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Biomedical subjects

A Carmichael

Publications and source records attributed to A Carmichael.

At least 19 recordsLinked to original sources

Critical dependence of acetate thermal mattress on gel activation temperature.

BACKGROUND: Sodium acetate gel mattresses provide an active method of warming patients through release of latent heat of crystallisation. They can be used as an adjunct to incubator care or as an exclusive heat source. OBJECTIVE: To determine activation temperatures of the Transwarmer mattress needed to achieve plateau temperatures of 38-42 degrees C. DESIGN AND SETTING: In vitro testing of mattress temperature. METHODS AND OUTCOME MEASURES: Transwarmer mattresses were activated at initial temperatures ranging from 5 to 40 degrees C. Mattress temperature was recorded up to 4 h to determine peak and plateau temperatures. Peak and plateau temperatures achieved by the mattress were related to the initial starting temperature. RESULTS: The starting temperature of the mattress was strongly correlated with peak and plateau temperature (r = 0.99, p<0.001). To achieve the target temperature of 38-42 degrees C, the Transwarmer mattress requires activation between 19.2 degrees C and 28.3 degrees C. A temperature of 37 degrees C could be generated by activation at 17 degrees C. CONCLUSIONS: Safe use of this device is critically dependent on gel temperature at the point of activation. To ensure warming of a hypothermic neonatal patient without running any risk of burns, the mattress should be activated with a gel temperature between 19 degrees C and 28 degrees C.

Beds↗

Endotracheal tube position in neonates requiring emergency interhospital transfer.

A malpositioned endotracheal tube (ETT) is common following initial intubation. This study assessed ETT position in 53 orotracheally intubated neonates referred for interhospital transfer during a 3-month period. Position of the ETT on first chest radiograph (CXR) after intubation was assessed and related to radiographic lung expansion, with documentation that the final ETT length had achieved a satisfactory position. At the time of first CXR, median ETT length at the lips was 7.0 cm (range, 5 to 12 cm) with median tip position at T3.0 (range, C7 to T6). The ETT required repositioning in 58% of patients. Most malpositioned tubes were too low (26 were withdrawn and only four were advanced; p < 0.001), with lung expansion more closely related to vertebral than clavicular position of the ETT. Final ETT length correlated well with corrected gestation ( r = 0.83; p < 0.01) and marginally less well with weight ( r = 0.79; p < 0.01). From the regression analysis, we provide a table of recommended tube lengths by gestation.

Airway Obstruction↗

Lentivirus-mediated gene transfer of viral interleukin-10 delays but does not prevent cardiac allograft rejection.

Human immunodeficiency virus (HIV)-based lentiviral vectors expressing viral interleukin-10 (vIL-10) were used to transduce rat cardiac allografts with the aim of extending graft survival. vIL-10 expression was first shown, by RT-PCR, to persist in transduced heart isografts for at least 28 days after transduction. Cardiac transplants were performed in a fully allogeneic rat strain combination (Lewis to DA); allografts transduced by vectors expressing vIL-10 showed significantly prolonged survival (14.5 vs 7.5 days median survival time). Mixed lymphocyte reactions (MLRs) were used to determine the influence, in vitro, of vIL-10 on alloantigen-induced T-cell proliferation. Bioactive vIL-10, produced by DA rat aortic endothelial cells transduced with HIV-PGK-vIL-10, was added to MLRs at different time points and lymphocyte proliferation was assessed by uptake of [3H]thymidine. T-cell proliferation was inhibited by >80% when vIL-10 was added to the MLR at day 1, 2 or 3 of coculture. The inhibitory effect was significantly decreased when addition of vIL-10 was delayed until day 4 or 5 (47 and 35% inhibition, respectively). The extended graft survival time is comparable to that using adenoviral vectors delivering vIL-10 in a similar rat strain combination. The limited improvement in survival may be due to lack of inhibition of the early phase of the alloimmune response as suggested by in vitro studies confirming that maximum suppression of the MLR by vIL-10 can only be achieved if the cytokine is present at the initiation of alloimmune recognition. The delay in expression of vIL-10 from the lentiviral vector means that protocols must be developed to suppress the early stages of alloimmune stimulation before vIL-10 is produced.

Animals↗

A differing pattern of association between dietary fish and allergen-specific subgroups of atopy.

BACKGROUND: We examined the role of fish intake in the development of atopic disease with particular reference to the possibility of differential effects on allergen-specific subgroups of sensitization. METHODS: The exposure of interest was parental report of fish intake by children aged 8 years at the 1997 Childhood Allergy and Respiratory Health Study (n = 499). The outcomes of interest were subgroups of atopy: house dust mite (HDM)-pure sensitization [a positive skin-prick test (SPT) > or = 2 mm to Der p or Der f only], ryegrass-pure sensitization (a positive SPT > or = 2 mm to ryegrass only); asthma and hay fever by allergen-specific sensitization. RESULTS: A significant association between fish intake and ryegrass-pure [adjusted odds ratio (AOR) 0.37 (0.15-0.90)] but not HDM-pure sensitization [AOR 0.87 (0.36-2.13)] was found. Fish consumption significantly decreased the risk for ryegrass-pure sensitization in comparison with HDM-pure sensitization [AOR 0.20 (0.05-0.79)]. CONCLUSIONS: We have demonstrated a differential effect of fish intake for sensitization to different aeroallergens. This may be due to the different timing of allergen exposure during early life. Further investigation of the causes of atopic disease should take into account allergen-specific subgroups.

Allergens↗

FMR1 alleles in Tasmania: a screening study of the special educational needs population.

The distribution of fragile X mental retardation-1 (FMR1) allele categories, classified by the number of CGG repeats, in the population of Tasmania was investigated in 1253 males with special educational needs (SEN). The frequencies of these FMR1 categories were compared with those seen in controls as represented by 578 consecutive male births. The initial screening was based on polymerase chain reaction analysis of dried blood spots. Inconclusive results were verified by Southern analysis of a venous blood sample. The frequencies of common FMR1 alleles in both samples, and of grey zone alleles in the controls, were similar to those in other Caucasian populations. Consistent with earlier reports, we found some (although insignificant) increase of grey zone alleles in SEN subjects compared with controls. The frequencies of predisposing flanking haplotypes among grey zone males FMR1 alleles were similar to those seen in other Caucasian SEN samples. Contrary to expectation, given the normal frequency of grey zone alleles, no premutation (PM) or full mutation (FM) allele was detected in either sample, with only 15 fragile X families diagnosed through routine clinical admissions registered in Tasmania up to 2002. An explanation of this discrepancy could be that the C19th founders of Tasmania carried few PM or FM alleles. The eight to ten generations since white settlement of Tasmania has been insufficient time for susceptible grey zone alleles to evolve into the larger expansions.

Adolescent↗

Cerebral vasculitis caused by Aspergillus species in an immunocompetent adult.

We describe a case of cerebral vasculitis due to Aspergillus infection in an immunocompetent adult, in whom the probable source was paranasal sinus infection. At postmortem there was widespread endovascular Aspergillus infection of the cerebral arteries with occlusion of the basilar artery. We review the literature regarding intracranial Aspergillus infection and new approaches to diagnosis.

Aged↗

A prospective association between cocoon use in infancy and childhood asthma.

There is increasing evidence for a role for bedding items in the development of asthma. The use of some forms of synthetic bedding, such as foam mattresses and pillows, is associated with a significantly increased risk of childhood wheeze. Our aim was to examine prospectively whether the use of synthetic cocoon/baby nests in infancy is associated with the subsequent development of wheeze in childhood. Data collected in 1988 as part of the Tasmanian Infant Health Survey were linked to the cross-sectional Childhood Asthma Survey conducted in 1995 in Tasmania, Australia. We were able to match 863 records out of the 1111 in the 1988 survey. Information including parental, child-care, and the infant's sleeping environment was collected at home interview in 1988 when the infant was 1 month of age. Data including sleep environment and asthma symptoms were available for each child at age 7 years. A generalised linear model was used to calculate the adjusted relative risk (RR) estimates for symptoms of wheeze and infant cocoon use. For children who were placed in a cocoon in infancy, there was an increased risk of recent wheeze (adjusted RR = 4.33 [95% CI 2.08, 9.02]) and night wheeze (adjusted RR = 3.35 [95% CI 1.52, 7.39]) at age 7 years. In view of the increasing prevalence of childhood asthma, the identification of potentially modifiable environmental factors which might operate in infancy is of importance. The present findings implicate infant bedding choice as a significant factor and further studies on the infant sleeping environment are indicated.

Asthma↗

The use of thalidomide in the treatment of intracranial tuberculomas in adults: two case reports.

We present two cases of tuberculous meningitis (TBM) in adults complicated by focal neurological deficits which showed progression whilst on steroids. In case 1 an MRI demonstrated multiple ring-enhancing lesions compressing the optic chiasm leading to a bitemporal hemianopia. After the introduction of thalidomide serial imaging and field perimetry at 6, 9, 12 and 24 months into treatment showed progressive improvement. In case 2, two months into anti-tuberculous treatment with steroids, the patient developed fluctuating right sided paralysis with the MRI demonstrating a large ring-enhancing mass encasing the left internal carotid and middle cerebral arteries. Thalidomide was introduced as an immunomodulatory adjunct and subsequently the patient made a complete neurological recovery. The immunomodulatory effects of thalidomide may have a role in the acute and chronic management of TBM complicated by intracranial tuberculomas.

Adult↗

Breast cancer risk among the survivors of atomic bomb and patients exposed to therapeutic ionising radiation.

Radiation induced breast cancer is a highly complex phenomenon, which most likely involves the accumulation of several genetic and epigenetic events. Studies of atomic bomb survivors, patients who underwent multiple fluoroscopic examinations during treatment for pulmonary tuberculosis, those who received therapeutic radiation for benign breast disease, such as acute post-partum mastitis, or those with an enlarged thymus or skin haemangioma and patients with Hodgkin's disease treated by mantle radiotherapy established that the risk of breast cancer increases with exposure to ionising radiation. The carcinogenic effect of therapeutic or accidental radiation is highest when exposure occurs during childhood and exposure after age 40 imparts low or minimal risk. The risk of bilateral breast cancer is not significantly increased in the survivors of atomic bomb and therapeutic radiations. Fractionated exposures for therapeutic radiation are similar to a single exposure of the same total dose in their ability to induce breast cancer; this risk remains high for many years after exposure. Younger age at first full term pregnancy confers a protective effect against the risk of breast cancer in the survivors of atomic bomb but long-term data on this beneficial effect after therapeutic radiation is not available.

Age Factors↗

Prolonged survival in AIDS-related progressive multifocal leucoencephalopathy following anti-retroviral therapy and cidofovir.

We describe the case of a 44-year-old man who developed sub-acute cerebellar ataxia due to AIDS-related progressive multifocal leucoencephalopathy (PML) caused by JC virus. Following treatment with highly active anti-retroviral therapy (HAART) and cidofovir, he made a marked neurological improvement and is leading an independent life 18 months after the diagnosis of PML. Early recognition of AIDS-related PML and treatment with HAART improves prognosis. Cidofovir, an inhibitor of viral DNA polymerase, appears to have an additive beneficial effect and should be considered especially in patients who fail to improve despite treatment with HAART and in patients who have a high JC virus load in CSF.

AIDS-Related Opportunistic Infections↗

An association between plastic mattress covers and sheepskin underbedding use in infancy and house dust mite sensitization in childhood: a prospective study.

BACKGROUND: Higher house dust mite (HDM) allergen exposure during infancy has been associated with increased HDM sensitization. Infant bedding has been associated with the accumulation of varying levels of HDM. Prospective data on the relationship between infant bedding and the development of HDM sensitization has not been previously examined. OBJECTIVES: To determine if particular types of bedding used in infancy are associated with increased risk of house dust mite sensitization in childhood. METHODS: A population-based sample (n = 498) of children born in 1988 or 1989, and who were resident in Northern Tasmania in 1997, participated in this study. These children were part of a birth cohort study (1988-95), the Tasmanian Infant Health Survey. Data on infant underbedding and mattresses was available on 460 and 457 children, respectively. The main outcome measure was HDM sensitization defined as a skin prick test (SPT) reaction of 3 mm or more to the allergens of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. RESULTS: The use of either sheepskin underbedding or plastic mattress covers in infancy was associated with an increased risk of sensitization to HDM allergens at age 8 years. The adjusted risk ratio (RR) for sensitization to HDM with sheepskin in infancy was 2.27 (95% CI: 1.14, 4.55), P = 0.020. The adjusted RR for sensitization to HDM with the use of plastic mattress covers in infancy was 2.06 (95% CI: 1.22, 3.51), P = 0.007. The use of a foam mattress in infancy was not related to subsequent HDM sensitization. CONCLUSION: Infant's bedding plays a role in the development of HDM sensitization in childhood. Intervention studies to examine mite allergen levels and the role of underbedding on the development of HDM sensitization are required.

Animals↗

A prospective study of the association between home gas appliance use during infancy and subsequent dust mite sensitization and lung function in childhood.

BACKGROUND: Home gas appliance use has been associated with child respiratory illness but prospective data on the relationship between infant exposure and the development of child allergic disease has not been readily available. OBJECTIVES: (a) To determine if home gas appliance use is associated with increased risk of house dust mite (HDM) sensitization. (b) To examine whether any association between current home gas use and airway obstruction is influenced by HDM sensitization. METHODS DESIGN: an 8-year follow-up birth cohort study of children born during 1988 and 1989. PARTICIPANTS: a population-based sample (n = 498) of children who participated in the Tasmanian Infant Health Survey (TIHS) and resided in Northern Tasmania in 1997 (84% of eligible children). MAIN OUTCOME MEASURES: (a) Skin prick test reaction to nine allergens, including Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1). (b) Spirometric lung function indices, including forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). RESULTS: The relative risk for home gas appliance use at 1 month of age and HDM sensitization was 1.98 (1.04, 3.79) in a cohort analysis with confounder matching. Current home gas use was also associated with HDM sensitization (ARR 1.73 (1.43, 2.76)). Current home gas use was related to a stronger (P = 0.006) reduction in the FEV(1) : FVC ratio among HDM-sensitive children (adjusted difference - 6.2% (- 10.0 to - 2.4)) than non-HDM-sensitive children (adjusted difference - 0.3% (- 2.5 to 1.8)). CONCLUSION: Indoor pollutants from gas combustion may increase the likelihood of initial sensitization to HDM and play a role in the development of atopic asthma. HDM-sensitized children may be more vulnerable to indoor pollutant-induced airway obstruction. The ability of this study to detect such effects may partly reflect unflued gas appliance use among this sample.

Age Factors↗

Multiple and independent cessation of recombination between avian sex chromosomes.

Birds are characterized by female heterogamety; females carry the Z and W sex chromosomes, while males have two copies of the Z chromosome. We suggest here that full differentiation of the Z and W sex chromosomes of birds did not take place until after the split of major contemporary lineages, in the late Cretaceous. The ATP synthase alpha-subunit gene is now present in one copy each on the nonrecombining part of the W chromosome (ATP5A1W) and on the Z chromosome (ATP5A1Z). This gene seems to have evolved on several independent occasions, in different lineages, from a state of free recombination into two sex-specific and nonrecombining variants. ATP5A1W and ATP5A1Z are thus more similar within orders, relative to what W (or Z) are between orders. Moreover, this cessation of recombination apparently took place at different times in different lineages (estimated at 13, 40, and 65 million years ago in Ciconiiformes, Galliformes, and Anseriformes, respectively). We argue that these observations are the result of recent and traceable steps in the process where sex chromosomes gradually cease to recombine and become differentiated. Our data demonstrate that this process, once initiated, may occur independently in parallel in sister lineages.

Amino Acid Sequence↗

Identical or overlapping sequences in the primary structure of human alpha(2)-macroglobulin are responsible for the binding of nerve growth factor-beta, platelet-derived growth factor-BB, and transforming growth factor-beta.

alpha(2)-Macroglobulin (alpha(2)M) functions as a proteinase inhibitor and as a carrier of diverse growth factors. In this study, we localized binding sites for platelet-derived growth factor-BB (PDGF-BB) and nerve growth factor-beta (NGF-beta) to a linear sequence in the 180-kDa human alpha(2)M subunit which includes amino acids 591-774. A glutathione S-transferase fusion protein containing amino acids 591-774 (FP3) bound PDGF-BB and NGF-beta in ligand blotting assays whereas five other fusion proteins, which collectively include amino acids 99-590 and 775-1451 did not. The K(D) values for PDGF-BB and NGF-beta binding to immobilized FP3 were 300 +/- 40 and 180 +/- 30 nM, respectively; these values were comparable with those determined using methylamine-modified alpha(2)M, suggesting that higher-order alpha(2)M structure is not necessary for PDGF-BB and NGF-beta binding. PDGF-BB and NGF-beta blocked the binding of transforming growth factor-beta1 (TGF-beta1) to FP3. Furthermore, murinoglobulin, which is the only known member of the alpha-macroglobulin family that does not bind TGF-beta, also failed to bind PDGF-BB and NGF-beta. These results support the hypothesis that either a single linear sequence in human alpha(2)M or overlapping sequences are responsible for the binding of TGF-beta, PDGF-BB, and NGF-beta, even though there is minimal sequence identity between these three growth factors. FP3 blocked the binding of PDGF-BB to a purified chimeric protein, in which the extracellular domain of the PDGF beta receptor was fused to the IgG(1) Fc domain, and to PDGF receptors on NIH 3T3 cells. Thus, FP3 may inhibit the activity of PDGF-BB.

3T3 Cells↗

A phase I trial in HIV negative healthy volunteers evaluating the effect of potent adjuvants on immunogenicity of a recombinant gp120W61D derived from dual tropic R5X4 HIV-1ACH320.

Thirty healthy HIV negative volunteers were randomised to receive 200 micrograms of rgp120W61D in either: 3D-MPL and QS21, with an oil and water emulsion (SBAS-2) (13); or 3D-MPL and QS21 (SBAS-1) (11); or alum (six). Immunizations were given at 0, 4 and 28 weeks and 23 (77%) participants completed the schedule. Adverse events were more frequent (P < 0.001) and more severe (P < 0.001) in the SBAS-2 group. Binding antibodies to the homologous rgp120W61D were detected after the first immunisation only in those receiving SBAS-1 and SBAS-2, were maximal after the third immunization in all three groups, and persisted to week 84 only in the novel adjuvant groups. These differences were significant (p = 0.02). Neutralising antibodies to TCLA-strains of HIV-1 were observed after the second immunization in all three groups, were maximal after the third immunization, but did not neutralise homologous or heterologous PBMC derived primary HIV-1 isolates. Proliferative T-cell responses to rgp120W61D were maximal after the second immunization and reached very high values in the SBAS-2 group. HIV-1 specific CD8+ MHC Class I restricted cytotoxic T-lymphocytes were not seen in a subset of participants tested at a single timepoint. SBAS-2 with rgp120W61D induced antibody titres as high as those seen in HIV infection, but the quality of the antibodies remained different in that there was no evidence of primary isolate neutralisation. Although cell-mediated immunity was enhanced by SBAS-2 in terms of lymphoproliferative responses, HIV-1 specific CD8+ cytotoxicity was not demonstrated.

AIDS Vaccines↗

The relation between infant indoor environment and subsequent asthma.

Our aim was to examine the contribution of an infant's indoor environment to childhood asthma using prospective data. We conducted a cross-sectional asthma survey in 1995 on 92% (6,378/6,911) of 7-year-olds in Tasmania, Australia. We linked these data with data collected in 1988 as part of the Tasmanian Infant Health Survey, which was designed to investigate sudden infant death. We were able to match 863 records out of the 1,111 in the 1988 survey and the 6,378 in the 1995 survey. The former group was interviewed at home at 1 month of age. In homes where at least one adult smoked in 1988, reported infant exposure to smoking in the same room in 1988 was associated with increased asthma by 1995 (relative risk = 1.52; 95% confidence interval = 1.01-2.29) after adjustment for confounders. The associations between infant exposure to environmental tobacco smoke and asthma were not consistent, however. Gas heater use in 1988 was associated with asthma (relative risk = 1.92; 95% confidence interval = 1.33-2.76). Markers of aeroallergen exposure at 1 month of age were not materially associated with asthma or wheeze. In some settings, air circulation practice with regard to bedroom door closure appeared important. Poor indoor air quality may play an important role in the development of childhood asthma.

Adult↗

Asthma, inhaled corticosteroid use, and bone mass in prepubertal children.

The aim of this cross-sectional study was to describe the role of asthma, asthma severity, and medication usage in bone mineralization of prepubertal children. Asthma severity, medication usage, and physical activity were assessed by questionnaire and objective measures in 330 children. Bone densitometry and body composition were measured by dual-energy x-ray absorptiometry. Asthma ever was reported by 110 subjects (33%). A diagnosis of asthma was not associated with any deficit in bone mass, whereas usage of inhaled corticosteroids (ICS) in the last year (but not past use) was associated with deficits in bone in the total body (only after adjustment for confounders), particularly for doses of > or =400 microg/day. These observations support current recommendations with regard to ICS usage in children, but require confirmation in longitudinal studies.

Absorptiometry, Photon↗