Biomedical subjects
Publications and source records attributed to A Jackson.
Nurses need to be aware of their level of accountability when performing i.v. cannulation. Nurse cannulation should be incorporated into practice as part of holistic patient care. When introducing nurse cannulation into a department, a commitment is required from the individual nurse and the organisation. i.v. cannulation is a skilled technique, best performed as a staged process.
The purpose of this study was to assess the nasal volume and the cross-sectional areas of the nose in 7 to 12 year old children, and to identify factors that may influence those parameters. Specifically we investigated the effect of passive smoking at home, body mass, presence of allergies, and history of removal of the tonsils, controlling for the age, gender and race of the child. Fifty-four children participated in the study. Five consecutive nasal measurements were taken from each nostril in one visit, using the acoustic reflection technique (acoustic rhinometry). The nasal volume and the cross-sectional area were computed from the nasal readings. We observed that the minimal cross sectional area is located at the laminal valve, which has been considered one of the main anatomical structures that affect the regulation of breathing in the anterior part of the nose. We also concluded that body mass and exposure to environmental tobacco by-products play a significant role in determining reductions in a child's nasal volume. The clinical significance of such a finding and its effect to the normal craniofacial development of a growing child may force parents to reconsider smoking while at home.
Two distinct regimens of weekly chemotherapy for hormone-refractory prostate cancer were combined in an alternating schedule and tested in a Phase II trial to determine efficacy and toxic effects. Forty-six patients with hormone-refractory prostate cancer and rising prostate-specific antigen (PSA) levels entered the trial. Therapy consisted of doxorubicin (20 mg/m2/week) plus oral ketoconazole (400 mg three times a day) given at weeks 1, 3, and 5 and vinblastine (5 mg/m2/week) plus oral estramustine (140 mg three times a day) given at weeks 2, 4, and 6. No therapy was given at weeks 7 and 8. Replacement doses of hydrocortisone were administered throughout treatment to counteract potential adrenal insufficiency secondary to the ketoconazole. In 67% of patients (31 of 46), the PSA declined by 50% or greater for a minimum duration of 8 weeks (95% confidence interval, 52-80%). Among the 16 patients with measurable soft tissue disease, there were 12 responses (75%; 95% confidence interval, 47-92%). The median duration of response was 8. 4 months (1.8-14.9). The median survival for the entire group was 19 months. The median survival of PSA responders has not been reached, whereas that of nonresponders was 13 months (P = 0.010). Seventy-six percent of symptomatic patients noted improvement. Hematological toxicity was modest and was managed without growth factors. Peripheral edema (49%) and deep venous thrombosis (18%) were the most common nonhematological toxicities. The alternating weekly regimen of chemohormonal therapy is active for hormone-refractory prostate cancer, providing a high rate of symptom control, soft tissue response, and PSA decline.
We have shown in lung recipients that high levels of peripheral blood allogeneic microchimerism at 12 to 18 months posttransplant correlated with donor antigen-specific hyporeactivity (i.e., decreased proliferative response to donor antigen in MLC while response to 3rd-party cells remains unchanged); both parameters correlated with an obliterative bronchiolitis (OB)-free state. We have expanded these studies to determine any association of sequential microchimerism levels with concomitant clinical events. In this preliminary study of 7 lung recipients, we used limiting-dilution PCR to quantify peripheral blood microchimerism at serial timepoints ranging from 3 to >48 months posttransplant. These levels were compared with a variety of immunologic and clinical parameters: acute rejection, CMV infection, OB, donor antigen-specific hyporeactivity, and pulmonary function. Pulmonary function was measured per the International Society of Heart and Lung Transplantation: "current FEV1/ baseline FEV1" (FEV1: forced expiratory volume in 1 second). Of the clinical parameters, the association between microchimerism and pulmonary function was the most striking. We observed dynamic patterns of peripheral microchimerism, which reflected the general rise and fall of FEV1. In all 7 recipients, chimerism and FEV1 were high very early posttransplant, then dropped at various rates and to various degrees. After its initial decline, microchimerism increased with FEV1 for the 1 hyporesponsive recipient; for the other 6 recipients, both values declined. These results illustrate, for the first time, that the fluctuation of peripheral blood microchimerism levels is associated with the recipient's clinical condition.
As a glycoprotein hormone, human chorionic gonadotropic (hCG) is not a single molecular entity but this term rather comprises an array of molecular variants such as hCG, hCG beta, hCGn, hCG beta n, hCG beta cf, -CTPhCG, hCG beta CTP, deglyhCG, asialohCG, hCGav and the closely related molecules hLH, hLH beta and hLH beta ef. The advent of monoclonal antibodies (MCA), the availability of ultrasensitive detection systems and the recent determination of the crystal structure of hCG, made it possible to design special purpose diagnostic and clinical research immunoassays for hCG-like molecules. For more than a decade we and others have tried to refine epitope maps for hCG and related molecules by means of a large panel of MCA, naturally occurring metabolic variants of hCG (hCGn, hCG beta, hCG alpha, hCG beta cf, hCG beta CTP), homologous hormones and subunits of various species (e.g. hLH, hLH beta, hFSH, hTSH, oLH, rLH beta), chemically modified molecules (deglyhCG, asialohCG, tryptic and chymotryptic hCG beta and hCG alpha fragments) and synthetic peptides (octapeptides and longer). It appeared that all epitopes on molecular hCG-variants recognized by our MCA are determined by the protein backbone. Except for the two major epitopes on hCG beta CTP and parts of two antigenic domains on hCG alpha, epitopes on hCG-derived molecules are determined by the tertiary and quarternary structure. Operationally useful descriptive epitope maps were designed including information on assay suitability of antigenic determinants. On this basis we established ultrasensitive time-resolved fluoroimmuno-assays for hCG, hCG and hCGn, hCG beta and hCG beta n and hCG beta cf, hCG alpha and additional assays recognizing different spectra of hCG-variants. Such assay have been applied by us and others to the detection of pregnancy, early pregnancy loss, choriocarcinoma, testicular cancer, other cancers and prenatal diagnosis. However, as the molecular structure of many epitopes utilized in immunoassays of different laboratories was not resolved, comparability of results was not satisfactory. Consequently, attempts were made to compare schematic epitope maps from different research institutions. The situation has been much improved by solving the three-dimensional (3D) structure of hCG. It has been shown that hCG is a member of the structural superfamily of cystine knot growth factors like NGF, PDGF-B and TGF-beta. Each of its subunits is stabilized in its topology by three disulfide bonds forming a cystine knot. Moreover, it turned out that the disulfide bridges in their majority have previously been wrongly assigned. Computer molecular modeling of crystallographic coordinates of hCG and subsequent selective combined--PCR-based and immunological--mutational analyses of hCG beta expressed via the transmembrane region of a MHC molecule made it possible to more precisely localize epitopes on hCG-derived molecules. Although the entire surface of hCG has to be regarded as potentially immunogenic there seems to be hot spots where epitopes are clustered in antigenic domains. These are located on the first and third loops protuding from the cystine knots of both subunits and are possibly centered around the knot itself. Ultimate answers on epitope localizations will be given by the crystal structure determination of hCG complexed with different Fabs.
Autocrine/paracrine stimulation of cell growth by members of the fibroblast growth factor (FGF) family of polypeptides is dependent upon extracellular interactions with specific high affinity receptors at the cell surface. Acidic FGF (FGF-1) lacks a classical signal sequence for secretion, suggesting that intrinsic levels of this mitogen may not stimulate cell growth and utilizes a non-classical pathway to gain access to the extracellular compartment. To evaluate the biological potential of intracellular FGF-1 more rigorously, human cDNA sequences for the growth factor were introduced into primary murine embryonic fibroblasts using retrovirally mediated gene transfer. Heparin affinity, Western analysis, mitogenic assays, in situ immunohistochemical techniques, induction of tyrosine phosphorylation and antibody inhibition studies were used to demonstrate functionality of the FGF-1 transgene in this experimental model. Under normal culture conditions, cells constitutively expressing intracellular FGF-1 exhibited a slight growth advantage. In contrast, when maintained in reduced serum, these cells adopted a transformed phenotype and demonstrated an enhanced growth potential, induction of FGF-specific phosphotyrosyl proteins and the nuclear association of the growth factor. Analysis of the conditioned media from these stressed cells indicated that serum starvation induces the secretion of FGF-1 as latent high molecular mass complexes requiring reducing agents to activate its full biological potential.
About 40% (350 kb) of the human MHC class II region has been sequenced and a coordinated effort to sequence the entire MHC is underway. In addition to the coding information (22 genes/pseudogenes), the non-coding sequences reveal novel information on the organisation and evolution of the MHC as demonstrated here by the example of a 200 kb contig that has been analysed for local and global features. In conjunction with cross-species comparisons, our results present new evidence on the structure of isochores, the evolutionary dynamics of repeat-mediated recombination and its effect on certain MHC encoded genes, and a higher than average degree of natural polymorphism that has implications for sequencing the human genome. We also report the finding of a class I-related pseudogene (HLA-ZI) in the middle of the class II region, which provides the first direct evidence for DNA exchange between these two related regions in man.
The effects of repeated treatment with estradiol benzoate to ovariectomized rats on the lordosis-inhibiting action of the 5-HT1A agonist, 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT), were examined. In the first week of hormonal priming, when rats were injected with estradiol benzoate (2.5-50 micrograms) plus 500 micrograms progesterone, all groups were inhibited by intraperitoneal (i.p.) treatment with 0.15 mg/kg 8-OH-DPAT. However, in the second week of hormone treatment, the effects of 8-OH-DPAT on lordosis behavior were dose-dependently attenuated by estradiol benzoate. Such attenuation was present when animals were treated with estradiol benzoate on the day of ovariectomy and when the first estradiol benzoate treatment was delayed for 2 weeks after ovariectomy. At least 3 days after the first injection with estradiol benzoate were required before the inhibitory effects of i.p. treatment with 8-OH-DPAT were attenuated. Although the magnitude was reduced, higher doses of 8-OH-DPAT (0.4, 0.45, and 0.5 mg/kg) continued to inhibit lordosis behavior even after the second hormonal priming. When 8-OH-DPAT was infused directly into the ventromedial nucleus of the hypothalamus (VMN), the lordosis-inhibiting effects of 8-OH-DPAT were reduced as soon as 2 days after the first estradiol benzoate injection. These data are interpreted as evidence that (1) estradiol benzoate's attenuation of the effects of 8-OH-DPAT on lordosis behavior is both dose and time dependent; (2) 5-HT1A receptor action in the VMN is attenuated by the hormone treatment; and (3) female gonadal hormones reduce the potency of the 5-HT1A agonist, 8-OH-DPAT, in inhibiting lordosis behavior.
While considerable information is available regarding American Vietnam veterans, surprisingly little has appeared concerning veterans of other nationalities who served in the Vietnam war. This paper provides a preliminary profile of help-seeking Australian veterans in order to afford a comparison with the available American data. Collected in the context of a review of the Vietnam Veterans Counselling Service (VVCS), demographic data suggest that the client population is similar in many ways to that of the American posttraumatic stress disorder (PTSD) Clinical Teams. Problems commonly reported by clients of VVCS included posttraumatic stress, relationship difficulties, anxiety, depression, and problems with pensions and benefits. A postal survey of a sub-sample of current clients revealed a mean score on the Combat Exposure Scale of 19.27 and a mean score on the Mississippi Scale for PTSD of 118.43. Again, these findings are broadly comparable with those of American help-seeking veterans.
We sequenced the human MB1 gene from a cosmid clone mapping to chromosome 14q11.2-12. The gene spans about 6 kilobases and contains three exons and two introns. There was no evidence of an alternative leader exon, which is a characteristic of the major histocompatibility complex (MHC)-encoded LMP7 gene, the closest relative of MB1, with which it shares 67% amino acid identity. Conceptual translation of the 5' end of the gene calls for a cleaved leader sequence of 59 amino acids, consistent with western blot data. None of the MB1 gene's three exons were coincident with any of the six exons in LMP7. In contrast, in the delta-encoding gene and its counterpart, the MHC-encoded LMP2 gene (59% amino acid identity), all six exons are arranged at equivalent positions in respect to the coding frame. The unique structure of MB1 implies a separate origin or different selection pressures acting at this particular locus. DNA repeat analysis provides information on the minimum time of separation of the MB1/LMP7 pair of genes.
The effects of the AMPA-receptor antagonists NBQX and GYKI 52466 were compared with those of the NMDA-receptor channel blocker dizocilpine in two drug discrimination tests. In the first, rats were trained to discriminate morphine (2 mg/kg) from saline and in the second, to discriminate ketamine (7 mg/kg) from saline, using a two-lever food reinforced method. NBQX (1-6 mg/kg) did not substitute for either morphine or ketamine, even at a dose which reduced response rates (6 mg/kg). Likewise, the noncompetitive antagonist GYKI 52466 (5 and 10 mg/kg) produced only saline lever responding in the ketamine trained rats. When tested in combination with the training drug, NBQX (4.5 mg/kg) did not alter the morphine generalisation gradient, and similarly, neither NBQX (3 mg/kg) nor GYKI 52466 (5 and 10 mg/kg) interacted with the ketamine cue. In contrast, dizocilpine (0.05 mg/kg) significantly disrupted discrimination of morphine and produced clear drug lever responding (0.0125-0.1 mg/kg) in ketamine trained rats. These results suggest that AMPA-receptor antagonists and non-competitive NMDA-antagonists have different stimulus properties.
In proestrous rats, serotonin 1A (5-HT1A) receptor agonists inhibit lordosis behavior within 5-15 min following infusion into the ventromedial nucleus of the hypothalamus (VMN). In the present report, the lordosis-inhibiting effects of the 5-HT1A agonist [(+/-) 8-hydroxy-2- (di-n-propylamino) tetralin) (8-OH-DPAT] were shown to be attenuated with 5-HT1A receptor antagonists. Two compounds, propranolol and pindolol, that function as both beta-adrenergic and 5-HT1A receptor antagonists, and (+) WAY100135 (chiral N-t-butyl-3-(1-(4-(2-methoxy) phenyl)piperazinyl)-1-phenylpropionamide dihydrochloride, quarter hydrate), a more selective 5-HT1A receptor antagonist, were found to reduce the lordosis-inhibiting effects of 8-OH-DPAT infusion into the VMN. Proestrous rats were co-infused into the VMN with 200 ng 8-OH-DPAT plus 1000 ng or 2000 ng pindolol, 1000 ng or 2000 ng propranolol, or 2000 ng (+) WAY100135. Co-infusion with 1000 ng or 2000 ng pindolol attenuated the inhibitory effects of 8-OH-DPAT; co-infusion of 1000 ng, but not 2000 ng, propranolol, reduced the effects of 8-OH-DPAT; and co-infusion with 2000 ng (+) WAY100135 attenuated the effects of 8-OH-DPAT. Bilateral VMN infusion with 2500 ng (+) WAY100135 facilitated lordosis behavior in suboptimally, hormone-primed ovariectomized rats. These findings strengthen the argument that the inhibitory effect of 5-HT1A receptor agonists on lordosis behavior is the result of their activation of VMN 5-HT1A receptors.
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The authors assessed airway impedance responses to psychological stressors among 113 individuals: 61 with asthma only (AS), 10 with asthma and panic disorder (ASPD), 24 with panic disorder only (PD), and 18 controls with neither condition (CON). Individuals with either AS or PD were affected by psychological stressors as measured by the forced oscillation technique. Individuals with PD (with or without AS) displayed lower airway impedance than those without PD. These data suggest that the airways of individuals with PD are in a chronic state of preparedness, which may promote hyperventilation.
A 37-year-old woman presented with acute left-sided proptosis. Magnetic resonance imaging demonstrated a solid intraconal mass lesion with an associated 'capping' cyst. This lesion was resected and found on histological examination to be optic nerve sheath meningioma. Small perineural cysts have been reported with optic nerve sheath meningioma but we believe this to be the first reported case of a large peritumoral cyst associated with this type of mass lesion. We speculate on the aetiology of the cyst and the associated acute proptosis.
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Geographic, retrospective, and prospective epidemiologic studies have revealed evidence that the environment in utero is a major determinant of later degenerative disease. Observations from Britain, Sweden, Jamaica, Australia, India, and China support the hypothesis that disproportionate retardation of fetal growth results in increased blood pressure and increased risk of cardiovascular mortality. On the basis of what has been a limited pool of observations linking maternal undernutrition and fetal growth retardation, it has been proposed that hypertension and coronary heart disease are "programmed" by nutrition status.
PURPOSE: To determine the usefulness of a number of imaging features in the differentiation of patients with Graves ophthalmopathy who had optic neuropathy from those who did not. Intracranial herniation of orbital fat through the superior ophthalmic fissure and its clinical importance was also assessed. MATERIALS AND METHODS: The computed tomographic (CT) appearance of the orbital apex was examined in 50 patients without and in 50 patients with Graves ophthalmopathy. The clinical diagnosis of optic neuropathy was made by an ophthalmologist who was unaware of the imaging appearances and was based on clinical features and abnormalities of visual evoked potentials or changes at automated perimetry. RESULTS: Intracranial fat prolapse (P < .001) and optic nerve crowding (P < .05) were the only imaging features that were independently related to optic neuropathy. The presence of intracranial fat prolapse or optic nerve crowding on CT scans helped identify 16 of 17 patients with optic neuropathy. Sensitivity was 94%, specificity was 91%, positive predictive value was 69%, and negative predictive value was 98%. CONCLUSION: Intracranial fat prolapse correlates closely to the presence of optic neuropathy in Graves ophthalmopathy. This sign, in combination with optic nerve crowding, demonstrates a closer correlation to optic neuropathy than previously described imaging features.