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Biomedical subjects

S Hall

Publications and source records attributed to S Hall.

At least 55 records · Page 3Linked to original sources
PubMed2000

The use of school-based vaccination clinics to control varicella outbreaks in two schools.

School-based vaccination clinics were offered in 2 schools experiencing varicella outbreaks. The clinics raised coverage of susceptible children from 52.9% to 92.2% and from 68.8% to 85.3% in the 2 schools, respectively. Although routine immunization and school-entry requirements are the best strategies for preventing outbreaks, school-based vaccination clinics may greatly increase coverage and shorten outbreaks.

Adolescent↗
PubMed2000

Longterm methotrexate use in rheumatoid arthritis: 12 year followup of 460 patients treated in community practice.

OBJECTIVE: To extend our observations on the longterm tolerability of methotrexate (MTX) and reasons for discontinuation in a cohort of 460 patients with rheumatoid arthritis (RA). METHODS: We studied all patients with RA who started MTX before June 1986 and attended the community based private practices of 6 rheumatologists in Melbourne. Information to at least April 1, 1995, or within one year of death was updated from the patient's medical records to include MTX discontinuation and reasons for discontinuation. Addition of disease modifying antirheumatic drugs (DMARD) concomitant with MTX was noted. Survival analyses based upon life table methods were used with MTX discontinuation as the observable endpoint. Three different definitions of MTX discontinuation were used (1) according to whether the patient was taking the drug at last followup irrespective of any periods of temporary discontinuation; (2) MTX discontinuation for > 3 months considered to be a treatment endpoint; and (3) addition of concomitant DMARD considered to be only partial success of MTX (as a need for additional therapy to meet treatment goals). RESULTS: At 12 years, 53% of patients were continuing to take MTX (irrespective of any periods of temporary discontinuation). If discontinuation of the drug for 3 or more months was considered a treatment termination then 38% were still taking the drug at 12 years, and if addition of concomitant DMARD was regarded as a treatment endpoint only 17% of patients were continuing MTX at 12 years. Withdrawal for gastrointestinal toxicity declined over time but the risk of other adverse effects appeared to persist over time. CONCLUSION: MTX in RA is well tolerated over the longer term, with > 50% of patients starting MTX in a community based rheumatology private practice continuing to take it 12 years later. However, a substantial number of patients had 2nd line therapies added over this time. Monitoring for toxicity should continue throughout the course of therapy.

Antirheumatic Agents↗
PubMed1999

Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.

The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.

Animals↗
PubMed1999

Functionally different GPI proteins are organized in different domains on the neuronal surface.

We have investigated the organization, on the plasma membrane and in detergent-insoluble membrane vesicles, of two neuronal glycosylphosphatidylinositol-anchored (GPI) proteins: Thy-1, a negative regulator of transmembrane signalling; and prion protein, whose rapid endocytosis and Cu(2+) binding suggest that it functions in metal ion uptake. Prion protein occurred on the neuronal surface at high density in domains, located primarily at the cell body, which were relatively soluble in detergent. Thy-1, although much more abundantly expressed on neurons, occurred at lower density over much of the surface of neurites (and in lower abundance at the cell body) in domains that were highly resistant to detergent solubilization. Detergent-insoluble membrane vesicles contained Thy-1 at a density similar to that on the neuronal surface. Vesicles containing each protein could be separated by immunoaffinity isolation; lectin binding showed that they were enriched in different glycoproteins. Our results demonstrate a structural diversity of the domains occupied by functionally different GPI proteins.

Animals↗
PubMed1999

Prospective study of HTLV-I infection in an initially asymptomatic cohort.

A prospective clinical study of 20 initially asymptomatic HTLV-I-seropositive carriers was commenced in 1991 to determine the natural history of the infection in relation to HTLV-I proviral load, immune responses, and lymphocyte phenotype. Proviral load varied widely between carriers but was relatively constant within an individual over time. The lymphocyte phenotype and prevalence of activated lymphocytes were not predictive of disease and the magnitude of the cytotoxic T-lymphocyte response to HTLV-I was independent of proviral load. Incident conditions, some related to HTLV-I infection, including a case of HTLV-I-associated myelopathy (HAM), were documented in 9 carriers. Development of myelopathy and uveitis was associated with high peripheral blood HTLV-I proviral load that predated symptoms. Persistently high proviral load appears to predate the development of HTLV-I-associated inflammation in neuro-ophthalmic tissue.

Adult↗
PubMed1999

Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study.

BACKGROUND: Chlamydia pneumoniae commonly causes respiratory infection, is vasotropic, causes atherosclerosis in animal models, and has been found in human atheromas. Whether it plays a causal role in clinical coronary artery disease (CAD) and is amenable to antibiotic therapy is uncertain. METHODS AND RESULTS: CAD patients (n=302) who had a seropositive reaction to C pneumoniae (IgG titers >/=1:16) were randomized to receive placebo or azithromycin, 500 mg/d for 3 days, then 500 mg/wk for 3 months. Circulating markers of inflammation (C-reactive protein [CRP], interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha), C pneumoniae antibody titers, and cardiovascular events were assessed at 3 and 6 months. Treatment groups were balanced, with age averaging 64 (SD=10) years; 89% of the patients were male. Azithromycin reduced a global rank sum score of the 4 inflammatory markers at 6 (but not 3) months (P=0. 011) as well as the mean global rank sum change score: 531 (SD=201) for active drug and 587 (SD=190) for placebo (P=0.027). Specifically, change-score ranks were significantly lower for CRP (P=0.011) and IL-6 (P=0.043). Antibody titers were unchanged, and number of clinical cardiovascular events at 6 months did not differ by therapy (9 for active drug, 7 for placebo). Azithromycin decreased infections requiring antibiotics (1 versus 12 at 3 months, P=0.002) but caused more mild, primarily gastrointestinal, adverse effects (36 versus 17, P=0.003). CONCLUSIONS: In CAD patients positive for C pneumoniae antibodies, global tests of 4 markers of inflammation improved at 6 months with azithromycin. However, unlike another smaller study, no differences in antibody titers and clinical events were observed. Longer-term and larger studies of antichlamydial therapy are indicated.

Anti-Bacterial Agents↗
PubMed1999

Adult rat olfactory nerve ensheathing cells are effective promoters of adult central nervous system neurite outgrowth in coculture.

A coculture method is described for ensheathing glial cells from adult rat olfactory nerve, serving as a substrate for the regrowth of neurites from adult rat retinal ganglion cells. Immunocytochemically identified phenotypes present in primary cultures of olfactory nerve cells are described, and their ability to promote neurite outgrowth is compared with neonatal astrocytes and Schwann cells, with other nonglial cells, and with laminin. Ensheathing cell cultures were more effective than any other substrate tested and also directed the orientation of regrowing neurites. In comparison with cultured Schwann cells, which released neurotrophic factors into the culture medium, there was no evidence of a similar activity in ensheathing cell cultures. Combinations of ensheathing cell-conditioned medium and substrates of laminin, merosin, or 3T3 cells also failed to show the release of factors enhancing either survival or neurite outgrowth from retinal ganglion cells. Evidence is presented for a partial inhibition of neurite outgrowth in the presence of calcium channel antagonists or an intracellular calcium-chelating reagent. This provides evidence for a contribution from an intracellular calcium signaling mechanism, possibly implicating ensheathing cell adhesion molecules in promoting neurite outgrowth.

Animals↗
PubMed1999

Polymorphism of the vitamin D receptor gene and corticosteroid-related osteoporosis.

Corticosteroid therapy (CST) is associated with reduced intestinal calcium absorption, bone loss and increased fracture risk. As polymorphisms of the vitamin D receptor (VDR) gene may be associated with bone mineral density (BMD) and intestinal calcium absorption, we asked whether patients with a given VDR genotype receiving CST may be at increased or decreased risk for corticosteroid-related bone loss and osteoporosis. We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry in 193 women (50 premenopausal, 143 postmenopausal) and 70 men with rheumatoid arthritis (n = 44), obstructive airway diseases (n = 128) and other corticosteroid-treated diseases (n = 91). All patients received a cumulative dose greater than 1.8 g per year or a minimum of 5 mg daily of prednisolone or equivalent for at least 1 year. VDR alleles were typed by polymerase chain reaction assay based on the polymorphic BsmI and TaqI restriction sites. BMD in patients was expressed as a Z-score (mean +/- SEM) derived from age- and gender-matched controls. BMD was reduced in patients at the lumbar spine (bb, -0.52 +/- 0.12; Bb, -0.47 +/- 0.11; BB, -0.65 +/- 0.18 SD; p < 0.01), femoral neck (bb, -0.46 +/- 0.10; Bb, -0.34 +/- 0.10; BB, -0.54 +/- 0.14 SD; p < 0.01), Ward's triangle (bb, -0.44 +/- 0.10; Bb, -0.31 +/- 0.10; BB, -0.45 +/- 0.13 SD; p < 0.01), and trochanter (bb, -0.50 +/- 0.10; Bb, -0.30 +/- 0.10; BB, -0.44 +/- 0.14 SD; p < 0.01). However, there was no significant difference in the deficit in BMD in any of the genotypes, either before or after adjusting for age, sex, body mass index, disease type, age at onset of disease, disease duration, cumulative steroid dosage, smoking status and dietary calcium intake. Similarly, there were no detectable differences between the BsmI genotypes and the rate of bone loss in 79 patients with repeated BMD measurements at an interval of 4-48 months. The data suggest that the VDR genotypes may not be a means of identifying patients at greater risk of corticosteroid-related bone loss.

Adolescent↗
PubMed1999

Unique vascular morphology of the fourth aortic arches: possible implications for pathogenesis of type-B aortic arch interruption and anomalous right subclavian artery.

OBJECTIVE: Neural crest-derived cells were previously shown to participate in vessel wall formation of the great thoracic arteries, and their contribution was proposed to affect morphology and physiology of these vessels in the chick. The present investigation was undertaken to examine vascular differentiation and morphogenesis of the neural crest-derived aortic arches in mammals. METHODS: Using immunohistochemical markers for smooth muscle cell differentiation and a neurofilament marker, we examined morphogenesis of the great arteries in mice, ranging from embryonic day 11.5 to the adult. RESULTS: We observed that in the 4th aortic arch arteries early media formation differed from the other arteries, in that they almost completely lacked (or showed decreased) actin expression in certain areas. This discontinuity in actin expression persisted throughout much of foetal development, in the form of circular segments of cells displaying decreased staining for smooth muscle markers, both at the left and right side of the arterial tree. In adult mice, the 4th arch artery derivatives, segment B of the aortic arch and the proximal right subclavian artery, were observed to differ from adjoining vessels in their smooth muscle and elastic composition. Staining for neurofilaments revealed close association of the developing segments with apparent sensory afferent vascular innervation. CONCLUSION: The unique areas of the 4th arch artery identified here reflect the basic segmental patterning of the early embryonic pharyngeal arches. These segments correlate with sites that are predisposed to interruption or severe hypoplasia, and may thus reveal part of the aetiology of type-B aortic arch interruptions and arteria lusoria.

Actins↗
PubMed1999

Osmotic stress on dilution of acid injured Escherichia coli O157:H7.

To determine surviving numbers of Escherichia coli from cultures or food systems, dilution with 0.1% peptone is regularly used. Higher numbers of survivors could be obtained from an acid-treated culture if 0.5 mol l-1 sucrose was added to the 0.1% peptone. Sorbitol, glucose or sodium chloride, but not glycerol, could be used in place of sucrose. Using electron microscopy distinct differences could be seen between acid-treated and untreated cells. The osmolarity of the diluents ranged from 5 to 500 mosmol kg-1 H2O for the 0.5 mol l-1 sugar or glycerol solutions, to about 1000 mosmol kg-1 H2O for the salt solution. Maximum recovery diluent has an osmolarity of about 300 mosmol kg-1 H2O and resulted in recovery of similar numbers of injured cells as a 0.5 mol l-1 solution of sugar in 0.1% peptone. Taking into account the observed damage to acid-treated cells and the differences in osmolarity of the diluents, it is likely that dilution in 0.1% peptone imposed additional stress on the acid-injured cells which caused further cell damage. Dilution in a more osmotically stable solution alleviated this osmotic stress.

Bacteriological Techniques↗
PubMed1999

Identification of early self-injurious behaviour in young children with intellectual disability.

Very little is known about the early stages of self-injurious behaviour (SIB) in young children with developmental disabilities, even though there has been a great deal of research into the prevalence, assessment and treatment of well-established SIB in older individuals. In the present initial study, teachers in special schools for children under II years of age with severe intellectual disability and/or autism were asked to identify children who were beginning to show early self-injury (the index group). These children were then matched to classroom controls (of the same ability level and mobility), and teachers were interviewed about the children's behaviours and skills. The index children showed significantly more potential SIB than the control group children, but there was overlap between the groups in terms of percentage duration of potential SIB, suggesting that teachers do not find it easy to identify children with 'early' SIB. The index children's skills and problem behaviours, their sensory impairments and degree of autism did not differ significantly from those of the control group. When all the children showing any potential SIB were pooled together, it transpired that developmental age and degree of mobility were significantly correlated with percentage duration of SIB, suggesting that these characteristics may be important risk markers. The index children were also observed at 3-month intervals at school over the following 18 months and self-injury clearly escalated for some of the index children, while it did not do so for others. Using regression analysis, increases in SIB were shown to be associated only with the degree of concern expressed about the child's behaviour at time I by the teacher, no other variables predicting increases in SIB.

Age Factors↗
PubMed1999

Microscopic anatomy of the posterior interosseous and median nerves at sites of potential entrapment in the forearm.

We describe the macroscopic and microscopic anatomy of the posterior interosseous (PIN) and median nerves, at the arcade of Frohse and pronator arch respectively, in nerves obtained from five cadavers. Nerves were either constricted at sites of potential entrapment; appeared swollen proximal to these sites; or exhibited neither swelling nor constriction. Renaut bodies were present in all nerves. In the PIN, most Renaut bodies were found beneath a tendinous arcade of Frohse, whereas in the median nerve most were found proximal to the pronator arch. We propose that since Renaut bodies appear to displace normal endoneurial components, and may be associated with low-grade axonal drop-out, their presence may adversely affect the functional outcome of surgical decompression of either the PIN or median nerve.

Aged↗
PubMed1999

Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response.

Protective immunity to enterotoxigenic Escherichia coli (ETEC) is antibody (Ab) dependent; however, oral immunization with purified ETEC fimbriae fails to elicit protective immunity as a consequence of antigenic alteration by the gastrointestinal (GI) tract. Unless unaltered ETEC fimbriae can reach the inductive lymphoid tissues of the GI tract, immunity to ETEC cannot be induced. To produce immunity, live vectors, such as Salmonella typhimurium, can effectively target passenger antigens to the inductive lymphoid tissues of the GI tract. By convention, oral immunizations with Salmonella vectors induce CD4(+) T helper (Th) cell responses by gamma interferon (IFN-gamma)-dominated pathways both to the vector and passenger antigen, resulting in serum immunoglobulin G2a (IgG2a) and modest mucosal IgA Ab responses. In the present study, mice orally immunized with a Salmonella vector engineered to stably express ETEC colonization factor antigen I (CFA/I) showed initially elevated serum IgG1 and mucosal IgA anti-CFA/I Ab responses. As expected, mice orally immunized with an E. coli-CFA/I construct elicited poor anti-CFA/I Ab responses. In fact, the addition of cholera toxin during oral E. coli-CFA/I immunization failed to greatly enhance mucosal IgA Ab responses. Seven days after immunization with the Salmonella-CFA/I construct, cytokine-specific ELISPOT showed induction of predominant Th2-type responses in both mucosal and systemic immune compartments supporting the early IgG1 and IgA anti-CFA/I Abs. By 4 weeks, the Th cell response became Th1 cell dominant from the earlier Th2-type responses, as evidenced by increased mucosal and systemic IFN-gamma-producing T cells and a concomitant elevation of serum IgG2a Ab responses. This biphasic response offers an alternative strategy for directing Salmonella vector-induced host immunity along a Th2 cell-dependent pathway, allowing for early promotion of mucosal and systemic Abs.

Animals↗
PubMed1999

Common pain scenarios.

BACKGROUND: Vertebral fractures and fibromyalgia, while very different and unrelated clinical conditions, are common pain conditions that can, at times, be difficult to diagnose and manage. OBJECTIVE: To discuss the investigation and treatment of two common pain conditions. DISCUSSION: Following a structured program for assessment and treatment, most people with both of these conditions can experience substantial improvement in the quality of their life.

Adult↗
PubMed1998

Pseudarthrosis of the lumbar spine. Outcome after circumferential fusion.

STUDY DESIGN: Twenty-five patients with a pseudarthrosis after previous spinal fusion surgery were reviewed after a circumferential fusion was performed. OBJECTIVES: To determine the fusion rate and its relation to outcome, i.e., pain reduction and return to work, and associated complications. SUMMARY OF BACKGROUND DATA: Circumferential fusion has become a common procedure with more patients undergoing multiple operations. This operation is thought to improve the fusion rate with a low complication rate. However, the procedure has not been evaluated specifically for the management of pseudarthrosis. METHODS: Twenty-five patients were reviewed regarding age, gender, smoking status, previous back surgeries, extent of leg and back pain, occupation, levels of surgery, type of instrumentation, blood loss, and complications. A minimum follow-up period of 2 years included evaluation of radiographs, pain levels, medication, and return to work. RESULTS: Twenty percent of patients were heavy smokers. An average of 2.2 previous procedures had been performed, and the average follow-up period was 2.7 years. Eighty percent of patients underwent multiple-level fusions. A solid fusion was achieved in 100%. Complications included two painful instrumentation devices requiring removal, one retroperitoneal hematoma, one anterior abdominal wall dehiscence, and one case of pneumonia. Pain scores improved from 7.4 to 4.7 for back pain, and 5.4 to 2.8 for leg pain, respectively. Both improvements were statistically significant (P < 0.01 and 0.003, respectively). However, only 52% of patients reduced their pain by a full category. Forty-one percent were still taking narcotics intermittently or consistently, and 53% returned to work or were actively seeking employment. DISCUSSION: A fusion rate of 100% was noted in the face of factors often placing patients at high risk for developing a pseudarthrosis, namely multiple levels of previous spinal surgery, including previous pseudarthrosis, and a habit of heavy smoking. Complications were few. However, the satisfactory outcome rate was only somewhat better than 50%, based on a lack of substantial pain improvement and return to work.

Bone Screws↗
PubMed1998

Evidence that Ca2+-activated K+ channels play a major role in mediating the vascular effects of iloprost and cicaprost.

The role of K+ channels in mediating vasorelaxation induced by two prostacyclin analogues was investigated in guinea-pig aorta. Iloprost caused substantial relaxation of tissues contracted with phenylephrine or 25 mM K+ but not 60 mM K+. In endothelial-denuded tissues, maximal relaxations to iloprost, cicaprost or isoprenaline were inhibited by approximately 40-50% with tetraethylammonium or iberiotoxin, both blockers of large conductance Ca2+-activated K+ (BKCa) channels. In contrast, the response to forskolin, an activator of adenylate cyclase was marginally inhibited by tetraethylammonium. The K(ATP) channel blocker, glibenclamide significantly augmented the response to iloprost but not cicaprost. These effects were largely inhibited by the EP1 receptor antagonist, 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid 2-[1-oxo-3(4-pyridinyl)propyl]hydrazide, monohydrochloride (SC-51089) and partially by indomethacin, suggesting that iloprost relaxation is counterbalanced by activation of EP1 receptors, in part through a constrictor prostaglandin. We conclude that BKCa channels play an important role in mediating the effects of iloprost and cicaprost and raises the possibility that cyclic AMP-independent pathways might be involved.

Animals↗
PubMed1998

Excitatory action of N-methyl-D-aspartate on the rat locus coeruleus is mediated by nitric oxide: an in vivo voltammetric study.

Biochemical, electrophysiological and behavioural studies have provided evidence that activation of N-methyl-D-aspartate (NMDA) receptors contributes to the hyperactivity of noradrenergic neurons of the locus coeruleus (LC) in precipitated opioid withdrawal. Recently, it was demonstrated that central administration of nitric oxide (NO) synthase inhibitors suppresses this hyperactivity suggesting that NO mediates the NMDA receptor activation of LC in opioid withdrawal. Using a combination of microdialysis and in vivo voltammetry, this study examined whether local application of NMDA to the LC in opioid naive animals mimics the NO-dependent LC response seen in opioid withdrawal. In the urethane anaesthetized rat, perfusion of the LC (2 microliters min-1) with a solution of NMDA (5 mmol) via a microdialysis probe for 9 min resulted in a rapid and robust increase (290.1 +/- 32.2% above baseline) in the catechol oxidation current (CA.OC) recorded from the LC using differential normal pulse voltammetry (DNPV). The NMDA microdialysis also produced a large increase in the blood pressure (150.4 +/- 6.9% above baseline). An injection of the non-competitive NMDA receptor antagonist (+)MK-801 (0.5 mg kg-1 i.v.), given 45 min after the start of NMDA application, rapidly returned both the CA.OC signal and the blood pressure response to baseline levels. Pretreatment of animals with intraventricular nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) (100 micrograms) significantly inhibited NOS activity in the LC, PAG-PVG and cerebellum. This dose of L-NAME, administered prior to application of NMDA by microdialysis abolished the NMDA-induced rise in the CA.OC recorded in the LC and the increase in systolic blood pressure. The results show that in voltammetry experiments, NMDA produces hyperactivity of LC and hypertension, responses that are dependent upon the synthesis of NO. Thus, in opioid naive rats, regional NMDA application via microdialysis mimics characteristics of the LC response that occur during the antagonist-precipitated opioid withdrawal.

Animals↗