Perinatal blastomycosis: the rest of the story.
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Biomedical subjects
Publications and source records attributed to L Young.
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The pilot study for this project was established in February 1993 under a Health Communications Network initiative to improve the treatment results for asthmatics in Campbelltown, New South Wales. A user specific, standardized information environment was implemented across the community and hospital sectors linking General Practitioners, Specialist Consultants, and hospital doctors and nurses. The pilot included 20 General Practitioners, four pediatricians and respiratory physicians, and the nurses and doctors of a district hospital. ¿A multi-disciplinary team implemented the pilot, consisting of men and women from Campbelltown Health Service, Ernst & Young Health Services Consulting, and a major systems vendor. The team used process modeling tools to document the required changes to the roles and responsibilities of the individual practitioners and the impact of these changes on the cost of providing services and patient flow. Significant cost savings were anticipated from moving care out of the hospital and into the community. In the re-engineered environment, the General Practitioner became the case manager, responsible for guiding and coordinating the management of the patient's asthma, in consultation with the appropriate specialist consultants. The hospital continued to provide acute/emergency care. The level of sophistication of the information systems solutions was determined by the level of technical awareness of the users. Fax based communications were chosen to support the flow of timely and relevant information between the practitioners. A VAX based system was used as a data repository for the information collected by hospital staff and General Practitioners. The data repository acted as a clinical record for asthmatics who participated in the pilot. The clinical history of an asthmatic could then be viewed when a patient sought treatment from Campbelltown's Emergency Department during periods when the General Practitioner was not available. If a patient did seek emergency treatment, a record of the patient's visit was faxed immediately to the General Practitioner upon discharge from the hospital. Specialist consultants are independent practitioners in Australia. They were provided with a custom built application for their own personal computers. A key feature of this application was the automatic generation of letters to the General Practitioner to assist them in the management of asthmatics. The Specialist Consultants also identified a sub-group of high risk patients for whom additional clinical information was stored in the data repository at Campbelltown Hospital. Analysis of the patient information formed a core component of the project. Clinical outcomes for individual patients were forwarded to the General Practitioners regularly to assist them in their case management duties. System implementation in this re-engineered environment yielded the following: Strategies for managing the responses of clinicians and patients to the use of technology and a standardized information sharing environment. A means of assessing the system's impact on both the clinician-patient relationship and the professionals' relationship with other clinicians; The evolution of clinical use of information regarding individual patient's health outcome for the management of asthma; The integration of the information systems with policy and planning cycles for the Area Health Service; and The establishment of effective links with vendors of health service applications.
Previous studies in rats have implicated central oxytocin (OT) pathways in the onset of maternal behavior, female sexual receptivity, and the response of the pups to social separation. However, the rat is not ideal for studying effects of OT on attachment as rats fail to form selective, enduring social bonds. To study male-female pair bonds, our laboratory has focused on a microtine rodent, the prairie vole, which is monogamous and highly affiliative. Adult prairie voles form pair bonds after mating (with prolonged, repeated bouts of copulation). As mating releases OT in several species of mammals, we hypothesized that this release was important for pair bond formation in the prairie vole. Central administration of an OT antagonist (but not a V1 antagonist) prevents pair bonding without interfering with the mating behavior. Moreover, central infusion of OT (but not vasopressin, AVP) facilitates pair bonding n the absence of mating. In males, it is AVP (not OT) that appears necessary for pair bond formation. The pattern of OT (and AVP) receptor distribution in the prairie vole brain is entirely distinct from the pattern observed in the closely related non-monogamous montane vole. OT receptors (OTR) in these two species show virtually identical kinetics, specificities, and cDNA sequences (RNA from parturient uterus). In current studies, we are screening genomic libraries from prairie and montane voles to determine if species differences in OTR promoters account for the strikingly different patterns of regional expression in brain. These studies should ultimately provide insight into a neuroendocrine mechanism for pair bond formation.
Two human cytomegalovirus (HCMV) virion structural proteins and their associated reading frames have been identified with two human-derived monoclonal antibodies (HMAbs), X2-16 and X-16. HMAb X2-16 identified recombinant protein expressing molecular clones that mapped to the open reading frame (ORF) of the UL48 gene of HCMV, between amino acids 584 and 646 (nucleotides 65,084 and 65,272, Chee et al., 1990, "Current Topics in Microbiology and Immunology," Vol. 154, pp. 125-169). The UL48 gene product has an apparent molecular weight of 216 kDa. HMAb X-16 identified clones derived from the UL56 ORF between amino acids 380 and 425 (nucleotides 84,733 and 84,870). On immunoblots, HMAb X-16 detected two HCMV proteins of 96 and 60 kDa. Both UL48 and UL56 are highly conserved among the human herpesviruses and their products have been predicted to have essential functions for virus production and maturation. These results confirm that UL48 and UL56 are functional genes encoding essential viral proteins which also generate an immune response in the immunocompetent host.
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A gene, reaper (rpr), that appears to play a central control function for the initiation of programmed cell death (apoptosis) in Drosophila was identified. Virtually all programmed cell death that normally occurs during Drosophila embryogenesis was blocked in embryos homozygous for a small deletion that includes the reaper gene. Mutant embryos contained many extra cells and failed to hatch, but many other aspects of development appeared quite normal. Deletions that include reaper also protected embryos from apoptosis caused by x-irradiation and developmental defects. However, high doses of x-rays induced some apoptosis in mutant embryos, and the resulting corpses were phagocytosed by macrophages. These data suggest that the basic cell death program is intact although it was not activated in mutant embryos. The DNA encompassed by the deletion was cloned and the reaper gene was identified on the basis of the ability of cloned DNA to restore apoptosis to cell death defective embryos in germ line transformation experiments. The reaper gene appears to encode a small peptide that shows no homology to known proteins, and reaper messenger RNA is expressed in cells destined to undergo apoptosis.
The in vivo pharmacological profiles of the selective tachykinin NK1 receptor agonists, [Sar9,Met(O2)11]substance P and GR 73632, were examined in gerbils. Both agonists induced a pronounced chromodacryorrhea following intravenous injection which was stereoselectively antagonised by the tachykinin NK1 receptor antagonist, CP-99,994, but not by its inactive enantiomer, CP-100,263, or the rat-selective tachykinin NK1 receptor antagonist, RP 67,580. In contrast, chromodacryorrhea was not observed following intravenous injection of the selective tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A-(4-10), or the selective tachykinin NK3 receptor agonist, senktide. These results suggest that [Sar9,Met(O2)11]substance P-induced chromodacryorrhea results from activation of peripheral tachykinin NK1 receptors. Repetitive hind paw tapping was also observed in gerbils but only following intracerebroventricular injection of [Sar9,Met(O2)11]substance P or GR 73632. Furthermore, GR 73632-induced hind paw tapping was significantly attenuated by co-administration of the peptide tachykinin NK1 receptor antagonist, GR 82334, or intravenous injection of CP-99,994. Thus, in contrast to chromodacryorrhea, repetitive hind paw tapping may result from activation of central tachykinin NK1 receptors.
The role of hydrophobicity as a determinant of protein-protein interactions is examined. Surfaces of apo-protein targets comprising 9 classes of enzymes, 7 antibody fragments, hirudin, growth hormone, and retinol-binding protein, and their associated ligands with available X-ray structures for their complexed forms, are scanned to determine clusters of surface-accessible amino acids. Clusters of surface residues are ranked on the basis of the hydrophobicity of their constituent amino acids. The results indicate that the location of the co-crystallized ligand is commonly found to correspond with one of the strongest hydrophobic clusters on the surface of the target molecule. In 25 of 38 cases, the correspondence is exact, with the position of the most hydrophobic cluster coinciding with more than one-third of the surface buried by the bound ligand. The remaining 13 cases demonstrate this correspondence within the top 6 hydrophobic clusters. These results suggest that surface hydrophobicity can be used to identify regions of a protein's surface most likely to interact with a binding ligand. This fast and simple procedure may be useful for identifying small sets of well-defined loci for possible ligand attachment.
There is no precise scientific method for determining the correct edentulous occlusal vertical dimension. This study established the proportion between the ear-eye to chin-nose distance for determining reasonable occlusal vertical dimension. Two hundred white and 400 Asian men and women participated in this study. The ear-eye and chin-nose distances were measured with a modified craniometer. The results revealed that left ear-eye distance can be used to predict chin-nose distance with reasonable accuracy. However, the algorithm for making this prediction is not the same for combinations of sex and ethnic origin.
Four experiments in this study assess shade differences in acrylic resin denture and natural teeth. The first two examine the perceptual errors made by experienced dentists in their use of a manufacturer-provided shade guide for acrylic resin denture teeth. In the first of four experiments, dentists examine whether the numbering of a selected shade guide corresponds to the arrangement of the tabs from light to dark. In the second experiment, a visual discrimination task determines whether dentists can distinguish shade guide tabs from one another. The results from these two experiments revealed that the numbered progression of the shade tabs does not correspond to a light-to-dark order, that dentists have difficulty discriminating between several shade tabs, and that the shade tabs can be rearranged on an empirical basis. The third experiment demonstrated how the shade of natural teeth varies by age, gender, and complexion. The Biotone shade guide, rearranged in the manner suggested by the second experiment, was used to make these assessments. The fourth experiment examined whether the shades used for complete dentures were similar to shades found in natural teeth. The results from the last two experiments showed that shade selection can be facilitated by use of a rearranged set of shade guide tabs. The results also reveal that natural teeth significantly and clinically darken with age; however, selections made for denture teeth tend to be relatively constant in color, despite the age of the patient. Differences for gender and complexion do not appear to be clinically significant.
Different variations of the antigen retrieval technique using different retrieval solutions have been evaluated for their effectiveness in restoring the antigenicity of six intranuclear antigens, each of which is a potentially valuable prognostic indicator in formalin-fixed, paraffin-embedded tissue sections. The results of immunohistochemical staining for estrogen receptor, progesterone receptor, androgen receptor, p53 protein, proliferating cell nuclear antigen, and Ki-67 antigen were compared following the different antigen retrieval approaches. The strongest immunostaining signal with the clearest background was obtained by microwave heating of dewaxed paraffin sections for 10 minutes in 0.05 mol/L glycine HCl (pH 3.5) or in citrate buffer solution (pH 6). Urea solution, distilled water, and lead thiocyanate solution yielded improvements with some antigens, but less consistently and less impressively than glycine HCl buffer or citrate buffer. Following antigen retrieval nuclear staining was sharply defined and could be achieved consistently in a variety of tissues after formalin fixation for as long as 7 days. The duration of fixation, however, was an important variable; generally, the longer the fixation time the more vigorous the retrieval procedure required. This study demonstrates the ability to stain a variety of intranuclear antigens, which are not readily demonstrable otherwise, in formalin-paraffin sections with a high degree of consistency and reproducibility. The availability of methods that are effective in paraffin sections may facilitate studies of the possible value of these markers as prognostic indicators for predicting the response of major tumors to different forms of therapy. This study also provided insight into the basic principles of the antigen retrieval method, which may be helpful in attempts to develop a more uniformly standardized technique applicable to many different antigen systems.
Respondents in a stratified random sample of 750 males aged 18 to 27 in Calgary, Canada were asked to recall unwanted sexual contacts occurring before their 17th birthday: 117 (15.6%) had experienced one or more unwanted sexual contacts. Those recalling multiple events of abuse (52 individuals, 6.9% of all respondents) were distinguished from other respondents at a statistically significant level on the following indicators: emotional abuse in childhood, higher rates of current or recent depression, anxiety, suicidal feelings and behavior, and current sexual interest in or actual behavior involving minors. The combination of emotional abuse in the respondent's childhood with multiple events of sexual abuse was a relatively good predictor of both poor mental health, and later sexual interest in or sexual contact with children. Eight apparently active pedophiles were identified, using a computer response system that assured anonymity. This study underscores the need for preventive measures, and the prompt identification and treatment of victims before they enter the victim-to-abuser cycle.
We attempt to analyze whether experimental entropies, enthalpies and free energies of hydration of small uncharged molecules can be quantitatively rationalized with a continuum model including a classical reaction field formalism. We find that a simple proportionality to accessible surface with five different atom types allows satisfactory (within 1-1.5 kcal/mol) reproduction of hydration entropies (T delta S) of over 40 solutes. The agreement with experiment can possibly be improved if proximity effects and configurational contributions to transfer entropies are taken into account. In calculations of hydration enthalpies a reasonable agreement with experimental data can be obtained only when solute polarizability is taken into account. Electrostatic contributions to calculated hydration enthalpies exhibit strong dependencies on both the magnitude and the direction of molecular dipole moments. We demonstrate that for 20 molecules with experimentally measured vacuum dipole moments density functional calculations with DZVPD basis set including diffuse functions on d-orbitals allows prediction of experimental dipole moments within 0.1 D. At a fixed direction of the molecular dipole moment, mu, the electrostatic component of hydration enthalpy varies as mu 2. Thus an uncertainty of 0.1 D corresponds to uncertainties of 0.5-0.7 kcal/mol in hydration enthalpies of most small dipolar solutes. A 30 degree change in the direction of the molecular dipole together with the corresponding change in the quadrupole moment can result in a change of hydration enthalpy of 3 kcal/mol. Changes in the quadrupole moment alone can result in hydration enthalpy changes of over 1 kcal/mol. Representations of multipole expansions by point charges on nuclei fitted to molecular electrostatic potentials cannot accurately reproduce all these factors. Use of such point charges in calculations of hydration enthalpies predictably leads to discrepancies with experiment of approximately 3 kcal/mol for some solutes. However, errors in hydration enthalpies and hydration entropies are usually compensating leading in most cases to agreement between calculated and experimental free energies of hydration within 1.5 kcal/mol.
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The time-course of on-eye hydrogel lens movement has not been carefully scrutinized, despite the importance of lens movement in optimizing lens fit and corneal physiology. We conducted a study to define the time-course of soft lens movement using 26 subjects. Video slitlamp recordings were made of lens movement at 5-min intervals for 30-min wear and after 8-h wear of 38 or 67% water content lenses (N = 14 and 12, respectively). Lens mobility profiles were statistically indistinguishable for high and low water content lenses, and for experienced and neophyte lens wearers. Lens movement displayed biphasic temporal characteristics, decreasing significantly over the first 25 min from a median of 0.6 to 0.3 mm (Wilcoxon matched-pairs signed-rank test, p = 0.002), then increasing significantly to 0.5 mm after 8 h of wear (p = 0.03). Although some subjects exhibited little alteration in lens movement, 31% showed a decrease in lens movement > 0.25 mm during the first half-hour of wear. Optimal predictability of lens mobility after 8-h wear was achieved 5 min after insertion, with 77% of subjects displaying lens movement within +/- 0.25 mm of the final value. In-office assessment of lens movement is best achieved 5 min after insertion, although clinical and real world lens mobility will differ significantly in about one in four patients.
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Analytical procedures were developed to monitor furosemide concentrations in post-race serum and urine samples obtained from horses participating in an exercise-induced pulmonary haemorrhage (EIPH) program. High performance liquid chromatography with ultraviolet light detection proved a reliable, sensitive method for measuring urinary furosemide concentrations up to 12 h after administration of either 150 or 250 mg of the drug to race horses. However, this method was unreliable for determination of serum furosemide concentration. High performance liquid chromatography with fluorescence detection proved a reliable, sensitive method for measuring serum furosemide concentration in horses administered 250 mg of the diuretic, permitting detection of approximately 5-10 ng/ml 6 h after treatment. This method was applied to field conditions where furosemide was administered to horses (between 150 and 250 mg intravenously) 4 h prior to the race. Analytical results assisted in establishing a threshold concentration of 85 ng/ml for serum furosemide. It was found that serum furosemide concentrations are a valid measure of compliance with furosemide administration in the EIPH program.