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PubMed1983

Zinc and the skin.

Zinc is an essential trace element integrally involved in a wide range of metabolic processes required for tissue growth and repair as well as being necessary for maintaining host defences. Zinc deficiency can occur from lack of adequate dietary intake, decreased intestinal absorption, and increased losses in the gastrointestinal tract, urine, and sweat. The clinical signs of zinc deficiency can present in a florid manner with dermatitis, alopecia, and diarrhea, or they can be chronic changes with dwarfism and hypogonadism or, the signs may be barely perceptible with low growth rates and hypogeusia. As with all nutritional deficiencies, the possibility of its existence must be considered before the diagnosis can be made. It is not known how severe zinc deficiency must be or how long it has to be present before the characteristic rash appears. However, as biochemical changes of zinc deficiency occur before any clinical changes do, it is likely that metabolic processes have been affected before the rash heralds the presence of zinc deficiency.

Acrodermatitis↗

PubMed1993

Air transport.

Air transport has become an integral element of pediatric transport programs. The use of both fixed-wing (airplane) and rotorwing (helicopter) aircraft has increased. Appropriate vehicles configured for the safe and effective transfer of pediatric and neonatal patients are available. As the acuity of patients requiring air transport has increased, more sophisticated and specialized training in the areas of flight physiology and transport medicine is required. The limitations of air transport and air transport vehicles must be understood to assure that the optimal modality is selected for a specific transport.

Aircraft↗

PubMed1998

Crystal structure of the tyrosine phosphatase SHP-2.

The structure of the SHP-2 tyrosine phosphatase, determined at 2.0 angstroms resolution, shows how its catalytic activity is regulated by its two SH2 domains. In the absence of a tyrosine-phosphorylated binding partner, the N-terminal SH2 domain binds the phosphatase domain and directly blocks its active site. This interaction alters the structure of the N-SH2 domain, disrupting its phosphopeptide-binding cleft. Conversely, interaction of the N-SH2 domain with phosphopeptide disrupts its phosphatase recognition surface. Thus, the N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. Recognition of bisphosphorylated ligands by the tandem SH2 domains is an integral element of this switch; the C-terminal SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation.

Crystallography↗

PubMed1997

Cytogenetic analysis of adamantinoma of long bones: further indications for a common histogenesis with osteofibrous dysplasia.

Five adamantinomas of long bones were cytogenetically characterized to investigate the role of chromosomal aberrations in their histogenesis, as well as a putative relationship between adamantinoma and osteofibrous dysplasia (OFD). Three tumors had a classic histologic subtype, with abundant epithelium. Two of them revealed trisomies 7, 8, 12, and 19, combined with a balanced translocation, t(10;12), with centromere breakpoints in one tumor. The third showed a karyotype 51,XY, +X, +7, +12, +19, +21. The fourth tumor, of OFD-like subtype, showed trisomies 7, 8, and a small marker chromosome in a low percentage of cells. The fifth tumor, also of OFD-like subtype, displayed only a few keratin-positive cells from the multiple tissue blocks investigated. This latter tumor revealed a clonal abnormality with a karyotype 46,XX,t(2;11)(p23;q14)inv(11)(p14q14), which was confirmed with fluorescence in situ hybridization (FISH), using chromosome-specific library probes and chromosome 11 locus-specific probes. The trisomies 7, 8, and 12 also were described in OFD, which suggests a common histogenesis of OFD and adamantinoma. Our findings further support the probability of clonal origin of OFD. The OFD-like component may be an integral element of adamantinoma, rather than a tissue reaction to epithelial tumor cells.

Adolescent↗

PubMed2006

[Compliance and persistence].

PURPOSE: 1) To summarize the literature on compliance (the extent to which the patient's behaviors correspond with the provider's recommendations) and persistence (total time on therapy) in patients with open-angle glaucoma or ocular hypertension. 2) To suggest guidelines to improve these two parameters, which are both essential and integral elements of optimizing patient care. METHODS: Compliance-related research published between 1980 and March 2005. RESULTS: Medication compliance has mostly been investigated and measured using patient self-reports, electronic monitoring, and medication possession ratio. Noncompliance-related problems are underestimated, complex, unpredictable and frequent. Noncompliance rates of at least 25% have been reported. The main obstacles to medication compliance are situational/environmental or related to the side effects or complexity of the medication regimen. Persistence with glaucoma medications has also been proven to be poor. Based on retrospective studies using survival analyses, fewer than 25% of patients may be persistent over 12 months. Persistence rates differ from one treatment to another and may fluctuate with time in the same patient. CONCLUSIONS: Improving the quality of information, the patient-physician relationship, and educating patients are all crucial. Simplification of the treatment regimen and selection of medications with the fewest systemic and ocular side effects must be a priority. Accurately assessing patient compliance and persistence are indispensable to reducing mistakes from either medication noncompliance or lack of persistence with poor efficacy and to avoid unnecessary changes in a patient's therapeutic regimen or surgery.

Glaucoma, Open-Angle↗

PubMed2002

From retreat to health centre: legislation, commercial opportunity and the repositioning of a Victorian private asylum.

This paper examines the interplay of commercial imperatives and health care legislation in the survival of a privately owned psychiatric hospital in Guelph, Ontario, Canada. Using documentary and archival evidence, we show how the Homewood Retreat (later Sanitarium, and eventually Health Centre) was able to respond to and anticipate legislative developments through the agency of successive medical superintendents and the structural positioning of the institution as an inextricably integrated element in local and provincial mental health provision. Our case study is used to draw out wider lessons concerning agency, legislative context and treatment modality in the determination of organizational histories. We conclude by noting the important role of the private sector in ensuring the continued provision of an asylum form of mental health care.

Facility Regulation and Control↗

PubMed1998

R. D. Laing and the British anti-psychiatry movement: a socio-historical analysis.

In this paper I present a socio historical analysis of the rise of the British anti-psychiatry movement. I have three aims. Firstly, to establish what anti-psychiatry was. Secondly, to investigate and explain its emergence. Thirdly, to consider its relationship to other "new social movements". This analysis is important because criticism and opposition, such as that of the anti-psychiatrists, has been an integral element of the psychiatric field since its earliest developments but has seldom been studied by social scientists, particularly in relation to the post-war period. Power and dominant discourses have been the key focus of analysis, to the detriment of a proper consideration of resistance and counter-discourses. This omission is problematic and should be corrected as social movements introduce plurality, dynamism and the potential for change into the psychiatric field, thus contributing quite centrally to its constitution. Anti-psychiatry is, of course, only one of many movements which require analysis in this connection but it was an important movement and we must begin somewhere. In addition, an analysis of anti-psychiatry serves as an important case study for the sociology of social movements, and particularly for the concern with "new social movements" (NSMs). An analysis of it necessarily makes a contribution to our understanding of NSMs.

History, 20th Century↗

PubMed1998

Different effects of insulin and 2-deoxy-D-glucose administration on tyrosine hydroxylase gene expression in the locus coeruleus and the adrenal medulla in rats.

The major brain norepinephrinergic nucleus, locus coeruleus, is an important integrating element of extero- and interoceptive stimuli in organisms facing different physiological challenges. We investigated the effects of single and repeated (seven times) exposure to immobilization stress (120 min daily), insulin (5 IU/kg, i.p. daily) or 2-deoxy-D-glucose (500 mg/kg, i.p. daily) administration on tyrosine hydroxylase (TH) mRNA levels, the rate-limiting enzyme in catecholamine biosynthesis, by in situ hybridization in locus coeruleus and by Northern blot analysis in the adrenal medulla of rats. Both the single and repeated immobilization caused a significant increase in TH mRNA levels in the locus coeruleus (1.5-2-fold; p < 0.05) and in the adrenal medulla (about 4-fold; p < 0.05) when compared with unstressed controls. Hypoglycemia induced by a single or repeated insulin administration led to about fourfold (p < 0.01) elevation in adrenal medullary TH mRNA levels, whereas TH mRNA in locus coeruleus remained unchanged when compared with saline-treated controls. In contrast to the effect of insulin-induced hypoglycemia, cellular glucoprivation caused by a single or repeated 2-deoxy-D-glucose administration significantly elevated TH mRNA levels in both the adrenal medulla (fourfold; p < 0.01) and the locus coeruleus (twofold; p < 0.01). Our data suggest that in contrast to immobilization or cellular glucoprivation caused by 2-deoxy-D-glucose administration, insulin-induced hypoglycemia is not a specific or quantitatively sufficient stimulus for induction of TH gene expression in the locus coeruleus, although all these stressors strongly activate the process in the adrenal medulla.

Adrenal Medulla↗

PubMed1999

Gene organization in a central DNA fragment of Oenococcus oeni bacteriophage fOg44 encoding lytic, integrative and non-essential functions.

The nucleotide sequence of a DNA fragment previously shown to contain the attachment site (attP) of Oenococcus oeni phage fOg44 (. Arch. Virol. 143, 523-536) has been determined. Sequence analysis indicated that this 6226bp EcoRI fragment harbours an integrase gene, in the vicinity of a direct repeat rich region defining attP, as well as genes encoding a muramidase-related lysin (Lys) and a holin polypeptide (Hol). Transcriptional studies suggested that lys and hol are mainly co-expressed, late in the lytic cycle, from a promotor located upstream of lys. Between the lytic cassette and the phage integration elements three additional open reading frames were found: orf217 and orf252 of unknown function and orf72, the putative product of which bears 32% identity with acidic excisionases from other Gram positive phages. We have established that the first two orfs, as well as the predicted promotor of orf72, are included in a 2143-bp DNA segment missing from the genome of the deletion mutant fOg44Delta2. Although lysogens of fOg44 and fOg44Delta2 exhibited similar properties, each phage produced two distinguishable types of lysogenic strains, differing in inducibility and immunity to other oenophages.

Amino Acid Sequence↗

PubMed1998

Commercial toxicology prediction systems: a regulatory perspective.

The use of commercial toxicity prediction systems in a regulatory setting must consider both the limitations and capabilities of the methods, as well as the ultimate use of the predictions, e.g. for testing prioritization, screening, or supporting regulatory decisions. Current systems are better suited to hazard identification (i.e. positive identification of activity-conferring features) than to ruling out hazard. Two recent examples (an EPA testing prioritization exercise for water disinfection byproducts and a regulatory action on 2,4,6-tribromophenol) illustrate issues involved in regulatory applications of SAR and commercial prediction systems. The challenge for the future will be to improve technologies for prediction within the constraints of available data, make optimal use of new test data, and better integrate elements of quantitative modeling (QSAR), empirical association, and biological and chemical mechanisms towards the goal of toxicity prediction.

Disinfection↗

PubMed1988

Hospital risk management: the second decade.

Risk management is defined as the systematic process of identifying, evaluating and addressing potential and actual risk. Although introduced to the hospital industry nearly a decade ago, it status in Canadian hospitals remains uncertain, a position that is in sharp contrast to the American situation. Chiefly as a result of the medical malpractice crisis and associated circumstances in the mid-1970s, risk management has emerged as an integral element in the operational activities of American hospitals. The process is a mechanism for self-protection in co-operative, self-insurance arrangements and to secure commercial premium adjustments. Many trends have been recognized in canada that would suggest a predisposition toward the proliferation of risk management programs. These indicators include an increase in the number and size of claims against hospitals and physicians, a reduction in the availability of commercial health care insurance, and an increase in alternative insurance arrangements. Despite these indicators, movement toward risk management by Canadian hospitals has been minimal. A prime reason appears to be lack of financial incentives to stimulate the development of risk management programs. There is also an absence of specific accreditation standards pertaining to such programs. The case in support of risk management for Canadian hospitals continues to grow. The basic assumptions associated with a program are board, medical and staff support; a concerted effort to recognize and reduce potentially litigious situations and occurrences; and an ability to adapt. The initial steps to develop a risk management program include assessing current risk control activities and implementing structural elements. As well, a program must address its relationship to Quality Assurance activities in the hospital.

Canada↗

PubMed2003

Identification and characterization of RAD9B, a paralog of the RAD9 checkpoint gene.

RAD9 is an integral element of the PCNA-like HUS1-RAD1-RAD9 (9-1-1) complex that participates in genotoxin-induced CHK1 activation. We have identified a novel RAD9 paralog, dubbed RAD9B, in humans and mice. RAD9 and RAD9B share extensive amino acid homology throughout their entire sequences (36% identity, 48% similarity). Northern blotting revealed that RAD9B transcripts are highly expressed in human testes, with lower levels found in skeletal muscle. In contrast, RT-PCR analysis and immunoprecipitation demonstrated that RAD9B is also expressed in tumor cells. Like RAD9, RAD9B associates with HUS1, RAD1, and RAD17, suggesting that it is a RAD9 paralog that engages in similar biochemical reactions. In addition, we have also shown that RAD9 and RAD9B interact with the HUS1 paralog, HUS1B. Taken together, these results suggest that these proteins can combinatorially assemble into distinct 9-1-1 clamps that may have distinct biological functions.

Amino Acid Sequence↗

PubMed1997

HIV disease in pregnancy. Ethics, law, and policy.

Legal and ethical principles mandate that informed consent be an integral element of HIV-related education, counseling, testing, treatment, and intervention. Minimizing patient counseling and education (for economic reasons or otherwise) is likely to backfire. The presumption that a parent will act in her child's best interest, accepted in analogous contexts, should be foundational in the development of HIV policy in the obstetric and gynecologic setting. Most women, when provided with counseling, care, and confidentiality, consent to prenatal or perinatal testing and, most important, engage their families in HIV-related care and services. Because of the changing terrain of knowledge about and treatments of HIV disease, providers must thoroughly counsel women regarding the risks and benefits of available treatment and intervention.

Female↗

PubMed2000

Safety of recombinant and plasma-derived medicinals for the treatment of coagulopathies.

The introduction of advanced technologies (PCR testing, chromatography, and specific viral inactivation and removal techniques) has led to remarkable improvements in the quality and efficacy of biopharmaceutical products. The current safety strategies for both recombinant protein and PDP products depend on the extensive screening of the source material for infectious agents and the use of mild purification methods, specific mild viral-reduction techniques, GMP, QC, and QA. An appropriate system of pharmacologic vigilance is also an integral element for assuring product quality and safety in the marketplace. Such precautions make available high quality therapeutic recombinant proteins and PDP products. The risks in the clinical setting and the cost/benefit ratio must be considered in choosing a product for therapeutic use. The choice should be based on the analysis of data available for a specific product, because some variations in quality and safety can be observed in different brands. Overall, a much finer control of infectious risks has been achieved, and improvement will continue. With the new products, thrombotic episodes have become rare. Reducing immunogenic potential and improving yield to increase product supply could be the next challenges for producers of biopharmaceuticals.

Animals↗

PubMed1999

Conference overview: through the patient's eyes--improvement strategies that work.

BACKGROUND: To promote a continuing dialogue among innovators in patient-centered health care quality assessment and improvement, The Picker Institute (Boston) sponsored conferences in 1995 and 1996, and in July 1997 launched the first of its summer symposia designed primarily for its clients. This overview summarizes the work and ideas presented at The Picker Institute's second summer symposium, "Through the Patient's Eyes: Improvement Strategies That Work," held in Cambridge, Massachusetts, on July 9-10, 1998. ISSUES AND PARTICIPANTS: Plenary session speaker David H. Gustafson, PhD, emphasized four key themes in his discussion of breakthrough improvement and service-focus on customers, innovation through information technology, an empirical methodology for predicting success, and leadership. Donald M. Berwick, MD, argued that it is better to treat the consumer not as an inspector but as an integral element in the total system of health care. In the closing plenary session, John Stone, MD, stated that although physicians like to think of themselves as teachers, it is the patients who teach them with the stories they bring. "Listen to the patient," he concluded. "The patient is telling you the diagnosis." Health care researchers and professionals, representing a wide variety of settings and patient conditions, reported in breakout sessions on their practical experiences using patient-generated data on quality and strategies for improving care. Several presenters described their practical experience using patient-centered measures as part of a coordinated approach to systemwide improvement. In other sessions, presenters offered advice about how to present patient survey data to colleagues and encourage their participation in prioritizing and acting on improvement opportunities.

Boston↗

PubMed2001

Analysis of thymectomy for myasthenia gravis in older patients: a 20-year single institution experience.

BACKGROUND: Thymectomy has become recognized as an integral element in the care of the patient with myasthenia gravis. Although the number of elderly patients with myasthenia is substantial, little data exist demonstrating the efficacy and morbidity of thymectomy in this population. STUDY DESIGN: We retrospectively analyzed 126 cervicomediastinal thymectomies performed at a single university hospital from 1980 to 1998. Patients 55 years or older were compared with those less than 55. Efficacy was measured by determining the change in Osserman score, the rate of remission during followup, and the reduction in medication requirements after thymectomy. RESULTS: Older patients (n = 28) had similar Osserman scores (p = 0.8) and similar rates of complete and partial remission as the younger group (n = 98) at a mean +/- SEM followup of 58 +/- 5 months. The two groups did not differ in the number (p = 0.4) and doses of medications used to control myasthenic symptoms after operation. Older age was associated with an increased length of hospitalization (13.8 +/- 3.2 days versus 9.7 +/- 0.6 days, p = 0.05) and a higher incidence of reintubation, and longer ventilatory support (2.6 +/- 1.3 days versus 0.1 +/- 0.1 days, p = 0.001). CONCLUSIONS: Increased age does not alter the outcomes of thymectomy for myasthenia gravis. Older patients can expect to have similar responses and require a similar number of postoperative medications as younger patients, but with a higher short-term morbidity.

Adolescent↗

PubMed2003

High-content assays for ligand regulation of G-protein-coupled receptors.

High-content assays rely on the imaging of cellular events. They can be used to monitor the activation of G-protein-coupled receptors (or other receptors), their internalization into the cell, or alterations in their amount. In addition, multiplexed assays can provide further information about the characteristics of the receptor. Recent improvements in throughput using high-content screening platforms means that such assays are now an integral element of functional analysis in the drug discovery process.

Animals↗

PubMed1988

Osteoclast-type giant cell neoplasms of the parotid gland.

The parotid gland is added to the list of parenchymal organs, notably the pancreas, in which osteoclast-like cells appear as constituent cells in their neoplasms. The cells' role in the neoplasms is a reactive one or, more rarely, as an integral element in an osteoclast-type giant cell neoplasm or so-called osteoclastoma. Distinctive in histological appearance, the osteoclast-type giant cell neoplasm is a malignant lesion that, to date, has been described only in the pancreas and parotid glands. This report presents examples of each type of giant cell lesion in the parotid gland.

Aged↗