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Biomedical subjects

A J Holland

Publications and source records attributed to A J Holland.

At least 19 recordsLinked to original sources
PubMed2007

The course and outcome of psychiatric illness in people with Prader-Willi syndrome: implications for management and treatment.

BACKGROUND: This study is part of a larger UK-wide study investigating psychiatric illness in people with Prader-Willi syndrome (PWS), and describes the longitudinal aspect of psychiatric illness, in particular psychotic illness, and examines the use and role of psychotropic medication. METHOD: A total of 119 individuals with genetically confirmed PWS were included in the study. An informant-based questionnaire was administered for each participant to screen for a history of psychopathology. Those who screened positive were visited at their homes to obtain further information. This assessment included a full psychiatric history and mental state examination using the Psychiatric Assessment Schedule for Adults with Developmental Disability and the Operational Criteria Checklist for psychotic and affective illness to collect information regarding phenomenology and course of illness, and a modified life events questionnaire. At the end of the study period, informant-based telephone interviews were again carried out, up to 2.5 years after the initial screening. Information regarding medication usage was collected. RESULTS: The results confirm previous findings that psychiatric illness in people with PWS resembles an affective disorder. Individuals with the maternal uniparental disomy genetic subtype had a more severe course of illness than those with the deletion genetic subtype in terms of a greater risk of recurrence, more episodes, higher incidence and a possibly poorer response to medication with more side-effects. Individuals with a recurrent episode during the follow-up period had a poorer course of illness. Selective serotonin reuptake inhibitor medication is frequently used, and beneficial effects may reflect fundamental pathological processes in PWS. Mood-stabilizing medication was found to be of little benefit and reasons for this are examined. CONCLUSION: The longitudinal course of psychiatric illness and response to medication in people with PWS is fully described. Further research is needed regarding the effect of psychotropic medications, particularly mood-stabilizing medication. These data will enable informed decisions to be made regarding management options and provide information on the possible long-term outcome of illness.

Adolescent↗
PubMed2006

Neural representations of hunger and satiety in Prader-Willi syndrome.

OBJECTIVE: To investigate the neural basis of the abnormal eating behaviour in Prader-Willi syndrome (PWS), using brain imaging. We predicted that the satiety response in those with PWS would be delayed and insensitive to food intake. DESIGN AND PARTICIPANTS: The design of this study was based on a previous investigation of the neural activation associated with conditions of fasting and food intake in a nonobese, non-PWS group. The findings were used to generate specific hypotheses regarding brain regions of interest for the current study, in which 13 adults with PWS took part (mean +/- s.d. age = 29 +/- 6; BMI = 31.5 +/- 5.1; IQ = 71 +/- 8, six were female). MEASUREMENTS: Regional cerebral blood flow was measured using positron emission tomography in three sessions: one following an overnight fast and two following disguised energy controlled meals of similar volume and appearance--one of 1674 kJ (400 kcal) and another of 5021 kJ (1200 kcal). Subjective ratings of hunger, fullness and desire to eat, and blood plasma levels of glucose, insulin, leptin, ghrelin and PYY were measured before and after each imaging session. RESULTS: The neural representation of hunger, after an overnight fast, was similar to that found in nonobese individuals in the control study. In contrast, after food intake, the patterns of neural activation previously associated with satiety were not found, even after the higher-energy load. Lateral and medial orbitofrontal cortical activation was associated with consumption of the 400- and 1200-kcal meals, respectively. The medial orbitofrontal activation, however, was only found in those who had shown a large percentage change in fullness ratings following the higher-energy meal. CONCLUSION: We conclude that there is a dysfunction in the satiety system in those with PWS. These findings suggest that brain regions associated with satiety are insensitive even to high-energy food intake in those with the syndrome. This may be the neural basis of the hyperphagia seen in PWS.

Adult↗
PubMed2006

An investigation into food preferences and the neural basis of food-related incentive motivation in Prader-Willi syndrome.

BACKGROUND: Research into the excessive eating behaviour associated with Prader-Willi syndrome (PWS) to date has focused on homeostatic and behavioural investigations. The aim of this study was to examine the role of the reward system in such eating behaviour, in terms of both the pattern of food preferences and the neural substrates of incentive in the amygdala and orbitofrontal cortex (OFC). METHOD: Participants with PWS (n = 18) were given a food preference interview to examine food preferences and to inform the food-related incentive task to be conducted during the neuroimaging. Thirteen individuals with PWS took part in the positron emission tomography (PET) study, the design of which was based on a previous study of non-obese, non-PWS controls. For the task, participants were asked to consider photographs of food and to choose the food they would most like to eat in two conditions, one of high and one of low incentive foods, tailored to each participant's preferences. For comparison of the food preference data, 12 non-PWS individuals were given one part of the interview. RESULTS: Individuals with PWS expressed relative liking of different foods and showed preferences that were consistent over time, particularly for sweet foods. The participants with PWS did give the foods in the high incentive condition a significantly higher incentive value than the foods in the low incentive condition. However, activation of the amygdala and medial OFC was not associated with the prospect of highly valued foods as predicted in those with PWS. CONCLUSIONS: It would appear that incentive motivation alone plays a less powerful role in individuals with PWS than in those without the syndrome. This is likely to be due to the overriding intrinsic drive to eat because of a lack of satiety in those with PWS, and the impact of this on activity in the incentive processing regions of the brain. Activity in such reward areas may not then function to guide behaviour selectively towards the consumption of high preference foods.

Adolescent↗
PubMed2006

CD36 expression and its relationship with obesity in blood cells from people with and without Prader-Willi syndrome.

Although Prader-Willi syndrome (PWS) has been linked to the loss of function of imprinted genes in 15q11q13, very little is known about the pathogenesis. Using quantitative real-time PCR, we have confirmed the previous observation of an abnormality of CD36 expression in cells with maternal uniparental disomy 15, obtained from a proband with mosaicism for PWS, by demonstrating reduced expression levels in blood cells from a series of non-mosaic probands with PWS. Furthermore, we have extended these observations to show that CD36 expression in a non-PWS population is inversely correlated with body mass index but that this correlation does not hold in PWS. CD36 which maps to 7q11.2 is the first gene outside the 15q11q13 region whose level of expression appears to be reduced in people with PWS. Low CD36 expression levels in PWS point to an abnormal control of lipid and glucose homeostasis which may explain the insatiable hunger in these patients.

Adult↗
PubMed2006

Understanding of basic financial concepts among adults with mild learning disabilities.

OBJECTIVE: In the context of recent legal and social policy developments, which encourage clinicians to support vulnerable adults in making their own financial decisions, we explored understanding of basic financial concepts among adults with mild learning disabilities. METHOD: Using the literature about typically developing children, five measures entailing identification and ordering tasks were devised and were used to examine understanding of quantity, numbers and money among 30 men and women using specialist clinical services (mean FSIQ = 61.80; SD=10.59). RESULTS: The concept of quantity was easier to understand than those of numbers and money, and task difficulties increased with the magnitudes involved. The different types of conceptual understanding were closely related. CONCLUSIONS: These measures may be useful for analysing difficulties in, and informing interventions to maximize, independent financial decision making.

Adolescent↗
PubMed2005

Capacity to make financial decisions among people with mild intellectual disabilities.

BACKGROUND: Although there has been growing recognition of the importance of enabling people with intellectual disabilities (ID) to be more directly involved in managing their own financial affairs, so far, little is known about this aspect of their decision- making. METHOD: Using vignettes and semi-structured interviews, the financial decision-making abilities of men and women with mild ID (n=30; mean FSIQ =61.80; SD=10.59) were compared with those of their counterparts in the 'general population' (n=16; mean FSIQ=101.56; SD=7.62) and 'very able' individuals (n=14; mean FSIQ=123.93; SD=7.60). RESULTS: Whilst the financial decision-making abilities of participants with ID were generally weaker than those of other participants, the differences were not discrete, and many individuals were judged to be able to make at least some personal financial decisions. For all three groups, understanding information relevant to the decision, and reasoning with it, were the hardest parts of the process. CONCLUSIONS: The findings support a functional approach to the assessment of financial decision-making for both legal and clinical purposes, but raise concerns about mental incapacity legislation and assessment.

Adolescent↗
PubMed2005

The relationships among three factors affecting the financial decision-making abilities of adults with mild intellectual disabilities.

BACKGROUND: Among adults with intellectual disabilities (IDs), there is a need not only to assess financial decision-making capacity, but also to understand how it can be maximized. Although increased financial independence is a goal for many people, it is essential that individuals' decision-making abilities are sufficient, and many factors may affect the development of such abilities. METHOD: As part of a wider project on financial decision-making, we analysed previous data from a group of 30 adults with mild IDs, identifying correlations among four variables: (i) financial decision-making abilities; (ii) intellectual ability; (iii) understanding of some basic concepts relevant to finance; and (iv) decision-making opportunities in everyday life. RESULTS: The analysis indicated a direct relationship between ID and basic financial understanding. Strong relationships of a potentially reciprocal nature were identified between basic financial understanding and everyday decision-making opportunities, and between such opportunities and financial decision-making abilities. CONCLUSIONS: The findings suggest that the role of intellectual ability in determining financial decision-making abilities is only indirect, and that access to both basic skills education and everyday decision-making opportunities is crucial for maximizing capacity. The implications of this are discussed.

Adolescent↗
PubMed2004

The modified CAMDEX informant interview is a valid and reliable tool for use in the diagnosis of dementia in adults with Down's syndrome.

BACKGROUND: Dementia because of Alzheimer's disease (AD) commonly affects older adults with Down's syndrome (DS). Methods are needed, with established concurrent and predictive validity, to facilitate the diagnostic assessment of dementia, when it is complicated by pre-existing intellectual disabilities (ID). We report on the reliability and validity of a modified version of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) informant interview, for use when assessing people with DS suspected as having dementia. METHODS: As part of a previous epidemiological study of older people with DS, the CAMDEX informant interview was used to determine the prevalence of dementia. The 74 people with DS included at that time (Time 1) had also completed the Cambridge Cognitive Examination (CAMCOG), the neuropsychological assessment from the CAMDEX schedule. Fifty-six were assessed again 6 years later (Time 2). Based on the CAMDEX informant interview, nine of the 74 at Time 1, and 11 of the 56 at Time 2, were found to meet clinical criteria for AD. Forty-one scored above floor on the CAMCOG at Time 1 and were included in the analysis of cognitive decline. Concurrent validity was established by comparing diagnosis at Time 2 with independent evidence of objective decline on cognitive tasks since Time 1. Predictive validity was established by examining how accurately diagnosis at Time 1 predicted both cognitive decline and future diagnosis. Inter-rater reliability was determined by comparing the level of agreement between two raters. RESULTS: CAMDEX-based diagnosis of AD was shown to be consistent with objectively observed cognitive decline (good concurrent validity) and to be a good predictor of future diagnosis. Although numbers are small, some support is also provided for the accuracy with which diagnosis predicts cognitive decline. Inter-rater reliability was good with Kappa > 0.8 for 91% of items and > 0.6 for all items. CONCLUSIONS: The use of the modified CAMDEX informant interview enables the structured collection of diagnostic information, so that a valid and a reliable diagnosis of dementia can be made in those with pre-existing ID, using established diagnostic criteria.

Adult↗
PubMed2003

Behavioural phenotypes associated with specific genetic disorders: evidence from a population-based study of people with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder resulting in obesity, short stature, cryptorchidism, learning disabilities (mental retardation) and severe neonatal hypotonia. Associated with the syndrome are a number of behaviours that are sufficiently distinctive that the syndrome is considered to have a specific 'behavioural phenotype'. METHODS: Through multiple sources we attempted to identify all people with PWS living in one region in the U K. This cohort was augmented by people with PWS from other regions, and a contrast group of people with learning disabilities of varied aetiologies. The main carers were interviewed, using structured and semi-structured interview schedules, to establish the presence and severity of specific behaviours, and PWS diagnostic criteria. The intellectual functioning and attainments of all were determined. Blood samples were obtained for genetic diagnosis from all consenting participants. RESULTS: Although excessive eating was recognized as a potentially severe problem in those with PWS, it was almost universally controlled by food restriction, and therefore not seen as a 'problem behaviour'. Those with PWS differed from a learning disabled group of other aetiologies in the prevalence rates of skin picking, temper tantrums, compulsive behaviours and mood fluctuations, and also in the profile of their adaptive behaviours. CONCLUSIONS: The study confirms the distinct behavioural phenotype of PWS. Specific behaviours occurred significantly more frequently in PWS, compared with an age and BMI matched learning disabled comparison group. A factor analysis of the behaviours involved resulted in three factors that we hypothesized to be independent, and to arise from different mechanisms.

Adaptation, Psychological↗
PubMed2002

Prevalence of, and risk factors for, physical ill-health in people with Prader-Willi syndrome: a population-based study.

The medical findings from a population-based study of Prader-Willi syndrome (PWS) are discussed (in which birth incidence of PWS was estimated at 1:22,000 and death rate at over 3% per annum). In this study the prevalence of specific medical disorders that might account for a shortened life expectancy were investigated. Of all people with a possible diagnosis of PWS, only those meeting clinical criteria and/or with a confirmed genetic diagnosis were included in the study. Sixty-six individuals, 40 males and 26 females with a mean age of 19 years (range of 0 to 46 years) agreed to participate in the population-based study group. A prevalence rate of 25% for non-insulin dependent diabetes mellitus (NIDDM) was found in adults. Mean age at onset was 20 years. Those with NIDDM had a higher past maximum body weight and a greater likelihood of positive family history. Nearly 50% across the age groups reported a history of recurrent respiratory infections. High rates of fractures (29%), leg ulceration (22% in adults), sleep disorders (20%), and severe scoliosis (15% in childhood) were also reported. It is postulated that hypotonia is a possible contributory factor to the risk of strabismus, scoliosis, and respiratory infections. Other causes of morbidity, in particular the high rates of NIDDM, may be due to a failure to manage over-eating resulting in severe obesity. Early diagnosis and clear guidance to families about these risks and how they might be prevented is recommended. It is hypothesized that the high pain threshold may result in the presence of some illness not being apparent.

Adolescent↗
PubMed2002

Changes in appetite, food preference, and eating habits in frontotemporal dementia and Alzheimer's disease.

BACKGROUND: Despite numerous reports of changes in satiety, food preference, and eating habits in patients with frontotemporal dementia, there have been few systematic studies. OBJECTIVES: To investigate the frequency of changes in eating behaviours and the sequence of development of eating behaviours in frontotemporal dementia and Alzheimer's disease, using a caregiver questionnaire. METHODS: Three groups of patients were studied: frontal variant frontotemporal dementia (fv-FTD) (n = 23), semantic dementia (n = 25), and Alzheimer's disease (n = 43). Level of education and dementia severity was similar in the three groups. The questionnaire consisted of 36 questions investigating five domains: swallowing problems, appetite change, food preference, eating habits, and other oral behaviours. RESULTS: The frequencies of symptoms in all five domains, except swallowing problems, were higher in fv-FTD than in Alzheimer's disease, and changes in food preference and eating habits were greater in semantic dementia than in Alzheimer's disease. In semantic dementia, the developmental pattern was very clear: a change in food preference developed initially, followed by appetite increase and altered eating habits, other oral behaviours, and finally swallowing problems. In fv-FTD, the first symptom was altered eating habits or appetite increase. In Alzheimer's disease, the pattern was not clear although swallowing problems developed in relatively early stages. CONCLUSIONS: Change in eating behaviour was significantly more common in both of the frontotemporal dementia groups than in Alzheimer's disease. It is likely that the changing in eating behaviours reflects the involvement of a common network in both variants of frontotemporal dementia-namely, the ventral (orbitobasal) frontal lobe, temporal pole, and amygdala.

Aged↗
PubMed2001

Urethral trauma in children.

We report our 12-year experience in the management of urethral injuries in nine children, six boys and three girls. The most common mechanisms of injury were motor vehicle accidents, followed by straddle injuries. All the injuries in boys involved the anterior urethra, and in girls the proximal or mid-urethra. There were associated injuries in five, including three pelvic fractures. All children were investigated with a retrograde urethrogram. Four were treated non-operatively with insertion of a urethral catheter. Of the remaining five, one had drainage of a penile haematoma, one cystourethroscopy, two insertion of urinary and suprapubic catheters, and one open cystotomy and passage of a guide wire with antegrade passage of a urethral catheter. Complications included one urinary tract infection, one urethral fistula, one urethrovaginal fistula, and two urethral strictures. Final outcome was satisfactory in all nine children.

Adolescent↗
PubMed2001

HOSE: an objective scoring system for evaluating the results of hypospadias surgery.

OBJECTIVE: To determine the accuracy and utility of a scoring system designed to allow an objective appraisal of the outcome of hypospadias repair, based on evaluating meatal location, meatal shape, urinary stream, straightness of erection, and the presence and complexity of any complicating urethral fistula. PATIENTS AND METHODS: Twenty patients (median age 23 months) were randomly selected and reviewed at a median of 8.9 months after their hypospadias repair. Two paediatric surgeons, a nurse and one of the child's parents independently assessed each patient using the "hypospadias objective scoring evaluation" (HOSE) system. The results were collated and the level of interobserver variation assessed using the weighted kappa test. RESULTS: The mean weighted kappa was 0.66, indicating good agreement among observers. The level of agreement was highest between surgeon and nurse at 0.70, but remained good between surgeon and parent, at 0.65. CONCLUSIONS: Interobserver variation using the HOSE system was minimal, supporting its use as an objective outcome measure after hypospadias surgery, and facilitating an impartial evaluation of operations used in correcting hypospadias.

Child↗
PubMed2001

Noncervicofacial atypical mycobacterial lymphadenitis in childhood.

BACKGROUND/PURPOSE: Atypical mycobacterial (AM) lymphadenitis is common in children but rarely occurs outside the cervicofacial region. The authors report their experience in the diagnosis and management of noncervicofacial AM lymphadenitis. METHODS: A retrospective review was conducted of cases diagnosed at our institution between January 1976 and December 1999, based on positive culture of atypical mycobacteria or consistent histology with supportive skin testing. RESULTS: Thirty-seven patients were identified over the 23-year review period. The median age was 4.3 years (range, 8 months to 13 years and 5 months), with 19 boys and 17 girls. The median duration of symptoms was 4 weeks, and the most commonly affected sites were the inguinal region (n = 17), axilla (n = 8), and lower limb (n = 6). Preceding local trauma was described in 10 patients and a viral illness in 4. Laboratory culture for atypical mycobacteria was positive in 22, and skin testing suggestive in 21 and equivocal in 2. Treatment was by excision in 28 and drainage with or without curettage in 9. At a median follow-up of 19.7 months, disease had recurred in 4 patients, none of whom had been treated initially by excision. CONCLUSIONS: Atypical mycobacterial infection is an uncommon cause of noncervicofacial lymphadenitis in children. It typically presents with a 4-week history of painless regional lymphadenopathy that may follow penetrating trauma. If untreated, the overlying skin becomes involved with a violaceous discoloration, and ulceration may occur. Definitive treatment involves complete surgical excision, preferably before suppuration extending beyond the involved lymph nodes.

Age Distribution↗
PubMed2001

Facial fractures in children.

OBJECTIVE: To determine the pattern of injury of facial fractures in children, the relative contribution of plain radiography and CT scanning in the diagnosis of these injuries, and factors leading to delayed diagnosis. DESIGN: Retrospective case note review. PARTICIPANTS: All children with facial fractures identified using the trauma and medical record databases at our institution. RESULTS: Forty-six children with 59 facial fractures presented over a 4-year, 2-month period from November 1995 to December 1999. The median age was 10 years, with a range from 1 to 14. There was a 2-to-1 male-to-female sex ratio. A motor vehicle accident (MVA) involving a child as passenger, pedestrian, or cyclist accounted for 63% of cases. In seven of these, the child was either a front seat passenger or inappropriately restrained for their age and size. In all but one case, the presence of a fracture was associated with an overlying laceration, abrasion, or significant soft tissue edema. Initial examination and plain radiologic assessment by a pediatric clinician led to diagnostic delay in nine children. Facial CT was performed in 38 children, and all results were positive. Twenty-six patients required operative intervention for their facial fracture. Associated injuries, particularly of the head and limbs, were present in all but six patients. CONCLUSIONS: Facial fractures were uncommon overall but occurred more frequently in children with major trauma. Plain facial radiographs provided limited additional diagnostic information to careful clinical examination and often fail to detect or clearly define a facial fracture in children. In the correct clinical setting, a facial CT scan allows accurate diagnosis of the injury and can reveal previously unsuspected additional fractures.

Accidents, Traffic↗
PubMed2000

Driveway motor vehicle injuries in children.

OBJECTIVES: To describe the frequency, nature and outcome of driveway injuries in children. DESIGN: Retrospective case series of driveway-related injuries in children under 16 years of age admitted to the New Children's Hospital (NCH), New South Wales, from November 1995 to February 2000, and deaths reported to the New South Wales Paediatric Trauma Death (NPTD) Registry from January 1988 to December 1999. MAIN OUTCOME MEASURES: Circumstances of injury; type and number of injuries identified. RESULTS: 42 children were admitted to our institution with driveway-related injuries over four years and four months. These represent 12% of all children admitted with pedestrian motor vehicle injuries. Fourteen deaths (including one of the children admitted to NCH) were reported to the NPTD Registry over 12 years, accounting for 8% of all paediatric pedestrian motor vehicle deaths reported to the registry. Typically, the injury involved a parent or relative reversing a motor vehicle in the home driveway over a toddler or preschool-age child in the late afternoon or early evening. Four-wheel-drive or light commercial vehicles were involved in 42% of all injuries, although they accounted for just 30.4% of registered vehicles in NSW. These vehicles were associated with a 2.5-times increased risk of fatality. In 13 of the 14 deaths, the cause was a severe head injury not amenable to medical intervention. CONCLUSIONS: Driveway injuries in children account for a significant proportion of paediatric pedestrian motor vehicle injuries and deaths in NSW. Prevention represents the only effective approach to reducing deaths from this cause.

Accidents, Home↗