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Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 361 records · Page 20Linked to original sources
PubMed1994

Prevalence and risk factors for retinopathy in adolescents with type 1 diabetes.

OBJECTIVES: To establish the prevalence of, and risk factors associated with, diabetic retinopathy in an Australian adolescent diabetes clinic population. DESIGN: A prospective longitudinal study; baseline findings. PATIENTS: Two hundred and fifty-five patients with Type 1 (insulin-dependent) diabetes mellitus assessed by our service were studied. Entry criteria were: age 11.0-19.9 years; diabetes duration of at least two years; and gradable fundus photographs of at least one eye. MAIN OUTCOME MEASURES: The presence and severity of retinopathy, as assessed by the grading of stereoscopic fundus photographs. Possible risk factors assessed were age, sex, diabetes duration, pubertal stage, blood pressure, glycaemic control and total cholesterol level. RESULTS: The prevalence of retinopathy was 42%; all of those affected had mild background retinopathy. Highly significant associations were found with glycaemic control and both total and prepubertal duration of diabetes. No associations were found with age, sex, pubertal stage, blood pressure or total cholesterol level. CONCLUSIONS: The high prevalence of early diabetic retinopathy in this group of Australian adolescents is comparable to recent reports from other centres. The significant associations with glycaemic control and duration of diabetes provide further strong evidence for the benefit of optimal glycaemic control during adolescence. Our finding that the prepubertal years of diabetes contribute to the development of retinopathy suggests that glycaemic control before puberty should also be optimised. The planned follow-up of this cohort will establish the risk of progression to vision-threatening retinopathy and allow risk factors to be further evaluated.

Adolescent↗
PubMed1994

The POP1 gene encodes a protein component common to the RNase MRP and RNase P ribonucleoproteins.

Two forms of the yeast 5.8S rRNA are generated from a large precursor by distinct processing pathways. Cleavage at site A3 is required for synthesis of the major, short form, designated 5.8S(S), but not for synthesis of the long form, 5.8S(L). To identify components required for A3 cleavage, a bank of temperature-sensitive lethal mutants was screened for those with a reduced ratio of 5.8S(S):5.8S(L). The pop1-1 mutation (for processing of precursor RNAs) shows this phenotype and also inhibits A3 cleavage. The pre-rRNA processing defect of pop1-1 strains is similar to that reported for mutations in the RNA component of RNase MRP; we show that a mutation in the RNase MRP RNA also inhibits cleavage at site A3. This is the first site shown to require RNase MRP for cleavage in vivo. The pop1-1 mutation also leads to a block in the processing of pre-tRNA that is identical to that reported for mutations in the RNA component of RNase P. The RNA components of both RNase MRP and RNase P are underaccumulated in pop1-1 strains at the nonpermissive temperature, and immunoprecipitation demonstrates that POP1p is a component of both ribonucleoproteins. The POP1 gene encodes a protein with a predicted molecular mass of 100.5 kD and is essential for viability. POP1p is the first protein component of the nuclear RNase P or RNase MRP for which the gene has been cloned.

Amino Acid Sequence↗
PubMed1994

The decoding region of 16S RNA; a cross-linking study of the ribosomal A, P and E sites using tRNA derivatized at position 32 in the anticodon loop.

A photo-reactive diazirine derivative was attached to the 2-thiocytidine residue at position 32 of tRNA(Arg)I from Escherichia coli. This modified tRNA was bound under suitable conditions to the A, P or E site of E.coli ribosomes. After photo-activation of the diazirine label, the sites of cross-linking to 16S rRNA were identified by our standard procedures. Each of the three tRNA binding sites showed a characteristic pattern of cross-linking. From tRNA at the A site, a major cross-link was observed to position 1378 of the 16S RNA, and a minor one to position 936. From the P site, there were major cross-links to positions 693 and to 957 and/or 966, as well as a minor cross-link to position 1338. The E site bound tRNA showed major cross-links to position 693 (identical to that from the P site) and to positions 1376/1378 (similar, but not identical, to the cross-link observed from the A site). Immunological analysis of the concomitantly cross-linked ribosomal proteins indicated that S7 was the major target of cross-linking from all three tRNA sites, with S11 as a minor product. The results are discussed in terms of the overall topography of the decoding region of the 30S ribosomal subunit.

Anticodon↗
PubMed1994

Exclusion of close linkage of bipolar disorder to the Gs-alpha subunit gene in nine Australian pedigrees.

Growing evidence suggests that guanine nucleotide binding proteins (G proteins) may be involved in both the pathogenesis and treatment of bipolar affective disorder. Both overactive G proteins and increased levels of the alpha subunit of the stimulatory form (Gs-alpha) have been demonstrated in peripheral leucocytes of manic patients while an increase of Gs-alpha subunit levels has also been found in a postmortem study of bipolar disorder. The function of Gs and Gi alpha subunits has now been shown to be affected by lithium. The present study aimed to determine whether bipolar affective disorder was linked to the Gs-alpha subunit gene which has been mapped to chromosomal region 20q13.2. Linkage analysis utilized the PCR amplification of a portion of the Gs-alpha gene that contains a dinucleotide repeat (CA repeat) polymorphism. Linkage of bipolar disorder and recurrent depression to the Gs-alpha subunit gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective illness. Close linkage to the Gs-alpha subunit gene was strongly excluded using each model and definition. Thus, our study indicates that a genetic defect in the Gs-alpha subunit gene is unlikely to be the cause of bipolar disorder.

Adolescent↗
PubMed1994

A brief self-report depression measure assessing mood state and social impairment.

Many measures of depression severity appear confounded by including depressive sub-typing features. We report the design of a brief (11 item) self-report scale of depression severity (the AUSSI), assessing both mood state and social impairment domains, and designed to be independent of sub-typing features. Mood severity and functional impairment scores demonstrated some independence in a sample of 360 patients. Patients with a 'melancholic' depressive type (categorised by four differing systems) differed from residual 'non-melancholic' depressed patients by having higher impairment scores, but the assigned groups did not differ, in the main, by mood severity scores. Advantages of the measure are summarised.

Affect↗
PubMed1994

Nutritional risk in New England elders.

BACKGROUND: To better define nutritional risk among older Americans, a cross-sectional study of nutrition and health status was carried out in a probability sample of 1,156 free-living elders, 70 years and older, from 67 communities representing urban and rural areas of the six New England states. METHOD: All participants completed telephone interviews concerning demographic and health characteristics. A subsample of 1,156 individuals underwent in-home assessments of oral health, anthropometrics, and nutritional risk, including a 24-hour dietary recall. RESULTS: Nutrition-related problems were common and diverse among New England elders. Some 41.5% were overweight (BMI > 27 kg/m2), and mean dietary lipid intakes were considerably above recommended levels (Healthy People 2000 (National Health Promotion and Disease Prevention Objectives). Some 16% were underweight (BMI < 22 kg/m2), mean dietary calcium levels were low, and about 28% of older individuals failed to consume adequate levels (> 75% the Recommended Dietary Allowance for persons 51 years and older) for three or more key nutrients. Persons of advanced age or who smoked were more likely to have high dietary lipid intakes or less than adequate nutrient intake. Higher dietary lipid levels were also more common among men and individuals who lived with others. Low nutrient intake was more prevalent in those with lower educational attainment and dental problems. CONCLUSION: Nutrition policies and multidisciplinary interventions for older Americans need to emphasize the spectrum of nutritional problems in the elderly, including dietary excesses and potential nutrient deficiencies. The demographic and life-style characteristics that place older individuals at high nutritional risk need to be considered, particularly advanced age, gender, living situation, smoking, dietary behavior, educational attainment, and dental health.

Activities of Daily Living↗
PubMed1994

Defining melancholia: properties of a refined sign-based measure.

We hypothesised that psychomotor disturbance is specific to the melancholic subtype of depression and capable of defining melancholia more precisely than symptom-based criteria sets. We studied 413 depressed patients, and examined the utility of a refined, operationally driven set of clinician-rated signs, principally against a set of historically accepted symptoms of endogeneity. We specified items defining psychomotor disturbance generally as well as those weighted either to agitation or to retardation. We demonstrated the system's capacity to differentiate 'melancholic' and 'non-melancholic' depression (and the comparable success of DSM-III-R and Newcastle criteria systems) by reference to several patient, illness and treatment response variables, to an independent measure of psychomotor disturbance (reaction time) and to a biological marker (the dexamethasone suppression test).

Adult↗
PubMed1994

Patient satisfaction with a mood disorders unit: elements and components.

Patient satisfaction is an indicator of effective service provision and may influence compliance with treatment. Of 265 patients attending a specialised mood disorders unit and surveyed at least two years after their initial contact, 221 (83%) replied. Characteristics of responders and non-responders were compared on demographic and clinical information from index assessment and follow-up. Sixty-four percent of responders were very satisfied and 21% partly satisfied with their management. Components of satisfaction included perceived competence of clinical management; the unit's administrative and after-treatment accessibility; and the support of staff and other patients. Those with a more adequate personality and melancholic depression at baseline assessment were more satisfied. A low current mood state at time of survey was associated with lower satisfaction in non-melancholics only. There were interactions between improvement in condition, diagnosis, personality and satisfaction. The survey provided a framework for formulating treatment programmes and was a useful quality assurance tool.

Adolescent↗
PubMed1994

Treatment resistant depression in an Australian context. I: The utility of the term and approaches to management.

The concept of "treatment resistant depression" (TRD) has generally been defined in terms of failure to respond to a standard course of somatic therapy with little reference to diagnostic sub-types or relevant psychosocial factors. In this paper we examine problems with the use of the term "treatment resistant depression" and then outline an approach to TRD employed in an Australian mood disorders unit. After discussing the need for a biopsychosocial assessment, multimodal management strategies for melancholic and non-melancholic TRD patients are described.

Affective Disorders, Psychotic↗
PubMed1994

Treatment resistant depression in an Australian context. II: Outcome of a series of patients.

The clinical characteristics and treatment outcome of a series of 107 patients referred to a mood disorders unit with an episode of "treatment resistant" Major Depression are reviewed. Subjects were categorised by diagnosis (into melancholic and non-melancholic subtypes) and by adequacy of previous treatment. At subsequent review (mean period of 37.5 months) these patients were re-assessed both in terms of outcome and which treatments had been considered to be most effective. Forty one percent of the patient group were fully recovered and a further 43% were partially improved. Different treatments were considered effective for melancholic and non-melancholic sub-types.

Adult↗
PubMed1994

Combining lithium and sodium valproate for bipolar disorder.

We report two cases of severe bipolar disorder in which there was a dramatic response to the combination of lithium and sodium valproate. Both patients had failed to respond to the respective monotherapies. These cases suggest that the combination of lithium and sodium valproate may be more effective than each of these drugs used alone. There is a clear need for controlled outcome studies of the common clinical practice of combining lithium and the anticonvulsants.

Bipolar Disorder↗
PubMed1994

Cimetidine-induced myelosuppression after bone marrow transplantation.

A strong temporal correlation was observed between cessation of cimetidine and a sustained increase in blood counts in two marrow transplant recipients. Both were receiving cimetidine from the day of transplantation for prophylaxis of stress ulceration and gastritis. The blood counts of both patients were not increasing satisfactorily 5-6 weeks after marrow transplantation without any obvious cause of marrow suppression. A similar observation has been made with the use of ranitidine after marrow transplantation suggesting that histamine H2-receptor antagonists should be used very cautiously, if at all, in the setting of bone marrow transplantation.

Adolescent↗
PubMed1994

Fatal pneumococcal infections following allogeneic bone marrow transplant.

Six cases of fatal pneumococcal sepsis are described, occurring in the post-allograft setting, between 3 and 39 months after transplantation. Five of the six patients were suffering from chronic graft-versus-host disease and were receiving immunosuppressive therapy. Most were receiving prophylactic antibiotic therapy. This represents approximately 2% of the allograft population treated during the study period who survived for > 3 months after transplant. Pneumococcal sepsis is thus still a significant cause of death after allogeneic BMT and approaches to minimise its occurrence are discussed.

Acute Disease↗
PubMed1994

Graft failure after bone marrow transplantation from unrelated donors using busulphan and cyclophosphamide for conditioning.

Five patients received bone marrow allografts for leukaemia from serologically fully matched unrelated donors. The conditioning regimen was busulphan 16 mg/kg and cyclophosphamide (CY) 120 mg/kg. Engraftment was achieved in only two patients, with primary graft failure occurring in three patients. Two of the three patients with no evidence of myeloid engraftment on day 28 received GM-CSF without response. Both these patients required rescue with cryopreserved autologous material. Three patients remain alive, one died of relapse after a successful allograft and one died with pancytopenia. Although the number of patients is small, we conclude that the BuCY2 regimen with 120 mg/kg CY, while adequate for sibling allografts, may not be sufficiently immunosuppressive to permit consistent engraftment of bone marrow from unrelated donors.

Adult↗
PubMed1993

Giardiasis in Canterbury: the first nine months reported cases.

AIM: To obtain epidemiological information about giardiasis in Canterbury. METHOD: From October 1990 general practitioners were requested to report laboratory confirmed cases. The first 100 cases were sent a questionnaire and also asked to provide the details of two persons to be controls. RESULTS: In the first nine months 109 cases were reported. Eighty four cases completed questionnaires and 51 were matched with controls. The overall reported attack rate was 4.0 per 10,000 population per year. The rate was highest for preschool children and young adults and in rural areas. There was a significant risk associated with having contact with sewage or travelling overseas and a marginal risk for drinking water outside Christchurch. CONCLUSION: The results indicated that giardiasis was relatively common in Canterbury and confirmed that the major mechanisms of infection were probably the same as those previously identified overseas, namely person to person spread via faecal-oral transmission and the drinking of inadequately filtered water.

Adolescent↗
PubMed1993

Site-directed cross-linking studies on the E. coli tRNA-ribosome complex: determination of sites labelled with an aromatic azide attached to the variable loop or aminoacyl group of tRNA.

tRNA(Phe) from E. coli, modified with the photoreactive label N-(p-azidobenzoyl)-glycine (ABG) either at the naturally occurring nucleotide 3-(3-amino-3-carboxy-propyl) uridine (acp3U47) or the alpha-amino group of Phe-tRNA(Phe), was bound nonenzymatically to 70S ribosomes in the presence of poly (U) or short synthetic mRNA molecules prepared by T7 transcription. The noncovalent complexes were subjected to a mild ultraviolet irradiation treatment and the sites of photo-incorporation were analysed. When the photo-affinity label was attached to the aminoacyl group cross-linking was observed from both A- and P-site bound tRNA and involved exclusively the 50S subunit. In both cases the major target of cross-linking was a single site in 23S RNA, localized to position A-2439. A lower yield of cross-linking to L27 from both P- and A-sites was also observed. In contrast, cross-linking from the acp3U47 derivative was specific for P-site bound tRNA and involved mainly (but not exclusively) the 50S subunit. In this case rRNA and ribosomal protein were labelled in approximately equal yields, the sites of cross-linking involving A-2309 in 23S RNA and L33. These results are discussed in the light of our present knowledge concerning the structural arrangement of the tRNA-ribosome complex.

Affinity Labels↗