Biomedical subjects
Publications and source records attributed to M Starr.
We describe an immunocompetent adolescent who presented with exceptionally severe Bordetella holmesii infection, including previously undescribed manifestations. Sequelae included a severe restrictive lung defect due to pulmonary fibrosis.
During mouse embryogenesis, two waves of hematopoietic progenitors originate in the yolk sac. The first wave consists of primitive erythroid progenitors that arise at embryonic day 7.0 (E7.0), whereas the second wave consists of definitive erythroid progenitors that arise at E8.25. To determine whether these unilineage hematopoietic progenitors arise from multipotential precursors, we investigated the kinetics of high proliferative potential colony-forming cells (HPP-CFC), multipotent precursors that give rise to macroscopic colonies when cultured in vitro. No HPP-CFC were found at presomite stages (E6.5-E7.5). Rather, HPP-CFC were detected first at early somite stages (E8.25), exclusively in the yolk sac. HPP-CFC were found subsequently in the bloodstream at higher levels than the remainder of the embryo proper. However, the yolk sac remains the predominant site of HPP-CFC expansion (>100-fold) until the liver begins to serve as the major hematopoietic organ at E11.5. On secondary replating, embryonic HPP-CFC give rise to definitive erythroid and macrophage (but not primitive erythroid) progenitors. Our findings support the hypothesis that definitive but not primitive hematopoietic progenitors originate from yolk sac-derived HPP-CFC during late gastrulation.
Mean annual (1994-1996) budgets for Cd, Cu, Ni, Pb and Zn at two background, forested catchments, VK and HJ, in Finland are presented. Budgets for plots (VK3, HJ1 and HJ4) included throughfall (TF), litterfall (LF) and soil leaching fluxes, and for catchments terrestrial retention and leaching and lake sedimentation fluxes. Total deposition (TD) loads were relatively low (Cd < 0.1, Cu < 2, Ni < 1, Pb < 3 and Zn < 5 mg m-2 year-1) and that even in these areas almost half of the TD was in the form of dry deposition. Retention of TD within catchments was > or = 77% for all metals, except for Ni at VK (54%). For Cu and Pb, the retention was 94-97%. Most of the retention (74-97%) took place in the terrestrial part of the catchment, lake sedimentation accounting for the remainder. Plot-scale soil leaching fluxes at 40 cm of Cd, Cu (VK3) and Ni (VK3) were greater (> or = 100%) than TD inputs. Most of the catchment retention must therefore have taken place either deeper in the soil or in the lowland peatland areas. The humus layer was particularly effective in retaining Cu and Cd (65-81% and 51-78% of total inputs to the forest floor (TF + LF)). The retention of Pb by the humus layer was less than expected (26-54% of TF + LF). Litterfall was a particularly important internal flux for Zn.
Litterfall (LF) is usually collected by means of open traps. However, this litter will be subject to leaching by the throughfall which passes through the accumulated litter in the traps. The nutrients lost during this leaching are not taken into account in the calculation of LF nutrient fluxes. We report the results from a 2-month (August-September) study carried out in 8 northern coniferous forest stands to assess the possible importance of leaching from litter in LF traps. Compared to throughfall (TF), the litterfall leachate (LFLgross), which includes a throughfall component, had significantly (p < 0.05) higher concentrations and fluxes of Ca, Mg, Na and S. The average net LFL (i.e., LFLnet = LFLgross - TF) fluxes were 21 (Ca), 7 (Mg), 57 (K), 10 (Na), 10 (N), and 19 (S) mg m-2 mo-1. LFLnet accounted for 42%, 37% and 50% of the LFLgross flux, and for 91%, 51% and 49% of the total litterfall flux (i.e., LF + LFLnet) of Na, S and K, respectively. For Ca, Mg and N, the LFLnet flux accounted for 64%, 58% and 29% of the LFLgross flux, and for < 14% of the total litterfall flux. Compared to TF, LF was the dominant return pathway for Ca, Mg and N to the forest floor regardless of whether LFLnet was included or not. However, for K and S, taking LFLnet into account determined whether TF or LF was the dominant pathway. TF remained the dominant pathway for Na even when LFLnet was included.
OBJECTIVE: To undertake population pharmacokinetic modeling and to determine the safety and efficacy of once daily (OD) gentamicin dosing in children with severe urinary tract infections (UTI). METHODS: An open, randomized, controlled trial comparing OD with three times daily (TD) gentamicin dosing in hospitalized children ages 1 month to 12 years with UTI. Daily doses (milligrams per kg per day) of gentamicin in both groups were 7.5 (<5 years old), 6.0 (5 to 10 years old) and 4.5 (>10 years old). RESULTS: There were 179 children enrolled (90 OD, 89 TD). Baseline clinical characteristics and pathogens were similar, except that circulatory compromise and renal cortical scintigraphic defects were more common in the OD group. Median gentamicin treatment durations were 3.0 (OD) and 2.7 (TD) days. Mean peak gentamicin concentrations were 17.3 (OD) vs. 6.4 (TD) mg/l; 99% of peak concentrations were >7 mg/l in the OD group whereas 16% of peak concentrations were <5 mg/l in the TD group. Mean trough concentrations were 0.35 (OD) vs. 0.55 (TD) mg/l. In the OD group 4% of trough concentrations were > or = 2 mg/l, whereas in the TD group only 0.7% were > or = 2 mg/l. Age or prior elevated peak concentrations did not predict high trough concentrations. Population pharmacokinetic modeling of the data fitted a one-compartment model with first order elimination. There were no clinical or bacteriologic failures. The two disease-related complications were confined to the OD group. No nephro- or ototoxicity was identified. CONCLUSIONS: With age-appropriate dosing and measurement of serum trough concentrations before the second dose, OD gentamicin is safe and effective for the treatment of UTI requiring parenteral treatment in children aged 1 month to 12 years.
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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.
Extant models of oculomotor control during reading maintain that allocation of attention confines word recognition to one (target) word at a time, and that an eye movement to a new (posttarget) word is computed before attention is shifted to it. To test these assumptions, properties of the posttarget's preview were manipulated during the fixation of the preceding target word. The main results revealed longer target viewing durations when the posttarget preview was visually distinctive or when it was orthographically illegal. The meaning of posttarget text did not affect initial target word reading, although it affected the time spent rereading the target. To account for these findings, extant attention-shift models must assume that readers obtain at least visuospatial and orthographic information from a parafovelly visible word before it is attended. This view has shortcomings, however, and several considerations favor less restrictive model assumptions according to which attention can be allocated to more than one word at a time.
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.
OBJECTIVE: To compare the teaching value of rheumatology patients seen in either a community rheumatology practice or in a tertiary care university center. METHODS: Consecutive patients seen at the 2 sites over a one month period were assessed for rheumatology diagnosis, complexity of rheumatologic disease, and treatments received, including number of interventions performed. The overall pedagogic value of the encounter was rated by the rheumatologist for both medical students and postgraduate trainees. RESULTS: Rheumatology patients were comparable at the 2 sites for overall pedagogic value, rheumatology diagnostic category, and complexity of disease. At the community site, however, there were more patients evaluated, more procedures performed, and more new treatments introduced. CONCLUSION: Contrary to current perceptions, comparable pedagogic value of rheumatology patients was observed outside a tertiary care setting. In the changing climate of education, and considering resource limitations that influence current rheumatology practice, community based rheumatology has the potential to offer a valuable educational experience.
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.
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.
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.
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.
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.
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.
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.
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