Legislators realize need to eliminate proposed 15% cut for home health.
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Biomedical subjects
Publications and source records attributed to L Young.
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BACKGROUND: The objective of this study was to evaluate the epidemiology of antibiotic-resistant organisms among patients with spinal cord injury admitted to an acute rehabilitation unit for the first time. METHODS: After informed consent, 63 patients with spinal cord injury admitted to an acute rehabilitation unit between January 1997 and July 1998 had surveillance cultures (nares, urine, wounds or ulcers, and perineum) done on admission and every 2 weeks thereafter until discharge or as long as 6 weeks after admission. RESULTS: Of the 4 surveillance sites, perineal cultures most commonly grew one or more potential pathogens; however, antibiotic-resistant organisms were most often isolated from wounds or ulcers and least often in urine cultures. Staphylococcus aureus (methicillin-sensitive plus methicillin-resistant) and enterococci represented 44% of all organisms isolated in surveillance cultures. Methicillin-resistant S aureus was the most common resistant organism isolated. Less than 30% of the gram-negative bacilli isolated were considered antibiotic-resistant strains. Nosocomial infection as a result of any resistant organism was infrequent. After adjusting for various confounding factors in a logistic regression model, only the presence of a pressure ulcer predicted carriage of any resistant organism on admission to the rehabilitation unit. Acquisition of a resistant organism after admission to the unit at one or more surveillance sites occurred in 8 (22%) of 36 patients not colonized on admission. CONCLUSIONS: Methicillin-resistant S aureus was the most common resistant organism colonizing patients with spinal cord injury at the time of admission to an acute rehabilitation unit and throughout their stay. However, acquisition of any resistant organism after admission was uncommon on this unit, which used Standard Precautions in the routine care of patients. These findings have implications for the type of isolation procedures on acute rehabilitation units. The low rate of acquisition and infection with MRSA after admission argues against attempts at eradication as a method of control.
The objectives of this study were to define the epidemiology of nosocomial bacterial colonization and infection and to define predictors of nosocomial infection among a cohort (n=423) of admissions to an acute rehabilitation unit. Overall, methicillin-resistant Staphylococcus aureus (MRSA) and enterococci were the most commonly identified colonizing organisms. Escherichia coli and Pseudomonas aeruginosa were the most commonly identified colonizing gram-negative bacilli. During 70 (16.5%) of the 423 hospitalizations in the unit, 94 nosocomial infections occurred. The most common infections were those of the urinary tract (30% of 94 infections) or a surgical site (17%), Clostridium difficile diarrhea (15%), and bloodstream infection (12.8%). Antibiotic-resistant bacteria most commonly caused bloodstream infection (41.7%) and surgical site infection (56.3%). Independent predictors of nosocomial infection at the time of admission were functional status (measured with the functional independence measure), APACHE III score, and spinal cord injury. In conclusion, gram-positive organisms were the predominant strains causing nosocomial colonization and infection. The logistic model, if verified, may be useful in defining patients who should be targeted for measures to prevent nosocomial infection.
Adenosine released during cardiac ischemia exerts a marked protective effect in the heart that is mediated by the A(1) and A(3) subtypes of adenosine receptors. The signaling pathways activated by these adenosine receptors have now been characterized in a chick embryo ventricular myocyte culture model of cardioprotection against ischemia. Selective A(1) and A(3) receptor agonists were shown to activate phospholipases C and D, respectively, to achieve their distinct cardioprotective effects. The specificity of the A(3) receptor-phospholipase D interaction was also demonstrated in chick embryo atrial myocytes (which do not express endogenous A(3) receptors) that had been transfected with a vector encoding the human A(3) receptor. Activation of both endogenous A(1) and A(3) receptors in ventricular myocytes resulted in a protective response greater than that induced by stimulation of either receptor alone. Agonists that activate both adenosine A(1) and A(3) receptors may thus prove beneficial for the treatment of myocardial ischemia.
The incidence of hepatitis A virus (HAV) in south-eastern Sydney is one of the highest in Australia with large outbreaks previously associated with male-to-male sexual contact. We report HAV notification trends over the period 1 June 1997 to 31 May 1999 for this location. In the first twelve-month period, 233 cases were notified (crude rate 30.5/100,000 per year) with a peak incidence of 110/100,000 in males aged 20-39 years. Over 60% of male cases reported male-to-male sexual contact. The notification rate (crude rate 15.5/100,000) and proportion of males (61%) was considerably lower in the following twelve month period with 118 cases notified. Less than a third of males reported male-to-male sexual contact. An outbreak (n = 45) of HAV among illicit drug users and their contacts was detected in December 1998. The transmission of HAV remains endemic in south-eastern Sydney. Vaccination among high-risk groups remains an important preventive strategy.
Laser manipulation of neutral atoms has been used to count individual krypton-85 and krypton-81 atoms present in a natural krypton gas sample with isotopic abundances in the range of 10(-11) and 10(-13), respectively. This method of isotope trace analysis is free of contamination from other isotopes and elements and can be applied to several different isotope tracers for a wide range of applications. The demonstrated detection efficiency is 1 x 10(-7). System improvements could increase the efficiency by many orders of magnitude.
A simple and rapid enzyme-linked immunosorbent assay (ELISA) has been developed to provide an alternative to cell counting to detect increases in cell survival in primary neuronal cultures. This sensitive assay has the advantage of being less time consuming and labour intensive than cell counting, can be used to quantify cell survival and is more accurate than estimation methods of counting. The ELISA uses an antibody raised to GAP-43, a growth-associated protein which is strongly expressed by developing and regenerating neurones. The effects of nerve growth factor (NGF), neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) on GAP-43 immunoreactivity in dissociated primary cultures of rat and chick dorsal root ganglia have been compared to results obtained by cell counting. Data show that human NGF produced the greatest increase in GAP-43-immunoreactive neurones in both species; this increase in immunoreactivity correlated well with the increased survival shown by cell count data. Results prove that the ELISA can also be used to accurately detect small changes in cell survival as seen with NT-3 and BDNF, or potentiation of the effects obtained with the trophic factor NT-3. In conclusion, this ELISA may be a useful tool to detect neurotrophic effects of unknown agents or novel neurotrophins.
Neurite outgrowth from dorsal root ganglion (DRG) explants is a method of evaluating neurotrophic activity of growth factors and neurotrophin mimetics. The drawbacks to this approach are the difficulties in quantifying the response. Neurite counts are time consuming and labour intensive, and the accuracy is often questionable due to branching and fasciculation of the neurites. We report here a method of semi-quantitative analysis of neurite outgrowth from chick DRG explants, using image analysis to quantify the area occupied by neurites emanating from the ganglion. This method is rapid, takes into account both the length and number of neurites, and is unaffected by neurite fasciculation or branching. Primary explants of chick DRGs were treated with the neurotrophins nerve growth factor (NGF) or neurotrophin-3 (NT-3) and with the compound K252a. K252b was tested for potentiation of the response to NT-3. The results show a dose dependent outgrowth of neurites from explants treated with NGF, NT-3 and K252a, and potentiation of the NT-3 response by K252b. These responses were quantified by neurite area quantification using image analysis. We conclude that neurite area measurement using image analysis provides a robust means of evaluating neurotrophic activity of growth factors and neurotrophin mimetics in vitro.
The objective of this study was to describe the epidemiology and public health response to an apparent cluster of Neisseria meningitidis serogroup C infection in university students in a residential college. A conventional epidemiological approach was taken, supported by routine and novel diagnostic techniques. Over the two days of 21-22 August 1997, three cases of suspected meningococcal infection were notified from a residential college complex at a university campus in the Sydney metropolitan area. Neisseria meningitidis was grown from throat swabs of all three cases, and was isolated from the blood of one case only. All three isolates were typed as C:2a:P1.5,2. Seroconversion was demonstrated by a novel method in the three cases. Rifampicin was given to all identified contacts. Forty-seven days after the index case, a 19 year old female living in the same complex was diagnosed with bacterial meningitis, and identified contacts given rifampicin. When this isolate was found to be group C, it was decided to vaccinate residents of the college complex. Genotyping and serotyping (C:2a:P1.5) later revealed the fourth isolate to be distinct from isolates from Cases 1-3. In conclusion the authors note that Australia's increasing capacity to type meningococcal strains is essential to understanding the epidemiology of this disease. Furthermore, typing information is of critical importance when decisions are made regarding mass vaccination. As early antibiotic treatment may inhibit isolation of the organism, development of novel approaches to diagnosis and typing should be supported.
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This study aimed to investigate the effects of the subdermal levonorgestrel contraceptive implant Norplant on endometrial vascular density at different durations of exposure, and the relationship between endometrial histology, vascular density, and bleeding patterns. A prospective controlled trial of Norplant implant users compared endometrial vascular density in biopsies taken before and after Norplant implant insertion. A total of 34 women with regular menstrual cycles requesting long-term contraception were recruited at the Sydney Centre for Reproductive Health Research, Australia. A significant increase in mean endometrial microvascular density was observed from as early as 3 weeks after insertion of Norplant implants. Vascular density was increased from a control secretory phase value of 189.6 (7.0 vessels/mm2 (+/- SEM) to 253.80 +/- 7 vessels/mm2 at 2-13 weeks of Norplant implant exposure (t ratio = 2.08, p = 0.01) and 212.7 +/- 12.9 vessels/mm2 at 14-42 weeks of exposure (t ratio = 2.03, p = 0.02). In those with atrophic endometrium, or in whom myometrium and basalis only were found in biopsies (20 of 66, 30%), mean endometrial vascular density was increased at 273.1 +/- 16.1 vessels/mm2 compared with 210.9 +/- 11.7 vessels/mm2 in other histological groups (F ratio = 9.74, p = 0.0028). Bleeding and spotting in the previous 30 days were less common in those with this histological appearance at a mean of 4.95 days compared with 8.22 days. This is the first study to assess endometrial vascular density in the early months of Norplant implant use. The findings suggest that the endometrial vasculature is profoundly altered in the early months of Norplant implant exposure when bleeding problems are most common.
The putative neurotrophic effects of the immunophilin ligand GPI-1046 were evaluated in established experimental systems of neuron survival and axon growth in vitro and in vivo. GPI-1046 marginally increased neurite outgrowth of chick dorsal root ganglia in culture under conditions where a very robust effect of nerve growth factor was seen. GPI-1046 failed to protect dopaminergic neurons from 1-methyl-4-phenylpyridinium in culture or to protect cultured cortical neurons from experimentally induced apoptosis in vitro. In adult rats in vivo, daily administration of GPI-1046 (10 mg/kg, s.c.) for three days enhanced the maximal regeneration distance of both motor and large myelinated sensory axons measured using an electrophysiological assay. However, detailed morphometric analysis of these animals failed to provide evidence for an increase in axon numbers in GPI-1046-treated animals. The ability of GPI-1046 to promote the recovery of dopaminergic function following unilateral 6-hydroxydopamine lesions of the substantia nigra was also tested in rats. In the first study, the duration of amphetamine (3 mg/kg, s.c.)-induced circling, but not the maximal number of rotations, was significantly reduced in animals treated with GPI-1046 for five days (10 mg/kg/day). In a second study, testing the effects of delayed GPI-1046 administration, chronic treatment with GPI-1046 (10 mg/kg/day) for two weeks, beginning one month after surgery, did not alter circling responses. Morphometric analysis failed to reveal any changes in either the density of tyrosine hyroxylase-positive fibres in dopaminergic target areas or in cell numbers in the substantia nigra in both experiments. Thus, while GPI-1046 produced marginal effects on neurite outgrowth in dorsal root ganglia cultures and on functional paramaters of nerve regeneration in vivo, we failed to obtain evidence in support of the notion of a general neuroprotective effect of the compound or for an effect on morphologic nerve regeneration in vivo.
Two aquaporin genes were isolated from a cDNA library of canola (Brassica napus L.). The first aquaporin, BnPIP1 of 1094 bp, encoding a putative polypeptide of 287 amino acids with a predicted molecular mass of 30.4 kDa and a pI of 7.8, belongs to the family of plasma membrane intrinsic protein (PIPs) aquaporins. The B. napus aquaporin showed 85-94% identity to the Arabidopsis thaliana PIPs. ABA priming of seed induced high levels of BnPIP1 transcript which remained after subsequent re-drying of the seed. The second aquaporin, Bny-TIP2 of 1020 bp, encoded a putative polypeptide of 253 amino acids with a predicted molecular mass of 25.8 kDa and a pI of 5.8. Bngamma-TIP2 showed 83-90% identity to gamma-TIP genes from a variety of plant species. Bngamma-TIP2 was expressed only when radicle protrusion occurred in either untreated or primed seeds. Seeds primed with PEG or ABA germinated earlier and showed a higher final percentage of germination than unprimed seed, particularly under salt and osmotic stresses at low temperature. Transcripts of both BnPIP1 and Bngamma-TIP2 genes were present earlier during germination of primed seeds than non-primed seed. From these results, we conclude that BnPIP1 is related to the water transportation required for enzymatic metabolism of storage nutrients at the early stages of canola seed germination whereas Bngamma-TIP2 expression is related to cell growth associated with radicle protrusion. Priming induced the expression of BnPIP1 but had no effect on Bngamma-TIP2.
Australia's population is ageing. Statistics predict that by the year 2021, 17.8% of our population will be over the age of 65 years. These statistics are reflected in most Western nations. The elderly represent an increasing proportion of emergency department patients. They are generally more acute on presentation, they get admitted more frequently, and account for an increasing proportion of admissions to intensive care units. The elderly trauma patient will increasingly consume more resources than patients from any other age group. There are significant differences in physiology and response to trauma between the elderly patient and the young. Airway compromises, a decrease in lung compliance, a change in cardiovascular haemostasis and the prevalence of pre-existing disease all contribute to increase morbidity and mortality in a patient with an already limited physiological reserve. Many studies demonstrate an increased mortality in hospitalized elderly trauma patients. For those who die from traumatic insult, death is mainly due to multiorgan system failure. The long-term functional outcome of the elderly trauma patient has been investigated by a number of authors. One study showed that only 8% of survivors returned to independent living 1 year post-polytrauma. Another more encouraging study showed that 89% of survivors of blunt multiple trauma after 38 months were independent and living at home. Ethical issues have been raised regarding the appropriateness of care for the severely injured elderly patient given today's ever-shrinking hospital finances and bed shortages. Today's environment is very challenging as frequently, the clinician is forced to make an economic decision on who will take the last critical care bed, which is a far from optimal situation.
Progestogen-only contraception is almost invariably associated with changes in menstrual bleeding patterns. Changes in the endometrial vasculature, and in particular an increase in vascular fragility, may contribute to this bleeding. In this study, endometrial vascular density and endothelial cell basement membrane components were examined using immunohistochemistry before and after insertion of Norplant. Endometrial vascular density was increased from a mean (+/- SEM) of 189.6 +/- 7.0 vessels/mm2 during the control cycle to 253.9 +/- 80.7 vessels/mm2 at 2-13 weeks of Norplant exposure, and to 212.7 +/- 12.9 vessels/mm2 at 14-42 weeks. During the control cycle, a mean of 161.4 +/- 4.5 vessels/mm2 stained for collagen IV (85% of all vessels), while at 2-13 weeks, 144.5 +/- 13.0 vessels/mm2 stained for collagen IV (57% of all vessels) (t ratio = 2.08, P = 0.0057). By 14-42 weeks, 71% of vessels (151.0 +/- 9.8) vessels/mm2 were surrounded by collagen IV. This was not significantly different from control values (t ratio = 2.03). Endometrial vascular laminin was also reduced following Norplant insertion, from a mean of 176.0 +/- 4.2 vessels/mm2 in the control cycle (93% of vessels), to 156.3 +/- 6.7 vessels/mm2 at 2-13 weeks of exposure (57% of vessels) (t ratio = 2.08, P = 0.01). By 14-42 weeks of exposure to Norplant, 162.5 +/- 9 vessels/mm2 (76%) stained for laminin. This was not significantly different from control values (t ratio = 2.04). Endometrial vascular heparan sulphate proteoglycan (HSPG) was reduced from 58.6 +/- 3.0 vessels/mm2 during the control cycle (31% of vessels) to 43.6 +/- 5.6 vessels/mm2 (only 17% of vessels) at 2-13 weeks (t ratio = 2.08, P = 0.025). At 14-42 weeks, only 19% of vessels stained for HSPG (41.3 +/- 5.8 vessels/mm2; t ratio = 2.04, P = 0.009).
K-252b, a member of the staurosporine family of protein kinase inhibitors, selectively potentiates the activation of the nerve growth factor receptor, TrkA, by a nonpreferred ligand, neurotrophin-3 (NT-3), in a variety of cell types. At higher (micromolar) concentrations of K-252b, an inhibitory effect occurs because of the inhibitory action of K-252b on the Trk kinase. By examining analogs of K-252b, we identified the compound L-753,000 (NB-506), which potentiates the action of NT-3 on TrkA but is devoid of the inhibitory action of K-252b. L-753,000 was effective at nanomolar concentrations in a Chinese hamster ovary cell line that expressed TrkA but was devoid of p75, the low-affinity neurotrophin receptor. L-753,000 also potentiated the activation of mitogen-activating protein kinase signaling (downstream from Trk activation) by NT-3 in this cell line. Although L-753,000, like K-252b, had a negligible effect in the absence of NT-3, the compound was found to potentiate NT-3-induced survival in both rat and chick primary cultures of dissociated dorsal root ganglia (DRG) and on neurite outgrowth of chick DRG explants. Unlike K-252b, which at micromolar concentrations inhibits the survival response of NT-3 in dissociated rat DRG, L-753,000 continued to potentiate the actions of NT-3 up to a concentration of 10 microM. Furthermore, the compound, unlike K-252b, did not inhibit an unrelated protein kinase, protein kinase C, at concentrations up to 10 microM. Because L-753, 000 selectively potentiates the NT-3-induced stimulation of TrkA without inhibiting Trks and other protein kinases, it represents a novel class of selective modifiers of neurotrophin actions.