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Biomedical subjects

L A Roberts

Publications and source records attributed to L A Roberts.

At least 19 recordsLinked to original sources

An outbreak of measles in a rural Queensland town in 1997; an opportunity to assess vaccine effectiveness.

This report describes a measles outbreak in a rural town in south-east Queensland and presents the results of a vaccine effectiveness (VE) study performed during this outbreak. It is important to assess the effectiveness of a vaccine in an outbreak to determine if the outbreak is due to failure of the vaccine or failure to vaccinate. There were 44 cases of measles amongst local residents, which represents a notification rate of 396.7 per 100,000 population. Case investigations identified a group of people who had been exposed to measles at a seminar. The attack rate for the seminar cohort was 18% (11/61). This presented an opportunity to conduct a VE study using data about children aged less than 16 years who attended the seminar. In this cohort of 23 attendees, all 7 children who had not received any measles vaccinations became cases whilst the 6 who were fully vaccinated for their age according to NHMRC guidelines were protected from measles illness. Although there were insufficient fully vaccinated cohort members to reliably estimate VE for this group, the vaccine was 84.6% (95% CI: 15.0-99.7%) effective for those who had received at least one validated dose of vaccine. Despite the sample size limitations, the results support the view that failure to vaccinate rather than vaccine failure contributed to the high infection rate in the seminar cohort.

Adolescent↗

Middle ear effusion: rate and risk factors in Australian children attending day care.

There have been no previous longitudinal studies of otitis media conducted in non-Aboriginal Australian children. This paper describes the rate and risk factors for middle ear effusion (MEE) in children attending day care in Darwin, Australia. A prospective cohort study of 252 children under 4 years was conducted in 9 day care centres over 12 fortnights between 24 March and 15 September 1997. Tympanometry was conducted fortnightly and multivariate analysis used to determine risk factors predicting MEE. The outcome of interest was the rate of type B tympanograms per child detected in either ear at fortnightly examinations. After adjusting for clustering by child, MEE was detected on average 4.4 times in 12 fortnights (37% of all examinations conducted). Risk factors associated with presence of effusion were younger age, a family history of ear infection, previous grommets (tympanostomy tubes), ethnicity and the day care centre attended. A history of wheeze appeared protective. These effects were modest (RR 0.57-1.70). Middle ear effusion is very common in children attending day care in Darwin. This has clinical importance, since MEE during early childhood may affect optimal hearing, learning and speech development. There is little scope for modification for many of the risk factors for MEE predicted by this model. Further study of the day care environment is warranted.

Child Day Care Centers↗

Investigation of a cluster of Staphylococcus aureus invasive infection in the top end of the Northern Territory.

INTRODUCTION: Staphylococcus aureus invasive infection remains a serious condition associated with considerable morbidity and mortality. Following notification of five cases at Royal Darwin Hospital (RDH), we searched for related cases, determined their epidemiological characteristics and attempted to identify the source of this apparent cluster. METHODS: We reviewed RDH microbiology records between June 1996 and April 1997 for S. aureus isolates with similar antibiograms to notified cases. We used antibiotic resistance patterns, bacteriophage typing and two molecular typing techniques to subtype implicated isolates. Hospital records were reviewed for admission details and associated costs were estimated. RESULTS: Fifty-four cluster-related isolates occurred in 47 separate presentations. The peak incidence was in the wet season. The most important risk factor for staphylococcal invasive infection was the presence of skin sores/scabies in 17/54 cases (31%), followed by intravascular line use in 14/54 (26%), open trauma in 11/54 (20%), underlying end stage renal failure and alcoholism each in ten of 54 (18%). The mean admission length was 30 days and antibiotics were given for an average of 23 days. Death due to S. aureus infection occurred in eight of 47 (17%) presentations. S. aureus pneumonia was community acquired in 12/13 patients (92%) and six of 13 (46%) died. Ten of 13 (80%) pneumonia patients had at least one other focus of S. aureus infection. The cost of antibiotics and hospital bed per presentation was approximately $16,000. Presentations with skin sores/scabies cost considerably more ($31,000). No common epidemiologic features were found for community or hospital acquired cases. CONCLUSION: Considerable mortality and cost was attributable to cases of S. aureus invasive infection during this cluster; particularly those with community acquired pneumonia or skin sores/scabies. Staphylococcal antibiotic cover should be considered early for unwell patients presenting to hospital with pneumonia and other signs of potential S. aureus infection. It is appropriate to target public health efforts to prevent skin sores and to provide adequate treatment when they occur.

Adolescent↗

A retrospective search for lyssavirus in humans in the Northern Territory.

BACKGROUND: Following the 1996 discovery of a rabies-like lyssavirus in Australian flying foxes, it was unclear whether this was a new epizootic or an unrecognised, previously existing disease. OBJECTIVE: To review cases of unexplained encephalitis in the Northern Territory (NT) to test available clinical specimens for lyssavirus and survey the use of diagnostic tests by clinicians. METHODS: The NT hospital morbidity database was searched from January 1992 to September 1996 for all Royal Darwin Hospital (RDH) cases with an ICD-9 code encompassing encephalitis or viral meningitis. Final diagnoses were determined by hospital record review. For cases of unexplained encephalitis, we assessed the use of diagnostic tests and located clinical specimens for testing for lyssavirus-specific inclusion bodies via immunohistochemistry, immunofluorescence and reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Encephalitis occurred in 34/154 (22%) cases located by the search; 53% (18/34) of encephalitis cases were unexplained. Of these, 24% had no serology performed and 47% had no blood cultures taken. Four (22%) died and two had autopsies. These were the only two cases with clinical specimens available for testing. They were negative for lyssavirus. None of the 71 cases coded as viral meningitis had unexplained encephalitis. CONCLUSION: There was a considerable proportion of unexplained illness among NT cases of encephalitis. IMPLICATIONS: Clinicians should test for lyssavirus in patients with encephalitic symptoms and a postmortem should be sought where death is unexplained. Specimens should be stored to enable testing for emerging infectious diseases.

Diagnosis, Differential↗

Blood pressure and calcium intake are related to bone density in adult males.

Based on the premise that elevated blood pressure and low bone mass have both been associated with poor Ca nutriture and disturbances in Ca metabolism, a cross-sectional study was employed to determine if blood pressure and dietary Ca intake were significantly related to bone mass. Forty-seven men between 24-77 years of age with blood pressure values ranging from normal to mildly elevated comprised the study group. Blood pressure was measured with a random-zero sphygmomanometer. Bone mineral content (BMC) and density (BMD) of the hip, spine and total body were measured with dual-photon absorptiometry. Dietary intake and physical activity were also assessed. Multiple linear regression analysis was used for statistical analysis. After adjusting for known confounding variables (age, BMI, Ca intake, and others) diastolic blood pressure was negatively related to BMC (P < or = 0.05) and BMD (P < or = 0.01) of the total body, trochanteric region (P < 0.01) and Ward's triangle (P < 0.05), and to BMC of the femoral neck (P < 0.05) and lumbar spine, although the latter was just shy of statistical significance (P = 0.058). Systolic blood pressure was negatively related to trochanteric BMD (P = 0.04) and BMC (P = 0.06). Ca intake was positively related to total body BMD (P = 0.005), and BMC of the lumbar spine (P = 0.05). In this population of men, Ca intake was a positive predictor, and blood pressure was a negative predictor of regional measures of bone mass. These findings support the concept that independent of age, BMI and Ca intake, elevated blood pressure varies indirectly with bone mass and density, known predictors of osteoporotic fractures. Future studies are needed to determine whether elevated blood pressure is causally related to the development of low bone mass, and what role dietary Ca plays in that pathway.

Adult↗

Involvement of two isoforms of SNAP-25 in the expression of long-term potentiation in the rat hippocampus.

Induction of long-term potentiation (LTP) in the hippocampus is associated with changes in expression of a variety of different proteins and is thought to be the mechanism which underlies synaptic plasticity. The 25 kDa synaptosomal-associated protein (SNAP-25) is a presynaptic protein which is involved in neurotransmitter exocytosis at the nerve terminal. Two isoforms of SNAP-25 have so far been identified (a and b) which differ in their distribution and developmental regulation. Using in situ hybridization, we demonstrated that the mRNA levels of the two isoforms of this protein are increased 2 h after the induction of LTP in granule cells of the dentate gyrus following high frequency stimulation of the perforant path in vivo. These observations further demonstrate the involvement of both isoforms of SNAP-25 in functional synaptic plasticity, although their exact roles have yet to be fully determined.

Animals↗

Cesarean section.

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Body Mass Index↗

Increased expression of dendritic mRNA following the induction of long-term potentiation.

A small number of mRNAs, including Ca2+/calmodulin-dependent protein kinase II alpha-subunit (CamKIIalpha) mRNA and microtubule-associated protein 2 (MAP2) mRNA, are present in the dendrites of neurones as well as in the cell bodies. We show here that the induction of long-term potentiation (LTP) in the hippocampal perforant path/granule cell synapses in anaesthetised rats is associated with increased levels of CamKIIalpha mRNA and MAP2 mRNA in the granule cell dendrites after 2 h. Similarly, induction of LTP in the Schaffer collateral/CA1 pyramidal cell synapses in hippocampal slices maintained in vitro also results in elevated dendritic levels of CamKIIalpha mRNA and MAP2 mRNA 2 h later. In both models, the levels of various other mRNA species restricted to the cell body region were unaffected by the induction of LTP. Increased expression of dendritic CamKIIalpha mRNA and MAP2 mRNA appears to be a general feature of hippocampal plasticity, since it occurs following LTP induction in both the dentate gyrus and the CA1 region. The elevation of mRNA levels in a restricted region close to the afferent synapses would allow a highly-localised enhancement of the synthesis of the corresponding proteins, providing an elegant mechanism for protein-synthesis-dependent synaptic plasticity to maintain a high degree of anatomical specificity.

Animals↗

Two Afro-Trinidadian siblings with end-stage renal disease.

The case histories of two Afro-Trinidadian brothers aged 8 and 11 years who developed end-stage renal disease (ESRD) are presented. Neither had had cause in the past to seek medical attention for any renal-related illness. At presentation both had anaemia, growth failure and other clinical and laboratory evidence of ESRD. Kidney histology in one child was consistent with familial juvenile nephronophthisis (NPH). This is a common cause of ESRD in children in other countries but it has not been recognized previously in Trinidadian and other West Indian children, and should be considered as a possible aetiology in West Indian children presenting with renal failure.

Anemia↗

Long-term potentiation in perforant path/granule cell synapses is associated with a post-synaptic induction of proenkephalin gene expression.

Enkephalin peptides released from hippocampal mossy fibres lower the threshold for the generation of long-term potentiation (LTP) at the mossy fibre synapses. High frequency stimulation of the hippocampal dentate gyrus, sufficient to induce mossy fibre LTP, is associated with increased expression of the proenkephalin gene in the granule cells. We show here that a similar elevation in proenkephalin mRNA levels is observed, in anaesthetised rats, following stimulation of the perforant path sufficient to induce LTP in the perforant path/granule cell synapses. This strengthens the evidence implicating granule cell enkephalins as mediators of functional plasticity in the hippocampus. Furthermore. the results hint at a form of 'domino plasticity', where potentiation of transmission at the perforant path/granule cell synapses is subsequently followed by an enkephalin-mediated potentiation of transmission at the mossy fibre synapses.

Action Potentials↗

Evidence for the presence of smooth muscle alpha-actin within pericytes of the renal medulla.

This study was designed to determine whether smooth muscle alpha-actin mRNA and smooth muscle alpha-actin contractile protein elements were present within the renal medullary pericytes. Extraction of total RNA from microdissected outer medullary descending vasa recta allowed for the detection of smooth muscle alpha-actin mRNA expression using reverse transcription-polymerase chain reaction (RT-PCR). Expression of smooth muscle alpha-actin was specific to the descending vasa recta and not a result of tubular contamination because RT-PCR amplification of the vasopressin V2 receptor, which is a specific tubular marker, did not occur. To determine the exact cell type(s) that translate the mRNA into protein, we performed immunohistochemistry on the renal outer and inner medulla using a monoclonal smooth muscle alpha-actin antibody, whose specificity was determined by immunoblot analysis. Smooth muscle alpha-actin protein was found selectively within the pericytes surrounding the descending vasa recta from the outer and inner medullary tissue sections. This study demonstrates that the pericytes alone that surround the descending vasa recta within the outer and inner medulla contain smooth muscle alpha-actin mRNA and protein and are therefore the site of the contractile elements that could play a vasomodulatory role in the control of renal medullary blood flow and its distribution within the renal medulla.

Actins↗

Discrepancies in normative data between Lunar and Hologic DXA systems.

Many studies have shown the high correlation between Lunar and Hologic DXA bone mineral density (BMD) measurements despite differences in absolute calibration. However, in clinical practice, raw BMD values (in g/cm2) are not normally used for assessing skeletal status and fracture risk. Instead, the BMD values are expressed in terms of the number of standard deviations above or below the young normal value (commonly referred to as the T-score). If the normative populations of the various systems are consistent, the standard deviation scores should also be consistent. For this reason, the World Health Organization (WHO) recently established diagnostic criteria for osteoporosis based on T-scores and not BMD. However, few studies have compared the instruments in terms of their standard deviation scores. In this study, we used linear regression to compare T-scores in 83 women at L1-4 and 120 women at the femoral neck obtained on a Lunar DPX and a Hologic QDR-1000/W system. patient BMD and T-score measurements were highly correlated between the two systems (r > 0.95). No clinically significant difference in L1-4 T-scores was seen (less than 0.1 SD). However, linear regression analysis confirmed a systematic difference of 0.9 SD between the femoral neck T-scores. This discrepancy is caused by: (1) differences in the normal populations, and (2) differences in statistical models used to determine the young normal mean and standard deviation. In an attempt to correct the discrepancy, the female young normal mean and standard deviation were recalculated for the femoral neck using published epidemiological data from NHANES and existing DXA cross-calibration equations. The Hologic young normal value (mean +/- SD) was redefined as 0.85 +/- 0.11 g/cm2, while the Lunar value was redefined as 1.00 +/- 0.11 g/cm2. When the femoral neck T-scores for the study population were recalculated on the basis of these new values, the results were equivalent between manufactures, effectively eliminating the discrepancy. However, the revised values should be confirmed by additional measurements in young normal adults.

Absorptiometry, Photon↗

Changes in hippocampal gene expression associated with the induction of long-term potentiation.

The expression of four genes: zif/268, c-fos, tubulin and alpha Ca2+/calmodulin-dependent protein kinase II (alpha CAMKII) was studied following the induction of LTP in Schaffer collateral CA1 neurone synapses in rat hippocampal slices maintained in vitro. Levels of c-fos mRNA and tubulin (T26) mRNA in area CA1 were unchanged after induction of LTP, however, zif/268 and alpha CAMKII mRNA levels showed a significant increase compared to non-potentiated controls. It is possible, therefore, to measure changes in gene expression using in situ hybridisation following induction of LTP in vitro and these results strengthen the theory that zif/268 and alpha CAMKII are involved in some aspect of the induction or maintenance of hippocampal LTP.

Animals↗

Densitometry of the radius using single and dual energy absorptiometry.

Though spinal and femoral measurements are typically preferred for evaluating skeletal density, an abundance of forearm data exists, primarily from single photon absorptiometry (SPA) devices. Most dual X-ray absorptiometry (DXA) scanners are capable of scanning the forearm and provide analysis tools to duplicate conventional SPA measurements. In this study, we have compared the radius density measurements from three commonly available densitometers: a Norland 278 SPA, a Lunar DPX-L, and a Hologic 1000/W. Radius bone mineral density (BMD) on the nondominant forearm was measured in 28 volunteers (21 women and 7 men) aged 24-78, with an average age of 51 +/- 17 years. Values were compared and regression relationships derived at corresponding measurement sites. SPA and DXA BMD values were found to be highly correlated (r = 0.99) with small standard errors (0.014 g/cm2-0.021 g/cm2), though significant absolute differences were observed at most measurement regions. Correlation slopes ranged from 0.85 to 1.04, with intercepts from 0.01 to 0.08 g/cm2. Using the resultant regression equations, SPA BMD values can be converted to DXA values with an expected error of roughly 3%. DXA BMD can also be interconverted between Lunar and Hologic with a similar expected error. In situations where this level of imprecision is acceptable, patient forearm measurements obtained on different systems can be interconverted.

Absorptiometry, Photon↗

Human immune response to cationized proteins. I. Characterization of the in vitro response to cationized diphtheria toxoid.

Cationization of proteins, i.e., increasing net positive charge by the substitution of carboxyl groups with positively charged residues, has been reported to enhance protein immunogenicity in animal model systems. In the present study, we have investigated the effect of cationization on the in vitro cell-mediated immune response of human mononuclear cells to diphtheria toxoid. A series of cationized DT preparations were generated by covalent modification with ethylenediamine, with pIs ranging from 4.6 to > 9.3, and tested for their ability to induce proliferation of normal human peripheral blood mononuclear cells. Cationized DT (cDT) was found to induce an antigen-specific, augmented proliferative response, relative to native antigen, which was directly proportional to the degree of cationization. Further characterization of the response to cDT demonstrated that (1) proliferative responses could be detected considerably earlier, and typically at much lower antigen concentrations, than the response to native DT; (2) the response was dependent on HLA-DR; (3) production of a number of cytokines, sp. IL-1 beta, IL-2, and IFN-gamma, was also elevated in cDT-stimulated cultures; and (4) the enhanced proliferative response to cDT could be attributed to CD4+ helper T cells. These results demonstrate that cationization of proteins enhances the ability to generate a cell-mediated immune response in humans and suggest that cationization may have utility in the design of more effective carrier proteins for human vaccines.

CD4 Antigens↗

Human immune response to cationized proteins. II. Characterization of interaction of cationized diphtheria toxoid with human mononuclear cells.

Cationized diphtheria toxoid (cDT) has previously been shown to be more effective than the native protein as an inducer of human antigen-specific T cell responses. In the present study, biotin-labeled antigen and flow cytometric analysis were used to examine the possibility that enhanced immunogenicity of cDT may be a consequence of preferential binding to antigen-presenting cells. Strong binding of cDT, relative to native antigen, was noted for both monocytes and B cells. Characteristics of binding were similar for both cell types, including rapid saturation, temperature independence, and inhibition by unlabeled cationized proteins. Although both B cells and monocytes bound cDT, only monocytes were effective in triggering T cell proliferation, possibly as a result of slow internalization of bound antigen by B cells. Definition of the target structures of cationized proteins may allow for the design of more efficient vaccines, which would be specifically targeted to antigen-presenting cells in vivo.

Antigen-Presenting Cells↗

Reaction time during cocaine versus alcohol withdrawal: longitudinal measures of visual and auditory suppression.

Visual and auditory stimulus discrimination tasks, analogous to those used in the Reitan-Klove Sensory Perceptual Examination, were performed by 12 cocaine-dependent and 5 alcohol-dependent patients after 1 week, 3 weeks, and 3 months of verified abstinence. Sixteen control subjects, who were not substance-dependent, performed the same tasks after comparable intervals. During each task, either visual or auditory stimuli were presented in the left, in the right, or in both sensory fields. A simple key press was made to discriminate these conditions. Cocaine-dependent patients responded more slowly than control subjects during both tasks. The reaction-time slowing persisted across all three sessions, spanning a 3-month period of abstinence. There were no significant differences between the cocaine-dependent and control groups in response accuracy. In the context of other findings, these findings are interpreted as reflecting an enduring effect of prior cocaine dependence on motor as opposed to sensory functioning.

Acoustic Stimulation↗