC and evidence of genetic susceptibility (seven with familial PC only, one with familial PC and HNPGL, 10 sporadic cases with multiple PC and four cases of isolated paediatric onset PC) for germline SDHB, SDHC and SDHD mutations. In addition, we analysed 34 cases of HNPGL (30 isolated cases with single tumours, three isolated cases with multiple tumours and one familial case with multiple tumours) for somatic and germline mutations in SDHB, SDHC and SDHD.

results  We identified four germline mutations (three SDHB and one SDHD, three novel) in the 22 PC probands. Combining these results with our previous series, we have detected germline SDHB or SDHD mutations in 2/12 (17%) of familial PC only kindreds, 4/5 (80%) of familial PC and HNPGL cases, 1/10 of sporadic multiple PC cases and 2/4 (50%) of paediatric PCs. No somatic mutations were detected in the HNPGL tumours, but four cases with multiple HNPGL had the common P81L germline SDHD mutation. Intriguingly a silent SNP (c.204C > T) in SDHD was significantly more common in HNPGL cases (6/34) than in controls (1/100, P= 0·0011). Combining our results with those from two other large studies in which both SDHB and SDHD have been analysed, SDHB mutations were most commonly associated with phaeochromocytoma susceptibility and SDHD with the development of HNPGL (P = 0·025). However, germline SDHB and SDHD mutations demonstrate considerable phenotypic variability and genotype‐phenotype correlations are complex.

conclusion  The significantly lower frequency (P = 0·028) of germline SDH subunit mutations in familial PC only cases compared to those with familial PC and HNPGL suggests that further PC susceptibility gene(s) remain to be identified.
Fasting insulin sensitivity and post‐oral glucose hyperinsulinaemia related to cardiovascular risk factors in adolescents with precocious pubarche
Authors: Potau Neus , Williams Rachel , Ong Ken , Sánchez‐Ufarte Carmen , De Zegher Francis , Ibáñez Lourdes , Dunger David
Published: November 2003

objective  Adolescents and young women with a history of precocious pubarche (PP, appearance of pubic hair before 8 years) exhibit hyperlipidaemia, and ovarian hyperandrogenism, indicating increased risk of coronary heart disease in the long term. The aim of this study was to determine the relative contribution of fasting insulin sensitivity, and post oral glucose tolerance test (OGTT) measures of insulin secretion to metabolic risk markers of adult disease.

patients and design  We have analysed data from 51 young women presenting with isolated PP (age range, 5·9–19·0 years) in early, mid and late puberty and 68 puberty‐matched controls (age range, 6·2–16·8 years). Body composition data from a further 67 girls with PP are also presented.

measurements  The homeostasis model of assessment insulin sensitivity index (HOMA Si) based on fasting glucose and insulin measurements and MSI120 based on insulin levels over the first 120 min following standard oral glucose load were selected as measures of fasting insulin sensitivity and 0–120‐min insulinaemia, respectively. ISI30 was used as an index of insulin secretion 30 min following oral glucose load.

results  The physiological decrease in fasting insulin sensitivity, 30‐min insulin secretion and 0–120‐min insulinaemia during puberty were exaggerated in PP girls. The relationship between fasting insulin sensitivity and 0–120‐min insulinaemia was similar in PP girls and in controls but at each level of fasting insulin sensitivity the PP girls had a higher level of insulin secretion in response to an oral glucose load (P < 0·001). Fasting insulin sensitivity and 0–120 minute insulinaemia but not 30‐min insulin secretion were strongly related to known cardiovascular risk factors. In a multivariate model incorporating fasting insulin sensitivity, 0–120‐min insulinaemia, pubertal stage and body mass index (BMI) SDS as covariates, 0–120‐min insulinaemia was strongly associated with elevated free androgen index, total cholesterol and truncal fat mass (P < 0·001) whereas fasting insulin sensitivity was associated only with reduced free androgen index (P < 0·02).

conclusions  Chronic exposure to insulin as reflected by 0–120 min hyperinsulinaemia, rather than 30 min insulin secretion, or fasting insulin senstivity, was most closely related cardiovascular disease risk in girls with PP.
Octreoscan in patients with bronchial carcinoid tumours
Authors: Granberg Dan , Sundin Anders , Janson Eva Tiensuu , Öberg Kjell , Skogseid Britt , Westlin Jan‐Erik
Published: November 2003

objectives  Scintigraphy with radiolabelled octreotide (octreoscan) is useful for imaging various neuroendocrine tumours, especially in patients with midgut carcinoids. We were interested in estimating the efficacy of octreoscan for detection of the primary tumour and metastases in patients with bronchial carcinoids.

patients and methods  Twenty‐eight patients with histologically verified bronchial carcinoids underwent octreoscan and the imaging results were compared to CT regarding soft tissue metastases, and to bone scan and MRI regarding bone metastases. The primary tumour had been removed prior to the octreoscan in 12 patients. Metastatic disease was diagnosed in 22 patients.

results  Altogether, 20 patients (71%) had octreoscan‐positive tumours, including 2/5 patients with ectopic ACTH secretion resulting in Cushing's syndrome and 8/9 patients with carcinoid syndrome. The primary tumour was octreoscan‐positive in 13/16 patients and could be detected on CT in 15/16 patients. CT failed to localize the primary tumour in one octreoscan‐positive patient, presenting with ectopic ACTH secretion and Cushing's syndrome. Intrathoracic recurrences/metastases were visualized by octreoscan in 7/9 patients and by CT in 8/9 patients. CT showed liver metastases in 14 patients; nine of these patients (64%) had octreoscan‐positive liver metastases. Ten patients had bone metastases; octreoscan was positive in seven and bone scan in nine of these 10.

conclusions  Octreoscan may be used for follow‐up and detection of recurrent disease in patients with somatostatin receptor‐positive bronchial carcinoids. In our limited patient material, CT however, seems to be better than octreoscan for visualization of the primary tumour as well as liver metastases.
Meta‐analysis of observational studies of full‐length and B‐domain‐deleted factor VIII for prophylaxis – a standard statistical approach
Authors: Gruppo R. A. , Brown D. , Wilkes M. M. , Navickis R. J.
Published: November 2003

Summary.  Meta‐analyses of observational studies have become increasingly common to support evidence‐based clinical decisions. We analyzed currently available clinical and pharmacokinetic studies of full‐length factor VIII (FL‐FVIII) vs B‐domain deleted recombinant factor VIII (BDD‐rFVIII) to investigate possible differences in clinical efficacy. A standard approach to observational study meta‐analysis was used as recommended by the Meta‐analysis Of Observational Studies in Epidemiology (MOOSE) consensus group. Data from included studies were combined using a random effects model to accommodate between‐study heterogeneity. A multivariate Poisson regression analysis was used to calculate the incidence rate ratio for bleeding. Justification for the appropriate use of this statistical approach is given. The meta‐analysis suggested reduced haemostatic efficacy during prophylaxis and shortened half‐life of BDD‐rFVIII as compared with FL‐FVIII. This analysis was rigoroulsy conducted using well‐accepted statistical methodology and presents the most comprehensive evidence‐based assessment currently available on risk factors for breakthrough bleeding under factor VIII prophylaxis. Our conclusions have been strengthened by subsequently introduced prescribing information and regulatory action for BDD‐rFVIII.
Molecular characterization of a membrane‐bound cGMP dependent protein kinase from the silk moth Bombyx mori
Authors: Tanoue S. , Nishioka T.
Published: November 2003

The cGMP signalling pathway has been suggested to be involved in the signal transduction of various physiological functions in insects; olfaction, antidiuresis and eclosion. However, the cGMP signalling mechanism has remained elusive. We isolated two cDNAs of the cGMP dependent protein kinase, designated BmPKG‐Iα and BmPKG‐Iβ. The deduced amino acid sequences indicate that both BmPKG‐Iα and BmPKG‐Iβ appear to consist of an amino terminal region, a cGMP binding domain and a protein kinase domain. Transcripts of BmPKG‐Iα and BmPKG‐Iβ were detected in various tissues: flight muscles, antennae, midgut, legs, head, thoracic ganglia and Malphighian tubules. Recombinant BmPKG‐Iα bound to lipid membranes, while BmPKG‐Iα with a deleted amino terminal region failed to bind to lipid membranes.
Intraspecific DNA variation in nuclear genes of the mosquitoAedes aegypti
Authors: Morlais I. , Severson D. W.
Published: November 2003

Single nucleotide polymorphisms (SNPs) are an abundant source of genetic variation among individual organisms. To assess the usefulness of SNPs for genome analysis in the yellow fever mosquito,Aedes aegypti, we sequenced 25 nuclear genes in each of three strains and analysed nucleotide diversity. The average frequency of nucleotide variation was 12 SNPs per kilobase, indicating that nucleotide variation inAe. aegyptiis similar to that in other organisms, includingDrosophilaand the malaria vectorAnopheles gambiae. Transition polymorphisms outnumbered transversion polymorphisms, at a ratio of about 2 : 1. We examined codon usage and confirmed that mutational bias favours G and C ending codons. Codon bias was most pronounced in highly expressed genes. Nucleotide diversity estimates indicated that substitution rates are positively correlated in coding and non‐coding regions. Nucleotide diversity varied from one gene to another. The unequal distribution of SNPs amongAe. aegyptinuclear genes suggests that single base variations are non‐neutral and are subject to selective constraints. Our analysis showed that ubiquitously expressed genes have lower polymorphism rates and are likely under strong purifying selection, whereas tissue specific genes and genes with a putative role in parasite defence exhibit higher levels of polymorphism that may be associated with diversifying selection.
Caffeine ingestion and fluid balance: a review
Authors: Maughan R. J. , Griffin J.
Published: November 2003

Background Caffeine and related methylxanthine compounds are recognized as having a diuretic action, and consumers are often advised to avoid beverages containing these compounds in situations where fluid balance may be compromised. The aim of this review is to evaluate the available literature concerning the effect of caffeine ingestion on fluid balance and to formulate targeted and evidence‐based advice on caffeinated beverages in the context of optimum hydration.

Method A literature search was performed using the Medline database of articles published in the medical and scientific literature for the period of January 1966–March 2002. Subject headings and key words used in this search were: tea, coffee, caffeine, diuresis, fluid balance and water‐electrolyte balance. A secondary search was performed using the bibliographies of publications identified in the initial search.

Results The available literature suggests that acute ingestion of caffeine in large doses (at least 250–300 mg, equivalent to the amount found in 2–3 cups of coffee or 5–8 cups of tea) results in a short‐term stimulation of urine output in individuals who have been deprived of caffeine for a period of days or weeks. A profound tolerance to the diuretic and other effects of caffeine develops, however, and the actions are much diminished in individuals who regularly consume tea or coffee. Doses of caffeine equivalent to the amount normally found in standard servings of tea, coffee and carbonated soft drinks appear to have no diuretic action.

Conclusion The most ecologically valid of the published studies offers no support for the suggestion that consumption of caffeine‐containing beverages as part of a normal lifestyle leads to fluid loss in excess of the volume ingested or is associated with poor hydration status. Therefore, there would appear to be no clear basis for refraining from caffeine containing drinks in situations where fluid balance might be compromised.
A simple model of pea (Pisum sativum) growth affected by Mycosphaerella pinodes
Authors: Béasse C. , Ney B. , Tivoli B.
Published: November 2003

The effect of epidemics of Mycosphaerella pinodes on crop growth, radiation interception efficiency (RIE) and radiation use efficiency (RUE) was studied in field conditions and the growth of diseased crop was modelled. Natural epidemics were simulated in field plots by dispersion on the ground of barley grains colonized by the fungus. Growth and leaf area index (LAI) were measured in healthy and diseased plots during the growth season. Epidemics affected crop growth mainly by decreasing RUE, with a slight decrease in RIE. This was probably due to the strong effect of M. pinodes on leaf photosynthesis and the lateness of Mycosphaerella blight epidemics on spring pea, which became serious when the canopy was already formed, thus decreasing RIE only by accelerating the senescence of leaves. The data were used to evaluate the performance of a crop growth model for diseased pea crops. The model comprised the decrease in photosynthesis rate in the leaves, the vertical gradient of disease intensity and the differences in photosynthetic function of the various layers of the canopy. This model, validated over 2 years in the field, accurately simulated the crop growth in diseased plots. Thus the decrease in RUE may be accounted for solely by photosynthesis losses in diseased leaves. This simple model may be used for disease management, defining damage thresholds for chemical application and criteria for tolerant variety selection.
Development and characterization of potent and specific peptide inhibitors of p60c‐src protein tyrosine kinase using pseudosubstrate‐based inhibitor design approach
Authors: Kamath J.R. , Liu R. , Enstrom A.M. , Lou Q. , Lam K.S.
Published: November 2003

Abstract:  The cytoplasmic protein p60c‐src, an ubiquitous non‐receptor protein tyrosine kinase (PTK) is a potential anticancer target as it is over‐expressed and/or constitutively active in several cancer types. In addition, the phenotype of c‐src knock‐out mice is consistent with osteopetrosis, which suggests that inhibitors against this enzyme may also be therapeutic for osteoporosis. Using a known peptide substrate for c‐src, MIYKYYF, as a template, we have developed a series of pseudosubstrate‐based peptide inhibitors. Structure–activity relationship studies have been performed on one of these inhibitors, CIYKYYF. In a kinase assay using YIYGSFK as the substrate, CIYKYY has been demonstrated to inhibit p60c‐src, with an IC50 of 0.6 μm. Further truncation has led to the determination that even the smaller peptide, CIYK, is a moderately potent inhibitor with IC50 of 15 μm. Some improvement in inhibitory potency (IC50 = 11.8 μm) has been observed with the replacement of Tyr3 in CIYK with β‐phenylalanine (β‐Phe). The tetrapeptide CI(β‐Phe)K will be used as a lead compound for future development of peptidomimetics and small molecule inhibitors that have the capacity to penetrate the plasma membrane of intact cells.
Purification, characterization of two peptides from Buthus martensi Karch
Authors: Cao Z.Y. , Pan Y.P. , Xiao X. , Liu X.M. , Wang X.L. , Liang X.T. , Yu D.Q. , Shen W.Q.
Published: November 2003

Abstract:  A new peptide named Martentoxin I and an analogue Martentoxin were purified and characterized from the venom of Buthus martensi Karch. Martentoxin I consisted of 36 amino acid residues with molecular mass as 3908.0 Da determined by matrix‐assisted laser desorption ionization time‐of‐flight‐MS. The amino acid sequence was determined as GLIDVKCFASSECWTACKKVTGSGQGKCQNNQCRCY by Edman degradation. Martentoxin consisted of 37 amino acid residues with a molecular mass as 4055.3 Da and it showed highly sequence identity to Martentoxin I as FGLIDVKCFASSECWTACKKVTGSGQGKCQNNQCRCY. Estimation from circular dichroism spectra indicated Martentoxin I owned 18.0%α‐helix, 53.0%β‐sheet structure and 3.9% turn while Martentoxin contained 13.3%α‐helix, 64.3%β‐sheet structure and 1.1% turn. The toxicity assay showed both peptides had no toxic effects on mice up to the dose of 10 mg/kg. Electrophysiological studies showed that Martentoxin I and Martentoxin at the concentration of 1 μm significantly inhibited voltage‐dependent Na+ current (INa) and voltage‐dependent delayed rectifier K+ current (IK) but had no effects on transient K+ current (IA). Both interactions with Na+ and K+ channels were irreversible.
Biological Properties of Allogenic Articular Chondrocytes on the Surface of Bovine Cartilage Explantsin vitro
Authors: Kim G. , Okumura M. , Bosnakovski D. , Ishiguro T. , Kadosawa T. , Fujinaga T.
Published: November 2003

Bovine cartilage explants were co‐cultured with or without allogenic chondrocytes for 4 weeks. The attachment of the applied chondrocytes to cartilage after labelling with fluorescence was assessed using a confocal laser microscope. Morphological changes and the production of extracellular matrix (ECM) of co‐cultured chondrocytes on intact and damaged surfaces of cartilage were evaluated by histological and immunohistochemical methods. Co‐cultured chondrocytes attached to and proliferated on the intact and damaged areas of cartilage, and a new layer was created there. The defects were also filled with ECM produced by the co‐cultured chondrocytes. Glycosaminoglycans and collagen type II were detected in the newly formed ECM, and large numbers of rounded chondrocytes were observed at primitive lacunae in this matrix at 4 weeks of culture. The results suggest that chondrocytes have the ability to attach to, to proliferate on and to establish a new matrix on the intact and damaged surfaces of cartilage explants.
Mechanisms of increased insulin resistance in non‐cirrhotic patients with chronic hepatitis C virus infection
Authors: MAENO TADASHI , OKUMURA AKIHIKO , ISHIKAWA TETSUYA , KATO KOICHI , SAKAKIBARA FUMIHIKO , SATO KEN , AYADA MINORU , HOTTA NAOKI , TAGAYA TSUNEAKI , FUKUZAWA YOSHITAKA , KAKUMU SHINICHI
Published: November 2003

Background and Aim:  Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non‐cirrhotic and non‐diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance.

Methods:  Fifty‐six patients diagnosed with HCV‐related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)‐α and HCV‐RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA‐IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA‐IR, and the clinical factors responsible for the increase in HOMA‐IR in non‐diabetic patients was investigated.

Results:  Homeostasis  model  assessment  of  insulin  resistance  and  IRI  levels  increased  parallel  with the progression of fibrosis. Among the non‐diabetic patients with mild to moderate liver fibrosis, BMI,  serum  levels  of  AST  and  TNF‐α were  related  with  HOMA‐IR  (BMI:  r = 0.395,  P = 0.041; AST: r = 0.465, P = 0.014; TNF‐α: r = 0.396, P = 0.040). In contrast, HOMA‐IR related to TNF‐α (r = 0.526, P = 0.013) in non‐diabetic patients with advanced liver fibrosis.

Conclusion:  Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.