bluuebunny/crossref_metadata_2025 huggingface dataset:
Rewards and gratifications among family caregivers: towards a refined model of caring and coping
Authors: Grant G. , Ramcharan P. , McGrath M. , Nolan M. , Keady J.
Published: March 2003

Supplemented by a case illustration, findings from a study in Wales are reported for the first time from the application of two new instruments for measuring rewards and stresses among family caregivers. The paper takes as its starting point a critique of models of caregiving which emphasize instrumental and pathological dimensions. Findings suggest that caregivers report the existence of pervasive rewards and gratifications, as well as stresses, as part of the caregiving experience, and that these stem from varying sources. The role of rewards and satisfactions in stress‐coping models is briefly discussed, and implications for changed practice and policy thinking are reviewed.
Investigating the relationship between stress and worker behaviour
Authors: Rose J. , Jones F. , Fletcher B.
Published: March 2003

Direct care staff working in six residential group homes for people with intellectual disability were asked to complete a questionnaire which asked for information on levels of stress (anxiety and depression), the types of demand experienced by the staff, the support they received and the constraints they faced at work. Staff were also observed at work using a schedule which detailed who they interacted with, the content and type of interaction, and what activities staff were involved in. Measurement of workers' anxiety and depression levels confirmed management assessments of staff stress levels in the homes: two residential group homes were classified as ‘low stress’ and four as ‘high stress’. A number of differences emerged between the two groups. Staff in the high stress homes reported greater demands and less support than those in the low stress homes. Higher levels of interaction were found between staff and residents in low stress houses, where more of the interaction was given as assistance and positive interactions. However, activities in higher‐stress group homes appeared to be more community oriented, with staff spending a much greater amount of time out of the house. The importance of these results for both staff and residents is discussed, and suggestions for further work are made.
Distinctiveness and correlates of maladaptive behaviour in children and adolescents with Smith–Magenis syndrome
Authors: Bouras N. , Dykens E. M. , Smith A. C. M.
Published: March 2003

This two‐part study examines the distinctiveness and correlates of maladaptive behaviour in 35 children and adolescents with Smith–Magenis syndrome, a developmental disorder caused by an interstitial deletion of chromosome 17 (p11.2). Study I compares Child Behavior Checklist scores in 35 children with Smith–Magenis syndrome to age‐ and gender‐matched subjects with Prader–Willi syndrome and mixed intellectual disability. Subjects with Smith–Magenis syndrome had significantly higher levels of maladaptive behaviour than the other groups. Although some problems were shared across groups, 12 behaviours differentiated the three groups with 100% accuracy. Study 2 assessed the frequency and correlates of self‐injurious and stereotypical behaviours, including unusual features such as nail‐yanking, inserting objects into bodily orifices, self‐hugging and a ‘lick‐and flip’ behaviour. Nail‐yanking and bodily insertions were less common than other types of self‐injury, and self‐hugs and the ‘lick‐and flip’ stereotypies were seen in about half the sample. Although age and degree of delay were correlated with problem behaviours, sleep disturbance emerged as the strongest predictor of maladaptive behaviour. The implications are discussed for clinical diagnostic ambiguities between the Smith–Magenis and Prader–Willi syndromes, and for intervention.
Communications between staff and adults with intellectual disabilities in naturally occurring settings
Authors: McConkey R. , Morris I. , Purcell M.
Published: March 2003

Videotapes were made of 43 staff‐client dyads in small‐scale residential and day service settings. Frequency counts were made of carers’ communicative acts, and two experienced speech and language therapists rated these for appropriateness. Recommendations for enhancing communication were also noted. The results showed that clients were presented with few opportunities to engage as equal partners in the conversational interchanges: staff overly relied on verbal acts, even when they were communicating with predominantly non‐verbal clients; they tended to favour the use of directives and questions, and the majority of staff failed to adjust their language to the client’s level of understanding. The most commonly recommended changes for staff were to use simpler sentences and words, to increase their use of non‐verbal signals and open questions, to provide more opportunities for clients to initiate topics, and to increase their responsiveness to client’s non‐verbal signals. The explanations for staff behaviour are reviewed and the implications for changing practice are discussed.
Effect of divalproex sodium on aggression and self‐injurious behaviour in adults with intellectual disability: a retrospective review
Authors: Ruedrich S. , Swales T. P. , Fossaceca C. , Toliver J. , Rutkowski A.
Published: March 2003

The aim of the present study was to evaluate the efficacy of divalproex sodium treatment in adults with intellectual disability, and aggressive or self‐injurious behaviour. Twenty‐eight adults aged between 20 and 63 years of age with severe, long‐lasting behavioural problems were treated with divalproex sodium (dosage 500–4000 mg day − 1). Clinical changes were assessed at 2–73 months into the pharmacological treatment utilizing the Clinical Global Impression Severity (CGI‐S) scale, and monthly behavioural counts of aggressive and self‐injurious acts. Seventy‐one percent of subjects demonstrated a moderate or marked improvement on the CGI‐S; another 21% demonstrated mild benefits. Among the patients for whom objective prospective behavioural counts were available, 88% showed a significant reduction in aggression and self‐injurious behaviour, 46% had other psychotropic medications discontinued, and another 39% had psychotropic medications decreased. One patient had serious thrombocytopenia which required the discontinuation of divalproex sodium, and one other had vomiting and worsened aggression. The present preliminary, uncontrolled study suggests that adults with intellectual disability, and aggressive or self‐injurious behaviour may respond to divalproex sodium, and that this drug is well‐tolerated in the majority of subjects.
Social comparison, self‐esteem and depression in people with intellectual disability
Authors: Dagnan D. , Sandhu S.
Published: March 2003

The present study explores the relationship between social comparison processes, self‐esteem and depression in people with intellectual disability. Forty‐three people with mild and moderate intellectual disability completed adapted measures of self‐esteem and social comparison. The social comparison scale offers subscale scores on achievement, social attractiveness and group belonging dimensions. The self‐esteem scale offers subscale scores for positive and negative self‐esteem. A significant positive correlation was found between positive self‐esteem and social comparison on the achievement dimension. Depression was significantly negatively correlated with social comparison on the social attractiveness and group belonging dimensions, and with positive self‐esteem. Regression analysis showed that depression was significantly and independently predicted only by social comparison on the social attractiveness dimension. The present authors conclude that social comparison is associated with self‐esteem and depression in people with intellectual disability in the same way as it is for people without intellectual disability. Further exploration of social comparison process in people with intellectual disability may inform cognitive behavioural interventions for this group of people.
Supporting individuals with intellectual disability and challenging behaviour in integrated work settings: an overview and a model for service provision
Authors: Stevens P. , Martin N.
Published: March 2003

An overview of supported employment and its historical context is examined, and supported employment for individuals with both intellectual disability and challenging behaviour is discussed. A proposed model for working with such individuals is briefly outlined. This model is based on previous work in the field, and is characterized by a multi‐component approach which addresses the issues of both support and behavioural intervention.
Factors affecting the risk of behaviour problems in children with severe intellectual disability
Authors: Chadwick O. , Walker N. , Bernard S. , Taylor E.
Published: March 2003

In order to examine the importance of a range of potential risk factors for behaviour problems in children with severe intellectual disability, a sample was identified by the administration of a screening version of the Vineland Adaptive Behaviour Scales (VABS) to the parents of children aged 4–11years attending six special needs schools in three adjacent inner London boroughs. Parents whose children had a VABS standard score of 50 were interviewed using the Disability Assessment Schedule and both parents and teachers completed the Aberrant Behaviour Checklist. Most behaviour problems were more common in ambulant children, but problems less dependent on the ability to walk, such as sleeping difficulties, screaming and self‐injury, were equally common in ambulant and non‐ambulant children. Among ambulant children, there were few significant associations between the severity of the child's behaviour problems and the age or sex of the child, the presence or absence of epilepsy, and various indices of socio‐economic disadvantage. Sleeping difficulties, overactivity, self‐injury, destructive behaviour and autistic features, such as social withdrawal and stereotypies, were strongly associated with skills deficits, but aggression, temper tantrums and general disruptive behaviour were not. Limitations in daily living skills were better predictors of behaviour problems than were poor communication skills.
Speech disorder in children with Down's syndrome
Authors: Dodd B. , Thompson L.
Published: March 2003

The speech of children with Down's syndrome (DS) is often unintelligible, unlike many other children who have an intellectual disability. However, the nature of their speech disorder is controversial. The speech error patterns of children with DS were compared to those of intellectually average chil‐dren with phonological disorder whose errors were characterized by inconsistency. The groups were matched for percentages of consonants produced in error. The data revealed no differences between the groups in terms of the number of words which were produced inconsistently on repeated productions in a picture‐naming task. However, further analyses revealed differences in the type of errors made by the groups in that the children with phonological disorder characterized by inconsistent errors made more changes to words on repeated production than the group with DS. The deficits underlying inconsistent pronunciation of words in the two groups of children under investigation would appear to differ. Intervention strategies should target the deficits identified.
Randomized trial of psychotropic medication information leaflets for people with intellectual disability
Authors: Strydom A. , Hall I.
Published: March 2003

People with intellectual disability (ID), like other patient groups, are known to have a limited knowledge of medication. Leaflets are seen as an appropriate means of providing patient information. To test the hypothesis that medication information leaflets would improve the knowledge and care of the target group, the present authors designed a randomized trial and planned to do subgroup analyses where appropriate. The participants were individually randomized to two groups. A control group was given verbal medication information by their nurse or psychiatrist, and a study group was given specifically designed leaflets in addition to verbal information. The present authors recruited 54 people with mild to moderate ID and mental illness, aged 18 years and older, who were taking psychiatric medications. Questionnaires administered by a blind interviewer recorded outcomes such as medication knowledge and satisfaction at two time points. The participants with mild ID in the leaflet group had significantly reduced medication knowledge and understanding. There were no significant differences in satisfaction with clinicians and medication. Patient information leaflets may confuse people with mild ID in the short term. Other patient groups with cognitive deficits may have similar outcomes. Evaluation of outcomes of health education initiatives is important.
Depressive mood in students with mild intellectual disability: students’ reports and teachers’ evaluations*
Authors: Heiman T.
Published: March 2003

The present study examined 310 students with mild intellectual disability (ID) who attended special schools and self‐contained classes in mainstream schools with regard to their reports of depressive mood, and loneliness and social skills, and teachers’ perception of the students’ academic, social and behavioural competencies. A multivariate analysis of variance (MANOVA) revealed that: students in special schools reported higher levels of depression and felt lonelier than mainstream school students; girls exhibited a greater sense of depressive mood than boys; teachers assessed boys as having higher academic competencies than girls; and boys were considered more easily distracted and less independent. However, teachers considered girls to have more adequate social adjustment, and be more task‐oriented and more independent. For both groups, depressive mood can be predicted by distractibility and loneliness; by gender and lower academic competencies for special school students; or mainly by difficulties in social adjustment in the case of mainstream school students.
Neurological changes and emotional functioning in adults with Down Syndrome
Authors: Nelson Linda D. , Orme Denise , Osann Kathryn , Lott Ira T.
Published: March 2003

This study was designed to examine emotional changes in adults with Down Syndrome (DS) over time and whether changes in these psychological variables were associated with brain atrophy on MRI scan and the presence of pathological reflexes on the neurological examination. Participants were 26 adults with DS and their caregivers. Caregivers completed a measure of emotional functioning about individuals with DS at two different time points (1 year apart). Levels of cognitive functioning were measured and neurological and MRI examinations were performed on all subjects at initial testing. Significant group effect separated those with and without pathological findings on MRI and neurological exam across three different scales: depression, indifference, and pragmatic language functioning. Problems of poor pragmatic language functioning appeared later in the course of suspected Alzheimer's disease (AD), as demonstrated by a significant group effect at time 2, but not at initial testing. In these subjects, the primary emotional change was a decline in social discourse (e.g. conversational style, literal understanding, verbal expression in social contexts). These emotional levels were stable over time, regardless of degree of cognitive decline. Specific emotional changes occur during the course of AD which were associated with abnormal findings from MRI and from neurological examination. These results, along with abnormalities in brain imaging and the presence of pathological reflexes, suggested that frontal lobe dysfunction is likely to be an early manifestation of Alzheimer's Disease in Down Syndrome.
Mothers with learning difficulties and their support networks
Authors: Llewellyn G , McConnell D
Published: March 2003

Mothers with learning difficulties1are thought to be among the most socially isolated parents in the community. A great deal of attention has been directed to assessing their parenting abilities and teaching parenting skills, but less has been given to the support that mothers may (or may not) receive from family, friends and the service system. The present paper investigates mothers' views about the types of support which they receive and from whom they receive it. Data were derived from 70 mothers who participated in interviews using a support interview guide designed to accommodate the mothers' cognitive difficulties. The primary purpose of the interview was to explore the quantity and composition of the mothers' support networks, the frequency of contact and geographical proximity of support people, and the type of support provided. Key findings include: the central place that family members have in these mothers' lives; the importance of service providers as sources of information and advice; and the relative absence of friends and neighbours. Briefly, mothers living alone have service‐centred networks, mothers living with a partner have family‐centred networks with relatively dispersed family ties, and mothers living in a parent/parent‐figure household have local, family‐centred networks. The overall conclusion to be drawn from the present results is that these mothers do not live in a social vacuum, but many are socially isolated. The finding that so few mothers could identify supportive ties with friends and neighbours suggests that these mothers are isolated from their local communities and are potentially vulnerable if a breakdown occurs in the support provided by their families. The need for service providers to be more actively involved in linking mothers to their communities is discussed.
Health characteristics and health services utilization in older adults with intellectual disability living in community residences
Authors: Janicki M. P. , Davidson P. W. , Henderson C. M. , McCallion P. , Taets J. D. , Force L. T. , Sulkes S. B. , Frangenberg E. , Ladrigan P. M.
Published: March 2003

Background The health status and health needs of adults with intellectual disability (ID) change with advancing age, and are often accompanied by difficulties with vision, hearing, mobility, stamina and some mental processes.

Aim The present study collected health status information on a large cohort of adults with ID aged ≥ 40 years living in small group, community‐based residences in two representative areas of New York State, USA.

Method Adult group home residents with ID aged between 40 and 79 years (n = 1371) were surveyed to determine their health status and patterns of morbidity.

Results Most subjects were characterized as being in good health. The frequency of cardiovascular, musculoskeletal and respiratory conditions, and sensory impairments increased with age, while neurological, endocrine and dermatological diseases did not. Psychiatric and behavioural disorders declined with increasing age, at least through 70 years of age. Although most conditions increased with age, their frequency varied by sex and level of ID. Frequencies of age‐related organ system morbidity were compared to data from the National Health and Nutrition Evaluation Survey III. It was found that adults with ID had a lower overall reported frequency of cardiovascular risk factors, including hypertension and hyperlipidaemia, and adult‐onset diabetes. Inconsistencies with mortality data among older adults with ID were observed (which showed equal if not greater prevalence of deaths as a result of cardiovascular disease and cancer).

Conclusion These results suggest that either a cohort effect is operating (i.e. contemporary populations are healthier than previous populations), or that there may be under‐recognition of select risk factors and diseases.
Family environment and cognitive abilities in girls with fragile‐X syndrome
Authors: Kuo A. Y. , Reiss A. L. , Freund L. S. , Huffman L. C.
Published: March 2003

Background There remains some variance in cognitive ability that is unexplained in children with fragile‐X syndrome (FXS). Studies in typically developing children suggest that family environment might be one contributor to this unexplained variance. However, the effect of family environment in relation to cognition in atypical children with FXS has been relatively unexplored to date.

Methods The present authors examined the putative genetic and environmental factors associated with cognition in a group of age‐matched children consisting of 26 females with FXS and 31 typically developing children. All subjects were administered the Wechsler Intelligence Scale for Children – Revised; and the subjects’ parents were administered the Wechsler Adult Intelligence Scale – Revised, and completed the Hollingshead Index of Social Status and the Moos & Moos Family Environment Scale.

Results Using a multiple regression analytic strategy, the present authors found that family environment contributed significantly to cognitive abilities in typically developing girls, but did not have a unique contribution to cognitive abilities in girls with FXS. There was a suggestion that, for girls with FXS, socio‐economic status, a measure of sociocultural environment, was correlated with IQ.

Conclusions The present study provides a basis for future research on the environmental contributions to cognitive abilities, particularly work related to verbal cognition.
Challenging behaviours should not be considered as depressive equivalents in individuals with intellectual disability
Authors: Tsiouris J. A. , Mann R. , Patti P. J. , Sturmey P.
Published: March 2003

Background  Depression is one of the most common forms of psychopathology in people with intellectual disability (ID). The present study evaluated the utility of an expanded assessment of psychiatric symptoms and challenging behaviours, as measured by the Clinical Behavior Checklist for Persons with Intellectual Disabilities (CBCPID).

Methods  The CBCPID was administered to 92 people with ID, 35 of whom were diagnosed with a depressive disorder.

Results  Item and factor analysis of the scale indicated that depression was best assessed using the core DSM‐IV symptoms of depressive disorder. Challenging behaviours such as self‐injury or aggression were not closely associated with depression. Short scales using the core DSM‐IV symptoms of depression were highly internally consistent. There was also evidence of the validity of these scales.

Conclusions  This study found no evidence that challenging behaviours were depressive equivalents in this population. The present authors conclude that the assessment of depression in people with ID should focus on the core DSM‐IV symptoms of depression.
Patients with and without intellectual disability seeking outpatient psychiatric services: diagnoses and prescribing pattern
Authors: Hurley A. D. , Folstein M. , Lam N.
Published: March 2003

Background  The present study examined the presenting problem of psychiatric outpatients, and resulting diagnostic and prescribing patterns, comparing patients with intellectual disability (ID) with non‐ID (N‐ID) patients seen in the same clinic.

Methods  This study was a retrospective medical chart review of information in the first psychiatric diagnostic evaluation for the most recent 100 adult patients with mild ID, 100 patients with moderate, severe or profound ID, and 100 matching N‐ID patients.

Results  There were significant differences in rates of medical illness, disabilities, history of marriage, children, independent living, and family history of psychiatric and neurological disorders. Individuals with ID were more likely to present with aggression, self‐injurious behaviour or physical complaints, whereas N‐ID subjects presented more frequently with depression and anxiety complaints. For all groups, depressive disorders were the most frequent class of diagnoses. For those with ID, antipsychotics were used in 32% of subjects, with mood stabilizers in 28% and antidepressants in 27%. The N‐ID subjects were most frequently prescribed antidepressants (40%) and anxiolytics (22%). Polypharmacy did not differ significantly among groups.

Conclusions  Psychiatric practitioners relied on the diagnostic examination to formulate their diagnosis, whereas the chief complaint reflected the view of caregivers of the subjects with ID. In contrast to previous studies, outpatient providers frequently diagnosed depression, and the prescribing pattern showed increased usage of antidepressants and mood stabilizers.
Management of the Zollinger–Ellison syndrome in patients with multiple endocrine neoplasia type 1
Authors: Jensen
Published: March 2003

Jensen RT (Bethesda, MD, USA). Management of the Zollinger–Ellison syndrome in patients with multiple endocrine neoplasia type 1 (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 477–88.

Zollinger–Ellison syndrome (ZES) is the most common symptomatic pancreatic endocrine tumour in patients with MEN‐1. Besides the treatment of the usual endocrinopathies seen in patients with MEN‐1, the treatment of the ZES requires attention be paid to controlling the gastric acid hypersecretion, to dealing with the gastrinomas per se which are malignant in 18–60% of cases, and to the diagnosis and treatment of gastric carcinoid tumours, that are increasingly seen in these patients. In this article the current management of each of the areas is reviewed and what is known or uncertain discussed, based on our studies at the NIH and data from others. Data from 231 patients including 45 with MEN‐1 and 186 without MEN‐1 is contrasted in this report. Gastric acid hypersecretion has been controlled in all patients medically with MEN‐1 and ZES at the NIH for up to 22 years. The current drugs of choice are H+‐K+ ATPase inhibitors and twice a day dosing is recommended. Periods of parenteral drug therapy (surgery, etc.) and pregnancy require important modifications. The appropriate surgical therapy of the gastrinoma is controversial. Eighty per cent of patients have a duodenal gastrinoma and 20–30% have a pancreatic tumour. Recent studies suggest gastrinoma enucleation combined with duodenotomy rarely results in cure. Aggressive surgery (Whipple resection) can result in cure of gastrinoma but effect on survival is unclear. There are important differences in gastrinoma location, extent, and percentage with aggressive disease in patients with or without MEN‐1, which are discussed. Confusion has occurred because of lack of information on the natural history of the gastrinoma compared to the other pancreatic endocrine tumours that occur in MEN‐1 and survival data from patients with and without MEN‐1 is contrasted. The occurrence of gastric carcinoids in patients with and without MEN‐1 with ZES is contrasted and the areas of certainty and disagreement reviewed.
Identification of homozygous lipoprotein lipase gene mutation in a woman with recurrent aggravation of hypertriglyceridaemia induced by pregnancy
Authors: Suga Shigeki , Tamasawa Naoki , Kinpara Ichiro , Murakami Hiroshi , Kasai Nobuhiko , Onuma Tomio , Ikeda Yasuyuki , Takagi Atsuko , Suda Toshihiro
Published: March 2003

Shigeki Suga, Naoki Tamasawa, Ichiro Kinpara, Hiroshi Murakami, Nobuhiko Kasai, Tomio Onuma, Yasuyuki Ikeda, Atsuko Takagi, Toshihiro Suda (Hirosaki University School of Medicine, Aomori; and National Cardiovascular Center Research Institute, Osaka, Japan). Identification of homozygous lipoprotein lipase gene mutation in a woman with recurrent aggravation of hyperglyceridaemia induced by pregnancy (Case Report). J Intern Med 1998; 243: 317–21.

We herein report a case of a 40‐year‐old Japanese woman (patient IT) with a history of recurrent aggravation of hypertriglyceridaemia, pancreatitis and miscarriages in three previous pregnancies. However, strict dietary intervention was applied during a fourth pregnancy. As a result, acute pancreatitis was avoided, and the patient gave birth to a healthy infant. In patient IT, the underlying etiology of the recurrent aggravation of hypertriglyceridaemia during pregnancy was a lipoprotein lipase (LPL) gene aberration. She was homozygous for LPL deficiency due to a nonsense mutation (TGG1401⇒TGA/Trp382⇒ Stop) in exon 8 of the LPL gene, which resulted in the absence of LPL activity and immunoreactive LPL mass. Our findings indicate that, in LPL deficiency, pregnancy seriously exacerbates hypertriglyceridaemia and increases the risk of acute pancreatitis, which endangers both the mother and fetus. Early diagnosis of LPL deficiency and appropriate management thereof are essential for normal childbirth.
The search for the MEN1 gene
Authors:   THE EUROPEAN CONSORTIUM ON MEN‐1, Lemmes  , Van De Ven  , Kas  , Zhang  , Zhang  , Giraud  , Wautot  , Buisson  , Buisson  , Pugeat  , Peix  , Caldener  , Caldener  , Parente  , Quincey  , Courseaux  , Carle  , Gaudray  , De Wit  , Lips  , Höppener  , Khodaei  , Grant  , Weber  , Teh  , Farnebo  , KytÖlä  , KytÖlä  , Grimmond  , Phelan  , Larsson  , Bassett  , Forbes  , Pannett  , Thakker
Published: March 2003

The European Consortium on MEN‐1. The search for the MEN1 gene (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 441–6.

The search for the gene whose mutations predispose individuals to multiple endocrine neoplasia type 1 (MEN‐1) started in 1988 when the MEN1 locus was assigned to 11q13, close to PYGM. It came to an end with the recent identification of a gene expressed ubiquitously which harbours inactivating mutations associated with MEN‐1. During these nine years, the genetic linkage interval had been slowly reduced, and losses of heterozygosity (LOH) in MEN‐1 tumours had given strong indications that MEN1 was a tumour suppressor gene. It is ironic that MEN1 was finally found to be located less than 100 kb telomeric to PYGM. From the beginning, this gene was the most tightly linked genetically to MEN‐1. In addition, LOH had already shown (in 1990) that it was the most likely centromeric boundary of the MEN1 minimal region. We recently narrowed the critical region to 900 kb through meiotic mapping, and established a 1200‐kb sequence‐ready contig consisting of cosmids, bacterial artificial chromosomes (BACs) and P1‐derived artificial chromosomes (PACs), including three gene clusters (19 genes and 3 expressed sequence tags). Taking LOH results into account, the gene was likely to be present in the 300‐kb area telomeric to PYGM that we had covered with BACs. One of the novel genes that we have identified by cDNA selection in this region, SCG2 (Suppressor Candidate Gene 2), proved to be identical to the recently published MEN1 gene. Mutation analysis of SCG2 in 11 unrelated MEN‐1 families identified one nucleotide sequence polymorphism and 10 different mutations that segregated with the disease.
High prevalence of undiagnosed coeliac disease in adults: a Swedish population‐based study
Authors: IVARSSON A. , Persson L. Å. , Juto P. , Peltonen M. , Suhr O. , Hernell O.
Published: March 2003

Objective. To determine the prevalence of coeliac disease in a population‐based sample of Swedish adults.

Design. Population‐based cross‐sectional study.

Setting. Northern Sweden.

Subjects. A total of 1894 adults (76%) out of 2500 invited, randomly selected from the population register after stratification for age and sex.

Main outcome measures. Prevalence of biopsy verified coeliac disease, symptoms of undiagnosed cases, and results of antiendomysium and antigliadin serum antibody tests.

Results. Coeliac disease was confirmed by intestinal biopsy showing enteropathy in 10 individuals (seven women and three men), corresponding to a prevalence of 5.3 per 1000 (95% CI = 2.5–9.7). The majority of cases (eight out of 10) had not been diagnosed prior to the screening, although many had symptoms compatible with coeliac disease. All individuals with antiendomysium antibody positivity who were subjected to a small intestinal biopsy had enteropathy. Furthermore, all of them also had elevated levels of antigliadin antibodies type IgA and/or IgG.

Conclusions. Coeliac disease is common, albeit mostly undiagnosed, in Swedish adults. It is likely that the situation is no better in other countries. This highlights the importance of keeping coeliac disease in mind, and of promptly investigating individuals with unexplained, even mild, symptoms compatible with the disease. Serological markers, e.g. antigliadin and antiendomysium antibodies, are useful tools within this active case‐finding strategy, although the final diagnosis should be based on an intestinal biopsy demonstrating enteropathy.
Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs
Authors: Claesson H.‐E. , Dahlén S.‐E.
Published: March 2003

Abstract. Claesson H‐E, Dahlén S‐E (Karolinska Institute, Stockholm, Sweden). Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs (Review). J Intern Med 1999; 245: 205–27.
Colonic endocrine cells in patients with familial amyloidotic polyneuropathy
Authors: Anan I. , El‐Salhy M. , Ando Y. , Nyhlin N. , Terazaki H. , Sakashita N. , Suhr O.
Published: March 2003

Abstract. Anan I, El‐Salhy M, Ando Y, Nyhlin N, Terazaki H, Sakashita N, Suhr O (University Hospital, Umeå, Sweden, and University Hospital, Kumamoto, Japan). Colonic endocrine cells in patients with familial amyloidotic polyneuropathy. J Intern Med 1999; 245: 469–473.

Objective.  To establish whether the endocrine cell number is affected in the colon in Japanese FAP patients.

Setting.  Department of Medicine, Umeå University Hospital and Department of Internal Medicine and Pathology, University Hospital, Kumamoto, Japan.

Subjects.  Autopsy colon tissue specimens from 11 FAP patients and nine controls as well as 12 control biopsy specimens were included in the study.

Measurements.  Endocrine cells in the colon were detected by immunohistochemistry and quantified by computerized image analysis.

Results.  The autopsy material showed a slight autolysis. Neither enteroglucagon nor pancreatic polypeptide positive cells could be detected in the autopsy material, but were present in biopsy material. There was no statistical difference between autopsy and biopsy specimens regarding the number of peptide YY (PYY), somatostatin and serotonin cells. No significant differences were noted in PYY, somatostatin and serotonin immunoreactive cells in FAP patients compared to autopsy controls, though PYY cells tended to be decreased and serotonin and somatostatin cells tended to be increased in FAP patients.

Conclusion.  The difference between the Swedish and Japanese patients in the endocrine cell content points to the possibility of involvement of other factors than the endocrine cell depletion of the colon might be involved in the pathogenesis of gastrointestinal dysfunction in FAP. The tendency of PYY to decrease in Japanese FAP might contribute to the development of diarrhoea in these patients.
Insulin‐mediated vasodilation and glucose uptake are independently related to fasting serum nonesterified fatty acids in elderly men
Authors: Andersson P.‐E. , Lind L. , Berne C. , Berglund L. , Lithell H. O.
Published: March 2003

Abstract.

Andersson P‐E, Lind L, Berne C, Berglund L, Lithell HO (Uppsala University, Uppsala, Sweden). Insulin‐mediated vasodilation and glucose uptake are independently related to fasting serum nonesterified fatty acids in elderly men. J Intern Med 1999; 246: 529–537.

Objectives. To investigate candidate predictors for insulin sensitivity in healthy elderly males, with special reference to the influence of insulin‐mediated skeletal muscle blood flow and serum nonesterified fatty acids (NEFA).

Subjects. From the participants in a health survey of 70‐year‐old males, focusing on cardiovascular risk factors, a subgroup of 46 men was sampled. Only men who declared themselves healthy and without medication were included.

Interventions. Insulin sensitivity was measured with the euglycaemic hyperinsulinaemic clamp. Leg blood flow was measured before and during the clamp, using the Doppler ultrasound technique.

Results. Hyperinsulinaemia [steady‐state plasma insulin 105(15) mU L–1] increased leg blood flow by 10% (P < 0.004). When tested in bivariate analysis incremental leg blood flow was only significantly related to the serum NEFA concentration (r = – 0.38, P < 0.01) amongst a number of measured variables. Insulin‐mediated glucose disposal was related to body mass index (BMI) (r = –0.49, P = 0.0006), waist/hip ratio (r = – 0.31, P = 0.036), NEFA (r = – 0.50, P = 0.0004) and heart rate (r = – 0.34, P = 0.02). In multivariate analysis only BMI and NEFA remained significantly related to whole‐body glucose uptake.

Conclusions. The study demonstrates that in elderly men BMI and fasting serum NEFA but not insulin‐induced vasodilation are related to insulin sensitivity. High fasting levels of NEFA relate to both impaired insulin‐mediated vasodilation and impaired glucose disposal, respectively. These two insulin actions were not interrelated, however, a finding which may indicate dissociated mechanisms.
Silent cerebral infarction: a potential risk for pneumonia in the elderly
Authors: Nakagawa T. , Sekizawa K. , Nakajoh K. , Tanji H. , Arai H. , Sasaki H.
Published: March 2003

Abstract. Nakagawa T, Sekizawa K, Nakajoh K, Tanji H, Arai H, Sasaki H (Tohoku University, Sendai, Japan). Silent cerebral infarction: a potential risk factor for development of pneumonia in the elderly. J Intern Med 2000; 247: 255–259.

Objective. To determine whether patients who have silent cerebral infarction are more likely to develop pneumonia than are controls without silent cerebral infarction.

Design. We examined 269 community‐residing participants of the senior day‐care centre without history of previous stroke, and then followed them over a two‐year period to assess pneumonia. On the basis of computerized tomography scans, they were divided into two groups: no infarction (n = 102) and cerebral hemispheric infarction (n = 167). Cerebral infarcts were further divided into deep and superficial infarcts.

Results. The incidence of pneumonia was significantly higher in subjects with silent cerebral infarction (19.8%) than in controls (4.9%) (odds ratio, 4.67 [95% CI, 1.87–11.67]; P < 0.01). Deep infarcts were more closely associated with the incidence of pneumonia (29.1%) than superficial infarcts (7.6%) (odds ratio, 5.00 [CI, 1.91–13.08]; P < 0.01).

Conclusions. Elderly subjects with silent cerebral infarction were more likely to develop pneumonia than were controls without silent cerebral infarction. Amongst hemispheric silent cerebral infarcts, those located in the deep brain structures may be an important predictor of the development of pneumonia.
Molecular aspects of the inherited porphyrias
Authors: Sassa S. , Kappas A.
Published: March 2003

Abstract. Sassa S, Kappas A (The Rockefeller University, New York, USA). Molecular aspects of the inherited porphyrias (Review). J Intern Med 2000; 247: 169–178.

The porphyrias are diseases due to marked deficiencies of enzymes of the haem biosynthetic pathway ( Fig. 1). Except for the first enzyme of the pathway, δ‐aminolevulinate synthase (ALAS), deficiencies in seven other enzymes are associated with the various forms of porphyria
(
Fig. 2). Porphyrias can be classified as either hepatic or erythroid, depending on the major site of production of porphyrins or their precursors. The pathogenesis of all inherited porphyrias has now been defined at the molecular level, and it is clear that there is a great deal of genetic heterogeneity in each porphyria [1].

Structure of major porphyrins: (a) uroporphyrin III; (b) corpoporphyrin III; (c) protoporphyrin IX.

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Diseases due to enzymatic deficiency of the haem biosynthetic pathway. XLSA, X‐linked sideroblastic anaemia; Zn‐PP, zinc protoporphyrin IX; Free PP, free protoporphyrin IX; 7‐C porphyrin, 7‐carboxylate porphyrin. Other abbreviations are defined in the text.

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Angiotensin‐converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis
Authors: Schürmann M. , Reichel P. , Müller‐Myhsok B. , Dieringer T. , Wurm K. , Schlaak M. , Müller‐Quernheim J. , Schwinger E.
Published: March 2003

Abstract.Schürmann M, Reichel P, Müller‐Myhsok B, Dieringer T, Wurm K, Schlaak M, Müller‐Quernheim J, Schwinger E (Medical University Lübeck; Bernhard Nocht Institute, Hamburg; St. Georgs Hospital, Höchenschwand; and Medical Hospital, Research Center Borstel, Germany). Angiotensin‐converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis.J Intern Med2001;249:77–83.

Objectives.The aim of this study was to test for genetic linkage and association between polymorphisms of the angiotensin‐converting enzyme (ACE) gene and familial occurrence of sarcoidosis.

Design, setting and subjects.German families with more than one member suffering from sarcoidosis were contacted and a DNA bank was established. Sixty‐two families (140 patients, 77 females and 63 males, and 104 unaffected relatives) were genotyped for the ACE gene insertion/deletion (I/D) polymorphism and for two flanking variable sites (ACE A‐5466C and ACE 4656(CT)2/3). As controls, 100 DNAs from unrelated resident Caucasians (50 females, 50 males) were analysed. ACE allele and genotype frequencies were determined, and parametric linkage and affected sib pair analyses and transmission disequilibrium tests were performed.

Results.There was a striking over‐representation of the ACE I/D genotype DD in patients with sarcoidosis and their families as compared with controls of the study and well founded genotype frequencies from the literature. The same was evident for the accompanying genotypes CC and 2,2 of the flanking polymorphisms. Linkage between the segregation of ACE alleles and the disorder within families was clearly excluded for simple models of inheritance. However, there was a suggestive but not significant (P = 0.06) excess of allele sharing amongst affected siblings. There was no transmission disequilibrium for any ACE allele or haplotype.

Conclusions.ACE is involved in the pathogenesis of sarcoidosis, but the ACE polymorphisms are not an inherited main cause of the disease. They are more likely to modify the development of the disorder, and the ACE I/D genotype DD might be a promoter to clinical manifestation.
Use of suicide gene‐expressing donor T‐cells to control alloreactivity after haematopoietic stem cell transplantation
Authors: Tiberghien P.
Published: March 2003

Abstract. Tiberghien P. (Etablissement Français du Sang de Bourgogne/Franche‐Comté, Université de Franche‐Comté, Besançon, France). Use of suicide gene‐expressing donor T‐cells to control alloreactivity after haematopoietic stem cell transplantation (Minisymposium). J Intern Med 2001; 249: 369–377.

Conditional ablation of alloreactive donor T‐cells to prevent or treat graft‐versus‐host disease (GvHD) in the context of allogeneic haematopoietic stem cell transplantation could significantly contribute to expand the use of alloreactivity as a treatment modality. The prevention and treatment of GvHD induced by herpes simplex virus 1‐thymidine kinase (HS‐tk)‐expressing donor T‐cells by ganciclovir (GCV) has been demonstrated. Early clinical findings suggest that the use of such cells early or late after transplantation is associated with no acute toxicity, persistent circulation of the gene‐modified cells (GMC) and GCV‐sensitive GvHD. However, a number of limitations such as reduced immune function of gene‐modified T‐cells, immunogenicity of GMC as well as presence of a truncated HS‐tk gene have emerged and need to be addressed.
The dysmetabolic syndrome
Authors: Groop L. , Orho‐Melander M.
Published: March 2003

Abstract. Groop L, Orho‐Melander M (Wallenberg Laboratory, Lund University, Malmö, Sweden). The dysmetabolic syndrome. J Intern Med 2001; 250: 105–120.

The first unifying definition for the metabolic syndrome was proposed by WHO in 1998. In accordance to this, patients with type 2 diabetes mellitus or impaired glucose tolerane have the syndrome if they fulfil two of the criteria: hypertension, dyslipidaemia, obesity/abdominal obesity and microalbuminuria. Persons with normal glucose tolerance (NGT) should also be insulin resistant. About 40% of persons with impaired glucose tolerance (IGT) and 70% of patients with type 2 diabetes have features of the syndrome. Importantly, presence of the dysmetabolic syndrome is associated with reduced survival, particularly because of increased cardiovascular mortality. The dysmetabolic syndrome most likely results from interplay between several genes and an affluent environment. Compatible with the thrifty gene theory, common variants in genes regulating lipolysis, thermogenesis and glucose uptake in skeletal muscle account for a large part of such thrifty genes. However, hitherto unknown genes may still be identified by random gene approaches.
Serum lipids, lipoprotein(a) level, and apolipoprotein(a) isoforms as prognostic markers in patients with coronary heart disease
Authors: Lundstam U. , Herlitz J. , Karlsson T. , Lindén T. , Wiklund O.
Published: March 2003

Abstract. Lundstam ULF, Herlitz J, Karlsson T, Lindén T, Wiklund O (Sahlgrenska University Hospital, Göteborg University, Göteborg; Sweden) Serum lipids, lipoprotein(a) level, and apolipoprotein(a) isoforms as prognostic markers in patients with coronary heart disease. J Intern Med 2002; 251: 111–118.

Objective. Our objective was to study prognostic factors for death in patients with coronary heart disease (CHD), focusing on serum lipids and lipoproteins.

Design and subjects. The study subjects were 964 patients with angina pectoris who underwent coronary angiography between 1985 and 1987. Follow‐up, including survival and cause of death, was carried out in April 1998.

Results. A total of 363 patients died. Increasing age, diabetes and low levels of HDL cholesterol and of apolipoprotein (apo) AI were associated with increased risk of total mortality and cardiac mortality. In men, low levels of LDL cholesterol and of apoB were associated with increased risk of death, but not of cardiac death only; high levels of lipoprotein(a) [Lp(a)] were not associated with increased risk. In women, however, there was a trend towards increased risk with increasing Lp(a) levels (P=0.054); the smallest isoform of apo(a) was associated with a twofold increase in risk. In women, but not in men, risk decreased with increasing molecular weight of the apo(a) isoforms.

Conclusions. Amongst lipoprotein variables, low levels of HDL cholesterol and of apoAI and the presence of low‐molecular weight isoforms of apo(a) are associated with increased risk of death in patients with CHD. Apo(a) isoforms and Lp(a) levels seem to be more important as risk factors amongst women. Low LDL cholesterol and apoB levels were associated with increased risk, but only in men. These findings demonstrate the importance of a gender‐specific analysis of risk factors for CHD.