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Biomedical subjects

L Wing

Publications and source records attributed to L Wing.

At least 19 recordsLinked to original sources
PubMed2001

A clinical inflammatory syndrome attributable to aerosolized lipid-DNA administration in cystic fibrosis.

Immunologic reactivity to lipid-DNA conjugates has traditionally been viewed as less of an issue than with viral vectors. We performed a dose escalation safety trial of aerosolized cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to the lower airways of eight adult cystic fibrosis patients, and monitored expression by RT-PCR. The cDNA was complexed to a cationic lipid amphiphile (GL-67) consisting of a cholesterol anchor linked to a spermine head group. CFTR transgene was detected in three patients at 2-7 days after gene administration. Four of the eight patients developed a pronounced clinical syndrome of fever (maximum of 103.3EF), myalgias, and arthralgia beginning within 6 hr of gene administration. Serum IL-6 but not levels of IL-8, IL-1, TNF-alpha, or IFN-gamma became elevated within 1-3 hr of gene administration. No antibodies to the cationic liposome or plasmid DNA were detected. We found that plasmid DNA by itself elicited minimal proliferation of peripheral blood mononuclear cells taken from study patients, but led to brisk immune cell proliferation when complexed to a cationic lipid. Lipid and DNA were synergistic in causing this response. Cellular proliferation was also seen with eukaryotic DNA, suggesting that at least part of the immunologic response to lipid-DNA conjugates is independent of unmethylated (E. coli-derived) CpG sequences that have previously been associated with innate inflammatory changes in the lung.

Administration, Inhalation↗
PubMed2001

Country report: Australia.

The last 10 years has been an interesting time for Australian medical education despite reduced funding. WORKFORCE: There are five main workforce trends: a rural/urban maldistribution, a need for more specialists, public hospital staffing difficulties, increasing female practitioners and under-representation of indigenous practitioners. ISSUES FACING THE DEANS: Lack of resources is a problem facing Deans, with pressure for clinical service in teaching hospitals. Entrepreneurial activities have been undertaken including the enrollment of overseas students. Medical schools have also responded to important government initiatives. DEVELOPMENTS IN MEDICAL EDUCATION: Australia's 11 medical schools have undergone significant reform in the last decade. There is a mix of four (graduate), five and six year courses. AUSTRALIA'S NEW MEDICAL SCHOOL: James Cook University opened the first medical school in northern Australia in 2000. The School admits students from rural, northern Australian and indigenous backgrounds. It has a strong regional mission. RURAL AND COMMUNITY-BASED EDUCATION: Government funding to address the maldistribution of the workforce has led to the establishment of rural clubs, Departments of Rural Health and community-based programs. THE FIRST TWO POSTGRADUATE YEARS: There have been recent moves to improve education in the two years following graduation. This includes the initiation of national projects in curriculum and assessment. POSTGRADUATE AND CONTINUING MEDICAL EDUCATION: Postgraduate programs in Australia are being reformed to build on the changes in undergraduate education. CME is also under review. CONCLUSION: Australian medical educators should build on the recent reforms and take on some of the new directions in medical education.

Australia↗
PubMed2001

Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis.

Here we report the effects of gentamicin treatment on cystic fibrosis transmembrane regulator (CFTR) production and function in CF airway cells and patients with CF with premature stop mutations. Using immunocytochemical and functional [6-methoxy-N- (3-sulfopropyl) quinolinium (SPQ)-based] techniques, ex vivo exposure of airway cells from stop mutation CF patients led to the identification of surface-localized CFTR in a dose-dependent fashion. Next, five patients with CF with stop mutations and five CF control subjects were treated with parenteral gentamicin for 1 wk, and underwent repeated in vivo measures of CFTR function (nasal potential difference [PD] measurements and sweat chloride [Cl(-)] testing). During the treatment period, the number of nasal PD readings in the direction of Cl(-) secretion was increased approximately 3-fold in the stop mutation patient group compared with controls (p < 0.001), and four of five stop mutation patients with CF had at least one reading during gentamicin treatment with a Cl(-) secretory response of more than -5 mV (hyperpolarized). A response of this magnitude was not seen in any of the CF control subjects (p < 0.05). In an independent series of experiments designed to test the ability of repeat nasal PDs to detect wild-type CFTR function, evidence of Cl(-) secretion was seen in 88% of control (non-CF) nasal PDs, and 71% were more than -5 mV hyperpolarized. Together, these results suggest that gentamicin treatment can suppress premature stop mutations in airway cells from patients with CF, and produce small increases in CFTR Cl(-) conductance (as measured by the nasal PD) in vivo.

Adolescent↗
PubMed2000

Changes in skills for people with intellectual disability: a follow-up of the Camberwell Cohort.

The skills of a total population of children with severe intellectual disability and/or autism from Camberwell, South London, UK, and the initial follow-up data, taken when the subjects were adolescents and young adults (Shah 1986), are described in the present study. Changes in skills over time are presented within the categories of communication, self-care, and educational and cognitive skills, as assessed by the Handicaps, Behaviours and Skills schedule. The results indicated that skills had improved in many areas between times 1 and 2, but that this improvement was more noticeable for the children who had been youngest at time 1. The implications of these results and predictions for a further follow-up study are discussed.

Adolescent↗
PubMed2000

Catatonia in autistic spectrum disorders.

BACKGROUND: The clinical pictures of autistic spectrum disorders include features described in catatonia. AIMS: To examine the severe exacerbation of the catatonic features of autistic disorders in adolescence or early adult life, which occurs in some individuals. METHOD: A semi-structured interview schedule was used to collect information from parents or other care-givers concerning 506 referrals to a specialist clinic for autistic spectrum disorders. Individuals with severe exacerbation of catatonic features were compared with a same-age group of referrals without this type of deterioration in skills and behaviour. RESULTS: Seventeen per cent of referrals aged 15 or over had severe exacerbation of catatonic features. They were significantly more likely than the comparison group to have had, before the onset of the change in behaviour, impaired language and passivity in social interaction. CONCLUSIONS: Catatonia is a later complication of autistic spectrum disorders, which adds considerably to the burden of caring. More research is needed to identify causes, neuropathology, and early signs of vulnerability.

Activities of Daily Living↗
PubMed1999

A screening questionnaire for Asperger syndrome and other high-functioning autism spectrum disorders in school age children.

The high-functioning Autism Spectrum Screening Questionnaire (ASSQ) is a 27-item checklist for completion by lay informants when assessing symptoms characteristic of Asperger syndrome and other high-functioning autism spectrum disorders in children and adolescents with normal intelligence or mild mental retardation. Data for parent and teacher ratings in a clinical sample are presented along with various measures of reliability and validity. Optimal cutoff scores were estimated, using Receiver Operating Characteristic analysis. Findings indicate that the ASSQ is a useful brief screening device for the identification of autism spectrum disorders in clinical settings.

Adolescent↗
PubMed1999

Autism: not an extremely rare disorder.

OBJECTIVE: To study autism over time in order to ascertain whether there has been an increase in its prevalence in recent years. METHOD: All English language papers on the prevalence of autism were reviewed. Ten of the studies retrieved were not used in the final analysis because they did not meet full criteria for inclusion in the review. The remaining 20 studies, published between 1966 and 1997, were subdivided into US studies (n=2) and non-US studies (n=18), and the latter group was subdivided into four 8-year periods. RESULTS: The early studies yielded prevalence rates of under 0.5 in 1000 children, whereas the later ones showed a mean rate of about 1 in 1000. There was a marked difference in prevalence rates between those studies that included some children born before 1970 (low rates) and those that included only children born in 1970 and after (high rates). This is probably due to the lower rates obtained by use of criteria strictly based on Kanner's description of his syndrome. The US studies reported atypically low rates. There was a highly significant estimated increase with calendar year in the non-US studies (3.8% per year). CONCLUSION: It is concluded that autism is considerably more common than was previously believed. The possible reasons for the higher reported rates are discussed.

Adolescent↗
PubMed1999

Control and cardiovascular risk factors of hypertension. An assessment of a sample of patients.

OBJECTIVES: To monitor the documentation of blood pressure measurements and other cardiovascular risk factors in general practice patients with hypertension. METHOD: Twenty-five case notes of patients diagnosed as hypertensive were randomly selected from each of 58 participating general practitioners in suburban general practice in Adelaide, South Australia and were monitored by two registered nurses. MAIN OUTCOME MEASURES: to assess whether blood pressure readings, weight, smoking history, alcohol intake and family history were documented, and whether electrocardiogram, plasma lipids, urinalysis and biochemical screen (which includes blood urea nitrogen, creatinine, glucose, electrolytes and uric acid) had been undertaken. RESULTS: Data from 1446 hypertensive patients showed that for the last three blood pressure values recorded, 483 (33%) had an average level of 140/90 mm Hg or less and 1100 (76%) had an average of 160/95 mm Hg or less. The other cardiovascular risk factors selected were variably recorded, with biochemical screen being most commonly recorded [1198 (83%)] and family history [423 (29%)] the least. CONCLUSIONS: Inadequacies in the control of hypertension and in the documentation of other cardiovascular risk factors suggest that further educational initiatives are required in this common chronic illness.

Adult↗
PubMed1998

Delayed language onset as a predictor of clinical symptoms in pervasive developmental disorders.

DSM-IV states that Asperger Disorder may be distinguished from Autistic Disorder by a lack of a delay in early language development. The aim of this study was to establish whether the presence or absence of early language delay would predict autistic symptomatology in children diagnosed with a PDD/autism spectrum disorder. Forty-six language-delayed and 62 normal language onset individuals (M age 11 years) were compared on ICD-10 research criteria and DSM-IV criteria, receptive language, and developmental history variables. Retrospective data were also obtained to determine whether language onset predicted autism symptomatology when young (< 6 years). We found that early language delay predicts more autistic symptomatology when young, but not at an older age. Early language delay is also associated with developmental motor milestone delays and lower receptive language abilities. The results question the use of early language delay as a valid discriminating variable between PDD subgroups.

Adolescent↗
PubMed1998

Are there subgroups within the autistic spectrum? A cluster analysis of a group of children with autistic spectrum disorders.

Comprehensive data on the developmental history and current behaviours of a large sample of high-functioning individuals with diagnoses of autism, Asperger's syndrome, or other related disorder were collected via parent interviews. This provided the basis for a taxonomic analysis to search for subgroups. Most participants also completed theory of mind tasks. Three clusters or subgroups were obtained; these differed on theory of mind performance and on verbal abilities. Although subgroups were identified which bore some relationship to clinical differentiation of autistic, Asperger syndrome, and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) cases, the nature of the differences between them appeared strongly related to ability variables. Examination of the kinds of behaviours that differentiated the groups suggested that a spectrum of autistic disorders on which children differ primarily in term of degrees of social and cognitive impairments could explain the findings.

Adolescent↗
PubMed1997

The addition of mibefradil to chronic hydrochlorothiazide therapy in hypertensive patients is associated with a significant antihypertensive effect.

OBJECTIVE: To evaluate the antihypertensive efficacy, tolerability, safety, and dose-response characteristics of the novel calcium antagonist, mibefradil, in combination with a diuretic regimen. DESIGN: A multinational, double-blind, randomised, placebo-controlled, parallel-design trial. METHODS: Three hundred and seven patients whose mild-to-moderate essential hypertension remained uncontrolled after 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg/day and placebo were randomised to receive combined treatment with HCTZ and once-daily doses of 12.5, 25, 50, or 100 mg of mibefradil or placebo. After 8 weeks of combined treatment, HCTZ was withdrawn and the mibefradil groups continued on their respective doses for an additional 6 weeks. RESULTS: After 8 weeks, the addition of once-daily doses of mibefradil to the initial HCTZ regimen resulted in clinically relevant, dose-related reductions in sitting diastolic blood pressure (SDBP) and sitting systolic blood pressure (SSBP) at trough, which were significantly greater in the 50 and 100 mg dose groups compared to the placebo group (P < or = 0.003). Placebo-corrected treatment effects on SDBP and SSBP at the end of the combined treatment period relative to baseline were, respectively, -4.1 and -8.0 mm Hg in the 50 mg mibefradil group and -9.5 and -8.0 mm Hg in the 100 mg mibefradil group. Therapeutic response rates to combination mibefradil and HCTZ therapy were high and dose related, reaching 82% for SDBP in the 100 mg group. CONCLUSIONS: The addition of once-daily doses of 50 or 100 mg of mibefradil to patients whose hypertension is not controlled by HCTZ alone is well tolerated and effective in improving BP control.

Adult↗
PubMed1996

Diagnosis and classification in autism.

This study compared four systems for the diagnosis of autism (DSM-III, DSM-III-R, DSM-IV, and ICD-10) with two empirically derived taxa of autism, and with three social subgroups of autism (Aloof, Passive, and Active-but-Odd) in 194 preschool children with salient social impairment. There were significant behavior and IQ differences between autistic and other-PDD groups for all four diagnostic systems, and a significant association was found (a) for Taxon B, diagnoses of autism, and the Aloof subgroup, and (b) for Taxon A, other-PDD, and the Active-but-Odd subgroup. Findings offer support for two major overlapping continua within idiopathic Pervasive Developmental Disorder.

Algorithms↗
PubMed1996

Comparison of clinical symptoms in autism and Asperger's disorder.

OBJECTIVE: To determine what clinical symptoms clinicians have been using to distinguish between Asperger's disorder (AsD) and autistic disorder (AD). METHOD: Parents of children and adolescents with high-functioning AD (n = 48) and AsD (n = 69) were given a structured interview based on DSM-III-R and ICD-10 diagnostic criteria. Information regarding early and current symptom presentation and family, developmental, and verbal mental age information were collected. Logistic regression analyses were conducted to determine which variables best predicted clinician's diagnosis. RESULTS: A number of clinical variables predicted diagnosis. Delayed language onset was the only variable of the family and developmental variables that predicted diagnosis. The AsD group was also significantly higher than the AD group in verbal mental age. CONCLUSION: Clinicians appear to be diagnosing AsD and AD on the basis of published research and case study accounts. The findings question whether DSM-IV and ICD-10 criteria adequately describe the AsD individual, particularly in the communication domain.

Adolescent↗
PubMed1996

An audit of third generation cephalosporin prescribing in a tertiary care hospital.

BACKGROUND: There is increasing resistance to commonly used antibiotics, including third generation cephalosporins, and an increasing cost burden. AIMS: To assess the appropriateness of prescribing of third generation cephalosporin antibiotics in a tertiary teaching hospital. METHODS: Prescriptions of third generation cephalosporins (ceftriaxone, cefotaxime and ceftazidime) to inpatients were identified prospectively by the Hospital Pharmacy Department for a six week period during May-June 1994. Clinical data and indications were obtained from patient records and, when necessary, by interviewing the prescriber and by patient assessment. Criteria for appropriate prescribing were according to nationally accepted criteria outlined in the 1994-95 Antibiotic Guidelines handbook. All inpatients who were prescribed a third generation cephalosporin at Flinders Medical Centre for the duration of the audit period were eligible. This included medical, surgical, paediatric, obstetric and gynaecology inpatients. RESULTS: Sixty-five per cent of prescriptions for third generation cephalosporins were judged appropriate, 31% inappropriate and 4% doubtful. Inappropriate use was found particularly in the treatment of respiratory tract infections and abdominal sepsis, and in surgical prophylactic use. CONCLUSION: Third generation cephalosporin prescribing in a tertiary care teaching hospital is frequently inappropriate, as judged against widely available Australian guidelines.

Adult↗
PubMed1996

Management of isolated systolic hypertension.

Isolated systolic hypertension (ISH) [systolic blood pressure (SBP) > or = l60mm Hg with diastolic blood pressure (DBP) <90mm Hg] is the commonest form of hypertension in the elderly, and accounts for about 60% of all hypertensive conditions in the population aged over 65 years. It is associated with a significantly increased risk of cardiovascular and cerebrovascular morbidity and mortality. The landmark Systolic Hypertension in the Elderly Program (SHEP) study, published in 1991, has shown that lowering the SBP in elderly patients with ISH results in a significant reduction in cardiovascular events. These results have had a major impact on clinical practice in hypertension. On theoretical grounds, considering the pathophysiological mechanisms of ISH in the elderly, any drug which lowers total peripheral resistance and/or arterial stiffness should reduce SBP effectively in these patients. This effect has been observed in outcome studies and short term clinical trials using a variety of drugs from the 4 major antihypertensive classes: diuretics, beta(1)-blockers, calcium channel antagonists and ACE inhibitors. Other drugs, including alpha antagonists, may also be effective. In general, there is compelling evidence to support active treatment of any individual with an SBP > or = 160mm Hg. As in essential hypertension, the maximum benefit is gained by aggressive treatment of those individuals at highest risk because of coexisting cardiovascular risk factors. In these people, an SBP of 140 to 159mm Hg should be considered to be an indication for active management. Initial management should be by manipulation of lifestyle factors such as bodyweight, salt and alcohol intake and aerobic exercise. Drug therapy, generally well tolerated in low doses, should be considered if SBP remains > or = 160mm Hg, or > or = 140mm Hg in the presence of multiple risk factors. The choice of initial drug therapy should be influenced by the particular clinical situation. If there are no coexisting contraindications or co-indications for particular drugs, it is reasonable to begin treatment with a low dose of a thiazide-like diuretic, as used in the SHEP study. However, in short term treatment trials calcium channel antagonists and ACE inhibitors have been shown to lower SBP effectively and can be used in the appropriate clinical context. Beta-blockers appear to be less effective as monotherapy in ISH. Combination therapy is frequently required and can be effective and well tolerated if carefully chosen.

Antihypertensive Agents↗