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Biomedical subjects

M Starr

Publications and source records attributed to M Starr.

At least 19 recordsLinked to original sources

Attentional function in secondary school students receiving isoniazid prophylaxis for tuberculosis infection.

Reports have suggested that isoniazid treatment may be associated with poor concentration and subtle reduction in memory. This study examines attentional function and processing speed in a group of 25 adolescents who received isoniazid prophylaxis for at least 6 months. As adolescents often face major educational assessment milestones, such cognitive side effects may have important implications. Participants were assessed before treatment, 1 month into treatment and at least 1 week after treatment cessation. Measures included the Paced Auditory Serial Addition Test and subtests of the appropriate Wechsler scale sensitive to attention and speed of information processing. Isoniazid does not appear to cause significant adverse effects on attentional function in adolescents.

Adolescent↗

A rash of exanthems. How they affect children and pregnant women.

BACKGROUND: Viral exanthems are a common problem for children, particularly during preschool years. Many of these infections have a dramatic impact on siblings, parents and other contacts. There may also be particular ramifications for pregnant contacts. OBJECTIVE: To discuss some of the most common viral exanthems affecting children, in terms of the epidemiology, clinical features, diagnosis, and the management of both the patient and the contacts. DISCUSSION: Recommendations are made for measles, rubella, parvovirus and varicella regarding immunisations, use of immunoglobulin, serological diagnosis and management of pregnant contacts.

Chickenpox↗

A novel approach to monitoring adherence to preventive therapy for tuberculosis in adolescence.

OBJECTIVES: To evaluate the usefulness of a microelectronic tablet-dispenser for monitoring adherence to preventive therapy for tuberculosis infection in adolescents. METHODOLOGY: Twenty-one patients with positive Mantoux tests were treated with isoniazid (INH), dispensed in a microelectronic tablet-dispenser that recorded the date, time and duration that the container was opened. Other measures of adherence included attendance at clinic, patient self-report, tablet count, and measurement of urinary INH metabolites. RESULTS: The mean adherence rates were: 83% using attendance at clinic, 91% using tablet counts, 79% using urine assays, and 66% using the electronic tablet-dispenser. Self-reporting appeared to over-estimate adherence. CONCLUSION: Adherence to 6 months of INH calculated using different measures is higher in this study than in previous reports. Microelectronic tablet-dispensers are an effective method to objectively measure adherence on a daily basis. Other measures are less helpful.

Adolescent↗

The incidence of drug-related problems as a cause of hospital admissions in children.

OBJECTIVES: To determine the incidence of hospital admissions for drug-related problems (DRPs) among children, and to examine cases for causality, preventability and clinical severity. DESIGN: Prospective assessment involving review of case notes and parent interview to determine if an admission was associated with a DRP. PATIENTS AND SETTING: All patients admitted to a large university-affiliated paediatric hospital in Melbourne, Victoria, for medical reasons (i.e., not surgical, trauma or oncology patients) during 56 consecutive days from 24 June to 19 August 1996 for which a DRP could be identified. Patients whose parents or guardians could not communicate adequately in English were excluded. MAIN OUTCOME MEASURES: The incidence, type, causality, preventability and clinical severity of DRPs associated with admission. RESULTS: Of 1682 eligible patients admitted to the Royal Children's Hospital during the study period, 58 admissions (3.4%) were associated with DRPs. Non-compliance was implicated in 50%. Causality was ranked as "definite" (34.5%), "possible" (56.9%) and "doubtful" (8.6). Two-thirds of admissions associated with DRPs were deemed preventable. Although no patients died from DRPs, four were admitted to the intensive care unit. CONCLUSIONS: The incidence of DRPs as a cause of hospital admission in this study falls within the range of incidences published for the Australian adult population (range, 2.4%-22%). In contrast to findings among Australian adults, a high proportion of admissions for DRPs in this study were associated with non-compliance. The high percentage of preventable admissions indicates that further study is necessary to characterise risk factors within this population and to test prevention strategies.

Adolescent↗

Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor.

BACKGROUND: Vav is a guanine-nucleotide exchange factor for the Rho-like small GTPases RhoA, Rac1 and Cdc42, which regulate cytoskeletal reorganization and activation of stress-activated protein kinases (SAPK/JNKs). Vav is expressed in hematopoietic cells and is phosphorylated in T and B cells following activation of various growth factor or antigen receptors. Vav interacts with several signaling molecules in T cells, but the functional relevance of these interactions is established only for Slp76: they cooperate to induce activity of the transcription factor NF-AT and interleukin-2 expression. We have investigated the role of Vav in T cells by generating vav-/- mice. RESULTS: Mice deficient for vav were viable and healthy, but had impaired T-cell development. In vav-/- T cells, in response to activation of the T-cell receptor (TCR), cell cycle progression, induction of NF-ATc1 activity, downregulation of the cell-cycle inhibitor p27Kip1, interleukin-2 production, actin polymerization and the clustering of TCRs into patches and caps--a cytoskeletal reorganization process--were defective. TCR-mediated activation of mitogen-activated protein kinase and SAPK/JNK was unaffected. Ca2+ mobilization was impaired in vav-/- thymocytes and T cells. In wild-type cells, Vav constitutively associated with the cytoskeletal membrane anchors talin and vinculin. In the absence of Vav, phosphorylation of Slp76, Slp76-talin interactions, and recruitment of the actin cytoskeleton to the CD3 zeta chain of the TCR co-receptor were impaired. CONCLUSIONS: Vav is a crucial regulator of TCR-mediated Ca2+ flux, cytoskeletal reorganization and TCR clustering, and these are required for T-cell maturation, interleukin-2 production and cell cycle progression.

Actins↗

Prevalence of tuberculosis infection in Melbourne secondary school students.

OBJECTIVE: To estimate the prevalence of asymptomatic Mycobacterium tuberculosis infection in Melbourne secondary school students. DESIGN: Cross-sectional Mantoux testing of a partly random and partly targeted sample of secondary school students, designed to enable estimation of prevalence by region of birth. SETTING: Fifty-one State and Catholic secondary schools in metropolitan Melbourne during 1995. PARTICIPANTS: Australian and overseas-born students in Years 9 and 10. OUTCOME MEASURES: Proportions of students with positive Mantoux reactions (defined as induration at 48 hours of > or = 5 mm with a history of recent exposure; > or = 10 mm and no prior BCG vaccination; > or = 15 mm and prior BCG vaccination). RESULTS: Of 2586 students potentially eligible for testing, evaluable results were obtained from 1274 (49%). The overall prevalence of infection for Melbourne students in Years 9 and 10 was 2.5% (95% CI, 1.1-3.9%). Main predictors of a positive test were birth overseas and number of years residing overseas. Prevalence varied considerably by region of birth, and was very low in students born in Australia (0.7%), "other developed countries" (0.7%), and Southern Europe (0). The highest rates were observed in students born in Indochina (15.9%), other countries in South East Asia (10.2%), and Eastern Europe (10.2%). CONCLUSIONS: The risk of a young person becoming infected with M. tuberculosis while living in Melbourne is very low. Our results do not indicate a need for the reintroduction of mass screening in Victorian schools. If targeted screening were to be considered, the group most likely to benefit would be recently arrived migrants from Indochina.

Adjuvants, Immunologic↗

Hemolytic-uremic syndrome following urinary tract infection with enterohemorrhagic Escherichia coli: case report and review.

A 6-week-old child with acute urinary tract infection caused by Shiga toxin-producing Escherichia coli (STEC) O5:H-developed hemolytic-uremic syndrome (HUS). Molecular and phenotypic analysis of the urinary isolate indicated that it lacked uropathic properties and that it was probably of intestinal origin. Nevertheless, the patient did not experience a diarrheal prodrome, nor was STEC or Shiga toxin detected in his feces at any time. Examination of the patient's serum pointed to recent infection with E. coli O5, with no evidence of exposure to E. coli O157, O111, or O26. A review of 13 previously reported cases of HUS associated with acute urinary tract infection indicated that this was the first case of nondiarrheal HUS in which infection with the most common STEC serogroups was specifically excluded. This case illustrates the need to investigate patients with nondiarrheal HUS for infection with STEC.

DNA, Bacterial↗

Infant nutrition program effectively prevents iron-deficiency anemia in a First Nations community.

Iron-deficiency anemia (IDA) has received relatively little attention in Canada, with no national public health initiatives even among high-risk infants. IDA has a high prevalence in First Nations children and has been shown to cause developmental delay. This study is a before/after prevalence survey studying the effect of a public health intervention, conducted on a First Nations reserve off the central coast of British Columbia (BC). We screened for IDA one cohort of infants born January 1993 to August 1994 and between the ages of 6 and 24 months. Twenty-five of a possible 37 infants were screened. We found 13 (52%) of the 25 had anemia, with a hemoglobin less than 100 g/L. The average hemoglobin was 98.9 +/- 19.2 g/L. The subsequent implementation of an infant nutrition program focused on educating parents and encouraging the use of iron-fortified formula for nonbreast-fed infants. In the year following program implementation, the cohort of infants born between September 1994 and September 1995 were screened for IDA when they were between the ages of 6 and 15 months. Twenty-four of 27 infants participated. Only one infant was anemic with a hemoglobin less than 100 g/L. The average hemoglobin was 116.6 +/- 11.6 g/L. The increase in the average hemoglobin and the decrease in the prevalence of anemia were both highly significant (p < .01). We judged our intervention to be very effective and would recommend similar programs for other First Nations communities.

Anemia, Iron-Deficiency↗

MK 801 reverses haloperidol-induced catalepsy from both striatal and extrastriatal sites in the rat brain.

The present study investigated whether the anticataleptic effect of (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine (MK 801) is due to a blockade of N-methyl-D-aspartate (NMDA) receptors in striatal output pathways as well as in the striatum. Catalepsy induced by haloperidol (1 mg/kg i.p.) was more effectively reversed by MK 801 (0.2 mg/kg i.p.) given 10 min prior to rather than 45 min after the neuroleptic. Catalepsy evoked by intrastriatal haloperidol (7 micrograms/side) was also strongly attenuated by systemic MK 801 (0.2 mg/kg i.p.). We also found that the cataleptic rigidity induced by systemic haloperidol (1 mg/kg i.p.) could be prevented by prior injection of MK 801 into the striatum (10 micrograms), subthalamic nucleus (5 micrograms), entopeduncular nucleus (5 micrograms) or substantia nigra pars reticulata (1 microgram). These results suggest that the anticataleptic action of systemic MK 801 versus haloperidol, is due to the blockade of NMDA receptors in the striatum as well as in striatal output circuits through the subthalamus. However, systemic MK 801 (0.2 mg/kg i.p.) was without effect on the catalepsy elicited by injecting muscimol into the globus pallidus (25 ng) or ventromedial thalamus (50 ng). These findings suggest that MK 801 has little influence over thalamic excitatory feedback to the cortex, and that hypoactivity of the pallidum may not be a prerequisite for hyperactivity in the subthalamus.

Animals↗

Motor effects of lamotrigine in naive and dopamine-depleted mice.

Lamotrigine (3,5-diamino-6-[2,3-dichlorphenyl]-1,2,4-triazine) has been hypothesised to possess antiparkinsonian activity, by inhibiting the release of glutamate from basal ganglia neurones. This study therefore examined the motor effects of lamotrigine in naive and reserpine-treated mice and its interactions with dopaminergic agonists. In normal mice, lamotrigine (5-80 mg/kg i.p.) decreased spontaneous locomotor activity with high doses (> or = 40 mg/kg) causing moderately severe impairment to posture and gait. In mice treated 24 h beforehand with reserpine (5 mg/kg i.p.), lamotrigine (5-40 mg/kg i.p.) had no effect on akinesia by itself and did not alter the locomotion induced with the selective dopamine D1 receptor agonist 2,3,4, 5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine hydrochloride (SKF 38393, 30 mg/kg i.p.). By contrast, motor responses to the dopamine D2 receptor-selective agonist N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)ethylamine (RU 24213, 5 mg/kg s.c.) and to the dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA, 150 mg/kg i.p. in the presence of benserazide, 100 mg/kg i.p.), were significantly potentiated by 10 and 40 mg/kg i.p. lamotrigine respectively. It is suggested that lamotrigine may enhance the antiakinetic action of L-DOPA in parkinson-like mice by increasing motor responding mediated by dopamine D2 but not dopamine D1 receptors. This interaction profile of lamotrigine with dopamine D1 and D2 receptor mechanisms is opposite to what one sees with antagonists of glutamate receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Excimer laser phototherapeutic keratectomy.

The objective of this study was to evaluate the safety and efficacy of excimer laser phototherapeutic keratectomy in the treatment of anterior corneal pathology in a group of 45 patients. Forty-five patients were treated with the Visx Excimer Laser System for various types of anterior corneal pathology including postinflammatory and postsurgical scars, stromal dystrophies, surface degenerations, pterygia, and epithelial basement membrane dystrophies. Excimer laser phototherapeutic keratectomy (PTK) has been used to treat anteriorly located corneal pathology since 1990; however, most published studies thus far have been composed of small numbers of patients with limited duration of follow-up. The present study is one of the largest domestic PTK series with one of the longest mean follow-ups. Forty patients were followed for > or = 6 months with a mean follow-up of just less than 1 year (11.25 months). Statistically significant improvement was achieved in irritative symptoms and visual acuity. Best spectacle corrected visual acuity (BSCVA) improved a mean of two lines (range, -3 to +7) with 20/50 or better BSCVA present in 29% of patients preoperatively improving to 60% postoperatively. Refractive changes were unpredictable. Mean spherical equivalent underwent a hyperopic shift of 2.81 diopters (D). Fifty percent of patients developed > or = 1 D of refractive astigmatism. Complications occurred in six patients with loss of BSCVA, three patients with topical corticosteroid associated increased intraocular pressure, and three patients with recurrent herpes simplex stromal keratouveitis. Excimer laser phototherapeutic keratectomy can consistently achieve a modest to a more substantial improvement in irritative ocular symptoms and/or visual acuity with significant potential for adverse results that appear to be less severe than the complications associated with alternative treatment by keratoplasty.

Adolescent↗

Choosing death.

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Boston↗

Bilateral epibulbar rheumatoid nodulosis. A new ocular entity.

A 61-year-old woman, whose rheumatoid arthritis had been quiescent for 9 years, developed a crop fo 16 painless bilateral episcleral rheumatoid nodules without any flareup of her joint disease. Biopsy of the lesions disclosed lymphocytic and plasmacytic infiltration within the conjunctiva, overlying palisading granulomas with elongated epithelioid histiocytes, multinucleated giant cells, and central necrobiotic degeneration of the collagen of the episclera and superficial sclera. The rheumatologic designation for the development of groups of subcutaneous nodules in inactive rheumatoid arthritis is rheumatoid nodulosis. This report is the first description of this entity in the ocular adnexa.

Arthritis, Rheumatoid↗

Opposing roles of dopamine D1 and D2 receptors in nigral gamma-[3H]aminobutyric acid release?

This study examined the effects of dopamine D1 and D2 receptor agonists and antagonists on the spontaneous and calcium-dependent, K+-induced release of gamma-[3H]aminobutyric acid [( 3H]GABA) accumulated by slices of rat substantia nigra. SKF 38393 (D1 agonist) and dopamine (dual D1/D2 agonist) were without effect on [3H]GABA efflux by themselves (1-40 microM), or in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) (0.5 mM), but potentiated evoked release in the presence of forskolin (0.5 microM), an adenylate cyclase activator. These increases in release were prevented by the D1 antagonist SCH 23390 (0.5 microM), but not by the D2 antagonist metoclopramide (0.5 microM). Higher concentrations of forskolin (10-40 microM) augmented stimulus-evoked [3H]GABA release directly, whereas dibutyryl cyclic AMP (100-200 microM) depressed it. Apomorphine, noradrenaline, and 5-hydroxytryptamine (1-40 microM) had no effect. The D2 stimulants lisuride, RU 24213, LY 171555, and bromocriptine dose-dependently inhibited depolarisation-induced but not basal [3H]GABA outflow. These inhibitory responses were not modified by the additional presence of SKF 38393 (10 microM) or SCH 23390 (1 microM), or by injection of 6-hydroxydopamine into the medial forebrain bundle 42 days earlier, but were attenuated by metoclopramide (0.5 microM). Higher amounts (10 microM) of SCH 23390, metoclopramide, or other D2 antagonists (loxapine, haloperidol) reduced evoked GABA release by themselves, probably by nonspecific mechanisms. These results suggest D1 and D2 receptors may have opposing effects on nigral GABA output and could explain the variable effects of mixed D1/D2 dopaminomimetics in earlier release and electrophysiological experiments.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗